Detailed Family History of Premature Atherosclerotic Cardiovascular Disease to Guide Lipoprotein(a) Testing: The Multi-Ethnic Study of Atherosclerosis

Background/Synopsis

One in five individuals have elevated lipoprotein(a) [Lp(a)], an inherited risk factor for atherosclerotic cardiovascular disease (ASCVD). However, there is no clear consensus involving the appropriate testing criteria for Lp(a), specifically related to the role of a detailed family history of premature ASCVD for guidance.

Objective/Purpose

To assess the independent association between a detailed family history of premature ASCVD and Lp(a).

Methods

We studied 4,244 participants from the Multi-Ethnic Study of Atherosclerosis who had measures of Lp(a) (Visit 1) and completed detailed family history questionnaires (Visit 2). Family history of premature ASCVD (<55 years old in men, <65 years old in women) was defined as any myocardial infarction or stroke in a first-degree relative (mother, father, sibling). A combined family history of premature ASCVD score (0, 1, >2 first-degree relatives) was constructed. Modified Poisson regression modeling calculated prevalence ratios (PR) for Lp(a) >50 mg/dL according to family history of premature ASCVD after adjusting for age, sex, race/ethnicity, health insurance status, estimated glomerular filtration rate, and lipid-lowering medications.

Results

The mean age of participants was 61.7 years old, 52% were women, 28% were Black, and the median Lp(a) was 18 mg/dL (Q1: 8, Q3: 40). One in five individuals (21%) reported a family history of premature ASCVD, but the proportion of individuals who reported two or more first-degree relatives affected by premature ASCVD was two-fold higher among those with Lp(a) >50 versus <50 (4% versus 2%, p=0.003). There was a stepwise increment of Lp(a) and greater prevalence of Lp(a) >50 as the number of reported family members with premature ASCVD increased (Figure). In multivariable analyses considering individuals without a family history of premature ASCVD as reference, there was no significantly higher prevalence of Lp(a) >50 for individuals reporting one family member with premature ASCVD (PR=1.05, 95% CI: 0.90-1.22), though persons who had two or more family members affected by premature ASCVD had a 38% higher prevalence of Lp(a) >50 (PR=1.38, 95% CI: 1.03-1.84).

Conclusions

Consideration of an ordinal family history of premature ASCVD score may help to better identify those most likely to have elevated Lp(a) compared to current binary family history questionnaires. Detailed documentation involving family history of premature ASCVD may facilitate targeted use of Lp(a)-specific risk assessment in clinical practice.