Antihypertensive Medication Use and Its Effects on Blood Pressure and Haemodynamics in a Tri-ethnic Population Cohort: Southall and Brent Revisited (SABRE)

Objectives: We characterised differences in BP control and use of antihypertensive medications in European (EA), South Asian (SA) and African-Caribbean (AC) people with hypertension and investigated the potential role of type 2 diabetes (T2DM), reduced arterial compliance (Ca), and antihypertensive medication use in any differences. Methods: Analysis was restricted to individuals with hypertension [age range 59-85 years; N = 852 (EA = 328, SA = 356, and AC =168)]. Questionnaires, anthropometry, BP measurements, echocardiography, and fasting blood assays were performed. BP control was classified according to UK guidelines operating at the time of the study. Data were analysed using generalised structural equation models, multivariable regression and treatment effect models. Results: SA and AC people were more likely to receive treatment for high BP and received a greater average number of antihypertensive agents, but despite this a smaller proportion of SA and AC achieved control of BP to target [age and sex adjusted odds ratio (95% confidence interval) = 0.52 (0.38, 0.72) and 0.64 (0.43, 0.96), respectively]. Differences in BP control were partially attenuated by controlling for the higher prevalence of T2DM and reduced Ca in SA and AC. There was little difference in choice of antihypertensive agent by ethnicity and no evidence that differences in efficacy of antihypertensive regimens contributed to ethnic differences in BP control. Conclusions: T2DM and more adverse arterial stiffness are important factors in the poorer BP control in SA and AC people. More effort is required to achieve better control of BP, particularly in UK ethnic minorities

Ethnic disparities in initiation and intensification of diabetes treatment in adults with type 2 diabetes in the UK, 1990-2017: A cohort study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) disproportionately affects individuals of nonwhite ethnic origin. Timely and appropriate initiation and intensification of glucose-lowering therapy is key to reducing the risk of major vascular outcomes. Given that ethnic inequalities in outcomes may stem from differences in therapeutic management, the aim of this study was to identify ethnic differences in the timeliness of initiation and intensification of glucose-lowering therapy in individuals newly diagnosed with T2DM in the United Kingdom. METHODS AND FINDINGS: An observational cohort study using the Clinical Practice Research Datalink was conducted using 162,238 adults aged 18 and over diagnosed with T2DM between 1990 and 2017 (mean age 62.7 years, 55.2% male); 93% were of white ethnicity (n = 150,754), 5% were South Asian (n = 8,139), and 2.1% were black (n = 3,345). Ethnic differences in time to initiation and intensification of diabetes treatment were estimated at three time points (initiation of noninsulin monotherapy, intensification to noninsulin combination therapy, and intensification to insulin therapy) using multivariable Cox proportional hazards regression adjusted for factors a priori hypothesised to be associated with initiation and intensification: age, sex, deprivation, glycated haemoglobin (HbA1c), body mass index (BMI), smoking status, comorbidities, consultations, medications, calendar year, and clustering by practice. Odds of experiencing therapeutic inertia (failure to intensify treatment within 12 months of HbA1c >7.5% [58 mmol/mol]), were estimated using multivariable logistic regression adjusted for the same hypothesised confounders. Noninsulin monotherapy was initiated earlier in South Asian and black groups (South Asian HR 1.21, 95% CI 1.08-1.36, p < 0.001; black HR 1.29, 95% CI 1.05-1.59, p = 0.017). Correspondingly, no ethnic differences in therapeutic inertia were evident at initiation. Intensification with noninsulin combination therapy was slower in both nonwhite ethnic groups relative to white (South Asian HR 0.80, 95% CI 0.74-0.87, p < 0.001; black HR 0.79, 95% CI 0.70-0.90, p < 0.001); treatment inertia at this stage was greater in nonwhite groups relative to white (South Asian odds ratio [OR] 1.45, 95% CI 1.23-1.70, p < 0.001; black OR 1.43, 95% CI 1.09-1.87, p = 0.010). Intensification to insulin therapy was slower again for black groups relative to white groups (South Asian HR 0.49, 95% CI 0.41-0.58, p < 0.001; black HR 0.69, 95% CI 0.53-0.89, p = 0.012); correspondingly, treatment inertia was significantly higher in nonwhite groups at this stage relative to white groups (South Asian OR 2.68, 95% CI 1.89-3.80 p < 0.001; black OR 1.82, 95% CI 1.13-2.79, p = 0.013). At both stages of treatment intensification, nonwhite groups had fewer HbA1c measurements than white groups. Limitations included variable quality and completeness of routinely recorded data and a lack of information on medication adherence. CONCLUSIONS: In this large UK cohort, we found persuasive evidence that South Asian and black groups intensified to noninsulin combination therapy and insulin therapy more slowly than white groups and experienced greater therapeutic inertia following identification of uncontrolled HbA1c. Reasons for delays are multifactorial and may, in part, be related to poorer long-term monitoring of risk factors in nonwhite groups. Initiatives to improve timely and appropriate intensification of diabetes treatment are key to reducing disparities in downstream vascular outcomes in these populations

Impact of kidney function on cardiovascular risk and mortality: a comparison of South Asian and European cohorts

Evidence is limited on ethnic differences in associations between kidney function markers and mortality or cardiovascular disease (CVD). Baseline cross-sectional analysis and longitudinal follow-up study of a UK population-based cohort of 1,116 Europeans and 1,104 South Asians of predominantly Indian descent, age 52 ± 7 years at baseline (1988-1991). Kidney function was estimated using Cystatin C and creatinine-based chronic kidney disease (CKD) Epidemiology Collaboration estimated glomerular filtration rate (eGFR) equations, and urinary albumin-creatinine ratio (ACR). Mortality was captured at 27 years, and incident CVD at 22 years, from death certification, medical records and participant report. Longitudinal associations between eGFR/ACR and mortality/incident CVD were examined using Cox models. eGFRcys was lower and ACR higher in South Asians than Europeans. eGFRcys and -eGFRcreat were more strongly associated with outcomes in Europeans than South Asians. Conversely, associations between ACR and outcomes were greater in South Asians than Europeans, for example, for CVD mortality: HRs (95% CI) adjusted for CVD risk factors and ACR/eGFRcys as appropriate, p for ethnicity interaction: eGFRcys: Europeans: 0.76 (0.62-0.92), South Asians: 0.92 (0.78-1.07), p = 0.05, eGFRcreat: Europeans 0.81 (0.67-0.99), South Asians 1.18 (0.97-1.41), p = 0.002, ACR: -Europeans: 1.24 (1.08-1.42), South Asians: 1.39 (1.25-1.57), p= 0.23. Addition of all CKD measures to a standard CVD risk factor model modestly improved prediction capability in -Europeans; in South Asians only ACR contributed to improvement. Strong associations between ACR and outcomes in South Asians of predominantly Indian origin, and null associations for eGFRcys and eGFRcreat, suggest that ACR may have greater utility in CVD risk prediction in South Asians. Further work is needed to validate these -findings. [Abstract copyright: © 2019 S. Karger AG, Basel.

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

Risk of 16 cancers across the full glycemic spectrum: a population-based cohort study using the UK Biobank.

INTRODUCTION: Diabetes is observed to increase cancer risk, leading to hypothesized direct effects of either hyperglycemia or medication. We investigated associations between glycosylated hemoglobin (HbA1c) across the whole glycemic spectrum and incidence of 16 cancers in a population sample with comprehensive adjustment for risk factors and medication. RESEARCH DESIGN AND METHODS: Linked data from the UK Biobank and UK cancer registry for all individuals with baseline HbA1c and no history of cancer at enrollment were used. Incident cancer was based on International Classification of Diseases - 10th Edition diagnostic codes. Age-standardized incidence rates were estimated by HbA1c category. Associations between HbA1c, modeled as a restricted cubic spline, and cancer risk were estimated using Cox proportional hazards models. RESULTS: Among 378 253 individuals with average follow-up of 7.1 years, 21 172 incident cancers occurred. While incidence for many of the 16 cancers was associated with hyperglycemia in crude analyses, these associations disappeared after multivariable adjustment, except for pancreatic cancer (HR 1.55, 95% CI 1.22 to 1.98 for 55 vs 35 mmol/mol), and a novel finding of an inverse association between HbA1c and premenopausal breast cancer (HR 1.27, 95% CI 1.00 to 1.60 for 25 vs 35 mmol/mol; HR 0.71, 95% CI 0.54 to 0.94 for 45 vs 35 mmol/mol), not observed for postmenopausal breast cancer. Adjustment for diabetes medications had no appreciable impact on HRs for cancer. CONCLUSIONS: Apart from pancreatic cancer, we did not demonstrate any independent positive association between HbA1c and cancer risk. These findings suggest that the potential for a cancer-inducing, direct effect of hyperglycemia may be misplaced

Sex-specific risks for cardiovascular disease across the glycaemic spectrum: a population-based cohort study using the UK Biobank

Background: We sought to examine sex-specific risks for incident cardiovascular disease (CVD) across the full glycaemic spectrum. Methods: Using data from UK Biobank, we categorised participants’ glycated haemoglobin (HbA1c) at baseline as low-normal (<35 mmol/mol), normal (35–41 mmol/mol), pre-diabetes (42–47 mmol/mol), undiagnosed diabetes (≥48 mmol/mol), or diagnosed diabetes. Our outcomes were coronary artery disease (CAD), atrial fibrillation, deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, heart failure, and a composite outcome of any CVD. Cox regression estimated sex-specific associations between HbA1c and each outcome, sequentially adjusting for socio-demographic, lifestyle, and clinical characteristics. Findings: Among 427,435 people, CVD rates were 16.9 and 9.1 events/1000 person-years for men and women, respectively. Both men and women with pre-diabetes, undiagnosed diabetes, and, more markedly, diagnosed diabetes were at higher risks of CVD than those with normal HbA1c, with relative increases more pronounced in women than men. Age-adjusted HRs for pre-diabetes and undiagnosed diabetes ranged from 1.30 to 1.47; HRs for diagnosed diabetes were 1.55 (1.49–1.61) in men and 2.00 (1.89–2.12) in women (p-interaction <0.0001). Excess risks attenuated and were more similar between men and women after adjusting for clinical and lifestyle factors particularly obesity and antihypertensive or statin use (fully adjusted HRs for diagnosed diabetes: 1.06 [1.02–1.11] and 1.17 [1.10–1.24], respectively). Interpretation: Excess risks in men and women were largely explained by modifiable factors, and could be ameliorated by attention to weight reduction strategies and greater use of antihypertensive and statin medications. Addressing these risk factors could reduce sex disparities in risk of CVD among people with and without diabetes. Funding: Diabetes UK (#15/0005250) and British Heart Foundation (SP/16/6/32726)

HbA1c and brain health across the entire glycaemic spectrum.

AIM: To understand the relationship between HbA1c and brain health across the entire glycaemic spectrum. MATERIALS AND METHODS: We used data from the UK Biobank cohort consisting of 500,000 individuals aged 40-69?years. HbA1c and diabetes diagnosis were used to define baseline glycaemic categories. Our outcomes included incident all-cause dementia, vascular dementia (VD), Alzheimer's dementia (AD), hippocampal volume (HV), white matter hyperintensity (WMH) volume, cognitive function and decline. The reference group was normoglycaemic individuals (HbA1c ?35 & <42 mmol/mol). Our maximum analytical sample contained 449,973 individuals with complete data. RESULTS: Prediabetes and known diabetes increased incident VD (HR 1.54; 95% CI = 1.04, 2.28 and HR 2.97; 95% CI = 2.26, 3.90, respectively). Known diabetes increased all-cause and AD risk (HR 1.91; 95% CI = 1.66, 2.21 and HR 1.84; 95% CI = 1.44, 2.36, respectively). Prediabetes and known diabetes elevated the risks of cognitive decline (OR 1.42; 1.48, 2.96 and OR 1.39; 1.04, 1.75, respectively). Prediabetes, undiagnosed and known diabetes conferred higher WMH volumes (3%, 22% and 7%, respectively) and lower HV (36, 80 and 82?mm3 , respectively), whereas low-normal HbA1c had 1% lower WMH volume and 12?mm3 greater HV. CONCLUSION: Both prediabetes and known diabetes are harmful in terms of VD, cognitive decline and AD risks, as well as lower HV. Associations appeared to be somewhat driven by antihypertensive medication, which implies that certain cardiovascular drugs may ameliorate some of the excess risk. Low-normal HbA1c levels, however, are associated with more favourable brain health outcomes and warrant more in-depth investigation

Is glycaemia associated with poorer brain health and risk of dementia? Cross sectional and follow-up analysis of the UK Biobank

ABSTRACTINTRODUCTIONTo understand the relationship across the glycaemic spectrum, with brain health.METHODSUK Biobank participants. HbA1c and diabetes diagnosis define baseline glycaemic categories. Outcomes: incident vascular dementia (VD), Alzheimer’s dementia (AD), hippocampal volume (HV), white matter hyperintensity (WMH) volume, cognitive function and decline. Reference group: normoglycaemic individuals (HbA1c 35-&lt;42 mmol/mol).RESULTSPre- and known diabetes increased incident VD, (HR 1.54, 95%CI=1.04;2.28 and 2.97, 95%CI=2.26;3.90). Known diabetes increased AD risk (HR 1.84, 95%CI=1.44;2.36). Pre- and known diabetes elevated risks of cognitive decline (OR 1.42, 1.48;2.96 and 1.39, 1.04;1.75). Pre-diabetes, undiagnosed and known diabetes conferred higher WMH volumes (4%, 26%, 5%,) and lower HV (22.4mm3, 15.2mm3, 62.2mm3). Low-normal HbA1c had 2% lower WMH volume and 13.6mm3 greater HV.DISCUSSIONPre and known diabetes increase VD risks; known diabetes increases AD risk. Low-normal HbA1c associates with favourable neuroimaging outcomes. Our findings may have implications for cardiovascular medication in hyperglycaemia for brain health.</jats:sec

Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank.

Background The "healthy obese" hypothesis suggests the risks associated with excess adiposity are reduced in those with higher muscle quality (mass/strength). Alternative possibilities include loss of muscle quality as people become unwell (reverse causality) or unmeasured confounding. Methods and Results We conducted a cohort study using the UK Biobank (n=452 931). Baseline body mass index ( BMI) was used to quantify adiposity and handgrip strength ( HGS ) used for muscle quality. Outcomes were fatal and non-fatal cardiovascular disease, and mortality. As a secondary analysis we used waist-hip-ratio or fat mass percentage instead of BMI , and skeletal muscle mass index instead of HGS . In a subsample, we used gene scores for BMI , waist-hip-ratio and HGS in a Mendelian randomization ( MR ). BMI defined obesity was associated with an increased risk of all outcomes (hazard ratio [ HR ] range 1.10-1.82). Low HGS was associated with increased risks of cardiovascular and all-cause mortality ( HR range 1.39-1.72). HR s for the association between low HGS and cardiovascular disease events were smaller ( HR range 1.05-1.09). There was no suggestion of an interaction between HGS and BMI to support the healthy obese hypothesis. Results using other adiposity metrics were similar. There was no evidence of an association between skeletal muscle mass index and any outcome. Factorial Mendelian randomization confirmed no evidence for an interaction. Low genetically predicted HGS was associated with an increased risk of mortality ( HR range 1.08-1.19). Conclusions Our analyses do not support the healthy obese concept, with no evidence that the adverse effect of obesity on outcomes was reduced by improved muscle quality. Lower HGS was associated with increased risks of mortality in both observational and MR analyses, suggesting reverse causality may not be the sole explanation

Ethnic Differences in the Association Between Age at Natural Menopause and Risk of Type 2 Diabetes Among Postmenopausal Women: A Pooled Analysis of Individual Data From 13 Cohort Studies

OBJECTIVE: To investigate associations between age at natural menopause, particularly premature ovarian insufficiency (POI; natural menopause before age 40 years), and incident type 2 diabetes (T2D) and identify any variations by ethnicity. RESEARCH DESIGN AND METHODS: We pooled individual-level data of 338,059 women from 13 cohort studies without T2D before menopause from six ethnic groups: White (n = 177,674), Chinese (n = 146,008), Japanese (n = 9,061), South/Southeast Asian (n = 2,228), Black (n = 1,838), and mixed/other (n = 1,250). Hazard ratios (HRs) of T2D associated with age at menopause were estimated in the overall sample and by ethnicity, with study as a random effect. For each ethnic group, we further stratified the association by birth year, education level, and BMI. RESULTS: Over 9 years of follow-up, 20,064 (5.9%) women developed T2D. Overall, POI (vs. menopause at age 50-51 years) was associated with an increased risk of T2D (HR 1.31; 95% CI 1.20-1.44), and there was an interaction between age at menopause and ethnicity (P < 0.0001). T2D risk associated with POI was higher in White (1.53; 1.36-1.73), Japanese (4.04; 1.97-8.27), and Chinese women born in 1950 or later (2.79; 2.11-3.70); although less precise, the risk estimates were consistent in women of South/Southeast Asian (1.46; 0.89-2.40), Black (1.72; 0.95-3.12), and mixed/other (2.16; 0.83-5.57) ethnic groups. A similar pattern, but with a smaller increased risk of T2D, was observed with early menopause overall (1.16; 1.10-1.23) and for White, Japanese, and Chinese women born in 1950 or later. CONCLUSIONS: POI and early menopause are risk factors for T2D in postmenopausal women, with considerable variation across ethnic groups, and may need to be considered in risk assessments of T2D among women