{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T14:20:12Z","timestamp":1765808412486,"version":"3.41.2"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","award":["2019079"],"award-info":[{"award-number":["2019079"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Statin\u2010associated muscle symptoms are frequently reported and often lead to discontinuation of statin therapy with an increased risk of cardiovascular events. In\u00a0vitro studies suggest that statin\u2010mediated inhibition of the mevalonate pathway leads to muscle cell toxicity. We aimed to determine the relationship between mevalonate, LDL\u2010cholesterol, and atorvastatin metabolites in patients with coronary heart disease and self\u2010perceived muscle side effects. Furthermore, we assessed the correlation between mevalonate in blood and muscle and the relationship to statin intolerance due to muscle symptoms. We used blood plasma from a randomized crossover trial (<jats:italic>n<\/jats:italic>\u2009=\u200970) and muscle biopsies and plasma from a subgroup in a subsequent open intervention study (<jats:italic>n<\/jats:italic>\u2009=\u200926). Both studies tested atorvastatin 40\u2009mg\/day. Seven patients did not tolerate \u22653 statins throughout the follow\u2010up and were classified as statin\u2010intolerant. Mevalonate in blood plasma decreased during atorvastatin treatment (median difference \u221238%, range \u221277% to 43%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), whereas mevalonate in muscle tissue was not lowered (0.05%, range \u221247% to 145%). Mevalonate correlated poorly with LDL\u2010cholesterol and atorvastatin metabolites (Spearman's rho \u22120.28 to 0.10). The statin\u2010intolerant patients had a smaller reduction in circulating mevalonate compared with the tolerant patients; median difference \u22128.1 (\u221222 to 3.5) nmol\/L versus \u221225 (\u221293 to 12) nmol\/L, <jats:italic>p<\/jats:italic>\u2009=\u20090.028. A similar observation was made for LDL\u2010cholesterol. Cutoffs based on these biomarkers classified &gt;50% correctly as tolerant. Inhibition of the mevalonate pathway does not appear to be the mechanism underlying statin intolerance in the present study. Further studies of mevalonate as a biomarker for statin tolerance are needed to clarify the potential.<\/jats:p>","DOI":"10.1111\/cts.70025","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T05:40:39Z","timestamp":1729748439000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mevalonate in blood and muscle: Response to atorvastatin treatment and the relationship to statin intolerance in patients with coronary heart disease"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-3295","authenticated-orcid":false,"given":"Trine","family":"Lauritzen","sequence":"first","affiliation":[{"name":"Department of Medicine Vestre Viken Trust, Drammen Hospital  Drammen Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"Department of Laboratory Medicine Vestre Viken Trust, Drammen Hospital  Drammen 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