Interaction of age with lipoproteins as predictors of aortic valve calcification in the multi-ethnic study of atherosclerosis

Abstract

Background: Previous epidemiologic studies have shown that low-density lipoprotein is an independent risk factor for prevalent aortic valve calcification (AVC); however, to our knowledge, the interactions between plasma lipoprotein concentrations and age on the relative risks (RRs) for AVC prevalence and severity have not been examined in a large, racially and ethnically diverse cohort.

Methods: Using stepwise RR regression, the relationships of baseline fasting lipid levels and lipoprotein levels to baseline prevalence and severity of AVC were determined in 5801 non-statin-using participants in the Multi-Ethnic Study of Atherosclerosis (MESA).

Results: In age-stratified, adjusted analyses, the low-density lipoprotein-associated RRs (95% confidence intervals) for prevalent AVC were higher for younger compared with older participants (age 45-54 years, 1.69 [1.19-2.39]; age 55-64 years, 1.48 [1.24-1.76]; age 65-74 years, 1.09 [0.95-1.25]; and age 75-84 years, 1.16 [0.99-1.36]; P interaction = .04]. There was a similar, significant interaction of age with total cholesterol-associated RR for prevalent AVC (P interaction = .04). In contrast, total- to high-density lipoprotein cholesterol ratio RRs were similar across all age strata (P interaction = .68). At multivariate analyses, no lipoprotein parameter was associated with AVC severity.

Conclusions: In this racially and ethnically diverse, preclinical cohort, low-density lipoprotein was a risk factor for AVC only in participants younger than 65 years, whereas the total cholesterol/high-density lipoprotein cholesterol ratio was associated with a modest increased risk of AVC across all ages. These findings may have important implications for the efficacy of and targets for dyslipidemia therapies in calcific aortic valve disease.

Trial registration: ClinicalTrials.gov NCT00005487.

Figures

Figure 1. Age-stratified, lipoprotein-associated relative risk of prevalent AVC

Shown are point estimates (squares) and 95% confidence intervals for adjusted relative risks per one standard deviation increase in Total cholesterol (Fig. 1A), low density lipoprotein (LDL, Fig. 1B), high density lipoprotein (HDL, Fig. 1C), triglycerides (Fig. 1D) and Total/HDL cholesterol ratio (Fig. 1E), stratified by decade of age.