ABSTRACT
AIMS: To determine the effect of extended release (ER) niacin on endothelial and vascular function assessed by brachial flow-mediated dilatation (FMD), peak hyperemic velocity (VTiRH) and pulse arterial tonometry (PAT) in patients with established coronary artery disease (CAD), already treated with high dose statins. Endothelial dysfunction is common in patients with established coronary artery disease (CAD) and has prognostic implications. Niacin has proven clinical benefit in patients with CAD, but its additive effect in patients on statin therapy is being evaluated. The effect of niacin on endothelial function, in the presence of optimal LDL cholesterol is unclear. METHODS AND RESULTS: Sixty-six patients with CAD (mean age 57.9 ± 8.5 yrs) received ER niacin (1500 mg per day) and placebo in a randomized crossover fashion for 3 months of each therapy. All patients received atorvastatin 80 mg per day. FMD, VTiRH and PAT measurements were performed at baseline and after each treatment period. Treatment with niacin improved dyslipidemia parameters (LDL placebo 1.52 ± 0.51 vs. niacin 1.30 ± 0.43; p = 0.004; HDL placebo 0.95 ± 0.16 vs. niacin 1.11 ± 0.22; p < 0.001). However, there was no observed improvement in endothelial function as assessed by FMD (placebo 6.1 ± 4.9 vs. niacin 6.6 ± 4.8%; p = 0.48), VTiRH (placebo 75 ± 28 vs. niacin 78 ± 26 cm; p = 0.23) or PAT (placebo 1.8 ± 0.42 vs. niacin 1.79 ± 0.5; p = 0.43). CONCLUSION: Niacin as add-on treatment to high dose statins in patients with established CAD significantly improves lipid profile. However, these changes were not associated with improved endothelial or microvascular function. Registered clinical trial with clinicaltrials.gov: NCT00150722.
Subject(s)
Coronary Artery Disease/drug therapy , Endothelium, Vascular/drug effects , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Niacin/administration & dosage , Pyrroles/therapeutic use , Aged , Atorvastatin , Endothelium, Vascular/physiopathology , Female , Humans , Hypoalphalipoproteinemias/drug therapy , Hypolipidemic Agents/therapeutic use , Lipids/blood , Male , Middle AgedABSTRACT
BACKGROUND & AIMS: Chronic inflammation has a major role in the development and propagation of endothelial dysfunction, which can lead to coronary artery disease. Endothelial dysfunction has been described in patients with various and diverse chronic inflammatory conditions. Altered vascular flow has been proposed to mediate inflammation in inflammatory bowel disease (IBD), although the role of endothelial dysfunction remains obscure. The purpose of our study was to assess endothelial function in patients with IBD. METHODS: Ninety-eight subjects were included in this study; 48 with IBD (17 with ulcerative colitis and 31 with Crohn's disease) and 50 healthy controls. Endothelial function was assessed by pulse arterial tonometry (PAT) and brachial ultrasound to determine flow-mediated dilation and shear stress reactive hyperemia. The impact of disease activity, disease duration, and IBD therapy also was assessed. RESULTS: Baseline demographic characteristics, including cardiovascular risk factors, were similar in all groups. IBD patients showed microvascular endothelial dysfunction, with lower PAT indices (P < .01) and shear stress reactive hyperemia (P < .05) compared with controls. There was no relationship between microvascular endothelial dysfunction, disease duration, underlying therapy, or clinical disease activity. There was a positive association between lower PAT scores and recent abdominal pain (P < .05). CONCLUSIONS: This was a large study assessing endothelial dysfunction in IBD. Both ulcerative colitis and Crohn's disease patients showed evidence of microvascular endothelial dysfunction. Future research could determine whether endothelial dysfunction is involved in the pathogenesis of IBD or increases the risk of cardiovascular events in this patient population.
