Use of novel biomarkers to explore cardiovascular risk and drug effects

Abstract

Cardiovascular disease causes immense health care costs and production losses, underscoring the need to identify individuals at risk requiring preventive treatment. This thesis aims to identify novel cardiovascular biomarkers and to advance understanding of the pathophysiological mechanisms underlying cardiovascular disease progression. Moreover, we used high-throughput metabolic profiling to study molecular drug effects. Chapter 2 relates altered monocyte gene expression in childhood obesity to atherosclerotic disease complexity in adult patients. Chapter 3 investigates the association of loss of chromosome Y with atherosclerotic plaque characteristics and clinical outcome after endarterectomy. Chapter 4 explores the ability of routinely measured hematological parameters to improve prediction of recurrent vascular events in vascular patients. The remaining chapters report results from metabolic profiling studies. Chapter 5 presents findings from a prospective study of two angiographic cohorts, in which we identified biomarkers that improve prediction of subsequent cardiovascular events. In Chapter 6, we use clinical trial data to explore the effect of metformin on metabolic profiles and to study biomarkers of infarct size and left ventricular ejection fraction after myocardial infarction. In Chapter 7, we investigate the longitudinal effect of pravastatin treatment on metabolic profiles, using data from a randomized clinical trial.