Approximately 35% of all deaths in women worldwide are caused by cardiovascular disease. This roughly translates to one in three women we encounter every day.


By Asst Prof Chanchal Chandramouli, Research Fellow, NHRIS

Global Burden of Diseases Study in 2019 showed that 275 million women were diagnosed with cardiovascular disease (CVD) and 8.9 million demised due to CVD. Despite the advancement in care and therapies over the last 30 years, the benefit seen is limited to developed nations with high socio-demographic indices. CVD in women remains understudied, under-recognised, under-diagnosed, and undertreated.

Cardiovascular Risk Factors in Women

Early detection and management of cardiovascular risk factors are paramount in reducing CVD burden in women. Known classical risk factors of CVD such as hypertension, dyslipidaemia, diabetes, obesity, unhealthy diet, sedentary lifestyle and smoking, which are common to both men and women, however, often affect women differently.

While hypertension is chiefly incriminated as CVD risk, it is the most neglected health burden in women. Women experience more rapid increases of progressive blood pressure, as compared to men beginning as young as 30 to 40 years. Elevated cholesterol levels are unequivocally recognised as risk factor of myocardial infarction in women, with a more pronounced increase post-menopause. Likewise, type 2 diabetes escalates the risk of CVD by two-fold in men but five-fold in women. Importantly, Asian women are predisposed to a “lean diabetic phenotype”, wherein diabetes is present in absence of an overt body mass index.

In addition to the classical risk factors, sex-specific risk (in women) further increases the risk of CVD later in life. The INTERHEART study documented that CVD in women manifests almost a decade later in women than men1. Although the risk appears lower in women who are premenopausal (compared to age-matched men), the risk escalates rapidly after menopause. Literature evidence on hormone replacement therapy stand divided, with some observational studies showing benefit but randomised clinical trials have yet to confirm them.

Other pregnancy and reproductive hormone related risk factors in women include pre-term delivery, gestational hypertensive disorders, gestational diabetes, polycystic ovary syndrome, systemic inflammatory and autoimmune disorders.

Beyond these classical and sex-specific risk factors, underrecognised risk factors are also prevalent in women. Depression is an independent and long-term risk factor of both obstructive and non-obstructive coronary artery disease in women. Intimate partner violence and low socioeconomic status disproportionately affect women as compared to men and are emerging as important considerations in the development and manifestation of CVD in women. In the Asian context, sociocultural gender norms and expectations of women to be selfless ‘caregivers’ often confine them to the ‘giving’ end only. Low awareness of self-care and poor CVD health literacy in women also fuel this further.

Representation of Women in Cardiovascular Clinical Trials

Importantly, women continue to be under-represented in CV clinical trials. In a systematic assessment (study by NHCS and Duke Kunshan University) of 740 completed CV clinical trials registered at ClinicalTrials.gov between 2010 and 2017, it was found that only 38% of the participants were women. Relative to the respective realworld disease prevalence, participation of women was comparable for pulmonary hypertension and hypertension trials but low in stroke, arrhythmia, coronary heart disease, acute coronary syndrome and lowest in heart failure trials. In recent years, there has been significant increases in recruitment of women into stroke and heart failure trials2, a commendable effort in the right direction!

The low representation of women in trials were due to various reasons including inadequate information or referrals, the lack of support such as transportation and childcare help and the misperceptions surrounding risks and benefit. Most of these can be simply addressed by the physician or clinical coordinators spending time to explain the trial and convincing them to participate.

In 2021, Prof Carolyn Lam, Senior Consultant from the NHCS, the only Lancet Commission Ambassador from Asia, together with 16 ambassadors from 11 countries authored the first-ever global report on CVD in women3. This Commission outlines 10 key significant recommendations to overcome inequities in targeting diagnosis, treatment, and prevention to reduce CVD in women. The recommendations span a huge spectrum from increasing awareness, educating healthcare providers and patients on early identification to prevent heart disease in women to scaling up heart health programmes in highly populated and underdeveloped regions; and prioritising sex-specific research and intervention strategies to prevent CVD in women.

Together, these studies serve as a loud and necessary reminder for physicians and the public to be mindful of sex differences in CVD disease diagnosis, manifestation, treatment, and prognosis. Interventions to reduce CVD should be tailored for the most vulnerable populations globally, including women from minority or indigenous populations and those whose roles in society are strongly defined by traditional or religious norms. The Women’s Heart Clinic at NHCS is one such initiative, which aims to empower women to take charge of their heart health through greater awareness of their risk factors and symptoms. The clinic offers end-to-end services, from prevention to diagnosis, treatment and rehabilitation, customised to the specific needs of women using a holistic approach of physical and psychosocial care. At National Heart Research Institute Singapore (NHRIS), there is also a dedicated research theme on “Heart Failure and Women’s Health” which rigorously publishes basic, translational and clinical studies on women’s heart health.

Top 10 Recommendations from Lancet Commission to Reduce CVD burden in Women4

Issue

Recommendation

​Accurate data on global prevalence and outcomes of cardiovascular disease in women are absent
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Direct funding for real-time and accurate data collection on prevalence and outcomes of cardiovascular disease in women globally

​Women with cardiovascular disease remain understudied, under-recognised, underdiagnosed, and undertreated
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Develop educational programmes on cardiovascular disease in women for physicians, scientists, allied health-care providers, and communities

​Sex-specific mechanisms in the pathophysiology and natural history of cardiovascular disease remain poorly understood
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​Prioritise sex-specific research focused on identifying the pathophysiology and natural history of cardiovascular disease

Women are under-represented in the majority of cardiovascular clinical trials

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​Develop strategies to improve enrolment and retention of women in cardiovascular clinical trials

Socioeconomic deprivation contributes substantially to the global burden of cardiovascular disease in women
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​Prioritise funding in global health organisations for cardiovascular disease health programmes in women from socioeconomically deprived regions

Myocardial infarction and cardiovascular disease mortality are increasing in young women
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​Educate healthcare providers and patients regarding early detection and prevention of cardiovascular disease in young women

Hypertension, dyslipidaemia, and diabetes are the most crucial risk factors contributing to cardiovascular disease death in women
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​Establish policy-based initiatives and medical and community outreach cardiovascular disease risk factor programmes in settings frequented by women

Sex-specific and other under-recognised cardiovascular disease risk factors, such as psychosocial and socioeconomic factors, appear to contribute to the global burden of cardiovascular disease in women
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​Research is needed to identify the effect of sex-specific, psychosocial, and socioeconomic risk factors on cardiovascular disease in women, and evaluate intervention strategies

​Age-adjusted prevalence of cardiovascular disease in women is increasing in some of the most populous countries of the world
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​Scale up healthy heart programmes in highly populated and progressively industrialised regions

​There is no current established global policy to coordinate prevention and treatment of cardiovascular disease in women
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​Embrace public–private partnerships to develop broad-scale programmes to save lives in women with cardiovascular disease



1 Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the interheart study): Case-control study. Lancet. 2004;364:937–952

2
 Jin X, Chandramouli C, Allocco B, Gong E, Lam CSP, Yan LL. Women's Participation in Cardiovascular Clinical Trials From 2010 to 2017. Circulation. 2020 Feb 18;141(7):540-548. doi: 10.1161/
CIRCULATIONAHA.119.043594. Epub 2020 Feb 17. PMID: 32065763.

3
 Vogel B, Acevedo M, Appelman Y, Merz CN, Chieffo A, Figtree GA, Guerrero M, Kunadian V, Lam CS, Maas AH, Mihailidou AS. The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. The Lancet. 2021 Jun 19;397(10292):2385-438.

4
 Vogel B, Acevedo M, Appelman Y, Merz CN, Chieffo A, Figtree GA, Guerrero M, Kunadian V, Lam CS, Maas AH, Mihailidou AS. The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. The Lancet. 2021 Jun 19;397(10292):2385-438. DOI: https://doi.org/10.1016/S0140-6736(21)00684-X


     
This article is from Murmurs Issue 41 (September – December 2021). Click here to read other articles or issues.