The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

Resting Heart Rate Is Not a Good Predictor of a Clustered Cardiovascular Risk Score in Adolescents: The HELENA Study

<div><p>Background</p><p>Resting heart rate (RHR) reflects sympathetic nerve activity a significant association between RHR and all-cause and cardiovascular mortality has been reported in some epidemiologic studies.</p><p>Methods</p><p>To analyze the predictive power and accuracy of RHR as a screening measure for individual and clustered cardiovascular risk in adolescents. The study comprised 769 European adolescents (376 boys) participating in the HELENA cross-sectional study (2006–2008) were included in this study. Measurements on systolic blood pressure, HOMA index, triglycerides, TC/HDL-c, VO₂máx and the sum of four skinfolds were obtained, and a clustered cardiovascular disease (CVD) risk index was computed. The receiver operating characteristics curve was applied to calculate the power and accuracy of RHR to predict individual and clustered CVD risk factors.</p><p>Results</p><p>RHR showed low accuracy for screening CVD risk factors in both sexes (range 38.5%–54.4% in boys and 45.5%–54.3% in girls). Low specificity’s (15.6%–19.7% in boys; 18.1%–20.0% in girls) were also found. Nevertheless, the sensitivities were moderate-to-high (61.4%–89.1% in boys; 72.9%–90.3% in girls).</p><p>Conclusion</p><p>RHR is a poor predictor of individual CVD risk factors and of clustered CVD and the estimates based on RHR are not accurate. The use of RHR as an indicator of CVD risk in adolescents may produce a biased screening of cardiovascular health in both sexes.</p></div

Abdominal musculature segmentation and surface prediction from CT using deep learning for sarcopenia assessment

International audiencePurpose :The purpose of this study was to build and train a deep convolutional neural networks (CNN) algorithm to segment muscular body mass (MBM) to predict muscular surface from a two-dimensional axial computed tomography (CT) slice through L3 vertebra.Materials and methods :An ensemble of 15 deep learning models with a two-dimensional U-net architecture with a 4-level depth and 18 initial filters were trained to segment MBM. The muscular surface values were computed from the predicted masks and corrected with the algorithm's estimated bias. Resulting mask prediction and surface prediction were assessed using Dice similarity coefficient (DSC) and root mean squared error (RMSE) scores respectively using ground truth masks as standards of reference.Results :A total of 1025 individual CT slices were used for training and validation and 500 additional axial CT slices were used for testing. The obtained mean DSC and RMSE on the test set were 0.97 and 3.7 cm2 respectively.Conclusion :Deep learning methods using convolutional neural networks algorithm enable a robust and automated extraction of CT derived MBM for sarcopenia assessment, which could be implemented in a clinical workflow

Final sample size flowchart.

<p>*Missing data for accelerometry datas.</p

Accuracy of resting heart rate in screening of individual and clustered cardio-metabolic risk factors in adolescents from HELENA study.

<p>CI 95% = confidence interval 95%; SE = Standard error;HDLc = High-density lipoprotein cholesterol; TC = total cholesterol.</p><p>Accuracy of resting heart rate in screening of individual and clustered cardio-metabolic risk factors in adolescents from HELENA study.</p

Association between resting heart rate and individual and clustered cardio-metabolic risk factors in adolescents from HELENA study.

<p>CI 95% = confidence interval 95%; SE = Standard Error; HDLc = High-density lipoprotein cholesterol; TC = total cholesterol.</p><p>Association between resting heart rate and individual and clustered cardio-metabolic risk factors in adolescents from HELENA study.</p

Socioeconomically disadvantaged groups and metabolic syndrome in European adolescents: The HELENA study

The present paper was presented as a poster in the 13th European Nutrition Conference in Dublin (Ireland).[Purpose]: Psychosocial stressors derived from socioeconomic disadvantages in adolescents can result in higher risk of metabolic syndrome (MetS). We aimed to examine whether socioeconomic disadvantages were associated with MetS independent of lifestyle and whether there was a dose-response relationship between the number of cumulated socioeconomic disadvantages and risk of MetS.[Methods]: This study included 1,037 European adolescents (aged 12.5–17.5 years). Sociodemographic variables and lifestyle were assessed by self-reported questionnaires. Disadvantaged groups included adolescents with low-educated parents, low family affluence, migrant origin, unemployed parents, and nontraditional families. MetS risk score was calculated as the sum of sex- and age-specific z-scores of waist circumference, blood pressure, lipids, and insulin resistance. Linear mixed-effects models adjusted for sex, age, pubertal status, and lifestyle were used to study the association between social disadvantages and MetS risk score.[Results]: Adolescents with low-educated mothers showed a higher MetS score (.54 [.09–.98]; β estimate and 99% confidence interval) compared to those with high-educated mothers. Adolescents who accumulated more than three disadvantages (.69 [.08–1.31]) or with missing information on disadvantages (.72 [.04–1.40]) had a higher MetS risk score compared to nonsocioeconomically disadvantaged groups. Stronger associations between socioeconomic disadvantages and MetS were found in male than in female adolescents.[Conclusions]: Adolescents with low-educated mothers or with more than three socioeconomic disadvantages had a higher MetS risk, independent of lifestyle, potentially due to higher psychosocial stress exposure. Policy makers should focus on improving low-educated familiesa and more disadvantaged families' knowledge on nutrition and physical activity to help them cope better with stress.The HELENA Study was conducted with the financial support of the European Community sixth RTD Framework Programme (Contract FOOD-CT-2005-007034).Peer reviewe

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation