Is fatty acid intake a predictor of arterial stiffness and blood pressure in men? Evidence from the Caerphilly Prospective Study.

BACKGROUND AND AIMS: Arterial stiffness is an independent predictor of cardiovascular disease (CVD) events and all-cause mortality and may be differentially affected by dietary fatty acid (FA) intake. The aim of this study was to investigate the relationship between FA consumption and arterial stiffness and blood pressure in a community-based population. METHODS AND RESULTS: The Caerphilly Prospective Study recruited 2398 men, aged 45-59 years, who were followed up at 5-year intervals for a mean of 17.8-years (n 787). A semi-quantitative food frequency questionnaire estimated intakes of total, saturated, mono- and poly-unsaturated fatty acids (SFA, MUFA, PUFA). Multiple regression models investigated associations between intakes of FA at baseline with aortic pulse wave velocity (aPWV), augmentation index (AIx), systolic and diastolic blood pressure (SBP, DBP) and pulse pressure after a 17.8-year follow-up--as well as cross-sectional relationships with metabolic markers. After adjustment, higher SFA consumption at baseline was associated with higher SBP (P = 0.043) and DBP (P = 0.002) and after a 17.8-year follow-up was associated with a 0.51 m/s higher aPWV (P = 0.006). After adjustment, higher PUFA consumption at baseline was associated with lower SBP (P = 0.022) and DBP (P = 0.036) and after a 17.8-year follow-up was associated with a 0.63 m/s lower aPWV (P = 0.007). CONCLUSION: This study suggests that consumption of SFA and PUFA have opposing effects on arterial stiffness and blood pressure. Importantly, this study suggests that consumption of FA is an important risk factor for arterial stiffness and CVD.

Oral vitamin C reduces arterial stiffness and platelet aggregation in humans.

Atherosclerosis is associated with stiffening of conduit arteries and increased platelet activation, partly as a result of reduced bioavailability of nitric oxide (NO), a mediator that normally has a variety of protective effects on blood vessels and platelets. Increased levels of oxygen free radicals are a feature of atherosclerosis that contributes to reduced NO bioavailability and might lead to increased arterial stiffness and platelet activation. Vitamin C is a dietary antioxidant that inactivates oxygen free radicals. This placebo-controlled, double-blind, randomized study was designed to establish whether acute oral administration of vitamin C (2 g), would reduce arterial stiffness and in vitro platelet aggregation in healthy male volunteers. Plasma vitamin C concentrations increased from 42+/-8 to 104+/-8 microM at 6 h after oral administration, and were associated with a significant reduction in augmentation index, a measure of arterial stiffness (by 9.6+/-3.0%; p = 0.016), and ADP-induced platelet aggregation (by 35+/-13%; p = 0.046). There was no change in these parameters after placebo. Vitamin C, therefore, appears to have beneficial effects, even in healthy subjects. The mechanism responsible is likely to involve protection of NO from inactivation by oxygen free radicals, but this requires confirmation. If similar effects are observed in patients with atherosclerosis or risk factors, vitamin C supplementation might prove an effective therapy in cardiovascular disease.

Effect of oral vitamin E (alpha-tocopherol) supplementation on vascular endothelial function in Type 2 diabetes mellitus.

AIMS: Vascular endothelial dysfunction, an early marker of atherosclerosis, has been demonstrated in Type 2 diabetes mellitus (DM). Vitamin E preserves endothelial function in animal models of diabetes and reduces cardiovascular risk. We examined endothelial function and the effect of vitamin E supplements in uncomplicated Type 2 DM. METHODS: Forty-eight subjects with Type 2 DM and 21 controls had endothelial function assessed using forearm venous occlusion plethysmography with endothelium-independent (sodium nitroprusside) and dependent (acetylcholine, bradykinin) vasodilators. Those with diabetes received 1600 i.u. daily oral alpha-tocopherol or placebo, double-blind for 8 weeks, and had endothelial function reassessed. RESULTS: The diabetic group had higher HbA1c (6.9+/-1.4 vs 4.8+/-0.6%; P<0.01) and systolic (145+/-15 vs. 130+/-16 mm Hg; P<0.01) but not diastolic blood pressure (79+/-8 vs. 76+/-9 mm Hg; P = 0.15). There was blunted vasodilation to acetylcholine (15 microg/min; P<0.01) in subjects with diabetes. Vasodilation to sodium nitroprusside and bradykinin was similar (all P>0.1). Alpha-tocopherol did not affect vasodilation to nitroprusside (P>0.1), acetylcholine (P>0.1) or bradykinin (P>0.1). CONCLUSIONS: There may be receptor-specific endothelial dysfunction in subjects with uncomplicated Type 2 DM. This is not improved by treatment with alpha-tocopherol.

Inhibition of acetylcholinesterase selectively potentiates NG-monomethyl-L-arginine-resistant actions of acetylcholine in human forearm vasculature.

1. NG-monomethyl-L-arginine (L-NMMA, a nitric oxide synthase inhibitor) inhibits vasodilator responses to acetylcholine but not methacholine in human forearm vasculature. To investigate whether this difference results from the relative susceptibility of these agonists to hydrolysis by acetylcholinesterase, we studied vasodilator responses to brachial artery administration of acetylcholine alone and in the presence of the acetylcholinesterase inhibitor edrophonium. 2. Vasodilator responses to constant-rate brachial artery infusions of acetylcholine were biphasic, with an initial peak response fading over 2 min to a plateau. Fade [(peak-plateau)/peak x 100%] was dose dependent (P < 0.02), ranging from 43 +/- 7% (mean +/- SEM) at low dose (16 nmol/min) to 9 +/- 8% at high dose (83 nmol/min). 3. Edrophonium (0.5 mumol/min intra-arterially) alone produced no change in forearm blood flow but increased blood flow responses to acetylcholine (P < 0.01), causing an approximately 10-fold reduction in the dose required to increase plateau blood flow by 10 ml min-1 100 ml-1. 4. Responses to low doses of acetylcholine alone (16 and 41 nmol/min) faded more (P < 0.01) than those to doses of acetylcholine with edrophonium chosen to produce similar plateau blood flows. Responses to acetylcholine (41 nmol/min) also faded more (P < 0.01) than those to methacholine (5 nmol/min), producing matched plateau flows. 5. Peak and plateau responses to acetylcholine (41 nmol/min) were reduced (P < 0.01) by similar amounts (47 +/- 15%, and 37 +/- 13% respectively, P = 0.39) by coinfusion of L/NMMA (4 mumol/min).(ABSTRACT TRUNCATED AT 250 WORDS)