Relative Value of Inflammatory, Hemostatic, and Rheological Factors for Incident Myocardial Infarction and Stroke

TLDR

Inflammatory, hemostatic, and rheological biomarkers are increasingly studied for their potential to predict cardiovascular disease. The authors aim to compare the associations of 17 such biomarkers with incident heart disease and stroke, adjusting for subclinical atherosclerosis and traditional risk factors, and to assess their incremental predictive value. Using the Edinburgh Artery Study cohort of 1,592 adults aged 55–74, participants were followed for an average of 17 years, during which 416 experienced at least one cardiovascular event. After adjustment, several biomarkers—including CRP, IL‑6, fibrinogen, D‑dimer, t‑PA, leukocyte elastase, lipoprotein(a), von Willebrand factor, and plasma viscosity—were significantly associated with incident CVD, but adding them to conventional risk factors and ankle‑brachial index provided only modest discrimination.

Abstract

Background— The aim of our present study was to compare the association of a wide range of 17 biomarkers of inflammation, hemostasis, and blood rheology with incident heart disease and stroke after accounting for an indicator of subclinical atherosclerotic disease and traditional risk factors and also to determine their incremental predictive ability. Methods and Results— We used data from the Edinburgh Artery Study, a population cohort study started in 1987 that comprised 1592 men and women aged 55 to 74 years. Subjects were followed for a mean of 17 years, and 416 of them suffered at least 1 cardiovascular event. In analyses adjusted for cardiovascular risk factors and history of cardiovascular disease (CVD): C-reactive protein, interleukin-6, fibrinogen, fibrin D-dimer, tissue plasminogen activator (t-PA), leukocyte elastase, and lipoprotein(a) (all P <0.01), as well as von Willebrand factor and plasma viscosity (both P <0.05), had significant hazard ratios for incident CVD. Further adjustment for a measure of subclinical atherosclerosis (ankle brachial index) had little impact on these associations. The hazard ratios (95% CI) for incident CVD between top and bottom tertiles in the latter analysis were 1.78 (1.30 to 2.45) for C-reactive protein, 1.85 (1.33 to 2.58) for interleukin-6, and 1.76 (1.35 to 2.31) for fibrinogen. Single biomarkers provided little additional discrimination of incident CVD to that obtained from cardiovascular risk factors and the ankle brachial index. An incremental score of multiple markers [interleukin-6, t-PA, intercellular adhesion molecule 1, and lipoprotein(a)] provided some added discrimination. Conclusions— Several “novel” risk factors predicted CVD after adjustments for conventional risk factors and also for a measure of asymptomatic disease. However, their incremental predictive ability was modest and their clinical utility remains uncertain.