REVIEW PAPER
High-density lipoprotein (HDL) cholesterol – more complicated than we think?
 
More details
Hide details
1
Department of Family Medicine, Chair of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow, Poland
2
Department of Cardiac Rehabilitation, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
3
Burns and Plastic Surgery Centre of Malopolska, Rydygier Memorial Hospital, Krakow, Poland
4
Department of Coronary Disease and Heart Failure, Institute of Cardiology, Jagiellonian University Medical College, John Paul II Hospital, Krakow, Poland
CORRESPONDING AUTHOR
Katarzyna Nessler   

Department of Family Medicine, Chair of Internal Medicine and Gerontology, Jagiellonian University Medical College in Krakow, 4 Bochenska str, 31-061 Krakow, Poland, Bocheńska 4, 31-061 Kraków, Poland
 
Ann Agric Environ Med. 2018;25(3):517–526
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
There are some clinical situations where a high level of HDL cholesterol (HDL-C) may be unfavourable. In these situations, HDL-C may undergo some changes, and even if its quantity is within the reference range, its quality is no longer the same.

Brief description of state of knowledge:
Diabetes is the state of elevated oxidative stress. Studies conducted to-date have revealed an increased production of the reactive forms of oxygen as the result of tissue damage in diabetes patients. The expression ‘dysfunctional HDL’ has been coined in the literature to describe high-density lipoproteins that lose their antioxidative and anti-inflammatory properties, that is, HDL-C that loses its basic functions. Recent observational studies have confirmed that the atheroprotective activity of properly functioning HDL-C is frequently impaired in clinical situations associated with oxidative stress. The presented review lays the foundation for a new approach to understanding how the functional properties of HDL help reduce cardiovascular risk.

Conclusions:
In the light of presented findings it seems that there is a need to seek a better diagnostic marker than HDL-C level. This study presents some possible directions for future research to bring us closer to the full understanding of the HDL particle and its role in patients with ischemic heart disease and type 2 diabetes.

 
REFERENCES (107)
1.
International Diabetes Federation. http://www.diabetesatlas.org/A... 14 Jun 2018.
 
2.
Guariguata L, Whiting DR, Hambleton I, et al. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014; 103(2): 137-149.
 
3.
Danaei G, Lawes CM, Vander Hoorn S, et al. Global and regional mortality from ischaemic heart disease and stroke attributable to higher-than-optimum blood glucose concentration: comparative risk assessment. Lancet 2006; 368(9548): 1651-1659.
 
4.
Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics–2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009; 119(3): e21-181.
 
5.
Xiao C, Dash S, Morgantini C. Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol. Diabetes. 2016; 65(7): 1767-78.
 
6.
Ference BA, Ginsberg HN, Graham, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017; 38: 2459–2472.
 
7.
Ference BA, Yoo W, Alesh I et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012; 60: 2631-2639.
 
8.
Ragbir S, Farmer JA. Dysfunctional High-Density Lipoprotein and Atherosclerosis. Curr. Atheroscler Rep. 2010; 12(5): 343–348.
 
9.
Farmer JA, Liao J. Evolving concepts of the role of high-density lipoprotein in protection from atherosclerosis. Curr Atheroscler Rep. 2011; 13(2): 107-114.
 
10.
Brewer Jr HB, Remaley AT, Neufeld EB, et al. Regulation of plasma high-density lipoprotein levels by the ABCA1 transporter and the emerging role of high-density lipoprotein in the treatment of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2004; 24: 1755–60.
 
11.
Rigotti A, Miettinen HE, Krieger M. The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues. Endocr Rev. 2003; 24: 357–87.
 
12.
Castro G, Nihoul LP, Dengremont C, et al. Cholesterol efflux, lecithin-cholesterol acyltransferase activity, and pre-beta particle formation by serum from human apolipoprotein A-I and apolipoprotein A-I/apolipoprotein A-II transgenic mice consistent with the latter being less effective for reverse cholesterol transport. Biochemistry 1997; 36(8): 2243-2249.
 
13.
Asztalos BF, Roheim PS, Milani RL, et al. Distribution of apo A-I-containing HDL subpopulations in patients with coronary heart disease. Arterioscler Thromb Vasc Biol. 2000; 20(12):2670–2676.
 
14.
Chrysohoou C, Pitsavos C, Skoumas J, et al. The emerging anti-inflammatory role of HDL-cholesterol, illustrated in cardiovascular disease free population; the ATTICA study. Int J Cardiol. 2007; 122(1): 29–33.
 
15.
Castelli WP. Cholesterol and lipids in the risk of coronary artery disease-the Framingham Heart Study. Can J Cardiol. 1988; 4(Suppl. A): 5A-10A.
 
16.
Farmer JA, Liao J. Evolving concepts of the role of high-density lipoprotein in protection from atherosclerosis. Curr Atheroscler Rep. 2011; 13(2): 107–11.
 
17.
Fielding CJ, Fielding PE. Molecular physiology of reverse cholesterol transport. J Lipid Res. 1995; 36(2): 211–228.
 
18.
Phillips MC, Gillotte KL, Haynes MP, Johnson WJ, Lund-Katz S, Rothblat GH. Mechanisms of high density lipoprotein-mediated efflux of cholesterol from cell plasma membranes. Atherosclerosis 1998; 137(Suppl.): S13–17.
 
19.
Baigent C, Keech A, Kearney PM, et al. 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(9493): 1267-1278.
 
20.
Farnier M. An evaluation of alirocumab for the treatment of hypercholesterolemia. Expert Rev Cardiovasc Ther. 2015; 13(12): 1307-1323.
 
21.
Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Eng J Med. 2000; 342(12): 836–843.
 
22.
HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014; 371(3): 203-212.
 
23.
HPS2-THRIVE Collaborative Group1. 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(17): 1279-1291.
 
24.
Mooradian AD, Haas MJ. Targeting high-density lipoproteins: increasing de novo production versus decreasing clearance. Drugs 2015; 75(7): 713-722.
 
25.
Barter P. Lessons learned from the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial. Am J Cardiol. 2009; 104: 10E–15E.
 
26.
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 2007; 370: 153-60.
 
27.
Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012; 367: 2089-99.
 
28.
Hovingh GK, Kastelein J, van Deventer SJ, et al. 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(9992): 452-60.
 
29.
Keene D, Price C, Shun-Shin MJ, et al. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. BMJ Br Med J. 2014; 349: g4379.
 
30.
Teslovich TM, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010; 466: 707–713.
 
31.
Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009; 461: 747–753.
 
32.
Voight BF, Peloso GM, Orho-Melander M, et al. Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci. Am J Hum Genet. 2012; 91: 823–838.
 
33.
Holmes MV, Asselbergs FW, Palmer TM, et al. Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J. 2015; 36: 539–550.
 
34.
Boekholdt SM, Arsenault BJ, Hovingh GK, et al. Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: a meta-analysis. Circulation. 2013; 128(14): 1504-12.
 
35.
Ray K, Wainwright NW, Visser L, et al. Changes in HDL cholesterol and cardiovascular outcomes after lipid modification therapy. Heart. 2012; 98: 780–785.
 
36.
Briel M, Ferreira-Gonzalez I, You JJ, et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis. BMJ. 2009; 16: 338:b92.
 
37.
Grover SA, Kaouache M, Joseph L, et al. Evaluating the incremental benefits of raising high-density lipoprotein cholesterol levels during lipid therapy after adjustment for the reductions in other blood lipid levels. Arch Intern Med. 2009; 169(19): 1775-80.
 
38.
Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011; 365(24): 2255-67.
 
39.
Nissen SE, Tardif JC, Nicholls SJ, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007; 356(13): 1304-16.
 
40.
Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007; 357: 2109–2122.
 
41.
Asztalos BF, Tani M, Schaefer EJ. Metabolic and functional relevance of HDL subspecies. Curr Opin Lipidol. 2011; 22(3): 176-85.
 
42.
Mora S, Glynn RJ, Ridker PM. High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy. Circulation. 2013; 128(11): 1189-97.
 
43.
Vergeer M, Holleboom AG, Kastelein JJ. The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis? J Lipid Res. 2010; 51(8): 2058-73.
 
44.
Mackey RH, Greenland P, Goff DC Jr, et al. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis). J Am Coll Cardiol. 2012; 60(6): 508-16.
 
45.
deGoma EM, deGoma RL, Rader DJ. Beyond high-density lipoprotein cholesterol levels evaluating high-density lipoprotein function as influenced by novel therapeutic approaches. J Am Coll Cardiol. 2008; 51(23): 2199-211.
 
46.
Rader DJ, Alexander ET, Weibel GL. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. J Lipid Res. 2009; 50: S189-94.
 
47.
Saddar S, Carriere V, Lee WR, et al. Scavenger receptor class B type I is a plasma membrane cholesterol sensor. Circ Res. 2013; 112(1): 140-51.
 
48.
Murphy AJ, Bijl N, Yvan-Charvet L, et al. Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis. Nat Med. 2013; 19(5): 586-94.
 
49.
Tall AR. Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins. J Intern Med. 2008; 263(3): 256-73.
 
50.
Khera AV, Cuchel M, de la Llera-Moya M, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011; 364(2): 127–135.
 
51.
Rohatgi A, Khera A, Berry JD, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014; 371(25): 2383-93.
 
52.
Hutchins PM, Heinecke JW. Cholesterol efflux capacity, macrophage reverse cholesterol transport and cardioprotective HDL. Curr Opin Lipidol. 2015; 26(5): 388-93.
 
53.
Cuchel M, Rader DJ. Macrophage reverse cholesterol transport: key to the regression of atherosclerosis? Circulation. 2006; 113(21): 2548-55.
 
54.
Sorci-Thomas MG, Bhat S, Thomas MJ. Activation of lecithin: cholesterol acyltransferase by HDL ApoA-I central helices. Clin Lipidol. 2009; 4(1): 113-124.
 
55.
Hoang A, Murphy AJ, Coughlan MT, et al. Advanced glycation of apolipoprotein A-I impairs its anti-atherogenic properties. Diabetologia 2007; 50(8): 1770– 1779.
 
56.
Ansell BJ, Navab M, Hama S,. et al. Inflammatory/anti-inflammatory 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. 2003; 108: 2751–6.
 
57.
Sorrentino SA, Besler C, Rohrer L, et al. Endothelial-vasoprotective effects of high density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy. Circulation 2010; 121(1): 110–122.
 
58.
Riwanto M, Rohrer L, Roschitzki B, et al. Altered activation of endothelial anti- and proapoptotic pathways by high-density lipoprotein from patients with coronary artery disease: role of high-density lipoprotein proteome remodeling. Circulation 2013; 127(8): 891–904.
 
59.
Tan HC, Tai ES, Sviridov D, et al. Relationships between cholesterol efflux and high-density lipoprotein particles in patients with type 2 diabetes mellitus. J Clin Lipidol. 2011; 5(6): 467-73.
 
60.
Smith J. Myeloperoxidase, inflammation, and dysfunctional HDL. J. Clin. Lipidol. 2010; 4(5): 382-388.
 
61.
Navab M, Anantharamaiah G, Fogelman A. The role of High-Density Lipoprotein in Inflammation. Trends. Cardiovasc Med. 2005; 15(4): 158-161.
 
62.
Morgantini C, Natali A, Boldrini B, et al. Anti-inflammatory and Antioxidant Properies of HDLs are impaired in Type 2 Diabetes. Diabetes 2011; 60(10): 2617-2623.
 
63.
Ragbir S, Farmer JA. Dysfunctional High-Density Lipoprotein and Atherosclerosis. Curr Atheroscler Rep. 2010; 12(5): 343–348.
 
64.
Van Lenten BJ, Hama SY, de Beer FC, et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest. 1995; 96(6): 2758-2767.
 
65.
Barter PJ, Nicholls S, Rye KA, et al. Antiinflammatory properties of HDL. Circ Res. 2004; 95(8): 764–772.
 
66.
Shao B, Oda MN, Oram JF, et al. Myeloperoxidase: an oxidative pathway for generating dysfunctional high-density lipoprotein. Chem Res Toxicol. 2010; 23(3): 447–454.
 
67.
Patra SK, Singh K, Singh R. Paraoxonase 1: A better atherosclerotic risk predictor than HDL in type 2 diabetes mellitus. Diabetes Metab Syndr. 2013; 7(2): 108-111.
 
68.
Podrez EA. Anti-oxidant properties of high-density lipoprotein and atherosclerosis. Clin Exp Pharmacol Physiol. 2010; 37(7): 719-25.
 
69.
Zheng L, Nukuna B, Brennan ML, et al. Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J Clin Invest. 2004; 114(4): 529-41.
 
70.
Shao B, Pennathur S, Heinecke JW. Myeloperoxidase Targets Apolipoprotein A-I, the Major High Density Lipoprotein Protein, for Site-Specific Oxidation in Human Atherosclerotic Lesions . J Biol Chem. 2012; 287(9): 6375-6386.
 
71.
Song P, Xu J, Song Y, et al. Association of Plasma Myeloperoxidase Level with Risk of Coronary Artery Disease in Patients with Type 2 Diabetes. Dis Markers. 2015; 2015: 761939.
 
72.
Jamuna Rani A, Mythili SV, Nagarajan S. Study on paraoxonase 1 in type 2 diabetes mellitus. Indian J Physiol Pharmacol. 2014; 58(1): 13-16.
 
73.
Yunoki K, Naruko T, Inaba M, et al. Gender-specific correlation between plasma myeloperoxidase levels and serum high-density lipoprotein-associated paraoxonase-1 levels in patients with stable and unstable coronary artery disease. Atherosclerosis 2013; 231(2): 308-314.
 
74.
Singh M, Kapoor A, Bhatnagar A. Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls. Chem Biol Interact. 2015; 234: 261-273.
 
75.
Shao B, Pennathur S, Pagani I, et al. Modifying Apolipoprotein A-I by Malondialdehyde, but Not by an Array of Other Reactive Carbonyls, Blocks Cholesterol Efflux by the ABCA1 Pathway. J Biol Chem. 2010; 285(24): 18473–18484.
 
76.
Shao B. Site-specific oxidation of apolipoprotein A-I impairs cholesterol export by ABCA1, a key cardioprotective function of HDL. Biochim Biophys Acta. 2012; 1821(3): 490-501.
 
77.
Slatter DA, Bolton CH, Bailey AJ. The importance of lipid-derived malondialdehyde in diabetes mellitus. Diabetologia 2000; 43(5): 550–557.
 
78.
Viswambharan H, Ming XF, Zhu S, et al. Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/endothelial nitric oxide synthase. Circ Res. 2004; 94(7): 918-25.
 
79.
Mineo C, Deguchi H, Griffin JH, et al. Endothelial and antithrombotic actions of HDL. Circ Res. 2006; 98(11): 1352-64.
 
80.
Zimman A, Podrez EA. Regulation of platelet function by class B scavenger receptors in hyperlipidemia. Arteriosclerosis Thromb Vasc Biol. 2010; 30(12): 2350-6.
 
81.
Moore RE, Navab M, Millar JS, et al. Increased atherosclerosis in mice lacking apolipoprotein A-I attributable to both impaired reverse cholesterol transport and increased inflammation. Circ Res. 2005; 97(8): 763-71.
 
82.
Marcel YL, Kiss RS. Structure-function relationships of apolipoprotein A-I: a flexible protein with dynamic lipid associations. Curr Opin Lipidol. 2003; 14(2): 151-7.
 
83.
Nicholls SJ, Zheng L, Hazen SL, et al. Formation of dysfunctional high-density lipoprotein by myeloperoxidase. Trends Cardiovasc Med. 2005; 15(6): 212-9.
 
84.
Gotto AM Jr, Whitney E, Stein EA, et al. 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(5): 477-84.
 
85.
Peng DQ, Brubaker G, Wu Z, et al. Apolipoprotein A-I tryptophan substitution leads to resistance to myeloperoxidase-mediated loss of function. Arterioscler Thromb Vasc Biol. 2008; 28(11): 2063-70.
 
86.
Durbin DM, Jonas A. Lipid-free apolipoproteins A-I and A-II promote remodeling of reconstituted high density lipoproteins and alter their reactivity with lecithin: cholesterol acyltransferase. J Lipid Res. 1999; 40: 2293–2302.
 
87.
Lagrost L, Perségol L, Lallemant C, et al. Influence of apolipoprotein composition of high density lipoprotein particles on cholesterol ester transfer protein activity. J Biol Chem. 1994; 269: 3189–3197.
 
88.
Castellani LW, Navab M, Lenten BJ, et al. Overexpression of apolipoprotein AII in transgenic mice converts high density lipoproteins to proinflammatory particles. J Clin Invest. 1997; 100: 464–474.
 
89.
Valiyaveettil M, Kar N, Ashraf MZ, et al. Oxidized high- density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI. Blood. 2008; 111: 1962–1971.
 
90.
Caughey GE, Cleland LG, Penglis PS, et al. Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoidproduction by humanendothelialcells: selectiveup-regulation of prostacyclinsynthesis by COX-2. J Immunol. 2001; 167: 2831 – 2838.
 
91.
Mineo C, Deguchi H, Griffin JH, et al. Endothelial and antithrombotic actions of HDL. Circ Res. 2006; 98: 1352–1364.
 
92.
Rosenson RS. Functional assessment of HDL: Moving beyond static measures for risk assessment. Cardiovasc Drugs Ther. 2010; 24(1): 71-5.
 
93.
Schäfer A, Flierl U, Kössler J, et al. Early determination of clopidogrel responsiveness by platelet reactivity indexidentifies patients at risk for cardiovascular events after myocardial infarction. Thromb Haemost. 2011; 106(1): 141-8.
 
94.
Schäfer A, Weinberger S, Flierl U, et al. ADP-induced platelet aggregation frequently fails to detect impaired clopidogrel-responsiveness in patients with coronary artery disease compared to a P2Y12-specific assay. Thromb Haemost. 2008; 100(4): 618-25.
 
95.
Chen L, Pei JH, Kuang J, et al. Effect of lifestyle intervention in patients with type 2 diabetes: a meta-analysis. Metabolism 2015; 64(2): 338-47.
 
96.
Angermayr L, Melchart D, Linde K. Multifactorial lifestyle interventions in the primary and secondary prevention of cardiovascular disease and type 2 diabetes mellitus—a systematic review of randomized controlled trials. Ann Behav Med 2010; 40: 49–64.
 
97.
Schellenberg ES, Dryden DM, Vandermeer B, et al. Lifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013; 159: 543–51.
 
98.
Yang Z, Scott CA, Mao C, et al. Resistance exercise versus aerobic exercise for type 2 diabetes: a systematic review and meta-analysis. Sports Med. 2014; 44(4): 487–99.
 
99.
Look AHEAD Research Group, Wing R.R. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010; 170(17): 1566-75.
 
100.
Falconer CL, Page AS, Andrews RC, et al. The Potential Impact of Displacing Sedentary Time in Adults with Type 2 Diabetes. Med Sci Sports Exerc. 2015; 47(10): 2070-5.
 
101.
Knopp RH, Paramsothy P, Retzlaff BM, et al. Gender differences in lipoprotein metabolism and dietary response: basis in hormonal differences and implications for cardiovascular disease. Curr Atheroscler Rep. 2005; 7(6): 472-9.
 
102.
Lapointe A, Balk EM, Lichtenstein AH. Gender differences in plasma lipid response to dietary fat. Nutr Rev. 2006; 64(5): 234-49.
 
103.
Bédard A, Riverin M, Dodin S, et al. Sex differences in the impact of the Mediterranean diet on cardiovascular risk profile. Br J Nutr. 2012; 108(8): 1428-34.
 
104.
Lüscher TF. Lipoproteins and diabetes. Eur Heart J. 2015; 36(9): 529-31.
 
105.
Cuchel M, Bruckert E, Ginsberg HN, et al. European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014; 35: 2146–2157.
 
106.
Luscher TF, Taddei S, Kaski JC, et al. Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial. Eur Heart J. 2012; 33: 857–865.
 
107.
Simic B, Hermann M, Shaw SG, et al. Torcetrapib impairs endothelial function in hypertension. Eur Heart J. 2012; 33: 1615–1624.
 
eISSN:1898-2263
ISSN:1232-1966