Key takeaways:

• HeFH is up to seven times more prevalent in South Asians vs. the general population.
• In a cohort of South Asian individuals, those with HeFH had an up to twofold increased risk for adverse CV outcomes and death.

SCOTTSDALE, Ariz. — The prevalence of genetic high cholesterol is estimated to be approximately sevenfold higher in the South Asian population compared with previous estimations in the global general population, a speaker reported.

Compared with South Asian individuals without heterozygous familial hypercholesterolemia, those with heterozygous FH (HeFH) may have an up to twofold greater risk for major adverse CV events, premature atherosclerotic CVD, CV death and all-cause death, according to a presentation.

Data derived from Bennett J, et al. Early career research presentations. Presented at: American Society for Preventive Cardiology Congress on CVD Prevention; July 31-Aug. 2, 2026; Scottsdale, Ariz.

At the American Society for Preventive Cardiology Congress on CVD Prevention, Josiah Bennett, MD, cardiovascular disease fellow at Emory University, presented new data on the burden of HeFH among South Asians, a population that has not previously been well characterized. Bennett took second place in the Best Early Career Abstract award contest at the meeting.

“Familial hypercholesterolemia is among the most common autosomal dominant disorders, driven primarily by mutations in LDL receptors, [apolipoprotein B] and PCSK9 in Western populations primarily. The global prevalence is one in 313. South Asians represent about one-quarter of our world’s population right now, and they have a two times baseline ASCVD risk,” Bennett said during the presentation. “It’s been difficult to characterize the South Asian gap. So over half of the clinically diagnosed heterozygous FH mutations in cohorts from South Asia carry almost no Western LDL, ApoB or PCSK9 variants. Instead, they harbor novel population-specific mutations.”

Results of a prior global meta-analysis published in the Journal of the American College of Cardiology indicated that the prevalence of HeFH in the general population was one in 313. Therefore, Bennett and colleagues conducted an analysis of the Precision Center for Cardiometabolic Risk Reduction in South Asia, a population-based cohort including more than 21,860 residents of New Delhi and Chennai, India (mean age, 44 years; 54% women).

The researchers evaluated the estimated prevalence of HeFH and its association with adverse CV outcomes over a median follow-up of 8.6 years. Phenotypic HeFH prevalence was estimated using both the National Lipid Association (NLA) criteria — LDL of 190 mg/dL or more or non-HDL of 220 mg/dL or more — or a modified Dutch Lipid Clinic Network (DLCN) score, which utilized a point system for the diagnosis of HeFH including family history, clinical history and LDL levels. The modification was necessary because data from physical exams and genetic testing were not available, Bennett said during the presentation.

Less than 4% of the overall cohort was on lipid-lowering therapies at baseline, according to the presentation.

The researchers reported that the prevalence of phenotypic HeFH was approximately sevenfold higher in the Precision Center for Cardiometabolic Risk Reduction in South Asia cohort compared with the prior meta-analysis of the general population. The estimated prevalence was one in 42 based on the NLA definition and one in 62 based on the modified DLCN score, according to the presentation.

After adjusting for age, sex, modifiable risk factors and ASCVD, researchers reported significant associations between phenotypic HeFH diagnosis based on the NLA and DLCN definitions, respectively, and elevated risk for the following:

• major adverse CV events (adjusted HR for NLA = 1.64; 95% CI, 1.21-2.24; aHR for DCLN = 1.75; 95% CI, 1.23-2.5);
• premature ASCVD (aHR for NLA = 1.76; 95% CI, 1.1-2.82; aHR for DLCN = 2.02; 95% CI, 1.15-3.53);
• CV death (aHR for NLA = 1.77; 95% CI, 1.25-2.51; aHR for DLCN = 1.81; 95% CI, 1.2-2.74); and
• all-cause death (aHR for NLA = 1.31; 95% CI, 1.02-1.7; aHR for DCLN = 1.3; 95% CI, 0.94-1.8).

“South Asian phenotype heterozygous FH, by modified Dutch Lipid criteria, yields a 1.6 to two times increased risk of MACE, and this is concordant with genetically confirmed HeFH. Of note, 7% of these patients are not on lipid-lowering therapy,” Bennet said during the presentation. “Overall, we should screen broadly [and] treat aggressively. We may need to encourage genetic counseling and develop South Asian-specific family cascade screening. We should not wait for the genetics to catch up. The phenotype is showing that it’s killing people now.”