Moderate Hypertriglyceridemia Research Articles

A rare presentation of type 2 diabetes: diabetic ketoacidosis, acute pancreatitis, and hypertriglyceridaemia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Clinical features and genetic analysis of three patients with severe hypertriglyceridaemia

Hypertriglyceridaemia is a common biochemical abnormality that can be due to primary causes or, more commonly, secondary causes. Moderate hypertriglyceridaemia is a risk factor for cardiovascular disease and can develop into severe hypertriglyceridaemia which is a risk factor for acute pancreatitis. Familial chylomicronaemia is a rare autosomal recessive disorder, usually diagnosed in childhood and is characterized by marked hypertriglyceridaemia and biochemical deficiency of lipoprotein lipase (LPL), apolipoprotein (apo) C-II, homozygous (or compound heterozygous) gene mutations in LPL or more rarely, APOC2. Recently, loss-of-function mutations in the APOA5 gene have been reported in patients with severe hypertriglyceridaemia in whom LPL or APOC2 mutations were not found. We describe the clinical features and genetic analysis of three patients with severe hypertriglyceridaemia including novel mutations LPL c.464T>C (p.Leu155Pro) and APOA5 c.823C>T (p.Gln275*).

Relationship between Lipoprotein(a) and Thyroid Hormones in Hypothyroid Patients

Changes in plasma lipid concentrations are well known metabolic consequences of thyroid dysfunction. The alterations are most prominent in hypothyroidism which is typically associated with pronounced hypercholesterolaemia and frequently with moderate hypertriglyceridaemia. In cases of hypothyroidism, how the serum Lp(a) levels are influenced by thyroid hormone remains unknown and contradictory results on the effect of thyroid hormone on serum Lp(a) levels have been reported. There is substantial evidence to suggest that elevated serum Lp(a) levels contribute significantly to the development of CHD. The present study was designed to determine the lipoprotein(a) [Lp(a)], lipid profile and thyroid hormone levels in newly diagnosed hypothyroid patients and to find any correlation that existed between Lp(a) and other parameters. Untreated hypothyroid (n=50) patients were included in the study. We also included 40 normal healthy subjects as controls. Lipid profile, Lp(a) and thyroid profile were estimated by using autoanalyzers. The results of this study showed that levels of HDL-cholesterol were significantly decreased (p<0.001), whereas those of other lipid parameters and Lp(a) levels were found to be significantly increased (p<0.001) in hypothyroid patients as compared to those in controls. Correlation study revealed a significant positive correlation between Lp(a) and TSH levels in hypothyroid patients. Our present findings indicated that hypothyroidism could be strongly associated with lipid abnormalities that enhanced the development of cardiovascular diseases. Also, Lp(a) and non-HDL-C should be estimated with other lipid parameters as a useful index for measuring the cardiac risk in hypothyroid patients. A recommended screening should be advised for any patient with thyroid dysfunction, especially hypothyroidism, to assess lipid abnormalities by using Lp(a) and non- HDL-C and he/she should treated at the earliest.

An APOA5 3′ UTR Variant Associated with Plasma Triglycerides Triggers APOA5 Downregulation by Creating a Functional miR-485-5p Binding Site

APOA5 c.*158C>T (rs2266788), located in the 3' UTR, belongs to APOA5 haplotype 2 (APOA5*2), which is strongly associated with plasma triglyceride levels and modulates the occurrence of both moderate and severe hypertriglyceridemia. Individuals with APOA5*2 display reduced APOA5 expression at the posttranscriptional level. However, the functionality of this haplotype remains unclear. We hypothesized that the hypertriglyceridemic effects of APOA5*2 could involve miRNA regulation in the APOA5 3' UTR. Bioinformatic studies have identified the creation of a potential miRNA binding site for liver-expressed miR-485-5p (MIRN485-5p) in the mutant APOA5 3' UTR with the c.*158C allele. In human embryonic kidney 293T (HEK293T) cells cotransfected with an APOA5 3' UTR luciferase reporter vector and a miR485-5p precursor, c.*158C allele expression was significantly decreased. Moreover, in HuH-7 cells endogenously expressing miR-485-5p, we observed that luciferase activity was significantly lower in the presence of the c.*158C allele than in the presence of the c.*158T allele, which was completely reversed by a miR-485-5p inhibitor. We demonstrated that the rare c.*158C APOA5 allele creates a functional target site for liver-expressed miR-485-5p. Therefore, we propose that the well-documented hypertriglyceridemic effect of APOA5*2 involves an APOA5 posttranscriptional downregulation mediated by miR-485-5p.

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Introduction: Hypertriglyceridemia-induced pancreatitis (HTGP) is associated with a higher severity of illness and more complications than acute pancreatitis (AP) without hypertriglyceridemia (HTG). Diabetic ketoacidosis (DKA) may be a risk factor for AP, but it is uncertain if AP triggers DKA or vice-versa. We describe a patient with DKA and AP managed with continuous IV insulin and apheresis. A 30 year-old male with type 1 diabetes, familial HTG, and AP presented with a 10 day history of worsening epigastric pain. Laboratory and imaging studies were consistent with HTGP and DKA. He was started on IV insulin and intubated for respiratory distress. On day 2 ketosis resolved, but he was continued on IV insulin for HTGP. Renal replacement therapy was started for acute kidney injury. Due to severity of illness and lack of adequate response to insulin, apheresis was initiated. After 2 sessions, TG decreased from 3362 mg/dl to 192 mg/dl. On day 9 he was transitioned from IV to subcutaneous insulin and TG remained <500 mg/dl. The remainder of his hospitalization was complicated by severe hemorrhagic pancreatitis, candidemia, and pneumonia. On day 11 he was extubated and on day 17 he left the ICU. On day 38 he was discharged on insulin detemir and omega-3 fish oil. The relationship between AP, DKA, and HTG is complicated, making identification of the primary cause difficult. AP can exacerbate DKA and moderate HTG in DKA is common. Optimal management of these patients is unknown since there are no large trials or consensus statements to guide treatment. Common strategies include apheresis and insulin. As seen in our patient, use of apheresis results in immediate reduction in TG levels, but large well-conducted trials are necessary to support this practice. Use of IV insulin to control DKA and HTGP appears safe and effective. However, once ketosis resolves and blood glucose normalizes, the insulin infusion may be inappropriately stopped while TG are still critically elevated. Thus, communication of clear goals of therapy is paramount. Although the most appropriate length of time to provide IV insulin is uncertain, it is reasonable to continue therapy until TG <1000 mg/dl.

Correction of omega-3 nutritional deficiency in cardiovascular disease patients through treatment with a unique omega-3 formulation: effects on risk factors in a double blind, placebo-controlled study

Purpose: Severe Omega-3 (OM3) nutritional deficiency has been previously correlated to an increased of sudden death and based upon plasma OM3 levels, risk quartiles have been defined. However, studies that monitor the correction of OM3 deficiency (measured as Omega-Score, OS) with treatment with an OM3 formulation, and improvement of Cardiovascular Disease (CVD) factors have not been systematically evaluated. The purpose of this study was to determine the extent of OM3 deficiency in the general and CVD populace and to investigate how treatment with a unique OM3 formulation comprised of >90% pure OM3, with a 6:1 EPA: DHA ratio (eicosapentaenoic acid: docosapentaenoic acid, 6:1-OM3) corrects this deficiency, and improves CVD factors. Methods: The primary endpoints of this randomized, double blind, placebo-controlled trial were the change in the OS (plasma EPA + DHA + docosapentaenoic acid) with secondary endpoints including the change in serum TG, lipoprotein cholesterol (VLDL, LDL, HDL, ApoB, and subfractions), and hsCRP. 655 subjects were screened, and 110 subjects that met all study criteria (including OS <6.1%) were randomized and stratified by baseline TG levels (Cohort 1: 90-199 mg/dL, and Cohort 2: 200-500mg/dL). Treatment included placebo (4g/day corn oil, n=54) and 6:1-OM3 (4g/day; n=56) for an 8-week study period. Results: 89% of screened (n=655) CVD subjects were found to be nutritionally deficient in OM3 (OS <6.1%). The median baseline OS was 3.64% for Cohort 1, and 3.15% for Cohort 2. After 8 weeks of treatment, a significant (p<0.0001) increase was observed for both Cohorts, resulting in an OS increase of 134% for Cohort 1 and 120% for Cohort 2. In normal and mildly hypertriglyceridemic subjects (90-199 mg TG/dL), no significant changes in lipid profiles were observed. However in moderately hypertriglyceridemic subjects (200-500 mg TG/dL), a placebo-corrected TG reduction of 48% (p=0.0005), VLDL-C reduction of 30% (p=0.0023) and HDL-C increase of 9% (p=0.0069) without significantly affecting LDL-C, ApoB or hsCRP levels was observed. Conclusions: This study confirms that OM3 deficiency is highly prevalent in patients with CVD. In patients with moderate hypertriglyceridemia, treatment with 6:1-OM3 corrects the deficiency and results in a concomitant and significant placebo-corrected reduction in TG and VLDL, and increase in HDL-C without adversely affecting LDL-C.

Effects of Omega-3 Fatty Acid Supplementation on Heart Rate Variability at Rest and During Acute Stress in Adults With Moderate Hypertriglyceridemia

This study examined the dose-dependent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on heart rate variability (HRV) at rest and during standard laboratory stress tasks. We also investigated whether EPA + DHA supplementation was associated with changes in mood state. This placebo-controlled, double-blind, randomized, three-period crossover trial (8-week treatment, 6-week washout) compared two doses of EPA + DHA supplementation (0.85 and 3.4 g/d) in 26 adults with elevated triglycerides. After each treatment period, HRV was assessed during an acute stress protocol that included a resting baseline, standard laboratory stress tasks (speech task and cold pressor), and recovery periods. In addition, mood state was assessed. Root mean square of successive differences in interbeat interval and total power increased 9.9% and 20.6%, respectively, after the high dose relative to placebo (Tukey p = .016 and .012, respectively). The low dose was not significantly different from the high dose or placebo dose. There was a trend for a treatment effect on high-frequency HRV (p = .058), with 21.0% greater power observed after the high dose compared with placebo (Tukey p = .052). Mood did not differ between treatments, and there was no association between mood state and HRV. In healthy adults with elevated triglycerides, supplementation of 3.4 g/d EPA + DHA resulted in greater HRV, whereas 0.85 g/d EPA + DHA had no effect. These results indicate that EPA + DHA supplementation may improve autonomic tone in adults at increased risk for cardiovascular disease within 8 weeks. NCT00504309 (ClinicalTrials.gov).

Hypertriglyceridemia

Hypertriglyceridemia (HTG) is commonly encountered in lipid and cardiology clinics. Severe HTG warrants treatment because of the associated increased risk of acute pancreatitis. However, the need to treat, and the correct treatment approach for patients with mild to moderate HTG are issues for ongoing evaluation. In the past, it was felt that triglyceride does not directly contribute to development of atherosclerotic plaques. However, this view is evolving, especially for triglyceride-related fractions and variables measured in the non-fasting state. Our understanding of the etiology, genetics and classification of HTG states is also evolving. Previously, HTG was considered to be a dominant disorder associated with variation within a single gene. The old nomenclature includes the term “familial” in the names of several hyperlipoproteinemia (HLP) phenotypes that included HTG as part of their profile, including combined hyperlipidemia (HLP type 2B), dysbetalipoproteinemia (HLP type 3), simple HTG (HLP type 4) and mixed hyperlipidemia (HLP type 5). This old thinking has given way to the idea that genetic susceptibility to HTG results from cumulative effects of multiple genetic variants acting in concert. HTG most is often a “polygenic” or “multigenic” trait. However, a few rare autosomal recessive forms of severe HTG have been defined. Treatment depends on the overall clinical context, including severity of HTG, concomitant presence of other lipid disturbances, and the patient's global risk of cardiovascular disease. Therapeutic strategies include dietary counselling, lifestyle management, control of secondary factors, use of omega-3 preparations and selective use of pharmaceutical agents.

Association Between Lipids, Lipoproteins Composition of HDL Particles and Triglyceride-Rich Lipoproteins, and LCAT and CETP Activity in Post-renal Transplant Patients

High-density lipoprotein (HDL) remodeling within the plasma compartment and the association between lecithin-cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) activity, and lipid, lipoprotein concentrations and composition were investigated. The aim was to examine the high sensitivity of C-reactive protein (hsCRP), lipid, apolipoprotein B (apoB), apoAI, total apoAII, apoAIInonB, apoB-containing apoAII (apoB:AII), total apoCIII, apoCIIInonB, apoB-containing apoCIII (apoB:CIII) concentration and LCAT and CETP activity to gain an insight into the association between them and LCAT and CETP, 57 post-renal transplant (Tx) patients with and without statin therapy and in 15 healthy subjects. Tx patients had moderate hypertriglyceridemia, hypercholesterolemia, and dyslipoproteinemia, disturbed triglyceride-rich lipoproteins (TRLs) and HDL composition, decreased LCAT, and slightly increased hsCRP but no CETP activity. Spearman’s correlation test showed the association between lipids and lipoproteins and LCAT or CETP, and multiple ridge stepwise forward regression showed that immunosuppressive therapy in Tx patients can disturb HDL and TRLs composition. The results suggest that inhibition or activation of LCAT is due, in part, to HDL-associated lipoprotein. Lipoprotein composition of apoAI, apoAIInonB, and apoCIIInonB in HDL particle and apoB:AII TRLs can contribute to decrease LCAT mass in Tx patients. Tx patients without statin and with lower triglycerides but higher HDL cholesterol concentration and disturbed lipoprotein composition of ApoAI and apoAII in HDL particle can decrease LCAT, increase LDL cholesterol, aggravate renal graft, and accelerate atherosclerosis and chronic heart diseases.

Drug Treatment of Asymptomatic Hypertriglyceridemia to Prevent Pancreatitis: Where Is the Evidence?

Drug treatment of asymptomatic hypertriglyceridemia has long been controversial. In the absence of evidence that drug treatment of moderate hypertriglyceridemia reduces vascular events, guidelines ...

Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline

The aim was to develop clinical practice guidelines on hypertriglyceridemia. The Task Force included a chair selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), five additional experts in the field, and a methodologist. The authors received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence, e-mail discussion, conference calls, and one in-person meeting. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. The Task Force recommends that the diagnosis of hypertriglyceridemia be based on fasting levels, that mild and moderate hypertriglyceridemia (triglycerides of 150-999 mg/dl) be diagnosed to aid in the evaluation of cardiovascular risk, and that severe and very severe hypertriglyceridemia (triglycerides of > 1000 mg/dl) be considered a risk for pancreatitis. The Task Force also recommends that patients with hypertriglyceridemia be evaluated for secondary causes of hyperlipidemia and that subjects with primary hypertriglyceridemia be evaluated for family history of dyslipidemia and cardiovascular disease. The Task Force recommends that the treatment goal in patients with moderate hypertriglyceridemia be a non-high-density lipoprotein cholesterol level in agreement with National Cholesterol Education Program Adult Treatment Panel guidelines. The initial treatment should be lifestyle therapy; a combination of diet modification and drug therapy may also be considered. In patients with severe or very severe hypertriglyceridemia, a fibrate should be used as a first-line agent.

Phenotypes of hypertriglyceridemia caused by excess very-low-density lipoprotein

To characterize the composition of very-low-density lipoprotein (VLDL) particles and the proportion of VLDL to total apolipoprotein B (apoB) particles in patients with hypertriglyceridemia caused by excess VLDL. Subjects were selected from 2023 consecutive patients attending the Lipid Clinic at the Laval University Centre. Plasma lipids, apoB, and apoA-I were measured and chylomicron lipids and VLDL and LDL lipids and apoB determined after ultracentrifugation. Patients with hypertriglyceridemia caused by excess VLDL were divided into four groups on the basis of triglyceride and apoB. A total of 440 controls, 387 subjects with normotriglyceridemic hyperapoB, 38 with type III dysbetalipoproteinemia, 270 with mild hypertriglyceridemic normoapoB, 163 with moderate hypertriglyceridemic normoapoB, 458 with mild hypertriglyceridemic hyperapoB, and 295 subjects with moderate hypertriglyceridemic hyperapoB were compared. In patients with hypertriglyceridemia caused by excess VLDL, the VLDL particles were triglyceride and cholesterol-enriched. HyperapoB is associated with greater low-density lipoprotein (LDL) apoB than normoapoB, whereas greater triglycerides are associated with greater VLDL apoB. Thus, the ratio of VLDL apoB/total apoB was significantly less in those with mild hypertriglyceridemia compared with those with moderate hypertriglyceridemia, irrespective of the plasma apoB. The apoB phenotypes in hypertriglyceridemia caused by excess VLDL appear to be determined by the extent to which VLDL secretion increases, the extent to which VLDL particles can be converted to LDL particles, and the effects of core lipid exchange. More accurate characterization of hypertriglyceridemia caused by excess VLDL should lead to a better understanding of the determinants of VLDL clearance and conversion to LDL as well as of the atherogenic potential of VLDL.

Hyperlipidaemia and cardiovascular disease

Fibrates continue to be a viable treatment option for mixed atherogenic dyslipidemia, and recent reports from clinical studies have shed new light on the therapeutic utility of fibrates for the prevention of microvascular and macrovascular disease, especially in combination with statins. Data from randomized placebo-controlled trials have shown that fibrates reduce nonfatal coronary events but do not confer any benefit on mortality or other adverse cardiovascular outcomes. The ACCORD Lipid trial studied the additive effect of fenofibrate therapy along with low-dose simvastatin therapy in 5,518 patients with type 2 diabetes mellitus, and found that fenofibrate did not affect any of the adverse cardiovascular outcomes, either individually or as part of a composite outcome, after 4.7 years of follow-up. An a priori subgroup analysis showed a significant benefit from fenofibrate-simvastatin combination therapy over simvastatin alone in participants with moderate hypertriglyceridemia and low HDL-cholesterol on major cardiovascular events, consistent with post-hoc analyses of previous fibrate trials. The ACCORD-Eye study adds to the sparse clinical data on the effect of fenofibrate on diabetic retinopathy, and showed that fenofibrate may be used to reduce the risk of progression of diabetic retinopathy even in patients with established disease. The combination of statin and fibrate was well tolerated. Fibrate therapy does not reduce mortality but may reduce nonfatal coronary events in patients at risk for cardiovascular disease, including those with type 2 diabetes. The ACCORD Lipid study shows that the combination of low-dose simvastatin and fenofibrate is well tolerated, and is potentially cardioprotective in patients with atherogenic 'mixed' dyslipidemia.

Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients

Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I (apoA-I) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-β-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.

Impact of Mild hypertriglyceridemia on fibrinolysis, Lp(a), and platelet activation indexes in mildly hypercholesterolemic patients

The relationship between high triglyceride values and alterations of the fibrinolytic system in cardiovascular heart disease (CHD) patients is well known. The aim of the study was to evaluate the effect of moderate hypertriglyceridemia on fibrinolysis, lipoprotein(a) [(Lp(a)], and platelet activation indexes in asymptomatic patients. To this end, 46 nondiabetic, dyslipidemic patients (age 51±8 years), with no associated pathologies and 23 normolipidemic, homogeneus patients (in terms of age, sex, and smoke habits) were studied. The dyslipidemic patients were split up into two groups: 23 type IIb hyperlipoproteinemia patients (Group I), and 23 type IIa hyperlipoproteinemia patients (Group 2). The control group had total cholesterol values of <5.18 mmol/L and triglyceride concentrations of <2.25 mmol/L. The result showed a significant difference (p<0.05) in the baseline plasminogen tissue activator inhibitor (PAI-1 b) values for the Group 1 patients as compared with the Group 2 and the controls, in the baseline tissue plasminogen activator (t-PA b) values for the Group 1 patients as compared with the Group 2 patients and in the lipoprotein (a) (Lp(a)) (p<0.01) values for the Group 2 as compared with the controls. On the other hand, no statistically significant difference was observed in β-thromboglobulin (β-TG), platelet factor 4 (PF4). This study shows that mild hypertriglyceridemia in asymptomatic hypercholesterolemic patients is associated with a different regulation of the fibrinolytic mechanism. In patients with moderate hypercholesterolemia, higher blood concentrations of Lp(a) were found than in the controls.

Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to reduce cardiovascular mortality at a dose of ≈1 g/d. Studies using higher doses have shown evidence of reduced inflammation and improved endothelial function. Few studies have compared these doses. The objective of this study was to compare the effects of a nutritional dose of EPA+DHA (0.85 g/d) with those of a pharmaceutical dose (3.4 g/d) on serum triglycerides, inflammatory markers, and endothelial function in healthy subjects with moderately elevated triglycerides. This was a placebo-controlled, double-blind, randomized, 3-period crossover trial (8 wk of treatment, 6 wk of washout) that compared the effects of 0.85 and 3.4 g EPA+DHA/d in 23 men and 3 postmenopausal women with moderate hypertriglyceridemia (150-500 mg/dL). The higher dose of EPA+DHA lowered triglycerides by 27% compared with placebo (mean ± SEM: 173 ± 17.5 compared with 237 ± 17.5 mg/dL; P = 0.002), whereas no effect of the lower dose was observed on lipids. No effects on cholesterol (total, LDL, and HDL), endothelial function [as assessed by flow-mediated dilation, peripheral arterial tonometry/EndoPAT (Itamar Medical Ltd, Caesarea, Israel), or Doppler measures of hyperemia], inflammatory markers (interleukin-1β, interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein), or the expression of inflammatory cytokine genes in isolated lymphocytes were observed. The higher dose (3.4 g/d) of EPA+DHA significantly lowered triglycerides, but neither dose improved endothelial function or inflammatory status over 8 wk in healthy adults with moderate hypertriglyceridemia. The trial was registered at clinicaltrials.gov as NCT00504309.

Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia

Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia

Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia

Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia

Comparison of the efficacy of fibrates on hypertriglyceridemic phenotypes with different genetic and clinical characteristics

Hypertriglyceridemia is a frequent and heterogeneous clinical trait, which modulates the risk of disease. Fibrates constitute an effective class of triglyceride-lowering agents. To evaluate the effect of fibrates on fasting plasma triglycerides and other lipids levels in hypertriglyceridemia phenotypes with different genetic and clinical characteristics. This study included 146 fasting adults: 15 with lactescent plasma and severe hypertriglyceridemia (triglyceride ≥ 10 mmol/l) and 131 with clear plasma and moderate hypertriglyceridemia (2 ≤ triglycerides <10 mmol/l). Expost comparisons of the effect of fibrates on fasting triglycerides and other lipids were made using Student's paired two-tailed t-test. Response to these fibrates differed significantly across the studied hypertriglyceridemia subtypes: patients with severe hypertriglyceridemia because of lipoprotein lipase deficiency and those with moderate hypertriglyceridemia because of glycerol kinase deficiency did not respond at all, whereas patients with palmar xanthomas and severe or moderate hypertriglyceridemia because of apolipoprotein (apo) E resistance (type-III dysbetalipoproteinemia, most often associated with the apo E2 allele) responded significantly better (P<0.001) than all other subtypes on several lipid fractions. These results indicate that genetic factors known to contribute to the etiology and clinical expression of hypertriglyceridemia subtypes also modulate the response to triglyceride-lowering drugs.

Fibrates: no ACCORD on their use in the treatment of dyslipidaemia

New data have emerged over the last few years about the role of fibrates in treatment of microvascular and macrovascular disease. Endpoint studies have been conducted with fibrates in coronary heart disease since 1971 and results have been contradictory. Fibrates have shown benefits in patients with low HDL-cholesterol and low LDL-cholesterol. Fibrates remain topical, given their actions on the lipid triad present in the metabolic syndrome and in diabetes. In the Fenofibrate Intervention in Endpoint Lowering in Diabetes study of mixed primary and secondary prevention cohorts, fenofibrate therapy resulted in an 11% reduction in coronary or cardiovascular events in monotherapy. Despite frequent use, there was little endpoint data on fibrate-statin combination therapy until recently. The Action to Control Cardiovascular Risk in Diabetes trial of fenofibrate added to baseline simvastatin therapy in diabetes showed a nonsignificant 8% reduction in cardiovascular events. The benefits were concentrated in men, and women did slightly worse with fibrate therapy. In post-hoc analysis, slight beneficial effects of fenofibrate were seen in patients with moderate hypertriglyceridaemia (>2.3 mmol/l) and low HDL-cholesterol (<0.88 mmol/l). The safety profile of fibrate-simvastatin combination was good. Fenofibrate and bezafibrate are reasonable second-line therapies for dyslipidaemia and in diabetes. They are safe in combination therapy with statins but add little endpoint benefit except possibly in patients with a significant degree of atherogenic dyslipidaemia (high triglycerides and low HDL-cholesterol). The benefits of fibrates on microvascular disease remain to be fully explored.