Risk factors,lab parameters,angiographic characteristics and outcomes of coronary artery disease in young South Asian patients: a systematic review

Abstract

This systematic review provides a qualitative summary of the risk factors, angiographic characteristics, treatment, and complications of young South Asians with coronary artery disease (CAD). PubMed, Embase, and Google Scholar were searched to identify research articles published between 1 January 2010 and 13 November 2022. Studies in patients aged 18 to 45 years that were conducted in South Asian countries, were published in the English language, and included information on patients’ clinical profiles and at least two risk factors for young CAD were included in the review. Smoking, dyslipidemia, high body mass index, increased high-sensitivity C-reactive protein, and hyperhomocysteinemia were observed in high proportions in young patients with CAD. Single-vessel disease was more common than multi-vessel disease in young CAD. The complications of CAD such as arrhythmias, cardiogenic shock, and heart failure were also commonly observed in young patients. Large-scale health promotion activities that curb modifiable risk factors such as smoking, obesity, and a sedentary lifestyle should be conducted in South Asian countries.

Keywords

Atherosclerosis coronary artery disease South Asia young myocardial infarction risk factor smoking obesity dyslipidemia diabetes mellitus

Introduction

Coronary artery disease (CAD) is an atherosclerotic cardiovascular disease (CVD) that includes stable angina, unstable angina, acute myocardial infarction (AMI), and sudden cardiac death.¹ Unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI) are myocardial ischemic states that are classified as acute coronary syndrome.² At present, CAD accounts for the highest number of deaths worldwide.^3,4 Low- and middle-income countries account for more than 80% of the global burden of CVD.⁵ The South Asian region comprises eight low- or lower-middle-income countries: Nepal, India, Afghanistan, Pakistan, Bhutan, Sri Lanka, the Maldives, and Bangladesh. South Asian ethnicity has been identified as a risk factor for various non-communicable diseases including CAD.⁶

Although CAD is commonly observed in the adult population above 60 years of age, South Asians have a lower age of presentation of first AMI compared with other individuals in other regions.⁷ The age of occurrence of CAD in the young population has been defined in various ways and ranges from below 60 years to below 30 years. A universally accepted age cut-off that defines a “young” patient is unavailable, but the age cut-off of 45 years has been used in multiple studies to define a “young” patient with CAD.^8–11 The commonly identified risk factors for young CAD include smoking, hypertension, diabetes, dyslipidemia, obesity, and family history.^12–15 However, other less common risk factors such as vasculitis, drug abuse, and coagulation abnormalities are also implicated in young CAD.¹³

National surveys in South Asian countries have revealed an upward trend in these risk factors and the prevalence of CAD.¹⁶ Additionally, hospital-based studies in South Asia have reported that young patients comprise up to one-quarter of all patients with CAD.¹⁵ Young or premature CAD was more prevalent in developed nations than in other countries until the mid-20^th century.^17,18 However, the burden of young CAD has shifted geographically to developing nations worldwide in recent decades. Despite the publication of numerous South Asian studies, only a limited number of systematic reviews that explore the salient features of young CAD exist in the literature. This systematic review provides a qualitative summary of the risk factors, angiographic characteristics, treatment, and complications of young South Asian patients with CAD.

Materials and methods

This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and follows the statement’s checklist and flow diagram.¹⁹ The study was not prospectively listed in any register.

Literature search

An extensive search of three standard electronic databases (PubMed, Embase, and Google Scholar) was conducted to identify peer-reviewed research articles published between 1 January 2010 and 13 November 2022. The search strategies were developed using Medical Subject Heading and Emtree terms in PubMed and Embase, respectively. The terms “premature coronary artery disease,” “young coronary artery disease,” “epidemiology,” “extremely premature coronary artery disease,” “malignant coronary artery disease,” and “young myocardial infarction” were searched together with the names of various South Asian countries under Medical Subject Heading terms. The search strategy is provided in Supplementary File S1. To identify additional relevant studies that could have been missed by the database search, reference and citation searches of the retrieved articles were performed. All of the studies obtained were imported into EndNote reference software version 20 (Thomson Reuters, Stamford, CT, USA) in compatible formats, and duplicates were removed as required.

Eligibility criteria

Studies in patients aged 18 to 45 years that were conducted in South Asian countries, published in the English language between 2010 and 2022 and that included information on patients’ clinical profile and at least two risk factors for young CAD were considered eligible for inclusion in the review. Observational studies, irrespective of the setting and the sample size, were included in the review. Studies that involved any of the following were excluded from the systematic review: (1) studies with insufficient or unclear information; (2) case reports and series; (3) conference abstracts, reviews, meta-analyses, editorials, and commentaries; (4) studies that investigated a single risk factor; (5) studies with data on angiography only; and (6) studies for which the full text was irretrievable. When two or more studies included the same set of patients, the study with the larger number of patients was considered for review.

Data extraction and management

After the removal of duplicates, two independent authors (AA and PL) screened the remaining articles according to the pre-specified inclusion and exclusion criteria. The full text of the relevant articles was retrieved, and studies were shortlisted for inclusion in the review. To retrieve full texts and missing data, the authors of the respective studies were contacted via email when required. Any discrepancies between the assessments of the two authors were resolved by consultation with a third author (RK). The data were extracted using the data abstraction spreadsheet in Microsoft Excel 2013 (Microsoft Corp., Redmond, WA, USA) and classified as the following variables: author name, country, year of publication, study design, study population, age group, sample size, diagnosis of patients, risk factors, lab parameter values, angiography findings, outcomes, and treatment.

Results

Study selection

The search strategy initially identified a total of 1543 articles in the databases that were utilized for the review. After the exclusion of duplicates and studies that did not meet the inclusion criteria, 70 studies were reviewed for data collection. Figure 1 shows the results of our literature search and selection.

Figure 1.

PRISMA flow diagram of the studies selected for review.

Study characteristics

A total of 13,071 South Asian participants across 70 observational studies were investigated to explore risk factors, lab parameters, angiographic characteristics, treatment, and outcomes in young CAD. The sample size ranged from 22 to 1628 and the publication years were from 2010 to 2022. The studies were conducted in four South Asian countries: Bangladesh, India, Nepal, and Pakistan. No studies from the remaining four countries (Afghanistan, Bhutan, Sri Lanka, and the Maldives) qualified for the review. Of the 70 articles, 34 articles were from India, 16 were from Bangladesh, 11 were from Pakistan, and eight were from Nepal. A detailed description of the characteristics of individual studies is provided with references in Table 1 in Supplementary File S2.

Risk factors for young CAD

All of the 70 studies investigated at least two risk factors for young CAD. The known risk factors explored in this review were smoking, smokeless tobacco consumption, hypertension, diabetes mellitus, high body mass index (BMI), dyslipidemia, alcohol consumption, sedentary lifestyle, a family history of CAD or young CAD, coagulation abnormalities, vasculitis, connective tissue disorders, and drug abuse.

Smoking and smokeless tobacco consumption

Sixty-nine studies reported a frequency of smoking among young patients with CAD that ranged from 4.8%²⁰ to 81.71%.²¹ Both the lowest and highest percentages of smokers in the South Asian study population were reported in India. Nepalese patients who were smokers were observed in 58.6%²² to 80.8%¹⁴ of the study population. Similarly, smoking was prevalent in 14.3%²³ to 64.7%²⁴ of Pakistani patients and in up to 77.4%²⁵ of Bangladeshi patients. However, 12 studies also mentioned the use of smokeless tobacco—with a frequency ranging from 0.3%²⁶ to 60.6%²⁷—as a risk factor in patients. An Indian study further reported that as many as 93.8% of the patients were either smokers or consumed some form of smokeless tobacco.²⁸

Hypertension

Sixty-eight studies showed an 8.8%²⁹ to 80.0%³⁰ prevalence of hypertension among the patients. Seven studies reported that 27.8%³¹ to 57.5%¹³ of Nepalese patients were hypertensive. Similarly, the prevalence of hypertension ranged between 10.2%²³ and 75.0%³² in patients from Pakistan. Sixteen Bangladeshi studies further reported a hypertension prevalence range of 14.0%³³ to 80.0%,³⁰ and Indian studies showed that 8.8%²⁹ to 44.7%³⁴ of young patients with CAD had hypertension.

Diabetes mellitus

Sixty-eight studies from South Asia described diabetes mellitus as a risk factor for young CAD and reported frequencies ranging from 2.4%³⁵ to 80.6%.³⁶ Eight Nepalese studies found that 14%³⁷ to 47.4%³⁸ of patients had diabetes mellitus. Studies in Pakistan and Bangladesh reported the highest prevalence of diabetes in well above 50% of patients.^30,32 Similarly, 34 Indian studies explored the prevalence of diabetes in young patients with CAD. Bhardwaj et al. reported that up to 80.6% of young Indian patients with CAD had diabetes mellitus.³⁶

High body mass index

According to 43 studies, high BMI (≥23 kg/m²) was observed in 1.7%³⁹ to 97.1%⁴⁰ of young South Asian patients with CAD. According to two studies, approximately 13.3%⁴¹ and 25.0%¹³ of Nepalese patients had a high BMI, respectively. Pakistani patients were reported to have high BMI that ranged from 15.6%⁴² to 97.1%⁴⁰, and up to 60.7%¹¹ of Bangladeshi patients had a high BMI. Similarly, the proportion of patients with high BMI ranged from as low as 1.7%³⁹ to as high as 69.0%⁴³ in India, according to 24 studies.

Dyslipidemia

According to 55 studies, dyslipidemia was present in 2.5%¹⁵ to 97.3%⁴⁴ of young patients with CAD. The prevalence of dyslipidemia in Nepalese patients was in the range of 9.6%³¹ to 46.8%.³⁷ According to Adam et al., up to 84.3% of Pakistani patients had dyslipidemia.⁴⁵ According to 15 studies, 11.9%⁴⁶ to 97.3%⁴⁴ of patients in Bangladesh had dyslipidemia. Similarly, dyslipidemia was found in 88.3% of Indian patients.²⁹

Additionally, 17 studies were used to identify a prevalence range of 4.6%⁴⁷ to 60%²⁹ for hypercholesterolemia among patients. A study by Gopalakrishnan et al. reported a 79% prevalence of low high-density lipoprotein (HDL) in patients.²⁹ Hypertriglyceridemia was reported in 77.7% of young patients with CAD in a study by Ahmed et al., whereas Laudari et al. reported hypertriglyceridemia in only 5% of patients.^13,40

Family history of CAD or young CAD

Of the 70 studies, 58 assessed whether patients had a positive family history of CAD or young CAD. Positive family histories were observed in as many as 60% of the patients.³⁰ Only five studies in Nepal reported the prevalence of young patients with CAD who had a positive family history; prevalences ranged from 2.9%²² to 31.6%.³⁸ The prevalences of a positive family history of CAD or young CAD in Pakistani and Bangladeshi populations were 57.1%³² and 60.0%³⁰, respectively. The lowest frequency of a family history of CAD or young CAD in India was reported in a study by Wadhkar et al.⁴⁸ (6.0%), whereas a study by Sinha et al.⁴⁹ reported a frequency of 46.8%.

Alcohol consumption

Seventeen studies reported alcohol consumption in young patients with CAD. The lowest frequency (approximately 1.7%) was reported in an Indian study.⁵⁰ However, a study in Nepal reported alcohol consumption in more than 75% of the patients.¹⁴

Sedentary lifestyle or physical inactivity

Thirteen studies reported the frequency of a sedentary lifestyle in patients. An Indian study⁵¹ reported a frequency of only 5%, whereas a study in Pakistan²⁴ indicated physical inactivity in 86% of the study patients.

Drug abuse

Five studies reported a history of drug abuse in 4.3%³¹ to 9.5%⁵² of patients.

Miscellaneous

Only three studies explored coagulation abnormalities among young patients with CAD. Chhabra et al.⁵³ in India reported coagulation abnormalities in only 1.8% of patients, whereas Laudari et al.¹³ in Nepal reported coagulation abnormalities in 7.5% of patients. Two additional studies further investigated the presence of connective tissue disorders, which were observed in 0.8%³⁴ and 1.6%⁴¹ of patients. A single South Asian study, one conducted in Nepal, reported vasculitis (5%) as a risk factor for young CAD.¹³

Lab parameters in young CAD

Fifteen studies reported at least one lab parameter of significance in the young population with CAD. The parameters were high-sensitivity C-reactive protein (hs-CRP), homocysteine level, and lipoprotein A levels.

CRP level

Six studies reported the frequency of increased hs-CRP and C-reactive protein levels in patients diagnosed with young CAD. Dahal et al.³⁸ observed an 89.5% prevalence of increased hs-CRP levels among patients. A study by Sherpa et al. reported increased CRP (>6 mg/L) in 43.3% of patients.⁵⁴ However, an Indian study reported increased hs-CRP levels in only 7.5% of study patients.⁴⁷

Homocysteine levels

Eight studies reported increased homocysteine levels (>15 µmol/L) in young patients with CAD. A Bangladeshi study concluded that 100% of young patients with CAD had hyperhomocysteinemia.⁵⁵ Other studies have reported hyperhomocysteinemia prevalence in the range of 0.9% to 58.5%.

Lipoprotein (a) levels

Four studies described the proportion of patients with increased lp(a) levels. Three of the studies reported increased lp(a) levels in more than 40% of all patients.^36,56,57 Wadhwa et al. in India reported that 70% of patients had increased lp(a) above 20mg/dL.⁵⁷

Angiography findings

Fifty-nine studies described angiographic findings in the patients. The findings are described based on the number and type of vessels involved.

Number of vessels involved

Single-vessel disease (SVD) has been reported in 16.7% to 88.3%¹⁵ of study populations.³⁰ Except for the findings of Pramanik et al.,³⁰ the prevalence of SVD was higher than that of double-vessel disease (DVD) and triple-vessel disease (TVD) in all of the studies. Alexander et al. in South India reported the highest prevalence of SVD (88.3%).¹⁵ Other studies in the Indian population have also reported a high percentage of patients with SVD among their study cohorts. Kalimuddin et al. ⁵² reported a 68.3% rate of SVD in their patients, the highest reported rate in Bangladeshi patients. The highest prevalences of SVD in Nepalese and Pakistani patients were 65.0%⁴¹ and 63.4%⁵⁸, respectively.

The percentage of patients with DVD was between 4.9%⁵⁹ and 36.9%³¹ in South Asia in 45 studies. The highest prevalences of DVD were reported in Nepal (36.9%)³¹ and India (36.4%).⁶⁰ The highest reported rates of DVD in Bangladesh and Pakistan were 31.1%¹¹ and 27.5%⁴⁵ of patients, respectively.

The highest prevalences of TVD were reported in India by Pramanik et al.³⁰ (55.0%) and Pakistan (30.4%). The highest rate of TVD reported in Bangladesh was 21.1%.⁶¹ Pandey et al. ²² reported Nepal’s highest prevalence of TVD (only 12.5%). The details of each study of SVD, DVD, and TVD are described in Table 1 of Supplementary File S1.

Normal coronaries were observed in 2.8%⁴⁸ to 32.7% of South Asians with young CAD. Moreover, the prevalence of non-obstructive CAD (<70% stenosis) ranged from 10.3%²⁵ to 31.7%.⁶² Mild or non-significant stenosis (<50% stenosis), which is part of non-obstructive CAD, was reported in 1.4%⁶² to 41.2%⁴⁷ of patients in the studies.

Type of artery involved

The three common vessels investigated in the studies were the left anterior descending artery (LAD), the left circumflex artery (LCX), and the right coronary artery (RCA). Few articles have described the disease affecting the left main artery (LMA).

The LAD was the most common vessel involved in South Asians with young CAD. The proportion of patients with LAD involvement ranged from 27.6%³¹ to 83.5%.⁶³ All of the 38 studies that reported the type of vessel involved described the LAD as the vessel most commonly involved in young CAD. The RCA was the second most common vessel involved in young South Asian patients with CAD. The proportion of patients with RCA involvement ranged from 10.3%²⁵ to 58.6%.²² Except for six studies, RCA involvement was more frequent than LCX involvement. Similarly, LCX was involved in 1.3%⁶³ to 51.0%⁶⁰ of the South Asian population. LMA involvement was reported in 26 studies and had a frequency that ranged from 0.5%⁴⁸ to 11.3%.⁶⁶ Eight studies reported no stenosis in the LMA of patients. Further details on the types of arteries involved in young CAD are provided in Table 1 of Supplementary File S1.

Outcomes and complications of young CAD

Thirty studies reported the in-hospital complications and outcomes of patients treated for young CAD. Complications and outcomes included cardiogenic shock, heart failure, arrhythmias, in-hospital mortality, mechanical complications, acute pericarditis, and stent thrombosis.

Cardiogenic shock

Twenty-seven studies reported cardiogenic shock, with frequencies ranging from 0.2%⁵⁷ to 36.9%.⁴⁸ The highest and lowest frequencies among the South Asian population were reported in India. Among these, five studies in Nepal reported cardiogenic shock in 4.5%⁵⁸ to 12.5%¹³ of the patients. A single study in Pakistan reported cardiogenic shock in 0.4% of patients.⁴² Seven studies in Bangladesh provided a cardiogenic shock prevalence range of 0.8%⁴⁶ to 6.0%⁵⁹ among young patients with CAD.

Arrhythmia

Twenty-two studies reported arrhythmia (tachycardia or bradycardia) as a complication in young patients with CAD. In these studies, arrhythmias were recorded in 1.7%⁴¹ to 64.3%⁴⁸ of the patients. The frequency of arrhythmias in young patients with CAD ranged from 1.7%⁴¹ to 12.5%¹³ in four studies in Nepal. Batra et al. in Pakistan reported that 8.0% of patients developed arrhythmia as a complication of CAD.⁶⁴ Similarly, seven studies in Bangladesh reported arrhythmia in patients in the range of 3.3%⁴⁶ to 10.0%.³³ Ten studies in India reported arrhythmia in patients with frequencies ranging from 3.0%⁶⁰ to 64.3%.⁴⁸

Heart failure

Twenty-three studies reported a heart failure frequency range of 0.4%⁴² to 54.0% in young people with CAD.²⁸ Among the studies, three were in Nepal, where heart failure was reported in up to 6.0%⁶⁴ of patients. Two studies in Pakistan reported heart failure in 14.0% of patients. ^42,67 Seven studies were conducted in Bangladesh with frequencies ranging from 4.8%⁶³ to 40.7%.⁴⁶ Moreover, Indian patients had heart failure in the range of 0.8%¹⁵ and 54.0%,²⁸ according to 11 studies.

Mortality

Thirty studies reported an in-hospital mortality rate ranging from as low as 0.2%⁵⁹ to as high as 12.0%.²⁸ The lowest and highest mortality rates were observed in the South Indian population. According to five studies, the Nepalese population had a mortality rate that ranged from 1.7%³¹ to 5.0%.¹³ Similarly, two studies in Pakistan reported mortality rates of 1.2%⁴² and 2.0%.⁶⁷ According to Rahman et al.,⁶⁸ the highest mortality rate in Bangladeshi patients was 6%.

Mechanical complications

Only six studies reported mechanical complications among young patients with CAD, with the lowest frequency reported in a study by Sinha et al.⁴⁹ (0.2%) and the highest frequency reported in a study by Kalimuddin et al.²⁵ (16.2%).

Acute pericarditis

Four studies reported acute pericarditis as a complication in young patients with CAD. The percentage of patients who developed pericarditis ranged from 2.5%⁴⁹ to 12.7%.⁶⁹

Stent thrombosis

Two studies further reported stent thrombosis in patients following percutaneous coronary intervention (PCI). A study in India by Sinha et al.⁴⁹ reported a frequency of 0.2%, whereas a study by Chhabra et al.⁵³ reported a frequency of 0.9%.

Treatment of young CAD

Multiple treatment modalities, such as thrombolysis, PCIs, medical treatment, and coronary artery bypass graft (CABG) surgery, were selected in the studies in this review.

Thrombolysis

Twenty studies reported thrombolysis as a treatment for patients with AMI. The rate of thrombolysis differed across the studies. Thrombolysis was performed in 0.4%²⁰ to 100.0%⁷⁰ of the patients, according to the studies. Khan et al.⁷⁰ in Pakistan reported 100% use of thrombolytic agents in patients who were diagnosed with AMI. The second-highest thrombolysis rate (78.7%) was reported by Vaidya et al. in India.⁵⁰ Only a handful of studies mentioned the type of thrombolytic agent used. Streptokinase was the most commonly reported thrombolytic used in South Asia. The studies reported the use of streptokinase in 15%¹³ to 100%⁷⁰ of the study patients with AMI. Other less commonly used agents for thrombolysis were tenecteplase and reteplase.

Optimal medical treatment only

Fifteen studies described medical management as a treatment option in young patients with CAD. Up to 65.9% of the patients were managed with only optimal medical treatment, as reported by Patil et al.⁵⁹

Percutaneous coronary intervention

PCI was a commonly employed treatment option in patients, as reported in 20 studies. Primary PCI was provided to 0.8% to 81.0% of all of the patients who presented to institutions within the window period. Additionally, routine and elective PCI was offered to many patients, according to the studies. In five studies, more than two-thirds of young patients with CAD received primary, rescue, or routine PCI.

CABG surgery

Ten studies reported CABG surgery in young patients with CAD. Eight of the studies were conducted in India, and the remaining two were in Nepal. CABG surgery was performed in 0.5% to 10.4% of the patients.

Discussion

To the best of our knowledge, this is the first systematic review to qualitatively summarize the risk factors, lab parameters, characteristics, and outcomes in young South Asian patients with CAD. According to our review, the most common risk factor among young patients with CAD was smoking and use of smokeless tobacco, followed by diabetes mellitus, hypertension, a family history of CAD or young CAD, dyslipidemia, a high BMI, alcohol consumption, and a sedentary lifestyle. A meta-analysis by Liu et al. identified smoking, a positive family history of CAD, obesity, and alcohol consumption as common risk factors in young patients.⁷¹ Another meta-analysis in Iranian patients identified diabetes mellitus as the strongest risk factor for young CAD.⁷² However, both studies did not review the less common risk factors. These uncommon yet important risk factors, such as drug abuse, coagulation abnormalities, connective tissue disease, and vasculitis, in young patients with CAD are also discussed in our review. The association of these unconventional risk factors with CAD remains largely unexplored.

Our review indicated that almost two-thirds of patients from each South Asian country studied used some form of tobacco. Sau et al. in India reported that 93.8% of young patients with CAD were either smokers or consumed some form of smokeless tobacco.²⁸ An increased prevalence of smoking among young adults was associated with a five-fold higher risk of developing CAD compared with nonsmokers. Furthermore, smoking was associated with a 1.6-fold increased risk for premature CAD.⁷² The use of smokeless tobacco in Nepal has grown from 38.2% to 40.1% among adults during the last decade.⁷³ A study by Luhua et al. reported that smokeless tobacco was used by 40.3%, 58.4%, and 74.7% of the populations of Pakistan, Bangladesh, and India, respectively.⁷⁴ Multiple studies in Western countries have also reported smoking as a major risk factor among young patients with CAD.^75,76 However, the problem is grave in South Asian countries such as India, where initiation of tobacco use, especially smoking, is common even among school-age children.⁷⁷

Based on our review, diabetes mellitus was the second most common risk factor for CAD in young adults in South Asia. South Asia is known as the epicenter of the global diabetes pandemic given the very high and increasing prevalence of type 2 diabetes mellitus among young adults. Bhardwaj et al. in India reported that approximately 80.6% of young patients with CAD were diagnosed with diabetes mellitus.³⁶ Moreover, Asian Indians have a higher insulin resistance than Whites, as shown by their higher glucose disposal rate (3.7 ± 1.3 mg/minute/kg lean body mass, compared with 5.3 ± 2.0 mg/minute/kg lean body mass in Whites).⁷⁸ The “South Asian phenotype” that describes the native South Asian population refers to a state of greater total body and visceral fat, higher insulin resistance, and a greater predisposition for type 2 diabetes mellitus at a given BMI compared with Whites. In addition, a decline in nutrition quality, reduced physical activity, and increased sedentary behaviors that cause disturbances in adipokine and lipid levels lead to insulin resistance and compensatory hyperinsulinemia from an early age in this population.^79,80 A meta-analysis identified diabetes mellitus as the most common and strongest risk factor for premature CAD in Iranians, with an associated two-fold increase in risk compared with healthy controls.⁷²

Our review further identified hypertension as an important risk factor for developing young CAD. In our study, more than half of the young CAD population from any South Asian country had hypertension. Approximately 80% of the young patients with CAD in Bangladesh were reported to be hypertensive. A case–control study in India indicated that the prevalence of hypertension was higher in young patients with CAD (25%) compared with individuals without CAD (13%).⁸² High BMI (≥25 kg/m²), frequent consumption of red meat and alcohol, and positive family history were common risk factors for the development of hypertension among young adults in South Asia. South Asian nations have low rates of hypertension screening, awareness, and treatment and a high burden of untreated and uncontrolled hypertension.^82,83 Improved patient education, enhanced doctor–patient relationships and communication, and increased accessibility and affordability to healthcare can improve therapeutic adherence in patients.⁸⁴

A family history of CAD or premature CAD is an independent risk factor for developing premature CAD in young adults. A positive family history of CAD increased the risk of premature CAD twofold in the Iranian population.⁷² Similarly, a high prevalence of family history in up to 60% of patients was observed in our study. A wealth of studies conducted in other parts of Asia and European countries reported a similar association between positive family history and CAD. A family history of CAD increased the risk of developing CAD by 12-fold in young Chinese patients.⁸⁵ Additionally, the Second Northwick Park Heart Study found that the risk of CAD was three times higher among current smokers with a positive family history compared with nonsmokers without a family history. Such an association between family history and CVD can be attributable to genetic linkage, the aggregation of familial risk factors, or both.⁸⁶ Thus, assessing a patient's family history can be a powerful predictive tool for CAD in South Asians.

Another important modifiable risk factor for young CAD is dyslipidemia with low HDL and high low-density lipoprotein (LDL) and triglyceride levels. A dyslipidemic population has a twofold increased risk of premature CAD compared with people with normal lipid levels.⁷² Our study highlighted that more than 80% of young patients with CAD in three South Asian countries (India, Pakistan, and Bangladesh) with substantial populations have dyslipidemia. A multicenter study found that patients with CAD and type 2 diabetes mellitus had higher triglyceride levels and lower HDL and LDL cholesterol levels compared with non-diabetic patients.⁸⁷ Other Asian populations such as those in China and Japan also had a higher risk of CAD among individuals with hypertriglyceridemia and low HDL cholesterol compared with their healthy peers.^85,88 Similarly, a history of hypercholesterolemia was independently associated with premature CAD in a population cohort in the United States.⁸⁹

Our review further included a few studies that reported alcohol consumption as an independent predisposing factor for young CAD. A study in Nepal showed that 75% of (mostly male) young patients with CAD were alcohol consumers.¹⁴ Socio-cultural acceptance of alcoholic beverages in many ethnic communities of Nepal is a reason for increased consumption among the Nepalese population. Alcohol consumption has been linked to hypertension, dyslipidemia, and CAD.⁹⁰ Studies have reported that non-alcohol drinkers are 70% less likely than alcohol drinkers to have hypertension.⁹¹

High BMI, obesity, and a sedentary lifestyle are interconnected risk factors for non-communicable diseases such as diabetes, metabolic syndrome, and atherosclerotic CVDs. Patients with obesity had a 5.94-fold greater risk of developing obstructive coronary disease than patients with normal weight.⁹² This study similarly reported a high prevalence of these factors in the young population with CAD. According to the studies included in our review, more than 80% of young patients with CAD in Pakistan had a high BMI, dyslipidemia, and sedentary lifestyles. Other countries have reported similar proportions of these risk factors in their populations. High BMI and an inactive lifestyle are highly common in the South Asian general population, according to national surveys.^93–95

CAD is an atherosclerotic vascular disease characterized by endothelial cell dysfunction due to a rise in inflammatory cells such as monocytes, which leads to significant inflammation and vessel injury.⁹⁶ Hs-CRP, homocysteine, and lp(a) are established biomarkers of inflammation for young CAD that were briefly investigated in this study. When used with the traditional risk factors, these markers assist in the accurate assessment of patients. CRP and homocysteine are the markers of inflammation in premature CAD. This study established that hs-CRP and homocysteine can also be useful markers in young CAD. Various studies have demonstrated a positive correlation between CRP levels and premature CAD.^97,98 The levels of serum homocysteine and hs-CRP are also positively correlated with CAD severity, and levels increase with an increase in the number of coronary artery lesions.^98,99 Similarly, elevated lp(a) may confer an increased risk for incident CAD even in the absence of a positive family history of CAD or a guideline-lowered LDL cholesterol level (<70 mg/dL).^100,101 Our study showed that up to 70% of patients can have increased lp(a) levels. Given that lowering lp(a) levels with lifestyle modification and statin therapy remains ineffective, newer treatment modalities should be sought.¹⁰⁰

In addition to the risk factors explored in our study, the relationship between psychiatric illnesses and the risk of developing CAD in a young population deserves recognition. A review showed that the prevalence of depressive disorders among South Asians ranges from 0.5% to 97.0% of the population.¹⁰² Similarly, anxiety disorders were reported in as many as 66% of South Asians.¹⁰² According to Ren et al.,¹⁰³ these psychiatric disorders are more prevalent in patients with CAD than in the general population. The chronic exposure of the cardiovascular system to autonomic and endocrine dysregulation may explain the apparent relationship between depressive disorders and CAD. Patients with CAD and high depression and anxiety scores on psychological symptom scales may show improvement following treatment for CAD. Furthermore, the psychiatric treatment of these patients may improve the overall prognosis of CAD.¹⁰⁴

With regard to angiographic features, young patients with CAD from South Asia were more likely to have SVD than DVD or TVD. A similar distribution of angiographic characteristics was reported in young White patients.¹⁰⁵ However, multi-vessel disease is more common in older patients with CAD.^106,107 Atherosclerotic lesions in young patients that are present in the LAD and are proximal in location have been identified as important determinants of low left ventricular ejection fraction, which in turn increases mortality in STEMI.¹⁰⁸ According to our review, the common complications in young patients with CAD were heart failure, cardiogenic shock, arrhythmias, and mechanical complications. The young population with CAD experiences a significantly lower proportion of complications such as cardiogenic shock, heart failure, and arrhythmias than older patients.^15,46,109 However, some studies could not identify statistically significant differences in these complications.^8,15 Our study demonstrated that the mortality rate of young patients with CAD ranges from 0.2% to 12.0% in the South Asian region. Studies have reported a significantly lower mortality rate in South Asian patients under 45 years of age than those above 45 years of age.^8,15,46 However, the differences in post-acute coronary syndrome complications including death were not statistically significant between young and older patients in other studies.^8,109

Our study had a few limitations. We provided a qualitative summary without quantifying the association of the risk factors with young CAD. The use of a single age cut-off value of 45 years led to the exclusion of several studies with a relatively high age threshold for “young” patients with CAD and a lack of consideration of sex-based differences in the age of CAD onset.

Conclusion

Smoking and the use of smokeless tobacco, diabetes mellitus, hypertension, a family history of CAD or young CAD, dyslipidemia, high BMI, increased hs-CRP, and hyperhomocysteinemia were observed in a high proportion of young patients with CAD. SVD was more common than multi-vessel disease in young South Asian patients with CAD. Complications such as arrhythmia, cardiogenic shock, and heart failure were commonly observed in the study patients. Secondary prevention is crucial for reducing disease burden, psychological effects, and economic liability for patients, especially among young patients with CAD. Furthermore, strategies to reduce the prevalence of modifiable risk factors that are more common in young people with CAD must be implemented. Large-scale health promotion activities to curb modifiable risk factors such as smoking, obesity, and sedentary lifestyles should be conducted in South Asian countries. The strict implementation of dyslipidemia screening programs that start at a young age for vulnerable young populations is warranted in the South Asian region.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605231187806 - Supplemental material for Risk factors, lab parameters, angiographic characteristics and outcomes of coronary artery disease in young South Asian patients: a systematic review

Supplemental material, sj-pdf-1-imr-10.1177_03000605231187806 for Risk factors, lab parameters, angiographic characteristics and outcomes of coronary artery disease in young South Asian patients: a systematic review by Anushka Agrawal, Pratik Lamichhane, Mason Eghbali, Roshni Xavier, Daniel Elkin Cook, Reem Maged Elsherbiny, Loveleen Kaur Jhajj and Rajaram Khanal in Journal of International Medical Research

Supplemental Material

sj-pdf-2-imr-10.1177_03000605231187806 - Supplemental material for Risk factors, lab parameters, angiographic characteristics and outcomes of coronary artery disease in young South Asian patients: a systematic review

Supplemental material, sj-pdf-2-imr-10.1177_03000605231187806 for Risk factors, lab parameters, angiographic characteristics and outcomes of coronary artery disease in young South Asian patients: a systematic review by Anushka Agrawal, Pratik Lamichhane, Mason Eghbali, Roshni Xavier, Daniel Elkin Cook, Reem Maged Elsherbiny, Loveleen Kaur Jhajj and Rajaram Khanal in Journal of International Medical Research

Footnotes

Author contributions

A. Agrawal and P. Lamichhane contributed to the conceptualization of the study, the literature review, data acquisition, data analysis, and article writing. M. Eghbali, R. Xavier, D. Cook, R.M. Elsherbiny, and L.K. Jhajj contributed to the methodology, data acquisition, article writing, and article editing and revision. R. Khanal contributed to article writing, supervision, and article editing and revision. All authors have read and approved the final manuscript.

Declaration of conflicts of interest

The authors of the study have no conflict of interest to declare.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

ORCID iDs

Pratik Lamichhane

Mason Eghbali

Loveleen Kaur Jhajj

Supplementary Materials

The supplementary materials can be found in Supplementary files S1 and S2.

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