Does homocysteine cause hypertension?

Several studies, some populationbased, have plasma homocysteine levels linked to blood pressure, especially systolic pressure. In one large and carefully conducted epidemiological study, each 5 mol/l increase in plasma homocysteine was associated with an increase in systolic and diastolic blood pressure of 0.7/0.5 mmHg in men and 1.2/0.7 mmHg in women, which was independent of renal function and B vitamin status. In addition, observations that homocysteinelowering therapies with folic acidbased treatments have been followed by decreases in blood pressure raise the possibility that the link between homocysteine and blood pressure is causal, which is important since homocysteine levels can easily be lowered by folic acidbased regimens. Mechanisms that could explain the relationship between homocysteine and blood pressure include homocysteineinduced arteriolar constriction, renal dysfunction and increased sodium reabsorption, and increased arterial stiffness. However, there is only circumstantial evidence that these mechanisms are operative in humans. In addition, confounding by subtle renal dysfunction or by unmeasured dietary and lifestyle factors cannot be excluded as an explanation for the association between homocysteine and blood pressure. At present, therefore, the hypothesis that homocysteine increases blood pressure must be considered unproven. Ongoing large intervention studies with homocysteinelowering vitamins may show whether blood pressure is indeed lowered by these vitamins, whether the blood pressure decrease, if any, is explained by the decrease in homocysteine levels, and whether a vitamin treatmentassociated decrease in cardiovascular morbidity, if any, is explained by the decrease in blood pressure.