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Background: Digital health interventions (DHIs) could support prevention and management of cardiometabolic disease. However, those who may benefit most often experience barriers to awareness and adoption of these interventions., Objective: Among South Asian individuals, we evaluated user experience of DHIs for prevention and management of cardiometabolic disease, aiming to understand barriers and facilitators to initial and ongoing use., Methods: Among South Asian individuals recruited via primary care, community organizations, and snowball methods (n=18), we conducted "think-aloud" interviews using a reflective and reactive approach. Participants included nonusers, as well as those that used a range of DHIs as part of monitoring and improving their health. Participants were asked to think aloud while completing a task they routinely do in a familiar DHI, as well as while setting up and completing a search task in a novel DHI; they were encouraged to behave as if unobserved., Results: Lack of cultural specificity was highlighted as reducing relevance and usability, particularly relating to dietary change. Preferred features reflected individual health beliefs and behaviors, digital skills, and trust in DHIs. For example, tracking blood glucose was considered by some to be positive, while for others it caused distress and anxiety. Similarly, some users found the novel DHI to be extremely simple to set up and use, and others grew frustrated navigating through initial interfaces. Many participants raised concerns about data privacy and needing to agree to terms and conditions that they did not understand. Participants expressed that with information and support from trusted sources, they would be interested in using DHIs as part of self-management., Conclusions: DHIs may support South Asians to prevent and manage cardiometabolic disease, but it is important to consider the needs of specific user groups in DHI development, design, and implementation. Despite motivation to make health changes, digital barriers are common. Cultural appropriateness and trusted sources (such as health care providers and community organizations) have roles in increasing awareness and enabling individuals to access and use DHIs., (© Mel Ramasawmy, Dan Roland Persson, David Sunkersing, Paramjit Gill, Kamlesh Khunti, Lydia Poole, Wasim Hanif, Ann Blandford, Madiha Sajid, Fiona Stevenson, Nushrat Khan, Amitava Banerjee. Originally published in JMIR Human Factors (https://humanfactors.jmir.org).)

Aim: To assess mortality and complication trends in people with type 1 diabetes during the 11 years before the SARS-CoV2 pandemic (2009-2019)., Materials and Methods: Sequential cohorts of people in England with type 1 diabetes aged ≥20 years from the National Diabetes Audit (2006/2007 to 2016/2017) were analysed. Discretized Poisson regression models, adjusted for age, sex, ethnicity, socioeconomic deprivation and duration of diabetes, were used to calculate mortality and hospitalization rates., Results: Demographic characteristics changed little; average diabetes duration increased. All-cause mortality was unchanged. Cardiovascular and kidney disease mortality declined. Mortality from respiratory disease, diabetes and dementia increased in younger people (aged 20-74 years) as did mortality from liver disease and dementia in the elderly (aged ≥75 years). Younger Asian and Black people had lower all-cause mortality than those of White ethnicity; elderly Mixed, Asian and Black people had lower all-cause mortality. People from more deprived areas had higher all-cause mortality. The deprivation gradient for mortality was steeper at younger ages. In younger people, rates of hospitalization increased for myocardial infarction, stroke, heart failure and kidney disease but only for kidney disease in the elderly. Rates of a composite measure of cardiovascular hospitalizations increased in younger people (rate ratio [RR] 1.07, 95% confidence interval [CI] 1.03-1.11) but declined in the elderly (RR 0.91, 95% CI 0.86-0.95)., Conclusion: Between 2009 and 2019, hospitalizations for cardiovascular disease increased at younger ages (20-74 years) and hospitalizations for kidney disease increased at all ages, but mortality from cardiovascular and kidney disease declined. All-cause mortality rates were unchanged., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: Health education is integral to cardiometabolic disease (CMD) management. This study aimed to assess whether and how education preferences have changed over time, and whether trends differ by sociodemographic characteristics (education status, age, ethnicity, and sex)., Methods: A cross-sectional questionnaire was deployed across five counties in the East Midlands, UK between 2017 and 2022 to adults with CMD (type 2 diabetes, cardiovascular disease or cerebrovascular disease). Respondent demographic data were collected alongside health education preferences. Statistical analyses ascertained whether demographic characteristics influenced preferences. The distribution of preferences over time was charted to identify trends., Results: A total of 4301 eligible responses were collected. Face-to-face one-to-one education was preferred (first choice for 75.1% of participants) but popularity waned over the five-year period. Trends were similar amongst demographic groups. Online education showed a U-shaped trend: In 2017, 44% of respondents ranked it as acceptable, peaking at 53% in 2019, but declining again, to below base line, 43%, by 2022. This modality was more popular with participants aged younger than 65 years, but popularity in people older than 65 years increased over the study period. The popularity of printed information also declined over time across all demographic groups except those of South Asian ethnicity, for whom it remained static., Conclusions: The overwhelming preference for face-to-face one-to-one health education from a doctor or nurse highlights the importance of preserving access to this modality, even in the face of current NHS pressures and trends towards digitalisation. Trends are changing, and should continue to be monitored, including between different sociodemographic groups., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background and Aims: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown., Methods: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone., Results: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores., Conclusions: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD)., Methods: Using national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions., Results: Hospitalization and mortality were 15.3% and 2.0% among 17,373,850 individuals with COVID-19 (LC rate 1.3%), and 16.8% and 1.4% among 301,115 with LC. Adjusted risk of mortality and hospitalization were reduced with COVID-19 vaccination ≥ 2 doses(COVID-19:HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalization (COVID-19:0.86 and 1.01, and LC:0.72 and 1.05). Mortality and hospitalization were reduced by CVD prevention in those with CVD, e.g., anticoagulants- COVID:19:0.69 and 0.92; LC:0.59 and 0.88; lipid lowering- COVID-19:0.69 and 0.86; LC:0.68 and 0.90. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively., Interpretation: Prior CVD and high CV risk are associated with increased hospitalization and mortality in COVID-19 and LC. Targeted COVID-19 vaccination and CVD prevention are priority interventions., Funding: NIHR. HDR UK., Competing Interests: Declarations of competing interest KK is chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and is a member of SAGE. KK (Chair) and AB are members of the LC Research Group that reports to the Chief Medical Officer for England. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and ethnic groups are not well defined. By conducting a systematic review and meta-analysis of all randomised, placebo-controlled, cardiovascular disease (CVD) outcomes trials (CVOTs), we aimed to compare racial/ethnic as well as regional patterns in the effects of SGLT2-Is and GLP1-RAs on cardiovascular and renal outcomes in patients with type 2 diabetes (T2D)., Design: Trials were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to 7 July 2023. Setting North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa., Setting: North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa., Participants: people with type 2 diabetes enrolled in cardiovascular outcome trials of SGLT2-Is and GLP1-RAs., Main Outcome Measures: Outcomes were (i) major adverse cardiovascular events (MACE), (ii) composite CVD death/heart failure (HF) hospitalization; (iii) composite renal outcome; and (iv) their components. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled., Results: In total, 14 unique CVOTs (7 comparing SGLT2-Is vs placebo and 7 comparing GLP1-RAs vs placebo) were eligible. The proportion of participants enrolled in the trials ranged from 66.6-93.2% for White populations, 1.2-21.6% for Asian populations, 2.4-8.3% for Black populations and 0.9-23.1% for Other populations. The HR (95% CI) for MACE comparing SGLT2-Is vs placebo was 0.92 (0.86-0.98), 0.69 (0.53-0.92) and 0.70 (0.54-0.91) for White, Asian and Hispanic/Latino populations, respectively. Comparing GLP1-RAs vs placebo, the corresponding HR (95% CI) was 0.88 (0.80-0.97), 0.76 (0.63-0.93) and 0.82 (0.70-0.95), respectively. SGLT2-Is reduced the risk of all other cardiorenal outcomes in White and Asian populations, except for HF hospitalizations in Asians. No effects were observed in Black populations except for a reduced risk of HF hospitalizations by SGLT2-I. SGLT1-Is reduced the risk of composite CVD death/HF hospitalization in North America and Europe, whereas GLP1-RAs reduced the risk of MACE in Europe. GRADE certainty of evidence ranged from moderate to high., Conclusions: There appears to be substantial racial/ethnic differences in the cardiorenal effects of SGLT2-Is and GLP1-RAs in patients with T2D, with consistent benefits observed among White and Asian populations and consistent lack of benefits in Black populations. Whether the differences are due to issues with under-representation of Black populations and low statistical power or racial/ethnic variations in the pharmacokinetics, pharmacodynamics and safety of SGLT2-Is and GLP1-RAs need further investigation.PROSPERO Registration: CRD42023401734.

The first dose of COVID-19 vaccines led to an overall reduction in cardiovascular events, and in rare cases, cardiovascular complications. There is less information about the effect of second and booster doses on cardiovascular diseases. Using longitudinal health records from 45.7 million adults in England between December 2020 and January 2022, our study compared the incidence of thrombotic and cardiovascular complications up to 26 weeks after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273). These findings support the wide uptake of future COVID-19 vaccination programs., (© 2024. The Author(s).)

Objective: To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19., Design: Population based study., Setting: UK., Participants: 1 650 052 individuals registered with a general practice contributing to Clinical Practice Research Datalink and newly diagnosed with at least one CVD from 1 January 2000 to 30 June 2019., Main Outcome Measures: The primary outcome was incident diagnosis of CVD, comprising acute coronary syndrome, aortic aneurysm, aortic stenosis, atrial fibrillation or flutter, chronic ischaemic heart disease, heart failure, peripheral artery disease, second or third degree heart block, stroke (ischaemic, haemorrhagic, and unspecified), and venous thromboembolism (deep vein thrombosis or pulmonary embolism). Disease incidence rates were calculated individually and as a composite outcome of all 10 CVDs combined and were standardised for age and sex using the 2013 European standard population. Negative binomial regression models investigated temporal trends and variation by age, sex, and socioeconomic status., Results: The mean age of the population was 70.5 years and 47.6% (n=784 904) were women. The age and sex standardised incidence of all 10 prespecified CVDs declined by 19% during 2000-19 (incidence rate ratio 2017-19 v 2000-02: 0.80, 95% confidence interval 0.73 to 0.88). The incidence of coronary heart disease and stroke decreased by about 30% (incidence rate ratios for acute coronary syndrome, chronic ischaemic heart disease, and stroke were 0.70 (0.69 to 0.70), 0.67 (0.66 to 0.67), and 0.75 (0.67 to 0.83), respectively). In parallel, an increasing number of diagnoses of cardiac arrhythmias, valve disease, and thromboembolic diseases were observed. As a result, the overall incidence of CVDs across the 10 conditions remained relatively stable from the mid-2000s. Age stratified analyses further showed that the observed decline in coronary heart disease incidence was largely restricted to age groups older than 60 years, with little or no improvement in younger age groups. Trends were generally similar between men and women. A socioeconomic gradient was observed for almost every CVD investigated. The gradient did not decrease over time and was most noticeable for peripheral artery disease (incidence rate ratio most deprived v least deprived: 1.98 (1.87 to 2.09)), acute coronary syndrome (1.55 (1.54 to 1.57)), and heart failure (1.50 (1.41 to 1.59))., Conclusions: Despite substantial improvements in the prevention of atherosclerotic diseases in the UK, the overall burden of CVDs remained high during 2000-19. For CVDs to decrease further, future prevention strategies might need to consider a broader spectrum of conditions, including arrhythmias, valve diseases, and thromboembolism, and examine the specific needs of younger age groups and socioeconomically deprived populations., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: NC is funded by a personal fellowship from the Research Foundation Flanders and a research grant from the European Society of Cardiology. JMF, PSJ, JGC, NS, and JJVM are supported by British Heart Foundation Centre of Research Excellence. PSJ and JJVM are further supported by the Vera Melrose Heart Failure Research Fund. JJVM has received funding to his institution from Amgen and Cytokinetics for his participation in the steering sommittee for the ATOMIC-HF, COSMIC-HF, and GALACTIC-HF trials and meetings and other activities related to these trials; has received payments through Glasgow University from work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; and has received personal lecture fees from the Corpus, Abbott, Hikma, Sun Pharmaceuticals, Medscape/Heart.Org, Radcliffe Cardiology, Alkem Metabolics, Eris Lifesciences, Lupin, ProAdWise Communications, Servier Director, and Global Clinical Trial Partners. NS declares consulting fees or speaker honorariums, or both, from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and grant support paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics. KK has acted as a consultant or speaker or received grants for investigator initiated studies for Astra Zeneca, Bayer, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals, Roche, and Applied Therapeutics. KK is supported by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and the NIHR Leicester Biomedical Research Centre (BRC). CL is funded by an NIHR Advanced Research Fellowship (NIHR-300111) and supported by the Leicester BRC. PSJ has received speaker fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals, and Intas Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices; his employer, the University of Glasgow, has been remunerated for clinical trial work from AstraZeneca, Bayer, Novartis, and Novo Nordisk; and is the Director of Global Clinical Trial Partners. HS is supported by the China Scholarship Council. Other authors report no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Cardiovascular disease (CVD) disproportionately affects ethnic-minority groups globally. Ethnic-minority groups face particularly high CVD burden and mortality, exacerbated by disparities across modifiable risk factors, wider determinants of health, and limited access to preventative interventions. This narrative review summarizes evidence on modifiable risk factors, such as physical activity, hypertension, diet, smoking, alcohol consumption, diabetes, and the polypill for the primary prevention of CVD in ethnic minorities. Across these factors, we find inequities in risk factor prevalence. The evidence underscores that inequalities in accessibility to interventions and treatments impede progress in reducing CVD risk using primary prevention interventions for ethnic-minority people. Although culturally tailored interventions show promise, further research is required across the different risk factors. Social determinants of health and structural inequities also exacerbate CVD risk for ethnic-minority people and warrant greater attention. Additionally, we find that only limited ethnicity-specific data and guidelines are available on CVD primary prevention interventions for most risk factors. To address these gaps in research, we provide recommendations that include the following: investigating the sustainability and real-world effectiveness of culturally sensitive interventions; ensuring that ethnic-minority peoples' perspectives are considered in research; longitudinal tracking of risk factors; interventions and outcomes in ethnic-minority people; and ensuring that data collection and reporting of ethnicity data are standardized., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known., Objectives: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors., Methods: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health., Results: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86)., Conclusion: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need., Trail Registration Number: ISRCTN10980107., Competing Interests: Competing interests: KK is chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and is a member of SAGE. KK (Chair) and RE are members of the Long COVID Epidemiological Research Group that reports to the CMO. CB is an author of the COVID-19 rapid guideline: managing the long-term effects of COVID-19 NICE guideline (NG188) https://www.nice.org.uk/guidance/ng188/history. CB is a member of the NHS National Services Scotland Long COVID group and his employer, the University of Glasgow, holds a research agreement with AstraZeneca and Somalogic for research in COVID-19. AJM is an employee of AstraZeneca., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Cardiovascular disease (CVD) risk in those with diabetic foot disease is very high. Non-pharmacological interventions may improve this risk, though no previous evidence synthesis has been completed. This systematic review aimed to investigate the impact of non-pharmacological interventions on CVD risk factors in diabetic ulcer disease. Multiple databases and trials registers were searched from inception to December 6th 2023. We included reports of randomised controlled trials investigating the impact of non-pharmacological interventions on cardiovascular risk in those with type 1 or type 2 diabetes and current or previous diabetic foot disease. Twenty studies were included. Extracted data included: study design and setting; participant sociodemographic factors; and change in cardiovascular risk factors. Data were synthesised using random effects meta-analyses and narrative syntheses. Interventions included nutritional supplementation, collaborative care, hyperbaric oxygen therapy, patient education, nurse-led intervention, self-management, family support, relaxation and exercise, over a median duration of 12 weeks. Significant post-intervention changes were observed in fasting plasma glucose, serum insulin levels, insulin sensitivity and resistance, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein-cholesterol and C-reactive protein. No effects were detected in very low- or high-density lipoprotein-cholesterol or body mass index. Non-pharmacological interventions show promise in improving CVD risk in diabetic foot disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JV is National Clinical Director for Diabetes and Obesity at NHS England. JV is supported by the NW London NIHR Applied Research Collaboration and the Imperial NIHR Biomedical Research Centre. MD has acted as consultant, advisory board member and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi, an advisory board member Lexicon, Pfizer, ShouTi Pharma Inc, AstraZeneca and Medtronic and as a speaker for AstraZeneca, Napp Pharmaceuticals, Novartis and Amgen, and has received grants from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Janssen and Sanofi-Aventis and Eli Lilly. KK has acted as a consultant, speaker or received grants for investigator-initiated studies for Astra Zeneca, Bayer, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals, Roche and Applied Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To estimate time spent in various cardiovascular disease (CVD) and cancer states, according to self-reported walking pace., Methods: In total, 391,744 UK Biobank participants were included (median age = 57 years; 54.7% women). Data were collected 2006-2010, with follow-up collected in 2021. Usual walking pace was self-defined as slow, steady, average, or brisk. Multistate modeling determined the transition rate and mean sojourn time in and across three different states (healthy, CVD or cancer, and death) upon a time horizon of 10 years., Results: The mean sojourn time in the healthy state was longer, while that in the CVD or cancer state was shorter in individuals reporting an average or brisk walking pace (vs. slow). A 75-year-old woman reporting a brisk walking pace spent, on average, 8.4 years of the next 10 years in a healthy state; an additional 8.0 (95% CI: 7.3, 8.7) months longer than a 75-year-old woman reporting a slow walking pace. This corresponded to 4.3 (3.7, 4.9) fewer months living with CVD or cancer. Similar results were seen in men., Conclusions: Adults reporting an average or brisk walking pace at baseline displayed a lower transition to disease development and a greater proportion of life lived without CVD or cancer., Availability of Data and Materials: Research was conducted using the UK Biobank resource under Application #33266. The UK Biobank resource can be accessed by researchers on application. Variables derived for this study have been returned to the UK Biobank for future applicants to request. No additional data are available., Competing Interests: Declaration of Competing Interest The authors declare no competing interests, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In randomized controlled trials (RCTs), treatment effects are commonly reported as hazard ratio, a measure often misinterpreted as a relative risk reduction. The acceleration factor (AF) indicates the extent to which a treatment increases/decreases the time before the occurrence of an outcome and gives useful insights in the interpretation of trials' results., Methods: Using individual time-to-event data reconstructed from Kaplan-Meier plots, we estimated AFs for the primary outcomes (POs) and all-cause mortality in glucagon-like peptide-1 receptor agonists (GLP1-RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2-is) cardiorenal outcome trials in subjects with type 2 diabetes., Results: AFs were estimated from 28 Kaplan-Meier plots of 19 RCTs. Compared to placebo, most GLP1-RAs increased the time before the onset of POs (from 9 % to 59 %) and all-cause mortality (from 8 to 13 %). Similarly, SGLT2-is increased time before the onset of POs (from 19 % to 87 %) and all-cause mortality (from 13 % to 42 %)., Conclusions: The AFs provide a complementary and easier-to-interpret measure of treatment effect that could be useful to improve the shared decision-making., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alessandro Rizzi reports a relationship with Novo Nordisk Inc that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Alessandro Rizzi reports a relationship with Medtronic Inc that includes: speaking and lecture fees. Alessandro Rizzi reports a relationship with Boehringer Ingelheim GmbH that includes: speaking and lecture fees. Alessandro Rizzi reports a relationship with LifeScan Inc that includes: consulting or advisory and speaking and lecture fees. Dario Pitocco, Kamlesh Khunti, Melanie J Davies reports a relationship with Novo Nordisk Inc that includes: consulting or advisory and speaking and lecture fees. Dario Pitocco, Melanie J Davies reports a relationship with Medtronic Inc that includes: consulting or advisory and speaking and lecture fees. Dario Pitocco, Kamlesh Khunti, Melanie J Davies reports a relationship with Boehringer Ingelheim GmbH that includes: consulting or advisory and speaking and lecture fees. Dario Pitocco, Kamlesh Khunti, Melanie J Davies reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and speaking and lecture fees. Dario Pitocco, Kamlesh Khunti, Melanie J Davies reports a relationship with Eli Lilly and Company that includes: consulting or advisory and speaking and lecture fees. Dario Pitocco, Kamlesh Khunti, Melanie J Davies reports a relationship with Sanofi that includes: consulting or advisory and speaking and lecture fees. Kamlesh Khunti reports a relationship with Merck & Co Inc that includes: consulting or advisory and speaking and lecture fees. Kamlesh Khunti reports a relationship with Bayer Corporation that includes: consulting or advisory and speaking and lecture fees. Kamlesh Khunti reports a relationship with Abbott that includes: consulting or advisory and speaking and lecture fees. Kamlesh Khunti reports a relationship with Roche that includes: consulting or advisory and speaking and lecture fees., (Copyright © 2024. Published by Elsevier Ltd.)

We conduct a systematic review to investigate current deprescribing practices and evaluate outcomes and adverse events with deprescribing of preventive medications in older patients with either an end-of-life designation or residing in long-term care facilities with cardiometabolic conditions. Studies were identified using a literature search of MEDLINE, EMBASE, Web of Science, clinicaltrials.gov.uk, CINAHLS, and the Cochrane Register from inception to March 2022. Studies reviewed included observational studies and randomised control trials (RCTs). Data was extracted on baseline characteristics, deprescribing rates, adverse events and outcomes, and quality of life indicators, and was discussed using a narrative approach. Thirteen studies were identified for inclusion. Deprescribing approaches included complete withdrawal, dose reduction or tapering, or switching to an alternative medication, for at least one preventive medication. Deprescribing success rates ranged from 27 to 94.7%. The studies reported no significant changes in laboratory values or adverse outcomes but did find mixed outcomes for hospitalisations and a slight increase in mortality rates when comparing the intervention and control groups. Lack of good-quality randomised control trials suggests that deprescribing in the older population residing in long-term care facilities with cardiometabolic conditions and multimorbidity is feasible when controlled and regularly monitored by an appropriate healthcare clinician, and that the benefits outweigh the potential harm in this cohort of patients. Due to the limited evidence and the heterogeneity of studies, a meta-analysis was not performed and as such further research is required to assess the benefits of deprescribing in this patient population. Systematic review registration: PROSPERO CRD42021291061., (© 2023. The Author(s).)

Background Social vulnerability impacts the natural history of diabetes as well as cardiovascular disease (CVD). However, there are little data regarding the social vulnerability association with diabetes-related CVD mortality. Methods and Results County-level mortality data (where CVD was the underlying cause of death with diabetes among the multiple causes) extracted from the Centers for Disease Control multiple cause of death (2015-2019) and the 2018 Social Vulnerability Index databases were aggregated into quartiles based on their Social Vulnerability Index ranking from the least (first quartile) to the most vulnerable (fourth quartile). Stratified by demographic groups, the data were analyzed for overall CVD, as well as for ischemic heart disease, hypertensive disease, heart failure, and cerebrovascular disease. In the 5-year study period, 387 139 crude diabetes-related cardiovascular mortality records were identified. The age-adjusted mortality rate for CVD was higher in the fourth quartile compared with the first quartile (relative risk [RR], 1.66 [95% CI, 1.64-1.67]) with an estimated 39 328 excess deaths. Among the youngest age group (<55 years), those with the highest social vulnerability had 2 to 4 times the rate of cardiovascular mortality compared with the first quartile: ischemic heart disease (RR, 2.07 [95% CI, 1.97-2.17]; heart failure (RR, 3.03 [95% CI, 2.62-3.52]); hypertensive disease (RR, 3.79 [95% CI, 3.45-4.17]; and cerebrovascular disease (RR, 4.39 [95% CI, 3.75-5.13]). Conclusions Counties with greater social vulnerability had higher diabetes-related CVD mortality, especially among younger adults. Targeted health policies that are designed to reduce these disparities are warranted.

Objective: To investigate associations of self-reported walking pace (SRWP) with relative and absolute risks of cause-specific mortality., Patients and Methods: In 391,652 UK Biobank participants recruited in 2006-2010, we estimated sex- and cause-specific (cardiovascular disease [CVD], cancer, other causes) mortality hazard ratios (HRs) and 10-year mortality risks across categories of SRWP (slow, average, brisk), accounting for confounders and competing risk. Censoring occurred in September 30, 2021 (England, Wales) and October 31, 2021 (Scotland)., Results: Over a median follow-up of 12.6 years, 22,413 deaths occurred. In women, the HRs comparing brisk to slow SRWP were 0.74 (95% CI: 0.67, 0.82), 0.40 (0.33, 0.49), and 0.29 (0.26, 0.32) for cancer, CVD, and other causes of death, respectively, and 0.71 (0.64, 0.78), 0.38 (0.33, 0.44), and 0.29 (0.26, 0.32) in men. Compared to CVD, HRs were greater for other causes (women: 39.6% [6.2, 72.9]; men: 31.6% [9.8, 53.5]) and smaller for cancer (-45.8% [-58.3, -33.2] and - 45.9% [-54.8, -36.9], respectively). For all causes in both sexes, the 10-year mortality risk was higher in slow walkers, but varied across sex, age, and cause, resulting in different risk reductions comparing brisk to slow: the largest were for other causes of death at age 75 years [women: -6.8% (-7.7, -5.8); men: -9.5% (-10.6, -8.4)]., Conclusion: Compared to slow walkers, brisk SRWP was associated with reduced cancer (smallest reduction), CVD, and other (largest) causes of death and may therefore be a useful clinical predictive marker. As absolute risk reductions varied across age, cause, and SRWP, certain groups may particularly benefit from interventions to increase SRWP., Competing Interests: Declaration of Competing Interest The authors had financial support from the funders listed above for the submitted work. The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To investigate associations between 4-yr change in step cadence and markers of cardiometabolic health in people with a history of prediabetes and to explore whether these associations are modified by demographic factors., Methods: In this prospective cohort study, adults, with a history of prediabetes, were assessed for markers of cardiometabolic health (body mass index, waist circumference, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], triglycerides, and glycated hemoglobin A1c [HbA1c]), and free-living stepping activity (activPAL3™) at baseline, 1 yr, and 4 yr. Brisk steps per day were defined as the number of steps accumulated at ≥100 steps per minute and slow steps per day as those accumulated at <100 steps per minute; the mean peak stepping cadence during the most active 10 minutes of the day was also derived. Generalized estimating equations examined associations between 4-yr change in step cadence and change in cardiometabolic risk factors, with interactions by sex and ethnicity., Results: Seven hundred ninety-four participants were included (age, 59.8 ± 8.9 yr; 48.7% women; 27.1% ethnic minority; total steps per day, 8445 ± 3364; brisk steps per day, 4794 ± 2865; peak 10-min step cadence, 128 ± 10 steps per minute). Beneficial associations were observed between change in brisk steps per day and change in body mass index, waist circumference, HDL-C, and HbA1c. Similar associations were found between peak 10-min step cadence and HDL-C and waist circumference. Interactions by ethnicity revealed change in brisk steps per day and change in peak 10-min step cadence had a stronger association with HbA1c in White Europeans, whereas associations between change in 10-min peak step cadence with measures of adiposity were stronger in South Asians., Conclusions: Change in the number of daily steps accumulated at a brisk pace was associated with beneficial change in adiposity, HDL-C, and HbA1c; however, potential benefits may be dependent on ethnicity for outcomes related to HbA1c and adiposity., (Copyright © 2023 by the American College of Sports Medicine.)

Background: Studies that have reported lower risk for cardiovascular outcomes in users of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF)., Methods and Results: Adults initiating empagliflozin and DPP-4i in 2014-2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64-0.86), CVM (HR 0.55; 95% CI 0.38-0.80), HHF or CVM (HR 0.57; 95% CI 0.48-0.67) and stroke (HR 0.79; 95% CI 0.67-0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF., Conclusion: These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Physical activity is increasingly being captured by accelerometers worn on different body locations. The aim of this study was to examine the associations between physical activity volume (average acceleration), intensity (intensity gradient) and cardiometabolic health when assessed by a thigh-worn and wrist-worn accelerometer. A sample of 659 office workers wore an Axivity AX3 on the non-dominant wrist and an activPAL3 micro on the right thigh concurrently for 24 h a day for 8 days. An average acceleration (proxy for physical activity volume) and intensity gradient (intensity distribution) were calculated from both devices using the open-source raw accelerometer processing software GGIR. Clustered cardiometabolic risk (CMR) was calculated using markers of cardiometabolic health, including waist circumference, triglycerides, HDL-cholesterol, mean arterial pressure and fasting glucose. Linear regression analysis assessed the associations between physical activity volume and intensity gradient with cardiometabolic health. Physical activity volume derived from the thigh-worn activPAL and the wrist-worn Axivity were beneficially associated with CMR and the majority of individual health markers, but associations only remained significant after adjusting for physical activity intensity in the thigh-worn activPAL. Physical activity intensity was associated with CMR score and individual health markers when derived from the wrist-worn Axivity, and these associations were independent of volume. Associations between cardiometabolic health and physical activity volume were similarly captured by the thigh-worn activPAL and the wrist-worn Axivity. However, only the wrist-worn Axivity captured aspects of the intensity distribution associated with cardiometabolic health. This may relate to the reduced range of accelerations detected by the thigh-worn activPAL.

Background In the past few decades, diabetes-related cardiovascular mortality has been steadily declining. However, the impact of the COVID19 pandemic on this trend has not been previously defined. Methods and Results Diabetes-related cardiovascular mortality data were extracted for each year between 1999 and 2020 from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database. Regression analysis was used to calculate the trend in the 2 decades before the pandemic (1999-2019) and thereby estimate the excess cardiovascular mortality in 2020. There was a 29.2% fall in the diabetes-related cardiovascular age-adjusted mortality rate between 1999 to 2019, largely driven by a 41% decrease in ischemic heart disease deaths. In comparison to 2019, there was an overall 15.5% increase in the diabetes-related cardiovascular age-adjusted mortality rate in the first year of the pandemic, mainly due to a 14.1% rise in ischemic heart disease deaths. Younger patients (under 55 years) and the Black population experienced the greatest increase in diabetes-related cardiovascular age-adjusted mortality rate (24.0% and 25.3%, respectively). Trend analysis estimated 16 009 excess diabetes-related cardiovascular deaths in 2020, with the majority due to ischemic heart disease (8504). Black and Hispanic or Latino populations had at least one-fifth of their 2020 diabetes-related cardiovascular age-adjusted mortality rate as excess deaths (22.3% and 20.2%, respectively). Conclusions There was a sharp rise in diabetes-related cardiovascular mortality during the first pandemic year. Black, Hispanic or Latino, and young people showed the largest increases in diabetes-related cardiovascular mortality. Targeted health policies could help address the disparities observed in this analysis.

Background and Aims: We aimed to evaluate the life expectancy following the first cardiovascular disease (CVD) event by type 2 diabetes (T2D) status and ethnicity., Methods and Results: We used the Clinical Practice Research Datalink database in England (UK), linked to the Hospital Episode Statistics information, to identify individuals with and without T2D who survived a first CVD event between 1st Jan 2007 and 31st Dec 2017; subsequent death events were extracted from the Office for National Statistics database. Ethnicity was categorised as White, South Asian (SA), Black, or other. Flexible parametric survival models were used to estimate survival and predict life expectancy. 59,939 individuals with first CVD event were included: 7596 (12.7%) with T2D (60.9% men; mean age at event: 69.7 years [63.2 years in SA, 65.9 in Black, 70.2 in White]) and 52,343 without T2D (56.7% men; 65.9 years [54.7 in Black, 58.2 in SA, 66.3 in White]). Accounting for potential confounders (sex, deprivation, lipid-lowering medication, current smoking, and pre-existing hypertension), comparing individuals with vs without T2D the mortality rate was 53% higher in White (hazard ratio [HR]: 1.53 [95% CI: 1.44, 1.62]), corresponding to a potential loss of 3.87 (3.30, 4.44) life years at the age of 50 years in individuals with T2D. No evidence of a difference in life expectancy was observed in individuals of SA (HR: 0.82 [0.52, 1.29]; -1.36 [-4.58, 1.86] life years), Black (HR: 1.26 [0.59, 2.70]; 1.21 [-2.99, 5.41] life years); and other (HR: 1.64 [0.80, 3.39]; 3.89 [-2.28, 9.99] life years) ethnic group., Conclusion: Following a CVD event, T2D is associated with a different prognosis and life years lost among ethnic groups., Competing Interests: Declaration of competing interest Professor Khunti is the National Lead for multiple long-term conditions for National Institute for Health Research Applied Research Collaboration (NIHR ARC). Professor Khunti has acted as a consultant, speaker or received grants for investigator-initiated studies for Astra Zeneca, Abbott, Amgen, Bayer, Novartis, Novo Nordisk, Roche, Servier, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals and Applied Therapeutics. Dr Zaccardi is a speaker fees from Napp Pharmaceuticals and Boehringer Ingelheim. Professor Davies has acted as a consultant, advisory board member and speaker for Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and Janssen, an advisory board member for Servier and Gilead Sciences Ltd and as a speaker for Napp Pharmaceuticals, Mitsubishi Tanabe Pharma Corporation and Takeda Pharmaceuticals International Inc. Professor Davies has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca and Janssen. All other authors have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: While cardiovascular disease in patients with type 2 diabetes commonly progresses with the occurrence of repeated events, most trials consider the effect of glucose-lowering strategies only on the first event. We examined the Action to Control Cardiovascular Risk in Diabetes trial and its observational follow-up study (ACCORDION) to investigate the effect of intensive glucose control on multiple events and further identify any subgroup effects., Materials and Methods: A recurrent events analysis, using a negative binomial regression model, was applied to estimate the treatment effect on different consecutive cardiovascular disease events, including non-fatal myocardial infarction, non-fatal stroke, hospitalisation from heart failure, and cardiovascular death. Interaction terms were used to identify potential effect modifiers. The robustness of the results was confirmed in sensitivity analyses using alternative models., Results: The median duration of follow-up was 7.7 years. Of the 5128 participants in the intensive and 5123 in the standard glucose control arm, respectively, 822 (16.0%) and 840 (16.4%) participants experienced a single event; 189 (3.7%) and 214 (4.2%) participants experienced two events; 52 (1.0%) and 40 (0.8%) experienced three events; and 1 (0.02%) and 1 (0.02%) experienced four events. There was no evidence of a treatment effect, with a rate difference of 0.0 (-0.3, 0.3) per 100 person-years comparing intensive versus standard intervention, although with non-significantly lower event rates in younger patients with HbA1c < 7% and higher event rates in older patients with HbA1c ≥ 9%., Discussion: Intensive glucose control may not affect cardiovascular disease progression except in select subgroups. Since time-to-first event analysis may miss beneficial or harmful effects of glucose control on the risk of cardiovascular disease, recurrent events analysis should be routinely analysed in cardiovascular outcome trials, particularly when investigating long-term treatment effects., Clinical Trial Reg No: NCT00000620, clinicaltrials.gov., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described., Methods and Results: Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions., Conclusion: The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Currently, there is uncertainty as to whether blood pressure control in patients with type 2 diabetes should be treated to standard recommended levels or more intensively., Methods: Medline, EMBASE, CENTRAL, and Clinicaltrials.gov were searched between January 1, 2000 and April 20th, 2023. Outcomes considered were all-cause mortality, stroke, heart failure, cardiovascular disease, albuminuria, coronary heart disease, and renal outcomes. Random-effects meta-analyses estimated pooled relative risks and mean differences., Results: Nine trials enrolling 11,005 participants with type 2 diabetes were included. The pooled mean difference between the intensive and standard treatment groups at follow-up were -7.98 mmHg (95% CI: 12.19 to -3.76) in systolic blood pressure, and -5.08 mmHg (-7.00 to -3.17) in diastolic blood pressure; although between study heterogeneity was high for both meta-analyses (I 2 >85%). Intensive blood pressure lowering resulted in a reduction in risk of stroke (risk ratio 0.64; 0.52 to 0.79), and macro-albuminuria (0.77; 0.63 to 0.93). More intensive blood pressure control did not result in a statistically significant reduction in risk of all-cause mortality, heart failure, cardiovascular death, cardiovascular events, renal outcomes, and micro-albuminuria; although the direction of estimated effect was beneficial for all outcomes., Conclusions: The use of intensive compared with standard blood pressure targets resulted in a significant reduction in blood pressure, stroke, and macro-albuminuria in patients with type 2 diabetes. The post-treatment blood pressure level in the intensive group was 125/73 mmHg, suggesting the current recommendations of 130/80 mmHg blood pressure or lower if tolerated, could be reduced further., Competing Interests: Declaration of competing interest KK has acted as a consultant and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Servier and Merck Sharp & Dohme. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim and Merck Sharp & Dohme. KK has received funds for research, honoraria for speaking at meetings and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme and Novo Nordisk. MJD has acted as consultant, advisory board member and speaker for Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and Janssen and as a speaker for Mitsubishi Tanabe Pharma Corporation. She has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis and Lilly. KKR reports personal fees from Abbvie, AstraZeneca, Medco, Resverlogix, Akcea, Boehringer Ingelheim, Novo Nordisk, Takeda, Kowa, Algorithm, Cipla, Cerenis, Dr Reddys, Lilly, and Zuellig Pharma, Novartis and Silence Therapeutics; and grants and personal fees from Amgen, Sanofi, Regeneron Pharmaceuticals, MSD, Daiichi Sankyo and Pfizer. All other authors declare no competing interests and no duality of interest in connection with their involvement in this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent health policies in the United Kingdom (UK) and internationally have focussed on digitisation of healthcare. We examined UK policies for evidence of government action addressing health inequalities and digital health, using cardiometabolic disease as an exemplar. Using a systematic search methodology, we identified 87 relevant policy documents published between 2010 and 2022. We found increasing emphasis on digital health, including for prevention, diagnosis and management of cardiometabolic disease. Several policies also focused on tackling health inequalities and improving digital access. The COVID-19 pandemic amplified inequalities. No policies addressed ethnic inequalities in digital health for cardiometabolic disease, despite high prevalence in minority ethnic communities. Our findings suggest that creating opportunities for digital inclusion and reduce longer-term health inequalities, will require future policies to focus on: the heterogeneity of ethnic groups; cross-sectoral disadvantages which contribute to disease burden and digital accessibility; and disease-specific interventions which lend themselves to culturally tailored solutions., (© 2023. The Author(s).)

Objective: The aim of the study was to assess the clinical effectiveness of the national cardiovascular disease (CVD) prevention programme-National Health Service Health Check (NHSHC) in reduction of CVD risk., Design: Prospective cohort study., Setting: 147 primary care practices in Leicestershire and Northamptonshire in England, UK., Participants: 27 888 individuals undergoing NHSHC with a minimum of 18 months of follow-up data., Outcome Measures: The primary outcomes were NHSHC attributed detection of CVD risk factors, prescription of medications, changes in values of individual risk factors and frequency of follow-up., Results: At recruitment, 18% of participants had high CVD risk (10%-20% 10-year risk) and 4% very high CVD risk (>20% 10-year risk). New diagnoses or hypertension (HTN) was made in 2.3% participants, hypercholesterolaemia in 0.25% and diabetes mellitus in 0.9%. New prescription of stains and antihypertensive medications was observed in 5.4% and 5.4% of participants, respectively. Total cholesterol was decreased on average by 0.38 mmol/L (95% CI -0.34 to -0.41) and 1.71 mmol/L (-1.48 to -1.94) in patients with initial cholesterol >5 mmol/L and >7.5 mmol/L, respectively. Systolic blood pressure was decreased on average by 2.9 mm Hg (-2.3 to -3.7), 15.7 mm Hg (-14.1 to -17.5) and 33.4 mm Hg (-29.4 to -37.7), in patients with grade 1, 2 and 3 HTN, respectively. About one out of three patients with increased CVD risk had no record of follow-up or treatment., Conclusions: Majority of patients identified with increased CVD risk through the NHSHC were followed up and received effective clinical interventions. However, one-third of high CVD risk patients had no follow-up and therefore did not receive any treatment. Our study highlights areas of focus which could improve the effectiveness of the programme., Trial Registration Number: NCT04417387., Competing Interests: Competing interests: KK was a national advisor for the NHS Health Checks programme., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Aims: We used N-terminal pro-B-type natriuretic peptide (NT-proBNP) point-of-care testing (POCT) for heart failure risk stratification of individuals with type 2 diabetes for >10 years and hypertension., Methods: Overall 259 participants aged 50 years or older with type 2 diabetes (duration of >10 years), hypertension, and no overt cardiovascular disease (CVD) were recruited at two study centers. Patients' data were acquired and NT-proBNP levels were measured using the CARDIAC proBNP+ test (Roche) and the cobas h232 instrument (Roche). Participants were clustered into two groups according to their NT-proBNP concentration value: with NT-proBNP <125 pg/ml and with NT-proBNP ≥125 pg/ml., Results: Mean age of the participants was 66.1 ± 9.2 years, 55.2 % were female, 60.6 % (n = 157) had a NT-proBNP <125 pg/ml and 39.4 % (n = 102 ≥ 125 pg/ml). Differences were observed among those with low and high NT-proBNP in mean age (63.4 ± 8.8 years vs. 70.1 ± 8.2 years, p < 0.001), diabetes duration (15.4 ± 5.9 years vs. 17.9 ± 7.3 years, p = 0.003), and estimated glomerular filtration rate (eGFR) (86 ± 16 ml/min/1.73 m 2 vs. 76 ± 20 ml/min/1.73 m 2 , p < 0.001)., Conclusions: NT-proBNP POCT is practical and can be pragmatically targeted for screening people with type 2 diabetes and hypertension for heart failure risk stratification in routine clinical practice., Competing Interests: Declaration of competing interest AC discloses participating in advisory board meetings, consulting, and lecturing for AstraZeneca, Bayer, Berlin Chemie, Eli Lilly, Elsevier, Merck, Novo Nordisk, Roche Diagnostics, Servier, and Theras. NL has no relevant interest to disclose. EM reports serving on scientific advisory boards, consulting for, lecturing for and/or receiving research grants from Menarini, Merk Sharp & Dohme, Novo Nordisk, and Sanofi. PV discloses lectures for Abbott, AstraZeneca, Bayer, Eli Lilly, Hikma Pharmaceuticals, Merck Sharp & Dohme, Novo Nordisk, Novartis, Pfizer, Sanofi, Servier; research grants from Abbott, AstraZeneca, Bristol-Myers Squibb, Novo Nordisk, Stendo company; participation in expert committees for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Novo Nordisk, Sanofi, Servier. KK has acted as a consultant, speaker or received grants for investigator-initiated studies for Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Oramed Pharmaceuticals and Sanofi-Aventis. MH has acted as a consultant and/or speaker for AstraZeneca, Bayer, Lilly, Novo Nordisk and Sanofi-Aventis. OS is founder and CEO of Sciarc GmbH., (Copyright © 2023. Published by Elsevier Inc.)

Background: Digital health interventions (DHIs) for the prevention and management of cardiometabolic diseases have become increasingly common. However, there is limited evidence for the suitability of these approaches in minority ethnic populations, who are at an increased risk of these diseases., Objective: This study aimed to investigate the use of DHIs for cardiovascular disease and type 2 diabetes among minority ethnic populations in countries with a majority of White, English-speaking populations, focusing on people who identified as South Asian, Black, or African American., Methods: A realist methodology framework was followed. A literature search was conducted to develop context-mechanism-outcome configurations, including the contexts in which DHIs work for the target minority ethnic groups, mechanisms that these contexts trigger, and resulting health outcomes. After systematic searches, a qualitative analysis of the included studies was conducted using deductive and inductive coding., Results: A total of 15 studies on the uptake of DHIs for cardiovascular disease or diabetes were identified, of which 13 (87%) focused on people with an African-American background. The review found evidence supporting the use of DHIs in minority ethnic populations when specific factors are considered in implementation and design, including patients' beliefs, health needs, education and literacy levels, material circumstances, culture, social networks, and wider community and the supporting health care systems., Conclusions: Our context-mechanism-outcome configurations provide a useful guide for the future development of DHIs targeted at South Asian and Black minority ethnic populations, with specific recommendations for improving cultural competency and promoting accessibility and inclusivity of design., (©Aumeya Goswami, Lydia Poole, Zareen Thorlu-Bangura, Nushrat Khan, Wasim Hanif, Kamlesh Khunti, Paramjit Gill, Madiha Sajid, Ann Blandford, Fiona Stevenson, Amitava Banerjee, Mel Ramasawmy. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.01.2023.)

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC., (© 2022 by the American Diabetes Association.)

How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aims: This study aimed to explore associations between frailty components and mortality and rank prognostic relevance of each frailty component in predicting mortality in adults with and without type 2 diabetes (T2D)., Methods: We used data from the UK Biobank. Associations and prognostic discrimination of individual Fried's frailty components and the overall frailty status with all-cause and cardiovascular (CVD) mortality were investigated using Cox proportional-hazard models and C-index in adults with and without T2D., Results: In both populations the strongest association with all-cause mortality across all frailty components and overall frailty status was observed for slow walking pace (without T2D Hazard Ratio [HR] 2.25, 95 %CI: 2.12-2.38 and with T2D HR 1.95, 95 %CI: 1.67-2.28). Similarly, slow walking pace was associated with a greater risk of CVD mortality. The combination of T2D and slow walking pace had the strongest association with all-cause and CVD mortality, compared to the combination of T2D and other frailty components or overall frailty status. Slow walking pace also provided the greatest prognostic discrimination., Conclusion: Slow walking pace has a stronger predictive factor for all-cause and CVD mortality compared to other frailty components and overall frailty status, especially when simultaneously present with T2D., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate how sociodemographic factors influence educational modality preferences in people with cardiometabolic disease., Methods: This was a cross-sectional study performed in people with diabetes and cardiovascular disease, who completed a questionnaire to denote their previous experience and ranked preferences for different educational modalities., Results: The questionnaire was completed by 3751 people, of whom 59% were men, median (interquartile range) age was 68 (59-76) years, and 78% were White European. In total, 73% had diabetes, 35% had heart disease, and 10% had history of stroke; the majority (83.4%) had one of these conditions. Overall preference was for one-to-one education (77% ranked first choice), and telephone education ranked the lowest. People tended to prefer modalities they had previously experienced., Conclusions: We highlight the importance of considering factors that could influence selection of educational modalities including age, ethnicity, gender and educational level. We anticipate this approach will aid in the design, delivery and tailoring of educational programmes that are accessible to the diverse cohort of people living with chronic diseases, including diabetes and cardiovascular disease., Practice Implications: Given the influence of multiple demographic factors and previous experiences on expressed preferences, providers should support individuals to make informed decisions about educational interventions to maximise engagement., Competing Interests: Declaration of competing interests L.Q, A.K.W and M.H have no conflict of interests to declare. D.B does not hold any conflicts of interest, however, for transparency, D.B is an independent consultant and therefore has worked on projects for multiple small biotech companies. M.J.D. does not hold any conflicts of interest, however, for transparency we provide the following statement of conflict: M.J.D. is the Principal Investigator on the DESMOND programme (Diabetes education and self‐management for people with newly diagnosed type 2 diabetes mellitus). KK is co-investigator on DESMOND. All authors are actively engaged in research and have previously received grants from the NIHR, the Medical Research Council and Diabetes UK to develop and test diabetes self‐management education and support programmes like DESMOND. The University Hospitals of Leicester NHS Trust (with which S.S. has an honorary contract) receives licensing fees to support implementation of the DESMOND programme in clinical commissioning groups in the UK, Ireland, and Australia., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: To describe sociodemographic, lifestyle, environmental and traditional clinical risk factor differences between ethnic groups and to investigate the extent to which such differences confound the association between ethnic groups and the risk of cardiovascular disease (CVD) METHODS AND RESULTS: A total of 440,693 white European (55.9% women), 7305 South Asian (48.6%) and 7628 black African or Caribbean (57.7%) people were included from UK Biobank. Associations between ethnicity and cardiovascular outcomes (composite of non-fatal stroke, non-fatal myocardial infarction and CVD death) were explored using Cox-proportional hazard models. Models were adjusted for sociodemographic, lifestyle, environmental and clinical risk factors. Over a median (IQR) of 12.6 (11.8, 13.3) follow-up years, there were 22,711 (5.15%) cardiovascular events in white European, 463 (6.34%) in South Asian and 302 (3.96%) in black African or Caribbean individuals. For South Asian people, the cardiovascular hazard ratio (HR) compared to white European people was 1.28 (99% CI [1.16, 1.43]). For black African or Caribbean people, the HR was 0.80 (0.66, 0.97). The elevated risk of CVD in South Asians remained after adjusting for differences in sociodemographic, lifestyle, environmental and clinical factors, whereas the lower risk in black African or Caribbean was largely attenuated., Conclusions: South Asian, but not black African or Caribbean individuals, have a higher risk of CVD compared to white European individuals. This higher risk in South Asians was independent of sociodemographic, lifestyle, environmental and clinical factors., Competing Interests: Declaration of competing interest TY, MJD are supported by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre (BRC). KK is Director for the University of Leicester Centre for Ethnic Health Research, Trustee of the South Asian Health Foundation, national NIHR Applied Research Collaborations – East Midlands (ARC-EM) lead for Ethnicity and Diversity and a member of SAGE and Chair of the SAGE subgroup on ethnicity and COVID-19. AH acknowledges funding from the NIHR Health Protection Research Unit in Environmental Exposures and Health Development Award at University of Leicester. Other authors declare no conflicts of interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Evidence on therapeutic interventions and factors driving treatment intensification (TI) in people with incident depression in UK are scarce., Aims: To explore antidepressant prescribing patterns and factors influencing TI., Design: and setting: Retrospective cohort study of adults with incident depression diagnosed between 2006 and 2017 using UK primary care database., Methods: Patterns of antidepressant prescriptions, and factors influencing TI were evaluated by sex., Results: In 931,302 people with depression (90% initiating antidepressants), mean age was 39 years, 41% were male, 14% had cardiometabolic multimorbidity (CMM), and 54% were diagnosed at &lt; 40 years. Being the most prescribed first-line antidepressant (62%), SSRI prescribing rate increased from 66 per 1000 person-years to 170 per 1000 person-years; 24% (2% dose escalation, 4% adding, 18% switching) of first-line antidepressant initiators intensified with 13 months median time to TI. Compared to 60-70 years, younger adults had significantly higher TI risk (range of hazards ratio, HR: 1.08-1.42). CMM and anxiety were associated with 15-24% and 39-49% significantly higher TI risks respectively. First-line antidepressant and deprivation status influenced TI differently by gender., Conclusions: Men and women with depression in UK have different antidepressant prescription patterns in real-world. Age at diagnosis, deprivation status and cardiometabolic multimorbidity are the major sociodemographic and non-psychiatric risk factors for therapeutic changes., Competing Interests: Declaration of competing interest SKP has acted as a consultant and/or speaker for Novartis, GI Dynamics, Roche, AstraZeneca, Guangzhou Zhongyi Pharmaceutical and Amylin Pharmaceuticals LLC. He has received grants in support of investigator and investigator initiated clinical studies from Merck, Novo Nordisk, AstraZeneca, Hospira, Amylin Pharmaceuticals, Sanofi-Avensis and Pfizer. KK has acted as a consultant, speaker or received grants for investigator-initiated studies for Astra Zeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG/Menarini Group, Janssen, and Napp .JD, KLC, and OM have no conflict of interest to declare., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Phosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in patients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM., Methods: Studies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled., Results: Eighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31-1.55), 1.47 (1.31-1.65), 1.59 (1.39-1.82), and 1.34 (1.15-1.56), respectively. The respective estimates were 1.68 (1.15-2.45), 1.40 (0.90-2.18), 1.41 (1.24-1.61) and 1.32 (1.09-1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovascular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95% CIs) of 3.47 (0.17-69.19), 1.31 (0.10-16.54) and 0.35 (0.12-1.05), respectively., Conclusions: ED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM. PROSPERO Registration: CRD42022324537., Competing Interests: Conflict of Interest The authors have no relevant conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Higher levels of physical activity are associated with lower cardiometabolic risk. However, the relative contribution of overall activity and the intensity of activity are unclear. Our aim was to determine the relative contribution of overall activity and intensity distribution of activity to cardiometabolic risk in a cross-sectional analysis of apparently healthy office workers and in people with one or more chronic disease., Methods: Clustered cardiometabolic risk score was calculated from mean arterial pressure, high-density lipoprotein cholesterol, triglycerides and HbA1c. Open-source software (GGIR) was used to generate average acceleration and intensity gradient from wrist-worn accelerometer data for two data sets: office-workers who did not have a self-reported medical condition ( n = 399, 70% women) and adults with one or more chronic disease ( n = 1137, 34% women). Multiple linear regression analyses were used to assess the relative contribution of overall activity and intensity of activity to cardiometabolic risk., Results: When mutually adjusted, both overall activity and intensity of activity were independently associated with cardiometabolic risk in the healthy group ( P < 0.05). However, for the CD group, although mutually adjusted associations for average acceleration were significantly associated with cardiometabolic risk ( P < 0.001), intensity was not. In healthy individuals, cardiometabolic risk was lower in those with high overall activity and/or intensity of activity, and who also undertook at least 10 min brisk walking. In those with a chronic disease, risk was lower in those who undertook at least 60 min slow walking., Conclusions: These findings suggest interventions aiming to optimize cardiometabolic health in healthy adults could focus on increasing both intensity and amount of physical activity. However, in those with chronic disease, increasing the amount of activity undertaken, regardless of intensity, may be more appropriate., (Copyright © 2022 by the American College of Sports Medicine.)

Background: We sought to describe global patterns in achievement of risk factor control for primary prevention in patients with T2D and explore the association of country's GNI/capita with risk factor control., Methods: The DISCOVER study is a prospective, observational study of patients with T2D from 38 countries enrolled at initiation of second-line glucose-lowering therapy. We examined achievement of risk factor control (glycosylated hemoglobin <7%, blood pressure <140/90 mmHg, prescription of a statin) at 3 years among those without optimal control at baseline. Countries were stratified by gross national income (GNI)/capita, from 2017). We examined the impact of country GNI/capita with achievement of risk factor control., Findings: Our cohort included 9613 patients with T2D and without baseline cardiovascular disease (mean age 57.2 ± 8.7 years, 47.9% women). At baseline, 6354/7646 patients (83.1%) had suboptimal glucose control, 3449/9200 patients (37.5%) had suboptimal BP control, and 2800/4221 patients (66.7%) were not on an appropriate statin (sample sizes differed due to missing covariate data). Optimal control at 3 years of follow-up was achieved in 41% (glucose), 56% (blood pressure), and 29% (statins) of patients. There was significant variability in achievement of risk factor control across countries but no association between country GNI/capita with achievement of risk factor control (p > 0.08 for all)., Interpretation: In a global, prospective study of patients with T2D, we found that cardiovascular risk factor control achievement was suboptimal despite 3 years of follow-up in specialized health care systems. Neither country-level nor patient-level socioeconomic factors fully explained this finding., (Copyright © 2022 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Aims: Most trials leading to the approval of glucagon-like peptide receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2is) were primarily designed to confirm their non-inferiority to placebo (commonly using an upper 95% confidence limit threshold of 1.3) and, if confirmed, superiority (threshold 1): this asymmetry of margins (1 vs. 1.3) favours the active intervention. We aimed to quantify the probability of clinical superiority of the active treatment by applying the same threshold used to claim non-inferiority., Materials and Methods: We searched PubMed and Cochrane CENTRAL for cardiorenal outcome trials in subjects with type 2 diabetes published before 5 December 2021, to reconstruct from Kaplan-Meier plots individual-level data for the primary outcome or all-cause mortality. We calculated Bayesian posterior densities to obtain the probability for a treatment effect (hazard ratio) <0.769, which is symmetric to the 1.3 threshold (i.e. its reciprocal 1/1.3), emulating a scenario where the active treatment is placebo and placebo is the active treatment., Results: We extracted data from 27 Kaplan-Meier plots (18 for the primary outcome, nine for mortality). Probabilities of clinical superiority to placebo varied significantly: for GLP-1RAs, from a minimum of 0% to a maximum of 69% for the primary outcome and from 0% to 8% for mortality; corresponding estimates for SGLT2is were 0% to 96% and 0% to 93%. Probabilities were on average greater for SGLT2is, particularly in trials investigating kidney or heart failure outcomes., Conclusions: The probability of clinical superiority to placebo varies widely across trials previously reported as showing superiority of GLP-1RAs or SGLT2is compared with placebo. These results showed within- and between-class differences, highlight the drawbacks of a binary interpretation of the results, particularly in the context of the current designs of non-inferiority trials, and have implications for decision makers and future clinical recommendations., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To quantify ethnic differences in the risk of all-cause mortality and cardiovascular disease (CVD) events following a first CVD event in people with and without type 2 diabetes., Methods: We identified 5,349,271 subjects with a first CVD between 1 January 2002 and 31 May 2020 in England; CVD included aortic aneurism, cerebrovascular accident, heart failure, myocardial infarction, peripheral vascular disease, and other cardiovascular diseases. We estimated adjusted hazard ratios (HRs) for type 2 diabetes and ethnicity of three outcomes: fatal and nonfatal second CVD event (different phenotype compared to the first) and all-cause mortality., Results: Relative to White, HRs indicated lower rates in all ethnicities and for all outcomes in both men (from 0.64 to 0.79 for all-cause death; 0.78-0.79 for CVD-related death; and 0.85-0.98 for a second CVD event) and women (0.69-0.77; 0.77-0.83; 0.83-0.95, respectively). Irrespective of ethnicity and sex, type 2 diabetes increased rates of all outcomes by around a third., Conclusions: Prognosis following a CVD event was consistently worse in subjects with type 2 diabetes while varied across ethnicities, suggesting the implementation of different strategies for the secondary prevention of CVD in different ethnic groups., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Omega-3 polyunsaturated fatty acids′ concurrent benefits for cardiometabolic and mental health are equivocal. Despite lack of evidence, up to a third of adults consume Omega-3 supplements. No review has yet been published to report effect on depression in this cardiometabolic population. Methods: We conducted a systematic review of double-blinded, controlled randomised trials to investigate the safety and effect of Omega-3 supplementation on depression scores in people with cardiometabolic diseases. Primary outcome was change in depression scores versus placebo. Secondary outcomes were side-effects, concurrent medication and adherence. Results: Seven trials reporting on 2575 (672 female) adults aged 39−73 were included. Omega-3 dosages ranged from 1−3 g with an intervention duration of 10−48 weeks. Six out of seven trials found no statistically or clinically significant change to depression scores compared to placebo. One trial favoured intervention (Relative Risk Reduction: 47.93%, 95% CI: 24.89−63.98%, p < 0.001). Sub-analyses showed clinically meaningful reductions in depression scores for those on antidepressants (Intervention: 20.9 (SD: 7.1), Placebo: 24.9 (SD: 8.5) p < 0.05) or with severe depression (−1.74; 95% CI −3.04 to −0.05, p < 0.05) in two separate trials. Side effects were comparable between treatment arms. Conclusions: Omega-3 supplementation is safe to use but not superior to placebo for depression in adults with concurrent cardiometabolic disease.

Aims: To characterise the cardiovascular risk of people with type 2 diabetes without established cardiovascular disease but with risk factors, relative to those with established cardiovascular disease, to provide information on which patients could benefit from early use of glucose-lowering therapies that also reduce cardiovascular risk., Methods: Data from people with type 2 diabetes initiating second-line glucose-lowering medication were retrieved from the UK Clinical Practice Research Datalink GOLD database and linked with Hospital Episode Statistics and Office for National Statistics (2001-2016). Cox proportional hazards models were used to estimate relative risks of major adverse cardiovascular events within groups defined by the presence of selected risk factors in people without versus with established cardiovascular disease., Results: Of 53,182 individuals, 19.4% had established cardiovascular disease (i.e. a prior cardiovascular event). Over 5-7 years' follow-up, the rate of major adverse cardiovascular events was 14.0 and 49.6 events/1000 person-years without and with established cardiovascular disease, respectively (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.26, 0.29). Compared with a reference HR 1.0 for participants with established cardiovascular disease, estimated glomerular filtration rate <60 mL/min was the single factor associated with the highest risk of major adverse cardiovascular events (HR 0.75, 95% CI 0.70, 0.81) and mortality (HR 1.12, 95% CI 1.07, 1.18) in people with type 2 diabetes without established cardiovascular disease. The combination of chronic kidney disease with older age, smoking and/or dyslipidaemia was associated with a similarly high risk of cardiovascular events in people with type 2 diabetes and without cardiovascular disease compared with those having established cardiovascular disease., Conclusions: These analyses provide important information to identify people who may benefit from primary prevention of cardiovascular disease. Modifiable cardiovascular risk factors should be controlled early in all individuals with type 2 diabetes (as well as in all individuals with cardiovascular disease)., (© 2021 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aims: Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both 'direct', through infection, and 'indirect', through changes in healthcare., Methods and Results: We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths., Conclusion: Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: To assess if sodium-glucose co-transporter-2 inhibitors (SGLT2is) reduce the risk of all-cause mortality, cardiovascular death and hospitalization for heart failure (HF) or chronic kidney disease (CKD) to a greater extent than dipeptidyl peptidase-4 inhibitors (DPP4is) in people with type 2 diabetes (T2D) with or without established cardiovascular and/or renal disease (CVRD)., Methods: This retrospective cohort study propensity-matched 24 438 patients receiving an SGLT2i 1:1 to a patient receiving a DDP4i, stratified based on the presence of CVRD. The primary outcomes were the time to each of the following: all-cause mortality, cardiovascular death or hospitalization for HF, myocardial infarction, stroke and CKD., Results: Overall, SGLT2is were associated with reductions in all-cause mortality, cardiovascular mortality, hospitalization for HF and hospitalization for CKD compared with DPP4is. In patients with no CVRD history, SGLT2is were associated with reductions in all-cause mortality (HR 0.71, 95% CI 0.57-0.88; P = .002), hospitalization for HF (HR 0.76, 95% CI 0.59-0.98; P = .035) and hospitalization for CKD (HR 0.75, 95% CI 0.63-0.88; P < .001). In patients with established cardiovascular disease (CVD) or at high risk, SGLT2is were associated with reductions in all-cause mortality (HR 0.69, 95% CI 0.59-0.82; P < .001), cardiovascular mortality (HR 0.76, 95% CI 0.62-0.95; P = .014), hospitalization for HF (HR 0.73, 95% CI 0.63-0.85; P < .001), hospitalization for stroke (HR 0.75, 95% CI 0.59-0.94; P = .013) and hospitalization for CKD (HR 0.49, 95% CI 0.43-0.54; P < .001)., Conclusion: There was consistency across subgroups and sensitivity analyses. SGLT2is were associated with a reduced risk of all-cause mortality and hospitalization for HF and CKD compared with DPP4-is, highlighting the need to introduce SGLT2is early in the management of patients with T2D., (© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Microvascular complications of diabetes present a significant challenge due to their diverse presentations, significant morbidity, and as strong predictors of cardiovascular disease. Prevention and management strategies should focus on lifestyle modification, education and awareness, systematic screening for early complications, and intensive management of modifiable risk factors. This review discusses the microvascular complications of diabetes, including diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy, and provides best practice clinical care recommendations to guide health care professionals to better manage people with these conditions., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Aims: Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated., Methods and Results: After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years., Conclusion: The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect., Trial Registration Number: NCT00468923., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The Coronavirus disease 2019 (COVID-19) pandemic has led to a dramatic crisis in health care systems worldwide. These may have significant implications for the management of cardiometabolic diseases. We conducted a systematic review of published evidence to assess the indirect impact of the COVID-19 pandemic on hospitalisations for cardiovascular diseases and their management., Methods: Studies that evaluated volume of hospitalisations for cardiometabolic conditions and their management with comparisons between the COVID-19 and pre-COVID periods were identified from MEDLINE, Embase and the reference list of relevant studies from January 2020 to 25 February 2021., Results: We identified 103 observational studies, with most studies assessing hospitalisations for acute cardiovascular conditions such as acute coronary syndrome, ischemic strokes and heart failure. About 89% of studies reported a decline in hospitalisations during the pandemic compared to pre-pandemic times, with reductions ranging from 20.2 to 73%. Severe presentation, less utilization of cardiovascular procedures, and longer patient- and healthcare-related delays were common during the pandemic. Most studies reported shorter length of hospital stay during the pandemic than before the pandemic (1-8 vs 2-12 days) or no difference in length of stay. Most studies reported no change in in-hospital mortality among hospitalised patients., Conclusion: Clinical care of patients for acute cardiovascular conditions, their management and outcomes have been adversely impacted by the COVID-19 pandemic. Patients should be educated via population-wide approaches on the need for timely medical contact and health systems should put strategies in place to provide timely care to patients at high risk., Systematic Review Registration: PROSPERO 2021: CRD42021236102., (Copyright © 2021 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics., Methods: De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects., Results: Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58-0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45-0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53-0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78-0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72-0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region., Conclusions: This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614., (© 2021. The Author(s).)

Objective: To investigate trends in the prevalence of hypertension and dyslipidaemia in incident type 2 diabetes (T2DM), time to antihypertensive (AHT) and lipid-lowering therapy (LLT), and the association with systolic blood pressure (SBP) and lipid control., Research Design and Methods: Using The Health Improvement Network UK primary care database, 254 925 people with incident T2DM and existing dyslipidaemia or hypertension were identified. Among those without atherosclerotic cardiovascular disease (ASCVD) history and not on AHT or LLT at diagnosis, the adjusted median months to initiating an AHT or an LLT, and the probabilities of high SBP or lipid levels over 2 years in people initiating therapy within or after 1 year were evaluated according to high and low ASCVD risk status., Results: At diabetes diagnosis, 66% and 66% had dyslipidaemia and hypertension, respectively. During 2005 to 2016, dyslipidaemia prevalence increased by 10% in people aged <60 years, while hypertension prevalence remained stable in all age groups. Among those with high ASCVD risk status in the age groups 18 to 39, 40 to 49, and 50 to 59 years, the median number of months to initiation of therapy were 20.4 (95% confidence interval [CI] 20.3-20.5), 10.9 (95% CI 10.8-11.0), and 9.5 (95% CI 9.4-9.6) in the dyslipidaemia subcohort, and 28.1 (95% CI 28.0-28.2), 19.2 (95% CI 19.1-19.3), and 19.9 (95% CI 19.8-20.0) in the hypertension subcohort. Among people with high and low ASCVD risk status, respectively, compared to early LLT initiators, those who initiated LLT after 1 year had a 65.3% to 85.3% and a 65.0% to 85.3% significantly higher probability of failing lipid control at 2 years of follow-up, while late AHT initiators had a 46.5% to 57.9% and a 40.0% to 58.7% significantly higher probability of failing SBP control., Conclusions: Significant delay in initiating cardioprotective therapies was observed, and time to first prescription was similar in the primary prevention setting, irrespective of ASCVD risk status across all T2DM diagnosis age groups, resulting in poor risk factor control at 2 years of follow-up., (© 2021 John Wiley & Sons Ltd.)

Despite growing awareness of the dangers of a dichotomous interpretation of trial results based on the 'statistical significance' of a treatment effect, the uptake of new approaches has been slow in diabetes medicine. We showcase a number of ways to interpret the evidence for a treatment effect applied to the cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT-2is): the P value function (or confidence curves), which depicts the treatment effect across the whole spectrum of confidence levels; the counternull value, which is the hazard ratio (i.e. treatment effect size) supported by the same amount of evidence as the null value (i.e. no treatment effect); and the S value, which quantifies the strength of the evidence against the null hypothesis in terms of the number of coin tosses yielding the same side. We show how this approach identifies potential treatment effects, highlights similarities among trials straddling the threshold of statistical significance, and quantifies differences in the strength of the evidence from trials reporting statistically significant results. For example, while REWIND, CANVAS and CREDENCE failed to reach statistical significance at the .05 level for all-cause mortality, their counternull values indicate that reduced death rates by 19%, 24% and 31%, respectively, are supported by the same amount of evidence as that indicating no treatment effect. Moreover, similarities among results emerge in trials of GLP-1RAs (REWIND, EXSCEL and LEADER) lying closely around the threshold of 'statistical significance'. Lastly, several S values, such as for the primary outcome in HARMONY Outcomes (S value 10.9) and all-cause death in EMPAREG-OUTCOME (S value 15.0), stand out compared with values for other outcomes and other trials, suggesting much larger differences in the evidence between these studies and several others that cluster around the .05 significance threshold. P value functions, counternull values and S values should complement the standard reporting of the treatment effect to help interpret clinical trials and make decisions among competing glucose-lowering medications., (© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)