Introduction

Coronary artery disease (CAD) remains unrecognized, particularly in young women. In the modern era, women are self-dependent and are well aware of their rights, but unfortunately their awareness and attitude toward their health especially cardiovascular diseases is largely ignored. Though the women constitute 48% of the total population in India, CAD remains a major formidable health problem in women. Indeed, it is rightly said that coronary heart disease (CHD), the most prevalent form of heart disease, is “underdiagnosed, undertreated, and underresearched” in women.1

Various studies on CAD in young patients labeled them as having “premature” CAD, but it is now better understood as a rapidly progressive form of the disease. According to the literature, most patients were males, but with changing scenario of CAD especially in females, the statement requires validation.2

From 1960 to 1995, the prevalence of CAD in adults increased from 3 to 10% in urban Indians and from 2% to 4% in rural Indians, with women having rates similar to men.3 It is estimated that 31% of women will die from CAD, yet approximately 70% of university-educated women consider their risk of CAD to be < 1%. Women have eight times higher risk of dying from heart disease than from breast cancer, yet they fear more of breast cancer and neglect symptoms of heart disease.4

Material and Methods

We retrospectively analyzed the data of young patients (< 45 years of age) who had undergone percutaneous coronary intervention (PCI) in our institute over the past 2 years. We noted the details of coronary risk factors, type of CAD presentation, coronary angiogram (CAG), and PCI and its outcome. Laboratory investigations in our study included complete blood picture, renal parameters, cardiac enzymes, and lipid profile. Anemia was defined as < 11 g/dL in females and < 13 g/dL in males. Electrocardiographic (ECG) and 2D echo findings were also analyzed. Left ventricular (LV) dysfunction was defined as LV ejection fraction < 50% (both by Simpson's and volume estimation). In CAG, culprit vessel, number of vessel involvement, lesion characteristics like calcium, complexity of lesion, etc. and tortuosity of vessels were analyzed. Immediate results of PCI like success of PCI and complications (including the puncture site complications) were also taken into consideration in our study.

Statistical Analysis

Univariate analysis of categorical variables was performed with the chi-square test, and continuous variables were analyzed by Student's t-test. Correlations among parameters were evaluated by linear regression analysis. Differences were considered significant at p value of < 0.05. Statistical analysis was performed using Minitab version 17 software.

Results

Out of 200 cases of “young” PCI patients, 42 were females (M:F::3.76:1). Hypertension was present in 29 (69.1%) females versus 69 (43.7%) males, diabetes mellitus in 14 (33.3%) females versus 36 (22.8%) males, and smoking in 2 (4.8%) females versus 75 (47.5%) males. Five female patients had early menopause, and rest of them were in premenopausal stage. Hypertension, diabetes, and anemia were more prevalent in young females than young male CAD patients (Table 1). Females with CAD were younger than males (p = 0.03).

Approximately 45.2% of young females presented as acute coronary syndrome (ACS) versus 62.7% of males. Prevalence of ST-elevation myocardial infarction (STEMI) was more predominant in males than in females (31.1% vs. 19.1%), which was statistically significant (p = 0.03). However, there was no difference in LV dysfunction on echo and number of vessel involvement on CAG (Table 2).

In our study, 53 lesions in 42 female patients and 198 lesions in 158 male patients were treated. Complexity of lesion (either B₂ or C) was greater in females, which was also statistically significant (p = 0.02). (Tables 3, 4;Fig. 1).

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Fig. 1 Bar chart showing the major differences of CAD in young female and male patients (y-axis—percentage, x-axis—different parameters). Acute coronary syndrome (ACS) denotes non–ST-elevation myocardial infarction (NSTEMI) and myocardial infarction (MI) denotes ST-elevation myocardial infarction (STEMI).

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Fig. 1 Bar chart showing the major differences of CAD in young female and male patients (y-axis—percentage, x-axis—different parameters). Acute coronary syndrome (ACS) denotes non–ST-elevation myocardial infarction (NSTEMI) and myocardial infarction (MI) denotes ST-elevation myocardial infarction (STEMI).

Even though lesion complexity was found greater in female patients, there was no increased or decreased incidence of any particular coronary artery territory involvement; also there was no difference in success or complication rates between both the groups (Table 5). Because most PCIs were transradial in both the groups, there was no difference in occurrence of local site hematomas.

Discussion

CAD occurring below the age of 45 years is termed as “young CAD.”5 However, various studies considered the age limit varying from 35 to 55 years in the spectrum of young CAD6 7 8 9 10 11 12 13 14 (Table 6).

Regardless of race or ethnicity, CAD is the leading cause of death in women. The worldwide INTERHEART study, a large cohort study of more than 52,000 individuals with myocardial infarction (MI), revealed that the first presentation of CHD in women is approximately 10 years later than men, most commonly after menopause. Even though there is this delay in onset, mortality from CHD is progressing more rapidly among women than men.15 In our study in young population with CAD, females were younger.

According to Iyengar et al (Coronary Artery Disease in the Young [CADY] registry),16 the prevalence of standard coronary risk factors (smoking, hypertension, diabetes, and dyslipidemia) is high in premature CAD in India, which is similar to previous case-control studies.17 Women with premature CAD have greater prevalence of metabolic risk factors than men. This study showed women to have more comorbidities such as hypertension, diabetes, dyslipidemia, and obesity, which are amenable to corrective preventive measures. Smoking among female population was less prevalent. These findings were similar to our observation.

GUSTO IIb (Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes), TIMI IIIB (Thrombolysis In Myocardial Infarction), and the EuroHeart Survey studies showed that women present more frequently with unstable angina and NSTEMI, whereas men have ACS with STEMI.18 19 20 It has been shown that women are less likely to undergo reperfusion therapy after ACS.21 22 In our study also, women had NSTEMI more frequently as compared with men.

Arzamendi et al in their autopsy series observed that among young individuals who died of CAD, three-vessel disease was observed in 39.7% of cases. Moreover, among the whole population < 40 years old, at least one significant coronary lesion was observed in 39.5% of cases, irrespective to the cause of death.23 Indeed, when a rigorous intravascular ultrasound-based investigation was undertaken in a cohort of recently transplanted hearts (mean donor age 33.4 ± 13.2 years) by Tuzcu et al,24 the prevalence of disease was more, with one in six teenagers manifesting with coronary lesions. Even in our study, females had multivessel involvement.

Diabetes and hyperlipidemia are also frequently present in young CAD patients.25 26 Young women with CAD comprise an especially interesting group even though there is the protective effect of estrogen, but predictive factors in this distinctly unusual cohort is poorly understood. In the present study, diabetes mellitus (DM) was more prevalent in females than in young males, but that was not statistically significant.

According to previous studies, hypertension and lack of exercise are both firmly established risk factors for CAD, but they appear to contribute only marginally in young adults. On the contrary, in our study, hypertension was more prevalent in young females (69.1%) than young males, which was significant statistically.

In young males, smoking is considered as a strong risk factor for CAD. According to the Framingham study, repeated exposure to cigarettes and the resulting frequent catecholamine surges damage endothelial cells, leading to dysfunction and injury to the vascular intima.27 In our series, smoking was less in females, so metabolic factors played an important role in female CAD. Women who smoke have a quantitatively similar risk as men,28 but more than five times the risk of nonsmoking women.29 Smoking in combination with oral contraceptives poses a 13-fold increase in CAD mortality.30

Truncal obesity and increased body mass index (BMI) have recently been proposed as potential independent risk factors, particularly in young women with CAD. Sagittal abdominal diameter to skin fold ratio seems to be a good indicator in predicting premature CAD, even better than BMI and waist circumference.31

Presence of calcium at lesion site and tortuous vessels are features of elderly but in a subgroup analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) study, high objective hostility scores were associated with the presence of coronary artery calcification. However, the interaction between a genetic propensity to form vulnerable plaque combined with acute stress and/or an active infectious/inflammatory process needs further study.32

Huang et al in their study showed that left main, left anterior descending, and bifurcation lesions were more common whereas type C lesions and right coronary lesions were less common in young female CAD group than in young male CAD group (p < 0.01–0.05). The average lesion length in female patients was significantly longer than that in male patients ([20.36 +/− 13.37] mm vs. [23.04 +/− 13.86] mm, p < 0.05).33 In this study also, complexity of lesion was greater in young female CAD patients, but there was no involvement of any particular coronary territory.

In females, one of the mechanisms of acute presentation is spontaneous coronary artery dissection in 35 to 40 years age group. The patients are divided into three groups: peripartum, atherosclerotic, and idiopathic groups.34 Dissection occurs in tunica intima of the coronary arteries, and the blood penetrates and results in intramural hematoma in tunica media, resulting in restriction in the size of lumen leading to reduction in blood flow and MI. However, we have not encountered any coronary dissections in our young females who presented with MI in our study.

Mortality after an acute coronary event is two times higher in women than in men aged < 50 years.35 36 The cause of increased incidence of adverse event in women with premature CAD is still unknown.

Major limitation of our study was that we analyzed only the young patients who underwent PCI, which means that the incidence of coronary obstructive lesions in the real world is even higher. Second, all these patients belong to single ethnic Asian population. Also, only the conventional risk factors were included, but the other risk factors specific for females as suggested by Jairath N., such as depression and thyroid function, were not taken into consideration37 in our study. Sagittal abdominal diameter to skin fold ratio that seems to be a good indicator in predicting premature CAD, even better than BMI and waist circumference, was not taken into consideration in our study.

Conclusion

In our study, metabolic risk factors contributed to CAD in young females. Also, these patients presented with NSTEMI and had complex coronary lesions than young males. However, the success and complication rates of PCI were the same in both the groups.

Our data highlights the potential to prevent cardiovascular disease in women by creating awareness and publicity about the modifiable risk factors, and hence it can create an impact on the future of cardiovascular disease in women in future. Conventional and female-specific risk factors, novel biomarkers, and genetic analysis should be evaluated for better patient outcome and prognosis.