Histopathology of familial versus nonfamilial dilated cardiomyopathy

Idiopathic dilated cardiomyopathy is most likely a heterogenous group of diseases characterized by ventricular dilatation and dysfunction. Approximately 20% of patients with idiopathic dilated cardiomyopathy have familial disease, which may be inapparent by review of the family history alone. It has been suggested that histopathologic features, particularly the presence of bizarrely shaped mitochondria, may be useful in distinguishing familial from nonfamilial disease.We investigated 57 patients with dilated cardiomyopathy, 13 familial and 43nonfamilial or indeterminate. Pathologic examination of right endomyocardial biopsy specimens showed no significant differences between the familial, nonfamilial, or indeterminate groups by light microscopy or electron microscopy. We conclude that the distinction between familial and nonfamilial dilated cardiomyopathy cannot be made by histopathologic examination in most cases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30544/1/0000177.pd

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Total Daily Energy Expenditure Has Declined over the Past Three Decades Due to Declining Basal Expenditure, Not Reduced Activity Expenditure

Obesity is caused by prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes, is debated3,4. Here we used the IAEA DLW database on energy expenditure of adults in the USA and Europe (n = 4799) to explore patterns in total (TEE: n=4799), basal (BEE: n = 1432) and physical activity energy expenditure (AEE: n = 1432) over time. In both sexes total energy expenditure (TEE) adjusted for body composition and age declined with time, while adjusted AEE increased over time. In males adjusted BEE decreased significantly, but in females this didn’t reach significance. A larger dataset of basal metabolic rate (BMR equivalent to BEE) measurements of 9912 adults across 163 studies spanning 100 years replicated the decline in BEE in both sexes. Increasing obesity in the USA/Europe has probably not been fueled by reduced physical activity leading to lowered TEE. We identify here decline in adjusted BEE, as a previously unrecognized novel factor

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Measuring plasma B-type natriuretic peptide in heart failure Good to go in 2004?

Elevated plasma brain natriuretic (BNP) concentrations correlate with increased cardiac filling pressures. Therefore, increased BNP has been proposed as a marker for asymptomatic ventricular dysfunction, as an aid in the diagnosis of cardiac dyspnea, as an end point to assess the efficacy of heart failure therapy, and as a prognostic marker in heart failure. An understanding of the utility of BNP requires an appreciation of the sensitivity, specificity, and diagnostic accuracy of BNP in each of these clinical situations. At this time, there is strong evidence for the value of BNP in the evaluation of dyspnea of uncertain cause. Further population studies will need to be performed to refine the application of BNP to community cohorts and to determine its clinical value and cost-effectiveness as a screening tool in the early diagnosis of ventricular dysfunction. To make optimal use of BNP for the assessment of heart failure therapy and prognosis in individual patients, physicians will require additional information on the biological variability of BNP. Studies comparing the sensitivity, specificity, and predictive value of the available BNP and N-terminal pro-BNP assays need to be conducted in each of these clinical settings

Reassessing the clinical significance of electrocardiographically unrecognized myocardial infarctions: Radionuclide infarct size and its impact on long-term prognosis

Background:Silent or unrecognized myocardial infarction (UMI) diagnosed by surveillance electrocardiography (ECG) carries similarly poor prognosis as recognized MI (RMI) for poorly understood reasons. Methods:This study included 5430 consecutive patients who presented to the nuclear laboratory and underwent 2-day stress and rest Tc-99m sestamibi and ECG studies between March 1991 and June 1999. UMI was diagnosed if ECG showed Q-wave MI in the absence of a history of RMI. We measured infarct size (% defect size as compared with the entire left ventricular sestamibi uptake), ejection fraction (EF, %), and summed difference score (SDS, sestamibi uptake by myocardium in stress minus sestamibi uptake in rest images as a marker of ischemia). Survival was determined by follow-up survey (median 6 years). Results:We identified 346 UMIs, 628 RMIs, and 4456 subjects without MI (No MI). As compared with RMI, UMI patients had lesser abnormalities on nuclear scans (p \u3c .0001 for all), including smaller infarct size (5.7% vs. 12.2%), higher EF (58% vs. 53%), and lesser ischemia (SDS; 3.9% vs. 2.7%). UMI prognosis was as poor as that of RMI (annual mortality rate 4.7% vs. 4.8% with No MI rate of 2.9%; p \u3c .001 for all comparisons), and this persisted after multivariate analysis. Infarct size quantification successfully risk-stratified ECG-UMI patients, but UMI patients continued to predict mortality even if the infarct size was 0%. Conclusions:Although UMI patients have lesser abnormalities on nuclear scans, ECG-based UMI continues to independently predict mortality, indicating the continuing relevance of ECG in clinical practice