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 homocysteine, we searched the MEDLINE database from January 1990 to January 2003. Conference proceedings, abstract booklets, bibliographies of pertinent articles and books, and personal files were hand searched to identify additional articles. Study SelectionOriginal investigations and reviews of the epidemiology of atherosclerosis 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, crosssectional, and mechanistic studies. Data extraction was performed by one of the authors. Data SynthesisThe 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 additive yield of screening for these factors over that of validated global risk assessment strategies currently in use. Furthermore, controlled intervention studies targeting individuals with these factors for proven risk-reduction therapies, or specifically treating these factors with available therapies, are few. The explanatory power of the major, established cardiovascular risk factors has been systematically underestimated.Conclusions Although C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine are associated with vascular disease risk, their optimal use in routine screening and risk stratification remains to be determined.

Calcium supplementation and the risks of atherosclerotic vascular disease in older women: Results of a 5-year RCT and a 4.5-year follow-up

“…(13,15) Another problem with reporting ASVD is that it consists of several categories, including coronary heart disease, cerebrovascular disease, and peripheral arterial disease. (16) These broad categories of atherosclerotic vascular disease are further broken down into subcategories of disease by the ICD coding system. Given the relatively low frequency of events in these subcategories of disease, it is possible to find statistical differences between groups owing to the problem of multiple statistical testing.…”

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“…Increasingly, studies in primarily white-American populations suggest that inflammatory markers such as CRP levels have shown to independently predict cardiovascular disease and adverse cardiovascular outcomes (14)(15)(16)(17). Although the magnitude of the predictive contribution of inflammation beyond that of traditional cardiovascular risk factors is being debated (32,33), one of the mechanisms by which obesity and adiposity confer cardiovascular risk is likely through heightened inflammation.…”

Antioxidant status in patients with acute myocardial infarction

“…Fibrinogen is an acute phase reactant that is increased in inflammatory states (24). Hepatic synthesis of fibrinogen can increase up to 4-fold in response to inflammatory or infectious triggers (25). Some earlier studies have identified fibrinogen as a major independent risk factor for cardiovascular diseases (26,27).…”