Abstract
Little is known about circulating biomarkers of vascular injury in relation to cardiovascular disease risk. Thus, we evaluated associations between six novel markers (E-Selectin, P-Selectin, thrombomodulin, thrombopoietin, intercellular adhesion molecule 3 and GPIIb/IIIa) and established cardiovascular risk factors as well as the risk of myocardial infarction (MI) in a population-based study. Biomarkers were measured in pre-diagnostic plasma samples of a case-cohort subset of EPIC-Heidelberg (incident MI cases: n = 369, random sub-cohort: n = 2,418). Generalized Linear models were used to analyse cross-sectional associations between biomarkers and cardiovascular risk factors. Multivariable Cox Regression analyses were carried out to obtain Hazard Ratios (HRs) of MI across quartiles of biomarkers levels. Cross-sectional analyses showed that sex, smoking, alcohol consumption, diabetes and exogenous hormone use were associated with biomarker levels. However, while fibrinogen was associated with MI risk (HR per standard deviation: 2.97 [95% confidence interval: 1.61, 5.46]), none of the six novel biomarkers was associated with MI risk after multivariable adjustment. In a population-based cohort, biomarkers of vascular injury were associated with established cardiovascular risk factors, but not MI risk. The tested biomarkers may reflect pathophysiological alterations in cardiovascular disease development rather than constituting independent MI risk factors.
Highlights
Little is known about circulating biomarkers of vascular injury in relation to cardiovascular disease risk
For the present prospective study on myocardial infarction (MI) risk, we selected the following six circulating factors implicated in vascular injury and primary haemostasis as candidate biomarkers of MI risk: E-Selectin, P-Selectin, thrombomodulin (TM), thrombopoietin (TPO), intercellular adhesion molecule 3 (ICAM3), and glycoprotein IIb/IIIa (GPIIb/IIIa)
Mediation analyses did not suggest that associations between established CVD risk factors and MI risk could be mediated by the six biomarkers, whereas they did indicate that fibrinogen partially mediates the associations between smoking, alcohol consumption, and BMI with MI risk
Summary
Little is known about circulating biomarkers of vascular injury in relation to cardiovascular disease risk. We evaluated associations between six novel markers (E-Selectin, P-Selectin, thrombomodulin, thrombopoietin, intercellular adhesion molecule 3 and GPIIb/IIIa) and established cardiovascular risk factors as well as the risk of myocardial infarction (MI) in a population-based study. For the present prospective study on MI risk, we selected the following six circulating factors implicated in vascular injury and primary haemostasis as candidate biomarkers of MI risk: E-Selectin, P-Selectin, thrombomodulin (TM), thrombopoietin (TPO), intercellular adhesion molecule 3 (ICAM3), and glycoprotein IIb/IIIa (GPIIb/IIIa). Given the lack of epidemiological studies on the above-mentioned plasma markers, we used the population-based EPIC-Heidelberg cohort to evaluate associations (a) between the markers and established cardiovascular risk factors in cross-sectional analyses, and (b) between the markers and MI risk in prospective analyses. We carried out mediation analyses to investigate whether relationships between established cardiovascular risk factors and MI risk could be mediated by the proposed biomarkers
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