Screening for heart disease in diabetic subjects

Background The prevalence of left ventricular hypertrophy (LVH), coronary artery disease, and subclinical cardiomyopathy in diabetic patients without known cardiac disease is unclear. We sought the frequency of these findings to determine whether plasma brain natriuretic peptide (BNP) could be used as an alternative screening tool to identify subclinical LV dysfunction. Methods Asymptomatic patients with diabetes mellitus without known cardiac disease (n = 10 1) underwent clinical evaluation, measurement of BNP, exercise stress testing, and detailed echocardiographic assessment. After exclusion of overt dysfunction or ischemia, subclinical myocardial function was sought on the basis of myocardial systolic (Sm) and diastolic velocity (Em). Association was. sought between subclinical dysfunction and clinical, biochemical, exercise, and echocardiographic variables. Results Of 101 patients, 22 had LVH and 16 had ischemia evidenced by exercise-induced wall motion abnormalities. Only 4 patients had abnormal BNP levels; BNP was significantly increased in patients with LVH. After exclusion of LVH and coronary artery disease, subclinical cardiomyopathy was identified in 24 of 66 patients: Subclinical disease could not be predicted by BNP. Conclusions Even after exclusion of asymptomatic ischemia and hypertrophy, subclinical systolic and diastolic dysfunction occurs in a significant number of patients with type 2 diabetes. However, screening approaches, including BNP, do not appear to be sufficiently sensitive to identify subclinical dysfunction, which requires sophisticated echocardiographic analysis.

Relationship between laboratory-measured variables and heart rate during an ultra-endurance triathlon

The aim of the present study was to examine the relationship between the performance heart rate during an ultra-endurance triathlon and the heart rate corresponding to several demarcation points measured during laboratory-based progressive cycle ergometry and treadmill running. Less than one month before an ultra-endurance triathlon, 21 well-trained ultra-endurance triathletes (mean +/- s: age 35 +/- 6 years, height 1.77 +/- 0.05 in, mass 74.0 +/- 6.9 kg, (V) over dot O-2peak = 4.75 +/- 0.42 1 center dot min(-1)) performed progressive exercise tests of cycle ergometry and treadmill running for the determination of peak oxygen uptake ((V) over do O-2peak), heart rate corresponding to the first and second ventilatory thresholds, as well as the heart rate deflection point. Portable telemetry units recorded heart rate at 60 s increments throughout the ultra-endurance triathlon. Heart rate during the cycle and run phases of the ultra-endurance triathlon (148 +/- 9 and 143 +/- 13 beats center dot min(-1) respectively) were significantly (P < 0.05) less than the second ventilatory thresholds (160 +/- 13 and 165 +/- 14 beats center dot min(-1) respectively) and heart rate deflection points (170 +/- 13 and 179 +/- 9 beats center dot min(-1) respectively). However, mean heart rate during the cycle and run phases of the ultra-endurance triathlon were significantly related to (r = 0.76 and 0.66; P < 0.01), and not significantly different from, the first ventilatory thresholds (146 +/- 12 and 148 +/- 15 beats center dot min(-1) respectively). Furthermore, the difference between heart rate during the cycle phase of the ultra-endurance triathlon and heart rate at the first ventilatory threshold was related to marathon run time (r = 0.61; P < 0.01) and overall ultra-endurance triathlon time (r = 0.45; P < 0.05). The results suggest that triathletes perform the cycle and run phases of the ultra-endurance triathlon at an exercise intensity near their first ventilatory threshold

Fundamental considerations of beta-adrenoceptor subtypes in human heart failure

beta-Adrenoceptor antagonists have revolutionized the management of heart failure in humans. However, fundamental questions remain concerning their use. Currently, there is considerable debate about the role of beta(2)-adrenoceptors in heart failure and whether incremental clinical benefit can be obtained by blockade of beta(2)-adrenoceptors in addition to beta(1)-adrenoceptors. Polymorphic forms of beta(1)- and beta(2)-adrenoceptors exist, which might contribute to the variable clinical outcomes that are observed with P-adrenoceptor antagonists. There is evidence for a low-affinity state of beta(1)-adrenoceptors and ventricular beta(3)-adrenoceptors, and these are discussed in the context of heart failure. Finally, there is seemingly paradoxical evidence that restoration and normalization of the beta-adrenoceptor system is beneficial in animal models of heart failure. We reconcile this view with the current clinical use and proven benefit of beta-adrenoceptor antagonists.

Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II

1 The calcineurin (CaN) enzyme-transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. 2 Human right ventricular trabeculae from explanted human ( 14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 mu M, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. 3 ET-1 increased contractile force in all 13 patients (P < 0.001). Ang II and hUII increased contractile force in three out of eight and four out of 10 patients but overall nonsignificantly (P > 0.1). FK506 had no effect on contractile force (P = 0.12). 4 ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P = 0.1). 5 There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKC epsilon compared to samples incubated without PKCe. 6 Endogenous cardiostimulants which activate G alpha q-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate.

Rethinking the "diseases of affluence" paradigm: Global patterns of nutritional risks in relation to economic development

Background Cardiovascular diseases and their nutritional risk factors-including overweight and obesity, elevated blood pressure, and cholesterol-are among the leading causes of global mortality and morbidity, and have been predicted to rise with economic development. Methods and Findings We examined age-standardized mean population levels of body mass index (BMI), systolic blood pressure, and total cholesterol in relation to national income, food share of household expenditure, and urbanization in a cross-country analysis. Data were from a total of over 100 countries and were obtained from systematic reviews of published literature, and from national and international health agencies. BMI and cholesterol increased rapidly in relation to national income, then flattened, and eventually declined. BMI increased most rapidly until an income of about I$5,000 (international dollars) and peaked at about I$12,500 for females and I$17,000 for males. Cholesterol's point of inflection and peak were at higher income levels than those of BMI (about I$8,000 and I$18,000, respectively). There was an inverse relationship between BMI/cholesterol and the food share of household expenditure, and a positive relationship with proportion of population in urban areas. Mean population blood pressure was not correlated or only weakly correlated with the economic factors considered, or with cholesterol and BMI. Conclusions When considered together with evidence on shifts in income-risk relationships within developed countries, the results indicate that cardiovascular disease risks are expected to systematically shift to low-income and middle-income countries and, together with the persistent burden of infectious diseases, further increase global health inequalities. Preventing obesity should be a priority from early stages of economic development, accompanied by population-level and personal interventions for blood pressure and cholesterol.

White blood cell count predicts reduction in coronary heart disease mortality with pravastatin

Background-Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment. Methods and Results-We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1 X 10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2X10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased ( by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively). Conclusions-These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.

Effects of aldosterone on forearm vasculature in treated chronic heart failure

The nongenomic effects of aldosterone in disease states associated with endothelial dysfunction may differ from those in healthy subjects. The effects of locally infused aldosterone on the forearm blood flow and volume were studied in optimally treated patients with chronic heart failure (CHF). At baseline and after incremental intrabrachial aldosterone, forearm blood flow was assessed using conventional strain gouge plethysmography, and forearm venous volume was assessed by radionuclide plethysmography. Constriction of the resistance vasculature of the forearm without significant effect on forearm venous capacitance was demonstrated in response to aldosterone in patients treated for CHF. (C) 2005 by Excerpta Medica Inc.

Carvedilol blocks beta(2)- more than beta(1)-adrenoceptors in human heart

Objective: To understand the basis of the effectiveness of carvedilol in heart failure by determining its specific properties at human heart and beta(2)-adrenoceptors. Methods: The positive inotropic effects of noradrenaline (in the presence of the beta(2)-selective antagonist ICI118551) and adrenaline (in the presence of the beta(1)-selective antagonist CGP20712), mediated through beta(1)- and beta(2)-adrenoceptors, respectively, were investigated in atrial and ventricular trabeculae. The patch-clamp technique was used to investigate effects of noradrenaline and adrenaline on L-type Ca2+ current in human atrial myocytes. Results: Carvedilol was a 13-fold more potent competitive antagonist of the effects of adrenaline at 1 2-adrenoceptors (-logK(B) = 10.13 +/- 0.08) than of noradrenaline at beta(1)-adrenoceptors (-logK(B) = 9.02 +/- 0.07) in human right atrium. Chronic carvedilol treatment of patients with non-terminal heart failure reduced the inotropic sensitivity of atrial trabeculae to noradrenaline and adrenaline 5.6-fold and 91.2-fold, respectively, compared to beta(1)-blocker-treated patients, consistent with persistent preferential blockade of beta(2)-adrenoceptors. In terminal heart failure carvedilol treatment reduced 1.8-fold and 25.1-fold the sensitivity of right ventricular trabeculae to noradrenaline and adrenaline, respectively, but metoprolol treatment did not reduce the sensitivity to the catecholamines. Increases of current (I-Ca,I-L) produced by noradrenaline and adrenaline were not different in atrial myocytes obtained from non-terminal heart failure patients treated with metoprolol or carvedilol, consistent with dissociation of both beta-blockers from the receptors. Conclusions: Carvedilol blocks human cardiac beta(2)-adrenoceptors more than beta(1)-adrenoceptors, thereby conceivably contributing to the beneficial effects in heart failure. The persistent blockade of beta-adrenoceptors is attributed to accumulation of carvedilol in cardiac tissue. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.