The high-density lipoprotein puzzle: Why classic epidemiology, genetic epidemiology, and clinical trials conflict?

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 36, Issue 5, 2016, Pages 777-782

  Rosenson, Robert S ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

clinical trial; genetics; HDL particle size; high density lipoprotein; high density lipoprotein cholesterol

Indexed keywords

ABC TRANSPORTER; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIPIDOME; NICOTINIC ACID; PROTEOME; BIOLOGICAL MARKER;

ARTICLE; CARDIOVASCULAR RISK; CLINICAL TRIAL (TOPIC); CORONARY ARTERY ATHEROSCLEROSIS; GENETIC EPIDEMIOLOGY; HEART INFARCTION; HUMAN; MACROPHAGE; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RISK; ATHEROSCLEROSIS; BLOOD; CARDIOVASCULAR DISEASES; DYSLIPIDEMIAS; EVIDENCE BASED MEDICINE; GENETIC PREDISPOSITION; GENETICS; MOLECULAR EPIDEMIOLOGY; PARTICLE SIZE; PHENOTYPE; PROCEDURES; PROGNOSIS; RISK ASSESSMENT; RISK FACTOR;

ATHEROSCLEROSIS; BIOMARKERS; CARDIOVASCULAR DISEASES; CHOLESTEROL, HDL; CLINICAL TRIALS AS TOPIC; DYSLIPIDEMIAS; EVIDENCE-BASED MEDICINE; GENETIC PREDISPOSITION TO DISEASE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MOLECULAR EPIDEMIOLOGY; PARTICLE SIZE; PHENOTYPE; PROGNOSIS; RISK ASSESSMENT; RISK FACTORS;

EID: 84960405548     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.116.307024     Document Type: Article

References (46)

1. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009 302 1993 2000
2. Otvos JD, Jeyarajah EJ, Cromwell WC, Measurement issues related to lipoprotein heterogeneity. Am J Cardiol 2002 90 8A 22i 29i
3. Gotto AM Jr, Whitney E, Stein EA, Shapiro DR, Clearfield M, Weis S, Jou JY, Langendörfer A, Beere PA, Watson DJ, Downs JR, de Cani JS, Relation between baseline and on-Treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 2000 101 477 484
4. Otvos JD, Collins D, Freedman DS, Shalaurova I, Schaefer EJ, McNamara JR, Bloomfield HE, Robins SJ, Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation 2006 113 1556 1563. doi: 10.1161/CIRCULATIONAHA.105.565135
5. Rosenson RS, Davidson MH, Le NA, Burkle J, Pourfarzib R, Underappreciated opportunities for high-density lipoprotein particles in risk stratification and potential targets of therapy. Cardiovasc Drugs Ther 2015 29 41 50. doi: 10.1007/s10557-014-6567-0
6. Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, Kastelein JJ, Bittner V, Fruchart JC, Treating to New Targets Investigators HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007 357 1301 1310. doi: 10.1056/NEJMoa064278
7. Schwartz GG, Olsson AG, Abt M, dal-OUTCOMES Investigators Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012 367 2089 2099. doi: 10.1056/NEJMoa1206797
8. Ridker PM, Genest J, Boekholdt SM, Libby P, Gotto AM, Nordestgaard BG, Mora S, MacFadyen JG, Glynn RJ, Kastelein JJ, JUPITER Trial Study Group HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial. Lancet 2010 376 333 339. doi: 10.1016/S0140-6736(10)60713-1
9. Voight BF, Peloso GM, Orho-Melander M, Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012 380 572 580. doi: 10.1016/S0140-6736(12)60312-2
10. Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub W, AIM-HIGH Investigators Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011 365 2255 2267. doi: 10.1056/NEJMoa1107579
11. Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, Wallendszus K, Craig M, Jiang L, Collins R, Armitage J, HPS2-THRIVE Collaborative Group Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014 371 203 212. doi: 10.1056/NEJMoa1300955
12. Anderson TJ, Boden WE, Desvigne-Nickens P, Fleg JL, Kashyap ML, McBride R, Probstfield JL, AIM-HIGH Investigators Safety profile of extended-release niacin in the AIM-HIGH trial. N Engl J Med 2014 371 288 290. doi: 10.1056/NEJMc1311039
13. Barter PJ, Caulfield M, Eriksson M, 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
14. Lilly Provides Update on Evacetrapib Phase 3 Trial. www.prnewswire.com/.releases/lilly-provides-update-on-evacetrapib-ph. July 27, 2015
15. Nicholls SJ, Ruotolo G, Brewer HB, Kane JP, Wang MD, Krueger KA, Adelman SJ, Nissen SE, Rader DJ, Cholesterol Efflux Capacity and Pre-Beta-1 HDL Concentrations Are Increased in Dyslipidemic Patients Treated With Evacetrapib. J Am Coll Cardiol 2015 66 2201 2210. doi: 10.1016/j.jacc.2015.09.013
16. Rosenson RS, Brewer HB Jr, New challenges for HDL-modifying therapies as a strategy to lower cardiovascular disease events in statin-Treated patients. Cardiovasc Drugs Ther 2015 29 1 3. doi: 10.1007/s10557-015-6576-7
17. Niesor EJ, Schwartz GG, Perez A, Stauffer A, Durrwell A, Bucklar-Suchankova G, Benghozi R, Abt M, Kallend D, Statin-induced decrease in ATP-binding cassette transporter A1 expression via microRNA33 induction may counteract cholesterol efflux to high-density lipoprotein. Cardiovasc Drugs Ther 2015 29 7 14. doi: 10.1007/s10557-015-6570-0
18. Rosenson RS, Brewer HB Jr, Chapman MJ, Fazio S, Hussain MM, Kontush A, Krauss RM, Otvos JD, Remaley AT, Schaefer EJ, HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clin Chem 2011 57 392 410. doi: 10.1373/clinchem.2010.155333
19. Rosenson RS, Brewer HB Jr, Davidson WS, Fayad ZA, Fuster V, Goldstein J, Hellerstein M, Jiang XC, Phillips MC, Rader DJ, Remaley AT, Rothblat GH, Tall AR, Yvan-Charvet L, Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 2012 125 1905 1919. doi: 10.1161/CIRCULATIONAHA.111.066589
20. Camont L, Lhomme M, Rached F, Le Goff W, Nègre-Salvayre A, Salvayre R, Calzada C, Lagarde M, Chapman MJ, Kontush A, Small, dense high-density lipoprotein-3 particles are enriched in negatively charged phospholipids: relevance to cellular cholesterol efflux, antioxidative, antithrombotic, anti-inflammatory, and antiapoptotic functionalities. Arterioscler Thromb Vasc Biol 2013 33 2715 2723. doi: 10.1161/ATVBAHA.113.301468
21. Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, Neeland IJ, Yuhanna IS, Rader DR, de Lemos JA, Shaul PW, HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med 2014 371 2383 2393. doi: 10.1056/NEJMoa1409065
22. Saleheen D, Scott R, Javad S, Zhao W, Rodrigues A, Picataggi A, Lukmanova D, Mucksavage ML, Luben R, Billheimer J, Kastelein JJ, Boekholdt SM, Khaw KT, Wareham N, Rader DJ, Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study. Lancet Diabetes Endocrinol 2015 3 507 513. doi: 10.1016/S2213-8587(15)00126-6
23. Rosenson RS, Brewer HB Jr, Ansell B, Barter P, Chapman MJ, Heinecke JW, Kontush A, Tall AR, Webb NR, Translation of high-density lipoprotein function into clinical practice: current prospects and future challenges. Circulation 2013 128 1256 1267. doi: 10.1161/CIRCULATIONAHA.113.000962
24. Rosenson RS, Brewer HB Jr, Ansell BJ, Barter P, Chapman MJ, Heinecke JW, Kontush A, Tall AR, Webb NR, Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol 2016 13 48 60. doi: 10.1038/nrcardio.2015.124
25. Mackey RH, Greenland P, Goff DC Jr, Lloyd-Jones D, Sibley CT, Mora S, High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis). J Am Coll Cardiol 2012 60 508 516. doi: 10.1016/j.jacc.2012.03.060
26. Mora S, Glynn RJ, Ridker PM, High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy. Circulation 2013 128 1189 1197. doi: 10.1161/CIRCULATIONAHA.113.002671
27. Chandra A, Neeland IJ, Das SR, Khera A, Turer AT, Ayers CR, McGuire DK, Rohatgi A, Relation of black race between high density lipoprotein cholesterol content, high density lipoprotein particles and coronary events (from the Dallas Heart Study). Am J Cardiol 2015 115 890 894. doi: 10.1016/j.amjcard.2015.01.015
28. Rached F, Lhomme M, Camont L, Gomes F, Dauteuille C, Robillard P, Santos RD, Lesnik P, Serrano CV Jr, Chapman MJ, Kontush A, Defective functionality of small, dense HDL3 subpopulations in ST segment elevation myocardial infarction: Relevance of enrichment in lysophosphatidylcholine, phosphatidic acid and serum amyloid A. Biochim Biophys Acta 2015 1851 1254 1261. doi: 10.1016/j.bbalip.2015.05.007
29. Huang Y, DiDonato JA, Levison BS, An abundant dysfunctional apolipoprotein A1 in human atheroma. Nat Med 2014 20 193 203. doi: 10.1038/nm.3459
30. Shao B, Tang C, Sinha A, Mayer PS, Davenport GD, Brot N, Oda MN, Zhao XQ, Heinecke JW, Humans with atherosclerosis have impaired ABCA1 cholesterol efflux and enhanced high-density lipoprotein oxidation by myeloperoxidase. Circ Res 2014 114 1733 1742. doi: 10.1161/CIRCRESAHA.114.303454
31. Vergeer M, Boekholdt SM, Sandhu MS, Genetic variation at the phospholipid transfer protein locus affects its activity and high-density lipoprotein size and is a novel marker of cardiovascular disease susceptibility. Circulation 2010 122 470 477. doi: 10.1161/CIRCULATIONAHA.109.912519
32. Kim DS, Crosslin DR, Auer PL, on behalf of the NHLBI Exome Sequencing Project Rare coding variation in paraoxonase-1 is associated with ischemic stroke in the NHLBI Exome Sequencing Project. J Lipid Res 2014 55 1173 1178. doi: 10.1194/jlr.P049247
33. Kim DS, Burt AA, Ranchalis JE, Vuletic S, Vaisar T, Li WF, Rosenthal EA, Dong W, Eintracht JF, Motulsky AG, Brunzell JD, Albers JJ, Furlong CE, Jarvik GP, PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity. J Lipid Res 2015 56 1351 1362. doi: 10.1194/jlr.P058032
34. Kim DS, Burt AA, Rosenthal EA, Ranchalis JE, Eintracht JF, Hatsukami TS, Furlong CE, Marcovina S, Albers JJ, Jarvik GP, HDL-3 is a superior predictor of carotid artery disease in a case-control cohort of 1725 participants. J Am Heart Assoc 2014 3 e000902. doi: 10.1161/JAHA.114.000902
35. Robins SJ, Collins D, Wittes JT, Papademetriou V, Deedwania PC, Schaefer EJ, McNamara JR, Kashyap ML, Hershman JM, Wexler LF, Rubins HB, VA-HIT Study Group. Veterans Affairs High-Density Lipoprotein Intervention Trial Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 2001 285 1585 1591
36. Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R, Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003 290 2292 2300. doi: 10.1001/jama.290.17.2292
37. Waksman R, Torguson R, Kent KM, Pichard AD, Suddath WO, Satler LF, Martin BD, Perlman TJ, Maltais JA, Weissman NJ, Fitzgerald PJ, Brewer HB Jr, A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome. J Am Coll Cardiol 2010 55 2727 2735. doi: 10.1016/j.jacc.2009.12.067
38. Jafri H, Alsheikh-Ali AA, Mooney P, Kimmelstiel CD, Karas RH, Kuvin JT, Extended-release niacin reduces LDL particle number without changing total LDL cholesterol in patients with stable CAD. J Clin Lipidol 2009 3 45 50. doi: 10.1016/j.jacl.2008.12.003
39. Khera AV, Patel PJ, Reilly MP, Rader DJ, The addition of niacin to statin therapy improves high-density lipoprotein cholesterol levels but not metrics of functionality. J Am Coll Cardiol 2013 62 1909 1910. doi: 10.1016/j.jacc.2013.07.025
40. Yvan-Charvet L, Kling J, Pagler T, Li H, Hubbard B, Fisher T, Sparrow CP, Taggart AK, Tall AR, Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib. Arterioscler Thromb Vasc Biol 2010 30 1430 1438. doi: 10.1161/ATVBAHA.110.207142
41. Yvan-Charvet L, Matsuura F, Wang N, Bamberger MJ, Nguyen T, Rinninger F, Jiang XC, Shear CL, Tall AR, Inhibition of cholesteryl ester transfer protein by torcetrapib modestly increases macrophage cholesterol efflux to HDL. Arterioscler Thromb Vasc Biol 2007 27 1132 1138. doi: 10.1161/ATVBAHA.106.138347
42. Catalano G, Julia Z, Frisdal E, Vedie B, Fournier N, Le Goff W, Chapman MJ, Guerin M, Torcetrapib differentially modulates the biological activities of HDL2 and HDL3 particles in the reverse cholesterol transport pathway. Arterioscler Thromb Vasc Biol 2009 29 268 275. doi: 10.1161/ATVBAHA.108.179416
43. Niesor EJ, Magg C, Ogawa N, Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport. J Lipid Res 2010 51 3443 3454. doi: 10.1194/jlr.M008706
44. Ray KK, Ditmarsch M, Kallend D, Niesor EJ, Suchankova G, Upmanyu R, Anzures-Cabrera J, Lehnert V, Pauly-Evers M, Holme I, Štásek J, van Hessen MW, Jones P, dal-ACUTE Investigators The effect of cholesteryl ester transfer protein inhibition on lipids, lipoproteins, and markers of HDL function after an acute coronary syndrome: the dal-ACUTE randomized trial. Eur Heart J 2014 35 1792 1800. doi: 10.1093/eurheartj/ehu105
45. Hovingh GK, Kastelein JJ, van Deventer SJ, Round P, Ford J, Saleheen D, Rader DJ, Brewer HB, Barter PJ, Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet 2015 386 452 460. doi: 10.1016/S0140-6736(15)60158-1
46. Rosenson RS, Koenig W, Mendelian randomization analyses for selection of therapeutic targets for cardiovascular disease prevention: a note of circumspection. Cardiovasc Drugs Ther 2016. [Epub ahead of print