Abstract
Background
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.
Mitral annular disjunction is the atrial displacement of the mural mitral valve leaflet hinge point within the atrioventricular junction. Said to be associated with malignant ventricular arrhythmias ...and sudden death, its prevalence in the general population is not known.
The purpose of this study was to assess the frequency of occurrence and extent of mitral annular disjunction in a large population cohort.
The authors assessed the cardiac magnetic resonance (CMR) images in 2,646 Caucasian subjects enrolled in the UK Biobank imaging study, measuring the length of disjunction at 4 points around the mitral annulus, assessing for presence of prolapse or billowing of the leaflets, and for curling motion of the inferolateral left ventricular wall.
From 2,607 included participants, the authors found disjunction in 1,990 (76%) cases, most commonly at the anterior and inferior ventricular wall. The authors found inferolateral disjunction, reported as clinically important, in 134 (5%) cases. Prolapse was more frequent in subjects with disjunction (odds ratio OR: 2.5; P = 0.02), with positive associations found between systolic curling and disjunction at any site (OR: 3.6; P < 0.01), and systolic curling and prolapse (OR: 71.9; P < 0.01).
This large-scale study shows that disjunction is a common finding when using CMR. Disjunction at the inferolateral ventricular wall, however, was rare. The authors found associations between disjunction and both prolapse and billowing of the mural mitral valve leaflet. These findings support the notion that only extensive inferolateral disjunction, when found, warrants consideration of further investigation, but disjunction elsewhere in the annulus should be considered a normal finding.
Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping cT1) were ...associated with an increased risk of major CVD events.
Liver disease activity (cT1) and fat (proton density fat fraction PDFF) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation AF, embolism/vascular events, heart failure HF and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).
A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m2, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years range: 0.002-5.1; follow-up: 2.5 years range:1.1-5.2). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03–1.26; p = 0.008), AF (1.30; 1.12–1.51; p <0.001); HF (1.30; 1.08–1.58; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02–1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01–1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).
Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.
Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.
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•Liver disease on cT1 MRI is associated with a high risk of CVD events, CVD-related hospitalization, and all-cause mortality.•The association between liver disease on cT1 and CVD is independent of liver function tests, fibrosis and metabolic risk.•Risk of CVD events is increased even in the early stages of chronic liver disease.
BackgroundExisting work, using indirect health measures, suggests independent links between brain and heart health within disease cohorts. We studied the links between MRI-derived heart and brain ...structure and function in the UK Biobank population-based cohort.MethodsImage acquisition and analysis was according to pre-defined protocols. We included the following cardiovascular metrics: left ventricular (LV) stroke volume (LVSV), LV global functional index (LVGFI), LV mass to LV end-diastolic volume ratio (LVM: LVEDV), global longitudinal strain (GLS), left atrial ejection fraction (LAEF), aortic distensibility (AoD). T1 and T2 structural images were used to determine overall brain volume, volume of white matter hyperintensities, and volumes of several subcortical structures. We considered microscopic features of white matter integrity assessed using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), across a range of white matter fibre tracts. Associations between heart and brain measures were computed using standardised betas from multivariable linear regression models, adjusted for age, sex, deprivation, obesity, education level, alcohol consumption, diabetes, hypertension, high cholesterol, smoking, physical activity, systolic blood pressure, total cholesterol, and glycosylated haemoglobin.ResultsWe studied 30,373 participants; average age was 63±7.5 years-old; 52% were women. Adverse cardiovascular phenotypes across all metrics were associated with larger volume of white matter hyperintensities (e.g., LV GFI: Beta=−0.049; 95% CI=−0.060, −0.039; p-value= 3.82×10−20). Higher LVSV (Beta= 0.031; 95% CI= 0.022, 0.039; p-value= 1.57×10−12) and greater AoD (Beta=0.027; 95% CI= 0.016, 0.039; p-value= 5.76×10−6) were associated with larger total grey matter volumes. Higher LV GFI, higher LAEF, and higher AoD were associated with healthier white matter microstructure as per higher neurite density and stronger myelin membranes (e.g., fractional anisotropy with LV GFI: Beta= 0.052; 95% CI= 0.040, 0.064; p-value= 1.79×10−17). Healthy white matter microstructure was associated with less concentric LV hypertrophy (LVM: LVEDV: Beta= −0.051; 95% CI= −0.064, −0.038; p-value= 2.94×10−15) and better GLS (Beta= −0.032; 95% CI= −0.044, −0.019; p-value= 4.89×10−7).ConclusionIn this large population cohort, we demonstrate independent links between heart and brain health using detailed MRI. Participants with healthier hearts had significantly less brain atrophy, less brain microvascular injury, and healthier neuronal structure.
ObjectiveTo examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.MethodsCompeting risk regression was ...used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7–12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight–MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.Results258 787 participants from white ethnicities (61% women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2 kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0×10–5) and attenuation to the null above this threshold. The birth weight–MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight–mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19 314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).ConclusionsLower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.
We evaluated independent associations of cardiovascular magnetic resonance (CMR)-measured pericardial adipose tissue (PAT) with cardiovascular structure and function and considered underlying ...mechanism in 42 598 UK Biobank participants.
We extracted PAT and selected CMR metrics using automated pipelines. We estimated associations of PAT with each CMR metric using linear regression adjusting for age, sex, ethnicity, deprivation, smoking, exercise, processed food intake, body mass index, diabetes, hypertension, height cholesterol, waist-to-hip ratio, impedance fat measures, and magnetic resonance imaging abdominal visceral adiposity measures. Higher PAT was independently associated with unhealthy left ventricular (LV) structure (greater wall thickness, higher LV mass, more concentric pattern of LV hypertrophy), poorer LV function (lower LV global function index, lower LV stroke volume), lower left atrial ejection fraction, and lower aortic distensibility. We used multiple mediation analysis to examine the potential mediating effect of cardiometabolic diseases and blood biomarkers (lipid profile, glycaemic control, inflammation) in the PAT-CMR relationships. Higher PAT was associated with cardiometabolic disease (hypertension, diabetes, high cholesterol), adverse serum lipids, poorer glycaemic control, and greater systemic inflammation. We identified potential mediation pathways via hypertension, adverse lipids, and inflammation markers, which overall only partially explained the PAT-CMR relationships.
We demonstrate association of PAT with unhealthy cardiovascular structure and function, independent of baseline comorbidities, vascular risk factors, inflammatory markers, and multiple non-invasive and imaging measures of obesity. Our findings support an independent role of PAT in adversely impacting cardiovascular health and highlight CMR-measured PAT as a potential novel imaging biomarker of cardiovascular risk.
Abstract
Aims
We evaluated the associations of left atrial (LA) structure and function with prevalent and incident cardiovascular disease (CVD), independent of left ventricular (LV) metrics, in 25 ...896 UK Biobank participants.
Methods and results
We estimated the association of cardiovascular magnetic resonance (CMR) metrics LA maximum volume (LAV), LA ejection fraction (LAEF), LV mass : LV end-diastolic volume ratio (LVM : LVEDV), global longitudinal strain, and LV global function index (LVGFI) with vascular risk factors (hypertension, diabetes, high cholesterol, and smoking), prevalent and incident CVDs atrial fibrillation (AF), stroke, ischaemic heart disease (IHD), myocardial infarction, all-cause mortality, and CVD mortality. We created uncorrelated CMR variables using orthogonal principal component analysis rotation. All five CMR metrics were simultaneously entered into multivariable regression models adjusted for sex, age, ethnicity, deprivation, education, body size, and physical activity. Lower LAEF was associated with diabetes, smoking, and all the prevalent and incident CVDs. Diabetes, smoking, and high cholesterol were associated with smaller LAV. Hypertension, IHD, AF (incident and prevalent), incident stroke, and CVD mortality were associated with larger LAV. LV and LA metrics were both independently informative in associations with prevalent disease, however LAEF showed the most consistent associations with incident CVDs. Lower LVGFI was associated with greater all-cause and CVD mortality. In secondary analyses, compared with LVGFI, LV ejection fraction showed similar but less consistent disease associations.
Conclusion
LA structure and function measures (LAEF and LAV) demonstrate significant associations with key prevalent and incident cardiovascular outcomes, independent of LV metrics. These measures have potential clinical utility for disease discrimination and outcome prediction.
Graphical Abstract
Graphical Abstract
Association of CMR metrics with incident cardiovascular disease considered separately (blue) and in models mutually adjusted for all the CMR metrics (green). The points indicate point estimate for the hazard ratio and the intervals indicate the corresponding 95% confidence intervals from Cox hazard proportional models. Confounders are age, sex, ethnicity, deprivation, education, body mass index, hypertension, high cholesterol, diabetes, physical activity, and smoking. The blue results are from models with individual adjustment for CMR metrics (Supplementary data online, Table S9). The green results are from models mutually adjusting for all the CMR metrics (Table 3). AF, atrial fibrillation; CMR, cardiovascular magnetic resonance; CVD, cardiovascular disease; LVGFI, left ventricular global function index; GLS, global longitudinal strain; i, indicates indexation to body surface area; IHD, ischaemic heart disease; LAEF, left atrial ejection fraction; LAV, maximum left atrial volume; LVEDV, left ventricular end-diastolic volume; LVM, left ventricular mass; MI, myocardial infarction.
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