Hispanic or Latino Population in US Experiences Significant Heterogeneity in Lp(a) Levels

Parag H. Joshi, MD

Credit: UT Southwestern Medical Center

New research reports significant heterogeneity in lipoprotein(a) levels, a genetically determined risk-enhancing factor for atherosclerotic cardiovascular disease (ASCVD), across the diverse Hispanic or Latino population residing in the United States by heritage group and genetic ancestry.¹

The findings suggest the heterogeneity may have important implications for its use in further ASCVD risk assessment in these populations historically undertreated in medicine, as the Lp(a) distribution has not been previously described.

“The reasons for associations of Lp(a) with some socioeconomic/acculturation variables in our study are likely to be complex and may reflect gene environment interactions modulating Lp(a) concentrations or confounding by age, sex, Hispanic or Latino background, or other unmeasured factors,” wrote the investigative team, led by Parag H. Joshi, MD from the division of cardiology at the University of Texas Southwestern Medical Center and Carlos J. Rodriguez, MD, MPH from the Albert Einstein College of Medicine.

Lp(a) is predominantly monogenically determined and is a strong, independent risk factor for ASCVD, with significant heterogeneity across ancestral groups. Previously reported data indicated the median Lp(a) levels ranged from highest to lowest among African, South Asian, White, Hispanic, and East Asian individuals.² However, the distribution of Lp(a) across Hispanic or Latino individuals in the US is not well-known and could be in part due to their diverse geographic background and varying genetic admixture of European, Native American, and West African ancestries.

To better understand this association, investigators assessed the distribution of Lp(a) levels in the diverse, population-based Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Participants aged 18 – 74 years were recruited between 2008 to 2011 from households across 4 metropolitan areas (New York, Chicago, Miami, and San Diego). The HCHS/SOL represents 16,415 self-identified Hispanic or Latino participants from diverse geographic and cultural backgrounds (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American.

Study data were analyzed from April 2021 – April 2023. After excluding 298 participants (1.8%) without laboratory data due to lack of consent or lack or stored blood, a total of 16,117 HCHS/SOL participants (mean age, 41 years; 9680 females [52%]) with an Lp(a) result were included in the analysis. Patients were 7.7% Central American, 21.1% Cuban, 10.3% Dominican, Mexican 39.1%, 16.6% Puerto Rican, and 5.1% South American.

Among the population, the median Lp(a) levels were 19.7 nmol/L, with higher median values among older age groups and women. Median Lp(a) levels were additionally higher in adults with prevalent clinical ASCVD vs. those without prevalent clinical ASCVD (24.7 nmol/L vs.19.3 nmol/L; P <.001).

When viewing Lp(a) by self-identified Hispanic or Latino background, the highest median Lp(a) values were seen in those identifying as Cuban (30.4 nmol/L), Dominican (41 nmol/L), or Puerto Rican (28 nmol/L) background. Meanwhile, lower median Lp(a) values were found in those identifying as Central American (16.5 nmol/L), Mexican (12.4 nmol/L), or South American (15.1 nmol/L) background (P <.001).

For the 9642 unrelated individuals in the ancestry analysis with Lp(a) results, the individuals had a median ancestry of 16.7% Amerindian, 55.9% European, and 7% West African (P <.001). The analysis showed median West African genetic ancestry was lowest in the first quintile of Lp(a) and highest in the fifth quintile (5.5% and 12.1%, respectively; P <.001). Moreover, the reverse was seen for Amerindian ancestry (32.8% and 10.7%, respectively; P <.001).

The investigative team noted an important implication of the findings concern the association of race and ethnicity and ancestry with Lp(a) thresholds to identify increased ASCVD risk. The results of a broad range of Lp(a) levels in the HCHS/SOL population by self-identified background groups could lead to under classification of ASCVD risk in individuals from some Hispanic or Latino backgrounds, compared with others.

“The associations of Lp(a) level with ASCVD risk across Hispanic or Latino background groups can clarify these concepts and will be assessed in future HCHS/SOL analyses when sufficient ASCVD events have accumulated,” Joshi and Rodriguez wrote.

The investigative team additionally noted the analysis may have important implications for the representation of Hispanic or Latino individuals in clinical trials of therapeutics enrolling by absolute levels of Lp(a).

“Consideration should be given to enrolling a diverse representative sample of Hispanic or Latino individuals by background and genetic ancestry,” investigators wrote.

References

Joshi PH, Marcovina S, Orroth K, et al. Heterogeneity of Lipoprotein(a) Levels Among Hispanic or Latino Individuals Residing in the US. JAMA Cardiol. Published online May 24, 2023. doi:10.1001/jamacardio.2023.1134

Tsimikas S, Marcovina SM. Ancestry, lipoprotein(a), and cardiovascular risk thresholds: JACC review topic of the week.J Am Coll Cardiol. 2022;80(9):934-946. doi:10.1016/j.jacc.2022.06. 019