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Is it Time to Enhance Assessment of Alcohol Intake in Patients Slated for Statin Therapy?

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Abstract

Use of statins significantly lowers low-density lipoprotein cholesterol levels, resulting in substantial reduction in cardiovascular event rates. Despite this great achievement, cardiovascular risk remains high, especially among the elderly (>65 years) and those with conditions such as diabetes and kidney disease. It is thus crucial to identify variables that modulate effectiveness and efficacy of statin therapy. Alcohol, a common dietary component, is widely consumed at varying amounts and often concomitantly with statin therapy. Since moderate alcohol consumption is associated with cardiovascular benefits while heavy intake increases risk for ill health, it is possible that moderate alcohol may enhance benefits from statins while heavy alcohol could diminish or even abrogate such benefits. Whether this is true remains unknown. In this commentary we present pathways through which alcohol may impact use and response to statins and suggest that enhancing screening for alcohol abuse among patients slated for statin therapy may improve therapeutic outcomes.

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References

  1. Reiner Z. Resistance and intolerance to statins. Nutr Metab Cardiovasc Dis. 2014;24(10):1057–66.

    Article  CAS  PubMed  Google Scholar 

  2. Fernandez G, Spatz ES, Jablecki C, Phillips PS. Statin myopathy: a common dilemma not reflected in clinical trials. Cleve Clin J Med. 2011;78(6):393–403. doi:10.3949/ccjm.78a.1007378/6/393.

    Article  PubMed  Google Scholar 

  3. Bitzur R, Cohen H, Kamari Y, Harats D. Intolerance to statins: mechanisms and management. Diabetes Care. 2013;36(2):S325–30. doi:10.2337/dcS13-203836/Supplement_2/S325.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus. N Engl J Med. 2010;362(17):1563–74. doi:10.1056/NEJMoa1001282.

    Article  Google Scholar 

  5. Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy. N Engl J Med. 2011;365(24):2255–67. doi:10.1056/NEJMoa1107579.

    Article  Google Scholar 

  6. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):S1–S45. doi:10.1161/01.cir.0000437738.63853.7a.

    Article  PubMed  Google Scholar 

  7. NIAAA. National Institute on Alcohol Abuse and Alcoholism (NIAAA) Releases Physicians' Guide. http://www.niaaanihgov/news-events/news-releases/niaaa-releases-physicians-guide (last accessed: 09/25/2014). 1995

  8. Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, de Gaetano G. Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Arch Intern Med. 2006;166(22):2437–45. doi:10.1001/archinte.166.22.2437.

    Article  PubMed  Google Scholar 

  9. Hansel B, Kontush A, Bruckert E. Is a cardioprotective action of alcohol a myth? Curr Opin Cardiol. 2012;27(5):550–5. doi:10.1097/HCO.0b013e328356dc30.

    Article  PubMed  Google Scholar 

  10. Judd SE, McClure LA, Howard VJ, Lackland DT, Halanych JH, Kabagambe EK. Heavy drinking is associated with poor blood pressure control in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Int J Environ Res Public Health. 2011;8(5):1601–12. doi:10.3390/ijerph8051601ijerph-08-01601.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Kabagambe EK, Baylin A, Ruiz-Narvarez E, Rimm EB, Campos H. Alcohol intake, drinking patterns and risk of nonfatal acute myocardial infarction in Costa Rica. Am J Clin Nutr. 2005;82(2):1336–45.

    CAS  PubMed  Google Scholar 

  12. Rimm E. Alcohol and cardiovascular disease. Curr Atheroscler Rep. 2000;2(6):529–35.

    Article  CAS  PubMed  Google Scholar 

  13. Mukamal KJ, Cushman M, Mittleman MA, Tracy RP, Siscovick DS. Alcohol consumption and inflammatory markers in older adults: the Cardiovascular Health Study. Atherosclerosis. 2004;173(1):79–87.

    Article  CAS  PubMed  Google Scholar 

  14. Mukamal KJ, Ascherio A, Mittleman MA, Conigrave KM, Camargo Jr CA, Kawachi I, et al. Alcohol and risk for ischemic stroke in men: the role of drinking patterns and usual beverage. Ann Intern Med. 2005;142(1):11–9.

    Article  PubMed  Google Scholar 

  15. Djousse L, Levy D, Benjamin EJ, Blease SJ, Russ A, Larson MG, et al. Long-term alcohol consumption and the risk of atrial fibrillation in the Framingham Study. Am J Cardiol. 2004;93(6):710–3. doi:10.1016/j.amjcard.2003.12.004S0002914903017090.

    Article  CAS  PubMed  Google Scholar 

  16. Zaridze D, Lewington S, Boroda A, Scelo G, Karpov R, Lazarev A, et al. Alcohol and mortality in Russia: prospective observational study of 151,000 adults. Lancet. 2014;383(9927):1465–73. doi:10.1016/S0140-6736(13)62247-3S0140-6736(13)62247-3.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Kiage JN, James LO, Kabagambe EK. Genetic modification of the effects of alcohol on metabolic and clinical phenotypes: A review. Current Nutrition Reports. 2014;3:213–22. doi:10.1007/s13668-014-0086-2.

    Article  CAS  Google Scholar 

  18. Neuman MG, French SW, French BA, Seitz HK, Cohen LE, Mueller S et al. Alcoholic and non-alcoholic steatohepatitis. Exp Mol Pathol. 2014. doi:S0014-4800(14)00146-4 [pii]10.1016/j.yexmp.2014.09.005

  19. Lieber CS. Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol. 2004;34(1):9–19.

    Article  CAS  PubMed  Google Scholar 

  20. Lieber CS. Alcohol and the liver: 1994 update. Gastroenterology. 1994;106(4):1085–105.

    CAS  PubMed  Google Scholar 

  21. Wang Z, Yao T, Song Z. Chronic Alcohol Consumption Disrupted Cholesterol Homeostasis in Rats: Down-Regulation of Low-Density Lipoprotein Receptor and Enhancement of Cholesterol Biosynthesis Pathway in the Liver. Alcohol Clin Exp Res. 2010;34(3):471–8. doi:10.1111/j.1530-0277.2009.01111.x.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Dashti N, Franklin FA, Abrahamson DR. Effect of ethanol on the synthesis and secretion of apoA-I- and apoB-containing lipoproteins in HepG2 cells. J Lipid Res. 1996;37(4):810–24.

    CAS  PubMed  Google Scholar 

  23. Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Mayo Clin Proc. 2010;85(4):349–56. doi:10.4065/mcp.2009.0365S0025-6196(11)60427-8.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Wijnia JW, Wielders JP, Lips P, van de Wiel A, Mulder CL, Nieuwenhuis KG. Is vitamin D deficiency a confounder in alcoholic skeletal muscle myopathy? Alcohol Clin Exp Res. 2013;37 Suppl 1:E209–15. doi:10.1111/j.1530-0277.2012.01902.x.

    Article  CAS  PubMed  Google Scholar 

  25. Vidyashankar S, Nandakumar KS, Patki PS. Alcohol depletes coenzyme-Q(10) associated with increased TNF-alpha secretion to induce cytotoxicity in HepG2 cells. Toxicology. 2012;302(1):34–9. doi:10.1016/j.tox.2012.07.009S0300-483× (12)00287-9.

    Article  CAS  PubMed  Google Scholar 

  26. Ridker PM. Moving toward new statin guidelines in a post-JUPITER world: principles to consider. Curr Atheroscler Rep. 2009;11(4):249–56.

    Article  PubMed  Google Scholar 

  27. Belfort R, Berria R, Cornell J, Cusi K. Fenofibrate reduces systemic inflammation markers independent of its effects on lipid and glucose metabolism in patients with the metabolic syndrome. J Clin Endocrinol Metab. 2010;2:829–36.

    Article  Google Scholar 

  28. Ye P, Li JJ, Su G, Zhang C. Effects of fenofibrate on inflammatory cytokines and blood pressure in patients with hypertriglyceridemia. Clin Chim Acta. 2005;1–2:229–32.

    Article  Google Scholar 

  29. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–42. doi:10.1016/S0140-6736(09)61965-6.

    Article  CAS  PubMed  Google Scholar 

  30. Jahangir E, Fazio S, Sampson UK. Incident Diabetes and Statins: The Blemish of an Undisputed Heavy Weight Champion? Br J Clin Pharmacol. 2012. doi:10.1111/j.1365-2125.2012.04445.x.

    PubMed Central  Google Scholar 

  31. Sewright KA, Clarkson PM, Thompson PD. Statin myopathy: incidence, risk factors, and pathophysiology. Curr Atheroscler Rep. 2007;9(5):389–96.

    Article  CAS  PubMed  Google Scholar 

  32. Amarenco P, Bogousslavsky J, Callahan 3rd A, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549–59. doi:10.1056/NEJMoa061894.

    Article  CAS  PubMed  Google Scholar 

  33. Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. Am J Clin Nutr. 2013;97(2):268–75. doi:10.3945/ajcn.112.040741.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Langsjoen PH, Langsjoen JO, Langsjoen AM, Lucas LA. Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation. Biofactors. 2005;25(1–4):147–52.

    Article  CAS  PubMed  Google Scholar 

  35. Allen RM, Vickers KC. Coenzyme Q10 Increases Cholesterol Efflux and Inhibits Atherosclerosis Through MicroRNAs. Arterioscler Thromb Vasc Biol. 2014;34(9):1795–7. doi:10.1161/atvbaha.114.303741.

    Article  CAS  PubMed  Google Scholar 

  36. Wang D, Yan X, Xia M, Yang Y, Li D, Li X, et al. Coenzyme Q10 Promotes Macrophage Cholesterol Efflux by Regulation of the Activator Protein-1/miR-378/ATP-Binding Cassette Transporter G1–Signaling Pathway. Arterioscler Thromb Vasc Biol. 2014;34(9):1860–70. doi:10.1161/atvbaha.113.302879.

    Article  CAS  PubMed  Google Scholar 

  37. American Heart Association and American Stroke Association. Statins after ischemic stroke and transient ischemic attack: an advisory statement from the Stroke Council. Stroke. 2004;35(4):1023. doi:10.1161/01.STR.0000122762.96972.DD35/4/1023.

    Google Scholar 

  38. Barter PJ, Brandrup-Wognsen G, Palmer MK, Nicholls SJ. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database. J Lipid Res. 2010;51(6):1546–53. doi:10.1194/jlr.P002816 jlr.P002816.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Hines LM, Stampfer MJ, Ma J, Gaziano JM, Ridker PM, Hankinson SE, et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med. 2001;344(8):549–55.

    Article  CAS  PubMed  Google Scholar 

  40. Wang L, Lee I, Manson JE, Buring JE, Sesso HD. ALcohol consumption, weight gain, and risk of becoming overweight in middle-aged and older women. Arch Intern Med. 2010;170(5):453–61. doi:10.1001/archinternmed.2009.527.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Salmela KS, Kessova IG, Tsyrlov IB, Lieber CS. Respective roles of human cytochrome P-4502E1, 1A2, and 3A4 in the hepatic microsomal ethanol oxidizing system. Alcohol Clin Exp Res. 1998;22(9):2125–32.

    Article  CAS  PubMed  Google Scholar 

  42. Willrich MA, Hirata MH, Hirata RD. Statin regulation of CYP3A4 and CYP3A5 expression. Pharmacogenomics. 2009;10(6):1017–24. doi:10.2217/pgs.09.42.

    Article  CAS  PubMed  Google Scholar 

  43. Meskar A, Plee-Gautier E, Amet Y, Berthou F, Lucas D. Alcohol-xenobiotic interactions. Role of cytochrome P450 2E1. Pathol Biol (Paris). 2001;49(9):696–702.

    Article  CAS  Google Scholar 

  44. Dubuc G, Chamberland A, Wassef H, Davignon J, Seidah NG, Bernier L, et al. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2004;24(8):1454–9. doi:10.1161/01.ATV.0000134621.14315.43.

    Article  CAS  PubMed  Google Scholar 

  45. Polo MP, de Bravo MG, de Alaniz MJ. Effect of ethanol on cell growth and cholesterol metabolism in cultured Hep G2 cells. Biochem Cell Biol. 2003;81(6):379–86. doi:10.1139/o03-066.

    Article  CAS  PubMed  Google Scholar 

  46. Feidt DM, Klein K, Hofmann U, Riedmaier S, Knobeloch D, Thasler WE, et al. Profiling induction of cytochrome p450 enzyme activity by statins using a new liquid chromatography-tandem mass spectrometry cocktail assay in human hepatocytes. Drug Metab Dispos. 2010;38(9):1589–97. doi:10.1124/dmd.110.033886.

    Article  CAS  PubMed  Google Scholar 

  47. McKnight-Eily LR, Liu Y, Brewer RD, Kanny D, Lu H, Denny CH, et al. Vital Signs: Communication Between Health Professionals and Their Patients About Alcohol Use — 44. States and the District of Columbia, 2011. Morbidity and Mortality Weekly Report (MMWR). 2014;63(01):16–22.

    Google Scholar 

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Acknowledgments

EKK was supported by a National Scientist Development grant (0635323 N) from the American Heart Association.

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Edmond Kato Kabagambe declares that he has no conflict of interest.

Sergio Fazio has received research support through grants from Isis Pharmaceuticals and Merck, and has received compensation from Merck, Kowa, Sanofi-Aventis, Roche, Amarin, Lupin, and BASF for service as a consultant.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37203, USA

    Edmond Kato Kabagambe

  2. Knight Cardiovascular Institute, Center of Preventive Cardiology, Oregon Health and Science University, Portland, OR, 97239, USA

    Sergio Fazio

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  1. Edmond Kato Kabagambe
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Correspondence to Edmond Kato Kabagambe.

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Kabagambe, E.K., Fazio, S. Is it Time to Enhance Assessment of Alcohol Intake in Patients Slated for Statin Therapy?. Curr Nutr Rep 4, 1–5 (2015). https://doi.org/10.1007/s13668-014-0107-1

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  • DOI: https://doi.org/10.1007/s13668-014-0107-1

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