Cardiovascular (CV) disease is the leading cause of death in women and the priority given to women has been upscaled in recent years. The need for increasing awareness, diagnosis and treatment of cardiac disease in women was highlighted by The Lancet Commission on Cardiac Disease in Women and its recommendations to improve care for women with cardiac diseases.1
Cardiomyopathy, a term used to describe a group of diseases that affect the heart muscle, is a leading cause of heart failure (HF) and sudden cardiac death worldwide.2,3 It is associated with high mortality, high morbidity, reduced quality of life starting at a young age, and substantial economic burden.4,5
People from South Asia (i.e. India, Pakistan, Bangladesh, Sri Lanka, Nepal and the Maldives) represent one of the fastest-growing ethnic groups worldwide and often exhibit unique genetic, cultural, socio-economic and lifestyle factors that may influence the prevalence, progression and outcomes of cardiomyopathy. Compared with white people from European countries, South Asian people with cardiomyopathy have a high burden of comorbidities.6 Hence, Asian countries saw an increase in the age-standardised prevalence rate of cardiomyopathies from 2009 to 2019, whereas a decline was observed in Western countries.7
Despite the growing burden of cardiomyopathy in South Asia and its diasporic communities, there is a significant gap in the epidemiological data specifically related to gender differences in prevalence, clinical course and outcomes.8,9 Few studies have comprehensively examined the intersection of genetic, sociocultural and gender-related factors that contribute to these disparities. This gap in the literature necessitates more targeted research to understand the specific risks and challenges faced by South Asian men and women living with cardiomyopathy.
In this scoping review, we discuss the gender disparities in the prevalence and mechanisms of cardiomyopathy affecting South Asian women, which may explain unique gender-based risk factors, patterns of diagnosis, barriers to healthcare access and disparities in outcomes. We also highlight gender-based inequities in preventive measures, with the aim of curbing and modifying these adverse trends in management approaches and improving the prognosis of prevalent cardiomyopathy; and discuss public health policies and future research initiatives.
This review includes dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC), but does not examine cardiomyopathy related to ischaemia.
Methods
Inclusion and Exclusion Criteria
Studies were included if they involved South Asian populations, specifically those from India, Pakistan, Bangladesh, Sri Lanka, Nepal and the Maldives. The research focused on cardiomyopathies such as HCM, DCM, RCM, PPCM and ARVC. Articles were included if they examined gender-specific differences in prevalence, risk factors, clinical presentation, disease progression or management. Only published articles in English between January 2000 and December 2023 were eligible. Those studies that focused exclusively on ischaemic cardiomyopathy, unrelated cardiac diseases or non-peer-reviewed publications were excluded.
Study Selection
The selection process was systematic and involved multiple stages. First, two independent reviewers conducted an initial screening of titles and abstracts from the identified records to determine potential relevance. Following this, full-text articles of potentially eligible studies were retrieved and reviewed in detail against the predefined inclusion and exclusion criteria. The PRISMA-ScR (PRISMA extension for Scoping Reviews) framework guided the entire study selection process, ensuring rigour and transparency.
Data Extraction
Data extraction was performed using a pre-designed standardised form to ensure consistency across all included studies. The following details were meticulously recorded: study characteristics, including author name(s), year of publication, country of study, and study design; participant demographics, capturing information on sample size, age distribution and gender composition; the type of cardiomyopathy being studied, such as HCM, DCM, RCM or PPCM; gender-specific findings, including data on prevalence, clinical characteristics, disease progression and outcomes; and insights into gender disparities in management strategies and interventions.
Results
In South Asian populations, a variety of genetic and environmental factors play a central role in the development of several types of cardiomyopathy; in particular, gender-specific genetic factors influence disease onset, progression and the severity of the cardiomyopathy.
Gender Differences in Cardiomyopathy Prevalence
Cardiomyopathies, especially HCM and DCM, are often more prevalent in men across various ethnic groups. This is partly due to hormone differences and may also be influenced by genetic factors. However, gender disparities are often also influenced by social and healthcare-related factors. Generally, South Asian women have better CV health than men, as indicated by higher STEPS-HEART index scores.10 For RCM, evidence from limited data suggests a similar prevalence in men and women. Amyloidosis leading to RCM is more prevalent in older age in men than in women.11
In a study conducted in Sri Lanka, PPCM was responsible for 20.7% of pregnancy-related deaths (59/284), of which 16.2% (46/284) occurred in the puerperium period.12 Binu et al. analysed the clinical profiles and outcomes of women with PPCM enrolled retrospectively from a tertiary care centre in southern India (2008–14).13 The incidence of PPCM was 1 per 1,541 live births. The study included 54 women with a mean age of 25.5 years. Maternal and fetal death rates were 9.3% and 24.1%, respectively. Reduced left ventricular ejection fraction and cardiogenic shock were significantly associated with adverse maternal outcomes.13
Some studies suggest that women develop DCM in the productive years of life secondary to PPCM in the last month of pregnancy or within 5 months after delivery.14 In South Asia, many women have limited access to prenatal care or may be discouraged from seeking medical attention due to cultural norms.
It cannot be ignored that cardiomyopathy may be underdiagnosed in women. This could be due to a combination of factors, including societal norms, atypical symptoms and underreporting of symptoms. Women often present with more subtle symptoms, and symptoms may be frequently dismissed or misattributed to non-cardiac causes, delaying diagnosis and treatment.15,16 The lack of awareness around female-specific symptoms may contribute to gender-based disparities in healthcare, including underdiagnosis.
Clinical Presentation of Cardiomyopathy
The clinical presentation of cardiomyopathy differs significantly between South Asian men and women. Men tend to present earlier with more severe symptoms, such as shortness of breath, fatigue and palpitations. This is likely to be due to testosterone, which accelerates myocardial remodelling and disease progression. Women, in contrast, tend to have a more insidious onset of symptoms, especially with HCM, which often presents at a later stage with symptoms that may be less pronounced.17 Women are more likely to develop complications, such as arrhythmias or HF with preserved ejection fraction (HFpEF), which is often linked to more prevalent diabetes and hypertension in South Asian women.18–22
ARVC is one phenotype of cardiomyopathy with a disparity in prevalence between the sexes. It is a complex cardiomyopathy with autosomal dominant inheritance and age-related incomplete penetrance.
Sharma et al. reviewed 41 studies, including 36 that used the Task Force Criteria to assess risk in family members.23 They found that the risk varied significantly depending on the family genotype for ARVC and concluded that the male gender was not associated with a higher prevalence of the disease. Recent professional consensus guidelines recommend lifelong serial clinical cardiac screening for at-risk family members, with adjustments based primarily on age. However, family genotype may also influence screening requirements. While genetic variations are not strictly gender specific, their expression in HCM often differs between men and women, as discussed in later sections.
Takotsubo cardiomyopathy (TCM) is another phenotype with a gender predisposition, disproportionately affecting women. Mishra et al. found that 87.5% of those affected were women, 40% had hypertension, and that these two factors increased the risk of TCM.24 The most common presenting symptom was dyspnoea (48%) following a trigger, most commonly emotional (45%). TCM was mainly seen in postmenopausal women following an emotional trigger, but a variety of other triggers were noted. A low ejection fraction that improves on subsequent follow-up further suggests a diagnosis of TCM.24
Genetic Influence on Cardiomyopathy
Genetic factors are central to the pathogenesis of most common types of inherited cardiomyopathy, such as HCM, DCM and familial cardiomyopathy. Understanding the genetic underpinnings of cardiomyopathy, particularly in relation to gender differences, is crucial for improving the outcomes of cardiomyopathy and for developing prevention strategies for South Asian populations with predisposing genetic mutations.8,9
Mutations in sarcomeric genes (such as MYH7, MYBPC3 and TNNT2) are well-established causes of HCM, while mutations in genes such as Ttn, LMNA and DSP are associated with DCM and play a role in the high burden of both HCM and DCM in South Asian women (Table 1). Viswanathan et al. conducted genetic screening of 2,401 US South Asian individuals and found an MYBPC3Δ25bp carrier frequency of 6%.25 A higher frequency of missense TTN variation was found in MYBPC3Δ25bp carriers compared with non-carriers. MYBPC3Δ25bp/D389V was associated with hyperdynamic left ventricular performance (mean [SEM] left ventricular ejection fraction, 66.7% [0.7%]; left ventricular fractional shortening, 36.6% [0.6%]; p<0.03) and stem cell-derived cardiomyocytes exhibited cellular hypertrophy with abnormal Ca2+ transients.25
One of the key factors influencing genetic sex differences in cardiomyopathy is the X chromosome, which carries a variety of genes involved in CV function. In women, the second X chromosome may offer a protective effect against X-linked mutations, thereby potentially modulating the severity of cardiomyopathies. X-linked genetic disorders, including lamin A and lamin C gene mutations (LMNA), have been shown to affect women differently, often resulting in less severe phenotypes or delayed onset of symptoms compared with men. In both Asian and white cohorts, similar genes accounted for the largest proportions of pathogenic or likely pathogenic mutations: MYBPC3 and MYH7 in the sarcomere thick filament for HCM, and for DCN, TTN encoding the sarcomere protein titin and LMNA encoding the nuclear membrane protein lamin A/C.26 However, the presence of X-inactivation, which may silence one of the X chromosomes in women, could lead to variable expression of these mutations, contributing to the observed gender-based differences in disease manifestation and severity.
In contrast, Y chromosome genes, although less frequently implicated in cardiomyopathies, could also influence disease risk in men. For instance, some studies suggest that SRY gene mutations or Y chromosome microdeletions might play a role in predisposing men to certain types of DCM, although the research in this area remains limited. Efforts to elucidate the genetic landscape of Asian cardiomyopathy have been led by studies of Japanese and mainland Chinese cohorts; new studies on other geographically distinct populations, especially South Asian, are required to identify possible disparities, especially those that are gender based.27
Oestrogen and Its Protective Role
Oestrogen is also thought to contribute to gender disparity in cardiomyopathy.28 It is the primary female sex hormone and has long been associated with protective effects on vascular health, lipid metabolism and myocardial function. In South Asian populations, in which premature menopause and early-onset CV diseases are common, the role of oestrogen in disease prevention and progression becomes even more critical.29,30 The interaction between genetic mutations and oestrogen-related pathways may help explain the heightened vulnerability of South Asian women to CV disease, including cardiomyopathy after menopause.
HCM and DCM typically present at an earlier age and with more severe manifestations in men than in premenopausal women, and it is hypothesised to be due to the absence of oestrogen’s protective effects in men. Postmenopausal women, however, have a sharp increase in the risk of cardiomyopathy due to the decline in oestrogen levels, leading to a convergence in risk between men and women. This hormone shift may be compounded by the increase in comorbidities after menopause, worsening the outcomes of postmenopausal women with cardiomyopathy.
Gender-based Prevalence of Risk Factors for Cardiomyopathy
Apart from the higher burden of cardiometabolic disorders (including hypertension, diabetes and coronary artery disease) in South Asian people, lifestyle factors, such as a high carbohydrate diet, lower physical activity levels, high rates of obesity and smoking, can exacerbate cardiomyopathies.31–33 The National Health Survey of Pakistan (1990–94) found that the prevalence of any CV risk factor was higher in women than men (20.9% versus 13.0%; p<0.001).34 In a 2014 survey in Sri Lanka, while most CV risk factors were similar between genders, daily tobacco smoking was higher in men and BMI was higher in women.35 Additionally, data from Bangladesh showed that the prevalence of hypertension and diabetes was also higher in women than in men.36
Zahid et al. conducted a study in Pakistan of 298 patients (194 men and 104 women) with left ventricular systolic dysfunction of New York Heart Association classes III and IV.37 The average follow-up time was 130 days. The Kaplan–Meier survival curves show a similar survival pattern for men and women. For the overall data, smoking, diabetes, blood pressure, platelet count and creatine phosphokinase were not significantly correlated with survival. Gender was also identified as non-significant. Analysis by gender showed differing findings. For men, smoking, diabetes and anaemia were not correlated with survival. However, female smokers had a 1.43-fold higher risk of death than non-smoking women, and the chances of death were 41% higher in women with diabetes than those who did not have diabetes in DCM. Platelet count was a significant risk factor for predicting survival in men only, with men who had abnormal counts having a 36% higher risk of death than their counterparts. Last, in women, ejection fraction, sodium and platelet count were non-significant.
Obesity is a growing problem in South Asia and there is compelling evidence for the presence of obesity cardiomyopathy, independent of various comorbid conditions as underlying mechanisms.38 This offers new insights into potential therapeutic approaches (pharmacological and lifestyle modification) for the clinical management of obesity cardiomyopathy in women.
A pooled study of four community-based cohorts (the Cardiovascular Health Study; the Framingham Heart Study; the Multi-Ethnic Study of Atherosclerosis; and the Prevention of REnal and Vascular ENdstage Disease) showed that obese women were more likely to develop HFpEF than HF with reduced ejection fraction (HFrEF), compared with obese men.20 In addition, sex also modified the relationship between abdominal obesity and metabolic abnormalities as well as haemodynamic perturbations, and a greater impact was noted for female HFpEF patients compared with male patients.21
The utility of methylation risk scores (MRS) in risk prediction of CV disease for Asian cohorts was demonstrated using an MRS for type 2 diabetes.39 In an epigenome-wide association study involving an Indian Asian cohort, five type 2 diabetes-associated markers were identified and used to construct the MRS, which predicted a fourfold higher risk of future type 2 diabetes between upper and lower quartiles of methylation score. Importantly, the MRS was higher in the Indian Asian cohort compared with the European cohort, and the difference in score was associated with an estimated 32% unexplained increased risk of incident type 2 diabetes among the Indian Asian women relative to European participants.39
Gender-related factors such as marital status and large household size are associated with poorer CV health and higher CV disease risk in men, especially DCM due to lifestyle-related risk factors such as alcohol abuse, tobacco use and higher rates of undiagnosed hypertension.40
Other Factors Affecting Gender Disparity in Cardiomyopathy
Susceptibility to cardiomyopathy is compounded by environmental and other factors in South Asia. Chronic inflammatory cardiomyopathy and tropical cardiomyopathy are more prevalent in South Asia due to specific infections, such as Chagas disease, Coxsackie virus and, recently, severe acute respiratory syndrome coronavirus 2, that can affect the heart muscle.41 Environmental influences such as diet, physical activity and access to healthcare, which may also show gender disparities, further complicate the gender differences in cardiomyopathy.42,43
Malnutrition may also play a role in gender disparities in South Asia. In areas of South Asia where malnutrition is common, there is a difference in the prognosis and outcomes of cardiomyopathy.44 Nutritional deficiencies (iron and folate) are common due to gender-based food allocation practices in patients with cardiomyopathy. A lack of adequate micronutrients, such as vitamin B1 (thiamine), which is essential for cardiac function, can lead to conditions such as beriberi, which may cause DCM, particularly in women.44
Cultural and socio-economic factors may play a role in gender disparities in South Asia. In South Asian cultures, traditional gender roles may prevent women from seeking medical help for symptoms that they might consider embarrassing or trivial. Women also face a combination of gender norms, and sociocultural and economic barriers including limited decision-making power, restricted mobility, low economic resources and economic dependency, which can limit their ability to afford care for cardiomyopathy or access to specialised treatments.45 Furthermore, gender biases in healthcare may result in less attention being paid to women’s heart health, even when they present with symptoms that should warrant early investigation. Patriarchal norms, prioritisation of male family members, and the prioritisation of family responsibilities over women’s own health can all delay the seeking of care until the disease has progressed significantly and may restrict access to healthcare.46
Figure 1 shows the interaction of the various factors leading to the development of cardiomyopathy and the evident gender-based disparities.
Gender Differences in the Progression and Quality of Care of Cardiomyopathy
Women in rural areas of South Asian countries face greater challenges with increased rates of CV mortality and morbidity compared with their urban counterparts and men, despite having a better overall CV risk profile.47 Gender differences in the progression of cardiomyopathy may be linked to both hormone and genetic factors (Table 2).
When diagnosed and treated earlier, women with some subtypes of cardiomyopathy (e.g. PPCM) may have better survival rates. However, limited access to tertiary healthcare facilities reduces survival in women with advanced cardiomyopathy. Women from South Asian backgrounds may face barriers to accessing healthcare due to cultural, socio-economic or linguistic factors. Factors such as increased obesity, poor healthcare access/policy, and environmental changes contribute to this disparity and result in lower rates of detection and management of metabolic risk factors in women than men. Current policies often lack a rural-specific approach, failing to address the unique challenges faced by rural populations.48
There are also gender-based differences in the management and treatment of cardiomyopathy received by South Asian people. Although the clinical guidelines for HF related to cardiomyopathy are generally the same for men and women, the underrepresentation of women in clinical trials means that gender-specific treatment regimens are often not well-tailored to women’s unique needs. Men tend to receive regular therapy and advanced treatments such as ICDs and heart transplants more often than women due to economic barriers.49
Addressing the Gender Disparity in Cardiomyopathy
Due to gender disparities driven by biological, sociocultural and healthcare-related factors, equitable healthcare strategies are needed to improve clinical outcomes in South Asian populations. Addressing these disparities requires targeted approaches focusing on early diagnosis, screening and complication management to prevent disease progression in both men and women.
In regions with a high prevalence of familial HCM, genetic testing and echocardiography can be valuable tools for early detection; however, in resource-limited settings, a more practical approach may involve targeted screening based on clinical risk factors and family history.50 Integrating screening for PPCM into routine maternal care, particularly through cost-effective clinical assessments and basic echocardiography where available, could also improve early diagnosis. Hormone replacement therapy, diuretics and aldosterone antagonists must be used with caution, particularly in pregnancy and postpartum care, when safety concerns are heightened.
Limited awareness and gender norms often hinder South Asian women’s access to timely care. Public health initiatives should prioritise health literacy and awareness campaigns, focusing on the early recognition of cardiomyopathy symptoms and risk factors. Community outreach programs may help bridge this gap, particularly for PPCM and postmenopausal heart disease. Given the pivotal role of the family in healthcare decision-making in South Asian cultures, family-based counselling can be a powerful tool for educating families about hereditary risk factors and the importance of early detection.
Governments in low-income and resource-constrained South Asian countries must strive for equitable access to cardiac care for both genders. Economic barriers, such as medication cost, transportation to specialised centres, and out-of-pocket expense, can prevent women from receiving appropriate care. Addressing these issues may involve subsidised healthcare programs for high-risk women, expanding telemedicine services and leveraging mobile health units to reach underserved populations.
Research and Clinical Trials
There are research and data gaps in South Asian countries due to the lack of comprehensive gender-specific data on cardiomyopathy, and women have been underrepresented in CV research. Existing studies often overlook the interplay of genetic predisposition and sociocultural dynamics. Therefore, it is crucial to ensure that women are included in clinical trials; genetic research is required to identify gender-specific genetic markers and mutations associated with familial cardiomyopathy in South Asian populations; and to explore the biological and hormone factors that influence disease progression in women.
Conclusion
Men and women in South Asia face distinct challenges, ranging from variations in biological factors to sociocultural factors and healthcare access barriers. Gender roles, economic disparities, and limited access to healthcare can hinder women’s ability to seek and receive appropriate care in South Asia. Addressing the gender disparity in cardiomyopathy in South Asian people is critical to improving both the diagnosis and outcomes of this debilitating disease.51 Early detection and diagnosis are key to improving patient outcomes, particularly in women. Targeted screening programmes are needed to recognise the unique presentations of the disease in both genders and to address the rates of underreported symptoms in women.52 Reducing barriers, improving healthcare infrastructure, ensuring equitable access to diagnosis and treatment, and tailoring long-term clinical care to meet the unique needs of both men and women will be essential for closing the gender gap in cardiomyopathy care in South Asia. Addressing the gender disparities in cardiomyopathy is not only a medical imperative but also a societal responsibility. Research and clinical trials with more representation of women, with a focus on understanding the gender-specific genetic, hormone and clinical factors that affect cardiomyopathy is needed to provide more relevant data to inform gender-specific guidelines for managing cardiomyopathy.
Finally, by empowering women to improve healthcare access, and tailoring clinical care to specific gender needs, we can ensure more equitable and effective management of cardiomyopathy, ultimately improving the quality of life and reducing mortality in South Asia.
Clinical Perspective
- South Asian women face challenges in cardiomyopathy management, including genetic predisposition, hormonal influences and socio-economic barriers.
- Cultural norms often delay diagnosis and treatment, leading to worse outcomes. In contrast, men have earlier disease onset, often linked to lifestyle factors such as smoking and alcohol use.
- Recommendations emphasise personalised gender-specific interventions, public health policies for targeted screening and equitable healthcare access.
- Tailored interventions for women, particularly for those in rural areas and who are at high risk, are crucial. Public health initiatives should prioritise health literacy and awareness campaigns, focusing on the early recognition of cardiomyopathy symptoms and risk factors.