Folic acid and B vitamins improve hyperhomocysteinemia‐induced cardiovascular risk profile in renal transplant recipients

Abstract

and reduction of tHcy by folic acid significantly decreases platelet activation.We extended previous findings demonstrating that enhanced platelet activation in the presence of elevated tHcy is detectable not only in vitro, but also in vivo at tHcy levels below 30 lmol L )1 when platelet activation is triggered by disruption of the blood vessel wall. No effect of tHcy on platelets in our model was found in the circulating venous blood. Decreasing platelet marker levels in shed blood after FA administration and correlations between the parameters of the platelet marker profiles and tHcy support the concept that in vivo homocysteine itself contributes to platelet hyperreactivity. In 1999, we demonstrated that in hyperhomocysteinemic subjects vitamin therapy is associated with decreased thrombin generation at the site of microvascular injury [9]. In the current study, using the same experimental approach, we provided evidence for platelet activation in hyperhomocysteinemic individuals and its attenuation as the FA-mediated effect. A model of microvascular injury can demonstrate an impact of various factors, including elevated tHcy, on the three major components of hemostasis, namely, circulating platelets, plasma coagulation proteins and the vessel wall.Profiles of both platelet markersÕ release in the current study were similar to those found in high-risk patients [9,10], although maximum levels and velocity of their increase were now lower, most likely as a result of the exclusion of subjects with a history of cardiovascular disease. Folic acid-related changes in these release profiles were subtle, although significant, which might suggest that in severe atherosclerosis or acute coronary syndromes, antiplatelet effects of vitamins could be overcome by the generation of other potent platelet agonists such as thrombin.In conclusion, we suggest that mild hyperhomocysteinemia may promote platelet activation induced by vascular injury in asymptomatic individuals and this effect can be abolished by FA. Whether similar observations can be made in patients with documented cardiovascular disease is under investigation. Disclosure of Conflict of InterestsThe authors state that they have no conflict of interest. Cardiovascular disease (CVD) is the single most common cause of death in renal transplant recipients (RTRs), accounting for 35-50% of all-cause mortality, and CVD mortality rates are at least twice as high as in an age-stratified sample of the general population [1]. The increased incidence of established cardiovascular risk factors, especially hypertension, diabetes and dyslipidemia, in RTRs may account, at least in part, for their Correspondence: Jose´A. Rodrı´guez,