Gender differences in coronary profiles of chronic coronary syndrome patients: A single-center pilot study from Kuwait

Maraam AlRashed; Rajesh Rajan; Mohammed Al-Jarallah; Raja Dashti; Salman Hussain; Ahmad Al Saber; Peter A Brady; Ibrahim Al Zakwani; Ibrahim El Khouly

doi:10.4103/ACCJ.ACCJ_16_21

ORIGINAL ARTICLE

Year : 2022 | Volume : 4 | Issue : 1 | Page : 20-26

Gender differences in coronary profiles of chronic coronary syndrome patients: A single-center pilot study from Kuwait

Maraam AlRashed¹, Rajesh Rajan², Mohammed Al-Jarallah², Raja Dashti², Salman Hussain³, Ahmad Al Saber⁴, Peter A Brady⁵, Ibrahim Al Zakwani⁶, Ibrahim El Khouly²
¹ Department of Medicine, Kuwait University, Kuwait City, Kuwait
² Department of Cardiology, Sabah Al Ahmad Cardiac Centre, Kuwait City, Kuwait
³ Department of Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland
⁴ Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK
⁵ Department of Cardiology, Illinois Masonic Medical Center, Chicago, IL, USA
⁶ Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman

Date of Submission	18-Jul-2021
Date of Decision	23-Aug-2021
Date of Acceptance	29-Oct-2021
Date of Web Publication	08-Dec-2021

Correspondence Address:
Maraam AlRashed
Faculty of Medicine, Kuwait University, Kuwait City
Kuwait

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ACCJ.ACCJ_16_21

Abstract

Background: Chronic coronary syndrome (CCS) is a recently defined entity that necessitates evaluating individual clinical risk factors in this cohort. Objective: The objective of the present study was to evaluate patients with CCS and examine their coronary profiles in order to delineate differences between genders. Methods: A cross-sectional analysis was conducted on 51 patients who met the criteria of CCS and have undergone both coronary angiography and CT coronary angiography. Analyses were conducted using univariate statistics. Results: The cohort consisted of mainly Kuwaiti nationals with an average age of 61 ± 10 years. Females consisted 41% of the cohort, were older by an average of 9 years (P = 0.001), and were overweight (67% vs. 44%). Males were more likely to be cigarette consumers (47% vs. 14%; P = 0.022). Females had more comorbidities such as hypertension (86% vs. 80%) and atrial fibrillation (24% vs. 10%), excluding stroke (0% vs. 3.3%), and coronary artery disease (71% vs. 83%). Males had an elevated level of creatinine (88 vs. 72 umol/L; P = 0.045). Other results were not significantly different between genders. Males were more likely to be prescribed aspirin upon admission (100% vs. 81%; P = 0.026), however, this difference decreased upon discharge (97% vs. 86%; P = 0.297). Recurrent ischemia (12%; n = 6) was the most common major outcome recorded. Conclusions: This study shows that females were more likely to be older than their male counterparts whereas males were more often on aspirin and more likely to be cigarette smokers. We found no significant differences in comorbidities, admission laboratory and imaging results, nor outcomes between genders.

Keywords: Chronic coronary syndrome, coronary artery disease, gender

How to cite this article:
AlRashed M, Rajan R, Al-Jarallah M, Dashti R, Hussain S, Al Saber A, Brady PA, Al Zakwani I, El Khouly I. Gender differences in coronary profiles of chronic coronary syndrome patients: A single-center pilot study from Kuwait. Ann Clin Cardiol 2022;4:20-6

How to cite this URL:
AlRashed M, Rajan R, Al-Jarallah M, Dashti R, Hussain S, Al Saber A, Brady PA, Al Zakwani I, El Khouly I. Gender differences in coronary profiles of chronic coronary syndrome patients: A single-center pilot study from Kuwait. Ann Clin Cardiol [serial online] 2022 [cited 2023 Jun 4];4:20-6. Available from: http://www.onlineacc.org/text.asp?2022/4/1/20/349444

Introduction

Coronary artery disease (CAD) is defined as a pathological process that is characterized by atherosclerotic plaque accumulation in the coronary arteries that can be obstructive or nonobstructive.^[1] It accounts for 610,000 annual deaths in the USA alone and is the 3^rd leading cause of mortality worldwide, accounting for 18.6 million deaths in 2019 alone, with as much as 58% of these occurring in Asia.^[2],[3] Numerous factors, both modifiable and nonmodifiable, contribute to the formation of this disease, but it is well established that no single factor is sufficient to directly establish clinically apparent disease. The nonmodifiable risk factors include age >35 in both men and women as well as the male gender, with females reaching the risk levels of males post menopause.^[3] It is a well-established fact that CAD can be modified by lifestyle changes, pharmacological interventions, and revascularization, which may result in either disease stabilization or regression.^[4] CAD has traditionally been described to have two subsets: stable angina and acute coronary syndrome (ACS), which encompasses unstable angina and myocardial infarction. In 2019, the European Society of Cardiology (ESC) introduced a new entity designated to take the place of stable angina, aptly termed chronic coronary syndrome (CCS), highlighting the fact that CAD is a dynamic process of plaque accumulation and functional alterations of coronary circulation characterized by relatively stable and unstable periods, that invariably progress with time, even in clinically apparently silent periods.^[4]

There has traditionally been a relative paucity of data specifically targeting profiles of female patients with CAD, and even less so of females with CCS, most probably due to the consensus that places premenopausal women in the category of those at lower risk for CAD than their male counterparts at a similar age. There has also been some data published indicating that females may have worse presentations or outcomes due to their perceived “low-risk” status.^[5] One study, conducted in Poland using an established registry, aimed to evaluate long-term outcomes of approximately 11,000 patients with CCS, reported that only 35% of their cohort were women.^[6] Therefore, we aimed to analyze the gender-related differences in those with CCS. Given the relative paucity of data involving CCS since the term was introduced, there have been minimal attempts to outline the coronary profile of individuals with CCS, and still further to delineate the gender differences, if any, in those with this syndrome, with the aim of clear differentiation in terms of their individual clinical risk factors.

Methods

Study subjects and setting

Our study was conducted as a retrospective review of routine information obtained and collated in medical files of patients treated at the Sabah Al Ahmed Cardiac Center at Al-Amiri Hospital in the State of Kuwait, a tertiary hospital for nationals and expatriates living in the health district of Kuwait City. Those eligible for recruitment into our study included patients of either gender and any nationality, aged between 25 and 95 years who met the criteria of CCS. We compiled a list of all patients who underwent both computed tomography coronary angiography (CTA) and coronary angiography (CAG) between January 2018 and January 2020. Using the criteria outlined below, we divided our cohort into those with ACS and/or severe valvular disease and those with CCS. We then compared individual factors related to the coronary risk profiles in a total of 51 patients with CCS.

Definition of chronic coronary syndrome

The criteria for inclusion of patients with CCS were based on the six clinical entities outlined by the ESC describing the most common clinical situations encountered in those who have or are suspected to have CCS as well as the clinical definition of stable angina, factoring out patients who present with acute coronary events. Patients were permitted to enroll if they fulfilled ≥1 of the ensuing criteria: (i) patients with symptoms of stable angina and CAD and/or dyspnea; (ii) patients with recent onset of left ventricular dysfunction or heart failure and suspected CAD; (iii) patients with stabilized symptoms <1 year after ACS or patients with recent revascularization, including those who are asymptomatic; (iv) patients with stabilized symptoms >1 year after diagnosis or revascularization, including those who are asymptomatic; (v) patients with angina and suspected vasospastic or microvascular disease; and (vi) asymptomatic patients found to have CAD during screening.^[4] All criteria constituting stable CAD were included in this definition, therefore including an established pattern of angina or a mismatch of blood flow causing ischemia to the myocardium, a history of myocardial infarction, and coronary obstruction indicated by either cardiac catheterization or CTA.^[7] Patient status was constituted stable if they were either asymptomatic or intervention in the form of medication or coronary revascularization alleviated their symptoms.

Definition of acute coronary syndrome and exclusion

Criteria for classification, and subsequent exclusion, of ACS patients included: (i) patients with new-onset angina or patients with unstable angina; (ii) patients with ST-elevation myocardial infarction; and (iii) patients with non-ST-elevation myocardial infarction, which is typically evaluated using various clinical examinations and biological markers.^[8] Additionally, patients with severe valvular disease necessitating surgical intervention were excluded.

Statistical analysis

Descriptive statistics were used to describe the data. For categorical variables, frequencies and percentages were reported. Differences between groups were analyzed using Pearson's χ² tests (or Fisher's exact tests for expected cells of <5). For continuous variables, mean and standard deviation were used to present the data while analysis was performed using Student's t-tests. For nonnormal distributed continuous variables, median and interquartile range were used to summarize the data and analysis performed using Wilcoxon–Mann–Whitney tests. An a priori two-tailed level of significance was set at < 0.05 level. Statistical analyses were performed using SPSS version 27 (SPSS, Inc., Chicago, IL, USA) and R statistics version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria).

Results

As shown in [Table 1], the overall mean age of the cohort was 61 ± 10 years, 59% (n = 30) were males, and 67% (n = 34) were Kuwaitis. The overall mean body mass index (BMI) was 32 ± 8 kg/m² and 33% (n = 17) were smokers. Females were significantly older compared to males (66 vs. 57 years; P = 0.001) while males were more likely to be smokers than females (47% vs. 14%; P = 022). No statistically significant differences were noted with regard to BMI (P = 0.213) and nationality (P = 0.763) between the genders.

Table 1: Baseline characteristics of the subjects (n=51)

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In terms of comorbidities, as shown in [Table 2], there were no statistically significant differences between the genders. However, caution should be exercised when interpreting the results due to low sample size. The majority (78%; n = 40) had established CAD at the time of presentation. The three other most prevalent comorbidities were hypertension (82%; n = 42), diabetes mellitus (63%; n = 32), and dyslipidemia (63%; n = 32). There were also no significant differences in admission vital signs between the genders [Table 3], with the overall mean heart rate, SBP, and DBP as 77 beats/min, 133 mmHg, and 72 mmHg, respectively. As shown in [Table 4], electrocardiogram findings showed that 16% (n = 8) of the patients had atrial fibrillation while 7.8% (n = 4) of the cohort had left bundle branch block myocardial infarction. Males had significantly higher levels of serum creatinine than females (88 vs. 72 μmol/L) while there were also no significant differences in the admission laboratory results between males and females [Table 5].

Table 2: Comorbidities associated with chronic coronary syndrome patients based on gender

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Table 3: Admission vitals in chronic coronary syndrome patients based on gender

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Table 4: Electrocardiogram finding of chronic coronary syndrome patients based on gender

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Table 5: Admission laboratory results of chronic coronary syndrome patients based on gender

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CT angiography (CTA) results [Table 6] showed that most of the patients exhibited blockage of the left anterior descending (LAD) artery (52%; n=24) followed by left circumflex artery (LCX) (33%; n=15), right coronary artery (RCA) (22%; n=10) and posterior descending artery (PDA) (6.7%; n=3). No statistically significant differences were observed in the CTA findings. In [Table 7], coronary angiogram (CAG) revealed that the most prevalent finding was also LAD blockages (48%; n = 23) followed by RCA (31%; n = 15) and LCX (21%; n = 10). No statistically significant differences were observed in the CAG findings.

Table 6: CT Coronary angiography results of chronic coronary syndrome patients based on gender

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Table 7: Coronary angiography results of chronic coronary syndrome patients based on gender

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[Table 8] outlines the medications that were prescribed within 24 h of admission. The most frequently prescribed medications were aspirin (92%; n = 46), beta-blockers (bisoprolol) (80%; n = 40), and clopidogrel (78%; n = 39). Males were more likely to be prescribed aspirin in the first 24 h of admission than females (100% vs. 81%; P = 0.026). When discharged [Table 9], the three most frequently prescribed medications were aspirin (92%; n = 46), beta-blockers (90%; n = 43), and statins (atorvastatin) (84%; n = 42). No notable differences between the genders were noted among the other prescribed medications [Table 8] and [Table 9].

Table 8: Medication prescribed in patients with chronic coronary syndrome during admission based on gender

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Table 9: Medication prescribed in patients with chronic coronary syndrome during discharge based on gender

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[Table 10] outlines the outcomes of the patients stratified by gender. The three most recorded outcomes were recurrent ischemia (12%; n = 6), atrial fibrillation/flutter (10%; n = 5), and heart failure (4%; n = 2). No notable differences between the genders were noted among the outcomes.

Table 10: Outcomes recorded in patients with chronic coronary syndrome based on gender

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Discussion

Our study highlights gender differences in patients with CCS. Based on previous studies and research conducted on patients with stable CAD, we expected to find that the coronary profile of CCS patients differs significantly based on gender. The mean age of our cohort was 60-year-old Kuwaiti nationals, and a significant proportion were female who presented at an older age than males and tended to be overweight compared with males who were more likely to smoke cigarettes. Females, however, tended to have more hypertension and dyslipidemia, and an abnormal ECG. Interestingly, there were no differences in the prevalence of stroke, sleep apnea, CAD, and peripheral vascular disease. Although males were more likely to be taking aspirin on admission, this difference decreased upon discharge, suggesting that once recognized females with CCS received appropriate medical therapy. Recurrent ischemia was the most common major outcome recorded in our cohort, followed by atrial fibrillation and heart failure, however, there were no statistically significant differences between genders.

According to the ESC, the population at the greatest risk of CCS consists of patients of an older age group, women, and those with multiple comorbidities. While CCS can be patients of all ages, elderly patients (>75 years as defined by the ECS) have the greatest morbidity and mortality risk attributable to CCS, especially given that they have the greatest risk of multiple comorbidities due to their old age.^[4] There has been a relative underrepresentation of women in most cardiovascular studies. One study, conducted using data from 45 countries around the world using information from a well-established registry (CLARIFY registry), found that only 22.4% of the 32,703 patients enrolled were female.^[9] In contrast, our cohort consisted of a substantially higher percentage of women, 41%, which allowed us to study this oft-underrepresented group. Females in our cohort were more likely to be older than their male counterparts, with a mean age of 66 years compared to 57 years in males. This is consistent with other bodies of information, as age is a long-established risk factor for cardiac disease. One study, conducted by the American Heart Association (AHA) in 2019, reported that the incidence of CVD was 77% in males, compared to 78% in females in those aged 60–79 years, a gap that widens with increased age to reach 89% and 92%, respectively, once they turn 80 or older.^[10] This has traditionally been credited to the withdrawal of estrogen from menopausal females' systems, taking with it its positive biochemical effect on the cardiovascular system, although many other theories are currently being investigated.^[11]

Additionally, males in our study tended to be less overweight (BMI > 25) than their female counterparts, a finding that is well established in multiple studies in different populations and is a well-established risk factor of CCS.^[4] Worldwide, more women are obese than men and are more evident in developing countries as well as some developed countries such as the UK. In the UK, approximately 31% of women are obese, compared to 29% of males,^[12] which is comparable to our results that showed 66% of females to be obese compared to only 44% of males. This can be attributed to sociocultural factors, often involving an excess of calorie-rich food consumption with a concomitant decrease in physical activity.^[13] Our study also found that in those with CCS, males were much more likely to be smokers compared to females. However, with respect to smoking, many females may not disclose their smoking habits due to cultural factors. Of note, a prior study conducted in Kuwait in the year 2000 found that 34% of males smoked while only 2% of females were classified as current smokers.^[14] This seems to be a consistent finding worldwide, with only 18% of working-age females in the United States smoking, compared to 23% of their male counterparts.^[15]

Our study results show that females tended to have a higher prevalence of comorbidities, with higher rates of hypertension, dyslipidemia, and diabetes specifically. In contrast, males tended to have an increased prevalence of CAD, sleep apnea, and stroke. This is in concordance with other observed patterns, with data from the CLARIFY registry of CCS patients showing that hypertension and diabetes mellitus are the two most common comorbidities associated with CCS.^[9] Furthermore, a systemic review, undergone by the AHA with data from 19 countries worldwide, showed similar results to our study, concluding that the prevalence of stroke was 41% higher in men than that in females.^[16]

As mentioned previously, females tended to be more likely to have ECG abnormalities upon admission, findings that do not correlate to the current body of data worldwide. One study, based in Europe using four community-based European studies, found that over a follow-up of 12 years, females were found to have fewer cases of AF (4%) than males (6%), the rate of which increased after age 60 in females and 50 in males, with a similar lifetime risk afterward.^[17] In the USA, the results of the Framingham study showed that men had a 1.5-fold increased risk of developing AF than women after adjustment for age and comorbidities.^[18] In contrast, another study, based on a cohort from Europe, found that women were more likely to suffer from symptomatic AF.^[19] The increased prevalence of AF in our female cohort may be due to increased age or the higher prevalence of comorbidities compared to males. In addition, males were found to have higher creatinine levels on admission than their female counterparts. Various studies conducted in China and the USA showed that elevated creatinine levels were more common in males and these levels were correlated with a higher risk of death and the development of ESRD, which is known to affect the cardiovascular system in various ways.^[20],[21]

Aspirin use is associated with reduced incidence of major adverse cardiovascular events.^[22] In our study, males with CCS were more likely to be on aspirin at the time of admission which may be due to age-related difference in incidence of CAD but also perhaps because females may have less access to health care. One study based in the United States, examining gender disparities in healthcare among older adults, found that women had a significantly increased need for healthcare services but had fewer economic resources available to access them, fewer physician visits, and hospital stays compared to males after controlling for both demographic differences and health needs.^[23] Another study from Europe reported that despite females having a greater prevalence of symptomatic AF, they were less likely to undergo treatment compared to males.^[19] As our cohort showed that a large proportion of those with CCS were female, this degree of participation can be related to the fact that Kuwait offers health-care services either for free or for heavily subsidized fees, thus increasing health-care access for either gender.

Studies have shown that women have traditionally experienced worse outcomes when compared to men, but the mechanism concerning this is incompletely understood, with older age, a higher prevalence of comorbidities, and an often delayed diagnosis affecting this.^[24] While women in our study tended to have a higher prevalence of comorbidities and were older, our study shows that men tended to be more likely to have abnormal CAG results than abnormal CTA results, which was more common in females. They also tended to be more likely to have recurrence of ischemia compared to females as well as recurrent MI and major bleeding. In a study conducted on patients with CCS from the CLARIFY registry, for example, males were reported as having a 0.6% increase in cardiovascular mortality rate as compared to their female counterparts, and were also more likely to have a history of MI as well as PCI, were more likely to be current smokers, and have untreated hypertension.^[9] The last few factors can likely be attributed to differences in psyches and even general cultural influences on the individual genders, with males generally reported as having a generally lower level of health literacy.^[25] A Finnish study showed that men are more unwilling to engage and embrace health information and change their behavior to reduce any risk factors.^[26] This may explain why males in our population had higher levels of significant outcomes, as they may have been more likely to disengage with given information regarding their health.

The present study has some limitations. This study was a retrospective cross-sectional study with relatively short follow-up. Furthermore, the cohort was from a governmental hospital that is completely free at the point of care to Kuwaiti citizens, while expatriates have to pay a nominal fee subsidized by the government. Since a large proportion of the expatriate population are migrant manual laborers, these fees may be seen as a deterrent to seeking health care and explain the relatively larger number of Kuwaiti patients in our cohort. However, it is important to note the differences in lifestyle, with Kuwaitis generally leading a more sedentary lifestyle and following a traditional high in fat and calorie diet contributing to the higher prevalence of CCS in this group. Finally, the sample size eligible for recruitment into the study was limited.

Conclusions

In Kuwait, females with CCS are older compared with males but were less likely to be taking aspirin on admission as well as smoking but were not otherwise different from males in terms of comorbidities, admission laboratory and diagnostic imaging results, nor outcome.

Statement of ethics

This study was except from Institutional Review Board approval (IRB No. 05-2015-129) as it used preexisting de-identified data. The procedures were in accordance with the Helsinki Declaration.

Data availability statement

All data generated or analyzed are included in this article. Further inquiries can be directed to the corresponding author.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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