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Genetics-based risk scores for prediction of premature coronary artery disease.

ABSTRACT: Premature coronary artery disease (CAD) is endemic in India. Global Burden of Diseases study has reported that it led to 286,000 deaths in 2019 in India. Many of these patients have standard risk factors but a third have none. Clinical risk algorithms and imaging provide limited risk information in premature CAD. CAD is multifactorial and studies have now focused on the predictive capability of clusters of genes and single nucleotide polymorphisms (SNPs) using gene risk score (GRS). Older studies combined data from 10 to 12 genes and 100-500 SNPs to calculate GRS, however, following the advent of genome-wide association studies (GWAS), millions of SNPs have been incorporated. Studies have reported that GWAS-based GRS may be more discriminative than conventional tools. Recent studies, especially among South Asians, have reported that GRS improves net reclassification by 15% (12-19%) for younger individuals. Aggressive lifestyle interventions and lipid-lowering therapies can ameliorate risk in high-GRS individuals and potentially prevent premature CAD.

SUBMITTER: Gupta R

PROVIDER: S-EPMC10568063 | biostudies-literature | 2023 Sep-Oct

REPOSITORIES: biostudies-literature

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Genetics-based risk scores for prediction of premature coronary artery disease.

Gupta Rajeev R

Indian heart journal 20230825 5

Premature coronary artery disease (CAD) is endemic in India. Global Burden of Diseases study has reported that it led to 286,000 deaths in 2019 in India. Many of these patients have standard risk factors but a third have none. Clinical risk algorithms and imaging provide limited risk information in premature CAD. CAD is multifactorial and studies have now focused on the predictive capability of clusters of genes and single nucleotide polymorphisms (SNPs) using gene risk score (GRS). Older studie ...[more]

PMID: 37633460

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Project description:ObjectivesThis study compared risk discrimination for the prediction of coronary heart disease (CHD) and cardiovascular disease (CVD) deaths for the Pooled Cohort Equations (PCE), the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score (with and without coronary artery calcium [CAC]), and of simple addition of CAC to the PCE.BackgroundThe PCE predict 10-year risk of atherosclerotic CVD events, and the MESA Risk Score predicts risk of CHD. Their comparative performance for the prediction of fatal events is poorly understood.MethodsWe evaluated 53,487 patients ages 45 to 79 years from the CAC Consortium, a retrospective cohort study of asymptomatic individuals referred for clinical CAC scoring. Risk discrimination was measured using C-statistics.ResultsMean age was 57 years, 35% were women, and 39% had CAC of 0. There were 421 CHD and 775 CVD deaths over a mean 12-year follow-up. In the overall study population, discrimination with the MESA Risk Score with CAC and the PCE was almost identical for both outcomes (C-statistics: 0.80 and 0.79 for CHD death, 0.77 and 0.78 for CVD death, respectively). Addition of CAC to the PCE improved risk discrimination, yielding the largest C-statistics. The MESA Risk Score with CAC and the PCE plus CAC showed the best discrimination among the 45% of patients with 5% to 20% estimated risk. Secondary analyses by estimated CVD risk strata showed modestly improved risk discrimination with CAC also among low- and high-estimated risk groups.ConclusionsOur findings support the current guideline recommendation to use, among available risk scores, the PCE for initial risk assessment and to use CAC for further risk assessment in a broad borderline and intermediate risk group. Also, in select individuals at low or high estimated risk, CAC modestly improved discrimination. Studies in unselected populations will lead to further understanding of the potential value of tools combining risk scores and CAC for optimal risk assessment.

Project description:BackgroundABCA1 genetic variation is known to play a role in HDL-C levels and various studies have also implicated ABCA1 variation in cardiovascular risk. The functional ABCA1/R230C variant is frequent in the Mexican population and has been consistently associated with low HDL-C concentrations. Although it has been associated with other cardiovascular risk factors such as obesity and type 2 diabetes mellitus, it is not known whether it is associated with coronary artery disease (CAD).AimThe purpose of the study was to analyze whether the ABCA1/R230C variant is associated with premature CAD in a case-control association study (GEA or Genetics of Atherosclerotic Disease), and to explore whether BMI modulates the effect of the C230 allele on other metabolic traits using a population-based design.ResultsThe C230 allele was significantly associated with both lower HDL-C levels and a lower risk of premature CAD as compared to controls (OR?=?0.566; P(add)?=?1.499×10(-5)). In addition, BMI modulated the effect of R230C on body fat distribution, as the correlation between BMI and visceral to subcutaneous adipose tissue (a metric of the propensity to store fat viscerally as compared to subcutaneously) was negative in RR homozygous individuals, but positive in premenopausal women bearing the C230 allele, with a statistically significant interaction (P?=?0.005). BMI-R230C interaction was also significant for triglyceride levels in women regardless of their menopausal status (P?=?0.036).ConclusionThis is the first study assessing the effect of the R230C/ABCA1 variant in remature CAD. C230 was associated with both decreased HDL-C levels and a lower risk of premature CAD, and gender-specific BMI-R230C interactions were observed for different metabolic traits. These interactions may help explain inconsistencies in associations, and underscore the need to further analyze interactions of this functional and frequent variant with diet, exercise and other environmental factors.

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Genetics-based risk scores for prediction of premature coronary artery disease.

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Genetics-based risk scores for prediction of premature coronary artery disease.

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