Effect of Bile Acid Sequestrants on the Risk of Cardiovascular Events: A Mendelian Randomization Analysis

Circulation: Cardiovascular Genetics

Volumn 8, Issue 4, 2015, Pages 618-627

  Ross, Stephanie ^a,b,c   D'Mello, Matthew ^a,b,c   Anand, Sonia S ^a,b,c,d   Eikelboom, John ^a,d   Stewart, Alexandre F R ^f,j   Samani, Nilesh J ^g,h   Roberts, Robert ^f,i,j   Paré, Guillaume ^a,b,c,d,e  

^a MCMASTER UNIVERSITY   (Canada)

^b Department of Clinical Epidemiology and Biostatistics Population Genomics Program   (United States)

^c MCMASTER UNIVERSITY   (Canada)

^d Department of Medicine ^*  (United States)

^e MCMASTER UNIVERSITY   (Canada)

^f MCMASTER UNIVERSITY   (Canada)

^g UNIVERSITY OF LEICESTER   (United Kingdom)

^h GLENFIELD HOSPITAL   (United Kingdom)

ⁱ UNIVERSITY OF OTTAWA   (Canada)

^j UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

more..

Author keywords

cholesterol lowering drugs; coronary artery disease; genetics; lipids; Mendelian randomization

Indexed keywords

COLESEVELAM; COLESTYRAMINE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; TRIACYLGLYCEROL; ABC TRANSPORTER; ABCG5 PROTEIN, HUMAN; ABCG8 PROTEIN, HUMAN; BILE ACID; HYPOCHOLESTEROLEMIC AGENT; LIPOPROTEIN;

ARTICLE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL SYNTHESIS; CORONARY ARTERY DISEASE; DRUG EFFECT; GENETIC ASSOCIATION; HEART INFARCTION; HUMAN; HYPERLIPIDEMIA; LIPID BLOOD LEVEL; MENDELIAN RANDOMIZATION ANALYSIS; META ANALYSIS; MULTICENTER STUDY (TOPIC); OUTCOME ASSESSMENT; PHARMACOGENETICS; PLEIOTROPY; PREDICTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK REDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTEMATIC REVIEW; TRIACYLGLYCEROL BLOOD LEVEL; ANTAGONISTS AND INHIBITORS; GENETICS; METABOLISM; PROCEDURES;

ANTICHOLESTEREMIC AGENTS; ATP-BINDING CASSETTE TRANSPORTERS; BILE ACIDS AND SALTS; CHOLESTEROL, LDL; CHOLESTYRAMINE RESIN; COLESEVELAM HYDROCHLORIDE; CORONARY ARTERY DISEASE; HUMANS; LIPOPROTEINS; MENDELIAN RANDOMIZATION ANALYSIS; POLYMORPHISM, SINGLE NUCLEOTIDE; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84940021344     PISSN: 1942325X     EISSN: 19423268     Source Type: Journal    
DOI: 10.1161/CIRCGENETICS.114.000952     Document Type: Article

References (59)

1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2013 update: A report from the American Heart Association. Circulation. 2013; 127: e6-e245.doi: 10. 1161/CIR. 0b013e31828124ad.
2. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 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.
3. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013; 1: CD004816.doi: 10. 1002/14651858. CD004816. pub5.
4. Davidson MH, Maki KC, Pearson TA, Pasternak RC, Deedwania PC, McKenney JM, et al. Results of the National Cholesterol Education (NCEP) Program Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations. Am J Cardiol. 2005; 96: 556-563. doi: 10. 1016/j. amjcard. 2005. 04. 019.
5. Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? BMJ. 2013; 347: f6123.
6. Insull W Jr. Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: A scientific review. South Med J. 2006; 99: 257-273. doi: 10. 1097/01. smj. 0000208120. 73327. db.
7. Steinmetz KL, Schonder KS. Colesevelam: Potential uses for the newest bile resin. Cardiovasc Drug Rev. 2005; 23: 15-30.
8. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA. 1984; 251: 351-364.
9. Andrade SE, Walker AM, Gottlieb LK, Hollenberg NK, Testa MA, Saperia GM, et al. Discontinuation of antihyperlipidemic drugs-do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med. 1995; 332: 1125-1131.doi: 10. 1056/NEJM199504273321703.
10. Watts GF, Lewis B, Brunt JN, Lewis ES, Coltart DJ, Smith LD, et al. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS). Lancet. 1992; 339: 563-569.
11. Brensike JF, Levy RI, Kelsey SF, Passamani ER, Richardson JM, Loh IK, et al. Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study. Circulation. 1984; 69: 313-324.
12. Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008; 27: 1133-1163.doi: 10. 1002/sim. 3034.
13. Smith GD, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003; 32: 1-22.
14. Sofat R, Hingorani AD, Smeeth L, Humphries SE, Talmud PJ, Cooper J, et al. Separating the mechanism-based and off-target actions of cholesteryl ester transfer protein inhibitors with CETP gene polymorphisms. Circulation. 2010; 121: 52-62.doi: 10. 1161/CIRCULATIONAHA. 109. 865444.
15. Hingorani AD, Casas JP. The interleukin-6 receptor as a target for prevention of coronary heart disease: A mendelian randomisation analysis. Lancet. 2012; 379: 1214-1224.
16. Schmitz G, Langmann T, Heimerl S. Role of ABCG1 and other ABCG family members in lipid metabolism. J Lipid Res. 2001; 42: 1513-1520.
17. Brown JM, Yu L. Opposing Gatekeepers of Apical Sterol Transport: Niemann-Pick C1-Like 1 (NPC1L1) and ATP-Binding Cassette Transporters G5 and G8 (ABCG5/ABCG8). Immunol Endocr Metab Agents Med Chem. 2009; 9: 18-29.doi: 10. 2174/187152209788009797.
18. Oram JF, Vaughan AM. ATP-Binding cassette cholesterol transporters and cardiovascular disease. Circ Res. 2006; 99: 1031-1043.doi: 10. 1161/01. RES. 0000250171. 54048. 5c.
19. IBC 50K CAD Consortium. Large-scale gene-centric analysis identifies novel variants for coronary artery disease. PLoS Genet. 2011; 7: e1002260. doi: 10. 1371/journal. pgen. 1002260.
20. Davidson MH, Toth P, Weiss S, McKenney J, Hunninghake D, Isaacsohn J, et al. Low-dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low-density lipoprotein cholesterol in patients with primary hypercholesterolemia. Clin Cardiol. 2001; 24: 467-474.
21. Cederberg H, Gylling H, Miettinen TA, Paananen J, Vangipurapu J, Pihlajamäki J, et al. Non-cholesterol sterol levels predict hyperglycemia and conversion to type 2 diabetes in Finnish men. PLoS One. 2013; 8: e67406. doi: 10. 1371/journal. pone. 0067406.
22. Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013; 45: 25-33.
23. Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010; 466: 707-713.doi: 10. 1038/nature09270.
24. Samani NJ, Deloukas P, Erdmann J, Hengstenberg C, Kuulasmaa K, Mc-Ginnis R, et al. Large scale association analysis of novel genetic loci for coronary artery disease. Arterioscler Thromb Vasc Biol. 2009; 29: 774-780.
25. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al; Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90, 056 participants in 14 randomised trials of statins. Lancet. 2005; 366: 1267-1278.doi: 10. 1016/S0140-6736(05)67394-1.
26. Betteridge DJ, Bhatnager D, Bing RF, Durrington PN, Evans GR, Flax H, et al. Treatment of familial hypercholesterolaemia. United Kingdom lipid clinics study of pravastatin and cholestyramine. BMJ. 1992; 304: 1335-1338.
27. Comparative efficacy and safety of pravastatin and cholestyramine alone and combined in patients with hypercholesterolemia. Pravastatin Multicenter Study Group II. Arch Intern Med. 1993; 153: 1321-1329.
28. Wiklund O, Angelin B, Fager G, Eriksson M, Olofsson SO, Berglund L, et al. Treatment of familial hypercholesterolaemia: A controlled trial of the effects of pravastatin or cholestyramine therapy on lipoprotein and apolipoprotein levels. J Intern Med. 1990; 228: 241-247.
29. Bays HE, Goldberg RB, Truitt KE, Jones MR. Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects. Arch Intern Med. 2008; 168: 1975-1983.doi: 10. 1001/archinte. 168. 18. 1975.
30. Davidson MH, Dillon MA, Gordon B, Jones P, Samuels J, Weiss S, et al. Colesevelam hydrochloride (cholestagel): A new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. Arch Intern Med. 1999; 159: 1893-1900.
31. Devaraj S, Autret B, Jialal I. Effects of colesevelam hydrochloride (WelChol) on biomarkers of inflammation in patients with mild hypercholesterolemia. Am J Cardiol. 2006; 98: 641-643.doi: 10. 1016/j. amjcard. 2006. 03. 043.
32. Handelsman Y, Goldberg RB, Garvey WT, Fonseca VA, Rosenstock J, Jones MR, et al. Colesevelam hydrochloride to treat hypercholesterolemia and improve glycemia in prediabetes: A randomized, prospective study. Endocr Pract. 2010; 16: 617-628.doi: 10. 4158/EP10129. OR.
33. Hunninghake D, Insull W Jr, Toth P, Davidson D, Donovan JM, Burke SK. Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively. Atherosclerosis. 2001; 158: 407-416.
34. Insull W Jr, Toth P, Mullican W, Hunninghake D, Burke S, Donovan JM, et al. Effectiveness of colesevelam hydrochloride in decreasing LDL cholesterol in patients with primary hypercholesterolemia: A 24-week randomized controlled trial. Mayo Clin Proc. 2001; 76: 971-982.doi: 10. 4065/76. 10. 971.
35. Knapp HH, Schrott H, Ma P, Knopp R, Chin B, Gaziano JM, et al. Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia. Am J Med. 2001; 110: 352-360.
36. Rosenstock J, Fonseca VA, Garvey WT, Goldberg RB, Handelsman Y, Abby SL, et al. Initial combination therapy with metformin and colesevelam for achievement of glycemic and lipid goals in early type 2 diabetes. Endocr Pract. 2010; 16: 629-640.doi: 10. 4158/EP10130. OR.
37. Zieve FJ, Kalin MF, Schwartz SL, Jones MR, Bailey WL. Results of the glucose-lowering effect of WelChol study (GLOWS): A randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes. Clin Ther. 2007; 29: 74-83.doi: 10. 1016/j. clinthera. 2007. 01. 003.
38. Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, Steinthorsdottir V, et al; Wellcome Trust Case Control Consortium; Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators; Genetic Investigation of ANthropometric Traits (GIANT) Consortium; Asian Genetic Epidemiology Network-Type 2 Diabetes (AGEN-T2D) Consortium; South Asian Type 2 Diabetes (SAT2D) Consortium; DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012; 44: 981-990.doi: 10. 1038/ng. 2383.
39. Scott RA, Lagou V, Welch RP, Wheeler E, Montasser ME, Luan J, et al; DIAbetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012; 44: 991-1005.doi: 10. 1038/ng. 2385.
40. Soranzo N, Sanna S, Wheeler E, Gieger C, Radke D, Dupuis J, et al; WTCCC. Common variants at 10 genomic loci influence hemoglobin A?© levels via glycemic and nonglycemic pathways. Diabetes. 2010; 59: 3229-3239.doi: 10. 2337/db10-0502.
41. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, et al; MAGIC; Procardis Consortium. Association analyses of 249, 796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010; 42: 937-948.doi: 10. 1038/ng. 686.
42. Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011; 478: 103-109.
43. Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011; 365: 2255-2267.
44. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al; ILLUMINATE Investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007; 357: 2109-2122. doi: 10. 1056/NEJMoa0706628.
45. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: Trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013; 34: 1279-1291.
46. Davidson MH. The use of colesevelam hydrochloride in the treatment of dyslipidemia: A review. Expert Opin Pharmacother. 2007; 8: 2569-2578. doi: 10. 1517/14656566. 8. 15. 2569.
47. Donovan JM, Stypinski D, Stiles MR, Olson TA, Burke SK. Drug interactions with colesevelam hydrochloride, a novel, potent lipid-lowering agent. Cardiovasc Drugs Ther. 2000; 14: 681-690.
48. Ooi CP, Loke SC. Colesevelam for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2012; 12: CD009361.doi: 10. 1002/14651858. CD009361. pub2.
49. Cannon CP. Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015; 372: 2387-2397.
50. Stitziel NO, Won HH, Morrison AC, Peloso GM, Do R, Lange LA, et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014; 371: 2072-2082.
51. Bays H, Dujovne C. Colesevelam HCl: A non-systemic lipid-altering drug. Expert Opin Pharmacother. 2003; 4: 779-790.doi: 10. 1517/14656566. 4. 5. 779.
52. Yu L, Li-Hawkins J, Hammer RE, Berge KE, Horton JD, Cohen JC, et al. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest. 2002; 110: 671-680.doi: 10. 1172/JCI16001.
53. Yu L, Hammer RE, Li-Hawkins J, Von Bergmann K, Lutjohann D, Cohen JC, et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci U S A. 2002; 99: 16237-16242.doi: 10. 1073/pnas. 252582399.
54. Staels B, Fonseca VA. Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration. Diabetes Care. 2009; 32 Suppl 2: S237-S245.doi: 10. 2337/dc09-S355.
55. Jørgensen NB, Dirksen C, Bojsen-Møller KN, Kristiansen VB, Wulff BS, Rainteau D, et al. Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations. J Clin Endocrinol Metab. 2015; 100: E396-E406.doi: 10. 1210/jc. 2014-1658.
56. Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, et al. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. 2000; 290: 1771-1775.
57. Lu K, Lee MH, Hazard S, Brooks-Wilson A, Hidaka H, Kojima H, et al. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am J Hum Genet. 2001; 69: 278-290.
58. Teupser D, Baber R, Ceglarek U, Scholz M, Illig T, Gieger C, et al. Genetic regulation of serum phytosterol levels and risk of coronary artery disease. Circ Cardiovasc Genet. 2010; 3: 331-339.doi: 10. 1161/ CIRCGENETICS. 109. 907873.
59. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al; American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease. Triglycerides and cardiovascular disease: A scientific statement from the American Heart Association. Circulation. 2011; 123: 2292-2333.doi: 10. 1161/CIR. 0b013e3182160726.