Investigating potential mediator between statin and coronary artery calcification

• Published in: PloS one Vol. 13; no. 9; p. e0203702
• Main Authors: Lee, Donghun, Joo, Hyung Joon, Jung, Ho-Won, Lim, Do-Sun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18-09-2018; Public Library of Science (PLoS)
• Subjects: Atherosclerosis; Biology and Life Sciences; C-reactive protein; Calcification; Calcification (ectopic); Cardiology; Cardiovascular disease; Cardiovascular diseases; CAT scans; Cholesterol; Computed tomography; Coronary artery; Coronary vessels; Cytokines; Density; Diabetes; Health risk assessment; Heart diseases; High density lipoprotein; Hospitals; Lipoprotein A; Low density lipoprotein; Medical treatment; Medicine and Health Sciences; Metabolic syndrome; Mortality; Patient outcomes; Physical Sciences; Physiological aspects; Prevention; Proteins; Research and Analysis Methods; Risk factors; Sensitivity analysis; Smooth muscle; Statins; Veins & arteries
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0203702

Statins are mainstay anti-lipidaemic treatments for preventing cardiovascular diseases but also known to increase coronary artery calcification (CAC). However, underlying relationship between statin and CAC is still unclear. This study explored the mediating role of five statin-related biochemical factors [i.e., low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, glucose, and high sensitivity C-reactive protein levels]. Seoul Metabolic Syndrome cohort study includes 1370 participants suspected of metabolic syndrome. For causal mediation analysis, the dataset for 2016 including 847 participants with coronary computed tomography without any missing value were analysed using the Mediation package in R software. This study identified a causal mediation mechanism of HDL-cholesterol among the five biochemical factors. It implied that statin treatment increases the HDL-cholesterol level, leading to decreasing the probability of CAC score > 0. Estimated values of interest in HDL-cholesterol mediation were (1) average causal mediation effect, -0.011 with 95% CI [-0.025, -0.003], (2) average direct effect, 0.143 with 95% CI [0.074, 0.219], and total effect, 0.132 with 95% CI [0.063, 0.209]. Its mediation effect was maintained regardless of statin intensity. Sensitivity analysis also provided a robustness of the results under potential existence of a confounder between HDL-cholesterol and CAC. This study suggests a potential causal pathway between statin and CAC (the positive association of statin on CAC) through HDL-cholesterol as an inhibitor.