High concordance in high Lp(a) levels among first- and second-degree relatives, finds study

The study, published in JAMA Cardiology, supports a recent recommendation for using this approach to identify individuals at risk of atherosclerotic cardiovascular disease (ASCVD) based on Lp(a) concentrations.

In the cross-sectional analysis, 47.0% of first-degree relatives of UK Biobank participants with a lipoprotein(a) concentration of at least 125 nmol/L were similarly affected, compared with 16.4% unrelated individuals.

Lp(a) concentrations are a highly heritable and potential causal risk factor for ASCVD. Recent consensus statements by the American Heart Association (AHA) and the European Atherosclerosis Society recommend screening of relatives of individuals with high Lp(a) concentrations, but in large populations, the expected yield of this approach has not been quantified. To determine the same, Laurens F. Reeskamp, University of Amsterdam, Amsterdam, the Netherlands, and colleagues aimed to measure the prevalence of high Lp(a) concentrations among first- and second-degree relatives of people with high Lp(a) concentrations compared with unrelated participants.

For this purpose, the researchers compared pairs of first-degree (n = 19 899) and second-degree (n = 9715) relatives with measured Lp(a) levels from the UK Biobank study and random pairs of unrelated individuals (n = 184 764). The data was collected from 2006 to 2010 and analyzed from 2021 to 2023. The analysis included a total of 52 418 participants (mean age, 57.3 years; 56.9% were women).

The main outcome of the study was determined as the concordance of clinically relevant high Lp(a) levels in first- and second-degree relatives of index participants having high Lp(a) levels.

The authors reported the following findings:

• Levels of Lp(a) were correlated among pairs of first-degree (Spearman ρ = 0.45) and second-degree (Spearman ρ = 0.22) relatives.
• 47.0% of first-degree and 31.8% of second-degree relatives of index participants with high Lp(a) levels also had elevated concentrations compared with 16.4% pairs of unrelated individuals.
• The concordance in high Lp(a) levels was generally consistent among subgroups (eg, those with prior ASCVD, postmenopausal women, and statin users).
• The odds ratios for relatives to have high Lp(a) levels if their index relative had a high Lp(a) level compared with those whose index relatives did not have high Lp(a) levels were 7.4 for first-degree relatives and 3.0 for second-degree relatives.

"Similar to familial hypercholesterolemia screening, these findings support the implementation of the cascade screening for high Lp(a) levels in relatives of people with high Lp(a) levels to identify and early and effectively treat patients at increased Lp(a)-attributable ASCVD risk," the researchers concluded.

Reference:

Reeskamp LF, Tromp TR, Patel AP, et al. Concordance of a High Lipoprotein(a) Concentration Among Relatives. JAMA Cardiol. Published online October 11, 2023. doi:10.1001/jamacardio.2023.3548