Clinical and Angiographic Profile of Women with Acute Coronary Syndrome from a Large Tertiary Cardiac Care Center in South India – An Observational Study

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INTRODUCTION

Coronary artery disease is the leading cause of mortality in both developed and developing countries. Women have a longer time from symptom onset to presentation and are less likely to have guideline-directed treatment. This causes poor outcome in women as compared to men. There are limited studies regarding the clinical and angiographic profile of acute coronary syndrome in women in Indian scenario.

Cardiovascular disease has emerged as a major public health burden and a major cause of mortality in women in both developed and developing countries.^[1,2] Significant differences in the prevalence of coronary artery disease (CAD) exist concerning gender, ethnicity, and age. It is predicted that more than half the worldwide cardiovascular disease risk burden will be borne by the Indian subcontinent in the next decade, according to a recent epidemiological study.^[1] At any given age, the prevalence of CAD is greater in men than in women. As compared to men, women receive less medical attention in both rural and urban areas. Atherosclerotic plaque characteristics may differ by gender. It is said that women are protected from CAD by the protective hormones till menopause. However, recently, we are seeing a changing trend with acute coronary syndrome (ACS) increasing even in premenopausal women. Certain risk factors such as diabetes, metabolic syndrome, low high-density lipoprotein cholesterol and smoking are more causally related to CAD in women.^[2,3]

A randomized sub-study of the Organization to Assess Strategies in Acute Ischemic Syndromes 5 trial in women presenting with an ACS suggests that women do worse with an early invasive strategy.^[4] Although large trials including the women’s health initiative and the women’s ischemia syndrome evaluation have shed light on clinical characteristics, diagnosis, and outcome in women, they are largely western studies. In a study undertaken in Kerala at a tertiary center, women with ST-elevation myocardial infarction (STEMI) had higher mortality rates than males with STEMI.^[5] In Kerala ACS registry,^[6] the largest ACS data till date in the Indian scenario involving 25,748 patients over 2 years and across 125 centers had 22.6% women enrolment. There are limited studies on ACS exclusively in Indian women. Most of the data were taken from combined studies. In the present study, we aim to prospectively analyze the demographic, clinical risk factors, and angiographic profile of ACS in South Indian women presenting with the ACS in a tertiary cardiac care center.

MATERIALS AND METHODS

It is a prospective observational single-center study conducted at Sri Jayadeva Institute of Cardiovascular Science and Research center, a tertiary cardiac center in Mysuru, Karnataka, India during the year 2020. Five hundred and twenty-nine consecutive women with a diagnosis of ACS after satisfying inclusion and exclusion criteria were chosen for the study. Baseline clinical, demographics, laboratory investigations, electrocardiogram, echocardiographic assessment, coronary angiogram (CAG) details, treatment data, and outcomes were recorded. STEMI, non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA) were diagnosed following current guidelines. The data were collected from the patients and recorded in a pre-prepared case report form. Baseline data were recorded. The primary outcome was the overall rate of hospital admissions for ACS and deaths associated with ACS.

RESULTS

The mean age of patients is 43.94 ± 6.85 years in premenopausal age and 63.89 ± 9.51in the postmenopausal age group. There are 21 patients with age less than 45 years of age. There are 72 patients with age above 75 years. About 80.3% of patients belonged to the below poverty line group. About 89.6% of patients had attained menopause.

The mean BMI in the premenopausal group is 22.16 ± 5.287 kg/m² and in the postmenopausal age group is 23.66 ± 4.584 kg/m². Underweight is seen in 27.27% in the premenopausal group and 12.66% in the postmenopausal group. Overweight is seen in 27.8% and class II obesity seen in 1.9% of the study population. There are 85.1% non-vegetarians. There are 55.4% patients from the rural area [Table 1].

Time of onset of symptoms to reach the hospital: 178 patients (33.65%) with ACS reached hospital in less than 24 hours after symptom onset. 119(22.49%) patients presented within 24-48hours time period. 95(17.96%) presented in 48-72hours time period. 25.9% patients presented late after 72 hours. Typical chest pain during presentation seen in 97.5% of the study population. Atypical chest pain seen in 2.5%. Exertional dyspnea and exertional fatigue seen in 23.5% and 50% of the patients, respectively. Hypertension (59.90%) followed by diabetes mellitus (DM) (54.80%) is the most common comorbidity in our study group [Figure 1].

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Figure 1:

Distribution of comorbidities among the study population.

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The presentation of ACS in our study group is STEMI – 62.38%, followed by NSTEMI – 24% and UA – 13.6%. Most common presentation is acute Anterior wall MI in the STEMI group followed by Inferior wall MI. Killip I presentation seen in 67.8% of the study population [Figure 2], followed by Killip’s III (5.8%) and Killip’s class IV (3.6%). In STEMI patients, moderate LV dysfunction seen in 25.7% and severe LV dysfunction seen in 2.27% [Tables 2 and 3].

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Figure 2:

Killip’s score distribution among the study population.

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CAG is done in 240 patients, in which non-obstructive CAD seen in 10.83%. About 36.67% presented with single-vessel disease. About 5.83% had LMCA involvement. Most common vessel involved is left anterior descending artery (LAD) (76.25%). PTCA procedure done in 69.17% of the patients who underwent CAG. Only 1% underwent CABG. Postprocedure access site hematoma is seen in three cases (0.75%) [Table 4].

Diabetes is seen in 42.86% in premenopausal versus 54.59% in the postmenopausal age group. Hypertension was seen in 47.61% of premenopausal women and in 63.5% of post menopausal women. About 66.67% presented with STEMI in premenopausal group versus 54% in the postmenopausal group. NSTEMI seen in 36.5% of the postmenopausal group. About 9.07% patients presented with Killip’s IV in the postmenopausal group [Table 5].

Antiplatelets aspirin and clopidogrel are given as loading doses across all ACS groups; it was switched over to ticagrelor in 57.28% of cases. About 0.75% was on Prasugrel. Rest of the patients were continued on clopidogrel. About 59.35% were on beta-blockers and 51.22% were on ACE inhibitors. All patients received Statins.

Eighty-three patients died in hospital. Most common age group is 65–75 years (38.55%). No mortality seen in patients aged <45 years. Eighty-one (97.59%) patients were postmenopausal. About 87.95% belonged to below poverty line socioeconomic group. In patients who died, 56.62 % were hypertensive and 60.24% were diabetics. About 24.09% of patients had prior IHD. Chronic kidney disease seen in 3.61%. Fourteen (16.86%) patients had free wall rupture. Two (2.4%) patients had ventricular septal rupture. Twenty-nine (34.93%) and 34 (40.96%) patients had severe and moderate LV dysfunction, respectively. Twenty-three (27.71%) were in Killip’s class III and 55 (66.26%) were in Killip’s IV at presentation. About 89.15% had STEMI, with majority having AWMI (57.83%). Sixty-six patients (79.5%) patients died within 24 h of admission. About 33.73% of patients died within 6 h of admission. Of the ten patients in the mortality group who underwent CAG, four of them had triple-vessel disease. Killip’s classes III and IV, moderate LV dysfunction, underweight patients, and those from the urban area were found to be independent predictors of death on risk estimate analysis of in-hospital mortality.

DISCUSSION

The present study is the largest single-center data of ACS in women from the country. Cardiovascular disease is presently the most common cause of mortality in women. The major ACS trials that guide daily clinical practice disproportionately enrolled men. Women with ACS have more comorbidities than men and traditional risk factors affect the cardiovascular system differently in women^[7] due to which the prognosis is also very poor in women. Receptors for estrogen, progesterone, and testosterone are expressed in varying numbers in both the endothelium and vascular smooth muscle of multiple vascular systems^[8] and are one of the proposed mechanisms responsible for gender difference in vascular tone.

The mean age of presentation in the present study is 43.94 ± 6.85 years in premenopausal age and 63.89 ± 9.51 years in the postmenopausal age group as compared to 64.4 + 11 years in a study done by Nanjappa et al.^[8] The mean age is higher when compared to a study done by Mahajan et al.^[8,9] Most women, in our study, were postmenopausal (84.25%), whereas it was 79.7% in a study by Mahajan et al.^[10] and Rissam et al.^[11] and 90.2% in Nanjappa et al.^[8] About 36.1% patients had obesity (BMI >25 kg/m²).

About 40% of premenopausal and 56.54% of the postmenopausal group had DM and 45.45% of premenopausal and 61.6% in the postmenopausal group had hypertension.

These were the most common comorbidities, which were comparable other studies.^[9] This contrasts with Mahajan et al.^[10] study, in which the prevalence of diabetes was only 20.6% and hypertension was 69.7%. This shows that diabetes was more prevalent in women in South India compared to North India. About 30.4% and 37.7% in CREATE registry^[12] and 30.2% and 29.6% in INTERHEART^[7] study had diabetes and hypertension, respectively. These registries encompassed both men and women.

In our study, LDL cholesterol level is above 100 mg/dl in both pre- and post-menopausal women with P-value being significant. We could not find significant increase in total cholesterol triglyceride level in our study which highlights that though there is no major dyslipedimia, but still females in our study group suffered ACS.

Majority of our patients were in postmenopausal age group. Killip class IV presentation is predominantly seen in postmenopausal women. About 38.6% of women had Killip’s class II–IV in SWEDEHEART study.^[13] Associations between higher androgen and lower estrogen levels with CAD risk factors in postmenopausal women, including, insulin resistance, C-reactive protein, and blood pressure exist.^[15-16] In the present study, anemia is seen in 55% of cases and dyslipidemia with elevated LDL cholesterol was seen in 66% cases.

STEMI (62.38%) is the most common presentation in our study, followed by NSTEMI (24%) and UA (13.6%) which are comparable to other studies.^[8] About 50.9% of premenopausal women and 54% of postmenopausal patients had STEMI at presentation.

In the present study, 45.36% of patients underwent CAG; the rest were treated medically. This contrasts with Nanjappa et al.^[8] study. The reason could be that the present study involved more of rural than urban population compared to the latter study which was conducted in purely urban population. Among patients who underwent CAG, majority had single-vessel disease (76.25%) with LAD being the most common culprit vessel in 36% of cases, which is comparable to a study from Singapore, where 90% of women with Indian ethnicity had single-vessel disease.^[14] Double-vessel disease and triple-vessel disease were seen in 25.83% and 25.41%, respectively. About 69.17% of CAG patients underwent percutaneous coronary intervention (PCI) procedure. In comparison, PCI was done in only 11.9% of patients in the Kerala ACS registry and 7.5% in CREATE registry. About 47.8% underwent PCI in a study by Sadowski et al.^[15]

LMCA involvement was seen in 5.83% which is comparable to Mahajan et al.^[9] study and 3.4% in a study by Ezhumalai and Jayaraman^[16] In the CADILLAC trial,^[17] female gender was an independent predictor of MACE and bleeding complications, although comorbid risk factors and body surface area, and not gender, predicted 1-year mortality.

Eighty-three deaths were noted. Deaths noted in our study were higher compared to the registry data. This could be explained by the fact that our center caters to 5–6 surrounding districts with a predominantly agrarian population. Most of the deaths happened within 24 h of admission. About 75.89% were in Killip’s classes III and IV at presentation. Delayed recognition of symptoms and presentation to the hospital at a later severe stage of the illness could explain the higher deaths. This study period overlapped with the COVID pandemic, and this could have also influenced the health-seeking behavior of patients. About 3.9% in the Kerala ACS^[6] registry had in-hospital mortality with 8.2% in the STEMI group. In the AMI-FLORENCE registry, the in-hospital mortality for women was 16%.^[18]

CONCLUSION

This prospective observational study in a large tertiary cardiac care center of South India illustrates significant differences in the clinical risk profile and angiographic disease pattern among premenopausal and postmenopausal women. Majority of the patients belonged to 55–65 years age group. Majority of the patients had typical chest pain and fatiguability as clinical manifestation. The most common comorbidities seen in our study group which is hypertension followed by DM. There is only a marginal difference in distribution of patients from urban and rural areas which are alarming, highlighting the fact that CAD is no more a disease limited to urban population. This fact will have cascading effect on health economic policies and the need for stringent addressal of risk factors and prevention of these risk factors at primary health-care level and robust system of linking the primary care to tertiary centers for better health-care delivery. The most common presentation is STEMI. Higher mortality is seen in patients presenting late to the hospital and with higher Killip’s class. More studies involving women with the focus on demographic, clinical risk profile, CAD, and treatment strategies pattern would help in the formulation of evidence-based guidelines to prevent and treat optimally.

“A heart-healthy woman for a healthy society.”