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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 85-92

Gender-based differences in coronary artery disease: A prospective observational study from a North Indian state


Department of Cardiology, SKIMS Soura, Srinagar, Jammu and Kashmir, India

Date of Submission22-Mar-2020
Date of Decision06-Jun-2020
Date of Acceptance11-Jun-2020
Date of Web Publication4-Aug-2020

Correspondence Address:
Dr. Mohd Iqbal Dar
Department of Cardiology, SKIMS Soura, Srinagar - 190 011, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_13_20

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  Abstract 


Introduction: Coronary artery disease (CAD) causes significant morbidity and mortality in both genders, however, the importance of CAD in females is underappreciated.
Aims and Objectives: This study is aimed at investigating the gender-based differences in presentation, evaluation, and outcome of CADs in a northern state of India.
Materials and Methods: This is a prospective study conducted over a period of 3 years. All the patients with CAD (acute coronary syndrome or chronic stable angina) enrolled in the study were evaluated for clinical profile, angiographic profile, and the outcome.
Results: A total of 3660 patients were enrolled in this study. There were 56.2% of males and 43.8% of females. Smoking as risk factor was noted in 69.6% of males and 7.9% of females, hypertension in 52.9% of males versus 65.4% of females, diabetes in 42.5% of males versus 60.7% of females, and obesity in 46.2% of males versus 57.3% of females. Male versus female mean body mass index was 24.7 versus 27.4, low-density lipoprotein 112.8 versus 123.7, high-sensitivity C-reactive protein 1.5 versus 2.9, and Lp(a) 274.9 versus 442.1, respectively. On coronary angiographic evaluation, male versus female single-vessel involvement was seen in 54.1% versus 58.8% of patients, double-vessel disease in 31.6% versus 27.6%, left main disease in 1.7% versus 3.6%, and spontaneous coronary artery dissection in 0.9% versus 1.5% patients, respectively. The overall mortality in males was 4.03% and 5.11% in females.
Conclusion: Despite its atypical presentation, CAD has the worst outcome in women than men. Greater awareness of these gender-based differences will significantly improve the management and outcome of CAD in women.

Keywords: Coronary artery disease, gender-based differences in coronary artery disease, outcome in coronary artery disease


How to cite this article:
Sharma AK, Dar MI, Iqbal M, Tramboo NA. Gender-based differences in coronary artery disease: A prospective observational study from a North Indian state. Heart India 2020;8:85-92

How to cite this URL:
Sharma AK, Dar MI, Iqbal M, Tramboo NA. Gender-based differences in coronary artery disease: A prospective observational study from a North Indian state. Heart India [serial online] 2020 [cited 2020 Oct 31];8:85-92. Available from: https://www.heartindia.net/text.asp?2020/8/2/85/291353




  Introduction Top


For many years, there was an underestimation of the importance of coronary artery disease (CAD) in women. Recent studies have shown that coronary heart disease (CHD) is the leading cause of death in women leading to approximately 400,000 deaths in women per year in the USA.[1] Women older than 50 years experiencing typical or atypical angina or women younger than 50 years with typical angina are classified as intermediate- or high-risk patients for CHD by the American Heart Association. Additionally it is stated that in absence of risk factors like diabetes or peripheral artery disease, the symptoms of CAD in women have low specificity irrespective of age.[2]

In general, there are many sex-related differences with regard to CHD. First, compared to men, older and smaller women are more prone to hypertension, diabetes mellitus, hypercholesterolemia, peripheral vascular disease, and unstable angina and have more severe angina (Canadian Cardiovascular Society Class III–IV).[3]

Moreover, despite women's less extensive or less severe disease among patients with stable and unstable angina pectoris compared to men, the former have more severe symptoms or they are more symptomatic independent of the extent of disease.[4]

Furthermore, although left ventricular systolic dysfunction is less frequent in women, they more often have congestive heart failure.[3] Women with CHD also receive less intensive treatment than men as their more increased home environment obligations make them neglect health-care needs.[5] Hence, despite a lower incidence of myocardial infarction and its later presentation in women than in men, the former are associated with higher mortality and morbidity rates.[6] Although men experience coronary events four times more than women, women are more likely to die after the first episode of an acute myocardial infarction (AMI).[5] Women are generally characterized by higher short-term mortality than men partly due to their higher age, higher comorbidity, and less aggressive treatment. Moreover, gender differences with regard to post-AMI mortality risk are even more apparent in young women compared with similarly aged men.[7] In addition, a significantly higher prevalence of adverse outcomes such as bleeding complications is reported in women after reperfusion therapies.[1],[3] Finally, women are more likely to be widowed or live alone and more frequently suffer from depression and less likely to return to their previous psychosocial status after an AMI.[7]

Aims and objectives

This study was aimed to evaluate differences in conventional risk factors, clinical profile, coronary angiography profile, management, and inhospital outcome in CAD based on gender.


  Materials and Methods Top


This prospective observational study was conducted over a period of 3 years from August 2017 to July 2019 and included the patients admitted with CAD who underwent coronary angiography and percutaneous coronary intervention (PCI).

Inclusion criteria

this study included patients of both genders with acute coronary syndrome (ACS) or chronic stable angina (CSA) and age >18 years and <80 years who were able to provide informed consent to participate in the study.

Exclusion criteria

patients aged <18 years and >80 years and patients suffering from end-stage diseases such as end-stage renal disease, chronic liver disease, and malignancy were excluded from the study.

Study variables

Data were collected regarding demographic characteristics, coronary risk factors (smoking, family history of premature cardiovascular disease, dyslipidemia, hypertension, and diabetes mellitus), and other comorbidities (body mass index (BMI)] in patients with both stable and unstable CAD. Cardiac status at presentation, inpatient clinical care (time to treatment), types of adjunctive treatment used, and angiographic severity were also noted. Coronary stenosis was described by the standard flow limitation definitions, a narrowing in diameter of 50%–70% in epicardial coronaries except in the left main was considered nonobstructive disease, and stenosis of >70% was considered obstructive CAD. In case of left main, stenosis of 20%–50% was considered nonobstructive and stenosis of >50% was considered obstructive CAD.[8]

The outcomes of interest were inhospital, 30-day, and 6-month mortality post-PCI. A multivariate logistic regression model was used to determine the risk association between variables identified and mortality for total population at discharge, 30 days, and 6 months. Collinearity between variables was assessed before including in the final model. Subsequently, a multivariate logistic regression model was also developed to determine the association between gender and mortality at discharge, 30 days, and 6 months.

The statistical data analysis was done using SPSS version 23 (Armonk, NY, USA: IBM Corp).

Observations

The overall design of the study is depicted in the flowchart given in [Figure 1].
Figure 1: Flowchart of the study

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The study included a total of 3660 consecutive patients which include 56.2% (2057) of males and 43.8% (1603) of females. Majority of male 795 (38.6%) and female 903 (56.3%) patients belonged to 60–79 years' age group. The mean age of male patients was 57.3 ± 18.72 and female patients was 62.9 ± 23.84 years. There were 1384 (37.8%) rural patients and 2276 (62.2%) urban patients in our study

The distribution of various risk factors for CAD in the study population is shown in [Table 1]. Smoking was the most common risk factor in males and hypertension was the most common risk factor in females. There were statistically significant gender-based differences noted in smoking, hypertension, diabetes, and obesity.
Table 1: Gender-wise distribution of risk factors of study population

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The clinical profile of the study population is depicted in [Table 2]. With respect to the patient characteristics, all the differences between sexes were significant. Female patients were more obese, with baseline BMI of 27.4 ± 4.27 versus 24.7 ± 3.91 of males.
Table 2: Gender-based differences in clinical profile of study population

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Xanthelasma/acanthosis nigricans were seen more commonly in 887 females (55.3%) versus 968 males (47.1%) with P < 0.001. Presentation as Killip Class I was seen in 1880 (91.4%) males versus 1348 (84.1%) females, Killip Class II in 126 (6.1%) males versus 171 (10.7%) females, Killip Class III in 24 (1.2%) males versus 45 (2.8%) females, and Killip Class IV in 27 (1.3%) males versus 39 (2.4%) females. Female patients mostly presented with Killip Class II–IV with statistically significant P value. ST-elevation myocardial infarction (STEMI) was clinical presentation in 912 (44.3%) males versus 430 (26.8%) females with P < 0.001, Non-STEMI744 (36.2%) males versus 911 (56.8%) females with P < 0.001, and CSA 312 (15.2%) males versus 197 (12.3%) females with P < 0.001.

Noninvasive investigations were compared with gender, and it was found that electrocardiogram (ECG) was abnormal in 1962 (95.4%) males and 1432 (89.3%) females. Exercise ECG was positive in 249 (12.1%) males versus 124 (7.7%) females (P < 0.001).

The angiographic profile of the study population is given in [Figure 2].
Figure 2: Angiographic profile of the study population

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Intervention profile was compared between the study population, and it was found that drug-eluting stents (DESs) were implanted in 1892 (92.0%) males versus 1282 (80.0%) females with P < 0.001, no bare-metal stent implanted in both the study groups. Plain old balloon angioplasty was performed in 178 (8.7%) males versus 306 (19.08%) females with P < 0.001. Intravascular ultrasound was performed in 477 (23.2%) males versus 252 (15.7%) females, P < 0.001. Intra-aortic balloon pump was used in 43 (2.1%) males versus 27 (1.7%) females, P < 0.001.

Treatment profile at discharge was compared between the study groups, and it was found that 2044 (99.4%) males versus 1592 (99.3%) females were on aspirin. Two thousand and thirty-four (98.9%) males versus 1471 (91.8%) females were on clopidogrel, 101 (4.9%) males versus 42 (2.6%) females on ticagrelor, and 59 (2.9%) males versus 14 (0.9%) females on prasugrel. Statin prescription was noted in 1941 (94.4%) males versus 1501 (93.6%) females, angiotensin-converting enzyme/angiotensin receptor blocker in 1386 (67.4%) males versus 1103 (68.8%) females, and beta-blockers in 1607 (78.1%) males versus 1504 (93.8%) females. Arrhythmic event was compared between the two study groups, and it was found that ventricular tachycardia was observed in 100 (4.9%) males versus 96 (6.0%) females, ventricular fibrillation was noted in 45 (2.2%) males versus 42 (2.6%) females, AF in 47 (2.3%) males versus 17 (1.1%) females, and CHB in 115 (5.6%) males versus 33 (2.1%) females, with statistically significant P value.

The outcome of the study in terms of hospital deaths, major adverse cardiac event (MACE), and access-related complication is shown in [Table 3]. The overall inhospital mortality in females (82 [5.11%]) was higher than in males (83 [4.03%]).
Table 3: Inhospital outcome of study population undergoing percutaneous transluminal coronary artery angioplasty

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  Discussion Top


The presentations, complications, prognoses, final diagnoses, and treatments of CAD differ between men and women; these dissimilarities present formidable challenges to experts involved in the domain of cardiology.[9] Unfortunately, for all the data in the existing literature on such differences,[10] there is a dearth of relevant information in Kashmir. CAD risk factors are relatively identical in both sexes; nevertheless, there are some gender-specific differences in response. Some studies have shown that age, diabetes, and levels of certain lipoproteins are stronger risk factors in women.[11] In our patients, except for cigarette smoking and family history of CAD, all the traditional risk factors were seen in the females more frequently. Among the risk factors that were more prevalent in our female participants, hypertension and diabetes mellitus had the highest ratio. Surprisingly, in contrast to Lewington et al.'s meta-analysis,[12] which reported that the association between hypertension and ischemic heart disease risk was only slightly stronger in women than men, our findings demonstrated a very strong association. Meanwhile, in our study, 65.4% of the females and 52.9% of the males with CAD were hypertensive, indicating that hypertension played a great role in the development of CAD in our patients, not least in the women. An incisive insight into why Kashmiri women with CAD are more prone to hypertension than Kashmiri men requires further research, but it could be argued that it is in consequence of differences in genetics, eating habits, and/or lifestyle. In the present study, the female CAD patients were more obese than the men and their BMI was higher than that of the men, which must have rendered them more susceptible to hypertension. Cardiovascular disorders are twice as common in women with diabetes mellitus as those in women without it. Mortality in patients with CAD is three to five times higher in diabetic women than that in nondiabetic ones, while the risk is two to three times more in diabetic men than that in nondiabetic ones.[13]

In our study, diabetes was much more prevalent in females than in males and had a greater association with CAD. In contrast to previous research reporting, the rate of diabetes was 60.7% in the females and 42.5% in males in our CAD patients. Diabetes can, therefore, be deemed a potent risk factor in our female patients. One likely culprit for the higher rate of diabetes among Kashmiri female CAD patients, aside from some genetic factors, is the fact that Kashmir women, especially at their older age, are less physically active and more overweight than men.[14] In our study, the rate of hypercholesterolemia in either sex was only slightly higher than what is seen in the general population. Unlike hypercholesterolemia, which is more prevalent in females in the general population of Kashmir, hypertriglyceridemia is more common in men (162.5 ± 16.93 men vs. 158 ± 18.5 in women). In our study, females have higher baseline low-density lipoprotein than males (123.7 ± 39.8 in females vs. 112.8 ± 27.64 in males). Females show higher high-sensitivity C-reactive protein (hsCRP) 2.9 ± 4.61 versus male 1.5 ± 2.47 (P < 0.001) consistent with previous study. As to the age of patients, it is a universal finding that ischemic heart disease is less prevalent in females before menopause and females tend to develop this disease later than males.[15] This chimes in with the findings of our study in that the CAD females were 5 years older than the males.

ACS and myocardial infarction (MI) had a higher frequency in our male patients, whereas the female patients presented with CSA and unstable angina more frequently. It means that the presentations of our female participants were less severe than those of our male patients. It can be argued that men may be more prone to severe or acute coronary events than women. On the other hand, there may be no definite difference between the two sexes, but men may seek medical advice late and thus exhibit more severe symptoms. Furthermore, the false positiveness of diagnostic measures such as the exercise tolerance test or cardiac perfusion scan could be to blame for the selection of women with less severe symptoms for coronary angiography. Since the false positiveness of these diagnostic tests is considerably high in women, many female patients undergo coronary artery angiography despite having minimal symptoms. The other possible reason for the less severe presentations of our female patients could be sought in their anxiety about developing CAD, which could prompt them to demand coronary angiography. Indubitably, further research is required to shed light on the factors responsible for the differences between men and women in terms of CAD presentations.

Medical treatment via noninvasive modalities was recommended to most of our female patients, where invasive procedures (especially PCI) were recommended to most of our male patients. Such dissimilarities in recommendations should come as no surprise given the presentations and angiographic results. In the study sample, both male and female patients with extensive CAD were recommended to undergo invasive procedures more frequently than noninvasive modalities, but medical treatment was recommended significantly more frequently to the females. One possible reason is that invasive treatments (either PCI or coronary artery bypass grafting) in women frequently tend to be complicated.[16]

There were no significant differences in the Lp(a) plasma level between men and women with negative angiography, while the women with positive findings had Lp(a) levels almost twice as high as men. Our findings suggest that Lp(a) measurement is of value in investigation of patients at risk for CAD and that it is a particularly useful predictor of risk in women. Our study also supports the widespread prevalence of low Vitamin D in this region. Low Vitamin D is associated with an increase in the rate of MI among males. Hypertension increases the risk of CAD in the presence of low Vitamin D regardless of gender.[17]

Despite the greater risk factor burden, women paradoxically have less severe obstructive epicardial CAD at elective angiography than men and have more incidence of microvascular disease, coronary spasm, and spontaneous coronary artery dissection.[18] In concordance with other studies, our study showed that women are less likely to present with STEMI than Non- ST Elevation Acute coronary syndrome compared with men.[19]

In concordance with other studies, major bleeding events in the hospital were significantly higher among females in our study. Reasons for this include more vascular access site bleeding due to smaller artery size, peripheral artery disease, and inappropriate doses of antithrombotic medications in women. Bleeding, the most significant nonischemic complication associated with PCI, is an independent predictor of inhospital and 1-year mortality.

Median (interquartile range) high-sensitive troponin T concentrations were significantly lower in women (10.2 ng/l than in men 14.5 ng/l; P < 0.0001), and a higher proportion of men (43.6%) than women (29.1%) were above the current established upper recommended limit of 14 ng/l (P < 0.0001). Compared with men, women were more likely to be obese, diabetic, and use insulin have higher glycosylated hemoglobin and high-density lipoprotein cholesterol, a hsCRP, and LPa.

For suspected CAD, treadmill testing (TMT) is the most common noninvasive test sought, but the value of TMT in the evaluation of coronary disease in women remains hugely debated. The sensitivity and specificity of TMT, as described by multiple meta-analyses in men and women, are 72% versus 61% and 77% versus 70%, respectively.[20] The sensitivity and specificity of TMT are clearly higher in males. The findings of our study were consistent with these observations.

Analysis of coronary angiographic findings showed that women most commonly suffered from single-vessel disease (58.8%), followed by double-vessel disease (27%), triple-vessel disease (07%), and left main disease (3.6%). Women most commonly involved right coronary artery, followed by the left circumflex artery, while in males, the most commonly involved vessel is left anterior descending artery. Chronic total occlusion (CTO) was more commonly seen in males (6.8%, n = 139). Both men and women show comparable type C lesion, bifurcation lesion, and calcification with insignificant P value. Premenopausal women more commonly show spontaneous coronary artery dissection (n = 24, 1.5%, P < 0.001).

The main outcome of the study showed that the mortality in male patients with CAD after PCI was lower than that of females; the male patients with CAD after PCI harbored a lower incidence of MACE. The male patients with CAD after PCI overwhelmed females in long-term revascularization. These gender-based differences in mortality were in agreement with multiple previous systematic reviews.[21],[22]

The high mortality in female patients with CAD after PCI had been largely attributed to more adverse cardiovascular risk profiles compared with males. This study has confirmed that the female patients with CAD were older than males and had more left main disease, which may also attribute to the high mortality of female patients, consistent with the National Cardiovascular Data Registry (ACTION Registry) of America.[23] Meanwhile, in this study, it had also been verified that the female participants were more prone to suffer from cardiogenic shock, which was considered as another important indicator for higher mortality in female patients with CAD after PCI. The same consequences were obtained by a meta-analysis by Conrotto etal.[24]

The incidence of MACE was higher in females than males. The reasons for the above differences should first be attributed to the fact that the mortality in female patients with CAD after PCI is higher than that of males. Moreover, possessing more adverse cardiovascular risk profile was also an important factor for high incidence of MACE in female patients with CAD; the baseline data of this study had witnessed this proposition. The study of Jakobsen etal.[25] also showed that female patients with CAD were burdened with more complications and worse hemodynamic status compared with males. The gender difference of MACE was still largely attributed to the higher incidence of heart failure in female patients with STEMI in some cohort.[26],[27],[28]

In summary, the above pathological factors had led to a high incidence of MACE in female patients with CAD after PCI. It is noteworthy that females had a worse clinical outcome, which reminds that physicians should pay more attention to female patients in clinical practice.

This study also showed that male patients with CAD after PCI had the disadvantages of revascularization compared with females in the long-term follow-up, which was consistent with the parts of previous observational studies.[25] This may be due to high smoking incidence in males as detailed in the baseline data of this study. On the contrary, the low incidence of revascularization in female participants may be contributed by lower follow-up rates, atypical symptoms, difficult identification of myocardial ischemia, unwillingness of receiving invasive examinations, as well as the prejudices of doctor that female participants might harbor a lower rate of coronary arteriography during follow-up.[29] In addition, female participants with CAD after PCI had higher mortality during short- and long-term follow-up, which might reduce the chance of next revascularization.

Moreover, a research had indicated that the application of DESs could decrease the probability of coronary artery revascularization in female patients with PCI. Furthermore, the coronary artery of male patients with CAD is prone to harbor complicated lesions, including bifurcation lesions, CTO, and discreet lesions, while female patients usually have diffuse nonobstructive atherosclerosis with associated microvascular dysfunction also known as female pattern CAD.[30]


  Conclusion Top


CAD continues to be a major contributor to mortality in both men and women. Majority of women present with atypical symptoms and are thus underevaluated. We need to be more aggressive in treating women with CADs, especially young women, as they may suffer significantly worse outcomes. This study emphasizes the need for greater awareness of these gender-based differences in the treating physician community for better outcome.

Acknowledgment

We would like to thank the staff of our department for their generous help throughout this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical Approval

The study protocol was reviewed and cleared by the Institutional Ethics Committee (IEC) and an informed consent was obtained from patients/relatives for utilization of data for research purposes (Ref no. IEC/SKIMS protocol101/2017).



 
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