{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:15:45Z","timestamp":1760058945150,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia in Katowice"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.<\/jats:p>","DOI":"10.3390\/nu17101674","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T04:39:16Z","timestamp":1747283956000},"page":"1674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low Vitamin D Status Attenuates Hypolipidemic and Pleiotropic Effects of Atorvastatin in Women"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-2620","authenticated-orcid":false,"given":"Robert","family":"Krysiak","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyk\u00f3w 18, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-4563","authenticated-orcid":false,"given":"Karolina","family":"Kowalcze","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, Academy of Silesia, Rolna 43, 40-555 Katowice, Poland"},{"name":"Department of Pediatrics in Bytom, Faculty of Health Sciences in Katowice, Medical University of Silesia, Stefana Batorego 15, 41-902 Bytom, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Witold","family":"Szkr\u00f3bka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyk\u00f3w 18, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-2906","authenticated-orcid":false,"given":"Bogus\u0142aw","family":"Okopie\u0144","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyk\u00f3w 18, 40-752 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.atherosclerosis.2021.05.016","article-title":"Trends in lipid-modifying agent use in 83 countries","volume":"328","author":"Blais","year":"2021","journal-title":"Atherosclerosis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1124\/pr.115.012203","article-title":"New era of lipid-lowering drugs","volume":"68","author":"Barter","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ecl.2022.02.005","article-title":"Assessment of cardiovascular disease risk: A 2022 update","volume":"51","author":"Goldsborough","year":"2022","journal-title":"Endocrinol. Metab. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/cvr\/cvab032","article-title":"Emerging views of statin pleiotropy and cholesterol lowering","volume":"118","author":"Yu","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s11883-021-00977-6","article-title":"Statins and inflammation","volume":"23","author":"Satny","year":"2021","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/01.mca.0000131573.31966.34","article-title":"The antioxidant effects of statins","volume":"15","author":"Davignon","year":"2004","journal-title":"Coron. Artery Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.atherosclerosis.2008.08.022","article-title":"The pleiotropic effects of statins on endothelial function, vascular inflammation, immunomodulation and thrombogenesis","volume":"203","author":"Blum","year":"2009","journal-title":"Atherosclerosis"},{"doi-asserted-by":"crossref","unstructured":"Siniscalchi, C., Basaglia, M., Riva, M., Meschi, M., Meschi, T., Castaldo, G., and Di Micco, P. (2023). Statins effects on blood clotting: A review. Cells, 12.","key":"ref_8","DOI":"10.3390\/cells12232719"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2174\/1568006043586170","article-title":"The role of statins in oxidative stress and cardiovascular disease","volume":"5","author":"Ng","year":"2005","journal-title":"Curr. Drug Targets Cardiovasc. Haematol. Disord."},{"doi-asserted-by":"crossref","unstructured":"Di Costanzo, A., Indolfi, C., Sorrentino, S., Esposito, G., and Spaccarotella, C.A. (2023). The Effects of statins, ezetimibe, PCSK9-Inhibitors, inclisiran, and icosapent ethyl on platelet function. Int. J. Mol. Sci., 24.","key":"ref_10","DOI":"10.3390\/ijms241411739"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","article-title":"Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein","volume":"359","author":"Ridker","year":"2008","journal-title":"N. Engl. J. Med."},{"doi-asserted-by":"crossref","unstructured":"Heart Protection Study Collaborative Group (2011). Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: A randomised controlled trial. Lancet, 378, 2013\u20132020.","key":"ref_12","DOI":"10.1016\/S0140-6736(11)61125-2"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1001\/jama.285.13.1711","article-title":"Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial","volume":"285","author":"Schwartz","year":"2001","journal-title":"JAMA"},{"doi-asserted-by":"crossref","unstructured":"Cholesterol Treatment Trialists\u2019 (CTT) Collaboration, Baigent, C., Blackwell, L., Emberson, J., Holland, L.E., Reith, C., Bhala, N., Peto, R., Barnes, E.H., and Keech, A. (2010). Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet, 376, 1670\u20131681.","key":"ref_14","DOI":"10.1016\/S0140-6736(10)61350-5"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0140-6736(09)61965-6","article-title":"Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials","volume":"375","author":"Sattar","year":"2010","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1210\/clinem\/dgac562","article-title":"Statins, type 2 diabetes, and body mass index: A univariable and multivariable mendelian randomization study","volume":"108","author":"Yang","year":"2023","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.chembiol.2013.12.016","article-title":"Vitamin D metabolism, mechanism of action, and clinical applications","volume":"21","author":"Bikle","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/nrcardio.2016.73","article-title":"Vitamin D and cardiovascular disease prevention","volume":"13","author":"Pilz","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_19","first-page":"144","article-title":"Vitamin D deficiency and cardiovascular pathology","volume":"90","author":"Podzolkov","year":"2018","journal-title":"Ter. Arkh."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.atherosclerosis.2016.04.007","article-title":"Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up","volume":"25","author":"Daraghmeh","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4330\/wjc.v9.i1.14","article-title":"Vitamin D and acute myocardial infarction","volume":"9","author":"Milazzo","year":"2017","journal-title":"World J. Cardiol."},{"doi-asserted-by":"crossref","unstructured":"Kim, H.A., Perrelli, A., Ragni, A., Retta, F., De Silva, T.M., Sobey, C.G., and Retta, S.F. (2020). Vitamin D deficiency and the risk of cerebrovascular disease. Antioxidants, 9.","key":"ref_22","DOI":"10.3390\/antiox9040327"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1161\/ATVBAHA.108.165886","article-title":"Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease results from NHANES 2001 to 2004","volume":"28","author":"Melamed","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/obr.12793","article-title":"Vitamin D and cardiometabolic disorders: A review of current evidence, genetic determinants and pathomechanisms","volume":"20","author":"Marquina","year":"2019","journal-title":"Obes. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.2337\/dc12-0962","article-title":"Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: A meta-analysis of prospective studies","volume":"36","author":"Song","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"54","DOI":"10.2174\/138945011793591617","article-title":"Vitamin D in atherosclerosis, vascular disease, and endothelial function","volume":"12","author":"Brewer","year":"2011","journal-title":"Curr. Drug Targets"},{"doi-asserted-by":"crossref","unstructured":"Melguizo-Rodr\u00edguez, L., Costela-Ruiz, V.J., Garc\u00eda-Recio, E., De Luna-Bertos, E., Ruiz, C., and Illescas-Montes, R. (2021). Role of vitamin D in the metabolic syndrome. Nutrients, 13.","key":"ref_27","DOI":"10.3390\/nu13030830"},{"doi-asserted-by":"crossref","unstructured":"Li, X., Liu, Y., Zheng, Y., Wang, P., and Zhang, Y. (2018). The effect of vitamin D supplementation on glycemic control in type 2 diabetes patients: A systematic review and meta-analysis. Nutrients, 10.","key":"ref_28","DOI":"10.3390\/nu10030375"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e075230","DOI":"10.1136\/bmj-2023-075230","article-title":"Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial","volume":"381","author":"Thompson","year":"2023","journal-title":"BMJ"},{"doi-asserted-by":"crossref","unstructured":"Krysiak, R., Basiak, M., Machnik, G., Szkr\u00f3bka, W., and Okopie\u0144, B. (2023). Vitamin D status determines cardiometabolic effects of cabergoline in women with elevated prolactin levels: A pilot study. Nutrients, 15.","key":"ref_30","DOI":"10.3390\/nu15102303"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/1440-1681.13428","article-title":"The impact of vitamin D status on cardiometabolic effects of fenofibrate in women with atherogenic dyslipidemia","volume":"48","author":"Krysiak","year":"2021","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/clc.22593","article-title":"Different cardiometabolic effects of atorvastatin in men with normal vitamin D status and vitamin D insufficiency","volume":"39","author":"Krysiak","year":"2016","journal-title":"Clin. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s11883-019-0776-8","article-title":"2018 cholesterol guidelines: Key topics in primary prevention","volume":"21","author":"Clark","year":"2019","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s43440-020-00135-w","article-title":"The impact of atorvastatin on cardiometabolic risk factors in brothers of women with polycystic ovary syndrome","volume":"73","author":"Krysiak","year":"2021","journal-title":"Pharmacol. Rep."},{"unstructured":"Food and Drug Administration (2009). Guidance for Clinical Investigators, Sponsors, and IRBs Adverse Effect Reporting to IRBs\u2014Improving Human Subject Protection.","key":"ref_35"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"7","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1001\/jamainternmed.2024.1302","article-title":"Atherosclerotic cardiovascular disease risk estimates using the predicting risk of cardiovascular disease events equations","volume":"184","author":"Anderson","year":"2024","journal-title":"JAMA Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.hlc.2020.09.003","article-title":"Combating inflammation in cardiovascular disease","volume":"30","author":"Sethwala","year":"2021","journal-title":"Heart Lung Circ."},{"key":"ref_39","first-page":"7","article-title":"Hyperhomocysteinemia and cardiovascular diseases","volume":"80","author":"Guieu","year":"2022","journal-title":"Ann. Biol. Clin."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.amjmed.2021.11.019","article-title":"Microalbuminuria constitutes a clinical action item for clinicians in 2021","volume":"135","author":"Rossing","year":"2022","journal-title":"Am. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.ahj.2009.08.009","article-title":"L-TAP 2 Investigators. Low- and high-density lipoprotein cholesterol goal attainment in dyslipidemic women: The Lipid Treatment Assessment Project (L-TAP) 2","volume":"158","author":"Santos","year":"2009","journal-title":"Am. Heart J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.amjcard.2014.02.018","article-title":"Gender differences in achieving optimal lipid goals in patients with coronary artery disease","volume":"113","author":"Victor","year":"2014","journal-title":"Am. J. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s41043-024-00668-3","article-title":"Serum vitamin D concentration and anthropometric indicators of adiposity in adults without or with low dose statin users: A cross-sectional study","volume":"43","author":"Ashraf","year":"2024","journal-title":"J. Health Popul. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.thromres.2016.12.019","article-title":"Impact of high-dose statins on vitamin D levels and platelet function in patients with coronary artery disease","volume":"150","author":"Verdoia","year":"2017","journal-title":"Thromb. Res."},{"doi-asserted-by":"crossref","unstructured":"Sygitowicz, G., Sitkiewicz, D., Wrzosek, K., and D\u0142u\u017aniewski, M. (2024). The impact of atorvastatin treatment on the distribution of low-density lipoprotein subfractions and the level of vitamin D in patients after acute myocardial infarction: Preliminary findings. Int. J. Mol. Sci., 25.","key":"ref_45","DOI":"10.3390\/ijms252011264"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2174\/1874192401408010055","article-title":"Comparative effect of atorvastatin and rosuvastatin on 25-hydroxy-vitamin D levels in non-diabetic patients with dyslipidaemia: A prospective randomized open-label pilot study","volume":"8","author":"Anagnostis","year":"2014","journal-title":"Open Cardiovasc. Med. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/lipd.12399","article-title":"Effects of high-intensity statin therapy on steroid hormones and vitamin D in type 2 diabetic men: A prospective self-controlled study","volume":"59","author":"Chihaoui","year":"2024","journal-title":"Lipids"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/eci.12698","article-title":"Effect of statins on serum vitamin D concentrations: A systematic review and meta-analysis","volume":"47","author":"Mazidi","year":"2017","journal-title":"Eur. J. Clin. Investig."},{"doi-asserted-by":"crossref","unstructured":"Delrue, C., and Speeckaert, M.M. (2023). Vitamin D and vitamin D-binding protein in health and disease. Int. J. Mol. Sci., 24.","key":"ref_49","DOI":"10.3390\/ijms24054642"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1080\/17425255.2020.1801634","article-title":"An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins","volume":"16","author":"Hirota","year":"2020","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_51","first-page":"320721","article-title":"Vitamin D levels and lipid response to atorvastatin","volume":"2010","author":"Vega","year":"2010","journal-title":"Int. J. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/eci.12390","article-title":"Calcifediol improves lipid profile in osteopenic atorvastatin-treated postmenopausal women","volume":"45","author":"Catalano","year":"2015","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0022-2275(20)38357-7","article-title":"Effect of vitamin D3 derivatives on cholesterol synthesis and HMG-CoA reductase activity in cultured cells","volume":"30","author":"Gupta","year":"1989","journal-title":"J. Lipid Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4239\/wjd.v10.i1.1","article-title":"Update on biomarkers of glycemic control","volume":"10","year":"2019","journal-title":"World J. Diabetes"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s40256-021-00492-8","article-title":"Association between vitamin D and statin-related myopathy: A meta-analysis","volume":"22","author":"Hou","year":"2022","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s40292-022-00526-5","article-title":"Association Between Vitamin D Supplementation and statin-associated muscle symptoms: A systematic review","volume":"29","author":"Teo","year":"2022","journal-title":"High Blood Press. Cardiovasc. Prev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e269","DOI":"10.1016\/j.jacl.2023.12.002","article-title":"No benefit of vitamin D supplementation on muscle function and health-related quality of life in primary cardiovascular prevention patients with statin-associated muscle symptoms: A randomized controlled trial","volume":"18","author":"Peyrel","year":"2024","journal-title":"J. Clin. 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