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Background: Quality of chronic care for cardiovascular disease (CVD) remains suboptimal worldwide. The Collaborative Quality ImProvement (C-QIP) trial aims to develop and test the feasibility and clinical effect of a multicomponent strategy among patients with prevalent CVD in India., Methods: The C-QIP is a clinic-based, open randomized trial of a multicomponent intervention vs usual care that was locally developed and adapted for use in Indian settings through rigorous formative research guided by Consolidated Framework for Implementation Research (CFIR). The C-QIP intervention consisted of 5 components: 1) electronic health records and decision support system for clinicians, 2) trained nonphysician health workers (NPHW), 3) text-message based lifestyle reminders, 4) patient education materials, 5) quarterly audit and feedback reports. Patients with CVD (ischemic heart disease, ischemic stroke, or heart failure) attending outpatient CVD clinics were recruited from September 2022 to September 2023 and were randomized to the intervention or usual care arm for at least 12 months follow-up. The co-primary outcomes are implementation feasibility, fidelity (ie, dose delivered and dose received), acceptability, adoption and appropriateness, measured at multiple levels: patient, provider and clinic site-level, The secondary outcomes include prescription of guideline directed medical therapy (GDMT) (provider-level), and adherence to prescribed therapy, change in mean blood pressure (BP) and LDL-cholesterol between the intervention and control groups (patient-level). In addition, a trial-based process and economic evaluations will be performed using standard guidelines., Results: We recruited 410 socio-demographically diverse patients with CVD from 4 hospitals in India. Mean (SD) age was 57.5 (11.7) years, and 73.0% were males. Self-reported history of hypertension (48.5%) and diabetes (41.5%) was common. At baseline, mean (SD) BP was 127.9 (18.2) /76.2 (11.6) mm Hg, mean (SD) LDLc: 80.3 (37.3) mg/dl and mean (SD) HbA1c: 6.8% (1.6%). At baseline, the GDMT varied from 62.4% for patients with ischemic heart disease, 48.6% for ischemic stroke and 36.1% for heart failure., Conclusion: This study will establish the feasibility of delivering contextually relevant, and evidence-based C-QIP strategy and assess whether it is acceptable to the target populations. The study results will inform a larger scale confirmatory trial of a comprehensive CVD care model in low-resource settings., Trial Registration: Clinical Trials Registry India: CTRI/2022/04/041847; Clinicaltrials.gov number: NCT05196659., Competing Interests: Declaration of competimng interest MDH has received travel support from the American Heart Association and World Heart Federation and consulting fees from PwC Switzerland. MDH has an appointment at The George Institute for Global Health, which has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy through its social enterprise business, George Medicines. MDH has pending patents for heart failure polypills., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally., Methods: We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised for marketing and/or included in EMLs and clinical guidelines. In each country, we collected retail and price data for polypills from at least one public-sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable if the lowest-paid worker spent more than a day's wage to purchase a monthly supply., Results: Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. In the four countries, no surveyed public pharmacies stocked polypills. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Private sector availability was 100% in Argentina and Spain. Most combinations (n = 5) identified were in India. Combinations found in India and Spain were affordable in the local context. A lowest-paid government worker would spend between 0.2 (India) and 2.8 (Mauritius) days' wages to pay the price for one month's supply of the polypills. Polypills were likely to be affordable if they were manufactured in the same country., Conclusion: Low availability and affordability of polypills in the public sector suggest that implementation remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies., Competing Interests: MDH has pending patents for heart failure polypills. Other authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Globally, cardiovascular disease (CVD) remains the leading cause of mortality and disability, with hypertension being the single most important modifiable risk factor. Hypertension is responsible for about 18% of global deaths from CVD, of which African regions are disproportionately affected, especially sub-Saharan Africa. This study assessed the burden of major CVD subtypes attributable to hypertension in Nigeria., Methods: The population attributable fractions (PAF) for myocardial infarction, all strokes, ischaemic stroke and intracerebral haemorrhagic stroke attributable to hypertension in Nigeria were calculated using published results from the INTERHEART and INTERSTROKE studies and prevalence estimates of hypertension in Nigeria. PAF estimates were obtained for age, sex, and geopolitical zones., Results: Overall, hypertension contributed to 13.2% of all myocardial infarctions and 24.6% of all strokes, including 21.6% of all ischaemic strokes and 33.1% of all intracerebral haemorrhagic strokes. Among men aged ≤55 years, the PAF for myocardial infarction ranged from 11.7% (North-West) to 14.6% (South-East), while in older men, it spanned 9.2% (North-West) to 11.9% (South-East). Among women aged ≤65 years, PAF varied from 18.6% (South-South) to 20.8% (South-East and North-Central), and among women aged >65 years, it ranged from 10.4% (South-South) to 12.7% (South-East)., Conclusion: Hypertension is a key contributor to the burden of CVD in Nigeria. Understanding the burden of hypertension in the Nigerian population overall and key subgroups is crucial to developing and implementing contextualised health policies to reduce the burden of CVD. Public health interventions and policies centred on hypertension will play a critical role in potentially alleviating the burden of cardiovascular diseases (CVD) in Nigeria., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

This commentary describes the potential impact of inclusion of polypills for prevention of cardiovascular disease in the 23rd WHO Model List of Essential Medicines, and provides a roadmap for adoption, implementation, sustainment, and scale-up. The World Health Organization's endorsement of polypills is essential for improving global access, particularly in low- and middle-income countries. The greatest health gains are expected in a primary prevention population which has a significantly higher burden of fatal and non-fatal cardiovascular disease compared with the population of individuals with prevalent cardiovascular disease. A focus on adoption, implementation, sustainment, and scale-up of polypills for prevention of cardiovascular disease is needed including increasing supply of available polypills and incorporating polypills into the World Health Organization HEARTS technical package for integration into primary care systems to realize these benefits for population health. Widespread implementation of polypills for prevention of cardiovascular disease has the potential to equitably reduce the impact of cardiovascular disease globally by simplifying treatment options and expanding accessibility across economic levels, both across and within countries., Competing Interests: MDH has received travel support from the American Heart Association and World Heart Federation and consulting fees from PwC Switzerland. MDH has an appointment at The George Institute for Global Health, which has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy through its social enterprise business, George Medicines. MDH and AA have pending patents for heart failure polypills., (Copyright: © 2024 The Author(s).)

Importance: Aspirin is an effective and low-cost option for reducing atherosclerotic cardiovascular disease (CVD) events and improving mortality rates among individuals with established CVD. To guide efforts to mitigate the global CVD burden, there is a need to understand current levels of aspirin use for secondary prevention of CVD., Objective: To report and evaluate aspirin use for secondary prevention of CVD across low-, middle-, and high-income countries., Design, Setting, and Participants: Cross-sectional analysis using pooled, individual participant data from nationally representative health surveys conducted between 2013 and 2020 in 51 low-, middle-, and high-income countries. Included surveys contained data on self-reported history of CVD and aspirin use. The sample of participants included nonpregnant adults aged 40 to 69 years., Exposures: Countries' per capita income levels and world region; individuals' socioeconomic demographics., Main Outcomes and Measures: Self-reported use of aspirin for secondary prevention of CVD., Results: The overall pooled sample included 124 505 individuals. The median age was 52 (IQR, 45-59) years, and 50.5% (95% CI, 49.9%-51.1%) were women. A total of 10 589 individuals had a self-reported history of CVD (8.1% [95% CI, 7.6%-8.6%]). Among individuals with a history of CVD, aspirin use for secondary prevention in the overall pooled sample was 40.3% (95% CI, 37.6%-43.0%). By income group, estimates were 16.6% (95% CI, 12.4%-21.9%) in low-income countries, 24.5% (95% CI, 20.8%-28.6%) in lower-middle-income countries, 51.1% (95% CI, 48.2%-54.0%) in upper-middle-income countries, and 65.0% (95% CI, 59.1%-70.4%) in high-income countries., Conclusion and Relevance: Worldwide, aspirin is underused in secondary prevention, particularly in low-income countries. National health policies and health systems must develop, implement, and evaluate strategies to promote aspirin therapy.

Background: Elevated depressive symptoms and cigarette smoking are independently associated with poorer cardiovascular health (CVH), but it is unknown whether their treatment can synergistically improve CVH. We sought to characterize CVH of adults with comorbid depression and smoking and examine changes in CVH associated with changes in smoking and depression., Methods: Participants (N = 300, 55 % women) were adult smokers (≥ 1 cigarette/day) with lifetime major depressive disorder enrolled in a 12-week intervention trial targeting depression and smoking. Multiple linear regression examined prospective associations between changes in depression (Beck Depression Inventory-II), smoking (past 24-hour cigarettes or smoking abstinence), and modified CVH score (per American Heart Association, excluding smoking: diet, physical activity, body mass index, blood glucose, cholesterol, blood pressure)., Results: Baseline mean CVH score was 5.87/12 points (SD = 2.13). No participants met "ideal" on all CVH components (blood glucose: 48 %, cholesterol: 46 %, physical activity: 38 %, body mass index: 24 %, blood pressure: 22 %, diet: 3 %). CVH scores did not change from baseline to end-of-treatment (M = 0.18 points, SD = 1.36, p = .177), nor did change in depression × smoking predict change in CVH (p = .978). However, greater reductions in depression were significantly associated with greater improvements in CVH (β = -0.04, SE = 0.01, p = .015)., Limitations: This study was limited by a short follow-up period, missing blood glucose and cholesterol data, and treatment-seeking smokers., Conclusions: Adults with comorbid depression and smoking had poor CVH. Although integrated treatment for depression and smoking improved both conditions, only reductions in depression were associated with improvements in CVH. These findings have implications for integrating psychosocial treatment into CVH promotion efforts., Registration: NCT02378714 (clinicaltrials.gov)., Competing Interests: Declaration of competing interest Drs. Schnoll and Hitsman have received varenicline and placebo free from Pfizer. Dr. Schnoll has provided consultation to Pfizer, GlaxoSmithKline, and Palliatech. In the last 3 years, Dr. Huffman has received support from the World Heart Federation through unrestricted education grants from Boehringer Ingelheim, Novartis, and Bupa and from the American Heart Association, Verily, and AstraZeneca for work unrelated to this research. Dr. Huffman has also received salary support from the American Medical Association for his role as an associate editor for JAMA Cardiology. Dr. Huffman has planned patents for combination therapy for the treatment of heart failure. The George Institute for Global Health has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy through its social enterprise business, George Medicines., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Asian American subgroups experience heterogeneity in cardiovascular disease, but differences in hypertension-related cardiovascular disease mortality between Asian American subgroups is not known., Methods: Among 1,194,648 deaths in the United States in 2018-2021 with cardiovascular disease as an underlying cause and hypertension-related diseases as contributing cause, sex-specific age-standardized mortality rates, proportional mortality, and proportional mortality ratios for non-Hispanic Asian and Asian subgroups, Hispanic, and non-Hispanic Black individuals were compared with non-Hispanic White individuals. The analysis was conducted in August 2022., Results: There were 37,746; 95,404; 193,899; and 867,599 hypertension-related cardiovascular disease deaths in non-Hispanic Asian; Hispanic; non-Hispanic Black; and non-Hispanic White groups, respectively. Among non-Hispanic Asian females, mortality rates ranged from 41.6 (95% CI 40.0-43.3) per 100,000 population in Japanese to 52.6 (51.0-54.2) per 100,000 in Filipina individuals. Among non-Hispanic Asian males, mortality rates ranged from 45.8 (43.3-48.2) per 100,000 in Korean to 81.0 (78.5-83.5) per 100,000 in Filipino individuals. Proportional mortality was higher for all Asian American subgroups compared to non-Hispanic White individuals. Proportional mortality ratios ranged from 1.11 (in Korean males, proportional mortality was 10.2% [95% CI 9.7-10.8] of all deaths) to 1.38 (in Filipino males, proportional mortality was 12.7% [12.4-13.1] of all deaths; in Chinese females, proportional mortality was 11.9% [11.6-12.3]; and in Filipina females, proportional mortality was 11.9% [12.3-13.0])., Conclusions: There was up to two-fold variation in hypertension-related cardiovascular disease mortality among Asian American subgroups. All subgroups experienced higher proportional mortality for hypertension-related cardiovascular disease compared with non-Hispanic White individuals., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Hypertension (high blood pressure) is a modifiable risk factor for cardiovascular disease. However, patients may lack confidence in their understanding of what constitutes normal/healthy blood pressure, potentially affecting intentions to seek necessary care. The American Heart Association defines normal/healthy blood pressure as <120/80 mm Hg, with a 130/80 mm Hg threshold for hypertension diagnosis., Methods: Our US sample ( N = 6,592) included 1,342 adults with hypertension alone and 795 with hypertension and relevant comorbidities (heart disease, kidney disease, and diabetes mellitus). We assessed confidence in understanding blood pressure numbers, knowledge of thresholds for normal/healthy blood pressure ("normal or healthy blood pressure is below . . ."; counting 120-130/80 mm Hg as correct), and intentions to seek care for randomly assigned blood pressure readings of 142/91 (stage 2 hypertension), 132/69 (stage 1 hypertension), or 118/78 mm Hg (normal/healthy blood pressure)., Results: Among nonhypertensive participants, 55% expressed confidence in their understanding of blood pressure numbers, but only 36% knew the upper thresholds for normal/healthy blood pressure. Among participants with hypertension alone, 78% were confident while 47% were knowledgeable. Among participants with hypertension and comorbidities, 81% were confident and 40% were knowledgeable. Participants who were confident (v. not) were more likely to express intentions to act on stage 2 hypertension readings but less likely to express intentions to act on stage 1 readings, even after adjustment for knowledge, hypertension diagnosis, and sociodemographics., Limitations: Confidence, knowledge, and intentions were each measured with 1 question., Conclusions: Independent of knowledge, confidence was associated with greater willingness to act on stage 2 hypertension readings but reduced willingness to act on stage 1 hypertension readings. Interventions aiming to improve hypertension care-seeking behavior should improve confidence in accurate knowledge., Highlights: Hypertension or high blood pressure is a major risk factor for heart disease.Most Americans do not know that normal/healthy blood pressure levels are ≤120/80 mm Hg, yet they are confident that they know this information.Inappropriate confidence in understanding of blood pressure numbers undermines intentions to seek care for stage 1 hypertension blood pressure readings.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) reduce cardiovascular events and mortality in patients with type 2 diabetes mellitus (T2DM). We sought to describe trends in prescribing for SGLT2is and GLP1-RAs in diverse care settings, including (1) the outpatient clinics of a midwestern integrated health system and (2) small- and medium-sized community-based primary care practices and health centers in 3 midwestern states. We included adults with T2DM and ≥1 outpatient clinic visit. The outcomes of interest were annual active prescription rates for SGLT2is and GLP1-RAs (separately). In the integrated health system, 22,672 patients met the case definition of T2DM. From 2013 to 2019, the overall prescription rate for SGLT2is increased from 1% to 15% (absolute difference [AD] 14%, 95% confidence interval [CI] 13% to 15%, p <0.01). The GLP1-RA prescription rate was stable at 10% (AD 0%, 95% CI -1% to 1%, p = 0.9). In community-based primary care practices, 43,340 patients met the case definition of T2DM. From 2013 to 2017, the SGLT2i prescription rate increased from 3% to 7% (AD 4%, 95% CI 3% to 6%, p <0.01), whereas the GLP1-RA prescription rate was stable at 2% to 3% (AD 1%, 95% CI -1 to 1%, p = 0.40). In a fully adjusted regression model, non-Hispanic Black patients had lower odds of SGLT2i or GLP1-RA prescription (odds ratio 0.56, 95% CI 0.34 to 0.89, p = 0.016). In conclusion, the increase in prescription rates was greater for SGLT2is than for GLP1-RAs in patients with T2DM in a large integrated medical center and community primary care practices. Overall, prescription rates for eligible patients were low, and racial disparities were observed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background The burden of cardiovascular diseases (CVDs) and response to health systems vary widely at the subnational level in India. Our study aimed to assess the variation in state-level access to medicines for CVDs by comparing the essential medicines lists (EMLs) at the national and subnational levels in India and by rapid appraisal of the existing policies and processes of drug procurement. Methods We assessed the inclusion of six classes of medicines for CVDs in the recent and publicly available national and subnational EMLs from July to September 2018 in the states of Telangana and Madhya Pradesh. We examined the drug procurement and distribution policies and processes using documentary review and five key informant interviews between March and June 2018. Results The WHO's EML, India's national EML, and 21 of 28 publicly available (75%) Indian state and Union Territory EMLs included all six classes of essential medicines for CVDs. However, some medicines were not included in the policy packages of essential medicines meant for primary health centres. Both the states used centralized tendering and decentralized distribution as part of the public sector drug procurement process. The requirement was based on the previous year's consumption. The approximate time between procurement planning and distribution was 7-8 months in both the states. Conclusion Substantial variation exists in the selection of drugs for CVDs in EMLs at the subnational level in India. Improving forecasting techniques for requirement of medicines and reducing time lags between forecasting and distribution to health facilities may allow for better access to essential medicines.

Background: Cardiovascular disease (CVD) is highly prevalent in India, and little is known about the perception of patients and providers about a package of collaborative quality improvement (C-QIP) strategies consisting of provider-focused electronic health records-decision support system (EHR-DSS), non-physician health workers (NPHW), and patient-facing text messages to enhance the CVD care., Objective: To explore the barriers and enablers of the C-QIP strategy from the perspective of providers, health administrators, patients, and care givers in India., Methods: We conducted a qualitative study using the consolidated framework for implementation research (CFIR) to understand the challenges and facilitators of implementing C-QIP strategy to enhance CVD care in the Indian context. A diverse sample of 38 physicians, 14 non-physician health workers (nurses, pharmacists), 4 health administrators, and 16 patients and their caregivers participated in semi-structured interviews. All interviews were audio-recorded, transcribed, translated, anonymised, and coded using MAXQDA software. We used the framework method and CFIR domains to analyze the qualitative data., Results: Barriers perceived from providers' and health administrators' perspectives in providing quality CVD care were high patient volume, physician burnout, lack of robust communication or referral system, paucity of electronic health records, lack of patient counsellors, polypharmacy, poor patient adherence to medications, and lack of financial incentives. Low health literacy, high cost of treatment, misinformation bias, and difficulty in maintaining lifestyle changes were barriers from patients' perspectives. The CFIR identified key enablers for the implementation of C-QIP such as standardized treatment protocol, reduced medication errors, improved physician-patient relationships, and enhanced patient self-care through trained and supported NPHW. Barriers included: heterogenous healthcare settings, diverse patient groups and comorbidities, associated costs of care and interoperability, confidentiality, and data privacy issues around the use of EHR-DSS., Conclusion: Strategies to enhance CVD care must be low-cost, culturally acceptable, and integrated into existing care pathways., Competing Interests: The George Institute for Global Health’s wholly owned enterprise, George Health Enterprises, has received investment funds to develop fixed-dose combination products containing aspirin, statin and blood pressure lowering drugs. MDH plan to submit patents for heart failure polypills. No potential conflict of interest was reported by other author(s)., (Copyright: © 2022 The Author(s).)

Background: Mendelian randomization studies use genetic variants as natural experiments to provide evidence about causal relations between modifiable risk factors and disease. Recent Mendelian randomization studies suggest each mmol/L reduction in low-density lipoprotein cholesterol (LDL-C) sustained over a lifetime can reduce the risk of cardiovascular disease by more than half. However, these findings have not been replicated in randomized clinical trials, and the effect of treatment duration on the magnitude of risk reduction remains uncertain. The aim of this article was to evaluate the relationship between lipid-lowering drug exposure time and relative risk reduction of major cardiovascular events in randomized clinical trials., Methods: We conducted a systematic review and meta-analysis of randomized clinical trials of statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors that report LDL-C levels and effect sizes for each year of follow-up. The primary end point was major vascular events, defined as the composite of cardiovascular death, myocardial infarction, stroke, and coronary revascularization. Hazard ratios during each year of follow-up were meta-analyzed using random-effects models., Results: A total of 21 trials with 184 012 patients and an average mean follow-up of 4.4 years were included. Meta-regression showed there was greater relative risk reduction in major vascular events with increasing duration of treatment ( P <0.001). For example, each mmol/L LDL-C lowered was associated with a relative risk reduction in major vascular events of 12% (95% CI, 8%-16%) for year 1, 20% (95% CI, 16%-24%) for year 3, 23% (95% CI, 18%-27%) for year 5, and 29% (95% CI, 14%-42%) for year 7., Conclusions: The benefits of LDL-C lowering do not seem to be fixed but increase steadily with longer durations of treatment. The results from short-term randomized trials are compatible with the very strong associations between LDL-C and cardiovascular events seen in Mendelian randomization studies.

Background: In the prevention of cardiovascular disease, a WHO target is that at least 50% of eligible people use statins. Robust evidence is needed to monitor progress towards this target in low-income and middle-income countries (LMICs), where most cardiovascular disease deaths occur. The objectives of this study were to benchmark statin use in LMICs and to investigate country-level and individual-level characteristics associated with statin use., Methods: We did a cross-sectional analysis of pooled, individual-level data from nationally representative health surveys done in 41 LMICs between 2013 and 2019. Our sample consisted of non-pregnant adults aged 40-69 years. We prioritised WHO Stepwise Approach to Surveillance (STEPS) surveys because these are WHO's recommended method for population monitoring of non-communicable disease targets. For countries in which no STEPS survey was available, a systematic search was done to identify other surveys. We included surveys that were done in an LMIC as classified by the World Bank in the survey year; were done in 2013 or later; were nationally representative; had individual-level data available; and asked questions on statin use and previous history of cardiovascular disease. Primary outcomes were the proportion of eligible individuals self-reporting use of statins for the primary and secondary prevention of cardiovascular disease. Eligibility for statin therapy for primary prevention was defined among individuals with a history of diagnosed diabetes or a 10-year cardiovascular disease risk of at least 20%. Eligibility for statin therapy for secondary prevention was defined among individuals with a history of self-reported cardiovascular disease. At the country level, we estimated statin use by per-capita health spending, per-capita income, burden of cardiovascular diseases, and commitment to non-communicable disease policy. At the individual level, we used modified Poisson regression models to assess statin use alongside individual-level characteristics of age, sex, education, and rural versus urban residence. Countries were weighted in proportion to their population size in pooled analyses., Findings: The final pooled sample included 116 449 non-pregnant individuals. 9229 individuals reported a previous history of cardiovascular disease (7·9% [95% CI 7·4-8·3] of the population-weighted sample). Among those without a previous history of cardiovascular disease, 8453 were eligible for a statin for primary prevention of cardiovascular disease (9·7% [95% CI 9·3-10·1] of the population-weighted sample). For primary prevention of cardiovascular disease, statin use was 8·0% (95% CI 6·9-9·3) and for secondary prevention statin use was 21·9% (20·0-24·0). The WHO target that at least 50% of eligible individuals receive statin therapy to prevent cardiovascular disease was achieved by no region or income group. Statin use was less common in countries with lower health spending. At the individual level, there was generally higher statin use among women (primary prevention only, risk ratio [RR] 1·83 [95% CI 1·22-2·76), and individuals who were older (primary prevention, 60-69 years, RR 1·86 [1·04-3·33]; secondary prevention, 50-59 years RR 1·71 [1·35-2·18]; and 60-69 years RR 2·09 [1·65-2·65]), more educated (primary prevention, RR 1·61 [1·09-2·37]; secondary prevention, RR 1·28 [0·97-1·69]), and lived in urban areas (secondary prevention only, RR 0·82 [0·66-1·00])., Interpretation: In a diverse sample of LMICs, statins are used by about one in ten eligible people for the primary prevention of cardiovascular diseases and one in five eligible people for secondary prevention. There is an urgent need to scale up statin use in LMICs to achieve WHO targets. Policies and programmes that facilitate implementation of statins into primary health systems in these settings should be investigated for the future., Funding: National Clinician Scholars Program at the University of Michigan Institute for Healthcare Policy and Innovation, and National Institute of Diabetes and Digestive and Kidney Diseases., Translation: For the Spanish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests JML reports graduate research funding from the German Academic Scholarship Foundation. RA reports contracts with Novo Nordisk, Union for International Cancer Control's, National Institute for Health Research, and Sloan Memorial Kettering Hospital, outside of the submitted work. RA also reports payments or honoraria from Merck, Novartis, and F Hoffmann-La Roche, outside of the submitted work. TWB reports support from the Alexander von Humboldt Foundation. MH reports grants from the National Institutes of Health and receives salary support from Physician for Human Rights. MDH received funding in the past 3 years from the World Heart Federation to serve as its senior programme advisor for the Emerging Leaders programme, which has been supported by Boehringer Ingelheim, Novartis, Bupa, and AstraZeneca. MDH also received support from the American Heart Association, Verily, AstraZeneca, and American Medical Association for work unrelated to this research. MDH plans to submit patents for heart failure polypill. MDH has received meeting or travel support from the American Heart Association and World Heart Federation. MDH has an appointment at The George Institute for Global Health, which has a patent, licence, and has received investment funding with intent to commercialise fixed-dose combination therapy through its social enterprise business, George Medicines. DF reports grant funding within the past 3 years from a Pilot and Feasibility Grant funded by the Michigan Center for Diabetes Translational Research (NIH Grant P30-DK092926) and a grant from the Swinmurn Foundation to implement a sustainable diabetes clinic in Guatemala. DF also reports volunteer affiliations with Wuqu’ Kawoq and GlucoSalud, outside of the submitted work. During the course of this study, DF has received research fellowship funding from National Clinician Scholars Program at the University of Michigan Institute for Healthcare Policy & Innovation. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Health care quality and insurance coverage have improved with economic development in China, but the burden of cardiovascular diseases (CVDs) continues to increase with ongoing gaps in prevention. We aimed to compare the uptake of secondary CVD prevention between stroke and coronary heart disease (CHD) patients in China., Methods: In a cross-sectional community-based survey of 47,841 adults (age ≥45 years) in 7 regions of China between 2014 and 2016, we identified those with a history of stroke or CHD to quantify disparities in conventional secondary CVD prevention strategies in multivariable logistic regression models., Results: There were 4,105 and 1,022 participants with a history of stroke and CHD, respectively. Compared to participants with CHD, those with a history of stroke were significantly less likely to be taking blood-pressure-lowering (39.7% vs. 53%), lipid-lowering (13.7% vs. 36.8%), and antiplatelet (20.8% vs. 50.6%) agents, at least one (48.9% vs. 70.8%) or all 3 recommended medicines (6.1% vs. 24.0%), and were less likely to achieve a lipid-cholesterol target (30.3% vs. 44.0%). Participants with a history of stroke achieved less optimal secondary prevention goals for medication use, either from any (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.44-0.66) or all 3 medications (aOR 0.27, 95% CI 0.20-0.36), as well as better blood pressure (aOR 0.81, 95% CI 0.66-0.98) and low-density lipoprotein cholesterol (aOR 0.34, 95% CI 0.27-0.43) levels of control. There were no significant differences in weight, smoking, or physical activity between the groups., Conclusion: Stroke patients had lower use of secondary CVD-preventive medication and achieved lower levels of risk factor control than those of CHD patients in China. Nationwide disease-specific strategies, and better education of participants and health care providers, may narrow these gaps., (© 2021 S. Karger AG, Basel.)

Background: We aimed to assess whether the modest major adverse cardiovascular events (MACE) reductions in previous trials testing combined blood pressure (BP) and low density lipoprotein cholesterol (LDL-C) reduction were due to modest risk factor reduction and/or a negative interaction, whereby the joint effects of therapy are less than expected., Methods: We performed a systematic review of randomized controlled trials comparing patients who received combination BP and cholesterol lowering treatment versus placebo. We calculated the expected relative risk reduction (RRR) in MACE based on the observed reductions in systolic BP and LDL-C in each trial and previous meta-analysis of the individual modalities., Results: All five included trials achieved small SBP reductions (range 1 to 6 mmHg) and small-to-moderate LDL-C reductions (range 0.5 to 1.1 mmol/L), which were all less than expected. Each of the three largest trials achieved significant reductions in MACE and the observed vs expected RRRs were closely aligned: - ASCOT observed RRR 32% (95% CI 18-43%) vs expected RRR 24% (95% CI 20-28%); HOPE-3 observed RRR 28%, (95% CI 10-42%) vs expected RRR 28% (95% CI 23%-31%); TIPS-3 observed RRR 20% (95% CI 0%-36%) vs expected RRR 21% (95% CI 18-24%)., Conclusions: MACE reductions seen in past trials of combined BP and LDL-C reflect the degree of risk factor reduction. Sustained and substantial reductions in BP and LDL-C (eg. ≥15 mmHg and ≥ 1.5 mmol/L) are required to halve cardiovascular risk, which in turn requires long-term adherence to intensive LDL-C lowering and combination BP therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: In randomised controlled trials, fixed-dose combination treatments (or polypills) have been shown to reduce a composite of cardiovascular disease outcomes in primary prevention. However, whether or not aspirin should be included, effects on specific outcomes, and effects in key subgroups are unknown., Methods: We did an individual participant data meta-analysis of large randomised controlled trials (each with ≥1000 participants and ≥2 years of follow-up) of a fixed-dose combination treatment strategy versus control in a primary cardiovascular disease prevention population. We included trials that evaluated a fixed-dose combination strategy of at least two blood pressure lowering agents plus a statin (with or without aspirin), compared with a control strategy (either placebo or usual care). The primary outcome was time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularisation. Additional outcomes included individual cardiovascular outcomes and death from any cause. Outcomes were also evaluated in groups stratified by the inclusion of aspirin in the fixed-dose treatment strategy, and effect sizes were estimated in prespecified subgroups based on risk factors. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to compare strategies., Findings: Three large randomised trials were included in the analysis (TIPS-3, HOPE-3, and PolyIran), with a total of 18 162 participants. Mean age was 63·0 years (SD 7·1), and 9038 (49·8%) participants were female. Estimated 10-year cardiovascular disease risk for the population was 17·7% (8·7). During a median follow-up of 5 years, the primary outcome occurred in 276 (3·0%) participants in the fixed-dose combination strategy group compared with 445 (4·9%) in the control group (hazard ratio 0·62, 95% CI 0·53-0·73, p<0·0001). Reductions were also observed for the separate components of the primary outcome: myocardial infarction (0·52, 0·38-0·70), revascularisation (0·54, 0·36-0·80), stroke (0·59, 0·45-0·78), and cardiovascular death (0·65, 0·52-0·81). Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. Treatment effects were similar at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity. Gastrointestinal bleeding was uncommon but slightly more frequent in the fixed-dose combination strategy with aspirin group versus control (19 [0·4%] vs 11 [0·2%], p=0·15). The frequencies of haemorrhagic stroke (10 [0·2%] vs 15 [0·3%]), fatal bleeding (two [<0·1%] vs four [0·1%]), and peptic ulcer disease (32 [0·7%] vs 34 [0·8%]) were low and did not differ significantly between groups. Dizziness was more common with fixed-dose combination treatment (1060 [11·7%] vs 834 [9·2%], p<0·0001)., Interpretation: Fixed-dose combination treatment strategies substantially reduce cardiovascular disease, myocardial infarction, stroke, revascularisation, and cardiovascular death in primary cardiovascular disease prevention. These benefits are consistent irrespective of cardiometabolic risk factors., Funding: Population Health Research Institute., Competing Interests: Declaration of interests SY reports grants from the Canadian Institutes of Health Research, Wellcome Trust, AstraZeneca, and Cadila Pharmaceuticals related to conducting the HOPE-3 or TIPS-3 studies. PJ, PG, EL, SIB, KT, and JB report institutional grants from the Wellcome Trust, Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Cadila Pharmaceuticals, and AstraZeneca related to the TIPS-3 or HOPE-3 studies (or both). RM and GR report institutional grant funding from Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou related to the PolyIran study. SY reports receiving honoraria and reimbursement for travel expenses from AstraZeneca, Bayer, Boehringer Ingelheim, and Ferrer. EL reports consulting fees from Amgen Canada, consulting fees and speaker honoraria from HLS Canada, institutional research grant from Boehringer Ingelheim, and consulting fees from NovoNordisk. MDH reports grants from the World Heart Federation via unrestricted educational grants from Boehringer Ingelheim and Novartis, grants from the American Heart Association, Verily, and AstraZeneca, and personal fees from the American Medical Association outside the submitted work. In addition, MDH has a patent pending for heart failure polypills. PP reports funding from St John's Research Institute, Bangalore, India, during the conduct of the study. AR reports that George Health Enterprises, the social enterprise arm of The George Institute for Global Health, has received investment to develop fixed-dose combination products containing aspirin, statin, and blood pressure lowering drugs. George Health Enterprises has submitted patents for low-dose blood pressure combinations, on which AR is listed as one of the inventors. AR is seconded part-time to George Medicines. All staff employed by The George Institute have an institutional interest to declare with respect to George Health Enterprises, although none of the staff have a direct financial interest in these investments. DX reports grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Coca-Cola India, Eli Lilly, the Indian Council of Medical Research, Pfizer, Sanofi, UK Medical Research Council, and Wellcome Trust, outside the submitted work. JB reports personal fees from Bayer, outside the submitted work. RD reports grants from Amarin, DalCor, and the Population Health Research Institute, outside the submitted work. VF and JMC report grants from H2020 related to the ongoing SECURE trial. JMC reports receiving honoraria and reimbursement for travel expenses from Ferrer, Pfizer, and Bayer. AA reports grants from Bayer, EMS Pharma, and the Population Health Research Institute; and consulting fees from Bayer, Eli Lilly, NovoNordisk, and EMS Pharma outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Heart failure is prevalent in those with type 2 diabetes and chronic kidney disease, and is associated with significant mortality and morbidity. In the CREDENCE trial, canagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular (CV) death by 31%. In the current analysis we sought to determine whether the effect of canagliflozin on HHF/CV death differed in subgroups defined by key baseline participant characteristics. Cox regression models were used to estimate hazard ratios and 95% confidence intervals. Canagliflozin was associated with a reduction in the relative risk of HHF/CV death regardless of age, sex, history of heart failure or CV disease, and the use of loop diuretics or glucagon-like peptide-1 receptor agonists (all p interaction  > .114). The absolute benefit of canagliflozin was greater in those at highest baseline risk, such as those with CV disease (50 fewer events/1000 patients treated over 2.5 years vs. 20 fewer events in those without CV disease) or advanced kidney disease (estimated glomerular filtration rate [eGFR] 30-45 mL/min/1.73m 2 : 61 events prevented/1000 patients treated over 2.5 years vs. 23 events in eGFR 60-90 mL/min/1.73m 2 ). Canagliflozin consistently reduces the proportional risk of HHF/CV death across a broad range of subgroups with greater absolute benefits in those at highest baseline risk., (© 2021 John Wiley & Sons Ltd.)

Importance: Clinical care quality improvement (QI) strategies are critical to prevent and control cardiovascular disease (CVD). However, there is limited evidence regarding which components of the health system-, clinician-, and patient-based QI strategies contribute to their impact on CVD., Objectives: To identify, map, and organize evidence on the effectiveness and implementation of cardiovascular QI strategies that seek to improve outcomes in patients with CVD., Evidence Review: Eight electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane Library, ProQuest, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform) were searched for studies published between January 1, 2009, and October 25, 2019. Eligible study designs included randomized trials and preintervention and postintervention evaluations. Descriptive findings of included studies were reported using several frameworks to map the intervention components stratified by target population, setting, outcomes, and overall results., Findings: From 8066 screened titles and abstracts, 456 unique studies with 150 148 unique patients (38.1% women and 61.9% men; mean [SD] age, 64.6 [7.1] years) were identified, including 427 randomized trials, 21 quasi-randomized studies, and 8 preintervention and postintervention studies. Of 336 studies from 45 countries that were classified, 255 (75.9%) were from high-income countries; 68 (20.2%), upper-middle-income countries; 13 (3.9%), lower-middle-income countries; and 0, low-income countries, with diverse clinical settings and target patient populations (post-myocardial infarction, stroke, heart failure). Patient support (311 studies), information communication technology (ICT) for health (78 studies), community support (18 studies), supervision (15 studies), and high-intensity training (14 studies) were the most commonly evaluated QI strategies. Other strategies were group problem-solving (7 studies), printed information (5 studies), strengthening infrastructure (4 studies), and financial incentives (3 studies). Patient support, ICT for health, training, and community support were strategies that had been evaluated the most for clinical end points and showed modest associations with several clinical outcomes. The other strategies did not have outcome-driven evaluations reported. Group problem-solving was associated with improved patient self-care and quality of life. Strengthening infrastructure was associated with improved treatment satisfaction. Printed information and financial incentives showed no meaningful effect., Conclusions and Relevance: This systematic review found that substantial variations exist in the types, effectiveness, and implementation of QI strategies for patients with CVD. A comprehensive map of QI strategies created by this study would be useful for researchers to identify where new knowledge is needed to improve cardiovascular outcomes. Outcome-driven evaluations and long-term studies are needed, particularly in low-income settings, to better understand the effects of QI strategies on prevention and control of CVD.

Background: Incarceration has been associated with higher cardiovascular risk, yet data evaluating its association with cardiovascular disease events are limited. The study objective was to evaluate the association between incarceration and incident fatal and non-fatal cardiovascular disease (CVD) events., Methods: Black and white adults from the community-based Coronary Artery Risk Development in Young Adult (CARDIA) study (baseline 1985-86, n = 5105) were followed through August 2017. Self-reported incarceration was measured at baseline (1985-1986) and Year 2 (1987-1988), and fatal and non-fatal cardiovascular disease events, including coronary heart disease, stroke, and heart failure, and all-cause mortality, were captured through 2017. Analyses were completed in September 2019. Cumulative CVD incidence rates and Cox proportional hazards were compared overall by incarceration status. An interaction between incarceration and race was identified, so results were also analyzed by sex-race groups., Results: 351 (6.9%) CARDIA participants reported a history of incarceration. Over 29.0 years mean follow-up, CVD incidence rate was 3.52 per 1000 person-years in participants with a history of incarceration versus 2.12 per 1000 person-years in participants without a history of incarceration (adjusted HR = 1.33 [95% CI, 0.90-1.95]). Among white men, incarceration was associated with higher risk of incident cardiovascular disease (adjusted HR = 3.35 [95% CI, 1.54-7.29) and all-cause mortality (adjusted HR = 2.52 [95% CI, 1.32-4.83]), but these associations were not statistically significant among other sex-race groups after adjustment., Conclusions: Incarceration was associated with incident cardiovascular disease rates, but associations were only significant in one sex-race group after multivariable adjustment.

Background: Consumption of nuts improves cardio-metabolic risk factors in clinical trials and relates to lower risk of cardiovascular disease (CVD) in prospective observational studies. However, there has not been an adequately powered randomized controlled trial to test if nuts supplementation actually reduces incident CVD. In order to establish the feasibility of such a trial, the current study aimed to assess the acceptability and adherence to long-term nut supplementation amongst individuals at high CVD risk in China., Methods: This protocol described a 6-month trial performed in Ningxia Province in China among participants with a history of CVD or older age (female ≥65 years, male ≥60 years) with multiple CVD risk factors. Participants were randomized to control (received non-edible gift), low dose walnut (30 g/d), or high dose walnut (60 g/d) groups in a 1:1:1 ratio. Walnuts were provided at no cost to participants and could be consumed according to personal preferences. Follow-up visits were scheduled at 2 weeks, 3 months and 6 months. The primary outcome was fasting plasma alpha linolenic acid (ALA) levels used as an indicator of walnut consumption. Secondary outcomes included self-reported walnut intake from the 24 h dietary recalls. The target sample size of 210 provided 90% statistical power with two-sided alpha of 0.05 to detect a mean difference of 0.12% (as percent of total fatty acid) in plasma ALA between randomized groups., Results: Two hundred and ten participants were recruited and randomized during October 2019. Mean age of participants was 65 years (SD = 7.3), 47% were females, and 94% had a history of CVD at baseline. Across the three study groups, participants had similar baseline demographic and clinical characteristics., Discussion: This trial will quantify acceptability and adherence to long-term walnut supplementation in a Chinese population at high risk of CVD. The findings will support the design of a future large trial to test the effect of walnut supplementation for CVD prevention., Trial Registration: NCT04037943 Protocol version: v3.0 August 14 2019.

Objective: This study comprehensively estimated the excess cardiovascular disease (CVD) mortality attributable to influenza in an older (age ≥65 years) population., Design: Ecological study., Setting: Aggregated data from administrative systems on CVD mortality, influenza surveillance and meteorological data in Beijing, China., Main Outcome Measure: Excess overall CVD, and separately for ischaemic heart disease (IHD), ischaemic stroke, haemorrhagic stroke mortality attributable to influenza, adjusting for influenza activity, time trend, seasonality and ambient temperature., Results: CVD (risk ratio (RR) 1.02, 95% CI 1.01, 1.02), IHD (RR 1.01, 95% CI 1.01, 1.02), ischaemic stroke (RR=1.03, 95% CI 1.02, 1.04), but not haemorrhagic stroke (RR=1.00, 95% CI 0.99, 1.01) mortality, were significantly associated with every 10% increase in influenza activity. An increase in circulating A(H1N1)09pdm, A(H3N2) and B type virus were all significantly associated with CVD and ischaemic stroke mortality, but only A(H3N2) and B type virus with IHD mortality. The strongest increase in disease mortality was in the same week as the increase in influenza activity. Annual excess CVD mortality rate attributable to influenza ranged from 54 to 96 per 100 000 population. The 3%-6% CVD mortality attributable to influenza activity was related to an annual excess of 916-1640 CVD deaths in Beijing, China., Conclusions: Influenza activity has moderate to strong associations with CVD, IHD and ischaemic stroke mortality in older adults in China. Promoting influenza vaccination could have major health benefit in this population., Background: Influenza may trigger serious CVD events. An estimation of excess CVD mortality attributable to influenza has particular relevance in China where vaccination is low and CVD burden is high., Methods: This study analysed data at the population level (age ≥65 years) using linked aggregated data from administrative systems on CVD mortality, influenza surveillance and meteorological data during 2011 to 2018. Quasi-Poisson regression models were used to estimate the excess overall CVD, and separately for IHD, ischaemic stroke, haemorrhagic stroke mortality attributable to influenza, adjusting for influenza activity, time trend, seasonality and ambient temperature. Analyses were also undertaken for influenza subtypes (A(H1N1)09pdm, A(H3N2) and B viruses), and mortality risk with time lags of 1-5 weeks following influenza activity in the current week., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (hs-CRP) levels are associated with cardiovascular disease (CVD) in the general population, even after adjusting for conventional CVD risk factors. However, data are limited regarding the distribution of Lp(a) and hs-CRP among patients with HIV in Ghana. We explored levels of Lp(a), hs-CRP and other cardiovascular risk factors among people who were HIV positive (HIV+) on ART (HIV+ART+), HIV+ART-, and HIV-ART- in a Ghanaian population., Methods: We conducted a cross sectional study, recruited individuals who were HIV+ART+ and HIV+ART- from the largest HIV clinic in central Ghana between August 2018 and December 2019. HIV negative controls were recruited from communities and adjoining suburbs of Kumasi. Lipoprotein(a) was measured using Immunoturbidimetric assay and high sensitive-CRP concentrations were determined using particle-enhanced turbidimetric assay. We compared levels of Lp(a), hs-CRP, and conventional CVD risk factors among these groups and used multivariable stepwise logistic regression models to explore associations between them., Results: Among HIV+ART+ (n = 156), HIV+ART- (n = 131), and HIV-ART- (n = 147), mean(SD) ages were 48 (9.1) years, 41 (11.1) years and 45 (11.9) years, p = <0.001, proportion of females were 71.2%, 67.9% and 73.5% respectively. Median(IQR) concentrations of hs-CRP in mg/L were 1.7 (0.8,4.5), 2.03 (0.5,8.58) and 1.0 (0.45,2.74) across respective groups and the proportion of elevated Lp(a) concentrations (Lp[a] > 30mg/dL) were 70%, 48% and 62% among HIV+ART+,HIV+ART- and HIV-ART- participants respectively. Diabetes mellitus, dyslipidemia, waist-to-hip ratio and metabolic syndrome were associated with higher hs-CRP levels. Compared to HIV-ART-, HIV+ patients had higher odds of having hs-CRP > 3mg/L while HIV+ART+ patients had higher odds of elevated Lp(a) than HIV+ART- after multivariable adjustment., Conclusion: PLWHA in Ghana are associated with higher odds of elevated hs-CRP, regardless of ART use. HIV+ART+ is significantly associated with higher odds of elevated Lp(a) levels compared to HIV+ART-; even after multivariable adjustments. Reasons for this and potential clinical implications merit further study., Competing Interests: The authors have no competing interest to declare., (Copyright: © 2020 The Author(s).)

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.

Background: Despite improvements in diagnostic and therapeutic interventions to combat cardiovascular disease (CVD) in recent decades, there are significant ongoing access gaps and sex disparities in prevention that have not been adequately quantified in China., Methods: A representative, cross-sectional, community-based survey of adults (aged ≥45 years) was conducted in 7 geographic regions of China between 2014 and 2016. Logistic regression models were used to determine sex differences in primary and secondary CVD prevention, and any interaction by age, education level, and area of residence. Data are presented as adjusted odds ratios (ORs) and 95% CIs., Results: Of 47 841 participants (61.3% women), 5454 (57.2% women) had established CVD and 9532 (70.5% women) had a high estimated 10-year CVD risk (≥10%). Only 48.5% and 48.6% of women and 39.3% and 59.8% of men were on any kind of blood pressure (BP)-lowering medication, lipid-lowering medication, or antiplatelet therapy for primary and secondary prevention, respectively. Women with established CVD were significantly less likely than men to receive BP-lowering medications (OR, 0.79 [95% CI, 0.65-0.95]), lipid-lowering medications (OR, 0.69 [95% CI, 0.56-0.84]), antiplatelets (OR, 0.53 [95% CI, 0.45-0.62]), or any CVD prevention medication (OR, 0.62 [95% CI, 0.52-0.73]). Women with established CVD, however, had better BP control (OR, 1.31 [95% CI, 1.14-1.50]) but less well-controlled low-density lipoprotein cholesterol (OR, 0.66 [95% CI, 0.57-0.76]), and were less likely to smoke (OR, 13.89 [95% CI, 11.24-17.15]) and achieve physical activity targets (OR, 1.92 [95% CI, 1.61-2.29]). Conversely, women with high CVD risk were less likely than men to have their BP, low-density lipoprotein cholesterol, and bodyweight controlled (OR, 0.46 [95% CI, 0.38-0.55]; OR, 0.60 [95% CI, 0.52-0.69]; OR, 0.55 [95% CI, 0.48-0.63], respectively), despite a higher use of BP-lowering medications (OR, 1.21 [95% CI, 1.01-1.45]). Younger patients (<65 years) with established CVD were less likely to be taking CVD preventive medications, but there were no sex differences by area of residence or education level., Conclusions: Large and variable gaps in primary and secondary CVD prevention exist in China, particularly for women. Effective CVD prevention requires an improved overall nationwide strategy and a special emphasis on women with established CVD, who have the greatest disparity and the most to benefit.

Introduction: Depression is associated with increased risk of incident and recurrent cardiovascular disease, while the association between depression and cardiovascular health (CVH) remains unknown. Because the natural course of depression varies widely, different patterns of depression, as well as co-occurring factors such as cigarette smoking, may influence this relationship. We examined potential interactions between longitudinal patterns of depression and smoking with CVH., Methods: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, we modeled trajectories of depression (Center for Epidemiologic Studies Depression scale scores; Years 5, 10, 15, 20) and smoking (cigarettes/day; Years 0, 2, 5, 7, 10, 15, 20). We calculated a modified American Heart Association (AHA) CVH Score (weight, blood glucose, cholesterol, blood pressure, physical activity, and diet; Year 20); higher scores indicate better CVH. Generalized linear models evaluated associations between depression trajectories, smoking trajectories, and their interaction with CVH Score., Results: The depression trajectory x smoking trajectory interaction was not associated with CVH Score, but main effects of depression trajectory (p < .001) and smoking trajectory (p < .001) were observed. Participants with patterns of subthreshold depression (β = -0.26, SE=0.08), increasing depression (β = -0.51 SE = 0.14), and high depression (β = -0.65, SE = 0.32) had lower CVH Scores than those without depression. Compared to never smokers, participants who quit smoking had higher CVH Scores (β = 0.38, SE = 0.11), while participants with the greatest smoking exposure had lower CVH Scores (β = -0.49, SE = 0.22)., Limitations: CVH Scores were adapted from the AHA guidelines based on the available CARDIA data., Conclusions: Deleterious depression and smoking trajectories are independently but not synergistically associated with worse CVH., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cardiovascular disease (CVD) poses a significant cause of morbidity and mortality among people living with human immunodeficiency virus (HIV). However, data are limited on CVD risk burden among HIV patients in Ghana. We describe the age- and sex-adjusted prevalence of CVD risk factors among HIV patients in Ghana., Methods: From January 2013 to May 2014, we identified eligible HIV patients 18 years and older, as well as uninfected adult blood donors presenting to the Komfo Anokye Teaching Hospital as controls. Using a standardized protocol, we collected demographic, clinical, laboratory, and electrocardiographic data. We created multivariable logistic regression models to compare the prevalence of abnormal risk factors between the two groups., Results: We recruited 345 patients with HIV (n = 173 on HAART, n = 172 not on HAART) and 161 uninfected adult blood donors. Patients with HIV were older (mean [SD] age: 41 [11] vs 32 [11] years) and were more likely to be female (72% vs 28%) than blood donors. Among patients on HAART, median (interquartile range) treatment duration was 17 (4-52) months. The prevalence of hypertension, hypercholesterolemia, and diabetes mellitus among HIV patients was 9%, 29%, and 5%, respectively, compared with 5%, 15%, and 0.6% among uninfected blood donors. Smoking was the least prevalent CVD risk factor (1%-2%). After adjustment for age, sex, and body mass index, HIV patients had a 10-fold higher odds of prevalent diabetes compared with controls, (adjusted OR = 10.3 [95% CI: 1.2, 86.7])., Conclusion: CVD risk factors are common among HIV patients in Ghana, demonstrating the urgent need for creation and implementation of strategic CVD interventions., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background Hospital management practices are associated with cardiovascular process of care measures and patient outcomes. However, management practices related to acute cardiac care in India has not been studied. Methods and Results We measured management practices through semistructured, in-person interviews with hospital administrators, physician managers, and nurse managers in Kerala, India between October and November 2017 using the adapted World Management Survey. Trained interviewers independently scored management interview responses (range: 1-5) to capture management practices ranging from performance data tracking to setting targets. We performed univariate regression analyses to assess the relationship between hospital-level factors and management practices. Using Pearson correlation coefficients and mixed-effect logistic regression models, we explored the relationship between management practices and 30-day major adverse cardiovascular events defined as all-cause mortality, reinfarction, stroke, or major bleeding. Ninety managers from 37 hospitals participated. We found suboptimal management practices across 3 management levels (mean [SD]: 2.1 [0.5], 2.0 [0.3], and 1.9 [0.3] for hospital administrators, physician managers, and nurse managers, respectively [ P=0.08]) with lowest scores related to setting organizational targets. Hospitals with existing healthcare quality accreditation, more cardiologists, and private ownership were associated with higher management scores. In our exploratory analysis, higher physician management practice scores related to operation, performance, and target management were correlated with lower 30-day major adverse cardiovascular event. Conclusions Management practices related to acute cardiac care in participating Kerala hospitals were suboptimal but were correlated with clinical outcomes. We identified opportunities to strengthen nonclinical practices to improve patient care.

Objective: The aim of the study was to evaluate associations between 15-year trajectories of co-occurring depressive symptoms and smoking with biomarkers of cardiovascular disease at year 15., Methods: In the Coronary Artery Risk Development in Young Adults study, we modeled trajectories of depressive symptoms (Center for Epidemiologic Studies-Depression scale [CES-D]) and smoking (cigarettes per day [CPD]) among 3614 adults followed from year 0 (ages 18-30 years) through year 15 (ages 33-45 years). Biomarkers of inflammation (high-sensitivity C-reactive protein), oxidative stress (superoxide dismutase, F2-isoprostanes), and endothelial dysfunction (soluble intercellular adhesion molecule 1, soluble P-selectin) were assessed at year 15. We conducted separate linear regression analyses with CES-D trajectory, CPD trajectory, and their interaction with each of the five biomarkers., Results: The sample was 56% women, 47% black, and 40 years old on average at year 15. The CES-D trajectory by CPD trajectory interaction was not associated with any of the biomarkers (all p's > .01). Removing the interaction term, CES-D trajectory was associated with inflammation: higher levels of high-sensitivity C-reactive protein were observed in the subthreshold (β = 0.57, p = .004) and increasing depressive symptoms (β = 1.36, p < .001) trajectories compared with the no depression trajectory. CPD trajectory was associated with oxidative stress and endothelial dysfunction: compared with never smokers, heavy smokers had significantly higher levels of F2-isoprostanes (β = 6.20, p = .001), soluble intercellular adhesion molecule 1 (β = 24.98, p < .001), and soluble P-selectin (β = 2.91, p < .001)., Conclusions: Co-occurring depressive symptoms and smoking do not seem to synergistically convey risk for cardiovascular disease via processes of inflammation, oxidative stress, or endothelial dysfunction. Nonetheless, these results advance our understanding of the complex relationships between modifiable risk factors and chronic disease.

Objective: To evaluate and compare the effect of interventions for improving adherence to medications for atherosclerotic cardiovascular disease (ASCVD) secondary prevention., Methods: We extracted eligible trials from a 2014 Cochrane systematic review on adherence for any condition. We updated the search from CENTRAL, Medline, Embase, PsycINFO, CINAHL, Sociological Abstracts and trial registers through November 2016. Study reports needed to be from a randomised controlled trial, incorporate participants identified as having ASCVD and interventions aimed at improving adherence to medicines for secondary prevention of ASCVD and measure both adherence and a clinical outcome. Two reviewers independently determined the eligibility of studies, extracted data and conducted a narrative synthesis., Results: We identified 17 trials (n=17 448 participants). Most trials had high risk of bias in at least one domain. The intervention group adherence rates ranged from 44%to99% and the comparator group adherence rates ranged from 13% to 96%. Three distinct interventions reported improvements in both adherence and clinical outcomes: short message service (65% vs 13% of participants with high adherence in the intervention vs control group), a fixed-dose combination pill (86% vs 65% adherence, risk ratio of being adherent, 1.33; 95% CI 1.26 to 1.41) and a community health worker-based intervention (97% in the intervention group compared with 92% in the control group; OR=2.62, 95% CI 1.32 to 5.19)., Conclusions: We identified three interventions that demonstrated improvements in adherence and clinical outcomes. Ongoing, longer-term trials will help determine whether short-term changes in adherence can be maintained and lead to differences in clinical events., Competing Interests: Competing interests: MDH receives grant support from the World Heart Federation to serve as its senior program advisor for the Emerging Leaders program, which is sponsored by Boehringer Ingelheim and Novartis with prior support from BUPA and AstraZeneca. MDH has received grant support from the Cochrane Collaboration to complete a systematic review update on fixed-dose combination, or polypills, and travel support from the World Heart Federation to attend a meeting on polypills. PP led several studies on improving adherence for cardiovascular prevention for which his institution has received grants. He is Senior Science Advisor at the World Heart Federation, which is supported, among other funders, by pharmaceutical companies., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

This review describes trends in the burden of cardiovascular diseases (CVDs) and risk factors in India compared with the United States; provides potential explanations for these differences; and describes strategies to improve cardiovascular health behaviors, systems, and policies in India. The prevalence of CVD in India has risen over the past 2 decades due to population growth, aging, and a stable age-adjusted CVD mortality rate. Over the same time period, the United States has experienced an overall decline in age-adjusted CVD mortality, although the trend has begun to plateau. These improvements in CVD mortality in the United States are largely due to favorable population-level risk factor trends, specifically with regard to tobacco use, cholesterol, and blood pressure, although improvements in secondary prevention and acute care have also contributed. To realize similar gains in reducing premature death and disability from CVD, India needs to implement population-level policies while strengthening and integrating its local, regional, and national health systems. Achieving universal health coverage that includes financial risk protection should remain a goal to help all Indians realize their right to health., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The World Health Organization (WHO) Model List of Essential Medicines (EML) is a key tool for improving global access to medicines for all conditions, including cardiovascular diseases (CVDs). The WHO EML is used by member states to determine their national essential medicine lists and policies and to guide procurement of medicines in the public sector. Here, we describe our efforts to modernize the EML for global CVD prevention and control. We review the recent history of applications to add, delete, and change indications for CVD medicines, with the aim of aligning the list with contemporary clinical practice guidelines. We have identified 4 issues that affect decisions for the EML and may strengthen future applications: 1) cost and cost-effectiveness; 2) presence in clinical practice guidelines; 3) feedback loops; and 4) community engagement. We share our lessons to stimulate others in the global CVD community to embark on similar efforts., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Platelet adhesion is mediated by von Willebrand factor (vWF), and disintegrin-like and metalloprotease domain with thrombospondin type-1 motif, number 13 (ADAMTS13) is a protease that cleaves vWF. A change in the balance between vWF and ADAMTS13 in favor of thrombosis might occur shortly before ischemic cardiovascular (CV) events., Objective: To determine whether vWF, ADAMTS13, and the ratio of vWF and ADAMTS13 change during the months preceding an acute CV event., Design: Prospective longitudinal observational study., Setting: Outpatient., Patients: A total of 595 participants with peripheral artery disease (PAD)., Measurements: Blood samples were obtained every 2 months for up to 3 years and hemostatic factors examined at intervals preceding events., Results: Sixty-one participants (cases) experienced events and were matched to 122 PAD controls. During the 2-month interval prior to an event, cases (n = 48) had higher levels of the vWF and ADAMTS13 than controls (n = 95; P = .05), but significance was lost after adjusting for the baseline differences in myocardial infarction, unstable angina, and stroke. During the 10 months prior to an event, median values for vWF and the ratio of vWF and ADAMTS13 were higher in cases than in controls, but the differences were not statistically significant. However, in a subset of 20 patients with complete bimonthly data, there was a trend toward an increase in the ratio in the 10 months prior to a CV event ( P = .04)., Conclusion: In patients with PAD experiencing an ischemic CV event, a significant increase in the ratio of vWF to ADAMTS13 prior to the event could not be confirmed, although there was a weak trend in this direction.

The Million Hearts Initiative has a goal of preventing 1 million heart attacks and strokes-the leading causes of mortality-through several public health and healthcare strategies by 2017. The American Heart Association and American College of Cardiology support the program. The Cardiovascular Risk Reduction Model was developed by Million Hearts and the Center for Medicare & Medicaid Services as a strategy to assess a value-based payment approach toward reduction in 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD) by implementing cardiovascular preventive strategies to manage the "ABCS" (aspirin therapy in appropriate patients, blood pressure control, cholesterol management, and smoking cessation). The purpose of this special report is to describe the development and intended use of the Million Hearts Longitudinal ASCVD Risk Assessment Tool. The Million Hearts Tool reinforces and builds on the "2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk" by allowing clinicians to estimate baseline and updated 10-year ASCVD risk estimates for primary prevention patients adhering to the appropriate ABCS over time, alone or in combination. The tool provides updated risk estimates based on evidence from high-quality systematic reviews and meta-analyses of the ABCS therapies. This novel approach to personalized estimation of benefits from risk-reducing therapies in primary prevention may help target therapies to those in whom they will provide the greatest benefit, and serves as the basis for a Center for Medicare & Medicaid Services program designed to evaluate the Million Hearts Cardiovascular Risk Reduction Model., (© 2016 by the American Heart Association, Inc., and the American College of Cardiology Foundation.)

Background: The current paradigm for cardiovascular disease (CVD) emphasises absolute risk assessment to guide treatment decisions in primary prevention. Although the derivation and validation of multivariable risk assessment tools, or CVD risk scores, have attracted considerable attention, their effect on clinical outcomes is uncertain., Objectives: To assess the effects of evaluating and providing CVD risk scores in adults without prevalent CVD on cardiovascular outcomes, risk factor levels, preventive medication prescribing, and health behaviours., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2016, Issue 2), MEDLINE Ovid (1946 to March week 1 2016), Embase (embase.com) (1974 to 15 March 2016), and Conference Proceedings Citation Index-Science (CPCI-S) (1990 to 15 March 2016). We imposed no language restrictions. We searched clinical trial registers in March 2016 and handsearched reference lists of primary studies to identify additional reports., Selection Criteria: We included randomised and quasi-randomised trials comparing the systematic provision of CVD risk scores by a clinician, healthcare professional, or healthcare system compared with usual care (i.e. no systematic provision of CVD risk scores) in adults without CVD., Data Collection and Analysis: Three review authors independently selected studies, extracted data, and evaluated study quality. We used the Cochrane 'Risk of bias' tool to assess study limitations. The primary outcomes were: CVD events, change in CVD risk factor levels (total cholesterol, systolic blood pressure, and multivariable CVD risk), and adverse events. Secondary outcomes included: lipid-lowering and antihypertensive medication prescribing in higher-risk people. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) or standardised mean differences (SMD) for continuous data using 95% confidence intervals. We used a fixed-effects model when heterogeneity (I²) was at least 50% and a random-effects model for substantial heterogeneity (I² > 50%). We evaluated the quality of evidence using the GRADE framework., Main Results: We identified 41 randomised controlled trials (RCTs) involving 194,035 participants from 6422 reports. We assessed studies as having high or unclear risk of bias across multiple domains. Low-quality evidence evidence suggests that providing CVD risk scores may have little or no effect on CVD events compared with usual care (5.4% versus 5.3%; RR 1.01, 95% confidence interval (CI) 0.95 to 1.08; I² = 25%; 3 trials, N = 99,070). Providing CVD risk scores may reduce CVD risk factor levels by a small amount compared with usual care. Providing CVD risk scores reduced total cholesterol (MD -0.10 mmol/L, 95% CI -0.20 to 0.00; I² = 94%; 12 trials, N = 20,437, low-quality evidence), systolic blood pressure (MD -2.77 mmHg, 95% CI -4.16 to -1.38; I² = 93%; 16 trials, N = 32,954, low-quality evidence), and multivariable CVD risk (SMD -0.21, 95% CI -0.39 to -0.02; I² = 94%; 9 trials, N = 9549, low-quality evidence). Providing CVD risk scores may reduce adverse events compared with usual care, but results were imprecise (1.9% versus 2.7%; RR 0.72, 95% CI 0.49 to 1.04; I² = 0%; 4 trials, N = 4630, low-quality evidence). Compared with usual care, providing CVD risk scores may increase new or intensified lipid-lowering medications (15.7% versus 10.7%; RR 1.47, 95% CI 1.15 to 1.87; I² = 40%; 11 trials, N = 14,175, low-quality evidence) and increase new or increased antihypertensive medications (17.2% versus 11.4%; RR 1.51, 95% CI 1.08 to 2.11; I² = 53%; 8 trials, N = 13,255, low-quality evidence)., Authors' Conclusions: There is uncertainty whether current strategies for providing CVD risk scores affect CVD events. Providing CVD risk scores may slightly reduce CVD risk factor levels and may increase preventive medication prescribing in higher-risk people without evidence of harm. There were multiple study limitations in the identified studies and substantial heterogeneity in the interventions, outcomes, and analyses, so readers should interpret results with caution. New models for implementing and evaluating CVD risk scores in adequately powered studies are needed to define the role of applying CVD risk scores in primary CVD prevention.

Polypills have been approved in more than 30 countries, but worldwide experience with and availability of polypills remain limited, unlike fixed-dose combinations in other diseases such as HIV, tuberculosis, and malaria. In this Series review, we aim to propose a guide for the use of polypills in future research and clinical activities and to synthesise contemporary evidence supporting the use of polypills for prevention of atherosclerosis. Polypill uses can be categorised by population and indication, both of which influence the balance between benefits and risks. Populations include secondary prevention, high-risk primary prevention based on formal risk assessment, and primary prevention based on single risk factor measurement, such as age, also known as mass treatment. For each population, potential indications are initiation, step-up of current drug therapy, and straight substitution of individual drug components. We summarise efficacy and safety results from 13 polypill trials (9059 participants) done in 32 countries. Polypills improve adherence, are generally well tolerated, and reduce risk factor levels, although heterogeneity limits the certainty of the effect on risk factors. Trials published to date have not been designed to detect differences in clinical outcomes, and thus no significant differences between polypill and comparator groups have been reported. Polypill therapy could be one of the most scalable strategies to reduce the risk of premature mortality from atherosclerosis by 25% by 2025 by improving medication adherence and access, but further trial data and clinical experience will be useful to determine how polypills can best be implemented to achieve this goal., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD., Objectives: To determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events. We also sought to determine the effect of fixed-dose combination therapy on blood pressure, lipids, adherence, discontinuation rates, health-related quality of life, and costs., Search Methods: We updated our previous searches in September 2016 of CENTRAL, MEDLINE, Embase, ISI Web of Science, and DARE, HTA, and HEED. We also searched two clinical trials registers in September 2016. We used no language restrictions., Selection Criteria: We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure-lowering and one lipid-lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults 18 years old or older, with no restrictions on presence or absence of pre-existing ASCVD., Data Collection and Analysis: Three review authors independently selected studies for inclusion and extracted the data for this update. We evaluated risk of bias using the Cochrane 'Risk of bias' assessment tool. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I 2 < 50%) and random-effects models when heterogeneity was high (I 2 ≥ 50%). We used the GRADE approach to evaluate the quality of evidence., Main Results: In the initial review, we identified nine randomised controlled trials with a total of 7047 participants and four additional trials (n = 2012 participants; mean age range 62 to 63 years; 30% to 37% women) were included in this update. Eight of the 13 trials evaluated the effects of fixed-dose combination (FDC) therapy in populations without prevalent ASCVD, and the median follow-up ranged from six weeks to 23 months. More recent trials were generally larger with longer follow-up and lower risk of bias. The main risk of bias was related to lack of blinding of participants and personnel, which was inherent to the intervention. Compared with the comparator groups (placebo, usual care, or active drug comparator), the effects of the fixed-dose combination treatment on mortality (FDC = 1.0% versus control = 1.0%, RR 1.10, 95% CI 0.64 to 1.89,  I 2 = 0%, 5 studies, N = 5300) and fatal and non-fatal ASCVD events (FDC = 4.7% versus control = 3.7%, RR 1.26, 95% CI 0.95 to 1.66, I 2 = 0%, 6 studies, N = 4517) were uncertain (low-quality evidence). The low event rates for these outcomes and indirectness of evidence for comparing fixed-dose combination to usual care versus individual drugs suggest that these results should be viewed with caution. Adverse events were common in both the intervention (32%) and comparator (27%) groups, with participants randomised to fixed-dose combination therapy being 16% (RR 1.16, 95% CI 1.09 to 1.25, 11 studies, 6906 participants, moderate-quality evidence) more likely to report an adverse event . The mean differences in systolic blood pressure between the intervention and control arms was -6.34 mmHg (95% CI -9.03 to -3.64, 13 trials, 7638 participants, moderate-quality evidence). The mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.61 mmol/L (95% CI -0.88 to -0.35, 11 trials, 6565 participants, low-quality evidence) and -0.70 mmol/L (95% CI -0.98 to -0.41, 12 trials, 7153 participants, moderate-quality evidence), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I 2 ≥ 80% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multidrug strategy by 44% (26% to 65%) compared with usual care (4 trials, 3835 participants, moderate-quality evidence)., Authors' Conclusions: The effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain. A limited number of trials reported these outcomes, and the included trials were primarily designed to observe changes in ASCVD risk factor levels rather than clinical events, which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, active comparator, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing, longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes.

The purpose of this review is to emphasize the role of tobacco prevention and control in cardiovascular health (CVH) promotion and cardiovascular disease (CVD) prevention, including the importance of these endpoints for measuring the full impact of tobacco-related policies, programs, and practices. In this review, we describe an overview of tobacco control interventions that have led to substantial declines in tobacco use and the relationship between these declines with CVH and CVD. We review interventions that have had success in high-income countries (HICs) as well as those that are gaining traction in low- and middle-income countries (LMICs). We emphasize the challenges to comprehensive tobacco prevention and control strategies faced by LMICs, and highlight the special role of cardiovascular health professionals in achieving CVH promotion and CVD prevention endpoints through tobacco control. Tobacco prevention and control strategies have a strong scientific basis, yet a distinct gap remains between this evidence and implementation of tobacco control policies, particularly in LMICs. Health professionals can contribute to tobacco control efforts, especially through patient-level clinical interventions, when supported by a health care system and government that recognize and support tobacco control as a critical strategy for CVH promotion and CVD prevention. Understanding, supporting, and applying current and evolving policies, programs, and practices in tobacco prevention and control is the province of all health professionals, especially those concerned with CVH promotion and CVD prevention. A new tobacco control roadmap from the World Heart Federation provides a strong impetus to the needed interdisciplinary collaboration., Competing Interests: statement We do not have any financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation. DRL and MDH receive grant support from the World Heart Federation to serve as a consultant and the senior program advisor, respectively, for the World Heart Federation’s Emerging Leaders program, which is supported by Boehringer Ingelheim and Bupa. BH has served on a scientific advisory board for Pfizer and receives study medication and placebo free of charge from Pfizer for use in ongoing National Institutes of Health funded clinical trials., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The Wellcome Trust, the World Health Organization, and cardiologists have advocated for the idea of a "polypill" containing multiple cardiovascular drugs to be co-formulated into a single pill for over a decade. Some cardiologists have asserted that the drugs commonly considered for inclusion into such a polypill are older and therefore free of patent protection. We tested this assertion. This project was requested by the World Heart Federation (WHF)., Methods, Data and Materials: Two cardiologists from the WHF provided a list of 48 cardiovascular drugs for evaluation. We designated the United States and Canada as the base jurisdictions for this patent study. We linked patent data from these countries' national medicine patent registers to patent information in over 96 other countries using Derwent and INPADOC via Thomson Innovation. We expanded our study beyond the aforementioned data linkage through a systematic search of the World Intellectual Property Organization's PatentScope, which was based primarily upon the drugs' active ingredient names., Results: In the United States and Canada, eight of the drugs were only available in the patent-protected, brand name formulation in one or both countries. Another 21 drugs had relevant patents, but generic equivalents were nevertheless available. Only 19 drugs (40 %) appeared entirely post-patent. Broadening the co-formulation searches globally, the overwhelming majority of drugs (40/48) were mentioned in patent applications for cardiovascular drug combinations., Conclusion: The assertion that most of these cardiovascular drugs are post-patent is accurate, but only in the sense that many of the original patents on these active ingredients have expired and that generic alternatives are usually available. The landscape of patents covering novel (co-) formulations is far more complex, however. Most research and development for cardiovascular combination medicines are likely to be undertaken by companies whose original patents on the active ingredient will soon expire or have recently expired. Cardiologists looking to accelerate polypill development may consider approaching such companies to partner.

In 2011, the United Nations set key targets to reach by 2025 to reduce the risk of premature noncommunicable disease death by 25% by 2025. With cardiovascular disease being the largest contributor to global mortality, accounting for nearly half of the 36 million annual noncommunicable disease deaths, achieving the 2025 goal requires that cardiovascular disease and its risk factors be aggressively addressed. The Global Cardiovascular Disease Taskforce, comprising the World Heart Federation, American Heart Association, American College of Cardiology Foundation, European Heart Network, and European Society of Cardiology, with expanded representation from Asia, Africa, and Latin America, along with global cardiovascular disease experts, disseminates information and approaches to reach the United Nations 2025 targets. The writing committee, which reflects Global Cardiovascular Disease Taskforce membership, engaged the Institute for Health Metrics and Evaluation, University of Washington, to develop region-specific estimates of premature cardiovascular mortality in 2025 based on various scenarios. Results show that >5 million premature CVD deaths among men and 2.8 million among women are projected worldwide by 2025, which can be reduced to 3.5 million and 2.2 million, respectively, if risk factor targets for blood pressure, tobacco use, diabetes mellitus, and obesity are achieved. However, global risk factor targets have various effects, depending on region. For most regions, United Nations targets for reducing systolic blood pressure and tobacco use have more substantial effects on future scenarios compared with maintaining current levels of body mass index and fasting plasma glucose. However, preventing increases in body mass index has the largest effect in some high-income countries. An approach achieving reductions in multiple risk factors has the largest impact for almost all regions. Achieving these goals can be accomplished only if countries set priorities, implement cost-effective population wide strategies, and collaborate in public-private partnerships across multiple sectors., (© 2016 American Heart Association, Inc.)

Importance: The Million Hearts initiative emphasizes ABCS (aspirin for high-risk patients, blood pressure [BP] control, cholesterol level management, and smoking cessation). Evidence of the effects of drugs used to achieve ABCS has not been synthesized comprehensively in the prevention of primary atherosclerotic cardiovascular disease (ASCVD)., Objective: To compare the efficacy and safety of aspirin, BP-lowering therapy, statins, and tobacco cessation drugs for fatal and nonfatal ASCVD outcomes in primary ASCVD prevention., Evidence Review: Structured search of the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), MEDLINE, EMBASE, and PROSPERO International Prospective Systematic Review Trial Register to identify systematic reviews published from January 1, 2005, to June 17, 2015, that reported the effect of aspirin, BP-lowering therapy, statin, or tobacco cessation drugs on ASCVD events in individuals without prevalent ASCVD. Additional studies were identified by searching the reference lists of included systematic reviews, meta-analyses, and health technology assessment reports. Reviews were selected according to predefined criteria and appraised for methodologic quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool (range, 0-11). Studies were independently reviewed for key participant and intervention characteristics. Outcomes that were meta-analyzed in each included review were extracted. Qualitative synthesis was performed, and data were analyzed from July 2 to August 13, 2015., Findings: From a total of 1967 reports, 35 systematic reviews of randomized clinical trials were identified, including 15 reviews of aspirin, 4 reviews of BP-lowering therapy, 12 reviews of statins, and 4 reviews of tobacco cessation drugs. Methodologic quality varied, but 30 reviews had AMSTAR ratings of 5 or higher. Compared with placebo, aspirin (relative risk [RR], 0.90; 95% CI, 0.85-0.96) and statins (RR, 0.75; 95% CI, 0.70-0.81) reduced the risk for ASCVD. Compared with placebo, BP-lowering therapy reduced the risk for coronary heart disease (RR, 0.84; 95% CI, 0.79-0.90) and stroke (RR, 0.64; 95% CI, 0.56-0.73). Tobacco cessation drugs increased the odds of continued abstinence at 6 months (odds ratio range, 1.82 [95% CI, 1.60-2.06] to 2.88 [95% CI, 2.40-3.47]), but the direct effects on ASCVD were poorly reported. Aspirin increased the risk for major bleeding (RR, 1.54; 95% CI, 1.30-1.82), and statins did not increase overall risk for adverse effects (RR, 1.00; 95% CI, 0.97-1.03). Adverse effects of BP-lowering therapy and tobacco cessation drugs were poorly reported., Conclusions and Relevance: This overview demonstrates high-quality evidence to support aspirin, BP-lowering therapy, and statins for primary ASCVD prevention and tobacco cessation drugs for smoking cessation. Treatment effects of each drug can be used to enrich discussions between health care professionals and patients in primary ASCVD prevention., Competing Interests: Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.