Showing papers by "Marcus Dörr published in 2020"
TL;DR: Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension.
Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
326 citations
University of Bordeaux1, Imperial College London2, Tohoku University3, University of Texas at Austin4, University of Texas Health Science Center at Houston5, Boston University6, Erasmus University Rotterdam7, University of Washington8, Osaka University9, University of Tokyo10, Greifswald University Hospital11, University of Pennsylvania12, University of Michigan13, Murdoch University14, Medical University of Graz15, Johns Hopkins University School of Medicine16, King's College London17, University of Edinburgh18, University of California, Davis19, Leiden University20, Leiden University Medical Center21, Delft University of Technology22, Menzies Research Institute23, University of Tasmania24, University of Alabama at Birmingham25, Rush University Medical Center26, University of Pittsburgh27, University of Queensland28, University of Sydney29, Mayo Clinic30, University of Minnesota31, Los Angeles Biomedical Research Institute32, University of New South Wales33, University of Glasgow34, German Center for Neurodegenerative Diseases35, Kaiser Permanente36, Royal Melbourne Hospital37, St George's Hospital38, Pasteur Institute of Lille39, French Institute of Health and Medical Research40, Neuroscience Research Australia41, Kyoto University42, Broad Institute43, Columbia University Medical Center44, University of Mississippi Medical Center45, National Institute for Health Research46, Queen Mary University of London47, University of Ioannina48, Monash University49, Johns Hopkins University50, University of Oxford51, University of Iceland52, National Institutes of Health53, McGill University54
TL;DR: Insight is provided into BP-independent biological pathways underlying SVD and potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials is suggested.
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
83 citations
TL;DR: It is shown that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation, and these findings advance the understanding of the polygenic basis of cardiac conduction, and the genetic relationship betweenPR interval duration and cardiovascular disease.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
45 citations
TL;DR: It is suggested that cardiorespiratory fitness might contribute to improved brain health and might, therefore, decelerate pathology-specific GM decrease.
44 citations
TL;DR: A link between ferritin and T2DM and MetS, which might be partially explained by hepatic dysfunction, is suggested.
14 citations
Greifswald University Hospital1, Goethe University Frankfurt2, University of Cambridge3, University of Eastern Finland4, University of Oslo5, Oslo University Hospital6, Tulane University7, University of Milan8, Utrecht University9, University Medical Center Groningen10, University College London11, University Hospital of Basel12, Technische Universität München13, University of Southern Denmark14, University of Paris15, Erasmus University Rotterdam16, University of Bern17, University Hospital of North Norway18, Tufts University19, University of Miami20, Maastricht University Medical Centre21, University of Sydney22, Aristotle University of Thessaloniki23, RMIT University24, University of Edinburgh25, Uppsala University26, French Institute of Health and Medical Research27, Columbia University28, Erasmus University Medical Center29, Sahlgrenska University Hospital30, Harvard University31
TL;DR: In this paper, an individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and high-density cholesterol with future cardiovascular disease risk in 13 prospective cohort studies.
Abstract: Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.
13 citations
Broad Institute1, Fred Hutchinson Cancer Research Center2, Johns Hopkins University School of Medicine3, University of Copenhagen4, Boston University5, Greifswald University Hospital6, Leiden University Medical Center7, UCLA Medical Center8, University of California, Los Angeles9, University of Washington10, Ludwig Maximilian University of Munich11, University of Groningen12, Utrecht University13, Maastricht University14, Queen Mary University of London15, National Institute for Health Research16, University of Glasgow17, Erasmus University Medical Center18, Kaiser Permanente19, University of Utah20, Emory University21, Stanford University22, University of Oxford23, University College London24, Frederiksberg Hospital25
TL;DR: Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF, and underscore the shared mechanisms of atrial conduction and AF.
Abstract: Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF)....
12 citations
TL;DR: The determinants for higher PA and lower PI differed between males and females, and strategies for improving PA and decrease PI are likely different with respect to sex and should take individual factors (e.g. age, BMI).
Abstract: BACKGROUND Low levels of physical activity (PA) and high levels of physical inactivity (PI) are associated with higher mortality and cardiovascular diseases. Higher age is associated with a decrease of PA, only 2.4-29% of ≥60 year-olds achieve the PA times recommended by WHO. The aim of this study was to identify levels of and determinants for moderate PA, overall PA and PI in a sample of individuals aged ≥65 years. METHODS We analyzed baseline data from an intervention-study aiming to increase PA and decrease PI by automatically generated feedback letters to objectively measured PA and PI. Recruitment was multimodal including re-contacting participants of previous studies and advertisements in regional public buses and newspapers. At baseline, participants wore an accelerometer over a period of 7 consecutive days. PA was categorized using cut-points suggested by Freedsoon 1998 in light, moderate and vigorous physical intensity as well as physical inactivity. Potential determinants (self-efficacy, education) were measured by questionnaires or in a physical examination (BMI). Multiple linear regression models were fitted to identify determinants for PA and PI. RESULTS N = 199 persons (mean age 71.0 years (SD 4.9), 59.3% female) participated in the study. The weekly amount of overall PA for men was on average 1,821 minutes (SD 479.1), for women on average 1,929 minutes (SD 448.8). 79.7% of the women and 72.8% of the men achieved the WHO recommendation of 30 minutes moderate PA/day at baseline. The time of PI during the observation time period of 7 days was on average 4,057 minutes in men and 3,973 minutes in women. In males, age was found to be a significant negative determinant for overall PA (p = 0.002) and for moderate PA (p<0.001). Higher education was positively associated with higher levels of overall PA (p = 0.013) and moderate PA (p = 0.06) in men. BMI was a significant negative determinant for overall PA both in men (p = 0.039) and women (p = 0.032) as well as for moderate PA for women (p = 0.009). Only in women, not in men, self-efficacy was to be a significant positive determinant for overall PA (p = 0.020) as well as negatively associated with PI (p = 0.006). DISCUSSION The participants of our study showed high levels of PA. This is likely due to selection bias in this convenience sample. However, also levels of PI are very high and those correspond with average levels in the German population. The determinants for higher PA and lower PI differed between males and females. Thus, strategies for improving PA and decrease PI are likely different with respect to sex and should take individual factors (e.g. age, BMI) into account. TRIAL REGISTRATION NUMBER DRKS00010410 Date: 17 May 2017.
12 citations
01 Jan 2020
10 citations
TL;DR: LD provided more information for all‐cause mortality compared with cIMT in a large population‐based sample and CIMT weakened all-cause mortality prediction compared with the LD model.
Abstract: Background Common carotid intima–media thickness (cIMT) is a biomarker for subclinical atherosclerosis and is associated with all‐cause as well as cardiovascular mortality. Higher cIMT is accompani...
9 citations
Greifswald University Hospital1, Augsburg College2, Leibniz Institute for Neurobiology3, University of Bremen4, University of Münster5, University of Lübeck6, University of Regensburg7, University Medical Center Freiburg8, Martin Luther University of Halle-Wittenberg9, Hochschule Hannover10, Charité11, University of Düsseldorf12, University of Duisburg-Essen13, University of Kiel14, Leipzig University15
TL;DR: The NAKO erhebt von allen Teilnehmenden selbst berichtete, ärztlich diagnostizierte kardiovaskuläre and metabolische Erkrankungen and stellt damit eine Datenressource für weitergehende kardiometabolische Forschungsfragestellungen dar.
Abstract: Aus der NAKO Gesundheitsstudie, der grosten deutschen bevolkerungsbasierten Studie zur Gesundheit, liegen die Daten zu selbst berichteten kardiovaskularen und metabolischen Erkrankungen der ersten ca. 100.000 Teilnehmenden vor. Beschreibung der Methoden zur Erhebung sowie Berechnung der Haufigkeit kardiovaskularer und metabolischer Erkrankungen in der NAKO. 101.806 Teilnehmende (20–75 Jahre, 46 % Manner) aus 18 bundesweiten Studienzentren wurden in einem computergestutzten, standardisierten personlichen Interview gebeten, anhand einer vorgegebenen Liste anzugeben, welche Erkrankungen bei ihnen jemals arztlich diagnostiziert wurden, darunter auch kardiovaskulare und metabolische Erkrankungen. Fur Letztere wurden deren geschlechtsspezifische relative Haufigkeiten berechnet und diese mit Referenzzahlen verglichen. Bezogen auf die kardiovaskularen Erkrankungen berichteten 3,5 % der Manner und 0,8 % der Frauen, jemals einen Herzinfarkt diagnostiziert bekommen zu haben, 4,8 % bzw. 1,5 % eine Angina pectoris, 3,5 % bzw. 2,5 % eine Herzinsuffizienz, 10,1 % bzw. 10,4 % Herzrhythmusstorungen, 2,7 % bzw. 1,8 % eine Claudicatio intermittens und 34,6 % bzw. 27,0 % eine arterielle Hypertonie. Die Haufigkeit berichteter diagnostizierter metabolischer Erkrankungen lag bei 8,1 % bzw. 5,8 % fur Diabetes mellitus, bei 28,6 % bzw. 24,5 % fur Hyperlipidamie, bei 7,9 % bzw. 2,4 % fur Gicht und bei 10,1 % bzw. 34,3 % fur Schilddrusenerkrankungen. Die beobachteten Haufigkeiten lagen insgesamt etwas niedriger als Vergleichsdaten fur Deutschland. Die NAKO erhebt von allen Teilnehmenden selbst berichtete, arztlich diagnostizierte kardiovaskulare und metabolische Erkrankungen und stellt damit eine Datenressource fur weitergehende kardiometabolische Forschungsfragestellungen dar.
University of Texas Health Science Center at Houston1, National Institutes of Health2, University of Washington3, Erasmus University Medical Center4, Washington University in St. Louis5, Johns Hopkins University School of Medicine6, Brigham and Women's Hospital7, University of Iceland8, Los Angeles Biomedical Research Institute9, Baylor College of Medicine10, Imperial College London11, Greifswald University Hospital12, Harvard University13
TL;DR: One known locus (ANGPTL4), four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation, and no loci were significantly associated with all-cause mortality following a MI or CHD event.
Abstract: Background
Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope
that common variants provide, we focused our investigation on low-frequency and rare
sequence variations primarily residing in coding regions of the genome.
Methods and results
Using samples of individuals of European ancestry from ten cohorts within the Cohorts for
Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both crosssectional and prospective analyses were conducted to examine associations between
genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and allcause mortality following these events. For prevalent events, a total of 27,349 participants of
European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were
used. For incident cases, a total of 55,736 participants of European ancestry were included
(3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause
deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis
of all-cause mortality. Single variant and gene-based analyses were performed separately
in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant
(rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10−7
). We conducted gene-based burden tests for
genes with a cumulative minor allele count (cMAC) � 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent
Brigham and Women's Hospital1, Leiden University Medical Center2, Washington University in St. Louis3, University of Regensburg4, National Institutes of Health5, Harvard University6, University of Copenhagen7, University of Texas Health Science Center at Houston8, University of São Paulo9, University of Washington10, Erasmus University Rotterdam11, Boston University12, Tulane University13, Duke University14, Pennington Biomedical Research Center15, University of Mississippi Medical Center16, University of North Carolina at Chapel Hill17, University of Tartu18, Northwestern University19, University of Edinburgh20, University of Groningen21, Queen Mary University of London22, Wake Forest University23, Helmholtz Zentrum München24, Vanderbilt University Medical Center25, University of Adelaide26, University of Maryland, Baltimore27, Johns Hopkins University School of Medicine28, University of Texas Health Science Center at San Antonio29, University of Minnesota30, Kaiser Permanente31, University of Alabama at Birmingham32, Los Angeles Biomedical Research Institute33, Erasmus University Medical Center34, Jackson State University35, Columbia University36, UCLA Medical Center37, George Washington University38, University of Iowa39, University of Eastern Finland40, University of Mainz41, Ludwig Maximilian University of Munich42, Greifswald University Hospital43, Sir Charles Gairdner Hospital44, University of Iceland45, University of Tennessee Health Science Center46, Fred Hutchinson Cancer Research Center47, Case Western Reserve University48, University Medical Center Groningen49, Public Health Research Institute50, University of Southern California51
TL;DR: It is indicated that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
Abstract: Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups using 1 degree of freedom (1df) interaction and 2df joint tests. Primary multi-ancestry analyses in 62,969 individuals in stage 1 identified 3 novel loci that were replicated in an additional 59,296 individuals in stage 2, including rs7955964 (FIGNL2/ANKRD33) showing significant 1df interactions with long sleep duration and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) showing significant 1df interactions with short sleep duration. Secondary ancestry-specific two-stage analyses and combined stage 1 and 2 analyses additionally identified 23 novel loci that need external replication, including 3 and 5 loci showing significant 1df interactions with long and short sleep duration, respectively. Multiple genes mapped to our 26 novel loci have known functions in sleep-wake regulation, nervous and cardiometabolic systems. We also identified new gene by long sleep interactions near five known BP loci (≤1Mb) including NME7, FAM208A, MKLN1, CEP164, and RGL3/ELAVL3. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
TL;DR: The IMAD trial investigates whether the removal of α1AR-AABs by a 5-day IA procedure has a positive effect (improvement or non-deterioration) on changes of hemodynamic, cognitive, vascular and metabolic parameters in patients with suspected Alzheimer's clinical syndrome within a one-year follow-up period.
Abstract: Background: agonistic autoantibodies (agAABs) against G protein-coupled receptors (GPCR) have been linked to cardiovascular disease In dementia patients, GPCR-agAABs against the α1- and s2-adrenoceptors (α1AR- and s2AR) were found at a prevalence of 50% Elimination of agAABs by immunoadsorption (IA) was successfully applied in cardiovascular disease The IMAD trial (Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor) investigates whether the removal of α1AR-AABs by a 5-day IA procedure has a positive effect (improvement or non-deterioration) on changes of hemodynamic, cognitive, vascular and metabolic parameters in patients with suspected Alzheimer’s clinical syndrome within a one-year follow-up period Methods: the IMAD trial is designed as an exploratory monocentric interventional trial corresponding to a proof-of-concept phase-IIa study If cognition capacity of eligible patients scores 19–26 in the Mini Mental State Examination (MMSE), patients are tested for the presence of agAABs by an enzyme-linked immunosorbent assay (ELISA)-based method, followed by a bioassay-based confirmation test, further screening and treatment with IA and intravenous immunoglobulin G (IgG) replacement We aim to include 15 patients with IA/IgG and to complete follow-up data from at least 12 patients The primary outcome parameter of the study is uncorrected mean cerebral perfusion measured in mL/min/100 gr of brain tissue determined by magnetic resonance imaging with arterial spin labeling after 12 months Conclusion: IMAD is an important pilot study that will analyze whether the removal of α1AR-agAABs by immunoadsorption in α1AR-agAAB-positive patients with suspected Alzheimer’s clinical syndrome may slow the progression of dementia and/or may improve vascular functional parameters
TL;DR: In this study, CRF and handgrip strength were not associated with AMD, and these associations were not modified by age, sex, smoking, body mass index and diabetes.
Abstract: Aim To assess whether cardiorespiratory fitness (CRF) and handgrip strength, two objective markers of physical fitness, are associated with age-related macular degeneration (AMD). Methods We analysed cross-sectional data from the population-based Study of Health in Pomerania (2008–2012) including 1173 adult men and women aged 20–79 years. Fundus photography of the central retina was recorded with a non-mydriatic camera, and images were graded according to an established clinical AMD classification scale by an experienced reader. CRF was measured using peak oxygen uptake (peakVO2), oxygen uptake at the anaerobic threshold (VO2@AT), and maximum power output (Wmax) from standardised cardiopulmonary exercise testing on a bicycle ergometer according to a modified Jones protocol. Handgrip strength was assessed using a handheld dynamometer. Adjusted prevalence ratios (PR) for the associations of peakVO2, VO2@AT, Wmax and handgrip strength with AMD were derived from multivariable Poisson regression models. Results PeakVO2, VO2@AT, Wmax and handgrip strength were not associated with AMD. Adjusted PR for AMD associated with a 1-SD increment in peakVO2, VO2@AT, Wmax and handgrip strength were 1.05 (95% CI 0.82 to 1.34), 0.96 (95% CI 0.78 to 1.18), 1.10 (95% CI 0.86 to 1.41) and 1.01 (95% CI 0.79 to 1.30), respectively. These associations were not modified by age, sex, smoking, body mass index and diabetes. Estimates in sensitivity analysis for confounding, selection bias and missing data were similar. Conclusion In our study, CRF and handgrip strength were not associated with AMD. Nevertheless, longitudinal studies with bigger sample sizes are needed to furtherly examine these associations.
TL;DR: The study indicates that diabetes in the family might not be a relevant risk factor for the incidence of CVD, and confirmed the relationship between a parental history of MI or stroke and the onset ofCVD.
Abstract: Since family history of diabetes is a very strong risk factor for type 2 diabetes, which is one of the most important risk factors for cardiovascular disease (CVD), it might be also useful to assess the risk for CVD. Therefore, we aimed to investigate the relationship between a familial (parents and siblings) history of diabetes and the risk of incident CVD. Data from four prospective German cohort studies were used: EPIC-Potsdam study (n = 26,054), CARLA study (n = 1,079), SHIP study (n = 3,974), and KORA study (n = 15,777). A multivariable-adjusted Cox regression was performed to estimate associations between familial histories of diabetes, myocardial infarction or stroke and the risk of CVD in each cohort; combined hazard ratios (HRMeta) were derived by conducting a meta-analysis. The history of diabetes in first-degree relatives was not related to the development of CVD (HRMeta 0.99; 95% CI 0.88–1.10). Results were similar for the single outcomes myocardial infarction (MI) (HRMeta 1.07; 95% CI 0.92–1.23) and stroke (HRMeta 1.00; 95% CI 0.86–1.16). In contrast, parental history of MI and stroke were associated with an increased CVD risk. Our study indicates that diabetes in the family might not be a relevant risk factor for the incidence of CVD. However, the study confirmed the relationship between a parental history of MI or stroke and the onset of CVD.
TL;DR: Findings on the association between cardiorespiratory fitness (CRF) and moderate-to-vigorous physical activity (MVPA) may be distorted if patterns of accumulated MVPA over a week exist but are ignored.
Abstract: Findings on the association between cardiorespiratory fitness (CRF) and moderate-to-vigorous physical activity (MVPA) may be distorted if patterns of accumulated MVPA over a week exist but are ignored. Our aim was to identify MVPA patterns and to associate them to CRF. Two hundred twenty-four 40–75-year-old adults wore accelerometers for 7 days. CRF was measured by peak oxygen uptake (V′O2,peak) assessed on a cycle ergometer via standardized cardiopulmonary exercise testing. Growth mixture modeling indicated four MVPA patterns: “low/stable” (57%, Mean MVPA time (M) = 21 min day−1), “medium/stable” (20%, M = 46 min day−1), “medium/weekend high” (14%, M = 47 min day−1), and “high/weekend low” (9%, M = 71 min day−1). V′O2,peak was higher for persons with “high/weekend low” and “medium/weekend high” patterns compared to “low/stable” and “medium/stable” (p values < 0.001). The same total amount of MVPA may have greater benefit if performed on fewer days during the week but with a longer duration than if performed every day but with a lower duration.
TL;DR: Heart failure was the most frequent disease-related reason for hospitalizations in Germany in 2017, again with marked differences between East and West Germany, and hospitalization rate due to HF in 2017 was higher in the East than in West Germany.
Abstract:
Heart failure (HF) is one of the most common diseases in the adult population with a prevalence of about 4% and a steady increase due to demographic and medical developments. In Germany, it is the most common primary diagnosis for inpatient treatment. Little was known so far about regional differences.
We retrospectively analyzed aggregated administrative data on the number and characteristics of in-patients in Germany for the period 2000 to 2017, obtained from the German Federal Health Monitoring, an annual complete census of in-patient routine data. The number and duration of hospitalizations as well as hospital mortality with the main diagnosis “I50” (HF) were analyzed over time with a special emphasis on regional differences between the federal states.
The number of HF-related hospitalizations in Germany increased continuously: from 239,694 in 2000 to 464,724 cases in 2017 (+94%). This increase was more pronounced in East Germany than in West Germany (119% vs. 88%) [Figure 1]. The proportion of HF-related hospitalizations in relation to the total number of hospitalizations rose from 1.4% to 2.3% (relative increase +67%) in whole Germany. Accordingly, HF was the most frequent disease-related reason for hospitalizations in Germany in 2017, again with marked differences between East and West Germany (relative increase +96% vs. +61%). Similar differences were found after age-standardization: hospitalization rate due to HF in 2017 was higher in the East than in West Germany (609 vs. 490 cases per 100,000 population), reflecting a major increase compared to year 2000 (49% vs. 36%).
Despite a continuous decrease in the length of stay (from 14.3 to 10.2 days; –29%), the total number of HF-related hospital days in Germany increased by 38% (4.72 million hospital days in 2017). In East Germany, the number of hospital days increased by 51%, in West Germany by 35% [Figure 1].
The in-hospital mortality rate of HF patients remained unchanged between 2000 and 2017 at about 38,000 cases per year, corresponding to 8.2% in 2017 (East Germany 8.4%, West Germany 8.2%). With a contribution of 8.9% of all hospital deaths, HF constituted the leading cause in 2017. Again, this proportion was higher in East compared to West Germany throughout the entire observation period (2017 10.8% vs. 8.5%). The rate of HF-related in-hospital deaths was also higher in East than in West Germany (2017: 65 vs. 43 per 100,000 population) [Figure 1].
HF continues to be the most common cause of hospitalization and hospital deaths in Germany. HF-related morbidity and mortality parameters are higher in East than in West Germany. Possible explanations for this finding are differences in the prevalence of risk factors and the structure of patient care between these regions. A more detailed understanding of these striking discrepancies 30 years after the German reunification requires further investigations.
Figure 1
Type of funding source: None
Leibniz Institute for Neurobiology1, Greifswald University Hospital2, Augsburg College3, Robert Koch Institute4, University of Bremen5, University of Münster6, Heidelberg University7, University of Düsseldorf8, Martin Luther University of Halle-Wittenberg9, University of Regensburg10, University of Freiburg11, Charité12, University of Würzburg13, University of Kiel14, Leipzig University15, Ludwig Maximilian University of Munich16
TL;DR: The current results show that using the second blood pressure measurement should be recommended for scientific analyses of GNC data, and this value leads to higher estimated hypertension frequencies.
Abstract: Background. Arterial hypertension is an important risk factor for cardiovascular diseases. Epidemiological studies typically perform three consecutive blood pressure measurements. The first measurement is discarded in subsequent analyses, as this value may be strongly affected by previous activities. Due to time constraints the German National Cohort (GNC NAKO) performed only two blood pressure measurements. Objectives. The present analysis examined the possible effects of methodological differences in blood pressure measurement by comparing the first 101,816 GNC participants (two blood pressure measurements) with those of five German population-based studies (three measurements). Materials andmethods. Blood pressure data from participants aged 20 to 79 years from the GNC, the German Health Interview and Examination Survey for Adults by the Robert Koch Institute (DEGS1), and four regional population-based cohort studies (CARLA, HNR, KORA, SHIP) were used to calculate ageand sex-specificmean blood pressure values and hypertension frequencies based on the second blood pressure measurement, the arithmetic mean of the first and second value and of the second and third (the latter not available in the GNC). Results. The mean blood pressure values of the two most recent studies (GNC, DEGS1) were very similar and lower than in the other studies. The difference of the second measurement and the mean of second and third measurement was small (maximum mean difference: 1.5mmHg systolic blood pressure), but leads to higher estimated hypertension frequencies. Conclusions. The current results show that using the second blood pressure measurement should be recommended for scientific analyses of GNC data.
TL;DR: It is suggested that sex and cardiometabolic risk factors moderate mere-measurement effects on PA and ST and researchers and practitioners using mere measurement for prevention purposes may address PA andST according to these individual characteristics.
Abstract: Participation in an assessment may change health behavior. This “mere-measurement effect” may be used for prevention purposes. However, little is known about whether individuals’ characteristics moderate the effect. The objective was to explore whether changes of physical activity (PA) and sedentary time (ST) after a cardiovascular assessment depend on sociodemographic variables and cardiometabolic risk factors. A sample of n = 175 adults aged 40 to 65 received baseline assessment including self-administered PA and ST questionnaires and standardized measurement of blood pressure, waist circumference, and blood parameters. After 5 weeks, participants again reported PA and ST without any prior treatment or intervention. Linear regression models were used to analyze the dependence of five-week changes in PA and ST on baseline sociodemographic and cardiometabolic variables. Men increased transport-related PA more than women (b = 9.3 MET-hours/week, P = .031). Men with higher triglycerides increased transport-related PA less than men with lower triglycerides (b = − 5.6 MET-hours/week, P = .043). Men with higher systolic blood pressure reduced ST more than those with lower systolic blood pressure (b = − 35.7 min/week, P = .028). However, this linear association ceased to exist at a level of approximately 145 mmHg (b of squared association = 1.0, P = .080). A similar relationship was found for glycated hemoglobin and ST. The findings suggest that sex and cardiometabolic risk factors moderate mere-measurement effects on PA and ST. Researchers and practitioners using mere measurement for prevention purposes may address PA and ST according to these individual characteristics. ClinicalTrials.govNCT02990039. Registered 7 December 2016. Retrospectively registered.
01 Jan 2020
TL;DR: Current data suggest that this experimental treatment option may be a promising novel approach for patients suffering from dilated cardiomyopathy with serum cardiac antibodies, but evidence from a placebo-controlled multicentre study is still needed.
Abstract: Myocardial inflammation is one of the leading causes of dilated cardiomyopathy. Thereby abnormalities of the cellular and humoral immune system play a crucial role in the development and disease progression leading to heart failure. Many experimental and clinical studies suggest that disturbances of the humoral immune system involving the production of circulating cardiac antibodies are a key factor for the deterioration of cardiac function. Elimination of such pathogenic antibodies by immunoadsorption results not only in an improvement of cardiac function but also decreases myocardial inflammation. Current data suggest that this experimental treatment option may be a promising novel approach for patients suffering from dilated cardiomyopathy with serum cardiac antibodies, but evidence from a placebo-controlled multicentre study is still needed.
TL;DR: The lower O2 requirement when running with BWS may help untrained individuals to adapt to an exercise regimen, and a significant correlation between HR and RPE independent of BWS is identified.
Abstract: Exercise reduces the future cardiometabolic disease risk. However, not everyone can participate in routine physical activity because of obesity or orthopedic impairments. Body weight-supported (BWS) exercise may be an option for these individuals. Unfortunately, very little data are available with regard to BWS running in untrained healthy individuals. Yet, this information is important to assess the potential use of lower-body positive pressure (LBPP) treadmill running for the prevention of cardiometabolic disease. Twenty healthy but untrained participants (10 females, mean age 31.5 yr) were included in this study. Participants completed two exercise tests (one with 100% and one with 60% body wt) in randomized order on a LBPP treadmill. Expired gas data and heart rate (HR) were collected continuously. Blood lactate, blood pressure (BP), pulse wave velocity (PWV), and rating of perceived exertion (RPE) were measured during a 2-min break after each stage. Oxygen uptake increased significantly independent of BWS but was lower with BWS. Furthermore, we identified a significant correlation between HR and RPE independent of BWS. BP and PWV showed a large heterogeneity in response to BWS. The lower O2 requirement when running with BWS may help untrained individuals to adapt to an exercise regimen. Future research needs to explore the heterogenetic response of blood pressure and pulse wave velocity to LBPP BWS between individuals.NEW & NOTEWORTHY Lower-body positive pressure body weight-supported exercise has a lower metabolic and cardiovascular demand. Furthermore, heart rate and rating of perceived exertion are highly correlated independent of body weight support. Our data support the further examination of lower-body positive pressure exercise training for cardiovascular disease risk groups.
Institute of Chartered Accountants of Nigeria1, University of Paris2, Utrecht University3, Greifswald University Hospital4, Charité5, Medical University of Vienna6, University of Regensburg7, University of Pennsylvania8, National Institutes of Health9, National University of Singapore10, Children's Hospital of Philadelphia11, Imperial College London12, Ludwig Maximilian University of Munich13, Technische Universität München14, University of Mainz15, Brigham and Women's Hospital16, Harvard University17, Heidelberg University18, French Institute of Health and Medical Research19, University of Lübeck20, University of Bordeaux21, Université Paris-Saclay22, Swedish University of Agricultural Sciences23, Honda24, Universidad Francisco de Vitoria25, University College London26
TL;DR: In silico annotation and functional 4C-sequencing analysis on iPSC-derived cardiomyocytes strongly suggest SLC6A6 as the most likely DCM gene at the 3p25.1 locus, and SMARCB1 appears as the strongest one at the 22q11.23 locus.
Abstract: Summary We present the results of the largest genome wide association study (GWAS) performed so far in dilated cardiomyopathy (DCM), a leading cause of systolic heart failure and cardiovascular death, with 2,719 cases and 4,440 controls in the discovery population. We identified and replicated two new DCM-associated loci, one on chromosome 3p25.1 (lead SNP rs62232870, p = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication step, respectively) and the second on chromosome 22q11.23 (lead SNP rs7284877, p = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication step, respectively) while confirming two previously identified DCM loci on chromosome 10 and 1, BAG3 and HSPB7. The genetic risk score constructed from the number of lead risk-alleles at these four DCM loci revealed that individuals with 8 risk-alleles were at a 27% increased risk of DCM compared to individuals with 5 risk alleles (median of the referral population). We estimated the genome wide heritability at 31% ± 8%. In silico annotation and functional 4C-sequencing analysis on iPSC-derived cardiomyocytes strongly suggest SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine and beta-alanine transporter whose involvement in myocardial dysfunction and DCM is supported by recent observations in humans and mice. Although less easy to discriminate the better candidate at the 22q11.23 locus, SMARCB1 appears as the strongest one. This study provides both a better understanding of the genetic architecture of DCM and new knowledge on novel biological pathways underlying heart failure, with the potential for a therapeutic perspective.
01 Jan 2020
TL;DR: Higher levels of physical activity (PA) and cardiorespiratory fitness (CRF) may be used as a treatment to prevent many of these cardiometabolic diseases and thereby lower all-cause and cause-specific mortality independent of patient population.
Abstract: Cardiovascular diseases (CVD) and cardiometabolic diseases like Type 2 Diabetes Mellitus (T2DM) are the main driver of morbidity and mortality worldwide. Sedentary behavior (physical inactivity) or, in other words, the lack of regular exercise causes many cardiometabolic diseases and increases the risk for all-cause and cause-specific mortality. Higher levels of physical activity (PA) and cardiorespiratory fitness (CRF) may be used as a treatment to prevent many of these cardiometabolic diseases and thereby lower all-cause and cause-specific mortality independent of patient population. Abnormally high levels of PA may have adverse consequences and do increase the risk for atrial fibrillation. In the general population only very few individuals will reach these levels. However, at least for cardiologists working with elite athletes, an increased CVD risk may be of concern. Even though the terms PA and CRF are sometimes used interchangeably, both parameters are not the same. And even though PA and CRF act through different biological mechanisms, there is a large amount of evidence that, independent of an individual's health status (e.g. blood lipid levels, blood pressure and smoking as well as dietary habits), higher levels of PA and CRF improve the overall CVD risk profile. With regards to occupational PA, there is sufficient evidence that leisure time and sports related PA are inversely associated with all-cause and cause-specific mortality, but the relationship between occupational PA on mortality, on the other hand, is currently unclear.
University of Texas Health Science Center at Houston1, National Institutes of Health2, University of Washington3, Erasmus University Medical Center4, Washington University in St. Louis5, Johns Hopkins University School of Medicine6, Brigham and Women's Hospital7, University of Iceland8, Los Angeles Biomedical Research Institute9, Human Genome Sequencing Center10, Imperial College London11, Greifswald University Hospital12, Harvard University13
TL;DR: This study confirmed previously reported loci influencing heart disease risk, and one single variant and three genes associated with MI and CHD were newly identified and warrant future investigation.
Abstract: Background Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To better understand etiological pathways that might lead to discovery of new treatments or prevention strategies, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome while also exploring associations with common variants. Methods and Results Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR=1.80, 95% confidence interval: 1.43, 2.27; P=7.12 × 10-7). Three common variants, rs9349379 in PHACTR1, and rs1333048 and rs4977574 in the 9p21 region, were significantly associated with prevalent CHD. Four common variants (rs4977574, rs10757278, rs1333049, and rs1333048) within the 9p21 locus were significantly associated with incident MI. We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) Conclusion This study confirmed previously reported loci influencing heart disease risk, and one single variant and three genes associated with MI and CHD were newly identified and warrant future investigation.
TL;DR: The major findings of the study were that a high PTAS capability was associated with a significantly larger right ventricular contractile reserve, a larger pulmonary vascular reserve and an enhanced maximal exercise capacity, and significant interindividual and sex differences have been reported with regard to theseright ventricular adaptations to endurance exercise.
Abstract: For a long time, the right ventricle was referred to as the ‘‘forgotten ventricle’’. In recent years, this has changed significantly. A growing number of studies have focussed on the investigation of the right ventricle in many diseases such as pulmonary hypertension or heart failure, and the pathophysiology of the right ventricle has gained a particularly high degree of attention in exercise medicine and science. Right ventricular properties have been shown consistently to play a central role in training-dependent adaptation processes in response to altered loading conditions, and represent an important determinant of individual exercise performance. Intense endurance exercise has been demonstrated to trigger acute dysfunction of the right ventricle, usually followed by a complete short-term recovery. In contrast, the left ventricle remains unaffected by such an acute form of physical stress. The differences regarding the capacities of the ventricles may be attributable to a high workload and wall stress of the right ventricle compared to the left ventricle. In some athletes, chronic changes of the right ventricular morphology (e.g. right ventricular enlargement) and the right ventricular myocardial structure (e.g. increased myocardial fibrosis) as well as a persistently reduced function and an increased frequency of arrhythmias have been demonstrated. In addition, significant interindividual and sex differences have been reported with regard to these right ventricular adaptations to endurance exercise. Thus, athletes performing similar amounts of exercise may demonstrate extremely different structural and functional right ventricular changes, varying from no to severe dysfunction. Interestingly, both an enhanced right ventricular contractile reserve as well as a less impaired right ventricular function in response to intense endurance exercise have been shown in female athletes as compared to male athletes. The mechanisms underlying these interindividual differences are still not well understood. One suggested explanation is pulmonary vascular adaptation processes. In particular, the capability of recruiting anatomical arterial-venous shunt vessels and the extent of the dilatation of the pulmonary capillaries during exercise have been discussed in this respect. These changes would reflect a larger pulmonary vascular reserve and, consequently, a lower exercise-related increase in pulmonary artery systolic pressure during exercise. This hypothesis has now been further investigated by Sanz-de la Garza et al. in an exploratory study, recently published in the European Journal for Preventive Cardiology. The authors evaluated the transpulmonary transit of agitated saline (PTAS) as a parameter of vascular reserve by echocardiography immediately after a symptom-limited incremental cardiopulmonary exercise test on a cycle ergometer in 100 highly trained female and male endurance athletes aged 20–45 years. For the final analyses, the data of 88 participants were available (11 athletes were excluded due to an intracardiac shunt at rest and one due to a chronic obstructive pulmonary disease). The athletes were stratified into two groups according to a high or low PTAS. The major findings of the study were that a high PTAS capability was associated with a significantly larger right ventricular contractile reserve, a larger pulmonary vascular reserve and an enhanced maximal exercise capacity. Athletes with a high PTAS capability also showed a more pronounced biventricular remodelling than those with a low PTAS. This was seen in both female and male athletes. Interestingly, female sex was the only significant independent determinant of a high PTAS capability in the multivariate analysis, while age and history of intense dynamic exercise training during childhood were additional significant correlates of a high PTAS only in the univariate analyses. With their results, Sanz-de la Garza et al. make an important contribution to clarifying the question of why there are such large interindividual differences in
TL;DR: It is indicated that local expression of cytosolic renin but not of secretory renin can play a functional role in the human heart.
Abstract: Secretory renin promotes hypertrophy, apoptosis, necrosis and fibrosis through angiotensin generation. It has been claimed that local expression of renin contributes to the deleterious effects of the renin-angiotensin system in the heart. Besides the classic renin transcript (renin-a), encoding for secretory renin, a putative brain-specific (renin-b) and a putative lung-specific (renin-c) transcript may exist in human. In contrast to secretory renin, renin-b cannot be secreted, remains within the cytosol and is imported into mitochondria. In contradiction to renin-a, renin-b exerts cardioprotective effects in hearts and in cardiac cells of the rat under ischemia related conditions. To date, available data on cardiac renin expression remain inconsistent. Nobody has yet investigated which renin transcripts are expressed in the human heart. We systematically analyzed the levels of renin transcripts using specific and sensitive nested reverse-transcriptase polymerase chain reactions (RT-PCR) in human ventricular biopsies obtained from patients with heart diseases. In the 33 biopsies available, neither the expression of classic renin-a, nor of the alternative renin-c was detected. In contrast, the renin-b transcript, which was previously classified as brain-specific, was found in 11/33 ventricular biopsies. Our data exclude the expression of secretory renin and indicate that local expression of cytosolic renin but not of secretory renin can play a functional role in the human heart.
01 Jan 2020
TL;DR: It is currently not clear whether assessment of the total CVD risk per se may help to reduce CVD events, but recommendations for preventive measures in subjects without existing CVD are based on the individual’s risk level.
Abstract: Cardiovascular disease (CVD) represents the most common cause of death worldwide. The underlying atherosclerosis starts already early in life and progresses over a long period until the first symptoms occur. Development and progression of CVD can be slowed down or prevented by improving modifiable risk factors by lifestyle modifications (e.g., promotion of physical activity, smoking cessation) and preventive medication (e.g., lipid-lowering drugs, antihypertensive medication). In apparently healthy people, CVD risk is most commonly the consequence of multiple interacting risk factors. Several multivariate risk estimation systems are available for evaluating the 10-year risk of future CVD events in apparently healthy individuals and for supporting individual management decisions. However, no single risk model is appropriate for all patients and a specific tool for CVD risk assessment has to be chosen based on patient-specific characteristics (e.g., age, gender, ethnicity). Since age alone is a strong CVD risk factor, younger people may have a low absolute risk but a very high relative risk, and calculating the lifetime risk may help in advising them of the need for intensive lifestyle modifications. Certain individuals are regarded as having a high CVD risk without the need for risk scoring and require immediate attention to their risk factors (e.g., patients with diabetes mellitus). Recommendations for preventive measures in subjects without existing CVD are based on the individual’s risk level. Improvement of risk factors reduces morbidity and mortality. It is currently not clear whether assessment of the total CVD risk per se may help to reduce CVD events.