|Year : 2018 | Volume
| Issue : 2 | Page : 40-44
Research progress of hypertriglyceridemia and coronary heart disease
Yanyue Ji, Chunlin Bai
Department of Cardiology, Second Hospital of Shanxi Medical University, Taiyuan, China
|Date of Web Publication||22-Aug-2019|
Dr. Chunlin Bai
Department of Cardiology, Second Hospital of Shanxi Medical University, Taiyuan
Source of Support: None, Conflict of Interest: None
At present, the relationship between hypertriglyceridemia (HTG) and coronary heart disease (CHD) is still uncertain. In recent years, many researchers have tried to clarify the relationship between HTG, atherosclerosis, and CHD. This article will review the relationship between HTG and CHD from the aspects of epidemiology, pathogenesis, and cardiovascular benefits of HTG treatment to further understand the relationship between the two. Dyslipidemia is closely related to the occurrence and development of the atherosclerotic cardiovascular disease. Elevated low-density lipoprotein cholesterol (LDL-C) has been recognized as an independent risk factor for cardiovascular events. Statins can effectively reduce LDL-C and reduce the incidence of cardiovascular events. HTG is the most common dyslipidemia in China, and the correlation between HTG and CHD deserves attention. Therefore, as for the progress of HTG and CHD in recent years, we will make a review on the relationship between HTC and CHD, the mechanism of atherosclerosis and the cardiovascular benefits of treatment, so as to further clarify the role and significance of triglyceride in the process of atherosclerosis and provide new ideas for the prevention an d treatment of CHD.
Keywords: Atherosclerosis, coronary heart disease, triglyceride
|How to cite this article:|
Ji Y, Bai C. Research progress of hypertriglyceridemia and coronary heart disease. Heart Mind 2018;2:40-4
| Epidemiological Study on Hypertriglyceridemia and Coronary Heart Disease|| |
Coronary heart disease (CHD) is a serious threat to human health. Although the death rate of CHD is decreasing after strong intervention measures and effective secondary prevention of risk factors, CHD is still the most common cause of death in the world, ranking the first cause of death.
Hypertension, diabetes, hypercholesterolemia, and smoking have been identified as independent risk factors of CHD, and hypertriglyceridemia (HTG) has been controversial for a long time. However, some prospective studies published in recent years support that HTG is an independent risk factor for CHD. A meta-analysis involving 26 studies in the Asia-Pacific region (a total of 96,244 people) found that the level of serum triglyceride (TG) is an important independent predictor of CHD. A meta-analysis of 29 prospective studies in the western population shows that TG is moderately or highly correlated with CHD. Another meta-analysis involving 61 prospective studies further confirmed that high TG levels were associated with all-cause death of cardiovascular diseases. JDCS study found that TG is a risk factor of CHD equivalent to low-density lipoprotein cholesterol (LDL-C) as for Japanese patients with type 2 diabetes. For every 1 mmol/L increase in TG and LDL-C levels, the risk of CHD increases by 63% and 64%, respectively. BIP study, which analysis death date of 15,355 patients with CHD, found that the level of TG was independently related to all-cause mortality of patients with CHD. A large sample cohort study with a follow-up of 15 years in many provinces and cities in China found that high TG was a predictor of CHD in low LDL-C population. The 23-year follow-up results of Daqing study showed that the study evaluated the cardiovascular disease risk of 833 subjects, 34% of whom were HTG (baseline plasma TG level ≥1.7 mmol/L), and the cardiovascular disease risk in high TG group was 27% higher than that in nonhigh TG group. If the basic level of TG increases by 1 mmol/L, the first cardiovascular disease risk increases by 8% in the following 20 years.
Some studies further show that since there is a closer relationship between postprandial TG level and plasma lipoprotein remnant concentration, postprandial TG level is more effective than fasting TG in predicting the risk of CHD in the general population. At the same time, Copenhagen Heart Institute randomly selected 13,981 subjects from 1976 to 1978 for follow-up until the end of 2004. The results showed that after being corrected by other risk factors such as hypertension, diabetes, body mass index, the increase of nonfasting TG level can predict the risks of myocardial infarction, ischemic heart disease, and death., It can be seen that observational prospective cohort studies, randomized controlled studies, and meta-analysis have confirmed that elevated TG is closely related to increased risk of cardiovascular diseases and is an independent risk factor for cardiovascular diseases.
In addition, many studies have shown that, even after statins control LDL-C, patients with high TG still have higher cardiovascular risks. In ACCORD study, the incidence of major cardiovascular events in patients with TG ≥2.3 mmol/L and high-density lipoprotein cholesterol (HDL-C) ≤0.9 mmol/L was 71% higher than that in other patients. PROVE IT-TIMI 22 study shows that as for acute coronary syndrome (ACS) patients who have been treated with statin and whose level of LDL-C <1.8 mmol/l, the risk of major cardiovascular events in HTG patients is 27% higher than that in patients with TG <2.3 mmol/L. A meta-analysis of data from 15,817 patients in the dal-OUTCOMES study and 1501 ACS patients in the MARICL study treatment group shows that fasting TG level is closely related to short-term and long-term risks of ACS patients: for every 0.113 mmol/L (10 mg/dl) increase in TG, the risk of long-term cardiovascular events increases by 1.8%, and the risk of short-term cardiovascular events in ACS increases by 1.4%. After-the-fact analysis of IDEAL and TNT studies shows that TG levels are associated with the risk of recurrence of cardiovascular events such as myocardial infarction in patients with stable CHD who have already used moderate or large doses of statin.
Analysis of data from two prospective randomized trials, namely, PERFORM and SPARCL, shows that among stroke or transient ischemic attack patients receiving the best drug treatment including statin, the residual risk of cardiovascular events in patients with HTG and low HDL-C is increased.
| Hypertriglyceridemia and Atherosclerosis|| |
At present, the mechanism of atherosclerosis caused by HTG is not clear, but according to many domestic and foreign studies, it may be related to the following aspects.
Promoting the formation of foam cells
External experiments have proved that very LDL (VLDL) and macrophages can aggregate intracellular TG and cholesterol ester (CE) and promote foam cell generation. VLDL can be oxidized into oxidized VLDL by vascular endothelial cells and smooth muscle cells. By damaging vascular endothelium, recruiting monocytes, promoting foam cell generation, promoting smooth muscle cell proliferation and migration, VLDL has the effect of atherosclerosis. In addition, due to the large size of chylomicrons (CM) and VLDL particles, it was thought that CM and VLDL could not penetrate through the arterial endothelium and enter the arterial wall, but after catabolism, CM and VLDL could generate remnant lipoprotein (RLP), which could not only penetrate through the arterial endothelium but also remain in the tissue matrix of the vascular subendothelial layer. Studies using rabbits and mice atherosclerosis experimental models have found that high-level CM and VLDL residues penetrate into the intima of blood vessels, remain in the tissue matrix of the vascular subendothelial layer, and form foam cells after being ingested by macrophages, thus promoting the occurrence and development of atherosclerosis. Zhang et al. knocked out lipoprotein lipase (LPL) in mice, and found that plasma TG of mice was significantly increased, and atherosclerosis plaque rich in foam cells appeared in the aortic root, suggesting that elevated TG can promote the occurrence and development of atherosclerosis.
Promoting lipid exchange
In the study of lipoprotein metabolism, it was found that the content of CM and VLDL in plasma of patients with high TG increased, which promoted the activity of cholesteryl ester transfer protein in plasma to increase. TG in CM and VLDL is exchanged with CE in HDL and LDL. The results of the lipid exchange were as follows: small dense low-density lipoprotein (SLDL) concentration increased, HDL and HDL-C levels decreased. HDL particles and HDL-C play a key role in maintaining endothelial vascular reactivity, resisting oxidative stress, inhibiting endothelial cell apoptosis, promoting repair of damaged endothelium, inhibiting monocyte activation, and reducing the expression of adhesion factors and cytokines, while the above effects can slow down the formation of atherosclerotic plaques. Moreover, the higher the TG level in plasma, the more active lipid exchange will be. The SLDL produced is an LDL with strong atherosclerosis effect. Experimental studies have clarified some mechanisms of SLDL-induced atherosclerosis: SLDL particles are small and easy to enter the arterial intima and SLDL is easy to combine with proteoglycan and remain in the arterial wall. SLDL has low affinity for LDL receptor. Therefore, SLDL clearance is slow, and the residence time in plasma is long. SLDL is highly sensitive to oxidation and is easily absorbed by scavenger receptors of macrophages after oxidation, thus promoting the formation of foam cells. These properties make SLDL have strong AS-inducing effect.
Promoting vascular endothelial dysfunction
VLDL and CM have direct cytotoxic effect on vascular endothelial cells, which can cause endothelial cell permeability to increase and deposit in the arterial wall through the endothelial barrier. Chen et al. found that increasing the negative charge of VLDL can induce up-regulation of reactive oxygen species expression in endothelial cells and promote endothelial cell apoptosis in patients with metabolic syndrome, suggesting that VLDL rich in negative charge has damaging effect on vascular endothelium. VLDL isolated from HTG patients' blood can increase the transcription and expression of plasminogen activator inhibitor-1 (PAI-1) cultured in vitro, suggesting that VLDL can reduce vascular endothelial fibrinolytic activity and increase the risk of AS formation. Other studies have shown that triglyceride rich lipoproteins residues can increase the expression of vascular endothelial adhesion molecules, reduce arterial vasodilation function, and cause vascular endothelial dysfunction. TRL residues can also inhibit telomerase activity, enhance vascular endothelial oxidative stress reaction, accelerate endothelial progenitor cell aging, and affect the repair function of endothelial progenitor cells on the vascular injury., Therefore, TRL and its residues can accelerate the formation of AS by promoting vascular endothelial injury, inhibiting endothelial repair, inhibiting endothelial relaxation, and inducing endothelial dysfunction.
Promoting inflammatory response
Many studies have shown that atherosclerosis caused by HTG may be related to inflammatory reaction. Some studies have observed that RLP can accelerate the aging of endothelial progenitor cells and affect their functions, and these cells play an important role in the repair of vascular wall injury. Postprandial TRL has been proved to increase the expression of inflammatory factors (such as interleukin [IL]-6, intercellular adhesion factor, and vascular cell adhesion factor 1) genes, induce cell apoptosis, and also enhance the inflammatory response of endothelial cells cultured in vitro α (tumor necrosis factor-α [TNF-α]). Research results support that the role of fatty acid binding proteins derived from adipocytes and macrophages in the body's inflammatory response can be enhanced by the high TG load generated by RLP decomposition. Macrophages were incubated with VLDL, and the expressions of various inflammatory factors such as α (TNF-α) and IL-1 β in macrophages were significantly up-regulated. TRL particles were separated from human postprandial serum and incubated with human aortic endothelial cells. Under the stimulation of low dose TNF-α, the expressions of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin on the cell membrane surface were up-regulated. Studies further show that CM residues can directly activate monocytes and increase monocyte migration by decreasing MCP-1 expression.
Promoting coagulation and inhibit fibrinolysis
Many studies have found that patients with high TG have various coagulation defects, such as enhanced platelet aggregation, increased factor VII, increased factor X activity, and excessive PAI-I release which promote coagulation under the participation of various tissue factors. The appearance of this procoagulant state will accelerate the development of atherosclerosis and increase the severity of myocardial infarction. TRL residue contains free fatty acid, which generates a large amount of negative charge. FVII is activated by endogenous coagulation pathway and activated FXII. The increase of activated FVII molecules triggers exogenous coagulation system. The concentration of VII molecules increases. Coagulation is easily generated under the action of excessive tissue factors, which is an independent risk factor for CHD onset. In vitro tests found that VLDL can induce vascular endothelial cells and hepatocytes to secrete PAI-1 to increase. Plasma PAI-1 level in patients with hyperthermia is significantly increased. Studies found that PAI-1 gene expression in human AS artery intima is increased. PAI-1 gene expression in smooth muscle cells is too high in developing atherosclerotic plaques. Excessive production of PAI-1 may inhibit local plasmin synthesis and promote intra-arterial fibrin deposition. Therefore, increased PAI-1 activity can lead to myocardial infarction.
| Cardiovascular Benefits After Hypertriglyceridemia Treatment|| |
Lifestyle improvement is the cornerstone for the treatment of HTG. For the treatment of HTG, artificial lifestyle intervention is more cost-effective and safer than drug therapy.
Fibrates regulate the expression of target genes LPL, apolipoprotein AI, and apolipoprotein AII by exciting peroxisome proliferator-activated receptor α, thus playing a role in lowering plasma TG level and increasing HDL-C level, transforming small and dense LDL particles into large and loose LDL particles, and promoting reverse transportation of cholesterol. In FIELD and ACCORD studies, fenofibrate can significantly reduce cardiovascular events in HTG patients with low HDL-C.,, In the FIELD study, subgroup analysis of HTG patients with low HDL-C showed that the risk of cardiovascular events in the fenofibrate group decreased by 27% compared with the placebo group. In the preset subgroup analysis of HTG patients with low HDL-C, compared with the placebo group, the risk of cardiovascular death, myocardial infarction or stroke in the fenofibrate group was reduced by 31% (P < 0.05). Multiple meta-analyses have shown that fenofibrate reduces the risk of cardiovascular events in patients with hypertriglyceridemia.,,,,,,,,,,,,, At the same time, many evidence-based medical evidences show that fibrate drugs can reduce coronary artery events or cardiovascular events.,,, Fibrate drugs can significantly reduce coronary artery events or cardiovascular events in diabetic patients. Three large-sample prospective clinical trials of fibrate drugs to reduce cardiovascular events, including Helsinki Heart Study, Benzene Zabyti Prevention of Infarct Study and US Veterans Administration HDL-C Intervention Test, have all shown that cardiovascular events are reduced and the curative effect of diabetic patients is better than that of nondiabetic patients.,,
Therefore, fibrates can improve blood lipid level and reduce the risk of cardiovascular events.
n-3 fatty acid
The main active components of n-3 fatty acid are eicosapentaenoic acid and docosahexenoic acid extracted from fish oil, which can reduce TG by 30%–40% when used alone or in combination with fibrates or statins. In the GISSI-P study, 11,324 patients after myocardial infarction received n-3 fatty acid or placebo randomly on the basis of statins. The results showed that n-3 fatty acid can reduce the mortality rate of cardiovascular diseases of patients after myocardial infarction: the overall mortality rate decreased by 20%, and the cardiovascular mortality rate decreased by 45%. Meta-analysis shows that increasing n-3 fatty acid in food and reducing saturated fatty acid can reduce the risk of CHD. Taking n-3 fatty acid or increasing the content of n-3 fatty acid in food can reduce the mortality of patients with CHD such as all-cause mortality, myocardial infarction, and death due to CHD. The adverse reactions of this drug are less, and the most common is slight dyspepsia.
Nicotinic acid and its derivatives
Nicotinic acid drugs belong to B vitamins, which can reduce TG level and increase HDL-C. AIM-HIGH study shows that on the basis of maintaining LDL-C at <1.8 mmol/L through intensive statin therapy, adding sustained-release nicotinic acid to increase HDL-C level cannot further reduce the risk of cardiovascular events in patients with stable CHD. Arterial physiology research results of cholesterol-lowering therapy suggest that in patients with known CHD or CHD and other dangerous diseases and treated with statins, the addition of sustained-release nicotinic acid therapy can delay or even partially reverse AS. Meta-analysis shows that nicotinic acid treatment can reduce cardiovascular events by about 25% and delay the progression of coronary AS by about 41%. HP2-THRIVE study also shows that the combination of nicotinic acid and statin drugs does not reduce the incidence of major cardiovascular events and increases the risk of serious adverse events compared with statin drugs alone. As a result, nicotinic acid has faded out of European and American markets.
To sum up, although the relationship between HTG and CHD is still inconclusive, it is proved that HTG is closely related to the occurrence and development of CHD from both epidemiological and pathophysiological perspectives. However, fibrates can reduce cardiovascular events in HTG patients treated with statins. Therefore, we should fully improve the understanding of HTG in cardiovascular diseases, which is helpful to control the risk factors of CHD, reduce the incidence of CHD, and improve the prognosis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Patel A, Barzi F, Jamrozik K, Lam TH, Ueshima H, Whitlock G, et al.
Serum triglycerides as a risk factor for cardiovascular diseases in the Asia-Pacific region. Circulation 2004;110:2678-86.
Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, 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.
Liu J, Zeng FF, Liu ZM, Zhang CX, Ling WH, Chen YM, et al.
Effects of blood triglycerides on cardiovascular and all-cause mortality: A systematic review and meta-analysis of 61 prospective studies. Lipids Health Dis 2013;12:159.
Sone H, Tanaka S, Tanaka S, Iimuro S, Oida K, Yamasaki Y, et al.
Serum level of triglycerides is a potent risk factor comparable to LDL cholesterol for coronary heart disease in Japanese patients with type 2 diabetes: Subanalysis of the Japan diabetes complications study (JDCS). J Clin Endocrinol Metab 2011;96:3448-56.
Klempfner R, Erez A, Sagit BZ, Goldenberg I, Fisman E, Kopel E, 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.
Liu J, Wang W, Wang M, Sun J, Liu J, Li Y, et al.
Impact of diabetes, high triglycerides and low HDL cholesterol on risk for ischemic cardiovascular disease varies by LDL cholesterol level: A 15-year follow-up of the Chinese multi-provincial cohort study. Diabetes Res Clin Pract 2012;96:217-24.
Jinping W, Xiaoxia S, Siyao H, Yali A, Qiuhong G, Hui L, et al
. Hypertriglyceridemia predicts cardiovascular events in China adults: 23-tear follow-up of Daqing diabetes and IGT study (DQDIS). Diabetes 2016;65 Suppl 1:A367.
Nakajima K, Nakano T, Moon HD, Nagamine T, Stanhope KL, Havel PJ, et al.
The correlation between TG vs. remnant lipoproteins in the fasting and postprandial plasma of 23 volunteers. Clin Chim Acta 2009;404:124-7.
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.
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.
Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E, et al.
Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 2008;51:724-30.
Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration, Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di Angelantonio E, et al.
Triglyceride-mediated pathways and coronary disease: Collaborative analysis of 101 studies. Lancet 2010;375:1634-9.
ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd
, Leiter LA, et al.
Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010;362:1563-74.
Schwartz GG, Abt M, Bao W, DeMicco D, Kallend D, Miller M, et al.
Fasting triglycerides predict recurrent ischemic events in patients with acute coronary syndrome treated with statins. J Am Coll Cardiol 2015;65:2267-75.
Faergeman O, Holme I, Fayyad R, Bhatia S, Grundy SM, Kastelein JJ, 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.
Sirimarco G, Labreuche J, Bruckert E, Goldstein LB, Fox KM, Rothwell PM, et al.
Atherogenic dyslipidemia and residual cardiovascular risk in statin-treated patients. Stroke 2014;45:1429-36.
Bojic LA, Sawyez CG, Telford DE, Edwards JY, Hegele RA, Huff MW, et al.
Activation of peroxisome proliferator-activated receptor δ inhibits human macrophage foam cell formation and the inflammatory response induced by very low-density lipoprotein. Arterioscler Thromb Vasc Biol 2012;32:2919-28.
Vine DF, Takechi R, Russell JC, Proctor SD. Impaired postprandial apolipoprotein-B48 metabolism in the obese, insulin-resistant JCR: LA-cp rat: Increased atherogenicity for the metabolic syndrome. Atherosclerosis 2007;190:282-90.
Weinstein MM, Yin L, Tu Y, Wang X, Wu X, Castellani LW, et al.
Chylomicronemia elicits atherosclerosis in mice – brief report. Arterioscler Thromb Vasc Biol 2010;30:20-3.
Zhang X, Qi R, Xian X, Yang F, Blackstein M, Deng X, et al.
Spontaneous atherosclerosis in aged lipoprotein lipase-deficient mice with severe hypertriglyceridemia on a normal chow diet. Circ Res 2008;102:250-6.
Rosenson RS, Brewer HB Jr., Chapman MJ, Fazio S, Hussain MM, Kontush A, et al.
HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clin Chem 2011;57:392-410.
Rosenson RS. Hypertriglyceridemia and coronaryheart disease risk. Cardiol Rev 1999;7:342-8.
Chen CH, Lu J, Chen SH, Huang RY, Yilmaz HR, Dong J, et al.
Effects of electronegative VLDL on endothelium damage in metabolic syndrome. Diabetes Care 2012;35:648-53.
Zhao R, Ma X, Shen GX. Transcriptional regulation of plasminogen activator inhibitor-1 in vascular endothelial cells induced by oxidized very low density lipoproteins. Mol Cell Biochem 2008;317:197-204.
Kawakami A, Osaka M, Tani M, Azuma H, Sacks FM, Shimokado K, et al.
Apolipoprotein CIII links hyperlipidemia with vascular endothelial cell dysfunction. Circulation 2008;118:731-42.
Liu L, Wen T, Zheng XY, Yang DG, Zhao SP, Xu DY, et al.
Remnant-like particles accelerate endothelial progenitor cells senescence and induce cellular dysfunction via an oxidative mechanism. Atherosclerosis 2009;202:405-14.
Yang DG, Liu L, Zhou SH, Ma MF, Wen T. Remnant-like lipoproteins may accelerate endothelial progenitor cells senescence through inhibiting telomerase activity via the reactive oxygen species-dependent pathway. Can J Cardiol 2011;27:628-34.
Furuhashi M, Fucho R, Görgün CZ, Tuncman G, Cao H, Hotamisligil GS. Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J Clin Invest 2008;118:2640-50.
Jinno Y, Nakakuki M, Kawano H, Notsu T, Mizuguchi K, Imada K. Eicosapentaenoic acid administration attenuates the pro-inflammatory properties of VLDL by decreasing its susceptibility to lipoprotein lipase in macrophages. Atherosclerosis 2011;219:566-72.
Wang YI, Schulze J, Raymond N, Tomita T, Tam K, Simon SI, et al.
Endothelial inflammation correlates with subject triglycerides and waist size after a high-fat meal. Am J Physiol Heart Circ Physiol 2011;300:H784-91.
Bentley C, Hathaway N, Widdows J, Bejta F, De Pascale C, Avella M, et al.
Influence of chylomicron remnants on human monocyte activation in vitro
. Nutr Metab Cardiovasc Dis 2011;21:871-8.
Grundy SM, Vega GL. Two different views of the relationship of hypertriglyceridemia to corenary artery disease: Implications for treatment. Arch Intern Med 1992;152:28.
Onat A, Sansoy V, Yildirim B. Which fasting triglyceride levels best reflect coronary risk? Evidence from the Turkish adult risk factor study. Clin Cardiol 2001;24:9-14.
Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, et al.
An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart 2001;85:544-8.
Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al.
2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2016;37:2999-3058.
Superko HR, Berneis KK, Williams PT, Rizzo M, Wood PD. Gemfibrozil reduces small low-density lipoprotein more in normolipemic subjects classified as low-density lipoprotein pattern B compared with pattern A. Am J Cardiol 2005;96:1266-72.
Barter PJ. Antiatherogenic properties of fibrates. Arterioscler Thromb Vasc Biol 2005;25:1095-6.
Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, 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 2005;366:1849-61.
Scott R, O'Brien R, Fulcher G, Pardy C, D'Emden M, Tse D, 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.
Sacks FM, Carey VJ, Fruchart JC. Combination lipid therapy in type 2 diabetes. N Engl J Med 2010;363:692-4.
Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet 2014;384:626-35.
Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ, et al.
Effects of fibrates on cardiovascular outcomes: A systematic review and meta-analysis. Lancet 2010;375:1875-84.
Maki KC, Guyton JR, Orringer CE, Hamilton-Craig I, Alexander DD, Davidson MH, et al.
Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia. J Clin Lipidol 2016;10:905-14.
Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Mänttäri M, Heinonen OP, et al.
Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki heart study. Implications for treatment. Circulation 1992;85:37-45.
Tenenbaum A, Motro M, Fisman EZ, Tanne D, Boyko V, Behar S. Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 2005;165:1154-60.
Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, 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 1999;341:410-8.
Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, et al.
Helsinki heart study: Primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987;317:1237-45.
Bezafibrate Infarction Prevention (BIP) study. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Circulation 2000;102:21-7.
Dietary supplementation with n-3 polyunsaturated fatty acids and Vitamin E after myocardial infarction: Results of the GISSI-prevenzione trial. Gruppo Italiano per lo Studio Della Sopravvivenza Nell'infarto Miocardico. Lancet 1999;354:447-55.
Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: A systematic review and meta-analysis of randomized controlled trials. Evid Based Med 2010;15:108-9.
AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, et al.
Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011;365:2255-67.
Karsdal MA, Henriksen K, Genovese F, Leeming DJ, Nielsen MJ, Riis BJ, et al.
Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes. Diabetologia 2017;60:50-9.
Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin 2006;22:2243-50.
Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis 2010;210:353-61.
HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, et al.
Effects of extended-release niacin with laropiprant in high-risk patients. N
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