Variations between women and men in risk factors, treatments, cardiovascular disease incidence, and death in 27 high-income, middle-income, and low-income countries (PURE): a prospective cohort study

Summary

Background

Some studies, mainly from high-income countries (HICs), report that women receive less care (investigations and treatments) for cardiovascular disease than do men and might have a higher risk of death. However, very few studies systematically report risk factors, use of primary or secondary prevention medications, incidence of cardiovascular disease, or death in populations drawn from the community. Given that most cardiovascular disease occurs in low-income and middle-income countries (LMICs), there is a need for comprehensive information comparing treatments and outcomes between women and men in HICs, middle-income countries, and low-income countries from community-based population studies.

Methods

In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35–70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death.

Findings

From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5–10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0–4·2] for women vs 6·4 [6·2–6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72–0·79]) and all-cause death (4·5 [95% CI 4·4–4·7] for women vs 7·4 [7·2–7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60–0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2–21·7] versus 27·7 [95% CI 25·6–29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p<0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease.

Interpretation

Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men.

Funding

Full funding sources are listed at the end of the paper (see Acknowledgments).

Introduction

Over the past two decades, substantial efforts have been made to improve the cardiovascular health of women under the assumption that women with cardiovascular disease are managed less aggressively than men. Several campaigns, coalitions, and programmes1, 2 have been initiated to improve awareness, advocacy, and research related to reducing the cardiovascular disease burden and to implement delivery care models and guidelines3, 4 that are specific to women. Despite these efforts, reported differences in the cardiovascular disease burden, management, and outcomes between women and men remain. Although some studies report that women have lower age-standardised cardiovascular disease incidence, prevalence, and death rates than men,5, 6 there are also reports that women with cardiovascular disease receive less care,7, 8, 9 fewer investigations,7, 8, 9 and have poorer outcomes9, 10 after a coronary event. These reports have led to renewed calls for intensified efforts to improve care for women.1, 2, 11 To date, a comprehensive report of cardiovascular disease risk factor burden, management, and outcomes in women and men with and without a history of cardiovascular disease drawn from a community-based population sample is not available. Such community-based studies are crucial because hospital registries, data from outpatient clinics, and administrative databases do not provide information on primary prevention strategies nor do they include information regarding cardiovascular events and deaths before hospitalisation. Moreover, studies on cardiovascular disease differences between women and men are mainly from high-income countries (HICs)—largely from North America and western Europe—with little data from other regions or low-income and middle-income countries (LMICs). Because the majority of cardiovascular disease deaths now occur in LMICs,¹² it is important to examine the differences between women and men regarding disease prevention, treatment, incidence, and related deaths globally.

Research in context

Evidence before this study

We searched the MEDLINE database, without language or publication date restrictions, for estimates of differences between women and men in cardiovascular disease risk factors, incidence, deaths, and use of treatments on Sept 15, 2019, and again on Nov 30, 2019. Our search terms were “gender” OR “sex” OR “women” AND “cardiovascular” OR “coronary heart disease” OR “coronary artery disease” OR “risk factor” OR “revascularization” OR “percutaneous coronary intervention” OR “coronary artery bypass grafting” OR “primary prevention” OR “statin” OR “secondary prevention”.

Studies have emphasised that women are less likely to undergo revascularisation procedures and receive fewer guideline recommended therapies than men upon having a cardiovascular disease event. These findings, when viewed in isolation, have raised concerns that women are disadvantaged when it comes to cardiovascular disease care. However, much of the existing evidence was from North America and Europe, and most of the published literature are based on hospital registries, outpatient clinics, or administrative databases. We did not find any comprehensive report on differences between women and men in risk factors, management, and outcomes in those with and without a history of cardiovascular disease drawn from community-based populations.

Added value of this study

We systematically examine differences in risk factors, treatments, cardiovascular disease incidence, and mortality in a large population with and without previous cardiovascular disease between women and men from high-income, middle-income, and low-income countries. Our findings indicate that the cardiovascular disease risk factor burden is lower in women; this is consistent across countries at all economic levels and geographical regions. Moreover, primary prevention strategies are used more frequently in women than in men, and are accompanied by lower incidence of cardiovascular disease and mortality. By contrast, use of secondary prevention treatments, cardiac investigations, and coronary interventions, are less frequent in women than in men, but are not associated with a higher rate of recurrent cardiovascular disease or death in women over a median follow-up time of 9·5 (IQR 8·5–10·9) years. The differences in treatments and in outcomes in both women and men from low-income and middle-income countries compared with high-income countries are much larger than the differences between sexes globally or within groups of countries.

Implications of all the available evidence

Although there are contrasting patterns in the differences in treatment rates between women and men in those with and without previous cardiovascular disease, our data indicate that women do not have worse cardiovascular disease outcomes compared with men. The differences in cardiovascular disease incidence, death, and use of treatments in both women and men between high-income compared with low-income and middle-income countries, and North America and Europe versus other regions is much larger. Understanding and narrowing these gaps deserve greater attention.

The aims of this Article are to describe differences between women and men from all countries and separately in those from HICs, middle-income countries (MICs), and low-income countries (LICs). Moreover, women and men will be compared by regions with regard to the burden of cardiovascular disease risk factors; the incidence of major cardiovascular disease (cardiovascular deaths, myocardial infarction, strokes, heart failure, and other major cardiovascular disease events) and all-cause death; case-fatality rates after an incident cardiovascular disease event; the use of preventive medicines, risk factor control, and healthy lifestyle behaviours in those with and without a history of cardiovascular disease; and differences in the rates of cardiac investigations, revascularisation procedures, and recurrent cardiovascular disease events in those with coronary artery disease over the 9·5 year follow-up.