Hyperhomocysteinemia is an independent predictor of sub-clinical carotid vascular damage in subjects with grade-1 hypertension

Abstract

Although the role of homocysteinemia (Hcy) as a coronary risk factor (RF) has been scaled down, hyper-Hcy and carotid vascular damage (CVD) are still considered as RFs for cerebrovascular events. In 276 grade-1 hypertensives (160 men and 116 women aged 59.6 ± 15.0 years) without known cardiovascular disease and having hyper-Hcy (≥15 μM/L), subclinical CVD was evaluated by ultrasonographic carotid-wall intima media thickness (IMT). Hcy was divided into quartiles and C667→T polymorphism codifying for methylenetetrahydrofolate reductase (MTHFR) was determined. According to the genotype, subjects were divided into CC (wild), CT (heterozygote) and TT (homozygous mutation). Differences between continuous variables were evaluated by analysis of variance, while gender specific odds ratio (OR) and 95 % confidence intervals (CI) of CVD (IMT >0.9 mm or plaque) were calculated by multivariate logistic regression analysis. Blood pressure (BP) values were not different across the quartiles of Hcy. In 46.4 % of cases, sub-clinical CVD was found, with a prevalence increasingly distributed in the quartiles of Hcy (31.9, 42, 52.2, 59.4 %, p < 0.001). Prevalence of TT allele of the MTHFR genotype was also significantly distributed in the quartiles of Hcy (13.6, 12.3, 23.5 and 50.6 %, p < 0.0001), whereas no relationship was found between genotype and CVD. The last quartile of Hcy predicted CVD (OR 1.32, CI 1.12-2.2, p = 0.02) independent of age (OR 1.23, CI 1.002-1.56, p = 0.0001), systolic BP (OR 1.52, CI 1.24-2.10), diabetes (OR 2.11, CI 1:32-2.88, p = 0.01) and smoking (OR 1.45, CI 1.14-1.98, p = 0.04). Adding gender did not modify the model. In hypertensives, Hcy values >36.5 μM/L independently predict CVD and in those who are also diabetic and smokers, Hcy assessment without MTHFR genotype should be recommended to obtain a better stratification of global cerebrovascular risk.