Genetic Architecture of Quantitative Cardiovascular Traits: Blood Pressure, ECG and Imaging Phenotypes

Background: We provide an overview of the genetic architecture of quantitative cardiovascular phenotypes such as blood pressure (BP), electrocardiogram (ECG) and cardiac imaging measurements which play a critical and prognostic role in the management of numerous diseases. Methods: The genetics of BP, ECG and cardiac imaging traits have been studied in large-scale genome-wide association studies (GWASs). Results: To-date more than 1,400 BP loci have been discovered. These genetic loci harbouring known and novel BP-regulating genes, several of which are linked to existing drugs, that can be repurposed for BP treatment. Regarding the ECG indices, 437 independent signals have been reported for resting heart rate (n 400,000), mainly modulating the autonomic nervous system, as well as 202 loci for PR interval, 29 loci for QRS duration and 35 loci for QT interval. The LV GWASs (n 17,000) identified 14 loci harbouring genes regulating the cardiac developmental pathways. Conclusion: Large-scale genetic analyses of quantitative cardiovascular traits have yielded hundreds of susceptibility loci, candidate genes and key biological pathways, which significantly advance our understanding of their genetic architecture and shed lights on potential novel therapeutic targets

Prognostic Significance of Different Ventricular Ectopic Burdens During Submaximal Exercise in Asymptomatic UK Biobank Subjects.

BACKGROUND: The consequences of exercise-induced premature ventricular contractions (PVCs) in asymptomatic individuals remain unclear. This study aimed to assess the association between PVC burdens during submaximal exercise and major adverse cardiovascular events (MI/HF/LTVA: myocardial infarction [MI], heart failure [HF], and life-threatening ventricular arrhythmia [LTVA]), and all-cause mortality. Additional end points were MI, LTVA, HF, and cardiovascular mortality. METHODS: A neural network was developed to count PVCs from ECGs recorded during exercise (6 minutes) and recovery (1 minute) in 48 315 asymptomatic participants from UK Biobank. Associations were estimated using multivariable Cox proportional hazard models. Explorative studies were conducted in subgroups with cardiovascular magnetic resonance imaging data (n=6290) and NT-proBNP (N-terminal Pro-B-type natriuretic peptide) levels (n=4607) to examine whether PVC burden was associated with subclinical cardiomyopathy. RESULTS: Mean age was 56.8±8.2 years; 51.1% of the participants were female; and median follow-up was 12.6 years. Low PVC counts during exercise and recovery were both associated with MI/HF/LTVA risk, independently of clinical factors: adjusted hazard ratio (HR), 1.2 (1-5 exercise PVCs, P20 exercise PVCs, P5 recovery PVCs, P20 exercise PVCs, P5 recovery PVCs, P<0.001). Complex PVC rhythms were associated with higher risk compared with PVC count alone. PVCs were also associated with incident HF, LTVA, and cardiovascular mortality, but not MI. In the explorative studies, high PVC burden was associated with larger left ventricular volumes, lower ejection fraction, and higher levels of NT-proBNP compared with participants without PVCs. CONCLUSION: In this cohort of middle-aged and older adults, PVC count during submaximal exercise and recovery were both associated with MI/HF/LTVA, all-cause mortality, HF, LTVAs, and cardiovascular mortality, independent of clinical and exercise test factors, indicating an incremental increase in risk as PVC count rises. Complex PVC rhythms were associated with higher risk compared with PVC count alone. Underlying mechanisms may include the presence of subclinical cardiomyopathy

Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank.

This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Public Health, following peer review. The version of record: Zahra Raisi-Estabragh, Celeste McCracken, Mae S Bethell, Jackie Cooper, Cyrus Cooper, Mark J Caulfield, Patricia B Munroe, Nicholas C Harvey, Steffen E Petersen, Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank, Journal of Public Health, fdaa095, https://doi.org/10.1093/pubmed/fdaa095 is available online at: https://doi.org/10.1093/pubmed/fdaa095BACKGROUND: We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and Black, Asian and Minority Ethnic (BAME) individuals is explained by cardiometabolic, socio-economic or behavioural factors. METHODS: We studied 4510 UK Biobank participants tested for COVID-19 (positive, n = 1326). Multivariate logistic regression models including age, sex and ethnicity were used to test whether addition of (1) cardiometabolic factors [diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking and body mass index (BMI)]; (2) 25(OH)-vitamin D; (3) poor diet; (4) Townsend deprivation score; (5) housing (home type, overcrowding) or (6) behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status. RESULTS: There was over-representation of men and BAME ethnicities in the COVID-19 positive group. BAME individuals had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and in flats/apartments. Male sex, BAME ethnicity, higher BMI, higher Townsend deprivation score and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations. CONCLUSIONS: In this study, sex and ethnicity differential pattern of COVID-19 was not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels or socio-economic factors. Factors which underlie ethnic differences in COVID-19 may not be easily captured, and so investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised

Psychosocial aspects of feeding children with neurodisability

The psychosocial support needs of parents considering a gastrostomy feeding tube for their disabled child are often overlooked, yet there is a growing body of evidence that attests to the decisional conflicts parents, often mothers, experience. This may be in addition to the stress associated with feeding a disabled child. The support needs of families and caregivers should be assessed, including the values parents attach to oral and tube feeding. Structured support should be embedded within the care pathway and both professionals, and service users, with appropriate training should be identified to ensure parental information needs, and any emotional, practical and financial issues are addressed

Cardiac Magnetic Resonance Radiomics Reveal Differential Impact of Sex, Age, and Vascular Risk Factors on Cardiac Structure and Myocardial Tissue

Background: Cardiovascular magnetic resonance (CMR) radiomics analysis provides multiple quantifiers of ventricular shape and myocardial texture, which may be used for detailed cardiovascular phenotyping. Objectives: We studied variation in CMR radiomics phenotypes by age and sex in healthy UK Biobank participants. Then, we examined independent associations of classical vascular risk factors (VRFs: smoking, diabetes, hypertension, high cholesterol) with CMR radiomics features, considering potential sex and age differential relationships. Design: Image acquisition was with 1.5 Tesla scanners (MAGNETOM Aera, Siemens). Three regions of interest were segmented from short axis stack images using an automated pipeline: right ventricle, left ventricle, myocardium. We extracted 237 radiomics features from each study using Pyradiomics. In a healthy subset of participants (n = 14,902) without cardiovascular disease or VRFs, we estimated independent associations of age and sex with each radiomics feature using linear regression models adjusted for body size. We then created a sample comprising individuals with at least one VRF matched to an equal number of healthy participants (n = 27,400). We linearly modelled each radiomics feature against age, sex, body size, and all the VRFs. Bonferroni adjustment for multiple testing was applied to all p-values. To aid interpretation, we organised the results into six feature clusters. Results: Amongst the healthy subset, men had larger ventricles with dimmer and less texturally complex myocardium than women. Increasing age was associated with smaller ventricles and greater variation in myocardial intensities. Broadly, all the VRFs were associated with dimmer, less varied signal intensities, greater uniformity of local intensity levels, and greater relative presence of low signal intensity areas within the myocardium. Diabetes and high cholesterol were also associated with smaller ventricular size, this association was of greater magnitude in men than women. The pattern of alteration of radiomics features with the VRFs was broadly consistent in men and women. However, the associations between intensity based radiomics features with both diabetes and hypertension were more prominent in women than men. Conclusions: We demonstrate novel independent associations of sex, age, and major VRFs with CMR radiomics phenotypes. Further studies into the nature and clinical significance of these phenotypes are needed

Universality, limits and predictability of gold-medal performances at the Olympic Games

Inspired by the Games held in ancient Greece, modern Olympics represent the world's largest pageant of athletic skill and competitive spirit. Performances of athletes at the Olympic Games mirror, since 1896, human potentialities in sports, and thus provide an optimal source of information for studying the evolution of sport achievements and predicting the limits that athletes can reach. Unfortunately, the models introduced so far for the description of athlete performances at the Olympics are either sophisticated or unrealistic, and more importantly, do not provide a unified theory for sport performances. Here, we address this issue by showing that relative performance improvements of medal winners at the Olympics are normally distributed, implying that the evolution of performance values can be described in good approximation as an exponential approach to an a priori unknown limiting performance value. This law holds for all specialties in athletics-including running, jumping, and throwing-and swimming. We present a self-consistent method, based on normality hypothesis testing, able to predict limiting performance values in all specialties. We further quantify the most likely years in which athletes will breach challenging performance walls in running, jumping, throwing, and swimming events, as well as the probability that new world records will be established at the next edition of the Olympic Games.Comment: 8 pages, 3 figures, 1 table. Supporting information files and data are available at filrad.homelinux.or

Repeatability of Cardiac Magnetic Resonance Radiomics: A Multi-Centre Multi-Vendor Test-Retest Study

Aims: To evaluate the repeatability of cardiac magnetic resonance (CMR) radiomics features on test-retest scanning using a multi-centre multi-vendor dataset with a varied case-mix. Methods and Results: The sample included 54 test-retest studies from the VOLUMES resource (thevolumesresource.com). Images were segmented according to a pre-defined protocol to select three regions of interest (ROI) in end-diastole and end-systole: right ventricle, left ventricle (LV), and LV myocardium. We extracted radiomics shape features from all three ROIs and, additionally, first-order and texture features from the LV myocardium. Overall, 280 features were derived per study. For each feature, we calculated intra-class correlation coefficient (ICC), within-subject coefficient of variation, and mean relative difference. We ranked robustness of features according to mean ICC stratified by feature category, ROI, and cardiac phase, demonstrating a wide range of repeatability. There were features with good and excellent repeatability (ICC ≥ 0.75) within all feature categories and ROIs. A high proportion of first-order and texture features had excellent repeatability (ICC ≥ 0.90), however, these categories also contained features with the poorest repeatability (ICC < 0.50). Conclusion: CMR radiomic features have a wide range of repeatability. This paper is intended as a reference for future researchers to guide selection of the most robust features for clinical CMR radiomics models. Further work in larger and richer datasets is needed to further define the technical performance and clinical utility of CMR radiomics

Light to moderate coffee consumption is associated with lower risk of death: a UK Biobank study

Aims: To study the association of daily coffee consumption with all-cause and cardiovascular (CV) mortality and major CV outcomes. In a subgroup of participants who underwent cardiovascular magnetic resonance (CMR) imaging, we evaluated the association between regular coffee intake and cardiac structure and function.Methods: UK Biobank participants without clinically manifested heart disease at the time of recruitment were included. Regular coffee intake was categorized into 3 groups: zero, light-to-moderate (0.5-3 cups/day) and high (&gt;3 cups/day). In the multivariate analysis, we adjusted for the main CV risk factors.Results: We included 468,629 individuals (56.2 ± 8.1 years, 44.2% male), 22.1% did not consume coffee on a regular basis, 58.4% had 0.5-3 cups per day and 19.5% had &gt;3 cups per day. Compared to non-coffee drinkers, light-to-moderate (0.5-3 cups per day) coffee drinking was associated with lower risk of all-cause mortality (multivariate HR = 0.88, 95%CI : 0.83-0.92; p &lt; 0.001) and CV mortality (multivariate HR = 0.83, 95%CI : 0.74-0.94; p = 0.006), and incident stroke (multivariate HR = 0.79, 95%CI : 0.63-0.99 p = 0.037) after a median follow-up of 11 years. CMR data were available in 30,650 participants. Both light-to-moderate and high coffee consuming categories were associated with dose-dependent increased left and right ventricular end-diastolic, end-systolic and stroke volumes, as well as greater left ventricular mass. Conclusion: Coffee consumption of up to 3 cups per day was associated with favorable CV outcomes. Regular coffee consumption was also associated with a likely healthy pattern of CMR metrics in keeping with the reverse of age-related cardiac alterations

Adverse cardiovascular magnetic resonance phenotypes are associated with greater likelihood of incident coronavirus disease 2019: findings from the UK Biobank.

BACKGROUND: Coronavirus disease 2019 (COVID-19) disproportionately affects older people. Observational studies suggest indolent cardiovascular involvement after recovery from acute COVID-19. However, these findings may reflect pre-existing cardiac phenotypes. AIMS: We tested the association of baseline cardiovascular magnetic resonance (CMR) phenotypes with incident COVID-19. METHODS: We studied UK Biobank participants with CMR imaging and COVID-19 testing. We considered left and right ventricular (LV, RV) volumes, ejection fractions, and stroke volumes, LV mass, LV strain, native T1, aortic distensibility, and arterial stiffness index. COVID-19 test results were obtained from Public Health England. Co-morbidities were ascertained from self-report and hospital episode statistics (HES). Critical care admission and death were from HES and death register records. We investigated the association of each cardiovascular measure with COVID-19 test result in multivariable logistic regression models adjusting for age, sex, ethnicity, deprivation, body mass index, smoking, diabetes, hypertension, high cholesterol, and prior myocardial infarction. RESULTS: We studied 310 participants (n = 70 positive). Median age was 63.8 [57.5, 72.1] years; 51.0% (n = 158) were male. 78.7% (n = 244) were tested in hospital, 3.5% (n = 11) required critical care admission, and 6.1% (n = 19) died. In fully adjusted models, smaller LV/RV end-diastolic volumes, smaller LV stroke volume, and poorer global longitudinal strain were associated with significantly higher odds of COVID-19 positivity. DISCUSSION: We demonstrate association of pre-existing adverse CMR phenotypes with greater odds of COVID-19 positivity independent of classical cardiovascular risk factors. CONCLUSIONS: Observational reports of cardiovascular involvement after COVID-19 may, at least partly, reflect pre-existing cardiac status rather than COVID-19 induced alterations