Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.
Apolipoprotein C-III ; Cardiovascular Diseases ; Diacylglycerol O-Acyltransferase ; Fatty Acids, Omega-3 ; Fibric Acids ; Hyperlipoproteinemia Type I ; Life Style ; Lipase ; Lipoprotein Lipase ; Lipoproteins ; Metabolism ; Mortality ; PPAR alpha ; Risk Factors ; Triglycerides

Hypertriglyceridemia a major cause of acute pancreatitis, accounting for up to 10% of all cases. The pathophysiological mechanism of hypertriglyceridemia-induced acute pancreatitis (HTGP) is presumed to involve the hydrolysis of triglycerides by pancreatic lipase resulting in an excess of free fatty acids and elevated chylomicrons, which are thought to increase plasma viscosity and induce ischemia and inflammation in pancreatic tissue. Although the clinical course of HTGP is similar to other forms of acute pancreatitis, the clinical severity and associated complications are significantly higher in patients with HTGP. Therefore, an accurate diagnosis is essential for treatment and prevention of disease recurrence. At present, there are no approved guidelines for the management of HTGP. Different treatment modalities such as apheresis/plasmapheresis, insulin, heparin, fibric acids, and omega-3 fatty acids have been successfully implemented to reduce serum triglycerides. Following acute phase management, lifestyle modifications including dietary adjustments and drug therapy are important for the long-term management of HTGP and the prevention of relapse. Additional studies are required to produce generalized and efficient treatment guidelines for HTGP.
Chylomicrons ; Diagnosis ; Drug Therapy ; Fatty Acids, Nonesterified ; Fatty Acids, Omega-3 ; Fibric Acids ; Heparin ; Humans ; Hydrolysis ; Hypertriglyceridemia ; Inflammation ; Insulin ; Ischemia ; Life Style ; Lipase ; Pancreatitis* ; Plasma ; Recurrence ; Triglycerides ; Viscosity

BACKGROUND: Fibrates are widely used to treat hypertriglyceridemia, a risk factor for arteriosclerosis, but these compounds have been associated with renal dysfunction. This study aimed to investigate the effects of fibrates on renal function in relatively healthy adult subjects with no cardiovascular diseases. METHODS: This retrospective study included 558 outpatients who were prescribed 160 mg fenofibrate (fenofibrate group) or 10 mg atorvastatin (control group) between August 2007 and October 2015. The groups were randomly matched using propensity scores at a 1:1 ratio. Serum creatinine levels and estimated glomerular filtration rates before and after treatment were compared between the two groups. RESULTS: Patients in the fenofibrate group showed greater changes in serum creatinine levels than those in the control group (9.73%±9.83% versus −0.89%±7.37%, P<0.001). Furthermore, 55.1% of patients in the fenofibrate group, but only 6.1% of those in the control group, exhibited a serum creatinine level increase ≥0.1 mg/dL (P<0.001). The fenofibrate group showed significantly greater declines in the estimated glomerular filtration rate than the control group (−10.1%±9.48% versus 1.42%±9.42%, P<0.001). Moreover, 34.7% of the fenofibrate group, but only 4.1% of the control group, exhibited an estimated glomerular filtration rate decrease ≥10 mL/min·1.73 m² (P<0.001). CONCLUSION: Fenofibrate treatment resulted in increased serum creatinine levels and reduced estimated glomerular filtration rates in a primary care setting. Therefore, regular renal function monitoring should be considered essential during fibrate administration.
Adult ; Arteriosclerosis ; Atorvastatin Calcium ; Cardiovascular Diseases ; Creatinine ; Fenofibrate* ; Fibric Acids ; Glomerular Filtration Rate ; Humans ; Hypertriglyceridemia ; Outpatients ; Primary Health Care ; Propensity Score ; Retrospective Studies ; Risk Factors

Residual cardiovascular risk and failure of high density lipoprotein cholesterol raising treatment have refocused interest on targeting hypertriglyceridemia. Hypertriglyceridemia, triglyceride-rich lipoproteins, and remnant cholesterol have demonstrated to be important risk factors for cardiovascular disease; this has been demonstrated in experimental, genetic, and epidemiological studies. Fibrates can reduce cardiovascular event rates with or without statins. High dose omega-3 fatty acids continue to be evaluated and new specialized targeting treatment modulating triglyceride pathways, such as inhibition of apolipoprotein C-III and angiopoietin-like proteins, are being tested with regard to their effects on lipid profiles and cardiovascular outcomes. In this review, we will discuss the role of hypertriglyceridemia, triglyceride-rich lipoproteins and remnant cholesterol on cardiovascular disease, and the potential implications for treatment stargeting hypertriglyceridemia.
Apolipoprotein C-III ; Cardiovascular Diseases* ; Cholesterol ; Cholesterol, HDL ; Epidemiologic Studies ; Fatty Acids, Omega-3 ; Fibric Acids ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypertriglyceridemia* ; Lipoproteins ; Risk Factors ; Triglycerides

OBJECTIVE: Limited information is available on the effectiveness of lipid-modifying therapy (LMT) for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) in the Korean population. The objective of this study was to describe the prevalence of different types of lipid disorders in Korean patients using LMT. METHODS: Eight hundred seventy-one dyslipidemia patients, who were LMT-naive for >1 year prior to retrospective enrollment, were included for analysis. Serum levels of LDL-C, HDL-C, TG and total cholesterol (TC) were assessed after >1 year of LMT. We also analyzed the therapeutic effects of LMT in the subjects with high cardiovascular risk factors (n=629), atherosclerotic cardiovascular disease (ASCVD) (n=296) or diabetes without ASCVD (n=316). RESULTS: The rates of elevated LDL-C without other abnormal lipids levels, elevated TG or decreased HDL-C (with normal LDL-C levels) and high LDL-C combined with elevated TG and/or decreased HDL-C were 33.4%, 13.0% and 53.6%, respectively. After at least one year on LMT (statin alone: 81%, statin and cholesterol absorption inhibitor: 10%, fibrates alone: 3%, others: 3%), 61% of patients had at least one lipid abnormality, with 3.4% failing to reach the therapeutic LDL-C target level or a normal level of HDL-C and TG. After LMT, 64.9% of patients with high cardiovascular risk factors, 64.5% of those with ASCVD or and 64.2% of those with diabetes without ASCVD also had at least one lipid abnormality. CONCLUSION: Approximately two-thirds of patients did not reach the target or normal lipid profile after taking LMT, irrespective of combining disease and high cardiovascular risk factors. Tight lipid control is required, especially in patients with dyslipidemia and high cardiovascular risk factors or comorbid diseases.
Absorption ; Cardiovascular Diseases ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Dyslipidemias* ; Fibric Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Korea* ; Lipoproteins ; Observational Study* ; Prevalence* ; Primary Health Care ; Retrospective Studies ; Risk Factors ; Therapeutic Uses ; Triglycerides

Latest guidelines on lipid management recommend statins as the first-line therapy. Because limited evidence is available on cardiovascular outcomes with varying statin-nonstatin combinations, recommendation levels for these regimens have been weak. However, a recent trial has demonstrated the additive effect of the statin-ezetimibe combination. The statin-fibrate combination has shown an effect in certain subgroups and on diabetic microangiopathy. Recent trials using the statin-niacin combination have been largely negative, whereas the statin-omega-3 fatty acids combination demonstrated a positive effect only in one study. Identifying the benefits and limitations of each combination is important for the best possible management of patients.
Diabetic Angiopathies ; Drug Therapy* ; Ezetimibe ; Fatty Acids ; Fibric Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Niacin

Although statins have demonstrated consistent and strong effects on cardiovascular prevention, non-statin drugs have failed to show additional clinical benefit. Consequently, statins are currently recommended as first-line therapy in dyslipidemia. On the contrary, non-statin drugs are indicated in limited cases in which statins are not sufficiently effective or intolerable. A recent trial on ezetimibe provides evidence supporting further prescription of this agent. Proprotein convertase subtilisin-kexin type 9 inhibitors have strong low-density lipoprotein-cholesterol-lowering effects and were just approved in Western countries. However, results of clinical outcomes are not yet available. Other non-statin lipid-modifying agents have their own roles and limitations. Thus, it is important to have correct knowledge on these agents for optimal treatment of dyslipidemic patients.
Cholesterol Ester Transfer Proteins ; Dyslipidemias* ; Fatty Acids, Omega-3 ; Fibric Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Niacin ; Prescriptions ; Proprotein Convertases ; Ezetimibe

Fenofibrate is one of PPAR-alpha (peroxisome proliferator activated receptor alpha) agonists. Fenofibrate decreases effectively triglyceride and increases high density lipoprotein cholesterol level through the effect on lipoprotein lipase, hepatic production and degradation of lipoproteins. Fenofibrate was recommended as the drug for hypertriglyceridemia treatment in European guideline released in 2011. But American heart association guideline in 2013 did not recommend non-statin therapy including fibrate for the prevention of atherosclerotic cardiovascular disease. But fenofibrate is still considered as the important drug for the management of atherogenic dyslipidemia especially in patients with metabolic syndrome and diabetes to reduce the residual risk after statin therapy from the evidence of many studies. Fibrates including bezafibrate, gemfibrozil, and fenofibrate increased serum creatinine level in several studies. But the mechanism of change in renal function is not clear till now. And the reversibility of renal function with drug discontinuation is dependent on the kinds of fibrate. Fenofibrate increased serum creatinine level, decreased albuminuria and renal function was reversible with the drug discontinuation in large clinical trials. In these days renal function change with fenofibrate therapy in Korean patients with hypertriglyceridemia was investigated. Fenofibrate treatment for 2 months increased serum creatinine level significantly and old age was associated with the change of renal function in multivariate analysis. Short-term therapy significantly increased serum creatinine level even within normal range, and this change may be important in some groups especially old age.
Albuminuria ; American Heart Association ; Bezafibrate ; Cardiovascular Diseases ; Cholesterol, HDL ; Creatinine ; Dyslipidemias ; Fenofibrate* ; Fibric Acids ; Gemfibrozil ; Glomerular Filtration Rate ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypertriglyceridemia ; Lipoprotein Lipase ; Lipoproteins ; Multivariate Analysis ; Reference Values ; Triglycerides

Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-alpha (PPAR-alpha) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication. This review will re-examine the metabolic role of PPAR-alpha, summarize data from clinical studies on the effect of PPAR-alpha agonist in diabetes, and will discuss the possible therapeutic role of PPAR-alpha activation.
Cardiovascular Diseases ; Diabetes Complications ; Fibric Acids ; Homeostasis ; Inflammation ; PPAR alpha*

Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-alpha (PPAR-alpha) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication. This review will re-examine the metabolic role of PPAR-alpha, summarize data from clinical studies on the effect of PPAR-alpha agonist in diabetes, and will discuss the possible therapeutic role of PPAR-alpha activation.
Cardiovascular Diseases ; Diabetes Complications ; Fibric Acids ; Homeostasis ; Inflammation ; PPAR alpha*