Muscle fiber-type distribution predicts weight gain and unfavorable left ventricular geometry: a 19 year follow-up study

BACKGROUND: Skeletal muscle consists of type-I (slow-twitch) and type-II (fast-twitch) fibers, with proportions highly variable between individuals and mostly determined by genetic factors. Cross-sectional studies have associated low percentage of type-I fibers (type-I%) with many cardiovascular risk factors. METHODS: We investigated whether baseline type-I% predicts left ventricular (LV) structure and function at 19-year follow-up, and if so, which are the strongest mediating factors. At baseline in 1984 muscle fiber-type distribution (by actomyosin ATPase staining) was studied in 63 healthy men (aged 32–58 years). The follow-up in 2003 included echocardiography, measurement of obesity related variables, physical activity and blood pressure. RESULTS: In the 40 men not using cardiovascular drugs at follow-up, low type-I% predicted higher heart rate, blood pressure, and LV fractional shortening suggesting increased sympathetic tone. Low type-I% predicted smaller LV chamber diameters (P ≤ 0.009) and greater relative wall thickness (P = 0.034) without increase in LV mass (concentric remodeling). This was explained by the association of type-I% with obesity related variables. Type-I% was an independent predictor of follow-up body fat percentage, waist/hip ratio, weight gain in adulthood, and physical activity (in all P ≤ 0.001). After including these risk factors in the regression models, weight gain was the strongest predictor of LV geometry explaining 64% of the variation in LV end-diastolic diameter, 72% in end-systolic diameter, and 53% in relative wall thickness. CONCLUSION: Low type-I% predicts obesity and weight gain especially in the mid-abdomen, and consequently unfavourable LV geometry indicating increased cardiovascular risk

QTLs of factors of the metabolic syndrome and echocardiographic phenotypes: the hypertension genetic epidemiology network study

<p>Abstract</p> <p>Background</p> <p>In a previous study of the Hypertension Genetic Epidemiology Network (HyperGEN) we have shown that metabolic syndrome (MetS) risk factors were moderately and significantly associated with echocardiographic (ECHO) left ventricular (LV) phenotypes.</p> <p>Methods</p> <p>The study included 1,393 African Americans and 1,133 whites, stratified by type 2 diabetes mellitus (DM) status. Heritabilities of seven factor scores based on the analysis of 15 traits were sufficiently high to pursue QTL discovery in this follow-up study.</p> <p>Results</p> <p>Three of the QTLs discovered relate to combined MetS-ECHO factors of "blood pressure (BP)-LV wall thickness" on chromosome 3 at 225 cM with a 2.8 LOD score, on chromosome 20 at 2.1 cM with a 2.6 LOD score; and for "LV wall thickness" factor on chromosome 16 at 113.5 with a 2.6 LOD score in whites. The remaining QTLs include one for a "body mass index-insulin (BMI-INS)" factor with a LOD score of 3.9 on chromosome 2 located at 64.8 cM; one for the same factor on chromosome 12 at 91.4 cM with a 3.3 LOD score; one for a "BP" factor on chromosome 19 located at 67.8 cM with a 3.0 LOD score. A suggestive linkage was also found for "Lipids-INS" with a 2.7 LOD score located on chromosome 11 at 113.1 cM in African Americans. Of the above QTLs, the one on chromosome 12 for "BMI-INS" is replicated in both ethnicities, (with highest LOD scores in African Americans). In addition, the QTL for "LV wall thickness" on chromosome 16q24.2-q24.3 reached its local maximum LOD score at marker D16S402, which is positioned within the 5th intron of the <it>cadherin 13 </it>gene, implicated in heart and vascular remodeling.</p> <p>Conclusion</p> <p>Our previous study and this follow-up suggest gene loci for some crucial MetS and cardiac geometry risk factors that contribute to the risk of developing heart disease.</p

Prevalence of left ventricular diastolic dysfunction in European populations based on cross-validated diagnostic thresholds

BACKGROUND: Different diagnostic criteria limit comparisons between populations in the prevalence of diastolic left ventricular (LV) dysfunction. We aimed to compare across populations age-specific echocardiographic criteria for diastolic LV dysfunction as well as their correlates and prevalence. METHODS: We measured the E and A peaks of transmitral blood flow by pulsed wave Doppler and the e' and a' peaks of mitral annular velocities by tissue Doppler imaging (TDI) in 2 cohorts randomly recruited in Belgium (n = 782; 51.4% women; mean age, 51.1 years) and in Italy, Poland and Russia (n = 476; 55.7%; 44.5 years). RESULTS: In stepwise regression, the multivariable-adjusted correlates of the transmitral and TDI diastolic indexes were similar in the 2 cohorts and included sex, age, body mass index, blood pressure and heart rate. Similarly, cut-off limits for the E/A ratio (2.5th percentile) and E/e' ratio (97.5th percentile) in 338 and 185 reference subjects free from cardiovascular risk factors respectively selected from both cohorts were consistent within 0.02 and 0.26 units (median across 5 age groups). The rounded 2.5th percentile of the E/A ratio decreased by ~0.10 per age decade in these apparently healthy subjects. The reference subsample provided age-specific cut-off limits for normal E/A and E/e' ratios. In the 2 cohorts combined, diastolic dysfunction groups 1 (impaired relaxation), 2 (possible elevated LV filling pressure) and 3 (elevated E/e' and abnormally low E/A) encompassed 114 (9.1%), 135 (10.7%), and 40 (3.2%) subjects, respectively. CONCLUSIONS: The age-specific criteria for diastolic LV dysfunction were highly consistent across the study populations with an age-standardized prevalence of 22.4% vs. 25.1%

GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells

<p>Abstract</p> <p>Background</p> <p>Growth-differentiation factor-15 (GDF-15) is a stress-responsive, transforming growth factor-β-related cytokine, which has recently been reported to be elevated in serum of patients with idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to examine the expression and biological roles of GDF-15 in the lung of patients with pulmonary arterial hypertension (PAH).</p> <p>Methods</p> <p>GDF-15 expression in normal lungs and lung specimens of PAH patients were studied by real-time RT-PCR and immunohistochemistry. Using laser-assisted micro-dissection, GDF-15 expression was further analyzed within vascular compartments of PAH lungs. To elucidate the role of GDF-15 on endothelial cells, human pulmonary microvascular endothelial cells (HPMEC) were exposed to hypoxia and laminar shear stress. The effects of GDF-15 on the proliferation and cell death of HPMEC were studied using recombinant GDF-15 protein.</p> <p>Results</p> <p>GDF-15 expression was found to be increased in lung specimens from PAH patients, com-pared to normal lungs. GDF-15 was abundantly expressed in pulmonary vascular endothelial cells with a strong signal in the core of plexiform lesions. HPMEC responded with marked upregulation of GDF-15 to hypoxia and laminar shear stress. Apoptotic cell death of HPMEC was diminished, whereas HPMEC proliferation was either increased or decreased depending of the concentration of recombinant GDF-15 protein.</p> <p>Conclusions</p> <p>GDF-15 expression is increased in PAH lungs and appears predominantly located in vascular endothelial cells. The expression pattern as well as the observed effects on proliferation and apoptosis of pulmonary endothelial cells suggest a role of GDF-15 in the homeostasis of endothelial cells in PAH patients.</p

Heritability and major gene effects on left ventricular mass in the Chinese population: a family study

BACKGROUND: Genetic components controlling for echocardiographically determined left ventricular (LV) mass are still unclear in the Chinese population. METHODS: We conducted a family study from the Chin-San community, Taiwan, and a total of 368 families, 1145 subjects, were recruited to undergo echocardiography to measure LV mass. Commingling analysis, familial correlation, and complex segregation analysis were applied to detect component distributions and the mode of inheritance. RESULTS: The two-component distribution model was the best-fitting model to describe the distribution of LV mass. The highest familial correlation coefficients were mother-son (0.379, P < .0001) and father-son (0.356, P < .0001). Genetic heritability (h(2)) of LV mass was estimated as 0.268 ± 0.061 (P < .0001); it decreased to 0.153 ± 0.052 (P = .0009) after systolic blood pressure adjustment. Major gene effects with polygenic components were the best-fitting model to explain the inheritance mode of LV mass. The estimated allele frequency of the gene was 0.089. CONCLUSION: There were significant familial correlations, heritability and a major gene effect on LV mass in the population-based families

Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: The HyperGEN Study

<p>Abstract</p> <p>Background</p> <p>We conducted a genome-wide association study (GWAS) and validation study for left ventricular (LV) mass in the Family Blood Pressure Program – HyperGEN population. LV mass is a sensitive predictor of cardiovascular mortality and morbidity in all genders, races, and ages. Polymorphisms of candidate genes in diverse pathways have been associated with LV mass. However, subsequent studies have often failed to replicate these associations. Genome-wide association studies have unprecedented power to identify potential genes with modest effects on left LV mass. We describe here a GWAS for LV mass in Caucasians using the Affymetrix GeneChip Human Mapping 100 k Set. Cases (N = 101) and controls (N = 101) were selected from extreme tails of the LV mass index distribution from 906 individuals in the HyperGEN study. Eleven of 12 promising (<it>Q </it>< 0.8) single-nucleotide polymorphisms (SNPs) from the genome-wide study were successfully genotyped using quantitative real time PCR in a validation study.</p> <p>Results</p> <p>Despite the relatively small sample, we identified 12 promising SNPs in the GWAS. Eleven SNPs were successfully genotyped in the validation study of 704 Caucasians and 1467 African Americans; 5 SNPs on chromosomes 5, 12, and 20 were significantly (<it>P </it>≤ 0.05) associated with LV mass after correction for multiple testing. One SNP (rs756529) is intragenic within <it>KCNB1</it>, which is dephosphorylated by calcineurin, a previously reported candidate gene for LV hypertrophy within this population.</p> <p>Conclusion</p> <p>These findings suggest <it>KCNB1 </it>may be involved in the development of LV hypertrophy in humans.</p

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration