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David S. Owens, MD; Ronit Katz, DPhil; Eric Johnson, BA; David M. Shavelle, MD; Jeffrey L. Probstfield, MD; Junichiro Takasu, MD, PhD; John R. Crouse, MD; J. Jeffrey Carr, MD, MSCE; Richard Kronmal, PhD; Matthew J. Budoff, MD; Kevin D. O’Brien, MD

Arch Intern Med. 2008;168(11):1200-1207.

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 Identifier: NCT00005487

Author Affiliations: Division of Cardiology, Department of Internal Medicine (Drs Owens, Probstfield, and O’Brien), and Department of Biostatistics (Drs Katz and Kronmal and Mr Johnson), University of Washington, Seattle; Division of Cardiology, Department of Medicine, Los Angeles Biomedical Research Institute at Harbor–University of California at Los Angeles Medical Center (Drs Shavelle, Takasu, and Budoff); and Division of Endocrinology and Metabolism, Department of Medicine (Dr Crouse), Department of Public Health Sciences (Dr Crouse), and Department of Radiology (Dr Carr), Wake Forest University School of Medicine, Winston-Salem, North Carolina.

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