Emerging Risk Factors for Atherosclerotic Vascular Disease

Abstract

Context Atherosclerotic vascular disease is an enormous public health problem. A number of emerging risk factors for atherosclerosis have recently been proposed to help identify high-risk individuals. Objective To review the epidemiological, basic science, and clinical trial evidence concerning 4 emerging risk factors: C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine. Data Sources Using the terms atherosclerosis, cardiovascular disease, risk factors, prevention, screening, C-reactive protein, lipoprotein(a), fibrinogen, and homocys- teine,we searched the MEDLINE database from January 1990 to January 2003. Con- ference proceedings, abstract booklets, bibliographies of pertinent articles and books, and personal files were hand searched to identify additional articles. Study Selection Original investigations and reviews of the epidemiology of athero- sclerosis and the association of conventional and novel risk factors with vascular risk were selected. On the basis of the search strategy, 373 relevant studies were identified. Data Extraction A diverse array of studies were examined, including randomized controlled trials, prospective cohort studies, systematic overviews, case-control, cross- sectional, and mechanistic studies. Data extraction was performed by one of the au- thors. Data Synthesis The available epidemiological and basic science evidence supports, to varying degrees, independent associations between these 4 candidate risk factors and atherosclerotic vascular disease. However, there is relatively little data regarding the ad- ditive yield of screening for these factors over that of validated global risk assessment strategies currently in use. Furthermore, controlled intervention studies targeting indi- viduals with these factors for proven risk-reduction therapies, or specifically treating these factors with available therapies, are few. The explanatory power of the major, estab- lished cardiovascular risk factors has been systematically underestimated. Conclusions Although C-reactive protein, lipoprotein(a), fibrinogen, and homocys- teine are associated with vascular disease risk, their optimal use in routine screening and risk stratification remains to be determined. JAMA. 2003;290:932-940 www.jama.com