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  • 1501.
    Wallert, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Madison, Guy
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Olsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Cognitive ability, lifestyle risk factors, and two-year survival in first myocardial infarction men: A Swedish National Registry study2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 15, no 231, p. 13-17Article in journal (Refereed)
    Abstract [en]

    Background: General cognitive ability (CA) is positively associated with later physical and mental health, health literacy, and longevity. We investigated whether CA estimated approximately 30 years earlier in young adulthood predicted lifestyle-related risk factors and two-year survival in first myocardial infarction (MI) male patients.

    Methods: Young adulthood CA estimated through psychometric testing at age 18–20 years was obtained from the mandatory military conscript registry (INSARK) and linked to national quality registry SWEDEHEART/RIKS-HIA data on smoking, diabetes, hypertension, obesity (BMI > 30 kg/m2) in 60 years or younger Swedish males with first MI. Patients were followed up in the Cause of Death registry. The 5659 complete cases (deceased = 106, still alive = 5553) were descriptively compared. Crude and adjusted associations were modelled with logistic regression.

    Results: After multivariable adjustment, one SD increase in CA was associated with a decreased odds ratio of being a current smoker (0.63 [0.59, 0.67], P < 0.001), previous smoker (0.79 [0.73, 0.84], P < 0.001), having diabetes (0.82 [0.74, 0.90], P < 0.001), being obese (0.90 [0.84, 0.95], P < 0.001) at hospital admission, and an increased odds ratio of two-year survival (1.26 [1.02, 1.54], P < 0.001). CA was not associated with hypertension at hospital admission (1.03 [0.97, 1.10], P = 0.283).

    Conclusions: This study found substantial inverse associations between young adulthood CA, and middle-age lifestyle risk factors smoking, diabetes, and obesity, and two-year survival in first MI male patients. CA assessment might benefit risk stratification and possibly aid further tailoring of secondary preventive strategy.

  • 1502.
    Wallert, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Psychology in Healthcare. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Tomasoni, Mattia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Madison, Guy
    Department of Psychology, Umeå University.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Predicting two-year survival versus non-survival after first myocardial infarction using machine learning and Swedish national register data2017In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 17, p. 1-11, article id 99Article in journal (Refereed)
    Abstract [en]

    Background: Machine learning algorithms hold potential for improved prediction of all-cause mortality in cardiovascular patients, yet have not previously been developed with high-quality population data. This study compared four popular machine learning algorithms trained on unselected, nation-wide population data from Sweden to solve the binary classification problem of predicting survival versus non-survival 2 years after first myocardial infarction (MI).

    Methods: This prospective national registry study for prognostic accuracy validation of predictive models used data from 51,943 complete first MI cases as registered during 6 years (2006–2011) in the national quality register SWEDEHEART/RIKS-HIA (90% coverage of all MIs in Sweden) with follow-up in the Cause of Death register (> 99% coverage). Primary outcome was AUROC (C-statistic) performance of each model on the untouched test set (40% of cases) after model development on the training set (60% of cases) with the full (39) predictor set. Model AUROCs were bootstrapped and compared, correcting the P-values for multiple comparisons with the Bonferroni method. Secondary outcomes were derived when varying sample size (1–100% of total) and predictor sets (39, 10, and 5) for each model. Analyses were repeated on 79,869 completed cases after multivariable imputation of predictors.

    Results: A Support Vector Machine with a radial basis kernel developed on 39 predictors had the highest complete cases performance on the test set (AUROC = 0.845, PPV = 0.280, NPV = 0.966) outperforming Boosted C5.0 (0.845 vs. 0. 841, P = 0.028) but not significantly higher than Logistic Regression or Random Forest. Models converged to the point of algorithm indifference with increased sample size and predictors. Using the top five predictors also produced good classifiers. Imputed analyses had slightly higher performance.

    Conclusions: Improved mortality prediction at hospital discharge after first MI is important for identifying high-risk individuals eligible for intensified treatment and care. All models performed accurately and similarly and because of the superior national coverage, the best model can potentially be used to better differentiate new patients, allowing for improved targeting of limited resources. Future research should focus on further model development and investigate possibilities for implementation. 

  • 1503.
    Wallin, Emma
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Olsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Burell, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Carlsson, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Treatment Activity, User Satisfaction, and Experienced Usability of Internet-Based Cognitive Behavioral Therapy for Adults With Depression and Anxiety After a Myocardial Infarction: Mixed-Methods Study2018In: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 20, no 3, article id e87Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Knowledge about user experiences may lead to insights about how to improve treatment activity in Internet-based cognitive behavioral therapy (iCBT) to reduce symptoms of depression and anxiety among people with a somatic disease. There is a need for studies conducted alongside randomized trials, to explore treatment activity and user experiences related to such interventions, especially among people with older age who are recruited in routine care.

    OBJECTIVE:

    The aim of the study was to explore treatment activity, user satisfaction, and usability experiences among patients allocated to treatment in the U-CARE Heart study, a randomized clinical trial of an iCBT intervention for treatment of depression and anxiety following a recent myocardial infarction.

    METHODS:

    This was a mixed methods study where quantitative and qualitative approaches were used. Patients were recruited consecutively from 25 cardiac clinics in Sweden. The study included 117 patients allocated to 14 weeks of an iCBT intervention in the U-CARE Heart study. Quantitative data about treatment activity and therapist communication were collected through logged user patterns, which were analyzed with descriptive statistics. Qualitative data with regard to positive and negative experiences, and suggestions for improvements concerning the intervention, were collected through semistructured interviews with 21 patients in the treatment arm after follow-up. The interviews were analyzed with qualitative manifest content analysis.

    RESULTS:

    Treatment activity was low with regard to number of completed modules (mean 0.76, SD 0.93, range 0-5) and completed assignments (mean 3.09, SD 4.05, range 0-29). Most of the participants initiated the introduction module (113/117, 96.6%), and about half (63/117, 53.9%) of all participants completed the introductory module, but only 18 (15.4%, 18/117) continued to work with any of the remaining 10 modules, and each of the remaining modules was completed by 7 or less of the participants. On average, patients sent less than 2 internal messages to their therapist during the intervention (mean 1.42, SD 2.56, range 0-16). Interviews revealed different preferences with regard to the internet-based portal, the content of the treatment program, and the therapist communication. Aspects related to the personal situation and required skills included unpleasant emotions evoked by the intervention, lack of time, and technical difficulties.

    CONCLUSIONS:

    Patients with a recent myocardial infarction and symptoms of depression and anxiety showed low treatment activity in this guided iCBT intervention with regard to completed modules, completed assignments, and internal messages sent to their therapist. The findings call attention to the need for researchers to carefully consider the preferences, personal situation, and technical skills of the end users during the development of these interventions. The study indicates several challenges that need to be addressed to improve treatment activity, user satisfaction, and usability in internet-based interventions in this population.

  • 1504. Wang, Tracy Y.
    et al.
    White, Jennifer A.
    Tricoci, Pierluigi
    Giugliano, Robert P.
    Zeymer, Uwe
    Harrington, Robert A.
    Montalescot, Gilles
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Van de Werf, Frans
    Armstrong, Paul W.
    Braunwald, Eugene
    Califf, Robert M.
    Newby, L. Kristin
    Upstream Clopidogrel Use and the Efficacy and Safety of Early Eptifibatide Treatment in Patients With Acute Coronary Syndrome An Analysis From the Early Glycoprotein IIb/IIIa Inhibition in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) Trial2011In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 126, no 7, p. 722-730Article in journal (Refereed)
    Abstract [en]

    Background-In the Early Glycoprotein IIb/IIIa Inhibition in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial, routine preangiography eptifibatide use was not superior to delayed provisional use but led to more bleeding. This analysis examines efficacy and safety of early eptifibatide in the setting of concurrent upstream clopidogrel use. Methods and Results-In EARLY-ACS, clopidogrel use and timing were determined by treating physicians, but randomization to early eptifibatide versus placebo was stratified by the intent to use upstream clopidogrel. Among 9166 non-ST-elevation acute coronary syndrome patients who underwent coronary angiography, intent to use upstream clopidogrel was declared in 6895 (75%), and 7068 (77%) received upstream clopidogrel. After multivariable adjustment, intended upstream clopidogrel use did not differentially influence the effect of early eptifibatide on the primary end point of 96-hour death/myocardial infarction/recurrent ischemia requiring urgent revascularization/thrombotic bailout (interaction P = 0.988). Early eptifibatide use reduced 30-day death/myocardial infarction among patients with intended upstream clopidogrel (adjusted odds ratio 0.85; 95% confidence interval 0.73 to 0.99) but not among those without intended upstream clopidogrel use (adjusted odds ratio 1.02; 95% confidence interval 0.80 to 1.30). However, the clopidogrel by randomized treatment interaction term was not significant (P = 0.23). Thrombolysis in Myocardial Infarction major bleeding risk was increased with early eptifibatide in the setting of upstream clopidogrel use. Results were similar using actual clopidogrel treatment strata. Conclusions-Routine early eptifibatide use, compared with delayed provisional use, may be associated with lower 30-day ischemic risk in non-ST-elevation acute coronary syndrome patients also treated with clopidogrel before angiography. The benefit-risk ratio of intensive platelet inhibition with combined early use of antiplatelet agents needs further evaluation in prospective randomized trials.

  • 1505.
    Wang, William T.
    et al.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Duke Box 3850,2400 Pratt St, Durham, NC 27705 USA..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wang, Tracy Y.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Duke Box 3850,2400 Pratt St, Durham, NC 27705 USA..
    A review of sex-specific benefits and risks of antithrombotic therapy in acute coronary syndrome2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 3, p. 165-171Article in journal (Refereed)
    Abstract [en]

    Over the past decade, more men than women have shown improved outcomes from antithrombotic therapies after acute coronary syndrome (ACS), which raises the question of whether there are sex-specific differences in treatment patterns and response to therapy. Differences in presenting clinical characteristics, pathophysiologic profile, and disparities in treatment may contribute to this outcomes discrepancy. Analyses of large trials and registry data suggest that male and female ACS patients experience similar benefits from antithrombotic therapy without significant difference in treatment utilization rates, yet women are consistently at higher risk of bleeding than men. Bleeding may result in antithrombotic treatment disruption, which increases the risk of long-term thrombotic events. Additionally, female ACS patients are more likely to receive suboptimal medication dosing and have lower rates of long-term medication adherence. These differences have significant clinical implications for women, indicating the need for strategies that will optimize initial treatment and long-term management attuned to these recognized sex-specific gaps.

  • 1506.
    Warensjö, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study2011In: BMJ (British edition), ISSN 1756-1833, Vol. 342, p. d1473-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis.

    DESIGN:

    A longitudinal and prospective cohort study, based on the Swedish Mammography Cohort, including a subcohort, the Swedish Mammography Cohort Clinical.

    SETTING:

    A population based cohort in Sweden established in 1987.

    PARTICIPANTS:

    61,433 women (born between 1914 and 1948) were followed up for 19 years. 5022 of these women participated in the subcohort.

    MAIN OUTCOME MEASURES:

    Primary outcome measures were incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort. Diet was assessed by repeated food frequency questionnaires.

    RESULTS:

    During follow-up, 14,738 women (24%) experienced a first fracture of any type and among them 3871 (6%) a first hip fracture. Of the 5022 women in the subcohort, 1012 (20%) were measured as osteoporotic. The risk patterns with dietary calcium were non-linear. The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake, and 14.0/1000 person years at risk in the third quintile, corresponding to a multivariable adjusted hazard ratio of 1.18 (95% confidence interval 1.12 to 1.25). The hazard ratio for a first hip fracture was 1.29 (1.17 to 1.43) and the odds ratio for osteoporosis was 1.47 (1.09 to 2.00). With a low vitamin D intake, the rate of fracture in the first calcium quintile was more pronounced. The highest quintile of calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture, hazard ratio 1.19 (1.06 to 1.32).

    CONCLUSION:

    Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis.

  • 1507.
    Washam, Jeffrey B.
    et al.
    Duke Univ, Sch Med, Duke Clin Res Inst, Duke Heart Ctr, Box 3943 DUMC, Durham, NC 27710 USA.
    Hohnloser, Stefan H.
    Goethe Univ Frankfurt, Frankfurt, Germany.
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Duke Heart Ctr, Box 3943 DUMC, Durham, NC 27710 USA.
    Wojdyla, Daniel M.
    Duke Univ, Sch Med, Duke Clin Res Inst, Duke Heart Ctr, Box 3943 DUMC, Durham, NC 27710 USA.
    Vinereanu, Dragos
    Univ & Emergency Hosp Bucharest, Bucharest, Romania.
    Alexander, John H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Duke Heart Ctr, Box 3943 DUMC, Durham, NC 27710 USA.
    Gersh, Bernard J.
    Mayo Clin, Coll Med, Rochester, MN USA.
    Hanna, Michael
    Bristol Myers Squibb Co, Princeton, NJ USA.
    Horowitz, John
    Univ Adelaide, Basil Hetzel Inst, Queen Elizabeth Hosp, Adelaide, SA, Australia.
    Hylek, Elaine M.
    Boston Univ, Sch Med, Boston, MA 02118 USA.
    Xavier, Denis
    St Johns Res Inst, Bengaluru, India.
    Verheugt, Freek W. A.
    Univ Med Ctr Nijmegen, Nijmegen, Netherlands.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Duke Heart Ctr, Box 3943 DUMC, Durham, NC 27710 USA.
    Interacting medication use and the treatment effects of apixaban versus warfarin: results from the ARISTOTLE Trial2019In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 47, no 3, p. 345-352Article in journal (Refereed)
    Abstract [en]

    Warfarin is dependent on multiple hepatic enzymes for metabolism while apixaban is a substrate for P-glycoprotein (P-gp) transport and hepatic CYP3A4 metabolism. The aim of this analysis was to assess the impact of interacting medication use on the treatment effects of apixaban versus warfarin. Outcomes were compared between apixaban and warfarin using Cox proportional hazards modeling according to the use of interacting medications at randomization in ARISTOTLE (n=18,201). Interacting medications for apixaban were identified as combined P-gp and 3A4 inhibitors or inducers while interacting medications for warfarin were defined as those highly probable for warfarin potentiation or inhibition. At randomization, 5547 (30.5%) patients were on an interacting medication, including 2722 on apixaban and 2825 on warfarin. Patients using an interacting medication were more likely to be female, taking aspirin, and have a history of prior bleeding and were less likely to have a prior stroke or transient ischemic attack. No significant differences were observed on the treatment effect of apixaban compared with warfarin in patients on and off interacting medications for outcomes including the primary efficacy outcome of stroke or systemic embolism (P for interaction=0.79) or the primary safety outcome of major bleeding (P for interaction=0.75). Use of interacting medications with anticoagulants occurs often in patients with atrial fibrillation. Despite the potential for altered exposure, interacting medication use was not associated with a significant change in the efficacy or safety of apixaban compared with warfarin in the ARISTOTLE trial.Trial registration ClinicalTrials.gov, NCT00412984

  • 1508. Waziri, H.
    et al.
    Joergensen, E.
    Kelbaek, H.
    Stagmo, M.
    Pedersen, F.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kober, L.
    Wachtell, K.
    Comparison of outcome in patients with ST-elevation myocardial infarction treated with PCI in Eastern Denmark with patients treated in Southern Sweden2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 133-133Article in journal (Refereed)
  • 1509. Waziri, H.
    et al.
    Stagmo, M.
    Joergensen, E.
    Kelbaek, H.
    Pedersen, F.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kober, L.
    Wachtell, K.
    Short- and long-term outcomes after PCI for young patients with ST-elevation myocardial infarction2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 469-469Article in journal (Refereed)
  • 1510.
    Waziri, Homa
    et al.
    Univ Copenhagen, Rigshosp, Ctr Heart, Dept Cardiol, DK-1168 Copenhagen, Denmark..
    Jorgensen, Erik
    Univ Copenhagen, Rigshosp, Ctr Heart, Dept Cardiol, DK-1168 Copenhagen, Denmark..
    Kelbaek, Henning
    Univ Copenhagen, Rigshosp, Ctr Heart, Dept Cardiol, DK-1168 Copenhagen, Denmark..
    Stagmo, Martin
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Malmo, Sweden..
    Pedersen, Frants
    Univ Copenhagen, Rigshosp, Ctr Heart, Dept Cardiol, DK-1168 Copenhagen, Denmark..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kober, Lars
    Univ Copenhagen, Rigshosp, Ctr Heart, Dept Cardiol, DK-1168 Copenhagen, Denmark..
    Wachtell, Kristian
    Univ Orebro, Fac Hlth, Dept Cardiol, SE-70182 Orebro, Sweden.;Glostrup Univ Hosp, Glostrup, Denmark..
    Short and long-term survival after primary percutaneous coronary intervention in young patients with ST-elevation myocardial infarction2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 203, p. 697-701Article in journal (Refereed)
    Abstract [en]

    The long-term prognosis of patients with ST-elevation myocardial infarction (STEMI) aged 45 years or younger and differences according to gender have not been well characterized. Methods: We included 16,685 consecutive STEMI patients from 2003 to 2012 (67,992 patient-years follow-up) from the Eastern Danish Heart Registry and the Swedish Coronary Angiography and Angioplasty Registry who were treated with primary percutaneous coronary intervention (PCI). Results: We identified 1026 (6.2%) patients up to 45 years of age (mean age: 40.7 vs. 66.3 years, P < 0.001). Patients in the young group were predominantly men (79.7% vs. 71.9%) and smokers (71.2% vs. 44.2%, P < 0.001) but with a lower prevalence of hypertension (17.3% vs. 39.3%), hyperlipidemia (18.0% vs. 23.8%), diabetes (9.0% vs. 12.4%) and previous myocardial infarction (6.9% vs. 12.2%, all P < 0.001) compared with older patients. Young patients had a 0.8% annualmortality. During the follow-up period 6.3% of young patients died vs. 28.5% of older patients (P < 0.001). Both 30-day-mortality (adjusted hazard ratio [HR] = 0.26, 95% confidence interval [CI]: 0.12-0.54, P < 0.001) and mortality after 30 days and onwards (HR = 0.25, CI: 0.17-0.37, P < 0.001) were significantly lower in the young group. There was no difference in short-term (HR = 0.78, CI: 0.32-1.90, P = 0.59) or long-term (HR = 0.62, CI: 0.33-1.91, P = 0.59) mortality between women and men in the young group (HR = 0.79, CI: 0.21-1.80, P = 0.39). Conclusions: STEMI patients, aged 45 years or younger, have an excellent prognosis after treatment with primary PCI. Long-termannual survival is more than 99% in these patients. Young women with STEMI do not have a worse long-term prognosis than young men with STEMI.

  • 1511.
    Weisz, Giora
    et al.
    Shaare Zedek Med Ctr, IL-91031 Jerusalem, Israel;Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA;Cardiovasc Res Fdn, New York, NY USA.
    Généreux, Philippe
    Cardiovasc Res Fdn, New York, NY USA; Univ Montreal, Hop Sacre Coeur Montreal, Montreal, PQ, Canada.
    Iñiguez, Andres
    Hosp Meixoeiro, Vigo, Spain.
    Zurakowski, Aleksander
    Amer Heart Poland SA, Katowice, Poland.
    Shechter, Michael
    Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
    Alexander, Karen P.
    Duke Clin Res Inst, Durham, NC USA; Duke Univ, Durham, NC USA.
    Dressler, Ovidiu
    Cardiovasc Res Fdn, New York, NY USA.
    Osmukhina, Anna
    Gilead Sci Inc, Foster City, CA 94404 USA.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ohman, E. Magnus
    Duke Clin Res Inst, Durham, NC USA; Duke Univ, Durham, NC USA.
    Ben-Yehuda, Ori
    Cardiovasc Res Fdn, New York, NY USA.
    Farzaneh-Far, Ramin
    Gilead Sci Inc, Foster City, CA 94404 USA.
    Stone, Gregg W.
    Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA; Cardiovasc Res Fdn, New York, NY USA.
    Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomised, double-blind, placebo-controlled trial2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10014, p. 136-145Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention.

    METHODS: We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≥18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≥50% diameter stenosis in a coronary artery ≥2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038.

    FINDINGS: Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04).

    INTERPRETATION: Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population.

    FUNDING: Gilead Sciences, Menarini.

  • 1512.
    Welsh, Robert C.
    et al.
    Mazankowski Alberta Heart Inst, Edmonton, AB, Canada.;Univ Alberta, Edmonton, AB, Canada..
    Roe, Matthew T.
    Duke Med, Duke Clin Res Inst, Div Cardiol, Durham, NC USA..
    Steg, Philippe Gabriel
    Univ Paris Diderot, Sorbonne Paris Cite, FACT, DHU FIRE,AP HP, Paris, France.;INSERM, U1148, Paris, France.;Imperial Coll, NHLI, Royal Brompton Hosp, London, England..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Povsic, Thomas J.
    Duke Med, Duke Clin Res Inst, Div Cardiol, Durham, NC USA..
    Bode, Christoph
    Univ Freiburg, Freiburg, Germany..
    Gibson, Charles Michael
    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Cardiovasc Div, Dept Med, Boston, MA USA..
    Ohman, Erik Magnus
    Duke Med, Duke Clin Res Inst, Div Cardiol, Durham, NC USA..
    A critical reappraisal of aspirin for secondary prevention in patients with ischemic heart disease2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 181, p. 92-100Article in journal (Refereed)
    Abstract [en]

    Aspirin was established more than a quarter century ago as an evidence-based therapy to reduce recurrent cardiovascular events in patients with coronary artery disease based on limited data by contemporary standards. Indeed it is unclear how regulatory agencies would define the optimal dose or duration of aspirin therapy if assessed in the current era. Subsequent clinical investigation has focused on the addition of antithrombotic agents on top of baseline aspirin therapy in the acute and chronic setting to reduce patient's risk of further ischemic events, at the cost of increased bleeding complications. The current armamentarium of potent and predictable antiplatelet and antithrombotic agents has ushered in a new era where clinicians and scientists are contemplating withdrawal of previously established agents to minimize bleeding risk while sustaining efficacy; indeed, subtraction may lead to the next advance in the treatment of acute and chronic ischemic vascular disease.

  • 1513.
    Wennström, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    The Met Needs Index: a new metric for outcome assessment in mental health care2010In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 45, no 3, p. 425-432Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: No apt method has been available to assess and monitor the responsiveness of services in meeting ongoing needs of patients with long-term mental illness. The present study examines the utility of a new metric for such a purpose, the Met Needs Index (MNI), applied to the Camberwell Assessment of Need (CAN). METHODS: The MNI was estimated as an aggregated measure of met need or beneficial outcome, based on annual staff rated CAN-assessments of 321 outpatients (76% psychotic disorders) in psychiatric care during 7 years. Corresponding confidence intervals were estimated with the bootstrap percentile method. RESULTS: The overall MNI was estimated at 0.71 (95% CI 0.69-0.74), indicating that identified needs in general were met during 71% of the intervals between the annual assessments. However, the MNI for specific need domains of the CAN ranged from 0.89 (95% CI 0.84-0.93) for 'food' to 0.11 (95% CI 0.07-0.16) for 'sexual expression', indicating a significant variation in responsiveness of services to different types of need in this patient population. CONCLUSIONS: The MNI seems to be a useful and powerful metric for outcome assessment and monitoring of psychiatric services from a needs assessment approach.

  • 1514.
    Wennström, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Wiesel, Frits-Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Deconstructing the 'black box' of the Camberwell assessment of need score in mental health services evaluation2008In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 43, no 9, p. 714-719Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of the study was to examine an alternative way of scoring the Camberwell Assessment of Need (CAN) for the purpose of service evaluation, using the by us defined Social Services (SI) and Psychiatric Services (PI) subindices. Methods: CAN assessments in 1997 and 1999 of 262 outpatients (mean age 45 years, 77.1% psychotic disorders) were reanalysed to fit the SI and the PI, which were compared to the full CAN. Results: The mean total needs on the full CAN decreased from 6.65 to 6.22 (P = 0.007), as did the mean unmet needs (1.55-1.81, P = 0.049). The mean total needs on the PI decreased from 2.42 to 2.22 (P = 0.006), as did the mean unmet needs (1.66-0.57, P < 0.001). No changes in mean needs occurred on the SI. Conclusions: All significant changes occurred on the PI, indicating a more beneficial outcome of the psychiatric care than the social care in terms of meeting needs, a result impossible to discern from the total scores of the CAN. Thus, output scores on subindices of the CAN might be useful as outcome measures in service evaluation.

  • 1515.
    Wernroth, Mona-Lisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Fall, Katja
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Fang, Fang
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Lung & Allergy Unit, Stockholm, Sweden..
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Dog Exposure During the First Year of Life and Type 1 Diabetes in Childhood2017In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 171, no 7, p. 663-669Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The association between early exposure to animals and type 1 diabetes in childhood is not clear. OBJECTIVE To determine whether exposure to dogs during the first year of life is associated with the development of type 1 diabetes in childhood. DESIGN, SETTING, AND PARTICIPANTS A nationwide cohort study utilizing high-quality Swedish national demographic and health registers was conducted. A total of 840 593 children born in Sweden from January 1, 2001, to December 31, 2010, were evaluated. Type 1 diabetes was identified using diagnosis codes from hospitals and dispensed prescriptions of insulin. Cox proportional hazards regression models were used to assess the association between exposure to dogs and risk of type 1 diabetes in childhood. The possible association was further investigated by performing dose-response and breed group-specific analyses. The cohort was followed up until September 30, 2012. Data analysis was conducted from October 15, 2015, to February 8, 2017. EXPOSURES Having a parent who was registered as a dog owner during the child's first year of life. MAIN OUTCOMES AND MEASURES Childhood-onset type 1 diabetes. RESULTS Of the 840 593 children reviewed, 408 272 (48.6%) were girls; mean (SD) age at diagnosis of type 1 diabetes was 5.1 (2.6) years. Dog exposure was identified in 102 035 children (12.1%). Follow-up started at age 1 year, and the children were followed up for as long as 10.7 years (median, 5.5 years). During follow-up, 1999 children developed type 1 diabetes. No association was found between exposure to dogs (adjusted hazard ratio [HR], 1.00; 95% CI, 0.86-1.16) and type 1 diabetes in childhood. The size of the dog (adjusted HR per 10-cm increase in height, 0.96; 95% CI, 0.86-1.06) or number of dogs in the household (1 dog: adjusted HR, 1.07; 95% CI, 0.91-1.26; 2 dogs: 0.79; 95% CI, 0.54-1.15; >= 3 dogs: 0.50; 95% CI, 0.23-1.12; compared with nonexposed children) also was not associated with type 1 diabetes risk. An analysis of children whose parent had type 1 diabetes (210 events) yielded an adjusted HR of 0.71 (95% CI, 0.43-1.17) for dog exposure. CONCLUSIONS AND RELEVANCE In a nationwide study, no evidence supporting an association of register-derived measures of dog exposure with childhood type 1 diabetes was identified.

  • 1516. Westenbrink, B. D.
    et al.
    Alings, M.
    Connolly, S. J.
    Eikelboom, J.
    Ezekowitz, M. D.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yang, S.
    Pongue, J.
    Yusuf, S.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    van Gilst, W. H.
    Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation: insights from the RE-LY trial2015In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, no 5, p. 699-707Article in journal (Refereed)
    Abstract [en]

    BackgroundAnemia may predispose to thromboembolic events or bleeding in anticoagulated patients with atrial fibrillation (AF). ObjectivesTo investigate whether anemia is associated with thromboembolic events and bleeding in patients with AF. Patients and methodsWe retrospectively analyzed the RE-LY trial database, which randomized 18113 patients with AF and a risk of stroke to receive dabigatran or warfarin for a median follow-up of 2years. Cox regression analysis was used to determine whether anemia predicted cardiovascular events and bleeding complications in these patients. ResultsAnemia was present in 12% of the population at baseline, and the presence of anemia was associated with a higher risk of thromboembolic cardiovascular events, including the composite endpoint of all-cause mortality or myocardial infarction (adjusted hazard ratio [HR]1.50, 95% confidence interval [CI]1.32-1.71) and the primary RE-LY outcome of stroke or systemic embolism (adjusted HR1.41, 95%CI1.12-1.78). Anemia was also associated with a higher risk of major bleeding complications (adjusted HR2.14, 95%CI1.87-2.46) and discontinuation of anticoagulants (adjusted HR1.40, 95%CI1.28-1.79). The association between anemia and outcome was similar irrespective of cardiovascular comorbidities, randomized treatment allocation, or prior use of warfarin. The incidence of events was lower in patients with transient anemia than in patients in whom anemia was sustained (adjusted HR0.66, 95%CI0.49-0.91). ConclusionsAnemia is associated with an increased risk of thromboembolic events, bleeding complications and mortality in anticoagulated patients with AF. These findings suggest that patients with anemia should be monitored closely during all types of anticoagulant treatment.

  • 1517.
    Westenbrink, B. Daan
    et al.
    Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands..
    Alings, Marco
    Working Grp Cardiovasc Res, Utrecht, Netherlands..
    Granger, Christopher B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Alexander, John H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Hylek, Elaine M.
    Boston Univ, Sch Med, Boston, MA USA..
    Thomas, Laine
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wojdyla, Daniel M.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA..
    Keltai, Matyas
    Hungarian Inst Cardiol, Budapest, Hungary..
    Steg, P. Gabriel
    Univ Paris Diderot, AP HP, Hop Bichat, INSERM,DHU FIRE, Paris, France..
    De Caterina, Raffaele
    Univ G dAnnunzio, Chieti, Italy.;Fdn Toscana G Monasterio, Chieti, Italy..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    van Gilst, Wick H.
    Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands..
    Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 185, p. 140-149Article in journal (Refereed)
    Abstract [en]

    Background Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes. Methods We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality. Results Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS2 and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P < .0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P <. 0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70-1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia. Conclusions Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia.

  • 1518.
    Wester, Axel
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Mohammad, Moman A.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Andell, Pontus
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Rylance, Rebecca
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Dankiewicz, Josef
    Lund Univ, Skane Univ Hosp, Dept Intens & Perioperat Care, Clin Sci, Lund, Sweden.
    Friberg, Hans
    Lund Univ, Skane Univ Hosp, Dept Intens & Perioperat Care, Clin Sci, Lund, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Omerovic, Elmir
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Coronary angiographic findings and outcomes in patients with sudden cardiac arrest without ST-elevation myocardial infarction: A SWEDEHEART study2018In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 126, p. 172-178Article in journal (Refereed)
    Abstract [en]

    Background/aim: Sudden cardiac arrest (SCA) has a substantial mortality rate and the acute coronary syndrome constitutes the major cause. Post-resuscitation electrocardiogram ST-elevation SCA (STE-SCA) is a strong indication for emergency coronary angiography, but the role of early angiography and PCI in patients without STelevation (NSTE-SCA) remains to be established. This paper aimed to describe this patient group and evaluate the prognostic effect of early PCI in a large nationwide cohort of NSTE-SCA patients undergoing coronary angiography. Methods: Data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) and RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) on 4308 SCA patients in Sweden between 2005 and 2016 were descriptively analyzed and related to mortality within 30-days in both unadjusted and adjusted analyses using Cox proportional hazard models. Results: NSTE-SCA patients had more often serious comorbidities than STE-SCA patients. Among NSTE-SCA patients, 36.4% had no significant coronary artery stenosis while severe coronary stenosis (>= 90%) was present in 43.9% (1271/2896). In NSTE-SCA patients with significant stenosis (>= 90%), PCI was performed in 59.2% (753/1271) with an increased unadjusted 30-day mortality (40.9% vs. 32.7%; p =. 011). However, after adjustments for confounders, no difference in mortality was observed (hazard ratio 1.07; 95% CI 0.84-1.36; p =. 57). Conclusion: In resuscitated SCA patients without ST-elevation who underwent coronary angiography, this large retrospective study found severe coronary artery stenosis in 43.9% but found no clear benefit of early PCI. Prospective randomized controlled trials are needed to accurately define the role of coronary angiography and PCI in post-resuscitation care.

  • 1519. Westerhout, Cynthia M.
    et al.
    Hernández, Adrián V.
    Steyerberg, Ewout W.
    Bueno, Héctor
    White, Harvey
    Théroux, Pierre
    Moliterno, David J.
    Armstrong, Paul W.
    Califf, Robert M.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Simoons, Maarten L.
    Boersma, Eric
    Predictors of stroke within 30 days in patients with non-ST-segment elevation acute coronary syndromes2006In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 27, no 24, p. 2956-2961Article in journal (Refereed)
    Abstract [en]

    AIMS: Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We aimed to identify predictors of stroke within 30 days in patients who suffered NSTE-ACS. METHODS AND RESULTS: We pooled data from six trials (n=31 402) that randomized NSTE-ACS patients either to platelet glycoprotein (GP) IIb/IIIa receptor blockers or to placebo/control therapy. Potential predictors of stroke included treatment, demographic, and clinical characteristics. We identified predictors using univariable and multivariable logistic models, and their performance was evaluated with calibration (Hosmer-Lemeshow test) and discrimination (c-statistic). We found 228 (0.7%) all-cause strokes: 155 (0.5%) non-haemorrhagic, 20 (0.06%) haemorrhagic, and 53 without computed tomography (CT) confirmation. Patients with any type of stroke had a 30-day mortality of 25%. Randomization to GP IIb/IIIa receptor blockers was not significantly associated with all-cause stroke [OR (95% CI) 1.08 (0.83-1.41)]. Older age [OR per 10-year increase 1.5 (1.3-1.7)], prior stroke [2.1 (1.4-3.1)], and elevated heart rate [per 10-beat increase 1.1 (1.0-1.2)] were the strongest predictors of 30-day all-cause stroke. Similar predictors were found for non-haemorrhagic and haemorrhagic strokes. Smoking, previous myocardial infarction, diabetes, and hypertension were not independent predictors of all-cause stroke. The multivariable model to predict all-cause stroke was well calibrated, but its discrimination was only moderate [c-statistic 0.69 (0.65-0.72)]. CONCLUSION: Stroke is a rare complication occurring early after NSTE-ACS, but is associated with high mortality. We found no evidence that GP IIb/IIIa receptor blockers increase stroke risks. A few clinical characteristics predicted higher stroke risks. Thus, incident strokes in NSTE-ACS patients remain largely unexplained.

  • 1520. Westerhout, Cynthia M.
    et al.
    Lauer, Michael S.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Fu, Yuling
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Armstrong, Paul W.
    Electrocardiographic left ventricular hypertrophy in GUSTO IV ACS: an important risk marker of mortality in women2007In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 28, no 17, p. 2064-2069Article in journal (Refereed)
    Abstract [en]

    AIM: To examine the association of left ventricular hypertrophy (LVH) on admission electrocardiography with adverse outcomes in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: A total of 7443 non-ST-elevation ACS patients in Global Utilization of STrategies to Open occluded arteries (GUSTO) IV ACS trial had admission electrocardiograms analysed at a core laboratory. LVH [>or=20 mm Cornell voltage (LV voltage) (women) or >or=28 mm (men) plus strain patterns] was observed in 586 (7.9%) patients, and women accounted for 74%. LVH patients were also older and had more co-morbidities, ST-depression >or= 0.5 mm, elevated C-reactive protein and N-terminal pro-brain naturetic peptide (NT-proBNP), and lower troponin T. Invasive procedures occurred less often in LVH patients (cardiac catheterization: 31 vs. 38%, P = 0.001; percutaneous coronary intervention: 12 vs. 20%, P < 0.001). Mortality was significantly higher in patients with LVH (30 day: 5 vs. 3%, P = 0.046; 1 year: 14 vs. 7%, P < 0.001), whereas 30 day myocardial infarction (MI) and death/MI did not differ. After baseline adjustment including NT-proBNP, LVH remained associated with increased hazard of 1 year mortality in women, but not in men [P-interaction = 0.033; women: adjusted hazard ratio (LVH vs. no LVH): 1.42 (1.04-1.94), P = 0.029]. CONCLUSION: Electrocardiographic-LVH identifies an important subset of ACS patients with a higher risk of long-term mortality, particularly among women. These novel findings highlight opportunities to improve treatment and outcome among similar ACS patients.

  • 1521. Westerhout, Cynthia M.
    et al.
    Pieper, Karen S.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mahaffey, Kenneth W.
    Van de Werf, Frans
    Califf, Robert M.
    Granger, Christopher B.
    Armstrong, Paul W.
    Dynamic modeling of 90-day mortality in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 165, no 3, p. 354-+Article in journal (Refereed)
    Abstract [en]

    Aims Dynamic risk models update the risk profile of ST-elevation myocardial infarction (STEMI) patients over the acute period following the event and have implications to clinical practice and research. Methods and Results Multivariable survival models were developed in 5,745 STEMI patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the APEX-AMI trial to predict 90-day mortality from 4 clinically relevant times: baseline, 2 hours, 24 hours, and 96 hours. Culprit coronary thrombolysis in myocardial infarction flow grade, 30-minute post-PCI worst-lead ST-elevation residual, and in-hospital clinical events were considered in the models. The 90-day mortality was 4.7%; the cumulative proportion of mortality occurring within 2, 24, and 96 hours was 8%, 22%, and 40% respectively. Relative to the baseline risk factors, age and systolic blood pressure remained highly ranked in the post-baseline models. However, the relative importance of heart rate, Killip class, and creatinine declined, whereas markers of coronary reperfusion and in-hospital events (shock, congestive heart failure) became increasingly influential. The c-index increased from 0.819 at baseline to 0.847 at 96 hours. Over the forecasting periods, the proportion of "low-risk" (<1.1% 90-day mortality) patients increased from 20% to 49%. This approach derived from an unfolding series of models reveals the shifting levels of mortality risk from baseline to 96 hours. Conclusion This novel approach in STEMI patients undergoing primary PCI demonstrates the dynamic nature of risk over time and may prove useful in understanding risk and in clinical decision making.

  • 1522. Whellan, David J.
    et al.
    Tricoci, Pierluigi
    Chen, Edmond
    Huang, Zhen
    Leibowitz, David
    Vranckx, Pascal
    Marhefka, Gregary D.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Nicolau, Jose C.
    Storey, Robert F.
    Ruzyllo, Witold
    Huber, Kurt
    Sinnaeve, Peter
    Weiss, A. Teddy
    Dery, Jean-Pierre
    Moliterno, David J.
    Van de Werf, Frans
    Aylward, Philip E.
    White, Harvey D.
    Armstrong, Paul W.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Strony, John
    Harrington, Robert A.
    Mahaffey, Kenneth W.
    Vorapaxar in Acute Coronary Syndrome Patients Undergoing Coronary Artery Bypass Graft Surgery2014In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 63, no 11, p. 1048-1057Article in journal (Refereed)
    Abstract [en]

    Objectives This study evaluated effects of protease-activated receptor-1 antagonist vorapaxar (Merck, Whitehouse Station, New Jersey) versus placebo among the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass grafting (CABG). Background Platelet activation may play a key role in graft occlusion, and antiplatelet therapies may reduce ischemic events, but perioperative bleeding risk remains a major concern. Although the TRACER study did not meet the primary quintuple composite outcome in the overall population with increased bleeding, an efficacy signal with vorapaxar was noted on major ischemic outcomes, and preliminary data suggest an acceptable surgical bleeding profile. We aimed to assess efficacy and safety of vorapaxar among CABG patients. Methods Associations between treatment and ischemic and bleeding outcomes were assessed using time-to-event analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox hazards model. Event rates were estimated using the Kaplan-Meier method. Results Among 12,944 patients, 1,312 (10.1%) underwent CABG during index hospitalization, with 78% on the study drug at the time of surgery. Compared with placebo CABG patients, vorapaxar-treated patients had a 45% lower rate of the primary endpoint (i.e., a composite of death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularizationduring index hospitalization) (HR: 0.55; 95% CI: 0.36 to 0.83; p = 0.005), with a significant interaction (p = 0.012). The CABG-related Thrombolysis In Myocardial Infarction major bleeding was numerically higher with vorapaxar, but not significantly different between vorapaxar and placebo (9.7% vs. 7.3%; HR: 1.36; 95% CI: 0.92 to 2.02; p = 0.12), with no excess in fatal bleeding (0% vs. 0.3%) or need for reoperation (4.7% vs. 4.6%). Conclusions In non-ST-segment elevation acute coronary syndrome patients undergoing CABG, vorapaxar was associated with a significant reduction in ischemic events and no significant increase in major CABG-related bleeding. These data show promise for protease-activated receptor 1 antagonism in patients undergoing CABG and warrant confirmatory evidence in randomized trials. (Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Acute Coronary Syndrome [TRA.CER] [Study P04736AM3]; NCT00527943) (C) 2014 by the American College of Cardiology Foundation

  • 1523. White, H. D.
    et al.
    Huang, Z.
    Tricoci, P.
    Van De Werf, F.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lokhnygina, Y.
    Moliterno, D.
    Aylward, P. E.
    Mahaffey, K.
    Armstrong, P. W.
    Reduction in recurrent ischemic events with vorapaxar: results from TRACER2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 880-880Article in journal (Other academic)
  • 1524. White, Harvey D.
    et al.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stewart, Ralph
    Tarka, Elizabeth
    Brown, Rebekkah
    Davies, Richard Y.
    Budaj, Andrzej
    Harrington, Robert A.
    Steg, P. Gabriel
    Ardis-Sino, Diego
    Armstrong, Paul W.
    Avezum, Alvaro
    Aylward, Philip E.
    Bryce, Alfonso
    Chen, Hong
    Chen, Ming-Fong
    Corbalan, Ramon
    Dalby, Anthony J.
    Danchin, Nicolas
    De Winter, Robbert J.
    Denchev, Stefan
    Diaz, Rafael
    Elisaf, Moses
    Flather, Marcus D.
    Goudev, Assen R.
    Granger, Christopher B.
    Grinfeld, Liliana
    Hochman, Judith S.
    Husted, Steen
    Kim, Hyo-Soo
    Koenig, Wolfgang
    Linhart, Ales
    Lonn, Eva
    Lopez-Sendon, Jose
    Manolis, Athanasios J.
    Mohler, Emile R., III
    Nicolau, Jose C.
    Pais, Prem
    Parkhomenko, Alexander
    Pedersen, Terje R.
    Pella, Daniel
    Ramos-Corrales, Marco A.
    Ruda, Mikhail
    Sereg, Mtys
    Siddique, Saulat
    Sinnaeve, Peter
    Smith, Peter
    Sritara, Piyamitr
    Swart, Henk P.
    Sy, Rody G.
    Teramoto, Tamio
    Tse, Hung-Fat
    Watson, David
    Weaver, W. Douglas
    Weiss, Robert
    Viigimaa, Margus
    Vinereanu, Dragos
    Zhu, Junren
    Cannon, Christopher P.
    Wallentin, Lars
    Survival with Cardiac-Resynchronization Therapy in Mild Heart Failure2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 18, p. 1702-1711Article in journal (Refereed)
    Abstract [en]

    Background: Elevated lipoprotein-associated phospholipase A(2) activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A(2). Methods: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). Results: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). ConclusionsIn patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.)

  • 1525. White, Harvey D
    et al.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stewart, Ralph
    Tarka, Elizabeth
    Brown, Rebekkah
    Davies, Richard Y
    Budaj, Andrzej
    Harrington, Robert A
    Steg, P Gabriel
    Ardissino, Diego
    Armstrong, Paul W
    Avezum, Alvaro
    Aylward, Philip E
    Bryce, Alfonso
    Chen, Hong
    Chen, Ming-Fong
    Corbalan, Ramon
    Dalby, Anthony J
    Danchin, Nicolas
    De Winter, Robbert J
    Denchev, Stefan
    Diaz, Rafael
    Elisaf, Moses
    Flather, Marcus D
    Goudev, Assen R
    Granger, Christopher B
    Grinfeld, Liliana
    Hochman, Judith S
    Husted, Steen
    Kim, Hyo-Soo
    Koenig, Wolfgang
    Linhart, Ales
    Lonn, Eva
    López-Sendón, José
    Manolis, Athanasios J
    Mohler, Emile R
    Nicolau, José C
    Pais, Prem
    Parkhomenko, Alexander
    Pedersen, Terje R
    Pella, Daniel
    Ramos-Corrales, Marco A
    Ruda, Mikhail
    Sereg, Mátyás
    Siddique, Saulat
    Sinnaeve, Peter
    Smith, Peter
    Sritara, Piyamitr
    Swart, Henk P
    Sy, Rody G
    Teramoto, Tamio
    Tse, Hung-Fat
    Watson, David
    Weaver, W Douglas
    Weiss, Robert
    Viigimaa, Margus
    Vinereanu, Dragos
    Zhu, Junren
    Cannon, Christopher P
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Darapladib for preventing ischemic events in stable coronary heart disease2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 18, p. 1702-1711Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2.

    METHODS:

    In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization).

    RESULTS:

    During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02).

    CONCLUSIONS:

    In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

  • 1526. White, Harvey D.
    et al.
    Huang, Zhen
    Tricoci, Pierluigi
    Van de Werf, Frans
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lokhnygina, Yuliya
    Moliterno, David J.
    Aylward, Philip E.
    Mahaffey, Kenneth W.
    Armstrong, Paul W.
    Reduction in Overall Occurrences of Ischemic Events With Vorapaxar: Results From TRACER2014In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 3, no 4, p. e001032-Article in journal (Refereed)
    Abstract [en]

    Background-Clinical trials traditionally use time-to-first-event analysis embedded within the composite endpoint of cardiovascular death (CVD), myocardial infarction (MI), or stroke. However, many patients have >1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER. Methods and Results-TRACER randomized 12 944 patients with non-ST-segment elevation acute coronary syndromes to placebo or to protease-activated receptor 1 antagonist vorapaxar with a median follow-up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar's effect on recurrent CVD, MI, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar did not reduce the first occurrence of the primary endpoint of CVD, MI, stroke, revascularization, or rehospitalization for recurrent ischemia, but reduced the secondary composite endpoint of CVD, MI, or stroke (14.7% vorapaxar vs. 16.4% placebo; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.02; number needed to treat [NNT], 81). Recurrent secondary events occurred in 2.7% of patients. Vorapaxar reduced overall occurrences of ischemic events, first and subsequent (HR, 0.88; 95% CI, 0.80 to 0.98; P=0.02; NNT, 51). Also, there was a trend indicating that vorapaxar reduced the expanded endpoint, including revascularization and rehospitalization for recurrent ischemia (HR, 0.92; 95% CI, 0.84 to 1.01; P=0.09). Vorapaxar increased overall occurrences of moderate and severe Global Use of Strategies to Open Occluded Coronary Arteries bleeding (HR, 1.42; 95% CI, 1.21 to 1.66; P<0.001) and Thrombolysis in Myocardial Infarction clinically significant bleeding (HR, 1.550; 95% CI, 1.403 to 1.713; P<0.001). Conclusions-Vorapaxar reduced overall occurrences of ischemic events, but increased bleeding. These exploratory findings broaden our understanding of vorapaxar's potential and expand our understanding of the value of capturing recurrent events.

  • 1527. White, Harvey
    et al.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stewart, Ralph
    Watson, David
    Harrington, Robert
    Budaj, Andrzej
    Steg, Ph. Gabriel
    Cannon, Christopher P.
    Krug-Gourley, Susan
    Wittes, Janet
    Trivedi, Trupti
    Tarka, Elizabeth
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 160, no 4, p. 655-661.e2Article in journal (Refereed)
    Abstract [en]

    Background Elevated plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with increased risk of cardiovascular (CV) events. Direct inhibition of this proinflammatory enzyme with darapladib may benefit CV patients when given as an adjunct to standard of care, including lipid-lowering and antiplatelet therapies. Methods STABILITY is a randomized, placebo-controlled, double-blind, international, multicenter, event-driven trial. The study has randomized 15,828 patients with chronic coronary heart disease (CHD) receiving standard of care to darapladib enteric-coated (EC) tablets, 160 mg or placebo. Results The primary end point is the composite of major adverse cardiovascular events (MACE): CV death, nonfatal myocardial infarction, and nonfatal stroke. The key secondary end points will include major coronary events, total coronary events, individual components of MACE, and all-cause mortality. Prespecified substudies include 24-hour ambulatory blood pressure monitoring, albuminuria progression, changes in cognitive function, and pharmacokinetic and biomarker analyses. Health economic outcomes and characterization of baseline lifestyle risk factors also will be assessed. The study will continue until 1,500 primary end points have occurred to achieve 90% power to detect a 15.5% reduction in the primary end point. The median treatment duration is anticipated to be 2.75 years. Conclusions STABILITY will assess whether direct inhibition of Lp-PLA(2) with darapladib added to the standard of care confers clinical benefit to patients with CHD.

  • 1528.
    Wiberg, Bernice
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cognitive Function Prior to Stroke is a Risk Factor for Post-Stroke Mortality but Not DependencyArticle in journal (Other academic)
  • 1529. Wieloch, Mattias
    et al.
    Jonsson, Karl M.
    Sjalander, Anders
    Lip, Gregory Y. H.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Peter J.
    Estimated glomerular filtration rate is associated with major bleeding complications but not thromboembolic events, in anticoagulated patients taking warfarin2013In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 131, no 6, p. 481-486Article in journal (Refereed)
    Abstract [en]

    Background: Decreased glomerular filtration rate is an established risk factor for bleeding but there are limited data on its association with bleeding risk in well-controlled anticoagulated patients taking warfarin. Objectives: The aim was to investigate the relationship between glomerular filtration rate, major bleeding and thromboembolic complications in patients with tight anticoagulation control. Patients/Methods: A cohort study of patients from a Swedish quality register for anticoagulation, including all the registered patients that received anticoagulation during 2008 in the anticoagulation center of Skane University Hospital, Malmo. Key outcome measures were major bleeding and arterial or venous thrombosis during 2008. A total of 3536 patients (2875 treatment years) were included. Results: Total rates of 2.6 (2.0-3.2) bleeding events and 1.8 (1.3-2.3) thrombotic events per 100 treatment years were recorded (75 bleeding and 51 thromboembolic events). Data on estimated glomerular filtration rate were available in 3349 patients. Mean time in therapeutic range (international normalized ratio 2.0-3.0) was 74.5% (n=2894). Major bleeding events were significantly related to age and percentage of time with international normalized ratio >3.0 (P<0.001). Glomerular filtration rate levels <30 ml/min/1.73 m(2) were particularly associated with high risk of bleeding, especially in elderly patients. No correlation between glomerular filtration rate and thromboembolic events was seen. Conclusions: With good anticoagulation control as measured by time in therapeutic range, patients had a relatively low risk for major bleeding if their renal function is normal. Despite good anticoagulation control, severely impaired kidney function is associated with a very high yearly risk of major bleeding events.

  • 1530. Wieloch, Mattias
    et al.
    Själander, Anders
    Frykman, Viveka
    Rosenqvist, Mårten
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Svensson, Peter J.
    Anticoagulation control in Sweden: reports of time in therapeutic range, major bleeding, and thrombo-embolic complications from the national quality registry AuriculA2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 18, p. 2282-2289Article in journal (Refereed)
    Abstract [en]

    Aims: In anticoagulation treatment with warfarin, the risk of thrombo-embolic events must be weighed against the risk of bleeding. Time in therapeutic range (TTR) is an important tool to assess the quality of anticoagulation treatment, and has been shown to correlate with less bleeding and thrombo-embolic complications. AuriculA, the Swedish national quality registry for atrial fibrillation and anticoagulation, is used for follow-up and dosage control of warfarin. This is the first report of TTR in AuriculA and, in a subgroup of two centres, bleeding and thrombo-embolic complications during 2008.

    Methods and results: Prothrombin complex (International normalized ratio) values from 18 391 patients in 67 different centres were analysed. The mean (SD) age was 70 (12) years. The main indications for warfarin treatment were: atrial fibrillation (64%), venous thromboembolism (19%), and heart valve dysfunction (13%). Time in therapeutic range for all patients was 76.2%. The mean weekly dose of warfarin decreased with age and TTR increased with age. In 4273 patients from two centres in AuriculA, the frequency of major bleedings and venous/arterial thrombo-embolism were 2.6 and 1.7% and for atrial fibrillation, 2.6 and 1.4%, per treatment year, respectively. A correlation between age and the risk of major bleeding (P < 0.001), but not thrombo-embolic complications (P = 0.147), was seen.

    Conclusion: Compared with prospective randomized trials of warfarin treatment, TTR in the AuriculA population was higher. Complications were low, probably due to the organization of anticoagulation treatment in Sweden. Use of the AuriculA dosing programme could have contributed to the results by keeping dosing regimens consistent over all centres.

  • 1531. Wijns, William
    et al.
    Kolh, Philippe
    Danchin, Nicolas
    Di Mario, Carlo
    Falk, Volkmar
    Folliguet, Thierry
    Garg, Scot
    Huber, Kurt
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Knuuti, Juhani
    Lopez-Sendon, Jose
    Marco, Jean
    Menicanti, Lorenzo
    Ostojic, Miodrag
    Piepoli, Massimo F
    Pirlet, Charles
    Pomar, Jose L
    Reifart, Nicolaus
    Ribichini, Flavio L
    Schalij, Martin J
    Sergeant, Paul
    Serruys, Patrick W
    Silber, Sigmund
    Sousa Uva, Miguel
    Taggart, David
    Vahanian, Alec
    Auricchio, Angelo
    Bax, Jeroen
    Ceconi, Claudio
    Dean, Veronica
    Filippatos, Gerasimos
    Funck-Brentano, Christian
    Hobbs, Richard
    Kearney, Peter
    McDonagh, Theresa
    Popescu, Bogdan A
    Reiner, Zeljko
    Sechtem, Udo
    Sirnes, Per Anton
    Tendera, Michal
    Vardas, Panos E
    Widimsky, Petr
    Kolh, Philippe
    Alfieri, Ottavio
    Dunning, Joel
    Elia, Stefano
    Kappetein, Pieter
    Lockowandt, Ulf
    Sarris, George
    Vouhe, Pascal
    Kearney, Peter
    von Segesser, Ludwig
    Agewall, Stefan
    Aladashvili, Alexander
    Alexopoulos, Dimitrios
    Antunes, Manuel J
    Atalar, Enver
    Brutel de la Riviere, Aart
    Doganov, Alexander
    Eha, Jaan
    Fajadet, Jean
    Ferreira, Rafael
    Garot, Jerome
    Halcox, Julian
    Hasin, Yonathan
    Janssens, Stefan
    Kervinen, Kari
    Laufer, Gunther
    Legrand, Victor
    Nashef, Samer A M
    Neumann, Franz-Josef
    Niemela, Kari
    Nihoyannopoulos, Petros
    Noc, Marko
    Piek, Jan J
    Pirk, Jan
    Rozenman, Yoseph
    Sabate, Manel
    Starc, Radovan
    Thielmann, Matthias
    Wheatley, David J
    Windecker, Stephan
    Zembala, Marian
    Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)2010In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 31, no 20, p. 2501-2555Article in journal (Refereed)
  • 1532. Willer, Cristen J.
    et al.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    Peloso, Gina M.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kanoni, Stavroula
    Ganna, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Chen, Jin
    Buchkovich, Martin L.
    Mora, Samia
    Beckmann, Jacques S.
    Bragg-Gresham, Jennifer L.
    Chang, Hsing-Yi
    Demirkan, Ayse
    Den Hertog, Heleen M.
    Do, Ron
    Donnelly, Louise A.
    Ehret, Georg B.
    Esko, Tonu
    Feitosa, Mary F.
    Ferreira, Teresa
    Fischer, Krista
    Fontanillas, Pierre
    Fraser, Ross M.
    Freitag, Daniel F.
    Gurdasani, Deepti
    Heikkila, Kauko
    Hyppoenen, Elina
    Isaacs, Aaron
    Jackson, Anne U.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnson, Toby
    Kaakinen, Marika
    Kettunen, Johannes
    Kleber, Marcus E.
    Li, Xiaohui
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Magnusson, Patrik K. E.
    Mangino, Massimo
    Mihailov, Evelin
    Montasser, May E.
    Mueller-Nurasyid, Martina
    Nolte, Ilja M.
    O'Connell, Jeffrey R.
    Palmer, Cameron D.
    Perola, Markus
    Petersen, Ann-Kristin
    Sanna, Serena
    Saxena, Richa
    Service, Susan K.
    Shah, Sonia
    Shungin, Dmitry
    Sidore, Carlo
    Song, Ci
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Strawbridge, Rona J.
    Surakka, Ida
    Tanaka, Toshiko
    Teslovich, Tanya M.
    Thorleifsson, Gudmar
    Van den Herik, Evita G.
    Voight, Benjamin F.
    Volcik, Kelly A.
    Waite, Lindsay L.
    Wong, Andrew
    Wu, Ying
    Zhang, Weihua
    Absher, Devin
    Asiki, Gershim
    Barroso, Ines
    Been, Latonya F.
    Bolton, Jennifer L.
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Burnett, Mary S.
    Cesana, Giancarlo
    Dimitriou, Maria
    Doney, Alex S. F.
    Doering, Angela
    Elliott, Paul
    Epstein, Stephen E.
    Eyjolfsson, Gudmundur Ingi
    Gigante, Bruna
    Goodarzi, Mark O.
    Grallert, Harald
    Gravito, Martha L.
    Groves, Christopher J.
    Hallmans, Goran
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Hernandez, Dena
    Hicks, Andrew A.
    Holm, Hilma
    Hung, Yi-Jen
    Illig, Thomas
    Jones, Michelle R.
    Kaleebu, Pontiano
    Kastelein, John J. P.
    Khaw, Kay-Tee
    Kim, Eric
    Klopp, Norman
    Komulainen, Pirjo
    Kumari, Meena
    Langenberg, Claudia
    Lehtimaki, Terho
    Lin, Shih-Yi
    Lindstrom, Jaana
    Loos, Ruth J. F.
    Mach, Francois
    McArdle, Wendy L.
    Meisinger, Christa
    Mitchell, Braxton D.
    Mueller, Gabrielle
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nieminen, Tuomo V. M.
    Nsubuga, Rebecca N.
    Olafsson, Isleifur
    Ong, Ken K.
    Palotie, Aarno
    Papamarkou, Theodore
    Pomilla, Cristina
    Pouta, Anneli
    Rader, Daniel J.
    Reilly, Muredach P.
    Ridker, Paul M.
    Rivadeneira, Fernando
    Rudan, Igor
    Ruokonen, Aimo
    Samani, Nilesh
    Scharnagl, Hubert
    Seeley, Janet
    Silander, Kaisa
    Stancakova, Alena
    Stirrups, Kathleen
    Swift, Amy J.
    Tiret, Laurence
    Uitterlinden, Andre G.
    van Pelt, L. Joost
    Vedantam, Sailaja
    Wainwright, Nicholas
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilsgaard, Tom
    Wilson, James F.
    Young, Elizabeth H.
    Zhao, Jing Hua
    Adair, Linda S.
    Arveiler, Dominique
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Bennett, Franklyn
    Bochud, Murielle
    Boehm, Bernhard O.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Bornstein, Stefan R.
    Bovet, Pascal
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chambers, John C.
    Chen, Yii-Der Ida
    Collins, Francis S.
    Cooper, Richard S.
    Danesh, John
    Dedoussis, George
    de Faire, Ulf
    Feranil, Alan B.
    Ferrieres, Jean
    Ferrucci, Luigi
    Freimer, Nelson B.
    Gieger, Christian
    Groop, Leif C.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Hamsten, Anders
    Harris, Tamara B.
    Hingorani, Aroon
    Hirschhorn, Joel N.
    Hofman, Albert
    Hovingh, G. Kees
    Hsiung, Chao Agnes
    Humphries, Steve E.
    Hunt, Steven C.
    Hveem, Kristian
    Iribarren, Carlos
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kaprio, Jaakko
    Kesaniemi, Antero
    Kivimaki, Mika
    Kooner, Jaspal S.
    Koudstaal, Peter J.
    Krauss, Ronald M.
    Kuh, Diana
    Kuusisto, Johanna
    Kyvik, Kirsten O.
    Laakso, Markku
    Lakka, Timo A.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia M.
    Martin, Nicholas G.
    Maerz, Winfried
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Metspalu, Andres
    Moilanen, Leena
    Morris, Andrew D.
    Munroe, Patricia B.
    Njolstad, Inger
    Pedersen, Nancy L.
    Power, Chris
    Pramstaller, Peter P.
    Price, Jackie F.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rauramaa, Rainer
    Saleheen, Danish
    Salomaa, Veikko
    Sanghera, Dharambir K.
    Saramies, Jouko
    Schwarz, Peter E. H.
    Sheu, Wayne H-H
    Shuldiner, Alan R.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Spector, Tim D.
    Stefansson, Kari
    Strachan, David P.
    Tayo, Bamidele O.
    Tremoli, Elena
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vollenweider, Peter
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wareham, Nicholas J.
    Whitfield, John B.
    Wolffenbuttel, Bruce H. R.
    Ordovas, Jose M.
    Boerwinkle, Eric
    Palmer, Colin N. A.
    Thorsteinsdottir, Unnur
    Chasman, Daniel I.
    Rotter, Jerome I.
    Franks, Paul W.
    Ripatti, Samuli
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Rich, Stephen S.
    Boehnke, Michael
    Deloukas, Panos
    Kathiresan, Sekar
    Mohlke, Karen L.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Abecasis, Goncalo R.
    Discovery and refinement of loci associated with lipid levels2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, p. 1274-1283Article in journal (Refereed)
    Abstract [en]

    Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

  • 1533.
    Williams, Rachel
    et al.
    GlaxoSmithKline, Worldwide Epidemiol, Collegeville, PA USA..
    Shearn, Shawn Patrick
    GlaxoSmithKline, Ophthalmol Res & Dev, Philadelphia, PA USA..
    Dowd, Michael
    Bogier Clin & IT Solut Inc, Raleigh, NC USA..
    Cicconetti, Greg
    GlaxoSmithKline, Quantitat Sci, Philadelphia, PA USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    White, Harvey
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Janmohamed, Salim
    Wurzelmann, John I.
    GlaxoSmithKline, Ophthalmol Res & Dev, Philadelphia, PA USA..
    McLaughlin, Megan M.
    GlaxoSmithKline, Ophthalmol Res & Dev, Philadelphia, PA USA..
    Post-hoc analyses of darapladib, an oral Lp-PLA(2) inhibitor, in phase III cardiovascular outcomes trials may inform investigation in diabetic macular edema2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7Article in journal (Other academic)
  • 1534. Wimo, Anders
    et al.
    Religa, Dorota
    Spångberg, Kalle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Edlund, Ann-Katrin
    Winblad, Bengt
    Eriksdotter, Maria
    Costs of diagnosing dementia: results from SveDem, the Swedish Dementia Registry2013In: International Journal of Geriatric Psychiatry, ISSN 0885-6230, E-ISSN 1099-1166, Vol. 28, no 10, p. 1039-1044Article in journal (Refereed)
    Abstract [en]

    Objective Diagnostic of different dementia disorders is an important part of dementia care. So far, there is limited knowledge about how dementia is diagnosed in clinical routine, and there are few reports on the costs of the dementia work-up leading to a diagnosis. Here, we examine the costs of diagnostic dementia work-up in Sweden. Methods The analyses were made on the data from the Swedish Dementia Registry (SveDem) and included 11,561 dementia patients diagnosed during 2007-2010, mainly not only in specialist care (SC) (n=53) but also some primary care centres (PC). We have studied differences in the use of investigations for dementia diagnostics such as cognitive tests, blood and cerebrospinal fluid analyses, radiological examinations and assessments of functions. Unit costs for each diagnostic investigation were combined with the use of these investigations for all cases in the database. Results are presented versus gender and stratified for age. Results The number of diagnostic tests performed was 2.8 in PC and 4.6 in SC. The average costs (Euro1=SEK9 and US$1=SEK7 in 2010) were SEK6777 in PC and SEK11,682 in SC. Age was the strongest cost predictor while there were no gender differences. There were also regional differences, ranging from SEK8231 to SEK14,734 in SC. Conclusions The SveDem database offers valuable information on the diagnostic procedures for dementia in daily clinical practice. The differences between PC and SC in diagnostic costs reflect national guidelines. The age effect needs to be studied more.

  • 1535.
    Winell, Henric
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    A general score-independent test for order-restricted inference2018In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 37, no 21, p. 3078-3090Article in journal (Refereed)
    Abstract [en]

    In the analysis of ordered categorical data, the categories are often assigned a set of subjectively chosen order-restricted scores. To overcome the arbitrariness involved in the assignment of the scores, several score-independent tests have been proposed. However, these methods are limited to 2 x K contingency tables, where K is the number of ordered categories. We present an efficiency robust score-independent test that is applicable to more general situations. The test is embedded into a flexible framework for conditional inference and provides a natural generalization of many familiar tests involving ordered categorical data, such as the generalized Cochran-Mantel-Haenszel test for singly or doubly ordered contingency tables, the Page test for randomized block designs and the Tarone-Ware trend test for survival data. The proposed method is illustrated by several numerical examples.

  • 1536. Wiren, Sara M.
    et al.
    Drevin, Linda I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carlsson, Sigrid V.
    Akre, Olof
    Holmberg, Erik C.
    Robinson, David E.
    Garmo, Hans G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stattin, Par E.
    Fatherhood status and risk of prostate cancer: Nationwide, population-based case-control study2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, no 4, p. 937-943Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown a decreased risk of prostate cancer for childless men; however, the cause of the association remains to be elucidated. The aim of our study was to assess the risk of prostate cancer by fatherhood status, also considering potential confounding factors. In a case-control study in Prostate Cancer data Base Sweden 2.0, a nationwide, population-based cohort, data on number of children, marital status, education, comorbidity and tumor characteristics obtained through nationwide healthcare registers and demographic databases for 117,328 prostate cancer cases and 562,644 controls, matched on birth year and county of residence, were analyzed. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for prostate cancer overall and by risk category, adjusting for marital status and education. Childless men had a decreased risk of prostate cancer compared to fathers, OR=0.83 (95% CI=0.82-0.84), and risk was lower for low-risk prostate cancer, OR=0.74 (95% CI=0.72-0.77), than for metastatic prostate cancer, OR=0.93 (95% CI=0.90-0.97). Adjustment for marital status and education attenuated the association in the low-risk category, adjusted OR=0.87 (95% CI=0.84-0.91), whereas OR for metastatic cancer remained virtually unchanged, adjusted OR=0.92 (95% CI=0.88-0.96). Our data indicate that the association between fatherhood status and prostate cancer to a large part is due to socioeconomic factors influencing healthcare-seeking behavior including testing of prostate-specific antigen levels.

  • 1537.
    Witt, Nils
    et al.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Unit of Cardiology, Södersjukhuset, Stockholm, Sweden.
    Rück, Andreas
    Department of Medicine, Karolinska Institutet, and Department of Cardiology, Karolinska University Hospital, Stockholm.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Koul, Sasha
    Department of Cardiology, Skåne University Hospital, Lund University, Lund, Sweden .
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sweden: coronary and structural heart interventions from 2010 to 20152017In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 13, no Z, p. Z70-Z74, article id EIJ-D-16-00830Article in journal (Refereed)
    Abstract [en]

    Sparsely populated and with wide non-urbanised areas, Sweden faces specific challenges in providing publicly financed, high-quality and equal healthcare to all parts of the country. As a result, a decentralised organisation for acute coronary care has been developed with coronary care units and catheterisation laboratories in several small- and medium-sized city areas. In contrast, highly specialised non-emergent interventional procedures are centralised to a few high-volume centres, mainly located at university hospitals in large city areas. Nationwide quality registries with nearly complete coverage facilitate healthcare quality improvement and form a basis for clinical research. In this report, we present an overview of demographics, healthcare organisation, quality registries and procedural data for coronary and structural heart interventions in Sweden over the past six years.

  • 1538. Wollert, Kai C
    et al.
    Kempf, Tibor
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Olofsson, Sylvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Allhoff, Tim
    Peter, Timo
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Drexler, Helmut
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Growth Differentiation Factor 15 for Risk Stratification and Selection of an Invasive Treatment Strategy in Non-ST-Elevation Acute Coronary Syndrome2007In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 116, no 14, p. 1540-1548Article in journal (Refereed)
    Abstract [en]

    Background— An invasive treatment strategy improves outcomein patients with non–ST-elevation acute coronary syndromeat moderate to high risk. We hypothesized that the circulatinglevel of growth differentiation factor 15 (GDF-15) may improverisk stratification.

    Methods and Results— The Fast Revascularization duringInStability in Coronary artery disease II (FRISC-II) trial randomizedpatients with non–ST-elevation acute coronary syndrometo an invasive or conservative strategy with a follow-up for2 years. GDF-15 and other biomarkers were determined on admissionin 2079 patients. GDF-15 was moderately elevated (between 1200and 1800 ng/L) in 770 patients (37.0%), and highly elevated(>1800 ng/L) in 493 patients (23.7%). Elevated levels ofGDF-15 independently predicted the risk of the composite endpoint of death or recurrent myocardial infarction in the conservativegroup (P=0.016) but not in the invasive group. A significantinteraction existed between the GDF-15 level on admission andthe effect of treatment strategy on the composite end point.The occurrence of the composite end point was reduced by theinvasive strategy at GDF-15 levels >1800 ng/L (hazard ratio,0.49; 95% confidence interval, 0.33 to 0.73; P=0.001), between1200 and 1800 ng/L (hazard ratio, 0.68; 95% confidence interval,0.46 to 1.00; P=0.048), but not <1200 ng/L (hazard ratio,1.06; 95% confidence interval, 0.68 to 1.65; P=0.81). Patientswith ST-segment depression or a troponin T level >0.01 µg/Lwith a GDF-15 level <1200 ng/L did not benefit from the invasivestrategy.

    Conclusions— GDF-15 is a potential tool for risk stratificationand therapeutic decision making in patients with non–ST-elevationacute coronary syndrome as initially diagnosed by ECG and troponinlevels. A prospective randomized trial is needed to validatethese findings.

  • 1539. Wollert, Kai C.
    et al.
    Kempf, Tibor
    Peter, Timo
    Olofsson, Sylvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Horn-Wichmann, Rüdiger
    Brabant, Georg
    Simoons, Maarten L.
    Armstrong, Paul W.
    Califf, Robert M.
    Drexler, Helmut
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome2007In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 115, no 8, p. 962-971Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury. Circulating levels of GDF-15 may provide prognostic information in patients with non-ST-elevation acute coronary syndrome. METHODS AND RESULTS: Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation who were included in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV Non-ST-Elevation Acute Coronary Syndrome trial and from a matching cohort of 429 apparently healthy individuals. GDF-15 levels were determined by immunoradiometric assay. Approximately two thirds of patients presented with GDF-15 levels above the upper limit of normal in healthy controls (1200 ng/L); one third presented with levels >1800 ng/L. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 1 year (1.5%, 5.0%, and 14.1%; P<0.001). By multiple Cox regression analysis, only the levels of GDF-15 and N-terminal pro-B-type natriuretic peptide, together with age and a history of previous myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses further illustrated that GDF-15 is a strong marker of 1-year mortality risk (area under the curve, 0.757; best cutoff, 1808 ng/L). At this cutoff value, GDF-15 added significant prognostic information in patient subgroups defined by age; gender; time from symptom onset to admission; cardiovascular risk factors; previous cardiovascular disease; and the risk markers ST-segment depression, troponin T, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and creatinine clearance. CONCLUSIONS: GDF-15 is a new biomarker of the risk for death in patients with non-ST-elevation acute coronary syndrome that provides prognostic information beyond that provided by established clinical and biochemical markers.

  • 1540.
    Wollert, Kai C.
    et al.
    Hannover Med Sch, Dept Cardiol & Angiol, Div Mol & Translat Cardiol, Hannover, Germany..
    Kempf, Tibor
    Hannover Med Sch, Dept Cardiol & Angiol, Div Mol & Translat Cardiol, Hannover, Germany..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 1, p. 140-151Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Growth differentiation factor 15 (GDF-15) is expressed and secreted in response to inflammation, oxidative stress, hypoxia, telomere erosion, and oncogene activation. Cardiovascular (CV) disease is a major. driver of GDF-15 production. GDF-15 has favorable preanalytic characteristics and can be measured in serum and plasma by immunoassay. CONTENT: In community-dwelling individuals higher concentrations of GDF-15 are associated with increased risks of developing CV disease, chronic kidney disease, and cancer, independent of traditional CV risk factors, renal function, and other biomarkers (C-reactive protein, B-type natriuretic peptide, cardiac troponin). Low concentrations of GDF-15 are closely associated with longevity. GDF-15 is as an independent marker of all-cause mortality and CV events in patients with coronary artery disease, and may help select patients with non-ST-elevation acute coronary syndrome for early revascularization and more intensive medical therapies. GDF-15 is, independently associated with mortality and nonfatal events in atrial fibrillation and heart failure (HF) with preserved or reduced ejection fraction. GDF-15 reflects chronic disease burden and acute perturbations in HF and responds to improvements in hemodynamic status. GDF-15 is independently associated with major bleeding in patients receiving antithrombotic therapies and has been included in a new bleeding risk score, which may become useful for decision support. SUMMARY: GDF-15 captures distinct aspects of CV disease development, progression, and prognosis, which are not represented by clinical risk predictors and other biomarkers. The usefulness of GDF-15 to guide management decisions and discover new treatment targets should be further explored.

  • 1541. Wormser, David
    et al.
    Kaptoge, Stephen
    Di Angelantonio, Emanuele
    Wood, Angela M
    Pennells, Lisa
    Thompson, Alex
    Sarwar, Nadeem
    Kizer, Jorge R
    Lawlor, Debbie A
    Nordestgaard, Børge G
    Ridker, Paul
    Salomaa, Veikko
    Stevens, June
    Woodward, Mark
    Sattar, Naveed
    Collins, Rory
    Thompson, Simon G
    Whitlock, Gary
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Danesh, John
    Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies2011In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 377, no 9771, p. 1085-1095Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Guidelines differ about the value of assessment of adiposity measures for cardiovascular disease risk prediction when information is available for other risk factors. We studied the separate and combined associations of body-mass index (BMI), waist circumference, and waist-to-hip ratio with risk of first-onset cardiovascular disease.

    METHODS:

    We used individual records from 58 cohorts to calculate hazard ratios (HRs) per 1 SD higher baseline values (4.56 kg/m(2) higher BMI, 12.6 cm higher waist circumference, and 0.083 higher waist-to-hip ratio) and measures of risk discrimination and reclassification. Serial adiposity assessments were used to calculate regression dilution ratios.

    RESULTS:

    Individual records were available for 221,934 people in 17 countries (14,297 incident cardiovascular disease outcomes; 1.87 million person-years at risk). Serial adiposity assessments were made in up to 63,821 people (mean interval 5.7 years [SD 3.9]). In people with BMI of 20 kg/m(2) or higher, HRs for cardiovascular disease were 1.23 (95% CI 1.17-1.29) with BMI, 1.27 (1.20-1.33) with waist circumference, and 1.25 (1.19-1.31) with waist-to-hip ratio, after adjustment for age, sex, and smoking status. After further adjustment for baseline systolic blood pressure, history of diabetes, and total and HDL cholesterol, corresponding HRs were 1.07 (1.03-1.11) with BMI, 1.10 (1.05-1.14) with waist circumference, and 1.12 (1.08-1.15) with waist-to-hip ratio. Addition of information on BMI, waist circumference, or waist-to-hip ratio to a cardiovascular disease risk prediction model containing conventional risk factors did not importantly improve risk discrimination (C-index changes of -0.0001, -0.0001, and 0.0008, respectively), nor classification of participants to categories of predicted 10-year risk (net reclassification improvement -0.19%, -0.05%, and -0.05%, respectively). Findings were similar when adiposity measures were considered in combination. Reproducibility was greater for BMI (regression dilution ratio 0.95, 95% CI 0.93-0.97) than for waist circumference (0.86, 0.83-0.89) or waist-to-hip ratio (0.63, 0.57-0.70).

    INTERPRETATION:

    BMI, waist circumference, and waist-to-hip ratio, whether assessed singly or in combination, do not importantly improve cardiovascular disease risk prediction in people in developed countries when additional information is available for systolic blood pressure, history of diabetes, and lipids.

    FUNDING:

    British Heart Foundation and UK Medical Research Council.

  • 1542. Woudstra, Pier
    et al.
    Grundeken, Maik J
    van de Hoef, Tim P
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Fox, Keith A
    de Winter, Robbert J
    Damman, Peter
    Prognostic relevance of PCI-related myocardial infarction2013In: Nature Reviews Cardiology, ISSN 1759-5002, E-ISSN 1759-5010, Vol. 10, no 4, p. 231-236Article in journal (Refereed)
    Abstract [en]

    Procedure-related myocardial infarction (pMI) is directly associated with a coronary revascularization procedure, such as percutaneous coronary intervention (PCI) or CABG surgery. In contrast to spontaneous myocardial infarction (MI), the prognostic relevance of pMI is the subject of ongoing debate. Data from retrospective analyses of large, randomized clinical trials, and large, contemporary cohort studies have several shortcomings that limit their extrapolation to clinical practice. In our opinion, the currently available evidence is insufficient to conclude that pMI during PCI, as currently defined, always has important prognostic implications. Until further evidence is available, we recommend adopting the definition for MI given in the third universal definition of MI, which differentiates between pMI and spontaneous MI. This is important not only for clinical decision-making but also for the interpretation of pMI as a surrogate end point in clinical trials. Further studies are essential to understand the pathophysiology and consequences of pMI.

  • 1543. Wu, Alan H B
    et al.
    Packer, Milton
    Smith, Andrew
    Bijou, Rachel
    Fink, Daniel
    Mair, Johannes
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Feldcamp, Carolyn S
    Haverstick, Doris M
    Ahnadi, Charaf E
    Grant, Andrew
    Despres, Normand
    Bluestein, Barry
    Ghani, Farooq
    Analytical and clinical evaluation of the Bayer ADVIA Centaur automated B-type natriuretic peptide assay in patients with heart failure: a multisite study2004In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 50, no 5, p. 867-873Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    B-Type natriuretic peptide (BNP) is released from the left ventricle of the heart into the circulation in response to ventricular stretching and volume overload. Increased BNP concentrations are associated with heart failure (HF).

    METHODS:

    We evaluated the analytical and clinical performance of the Bayer ADVIA Centaur BNP assay. Studies included precision, analytical correlation (against the Shionogi ShionoRIA and Biosite Triage BNP assays), BNP results for blood collected in plastic tubes containing EDTA vs other collection tubes, high-dose hook effect, detection limits, and interferences. The clinical performance was tested on 2243 blood samples collected from 983 apparently healthy individuals, 538 patients with chronic disease but without HF (renal insufficiency, chronic obstructive pulmonary disease, diabetes, and hypertension), and 722 patients with HF (New York Heart Association classes I-IV).

    RESULTS:

    The ADVIA Centaur assay had total imprecision (CV) of 3.4%, 2.9%, and 2.4% at BNP concentrations of 48, 461, and 1768 ng/L, respectively. The Passing-Bablok correlations to the ShionoRIA and Triage were as follows: ADVIA Centaur = 1.11(ShionoRIA) - 1.19 ng/L (r = 0.98); ADVIA Centaur = 0.78(Triage) + 5.89 ng/L (r = 0.92), respectively. Of the different blood collection tubes, only EDTA plastic tubes (with and without the barrier gel) were acceptable. The lower detection limit was 0.5 ng/L, and there were no interferences from common analytes, other neuropeptides, or unusual antibodies. BNP exhibited different reference intervals according to age and gender. BNP concentrations increased progressively as the severity of HF increased.

    CONCLUSIONS:

    The ADVIA Centaur is the first commercially available BNP assay for use on an automated immunochemistry platform. This assay has good analytical and clinical performance characteristics for diagnosing HF.

  • 1544.
    Wu, Jason H. Y.
    et al.
    Univ Sydney, George Inst Global Hlth, Sydney, NSW 2050, Australia..
    Foote, Celine
    Univ Sydney, George Inst Global Hlth, Sydney, NSW 2050, Australia.;Concord Repatriat Gen Hosp, Sydney, NSW, Australia..
    Blomster, Juuso
    Univ Sydney, George Inst Global Hlth, Sydney, NSW 2050, Australia.;Univ Turku, Turku, Finland.;Univ Gothenberg, Sahlgrenska Acad, Gothenburg, Sweden..
    Toyama, Tadashi
    Univ Sydney, George Inst Global Hlth, Sydney, NSW 2050, Australia..
    Perkovic, Vlado
    Univ Sydney, George Inst Global Hlth, Sydney, NSW 2050, Australia.;Royal Prince Alfred Hosp, Sydney, NSW, Australia..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Univ Sydney, George Inst Global Hlth, Sydney, NSW 2050, Australia..
    Neal, Bruce
    Univ Sydney, George Inst Global Hlth, Sydney, NSW 2050, Australia.;Univ London Imperial Coll Sci Technol & Med, London, England..
    Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis2016In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 4, no 5, p. 411-419Article in journal (Refereed)
    Abstract [en]

    Background In patients with type 2 diabetes, sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to reduce glucose concentrations, blood pressure, and weight, but to increase LDL cholesterol and the incidence of urogenital infections. Protection against cardiovascular events has also been reported, as have possible increased risks of adverse outcomes such as ketoacidosis and bone fracture. We aimed to establish the effects of SGLT2 inhibitors on cardiovascular events, death, and safety outcomes in adults with type 2 diabetes, both overall and separately for individual drugs. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and websites of US, European, and Japanese regulatory authorities from Jan 1, 1950, to Sept 30, 2015, for data from prospective randomised controlled trials assessing the effects of SGLT2 treatment compared with controls. We excluded duplicate reports, trials of compound drugs, trials that lasted 7 days or fewer, trials that did not report on outcomes of interest, and articles that presented pooled trial data for which the individual trials could not be identified. We extracted data in duplicate using a standardised approach. The primary outcome was major adverse cardiovascular events. Secondary outcomes were cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, admission to hospital for unstable angina, heart failure, and all-cause mortality. We estimated summary relative risks with fixed-effects meta-analysis, with the I-2 statistic used to estimate heterogeneity of results beyond chance. Findings The analyses included data from six regulatory submissions (37 525 participants) and 57 published trials (33 385 participants), which provided data for seven different SGLT2 inhibitors. SGLT2 inhibitors protected against the risk of major adverse cardiovascular events (relative risk 0.84 [95% CI 0.75-0.95]; p=0.006), cardiovascular death (0.63 [0.51-0.77]; p<0.0001), heart failure (0.65 [0.50-0.85]; p=0.002), and death from any cause (0.71 [0.61-0.83]; p<0.0001). No clear effect was apparent for non-fatal myocardial infarction (0.88 [0.72-1.07]; p=0.18) or angina (0.95 [0.73-1.23]; p=0.70), but we noted an adverse effect for non-fatal stroke (1.30 [1.00-1.68]; p=0.049). We noted no clear evidence that the individual drugs had different effects on cardiovascular outcomes or death (all I I-2 < 43%). Safety analyses showed consistent increased risks of genital infections (regulatory submissions 4.75 [4.00-5.63]; scientific reports 2.88 [2.48-3.34]), but findings for some safety outcomes varied depending on whether anlayses were based on data extracted from regulatory submissions or trials reported in the scientific literature. Interpretation These data suggest net protection of SGLT2 inhibitors against cardiovascular outcomes and death. The efficacy results were driven by findings for empagliflozin (the only SGLT2 inhibitor for which data from a dedicated long-term cardiovascular safety trial have been reported), although results for the other drugs in the class were not clearly different. Adverse events were more difficult to quantify than was efficacy, with the effects of individual drugs in the class seeming to differ for some safety outcomes. Results from ongoing studies will be crucial to substantiate these findings across the drug class, but the available data provide a strong rationale to expect benefit from use of SGLT2 inhibitors in patients with type 2 diabetes at high risk of cardiovascular events.

  • 1545. Wulaningsih, Wahyu
    et al.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hammar, Niklas
    Jungner, Ingmar
    Walldius, Göran
    van Hemelrijck, Mieke
    Serum Lipids and the Risk of Gastrointestinal Malignancies in the Swedish AMORIS Study2012In: Journal of cancer epidemiology, ISSN 1687-8566, Vol. 2012, p. 792034-Article in journal (Refereed)
    Abstract [en]

    Background.

    Metabolic syndrome has been linked to an increased cancer risk, but the role of dyslipidaemia in gastrointestinal malignancies is unclear. We aimed to assess the risk of oesophageal, stomach, colon, and rectal cancers using serum levels of lipid components.

    Methods.

    From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected 540,309 participants (> 20 years old) with baseline measurements of total cholesterol (TC), triglycerides (TG), and glucose of whom 84,774 had baseline LDL cholesterol (LDL), HDL cholesterol (HDL), apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Multivariate Cox proportional hazards regression was used to assess glucose and lipid components in relation to oesophageal, stomach, colon, and rectal cancer risk.

    Results.

    An increased risk of oesophageal cancer was observed in persons with high TG (e.g. HR: 2.29 (95% CI: 1.42-3.68) for the 4th quartile compared to the 1st) and low LDL, LDL/HDL ratio, TC/HDL ratio, log (TG/HDL), and apoB/apoA-I ratio. High glucose and TG were linked with an increased colon cancer risk, while high TC levels were associated with an increased rectal cancer risk.

    Conclusion.

    The persistent link between TC and rectal cancer risk as well as between TG and oesophageal and colon cancer risk in normoglycaemic individuals may imply their substantiality in gastrointestinal carcinogenesis.

  • 1546.
    Wulaningsih, Wahyu
    et al.
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.;Gadjah Mada Univ, Fac Med, Div Hematol Oncol, Yogyakarta, Indonesia..
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Garmo, Hans
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.;Reg Canc Ctr, Uppsala, Sweden..
    Karagiannis, Sophia N.
    Kings Coll London, Guys & St Thomass Hosp, NIHR Biomed Res Ctr, St Johns Inst Dermatol,Div Genet & Mol Med,Fac Li, London, England.;Kings Coll London, London, England..
    Ahlstedt, Staffan
    Karolinska Inst, Inst Environm Med, Ctr Allergy Res, Stockholm, Sweden..
    Malmstrom, Hakan
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden..
    Lambe, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Hammar, Niklas
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden.;AstraZeneca R&D, Molndal, Sweden..
    Walldius, Goran
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Jungner, Ingmar
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;CALAB Res, Stockholm, Sweden..
    Ng, Tony
    Kings Coll London, Randall Div, Richard Dimbleby Dept Canc Res, London, England.;Kings Coll London, Div Canc Studies, London, England..
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.;Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden..
    Investigating the association between allergen-specific immunoglobulin E, cancer risk and survival2016In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 5, no 6, article id e1154250Article in journal (Refereed)
    Abstract [en]

    Prior findings linking allergy and cancer have been inconsistent, which may be driven by diverse assessment methods. We used serum specific immunoglobulin E (IgE) against common inhalant allergens that was assessed prior to cancer diagnosis in studying this association. We selected 8,727 Swedish men and women who had measurements of serum allergen-specific IgE and total IgE between 1992 and 1996. Multivariable Cox regression using age as a timescale was performed to assess the associations of IgE sensitization, defined by any levels of serum specific IgE >= 35 kU/L, with risk of overall and specific cancers. A test for trend was performed by assigning scores derived from allergen-specific IgE levels at baseline as an ordinal scale. Kaplan-Meier curves and log-rank test were used to assess cancer survival by IgE sensitization status. During a mean follow-up of 16 year, 689 persons were diagnosed with cancer. We found an inverse association between IgE sensitization and cancer risk, with a hazard ratio (HR) of 0.83 and 95% confidence intervals (CI) of 0.70-0.99. A similar trend was seen with specific IgE scores overall (P-trend = 0.007) and in women (P-trend = 0.01). Although IgE sensitization was not associated with risk of common site-specific cancers, serum specific IgE scores were inversely associated with melanoma risk in men and women combined, and with risk of female breast and gynecological cancers combined. No association with survival was observed. The association between circulating IgE levels and incident cancer may point toward a role of T-helper 2 (T(H)2)-biased response in development of some cancers.

  • 1547. Wulaningsih, Wahyu
    et al.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmstrom, Håkan
    Lambe, Mats
    Hammar, Niklas
    Walldius, Göran
    Jungner, Ingmar
    Van Hemelrijck, Mieke
    Prediagnostic serum inflammatory markers in relation to breast cancer risk, severity at diagnosis and survival in breast cancer patients2015In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 36, no 10, p. 1121-1128Article in journal (Refereed)
    Abstract [en]

    Inflammation has been linked to cancer but its role in breast cancer is unclear. We investigated common serum markers of inflammation: C-reactive protein (CRP), albumin, haptoglobin and white blood cells (WBC) in relation to breast cancer incidence, severity and survival. A total of 155179 women aged 20 and older without any history of cancer were selected from a large Swedish cohort. Hazard ratios (HRs) for breast cancer were estimated with Cox regression, adjusting for potential confounders. Ordered and binomial logistic regression models were used to assess the associations of serum inflammatory markers with breast cancer severity and oestrogen receptor (ER) positivity at diagnosis, on the other. Cumulative incidence functions by levels of inflammatory markers were assessed for early death from breast cancer and all causes. During a mean follow-up of 18.3 years, 6606 women were diagnosed with breast cancer, of whom 1474 died. A positive association with incident breast cancer was seen for haptoglobin ≥ 1.4g/l [HR 1.09; 95% confidence interval (CI): 1.00-1.18] compared to lower levels. No association was observed between inflammatory markers and breast cancer severity or ER positivity. Higher haptoglobin was linked to risk of early death from breast cancer (HR: 1.27, 95% CI: 1.02-1.59), whereas higher risk of early death from all causes was additionally found with CRP ≥ 10mg/l (HR: 1.19, 95% CI: 1.04-1.36) and WBC ≥ 10×10(9)/l (HR: 1.57, 1.14-2.16). Our findings indicate that prediagnostic serum inflammatory markers were weakly linked to incident breast cancer but corresponded to worse survival after diagnosis.

  • 1548. Wulaningsih, Wahyu
    et al.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hammar, Niklas
    Jungner, Ingmar
    Walldius, Goran
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Van Hemelrijck, Mieke
    Inorganic phosphate and the risk of cancer in the Swedish AMORIS study2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. UNSP 257-Article in journal (Refereed)
    Abstract [en]

    Background: Both dietary and serum levels of inorganic phosphate (Pi) have been linked to development of cancer in experimental studies. This is the first population-based study investigating the relation between serum Pi and risk of cancer in humans. Methods: From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected all participants (>20 years old) with baseline measurements of serum Pi, calcium, alkaline phosphatase, glucose, and creatinine (n = 397,292). Multivariable Cox proportional hazards regression analyses were used to assess serum Pi in relation to overall cancer risk. Similar analyses were performed for specific cancer sites. Results: We found a higher overall cancer risk with increasing Pi levels in men (HR: 1.02 (95% CI: 1.00-1.04) for every SD increase in Pi), and a negative association in women (HR: 0.97 (95% CI: 0.96-0.99) for every SD increase in Pi). Further analyses for specific cancer sites showed a positive link between Pi quartiles and the risk of cancer of the pancreas, lung, thyroid gland and bone in men, and cancer of the oesophagus, lung, and nonmelanoma skin cancer in women. Conversely, the risks for developing breast and endometrial cancer as well as other endocrine cancer in both men and women were lower in those with higher Pi levels. Conclusions: Abnormal Pi levels are related to development of cancer. Furthermore, the inverse association between Pi levels and risk of breast, endometrial and other endocrine cancers may indicate the role of hormonal factors in the relation between Pi metabolism and cancer.

  • 1549. Wulaningsih, Wahyu
    et al.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hammar, Niklas
    Jungner, Ingmar
    Walldius, Goran
    Lambe, Mats
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Van Hemelrijck, Mieke
    Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study2013In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 13, p. 663-Article in journal (Refereed)
    Abstract [en]

    Background:

    Observational studies have indicated that high calcium intake may prevent colorectal cancer, but as for randomized trials the results are inconclusive. Meanwhile, limited data on the link between serum calcium and cancer risk is available. We investigated the relation between serum calcium and risk of different gastrointestinal cancers in a prospective study.

    Methods:

    A cohort based on 492,044 subjects with baseline information on calcium (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk (AMORIS) study. Multivariable Cox proportional hazard models were used to analyse associations between standardised levels, quartiles and age/sex-specific categories of serum calcium and risk of oesophageal, stomach, colon, rectal cancer and also colorectal cancer combined, while taking into account serum albumin and other comorbidities.

    Results:

    During 12 years of follow-up, we identified 323 incident oesophageal cancers, 782 stomach cancers, 2519 colon cancers, and 1495 rectal cancers. A positive association was found between albumin-adjusted serum calcium and risk of oesophageal [HR: 4.82 (95% CI: 2.07 - 11.19) for high compared to normal age-specific calcium levels] and colon cancer [e.g. HR: 1.07 (95% CI: 1.00 - 1.14) for every SD increase of calcium] as well as colorectal cancer [e.g. HR: 1.06 (95% CI: 1.02-1.11) for every SD increase of calcium] in women. In men there were similar but weaker non-statistically significant trends.

    Conclusion:

    The positive relation between serum calcium, oesophageal cancer and colorectal cancer calls for further studies including calcium regulators to evaluate whether there is a true link between calcium metabolism and development of gastrointestinal cancer.

  • 1550.
    Wulaningsih, Wahyu
    et al.
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London SE1 9RT, England..
    Sagoo, Harkiran K.
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London SE1 9RT, England..
    Hamza, Mustafa
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London SE1 9RT, England..
    Melvin, Jennifer
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London SE1 9RT, England..
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London SE1 9RT, England.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London SE1 9RT, England.
    Malmström, Håkan
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-17177 Stockholm, Sweden..
    Lambe, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Hammar, Niklas
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-17177 Stockholm, Sweden.;AstraZeneca R&D, S-43150 Molndal, Sweden..
    Walldius, Göran
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, S-17177 Stockholm, Sweden..
    Jungner, Ingmar
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, S-17177 Stockholm, Sweden.;CALAB Res, S-17177 Stockholm, Sweden..
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London SE1 9RT, England.;Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-17177 Stockholm, Sweden..
    Serum Calcium and the Risk of Breast Cancer: Findings from the Swedish AMORIS Study and a Meta-Analysis of Prospective Studies2016In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 17, no 9, article id 1487Article in journal (Refereed)
    Abstract [en]

    To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I-2 test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88-0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66-0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations.

2829303132 1501 - 1550 of 1579
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