Risk factor profile and disease pattern in premenopausal and postmenopausal Indian women presenting with acute coronary syndrome

Biji Soman; Muneer A Rahaman; Rajesh Rajan; Govindan Vijayaraghavan

doi:10.4103/2250-3528.191098

ORIGINAL ARTICLE

Year : 2016 | Volume : 5 | Issue : 3 | Page : 78-83

Risk factor profile and disease pattern in premenopausal and postmenopausal Indian women presenting with acute coronary syndrome

Biji Soman MBBS, MRCP (UK), D.Card ¹, Muneer A Rahaman MD, D.Card, FESC ², Rajesh Rajan MD, PhD, D.Card, FESC, FACC, FAHA ³, Govindan Vijayaraghavan MD, DM, FRCP (Lond), FRCP (Edin), FACC, FAHA ²
¹ Department of Cardiology, Sree Uthram Thirunal Royal Hospital, Kochulloor, Kerala, India
² Department of Cardiology, Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India
³ Department of Cardiology, Amiri Hospital, Kuwait City, Kuwait

Date of Web Publication

26-Sep-2016

Correspondence Address:
Biji Soman
Meditrina Hospital, Pallikkal (PO), Kottarakara - 691 566, Kerala
India

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/2250-3528.191098

Abstract

Introduction: More women die of cardiovascular diseases than from any other illness. Evaluation of coronary artery disease (CAD) among premenopausal women has been neglected, since it is been considered to be rare. The purpose of this study was to compare the risk factor profile for CAD in premenopausal and postmenopausal Indian women presenting with acute coronary syndrome.
Materials and Methods: This retrospective study was carried out at the Department of Cardiology, in a tertiary care cardiac center in Trivandrum, Kerala, India. Clinical and risk factor data were collected by reviewing hospital records. Coronary angiograms were assessed by two independent cardiologists.
Results: A total of 232 patients were included in the study, of which 66 were in the premenopausal group with mean age of (45.85 ± 4.25) years, and 166 in the postmenopausal group with mean age of (67.40 ± 6.40) years. The incidence of hypertension (31 [46.96%] vs. 133 [80.12%], P < 0.001) and diabetes mellitus (28 [42.42%] vs. 104 [62.65%], P < 0.005) was higher among the postmenopausal women. ST elevation myocardial infarction was significantly higher (5 [7.57%] vs. 31 [18.67%], P = 0.035) among postmenopausal women. Coronary angiography showed that the premenopausal women had higher incidence of angiographically normal coronaries (27 [40.90%] vs. 37 [22.29%], P = 0.004), whereas postmenopausal women had more atherosclerotic triple vessel disease (7 [10.60%] vs. 46 [27.71%], P = 0.005).
Conclusions: The CAD in premenopausal women is mostly nonatherosclerotic and nonobstructive. The conventional risk factors do not play a significant role among this subset of population.

Keywords: Acute coronary syndrome, coronary artery disease, premenopausal women, risk factors

How to cite this article:
Soman B, Rahaman MA, Rajan R, Vijayaraghavan G. Risk factor profile and disease pattern in premenopausal and postmenopausal Indian women presenting with acute coronary syndrome. J Clin Prev Cardiol 2016;5:78-83

How to cite this URL:
Soman B, Rahaman MA, Rajan R, Vijayaraghavan G. Risk factor profile and disease pattern in premenopausal and postmenopausal Indian women presenting with acute coronary syndrome. J Clin Prev Cardiol [serial online] 2016 [cited 2023 Jun 8];5:78-83. Available from: https://www.jcpconline.org/text.asp?2016/5/3/78/191098

Introduction

Unlike the rest of the world, the incidence of coronary artery disease (CAD) is on the rise in India, and the disturbing factor is that it is becoming more common among younger age groups. ^[1] Even though the men are more often affected, the women are not far behind. Evaluation of acute coronary syndrome (ACS) in premenopausal women has been overlooked, despite it being the leading killer of women in this age group, outpacing even breast cancer. ^[2]

The purpose of this study was to compare the risk factor profile for CAD in premenopausal and postmenopausal Indian women presenting with ACS.

Materials and Methods

This retrospective study was carried out at the Department of Cardiology, in a Tertiary Care Centre in Trivandrum, Kerala, India.

All female patients admitted over a 2-year period from 2012 January with chest pain and electrocardiography changes consistent with ischemic changes, and those who consented for undergoing coronary angiography (CAG) for diagnostic and/or revascularization purposes were included in the study. Cardiac troponin I was the biomarker used for the diagnosis of ACS. ACS was classified as myocardial infarction with either STEMI or non-STEMI (NSTEMI) based on the universal definition of myocardial infarction, ^[3] and unstable angina if there was evidence of ischemic chest pain occurring at rest or recent onset severe angina or had a crescendo pattern with no rise in cardiac biomarkers.

As the incidence of ACS was nonexistent in the female population under 30 years of age, patients under the age of 30 years, or with renal failure, postcoronary artery bypass graft status, and with any other contraindication for CAG, were excluded from the study. Also excluded were women between 50 and 60 years of age to allow for the weaning off of residual beneficial effect of circulating endogenous estrogen postmenopausal.

Collection of baseline risk factor data, including menstrual status, was done from the hospital records and also by obtaining relevant and detailed medical history from the patients. Since none of the patients from either group had smoking history, other conventional risk factors including diabetes mellitus (DM), hypertension, dyslipidemia, thyroid illness, and family history for premature CAD as per the American College of Cardiology/American Heart Association guidelines definitions were assessed in this study. Because of insufficient data nutritional status and obesity could not be assessed. The clinical presentations of patient were categorized as unstable angina and myocardial infarction as explained above.

Elective CAG was performed through standard femoral or radial artery approach. Angiographic data were collected by analyzing the angiograms by two interventional cardiologists. CAD was defined as >1 epicardial coronary segment with stenosis >50% and was diagnosed visually. All analyses were performed using Statistical Package for Social Sciences (SPSS) Version 16.0 (IBM) and Statistica software, version 12 (Statsoft, DELL). Results were expressed as mean ± standard deviation (SD) for numerical variables and frequencies and percentages for categorical variables in the forms of tables. Chi-squared P values below 0.05 were considered statistically significant.

Results

Of the 232 patients who were evaluated 66 were in the premenopausal group with age (range: 35-50 years) and mean of 45.85 ± 4.25 years (mean ± SD) and 166 were in the postmenopausal group with age (range: 60-94 years) mean age of 67.40 ± 6.40 years (mean ± SD), those in between 50 and 60 were excluded to allow for the weaning off of residual beneficial effect of endogenous estrogen postmenopausal. Upon comparing the risk factor profile [Table 1], it showed that 31 (46.96%) patients suffered from hypertension in the premenopausal age group, whereas the number was 133 (80.12%) in the postmenopausal age group; similarly, 28 (42.42%) and 104 (62.65%) women, respectively, had DM, 19 (28.78%) and 56 (33.73%) had dyslipidemia, 17 (25.75%) and 34 (20.48%) had history of thyroid illness, and 11 (16.66%) and 21 (12.65%) had family history for premature CAD. There was statistically significant association between age and history of hypertension (P < 0.001) and DM (P < 0.005), with greater incidence of heart transplant (HT) (31 [46.96%] vs. 133 [80.12%], P < 0.001) and DM (28 [42.42%] vs. 104 [62.65%], P < 0.005) in the postmenopausal group. Postmenopausal women have 0.367 and 0.558 times greater risk of CAD when compared to premenopausal women with hypertension and DM, respectively. There was statistically significant association between CAD and history of hypertension (95% confidence interval [CI] 0.248-0.544, P < 0.001) and DM (95% CI 0.369-0.844, P < 0.005) in the postmenopausal group.

Table 1: Risk factor profile of the study population

Click here to view

We further subdivided the premenopausal subset to have a closer look at the risk factor profile in the premenopausal age group [Table 2], we found that there was statistically significant association between the age and prevalence of systemic hypertension (2 [20%] vs. 29 [51.78%] P = 0.063) and DM (1 [10%] vs. 27 [48.21%] P = 0.024), with the association between the increasing age and DM being statistically significant. Interestingly, when we analyzed the pattern of the risk factor profile in the latter decade more closely [Table 3], we found that there was not much statistical significance in the incidence of DM (4 [40%] vs. 23 [50%], P = 0.566), whereas hypertension had significantly higher incidence in the above 45 age group (2 [20%] vs. 27 [58.69%], P = 0.026), inferring that diabetes occurs earlier than hypertension among premenopausal women. Occurrences of other risk factors were similar in both age groups. It was also observed that the conventional risk factors occurred with greater frequency as the age increased.

Table 2: Risk factor profile in premenopausal women

Click here to view

Table 3: Risk factor profile in 40-50 age groups

Click here to view

We also looked at the clinical presentation and initial diagnosis at presentation [Table 4] and found that more than three-fourth of the patients with ACS in the premenopausal age group presented with unstable angina 51 (77.27%) as against 112 (67.46%) in the postmenopausal group. There was statistically significant difference in the presentation with STEMI between the two groups (5 [7.57%] vs. 31 [18.67%], P = 0.035).

Table 4: Clinical presentation and initial diagnosis of the study population

Click here to view

Comparing the CAG [Table 5] revealed that 3% of the postmenopausal patients had left main stem (LMS) stenosis and nobody in the premenopausal group had LMS disease. The premenopausal women tended to have statistically significant percentage of angiographically normal coronaries (27 [40.90%] vs. 37 [22.29%], P = 0.004) and that postmenopausal women had more number of multi vessel disease, with statistically significant difference in the occurrence of triple vessel disease (TVD) (7 [10.60%] vs. 46 [27.71%], P = 0.005). Significantly higher incidence of nonatherosclerotic coronary lesions (muscle bridge) (7 [10.60%] vs. 5 [3.01%], P = 0.018) were seen among premenopausal women.

Table 5: Coronary angiographic profile of the study population

Click here to view

Discussion

In 2011, CVD caused one death per minute among women. ^[4] That represents about the same number of female deaths from cancer, chronic lower respiratory disease, and DM combined. ^[4]

Risk factors for ACS and CAD vary among men and women. Atypical presentation in women with vague and more generalized complaints makes it more difficult to diagnose CAD. ^[5],[6],[7] Incidence of CAD in the young is much higher among Indians as compared to the Westerns, (12-16% vs. 5%). ^[8],[9]

There is increasing evidence of age and gender disparity and also a lack of effective communication about heart disease risk factors and risk factor modification, even among patients with documented risk factors, particularly young women. ^[10],[11]

Hypertension and DM are the two major risk factors for CAD in women. ^[12]

In our study also, HT and DM along with dyslipidemia were the major risk factors to cause CAD; however, they were more prevalent among the postmenopausal women, also the percentage of women having HT and DM in the premenopausal group was significantly higher after 45 years of age. The proportion of patients with none of the above conventional risk factors and still having CAD was significantly higher in the premenopausal group signifying that there are factors other than the conventional risk factors contributing to the CAD of the young women.

Hypertension (71%) was the most common risk factor in our study as was observed in other studies. ^[13],[14] Hypertension is associated with 4-fold increased risk of ischemic heart disease (IHD) in females. ^[13],[15]

In our study, 57% females were diabetic, similar association of diabetes with IHD was observed in various other studies. ^{[9],[14],[16]} Diabetes carries a greater risk in females, as it is associated with platelet abnormalities, endothelial dysfunction in addition to negating the protective effects of estrogen. ^[17]

The coronary angiographic profile revealed a distinct difference in the pattern of CAD between the premenopausal and postmenopausal women, with greater incidence of angiographically normal epicardial coronaries in the premenopausal women, suggesting nonatherosclerotic pathology. Even in those with significant coronary lesions, single vessel disease was more common among premenopausal women, while among the postmenopausal women, multi-vessel disease was the norm, with majority of them having TVD.

Atherosclerotic burden is greater in postmenopausal women than premenopausal women as understood from the higher prevalence of obstructive CAD, especially multivessel disease in postmenopausal group ^[14] and that of normal epicardial coronaries in premenopausal group. In our study, the prevalence of multivessel disease (DVD and TVD) was 47.6% among postmenopausal women and 19.7% of premenopausal women had nonobstructive CAD and 41% had angiographically normal epicardial coronaries. Premenopausal women have lower incidence of IHD due to the protective effect of endogenous estrogen on the vascular endothelium, ^[18] whereas in the postmenopausal women, the risk of IHD doubles. ^[19],[20]

Many studies have found that the presence of obstructive CAD is less likely among women, when compared with men who undergo CAG. ^[21],[22] Normal or nonobstructive CAD is more commonly seen in younger premenopausal women, who may not have the conventional cardiac risk factors. ^[23],[24] More than 50% of these women with normal or nonobstructive CAD on CAG continue to have signs and symptoms of ischemia and do undergo repeat hospitalization and end up having repeat CAG at a later stage. ^[25],[26]

The National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation study revealed that women with nonobstructive coronary disease and evidence of myocardial ischemia have a relatively poor prognosis compared with women with nonobstructive coronary disease and no myocardial ischemia. ^[27] In spite of this, majority of the patients with normal or nonobstructive CAD are offered only reassurance. ^[28]

A lot of fallacies remain in treatment and prevention of IHD in women. Both the CRUSADE registry in UA/NSTEMI ^[29] and NRMI-1 investigators ^[30] in STEMI showed that compared to men, lesser number of women with CAD received the standard protocol medications for ACS and there was also delay in the use of fibrinolytic therapy. On their part, women defaulted from continuing the secondary prevention drugs for long-term, particularly aspirin, statins, and angiotensin-converting enzyme inhibitors. Women present more often with atypical symptoms, this coupled with their lack of awareness of the disease and the physicians' low awareness about the CAD in women often leads to misdiagnosis of CAD. ^[31]

In spite of a difference in risk factor profile and disease presentation, women in India continue to be treated based on the treatment guidelines and protocols based on trials which had predominantly males. ^[8],[9]

As reported in the VIRGO study, the importance of improved risk identification, clinical management, and patient education for adult women age ≤55 years, should be emphasized at all levels of healthcare interventions. ^[11]

Since the risk factor profile, pathology as well as the pattern of CAD is different in the premenopausal women, the treatment plan need to be different for this subset of the population and the management strategy needs to be tailor made for this population. It clearly shows that the preventive measures to reduce the CAD burden needs to be started at an earlier age and needs to be multipronged.

Limitations

Ours is a single center retrospective study and we included only those patients who came to the department with ACS, there was disparity in the baseline characteristics of the two groups studied, this is no way represents the true burden of the disease in the population and hence, our results may not be interpreted as the true reflection of the CAD in the population. Majority of our patients were the local population and as such they would not be representing the diverse disease pattern of the Indian population. Intravascular ultrasound (IVUS), optical coherence tomography or fractional flow reserve was not used in this study.

Conclusion

Our study revealed that the incidence of ACS among premenopausal Indian women is not as rare as has been perceived thus far. The risk factor profile may be same but there was a distinct difference in their prevalence in the two groups, the positive association of hypertension, DM, dyslipidemia, and CAD with increasing age was quite apparent. The study highlighted DM, hypertension, and dyslipidemia as major risk factors and also as potential targets for prevention. Majority of the premenopausal women presented with unstable angina and the incidence of MI (STEMI and NSTEMI) was much less. Even though the risk factors were the same, premenopausal women have a lower prevalence of obstructive CAD compared with postmenopausal women with similar symptoms and they had high incidence of angiographically normal epicardial coronaries, favoring vascular dysfunction, micro vascular coronary lesions, and more cases of nonatherosclerotic coronary lesions. Even among those with obstructive CAD, premenopausal women had fewer multi-vessel diseases, probably because of the protective effect of the endogenous circulating estrogen.

Women above the age of 30 years have CAD producing symptoms; however, these symptoms are often mistaken for noncardiac chest symptoms. The threshold for investigating young and middle aged women for CAD have to be brought down, so that the precise diagnosis is made possible. Identification of co-morbidities and risk factors of CAD in women will lead us to the correct diagnosis and early appropriate management. Noninvasive tests such as stress echocardiography and perfusion testing with cardiac magnetic resonance or single-photon emission computed tomography imaging should be used in identifying patients at risk, followed by further risk stratification by appropriate invasive testing such as CAG.

Better understanding of the risk factor profile, clinical presentation, and response to treatment is needed before devising an effective management plan for CAD in premenopausal women.

Acknowledgment

We would like to thank and acknowledge the contribution of Ms. Greeshma C Raveendran, biostatistician, in helping us with the advanced statistical analysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Krishnan MN. Coronary heart disease and risk factors in India - On the brink of an epidemic? Indian Heart J 2012;64:364-7.
2.	Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. For the National Registry of Myocardial Infarction 2 Participants. Sexbased differences in early mortality after myocardial infarction. N Engl J Med 1999;341:217-25. DOI: 10.1056/NEJM199907223410401.
3.	Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, et al. Third universal definition of myocardial infarction. Circulation 2012;126:2020-35.
4.	Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics-2015 update: A report from the American Heart Association. Circulation 2015;131:e29-322.
5.	Khan NA, Daskalopoulou SS, Karp I, Eisenberg MJ, Pelletier R, Tsadok MA, et al. Sex differences in acute coronary syndrome symptom presentation in young patients. JAMA Intern Med 2013;173:1863-71.
6.	Rubini Gimenez M, Reiter M, Twerenbold R, Reichlin T, Wildi K, Haaf P, et al. Sex-specific chest pain characteristics in the early diagnosis of acute myocardial infarction. JAMA Intern Med 2014;174:241-9.
7.	Canto JG, Rogers WJ, Goldberg RJ, Peterson ED, Wenger NK, Vaccarino V, et al. Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality. JAMA 2012;307:813-22.
8.	Dave TH, Wasir HS, Prabhakaran D, Dev V, Das G, Rajani M, et al. Profile of coronary artery disease in Indian women: Correlation of clinical, non invasive and coronary angiographic findings. Indian Heart J 1991;43:25-9.
9.	Gupta R, Puri VK, Narayan VS, Saran PK, Dwivedi SK, Singh S, et al. Cardiovascular risk profile in Indian women. Indian Heart J 1999;51:679.
10.	Lichtman JH, Leifheit-Limson EC, Watanabe E, Allen NB, Garavalia B, Garavalia LS, et al. Symptom recognition and healthcare experiences of young women with acute myocardial infarction. Circ Cardiovasc Qual Outcomes 2015;8 2 Suppl 1:S31-8.
11.	Leifheit-Limson EC, D'Onofrio G, Daneshvar M, Geda M, Bueno H, Spertus JA, et al. Sex differences in cardiac risk factors, perceived risk, and health care provider discussion of risk and risk modification among young patients with acute myocardial infarction: The VIRGO study. J Am Coll Cardiol 2015;66:1949-57.
12.	Bettegowda S. Clinical profile of ischemic heart disease in women with special reference to the risk factors. Sch J App Med Sci 2014;2:3020-5.
13.	Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet 2004;364:937-52.
14.	Oomman A, Sathyamurthy I, Ramachandran P, Verghese S, Subramanyan K, Kalarickal MS, et al. Profile of female patients undergoing coronary angiogram at a tertiary centre. J Assoc Physicians India 2003;51:16-9.
15.	Wenger NK. Coronary heart disease: The female heart is vulnerable. Prog Cardiovasc Dis 2003;46:199-229.
16.	Kalyani RR, Lazo M, Ouyang P, Turkbey E, Chevalier K, Brancati F, et al. Sex differences in diabetes and risk of incident coronary artery disease in healthy young and middle-aged adults. Diabetes Care 2014;37:830-8.
17.	Sowers JR. Diabetes mellitus and cardiovascular disease in women. Arch Intern Med 1998;158:617-21.
18.	Chakrabarti S, Morton JS, Davidge ST. Mechanisms of estrogen effects on the endothelium: An overview. Can J Cardiol 2014;30:705-12.
19.	Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE, et al. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study. N Engl J Med 1991;325:756-62.
20.	Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: A quantitative assessment of the epidemiologic evidence. Prev Med 1991;20:47-63.
21.	Hochman JS, Tamis JE, Thompson TD, Weaver WD, White HD, Van de Werf F, et al. Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global use of strategies to open occluded coronary arteries in acute coronary syndromes IIb investigators. N Engl J Med 1999;341:226-32.
22.	Bellasi A, Raggi P, Merz CN, Shaw LJ. New insights into ischemic heart disease in women. Cleve Clin J Med 2007;74:585-94.
23.	Sharaf BL, Pepine CJ, Kerensky RA, Reis SE, Reichek N, Rogers WJ, et al. Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] study angiographic core laboratory). Am J Cardiol 2001;87:937-41.
24.	Bugiardini R, Bairey Merz CN. Angina with "normal" coronary arteries: A changing philosophy. JAMA 2005;293:477-84.
25.	Johnson BD, Shaw LJ, Pepine CJ, Reis SE, Kelsey SF, Sopko G, et al. Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: Results from the NIH-NHLBI-sponsored Women's Ischaemia Syndrome Evaluation (WISE) study. Eur Heart J 2006;27:1408-15.
26.	Shaw LJ, Merz CN, Pepine CJ, Reis SE, Bittner V, Kip KE, et al. The economic burden of angina in women with suspected ischemic heart disease: Results from the National Institutes of Health - National Heart, Lung, and Blood Institute - Sponsored women's ischemia syndrome evaluation. Circulation 2006;114:894-904.
27.	Johnson BD, Shaw LJ, Buchthal SD, Bairey Merz CN, Kim HW, Scott KN, et al. Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: Results from the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation 2004;109:2993-9.
28.	Panza JA. Myocardial ischemia and the pains of the heart. N Engl J Med 2002;346:1934-5.
29.	Blomkalns AL, Chen AY, Hochman JS, Peterson ED, Trynosky K, Diercks DB, et al. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: Large-scale observations from the CRUSADE (can rapid risk stratification of Unstable angina patients suppress adverse outcomes with early implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol 2005;45:832-7.
30.	Vaccarino V, Rathore SS, Wenger NK, Frederick PD, Abramson JL, Barron HV, et al. Sex and racial differences in the management of acute myocardial infarction, 1994 through 2002. N Engl J Med 2005;353:671-82.
31.	Mosca L, Linfante AH, Benjamin EJ, Berra K, Hayes SN, Walsh BW, et al. National study of physician awareness and adherence to cardiovascular disease prevention guidelines. Circulation 2005;111:499-510.