Association of Lipoprotein(a) Levels With Myocardial Fibrosis in the Multi-Ethnic Study of Atherosclerosis

Lipoprotein(a) (Lp[a]) has been identified as an emerging risk factor for adverse cardiovascular (CV) outcomes, including heart failure. However, the connections among Lp(a), myocardial fibrosis (interstitial and replacement), and cardiac remodeling as pathways to CV diseases remains unclear. This study investigated the relationship between Lp(a) levels and myocardial fibrosis by cardiac magnetic resonance (CMR) T1 mapping and late gadolinium enhancement, as well as cardiac remodeling by cine CMR, in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort. The study included 2,040 participants with baseline Lp(a) measurements and T1 mapping for interstitial myocardial fibrosis (IMF) evaluation in 2010. Lp(a) was analyzed as a continuous variable (per log unit) and using clinical cutoff values of 30 and 50 mg/dL. Multivariate linear and logistic regression were used to assess the associations of Lp(a) with CMR measures of extracellular volume (ECV fraction [ECV%]), native T1 time, and myocardial scar, as well as parameters of cardiac remodeling, in 2,826 participants. Higher Lp(a) levels were associated with increased ECV% (per log-unit Lp[a]; β = 0.2%; P = 0.007) and native T1 time (per log-unit Lp[a]; β = 4%; P < 0.001). Similar relationships were observed between elevated Lp(a) levels and a higher risk of clinically significant IMF defined by prognostic thresholds per log-unit Lp(a) of ECV% (OR: 1.20; 95% CI: 1.04-1.43) and native T1 (OR: 1.2; 95% CI: 1.1-1.4) equal to 30% and 955 ms, respectively. Clinically used Lp(a) cutoffs (30 and 50 mg/dL) were associated with greater prevalence of myocardial scar (OR: 1.85; 95% CI: 1.1-3.2 and OR: 1.9; 95% CI: 1.1-3.4, respectively). Finally, higher Lp(a) levels were associated with left atrial enlargement and dysfunction. Elevated Lp(a) levels are linked to greater subclinical IMF, increased myocardial scar prevalence, and left atrial remodeling.