Low Vitamin D Status Attenuates Hypolipidemic and Pleiotropic Effects of Atorvastatin in Women

<i>Background/Objectives</i>: Low vitamin D status seems to be associated with increased cardiometabolic risk, and was found to attenuate cardiometabolic benefits of statins in men. The aim of the current study was to investigate whether a different vitamin D status determines the pleiotropic effects of statins in women. <i>Methods</i>: This pilot, single-center, prospective, matched-cohort study included 78 women with hypercholesterolemia requiring statin therapy, assigned into one of three age-, plasma lipid-, and body mass index-matched groups: women with vitamin D deficiency (group I), women with vitamin D insufficiency (group II), and women with normal vitamin D homeostasis (group III). Throughout the study (16 weeks), all patients were treated with atorvastatin. The outcome of interest included plasma lipids, glucose homeostasis markers (fasting glucose, HOMA-IR and glycated hemoglobin), plasma levels of 25-hydroxyvitamin D, creatine kinase, uric acid, high-sensitivity C-reactive protein, homocysteine, fibrinogen, urinary albumin-to-creatinine ratio (UACR), and computed values of a 10-year risk of atherosclerotic events. <i>Results</i>: Compared to the control group (group III), group I was characterized by higher values of HOMA-IR, glycated hemoglobin, uric acid, hsCRP, homocysteine, fibrinogen, a UACR, and a 10-year risk of atherosclerotic events, whereas group II had higher values of hsCRP, homocysteine and a UACR. Atorvastatin reduced plasma levels of total and LDL cholesterol and a 10-year risk of atherosclerotic events in all study groups, but this effect was weakest in group I and strongest in group III. In group III, the drug decreased uric acid, hsCRP, homocysteine, fibrinogen, and the UACR. In the remaining groups, its effect was limited to a small decrease in only hsCRP (group I) or in hsCRP and homocysteine (group II). In group I, atorvastatin treatment was associated with an increase in HOMA-IR, glycated hemoglobin, and creatine kinase. <i>Conclusions:</i> Low vitamin D status may exert an unfavorable effect on the lipid-dependent and lipid-independent effects of atorvastatin in middle-aged or elderly women.