Ancestry, ethnicity, and race: explaining inequalities in cardiometabolic disease.

Population differences in cardiometabolic disease remain unexplained. Misleading assumptions over genetic explanations are partly due to terminology used to distinguish populations, specifically ancestry, race, and ethnicity. These terms differentially implicate environmental and biological causal pathways, which should inform their use. Genetic variation alone accounts for a limited fraction of population differences in cardiometabolic disease. Research effort should focus on societally driven, lifelong environmental determinants of population differences in disease. Rather than pursuing population stratifiers to personalize medicine, we advocate removing socioeconomic barriers to receipt of and adherence to healthcare interventions, which will have markedly greater impact on improving cardiometabolic outcomes. This requires multidisciplinary collaboration and public and policymaker engagement to address inequalities driven by society rather than biology per se.

Long COVID and financial outcomes: evidence from four longitudinal population surveys.

BACKGROUND: Long-term sequelae of COVID-19 (long COVID) include muscle weakness, fatigue, breathing difficulties and sleep disturbance over weeks or months. Using UK longitudinal data, we assessed the relationship between long COVID and financial disruption. METHODS: We estimated associations between long COVID (derived using self-reported length of COVID-19 symptoms) and measures of financial disruption (subjective financial well-being, new benefit claims, changes in household income) by analysing data from four longitudinal population studies, gathered during the first year of the pandemic. We employed modified Poisson regression in a pooled analysis of the four cohorts adjusting for a range of potential confounders, including pre-pandemic (pre-long COVID) factors. RESULTS: Among the 20 112 observations across four population surveys, 13% reported having COVID-19 with symptoms that impeded their ability to function normally-10.7% had such symptoms for <4 weeks (acute COVID-19), 1.2% had such symptoms for 4-12 weeks (ongoing symptomatic COVID-19) and 0.6% had such symptoms for >12 weeks (post-COVID-19 syndrome). We found that post-COVID-19 syndrome was associated with worse subjective financial well-being (adjusted relative risk ratios (aRRRs)=1.57, 95% CI=1.25, 1.96) and new benefit claims (aRRR=1.79, CI=1.27, 2.53). Associations were broadly similar across sexes and education levels. These results were not meaningfully altered when scaled to represent the population by age. CONCLUSIONS: Long COVID was associated with financial disruption in the UK. If our findings reflect causal effects, extending employment protection and financial support to people with long COVID may be warranted.

Inequalities in healthcare disruptions during the COVID-19 pandemic: evidence from 12 UK population-based longitudinal studies.

OBJECTIVES: We investigated associations between multiple sociodemographic characteristics (sex, age, occupational social class, education and ethnicity) and self-reported healthcare disruptions during the early stages of the COVID-19 pandemic. DESIGN: Coordinated analysis of prospective population surveys. SETTING: Community-dwelling participants in the UK between April 2020 and January 2021. PARTICIPANTS: Over 68 000 participants from 12 longitudinal studies. OUTCOMES: Self-reported healthcare disruption to medication access, procedures and appointments. RESULTS: Prevalence of healthcare disruption varied substantially across studies: between 6% and 32% reported any disruption, with 1%-10% experiencing disruptions in medication, 1%-17% experiencing disruption in procedures and 4%-28% experiencing disruption in clinical appointments. Females (OR 1.27; 95% CI 1.15 to 1.40; I2=54%), older persons (eg, OR 1.39; 95% CI 1.13 to 1.72; I2=77% for 65-75 years vs 45-54 years) and ethnic minorities (excluding white minorities) (OR 1.19; 95% CI 1.05 to 1.35; I2=0% vs white) were more likely to report healthcare disruptions. Those in a more disadvantaged social class were also more likely to report healthcare disruptions (eg, OR 1.17; 95% CI 1.08 to 1.27; I2=0% for manual/routine vs managerial/professional), but no clear differences were observed by education. We did not find evidence that these associations differed by shielding status. CONCLUSIONS: Healthcare disruptions during the COVID-19 pandemic could contribute to the maintenance or widening of existing health inequalities.

Genetic and observational evidence: No independent role for cholesterol efflux over static high-density lipoprotein concentration measures in coronary heart disease risk assessment.

BACKGROUND: Observational findings for high-density lipoprotein (HDL)-mediated cholesterol efflux capacity (HDL-CEC) and coronary heart disease (CHD) appear inconsistent, and knowledge of the genetic architecture of HDL-CEC is limited. OBJECTIVES: A large-scale observational study on the associations of HDL-CEC and other HDL-related measures with CHD and the largest genome-wide association study (GWAS) of HDL-CEC. PARTICIPANTS/METHODS: Six independent cohorts were included with follow-up data for 14,438 participants to investigate the associations of HDL-related measures with incident CHD (1,570 events). The GWAS of HDL-CEC was carried out in 20,372 participants. RESULTS: HDL-CEC did not associate with CHD when adjusted for traditional risk factors and HDL cholesterol (HDL-C). In contradiction, almost all HDL-related concentration measures associated consistently with CHD after corresponding adjustments. There were no genetic loci associated with HDL-CEC independent of HDL-C and triglycerides. CONCLUSION: HDL-CEC is not unequivocally associated with CHD in contrast to HDL-C, apolipoprotein A-I, and most of the HDL subclass particle concentrations.

Socioeconomic inequalities in prevalence and development of multimorbidity across adulthood: A longitudinal analysis of the MRC 1946 National Survey of Health and Development in the UK.

BACKGROUND: We aimed to estimate multimorbidity trajectories and quantify socioeconomic inequalities based on childhood and adulthood socioeconomic position (SEP) in the risks and rates of multimorbidity accumulation across adulthood. METHODS AND FINDINGS: Participants from the UK 1946 National Survey of Health and Development (NSHD) birth cohort study who attended the age 36 years assessment in 1982 and any one of the follow-up assessments at ages 43, 53, 63, and 69 years (N = 3,723, 51% males). Information on 18 health conditions was based on a combination of self-report, biomarkers, health records, and prescribed medications. We estimated multimorbidity trajectories and delineated socioeconomic inequalities (based on childhood and adulthood social class and highest education) in multimorbidity at each age and in longitudinal trajectories. Multimorbidity increased with age (0.7 conditions at 36 years to 3.7 at 69 years). Multimorbidity accumulation was nonlinear, accelerating with age at the rate of 0.08 conditions/year (95% CI 0.07 to 0.09, p < 0.001) at 36 to 43 years to 0.19 conditions/year (95% CI 0.18 to 0.20, p < 0.001) at 63 to 69 years. At all ages, the most socioeconomically disadvantaged had 1.2 to 1.4 times greater number of conditions on average compared to the most advantaged. The most disadvantaged by each socioeconomic indicator experienced an additional 0.39 conditions (childhood social class), 0.83 (adult social class), and 1.08 conditions (adult education) at age 69 years, independent of all other socioeconomic indicators. Adverse adulthood SEP was associated with more rapid accumulation of multimorbidity, resulting in 0.49 excess conditions in partly/unskilled compared to professional/intermediate individuals between 63 and 69 years. Disadvantaged childhood social class, independently of adulthood SEP, was associated with accelerated multimorbidity trajectories from age 53 years onwards. Study limitations include that the NSHD cohort is composed of individuals of white European heritage only, and findings may not be generalizable to the non-white British population of the same generation and did not account for other important dimensions of SEP such as income and wealth. CONCLUSIONS: In this study, we found that socioeconomically disadvantaged individuals have earlier onset and more rapid accumulation of multimorbidity resulting in widening inequalities into old age, with independent contributions from both childhood and adulthood SEP.

Ethnic differences in guideline-indicated statin initiation for people with type 2 diabetes in UK primary care, 2006-2019: A cohort study.

BACKGROUND: Type 2 diabetes is 2-3 times more prevalent in people of South Asian and African/African Caribbean ethnicity than people of European ethnicity living in the UK. The former 2 groups also experience excess atherosclerotic cardiovascular disease (ASCVD) complications of diabetes. We aimed to study ethnic differences in statin initiation, a cornerstone of ASCVD primary prevention, for people with type 2 diabetes. METHODS AND FINDINGS: Observational cohort study of UK primary care records, from 1 January 2006 to 30 June 2019. Data were studied from 27,511 (88%) people of European ethnicity, 2,386 (8%) people of South Asian ethnicity, and 1,142 (4%) people of African/African Caribbean ethnicity with incident type 2 diabetes, no previous ASCVD, and statin use indicated by guidelines. Statin initiation rates were contrasted by ethnicity, and the number of ASCVD events that could be prevented by equalising prescribing rates across ethnic groups was estimated. Median time to statin initiation was 79, 109, and 84 days for people of European, South Asian, and African/African Caribbean ethnicity, respectively. People of African/African Caribbean ethnicity were a third less likely to receive guideline-indicated statins than European people (n/N [%]: 605/1,142 [53%] and 18,803/27,511 [68%], respectively; age- and gender-adjusted HR 0.67 [95% CI 0.60 to 0.76], p < 0.001). The HR attenuated marginally in a model adjusting for total cholesterol/high-density lipoprotein cholesterol ratio (0.77 [95% CI 0.69 to 0.85], p < 0.001), with no further diminution when deprivation, ASCVD risk factors, comorbidity, polypharmacy, and healthcare usage were accounted for (fully adjusted HR 0.76 [95% CI 0.68, 0.85], p < 0.001). People of South Asian ethnicity were 10% less likely to receive a statin than European people (1,489/2,386 [62%] and 18,803/27,511 [68%], respectively; fully adjusted HR 0.91 [95% CI 0.85 to 0.98], p = 0.008, adjusting for all covariates). We estimated that up to 12,600 ASCVD events could be prevented over the lifetimes of people currently affected by type 2 diabetes in the UK by equalising statin prescribing across ethnic groups. Limitations included incompleteness of recording of routinely collected data. CONCLUSIONS: In this study we observed that people of African/African Caribbean ethnicity with type 2 diabetes were substantially less likely, and people of South Asian ethnicity marginally less likely, to receive guideline-indicated statins than people of European ethnicity, even after accounting for sociodemographics, healthcare usage, ASCVD risk factors, and comorbidity. Underuse of statins in people of African/African Caribbean or South Asian ethnicity with type 2 diabetes is a missed opportunity to prevent cardiovascular events.

Metabolic profiles of socio-economic position: a multi-cohort analysis.

BACKGROUND: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. METHODS: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies. RESULTS: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids. CONCLUSIONS: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities.

Modelling ethnic differences in the distribution of insulin resistance via Bayesian nonparametric processes: an application to the SABRE cohort study.

We analyse data from the Southall And Brent REvisited (SABRE) tri-ethnic study, where measurements of metabolic and anthropometric variables have been recorded. In particular, we focus on modelling the distribution of insulin resistance which is strongly associated with the development of type 2 diabetes. We propose the use of a Bayesian nonparametric prior to model the distribution of Homeostasis Model Assessment insulin resistance, as it allows for data-driven clustering of the observations. Anthropometric variables and metabolites concentrations are included as covariates in a regression framework. This strategy highlights the presence of sub-populations in the data, characterised by different levels of risk of developing type 2 diabetes across ethnicities. Posterior inference is performed through Markov Chains Monte Carlo (MCMC) methods.

Effectiveness and cost-effectiveness of a Yoga-based Cardiac Rehabilitation (Yoga-CaRe) program following acute myocardial infarction: Study rationale and design of a multi-center randomized controlled trial.

BACKGROUND: Cardiac rehabilitation (CR) is a standard treatment for secondary prevention of acute myocardial infarction (AMI) in high income countries (HICs), but it is inaccessible to most patients in India due to high costs and skills required for multidisciplinary CR teams. We developed a low-cost and scalable CR program based on culturally-acceptable practice of yoga (Yoga-CaRe). In this paper, we report the rationale and design for evaluation of its effectiveness and cost-effectiveness. METHODS: This is a multi-center, single-blind, two-arm parallel-group randomized controlled trial across 22 cardiac care hospitals in India. Four thousand patients aged 18-80 years with AMI will be recruited and randomized 1:1 to receive Yoga-CaRe program (13 sessions supervised by an instructor and encouragement to self-practice daily) or enhanced standard care (3 sessions of health education) delivered over a period of three months. Participants will be followed 3-monthly till the end of the trial. The co-primary outcomes are a) time to occurrence of first cardiovascular event (composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke and emergency cardiovascular hospitalization), and b) quality of life (Euro-QoL-5L) at 12 weeks. Secondary outcomes include need for revascularization procedures, return to pre-infarct activities, tobacco cessation, medication adherence, and cost-effectiveness of the intervention. CONCLUSION: This trial will alone contribute >20% participants to existing meta-analyses of randomized trials of CR worldwide. If Yoga-CaRe is found to be effective, it has the potential to save millions of lives and transform care of AMI patients in India and other low and middle income country settings.

Assessment of Exercise Capacity and Oxygen Consumption Using a 6 min Stepper Test in Older Adults.

It is often necessary to assess physical function in older adults to monitor disease progression, rehabilitation or decline in function with age. However, increasing frailty and poor balance that accompany aging are common barriers to exercise testing protocols. We investigated whether a 6-min stepper test (6MST) was acceptable to older adults and provided a measure of exercise capacity and a predicted value for peak aerobic capacity (VO2max). 635 older adults from a tri-ethnic UK population-based cohort were screened to undertake a self-paced 6MST. Expired gas analysis, heart rate and blood pressure monitoring were carried out. A sub-set of 20 participants performed a second 6MST for assessment of reproducibility and a further sub-set of 10 performed the 6-min walk test as verification against a well-recognized and accepted self-paced exercise test. 518 (82%) participants met inclusion criteria and undertook the 6MST (299 men, mean age 71.2 ± 6.4). Step rate showed a strong positive correlation with measured VO2 (r = 0.75, p < 0.001) and VO2 was lower in women (male-female difference in VO2 = 2.61 (95% confidence interval -3.6, -1.7) ml/min/kg; p < 0.001). 20 participants repeated a 6MST, step rate was higher in the second test but the predicted VO2max showed good agreement (mean difference = 0.1 [3.72, 3.95] ml/min/kg). In 10 participants who completed a 6MST and a 6-min walk test there was a strong positive correlation between walking rate and step rate (r = 0.77; p < 0.009) and weaker positive correlations between the tests for measured VO2 and peak heart rate. In conclusion, the 6MST is a convenient, acceptable method of assessing exercise capacity in older adults that allows VO2max to be predicted reproducibly. The test shows good correlation between performance and measured physiological markers of performance and can detect the expected gender differences in measured VO2. Furthermore, the 6MST results correlate with a previously verified and established self-paced exercise test.

Population trends in the 10-year incidence and prevalence of diabetic retinopathy in the UK: a cohort study in the Clinical Practice Research Datalink 2004-2014.

OBJECTIVES: To describe trends in the incidence and prevalence of diabetic retinopathy (DR) in the UK by diabetes type, age, sex, ethnicity, deprivation, region and calendar year. DESIGN: Cohort study using the Clinical Practice Research Datalink (CPRD). SETTING: UK primary care. PARTICIPANTS: 7.7 million patients ≥12 contributing to the CPRD from 2004 to 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Age-standardised prevalence and incidence of diabetes, DR and severe DR (requiring photocoagulation) by calendar year and population subgroup. Relative risk of developing DR and severe DR by population subgroup. RESULTS: The prevalence of DR was 48.4% in the population type 1 diabetes mellitus (T1DM) (14 846/30 657) and 28.3% (95 807/338 390) in the population with type 2 diabetes mellitus (T2DM). Prevalence of DR remained stable in people with T2DM and decreased in people with T1DM. Screening for DR increased over time for patients with T2DM and remained static for patients with T1DM Incidence of DR increased in parallel with the incidence of T2DM in both diabetic populations. Among patients with T2DM, relative risk of DR varied significantly by region, was increased for older age groups and in men compared with women, with risk of severe DR increased in South Asian groups and more deprived groups. Relative risk of DR for patients with T1DM varied by age and region, but not by gender, ethnic group or deprivation. CONCLUSIONS: This is the largest study to date examining the burden of DR in the UK. Regional disparities in incidence may relate to differences in screening delivery and disease ascertainment. Evidence that deprivation and ethnicity are associated with a higher risk of severe DR highlights a significant potential health inequality. Findings from this study will have implications for professionals working in the diabetes and sight loss sectors, particularly to inform approaches for diagnosis of retinopathy and campaigning to better tackle the disease for at risk groups.

Recent developments in near-infrared spectroscopy (NIRS) for the assessment of local skeletal muscle microvascular function and capacity to utilise oxygen.

PURPOSE OF REVIEW: Continuous wave near infrared spectroscopy (CW NIRS) provides non-invasive technology to measure relative changes in oxy- and deoxy-haemoglobin in a dynamic environment. This allows determination of local skeletal muscle O2 saturation, muscle oxygen consumption ([Formula: see text]) and blood flow. This article provides a brief overview of the use of CW NIRS to measure exercise-limiting factors in skeletal muscle. RECENT FINDINGS: NIRS parameters that measure O2 delivery and capacity to utilise O2 in the muscle have been developed based on response to physiological interventions and exercise. NIRS has good reproducibility and agreement with gold standard techniques and can be used in clinical populations where muscle oxidative capacity or oxygen delivery (or both) are impaired. CW NIRS has limitations including: the unknown contribution of myoglobin to the overall signals, the impact of adipose tissue thickness, skin perfusion during exercise, and variations in skin pigmentation. These, in the main, can be circumvented through appropriate study design or measurement of absolute tissue saturation. SUMMARY: CW NIRS can assess skeletal muscle O2 delivery and utilisation without the use of expensive or invasive procedures and is useable in large population-based samples, including older adults.

The effects of weight and physical activity change over 20 years on later-life objective and self-reported disability.

BACKGROUND: Weight and health behaviours are known to affect physical disability; however the evidence exploring the impact of changes to these lifestyle factors over the life course on disability is inconsistent. We aimed to explore the roles of weight and activity change between mid and later life on physical disability. METHODS: Baseline and 20-year clinical follow-up data were collected from 1418 men and women, aged 58-88 years at follow-up, as part of a population-based observational study based in north-west London. At clinic, behavioural data were collected by questionnaire and anthropometry measured. Disability was assessed using a performance-based locomotor function test and self-reported questionnaires on functional limitation and basic activities of daily living (ADLs). RESULTS: At follow-up, 39% experienced a locomotor dysfunction, 24% a functional limitation and 17% an impairment of ADLs. Weight gain of 10-20% or >20% of baseline, but not weight loss, were associated with increased odds of a functional limitation [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.14-2.49 and OR 2.74, 1.55-4.83, respectively], after full adjustment for covariates. The same patterns were seen for the other disability outcomes. Increased physical activity reduced, and decreased physical activity enhanced the likelihood of disability, independent of baseline behaviours and adiposity. The adverse effects of weight gain appeared to be lessened in the presence of increased later-life physical activity. CONCLUSION: Weight and activity changes between mid and later life have strong implications for physical functioning in older groups. These findings reinforce the importance of the maintenance of healthy weight and behaviour throughout the life course, and the need to promote healthy lifestyles across population groups.