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  • 1.
    Abedpour Dehkordi, Adel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Nayeri, H.
    Naderi, G. A.
    Dinani, N. Jafari
    Boshtam, M.
    Interleukin-6 reduces paraoxonase-1 activity in a dose-dependent manner: evidence for a potential novel lipoprotein-based modulatory mechanism2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 252, p. E113-E114Article in journal (Other academic)
    Abstract [en]

    Objectives: The anti-oxidant/anti-inflammatory nature of HDL is mainly associated with paraoxonase-1 (PON1). Previous studies have revealed an inverse correlation between Interleukin-6 (IL-6) and PON1 expression. The current study investigates the effect of IL-6 on serum PON1 activity in vitro, given the potential structural capability of PON1 to host multiple ligands. Methods: PON1 activity was measured spectrophotometrically (234 nm) using paraoxon substrate in the presence of concentrations of IL-6 than control samples. A sequence alignment using the FASTA sequence was manually conducted to identify possible homologies between PON1 and the IL-6-binding protein. Statistical analysis was conducted using GraphPad Prism v5.0. Results: PON1 enzyme activity decreased by 15%, 26% (P<0.05) and 55% (P<0.001) in the presence of 4, 10 and 20 pg/ml of IL-6, respectively. in comparison with the controls. Student t. test was used as statistical method (p<0.05: statistically significant). There are potential homologies between PON1 active sites and know IL-6-binding residues. Conclusions: This study shows that IL-6 directly reduce the PON1 activity in a dose-dependent manner. This observation supports some studies indicating inverse correlation between PON1 and IL-6. However, as opposed to the gene-mediated approach, this study suggest that IL-6 may act directly through specific binding to PON1 (biochemical modulation). X ray crystallography can further scrutinize the present finding.

  • 2.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessen, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sub-clinical atherosclerosis in the common carotid artery in women with/without previous pre-eclampsia: A seven-year follow-up.2019In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, article id S0021-9150(19)30449-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Pre-eclampsia is associated with increased risk of cardiovascular disease and premature death. However, conventional common carotid artery intima-media thickness (CCA-IMT) measurement does not reflect this. In contrast, measurement of the individual CCA intima and media thicknesses clearly indicates increased vascular risk both at diagnosis and about one year after pre-eclampsia. This study examined whether individual CCA wall layers, risk factors for cardiovascular disease, and markers of endothelial dysfunction had normalized or remained unfavorable seven years after pre-eclampsia.

    METHODS: The individual CCA intima and media thicknesses were measured using 22 MHz ultrasound. Conventional cardiovascular risk factors were recorded. A thick intima, thin media and high intima/media thickness ratio (I/M) are signs of sub-clinical atherosclerosis.

    RESULTS: The median age of women with previous pre-eclampsia (cases = 23) or normal pregnancies (controls = 35) was 39/37 years. At follow-up (median about seven years), the intima remained thicker and the I/M was higher in cases than in controls [all p < 0.0001; p < 0.001 after adjustment for time to follow-up, body mass index (BMI), and mean arterial pressure (MAP)], whereas the CCA-IMT was illogically thinner. Further, BMI, MAP, hip circumference, abdominal height, serum endostatin and apolipoprotein B levels were higher in cases (all p < 0.05). Intima and I/M measurements were correlated with age, MAP, endostatin and apolipoprotein B, whereas no logical correlations were found for CCA-IMT.

    CONCLUSIONS: The arteries in cases but not controls were still adversely affected after seven years. Measuring intima thickness and I/M appears preferable to measuring CCA-IMT for demonstrating vascular risk after pre-eclampsia.

  • 3.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with and without preeclampsia2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 275, p. E69-E70Article in journal (Other academic)
  • 4.
    Aldi, Silvia
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Eriksson, Linnea
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Kronqvist, Malin
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Lengquist, Mariette
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Löfling, Marie
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Folkersen, Lasse
    Tech Univ Denmark, Ctr Biol Sequence Anal, Copenhagen, Denmark.
    Matic, Ljubica P.
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Maegdefessel, Lars
    Karolinska Inst, Dept Med Solna, S-17176 Stockholm, Sweden;Tech Univ Munich, Dept Vasc Surg, D-80333 Munich, Germany.
    Grinnemo, Karl-Henrik
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Li, Jin-Ping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Österholm, C.
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Hedin, Ulf
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Dual roles of heparanase in human carotid plaque calcification2019In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 283, p. 127-136Article in journal (Refereed)
    Abstract [en]

    Background and aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-beta-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity. The present aim is to investigate HPSE expression in relation to genes associated with osteogenesis and osteolysis and the effect of elevated HPSE expression on calcification and osteolysis in vitro.

    Methods: Transcriptomic and immunohistochemical analyses were performed using the Biobank of Karolinska Endarterectomies (BiKE). In vitro calcification and osteolysis were analysed in human carotid smooth muscle cells overexpressing HPSE and bone marrow-derived osteoclasts from HPSE-transgenic mice respectively.

    Results: HPSE expression correlated primarily with genes coupled to osteoclast differentiation and function in human carotid atheromas. HPSE was expressed in osteoclast-like cells in atherosclerotic lesions, and HPSE-transgenic bone marrow-derived osteoclasts displayed a higher osteolytic activity compared to wild-type cells. Contrarily, human carotid SMCs with an elevated HPSE expression demonstrated markedly increased mineralization upon osteogenic differentiation.

    Conclusions: We suggest that HPSE may have dual functions in vascular calcification, depending on the stage of the disease and presence of inflammatory cells. While HPSE plausibly enhances mineralization and osteogenic differentiation of vascular smooth muscle cells, it is associated with inflammation-induced osteoclast differentiation and activity in advanced atherosclerotic plaques.

  • 5.
    Andersson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hellsten, Gideon
    Nilsson, Torbjörn K
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Effects of heavy endurance physical exercise on inflammatory markers in non-athletes2010In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 209, no 2, p. 601-605Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Physical activity has beneficial effects on cardiovascular disease but the mechanisms are still somewhat unclear. One possible pathway may be through the anti-inflammatory effects attributed to regular physical activity. Our primary aim was to study the effects of endurance physical exercise on C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNFalpha) during the acute and recovery phases. Secondarily, we studied the impact of diet on these inflammatory markers.

    METHODS: Twenty men, aged 18-55 years, participated in a 14 days cross-country skiing tour. They traveled 12-30km per day corresponding to about 10h of heavy physical activity. The participants were randomized to a diet with either 30 or 40% of energy derived from fat. Inflammatory variables were analysed at week 0, after 1 and 2 weeks and during the recovery phase at week 6 and 8.

    RESULTS: CRP and TNFalpha increased significantly during the two weeks of exercise (1.4-5.0mg/l, p=0.00 and 6.8-8.4pg/ml, p=0.00). CRP levels were significantly lower during recovery (median 0.7mg/l) compared to baseline (median 1.4mg/l) and did not correlate to metabolic variables. There were no significant changes in IL-6 levels during the study period. For dietary groups significant CRP changes were observed only in the high fat group during recovery.

    CONCLUSIONS: CRP and TNFalpha increased significantly but reacted differently during heavy physical activity while there seemed to be no significant changes in IL-6. No significant differences regarding inflammatory variables were found between the dietary groups.

  • 6. Antoniewicz, Lukasz
    et al.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kuhl, Jeanette
    Abdel-Halim, Samy M.
    Kiessling, Anna
    Mobarrez, Fariborz
    Lundback, Magnus
    Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 255, p. 179-185Article in journal (Refereed)
    Abstract [en]

    Background and aims: The use of electronic cigarettes is increasing dramatically on a global scale and its effects on human health remain uncertain. In the present study, we measured endothelial progenitor cells (EPCs) and microvesicles (MVs) in healthy young volunteers following short-term exposure to inhalation of e-cigarette vapor (ECV) to determine vascular changes.

    Methods: Sixteen healthy seldom smokers were randomized into two groups either exposed or not exposed to 10 puffs of ECV for 10 min, in a crossover design. Blood samples were obtained at baseline and 1, 4 and 24 h following exposure. EPCs (CD34 + CD309) and MVs were analyzed by flow cytometry. MVs were phenotyped according to origin (platelet (CD41), endothelial (CD144), leukocytes (CD45), monocytes (CD14)) and nuclear content (SYTO 13 dye). In addition, expression of inflammation markers such P-selectin (CD62P), E-selectin (CD62E), CD40-ligand (CD154) and HMGB1 was investigated. Fractional exhaled nitric oxide (FeNO) was also measured at baseline and after 24 h.

    Results: EPC levels in blood were significantly increased 1 h following exposure to ECV and returned to baseline values after 24 h. Only E-selectin positive MVs (endothelial origin) were slightly elevated (p < 0.038). FeNO was unaffected by exposure to ECV. Conclusions: In healthy volunteers, ten puffs of e-cigarette vapor inhalation caused an increase in EPCs. This increase was of the same magnitude as following smoking of one traditional cigarette, as we previously demonstrated. Taken together, these results may represent signs of possible vascular changes after short e-cigarette inhalation. Further studies analyzing potential cardiovascular health effects are critical as the e-cigarette market continues to burgeon.

  • 7.
    Bengrid, Tarek
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Zhao, Y.
    Ultrasound Department, Beijing Anzhen Hospital, Beijing, China.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Disturbed right ventricular function response to dobutamine stress in Syndrome X patients: a potential effect of coronary calcification2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E229-E229Article in journal (Other academic)
  • 8.
    Bengrid, Tarek
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zhao, Y.
    Ultrasound Department, Beijing Anzhen Hospital, Beijing, China.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Effect of coronary calcium score on subendocardial function in patients with Syndrome X: a tissue doppler dobutamine stress echocardiography study2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E68-E68Article in journal (Other academic)
  • 9.
    Bennet, A. M.
    et al.
    Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm.
    Van Maarle, M.
    Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm.
    Hallqvist, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Preventive Medicine.
    Morgenstern, R.
    Unit of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Frostegård, J.
    Wiman, B.
    Division of Coagulation Research, Karolinska University Hospital, Stockholm, Sweden.
    Prince, J. A.
    de Faire, U.
    Association of TNF-α serum levels and TNFA promoter polymorohisms with risk of myocardial infarction2006In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 187, no 2, p. 408-414Article in journal (Refereed)
    Abstract [en]

    Elevated levels of tumor necrosis factor-alpha (TNF-α), and presence of polymorphisms of the TNFA gene have been implicated in cardiovascular disease pathogenesis. We explored the relationship between polymorphisms in the TNFA gene (−1031C/T, −863C/A −857T/C, −308G/A, −238G/A), protein levels of TNF-α and their association to myocardial infarction (MI) using a sample of 1213 post-MI patients and 1561 healthy controls. MI risk was higher among men with elevated TNF-α levels, with the highest compared to the lowest TNF-α quartile giving a 70% risk increase (OR [95% CI]: 1.7 [1.1; 2.6]). Obese subjects who also had elevated TNF-α levels were at even higher risk for MI (OR [95% CI]: 3.4 [2.1; 5.6]). Higher TNF-α levels were seen among smokers (but not among non-smokers) carrying the −857T allele. Furthermore, a rare haplotype occurred more frequently among the cases than the controls. Elevated TNF-α levels are associated with increased MI risk. Obese subjects with elevated TNF-a levels, and carriers of polymorphisms in or near TNFA are particularly susceptible to the hazards of smoking, results which may have implications for cardiovascular preventive measures.

  • 10.
    Bergström, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Persson, L A
    Vessby, B
    Serum lipid values in adolescents are related to family history, infant feeding, and physical growth.1995In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 117, no 1, p. 1-13Article in journal (Refereed)
    Abstract [en]

    Total serum cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and lipoprotein (a) (Lp(a)) were analysed in 879 14- and 17-year-old healthy adolescents (477 boys and 402 girls), and related to family history of cardiovascular disease, early feeding, weight and length at birth, and physical growth during infancy and childhood. Mean TC was significantly higher in girls than in boys (4.4 and 4.2 mmol/l, respectively, both age-groups together). High TC values ( > 5.2 mmol/l) were more prevalent in girls than in boys: 14% and 17% compared to 6% and 12% in 14- and 17-year-old girls and boys, respectively. Mean TC and LDL-C values were lower during mid-puberty in both boys and girls while, in boys but not in girls, mean HDL-C values decreased and TG values increased successively with increasing pubertal stage. Girls who were taking oral contraceptives had higher mean values of TC (4.91/4.39 mmol/l), TG (1.32/0.83 mmol/l), and apo B (0.89/0.73 g/l). Boys with a family history of early deaths ( < 55 years) from myocardial infarction and girls with a family history of cerebral haemorrhage/thrombosis in fathers had higher mean values of TC (4.55/4.17 and 5.03/4.40 mmol/l, for boys and girls, respectively), LDL-C (2.84/2.47 and 3.08/2.56 mmol/l), and apo B (0.73/0.70 and 0.86/0.73 g/l). Adolescents with short duration of breast feeding ( < 6 months), or early introduction of infant formula, had higher mean values of TC (4.29/4.14 mmol/l) and apo B (0.72/0.68 g/l). There were no significant correlations between serum lipid values and body weight or length at birth, but adolescents with high LDL-C (upper quartile) seemed to have lower attained heights during infancy and childhood. In conclusion, this study shows that serum lipids in adolescence are primarily related to age and sex but also to early determinants like family history of cardiovascular diseases, infant feeding, and early physical growth.

  • 11.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Backteman, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Persistent accumulation of interferon-gamma-producing CD8(+)CD56(+) T cells in blood from patients with coronary artery disease2012In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, no 2, p. 515-520Article in journal (Refereed)
    Abstract [en]

    Objective: There is emerging evidence for CD8(+) T cell alterations in blood from patients with coronary artery disease (CAD). We examined whether the distribution and phenotype of CD8(+)CD56(+) T cells differed according to the clinical manifestation of CAD. less thanbrgreater than less thanbrgreater thanMethods: Patients with acute coronary syndrome (ACS, n = 30), stable angina (SA, n = 34) and controls (n = 36) were included. Blood was collected before and up to 12 months after referral for coronary investigation. CD8(+)CD56(+) T cells were assessed by flow cytometry for expression of surface markers, apoptosis, and intracellular expression of cytokines. less thanbrgreater than less thanbrgreater thanResults: The proportions of CD8(+)CD56(+) T cells were significantly higher in both ACS and SA patients compared with controls, and remained so after 3 and 12 months. This was independent of age, sex, systemic inflammation and cytomegalovirus seropositivity. CD8(+)CD56(+) T cells differed from CD8(+)CD56(-) T cells in terms of lower CD28 expression and fewer apoptotic cells. Both CD8(+) T cell subsets were positive for interferon (IFN)-gamma and tumor necrosis factor, although IFN-gamma was significantly more confined to the CD8(+)CD56(+) T cells. less thanbrgreater than less thanbrgreater thanConclusion: The persistent accumulation of CD8(+)CD56(+) T cells in ACS and SA patients share several features with immunological aging. It also contributes to a larger IFN-gamma(+) pool in blood, and may thereby hypothetically drive the atherosclerotic process in a less favorable direction.

  • 12. Björck, M
    et al.
    Ravn, H
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital.
    Wanhainen, A
    Nilsson, P M
    Blood cell telomere length among patients with an isolated popliteal artery aneurysm and those with multiple aneurysm disease2011In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 219, no 2, p. 946-950Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Short relative telomere length (RTL) is associated with vascular ageing, inflammation and cardiovascular risk factors. Previous studies have reported an association between abdominal aortic aneurysm and short RTL. The presence of atherosclerosis among patients with aneurysm disease may, however, be a confounder. The aim was to explore the associations between short RTL and aneurysm disease, by comparing patients with isolated popliteal artery aneurysms with those having multiple aneurysms.

    DESIGN AND PATIENTS: DNA was retrieved from 183 patients with popliteal artery aneurysm (PAA). They were all examined with ultrasound at the time of blood-sampling, and had a total of 423 aneurysms (range 1-7, mean 2.3/patient).

    METHODS: TL was measured with Real-Time PCR, RTL was calculated by comparing with three reference populations.

    RESULTS: Patients with bilateral PAAs had a mean RTL of 0.985 vs. 1.038 with unilateral PAAs (P = 0.326). Patients with abdominal aortic aneurysm had RTL 1.035, vs. 0.999 without (P = 0.513). No difference was seen with or without femoral or iliac aneurysms. Fifty-six patients with isolated PAA at surgery and at re-examination had RTL 0.974, vs. 1.033 who had >1 aneurysm (P = 0.308). RTL was not associated with the number of aneurysms at re-examination (P = 0.727, one-way ANOVA). There was a trend towards shorter RTL among active smokers (0.93 vs. 1.04, P = 0.066).

    CONCLUSIONS: No association between short RTL and multiple aneurysm disease was found. The previously reported association between AAA and short RTL may be secondary to cardiovascular risk factors, rather than by aneurysm disease.

  • 13.
    Björck, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Ravn, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Nilsson, T K
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Nilsson, P M
    Blood cell telomere length among patients with an isolated popliteal artery aneurysm and those with multiple aneurysm disease2011In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 219, no 2, p. 946-950Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Short relative telomere length (RTL) is associated with vascular ageing, inflammation and cardiovascular risk factors. Previous studies have reported an association between abdominal aortic aneurysm and short RTL. The presence of atherosclerosis among patients with aneurysm disease may, however, be a confounder. The aim was to explore the associations between short RTL and aneurysm disease, by comparing patients with isolated popliteal artery aneurysms with those having multiple aneurysms.

    DESIGN AND PATIENTS:

    DNA was retrieved from 183 patients with popliteal artery aneurysm (PAA). They were all examined with ultrasound at the time of blood-sampling, and had a total of 423 aneurysms (range 1-7, mean 2.3/patient).

    METHODS:

    TL was measured with Real-Time PCR, RTL was calculated by comparing with three reference populations.

    RESULTS:

    Patients with bilateral PAAs had a mean RTL of 0.985 vs. 1.038 with unilateral PAAs (P=0.326). Patients with abdominal aortic aneurysm had RTL 1.035, vs. 0.999 without (P=0.513). No difference was seen with or without femoral or iliac aneurysms. Fifty-six patients with isolated PAA at surgery and at re-examination had RTL 0.974, vs. 1.033 who had >1 aneurysm (P=0.308). RTL was not associated with the number of aneurysms at re-examination (P=0.727, one-way ANOVA). There was a trend towards shorter RTL among active smokers (0.93 vs. 1.04, P=0.066).

    CONCLUSIONS:

    No association between short RTL and multiple aneurysm disease was found. The previously reported association between AAA and short RTL may be secondary to cardiovascular risk factors, rather than by aneurysm disease.

  • 14.
    Carlson, Lars A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Fröberg, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Oro, L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    A case of massive hypertriglyceridemia corrected by nicotinic acid or nicotinamide therapy1972In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 16, no 3, p. 359-368Article in journal (Refereed)
    Abstract [en]

    A case of massive hypertriglyceridemia with fasting plasma triglycerides around 100 mmoles/l is described. Large amounts of chylomicra were present in fasting plasma and the amounts of low-density and high-density lipoproteins were very low. Postheparin plasma lipolytic activity was normal and intravenous heparin rapidly cleared the patient's abnormally prolonged alimentary lipemia with a concomitant rise in plasma free fatty acid levels.

    Nicotinic acid or nictotinamide given in doses of 3 g or more daily reduced plasma triglyceride levels to about 2–3 mmoles/1 and raised the reduced levels of low and high-density lipoproteins. The mode of onset of this therapeutic effect was slow and the effect persisted for several weeks after withdrawal of either nicotinic acid or nicotinamide.

    The pathogenesis of the hypertriglyceridemia as well as the mode of action of nicotinic acid and nicotinamide is discussed.

  • 15.
    Carlson, Lars A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Walldius, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Butcher, R.W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Effect of chlorophenoxyisobutyric acid (CPIB) on fat-mobilizing lipolysis and cyclic AMP levels in rat epididymal fat1972In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 16, no 3, p. 349-357Article in journal (Refereed)
    Abstract [en]

    High concentrations of chlorophenoxyisobutyric acid (CPIB) reduced basal glycerol release from rat epididymal fat pads in vitro and antagonized the lipolytic effects of noradrenaline. Furthermore, very high concentrations of CPIB significantly antagonized the effects or noradrenaline or ACTH on cyclic AMP accumulation by isolated rat adipocytes. These data are not incompatible with the hypothesis that a primary mechanism in the hypolipidemic action of CPIB is to lower the levels of cyclic AMP in adipose tissue, resulting in decreased hormone-sensitive lipase activity and/or increased lipoprotein lipase activity.

  • 16. Carlsson, Axel C.
    et al.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ruge, Toralph
    Larsson, Anders
    Arnlov, Johan
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, p. 41-46Article in journal (Refereed)
    Abstract [en]

    Background and aims: Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.& para;& para;Methods: We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.& para;& para;Results: An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.& para;& para;Conclusions: As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined. 

  • 17. Carlsson, Axel C
    et al.
    Jansson, Jan-Håkan
    Söderberg, Stefan
    Ruge, Toralph
    Larsson, Anders
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, p. 41-46Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.

    METHODS: We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.

    RESULTS: An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.

    CONCLUSIONS: As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined.

  • 18.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Jansson, Jan-Håkan
    Department of Public Health and Clinical Medicine, Research Unit Skellefteå, Umeå University, Umeå, Sweden.
    Söderberg, Stefan
    Department of Public Health and Clinical Medicine, Heart Centre, Umeå University, Umeå, Sweden.
    Ruge, Toralph
    Dept of Medicine Solna, Karolinska Institutet and Function of Emergency Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ärnlöv, Johan
    Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; School of Health and Social Sciences, Dalarna University, Falun, Sweden.
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, p. 41-46Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS:

    Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.

    METHODS:

    We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.

    RESULTS:

    An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.

    CONCLUSIONS:

    As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined.

  • 19.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Juhlin, C Christofer
    Larsson, Tobias E
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    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.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: Findings from two community based cohorts of elderly2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, no 1, p. 236-242Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

    METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

    RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

    CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.

  • 20. Carlsson, Axel C
    et al.
    Juhlin, C Christofer
    Larsson, Tobias E
    Larsson, Anders
    Ingelsson, Erik
    Sundström, Johan
    Lind, Lars
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: findings from two community based cohorts of elderly2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, no 1, p. 236-242Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

    METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

    RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

    CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.

  • 21. Chen, Yun
    et al.
    Dangardt, Frida
    Osika, Walter
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Berggren, Krister
    Gronowitz, Eva
    Friberg, Peter
    Age- and sex-related differences in vascular function and vascular response to mental stress. Longitudinal and cross-sectional studies in a cohort of healthy children and adolescents2012In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 220, no 1, p. 269-274Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Limited data, especially from longitudinal studies, are available regarding vascular health assessment in childhood. In this study, we performed longitudinal and cross-sectional studies in healthy children and adolescents to investigate age- and sex-related differences in vascular functions and vascular response to mental stress.

    METHODS: Pulse wave velocity (PWV) was measured by tonometry. Endothelial function and vascular response to mental arithmetic test were assessed using a peripheral artery tonometry device. Data were obtained in 162 adolescents (mean age of 17 years, 94 girls) in a 3-year follow-up study and 241 children (mean age of 10 years, 115 girls) in a first-time investigation. Physical activity was assessed in adolescents by a self-report questionnaire.

    RESULTS: Our 3-year follow-up study revealed that the increased PWV was greater in male adolescents (0.79±0.79m/s) than in females (0.27±0.89m/s, p<0.001). Adolescents who reported decreased physical activity over the 3-year period had increased arterial stiffness. Comparing the cross-sectional data, we found that sex-related differences in reactive hyperemic response was more apparent by evaluating the overall response curve than measuring the reactive hyperemic index from one arbitrary time point, with lower peak response and smaller area-under-curve found in boys. Moreover, we found that, in response to mental stress, male adolescents had a more vasoconstrictive response, followed by a less vasodilatory response, and needed longer time to return to baseline level than the females.

    CONCLUSION: These findings suggest that boys are likely to have adverse changes in vascular health earlier than the age-matched girls.

  • 22. Cherfan, P
    et al.
    Tompa, A
    Wikby, A
    Löfgren, S
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Effects of simvastatin on human T cells in vivo2007In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 193, no 1, p. 186-192Article in journal (Refereed)
    Abstract [en]

    Objective: The use of statins has shown several anti-inflammatory actions, including modulatory effects on T cells in vitro. Since the effects on human T cells in vivo are less clarified, our aim was to investigate the effects of simvastatin on human T cells in vivo and ex vivo. Methods and results: A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40 mg or placebo for 6 weeks. The serum levels of C-reactive protein (CRP) were significantly reduced by simvastatin. The proportions of CD4+ and CD8+ T cell subsets expressing early (CD25) or late (HLA-DR) activation markers, as assessed by flow cytometry, were not changed by simvastatin. However, simvastatin tended to increase the density of HLA-DR and L-selectin per CD8+ T cell. The T helper(h)1/Th2 response was evaluated by stimulatory assays followed by intra-cellular staining of interferon-γ and interleukin-4. Simvastatin treatment did not affect the Th1 response but the results indicated a potential to suppress Th2. Conclusion: Simvastatin treatment resulted in a few discrete changes as regards peripheral T cells. However, the findings do not provide evidence that simvastatin-induced anti-inflammatory actions are related to any significant modulatory effects on human T cells in clinically healthy men with hypercholesterolemia. © 2006 Elsevier Ireland Ltd. All rights reserved.

  • 23. Cherfan, Pierre
    et al.
    Tompa, Andrea
    Jönköping University, School of Health Science, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health Science, HHJ. Ageing - living conditions and health. Jönköping University, School of Health Science, HHJ. Biomedical Platform.
    Wikby, Anders
    Jönköping University, School of Health Science, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health Science, HHJ. Ageing - living conditions and health.
    Löfgren, Sture
    Jonasson, Lena
    Effects of simvastatin on human T cells in vivo2007In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 193, no 1, p. 186-192Article in journal (Refereed)
  • 24.
    Chung, Rosanna W S
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lundberg, Anna K
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lutein exerts anti-inflammatory effects in patients with coronary artery disease.2017In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 262, p. 87-93, article id S0021-9150(17)30197-1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Many coronary artery disease (CAD) patients exhibit chronic low-grade inflammation. Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we first assessed relationships between interleukin (IL)-6 and individual carotenoids in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from CAD patients.

    METHODS: Lutein + zeaxanthin (isomers with lutein being dominant), β-cryptoxanthin, lycopene, α- and β-carotene and IL-6 were measured in plasma from 134 patients with stable angina (SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements were also performed 3 months after coronary intervention. PBMCs from SA patients were pre-treated with lutein (1, 5 and 25 μM) for 24 h followed by 24 h incubation ± lipopolysaccharide (LPS). Cell pellets were collected for IL-6, IL-1β and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media.

    RESULTS: Only lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline (r = -0.366, p < 0.001) and follow-up (r = -0.546, p < 0.001). Ex vivo, lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner. Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6, IL-1β (p < 0.01) and TNF (p < 0.05), and also reduced IL-6, IL-1β and TNF mRNA expression (p < 0.05).

    CONCLUSIONS: Clinical findings highlighted the inverse association between lutein and IL-6 in CAD patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated in ex vivo experiments. Taken together, these results show that lutein has the potential to play a role in resolution of chronic inflammation in CAD patients.

  • 25. De Backer, G.
    et al.
    Catapano, A. L.
    Chapman, J.
    Graham, I.
    Reiner, Z.
    Perk, Joep
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences.
    Wiklund, O.
    Guidelines on CVD prevention: Confusing or complementary?2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 226, no 1, p. 299-300Article in journal (Other academic)
  • 26. Delgado-Lista, J.
    et al.
    Perez-Martinez, P.
    Garcia-Rios, A.
    Phillips, C. M.
    Williams, C. M.
    Gulseth, H. L.
    Helal, O.
    Blaak, E. E.
    Kiec-Wilk, B.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Drevon, C. A.
    Defoort, C.
    Saris, W. H.
    Wybranska, I.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lovegrove, J. A.
    Roche, H. M.
    Lopez-Miranda, J.
    Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome: From the LIPGENE study2011In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 214, no 1, p. 110-116Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Variants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceeding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR). Methods: Fasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS. Results: Several single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure. Conclusions/interpretation: SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR.

  • 27.
    den Hoed, Marcel
    et al.
    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
    Almgren, Peter
    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.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Engström, Gunnar
    de Faire, Ulf
    Hedblad, Bo
    Humphries, Steve E
    Lindgren, Cecilia M
    Morris, Andrew P
    Östling, Gerd
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Tremoli, Elena
    Hamsten, Anders
    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.
    Melander, Olle
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 239, no 2, p. 304-310Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Large-scale genome-wide association studies (GWAS) have so far identified 45 loci that are robustly associated with coronary heart disease (CHD) in data from adult men and women of European descent.

    OBJECTIVES: To examine whether the CHD-associated loci are associated with measures of atherosclerosis in data from up to 9582 individuals of European ancestry.

    METHODS: Forty-five SNPs representing the CHD-associated loci were genotyped in middle-aged to elderly individuals of European descent from four independent population-based studies (IMPROVE, MDC-CC, ULSAM and PIVUS). Intima-media thickness (IMT) was measured by external B-mode ultrasonography at the far wall of the bulb (sinus) and common carotid artery. Plaque presence was defined as a maximal IMT of the bulb >1.5 mm. We meta-analysed single-SNP associations across the four studies, and combined them in a genetic predisposition score. We subsequently examined the association of the genetic predisposition score with prevalent CHD and the three indices of atherosclerosis, adjusting for sex, age and Framingham risk factors.

    RESULTS: As anticipated, the genetic predisposition score was associated with prevalent CHD, with each additional risk allele increasing the odds of disease by 5.5% (p = 4.1 × 10(-6)). Moreover, each additional CHD-risk allele across the 45 loci was associated with a 0.24% increase in IMT (p = 4.0 × 10(-3)), and with a 2.8% increased odds of plaque presence (p = 7.4 × 10(-6)) at the far wall of the bulb. The genetic predisposition score was not associated with IMT of the common carotid artery (p = 0.47).

    CONCLUSIONS: Our results suggest that the association between the 45 previously identified loci and CHD at least partly acts through atherosclerosis.

  • 28. Dormandy, J. A.
    et al.
    Betteridge, D. J.
    Schernthaner, G.
    Pirags, V.
    Norgren, Lars
    Örebro University, School of Health and Medical Sciences.
    Impact of peripheral arterial disease in patients with diabetes: results from PROactive (PROactive 11)2009In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 202, no 1, p. 272-281Article in journal (Refereed)
    Abstract [en]

    We compared cardiovascular disease outcomes according to the presence of peripheral arterial disease (PAD) at baseline in a post hoc analysis from the PROactive study. Of the 5238 patients in PROactive (a study of pioglitazone versus placebo in patients with type 2 diabetes and macrovascular disease; mean follow-up=34.5 months), 1274 had PAD at baseline (619=pioglitazone; 655=placebo). Patients with PAD at baseline showed significantly higher rates of the primary endpoint, main secondary endpoint, all-cause mortality (all P<0.0001), and stroke (P=0.0175) than those with no PAD at baseline. The risk of PAD alone was similar to that of myocardial infarction alone. In patients with no PAD at baseline, the event rates of the primary endpoint (P=0.0160), main secondary endpoint (P=0.0453), and acute coronary syndrome (P=0.0287) were significantly lower with pioglitazone than with placebo. This beneficial effect of pioglitazone was not seen in patients with PAD at baseline. In the total population, there was a higher frequency of leg revascularizations with pioglitazone than placebo-this was wholly due to first events that occurred within the initial 12 months of treatment. The presence of PAD increased the risk of all major cardiovascular events. Those without PAD at baseline seemed to benefit more from pioglitazone treatment than the overall PROactive population.

  • 29.
    Dziewierz, Artur
    et al.
    Jagiellonian University, Poland .
    Mielecki, Waldemar
    Jagiellonian University, Poland .
    Siudak, Zbigniew
    Jagiellonian University, Poland .
    Rakowski, Tomasz
    Jagiellonian University, Poland .
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Birkemeyer, Ralf
    Schwarzwald Baar Klinikum, Germany .
    Zasada, Wojciech
    Jagiellonian University, Poland .
    Dubiel, Jacek S.
    Jagiellonian University, Poland .
    Dudek, Dariusz
    Jagiellonian University, Poland .
    Early abciximab administration before primary percutaneous coronary intervention improves clinical outcome in diabetic patients with ST-segment elevation myocardial infarction (EUROTRANSFER Registry)2012In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 223, no 1, p. 212-218Article in journal (Refereed)
    Abstract [en]

    Background: Diabetes is an important determinant of prognosis in patients with ST-segment elevation myocardial infarction (STEMI). Limited data are available concerning benefits and risks of upstream abciximab administration in diabetic patients. Thus, the objective of the study was to assess the impact of early abciximab administration before primary angioplasty (PCI) for STEMI in diabetic patients. Methods: Data were gathered for 1650 consecutive STEMI patients transferred for primary PCI from hospital networks in seven countries in Europe from November 2005 to January 2007 (the EURO-TRANSFER Registry population). Patients were stratified by diabetes mellitus presence and then by abciximab administration strategy (early - more than 30 min before PCI vs. late). Results: Diabetes mellitus was diagnosed in 262 (15.9%) patients. Patients with diabetes mellitus were high-risk individuals, with advanced age, higher prevalence of comorbidities and increased risk of ischemic events during follow-up in comparison to non-diabetic patients. A total of 1086 patients who received abciximab were identified. Strategy of early abciximab administration was associated with enhanced infarct-related artery patency before PCI, and improved epicardial flow after PCI in both diabetic and non-diabetic patients. Importantly, early abciximab in diabetic patients led to the decrease in ischemic events, including 30-day (OR 0.260, 95% CI 0.089-0.759, p = 0.012) and 1-year (OR 0.273, 95% CI 0.099-0.749, p = 0.012) mortality reduction. However, only a trend toward improved survival was confirmed after adjustment for potential confounders. On the contrary, the reduction of 30-day (OR 0.620, 95% CI 0.334-1.189, p = 0.16) and 1-year (OR 0.643, 95% CI 0.379-1.089, p = 0.10) mortality rates was not significant among non-diabetic patients. Conclusions: Early administration of abciximab improves infarct-related artery patency before and after primary PCI, and leads to improved survival in diabetic STEMI patients.

  • 30.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Apolipoprotein B/A-I ratio related to visceral but not to subcutaneous adipose tissue in elderly Swedes2010In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 211, no 2, p. 656-659Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate whether the amount of visceral (VAT) or subcutaneous adipose tissue (SAT) independently of the other can determine the apolipoprotein (apo)B/A-I ratio. METHODS: VAT and SAT areas were assessed using magnetic resonance imaging in 247 randomly selected 70-year-old men and women who did not use lipid-lowering drugs. Their adipose tissue areas were compared to their apoB and apo A-I levels and to their apoB/A-I ratios. RESULTS: The VAT area and the gender were significantly related to the apoB/A-I ratio whereas the SAT area was not. There was a positive relationship between the VAT area and the apoB/A-I ratio. CONCLUSION: A positive relationship was established between the amount of VAT and the apoB/A-I ratio, whereas there was no relationship between the amount of SAT and the apoB/A-I ratio. This observation supports the notion that VAT is metabolically active.

  • 31.
    Eriksson, Jan W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Burén, Jonas
    Svensson, Maria
    Olivecrona, Thomas
    Olivecrona, Gunilla
    Postprandial regulation of blood lipids and adipose tissue lipoprotein lipase in type 2 diabetes patients and healthy control subjects.2003In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 166, no 2, p. 359-67Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIM: In type 2 diabetes and other insulin-resistant conditions, postprandial hypertriglyceridaemia is an important metabolic perturbation. To further elucidate alterations in the clearance of triglyceride-rich lipoproteins in type 2 diabetes we focused on the nutritional regulation of adipose tissue lipoprotein lipase (LPL).

    SUBJECTS AND METHODS: Eight subjects with type 2 diabetes and eight age-, sex- and body mass index (BMI)-matched control subjects underwent subcutaneous abdominal adipose tissue biopsies in the fasting state and 3.5 h following a standardized lipid-enriched meal. LPL activity and mass were measured in adipose tissue and also in plasma after an intravenous injection of heparin.

    RESULTS: Postprandial, but not fasting, triglycerides were significantly higher in the diabetic subjects than in the control subjects (3.0+/-0.4 vs 2.0+/-0.2 mmol/l, P=0.028). Adipose tissue LPL activity was increased following the meal test by approximately 35-55% (P=0.021 and 0.004, respectively). There was no significant difference between the groups in this respect. The specific enzyme activity of LPL was not altered in the postprandial state. Fasting and postprandial adipose tissue LPL activity as well as post-heparin plasma LPL activity tended to be lower among the diabetes patients (NS). There was a significant and independent inverse association between insulin resistance (homeostasis model assessment insulin resistance (HOMA-IR) index) vs post-heparin plasma LPL activity and postprandial triglyceride levels, respectively. Adipose tissue LPL activity was related to insulin action in vitro on adipocyte glucose transport, but not to HOMA-IR.

    CONCLUSION: Following food intake adipose tissue LPL activity is enhanced to a similar degree in patients with type 2 diabetes and in healthy control subjects matched for BMI, age and gender. If LPL dysregulation is involved in the postprandial hypertriglyceridaemia found in type 2 diabetes, it should occur in tissues other than subcutaneous fat.

  • 32.
    Eriksson, Jan. W.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Svensson, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Postprandial regulation of blood lipids and adipose tissue lipoprotein lipase in type 2 diabetes patients and healthy control subjects2003In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 166, no 2, p. 359-367Article in journal (Refereed)
    Abstract [en]

    Background/aim: In type 2 diabetes and other insulin-resistant conditions, postprandial hypertriglyceridaemia is an important metabolic perturbation. To further elucidate alterations in the clearance of triglyceride-rich lipoproteins in type 2 diabetes we focused on the nutritional regulation of adipose tissue lipoprotein lipase (LPL).

    Subjects and methods: Eight subjects with type 2 diabetes and eight age-, sex- and body mass index (BMI)-matched control subjects underwent subcutaneous abdominal adipose tissue biopsies in the fasting state and 3.5 h following a standardized lipid-enriched meal. LPL activity and mass were measured in adipose tissue and also in plasma after an intravenous injection of heparin.

    Results: Postprandial, but not fasting, triglycerides were significantly higher in the diabetic subjects than in the control subjects (3.0±0.4 vs 2.0±0.2 mmol/l, P=0.028). Adipose tissue LPL activity was increased following the meal test by ∼35–55% (P=0.021 and 0.004, respectively). There was no significant difference between the groups in this respect. The specific enzyme activity of LPL was not altered in the postprandial state. Fasting and postprandial adipose tissue LPL activity as well as post-heparin plasma LPL activity tended to be lower among the diabetes patients (NS). There was a significant and independent inverse association between insulin resistance (homeostasis model assessment insulin resistance (HOMA-IR) index) vs post-heparin plasma LPL activity and postprandial triglyceride levels, respectively. Adipose tissue LPL activity was related to insulin action in vitro on adipocyte glucose transport, but not to HOMA-IR.

    Conclusion: Following food intake adipose tissue LPL activity is enhanced to a similar degree in patients with type 2 diabetes and in healthy control subjects matched for BMI, age and gender. If LPL dysregulation is involved in the postprandial hypertriglyceridaemia found in type 2 diabetes, it should occur in tissues other than subcutaneous fat.

  • 33.
    Feldreich, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. School of Health and Social Studies, Dalarna University, Falun, .
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. School of Health and Social Studies, Dalarna University, Falun, .
    The association between serum cathepsin L and mortality in older adults2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, p. 109-116Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Research suggests that the protease cathepsin L is causally involved in atherosclerosis. However, data on cathepsin L as a risk marker are lacking. Therefore, we investigated associations between circulating cathepsin L and cardiovascular mortality.

    METHODS: Two independent community-based cohorts were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77 years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up, and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n = 993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths during 10.0 years follow-up.

    RESULTS: Higher serum cathepsin L was associated with an increased risk for cardiovascular mortality in age- and sex-adjusted models in both cohorts (ULSAM: hazard ratio (HR) for 1-standard deviation (SD) increase, 1.17 [95% CI, 1.01-1.34], p = 0.032 PIVUS: HR 1.35 [95% CI, 1.07-1.72], p = 0.013). When merging the cohorts, these associations were independent of inflammatory markers and cardiovascular risk factors, but non-significant adjusting for kidney function. Individuals with a combination of elevated cathepsin L and increased inflammation, kidney dysfunction, or prevalent cardiovascular disease had a markedly increased risk, while no increased risk was associated with elevated cathepsin L, in the absence of these disease states.

    CONCLUSIONS: An association between higher serum cathepsin L and increased risk of cardiovascular mortality was found in two independent cohorts. Impaired kidney function appears to be an important moderator or mediator of these associations. Further studies are needed to delineate the underlying mechanisms and to evaluate whether the measurement of cathepsin L might have clinical utility.

  • 34. Ferguson, Jane F.
    et al.
    Phillips, Catherine M.
    McMonagle, Jolene
    Perez-Martinez, Pablo
    Shaw, Danielle I.
    Lovegrove, Julie A.
    Helal, Olfa
    Defoort, Catherine
    Gjelstad, Ingrid M. F.
    Drevon, Christian A.
    Blaak, Ellen E.
    Saris, Wim H. M.
    Leszczynska-Golabek, Iwona
    Kiec-Wilk, Beata
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lopez-Miranda, Jose
    Roche, Helen M.
    NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids2010In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 211, no 2, p. 539-544Article in journal (Refereed)
    Abstract [en]

    Objective: Omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against the development of cardiovascular disease (CVD). Genotype at key genes such as nitric oxide synthase (NOS3) may determine responsiveness to fatty acids. Gene-nutrient interactions may be important in modulating the development of CVD, particularly in high-risk individuals with the metabolic syndrome (MetS). Methods: Biomarkers of CVD risk, plasma fatty acid composition, and NOS3 single nucleotide polymorphism (SNP) genotype (rs11771443, rs1800783, rs1800779, rs1799983, rs3918227, and rs743507) were determined in 450 individuals with the MetS from the LIPGENE dietary intervention cohort. The effect of dietary fat modification for 12 weeks on metabolic indices of the MetS was determined to understand potential NOS3 gene-nutrient interactions. Results: Several markers of inflammation and dyslipidaemia were significantly different between the genotype groups. A significant gene-nutrient interaction was observed between the NOS3 rs1799983 SNP and plasma n-3 PUFA status on plasma triacylglycerol (TAG) concentrations. Minor allele carriers (AC + AA) showed an inverse association with significantly higher plasma TAG concentrations in those with low plasma n-3 PUFA status and vice versa but the major allele homozygotes (CC) did not. Following n-3 PUFA supplementation, plasma TAG concentrations of minor allele carriers of rs1799983 were considerably more responsive to changes in plasma n-3 PUFA, than major allele homozygotes. Conclusions: Carriers of the minor allele at rs1799983 in NOS3 have plasma TAG concentrations which are more responsive to n-3 PUFA. This suggests that these individuals might show greater beneficial effects of n-3 PUFA consumption to reduce plasma TAG concentrations.

  • 35. Garcia-Rios, Antonio
    et al.
    Delgado-Lista, Javier
    Perez-Martinez, Pablo
    Phillips, Catherine M.
    Ferguson, Jane F.
    Gjelstad, Ingrid M. F.
    Williams, Christine M.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kiec-Wilkh, Beata
    Blaak, Ellen E.
    Lairon, Denis
    Planells, Richard
    Malczewska-Malec, Malgorzata
    Defoort, Catherine
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Saris, Wim H. M.
    Lovegrove, Julie A.
    Drevon, Christian A.
    Roche, Helen M.
    Lopez-Miranda, Jose
    Genetic variations at the lipoprotein lipase gene influence plasma lipid concentrations and interact with plasma n-6 polyunsaturated fatty acids to modulate lipid metabolism2011In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 218, no 2, p. 416-422Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether seven common single nucleotide polymorphisms (SNPs) at the lipoprotein lipase (LPL) locus interact with total plasma fatty acids to modulate plasma lipid metabolism in metabolic syndrome (MetS) patients. Methods: Plasma fatty acid composition, plasma lipid concentrations and LPL SNPs were determined in 452 subjects with the MetS in the European LIPGENE human study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX Study. Results: Triglycerides (TG) were lower, and HDL higher in the carriers of rs328 and rs1059611 in the SUVIMAX cohort (all P < 0.001), and these findings showed a similar, non-significant trend in LIPGENE cohort. In this last cohort, we found a gene-fatty acids interaction, as the carriers of the minor allele displayed a lower fasting TG and triglyceride rich lipoproteins-TG (TRL-TG) concentrations only when they had n-6 polyunsaturated fatty acids below the median (all P < 0.05). Moreover, subjects carrying the minor allele for rs328 SNP and with a low level of n-6 PUFA displayed higher nonesterified fatty acid (NEFA) plasma concentrations as compared with homozygous for the major allele (P = 0.034). Interestingly, the n-6 PUFA-dependent associations between those SNPs and TG metabolism were also replicated in subjects without MetS from the SU.VI.MAX cohort. Conclusion: Two genetic variations at the LPL gene (rs328 and rs1059611) influence plasma lipid concentrations and interact with plasma n-6 PUFA to modulate lipid metabolism. The knowledge of new genetic factors together with the understanding of these gene-nutrient interactions could help to a better knowledge of the pathogenesis in the MetS. 

  • 36.
    Gistera, A.
    et al.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Robertson, A. K.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Andersson, J.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ketelhuth, D. F. J.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Oychinnikova, O.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Stefan K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Lundberg, A. M.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Li, M. O.
    Department of Immunobiology, Yale University School of Medicine, New Haven CT, USA.
    Flavell, R. A.
    Department of Immunobiology, Yale University School of Medicine, New Haven CT, USA.
    Hansson, G. K.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Transforming growth factor-beta signaling in t cells promotes stabilization of atherosclerotic plaques through an interleukin-17 dependent pathway2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E88-E89Article in journal (Other academic)
  • 37. Gonzalez, Manuel
    et al.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Soderberg, Stefan
    Leptin and endothelial function in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, no 2, p. 485-490Article in journal (Refereed)
    Abstract [en]

    Background: Leptin levels are elevated in obese humans. Several studies have shown an association between hyperleptinemia and development of atherosclerosis and cardiovascular disease (CVD), but the relationship between leptin and vascular function remains unclear. Aim: To evaluate associations between circulating plasma leptin and measures of vascular function in a large sample of elderly individuals from the community. Methods: This cross-sectional study included 1016 subjects aged 70 (50% women) from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The invasive technique forearm plethysmography with intra-arterial infusions of acetylcholine and sodium nitroprusside was used for estimation of endothelial dependent vasodilatation (EDV) and endothelial independent vasodilatation (EIDV), respectively, in resistance arteries, and the non-invasive technique ultrasound assessed flow mediated vasodilation (FMD) in conduit arteries. The aortic augmentation index (AoAI), a surrogate measure of arterial stiffness, was evaluated by pulse wave analysis. Associations of vascular function, arterial stiffness and blood pressure with leptin were explored. Results: In sex-adjusted models, high levels of leptin were inversely associated with EDV and EIDV. These associations remained after stratification for sex, traditional risk factors of CVD and insulin resistance, but were attenuated after taking a measure of obesity (body mass index) into account. In addition, leptin associated with arterial stiffness and systolic and diastolic blood pressure. Conclusion: Hyperleptinemia associated inversely with vasodilatation in resistance arteries. Furthermore, hyperleptinemia associated with arterial stiffness and hypertension. These associations were attenuated after adjusting for body mass index suggesting that leptin may be the mediator between obesity and impaired vascular function.

  • 38.
    Gonzalez, Manuel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lind, Lars
    Uppsala Univ, Dept Med, Uppsala, Sweden.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Leptin and endothelial function in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, no 2, p. 485-490Article in journal (Refereed)
    Abstract [en]

    Background: Leptin levels are elevated in obese humans. Several studies have shown an association between hyperleptinemia and development of atherosclerosis and cardiovascular disease (CVD), but the relationship between leptin and vascular function remains unclear.

    Aim: To evaluate associations between circulating plasma leptin and measures of vascular function in a large sample of elderly individuals from the community.

    Methods: This cross-sectional study included 1016 subjects aged 70 (50% women) from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The invasive technique forearm plethysmography with intra-arterial infusions of acetylcholine and sodium nitroprusside was used for estimation of endothelial dependent vasodilatation (EDV) and endothelial independent vasodilatation (EIDV), respectively, in resistance arteries, and the non-invasive technique ultrasound assessed flow mediated vasodilation (FMD) in conduit arteries. The aortic augmentation index (AoAI), a surrogate measure of arterial stiffness, was evaluated by pulse wave analysis. Associations of vascular function, arterial stiffness and blood pressure with leptin were explored.

    Results: In sex-adjusted models, high levels of leptin were inversely associated with EDV and EIDV. These associations remained after stratification for sex, traditional risk factors of CVD and insulin resistance, but were attenuated after taking a measure of obesity (body mass index) into account. In addition, leptin associated with arterial stiffness and systolic and diastolic blood pressure.

    Conclusion: Hyperleptinemia associated inversely with vasodilatation in resistance arteries. Furthermore, hyperleptinemia associated with arterial stiffness and hypertension. These associations were attenuated after adjusting for body mass index suggesting that leptin may be the mediator between obesity and impaired vascular function. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

  • 39.
    Hagström, Emil
    et al.
    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, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlström, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Parathyroid hormone and calcium are independently associated with subclinical vascular disease in a community-based cohort2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 238, no 2, p. 420-426Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Diseases with abnormal levels of parathyroid hormone (PTH) and calcium, such as primary and secondary hyperparathyroidism, are associated with an increased risk of cardiovascular morbidity and mortality. However, there is paucity on the association between calcium, PTH and abnormalities in the vascular system in the general population.

    METHODS:

    In the PIVUS study (Prospective Investigation of the Vasculature in Uppsala Seniors), a community based cohort of 70-year old men and women (n = 1016), the associations between s-calcium, p-PTH and endothelial function, arterial stiffness and blood pressures were investigated, adjusting for cardiovascular risk factors and mineral metabolism.

    RESULTS:

    In multivariable linear regression models 1 SD increase in calcium was associated with 1.1 units decrease in the stroke volume/pulse pressure ratio and 0.06 decrease in common carotid artery distensibility (p < 0.001) indicative of increased arterial stiffness. Further, calcium was associated with increasing calculated central pulse pressure with 1.3 mmHg elevation per 1 SD increase in calcium (p < 0.05). 1 SD increase in PTH was associated with 1.9 and 1.0 mmHg increase in intra-arterially measured brachial artery systolic and diastolic blood pressures, respectively (p < 0.01), as well as 1.6 and 0.9 mmHg increase in calculated central systolic and diastolic blood pressures (p < 0.05). PTH was not associated with arterial stiffness, endothelial function or pulse pressure.

    CONCLUSION:

    In a large community-based sample of elderly, calcium was independently associated with increased arterial stiffness, and PTH independently to intra-arterial peripheral and calculated central blood pressures. The findings indicate a possible link between the vasculature and mineral metabolism.

  • 40. Hansen, T
    et al.
    Ahlström, H
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hulthe, J
    Wikström, J
    Lind, L
    Johansson, L
    Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population2009In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 205, no 1, p. 163-167Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The principal aim of this study was to determine whether the amount of visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective was to investigate whether traditional risk factors, inflammation, or adipokines could explain the hypothesized relationship between VAT and atherosclerosis. METHODS: Men and women aged 70 were recruited from the general population into the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and 306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was assessed for degree of stenosis or occlusion and a total atherosclerotic score (TAS) was established. Information on risk factors and BMI and on SAT and VAT, segmented on an axial MR scan was collected. Adiponectin, leptin, and high sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used as a marker of insulin resistance. RESULTS: VAT was related to TAS independently of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional risk factors included in the Framingham risk score (FRS) in an elderly population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT, together with FRS was significantly related to TAS in a multiple censored regression model. CONCLUSION: Adiponectin attenuated the relationship between VAT and TAS, suggesting that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis.

  • 41.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Söderberg, S.
    Hulthe, J.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population2009In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 205, no 1, p. 163-167Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The principal aim of this study was to determine whether the amount of visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective was to investigate whether traditional risk factors, inflammation, or adipokines could explain the hypothesized relationship between VAT and atherosclerosis. METHODS: Men and women aged 70 were recruited from the general population into the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and 306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was assessed for degree of stenosis or occlusion and a total atherosclerotic score (TAS) was established. Information on risk factors and BMI and on SAT and VAT, segmented on an axial MR scan was collected. Adiponectin, leptin, and high sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used as a marker of insulin resistance. RESULTS: VAT was related to TAS independently of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional risk factors included in the Framingham risk score (FRS) in an elderly population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT, together with FRS was significantly related to TAS in a multiple censored regression model. CONCLUSION: Adiponectin attenuated the relationship between VAT and TAS, suggesting that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis.

  • 42.
    Hansen, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lymph nodes as a potential pitfall in carotid plaque imaging with FDG-PET/CT2011In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 215, no 1, p. 247-248Article in journal (Refereed)
  • 43. Harrison, Seamus C.
    et al.
    Zabaneh, Delilah
    Asselbergs, Folkert W.
    Drenos, Fotios
    Jones, Gregory T.
    Shah, Sonia
    Gertow, Karl
    Sennblad, Bengt
    Strawbridge, Rona J.
    Gigante, Bruna
    Holewijn, Suzanne
    De Graaf, Jacqueline
    Vermeulen, Sita
    Folkersen, Lasse
    van Rij, Andre M.
    Baldassarre, Damiano
    Veglia, Fabrizio
    Talmud, Philippa J.
    Deanfield, John E.
    Agu, Obi
    Kivimaki, Mika
    Kumari, Meena
    Bown, Matthew J.
    Nyyssonen, Kristiina
    Rauramaa, Rainer
    Smit, Andries J.
    Franco-Cereceda, Anders
    Giral, Philippe
    Mannarino, Elmo
    Silveira, Angela
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    de Borst, Gert J.
    van der Graaf, Yolanda
    de Faire, Ulf
    Baas, Annette F.
    Blankensteijn, Jan D.
    Wareham, Nicholas J.
    Fowkes, Gerry
    Tzoulaki, Ionna
    Price, Jacqueline F.
    Tremoli, Elena
    Hingorani, Aroon D.
    Eriksson, Per
    Hamsten, Anders
    Humphries, Steve E.
    A gene-centric study of common carotid artery remodelling2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 226, no 2, p. 440-446Article in journal (Refereed)
    Abstract [en]

    Background: Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized. Methods: Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IMPROVE study (n = 3427) using the Illumina 200k Metabochip was performed. Single nucleotide polymorphisms (SNPs) that met array-wide significance were taken forward for analysis in three further studies (n = 5704), and tested for association with Abdominal Aortic Aneurysm (AAA). Results: rs3768445 on Chromosome 1q24.3, in a cluster of protein coding genes (DNM3, PIGC, C1orf105) was associated with larger ICCAD in the IMPROVE study. For each copy of the rare allele carried, ICCAD was on average 0.13 mm greater (95% CI 0.08-0.18 mm, P = 8.2 x 10(-8)). A proxy SNP (rs4916251, R-2 = 0.99) did not, however, show association with ICCAD in three follow-up studies (P for replication = 0.29). There was evidence of interaction between carotid intima-media thickness (CIMT) and rs4916251 on ICCAD in two of the cohorts studies suggesting that it plays a role in the remodelling response to atherosclerosis. In meta-analysis of 5 case-control studies pooling data from 5007 cases and 43,630 controls, rs4916251 was associated with presence of AAA 1.10, 95% CI 1.03-1.17, p = 2.8 x 10(-3), I-2 = 18.8, Q = 0.30). A proxy SNP, rs4916251 was also associated with increased expression of PIGC in aortic tissue, suggesting that this may the mechanism by which this locus affects vascular remodelling. Conclusions: Common variation at 1q24.3 is associated with expansive vascular remodelling and risk of AAA. These findings support a hypothesis that pathways involved in systemic vascular remodelling play a role in AAA development.

  • 44.
    Helmersson, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Active smoking and a history of smoking are associated with enhanced prostaglandin F(2alpha), interleukin-6 and F(2)-isoprostane formation in elderly men2005In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 181, no 1, p. 201-207Article in journal (Refereed)
    Abstract [en]

    The underlying mechanisms by which smoking induces cardiovascular diseases are largely unknown. The effect of smoking status on the cyclooxygenase (COX)-mediated inflammatory indicator prostaglandin F(2alpha) (PGF(2alpha)) has never been studied. Associations of cytokines and antioxidants and smoking status, have shown conflicting results. Urinary 15-keto-dihydro-PGF(2alpha) (a major metabolite of PGF(2alpha)), serum interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), serum amyloid protein A (SAA), urinary 8-iso-PGF(2alpha) (an F(2)-isoprostane, indicator of oxidative stress), and serum alpha-tocopherol were quantified in a population-based sample (n = 642) of 77-year old men without diabetes. Fifty-five men were current smokers and 391 former smokers. Inflammatory indicators were increased in current smokers (15-keto-dihydro-PGF(2alpha), P < 0.001; IL-6, P = 0.01) than non-smokers. 8-iso-PGF(2alpha) was increased (P < 0.01) and alpha-tocopherol reduced (P < 0.001) in current smokers. Further, former smokers had increased formation of 15-keto-dihydro-PGF(2alpha), IL-6 and 8-iso-PGF(2alpha) compared non-smokers. This is the first study to show that smokers have increased PGF(2alpha) formation, thus enhanced COX-mediated inflammation, in addition to elevated levels of cytokines and isoprostanes. Subclinical COX- and cytokine-mediated inflammation and oxidative stress are ongoing processes not only in active smokers but also in former smokers which may contribute to the accelerated atherosclerosis associated with smoking.

  • 45. Helmersson-Karlqvist, Johanna
    et al.
    Larsson, Anders
    Carlsson, Axel C.
    Venge, Per
    Sundstrom, Johan
    Ingelsson, Erik
    Lind, Lars
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
    Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 227, no 2, p. 408-413Article in journal (Refereed)
    Abstract [en]

    Objective: Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known.

    Methods: This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes.

    Results: U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFR(CysC)) but not urinary Albumin (u-Alb). A combination of low eGFR(CysC) (<= 60 mL/min), high u-Alb (>= 3 mg/mmol Cr) and high u-NGAL (>= 1.19 mu g/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs. 1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFR(CysC) or u-Alb.

    Conclusion: This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

  • 46.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 227, no 2, p. 408-413Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known.

    METHODS

    This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes.

    RESULTS

    U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFRCysC) but not urinary Albumin (u-Alb). A combination of low eGFRCysC (≤60 mL/min), high u-Alb (≥3 mg/mmol Cr) and high u-NGAL (≥1.19 μg/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs.1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFRCysC or u-Alb.

    CONCLUSION

    This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice.

  • 47.
    Helmersson-Karlqvist, Johanna
    et al.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Department of Medical Sciences, Uppsala University, Uppsala, Sweden ; Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Carlsson, Axel C
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden ; Science for Life Laboratory, Uppsala University, Uppsala, Sweden ; Centre for Family and Community Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Härmä, Johan
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 234, no 1, p. 108-113Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Urinary cystatin C (u-CysC) is a new biomarker for acute tubular kidney dysfunction and may also indicate chronic tubular dysfunction. Chronic kidney disease is an important cardiovascular risk factor, however it is not known if u-CysC is a risk marker for cardiovascular death.

    METHODS: The association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes.

    RESULTS: High u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2-5.2, P < 0.05) in Cox regression models independent of cardiovascular risk factors, glomerular filtration rate (eGFR) and urinary Albumin. Participants with low eGFR (≤60 mL/min), albuminuria (≥3 mg/mmol Cr) and high u-CysC (>0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7-36, P < 0.001, compared to all three biomarkers normal).

    CONCLUSIONS: This study is the first to show that increased concentrations of the tubular kidney biomarker u-CysC indicated risk of cardiovascular death independently of other cardiovascular risk factors, glomerular filtration and albuminuria. Additional research is needed to further establish the usefulness of u-CysC in clinical practice.

  • 48.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Härmä, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 234, no 1, p. 108-113Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Urinary cystatin C (u-CysC) is a new biomarker for acute tubular kidney dysfunction and may also indicate chronic tubular dysfunction. Chronic kidney disease is an important cardiovascular risk factor, however it is not known if u-CysC is a risk marker for cardiovascular death.

    METHODS: The association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes.

    RESULTS: High u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2-5.2, P < 0.05) in Cox regression models independent of cardiovascular risk factors, glomerular filtration rate (eGFR) and urinary Albumin. Participants with low eGFR (≤60 mL/min), albuminuria (≥3 mg/mmol Cr) and high u-CysC (>0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7-36, P < 0.001, compared to all three biomarkers normal).

    CONCLUSIONS: This study is the first to show that increased concentrations of the tubular kidney biomarker u-CysC indicated risk of cardiovascular death independently of other cardiovascular risk factors, glomerular filtration and albuminuria. Additional research is needed to further establish the usefulness of u-CysC in clinical practice.

  • 49.
    Henein, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bengrid, Tarek
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zhao, Y.
    Ultrasound Department, Capital Medical University, Beijing, China.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmermund, A.
    Medicine, Bethanien Hospital, Frankfurt, Germany.
    Extensive coronary calcification compromises myocardial perfusion in the absence of high grade stenosis2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E68-E68Article in journal (Other academic)
  • 50.
    Henein, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hällgren, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sörensen, Karen
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Kofoed, Klaus Fuglsang
    Larsen, Linnea Hornbech
    Hassager, Christian
    Aortic root, not valve, calcification correlates with coronary artery calcification in patients with severe aortic stenosis: a two-center study2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 243, no 2, p. 631-637Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The underlying pathology in aortic stenosis (AS) and coronary artery stenosis (CAS) is similar including atherosclerosis and calcification. We hypothesize that coronary artery calcification (CAC) is likely to correlate with aortic root calcification (ARC) rather than with aortic valve calcification (AVC), due to tissue similarity between the two types of vessel rather than with the valve leaflet tissue.

    MATERIAL AND METHODS: We studied 212 consecutive patients (age 72.5 ± 7.9 years, 91 females) with AS requiring aortic valve replacement (AVR) in two Heart Centers, who underwent multidetector cardiac CT preoperatively. CAC, AVC and ARC were quantified using Agatston scoring. Correlations were tested by Spearman's test and Mann-Whitney U-test was used for comparing different subgroups; bicuspid (BAV) vs tricuspid (TAV) aortic valve.

    RESULTS: CAC was present in 92%, AVC in 100% and ARC in 82% of patients. CAC correlated with ARC (rho = 0.51, p < 0.001) but not with AVC. The number of calcified coronary arteries correlated with ARC (rho = 0.45, p < 0.001) but not with AVC. 29/152 patients had echocardiographic evidence of BAV and 123 TAV, who were older (p < 0.001) but CAC was associated with TAV even after adjusting for age (p = 0.01). AVC score was associated with BAV after adjusting for age (p = 0.03) but ARC was not. Of the total cohort, 82 patients (39%) had significant coronary stenosis (>50%), but these were not different in the pattern of calcification from those without CAS. CAC was consistently higher in patients with risk factors for atherosclerosis compared to those without.

    CONCLUSION: The observed relationship between coronary and aortic root calcification suggests a diffuse arterial disease. The lack of relationship between coronary and aortic valve calcification suggests a different pathology.

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