Attenuation of homocysteine serum levels after short-term administration of simvastatin in essential hypertensives: Another pathway to cardiovascular risk reduction?

Abstract

Hyperhomocysteinemia has been recognised as an independent cardiovascular risk factor, while statins have been reported to have pleiotropic effects other than lipid lowering. In our study we sought to evaluate the possible effect of short-term administration of simvastatin on homocysteine (Hcy) and other established serum proatherogenic and inflammatory markers in essential hypertensive patients. Our study population consisted of 18 untreated mild essential hypertensive patients (9 men, mean age: 51.2±10.9 years, office blood pressure = 149/96 mmHg). All subjects received simvastatin (40mg/day) for a period of 1 month. Venous blood samples were drawn before and after the period of treatment with simvastatin in order to evaluate lipid, lipoprotein-a (Lp-a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), fibrinogen, uric acid, homocysteine, folic acid, vitamin B12, high sensitivity-CRP (hsCRP) levels, by standard methodology. For the pooled population BMI was 27.2±3.6 kg/m2, left ventricular mass index was 106±35.1 g/m2, relative wall thickness was 0.45±0.07 and hsCRP levels were 1.5±0.3 mg/l. After 1 month on simvastatin, there was a significant reduction in total cholesterol (215.1±40.7 vs 156.0±29.2 mg/dl, p<0.001), triglycerides (114.1±30.9 vs 89.6±27.8 mg/dl, p<0.05), LDL (141.4±29 vs 89.6±21.6 mg/dl, p<0.001), ApoB (101.6±19.2 vs 71.8±15 mg/dl, p<0.001), uric acid (5.8±1.2 vs 5.4±1.1 mg/dl, p<0.05), homocysteine (13.6±7.3 vs 12.7±7.4 μmol/l, p<0.05). In all subjects, apoA1 and hs-CRP did not exhibit any statistically significant attenuation (p=NS, for all cases). Moreover, the reduction of Hcy serum levels was not correlated with the observed reductions in total cholesterol, triglycerides, LDL, ApoB and uric acid values (p=NS, for all cases). Even in newly diagnosed essential hypertensive subjects, short-term administration of simvastatin resulted in a significant and independent attenuation of Hcy serum levels. These findings may elucidate the diverse pathophysiological mechanisms by which statins reduce cardiovascular risk, in this setting.