Impact of SLCO1B1 Polymorphism and Vitamin D Status on Statin Efficacy and Tolerability in Postmenopausal Women

<b>Background</b>: Interindividual differences in statin efficacy and tolerability are partly determined by genetic and metabolic factors. The <i>SLCO1B1</i> c.521T>C polymorphism affects hepatic statin transport, while vitamin D deficiency may influence lipid metabolism and muscular tolerance. This study aimed to assess the impact of <i>SLCO1B1</i> genotype and vitamin D status on lipid-lowering response and adverse events in postmenopausal women treated with atorvastatin or rosuvastatin. <b>Methods</b>: A total of 145 Croatian postmenopausal women were prospectively followed for 16 weeks. Participants received atorvastatin or rosuvastatin with dose titration to achieve low-density lipoprotein cholesterol (LDL-C) targets. Serum lipids, liver enzymes, and creatine kinase were monitored monthly. Serum levels of 25-hydroxyvitamin D were quantified by LC-MS/MS, while <i>SLCO1B1</i> c.521T>C genotyping was performed using real-time PCR. <b>Results</b>: Rosuvastatin achieved a higher LDL-C target attainment rate compared with atorvastatin (81.1% vs. 67.6%, <i>p</i> = 0.02). The <i>SLCO1B1</i> genotype was not associated with lipid response but was significantly associated with adverse effects. In multivariable regression analysis, patients with the T/C genotype had a significantly higher risk of developing adverse effects compared with those with the T/T genotype (OR 7.4, 95% Cl 2.1-26.7, <i>p</i> = 0.002). Vitamin D status showed no significant association with lipid outcomes or adverse events, although participants with severe deficiency exhibited a weaker LDL-C response. <b>Conclusions</b>: Rosuvastatin demonstrated superior lipid-lowering efficacy and tolerability compared with atorvastatin in postmenopausal women. The <i>SLCO1B1</i> c.521T>C variant primarily affected safety rather than efficacy, while severe vitamin D deficiency might contribute to diminished statin response. Integrating pharmacogenetic and endocrine profiling could enhance individualized statin therapy and cardiovascular prevention in women.