Why might visit-to visit variability of lipoproteins have an effect on cardiovascular events?

Recently, an increased visit-to-visit variability in LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels has been identified as an independent predictor of adverse cardiovascular disease (CVD) events, and a higher visit-to-visit LDL-C variability was found to be associated with increasing all-cause mortality and composite endpoints, MI, and coronary revascularization as well [ 1 Boey E. Gay G.M. Poh K.K. Yeo T.C. Tan H.C. Lee C.H. Visit-to-visit variability in LDL- and HDL-cholesterol is associated with adverse events after ST-segment elevation myocardial infarction:A 5-year follow-up study. Atherosclerosis. 2016; 244: 86-92 Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar , 2 Kim M.K. Han K. Kim H.S. Park Y.M. Kwon H.S. Yoon K.H. et al. Cholesterol variability and the risk of mortality, myocardial infarction, and stroke:a nationwide population-based study. Eur. Heart J. 2017; 38: 3560-3566 Crossref PubMed Scopus (83) Google Scholar , 3 Gu J. Yin Z.F. Pan J.A. Zhang J.F. Wang C.Q. Visit-to-visit variability in low-density lipoprotein cholesterol is associated with adverse events in non-obstructive coronary artery disease. Anatol. J. Cardiol. 2019; 22: 117-124 PubMed Google Scholar ]. Most of these studies were performed on patients with CVD and there are very few studies on subjects without proven CVD. The largest study was performed in China on 51,620 general population subjects who had no history of acute myocardial infarction (AMI), stroke or cancer, and the results are presented in the paper published by Liu et al. in this issue of Atherosclerosis [ [4] Liu X. Wu S. Song Q. Wang X. Visit-to-visit variability of lipid measurements and the risk of myocardial infarction and all-cause mortality: a prospective cohort study. Atherosclerosis. 2020; Abstract Full Text Full Text PDF Scopus (4) Google Scholar ]. The subjects were followed up for a median 7.03 years, and according to these authors high visit-to-visit LDL-C and HDL-C variability was associated with an increased incidence of AMI and all-cause mortality while no significant associations were seen for triglycerides. Visit-to-visit variability of lipid measurements and the risk of myocardial infarction and all-cause mortality: A prospective cohort studyAtherosclerosisVol. 312PreviewPrevious studies suggested that increased visit-to-visit variability in lipid measurements is associated with cardiovascular disease in specific or high-risk populations. Because it is unknown whether this notion applies to the general population, we investigated whether lipid variability has additive effects on the risk of all-cause mortality and myocardial infarction (MI) in the general population. Full-Text PDF