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REVIEW ARTICLE
Year : 2023 | Volume
: 9
| Issue : 1 | Page : 11-17
Recommendations for cardiovascular disease prevention in women: An Indian perspective
Zakia Khan1, Sarita Rao2, Ritu Bhatia3, Saumitra Ray4, Jamshed J Dalal5
1 Department of Cardiology, Fortis Hospital, Kalyan, Maharashtra, India
2 Department of Cardiology, Rajshri Apollo Hospital, Indore, Madhya Pradesh, India
3 Department of Cardiology, Narendra Heart Clinic, Pune, Maharashtra, India, India
4 Department of Cardiology, AMRI Hospitals, Kolkata, West Bengal, India
5 Department of Cardiology, Kokilaben Dhirubhai Ambani Hospital, Mumbai, Maharashtra, India
Correspondence Address:
Zakia Khan
Department of Cardiology, Fortis Hospital Kalyan, Kalyan, Maharashtra
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/jpcs.jpcs_80_22
Cardiovascular disease (CVD) is one of the leading causes of death in women. On an average, coronary artery disease develops 10 years later in women than men, but they represent the majority of patients when age above 75 years is considered. Men and women share most of the classic cardiovascular risk factors, but the relative importance of each risk factor may be gender specific. This review explores the recommendations for the management of cardiovascular risk and CVD prevention in women in the Indian clinical setting based on multiple advisory board meetings conducted with cardiology experts across India. The experts concurred that women have distinct patterns of ischemic heart disease (IHD) and that the presence of traditional risk factors, female-specific risk factors, and nontraditional risk variables may add to the increasing risk of IHD. Transition to postmenopausal status is associated with a worsening coronary heart disease risk profile in women. Evidence suggests that both traditional and novel cardiovascular risk factors are often under recognized and undertreated in women. Several female-specific risk factors such as preterm delivery, preeclampsia, gestational diabetes, and polycystic ovary syndrome are not included in primary prevention nor are they routinely considered in a cardiovascular assessment at the clinical level. Understanding and good diagnostic tools are necessary to evaluate the different pathophysiological aspects and early detection of CVD in women.
Keywords: Cardiovascular disease prevention, hypertension risk in women, ischemic heart disease pattern, postmenopausal status
Cardiovascular disease (CVD) is a leading cause of death in women. Even though CVD occurs 3–4 times more often in men than in women under the age of 60 years, after the age of 75 years, women form the majority of patients with CVD. On an average, coronary artery disease (CAD) develops 10 years later in women, but CAD is responsible for approximately 20% of the deaths in both men and women. Mortality rate due to CVD in women surpasses men at 51% versus 42%.[1]
Men and women share most of the classic cardiovascular risk factors, but the relative importance of each risk factor may be gender specific.[2] The presence of traditional risk factors, female-specific risk factors, and nontraditional risk variables may add to the increasing risk of ischemic heart disease (IHD). Reproductive, hormonal, and pregnancy-related factors predispose to earlier signs of endothelial dysfunction, vascular inflammation, and atherosclerosis. These include genetic predisposition; early/late menarche or migraine during teens; reproductive disorders during adolescence; early menopause, premature hypertension, metabolic syndrome, endocrine disorders, rheumatic disorders, thyroid disorders, or inflammatory bowel disease during the forties; and type 1 coronary microvascular dysfunction, persistent vasomotor symptoms, stroke, or acute coronary syndrome in the early and mid-fifties. At older age (>65 years), there is a shift in the pattern of IHD to more obstructive disease.[3]
Women with diabetes have a 3-fold excess risk of fatal CAD risk compared with nondiabetic women owing to impaired endothelium-dependent vasodilation, a hypercoagulable state, worse atherogenic dyslipidemia, more metabolic syndrome, and often suboptimal management of diabetes in women. Tobacco use represents an important risk factor for both men and women. Obesity and overweight are also the risk factors for CAD. The prevalence of obesity is higher among women than men. Women develop hypertension about a decade after men owing to the protective effect of estrogen, but hypertension becomes more prevalent in elderly women than elderly men resulting in a higher risk of CVD and related morbidity due to left ventricular hypertrophy, diastolic heart failure, and cerebrovascular disease. Dyslipidemia has the highest population-adjusted risk among women compared to all other known risk factors, but this greater risk is typically not observed before menopause, even if cholesterol levels are quite elevated.[4]
Evidence suggests that both traditional and novel cardiovascular risk factors are often under recognized and undertreated in women. Several female-specific risk factors such as preterm delivery, preeclampsia, gestational diabetes, and polycystic ovary syndrome are not included in primary prevention nor are they routinely considered in a cardiovascular assessment at a clinical level.[5] In India, guidelines for the primary prevention of CVD in women are lacking.[6]
Therefore, multiple advisory board meetings were held across India with experts from the field of cardiology. During these meetings, there was a discussion regarding cardiovascular risk in women. As an outcome, expert consensus was laid down as a path of recommendations for the management of cardiovascular risk in women considering the prevailing health-care service infrastructure, local evidence-based studies as well as major international guidelines.
Risk Factors for Cardiovascular Disease in WomenPrevention and management of CVD in women should begin with awareness of the problem and an understanding unique disease characteristics and challenges in women. The risk factors can be nonmodifiable like age or modifiable such as smoking, obesity, hypertension, diabetes, or dyslipidemia. Optimal control of modifiable risk factors can reduce the risk of CVD and help in its management. [Table 1] summarizes the targets for lifestyle modification and control of clinical risk factors in women.[7]
Table 1: Targets for lifestyle modification and control of clinical risk factors associated with cardiovascular disease risk in womenThe 2011 American Heart Association guidelines for the prevention of CVD in women highlight the importance of lifestyle modification, smoking cessation, and diet to reduce the morbidity and mortality related to CVD.[2] The United States Preventive Services Task Force recommends aspirin for women aged 50–59 years with 10-year CVD risk of ≥10% without an increased risk of bleeding.[7] For women aged >65 years, low-dose aspirin therapy may be recommended if benefits outweigh the risks. Antioxidant supplements, such as Vitamin C and E supplements, should not be used for the primary or secondary prevention of CVD. Dietary intake of oily fish at least twice a week and limiting the intake of saturated fats are also recommended.[2]
Management of Cardiovascular Risk in WomenCoronary artery disease
Angina is the most frequent initial and subsequent manifestation of IHD in women.[8] Women often experience “atypical chest pain” radiations and angina-equivalent symptoms such as dyspnea, weakness, fatigue, and indigestion [Table 2]. Gender differences in communication frequently hamper the early recognition of angina in women.[3] In the presence of typical angina, women may experience squeezing, tight, chest discomfort, which radiates to chest, jaws, left armpit and/or left arm, neck, shoulders, and inter-scapular area. It may last longer than minutes and could have a crescendo/decrescendo character (spasm). Dyspnea, anxiety, and mental stress-related extreme tiredness also may be experienced often after angina episode. Both typical and atypical symptoms in nonobstructive CAD (NOCAD) may be observed in women. In the presence of nonanginal chest pain in women, clinicians should be aware of cardiac anxiety disorder.
Women have a smaller diameter of the coronary arteries than men, when corrected for body surface area. Further, women have fewer calcifications, less focal obstruction, and a more diffuse pattern of atherosclerosis with “outward remodeling” and “soft” plaques than men at all ages. Women also present with NOCAD and functional IHD in the coronary (micro-) circulation more frequently than men, which often remains under diagnosed and undertreated.[3]
Women have poorer outcomes after percutaneous coronary intervention (PCI) probably because PCI in small vessels is associated with a higher rate of restenosis and target vessel failure.[9]
Consensus and recommendations
Women present with atypical chest pain and other symptoms leading to delay in treatmentAssessment and modification of traditional and nontraditional risk factors should be performed for every woman to determine cardiovascular riskLifestyle modifications must be advised even for women with low risk and normal functional testsWomen with moderate-to-severe risk should undergo invasive/computed tomography angiography to aid in the evaluation of coronary obstruction, microvascular dysfunction, or vasospastic anginaPerimenopausal women should be evaluated on a yearly basis, and women with cardiovascular risk factors should receive aggressive treatment.Hypertension
Hypertension is a major risk factor for CVD, and an elevated blood pressure (BP) >140/90 mmHg has been demonstrated in approximately 69% of people who had a first heart attack, 77% of those who had a first stroke, and 74% of those who had heart failure. On an average, <50% of adults with hypertension receive BP-lowering medication, even though a difference in BP of 20/10 mmHg is associated with a 50% difference in cardiovascular risk.[10],[11] Hypertension is more common in men than in women, among those younger than 45 years of age, but the situation is reversed in those who are 65 years and older. Life expectancy is approximately 5 years shorter for hypertensive women compared with normotensive women at 50 years of age.[12] A report from the Women's Health Initiative that included data from >160,000 postmenopausal women identified hypertension as a major independent risk factor for sudden cardiac death.[13],[14] Hypertension in postmenopausal women likely has multiple etiologies and contributing factors. Observational studies have shown that menopause is associated with an age-independent increase of 4–5 mmHg in systolic BP.[12],[15]
Combined estrogen and progestin oral contraceptive pills (OCPs) are associated with small but significant increases in BP and risk of cardiovascular events, particularly stroke, in the general population of women. The risk of developing OCP-induced hypertension increases significantly with age, cigarette smoking, duration of OCP use, and obesity. Hypertensive disorders in pregnancy include chronic hypertension, gestational hypertension, preeclampsia, and eclampsia. All of these have been associated with maternal, fetal, and neonatal morbidity and mortality.[12]
Hypertension of any type during pregnancy is associated with an increased risk of future CVD, diabetes, and/or chronic kidney disease (CKD). Preeclamptic women have up to 4-fold increased risk for developing chronic hypertension, and IHD risk is doubled at 15-year follow-up. Women with hypertensive disorders of pregnancy have >2 times excess IHD mortality risk [Table 3].[16],[17]
Table 3: 2018 European Society of Cardiology and European Society of Hypertension guidelines for the management of arterial hypertension in pregnancyConsensus and recommendations
Prehypertensive women with low-intermediate risk should be observed for 3 months, and lifestyle/diet modifications should be advised. Hypertensive patients with comorbidities and those with moderate-high risk must be initiated on antihypertensivesPolycystic ovarian syndrome is a risk factor for developing early hypertension; preeclampsia is a known independent risk factor for CVDWomen with a history of pregnancy-induced hypertension need stringent postpartum follow-up for 3–6 months and the next 1–2 yearsCombined estrogen and progestin OCPs are associated with small but significant increases in BP and risk of cardiovascular events.Heart failure
The prevalence of heart failure increases with age in both genders, but men are diagnosed at younger age, whereas heart failure is more common among women older than 75 years. Hypertension and coronary heart disease are the most common etiologic factors in heart failure for both genders, but hypertensive women appear to have a higher risk of developing heart failure than men. When comparing men and women who have heart failure and a low left ventricular ejection fraction (LVEF), women are more symptomatic and have a similarly poor outcome. Overall, women are generally underrepresented in clinical trials for heart failure.[18],[19],[20],[21],[22],[23]
Clinical trials on heart failure highlight many differences between men and women, and a particular concern was under the treatment of women compared with men.[24] Compared with men, women with heart failure had many unique anatomical and physiologic features like lower left ventricular mass, lower cell turnover/apoptosis, and lower BP but greater contractility. They had smaller coronary vessel caliber and higher resting heart rate; catecholamine-mediated vasoconstriction was also less for women.[23]
In a patient with new-onset heart failure with reduced ejection fraction (HFrEF), a common question is whether to initiate a beta-blocker or angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blocker (ARB) first. Data from clinical trials suggest that either is safe. Initiation of ACE inhibitors or ARBs is often better tolerated when the patient is still congested (”wet;” when renin-angiotensin-aldosterone system activation is less), whereas beta-blockers are better tolerated when the patient is less congested (”dry”) with adequate resting heart rate [Table 4].[25],[26]
Table 4: Guideline-directed medical therapy for heart failure with reduced ejection fraction per 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America guidelinesIn the PARAGON-HF study, which compared the combination of an angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril and the ARB valsartan versus valsartan in patients with symptomatic heart failure with preserved ejection fraction (HFpEF), the ARNI-ARB combination showed reduction in the risk of hospitalizations due to heart failure, but not cardiovascular mortality, more frequently in women than in men. Moreover, the sacubitril-valsartan combination was more effective across a broader range of LVEF in women than in men.[27]
Consensus and recommendations
Women tend to develop HFpEF more commonly than men, especially with comorbidities like hypertension, diabetes, obesity, sleep apnea, or CKDWhen women complain of shortness of breath with associated hypertension, diabetes, and/or obesity, they should be suspected to have heart failure and could be diagnosed earlyHeart failure in women needs to be optimally managed (via drugs/devices) to prevent complications and recurrent hospitalizationsHFrEF is less common in women than in menARNIs, BBs, sodium/glucose cotransporter-2 is inhibitors, and mineralocorticoid receptor antagonists could be recommended as disease modifying drugsWomen respond better with cardiac resynchronization therapy device than men.Peripartum cardiomyopathy
Peripartum cardiomyopathy (PPCM) is a rare, often dilated, cardiomyopathy with systolic dysfunction that presents in late pregnancy, or more commonly, the early postpartum period. Risk factors include preeclampsia, advanced maternal age, and multiple gestation pregnancy. Complete pathophysiology of PPCM remains unclear; research suggests the importance of vasculo-hormonal pathways.[28]
The treatment of PPCM follows standard heart failure therapy that is used to optimize the volume status of a patient. Beta 1 selective blockers and ACE inhibitors have shown to lower mortality. Diuretics are often used to ease symptoms related to heart failure. Sacubitril/valsartan has been reported to improve heart failure symptoms in pregnancy-related cardiomyopathies. Bromocriptine, a dopamine receptor agonist with prolactin-blocking properties, has been associated with better outcomes in small studies. Cardiac resynchronization therapy has also shown to improve ejection fraction and outcomes when medical therapy alone is ineffective.[29] Traditionally, one third of PPCM recovers completely, one third has partial recovery, and one third has no improvement. However, with newer therapies, an improved prognosis is anticipated.
Consensus and recommendations
Dilated heart, severe left ventricular dysfunction, and ejection fraction <30%–35% is seen in pregnancy and at 3–6 months in the postpartum periodARNI can be prescribed in the postpartum period with no breast-feeding; enalapril and bromocriptine can be prescribed in the postpartum periodSymptomatic patients with low EF and those who have not recovered from PPCM should be advised against future pregnancies; asymptomatic patients with normal EF need to be cautioned/counseled for future pregnanciesSome genetic factors are common in dilated cardiomyopathy and PPCM.Arrhythmias
There is an increasing awareness that sex is a major determinant of the incidence, etiology, and clinical presentation of arrhythmias. Women are more likely to present with atypical symptoms, such as weakness and fatigue, have longer duration of symptoms, and report worse quality of life and more-frequent depression than men. Female sex has been shown to be a risk factor for atrial fibrillation (AF)-related stroke or thromboembolism, myocardial infarction, and mortality, but has not been associated with incident heart failure or dementia.[30]
The pathophysiological mechanisms that explain the sex differences in AF have been incompletely studied. The potential mechanisms identified that might help explain why women have a lower incidence and prevalence of AF are presented in [Table 5]. AF causes electrical and structural remodeling that promotes AF, thereby exacerbating the risk of further AF.[30]
Consensus and recommendations
Supraventricular tachycardia (SVT), sinus node dysfunction, and atrioventricular nodal reentry tachycardia (a type of SVT) are more common in women compared to menNew-onset SVT is common in pregnancy due to estrogen sensitivity, stress, and treatment with drugs like oxytocinAF is common in elderly women, whereas SVT is common in the youngElectrocardiogram findings in women are often abnormal (short PR interval, longer QT interval, and T-wave inversion), without clinical significanceAmiodarone, digoxin, and adenosine are safe antiarrhythmic drugs that can be used during pregnancy. Radiofrequency ablation can be undertaken postdelivery.Vasculature in pregnancy
Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism, remains a leading cause of maternal death in the developed world, causing 1.2–4.7 deaths per 100,000 pregnancies. The causal link between pregnancy and VTE is best explained by Virchow's triad, a framework that categorizes elements of the pathophysiology of VTE into three broad categories: venous stasis, vascular damage, and hypercoagulability of blood.[31] In pregnant women with suspected DVT, a positive D-dimer test, and high pretest probability (PTP), presence of noncompressible segment on compression ultrasound (CUS) confirms the presence of DVT. If CUS is normal, a filling defect confirmed by venography or magnetic resonance venography can confirm the presence of DVT. In pregnant with suspected DVT, but a negative D-dimer test or low PTP, presence of noncompressible segment on CUS confirms the presence of DVT. If CUS is normal, noncompressibility on serial CUS performed on days 3 and 7 can be used to confirm DVT.
The treatment and prevention of pregnancy associated VTE is challenging because of the potential for both fetal and maternal complications. Low molecular weight heparin (LMWH) is the treatment of choice in acute VTE unless contraindicated. In these cases, an infusion of unfractionated heparin may be more appropriate. Warfarin is generally avoided during pregnancy, especially in the first trimester and after 36 weeks of pregnancy. Direct oral anticoagulants such as the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban are not used during pregnancy.[32]
Consensus and recommendations
Adequate hydration, prevention of venous stasis, and scans to detect thrombi are recommendedDoppler is a simple bedside tool of investigation; magnetic resonance venogram is recommended to evaluate thrombosis in pelvic veinsLung or pulmonary ventilation and perfusion scans may be used to rule out pulmonary vein thrombosisLMWH is the safest choice; LMWH, warfarin, and acenocoumarol can be prescribed for lactating womenWarfarin therapy should be avoided during the first trimester (because of teratogenicity) and last trimester to reduce risk of hemorrhagic complications, but can be prescribed during lactationRest and LMWH for 3 months should be prescribed in women who have suffered from venous thrombosis bed during pregnancy. ConclusionCVD in women is under-recognized and under-treated in clinical practice due to several reasons. There is a need for the awareness about CVD among women as the natural history of CVD is different in women than in men. Women are protected from CVDs due estrogen, but postmenopause the risk is higher than men. Diabetes, metabolic syndrome, and obesity are common in women. Awareness and good diagnostic tools are necessary to evaluate the different pathophysiological aspects and for the early detection of CVD in women. Management of risk factors and optimal treatment of underlying conditions can reduce the risk of CVD in women.
Ethics clearance
Not applicable.
Acknowledgment
Authors gratefully acknowledge the following experts across India who gave their expert opinion in the advisory board meetings: Dr. Sheeba George, Dr. Asha Mahilmaran, Dr. Anupam Goel, Dr. JP Sawhney, Dr. Aparna Jaswal, Dr. Sameer Shrivastav, Dr. Simmy Minocha, Dr. Kavita Tyagi, Dr. Mamtesh Gupta, Dr. Sarita Gulati, Dr. Satbir Singh, Dr. Amit Pandarkar, Dr. Priti Sharma, Dr. Anupama V Hegde, Dr. Lalitha S, Dr. Roopa R, Dr. Tripti Deb, Dr. Veenu J, Dr. Ashida T. S, Dr. Monica E Florence, Dr. Deepthi, Dr. Dinesh David, Dr. Deepak Raju, Dr. Priya Palimkar, Dr. Jyoti K Kusnur, Dr. Survo Banerjee, Dr. Arindam Pande, Dr. Vivek Mahajan, Dr. Nikhila Pachani, Dr. Vidya Suratkal, Dr. Shalima Gautam.
The authors would like to thank Dr. Sivacharan from Magna for his medical writing and editorial assistance.
Financial support and sponsorship
Funding for writing support was provided by Abbott Healthcare Pvt. Ltd.
Conflicts of interest
All authors received honoraria from Abbott for participation in the advisory board meeting. Sarita Rao is a joint secretary of Win Caps and a board member of Asian Pacific Society of Interventional Cardiology WIN.
References
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