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South Asian Cardiovascular Disease & Cancer Risk: Genetics & Pathophysiology.

ABSTRACT: South Asians (SAs) are at heightened risk for cardiovascular disease as compared to other ethnic groups, facing premature and more severe coronary artery disease, and decreased insulin sensitivity. This disease burden can only be partially explained by conventional risk factors, suggesting the need for a specific cardiovascular risk profile for SAs. Current research, as explored through a comprehensive literature review, suggests the existence of population specific genetic risk factors such as lipoprotein(a), as well as population specific gene modulating factors. This review catalogues the available research on cardiovascular disease and genetics, anthropometry, and pathophysiology, and cancer genetics among SAs, with a geographical focus on the U.S. A tailored risk profile will hinge upon population customized classification and treatment guidelines, informed by continued research.

SUBMITTER: Palaniappan L

PROVIDER: S-EPMC6777562 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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South Asian Cardiovascular Disease & Cancer Risk: Genetics & Pathophysiology.

Palaniappan Latha L Garg Arun A Enas Enas E Lewis Henrietta H Bari Sehrish S Gulati Martha M Flores Cristina C Mathur Ashish A Molina Cesar C Narula Jagat J Rahman Shahid S Leng Jennifer J Gany Francesca F

Journal of community health 20181201 6

South Asians (SAs) are at heightened risk for cardiovascular disease as compared to other ethnic groups, facing premature and more severe coronary artery disease, and decreased insulin sensitivity. This disease burden can only be partially explained by conventional risk factors, suggesting the need for a specific cardiovascular risk profile for SAs. Current research, as explored through a comprehensive literature review, suggests the existence of population specific genetic risk factors such as ...[more]

PMID: 29948525

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Project description:BackgroundIndividuals of South Asian ancestry represent 23% of the global population, corresponding to 1.8 billion people, and have substantially higher risk of atherosclerotic cardiovascular disease compared with most other ethnicities. US practice guidelines now recognize South Asian ancestry as an important risk-enhancing factor. The magnitude of enhanced risk within the context of contemporary clinical care, the extent to which it is captured by existing risk estimators, and its potential mechanisms warrant additional study.MethodsWithin the UK Biobank prospective cohort study, 8124 middle-aged participants of South Asian ancestry and 449 349 participants of European ancestry who were free of atherosclerotic cardiovascular disease at the time of enrollment were examined. The relationship of ancestry to risk of incident atherosclerotic cardiovascular disease-defined as myocardial infarction, coronary revascularization, or ischemic stroke-was assessed with Cox proportional hazards regression, along with examination of a broad range of clinical, anthropometric, and lifestyle mediators.ResultsThe mean age at study enrollment was 57 years, and 202 405 (44%) were male. Over a median follow-up of 11 years, 554 of 8124 (6.8%) individuals of South Asian ancestry experienced an atherosclerotic cardiovascular disease event compared with 19 756 of 449 349 (4.4%) individuals of European ancestry, corresponding to an adjusted hazard ratio of 2.03 (95% CI, 1.86-2.22; P<0.001). This higher relative risk was largely consistent across a range of age, sex, and clinical subgroups. Despite the >2-fold higher observed risk, the predicted 10-year risk of cardiovascular disease according to the American Heart Association/American College of Cardiology Pooled Cohort equations and QRISK3 equations was nearly identical for individuals of South Asian and European ancestry. Adjustment for a broad range of clinical, anthropometric, and lifestyle risk factors led to only modest attenuation of the observed hazard ratio to 1.45 (95% CI, 1.28-1.65, P<0.001). Assessment of variance explained by 18 candidate risk factors suggested greater importance of hypertension, diabetes, and central adiposity in South Asian individuals.ConclusionsWithin a large prospective study, South Asian individuals had substantially higher risk of atherosclerotic cardiovascular disease compared with individuals of European ancestry, and this risk was not captured by the Pooled Cohort Equations.

Project description:ObjectivesThe 2018 and 2019 U.S. guidelines for the management of cholesterol and primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend consideration of cardiovascular risk-enhancing factors (REFs), including South Asian ancestry, to refine ASCVD risk estimation. However, the associations of REFs with atherosclerosis are unclear in South Asian American adults, who have a disproportionately elevated premature coronary heart disease risk. In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we investigated associations of individual REFs, or the number of REFs, with coronary artery calcium (CAC).MethodsUsing baseline and follow-up data from MASALA, we evaluated the association of REFs (family history of ASCVD, low-density lipoprotein cholesterol ≥160 mg/dL, triglycerides ≥175 mg/dL, lipoprotein(a) >50 mg/dL, high-sensitivity C-reactive protein [hsCRP] ≥2.0 mg/dL, ankle-brachial index <0.9, chronic kidney disease, metabolic syndrome), individually and combined, with baseline prevalent CAC, any CAC progression (including incident CAC and CAC progression), and annual CAC progression rates using multivariable logistic regression and generalized linear models.ResultsAmong 866 adults, mean age was 55 [SD 9] years and 47% were female. There were no significant associations of REFs with baseline prevalent CAC or any CAC progression (incident CAC and CAC progression at Exam 2) after adjustment. Among the 56% of participants who had any CAC progression, having 3+ REFs was associated with a significantly higher annual CAC progression rate (adjusted rate ratio [aRR] 1.94, 95% CI 1.39-2.72) vs. having 0 REFs. The annual CAC progression rate was 20% higher per additional REF (aRR 1.20, 95% CI 1.09-1.32). Findings were similar after excluding statin users, and among those with low 10-year ASCVD risk (<5%).ConclusionsAmong South Asian American adults, we found no association of REFs with prevalent CAC at baseline or having any CAC progression. Among those with any CAC progression, a higher number of REFs was associated with higher annual CAC progression rates.

Dataset Information

South Asian Cardiovascular Disease & Cancer Risk: Genetics & Pathophysiology.

Publications

South Asian Cardiovascular Disease & Cancer Risk: Genetics & Pathophysiology.

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