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Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment.Analysis of data from over 400,000 UK Biobank participants shows that eGFR measured by cystatin C, but not serum creatinine, is strongly associated with cardiovascular disease outcomes and mortality.

COVID-19 vaccination in many countries, including England, has been prioritised primarily by age. However, people of the same age can have very different health statuses. Frailty is a commonly used metric of health and has been found to be more strongly associated with mortality than age among COVID-19 inpatients. We compared the number of first vaccine doses administered across the 135 NHS Clinical Commissioning Groups (CCGs) of England to both the over 50 population and the estimated frail population in each area. Area-based frailty estimates were generated using the English Longitudinal Survey of Ageing (ELSA), a national survey of older people. We also compared the number of doses to the number of people with other risk factors associated with COVID-19: atrial fibrillation, chronic kidney disease, diabetes, learning disabilities, obesity and smoking status. We estimate that after 79 days of the vaccine program, across all Clinical Commissioning Group areas, the number of people who received a first vaccine per frail person ranged from 4.4 (95% CI 4.0-4.8) and 20.1 (95% CI 18.3-21.9). The prevalences of other risk factors were also poorly associated with the prevalence of vaccination across England. Vaccination with age-based priority created area-based inequities in the number of doses administered relative to the number of people who are frail or have other risk factors associated with COVID-19. As frailty has previously been found to be more strongly associated with mortality than age for COVID-19 inpatients, an age-based priority system may increase the risk of mortality in some areas during the vaccine roll-out period. Authorities planning COVID-19 vaccination programmes should consider the disadvantages of an age-based priority system.

To investigate whether the addition of grip strength and/or self-reported walking pace to established cardiovascular disease (CVD) risk scores improves their predictive abilities. A total of 406,834 participants from the UK Biobank, with baseline measurements between March 13, 2006, and October 1, 2010, without CVD at baseline were included in this study. Associations of grip strength and walking pace with CVD outcomes were investigated using Cox models adjusting for classical risk factors (as included in established risk scores), and predictive utility was determined by changes in C-index and categorical net reclassification index. Over a median of 8.87 years of follow-up (interquartile range 3, 8.25-9.47 years), there were 7274 composite fatal/nonfatal events (on the basis of the American College of Cardiology/American Heart Association [ACC/AHA] outcome) and 1955 fatal events (on the basis of the Systematic Coronary Risk Evaluation [SCORE] risk score). Both grip strength and walking pace were inversely associated with CVD outcomes after adjusting for classical risk factors. Addition of grip strength (change in C-index: ACC/AHA, +0.0017; SCORE, +0.0047), usual walking pace (ACC/AHA, +0.0031; SCORE, +0.0130), and both combined (ACC/AHA, +0.0041; SCORE, +0.0148) improved the C-index and also improved the net reclassification index (grip, +0.55%; walking pace, +0.53%; combined, 1.12%). The present study has found that the addition of grip strength or usual walking pace to existing risk scores results in improved CVD risk prediction, with an additive effect when both are added. As both these measures are cheap and easy to administer, these tools could provide an important addition to CVD risk screening, although further external validation is required.

ObjectivesTo examine how ecological inequalities in COVID-19 mortality rates evolved in England, and whether the first national lockdown impacted them. This analysis aimed to provide evidence for important lessons to inform public health planning to reduce inequalities in any future pandemics.DesignLongitudinal ecological study.Setting307 lower-tier local authorities in England.Primary outcome measureAge-standardised COVID-19 mortality rates by local authority, regressed on Index of Multiple Deprivation (IMD) and relevant epidemic dynamics.ResultsLocal authorities that started recording COVID-19 deaths earlier were more deprived, and more deprived authorities saw faster increases in their death rates. By 6 April 2020 (week 15, the earliest time that the 23 March lockdown could have begun affecting death rates) the cumulative death rate in local authorities in the two most deprived deciles of IMD was 54% higher than the rate in the two least deprived deciles. By 4 July 2020 (week 27), this gap had narrowed to 29%. Thus, inequalities in mortality rates by decile of deprivation persisted throughout the first wave, but reduced during the lockdown.ConclusionsThis study found significant differences in the dynamics of COVID-19 mortality at the local authority level, resulting in inequalities in cumulative mortality rates during the first wave of the pandemic. The first lockdown in England was fairly strict—and the study found that it particularly benefited those living in more deprived local authorities. Care should be taken to implement lockdowns early enough, in the right places—and at a sufficiently strict level—to maximally benefit all communities, and reduce inequalities.

ObjectivesTo identify and map evidence about the consequences of unpaid caring for all carers of older people, and effective interventions to support this carer population.DesignA rapid review of systematic reviews, focused on the consequences for carers of unpaid caring for older people, and interventions to support this heterogeneous group of carers. Reviews of carers of all ages were eligible, with any outcome measures relating to carers’ health, and social and financial well-being. Searches were conducted in MEDLINE, PsycInfo and Epistemonikos (January 2000 to January 2020). Records were screened, and included systematic reviews were quality appraised. Summary data were extracted and a narrative synthesis produced.ResultsTwelve systematic reviews reporting evidence about the consequences of caring for carers (n=6) and assessing the effectiveness of carer interventions (n=6) were included. The review evidence typically focused on mental health outcomes, with little information identified about carers’ physical, social and financial well-being. Clear estimates of the prevalence and severity of carer outcomes, and how these differ between carers and non-carers, were absent. A range of interventions were identified, but there was no strong evidence of effectiveness. In some studies, the choice of outcome measure may underestimate the full impact of an intervention.ConclusionsCurrent evidence fails to fully quantify the impacts that caring for older people has on carers’ health and well-being. Information on social patterning of the consequences of caring is absent. Systematic measurement of a broad range of outcomes, with comparison to the general population, is needed to better understand the true consequences of caring. Classification of unpaid caring as a social determinant of health could be an effective lever to bring greater focus and support to this population. Further work is needed to develop and identify suitable interventions in order to support evidence-based policymaking and practice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BackgroundReducing avoidable systematic differences in population health requires first understanding which populations are currently disadvantaged. Although the health of coastal communities in England has been of concern for some years, an operationalised definition of ‘coastal’ is lacking. This study aims to use national cancer statistics to define and validate a small area-level definition of ‘coastal’ that could be used to better report cancer-related health inequalities in England.MethodsInformation on the geography and demography of English populations at the Lower Super Output Area (LSOA) level were used to define a suite of candidate coastal variables that considered foreshore proximity, resident population location, rurality and deprivation. Adjusted linear models of LSOA-level statistics of cancer incidence, prevalence and mortality in England (2016 to 2020) were used to identify candidate coastal variable(s) that explained the greatest proportion of variation in cancer outcomes after adjustment.ResultsThe candidate ‘G_25_5’ (LSOA’s designated as ‘coastal’ if 25% or more of postcodes were within 5 km of the coastline) was selected as the candidate that explained the most residual variation in cancer incidence and prevalence after adjustment. This variable would assign 7377 2011 LSOAs as coastal, whose populations summed to 12.3 million people (22% of England’s population, in 2016). This candidate variable was not significantly associated with cancer mortality.ConclusionsThe coastal variable that we identify can explain some of the ‘coastal excess’ in poor cancer outcomes. We propose that this variable is now embedded into health inequalities reporting and adopted as the working definition of ‘coastal’ implicated in NHS England’s ‘Core20PLUS5’ approach for use in cancer data reporting.

Background Multimorbidity [the presence of two or more long-term conditions (LTCs)] is associated with a heightened risk of mortality, but little is known about its relationship with the risk of kidney events. Methods Associations between multimorbidity and major adverse kidney events [MAKE: the need for long-term kidney replacement therapy, doubling of serum creatinine, fall of estimated glomerular filtration rate (eGFR) to <15 mL/min/1.73 m2 or 30% decline in eGFR] were studied in 68 505 participants from the UK Biobank cohort. Participants were enrolled in the study between 2006 and 2010. Associations between LTC counts and MAKE were tested using survival analyses accounting for the competing risk of death. Results Over a median follow-up period of 12.0 years, 2963 participants had MAKE. There were associations between LTC count categories and the risk of MAKE [one LTC adjusted subhazard ratio (sHR) = 1.29, 95% confidence interval (CI) 1.15–1.45; two LTCs sHR = 1.74 (95% CI 1.55–1.96); and three or more LTCs sHR = 2.41 (95% CI 2.14–2.71)]. This finding was more pronounced when only cardiometabolic LTCs were considered [one LTC sHR = 1.58 (95% CI 1.45–1.73); two LTCs sHR = 3.17 (95% CI 2.80–3.59); and three or more LTCs sHR = 5.24 (95% CI 4.34–6.33)]. Combinations of LTCs associated with MAKE were identified. Diabetes, hypertension and coronary heart disease featured most commonly in high-risk combinations. Conclusions Multimorbidity, and in particular cardiometabolic multimorbidity, is a risk factor for MAKE. Future research should study groups of patients who are at high risk of progressive kidney disease based on the number and type of LTCs. Graphical Abstract GRAPHICAL ABSTRACT

IntroductionEarly detection and treatment of diabetes as well as its prevention help lessen longer-term complications. We determined the prevalence of pre-diabetes and undiagnosed diabetes in the UK Biobank and standardized the results to the UK general population.Research design and methodsThis cross-sectional study analyzed baseline UK Biobank data on plasma glycated hemoglobin (HbA1c) to compare the prevalence of pre-diabetes and undiagnosed diabetes mellitus in white, South Asian, black, and Chinese participants. The overall and ethnic-specific results were standardized to the UK general population aged 40–70 years of age.ResultsWithin the UK Biobank, the overall crude prevalence was 3.6% for pre-diabetes, 0.8% for undiagnosed diabetes, and 4.4% for either. Following standardization to the UK general population, the results were similar at 3.8%, 0.8%, and 4.7%, respectively. Crude prevalence was much higher in South Asian (11.0% pre-diabetes; 3.6% undiagnosed diabetes; 14.6% either) or black (13.8% pre-diabetes; 3.0% undiagnosed diabetes; 16.8% either) participants. Only six middle-aged or old-aged South Asian individuals or seven black would need to be tested to identify an HbA1c result that merits action.ConclusionsSingle-stage population screening for pre-diabetes or undiagnosed diabetes in middle-old or old-aged South Asian and black individuals using HbA1c could be efficient and should be considered.

Few data compare cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in a general population. We sought to evaluate the distribution and association between cTnT, cTnI, and cardiovascular risk factors in a large general population cohort. High-sensitivity cTnT and cTnI were measured in serum from 19501 individuals in the Generation Scotland Scottish Family Health Study. Associations with cardiovascular risk factors were compared using age- and sex-adjusted regression. Observed age- and sex-stratified 99th centiles were compared with 99th centiles for cTnT (men, 15.5 ng/L; women, 9.0 ng/L) and cTnI (men, 34.2 ng/L; women, 15.6 ng/L) used in clinical practice. cTnT and cTnI concentrations were detectable in 53.3% and 74.8% of participants, respectively, and were modestly correlated in unadjusted analyses ( = 21.3%) and only weakly correlated after adjusting for age and sex ( = 9.5%). Cardiovascular risk factors were associated with both troponins, but in age- and sex-adjusted analyses, cTnI was more strongly associated with age, male sex, body mass index, and systolic blood pressure ( < 0.0001 for all vs cTnT). cTnT was more strongly associated with diabetes ( < 0.0001 vs cTnI). The observed 99th centiles were broadly consistent with recommended 99th centiles in younger men and women. After the age of 60 years, observed 99th centiles increased substantially for cTnT, and beyond 70 years of age, the 99th centiles approximately doubled for both troponins. In the general population, cTnT and cTnI concentrations are weakly correlated and are differentially associated with cardiovascular risk factors. The 99th centiles currently in use are broadly appropriate for men and women up to but not beyond the age of 60 years.