Insulin and extremity muscle mass in overweight and obese women.

BACKGROUND: Obesity disproportionately affects women, especially those of African descent, and is associated with increases in both fat and muscle masses. OBJECTIVE: Although increased extremity muscle mass may be compensatory to fat mass load, we propose that elevated insulin levels resulting from diminished insulin sensitivity may additionally contribute to extremity muscle mass in overweight or obese women. METHODS: The following measurements were performed in 197 non-diabetic women (57% black, 35% white; age 46±11 years (mean±s.d.), body mass index (BMI) range 25.0-57.7 kg m(-2)): dual-energy X-ray absorptiometry for fat and extremity muscle masses; exercise performance by duration and peak oxygen consumption (VO2 peak) during graded treadmill exercise; fasting insulin and, in 183 subjects, insulin sensitivity index (SI) calculated from the minimal model. RESULTS: SI (range 0.5-14.1 l mU(-1 )min(-1)) was negatively, and fasting insulin (range 1.9-35.6 µU ml(-1)) positively associated with extremity muscle mass (both P<0.001), independent of age and height. Sixty-seven percent of women completed 6 months of participation in a weight loss and exercise program: we found a significant association between reduction in fasting insulin and a decrease in extremity muscle mass (P=0.038), independent of reduction in fat mass or improvement in exercise performance by VO2 peak and exercise duration, and without association with change in SI or interaction by race. CONCLUSIONS: Hyperinsulinemia in overweight or obese women is associated with increased extremity muscle mass, which is partially reversible with reduction in fasting insulin concentration, consistent with the stimulatory effects of insulin on skeletal muscle.

Coronary vasodilation and improvement in endothelial dysfunction with endothelin ET(A) receptor blockade.

The endothelium-derived peptide endothelin-1 (ET-1) causes vasoconstriction predominantly via smooth muscle ET(A) receptor activation. We hypothesized that ET(A) receptor inhibition would improve human coronary vascular function. We studied unobstructed coronary arteries of 44 patients with atherosclerosis or its risk factors. Epicardial diameter (D) and Doppler flow velocity were measured, and coronary vascular resistance (CVR) was calculated during intracoronary infusions of acetylcholine (ACH) and sodium nitroprusside (SNP), and during cold pressor testing, before and after a 60-minute intracoronary infusion of the ET(A) receptor antagonist BQ-123. BQ-123 dilated the coronary circulation; D increased by 5.6+/-1.0% (P<0.0001), and CVR fell by 12+/-3% (P<0.01). The D response to ACH, corrected for the SNP response, improved in segments that constricted with ACH at baseline (P=0.03), whereas segments that initially dilated with ACH did not change with BQ-123 (P=NS). Improvement in D and CVR responses to ACH with BQ-123 inversely correlated with baseline ACH responses (r=-0.44 [P=0.006] and r=-0.78 [P=0.001], respectively), indicating greater improvement in those with endothelial dysfunction. Similarly, cold pressor testing-mediated epicardial vasoconstriction (-2.0+/-1.1%) was reversed after BQ-123 (+1.0+/-0.7%), especially in dysfunctional segments (from -5.6+/-0.9% to +2.2+/-0.9%, P<0.001). There was no correlation between any risk factor and the response to BQ-123. An arteriovenous difference in ET-1 levels developed after BQ-123, which was consistent with enhanced cardiac clearance of ET-1, probably via ET(B) receptors. Thus, ET-1 acting via the ET(A) receptor contributes to basal human coronary vasoconstrictor tone and endothelial dysfunction. This suggests that ET(A) receptor antagonism may have therapeutic potential in the treatment of endothelial dysfunction and atherosclerosis.

Blood pressure changes during transient myocardial ischemia: insights into mechanisms.

OBJECTIVES: We investigated the contribution of changes in systemic blood pressure to the genesis of spontaneous myocardial ischemia. BACKGROUND: Although increases in heart rate often precede the development of spontaneous myocardial ischemia, it remains a subject of controversy whether these are accompanied by simultaneous changes in blood pressure. METHODS: Using an ambulatory monitoring device that triggered blood pressure recordings from the level of the ST segment, we documented systolic and diastolic blood pressure and heart rate changes related to episodes of ST segment depression in 17 patients with stable coronary artery disease. RESULTS: Systolic blood pressure and heart rate, but not diastolic pressure, increased significantly before the onset of ST segment depression and persisted throughout the ischemic episode. There was a significant correlation between the changes in heart rate and systolic blood pressure during episodes of myocardial ischemia (r = 0.5, p = 0.0005) and between heart rate and systolic blood pressure changes at 1-mm ST segment depression during treadmill exercise testing and ambulatory monitoring (r = 0.73, p = 0.0005 for heart rate; r = 0.77, p = 0.0008 for systolic blood pressure), indicating that patients with a low heart rate threshold during ischemic episodes also had a lower systolic blood pressure threshold before ischemia during both tests. Circadian changes in systolic blood pressure paralleled the variations in heart rate and ischemic episodes, with the lowest values at night. CONCLUSIONS: Significant increases in myocardial oxygen demand, including systolic blood pressure, occur during episodes of spontaneous myocardial ischemia. Patients with a lower heart rate threshold during ischemic episodes had a lower systolic blood pressure threshold during both ambulatory monitoring and treadmill exercise. The effects of antianginal therapy on blood pressure changes during ischemia need to be explored further.

Patterns and behavior of transient myocardial ischemia in stable coronary disease are the same in both men and women: a comparative study.

OBJECTIVES: This study sought to compare the circadian variations in transient ischemic activity, mean heart rate and ischemic threshold between women and men with coronary artery disease. BACKGROUND: There is a circadian variation in ischemic activity, onset of myocardial infarction and sudden cardiac death in patients with coronary artery disease, but studies assessing ischemia have incorporated predominantly male subjects. METHODS: Thirty-one women and 45 men underwent at least 48 h of ambulatory ST segment monitoring. RESULTS: There was a similar and significant circadian variation in ischemic activity in both women and men (p < 0.0001 and p < 0.0001, respectively), with a trough at night, a surge in the morning and a peak between 1 and 2 PM, corresponding to a similar circadian variation in mean hourly heart rate (p < 0.0001) that was not different between men and women (p = 0.28, power to detect a shift 99.9%). Mean heart rate at onset of ischemia (ischemic threshold) had similar variability in women and men (p = 0.96), and harmonic regression analysis confirmed a significant circadian variation (p < 0.0001), with a trough at night and a peak during activity hours. Heart rate increased significantly in the 5 min before ischemia throughout the 24 h (p < 0.0001), with no gender differences in the pattern of preonset to onset heart rate changes over time (p = 0.52); the smallest differences were recorded in the middle of the night. The majority of ischemic episodes (80%) had a heart rate increase > 5 beats/min in the 5 min before ischemia, but there were no gender differences. CONCLUSIONS: Women with coronary artery disease have a pattern of ischemic activity and underlying pathophysiologic mechanisms very similar to men. The importance of increase in myocardial oxygen demand in the genesis of ischemia in both men and women is reflected by similar magnitude of heart rate increases before ischemia. The lower ischemic threshold during the nocturnal hours, when blood pressure is also lower, is consistent with a circadian variation in underlying coronary vascular tone.

Randomized trial of nutrition education added to internet-based information and exercise at the work place for weight loss in a racially diverse population of overweight women.

OBJECTIVE: Obesity in the United States is highly prevalent, approaching 60% for black women. We investigated whether nutrition education sessions at the work place added to internet-based wellness information and exercise resources would facilitate weight and fat mass loss in a racially diverse population of overweight female employees. METHODS: A total of 199 (average body mass index 33.9±6.3 kg m(-2)) nondiabetic women (57% black) at our institution were randomized to a 6-month program of either internet-based wellness information (WI) combined with dietitian-led nutrition education group sessions (GS) weekly for 3 months and then monthly with shift in emphasis to weight loss maintenance (n=99) or to WI alone (n=100). All were given access to exercise rooms convenient to their work site. Fat mass was measured by dual-energy X-ray absorptiometry. RESULTS: WI+GS subjects lost more weight than WI subjects at 3 months (-2.2±2.8 vs -1.0±3.0 kg, P>0.001). Weight (-2.7±3.9 vs -2.0±3.9 kg) and fat mass (-2.2±3.1 vs -1.7±3.7 kg) loss at 6 months was significant for WI+GS and WI groups (both P<0.001), but without significant difference between groups (both P>0.10); 27% of the WI+GS group achieved 5% loss of initial weight as did 18% of the WI group (P=0.180). Blacks and whites similarly completed the study (67 vs 74%, P=0.303), lost weight (-1.8±3.4 vs -3.3±5.2 kg, P=0.255) and fat mass (-1.6±2.7 vs -2.5±4.3 kg, P=0.532), and achieved 5% loss of initial weight (21 vs 32%, P=0.189), irrespective of group assignment. CONCLUSION: Overweight women provided with internet-based wellness information and exercise resources at the work site lost weight and fat mass, with similar achievement by black and white women. Additional weight loss benefit of nutrition education sessions, apparent at 3 months, was lost by 6 months and may require special emphasis on subjects who fail to achieve weight loss goals to show continued value.

Ischemia during ambulatory monitoring as a prognostic indicator in patients with stable coronary artery disease.

OBJECTIVE: To assess long-term prognostic significance of transient ischemia in patients with documented coronary artery disease and stable symptoms and to examine the relation between transient ischemia and the site of angiographic disease progression following acute cardiac events. DESIGN: Cohort study with a mean+/-SD follow-up of 51.5+/-23.8 months. SETTING: Ambulatory patients with stable coronary artery disease, assigned to medical therapy. PATIENTS: A total 221 patients (173 men; mean age, 60.8 years) were recruited. Of the 221 patients, 101 (45.7%) had single-vessel, 86 (38.9%) had 2-vessel, and 34 (15.4%) had 3-vessel disease. A total of 135 had a positive exercise test for ischemia, and mean+/-SD resting left ventricular ejection fraction (LVEF) was 49.8%+/-11.4%. Using conventional criteria, patients were prospectively stratified as low risk for continued medical therapy (single-vessel disease, 2-vessel disease with negative exercise test, or LVEF> or =40%; n=189 [85.5%]) or high risk for continued medical therapy (multivessel disease with ischemia and/or left ventricular dysfunction; n=32 [14.5%]). INTERVENTIONS: Ambulatory ST-segment monitoring, treadmill exercise testing, radionuclide ventriculography, and coronary angiography. MAIN OUTCOME MEASURES: Demographic, clinical, ambulatory monitoring, treadmill exercise, and left ventricular function variables as independent predictors of acute (cardiac death, myocardial infarction, or unstable angina) or all (including revascularization) cardiac events in the overall and the low-risk population. RESULTS: None of the clinical or noninvasive measures of ischemia were of prognostic significance in the overall or the low-risk group. The only significant independent predictor of outcome in all patients for all events, including revascularization, was the number of diseased vessels (X2=13.5 [df=1]; P<.001). Exclusion of vessel disease resulted in conventional risk stratification as the most significant predictor of outcome from all events in all patients (X2= 10.3 [df= 1]; P=.001). In the low-risk group, the number of diseased vessels was the only predictor for all events (X2=4.6; P=.03). For acute cardiac events, none of the variables tested were of prognostic significance. Based on the frequency of events in the low-risk patients, a 2-fold increase in the rate of cardiac events in patients with transient ischemia compared with those without transient ischemia during ambulatory monitoring could be excluded with greater than 85% power and alpha of .05. Of 30 patients suffering acute nonfatal cardiac events during follow-up, angiography was performed in 27, revealing significant progression of coronary disease in 24 (88.8%) and the development of new significant lesions at sites remote from previously significant lesions in 20 (74%) cases. These new lesions were equally likely to occur in those with or without transient ischemia at initial assessment. CONCLUSIONS: Acute cardiac events in predominantly low-risk stable angina patients with confirmed coronary disease are unpredictable, and those more likely to suffer such an event cannot be identified by the detection of ambulatory ischemia. Acute nonfatal cardiac events result predominantly from the development of significant new coronary lesions, not initially severe enough to cause ischemia. Patients categorized as high risk for long-term medical therapy have an increased rate of cardiac events (mainly revascularization) when compared with low-risk patients.