Abstract Body (Do not enter title and authors here): Background: Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown.

Objectives: This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease.

Methods: 2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[<7.6 mg/dL], Q2[7.6-16.7 mg/dL], Q3[16.8-38.8 mg/dL], Q4[>38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling (Table).

Results: Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m²; P = 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m²; P = 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %; P = 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors (Table). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m²; P = 0.01), LV indexed mass (β 1.17 g/m²; P = 0.02) and a decrease in LV ejection fraction (β -1.01 %; P = 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 (Table - Model 3), and baseline coronary artery calcium score and interim myocardial infarction (Table - Model 4).

Conclusions: In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.