The association of lipoprotein(a) with incident heart failure hospitalization: Atherosclerosis Risk in Communities study

Abstract

Background and aims Lipoprotein(a) [Lp(a)] is a proatherogenic lipoprotein associated with coronary heart disease, ischemic stroke, and more recently aortic stenosis and heart failure (HF). We examined the association of Lp(a) levels with incident HF hospitalization in the Atherosclerosis Risk in Communities (ARIC) study. We also assessed the relationship between Lp(a) levels and arterial stiffness as a potential mechanism for development of HF. Methods Lp(a) was measured in 14,154 ARIC participants without prevalent HF at ARIC visit 1 (1987–1989). The association of Lp(a) quintiles with incident HF hospitalization was assessed using Cox proportional-hazards models. Arterial stiffness parameters were stratified based on Lp(a) quintiles, and p-trend was calculated across ordered groups. Results At median follow-up of 23.4 years, there were 2,605 incident HF hospitalizations. Lp(a) levels were directly associated with incident HF hospitalization in models adjusted for age, race, gender, systolic blood pressure, history of hypertension, diabetes, smoking status, body mass index, heart rate, and high-density lipoprotein cholesterol (quintile 5 vs. quintile 1: hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.09–1.41; p-trend across increasing quintiles <0.01), but not after excluding prevalent and incident myocardial infarction cases (HR 1.07, 95% CI 0.91–1.27; p-trend = 0.70). When adjusted for age, gender, and race, Lp(a) quintiles were not significantly associated with arterial stiffness parameters. Conclusions Increased Lp(a) levels were associated with increased risk of incident HF hospitalization. After excluding prevalent and incident myocardial infarction, the association was no longer significant. Lp(a) levels were not associated with arterial stiffness parameters.

Lp(a) [Lipoprotein(a)]-Related Risk of Heart Failure Is Evident in Whites but Not in Other Racial/Ethnic Groups

“…Excluding individuals with previous MI or aortic valve stenosis showed that they mediated approximately two-thirds of HF risk, yet the association between Lp(a) and HF remained significant. Similarly, in Atherosclerosis Risk in Communities (ARIC) participants (9), Agarwala et al (2017) showed that individuals in the top quintile of Lp(a) (23.1–108.2 mg/dL) were at greater risk of HF hospitalization compared to those in the referent quintile (0.02–2.4 mg/dL); however, upon excluding those with prevalent or incident MI, the relationship was rendered non-significant. In addition, and in stark contrast to our findings, ARIC investigators found no evidence of a race interaction with Lp(a) and HF hospitalization ( p for race interaction=0.65).…”

“…The mechanism through which Lp(a) may influence HF remains unknown, but it was hypothesized that ischemia-related events such as MI would have a mediating influence on Lp(a)-related risk of HF. In a secondary analysis, we used an approach similar to that of previous investigators (8, 9) and excluded individuals who suffered an MI (Table 3, model 1). In a subsequent model (Table 3, model 2), we next excluded those who suffered an MI, underwent coronary artery bypass grafting or percutaneous transluminal coronary angioplasty.…”

“…Lp(a) has been well-characterized for its causal role in coronary heart disease and aortic valve stenosis (6, 7), but was only recently shown to be associated with greater risk of incident HF (8) and HF hospitalizations (9). Potentially complicating this observation, Lp(a) distributions are known to vary widely based on race/ethnicity.…”

“…Analyses were further conducted to determine whether observed relationships were mediated by ischemic-related events. Finally, previous studies (8, 9) have been unable to interrogate HF categorized by reduced ejection fraction (HFrEF) and preserved EF (HFpEF), and these outcomes were examined here.…”

ApoB, small-dense LDL-C, Lp(a), LpPLA 2 activity, and cognitive change

“…20 Lp(a) was measured using a commercially available automated isoform insensitive immunoturbidimetric assay (Denka Seiken). 32 Plasma LpPLA 2 activity was measured at −70°C using an automated Colorimetric Activity Method assay (diaDexus, South San Francisco, CA) using a Beckman Coulter (Sharon Hill, PA) (Olympus) AU400e AutoAnalyzer. We excluded 2 individuals with implausible values of ApoB and LpPLA 2 activity.…”