Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for coronary heart disease (CHD). Dietary supplementation with B vitamins lowers plasma homocysteine by up to 30%. However, little is known about the potential beneficial effects of homocysteine lowering on vascular function in patients with CHD. METHODS AND RESULTS: We investigated 89 men with CHD (aged 56 [range 39 to 67] years). Brachial artery flow-mediated dilatation (endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured before and 8 weeks after treatment with either (1) folic acid (5 mg) and vitamin B(12) (1 mg) daily (n=59) or (2) placebo (n=30). Total, protein-bound, and free plasma homocysteine, serum folate, and vitamin B(12) were measured at baseline and at 8 weeks. Flow-mediated dilatation improved after treatment with B vitamins (2.5+/-3.2% to 4.0+/-3.7%, P:=0.002) but not placebo (2.3+/-2.6% to 1.9+/-2.6%, P:=0.5). Vitamin therapy lowered plasma concentrations of total homocysteine (from 13.0+/-3.4 to 9.3+/-1.9 micromol/L, P:<0.001), protein-bound homocysteine (from 8.7+/-2.8 to 6.2+/-1.4 micromol/L, P:<0.001), and free homocysteine (from 4.3+/-1.2 to 3.0+/-0.6 micromol/L, P:<0.001) and raised concentrations of serum folate (from 10.3+/-4.3 to 31.2+/-10.8 ng/mL, P:<0.001) and vitamin B(12) (from 314+/-102 to 661+/-297 pg/mL, P:<0.001). In regression analysis, improved flow-mediated dilatation correlated closely with the reduction in free plasma homocysteine (r=-0.26, P:=0.001), independent of changes in protein-bound homocysteine, folate, and vitamin B(12). Nitroglycerin-induced dilatation was unchanged after both B vitamins and placebo. CONCLUSIONS: Folic acid and vitamin B(12) supplementation improves vascular endothelial function in patients with CHD, and this effect is likely to be mediated through reduced concentrations of free plasma homocysteine concentrations. Our data support the view that lowering homocysteine, through B vitamin supplementation, may reduce cardiovascular risk.

Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asian and European men.

BACKGROUND: Reasons for the increase in mortality due to coronary heart disease (CHD) in UK Indian Asians are not well understood. In this study, we tested the hypotheses that elevated plasma homocysteine concentrations are a risk factor for CHD in Indian Asians, and explain part of their increased CHD risk, compared with Europeans. METHODS: We undertook two parallel case-control studies, one in Europeans and one in Indian Asians. We recruited 551 male cases (294 European, 257 Indian Asian) and 1025 healthy male controls (507 European, 518 Indian Asian). Fasting and post-methionine load homocysteine, vitamin B12 and folate concentrations, and conventional CHD risk factors were measured. FINDINGS: Fasting homocysteine concentrations were 8% higher (95% CI 3-14) in cases compared with controls, in both ethnic groups. The odds ratio of CHD for a 5 micromol/L increment in fasting plasma homocysteine was 1.3 (1.1-1.6) in Europeans and 1.2 (1.0-1.4) in Indian Asians. The association between fasting plasma homocysteine and CHD was independent of conventional CHD risk factors in both ethnic groups. Post-load homocysteine concentrations were not significantly different in cases compared with controls. Among the controls, fasting homocysteine concentrations were 6% (2-10) higher in Indian Asians than in Europeans. From the results we estimate that elevated homocysteine may contribute to twice as many CHD deaths in Indian Asians, compared with Europeans. The differences in homocysteine concentrations between the two ethnic groups were explained by lower vitamin B12 and folate levels in Asians. INTERPRETATION: Plasma homocysteine is a novel and independent risk factor for CHD in Indian Asians, and may contribute to their increased CHD risk. Raised homocysteine concentrations in Indian Asians may be related to their reduced vitamin B12 and folate levels, implying that the increased CHD risk in this group may be reduced by dietary vitamin supplementation.

Serum calcium, phosphorus and albumin levels in relation to the angiographic severity of coronary artery disease.

Though calcium plays an important role in a number of biologic processes related to the pathogenesis of atherosclerosis, the relationship of serum calcium and phosphorus levels with the angiographic severity of coronary artery disease (CAD) is not known. We retrospectively studied 376 stable patients (age range 31-86 years, mean 59.2 +/- 10.5 years; 68% males) undergoing routine coronary angiography and related the angiographic severity of CAD with the serum levels of total and corrected calcium, phosphorus, albumin, total protein and bicarbonate. The primary variable studied was the number of vessels with haemodynamically significant disease. On univariate analysis, total serum calcium and serum albumin levels had a negative association with the number of vessels diseased (P = 0.046 and 0.057, respectively). Multiple regression analysis using age, sex, smoking, diabetes, hypertension, hyperlipidaemia, ethnicity and family history, in addition to serum calcium, phosphorus and albumin levels as the predictor variables, showed that serum albumin has an independent negative and serum phosphorus has an independent positive association with the angiographic severity of CAD (P = 0.04 and 0.003, respectively; n = 294). Serum phosphorus level also showed highly significant positive associations with the presence of total or subtotal occlusion and with most severe stenosis observed on angiography. A moderate change in the serum level of albumin or phosphorus confers a risk similar to that associated with smoking, as estimated by the odds ratios.