Examining controversies and new frontiers in lipid management

References

• Baigent C, Blackwell L, Emberson J et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376, 1670–1681 (2010).
   Google Scholar
• Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J. Am. Coll. Cardiol. 46, 1225–1228 (2005).
   Google Scholar
• Goodman SG, Langer A, Bastien NR et al. Prevalence of dyslipidemia in statin-treated patients in Canada: results of the DYSlipidemia International Study (DYSIS). Can. J. Cardiol. 26, e330–e335 (2010).
   Google Scholar
• Wei MY, Ito MK, Cohen JD et al. Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education. J. Clin. Lipidol. 7, 472–483 (2013).
   Google Scholar
• Ridker PM, Pradhan A, MacFadyen JG et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 380, 565–571 (2012).
   Google Scholar
• Richardson K, Schoen M, French B et al. Statins and cognitive function: a systematic review. Ann. Intern. Med. 159, 688–697 (2013).
   Google Scholar
• Nicholls SJ, Ballantyne CM, Barter PJ et al. Effect of two intensive statin regimens on progression of coronary disease. N. Engl. J. Med. 365, 2078–2087 (2011).
   Google Scholar
• Nissen SE, Nicholls SJ, Sipahi I et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 295, 1556–1565 (2006).
   Google Scholar
• Guyton JR, Campbell KB, Lakey WC. Statin intolerance: more questions than answers. Expert Rev. Clin. Pharmacol. 7, 1–3 (2014).
   Google Scholar
• Cannon CP, Giugliano RP, Blazing MA et al. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am. Heart J. 156, 826–832 (2008).
   Google Scholar
• Stein EA, Dufour R, Gagne C et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation 126, 2283–2292 (2012).
   Google Scholar
• Visser ME, Wagener G, Baker BF et al. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur. Heart J. 33, 1142–1149 (2012).
   Google Scholar
• Cuchel M, Bloedon LT, Szapary PO et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N. Engl. J. Med. 356, 148–156 (2007).
   Google Scholar
• Farnier M. PCSK9: from discovery to therapeutic applications. Arch. Cardiovasc. Dis. 107, 58–66 (2014).
   Google Scholar
• Hooper AJ, Marais AD, Tanyanyiwa DM, Burnett JR. The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis 193, 445–448 (2007).
   Google Scholar
• Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354, 1264–1272 (2006) • Clinical Data Supporting Lifelong Reduction In Cardiovascular Risk With Low Pcsk9 Levels.
   Google Scholar
• Koren MJ, Scott R, Kim JB et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, Phase 2 study. Lancet 380, 1995–2006. (2012) • Early Evidence Of Robust Ldl-C Lowering With Pcsk9 Inhibition.
   Google Scholar
• Raal F, Scott R, Somaratne R et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation 126, 2408–2417 (2012).
   Google Scholar
• Bansal S, Buring JE, Rifai N et al. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 298, 309–316 (2007).
   Google Scholar
• Chapman MJ, Ginsberg HN, Amarenco P et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur. Heart J. 32, 1345–1361 (2011) • Comprehensive Guideline Data Outlying The Evidence For Targeting Triglycerides And Hdl.
   Google Scholar
• Sarwar N, Sandhu MS, Ricketts SL et al. Triglyceridemediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 375, 1634–1639 (2010).
   Google Scholar
• Fruchart JC, Staels B, Duriez P. The role of fibric acids in atherosclerosis. Curr. Atheroscler. Rep. 3, 83–92 (2001).
   Google Scholar
• Manninen V, Elo MO, Frick MH et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA 260, 641–651 (1988).
   Google Scholar
• Rubins HB, Robins SJ, Collins D et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N. Engl. J. Med. 341, 410–418 (1999).
   Google Scholar
• Jun M, Foote C, Lv J et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 375, 1875–1884 (2010).
   Google Scholar
• The Bezafibrate Infarction Prevention (BIP) study. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Circulation 102, 21–27 (2000).
   Google Scholar
• Ginsberg HN, Elam MB, Lovato LC et al. Effects of combination lipid therapy in Type 2 diabetes mellitus. N. Engl. J. Med. 362, 1563–1574 (2010).
   Google Scholar
• Keech A, Simes RJ, Barter P et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with Type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366, 1849–1861 (2005).
   Google Scholar
• De Caterina R. n-3 fatty acids in cardiovascular disease. N. Engl. J. Med. 364, 2439–2450 (2011).
   Google Scholar
• Yokoyama M, Origasa H, Matsuzaki M et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised openlabel, blinded endpoint analysis. Lancet 369, 1090–1098 (2007).
   Google Scholar
• Estruch R, Ros E, Salas-Salvado J et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N. Engl. J. Med. 368, 1279–1290 (2013).
   Google Scholar
• Nissen SE, Nicholls SJ, Wolski K et al. Effects of a potent and selective PPAR-alpha agonist in patients with atherogenic dyslipidemia or hypercholesterolemia: two randomized controlled trials. JAMA 297, 1362–1373 (2007).
   Google Scholar
• Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med. 356, 2457–2471 (2007).
   Google Scholar
• Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with Type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 298, 1180–1188 (2007).
   Google Scholar
• Hsiao FY, Hsieh PH, Huang WF et al. Risk of bladder cancer in diabetic patients treated with rosiglitazone or pioglitazone: a nested case-control study. Drug Saf. 36, 643–649 (2013).
   Google Scholar
• Nissen SE, Wolski K, Topol EJ. Effect of muraglitazar on death and major adverse cardiovascular events in patients with Type 2 diabetes mellitus. JAMA 294, 2581–2586 (2005).
   Google Scholar
• Lincoff AM, Tardif JC, Neal B et al. Evaluation of the dual peroxisome proliferator-activated receptor alpha/gamma agonist aleglitazar to reduce cardiovascular events in patients with acute coronary syndrome and Type 2 diabetes mellitus: rationale and design of the AleCardio trial. Am. Heart J. 166, 429–434 (2013).
   Google Scholar
• Ooi EM, Barrett PH, Chan DC, Watts GF. Apolipoprotein C-III: understanding an emerging cardiovascular risk factor. Clin. Sci. (Lond). 114, 611–624 (2008).
   Google Scholar
• Kawakami A, Aikawa M, Alcaide P et al. Apolipoprotein CIII induces expression of vascular cell adhesion molecule-1 in vascular endothelial cells and increases adhesion of monocytic cells. Circulation 114, 681–687 (2006).
   Google Scholar
• van der Ham RL, Alizadeh Dehnavi R, Berbee JF et al. Plasma apolipoprotein CI and CIII levels are associated with increased plasma triglyceride levels and decreased fat mass in men with the metabolic syndrome. Diabetes Care 32, 184–186 (2009).
   Google Scholar
• Watts GF, Ooi EM, Chan DC. Demystifying the management of hypertriglyceridaemia. Nature Rev. Cardiol. 10, 648–661 (2013).
   Google Scholar
• DeVita RJ, Pinto S. Current status of the research and development of diacylglycerol O-acyltransferase 1 (DGAT1) inhibitors. J. Med. Chem. 56, 9820–9825 (2013).
   Google Scholar
• Gordon DJ, Probstfield JL, Garrison RJ et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 79, 8–15 (1989).
   Google Scholar
• Badimon JJ, Badimon L, Fuster V. Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit. J. Clin. Invest. 85, 1234–1241 (1990).
   Google Scholar
• Badimon JJ, Badimon L, Galvez A et al. High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits. Lab. Invest. 60, 455–461 (1989).
   Google Scholar
• Nicholls SJ, Cutri B, Worthley SG et al. Impact of short-term administration of high-density lipoproteins and atorvastatin on atherosclerosis in rabbits. Arterioscler. Thromb. Vasc. Biol. 25, 2416–2421 (2005).
   Google Scholar
• Plump AS, Scott CJ, Breslow JL. Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse. Proc. Natl. Acad. Sci. USA 91, 9607–9611 (1994).
   Google Scholar
• Rubin EM, Krauss RM, Spangler EA et al. Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature 353, 265–267 (1991).
   Google Scholar
• Barter PJ, Nicholls S, Rye KA et al. Antiinflammatory properties of HDL. Circ. Res. 95, 764–772 (2004).
   Google Scholar
• Nissen SE, Tsunoda T, Tuzcu EM et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290, 2292–2300 (2003).
   Google Scholar
• Tardif JC, Gregoire J, L’Allier PL et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 297, 1675–1682 (2007).
   Google Scholar
• Waksman R, Torguson R, Kent KM et al. 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. 55, 2727–2735 (2010).
   Google Scholar
• Kraus WE, Houmard JA, Duscha BD et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N. Engl. J. Med. 347, 1483–1492 (2002).
   Google Scholar
• Cui Y, Watson DJ, Girman CJ et al. Effects of increasing high-density lipoprotein cholesterol and decreasing low-density lipoprotein cholesterol on the incidence of first acute coronary events (from the Air Force/Texas Coronary Atherosclerosis Prevention Study). Am. J. Cardiol. 104, 829–834 (2009).
   Google Scholar
• Nicholls SJ, Tuzcu EM, Sipahi I et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA 297, 499–508 (2007).
   Google Scholar
• Clofibrate and niacin in coronary heart disease. JAMA 231, 360–381 (1975).
   Google Scholar
• Brown BG, Zhao X-Q, Chait A et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N. Engl. J. Med. 345, 1583–1592 (2001).
   Google Scholar
• Taylor AJ, Sullenberger LE, Lee HJ et al. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 110, 3512–3517 (2004).
   Google Scholar
• Boden WE, Probstfield JL, Anderson T et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N. Engl. J. Med. 365, 2255–2267 (2011).
   Google Scholar
• ThriveStudy. www.thrivestudy.org/hps2thrivereleaseuswireversionfinal.pdf
   Google Scholar
• Shaul PW, Mineo C. HDL action on the vascular wall: is the answer NO? J. Clin. Invest. 113, 509–513 (2004)
   Google Scholar
• Angelin B, Parini P, Eriksson M. Reverse cholesterol transport in man: promotion of fecal steroid excretion by infusion of reconstituted HDL. Atheroscler. Suppl. 3, 23–30 (2002).
   Google Scholar
• Nicholls SJ, Uno K, Kataoka Y, Nissen SE. ETC-216 for coronary artery disease. Expert Opin. Biol. Ther. 11, 387–394 (2011).
   Google Scholar
• Bailey D, Jahagirdar R, Gordon A et al. RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo. J. Am. Coll. Cardiol. 55, 2580–2589 (2010).
   Google Scholar
• Nicholls SJ, Gordon A, Johansson J et al. Efficacy and safety of a novel oral inducer of apolipoprotein A-I synthesis in statin-treated patients with stable coronary artery disease a randomized controlled trial. J. Am. Coll. Cardiol. 57, 1111–1119 (2011).
   Google Scholar
• Nicholls SJ, Gordon A, Johannson J et al. ApoA-I induction as a potential cardioprotective strategy: rationale for the SUSTAIN and ASSURE studies. Cardiovasc. Drugs Ther. 26, 181–187 (2012).
   Google Scholar
• Sherman CB, Peterson SJ, Frishman WH. Apolipoprotein A-I mimetic peptides: a potential new therapy for the prevention of atherosclerosis. Cardiol. Rev. 18, 141–147 (2010).
   Google Scholar
• Barter PJ. CETP and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 20, 2029–2031 (2000).
   Google Scholar
• Boekholdt SM, Kuivenhoven JA, Wareham NJ et al. Plasma levels of cholesteryl ester transfer protein and the risk of future coronary artery disease in apparently healthy men and women: the prospective EPIC (European Prospective Investigation into Cancer and nutrition)-Norfolk population study. Circulation 110, 1418–1423 (2004).
   Google Scholar
• Barter PJ, Brewer HB Jr. Chapman MJ et al. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 23, 160–167 (2003).
   Google Scholar
• Thompson A, Di Angelantonio E, Sarwar N et al. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 299, 2777–2788 (2008).
   Google Scholar
• Okamoto H, Yonemori F, Wakitani K et al. A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature 406, 203–207 (2000).
   Google Scholar
• Brousseau ME, Schaefer EJ, Wolfe ML et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N. Engl. J. Med. 350, 1505–1515 (2004).
   Google Scholar
• Barter PJ, Caulfield M, Eriksson M et al. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 357, 2109–2122 (2007).
   Google Scholar
• Bots ML, Visseren FL, Evans GW et al. Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet 370, 153–160 (2007).
   Google Scholar
• Kastelein JJ, van Leuven SI, Burgess L et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N. Engl. J. Med. 356, 1620–1630 (2007).
   Google Scholar
• Nissen SE, Tardif JC, Nicholls SJ et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N. Engl. J. Med. 356, 1304–1316 (2007).
   Google Scholar
• Brewer HB, Jr. HDL metabolism and the role of HDL in the treatment of high-risk patients with cardiovascular disease. Curr. Cardiol. Rep. 9, 486–492 (2007).
   Google Scholar
• Nicholls SJ, Tuzcu EM, Brennan DM et al. Cholesteryl ester transfer protein inhibition, high-density lipoprotein raising, and progression of coronary atherosclerosis: insights from ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation). Circulation 118, 2506–2514 (2008).
   Google Scholar
• Barter P. Lessons learned from the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial. Am. J. Cardiol. 104, e10–e15 (2009).
   Google Scholar
• Vergeer M, Stroes ES. The pharmacology and off-target effects of some cholesterol ester transfer protein inhibitors. Am. J. Cardiol. 104, E32–E38 (2009).
   Google Scholar
• Rhainds D, Arsenault BJ, Brodeur MR, Tardif JC. An update on the clinical development of dalcetrapib (RO4607381), a cholesteryl ester transfer protein modulator that increases HDL cholesterol levels. Future Cardiol. 8, 513–531 (2012).
   Google Scholar
• Cannon CP, Shah S, Dansky HM et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N. Engl. J. Med. 363, 2406–2415 (2010).
   Google Scholar
• Nicholls SJ, Brewer HB, Kastelein JJ et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA 306, 2099–2109 (2011).
   Google Scholar
• Barter PJ. Hugh sinclair lecture: the regulation and remodelling of HDL by plasma factors. Atheroscler. Suppl. 3, 39–47 (2002).
   Google Scholar
• Voight BF, Peloso GM, Orho-Melander M et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 380, 572–580 (2012). • Mendelian Randomization Data Suggesting That Hdl Cholesterol Does Not Lie On The Causative Pathway For Cardiovascular Disease.
   Google Scholar
• Khera AV, Cuchel M, de la Llera-Moya M et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N. Engl. J. Med. 364, 127–135 (2011).
   Google Scholar
• Nicholls SJ, Lundman P, Harmer JA et al. Consumption of saturated fat impairs the anti-inflammatory properties of high-density lipoproteins and endothelial function. J. Am. Coll. Cardiol. 48, 715–720 (2006).
   Google Scholar
• Ansell BJ, Navab M, Hama S et al. Inflammatory/ antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation 108, 2751–2756 (2003).
   Google Scholar
• Mora S, Buring JE, Ridker PM. Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events. Circulation 129, 553–561 (2014).
   Google Scholar
• Boekholdt SM, Arsenault BJ, Mora S et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA 307, 1302–1309 (2012).
   Google Scholar