Blood levels off homocysteine and increased risks of cardiovascular disease - Causal of casual?

Background: Accumulating data from epidemiological studies suggest that ind ividuals with elevated blood levels of homocysteine have increased risks of cardiovascular disease. We reviewed the currently available evidence of an association between homocysteine and cardiovascular disease and examined w hether the strength of the evidence Varies according to study design. Methods: We used a computerized MEDLINE literature search, 1966 through Sep tember 1998, to identify all epidemiological studies that examined the rela tionship of homocysteine level with risks of coronary heart or cerebrovascu lar disease. Two measures of plasma homocysteine level and its association with risk of cardiovascular disease were extracted: mean homocysteine level in cases and controls, and relative risk of cardiovascular disease for ele vated homocysteine level. Results: A total of 43 studies were reviewed. Most cross-sectional and case -control studies indicated higher mean homocysteine levels (either fasting or after methionine load) and/or a greater frequency of elevated homocystei ne level in persons with cardiovascular disease as compared with persons wi thout cardiovascular disease. Results of most prospective studies, however, indicated smaller or no association. The few prospective studies that repo rted a positive association between homocysteine level and risks of cardiov ascular disease included patients with preexisting vascular disease. Conclusions: In contrast to cross-sectional and case-control studies, resul ts of prospective studies indicated less or no predictive ability for plasm a homocysteine in cardiovascular disease. Instead, elevated homocysteine le vel may be an acute-phase reactant that is predominantly a marker of athero genesis, or a consequence of other factors more closely linked to risks of cardiovascular disease. Randomized trials are necessary to test reliably wh ether lowering homocysteine levels will decrease risks of cardiovascular di sease.