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Gender differences and disparities in all-cause and coronary heart disease mortality: Epidemiological aspects

https://doi.org/10.1016/j.beem.2013.05.013Get rights and content

This overview is primarily concerned with large recent prospective cohort studies of adult populations, not patients, because the latter studies are confounded by differences in medical and surgical management for men vs. women. When early papers are uniquely informative they are also included. Because the focus is on epidemiology, details of age, sex, sample size, and source as well as study methods are provided. Usually the primary outcomes were all-cause or coronary heart disease (CHD) mortality using baseline data from midlife or older adults.

Fifty years ago few prospective cohort studies of all-cause or CHD mortality included women. Most epidemiologic studies that included community-dwelling adults did not include both sexes and still do not report men and women separately. Few studies consider both sex (biology) and gender (behavior and environment) differences. Lifespan studies describing survival after live birth are not considered here. The important effects of prenatal and early childhood biologic and behavioral factors on adult mortality are beyond the scope of this review. Clinical trials are not discussed.

Overall, presumptive evidence for causality was equivalent for psychosocial and biological exposures, and these attributes were often associated with each other. Inconsistencies or gaps were particularly obvious for studies of sex or gender differences in age and optimal measures of body size for CHD outcomes, and in the striking interface of diabetes and people with the metabolic syndrome, most of whom have unrecognized diabetes.

Introduction

The main reason for increased longevity is reduced mortality from birth to adolescence. This is still true, as reported by Wang and colleagues [1] in the largest study of sex-specific trends in mortality between 1970 and 2010. Their study of 187 countries compares mortality in children age 5 or less with mortality in adults, age 15–99 years. Since 1970, global deaths in children declined by almost 60%. During a 20-year interval male life expectancy at birth increased from 56.4 years to 67.5 years, and female life expectancy at birth increased from 61.2 years to 73.3 years. This paper is concerned with mortality and CHD in this growing number of surviving adults.

As reviewed elsewhere [2], in 1900, only 4% of the U.S. population was aged 65 and older; by 2000 that proportion had tripled (12.4%), and is expected to be 20% by 2030. Resnick [3] calculated that more than half of all people who have ever lived to age 65 are alive now. The fastest growing segment of the U.S. adult population is now age 80 and older, with almost 20 million projected for 2030. The proportion of persons who survive to age 90 years is increasing dramatically over the past century in both sexes, but women still live longer than men in every Westernized birth cohort [4].

Section snippets

Coronary heart disease

As the population ages, there is increasing interest in biologic and behavioral factors associated with survival and cardiovascular disease. The most consistent sex differences in adult mortality are attributed to coronary heart disease (CHD), which is the most common vascular condition with consistently greater mortality rates and risks in men than women. Fig. 1 shows remarkably similar male to female CHD mortality ratios (2.5–4.5) in adults in 52 countries, despite very different sex specific

Heart disease risk factors

In general, men and women have the same heart disease risk factors, but men tend to have less favorable levels of these risk factors than women. For example, men in the Edinburgh Heart Study [10] had significantly (P < 0.001) less favorable patterns of cigarette smoking, dietary fiber, vitamin C, blood viscosity, uric acid, HDL cholesterol, and triglycerides than women. Only three cardio-protective factors were significantly more favorable in men than women: men reported more physical activity

Ethnicity and race

Over the past century, both men and women experienced tremendous if uneven increases in life expectancy at birth, as extensively reviewed by Rogers and colleagues [13] using data from the NHANES III Linked Mortality File – a nationally representative sample of the U.S. population in which both non-Hispanic blacks and Mexican Americans were oversampled. NHANES III participants age 20 or older at the time of the baseline evaluation were matched for mortality using record linkage to the U.S.

More psychosocial factors

Traditional (Framingham) risk factors – smoking, high blood pressure, and high cholesterol – do not fully explain the excess burden of cardiovascular diseases (CVD) in the population. In 2008, Everson-Rose and Lewis [15] elegantly reviewed the extensive literature on important psychosocial domains (negative emotional states—depression or depressive symptoms, anger and hostility, anxiety; chronic psychosocial stressors, including occupation or work-related stress, acute life stress; and social

Job stress

Kivimaki and colleagues [18] specifically addressed the importance of high psychological work demands versus low control on CHD risk, and whether any effect differs by sex. Individual data from the Individual Participant Data Meta-Analysis for the Working Populations Consortium, established in 2008, included published and unpublished data from13 European and Scandinavian cohorts with more than 197,000 participants (49% women). Job strain was defined using standard questionnaires. Information

Physical activity

Large long prospective studies of physical activity are challenging to conduct and interpret because few large cohorts used noninvasive methods to validate or quantitate physical function and exercise, and most questions were about male sports. The EPIC-Norfolk cohort study designed and tested a new four-part physical activity questionnaire, asking about 1) work-related physical activity; 2) leisure physical activity including house work; 3) amount of energy expended during exercise based on

Obesity

In the 1960s there was limited evidence that overweight or obesity was a heart disease risk factor. The Men's Pooling Project cohorts (12,381 men age 40–64 years), studied in the 1960s and 1970s and followed for 4.9–9.6 years for CHD, showed very different patterns and standardized incidence ratios for first major coronary events as shown in Fig. 6 [21]. These different patterns were not paralleled by cohort differences in the distribution of marked obesity, cigarette smoking, systolic blood

Central obesity

Although upper body or central obesity was clinically recognized as “male pattern obesity” for years before the diabetes epidemic, it was not commonly used to evaluate sex differences in large prospective studies of mortality or cardiovascular disease. The Rotterdam Study, one of the first large prospective population-based studies, included 6296 men and women from the Netherlands (baseline age 55–102 years) who were followed for an average of 5.4 years [25]. Because smoking is a major risk

Diet and lifestyle risk factors for weight gain

In order to identify specific lifestyle and dietary factors associated with long-term weight gain, and to evaluate the association between changes in lifestyle and weight change at 4-year intervals, Mozaffarian and colleagues [29] prospectively studied three separate published cohort studies that included 120,877 United States women and men free of chronic diseases and not obese at baseline. Cohort-specific and sex-specific results were similar and were pooled in their meta-analysis. Four-year

Smoking

The prevalence of smoking in the United States peaked around 1960 for men and 1980 for women. A substantial number quit smoking since then, allowing studies of the effects of smoking cessation on mortality. Jha and colleagues [35] reported smoking and smoking cessation history between 1997 and 2004 for 113,752 women and 88,496 men aged 25–79 years of age, using data from a representative sample of the U.S. population who were interviewed by telephone using the National Health Interview Survey

Alcohol

For many years population-based studies showed that moderate alcohol intake was associated with reduced cardiovascular mortality, with little attention to social circumstances. An interesting analysis from the Male Health Professionals Study [36] reported the protective association of alcohol consumption for the risk of myocardial infarction among 38,077 men who were free of known heart disease and cancer at baseline and had completed the Willett Harvard food frequency questionnaire at baseline

Multiple healthy behaviors

The first prospective population-based U.S. cohort study of multiple behaviors and sex-specific all-cause mortality was published in 2011 [38]. The cohort included 17,069 participants age 17 and older from the NHANES Survey III Mortality Study (1998–2006 evaluation) whose vital status was confirmed and whose underlying cause of death was ascertained using public use files. Four low-risk behaviors (never smoked, healthy diet, adequate physical activity, and moderate alcohol intake) were analyzed

Kidney disease

Although chronic renal disease affects at least 10% of the U.S. adult population and is a major cause of morbidity and mortality world-wide, few studies have reported kidney-related sex differences in mortality. A recent meta-analysis [39] from the NIH Chronic Kidney Disease Collaboration obtained individual data from 46 cohorts, including more than 2 million men and women age 18 and older from Europe, North America, South America, Asia, and Australasia. Except for participants with chronic

Diabetes

Gregg and colleagues [40] used data from four waves of National Health Interview Surveys telephone interviews (1997–8, 1999–2000, 2001–2002, 2003–2004; 50% women) to determine whether CVD mortality changed among U.S. adults age 18 and older who did or did not self-report diabetes. Between the earliest and latest waves the overall CVD death rate declined by 40% and the all-cause mortality rate declined by 23%. There was a greater decline (P = 0.02 test for interaction) among diabetic men (5.2

Testosterone

The epidemiology of plasma testosterone levels in adult men is complicated by long recognized associations with age, obesity, alcohol, and health, as elegantly described in a 1981 publication by Dai and colleagues [50]. The authors conducted three pilot studies to evaluate the reliability and repeatability of a single morning sample, and concluded that a single plasma testosterone level was sufficiently consistent to be used for epidemiologic studies, although others (cited in their review)

Summary

This paper reviews mostly recent large population-based prospective cohort studies of sex and gender differences in psychosocial and environmental exposures and in established biological risk factors for all-cause and CHD mortality in adults. Although more studies now include women, surprisingly few provide analyses stratified by sex. Overall, presumptive evidence for causality was equivalent for psychosocial and biological exposures, and these attributes were often associated with each other.

Acknowledgments

Elizabeth Barrett-Connor is Principle Investigator of The Rancho Bernardo Study, which was funded by research grants AG07181 and AG028507 from the National Institute on Aging, and grant DK31801 from the National Institute of Diabetes and Digestive and Kidney Diseases.

References (57)

  • E. Barrett-Connor

    Sex differences in coronary heart disease. Why are women so superior? The 1995 Ancel Keys Lecture

    Circulation

    (1997)
  • H. Hemingway et al.

    Prevalence of angina in women versus men: a systematic review and meta-analysis of international variations across 31 countries

    Circulation

    (2008)
  • R.H. Furman

    Are gonadal hormones (estrogens and androgens) of significance in the development of ischemic heart disease?

    Annals of the New York Academy of Sciences

    (1968)
  • D. Vaidya et al.

    Ageing, menopause, and ischaemic heart disease mortality in England, Wales, and the United States: modelling study of national mortality data

    British Medical Journal

    (2011)
  • F.G. Fowkes et al.

    Sex differences in susceptibility to etiologic factors for peripheral atherosclerosis. Importance of plasma fibrinogen and blood viscosity

    Arteriosclerosis Thrombosis

    (1994)
  • D.L. Wingard et al.

    The sex differential in mortality from all causes and ischemic heart disease

    American Journal of Epidemiology

    (1983)
  • R.G. Rogers et al.

    Social, behavioral, and biological factors, and sex differences in mortality

    Demography

    (2010)
  • M.M. Safford et al.

    Association of race and sex with risk of incident acute coronary heart disease events

    Journal of the American Medical Association

    (2012)
  • S.A. Everson-Rose et al.

    Psychosocial factors and cardiovascular diseases

    Annual Review of Public Health

    (2005)
  • A. Nicholson et al.

    Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies

    European Heart Journal

    (2006)
  • A. Case et al.

    Sex differences in morbidity and mortality

    Demography

    (2005)
  • T. Chandola et al.

    Work stress and coronary heart disease: what are the mechanisms?

    European Heart Journal

    (2008)
  • L.N. Broekhuizen et al.

    Physical activity, metabolic syndrome, and coronary risk: the EPIC-Norfolk prospective population study

    European Journal of Cardiovascular Prevention Rehabiliation

    (2011)
  • E.L. Barrett-Connor

    Obesity, atherosclerosis, and coronary artery disease

    Annals of Internal Medicine

    (1985)
  • A. Peeters et al.

    Is the health burden associated with obesity changing?

    American Journal of Epidemiology

    (2012)
  • K.M. Flegal et al.

    Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis

    Journal of the American Medical Association

    (2013)
  • T.L. Visscher et al.

    A comparison of body mass index, waist-hip ratio and waist circumference as predictors of all-cause mortality among the elderly: the Rotterdam study

    International Journal of Obesity and Related Metabolic Disorders

    (2001)
  • T. Pischon et al.

    General and abdominal adiposity and risk of death in Europe

    The New England Journal of Medicine

    (2008)
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