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Objectives: The purpose of this study was to establish the prevalence of insulin resistance (IR) among nondiabetic chronic heart failure (CHF) patients and to seek factors associated with IR in CHF, including the relationship of IR to functional class, exercise capacity, and disease severity in CHF., Background: Several lines of evidence suggest that CHF is an IR state. The prevalence of IR in CHF and its relation to CHF have not been fully defined., Methods: Fasting insulin resistance index (FIRI) was assessed in a cohort of 129 consecutive CHF patients (mean age 69.2 +/- 10.4 years; 76% males; body mass index 27.4 +/- 4.4 kg/m(2)). Patients underwent cardiopulmonary exercise testing and peripheral endothelial function testing by reactive hyperemia peripheral arterial tonometry (RH-PAT)., Results: Prevalence of IR as defined by FIRI > or =2.7 was 61% in our cohort of CHF patients. There was a significant correlation between IR and waist circumference (r = 0.37; p < 0.01), serum triglycerides (r = 0.34; p < 0.01), high-density lipoprotein cholesterol (r = -0.22; p = 0.02), and serum leptin (r = 0.39; p = 0.03). Insulin resistance increased significantly with worsening New York Heart Association functional class (p < 0.01). The CHF patients with IR had a significantly lower exercise capacity and peak oxygen consumption than patients with an FIRI <2.7. The RH-PAT ratio was significantly lower in CHF patients with IR compared with CHF patients with an FIRI <2.7 (1.6 +/- 0.3 vs. 2.0 +/- 0.5; p < 0.05)., Conclusions: Insulin resistance is highly prevalent among nondiabetic CHF patients and is associated with decreased exercise capacity in patients with CHF. (Insulin Resistance: Heart Failure; NCT00486967).

Hypertension is more frequent and more severe in some Black populations. Although many studies have focused on hypertension in black people in an attempt to understand the genetic and environmental factors that regulate blood pressure, this approach has not been productive. Study of the relationship between specific phenotypes and genotypes, both within and across ethnic groups, is more likely to advance our understanding of the regulation of blood pressure than studies focused on race and blood pressure.

Blood pressure reactivity is enhanced in young black subjects through mechanisms that are poorly understood. We compared alpha-adrenergic-mediated vasoconstrictor and ss-adrenergic vasodilator sensitivity and their relation to sympathetic activity in blacks and whites. Ten healthy black (age, 29.9+/-2.4 years) and 10 white (age, 28.3+/-1.9 years) men were studied. Forearm blood flow was measured with strain-gauge plethysmography after the intrabrachial artery administration of phenylephrine (1.25 to 20 microgram/min) and isoproterenol (60 and 400 ng/min) after application of lower-body negative pressure and after a cold pressor test. Forearm and systemic norepinephrine spillover were measured with a radioisotope dilution technique. alpha-Adrenergic vasoconstriction was markedly increased (ANOVA P=0.008) and ss-adrenergic vasodilation decreased (ANOVA P=0.02) in blacks. Phenylephrine (10 microgram/min) decreased forearm blood flow by 58.0+/-2.5% in blacks but only by 26.6+/-6.0% in whites (P<0.001). Vasoconstrictor response to endogenous norepinephrine, stimulated by a cold pressor test, resulted in a higher forearm vascular resistance in blacks than in whites (107.3+/-13 versus 64.8+/-13 mm Hg. mL(-)(1). 100 mL(-)(1), P=0.03). There were no significant ethnic differences in basal or stimulated forearm or systemic norepinephrine spillover. Increased vasoconstrictor and decreased vasodilator responses in blacks were not correlated. Increased sympathetically mediated vascular tone caused by enhanced vasoconstriction and attenuated vasodilation, effects that would be additive, and not increased sympathetic activity could enhance vascular reactivity and may play a role in the pathogenesis of hypertension in blacks.

A threefold higher area under the plasma drug concentration-time curve (AUC) of nifedipine, a substrate of cytochrome P4503A (CYP3A), has been shown in Southern Asians when compared with Caucasians. To determine if these differences are specific to nifedipine or apply to other substrates of CYP3A, we examined the pharmacokinetics and pharmacodynamics of 0.375 mg triazolam, another substrate of CYP3A, in eight healthy Caucasians and eight healthy Southern Asians in a double-blind placebo-controlled study. When compared with Caucasians, Southern Asians achieved higher maximum plasma concentration (Cmax) (8.0 +/- 2.6 vs 4.8 +/- 1.9 ng ml-1; the 95% confidence interval (CI) of the mean difference was 0.76 to 5.7; P < 0.01) and had a shorter time to reach maximal concentration (tmax) (45 min (range 30-75) vs 90 min (range 60-145); the 95% CI of the mean difference was -69 to -20; P < 0.002). Triazolam AUC, clearance and partial metabolic clearance did not differ significantly between Southern Asians and Caucasians. Significant differences were found in postural sway after triazolam when compared with placebo in both Caucasians (double stance: eyes open (DSEO): 172.9 +/- 82.9 vs 1138.9 +/- 1182.4; the 95% CI of the mean difference was -1897.2 to -34.4; P < 0.04; and Southern Asians (DSEO: 216.2 +/- 80.9 vs 1086.0 +/- 827.1; the 95% CI of the mean difference was -1564.2 to -175.6; P = 0.02; double stance: eyes closed (DSEC): 207.5 +/- 89.8 vs 1156.9 +/- 932.1; the 95% CI of the mean difference was -1718.5 to -178.5; P = 0.02; with no significant difference between the two ethnic groups. These results suggest that the large inter-ethnic difference in nifedipine clearance are not generalizable to all CYP3A4 substrates.