Joint Effects of Plasma Homocysteine Concentration and Traditional Cardiovascular Risk Factors on the Risk of New-Onset Peripheral Arterial Disease

PURPOSE: Hyperhomocysteinemia is an independent risk factor for cardio- and cerebrovascular diseases. However, the relationship between plasma homocysteine (Hcy) concentration and peripheral arterial disease (PAD) has not been completely characterized. The aim of the present study was to determine the relationship between plasma Hcy concentration and new-onset PAD and to assess the effects of combinations of Hcy and traditional cardiovascular risk factors. PATIENTS AND METHODS: We conducted a prospective community-based cohort study of 3119 Chinese participants who did not have PAD at baseline, with a median follow-up period of 2.30 years. We used multivariate logistic regression models to evaluate the relationship between high Hcy (≥10µmol/L) and new-onset PAD. The effects of combinations of high Hcy and traditional cardiovascular risk factors were assessed using logistic regression analysis. RESULTS: After adjustment for 14 covariates, high Hcy concentration was significantly associated with new-onset PAD (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.08–4.03, P=0.030). Smokers with high Hcy concentration were substantially more likely to have new-onset PAD than non-smokers with normal Hcy concentration (OR=4.44, 95% CI: 1.77–11.12, P=0.001). The effect of diabetes on PAD became significant when present in combination with high Hcy concentration (OR=3.67, 95% CI: 1.25–10.80, P=0.018). Participants with both elevated Hcy levels and older age had the highest risk of new-onset PAD (OR=4.28, 95% CI: 1.83–10.01, P<0.001). With regard to the joint effect of Hcy and hypertension, dyslipidemia or sex, there was also a trend towards increased risk across four different groups (P for trend=0.026, 0.035, 0.016, respectively). CONCLUSION: High plasma Hcy concentration independently predicts the incidence of PAD. Furthermore, there is a joint effect of high Hcy concentration and traditional cardiovascular risk factors such as smoking, diabetes and aging on the incidence of PAD.