Statin Intolerance in a Patient with Gilberts Syndrome and Hypercholesterolemia
received 23 May 2015
revised 22 June 2015
accepted 27 June 2016
13 September 2016 (eFirst)
Background: Statin intolerance especially myalgias can be a serious problem. Whilst it is well know that drugs that compete for Cytochrome 450 system can result in myalgias there is sparse data on the role of glucuronidation of statins contributing to statin intolerance We report on a 60 year old male with Hypercholesterolemia (HC) who was referred for management of his HC since he had statin intolerance manifesting as myalgias and was shown to have Gilbert’s Syndrome.
Case Report: Investigation of this patient revealed he had Familial Combined Hyperlipidemia with a LDL-cholesterol of 189 mg/dl. He was also diagnosed with Gilbert’s Syndrome since he had elevated unconjugated bilirubin with no evidence of liver disease or hemolysis. The combination of Niacin, Cholestyramine and ezetimibe resulted in a successful decrease in his LDL-cholesterol to 114 mg/dl.
Discussion: We believe that his Gilberts Syndrome resulted in an impairment in glucuronidation of statin drugs resulting in an increase in free drug levels and myalgias. We caution that clinicians should consider this possibility when confronted with a patient with both isolated elevations of unconjugated bilirubin and increase LDL-cholesterol levels before commencing statin therapy.
- 1 Sticova E, Jirsa M. New Insights in Bilirubin metabolism and their clinical implications. World J Gastroenterol 2013; 19: 6398-6407
- 2 Erlinger S, Arias IM, Dhumeaux D. Inherited disorders of Bilirubin transport and conjugation: new insights into molecular mechanisms and consequences. Gastroenterology 2014; 146: 1625-1638
- 3 Strassburg CP. Hyerbilirubinemia Syndromes (Gilbert-Meulengracht, Crigler-Naggar, Dubin –Johnson and Rotor syndromes. Best practice and research clinical. Gastroenterology 2010; 24: 555-571
- 4 Preuksaritanont T, Subrmanian R, Fang X. et al. Glucurodination of statins in animals and humans: A novel mechanism for statin. Lactonization Drug Metabolism and Disposition 2002; 30: 505-512
- 5 McKenney JM, Ganz P, Wiggins B. et al. Statins Chapter 22:253–280 in Clinical Lipidology, A companion to Braunwald’s Heart Diseases by CM Ballantyne. Saunders Press; 2009
- 6 Vaughan CJ, Gottto AM. Update on Statins. Circulation 2004; 110: 886-892
- 7 Cummings MH, Watts GF. Drug Treatment of Hypercholesterolemia in a patient with Gilbert’s syndrome. Ann Clin Biochem 1994; 31: 383-385
- 8 Boon AC, Hawkins CL, Bisht K. et al. Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilberts syndrome. Fee Radic Biol and Med 2012; 52: 2120-2127
- 9 Wallner M, Marculescu R, Doberer D. et al. Protection from age-related increase in lipid biomarkers and inflammation contributes to cardiovascular protection in Gilberts syndrome. Clin Sci 2013; 125: 257-264
- 10 Kundur AR, Singh L, Bulmer AC. Bilirubin, platelet activation and heart disease: A missing link to cardiovascular protection in Gilbert’s Syndrome. Atherosclerosis 2015; 239: 73-84
- 11 Lin JP, O’Donnell CJ, Schwaiger JP. et al. Association between the UGTIAI*28 allele, bilirubin levels and coronary artery disease in the Framingham Heart Study. Circulation 2006; 114: 1476-1481
- 12 Vitek L, Jirsa M, Brodanova M. et al. Gilberts Syndrome and ischemic heart disease: a protective effect of elevated bilirubin. Atherosclerosis 2002; 160: 449-456
- 13 Stender S, Frikke-Schmidt R, Nordestgaard BG. et al. Genetically elevated Bilirubin and risk of ischemic heart disease: Mendelian Randomization studies and a meta-analysis. J Intern Med 2013; 273: 59-68