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Context: The amino acid L-arginine is a substrate for nitric oxide synthase and is increasingly used as a health supplement. Prior studies suggest that L-arginine has the potential to reduce vascular stiffness.Objective: To determine whether the addition of L-arginine to standard postinfarction therapy reduces vascular stiffness and improves ejection fraction over 6-month follow-up in patients following acute ST-segment elevation myocardial infarction.Design and Setting: Single-center, randomized, double-blind, placebo-controlled trial with enrollment from February 2002 to June 2004.Patients: A total of 153 patients following a first ST-segment elevation myocardial infarction were enrolled; 77 patients were 60 years or older.Intervention: Patients were randomly assigned to receive L-arginine (goal dose of 3 g 3 times a day) or matching placebo for 6 months.Main Outcome Measures: Change in gated blood pool-derived ejection fraction over 6 months in patients 60 years or older randomized to receive L-arginine compared with those assigned to receive placebo. Secondary outcomes included change in ejection fraction in all patients enrolled, change in noninvasive measures of vascular stiffness, and clinical events.Results: Baseline characteristics, vascular stiffness measurements, and left ventricular function were similar between participants randomized to receive placebo or L-arginine. The mean (SD) age was 60 (13.6) years; of the participants, 104 (68%) were men. There was no significant change from baseline to 6 months in the vascular stiffness measurements or left ventricular ejection fraction in either of the 2 groups, including those 60 years or older and the entire study group. However, 6 participants (8.6%) in the L-arginine group died during the 6-month study period vs none in the placebo group (P = .01). Because of the safety concerns, the data and safety monitoring committee closed enrollment.Conclusions: L-arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. L-arginine should not be recommended following acute myocardial infarction. Clinical Trial Registration ClinicalTrials.gov, NCT00051376. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to determine the effect of age on the hemodynamic response to prolonged submaximal aerobic exercise in healthy volunteers.Background: Reductions in peak work rate, heart rate (HR), and left ventricular (LV) emptying but higher blood pressure (BP) and systemic vascular resistance occur in healthy older versus younger humans during short bursts of graded maximal aerobic exercise. However, the effect of aging on the cardiovascular response to prolonged exercise at submaximal work rates typical of daily aerobic activities remains unknown.Methods: We evaluated cardiovascular performance throughout prolonged submaximal upright cycle ergometry in 40 carefully screened healthy untrained volunteers, 8 men and 12 women <50 years old, mean = 37 +/- 8 years (younger), and 10 men and 10 women >/=50 years old, mean = 66 +/- 9 years (older), during upright cycle exercise at 70% of peak cycle oxygen consumption (VO(2)) to exhaustion or a maximum of 120 min. Cardiac volumes were acquired by gated blood pool scans with (99m)Tc at rest and every 10 min throughout exercise.Results: Duration of exercise was similar in younger ([81 +/- 28 min] versus older [71+/- 29 min] subjects, p = NS). At 10 min of exercise in the steady state, older subjects demonstrated lower VO(2) (1.1 +/- 0.2 l/min vs. 1.3 +/- 0.3 l/min) and lower HR (118 +/- 17 vs. 135 +/- 11 beats/min, p < 0.001) but larger end-diastolic (80 +/- 11 ml/m(2) vs. 73 +/- 8 ml/m(2), p = 0.03) and end-systolic volume index (ESVI) 20 +/- 6 ml/m(2) vs. 17 +/- 4 ml/m(2), p < 0.05) than younger ones. Between 10 min and exercise termination, with VO(2) held constant in both groups, increases in HR (14.0 +/- 12.4 beats/min vs. 5.9 +/- 11.5 beats/min, p = 0.04), cardiac index (1.6 +/- 1.0 l/min/m(2) vs. 0.8 +/- 1.1 l/min/m(2), p = 0.03), and LV ejection fraction (7.1 +/- 4.0% vs. 2.9 +/- 4.4%, p = 0.003) were greater in younger than older subjects, respectively, as was the reduction in ESVI (-5.1 +/- 3.0 ml/m(2) vs. -1.8 +/- 3.3 ml/m(2), p = 0.002), despite similar declines in systolic BP (-12.3 +/- 6.3 mm Hg vs. -12.1 +/- 15.0 mm Hg, p = NS).Conclusions: Thus, age-associated deficits in chronotropic and LV systolic reserve performance occur during prolonged submaximal upright cycle ergometry, analogous to those observed during graded maximal exercise. [ABSTRACT FROM AUTHOR]

Background: Transmyocardial revascularisation (TMR) is an operative treatment for refractory angina pectoris when bypass surgery or percutaneous transluminal angioplasty is not indicated. We did a prospective randomised trial to compare TMR with continued medication.Methods: We recruited 182 patients from 16 US centres with Canadian Cardiovascular Society Angina (CCSA) score III (38%) or IV (62%), reversible ischaemia, and incomplete response to other therapies. Patients were randomly assigned TMR and continued medication (n=92) or continued medication alone (n=90). Baseline assessments were angina class, exercise tolerance, Seattle angina questionnaire for quality of life, and dipyridamole thallium stress test. We reassessed patients at 3 months, 6 months, and 12 months, with independent masked angina assessment at 12 months.Findings: At 12 months, total exercise tolerance increased by a median of 65 s in the TMR group compared with a 46 s decrease in the medication-only group (p<0.0001, median difference 111 s). Independent CCSA score was II or lower in 47.8% in the TMR group compared with 14.3% in the medication-only group (p<0.001). Each Seattle angina questionnaire index increased in the TMR group significantly more than in the medication-only group (p<0.001).Interpretation: TMR lowered angina scores, increased exercise tolerance time, and improved patients' perceptions of quality of life. This operative treatment provided clinical benefits in patients with no other therapeutic options. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increased blood cholesterol, specifically high low-density lipoprotein cholesterol, increases risk for coronary heart disease (CHD). Persons with a positive family history of premature CHD also are at markedly increased risk. OBJECTIVE: To examine the prevalence of hypercholesterolemia based on the second report of the National Cholesterol Educational Program Adult Treatment Panel (ATP II) guidelines in the asymptomatic healthy siblings of people with premature CHD. METHODS: A total of 668 asymptomatic healthy siblings (354 men and 314 women) underwent screening for risk factors for CHD. Siblings were categorized into treatment categories for primary prevention defined by ATP II. The percentage who were candidates for intervention were compared with the published national estimates for those without CHD from the third National Health and Nutrition Examination Survey (NHANES III). RESULTS: Based on ATP II guidelines, 65% of the asymptomatic adult siblings required fasting lipoprotein analysis compared with 33% of adults without CHD in the national reference population. Of the siblings who met the criteria for fasting lipoprotein analysis, most (56%) were candidates for dietary therapy, more than twice the proportion of adults from NHANES III. The percentage of the siblings who qualified for drug intervention and dietary therapy was 3 times greater than the national sample, 33% vs 11%, respectively. Assuming a 10% hypothetical reduction in low-density lipoprotein cholesterol levels as the result of dietary modification, the proportion of the sibling sample who were possible candidates for drug therapy was 20%, still 4 times that predicted for the national sample. CONCLUSIONS: These results underscore the need for aggressive detection and treatment of hypercholesterolemia in this easily identifiable high-risk population of siblings of people with premature CHD. [ABSTRACT FROM AUTHOR]

Among persons with a family history of premature coronary heart disease (CHD), siblings bear an excess risk of CHD that is as high as 12 times that of the general population. Aggressive, new, national guidelines for CHD risk reduction have focused on high-risk families, yet little is known about actual remediable risk factors in siblings of persons with premature CHD. To determine the magnitude of the problem relative to the general population, we screened 846 unaffected siblings (ages 30 to 59 years) of persons with documented CHD before age 60 years and compared their risk factor values with population reference norms obtained in the Third National Health and Nutrition Examination Survey (NHANES III) and the National Health Interview Survey (NHIS). Mean levels of low-density lipoprotein cholesterol were 0.52 mmol/L (20 mg/dl) higher in siblings; the prevalence of low-density lipoprotein cholesterol > or =4.14 mmol/L (160 mg/dl) was nearly twice that of race, sex, and age-specific values from NHANES III. Levels of high-density lipoprotein cholesterol <0.91 mmol/L (35 mg/dl) were similar between siblings and NHANES III (11% and 12%, respectively). Only 4% of all siblings had triglyceride levels > or =4.52 mmol/L (400 mg/dl). Hypertension prevalence was twice as high among siblings as among the NHANES III. Current smoking was 33.9% in white siblings and 25.5% in the NHIS, whereas smoking in African-Americans was similar to that in the NHIS (31.1% vs 29.2%). A mere 13% to 29% of siblings were without any major remediable risk factors. The overwhelming need for risk factor modification in this easily identifiable high-risk population supports aggressive national guidelines and demonstrates the lack of adequate treatment of apparently healthy siblings of persons with premature CHD. [ABSTRACT FROM AUTHOR]

High-physical activity levels are associated with reduced risk of symptomatic coronary artery disease (CAD). However, there are a number of reports of exercise-related sudden death and myocardial infarction in aerobically trained athletes. This study compared the prevalence of exercise-induced silent myocardial ischemia on maximum graded exercise tests with tomographic thallium scintigraphy in 70 master male athletes (63 +/- 6 years, mean +/- SD) (maximum aerobic capacity, VO2max >40 ml/kg/min) and in 85 healthy untrained men (61 +/- 7 years) with no history of CAD. The prevalence of silent ischemia (exercise-induced ST-segment depression on electrocardiogram and perfusion abnormalities on thallium scintigraphy) was similar in athletes and untrained men; 16% of the athletes (11 of 70) had silent ischemia compared with 21% of the untrained men (chi-square = 0.81, p = 0.36). No athletes had hyperlipidemia, systemic hypertension, or diabetes mellitus. However, the apolipoprotein E4 allele was present in 9 of the 11 athletes with silent ischemia compared with 2 of 32 athletes with normal exercise tests (chi-square = 24, p = 0.0001). These results suggest that older male athletes with the apolipoprotein E4 allele are at increased risk for the development of exercise-induced silent ischemia. [ABSTRACT FROM AUTHOR]