Abstract 1148: Deleterious Effect of Vitamin Therapy on Myocardial Structure in Patients with Kidney Disease
Background: Renal dysfunction is associated with an elevated plasma homocysteine level as well as an increased incidence of cardiovascular disease. Recent data suggest that hyperhomocysteinemia contributes to adverse cardiac remodeling and failure. Hence we examined the hypothesis that in subjects with renal dysfunction, homocysteine-lowering would alter myocardial structure.
Methods: The Homocysteinemia in Kidney and End Stage Renal Disease (HOST) trial demonstrated that homocysteine lowering treatment utilizing the combination of high dose folic acid and vitamins B12 and B6 did not reduce all-cause mortality or the combined endpoint of myocardial infarction, stroke or lower-limb amputation (heart failure outcomes were not examined). We identified 220 (out of a total of 2056) subjects who had echocardiograms done for clinical reasons before study randomization and during the course of the study. In this cohort, we examined the relation of the plasma homocysteine level to baseline echocardiographic parameters, and the effect of vitamin treatment on echocardiographic parameters, adjusting for differences in time from randomization to performance of follow-up echocardiogram.
Results: Among baseline echocardiographic parameters, diastolic function was negatively correlated with plasma homocysteine level (R=−0.21; p=0.038), while left atrial size showed a negative relation of borderline significance (R=−0.14; p=0.052). During follow-up, left atrial size significantly increased in the vitamin group (+0.15±0.08 cm) compared to the placebo group (−0.13±0.07 cm; p=0.0095) in an analysis adjusted for baseline left atrial size, baseline mitral regurgitation, and change in degree of mitral regurgitation during follow-up. There were no significant changes in any other echocardiographic variable.
Conclusions: Lowering plasma homocysteine level with B-vitamin therapy increases left atrial size, a surrogate marker of worsening left ventricular diastolic function, in subjects with kidney disease. This could be due to an adverse effect of vitamin therapy (such as increased methylation), or due to a protective effect of homocysteine on left ventricular stiffness, possibly by altering redox balance via glutathione levels.