Abstract-Homocysteine is associated with atherothrombotic disease, which may be mediated through associations of homocysteine levels with blood pressure, endothelial function, or arterial stiffness. In a placebo-controlled, randomized clinical trial, we measured blood pressure, brachial artery endothelium-dependent vasodilation, and common carotid artery stiffness in 158 clinically healthy siblings of patients with premature atherothrombotic disease at baseline and after 1 and 2 years of homocysteine-lowering treatment with folic acid (5 mg) plus pyridoxine (250 mg). Intention-to-treat analyses limited to participants (nϭ130) who underwent at least 1 measurement after the baseline visit showed that compared with placebo, treatment with folic acid plus pyridoxine was associated with a 3.7-mm Hg (95% CI Ϫ6.8 to Ϫ0.6 mm Hg) lower systolic and a 1.9-mm Hg (95% CI Ϫ3.7 to Ϫ0.02 mm Hg) lower diastolic blood pressure over the 2-year trial period. Together with the decreased occurrence of abnormal exercise electrocardiography tests reported previously, our results support the hypothesis that homocysteine-lowering treatment with folic acid plus pyridoxine has beneficial vascular effects. Because no effects could be demonstrated on brachial artery endotheliumdependent vasodilation or on common carotid artery stiffness, the present study does not support the hypothesis that the cardiovascular effects of homocysteine are mediated through these factors, at least in clinically healthy individuals.

Abstract-Arterial stiffness may be influenced by sex steroids and insulin; the association with fasting insulin level may be stronger in women than in men. Therefore, we analyzed the effects of sex steroid administration on (1) arterial stiffness and (2) the relationship between fasting insulin level and arterial stiffness. Twelve male-to-female transsexuals were treated with ethinyl estradiol and cyproterone acetate, and 18 female-to-male transsexuals were treated with testosterone esters, with assessments made at baseline and after 4 and 12 months. Changes in distensibility and compliance coefficients (DC and CC, respectively) of the common carotid artery, femoral artery (FA), and brachial artery (BA) were analyzed in relation to changes in fasting plasma levels of glucose, insulin, HDL-cholesterol, and triglycerides. After 4 months of estrogens and antiandrogens in men, significant reductions in the CC and DC of the FA (Pϭ0.006 and Pϭ0.04, respectively) and BA (Pϭ0.04 and Pϭ0.04, respectively) were observed. In women, testosterone, on average, did not affect DC or CC, but the changes in fasting insulin level were strongly negatively associated with changes in the CC and DC, especially in the FA and BA. These associations were significantly less strong in genetic men and were independent of age, mean arterial pressure, and glucose and lipid levels. This experimental study shows (1) that short-term administration of estrogens and antiandrogens increases FA and BA stiffness in men and (2) that the fasting insulin level is a stronger determinant of arterial stiffness in women than in men.(Hypertension. 1999;34:590-597.)M en are at a higher risk of developing cardiovascular disease (CVD) than women, but in non-insulindependent diabetes mellitus, this gender difference is much less pronounced. 1-4 A core element of non-insulin-dependent diabetes mellitus is insulin resistance, and the question arises of whether insulin resistance or other elements clustered in the insulin resistance syndrome, 5 such as hyperinsulinemia, glucose intolerance, dyslipidemia, abdominal obesity, and hypertension, partially negate the normal gender difference in cardiovascular risk.Large-artery stiffening, a major determinant of cardiac workload and systolic blood pressure, 6 may contribute to the development of CVD. Data on a possible gender difference in arterial stiffness are contradictory. Measurement of pulsewave velocity, an estimate of regional arterial stiffness, indicates that arteries in men are stiffer than those in premenopausal women. [7][8][9] In contrast, local arterial stiffness of the common carotid artery (CCA), measured by ultrasound, 10 -12 and global vascular stiffness, derived from pulsepressure waveform analysis, 13 occur less in men than in women. Conflicting data on the modulating effects of endogenous 14 and exogenous 15-20 estrogens on regional 17-20 and local arterial stiffness 14 -16 in women have also been published. Currently, there is no prospective information on the effects of estrogen or testosterone ad...

In healthy first-degree relatives of patients with mild hyperhomocysteinaemia, the increase in homocysteine level after a methionine load is an independent predictor of endothelial dysfunction. The results also suggest that fasting and post-methionine homocysteine levels may reflect distinct disturbances in methionine metabolism, which may be linked to vascular dysfunction through distinct mechanisms.

In subjects with a recent history of impaired glucose tolerance, we observed an increase in carotid artery diameter and a decrease in distensibility. Change in blood pressure level and baseline fasting glucose and HbA1c levels were positively related to the increase in diameter. In men, but not in women, baseline fasting insulin levels were associated with an acceleration of these changes.