Abstract
Residual vascular risk exists despite the aggressive lowering of Low-Density Lipoprotein Cholesterol (LDL-C). A contributor to this residual risk may be elevated fasting, or non-fasting, levels of Triglyceride (TG)-rich lipoproteins. Therefore, there is a need to establish whethe a standardised Oral Fat Tolerance Test (OFTT) can improve atherosclerotic Cardiovascular (CV) Disease (ASCVD) risk prediction in addition to a fasting or non-fasting lipid profile.
An expert panel considered the role of postprandial hypertriglyceridaemia (as represented by an OFTT) in predicting ASCVD. The panel updated its 2011 statement by considering new studies and various patient categories. The recommendations are based on expert opinion since no strict endpoint trials have been performed.
Individuals with fasting TG concentration <1 mmol/L (89 mg/dL) commonly do not have an abnormal response to an OFTT. In contrast, those with fasting TG concentration ≥2 mmol/L (175 mg/dL) or nonfasting ≥2.3 mmol/L (200 mg/dL) will usually have an abnormal response. We recommend considering postprandial hypertriglyceridaemia testing when fasting TG concentrations and non-fasting TG concentrations are 1-2 mmol/L (89-175 mg/dL) and 1.3-2.3 mmol/L (115-200 mg/dL), respectively as an additional investigation for metabolic risk prediction along with other risk factors (obesity, current tobacco abuse, metabolic syndrome, hypertension, and diabetes mellitus). The panel proposes that an abnormal TG response to an OFTT (consisting of 75 g fat, 25 g carbohydrate and 10 g proteins) is >2.5 mmol/L (220 mg/dL).
Postprandial hypertriglyceridaemia is an emerging factor that may contribute to residual CV risk. This possibility requires further research. A standardised OFTT will allow comparisons between investigational studies. We acknowledge that the OFTT will be mainly used for research to further clarify the role of TG in relation to CV risk. For routine practice, there is a considerable support for the use of a single non-fasting sample.
Keywords: Postprandial hypertriglyceridaemia, non-fasting triglycerides, remnant cholesterol, fat tolerance test, atherosclerotic cardiovascular disease.
Graphical Abstract
[1]
Stone NJ, Robinson JG, Lichtenstein AH, 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. J Am Coll Cardiol 2014; 63: 2889-934.
[2]
National Institute for Health and Care Excellence (NICE). Clinical guideline CG181: Lipid modification - cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. National Clinical Guideline Centre 2014. Available at ( https://www.nice.org.uk/ guidance/cg181).
[3]
Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian cardiovascular society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2016; 32: 1263-82.
[4]
Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Statin use for the primary prevention of cardiovascular disease in adults: US preventive services task force recommendation statement. JAMA 2016; 316: 1997-2007.
[5]
Piepoli MF, Hoes AW, Agewall S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: The sixth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European association for cardiovascular prevention & rehabilitation (EACPR). Eur Heart J 2016; 37: 2315-81.
[6]
Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372: 2387-97.
[7]
Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376: 1713-22.
[8]
Ridker PM, Revkin J, Amarenco P, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med 2017; 376: 1527-39.
[9]
Bowman L, Hopewell JC, Chen F, et al. Effects of anacetrapib in patients with atherosclerotic vascular disease. N Engl J Med 2017; 377: 1217-27.
[10]
Ridker PM, Everett BM, Thuren T, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; 377: 1119-31.
[11]
Kolovou GD, Mikhailidis DP, Kovar J, et al. Assessment and clinical relevance of non-fasting and postprandial triglycerides: An expert panel statement. Curr Vasc Pharmacol 2011; 9: 258-70.
[12]
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 2011; 32: 1345-61.
[14]
Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: New insights from epidemiology, genetics, and biology. Circ Res 2016; 118: 547-63.
[15]
Rifai N, Warnick GR. Lipids, lipoproteins, apolipoproteins, and other cardiovascular risk factors.In: Burtis CA, Ashwood ER, Bruns DE, Eds. Tietz textbook of clinical chemistry and molecular diagnostics. Philadelphia: Elsevier Saunders 2006; pp. 903-82.
[16]
Simundic AM, Cornes M, Grankvist K, Lippi G, Nybo M. Standardization of collection requirements for fasting samples: for the working group on preanalytical phase (WG-PA) of the European federation of clinical chemistry and laboratory medicine (EFLM). Clin Chim Acta 2014; 432: 33-7.
[17]
Nordestgaard BG, Langsted A, Mora S, et al. Fasting is not routinely required for determination of a lipid profile: Clinical and laboratory implications including flagging at desirable concentration cut-points. A joint consensus statement from the EAS and EFLM. Eur Heart J 2016; 37: 1944-58.
[18]
Nordestgaard BG. A test in context: Lipid profile, fasting versus non-fasting. J Am Coll Cardiol 2017; 70: 1637-46.
[19]
Nordestgaard BG, Hilsted L, Stender S. Plasma lipids in non-fasting patients and signal values in laboratory responses. Ugeskr Laeger 2009; 171: 1093.
[20]
Nordestgaard BG, Langsted A, Mora S, et al. Fasting is not routinely required for determination of a lipid profile: Clinical and laboratory implications including flagging at desirable concentration cut-points - A joint consensus statement from the EAS and EFLM. Clin Chem 2016; 62: 930-46.
[21]
Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2016; 37: 2999-3058.
[22]
Leung AA, Nerenberg K, Daskalopoulou SS, et al. Hypertension Canada’s 2016 Canadian hypertension education program guidelines for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol 2016; 32: 569-88.
[23]
Scartezini M, Ferreira CEDS, Izar MCO, et al. Positioning about the flexibility of fasting for lipid profiling. Arq Bras Cardiol 2017; 108: 195-7.
[24]
Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: A scientific statement from the American Heart Association. Circulation 2011; 123: 2292-333.
[25]
Downs JR, O’Malley PG. Management of dyslipidemia for cardiovascular disease risk reduction: Synopsis of the 2014 U.S. Department of veterans’ affairs and U.S. department of defense clinical practice guideline. Ann Intern Med 2015; 163: 291-7.
[26]
Jellinger PS, Handelsman Y, Rosenblit PD, et al. American association of clinical endocrinologists and american college of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract 2017; 23: 1-87.
[27]
Grundy SM, Stone NJ, Bailey AL, et al. 2018.AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASP C/NLA/PCNA guideline on the management of blood cholesterol: Executive summary: A report of the American College of cardiology/ American Heart association task force on clinical practice guidelines. J Am Coll Cardiol 2018. pii: S0735-1097(18)39033-8.
[28]
Hegele R, Ginsberg HN, Chapman MJ, et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis and management. Lancet Diabetes Endocrinol 2014; 2: 655-66.
[29]
Bradford-Hill A. The environment and disease: Association or causation? Proc R Soc Med 1965; 58: 295-300.
[30]
Packard CJ, Ford I. Long-term follow-up of lipid-lowering trials. Curr Opin Lipidol 2015; 26: 572-9.
[31]
Klempfner R, Erez A, Sagit BZ, et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: Twenty-two-year follow-up of the bezafibrate infarction prevention study and registry. Circ Cardiovasc Qual Outcomes 2016; 9: 100-8.
[32]
Mora S, Wenger NK, Demicco DA, et al. Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: The treating to new targets (TNT) study. Circulation 2012; 125: 1979-87.
[33]
Vallejo-Vaz AJ, Fayyad R, Boekholdt SM, et al. Triglyceride-rich lipoprotein cholesterol and risk of cardiovascular events among patients receiving statin therapy in the treating to new targets (TNT) trial. Circulation 2018; 138: 770-81.
[34]
Faergeman O, Holme I, Fayyad R, et al. Plasma triglycerides and cardiovascular events in the treating to new targets and incremental decrease in end-points through aggressive lipid lowering trials of statins in patients with coronary artery disease. Am J Cardiol 2009; 104: 459-63.
[35]
Mora S, Caulfield MP, Wohlgemuth J, et al. Atherogenic lipoprotein subfractions determined by ion mobility and first cardiovascular events after random allocation to high-intensity statin or placebo: The justification for the use of statins in prevention: An intervention trial evaluating rosuvastatin (JUPITER) Ttrial. Circulation 2015; 132: 2220-9.
[36]
Lawler PR, Akinkuolie AO, Chu AY, et al. Atherogenic lipoprotein determinants of cardiovascular disease and residual risk among individuals with low-density lipoprotein cholesterol. J Am Heart Assoc 2017; 6: pii:e005549
[37]
Cholesterol Treatment Trialists’ (CTT) Collaborators.The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380: 581-90.
[38]
Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007; 357: 1301-10.
[39]
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 2012; 307: 1302-9.
[40]
Ooi EM, Watts GF, Ng TW, Barrett PH. Effect of dietary fatty acids on human lipoprotein metabolism: A comprehensive update. Nutrients 2015; 7: 4416-25.
[41]
Borén J, Matikainen N, Adiels M, Taskinen MR. Postprandial hypertriglyceridemia as a coronary risk factor. Clin Chim Acta 2014; 431: 131-42.
[43]
Rosenson RS, Helenowski IB, Tangney CC. Heterogeneous postprandial lipoprotein responses in the metabolic syndrome, and response to fenofibrate therapy. Cardiovasc Drugs Ther 2010; 24: 439-47.
[44]
Pavlidis AN, Kolovou GD, Anagnostopoulou KK, Petrou PC, Cokkinos DV. Postprandial metabolic heterogeneity in men with primary dyslipidaemia. Arch Med Sci 2010; 6: 879-86.
[45]
Kolovou GD, Anagnostopoulou KK, Pavlidis AN, et al. Metabolic syndrome and gender differences in postprandial lipaemia. Eur J Cardiovasc Prev Rehabil 2006; 13: 661-4.
[46]
Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 2007; 298: 309-16.
[47]
Lindman AS, Veierød MB, Tverdal A, Pedersen JI, Selmer R. Nonfasting triglycerides and risk of cardiovascular death in men and women from the norwegian counties study. Eur J Epidemiol 2010; 25: 789-98.
[48]
Stampfer MJ, Krauss RM, Ma J, et al. A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 1996; 276: 882-8.
[49]
Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA 2008; 300: 2142-52.
[50]
Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007; 298: 299-308.
[51]
Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 2007; 115: 450-8.
[52]
Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009; 302: 1993-2000.
[53]
Field Study Investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study); randomised controlled trial. Lancet 2005; 366: 1849-61.
[54]
Reyes-Soffer G, Ngai CI, Lovato L, et al. Effect of combination therapy with fenofibrate and simvastatin on postprandial lipemia in the ACCORD lipid trial. Diabetes Care 2013; 36: 422-8.
[55]
Elam MB, Ginsberg HN, Lovato LC, et al. Association of fenofibrate therapy with long-term cardiovascular risk in statin-treated patients with type 2 diabetes. JAMA Cardiol 2017; 2: 370-80.
[56]
Scott R, O’Brien R, Fulcher G, et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: The fenofibrate intervention and event lowering in diabetes (FIELD) study. Diabetes Care 2009; 32: 493-8.
[57]
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 1988; 260: 641-51.
[58]
Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: The bezafibrate infarction prevention (BIP) study. Circulation 2000; 102: 21-7.
[59]
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. N Engl J Med 1999; 341: 410-8.
[60]
Kolovou GD, Mikhailidis DP, Nordestgaard BG, Bilianou H, Panotopoulos G. Definition of postprandial lipaemia. Curr Vasc Pharmacol 2011; 9: 292-301.
[61]
Shaikh M, Wootton R, Nordestgaard BG, et al. Quantitative studies of transfer in vivo of low density, Sf 12-60, and Sf 60-400 lipoproteins between plasma and arterial intima in humans. Arterioscler Thromb 1991; 11: 569-77.
[62]
Nordestgaard BG, Tybjærg-Hansen A, Lewis B. Influx in vivo of low density, intermediate density, and very low density lipoproteins into aortic intimas of genetically hyperlipidemic rabbits: Roles of plasma concentration, extent of aortic lesion, and lipoprotein particle size as determinants. Arterioscler Thromb 1992; 12: 6-18.
[63]
Nordestgaard BG, Wootton R, Lewis B. Selective retention of VLDL, IDL and LDL in the arterial intima of genetically hyperlipidemic rabbits in vivo. Molecular size as a determinant of fractional loss from the intima-inner media. Arterioscler Thromb Vasc Biol 1995; 15: 534-42.
[64]
Toth PP. Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease. Vasc Health Risk Manag 2016; 12: 171-83.
[65]
Dallinga-Thie GM, Kroon J, Borén J, Chapman MJ. Triglyceride-rich lipoproteins and remnants: Targets for therapy? Curr Cardiol Rep 2016; 18: 67.
[66]
Hegele RA, Ginsberg HN, Chapman MJ, et al. The polygenic nature of hypertriglyceridaemia: Implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2014; 2: 655-66.
[67]
Mihas C, Kolovou GD, Mikhailidis DP, et al. Diagnostic value of postprandial triglyceride testing in healthy subjects: A meta-analysis. Curr Vasc Pharmacol 2011; 9: 271-80.
[68]
Perez-Martinez P, Alcala-Diaz JF, Kabagambe EK, et al. Assessment of postprandial triglycerides in clinical practice: Validation in a general population and coronary heart disease patients. J Clin Lipidol 2016; 10: 1163-71.
[69]
Niederwanger A, Ciardi C, Tatarczyk T, et al. Postprandial lipemia induces pancreatic α cell dysfunction characteristic of type 2 diabetes: studies in healthy subjects, mouse pancreatic islets, and cultured pancreatic α cells. Am J Clin Nutr 2014; 100: 1222-31.
[70]
Carlson LA, Rosenhamer G. Reduction of mortality in the stockholm ischaemic heart disease secondary prevention study by combined treatment with clofibrate and nicotinic acid. Acta Med Scand 1988; 223: 405-18.
[71]
Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010; 362: 1563-74.
[72]
Arbel Y, Klempfner R, Erez A, et al. Bezafibrate for the treatment of dyslipidemia in patients with coronary artery disease: 20-year mortality follow-up of the BIP randomized control trial. Cardiovasc Diabetol 2016; 15: 11.
[73]
Perez-Martinez P, Alcala-Diaz JF, Delgado-Lista J, et al. Metabolic phenotypes of obesity influence triglyceride and inflammation homoeostasis. Eur J Clin Invest 2014; 44: 1053-64.
[74]
Wojczynski MK, Parnell LD, Pollin TI, et al. Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI genetics of lipid lowering drugs and diet network (GOLDN). Metabolism 2015; 64: 1359-71.
[75]
Vors C, Pineau G, Gabert L, et al. Modulating absorption and postprandial handling of dietary fatty acids by structuring fat in the meal: A randomized crossover clinical trial. Am J Clin Nutr 2013; 97: 23-36.
[76]
Lozano A, Perez-Martinez P, Delgado-Lista J, et al. Body mass interacts with fat quality to determine the postprandial lipoprotein response in healthy young adults. Nutr Metab Cardiovasc Dis 2012; 22: 355-61.
[77]
Teng KT, Chang CY, Kanthimathi MS, Tan AT, Nesaretnam K. Effects of amount and type of dietary fats on postprandial lipemia and thrombogenic markers in individuals with metabolic syndrome. Atherosclerosis 2015; 242: 281-7.
[78]
Ryan MF, O’Grada CM, Morris C, et al. Within-person variation in the postprandial lipemic response of healthy adults. Am J Clin Nutr 2013; 97: 261-7.
[79]
Jackson KG, Walden CM, Murray P, et al. A sequential two meal challenge reveals abnormalities in postprandial TAG but not glucose in men with increasing numbers of metabolic syndrome components. Atherosclerosis 2012; 220: 237-43.
[80]
Maraki M, Aggelopoulou N, Christodoulou N, et al. Validity of abbreviated oral fat tolerance tests for assessing postprandial lipemia. Clin Nutr 2011; 30: 852-7.
[81]
Perez-Caballero AI, Alcala-Diaz JF, Perez-Martinez P, et al. Lipid metabolism after an oral fat test meal is affected by age-associated features of metabolic syndrome, but not by age. Atherosclerosis 2013; 226: 258-62.
[82]
Leon-Acuña A, Alcala-Diaz JF, Delgado-Lista J, et al. Hepatic insulin resistance both in prediabetic and diabetic patients determines postprandial lipoprotein metabolism: From the CORDIOPREV study. Cardiovasc Diabetol 2016; 15: 68.
[83]
Langsted A, Nordestgaard BG. Nonfasting lipids, lipoproteins, and apolipoproteins in individuals with and without diabetes: 58,434 individuals from the Copenhagen general population study. Clin Chem 2011; 57: 482-9.
[84]
Mohanlal N, Holman RR. A standardized triglyceride and carbohydrate challenge: the oral triglyceride tolerance test. Diabetes Care 2004; 27: 89-94.
[85]
Musso G, Gambino R, Durazzo M, et al. Adipokines in NASH: Postprandial lipid metabolism as a link between adiponectin and liver disease. Hepatology 2005; 42: 1175-83.
[86]
Sarwar N, Sandhu MS, Ricketts SL, et al. Triglyceride-mediated pathways and coronary disease: Collaborative analysis of 101 studies. Lancet 2010; 375: 1634-9.
[88]
Wittrup HH, Tybjaerg-Hansen A, Abildgaard S, Steffensen R, Schnohr P, Nordestgaard BG. A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease. J Clin Invest 1997; 99: 1606-13.
[89]
Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation 1999; 99: 2901-7.
[90]
Thomsen M, Varbo A, Tybjaerg-Hansen A, Nordestgaard BG. Low nonfasting triglycerides and reduced all-cause mortality: A Mendelian randomization study. Clin Chem 2014; 60: 737-46.
[91]
Varbo A, Benn M, Tybjaerg-Hansen A, Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013; 61: 427-36.
[92]
Jansen H, Samani NJ, Schunkert H. Mendelian randomization studies in coronary artery disease. Eur Heart J 2014; 35: 1917-24.
[93]
Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013; 61: 427-36.
[94]
Do R, Willer CJ, Schmidt EM, et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet 2013; 45: 1345-52.
[95]
Pollin TI, Damcott CM, Shen H, et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 2008; 322: 1702-5.
[96]
Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG, Tybjaerg-Hansen A. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med 2014; 371: 32-41.
[97]
Crosby J, Peloso GM, Auer PL, et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med 2014; 371: 22-31.
[98]
Dewey FE, Gusarova V, Dunbar RL, et al. Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease. N Engl J Med 2017; 377: 211-21.
[99]
Stitziel NO, Khera AV, Wang X, et al. ANGPTL3 deficiency and protection against coronary artery disease. J Am Coll Cardiol 2017; 69: 2054-63.
[100]
Khera AV, Won HH, Peloso GM, et al. Association of rare and common variation in the lipoprotein lipase gene with coronary artery disease. JAMA 2017; 317: 937-46.
[101]
Nordestgaard BG, Abildgaard S, Wittrup HH, Steffensen R, Jensen G, Tybjaerg-Hansen A. Heterozygous lipoprotein lipase deficiency: Frequency in the general population, effect on plasma lipid levels, and risk of ischemic heart disease. Circulation 1997; 96: 1737-44.
[102]
Varbo A, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation 2013; 128: 1298-309.
[103]
Helgadottir A, Gretarsdottir S, Thorleifsson G, et al. Variants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease. Nat Genet 2016; 48: 634-9.
[104]
Varbo A, Benn M, Smith GD, Timpson NJ, Tybjaerg-Hansen A, Nordestgaard BG. Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease. Circ Res 2015; 116: 665-73.
[105]
Monfort-Pires M, Delgado-Lista J, Gomez-Delgado F. Lopez-Miranda. Impact of the content of fatty acids of oral fat tolerance tests on postprandial triglyceridemia: Systematic review and meta-analysis. Nutrients 2016; 8pii:E580
[106]
Goldenberg I, Boyko V, Tennenbaum A, Tanne D, Behar S, Guetta V. Long-term benefit of high-density lipoprotein cholesterol-raising therapy with bezafibrate: 16-year mortality follow-up of the bezafibrate infarction prevention trial. Arch Intern Med 2009; 169: 508-14.
[107]
Nichols GA, Philip S, Reynolds K, Granowitz CB, Fazio S. increased cardiovascular risk in hypertriglyceridemic patients with statin-controlled LDL cholesterol. J Clin Endocrinol Metab 2018; 103: 3019-27.
[108]
Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019; 380: 11-22.
[109]
Borén J, Williams KJ. The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: A triumph of simplicity. Curr Opin Lipidol 2016; 27: 473-83.
[110]
Varbo A, Benn M, Nordestgaard BG. Remnant cholesterol as a cause of ischemic heart disease: Evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment. Pharmacol Ther 2014; 141: 358-67.
[111]
Rosenson RS, Davidson MH, Hirsh BJ, Kathiresan S, Gaudet D. Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease. J Am Coll Cardiol 2014; 64: 2525-40.
[112]
Murphy MC, Isherwood SG, Sethi S, et al. Postprandial lipid and hormone responses to meals of varying fat contents: Modulatory role of lipoprotein lipase? Eur J Clin Nutr 1995; 49: 578-88.
[113]
Gavra P, Melidonis A, Iraklianou S, et al. Alterations in plasma triglyceride concentrations following two oral meals with different fat content in patients with type 2 diabetes mellitus. Curr Vasc Pharmacol 2018; 16: 385-92.
[114]
Benítez-Santana T, Hugo SE, Schlegel A. Role of Intestinal LXRα in regulating postprandial lipid excursion and diet-induced hypercholesterolemia and hepatic lipid accumulation. Front Physiol 2017; 8: 280.
[115]
den Hartigh LJ, Altman R, Norman JE, Rutledge JC. Postprandial VLDL lipolysis products increase monocyte adhesion and lipid droplet formation via activation of ERK2 and NFκB. Am J Physiol Heart Circ Physiol 2014; 306: 109-20.
[116]
Ference BA, Ginsberg HN, Graham I, Isherwood SG, Sethi S. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic and clinical studies. A consensus statement from the European atherosclerosis society consensus panel. Eur Heart J 2017; 38: 2459-72.
[117]
Jorgensen AB, Frikke-Schmidt R, West AS, Grande P, Nordestgaard BG, Tybjærg-Hansen A. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J 2013; 34: 1826-33.
[118]
Jepsen AM, Langsted A, Varbo A, Bang LE, Kamstrup PR, Nordestgaard BG. Increased remnant cholesterol explains part of residual risk of all-cause mortality in 5414 patients with ischemic heart disease. Clin Chem 2016; 62: 593-604.
[119]
Varbo A, Freiberg JJ, Nordestgaard BG. Remnant cholesterol and myocardial infarction in normal weight, overweight, and obese individuals from the copenhagen general population study. Clin Chem 2018; 64: 219-30.
[120]
Varbo A, Freiberg JJ, Nordestgaard BG. Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors to cardiovascular disease and all-cause mortality in 90000 individuals from the general population. Clin Chem 2015; 61: 533-43.
[121]
Shen BW, Scanu AM, Kezdy FJ. Structure of human serum lipoproteins inferred from compositional analysis. Proc Natl Acad Sci USA 1977; 74: 837-41.
[122]
Mattes RD. Brief oral stimulation, but especially oral fat exposure, elevates serum triglycerides in humans. Am J Physiol Gastrointest Liver Physiol 2009; 296: 365-71.
[123]
Schneeman BO, Kotite L, Todd KM, Havel RJ. Relationships between the responses of triglyceride-rich lipoproteins in blood plasma containing apolipoproteins B-48 and B-100 to a fat-containing meal in normolipidemic humans. Proc Natl Acad Sci USA 1993; 90: 2069-73.
[124]
Cohn JS, Johnson EJ, Millar JS, et al. Contribution of apoB-48 and apoB-100 triglyceride-rich lipoproteins (TRL) to postprandial increases in the plasma concentration of TRL triglycerides and retinyl esters. J Lipid Res 1993; 34: 2033-40.
[125]
Adiels M, Taskinen MR, Packard C, et al. Overproduction of large VLDL particles is driven by increased liver fat content in man. Diabetologia 2006; 49: 755-65.
[126]
Timlin MT, Parks EJ. Temporal pattern of de novo lipogenesis in the postprandial state in healthy men. Am J Clin Nutr 2005; 81: 35-42.
[127]
Matikainen N, Adiels M, Söderlund S, et al. Hepatic lipogenesis and a marker of hepatic lipid oxidation, predict postprandial responses of triglyceride-rich lipoproteins. Obesity (Silver Spring) 2014; 22: 1854-9.
[128]
Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2012; 97: 2969-89.
[129]
Jacobson TA, Maki KC, Orringer CE, et al. National lipid association recommendations for patient-centered management of dyslipidemia: Part 2. J Clin Lipidol 2015; 9: 1-122.
[130]
Cohen JD, Cziraky MJ, Cai Q, et al. 30-year trends in serum lipids among United States adults: Results from the National Health and Nutrition Examination Surveys II, III, and 1999-2006. Am J Cardiol 2010; 106: 969-75.
[131]
White KT, Moorthy MV, Akinkuolie AO, et al. Identifying an optimal cutpoint for the diagnosis of hypertriglyceridemia in the nonfasting state. Clin Chem 2015; 61: 1156-63.
[132]
Langsted A, Freiberg JJ, Nordestgaard BG. Fasting and nonfasting lipid levels: Influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation 2008; 118: 2047-56.
[133]
Willer CJ, Schmidt EM, Sengupta S, et al. Discovery and refinement of loci associated with lipid levels. Nat Genet 2013; 45: 1274-83.
[134]
Weissglas-Volkov D, Aguilar-Salinas CA, Nikkola E, et al. Genome-wide association study in Mexicans identifies a new locus for triglycerides and refines European lipid loci. J Med Genet 2013; 50: 298-308.
[135]
Hegele R, Ginsberg HN, Chapman MJ, et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis and management. Lancet Diabetes Endocrinol 2014; 2: 655-66.
[136]
An P, Straka RJ, Pollin TI, et al. Genome-wide association studies identified novel loci for non-high-density lipoprotein cholesterol and its postprandial lipemic response. Hum Genet 2014; 133: 919-30.
[137]
Shia WC, Ku TH, Tsao YM, et al. Genetic copy number variants in myocardial infarction patients with hyperlipidemia. BMC Genomics 2011; 12: 23.
[138]
Aslam M, Aggarwal S, Sharma KK, Galav V, Madhu SV. Postprandial hypertriglyceridemia predicts development of insulin resistance glucose intolerance and type 2 diabetes. PLoS One 2016; 11e0145730
[139]
Pirillo A, Norata GD, Catapano AL. Postprandial lipemia as a cardiometabolic risk factor. Curr Med Res Opin 2014; 30: 1489-503.
[140]
Katsiki N, Kolovou G. Postprandial lipid profile in patients with type 2 diabetes. Curr Med Res Opin 2014; 30: 121.
[142]
Enkhmaa B, Ozturk Z, Anuurad E, Berglund L. Postprandial lipoproteins and cardiovascular disease risk in diabetes mellitus. Curr Diab Rep 2010; 10: 61-9.
[143]
Ng DS. Diabetic dyslipidemia: From evolving pathophysiological insight to emerging therapeutic targets. Can J Diabetes 2013; 37: 319-26.
[144]
Tushuizen ME, Pouwels PJ, Bontemps S, et al. Postprandial lipid and apolipoprotein responses following three consecutive meals associate with liver fat content in type 2 diabetes and the metabolic syndrome. Atherosclerosis 2010; 211: 308-14.
[145]
Valdivielso P, Puerta S, Rioja J, et al. Postprandial apolipoprotein B48 is associated with asymptomatic peripheral arterial disease: A study in patients with type 2 diabetes and controls. Clin Chim Acta 2010; 411: 433-7.
[146]
Tentolouris N, Stylianou A, Lourida E, et al. High postprandial triglyceridemia in patients with type 2 diabetes and microalbuminuria. J Lipid Res 2007; 48: 218-25.
[147]
Kolovou GD, Anagnostopoulou KK, Cokkinos DV. Pathophysiology of dyslipidaemia in the metabolic syndrome. Postgrad Med J 2005; 81: 358-66.
[148]
Kolovou GD, Anagnostopoulou KK, Salpea KD, Mikhailidis DP. The prevalence of metabolic syndrome in various populations. Am J Med Sci 2007; 333: 362-71.
[149]
Mikhailidis DP, Elisaf M, Rizzo M, et al. European panel on Low Density Lipoprotein (LDL) subclasses: A statement on the pathophysiology, atherogenicity and clinical significance of LDL subclasses: executive summary. Curr Vasc Pharmacol 2011; 9: 531-2.
[150]
Jackson KG, Poppitt SD, Minihane AM. Postprandial lipemia and cardiovascular disease risk: Interrelationships between dietary, physiological and genetic determinants. Atherosclerosis 2012; 220: 22-33.
[151]
Alcala-Diaz JF, Delgado-Lista J, Perez-Martinez P, et al. Hypertriglyceridemia influences the degree of postprandial lipemic response in patients with metabolic syndrome and coronary artery disease: From the CORDIOPREV study. PLoS One 2014; 9e96297
[152]
Grundy SM. Atherogenic dyslipidemia associated with metabolic syndrome and insulin resistance. Clin Cornerstone 2006; 8: 21-7.
[153]
Yubero-Serrano EM, Delgado-Lista J, Peña-Orihuela P, et al. Oxidative stress is associated with the number of components of metabolic syndrome: LIPGENE study. Exp Mol Med 2013; 45e28
[154]
Gambino R, Bugianesi E, Rosso C, et al. Different serum free fatty acid profiles in NAFLD subjects and healthy controls after oral fat load. Int J Mol Sci 2016; 17: 479.
[155]
Musso G, Gambino R, De Michieli F, et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003; 37: 909-16.
[156]
Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: Natural history of Non-Alcoholic Fatty Liver Disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 2011; 43: 617-49.
[157]
Katsiki N, Mikhailidis DP, Mantzoros CS. Non-alcoholic fatty liver disease and dyslipidemia: An update. Metabolism 2016; 65: 1109-23.
[158]
Simon TG, Corey KE, Chung RT, Giugliano R. Cardiovascular risk reduction in patients with nonalcoholic fatty liver disease: The potential role of ezetimibe. Dig Dis Sci 2016; 61: 3425-35.
[159]
Mager DR, Mazurak V, Rodriguez-Dimitrescu C, et al. A meal high in saturated fat evokes postprandial dyslipemia, hyperinsulinemia, and altered lipoprotein expression in obese children with and without nonalcoholic fatty liver disease. JPEN J Parenter Enteral Nutr 2013; 37: 517-28.
[160]
Lonardo A, Sookoian S, Pirola CJ, Targher G. Non-alcoholic fatty liver disease and risk of cardiovascular disease. Metabolism 2016; 65: 1136-50.
[161]
Athyros VG, Tziomalos K, Katsiki N, Doumas M, Karagiannis A, Mikhailidis DP. Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update. World J Gastroenterol 2015; 21: 6820-34.
[162]
Lauridsen KB, Stender S, Kristensen TS, et al. Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease: Mendelian randomization and meta-analysis of 279 013 individuals. Eur Heart J 2018; 39: 385-93.
[163]
Purcell R, Latham SH, Botham KM, Hall WL, Wheeler-Jones CP. High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2α concentrations relative to a control high-oleic acid meal: A randomized controlled trial. Am J Clin Nutr 2014; 100: 1019-28.
[164]
Slivkoff-Clark KM1,James AP, Mamo JC. The chronic effects of fish oil with exercise on postprandial lipaemia and chylomicron homeostasis in insulin resistant viscerally obese men. Nutr Metab (Lond) 2012; 9: 9.
[165]
Karupaiah T, Swee WC, Liew SY, Ng BK, Chinna K. Dietary health behaviors of women living in high rise dwellings: A case study of an urban community in Malaysia. J Community Health 2013; 38: 163-71.
[166]
Ooi TC, Nordestgaard BG. Methods to study postprandial lipemia. Curr Vasc Pharmacol 2011; 9: 302-8.
[167]
Freese EC, Gist NH, Cureton KJ. Effect of prior exercise on postprandial lipemia: An updated quantitative review. J Appl Physiol 2014; 116: 67-75.
[168]
Tsetsonis NV, Hardman AE, Mastana SS. Acute effects of exercise on postprandial lipemia: A comparative study in trained and untrained middle-aged women. Am J Clin Nutr 1997; 65: 525-33.
[169]
Kolovou GD, Salpea KD, Anagnostopoulou KK, Mikhailidis DP. Alcohol use, vascular disease, and lipid-lowering drugs. J Pharmacol Exp Ther 2006; 318: 1-7.
Call for Papers in Thematic Issues
07 May, 2024
Ischemic Cardiovascular Diseases: Mechanisms, Diagnosis and Therapy
Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
31 January, 2025
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...read more
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Current Drug Therapy
Related Books
Drug Addiction Mechanisms in the Brain
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Advanced Pharmacy
Plant-derived Hepatoprotective Drugs
The Role of Chromenes in Drug Discovery and Development
New Avenues in Drug Discovery and Bioactive Natural Products
Practice and Re-Emergence of Herbal Medicine
Blood Oxidant Ties: The Evolving Concepts in Myocardial Injury and Cardiovascular Disease
Article Metrics
111
8
1