Advances in Genetics, Proteomics, and Metabolomics Progressing From Risk Factors to Omics

Many factors contribute to the development of clinical atherosclerotic disease in adults. Observational studies conducted from the late 1940s onward have helped us to identify cigarette smoking, cholesterol levels, diabetes, blood pressure, and other factors as important determinants of cardiovascular disease (CVD) outcomes.1,2 The effects are multiplicative. For example, smoking, hypertension, and diabetes each double the risk of a heart attack, and having all 3 factors can lead to a risk that was 8 times that of an adult of similar age and sex who did not have any of the factors.3 A major focus in the earlier population and clinical studies was identification of persons at increased risk before the clinical atherosclerotic event. Less attention has been directed toward other types of events, such as occurrence of a myocardial infarction in persons presenting with chest pain, recurrent CVD events, and long-term vascular disease complications such as cardiac failure. The determinants of these vascular events are likely to include some of the classical risk factors, but new factors will no doubt be important as well. Improvements in outpatient and inpatient care, diagnosis, and biomarker discovery have reshaped the landscape. It is possible to visualize subclinical CVD with modern atherosclerotic imaging techniques such as carotid intima-media thickness and arterial calcification assessments. Clinical chemists and geneticists identify new biomarkers that promise to help refine assessments of CVD risk, but it is not clear how such tests should be used for research or for clinical care. This article addresses several of the questions posed above and takes the perspective of research and care for clinical atherosclerotic disease, emphasizing the progress we have made from traditional risk factor assessment to the present time that includes newer assessment methods such as genomics, metabolomics, and predictive medicine.