Commentary based on Tasdighi E, Dardari Z, Whelton SP, et al. Sex-specific coronary artery calcium percentiles across South Asian adults: combined analyses from MASALA and DILWALE. JACC Adv. 2025;4(6 Pt 2):101779. doi:10.1016/j.jacadv.2025.101779

South Asian individuals living in the United States (SAUS) have an increased risk of atherosclerotic cardiovascular disease (ASCVD), most of which can be attributed to a relatively higher prevalence of traditional risk factors, potentially occurring at an earlier age than in other racial and ethnic groups. Beyond traditional risk factors, a high coronary artery calcium (CAC) score independently increases ASCVD risk across various racial and ethnic groups. Despite its high predictive value, the distribution of sex-specific CAC scores among SAUS is unknown, and risk-prediction models rely on CAC scores collected from white adults.

Tasdighi et al. assessed the sex-specific distribution of CAC score percentiles in a combined analysis of the community-based MASALA (Mediators of Atherosclerosis in South Asians Living in America) study and the clinic-based cohort of the DILWALE (DIL Wellness and Arterial health Longitudinal Evaluation) Registry, which exclusively includes SAUS.¹ The investigators estimated the likelihood of CAC score >0 and calculated sex-specific CAC score percentiles as a function of age, employing nonparametric methods. The combined analysis included 2,743 SAUS (mean age 52 years [standard deviation 9 years]; 37.8% women) from the two cohorts. The prevalence of CAC score >0 was 41% in the combined cohort. For SAUS 33-45 years of age, the prevalence of CAC score 1-99 was 21.4% in men and 4.5% in women. By 55 years of age, the prevalence of CAC score >0 was 65% in men and 30% in women.

Men had an earlier onset of CAC score >0 and the prevalence of CAC score >0 was higher in men than women of any age, consistent with previous analyses of sex-specific cohorts in other racial/ethnic groups.² However, women demonstrated a notable catch-up in CAC burden with age. In women, the prevalence of CAC score >0 exceeded 50% in those 60-65 years of age. Regardless of sex, the CAC burden increased with age, with the probability of CAC score >0 being approximately 50% at 55 years of age and approximately 70% at 65 years of age.

Commentary

Growing evidence shows that South Asian ethnicity is an independent risk factor for atherosclerotic disease.³ Risk calculators such as PREVENT (AHA Predicting Risk of CVD Events), Pooled Cohort Equations (PCE), or QRISK®3 (QRESEARCH Cardiovascular Risk Algorithm 3 [University of Nottingham, EMIS Group Limited]) underestimate atherosclerotic risk in this cohort despite controlling for various factors, mainly due to an absence of South Asian data in derivation cohorts.⁴ The American College of Cardiology/American Heart Association (ACC/AHA) expert consensus panel added that South Asian race is a critical risk factor and an exception to the ASCVD PCE in 2022. Advantageously, this may help identify South Asian individuals at higher risk on the basis of the presence of traditional risk factors. Alternatively, this also carries a risk of possible overprescription of lipid-lowering therapy. Use of the CAC score may serve to better identify those who would benefit from lipid-lowering therapy.⁵

Sex differences in CAC onset and progression suggest that, whereas men might benefit from earlier CAC screening (before 45-50 years of age), SAUS women may benefit from targeted CAC assessments after 55 years of age, particularly if other risk factors are present. The delayed yet accelerated rise in CAC progression may reflect hormonal or metabolic shifts after menopause and aggregate role of heighted traditional risk factors of coronary artery disease, which are independently associated with CAC score >0.⁶

These data emphasize the importance of incorporating sex-specific CAC percentiles into risk-prediction algorithms to avoid underestimating ASCVD risk in SAUS women, particularly in their 60s, when CAC burden appears to catch up rapidly.

The prevalence of CAC score >0 in both men and women was high by 50 years of age (65% in men, 30% in women). Compared with the prevalence of CAC score >0 in Chinese, African American, and Hispanic individuals of similar age, SAUS in the present analyses showed a higher prevalence of CAC score >0, indicating an earlier development of coronary atherosclerosis and subsequent higher risk of ASCVD in SAUS.⁷ This provides more data to consider South Asian lineage as a risk factor for ASCVD, warranting earlier interventions to reduce lifetime ASCVD risk. Indeed, this study's acceleration of CAC burden with age (e.g., 50% probability of CAC score >0 at 55 years of age vs. 70% at 65 years of age) is notable.

Compared with adults in the MESA (Multi-Ethnic Study of Atherosclerosis), SAUS showed a similar CAC burden to that of white adults for age <45 years but comparable or slightly higher CAC scores for age >45 years. Comparing CAC percentiles for SAUS in the present analyses to that of white individuals in the MESA, the 50^th percentile score for a 55-year-old white man is 6 and for a male SAUS is 5. At 65 years of age, the 50^th percentile for a white man is 71 and for a male SAUS is 125. These findings emphasize the crucial role of age in CAC burden in SAUS and the need for focused attention to low-density lipoprotein lowering efforts and frequent monitoring in this population at high risk.

Despite the size of the study population, selection bias, underrepresentation of women, lack of disaggregated ethnic data, temporal/geographic variations in study population, and outcome validation represent limitations and indicate the scope of future studies. Researchers and clinicians can use and build on this dataset to improve the accuracy of the current risk calculators and inform patient-centered care.

Conclusion

Tasdighi et al. address a significant gap in the current literature by providing sex-specific CAC data on an exclusively SAUS combined cohort. The results of the analyses not only highlight the earlier onset and higher burden of coronary calcification in South Asian men but also underscore the urgent need for targeted screening and preventive strategies in this population at high risk. Although the present analyses were limited by the lack of outcome validation and subgroup detail, Tasdighi et al. lay a critical foundation for a new era of precision prevention in ethnic cardiology. This foundation calls for continued research into personalized risk calculators, outcome-based validation, and implementation across diverse care settings with the purpose of improving the accuracy of the current risk calculators, optimizing preventive strategies (including aggressive lipid lowering), and informing patient-centered care. These data certainly serve as a crucial step in understanding the heterogeneity of these findings and will form the scaffold of various disaggregation studies of the populations making up SAUS.

References

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