Association of Renin–Angiotensin–Aldosterone System inhibition with Covid‐19 hospitalization and all‐cause mortality in the UK Biobank

Aim: The risk-benefit profile of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (Covid-19) is still a matter of debate. With growing evidence on the protective effect of this group of commonly used antihypertensives in Covid-19, we aimed to thoroughly investigate the association between the use of major classes of antihypertensive medications and Covid-19 outcomes in comparison with the use of ACEIs and ARBs. Methods: We conducted a population-based study in patients with pre-existing hypertension in the UK Biobank. Multivariable logistic regression analysis was performed adjusting for a wide range of confounders. Results: The use of either beta-blockers (BBs), calcium-channel blockers (CCBs), or diuretics was associated with a higher risk of Covid-19 hospitalization compared to ACEI use (adjusted OR, 1.63; 95% CI, 1.40 to 1.90) and ARB use (adjusted OR, 1.50; 95% CI, 1.27 to 1.77). The risk of 28-day mortality among Covid-19 patients was also increased among users of BBs, CCBs or diuretics when compared to ACEI users (adjusted OR, 1.64; 95% CI, 1.23 to 2.19) but not when compared to ARB users (adjusted OR, 1.18; 95% CI, 0.87 to 1.59). However, no associations were observed when the same analysis was conducted among hospitalized Covid-19 patients only. Conclusion: Our results suggest protective effects of blocking of the renin-angiotensin-aldosterone system on Covid-19 hospitalization and mortality among patients with pharmaceutically treated hypertension, which should be addressed by randomized controlled trials. If confirmed, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.

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Advanced cardiometabolic & inflammatory markers for prediction of cardiovascular disease and cancer

European Heart Journal ◽

10.1093/ehjci/ehaa946.2921 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

D Radenkovic ◽

S.C Chawla ◽

G Botta ◽

A Boli ◽

M.B Banach ◽

...

Keyword(s):

Cardiovascular Disease ◽

Risk Score ◽

Cancer Incidence ◽

Risk Function ◽

Patient Characteristics ◽

Risk Scores ◽

Uk Biobank ◽

Training Set ◽

All Cause Mortality ◽

The Uk

Abstract The two leading causes of mortality worldwide are cardiovascular disease (CVD) and cancer. The annual total cost of CVD and cancer is an estimated $844.4 billion in the US and is projected to double by 2030. Thus, there has been an increased shift to preventive medicine to improve health outcomes and development of risk scores, which allow early identification of individuals at risk to target personalised interventions and prevent disease. Our aim was to define a Risk Score R(x) which, given the baseline characteristics of a given individual, outputs the relative risk for composite CVD, cancer incidence and all-cause mortality. A non-linear model was used to calculate risk scores based on the participants of the UK Biobank (= 502548). The model used parameters including patient characteristics (age, sex, ethnicity), baseline conditions, lifestyle factors of diet and physical activity, blood pressure, metabolic markers and advanced lipid variables, including ApoA and ApoB and lipoprotein(a), as input. The risk score was defined by normalising the risk function by a fixed value, the average risk of the training set. To fit the non-linear model >400,000 participants were used as training set and >45,000 participants were used as test set for validation. The exponent of risk function was represented as a multilayer neural network. This allowed capturing interdependent behaviour of covariates, training a single model for all outcomes, and preserving heterogeneity of the groups, which is in contrast to CoxPH models which are traditionally used in risk scores and require homogeneous groups. The model was trained over 60 epochs and predictive performance was determined by the C-index with standard errors and confidence intervals estimated with bootstrap sampling. By inputing the variables described, one can obtain personalised hazard ratios for 3 major outcomes of CVD, cancer and all-cause mortality. Therefore, an individual with a risk Score of e.g. 1.5, at any time he/she has 50% more chances than average of experiencing the corresponding event. The proposed model showed the following discrimination, for risk of CVD (C-index = 0.8006), cancer incidence (C-index = 0.6907), and all-cause mortality (C-index = 0.7770) on the validation set. The CVD model is particularly strong (C-index >0.8) and is an improvement on a previous CVD risk prediction model also based on classical risk factors with total cholesterol and HDL-c on the UK Biobank data (C-index = 0.7444) published last year (Welsh et al. 2019). Unlike classically-used CoxPH models, our model considers correlation of variables as shown by the table of the values of correlation in Figure 1. This is an accurate model that is based on the most comprehensive set of patient characteristics and biomarkers, allowing clinicians to identify multiple targets for improvement and practice active preventive cardiology in the era of precision medicine. Figure 1. Correlation of variables in the R(x) Funding Acknowledgement Type of funding source: None

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Unhealthy Lifestyle, Genetics and Risk of Cardiovascular Disease and Mortality in 76,958 Individuals from the UK Biobank Cohort Study

Nutrients ◽

10.3390/nu13124283 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4283

Author(s):

Katherine M. Livingstone ◽

Gavin Abbott ◽

Joey Ward ◽

Steven J. Bowe

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Polygenic Risk Score ◽

Nucleotide Polymorphisms ◽

Uk Biobank ◽

Unhealthy Lifestyle ◽

Hazard Ratios ◽

All Cause Mortality ◽

The Uk ◽

Cvd Mortality

To examine associations of unhealthy lifestyle and genetics with risk of all-cause mortality, cardiovascular disease (CVD) mortality, myocardial infarction (MI) and stroke. We used data on 76,958 adults from the UK Biobank prospective cohort study. Favourable lifestyle included no overweight/obesity, not smoking, physical activity, not sedentary, healthy diet and adequate sleep. A Polygenic Risk Score (PRS) was derived using 300 CVD-related single nucleotide polymorphisms. Cox proportional hazard ratios (HR) were used to model effects of lifestyle and PRS on risk of CVD and all-cause mortality, stroke and MI. New CVD (n = 364) and all-cause (n = 2408) deaths, and stroke (n = 748) and MI (n = 1140) events were observed during a 7.8 year mean follow-up. An unfavourable lifestyle (0–1 healthy behaviours) was associated with higher risk of all-cause mortality (HR: 2.06; 95% CI: 1.73, 2.45), CVD mortality (HR: 2.48; 95% CI: 1.64, 3.76), MI (HR: 2.12; 95% CI: 1.65, 2.72) and stroke (HR:1.74; 95% CI: 1.25, 2.43) compared to a favourable lifestyle (≥4 healthy behaviours). PRS was associated with MI (HR: 1.35; 95% CI: 1.27, 1.43). There was evidence of a lifestyle-genetics interaction for stroke (p = 0.017). Unfavourable lifestyle behaviours predicted higher risk of all-cause mortality, CVD mortality, MI and stroke, independent of genetic risk.

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MO023SARCOPENIA, CHRONIC KIDNEY DISEASE AND RISK OF MORTALITY: FINDINGS FROM 426,839 INDIVIDUALS IN THE UK BIOBANK

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa140.mo023 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Thomas Wilkinson ◽

Joanne Miksza ◽

Luke Baker ◽

Courtney Lightfoot ◽

Emma Watson ◽

...

Keyword(s):

Muscle Mass ◽

Early Stage ◽

Handgrip Strength ◽

Functional Decline ◽

Adverse Outcomes ◽

Survival Models ◽

Uk Biobank ◽

All Cause Mortality ◽

Comparative Group ◽

The Uk

Abstract Background and Aims Sarcopenia describes a degenerative and generalised skeletal muscle disorder involving the loss of muscle mass and function. In studies of the general population, sarcopenia is associated with adverse outcomes including falls, functional decline, frailty, and mortality. However it remains an under-recognised yet important clinical problem in an ever-increasing ageing and multimorbid renal population. Whilst sarcopenia has been widely studied in end-stage renal disease, there is limited evidence of its prevalence and effects in those not requiring dialysis, particularly in large cohort studies and using the latest sarcopenia definitions. Using the UK Biobank, we aimed to identify the prevalence of sarcopenia in individuals with non-dialysis CKD and its association with mortality. Method 426,839 participants were categorised into a CKD (defined as eGFR <60ml/min/1.73m2 not requiring dialysis) and a non-CKD comparative group (no evidence of CKD). Sarcopenia was diagnosed using criteria from the EWGSOP2: ‘probable sarcopenia’ (low handgrip strength (HGS) <27 and 16kg, males and females respectively); ‘confirmed sarcopenia’ (low HGS plus low muscle mass, appendicular lean mass <7.0 and 5.5 kg/m2 as measured by bioelectrical impedance); and ‘severe sarcopenia’ (low HGS and muscle mass plus slow gait speed). Patients requiring existing renal replacement therapy were excluded. All-cause mortality was extracted from data linkage to national death records with a median follow up of 9.0 years. Data were analysed using Cox survival models. Results CKD (non-dialysis dependent) was identified in n=7,623 individuals (mean age 62.7 (±5.9) years, 44% male, eGFR 52.5 (±7.7) ml/min/1.73m2) compared to n=419,216 in the non-CKD comparative group (mean age 56.1 (±8.1) years, 47% male). ‘Probable sarcopenia’ was identified in 9% of individuals with CKD compared to 5% in those without CKD (P<0.001). ‘Confirmed sarcopenia’ was observed in 0.3% of those with CKD (vs. 0.2% in the non-CKD group, P<0.001). 0.2% of CKD patients satisfied all three criteria (‘severe sarcopenia’) compared to 0.03% in those without CKD (P<0.001). In CKD, sarcopenia was significantly associated with all-cause mortality: ‘probable sarcopenia’, unadjusted hazard ratio (HR) 1.95 (95%CI 1.57 to 2.42), P<0.001 (Figure 1); ‘confirmed sarcopenia’, HR 5.1 (2.5 to 10.3) P<0.001; ‘severe sarcopenia’, HR 5.1 (1.9 to 13.5) P=0.001. Conclusion In the largest cohort of its kind, probable sarcopenia was present in 9% of individuals with non-dialysis CKD. The risk of sarcopenia was significantly higher in those with CKD than those without. Regardless of criteria used, CKD patients with sarcopenia were approximately 2-5 times more likely to die than those without sarcopenia. Worryingly, the risk of sarcopenia was elevated even in patients with early stage mild to moderate CKD. Our results show that sarcopenia, including just the presence of low muscle strength, is an important predictor of mortality in early non-dialysis CKD. Measuring sarcopenia as standard practice may identify those most at risk of future adverse events and in need of appropriate interventions to mitigate its negative effects.

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Diet-quality and its association with cardiovascular diseases and cancer incidence and all-cause mortality: a prospective cohort study from UK Biobank

Proceedings of The Nutrition Society ◽

10.1017/s0029665120000208 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Fanny Petermann-Rocha ◽

Stuart R. Gray ◽

Jill Pell ◽

Carlos Celis-Morales

Keyword(s):

Cancer Incidence ◽

Diet Quality ◽

Lower Risk ◽

Quality Score ◽

Confounding Factors ◽

Uk Biobank ◽

Healthy Group ◽

Oily Fish ◽

All Cause Mortality ◽

The Uk

AbstractIntroductionNewly available data from big scale studies conducted in the UK, such as the UK Biobank, offers the possibility to further explore the prospective association between a diet-quality score and health outcomes after accounting for the effect of important confounding factors. The aim of this work, therefore, was to investigate the association between a diet-quality score, with the incidence of cardiovascular diseases (CVDs), cancer and all-cause mortality.Material and methodsThis study includes 345,343 participants (age range: 39–73, 55.1% women) from the UK Biobank, a prospective population-based study. Using 21 standardised variables of diet (alcohol, bread, bread type, cereal, dried fruit, water, coffee, tea, cheese, oily fish, non-oily fish, salt added to food, spread type, fresh fruit, cooked vegetable, raw vegetables, milk type, poultry, beef, lamb, and pork) we created a diet-quality score (very healthy, healthy, unhealthy and very unhealthy) using principal-component factor analysis. Associations between the dietary-quality score (very unhealthy individuals were the reference group) and health outcomes (all-cause mortality, CVD and cancer incidence) were investigated using Cox-proportional hazard models. All analyses were performed using STATA 14 statistical software.ResultsIn comparison to individuals with a very unhealthy diet, those with a better diet-quality had a lower risk of all-cause mortality and cancer as well as incidence of CVD and cancer. For example, individuals classified in the very healthy group had a 12% lower risk of all-cause mortality (HR: 0.88 [95% CI: 0.82 to 0.95]), 12% lower risk of CVD incidence (HR: 0.88 [95% CI: 0.80 to 0.98]), 17% of all-cancer mortality (HR: 0.83 [95% CI: 0.75 to 0.93]), and 10% lower risk all-cancer incidence (HR: 0.90 [95% CI: 0.85 to 0.94]). Those in the healthy group had a 12% lower risk of all-cause (HR: 0.88 [95% CI: 0.83 to 0.93]) and 15% lower risk of all-cancer mortality (HR: 0.85 [95% CI: 0.78 to 0.93]). There was no significant association between CVD mortality and any diet-quality group. These findings were independent of major confounding factors including socio-demographic covariates, prevalent of diseases and lifestyle factors.DiscussionOur findings indicate that individuals with a healthy diet in the UK biobank cohort are associated with a lower risk of premature mortality, and incidence of CVDs and cancer independently of major confounding factors.

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Clinical Features of COVID-19 in Patients With Essential Hypertension and the Impacts of Renin-angiotensin-aldosterone System Inhibitors on the Prognosis of COVID-19 Patients

Hypertension ◽

10.1161/hypertensionaha.120.15289 ◽

2020 ◽

Vol 76 (3) ◽

pp. 732-741 ◽

Cited By ~ 12

Author(s):

Wei Pan ◽

Jishou Zhang ◽

Menglong Wang ◽

Jing Ye ◽

Yao Xu ◽

...

Keyword(s):

Cox Regression ◽

Medication History ◽

Renin Angiotensin Aldosterone System ◽

Cox Regression Analysis ◽

Renin Angiotensin ◽

Reactive Protein ◽

All Cause Mortality ◽

History Of ◽

Raas Inhibitors ◽

The Impact

Hypertension is one of the most common comorbidities in patients with coronavirus disease 2019 (COVID-19). This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19. A total of 996 patients with COVID-19 were enrolled, including 282 patients with hypertension and 714 patients without hypertension. Propensity score-matched analysis (1:1 matching) was used to adjust the imbalanced baseline variables between the 2 groups. Patients with hypertension were further divided into the RAAS inhibitor group (n=41) and non-RAAS inhibitor group (n=241) according to their medication history. The results showed that COVID-19 patients with hypertension had more severe secondary infections, cardiac and renal dysfunction, and depletion of CD8 + cells on admission. Patients with hypertension were more likely to have comorbidities and complications and were more likely to be classified as critically ill than those without hypertension. Cox regression analysis revealed that hypertension (hazard ratio, 95% CI, unmatched cohort [1.80, 1.20–2.70]; matched cohort [2.24, 1.36–3.70]) was independently associated with all-cause mortality in patients with COVID-19. In addition, hypertensive patients with a history of RAAS inhibitor treatment had lower levels of C-reactive protein and higher levels of CD4 + cells. The mortality of patients in the RAAS inhibitor group (9.8% versus 26.1%) was significantly lower than that of patients in the non-RAAS inhibitor group. In conclusion, hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19. Patients who previously used RAAS inhibitors may have a better prognosis.

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1563-P: Multimorbidity and Its Associations with All-Cause Mortality in People with Type 2 Diabetes: A Prospective Analysis of the UK Biobank

Diabetes ◽

10.2337/db19-1563-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1563-P

Author(s):

JASON I. CHIANG ◽

PETER HANLON ◽

BHAUTESH D. JANI ◽

JO-ANNE E. MANSKI-NANKERVIS ◽

JOHN FURLER ◽

...

Keyword(s):

Type 2 Diabetes ◽

Prospective Analysis ◽

Uk Biobank ◽

All Cause Mortality ◽

The Uk

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P3823Body mass index or waist and hip circumference as predictors of outcome in the UK biobank

European Heart Journal ◽

10.1093/eurheartj/ehz745.0665 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

P Pellicori ◽

B Stanley ◽

S Iliodromiti ◽

C A Celis-Morales ◽

D M Lyall ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Heart Failure ◽

Body Fat ◽

Uk Biobank ◽

Anthropometric Indices ◽

All Cause Mortality ◽

History Of ◽

Cv Disease ◽

The Uk

Abstract Background Controversies exist about the relationship between body habitus and mortality, especially for patients with cardiovascular disease. Purpose We evaluated the relations between different anthropometric indices and mortality amongst participants with and without cardiovascular (CV) risk factors, or established CV disease (stroke, myocardial infarction and/or heart failure), enrolled in the UK Biobank. Methods The UK Biobank is a large prospective study which, between 2006 and 2010, enrolled 502,620 participants aged 38–73 years. Participants filled questionnaires and had a medical history recorded, physical measurements done and biological samples taken. The UK Biobank is routinely linked to national death registries and updated on a quarterly basis. Data on death were coded according to the International Classification of Diseases, 10th Revision (ICD-10). The primary end-point was all-cause mortality (ACM) across three subgroups of men and women: those with, or without, one or more CV risk factors (smoking, diabetes and/or hypertension), and those with CV disease (history of stroke, myocardial infarction and/or heart failure) at recruitment. Presence, or absence, of CV risk factors and diagnoses of CV disease were self-reported by participants at enrolment. Associations between anthropometric indices (body mass index (BMI), waist circumference (WC), waist to hip ratio (WHiR), and waist to height ratio (WHeR)) and the risk of all-cause mortality were analysed using Cox regression models. Results After excluding those with history of cancer at baseline (n=45,222), 453,046 participants were included (median age: 58 (interquartile range: 50 - 63) years; 53% women), of whom 150,732 had at least one CV risk factor, and 17,884 established CV disease. During a median follow-up of 5 years, 6,319 participants died. Baseline BMI had a U-shaped relationship with ACM, with higher nadir-values for those with CV risk factors or CV disease, for both sexes (figure). WC, WHiR and WHeR (measures of central distribution of body fat) had more linear associations with ACM, regardless of CV risk factors, CV disease and sex. Conclusions For adults with or without CV risk factors or established CV disease, measures of central distribution of body fat are more strongly and more linearly associated with ACM than BMI. WC, or WHiR, rather than BMI, appear to be more appropriate variables for risk stratification.

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Walking pace improves all-cause and cardiovascular mortality risk prediction: A UK Biobank prognostic study

European Journal of Preventive Cardiology ◽

10.1177/2047487319887281 ◽

2019 ◽

Vol 27 (10) ◽

pp. 1036-1044 ◽

Cited By ~ 1

Author(s):

Stavroula Argyridou ◽

Francesco Zaccardi ◽

Melanie J Davies ◽

Kamlesh Khunti ◽

Thomas Yates

Keyword(s):

Risk Factors ◽

Risk Prediction ◽

Cardiovascular Mortality ◽

Smoking Status ◽

Density Lipoprotein ◽

Uk Biobank ◽

All Cause Mortality ◽

Lifestyle Measures ◽

European Society Of Cardiology ◽

The Uk

Aims The purpose of this study was to quantify and rank the prognostic relevance of dietary, physical activity and physical function factors in predicting all-cause and cardiovascular mortality in comparison with the established risk factors included in the European Society of Cardiology Systematic COronary Risk Evaluation (SCORE). Methods We examined the predictive discrimination of lifestyle measures using C-index and R2 in sex-stratified analyses adjusted for: model 1, age; model 2, SCORE variables (age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol). Results The sample comprised 298,829 adults (median age, 57 years; 53.5% women) from the UK Biobank free from cancer and cardiovascular disease at baseline. Over a median follow-up of 6.9 years, there were 2174 and 3522 all–cause and 286 and 796 cardiovascular deaths in women and men, respectively. When added to model 1, self-reported walking pace improved C-index in women and men by 0.013 (99% CI: 0.007–0.020) and 0.022 (0.017–0.028) respectively for all-cause mortality; and by 0.023 (0.005–0.042) and 0.034 (0.020–0.048) respectively for cardiovascular mortality. When added to model 2, corresponding values for women and men were: 0.008 (0.003–0.012) and 0.013 (0.009–0.017) for all-cause mortality; and 0.012 (–0.001–0.025) and 0.024 (0.013–0.035) for cardiovascular mortality. Other lifestyle factors did not consistently improve discrimination across models and outcomes. The pattern of results for R2 mirrored those for C-index. Conclusion A simple self-reported measure of walking pace was the only lifestyle variable found to improve risk prediction for all-cause and cardiovascular mortality when added to established risk factors.

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Effects of Renin‐Angiotensin–Aldosterone System Inhibitors on Long‐Term Major Adverse Cardiovascular Events in Sepsis Survivors

Journal of the American Heart Association ◽

10.1161/jaha.121.022870 ◽

2021 ◽

Author(s):

Shu‐Yu Ou ◽

Yi‐Jung Lee ◽

Yuan Lo ◽

Chen‐Hsiu Chen ◽

Yu‐Chi Huang ◽

...

Keyword(s):

Propensity Scores ◽

Major Adverse Cardiovascular Events ◽

Cardiac Events ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Adverse Cardiac Events ◽

All Cause Mortality ◽

Sepsis Survivors ◽

Renal Hypoperfusion

Background Sepsis is known to increase morbidity and duration of hospital stay and is a common cause of mortality worldwide. Renin‐angiotensin‐aldosterone system inhibitors (RAASis) are commonly used to treat hypertension but are usually discontinued during hospitalization for sepsis because of concerns about renal hypoperfusion. The aim of our study was to investigate whether RAASis should be continued after discharge in sepsis survivors and to identify the effects on the clinical outcomes. Methods and Results A total of 9188 sepsis survivors aged 20 years and older who were discharged from January 1, 2012 to December 31, 2019 were included in our analyses. We further divided sepsis survivors into RAASi users and nonusers. These groups were matched by propensity scores before the outcomes of interest, including all‐cause mortality and major adverse cardiac events (MACE), were examined. After propensity score matching, 3106 RAASi users and 3106 RAASi nonusers were included in our analyses. Compared with RAASi nonusers, RAASi users had lower risks of all‐cause mortality (hazard ratio [HR], 0.68; 95% CI, 0.62–0.75), MACEs (HR, 0.87; 95% CI, 0.81–0.94), ischemic stroke (HR, 0.85; 95% CI, 0.76–0.96), myocardial infarction (HR, 0.74; 95% CI, 0.61–0.90), and hospitalization for heart failure (HR, 0.84; 95% CI, 0.77–0.92). Subgroup analyses stratified by admission to the ICU and the use of inotropes showed similar results. Conclusions In our study, we found that RAASi users had reduced risks of all‐cause mortality and MACEs. These findings suggested a beneficial effect of RAASi use by sepsis survivors after discharge.

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