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Beyond the established risk factors of myocardial infarction: lifestyle factors and novel biomarkers
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Family Medicine.
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Age, male sex, hypertension, smoking, diabetes, dyslipidaemia, and obesity are considered as established risk factors for cardiovascular diseases. Several of these established cardiovascular risk factors are strongly influenced by lifestyle. Novel biomarkers from different mechanistic pathways have been associated with cardiovascular risk, but their clinical utility is still uncertain.

The overall objective of the thesis was to evaluate the associations between certain lifestyle factors (physical activity and snuff use), biomarkers reflecting the haemostatic and the inflammatory systems and risk of a future first-ever myocardial infarction.

 A prospective incident nested case-control study design was used with a total of 651 cases of myocardial infarction and 2238 matched controls from the population-based Northern Sweden Health and Disease Study.

 The effects of commuting activity, occupational and leisure time physical activity on risk of myocardial infarction were studied. A clearly increased risk of myocardial infarction was found for car commuting compared to active commuting (walking, cycling or going by bus). High versus low leisure time physical activity was associated with decreased risk of myocardial infarction. Low occupational physical activity was associated with risk of myocardial infarction in men.

 The risk of myocardial infarction or sudden cardiac death was studied in male snuff users compared to non-tobacco users. No increased risk was found for myocardial infarction or sudden cardiac death among snuff users without a previous history of smoking. However, for sudden cardiac death the study did not have statistical power to detect small differences in risk.

 Plasma levels of haemostatic markers have previously shown to be associated with risk of myocardial infarction, but as haemostatic markers are also acute-phase reactants, it is not clear if their association with myocardial infarction is independent of inflammatory markers. In the present study, the haemostatic markers D-dimer, von Willebrand factor (VWF), tissue plasminogen activator (t-PA), and tissue plasminogen activator/plasminogen activator inhibitor-1 complex (t-PA/PAI-1 complex) were associated with risk of myocardial infarction after adjustment for established risk factors and the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6). Furthermore, the addition of eight haemostatic and inflammatory markers could improve the predictive ability for future myocardial infarction beyond that of a model utilizing only established risk factors.

 Established risk factors and novel biomarkers were explored as potential mediators of the reduced risk of myocardial infarction related to active commuting. A combination of established risk factors, haemostatic and inflammatory markers appeared to explain a substantial proportion (40%) of the difference in risk for myocardial infarction between active commuters and car commuters. IL-6, t-PA, t-PA/PAI-1 complex, apo B/apo A-1 ratio, and BMI seemed to be the largest potential mediators when tested individually.

In conclusion, regular physical activity such as active commuting is associated with reduced risk of a first-ever myocardial infarction. This effect could in part be mediated through a beneficial influence on haemostasis and inflammation, as well as a positive impact on established risk factors. Several haemostatic markers are associated with risk of myocardial infarction independent of established risk factors and inflammatory markers. The combination of haemostatic and inflammatory markers may enhance predictive ability beyond established risk factors. Our findings do not support the hypothesis that snuff use increases the risk of myocardial infarction.

Place, publisher, year, edition, pages
Umeå: Folkhälsa och klinisk medicin , 2009. , 88 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1245
Keyword [en]
lifestyle factors, physical activity, commuting activity, leisure time physical activity, occupational physical activity, snuff use, haemostatic markers, inflammatory markers, myocardial infarction, epidemiology, primary prevention.
National Category
Family Medicine
Research subject
Family Medicine
Identifiers
URN: urn:nbn:se:umu:diva-21849ISBN: 978-91-7264-722-0 (print)OAI: oai:DiVA.org:umu-21849DiVA: diva2:212031
Distributor:
Allmänmedicin, 901 87, Umeå
Public defence
2009-05-15, FORUM-salen, Campus Skellefteå 931 77 Skellefteå, Skellefteå, 13:30 (Swedish)
Opponent
Supervisors
Available from: 2009-04-30 Created: 2009-04-20 Last updated: 2010-02-03Bibliographically approved
List of papers
1. The effects of commuting activity and occupational and leisure time physical activity on risk of myocardial infarction
Open this publication in new window or tab >>The effects of commuting activity and occupational and leisure time physical activity on risk of myocardial infarction
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2006 (English)In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 13, no 6, 924-930 p.Article in journal (Refereed) Published
Abstract [en]

AB Background: Risk reduction of myocardial infarction has been shown for leisure time physical activity. The results of studies on occupational physical activity and risk of myocardial infarction are incongruous and studies on commuting activity are scarce. The aim of this study was to investigate how commuting activity, occupational physical activity and leisure time physical activity were associated with risk of future first myocardial infarction.

Design: We used a prospective incident case-referent study design nested in Vasterbotten Intervention Program and the Northern Sweden MONICA study.

Methods: Commuting habits, occupational physical activity, leisure time physical activity and cardiovascular risk factors were assessed at baseline screening and compared in 583 cases (20% women) with a first myocardial infarction and 2098 matched referents.

Results: Regular car commuting was associated with increased risk of myocardial infarction versus commuting by bus, cycling or walking [odds ratio (OR) 1.74; 95% confidence interval (CI), 1.20-2.52] after multivariate adjustment. High versus low leisure time physical activity was associated with reduced risk of myocardial infarction (OR 0.69; 95% CI, 0.50-0.95) after adjustment for occupational physical activity and commuting activity, but the association was not statistically significant after further multivariate adjustment. After multivariate adjustment we observed a reduced risk for myocardial infarction in men with moderate (OR 0.70; 95% CI, 0.50-0.98) or high (OR 0.67; 95% CI, 0.42-1.08) versus low occupational physical activity.

Conclusions: We found a clear association between car commuting and a first myocardial infarction and a corresponding inverse association with leisure time physical activity, while the impact of occupational physical activity on the risk of myocardial infarction was weaker. (C) 2006 European Society of Cardiology

Place, publisher, year, edition, pages
Wolters Kluwer, 2006
Keyword
Chi-Square Distribution, Female, Humans, Leisure Activities, Logistic Models, Male, Middle Aged, Motor Activity, Myocardial Infarction/*epidemiology, Occupations, Prospective Studies, Risk Factors, Statistics; Nonparametric, Sweden/epidemiology, Transportation
National Category
Environmental Health and Occupational Health
Identifiers
urn:nbn:se:umu:diva-14663 (URN)10.1097/01.hjr.0000239470.49003.c3 (DOI)17143124 (PubMedID)
Available from: 2007-12-07 Created: 2007-12-07 Last updated: 2017-12-14Bibliographically approved
2. The risk of myocardial infarction and sudden cardiac death amongst snuff users with or without a previous history of smoking.
Open this publication in new window or tab >>The risk of myocardial infarction and sudden cardiac death amongst snuff users with or without a previous history of smoking.
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2007 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 262, no 3, 360-7 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To investigate the risk of a first myocardial infarction (MI) and sudden cardiac death (SCD) amongst male snuff users. DESIGN: We used a prospective incident case-referent study design nested in the population-based Västerbotten Intervention Program and the Northern Sweden MONICA study. SUBJECTS: Tobacco habits and cardiovascular risk factors were assessed at baseline screening and compared in 525 male MI cases (including 93 SCD cases) and 1798 matched referents. RESULTS: Myocardial infarction occurred on average 4 years and 2 months after the baseline screening. No increased risk for MI was found amongst snuff users without a previous history of smoking compared with nontobacco users after adjustments for body mass index, leisure time physical activity, educational level and cholesterol level (OR 0.82; 95% CI, 0.46-1.43). For snuff users with a previous history of smoking, the adjusted OR was 1.25 (95% CI, 0.80-1.96). Significantly increased risk for MI was found in current smokers with or without current snuff use. For SCD cases with survival time<24 h, the adjusted OR for snuff users without previous history of smoking was 1.18 (95% CI, 0.38-3.70) and for cases with survival time<1 h the OR was 0.38 (95% CI, 0.08-1.89). CONCLUSIONS: We found no increased risk for MI amongst snuff users without a previous history of smoking. Amongst snuff users with a previous history of smoking, the tendency towards an increased risk for MI may reflect the residual risk from former smoking. This study does not support the hypothesis that the risk for SCD is increased amongst snuff users.

Keyword
Death; Sudden; Cardiac/*epidemiology, Female, Humans, Male, Myocardial Infarction/*epidemiology, Risk Factors, Smoking/epidemiology, Sweden/epidemiology, Tobacco; Smokeless/*adverse effects
Identifiers
urn:nbn:se:umu:diva-17971 (URN)10.1111/j.1365-2796.2007.01813.x (DOI)17697157 (PubMedID)
Available from: 2007-11-28 Created: 2007-11-28 Last updated: 2017-12-14Bibliographically approved
3. Haemostatic and inflammatory markers are independently associated with a first-ever myocardial infarction in men and women
Open this publication in new window or tab >>Haemostatic and inflammatory markers are independently associated with a first-ever myocardial infarction in men and women
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2012 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 129, no 1, 68-73 p.Article in journal (Refereed) Published
Abstract [en]

Introduction: Previous studies have shown that plasma levels of haemostatic and inflammatory markers are associated with risk of coronary heart disease (CHD). As haemostatic markers are also acute-phase reactants, it is not clear if their association with CHD is independent of inflammatory markers and established cardiovascular risk factors.

Materials and Methods: We used a prospective incident case-control study design nested in two cohorts from Sweden. Baseline measurements of a panel of cardiovascular risk factors and eight established markers of haemostasis or inflammation were assessed in 469 first-ever myocardial infarction (MI) cases and 895 matched controls.

Results: After adjustment for baseline values of established risk factors, von Willebrand factor appeared to have the strongest association with MI among the haemostatic markers assayed, with an odds ratio of 2.52 (95% CI, 1.72-3.67) for a comparison of individuals in extreme thirds of baseline levels. For a similar comparison, after adjustment for established risk factors and haemostatic markers, odds ratios for IL-6 and CRP were 1.67 (95% CI, 1.08-2.60) and 1.58 (95% CI, 1.03-2.41), respectively. The relative predictive ability of the individual markers over and above established risk factors was modest according to comparisons of Area under the Receiver Operating Characteristic (AUROC) curves. However, when all eight markers were combined in a single model, the AUROC curve was significantly increased to 0.820 (95% CI, 0.795-0.846) compared to 0.762 (95% CI, 0.732-0.791) for established risk factors only.

Conclusions: These findings suggest that haemostasis and inflammation have at least partially separate roles in risk of myocardial infarction.

Keyword
Myocardial infarction; Risk factors; Haemostasis; Inflammation
National Category
Cardiac and Cardiovascular Systems
Research subject
Family Medicine
Identifiers
urn:nbn:se:umu:diva-21694 (URN)10.1016/j.thromres.2011.05.015 (DOI)
Available from: 2009-04-16 Created: 2009-04-16 Last updated: 2017-12-13Bibliographically approved
4. Reduced risk of myocardial infarction related to active commuting: inflammatory and haemostatic effects are potential major mediating mechanisms
Open this publication in new window or tab >>Reduced risk of myocardial infarction related to active commuting: inflammatory and haemostatic effects are potential major mediating mechanisms
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2010 (English)In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 17, no 1, 56-62 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Regular physical activity is inversely associated with risk of coronary heart disease, but the precise mechanisms remain unclear. Active commuting is an environmental friendly way to achieve the recommended 30 min of daily physical activity. The aim of this study was to explore the relative contribution of markers from different potential mediating pathways on the association between active commuting and risk of myocardial infarction (MI) in a general population. DESIGN: Prospective incident nested case-control study. METHODS: Commuting habits, traditional risk factors and biomarkers were assessed at baseline and compared in 204 MI cases and 327 matched controls. RESULTS: Car commuting was significantly associated with MI risk, even after adjusting for potential confounders (odds ratio: 1.77, 95% confidence interval: 1.05-2.99). When potential mediators were included in the model, the risk was substantially attenuated. Among the traditional risk factors, apolipoprotein B/apolipoprotein A-1 ratio seemed to be the largest mediator (26.0%), followed by body mass index (18.7%). The inflammatory and haemostatic markers similarly dampened the effect, with tissue plasminogen activator/plasminogen activator inhibitor-1 complex and IL-6 explaining 33.6 and 27.6% of MI risk, respectively. Combined, the potential mediators investigated seemed to explain 40.1% of MI risk related to car commuting. CONCLUSION: Overall, the traditional, inflammatory and haemostatic markers seemed to explain a substantial proportion of the reduction in MI risk related to active commuting in this study population. The predominant effect of the inflammatory and haemostatic markers supports the hypothesis that regular physical activity may work through additional biological mechanisms to reduce coronary risk beyond traditional risk factors. However, these findings need to be confirmed in larger studies.

Keyword
commuting, haemostasis, inflammation, myocardial infarction, physical activity
National Category
Cardiac and Cardiovascular Systems
Research subject
Family Medicine
Identifiers
urn:nbn:se:umu:diva-21695 (URN)10.1097/HJR.0b013e32832f3b11 (DOI)000275135600007 ()19820396 (PubMedID)
Available from: 2009-04-16 Created: 2009-04-16 Last updated: 2017-12-13Bibliographically approved

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