Visit-to-visit lipid variability: Clinical significance, effects of lipid-lowering treatment, and (pharmaco) genetics.

Roelof A J Smit, Johan Wouter Jukema, Iris Postmus, Ian Ford, Pieternella Eline Slagboom, Bastiaan T Heijmans, Saskia Le Cessie, Stella Trompet

Journal: Journal of clinical lipidology 2019;12(2):266-276.e3

PMID: 29422286

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Abstract

In recent years, visit-to-visit variability of serum lipids has been linked to both clinical outcomes and surrogate markers for vascular disease. In this article, we present an overview of the current evidence connecting this intraindividual variability to these outcome measures, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. In addition, we undertook an explorative genome-wide association analysis on visit-to-visit variability of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, examining additive effects in 2530 participants from the placebo arm of the PROspective Study of Pravastatin in the Elderly at Risk trial. While we identified suggestive associations (P < 1 × 10) at 3 different loci (KIAA0391, amiloride-sensitive cation channel 1 neuronal [ACCN1], and Dickkopf WNT signaling pathway inhibitor 3 [DKK3]), previously published data from the genome-wide association study literature did not suggest plausible mechanistic pathways. Given the large degree of both clinical and methodological heterogeneity in the literature, additional research is needed to harmonize visit-to-visit variability parameters across studies and to definitively assess the possible role of (pharmaco)genetic factors.

Address: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Section of Gerontology and Geriatrics, Department of Internal Medicine, LUMC, Leiden, The Netherlands. Electronic address: [email protected].; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, LUMC, Leiden, The Netherlands.; Section of Gerontology and Geriatrics, Department of Internal Medicine, LUMC, Leiden, The Netherlands.; Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.; Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics, LUMC, Leiden, The Netherlands.; Department of Clinical Epidemiology, LUMC, Leiden, The Netherlands; Department of Medical Statistics and Bioinformatics, LUMC, Leiden, The Netherlands.; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Section of Gerontology and Geriatrics, Department of Internal Medicine, LUMC, Leiden, The Netherlands.

DOI: 10.1016/j.jacl.2018.01.001