Lancet Women and CVD Commission: Reducing the global burden by 2030
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Despite advances in the prevention and treatment of CVD, it remains the leading cause of death in women and men worldwide. Additionally, the absolute burden of CVD mortality in the U.S. is higher in women than in men.
The underlying reasons for the observed health disparity between men and women are complex and reflect disparities in risk factor awareness, prevention and optimal medical treatment.
There has been an increasing focus on developing a sex-based approach to asking complex scientific questions that have led to an improved understanding of the underlying differences in the pathobiology of atherosclerotic vascular disease. American Heart Association scientific statements have highlighted the existence of important sex-based differences along the CV clinical spectrum.
The Lancet recently commissioned an international team of experts composed of 17 leading experts from 11 different countries to provide a global assessment of the inequities in CVD care in women and provide focused recommendations for improvement to decrease CVD inequities in prevention, diagnosis and treatment to reduce the global burden of CVD in women by 2030. What follows is a discussion of those key messages.
Accurate data on global prevalence and outcomes of CVD in women are absent
Understanding the current distribution and prevalence of global health depends on the accuracy and frequency of data available. Much of The Lancet article was based on data from the Global Burden of Disease (GBD) study, which is useful but incomplete in countries with inconsistent censuses and registration systems.
Moreover, the GBD does not report sex-specific risk factors that are important to gain a deeper understanding of CVD risk in women. For example, there are limited methods to ascertain a history of early menopause, preterm delivery or hypertensive disorders of pregnancy for women worldwide, which are important risk factors for elevated CVD risk. The commission recommends direct funding for real-time and accurate data collection on prevalence and outcomes of CVD in women globally.
Women with CVD remain understudied, underrecognized, underdiagnosed and undertreated
Within the past decade, data emerged that highlighted important sex-based differences in the pathophysiology, clinical presentation and clinical outcomes of CVD. Female patients are underrepresented in CVD research from diagnosis to treatment research. This results in women generally comprising only 20% of enrolled patients, even though women represent 40% to 50% of participants in longitudinal studies.
Unique sex-based clinical presentations among patients with ACS are also increasingly evident. For example, women more often present with angina equivalents such as dyspnea, weakness, fatigue and indigestion, which have downstream effects, including worse in-hospital mortality. The commission recommends developing educational programs on CVD in women for physicians, scientists, allied health care providers and laypersons.
Sex-specific mechanisms in the pathophysiology and natural history of CVD remain poorly understood
As recent data have revealed sex and gender differences in clinical presentation and outcomes of CVD, there has been increasing research on the sex-based differences affected by social, environmental and community factors. However, there are also physiologic variances between men and women that have been hypothesized to contribute to differences in CVD onset, susceptibility, prevalence and treatment responses.
Understanding sex-specific biological mechanisms of CVD in women will aid in early detection and targeted management of these diseases. The commission recommends a partnership between not only clinicians and researchers but also policymakers to improve the study of sex-specific mechanisms of CVD that focus on pathophysiology and the natural history of CVD.
Women are underrepresented in most CV clinical trials
There have been well-documented sex and gender differences in CVD pathophysiology, clinical presentation and outcomes prompting the NIH to mandate the inclusion of both men and women in clinical studies and, when the studied health condition affects both sexes, to analyze data by sex. Despite this mandate, women remain the minority of research subjects but the majority of persons dying of CVD.
Underrepresentation of women in these trials have led to uncertainty about the generalizability of CVD research, since women have unique physiology, and their responses to therapeutic interventions sometimes differ from men. For example, the recent PARAGON-HF trial was able to show a greater risk reduction of HF exacerbations in female participants than in male participants, likely because most participants were women. The authors of this commission recommend developing strategies to improve enrollment and retention of women in clinical trials.
Socioeconomic deprivation contributes substantially to the global burden of CVD in women
Women are more likely than men to be subject to the downstream impacts of socioeconomic issues and political conflicts. Women living in countries with a low sociodemographic index have a higher age-adjusted mortality than men.
Socioeconomic deprivation causes many factors that contribute to increased CVD risk, such as poor health literacy, increased fast or processed food intake, chronic stress and depression, intimate partner violence and premature menopause. The commission recommends prioritizing funding in global health organizations for CVD health programs in women from socioeconomic deprived regions.
MI and CVD mortality are increasing in young women
Although stringent risk factor modification and early recognition of CVD for aggressive secondary prevention have led to a significant reduction in overall CVD mortality over recent decades, alarmingly, the CVD mortality rates are rising in younger women (35 to 54 years). This trend was the target of investigation in the VIRGO study; it found that women aged 15 to 55 years with an acute MI were less likely than men to be told they were at risk or have a provider discuss risk modification.
The reasons for the rise in acute MI mortality is likely multifactorial, including misconceptions that CVD affects mainly men and under-recognition of CVD presentations in some women. Additionally, CVD risk estimation may be more challenging in young and middle-aged women, as validity is limited by small sample size. The commission recommends educating health care providers and patients regarding early detection and prevention in CVD.
Hypertension, dyslipidemia and diabetes are the most crucial risk factors contributing to CVD death in women
Some traditional risk factors of CVD may be more potent risk factors in women and portend increased mortality risk in women as well. The INTERHEART study found hypertension and diabetes were associated with a greater OR of CVD in women compared with men. Moreover, the ratios of apolipoprotein B to apolipoprotein A-I and of total cholesterol to HDL conferred a greater risk for acute MI in women.
Management of these disorders is challenging due to the sex-specific mechanisms contributing to the varying consequences of these diseases and the reason for underuse of statins in women. The commission article recommends establishing policy-based initiatives and medical and community-outreach CVD risk factor programs in settings frequented by women.
Sex-specific and other under-recognized risk factors, such as psychosocial and socioeconomic factors, contribute to the global burden of CVD in women
Women are usually affected by CVD about 10 years after men, which has been attributed in part to the protective effect of estrogen during reproductive years. However, there are an increasing number of under-recognized risk factors in women that have been associated with increased, and occasionally early-onset, CVD risk, including pregnancy-associated diseases such as preeclampsia and gestational diabetes.
Even though a prior diagnosis of preeclampsia has been associated with almost a fourfold increase in future incident HF, and twofold increased risk for CHD, many physicians do not include these pregnancy history and pregnancy-associated diseases in risk factor assessments, and low-income patients may have limited access to treatment of these issues.
Women are also disproportionally affected by systemic autoimmune diseases, which are associated with acceleration of atherosclerotic disease. Most deaths within patients with autoimmune disease are related to CVD, which is thought to be due to the chronic inflammatory effects accelerating atherosclerosis and chronic steroid therapy resulting in hyperglycemia and hypercholesterolemia. Increased coordination between rheumatologists and cardiologists would benefit patients with autoimmune disease.
Additionally, there are many under-recognized risk factors in women, including psychosocial risk factors such as depression and anxiety, intimate partner violence and health literacy. Women are also at higher risk to be affected by socioeconomic and cultural disparities, with women that live in countries with a low sociodemographic index having higher age-adjusted mortality.
These under-recognized and sex-specific risk factors have limited understanding, research, prevalence and effect on CVD. Further research in these topics is critical to be able to adequately improve health outcomes in women. The commission recommends research to identify the effect of sex-specific, psychosocial and socioeconomic risk factors on CVD in women, and to evaluate intervention strategies.
Age-adjusted prevalence of CVD in women is increasing in some of the most populous countries in the world
Although most places in the world have seen a decline in CVD prevalence in women, with increasing understanding and outreach regarding risk factor modification in CVD, there are several regions that had a paradoxical increase in CVD prevalence, including China, Indonesia and India. These areas are some of the most populous countries in the world and have been found to have a high prevalence of hypertension and diabetes. This has been attributed to a high salt diet and genetics.
Additionally, the rapid transformation to an urban society has led to major changes in lifestyle, creating a largely sedentary population. These changes may have contributed to this increased prevalence of modifiable risk factors like hypertension and diabetes. The commission recommends scaling up heart-healthy programs in highly populated and progressively industrialized regions.
There is no current established global policy to coordinate prevention and treatment of CVD in women
Six years ago, the U.N. General Assembly identified CVD as a specific target for achieving the goal of reducing premature mortality from noncommunicable diseases by one-third by 2030. Strategies are needed not only to modify risk factors of CVD, but also to identify sex-specific biologic mechanisms of CVD in women.
CVD policies specific to each region should be created to define priorities and goals for public health interventions to reduce CVD in women. This task will involve multiple stakeholders, including the individual governments, local health professionals, community leaders and patient advocacy organizations, to optimize the effort. The commission recommends embracing public-private partnerships to develop broad-scale programs to save lives in women with CVD.
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For more information:
Roger S. Blumenthal, MD, is director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease and professor of medicine at Johns Hopkins University School of Medicine. He is also the editor of the Prevention section of the Cardiology Today Editorial Board. Twitter: @rblument1.
Andrew Gagel, MD, is a resident physician at Johns Hopkins Hospital. Twitter: @andygagel.
Garima Sharma, MD, is assistant professor of medicine at Johns Hopkins University School of Medicine. Twitter: @garimavsharmamd.
Anjali A. Wagle, MD, is a resident physician at Johns Hopkins Hospital. Twitter: @anjali_wagle.
The authors can be reached at Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Halsted 560, Baltimore, MD 21827.
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