In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting–enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes.

This two-part article provides an overview of the global burden of atherothrombotic cardiovascular disease. Part I initially discusses the epidemiologic transition which has resulted in a decrease in deaths in childhood due to infections, with a concomitant increase in cardiovascular and other chronic diseases; and then provides estimates of the burden of cardiovascular (CV) diseases with specific focus on the developing countries. Next, we summarize key information on risk factors for cardiovascular disease (CVD) and indicate that their importance may have been underestimated. Then, we describe overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization. Part II of this article describes the burden of CV disease by specific region or ethnic group, the risk factors of importance, and possible strategies for prevention.

Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. Full funding sources are listed at the end of the paper (see Acknowledgments).