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  • Elevated Lipoprotein(a) Does Not Cause Low-Grade Inflammation Despite Causal Association With Aortic Valve Stenosis and Myocardial Infarction: A Study of 100,578 Individuals from the General Population.

Elevated Lipoprotein(a) Does Not Cause Low-Grade Inflammation Despite Causal Association With Aortic Valve Stenosis and Myocardial Infarction: A Study of 100,578 Individuals from the General Population.

The Journal of clinical endocrinology and metabolism (2015-05-06)
Anne Langsted, Anette Varbo, Pia R Kamstrup, Børge G Nordestgaard
ABSTRACT

It is unknown whether elevated lipoprotein(a) is causally associated with low-grade inflammation. We tested the hypothesis that elevated lipoprotein(a) is observationally and causally associated with low-grade inflammation together with aortic valve stenosis and myocardial infarction. Using a multidirectional Mendelian randomization approach, we studied 100,578 individuals from the Danish general population with plasma levels of and/or genotypes known to affect levels of lipoprotein(a) and C-reactive protein (CRP), and using information regarding diagnosis of aortic valve stenosis and of myocardial infarction (MI) from registries. Observationally, CRP increased by 29% (95% confidence interval [CI], 23-34) per 50-mg/dL increase in lipoprotein(a). However, two LPA single nucleotide polymorphisms (SNPs) and the kringle IV type 2 (KIV-2) genotype that were associated with 98, 95, and 68 mg/dL higher lipoprotein(a) levels were not causally associated with increased CRP levels. For aortic valve stenosis, a 1-SD increase in lipoprotein(a) levels was associated observationally with a multifactorially adjusted hazard ratio of 1.23 (95% CI, 1.06-1.41), with corresponding causal risk ratios of 1.38 (1.23-1.55) based on LPA SNPs and of 1.21 (1.06-1.40) based on LPA KIV-2 genotype. For myocardial infarction, corresponding values were 1.20 (1.10;1.31) observationally, and 1.18 (1.11;1.26) and 1.31 (1.22;1.42) causally, respectively. Observational hazard ratios for aortic valve stenosis and MI were similar after further adjustment for CRP levels. Elevated levels of lipoprotein(a) were not causally associated with increased low-grade inflammation as measured through CRP despite a causal association with increased risk of aortic valve stenosis and MI.

MATERIALS
Product Number
Brand
Product Description

SAFC
Cholesterol, Plant-Derived, SyntheChol®, NF, Ph. Eur., JP
Sigma-Aldrich
Cholesterol, from sheep wool, ≥92.5% (GC), powder
Sigma-Aldrich
Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
Sigma-Aldrich
Cholesterol, Sigma Grade, ≥99%
SAFC
Cholesterol, from sheep wool, Controlled origin, meets USP/NF testing specifications
Sigma-Aldrich
Cholesterol, Vetec, reagent grade, ≥92.5%