Lipid Level, Lipid Variability, and Risk of Multiple Myeloma: A Nationwide Population-Based Study of 3,527,776 Subjects

SIMPLE SUMMARY: There is preclinical evidence that abnormalities in lipid metabolism promote cancer development, and a few studies show the association between lipid levels and multiple myeloma (MM). However, to our knowledge, the role of lipid variability as a risk factor for MM has not been evaluated. We investigated whether lipid level and its variability are associated with the development of MM at a population level. Lower baseline lipid levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, and high variability in high-density lipoprotein cholesterol were all associated with increased risk of developing MM. These findings support the role of lipid metabolism in MM risk. ABSTRACT: (1) Background: There is evidence that abnormality in lipid metabolism promotes cancer development. This study investigated whether lipid level and its variability are associated with the development of MM at a population level. (2) Methods: A retrospective cohort study included a total of 3,527,776 subjects aged 40 and above who participated in ≥3 health examinations within the previous five years, including the index year (2012–2013). Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) were measured, and visit-to-visit lipid variability were calculated by variability independent of the mean (VIM) method. The study population was followed from the health examination date in the index year until the diagnosis of MM, death, or the last follow-up date (31 December 2017). (3) Results: During a median (5–95%) 5.1 years of follow-up, 969 subjects developed MM. A lower risk of MM was observed with higher quartiles of baseline lipid levels compared to the lowest quartile group (Q4 vs. Q1: adjusted hazard ratios (aHRs) 0.51, 95% confidence interval (CI) (0.42–0.61) for TC; 0.50 (0.41–0.61) for HDL-C; 0.65 (0.54–0.77) for LDL-C; and 0.72 (0.60–0.87) for TG in model (3). Among all lipid measures, only variability in HDL-C was associated with risk of MM: aHRs (95% CI) were 1.12 (0.91–1.38), 1.19 (0.97–1.46), and 1.34 (1.09–1.65) in the Q2, Q3, and Q4, respectively, compared to the Q1 of VIM of HDL-C. (4) Conclusions: This study shows that patients with lower lipid levels and high HDL-C variability are at increased risk of developing MM.