Abstract
Background
Gender disparity, with respect to women receiving less medical therapy, undergoing fewer invasive procedures, and experiencing worse outcome than men, has been noted in various observational and randomized trials, though guidelines on acute coronary syndrome (ACS) are gender-neutral. Indian data with focus on women with ACS are lacking.
Aim
This study was undertaken to give us an insight on the clinical presentation, risk factors, and in-hospital outcome of ACS in women and at 30 days.
Materials and methods
133 successive cases of women presenting with ACS, who met the inclusion criteria between 2012 and 2014, were included. Cases were grouped into ST elevation myocardial infarction (STEMI), non ST elevation myocardial infarction (NSTEMI), and unstable angina (UA).
Results and conclusion
The mean age was 64.4 ± 11 years. The mean BMI was 23.64 ± 3.23 kg/m2. Diabetes was present in 58.3% in NSTEMI, 65.1% in STEMI, and 57.1% in UA group. Hypertension was found in 75% of NSTEMI, 60.2% of STEMI, and 71.4% of UA group. Severe MR was found in 11.1% of NSTEMI and 3.6% of STEMI patients. 8.3% of NSTEMI and 15.7% of STEMI patients presented in Killips class IV. Single vessel disease was most commonly found across the spectrum of ACS. 68.7% patients in STEMI group underwent primary angioplasty. 5.6% of NSTEMI and 7.2% in STEMI group had contrast-induced nephropathy (CIN). All deaths were noted in STEMI group with eight in-hospital deaths and three during 30-day follow-up period. Killips class III and IV and higher grace score (>150) were predictors of in-hospital mortality. Chronic kidney disease, ischemic mitral regurgitation, LV clot, and in-hospital cardiac arrest were associated with higher risk.
Abbreviations: ACS, acute coronary syndrome; AWMI, anterior wall myocardial infarction; COPD, chronic obstructive pulmonary disease; CAD, coronary artery disease; CAG, coronary angiogram; CKD, chronic kidney disease; DM, diabetes mellitus; LDL, low density cholesterol; HDL, high density cholesterol; IABP, intra aortic balloon counter pulsation; IWMI, inferior wall myocardial infarction; MR, mitral regurgitation; MACE, major adverse cardiovascular events; NSTEMI, non ST elevation myocardial infarction; POBA, plain old balloon angioplasty; PAMI, primary angioplasty; PCI, percutaneous coronary intervention; PWMI, posterior wall myocardial infarction; STEMI, ST elevation myocardial infarction; TPI, temporary pacemaker; TVD, triple vessel disease; UA, unstable angina; VLDL, very low density cholesterol; VT, ventricular tachycardia; VF, ventricular fibrillation
Keywords: Acute coronary syndrome in women, Risk factors, In-hospital outcome, 30-day follow-up, Tertiary hospital data
1. Introduction
Cardiovascular disease has emerged as a major health burden in developing countries. Significant differences in the prevalence of coronary artery disease (CAD) exist with respect to gender, age, and ethnicity. 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 In 2003, the prevalence of CAD in India was estimated to be 3–4% in rural areas and 8–10% in urban areas (six-fold higher compared with 40 years ago). At any given age, the prevalence of CAD is greater in men than in women. Nonetheless, many recent reports concluded that women with CAD have a worse prognosis than men with this disease. The type of ischemic event shows gender-specific differences. Most clinical trials have enrolled primarily men, and the results have generally been extrapolated to women.
A randomized substudy of the OASIS 5 trial (Organization to Assess Strategies in Acute Ischemic Syndromes) and an accompanying meta-analysis of prior studies of percutaneous coronary intervention (PCI) in women presenting with an acute coronary syndrome (ACS) suggest that women do worse with an early invasive strategy. They have been reported to undergo cardiac catheterization and consequently revascularization procedures less often than men.2 There have been conflicting results when analyzed by gender in randomized and registry studies of primary PCI for ST elevation myocardial infarction (STEMI). Although large trials including 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 STEMI had higher mortality rates than males with STEMI.3 In Kerala ACS registry,4 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, and CREATE registry5 showed that 23.6% of ACS were women.
2. Materials and methods
This was an observational study with 30-day follow-up, conducted at Fortis Hospital, Cunningham Road, Bangalore. It aimed to provide information on the risk factors and treatment outcome in natural settings. The subjects were female patients, who were presenting for the first time with a diagnosis of ACS, at our hospital. Once the patients met the inclusion and exclusion criteria as defined, they were enrolled in the study after signing the informed consent. Women whose age is greater than 18 years and diagnosed with ACS were included. Age less than 18 years, prior heart failure, prior ischemic heart disease, and those unwilling to participate in the study or sign the informed consent were excluded. STEMI, non ST elevation myocardial infarction (NSTEMI), and unstable angina (UA) were diagnosed following current guidelines.
Data collection was done in two phases – in hospital and 30-day telephonic follow-up. The in-hospital survey was performed when the patient presented with ACS for the first time. The postdischarge survey was done at 30 days. The data were collected from the patients and recorded in a prepared Case Report Form (CRF). Demographic details, medical history, information on diet, substance use, and hospitalization details were collected.
2.1. Statistical analysis
Analysis of data was done using Statistical Package for Social Sciences (SPSS) software version 15. The descriptive results are displayed as subgroups of STEMI, NSTEMI, and UA. All the numerical data are presented as mean ± standard deviations. All the categorical data are presented as frequency and percentages. The results are presented in tables and graphs. Multivariate logistic regression analysis was done to assess the odds of variables affecting the in-hospital mortality.
3. Results
133 subjects were enrolled into the study after meeting the inclusion criteria. The recruitment period was from May 2011 to December 2013. The subjects were followed up for a period of 30 days. There were 11 patients who died during the study period. Most patients belonged to 61–70 years stratified age group across all ACS subtypes. The mean age was 64.4 ± 11 years. The mean BMI was 23.64 ± 3.23 kg/m2.
16.7% presented within 4 h after symptom onset and 58.3% presented more than 12 h after symptom onset in the NSTEMI group; 18.1% patients in STEMI group presented within 4 h of symptom onset and 38.6% after 12 h. 64.3% patients in UA group presented 12 h after symptom onset.
Most patients presented with typical chest discomfort in all 3 subgroups. 1 patient in NSTEMI and 6 patients in STEMI group presented with syncope.
38.9% in NSTEMI, 36.1% in STEMI, and 21.4% in UA group received premeditation with antiplatelets before reaching the hospital. 6% in STEMI group received thrombolysis at the point of first medical contact.
Echocardiography revealed moderate mitral regurgitation (MR) in 5.6% of NSTEMI and 6% of STEMI patients. Severe MR was found in 11.1% of NSTEMI and 3.6% of STEMI patients. Fig. 1 depicts the LV dysfunction in different ACS subtypes. Table 1 depicts the risk factor profile.
Fig. 1.
Distribution of LV systolic dysfunction in terms of EF in ACS subgroups.
Table 1.
Risk factor profile.
| Number (%) |
|||
|---|---|---|---|
| NSTEMI | STEMI | UA | |
| DM | 21 (58.3%) | 54 (65.1%) | 8 (57.1%) |
| Hypertension | 27 (75%) | 50 (60.2%) | 10 (71.4%) |
| Hypothyroidism | 5 (13.9%) | 14 (16.9%) | 1 (7.1%) |
| CKD | 1 (2.8%) | 7 (8.4%) | 2 (14.3%) |
| COPD | 1 (2.8%) | 6 (7.2%) | 0 |
| Anemia | 1 (2.8%) | 8 (9.6%) | 0 |
| Smoking | 0 | 1 (1.2%) | 0 |
| Tobacco | 0 | 2 (2.4%) | 0 |
| Family history of CAD | 20 (55.6%) | 43 (51.8%) | 3 (21.4%) |
Troponin positivity was documented in all patients with NSTEMI and in 75.9% of STEMI patients. Troponin T in our study was done at admission; serial values have not been considered in the present study. Fig. 2 depicts the distribution of MI type in STEMI.
Fig. 2.
Distribution of MI type in STEMI.
10.8% received thrombolysis in STEMI group. 115 patients underwent CAG, 80.6% in NSTEMI group, 90.4% in STEMI group, and 78.6% in UA group. Single vessel disease was most commonly found across the spectrum of ACS. 13.9% in NSTEMI, 10.8% in STEMI, and 14.3% in UA group had TVD. Left main involvement was seen in 3 patients each of STEMI and NSTEMI group. Of the patients who underwent PCI procedure, 39.2% had radial access approach and 60.8% via femoral approach.
69.4% in NSTEMI group underwent PCI; 7 patients of posterior wall MI underwent primary angioplasties. 68.7% (POBA+ PAMI) patients in STEMI group underwent primary angioplasty; 42.9% patients in UA group underwent PCI. Use of manual thrombus aspiration using export/thrombuster device was done in 8.3% of NSTEMI and 33.7% patients in STEMI group. Multivessel PCI was done in 8.3% NSTEMI and 6% STEMI patients and none in UA group. Staged PCI was done in 3.6% of STEMI patients. IABP was used in 3.6% of STEMI patients and TPI was used in 9.6% patients. 9 (6.77%) patients were put on assisted ventilation and all were in STEMI subgroup. GPIIb/IIIa inhibitors were used in 57.14% patients of ACS. Tirofiban was used in 61.1% in NSTEMI and 60.2% in STEMI.
All patients received aspirin across all ACS groups; Ticagrelor use was 11.1% in NSTEMI, 8.4% in STEMI, and 21.4% in UA group. 42.2% of STEMI patients received Prasugrel and 30.6% in NSTEMI group. Clopidogrel was used in 94.4% NSTEMI and 94% of STEMI patients; 39.9% of patients had a switch over. All patients initially received statins, and in 1 patient, it was later discontinued because of raised liver enzymes. 92.9% of UA, 77.1% in STEMI, and 75% in NSTEMI received beta-blockers. Use of angiotensin converting enzyme inhibitors was 83.3% in NSTEMI and 78.3% in STEMI group. Table 2 depicts in-hospital complications.
Table 2.
In-hospital complications.
| Number (%) |
|||
|---|---|---|---|
| NSTEMI | STEMI | UA | |
| Overall complications | 10 (27.8%) | 23 (27.7%) | 1 (7.1%) |
| Local hematoma | None | 2 (2.4%) | None |
| Bleeding | None | 2 (2.4%) | None |
| Contrast-induced nephropathy | 2 (5.6%) | 6 (7.2%) | None |
| Ischemic MR | 3 (8.3%) | 6 (7.2%) | None |
| Septal rupture | None | None | None |
| Free wall rupture | None | None | None |
| Left ventricle aneurysm | 1 (2.8%) | 1 (1.2%) | None |
| Left ventricle clot | None | 3 (3.6%) | None |
| Cardiac arrest | 2 (5.6%) | 3 (3.6%) | None |
| Hypoxic ischemic encephalopathy | None | 2 (2.4%) | None |
| Cardiac tamponade | 1 (2.8%) | None | None |
| Pericarditis | 1 (2.8%) | 2 (2.4%) | None |
| Raised liver enzymes | None | 1 (1.2%) | None |
| Sepsis | 6 (16.7%) | None | 1 (7.1%) |
| TIA/CVA | None | None | None |
| In-hospital death | 0 | 8 (9.6%) | None |
7 patients in STEMI (six of IWMI and one AWMI) group and 1 in NSTEMI had complete heart block. 4 patients in STEMI (three IWMI and one AWMI) and 1 in NSTEMI had VT/VF. All deaths were noted in STEMI group, with eight in-hospital deaths and three during 30-day follow-up period. 3 patients who died had atypical clinical presentation.
In-hospital mortality was noted to increase with increasing age in regression analysis. Chronic kidney disease (CKD) was found to increase the risk. On multivariate regression analysis, breathlessness and syncope were associated with increased risk. Tachycardia and hypotension increased the odds. Hypotension, Killips class III and IV and higher grace score (>150), and moderate and severe LV dysfunction were predictors of in-hospital mortality. Table 3 depicts risk estimate for in-hospital death.
Table 3.
Risk estimate for in-hospital death.
| OR | 95% confidence interval |
||
|---|---|---|---|
| Value | Upper | Lower | |
| Variables | |||
| Age group 51–60 (years) (Yes/No) | 0.359 | 0.043 | 2.986 |
| Age group 61–70 (years) (Yes/No) | 1.267 | 0.324 | 4.953 |
| Age group 71–80 (years) (Yes/No) | 1.579 | 0.305 | 8.186 |
| Age group >80 (years) (Yes/No) | 4.143 | 0.737 | 23.300 |
| Diabetes mellitus (Yes/No) | 1.221 | 0.291 | 5.115 |
| Hypertension (Yes/No) | 1.925 | 0.383 | 9.669 |
| Chronic kidney disease (Yes/No) | 8.357 | 1.718 | 40.650 |
| COPD/bronchial asthma (Yes/No) | 2.458 | 0.263 | 22.973 |
| Anemia (Yes/No) | 1.813 | 0.201 | 16.339 |
| Family history CAD (Yes/No) | 0.113 | 0.014 | 0.934 |
| Clinical variables | |||
| Complete heart block (Yes/No) | 2.089 | 0.228 | 19.128 |
| Ventricular tachycardia/ventricular fibrillation (Yes/No) | 3.750 | 0.374 | 37.599 |
| Systolic blood pressure ≤90 (Yes/No) | 6.286 | 1.508 | 26.202 |
| Systolic blood pressure >90 (Yes/No) | 0.159 | 0.038 | 0.663 |
| Killips Class III (Yes/No) | 5.813 | 1.403 | 24.081 |
| Killips Class IV (Yes/No) | 11.667 | 2.755 | 49.404 |
| Grace score group 100–49 (Yes/No) | 0.243 | 0.049 | 1.217 |
| Grace score group 150–199 (Yes/No) | 6.131 | 1.518 | 24.764 |
| Grace score group 200–249 (Yes/No) | 11.524 | 1.648 | 80.567 |
| Left main coronary artery (Yes/No) | 2.975 | 0.309 | 28.602 |
| Temporary pacemaker implantation (Yes/No) | 5.619 | 0.955 | 33.076 |
| Thrombus aspiration (Yes/No) | 2.207 | 0.296 | 16.446 |
4. Discussion
Gender disparity in cardiac diagnosis and treatment has been investigated thoroughly since Ayanian2 first described this phenomenon. This study highlights the prevalence of multiple risk factors in women, an underemphasized study group.
Majority of patients in our study belonged to the age strata of 61–70 years across all ACS subtypes. 7.5% patients were more than 80 years. Older the age, higher was the odds of in-hospital mortality. A majority of women in our study were postmenopausal (90.2%), which reinforces the observation by Rissam et al.6 that postmenopausal females need special attention as they constitute a distinct subgroup at a high risk for CAD.
Most patients presented with typical chest discomfort in all 3 subgroups (69.4% in NSTEMI, 72.3% in STEMI, and 71.4% in UA group). 1 patient in NSTEMI and 6 patients in STEMI group presented with syncope. In a study by Canto et al.,7 42% of women presented without typical chest discomfort, and gender-specific differences in MI presentation without chest discomfort became progressively smaller with advancing age. The in-hospital mortality rate was 14.6% for women and 10.3% for men. Younger women presenting without chest pain had greater hospital mortality than younger men without chest pain, and these sex differences decreased or even reversed with advancing age, with adjusted OR for 65–74 years, 0.91 (95% CI, 0.88–0.95), and 75 years or older, 0.81. All 3 patients who died and who had atypical clinical presentation had age more than 65 years in our study, which is concordant with the data.
The percentage of subjects with diabetes mellitus (58.3% in NSTEMI, 65.1% in STEMI, and 57.1% in UA) was much higher than in both CREATE registry5 (30.4%) and the INTERHEART study (30.2%).8 The mean glycosylated hemoglobin % was found to be 7.24 ± 2.03, suggesting that majority of diabetics had uncontrolled diabetes. The percentage of hypertensives (75% of NSTEMI, 60.2% of STEMI, and 71.4% of UA) was also high when compared to the CREATE registry (37.7%)5 and the INTERHEART study (29.6%). This difference in prevalence of the major risk factors is probably due to regional differences, in the Indian population. Compared with men, women were significantly older and had higher prevalence of hypertension and hyperlipidemia in HORIZON-AMI9 subgroup analysis.
25% of NSTEMI and 12% of STEMI presented in Killips class III. 8.3% of NSTEMI and 15.7% of STEMI patients presented in Killips class IV. 21.7% in Kerala ACS had Killips class >1; 38.6% women had Killips class II–IV in SWEDEHEART study.10
The mean total cholesterol level was higher in our study (184.4 ± 39.46 mg/dl) than that found among MI cases in Tirupati, India (177.07 ± 8.49).11 The same was noticed for mean LDL level also (121.6 ± 51.4 mg/dl). However, the levels of the protective HDL were also found to be lower in our study (35.2 ± 7.69 mg/dl) than in the earlier study (46 ± 1.55 mg/dl).11 The lipid abnormalities were present in 61.5% in the INTERHEART8 study and in 38.75% in a study by Bhasin et al. (38.75%).11 It suggests high prevalence of dyslipidemia in the general population.
Of the patients who underwent CAG, 66% received revascularization in their study in comparison to 83.6% in our study. The higher cumulative percentage is probably related to the fact that ours is a tertiary cardiac care hospital. PCI was done in only 11.9% of patients in Kerala ACS registry and in 7.5% in CREATE registry. 47.8% underwent PCI in a study by Sadowski et al.12 12% of STEMI patients received thrombolysis.
68.7% patients underwent primary angioplasty in our study. 82.8% received thrombolysis in a study at CMC Vellore13 involving 1320 patients where women constituted 16.2%. In a study by Mady Moriel et al.,14 in STEMI-patients, acute reperfusion was less frequent in women than in men (53% vs. 63%, respectively, p = 0.01; nonsignificant after age adjustment); reperfusion by thrombolysis was done in 30% patients and PAMI in 70% of STEMI. In CADILLAC trial,15 female gender was an independent predictor of MACE and bleeding complications, although co-morbid risk factors and body surface area, and not gender, predicted 1-year death. For women, primary stenting resulted in a reduction in 1-year MACE from 28.1% to 19.1%. Table 4 gives the comparison of registry data.
Table 4.
Comparison of acute coronary syndromes in developed and developing countries; the registry data are inclusive of both men and women and involve a large sample.
| STEMI | NSTEMI | Mean age (years) | Time taken for admission to thrombolysis (min) | PAMI | STEMI – 30-day mortality | NSTEMI – 30-day mortality | |
|---|---|---|---|---|---|---|---|
| Our study | 62.4% | 27.1% | 64.4 (SD 11) | 42.5 | 68.7% | 13.2% | 0 |
| CREATE | 61% | 39% | 57 | 50 | 8% | 9% | 4% |
| Global registry of ACS | 30–40% | 60–70% | 64–69 | – | 40% | 8% | 3% |
| European heart surveys | 42% | 51% | 63 | 40 | 40% | 7% | 1% |
| US National registry of MI | – | – | 68 | 32–38 | 36% | 8% | – |
11 deaths (8.3%) were noted; 8 (6%) in hospital and 3 (2.3%) in the follow-up period. All of them belonged to STEMI group. 3.9% in Kerala ACS registry had in-hospital mortality with 8.2% in STEMI group. The registry data encompass both men and women. In AMI-FLORENCE registry the in-hospital mortality for women was 16%.
More research with focus on treatment strategies, including invasive strategies, needs to be addressed.
Conflicts of interest
The authors have none to declare.
References
- 1.Gupta R., Joshi P., Mohan V., Reddy K.S., Yusuf S. Epidemiological and causation of coronary heart disease & stroke in India. Heart. 2008;94:16–26. doi: 10.1136/hrt.2007.132951. [DOI] [PubMed] [Google Scholar]
- 2.Ayanian J.Z., Epstein A.M. Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med. 1991;325:221–225. doi: 10.1056/NEJM199107253250401. [DOI] [PubMed] [Google Scholar]
- 3.Raihanathul Misiriya K.J., Sudhayakumar N., Abdul Khadar S., George R., Jayaprakasht V.L., Pappachan J.M. The clinical spectrum of acute coronary syndromes: experience from a major center in Kerala. J Assoc Physicians India. 2009;57:377–383. [PubMed] [Google Scholar]
- 4.Mohanan P.P., Mathew R., Harikrishnan S. Presentation, management, and outcomes of 25 748 acute coronary syndrome admissions in Kerala, India: results from the Kerala ACS Registry. Eur Heart J. 2013;34:121–129. doi: 10.1093/eurheartj/ehs219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Xavier D., Pais P., Devereaux P.J. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. Lancet. 2008;371:1435–1442. doi: 10.1016/S0140-6736(08)60623-6. [DOI] [PubMed] [Google Scholar]
- 6.Rissam H.S., Kishore S., Trehan N. Coronary artery disease in young Indians: the missing link. J Indian Acad Clin Med. 2001;2:128–132. [Google Scholar]
- 7.Canto J.G., Rogers W.J., Goldberg R.J. Association of age and sex with myocardial infarction symptom presentation and in hospital mortality. JAMA. 2012;307:813–822. doi: 10.1001/jama.2012.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Yusuf S., Hawken S., Ounpuu S. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (INTERHEART study): case control study. Lancet. 2004;364:937–952. doi: 10.1016/S0140-6736(04)17018-9. [DOI] [PubMed] [Google Scholar]
- 9.Yu J., Mehran R., Grinfeld L. Sex-based differences in bleeding and long term adverse events after percutaneous coronary intervention for acute myocardial infarction: three year results from the HORIZONS-AMI trial. Catheter Cardiovasc Interv. 2015;85:359–368. doi: 10.1002/ccd.25630. [DOI] [PubMed] [Google Scholar]
- 10.Lawesson S.S., Alfredsson J., Fredrikson M., Swahn E. Time trends in STEMI – improved treatment and outcome but still a gender gap: a prospective observational cohort study from the SWEDEHEART register. BMJ Open. 2012;2:e000726. doi: 10.1136/bmjopen-2011-000726. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Bhasin S.K., Dwivedi S., Dehghani A., Sharma R. Conventional risk factors among newly diagnosed coronary heart disease patients in Delhi. World J Cardiol. 2011;3:201–206. doi: 10.4330/wjc.v3.i6.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Sadowski M., Gasior M., Gierlotka M., Janion M., Poloński L. Gender-related differences in mortality after ST-segment elevation myocardial infarction: a large multicentre national registry. EuroIntervention. 2011;6:1068–1072. doi: 10.4244/EIJV6I9A186. [DOI] [PubMed] [Google Scholar]
- 13.Jose V.J., Gupta S.N. Mortality and morbidity of acute ST segment elevation myocardial infarction in the current era. Indian Heart J. 2004;56:210–214. [PubMed] [Google Scholar]
- 14.Moriel M., Tzivoni D., Behar S. Contemporary treatment and adherence to guidelines in women and men with acute coronary syndromes. Int J Cardiol. 2008;131:97–104. doi: 10.1016/j.ijcard.2007.09.005. [DOI] [PubMed] [Google Scholar]
- 15.Lansky A.J., Pietras C., Costa R.A. Gender differences in outcomes after primary angioplasty versus primary stenting with and without abciximab for acute myocardial infarction: results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Circulation. 2005;111:1611–1618. doi: 10.1161/01.CIR.0000160362.55803.40. [DOI] [PubMed] [Google Scholar]