Association of serum lipoprotein(a) and progression of structural heart disease: Insights from CARDIA study

Background/Synopsis

Lipoprotein (a) [Lp(a)] is an atherothrombotic and inflammatory lipoprotein associated with atherosclerosis and arterial stiffness, which may contribute to heart failure (HF). Few studies have focused on its role in HF progression.

Objective/Purpose

This study assessed the association between Lp(a) measured in young adulthood and HF stages over 25 years in the Coronary Artery Risk Development in Young Adults Study (CARDIA) study.

Methods

We identified CARDIA study participants with Lp(a) measurements at Year 7 (ages 25-37). Lp(a) was categorized as normal (< 75 nmol/L), intermediately elevated (75-124 nmol/L), or significantly elevated (> 124 nmol/L), aligned with NLA guidelines. HF stages at Year 5 and Year 30 were defined according to the 2013 AHA/ACC guidelines: stage 0, without risk factors; stage A, HF risk factors; stage B, asymptomatic cardiac structural or functional abnormalities; and stage C/D, symptomatic or end-stage HF. Among those with available data to classify HF stage at Year 5, we evaluated the cross-sectional association between Lp(a) and HF stage. Among those with available HF stages at both Year 5 and Year 30, we evaluated the association between Lp(a) and the change in HF stage from Year 5 to Year 30 (i.e., no increase, increase by 1 stage, increase by 2 or more stages) using ordinal logistic regression. All models were stratified by race (Black vs White). Base models adjusted for age and sex, with additional adjustment for HF risk factors (SBP, diabetes, smoking status, total & LDL cholesterol, lipid-lowering medication use).

Results

We identified 3501 CARDIA participants with both Lp(a) at Year 7 and HF stage at Year 5. 2275 (65%) had normal Lp(a), 584 (16.7%) had intermediately elevated, and 642 (18.3%) had significantly elevated Lp(a) (Figure). At Y5, intermediately elevated Lpa was not associated with higher HF stage in Black (odds ratio [OR]: 1.14, 95% confidence interval [CI]: 0.9, 1.45) or White (OR: 1.10, 95% CI: 0.77, 1.58) participants (interaction p=0.58). Significantly elevated Lp(a) was also not associated with HF stage, and point estimates were slightly but not significantly stronger in White (OR: 1.27, 95% CI: 0.91, 1.78) than in Black (OR: 1.03, 95% CI: 0.82, 1.31) participants. Point estimates for White participants were attenuated after further adjustment for cardiovascular risk factors. Among 2140 participants with available HF stages at both Y5 and Y30, intermediate and significantly elevated serum Lp(a) were not associated with progression of HF stages from Y5 to Y30 in Black (intermediately elevated: 1.02, 95% CI: 0.76, 1.37, significantly elevated: 1.07, 95% CI: 0.81, 1.42) or White (intermediately elevated: 0.96, 95% CI: 0.68, 1.37, significantly elevated: 0.86, 95% CI: 0.6, 1.22) participants (interaction p=0.23).

Conclusions

Lp(a) measured in young adulthood does not appear to be associated with subclinical HF stages in young adulthood and a progression of HF stages to midlife in Black or White participants after adjustment for traditional HF risk factors. Future studies should confirm these findings for clinical HF events.

Figure: Prevalence of HF Stages at Year 5 and Year 30 by Lp(a) categories and race.