No abstract available.
Dyslipidemias ; Fibric Acids ; Niacin

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*

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

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

Cardiovascular disease (CVD) is the leading cause of death worldwide and small dense low-density lipoprotein (sdLDL) has been suggested to be a potential risk factor for cardiovascular disease (CVD). We reviewed published studies on formation and measurement of sdLDL, as well as relationship between LDL subfractions and CVD. sdLDL particle formation is highly dependent on triglycerides (TG) levels, and the physicochemical properties of sdLDL particles provide a potential for increased atherogenicity. Various conditions (e.g. hypertriglyceridemia, diabetes mellitus, metabolic syndrome, chronic renal failure and HIV infections) with increased cardiometabolic risk are associated with increased sdLDLs. Most studies suggest that sdLDL particles are associated with increased prevalence of clinical and subclinical CVDs, as well as non-coronary forms of atherosclerosis. Moreover, LDL size seems to be an important determinant of the progression of CVD. Therapeutic modulation (mostly fibrates, but also some statins, as well as niacin and thiazolidinediones) of small LDL size, number and distribution may decrease CVD risk. However, no definitive causal relationship is yet established, probably due to the close association between sdLDL and triglycerides and other risk factors.
Atherosclerosis ; Cardiovascular Diseases ; Cause of Death ; Diabetes Mellitus ; Fibric Acids ; HIV ; Hypertriglyceridemia ; Kidney Failure, Chronic ; Lipoproteins ; Niacin ; Prevalence ; Risk Factors ; Triglycerides

The present study demonstrates the effect of fibrates, agonists of PPARalpha on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-1beta (10 ng/ml), IFNgamma (10 ng/ml), and TNF-alpha (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and 10 micrometer) reduced the IFNgamma and IL-1beta-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the IFNgamma and IL-1beta-induced cell proliferation, released IL-6 level was measured. IFNgamma and IL-1beta cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the IFNgamma and IL-1beta-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in IFNgamma and IL-1beta-stimulated astrocytes. Taken together, these results clearly suggest that activation of PPARalpha attenuates the IFNgamma and IL-1beta-induced cell proliferation through IL-6 independent pathway.
Astrocytes ; Bezafibrate ; Cell Proliferation ; Cytokines ; Fenofibrate ; Fibric Acids ; Interleukin-6 ; PPAR alpha ; RNA, Messenger ; Tumor Necrosis Factor-alpha

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

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

BACKGROUND/AIMS: Statins have been a mainstay of treatment for primary and secondary prevention of coronary heart disease through their beneficial effect on lipid profile. However, their effect on the HDL cholesterol level has been determined to be equivocal or unclear. This study sought to investigate HDL cholesterol response to statin treatment in type 2 diabetic patients. METHODS: We retrospectively assessed the effect of statins in 217 patients with type 2 diabetes and dyslipidemia through chart review. Patients who were using medications such as fibrates, niacin, or thiazolidinediones, or had a plasma creatinine concentration greater than 1.5 mg/dL, a fasting triglyceride level greater than 300 mg/dL, or chronic liver disease, were excluded from the study. RESULT: The mean level of LDL cholesterol was significantly decreased, and the percentage of patients who achieved the normal LDL cholesterol level was increased in this study. The mean HDL cholesterol level after statin treatment was decreased by 2.3%. The percent change of HDL cholesterol was affected by baseline HDL cholesterol level, percent change of total cholesterol, percent change of LDL cholesterol, and baseline total cholesterol level. When subjects were divided into quintiles according to baseline HDL cholesterol, HDL cholesterol level was found to be increased in the lowest two quintiles while it was decreased in the highest two quintiles. CONCLUSIONS: There were some patients whose HDL cholesterol level was decreased after statin treatment, depending on their baseline HDL cholesterol level. We think further study on the effect of statins on HDL level will be needed in the future.
Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Coronary Disease ; Creatinine ; Dyslipidemias ; Fasting ; Fibric Acids ; Humans ; Liver Diseases ; Niacin ; Plasma ; Retrospective Studies ; Secondary Prevention ; Thiazolidinediones