Relationship between homocysteine levels and atherosclerosis in the National Health and Nutrition Examination Survey (NHANES)

Introduction: Elevated homocysteine levels have been shown to be associated with atherosclerosis. Pathophysiologic mechanisms are believed to be different between coronary atherosclerosis and peripheral artery atherosclerosis. We aimed to examine the differences in the prevalence of coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD) across rising homocysteine levels.

Methods: Cross-sectional data from NHANES 1999-2000, 2001-2002, 2003-2004 and 2005-2006 were merged. Homocysteine levels were used to create three categories: normal (<10micromoles/L), borderline (10-15micromoles/L) and elevated (>15micromoles/L). CAD and CVD were determined using standardized questionnaires. PAD was defined as ankle brachial pressure index <0.9. Multivariate logistic regression analysis was performed using CAD, CVD or PAD as outcome and homocysteine category as the independent variable. Results: We observed increased odds of CAD among individuals with borderline [OR (95%CI):1.19(1.01-1.41)] or elevated [OR (95%CI):1.45(1.08-1.96)] homocysteine levels in comparison to those with normal homocysteine levels. Similarly, increased odds of CVD were observed among individuals with borderline [OR (95%CI):1.55(1.10-2.17)] or elevated [OR (95%CI):1.65(1.10-2.46)] homocysteine levels. Since, the odds of PAD were not elevated among the homocysteine categories defined above, we divided entire cohort into 10 quantiles according to the homocysteine levels to determine a cut-point above which the risk of PAD would be elevated. The risk of PAD appeared to increase only at homocysteine levels >27.5micromoles/L.

Conclusions: The risk of CAD and CVD appear to be elevated in patients with homocysteine levels >10micromoles/L. However, the risk of PAD increased only at significantly higher levels of serum homocysteine (>27.5micromoles/L).