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Introduction: Hyperhomocysteinemia is an important cardiovascular risk indicator in the oldest old, and is associated with elevated arterial stiffness in this age group. Since several intervention trials reported a lack of benefit of B-vitamin supplementation on cardiovascular outcomes, we aimed to investigate the effect of B-vitamin supplementation on arterial stiffness and atherosclerosis in hyperhomocysteinemic elderly patients., Methods: The B-PROOF study is a double-blind, randomized controlled trial, including 2919 elderly aged at least 65 years, with hyperhomocysteinemia (12-50  μmol/l), treated with B-vitamins (500  μg vitamin B12 and 400  μg folic acid) or placebo for 2 years. In a subgroup (n = 569), the effect of B-vitamins on pulse wave velocity (PWV) was investigated as a measurement of arterial stiffness. To measure atherosclerosis, carotid intima-media thickness (IMT) measures had been used. Incidents of cardiovascular and cerebrovascular events were determined via structured questionnaires, and blood pressure was also measured., Results: Compared to placebo, B-vitamin supplementation lowered serum homocysteine by 3.6  μmol/l (P < 0.001). Analysis of covariance showed no effect of supplementation on PWV levels, and this was not different for patients without increased arterial stiffness at baseline. Furthermore, no effect on carotid IMT was observed., Discussion: Vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly patients have no effect on PWV or carotid IMT. Further research will still be necessary to unravel the effects and pathways of homocysteine-lowering treatment on cardiovascular outcomes.

Objective: Generalized microvascular dysfunction may contribute to the development of salt sensitivity, insulin resistance and hypertension, and may thus link these cardiovascular risk factors. To test this hypothesis, we examined skin microvascular function, salt sensitivity, insulin sensitivity and blood pressure in 27 normotensive and 26 hypertensive individuals., Methods: Capillary density was examined by videomicroscopy during venous congestion and postocclusive reactive hyperaemia. Endothelium-(in)dependent vasodilation was assessed by iontophoresis of acetylcholine and sodium nitroprusside and by laser Doppler flowmetry. Salt sensitivity was determined as the difference in mean arterial pressure (MAP) between a 1-week high-salt diet (approximately 235 mmol NaCl/day) versus low-salt diet (approximately 55 mmol NaCl/day). Insulin sensitivity was measured with the hyperinsulinaemic, euglycaemic clamp, and blood pressure was assessed by 24-h ambulatory blood pressure monitoring., Results: Salt sensitivity of blood pressure was inversely associated with postocclusive capillary recruitment and endothelium-dependent vasodilation (r=-0.67, P<0.001 and r=-0.60, P<0.01, respectively), but not with capillary density during venous congestion or endothelium-independent vasodilation. Salt sensitivity was negatively associated with insulin sensitivity (r=-0.55, P<0.001) and positively with MAP (r=0.58, P<0.001). Multiple regression analyses suggested that associations between salt sensitivity and both insulin sensitivity and MAP were dependent on microvascular function., Conclusion: Our results suggest a close inverse association between skin microvascular function and salt sensitivity and a role for generalized microvascular defects as a link between salt sensitivity, insulin resistance and hypertension.