ApoE Polymorphism Analysis in Health and Disease of South Asian Populations: A Systematic Review and Meta-Analysis.

The Deadly Triad

Cardiovascular Disease Prevention in South Asia: Gathering the Evidence

To explore whether the placenta contributes to the lipoprotein metabolism of pregnant women, we took advantage of the fact that placental proteins are encoded from the fetal genome and examined the associations between lipids of 525 pregnant women and the presence, in their newborns, of genetic polymorphisms of LPL and apolipoprotein E (APOE), two genes expressed in placenta. After adjustment for maternal polymorphisms, newborn LPL*S447X was associated with lower triglycerides (-21 +/- 9 mg/dl), lower LDL-cholesterol (LDL-C; -12 +/- 5 mg/dl), lower apoB (-14 +/- 4 mg/dl), higher HDL-C (5 +/- 2 mg/dl), and higher apoA-I (9 +/- 4 mg/dl) in their mothers; newborn LPL*N291S was associated with higher maternal triglycerides (114 +/- 31 mg/dl); and newborn APOE*E2 (compared to E3E3) was associated with higher maternal LDL-C (14 +/- 6 mg/dl) and higher maternal apoB (14 +/- 5 mg/dl). These associations (all P < 0.05) were independent of polymorphisms carried by the mothers and of lipid concentrations in newborns and were similar in amplitude to the associations between maternal polymorphisms and maternal lipids. Such findings support the active role of placental LPL and APOE in the metabolism of maternal lipoproteins and suggest that fetal genes may modulate the risk for problems related to maternal dyslipidemia (preeclampsia, pancreatitis, and future cardiovascular disease).

We studied the relationship of apolipoprotein E (apoE) isoforms and coronary artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing diagnostic coronary angiography. The presence of CAD was defined as >50% stenosis in at least one artery. ApoE allele frequencies were 0.12, 0.62, and 0.26 for epsilon 2, epsilon 3, and epsilon 4, respectively, in African Americans and 0.08, 0.78, and 0.14 for epsilon 2, epsilon 3, and epsilon 4, respectively, in Caucasians. Among African Americans, CAD was present in 9 of 34 epsilon 2 carriers (26%), significantly smaller (P < 0.05) in proportion compared with 39 of 82 epsilon 3 carriers and 43 of 92 epsilon 4 carriers (48% and 47%, respectively), suggesting a protective effect of the epsilon 2 allele. No such difference was seen in Caucasians. In African Americans but not Caucasians, LDL cholesterol was lower in epsilon 2 carriers than in epsilon 3 and epsilon 4 carriers (106 vs. 127 and 134 mg/dl, respectively; P < 0.005). After adjusting for lipid levels, the association between apoE2 and CAD was no longer significant. Thus, the protective effect of apoE2 seen in African Americans could be explained by a favorable lipid profile in epsilon 2 carriers, whereas in Caucasians, the absence of such a protective effect could be attributable to the lack of effect of apoE2 on the lipid profile.

Obesity and Atherogenic Dyslipidemia

BackgroundSouth Asian individuals are at higher of risk heart disease compared to White British, however are under-represented in cardiac rehabilitation (CR) despite its proven benefits. Reduced attendance and completion rates...

Comparison of Age at Diagnosis, Cytogenetic Risk, and Overall Survival Between Acute Myeloid Leukemia Patients of White and South Asian Race/Ethnicity in the United States

Case presentation: A 36-year-old nonsmoking, normotensive South Asian man presented to the emergency department of a community hospital with retrosternal chest pain of &60 minutes’ duration. His 12-lead ECG demonstrated 10 mm of ST-segment elevation in leads V2 through V6, and he received fibrinolytic therapy within 90 minutes of symptom onset. His pain resolved, but his ST segments only partially normalized; he had a peak creatine kinase of 4564 IU/L, and he showed signs of early heart failure. LDL cholesterol was 135 mg/dL, HDL 32 mg/dL, triglycerides 20 mg/dL, and total cholesterol 206 mg/dL; his body mass index (BMI) was 24 kg/m2. Cardiac catheterization demonstrated severe and diffuse triple-vessel disease, including occlusion of the proximal left anterior descending artery, as well as moderate left ventricular dysfunction. While in the hospital, he was diagnosed with new-onset type 2 diabetes mellitus and subsequently underwent uncomplicated coronary bypass surgery. South Asians are individuals whose ethnic roots originate from the Indian subcontinent, a large geographic area that includes India, Pakistan, Sri Lanka, Nepal, and Bangladesh. Collectively, South Asians represent one fifth of the global population. In North America, more than 2 million South Asians reside in the United States and almost 1 million in Canada. It is important to recognize that the term “South Asian” refers to a heterogeneous population, with important differences in diet, culture, and lifestyle among different South Asian populations and religions. Multiple studies of migrant South Asian populations have, however, confirmed a 3- to 5-fold increase in the risk for myocardial infarction and cardiovascular death as compared with other ethnic groups.1–3 In an analysis of age-standardized coronary heart disease (CHD) mortality in Canada over a 15-year period, South Asians had the highest CHD mortality compared with individuals of Chinese and European descent.4 In …

Re: Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease

Background Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein linked to an increased risk of cardiovascular diseases (CVD), including early onset coronary artery disease (CAD) and stroke. South Asians, who experience a relatively higher burden of CVD, are particularly affected by elevated Lp(a) levels.Only a few landmark studies have analyzed the risk of Lp(a) in South Asians (ex: Masala study).There continues to be a paucity of data discerning Lp(a) induced cardiovascular risk in specific South Asian ethnic groups (ex: Bangladeshis,Indians,or Pakistanis). Understanding the implications of Lp(a) in certain demographics is key to preventing adverse cardiovascular events in them. Purpose This narrative review explores the role of Lp(a) in cardiovascular risk for South Asians, focusing on genetic factors, associations with CVD, and barriers for risk stratification in this high-risk group. Methods A thorough literature review was conducted on Lp(a) levels in South Asian populations, examining studies on genetic determinants, Lp(a)'s association with cardiovascular outcomes, and challenges in managing elevated Lp(a) in clinical settings.Databases such as PubMed, Cochrane, and Google Scholar were used, and studies were limited to those published in English. Results South Asians, encompassing people from India, Pakistan, Sri Lanka, and Bangladesh, exhibit higher median Lp(a) levels compared to other ethnic groups.Genetic variations in the LPA gene, which encodes the Lp(a) particle, primarily determine the Lp(a) levels,which can contribute to the increased prevalence of elevated Lp(a) in South Asians.High Lp(a) levels independently predict an increased risk of CAD,especially when combined with risk factors like diabetes and hypertension.(2)The BRAVE study published in the European Journal of Epidemiology in 2015, showed a high burden of myocardial infarction cases among Bangladeshi subjects less than 50 years of age.(1)Despite such striking statistics,there is a lack of widespread screening for elevated Lp(a) in South Asian individuals.Current guidelines for managing Lp(a)-associated risk are not specific to ethnicity, risking underdiagnosis and undertreatment of elevated Lp(a) levels in this population.Therapeutic options to lower Lp(a), including niacin and PCSK9 inhibitors, show promise but remain underused, partially because of cost and availability-especially in low-income countries. Conclusion Lipoprotein(a) is a significant, yet underappreciated, risk factor for coronary artery disease in South Asians.This review highlights the need for further research on Lp(a)’s genetic basis and the role it plays in cardiovascular risk, to mitigate adverse cardiovascular events in high risk patient populations.This can pave way for guidelines on diagnostic and treatment approaches for elevated Lp(a),with the potential to reduce its cardiovascular disease burdens.Pathogenesis of Lp(a) in CAD

How can we realise the potentially large public health benefit of screening for type 2 diabetes mellitus in south Asians?

Epidemiological studies observed a higher prevalence of coronary atherosclerosis in South Asians when compared to Caucasians, but quantitative computed tomography differences in aggregate plaque volume (APV) and epicardial fat volume (EFV) between South Asians, Southeast or East Asians (SEEAs) and Caucasians remain unknown. We aimed to compare APV and EFV quantified on computed-tomographic-coronary-angiography (CTCA) between South Asian, SEEA and Caucasian populations residing in Australia. Age, gender and body-mass-index matched subjects from three ethnic groups who underwent clinically indicated 320-detector CTCA were retrospectively analysed. Percentage APV in the first 5cm of the left anterior descending artery (LAD) and EFV were quantified using dedicated software (Vital Images, USA). One-hundred-and-fifty subjects (average age = 57.7 years, 56 % male, n = 50 in each ethnic group) were analysed. Mean LAD percentage APV was highest in South Asians (44.5 ± 8.4 % vs. 37.5 ± 6.5 % in SEEAs and 39.5 ± 6.4 % in Caucasians, P = 0.00001). South Asian ethnicity predicted LAD APV above traditional risk factors on multivariate analysis (P = 0.000002). EFV was significantly higher in both South Asians (103.2 ± 41.7cm3 vs. 85.8 ± 39.4cm3, P = 0.035) and SEEAs (110.8 ± 36.9cm3 vs. 85.8 ± 39.4cm3, P = 0.001) when compared with Caucasians. In this cohort LAD percentage APV and EFV, as quantified on CTCA, differs between South Asians, SEEA and Caucasian populations, with higher LAD APV observed in South Asians and lower EFV in Caucasians. Atherosclerotic volume in LAD was best predicted by South Asian ethnicity above traditional risk factors and EFV. Further research is required to establish whether APV and EFV quantification can improve cardiac risk prediction in the South Asian population.

Abdominal aortic aneurysm and coronary artery disease: Frequent companions, but an uneasy relationship

Coronary Artery Disease (CAD) is one of the leading causes of mortality among South Asians, who represent only 25% of the global population but account for approximately 60% of CAD cases worldwide. This disparity is attributed to both genetic predispositions and lifestyle factors that contribute to an atypical lipoprotein profile, particularly characterized by elevated Apolipoprotein B (ApoB) levels. A systematic meta-analysis was conducted using six interventional studies published between 2004 and 2024, sourced from Google Scholar, PubMed, and Elicit, to evaluate the diagnostic and therapeutic potential of ApoB as a biomarker for CAD in South Asians. Results consistently demonstrated higher ApoB concentrations and ApoB mRNA expression in individuals with severe CAD. One study by Rychlik-Sych et al. reported that women requiring coronary artery bypass grafts had significantly elevated ApoB, while men exhibited a four-fold increase in ApoB gene expression. Additionally, research from the University of Kansas Medical Center identified specific APOA1 gene polymorphisms more prevalent in South Asians, contributing to lower HDL cholesterol levels and an increased ApoB/ ApoA1 ratio—a strong predictor of cardiovascular risk. Despite its predictive value, ApoB remains underutilized in clinical settings. The discussion emphasizes the limitations of conventional lipid panels and argues for the integration of Apolipoprotein-100 tests and targeted therapies to enhance early detection and intervention. Ultimately, the study advocates for a shift toward ethnicity-specific cardiovascular care, where the inclusion of ApoB as a core biomarker could significantly reduce CAD burden in South Asian communities and lead to more equitable health outcomes.

Apolipoprotein C-III (apoC-III) is a marker of triglyceride (TG)-rich lipoproteins, which are often increased in metabolic syndrome (MS). The T-455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apoC-III levels. To evaluate the contribution of apoC-III levels and T-455C polymorphisms in the coronary artery disease (CAD) risk of MS patients, we studied 873 patients, 549 with CAD and 251 with normal coronary arteries. Patients were classified also as having or not having MS (MS, n = 270; MS-free, n = 603). Lipids, insulin, apolipoprotein levels, and APOC3 T-455C genotypes were evaluated. ApoC-III levels were significantly increased in MS patients, and the probability of having MS was correlated with increasing quartiles of apoC-III levels. MS patients with CAD had significantly higher apoC-III levels than did CAD-free MS patients. The carriership for the -455C variant multiplied the probability of CAD in MS in an allele-specific way and was associated with increased apoC-III and TG levels. Obesity was less frequent in MS carriers of the -455C allele than in MS noncarriers (21.6% vs. 34.8%, P < 0.05). In conclusion, apoC-III-rich lipoprotein metabolism and the APOC3 polymorphism have relevant impacts on the CAD risk of MS patents.