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Risk factors for cardiovascular events and incident hospital-treated diabetes in the population
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Well-established risk factors for CVD include increasing age, male sex, sedentary lifestyle, obesity, smoking, diabetes, hypertension, dyslipidaemia and low socio-economic status. Traditional risk factors do, however, not fully explain cardiovascular risk in general. In this thesis we focused on two conventional risk factors (smoking, blood pressure), and two unconventional risk markers (adiponectin, an adipocyte derived protein; and sialic acid (SA), a marker of systemic inflammation) for prediction of CVD events.

Aims: In Paper I we examined to what degree smoking habits modify the risk of CVD in relation to systolic blood pressure levels in middle-aged men. In Paper II we investigated the predictive role of adiponectin for risk of CVD as well as the cross-sectional associations between adiponectin and markers of glucose metabolism, also in men. In Paper III we examined if increasing pulse pressure (PP) and increasing levels of SA both increase the risk of CVD and whether their effects act in synergism. In Paper IV the association of SA with risk of incident diabetes mellitus and related complications, resulting in hospitalization, was studied.

Subjects and Methods: Two large-scale, population-based, screening studies with long follow-up periods have been used. The Malmö Preventive Project (MPP) was used with 22,444 individuals in Paper I and a sub cohort of 3,885 individuals in Paper II. The Värmland Health Survey (VHS) was used in Papers III and IV with 37,843 and 87,035 individuals, respectively.

Results: CVD risk increases with increasing systolic blood pressure levels and this risk is almost doubled in smokers. Total adiponectin level is not associated with increased risk of future CVD but it is inversely associated with markers of glucose metabolism. PP and SA both contribute to risk of future CVD. Adjustment for mean arterial pressure reduces the risk induced by PP. Elevated SA contributes to increased risk of incident diabetes and related complications leading to hospitalization.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2012. , 73 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 79
Keyword [en]
Adiponectin, blood pressure, cardiovascular risk, diabetes, inflammation, pulse pressure, sialic acid, smoking
National Category
Medical and Health Sciences Cardiac and Cardiovascular Systems
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-24173ISBN: 978-91-7668-905-9 (print)OAI: oai:DiVA.org:oru-24173DiVA: diva2:542231
Public defence
2012-12-14, Hörsal P1, Prismahuset, Örebro universitet, Fakultetsgatan 1, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-07-30 Created: 2012-07-30 Last updated: 2017-10-17Bibliographically approved
List of papers
1. Smoking as a modifier of the systolic blood pressure-induced risk of cardiovascular events and mortality: a population-based prospective study of middle-aged men
Open this publication in new window or tab >>Smoking as a modifier of the systolic blood pressure-induced risk of cardiovascular events and mortality: a population-based prospective study of middle-aged men
2002 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 20, no 9, 1759-1764 p.Article in journal (Refereed) Published
Abstract [en]

Objective To examine to what degree smoking habits modulate the relationship between systolic blood pressure (SBP) and risk for cardiovascular morbidity (first event) and mortality in middle-aged men. Design and methods In all, 22 444 middle-aged men were recruited from a population-based screening study (mean attendance rate 71%). Risk factor intervention was offered to about 20% of participants. Subjects were followed in local and national registers for cardiovascular morbidity and mortality during more than 17 years of follow-up. Lifestyle variables were investigated at baseline, including smoking habits. Event rates were calculated in relation to quintiles (Q1-Q5) of baseline SBP in untreated subjects, subdivided into categories of smoking habits, but also for 915 previously known, treated hypertensive (tHT) patients at baseline. Results We found an increasing incidence of first cardiovascular event (CE) with increasing SBP levels, ranging from 63.5 CE/10 000 person-years (Q1) to 62.3, 70.5,82.3 and 115.1 CE/10 000 person-years (Q2-Q5). The corresponding figure in tHTs; was 153 CE/10 000 person-years. If further subdivided into smokers/ex-smokers/non-smokers, the relative risks (RR) of smokers were 1.9 [95% confidence interval (Cl): 1.5-2.4], 2.1 (1.8-2.5), 2.3 (1.8-2.9), 1.8 (1.5-2.1), and 1.7 (1.5-2.0) compared to present non-smokers, in relation to SBP (Q1-Q5). In tHTs; the RR was 1.4 (1.1-1.8). Cardiovascular mortality rates differed in relation to SBP and smoking habits, from 40.3 (present non-smokers) and 70.7 (smokers) deaths/10 000 person-years in Q1, to 54.2 and 134.0 deaths/10 000 person-years in Q5. In tHTs the corresponding figures were 81.6 and 149.4 deaths/10 000 person-years, respectively. No difference in risk was found for never-smokers compared to ex-smokers in relation to SBP. The risk in moderate/heavy smokers (> 10 cigarettes/day) compared to other smokers (less than or equal to 10 cigarettes/day) was significantly (P < 0.005) increased only in Q5. Conclusion Increasing systolic blood pressure levels in middle-aged men is associated with an increasing risk of future cardiovascular events and mortality, an association modified by smoking habits. Patients with treated hypertension in the 1970-1980s were also at an increased risk in spite of healthcare efforts. This calls for a more comprehensive multiple risk factor approach for the management and reduction of cardiovascular risk in these patients. (C) 2002 Lippincott Williams Wilkins.

Keyword
hypertension, mortality, screening, smoking, systolic blood pressure
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-26693 (URN)10.1097/00004872-200209000-00019 (DOI)000178314900019 ()
Available from: 2012-12-18 Created: 2012-12-18 Last updated: 2017-12-06Bibliographically approved
2. Total adiponectin does not predict cardiovascular events in middle-aged men in a prospective, long-term follow-up study
Open this publication in new window or tab >>Total adiponectin does not predict cardiovascular events in middle-aged men in a prospective, long-term follow-up study
Show others...
2010 (English)In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 36, no 2, 137-143 p.Article in journal (Refereed) Published
Abstract [en]

Aim. Plasma total adiponectin is a marker of insulin resistance, but its role in predicting cardiovascular events is unclear. We aimed to investigate the role of adiponectin as a predictor of cardiovascular risk in middle-aged men, and to describe the association between adiponectin and glucose metabolism.

Methods. In this population-based prospective study of middle-aged men (n=3885), total adiponectin was analyzed. All individuals had undergone an oral glucose tolerance test (OGTTs), and the mean follow-up duration was 27 years. Regression analyses were carried out for indices of glucose metabolism in relation to quintiles (Q1-Q5) of total aliponectin levels. After stratification for smoking or not, the association between total adiponectin and the first incidence of fatal or non-fatal cardiovascular disease (CVD) was analyzed, using Cox's proportional-hazards regression model.

Results. In a separate multiple-regression analysis and after adjusting for possible confounders, the relationship between adiponectin levels and markers of glucose metabolism were found to be significant (P<0.05). However, adiponectin did not independently predict the risk of stroke, coronary events, or a combination of these two outcomes.

Conclusion. Levels of total plasma adiponectin are not useful for predicting long-term cardiovascular events in middle-aged men, but are strongly associated with glucose metabolism and markers of insulin resistance. (c) 2010 Elsevier Masson SAS. All rights reserved.

Keyword
Adiponectin, Cardiovascular events, Coronary events, Glucose metabolism, Stroke, Prospective study, Long-term
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-26692 (URN)10.1016/j.diabet.2009.10.004 (DOI)000277835800007 ()
Note

Payam Khalili  is also affiliated to Cent Hosp Karlstad, Dept Internal Med, S-65230 Karlstad, Sweden

J. Jendle is also affiliated to Cent Hosp Karlstad, Dept Internal Med, S-65230 Karlstad, Sweden

Peter M. Nilsson is also affiliated to  Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Malmo, Sweden

Available from: 2012-12-18 Created: 2012-12-18 Last updated: 2017-12-06Bibliographically approved
3. Combined effects of brachial pulse pressure and sialic acid for risk of cardiovascular events during 40 years of follow-up in 37 843 individuals
Open this publication in new window or tab >>Combined effects of brachial pulse pressure and sialic acid for risk of cardiovascular events during 40 years of follow-up in 37 843 individuals
Show others...
2012 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 30, no 9, 1718-1724 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Pulse pressure (PP) is a risk marker for cardiovascular disease (CVD) in individuals 50 years and older. Inflammation is suggested to influence atherosclerosis, but could also increase PP. We aimed to examine the combined effects of PP and the inflammatory marker sialic acid, and their independent roles on CVD risk.

Methods: From a population-based study in Sweden between 1962 and 1965, 18 429 men and 19 414 women at the age of 50 or older were selected and followed for first CVD event until 2005. We investigated the biological interactions between sialic acid and PP. The associations of PP and sialic acid with risk of CVD were calculated by using Cox proportional hazards model. Adjustments were made for conventional risk factors, mean arterial pressure (MAP) and socioeconomic status.

Results: The mean age was 59.5 (SD 6.5) years and the number of incident CVD events in men and women were 3641 and 3227, respectively. No biological interaction was seen between PP and sialic acid. In men, the adjusted hazard ratio for PP was 0.92 [95% confidence interval (CI) 0.88-0.96, P < 0.0001) for 1 SD of PP, and 1.09 (95% CI 1.05-1.13, P < 0.0001) for 1 SD of sialic acid. In women, the corresponding figures were 1.02 (95% CI 0.97-1.07, P = 0.48) and 1.09 (95% CI 1.05-1.13, P < 0.0001).

Conclusions: Sialic acid but not PP was an independent risk factor for CVD. The risk induced by PP is highly affected by MAP. This suggests that both estimated arterial stiffness and inflammation contribute through different pathways to risk of CVD.

Place, publisher, year, edition, pages
Philadelphia, USA: Lippincott Williams & Wilkins, 2012
Keyword
Blood pressure, cardiovascular, epidemiology, population, pulse pressure, risk, screening
National Category
Medical and Health Sciences Endocrinology and Diabetes
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-26691 (URN)10.1097/HJH.0b013e32835606ae (DOI)000308801600008 ()22743685 (PubMedID)2-s2.0-84865448740 (Scopus ID)
Note

 Payam Khalili is also affiliated to Cent Hosp Karlstad, Dept Cardiol & Acute Internal Med, S-65230 Karlstad, Sweden

Johan Jendle is also affiliated to  Cent Hosp Karlstad, Dept Cardiol & Acute Internal Med, S-65230 Karlstad, Sweden

Ingmar Jungner is also affiliated to CALAB Res, Stockholm, Sweden

Peter M. Nilsson is also affiliated to Lund Univ, Univ Lund Hosp, Dept Clin Sci, Malmo, Sweden

Available from: 2012-12-18 Created: 2012-12-18 Last updated: 2017-12-06Bibliographically approved
4. Siliac-acid and incidence of hospitalization for diabetes and its complications during 40-years of follow-up in a large cohort: the Värmland survey
Open this publication in new window or tab >>Siliac-acid and incidence of hospitalization for diabetes and its complications during 40-years of follow-up in a large cohort: the Värmland survey
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Aim To examine the association of sialic acid (SA) with first recorded diabetes mellitus-related hospitalization.

Methods From a population-based study in Värmland, Sweden, between 1962 and 1965, 87,035 men and women were selected and followed for first recorded diabetesrelated hospitalization until 2005. The association of SA was calculated and stratified for gender by Cox´s proportional hazards models. Adjustments were made for conventional risk factors and socioeconomic status. Association analyses were made for comparisons between SA-levels above and below median.

Results The mean age was 47.2 (SD 13.0) years and the total numbers of incident diabetes-related hospitalizations in men and women were 3445 and 3273, respectively. Hazard ratios per one standard deviation of SA were 1.12 (95% CI: 1.08 to 1.17, p<0.0001) in men and 1.17 (95% CI: 1.13 to 1.22, p<0.0001) in women. Interaction analyses indicated a relatively higher SA-associated risk in women than in men with above median SA levels.

Conclusions In this large population-based cohort followed for more than 40 years, elevated SA, as a marker of systemic inflammation, was independently associated with risk of diabetes and diabetes-related hospitalizations.

Keyword
epidemiology, diabetes, hospitalization, inflammation, risk
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-26694 (URN)
Note

Payam Khalili is also affiliated to Department od Cardiology and Acute Internal Medicine , Central Hospital , Karlstad, Sweden

Johan Jendle is also affiliated to Endocrine and Diabetes Center, Central Hospital, Karlstad, Sweden

Peter M. Nilsson is also affiliated to Department of Clinical Sciences, Lunds University, University Hospital, Malmö, Sweden

Available from: 2012-12-18 Created: 2012-12-18 Last updated: 2017-10-17Bibliographically approved

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