High-density Lipoprotein Cholesterol In Patients Research Articles

Targeted Proteomics Identifies Paraoxonase/Arylesterase 1 (PON1) and Apolipoprotein Cs as Potential Risk Factors for Hypoalphalipoproteinemia in Diabetic Subjects Treated with Fenofibrate and Rosiglitazone

Low levels of high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels contribute to the excess rate of cardiovascular events seen in subjects with type 2 diabetes. Fenofibrate treatment partially reverses dyslipidemia in these subjects. However, a paradoxical marked reduction in HDL-C and HDL's major protein, apolipoprotein A-I, is a complication of fenofibrate in combination with rosiglitazone, an insulin-sensitizing agent. Risk factors for this condition, termed hypoalphalipoproteinemia, have yet to be identified. Using a case-control study design with subjects enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we tested the hypothesis that alterations in HDL's protein cargo predispose diabetic subjects to fenofibrate/rosiglitazone-induced hypoalphalipoproteinemia. HDL was isolated from blood obtained from controls (no decreases or increase in HDL-C while receiving fenofibrate/rosiglitazone therapy) and cases (developed hypoalphalipoproteinemia after fenofibrate/rosiglitazone treatment) participating in the ACCORD study before they began fenofibrate/rosiglitazone treatment. HDL proteins were quantified by targeted parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) with isotope dilution. This approach demonstrated marked increases in the relative concentrations of paraoxonase/arylesterase 1 (PON1), apolipoprotein C-II (APOC2), apolipoprotein C-I, and apolipoprotein H in the HDL of subjects who developed hypoalphalipoproteinemia. The case and control subjects did not differ significantly in baseline HDL-C levels or other traditional lipid risk factors. We used orthogonal biochemical techniques to confirm increased levels of PON1 and APOC2. Our observations suggest that an imbalance in HDL proteins predisposes diabetic subjects to develop hypoalphalipoproteinemia on fenofibrate/rosiglitazone therapy.

Association between CETP gene polymorphism, insulin resistance and risk of diabetes mellitus in patients with vascular disease

IntroductionGenetic inhibition of Cholesteryl Ester Transfer Protein (CETP) might be associated with insulin resistance and incident type 2 diabetes mellitus (T2DM). This study investigated the relation between a genetic variant in the CETP gene and measures of insulin resistance and incident T2DM in patients with manifest cardiovascular disease (CVD). Furthermore the effect on risk of recurrent cardiovascular events was investigated. MethodsSMART is a prospective cohort study performed in 5601 patients with clinically manifest CVD. We selected a variant (rs3764261) associated with reduced CETP activity and increased levels of HDL cholesterol (HDL-C). Patients were divided in three groups: 2640 wild type patients (GG), 2420 heterozygotes for rs3764261 (GT) and 541 homozygotes for rs3764261 (TT). Regression analyses were performed using an additive model. ResultsThe study population consisted of 4656 patients without T2DM and 945 patients with T2DM at baseline. Presence of rs3764261 was associated with increased HDL-C in patients without T2DM (β 0.106, 95%CI 0.083–0.128) and with T2DM (β 0.043, 95%CI 0.007–0.078). During a median follow up of 7.2 years (IQR 4.7–10.2) 427 incident T2DM occurred. Presence of rs3764261 was not related to incident T2DM (HR 0.96, 95%CI 0.83–1.11) in patients without T2DM at baseline. Furthermore, presence of rs3764261 was not related to insulin resistance (glucose, insulin, HOMA-IR, HbA1c) or recurrent CVD (HR 0.92, 95%CI 0.84–1.02). ConclusionPresence of CETP SNP rs3764261 is not associated with insulin resistance and incident T2DM in patients with clinically manifest vascular disease. Furthermore, no effect of rs3764261 on the risk of recurrent CVD was observed.

Elevated Interleukin-10 and “Disappearing HDL Syndrome” in Lymphoproliferative Disorders

BACKGROUND: Acquired severe HDL deficiency is relatively uncommon. It may occur with use of high doses of anabolic steroids or in severe liver diseases, which can lead to low LCAT activity and decreased apoA-I production. “Disappearing HDL Syndrome”*, a term first used by Goldberg and Mendez, refers to cases of severe HDL deficiency in patients that are not critically ill, sometimes long before the clinical or biochemical features of the underlying primary disease become evident. Disappearing HDL Syndrome can also result from an idiosyncratic reaction to medications, such as peroxisome proliferation-activated receptor (PPAR) agonists. Additionally, autoantibodies against LCAT in non-Hodgkin lymphoma have been described as a possible cause. Low high-density lipoprotein-cholesterol (HDL-C) is a risk factor for coronary artery disease.OBJECTIVE: To determine the cause of low HDL-C in patients with severe acquired HDL deficiency noted as an incidental finding associated with lymphoma and autoimmune lymphoproliferative syndrome (ALPS)** as well as following recombinant human IL10 therapy in psoriatric arthritis patients. Investigating mechanisms underlying acquired severe HDL deficiency in non-critically ill patients (“Disappearing HDL Syndrome”) could provide new insights into HDL metabolism and its role in lymphomagenesis.PATIENTS AND RESULTS: Patients with intravascular large B-cell lymphoma (IVLBCL, n=2), diffuse large B-cell lymphoma (DLBCL, n=1), and ALPS-FAS (n=1) presenting with markedly decreased HDL-C, low LDL-C and elevated triglycerides were identified. The abnormal lipoprotein profile returned to normal following therapy in all four cases (Figure). All of them were found to have markedly elevated serum interleukin-10 (IL-10) levels at presentation that also normalized following therapy. Besides accumulation of abnormal lymphocytes in lymph nodes and spleen, ALPS patients have elevated serum IL-10. In a cohort of ALPS patients with genetic mutations in FAS (n=93), IL-10 showed a strong inverse correlation with HDL-C (R2=0á3720, P<0á0001). A direct causal role for increased serum IL-10 in inducing the observed changes in lipoproteins was established in a randomized, placebo-controlled clinical trial of recombinant human IL-10 (rhIL-10) in psoriatic arthritis patients (n=18). Within a week of initiating subcutaneous rhIL-10 injections, HDL-C precipitously decreased to near-undetectable levels. LDL-C also decreased by over 50% (P<0.0001) and triglycerides increased by approximately 2-fold (P<0.005). All values returned to baseline after stopping IL-10 therapy.CONCLUSION: Increased IL-10 causes severe HDL-C deficiency, low LDL-C and elevated triglycerides. IL-10 is thus a potent modulator of lipoprotein levels, a potential new biomarker for B-cell disorders, and a novel cause of Disappearing HDL Syndrome. Elevated IL-10 plays a key role in linking inflammation and lipoprotein metabolism. As evidence for its causality, rhIL-10 treatment in a clinical trial of psoriasitic arthritis patients precipitously lowered HDL-C. Finding elevated IL-10 as a cause of “Disappearing HDL Syndrome” in patients with 3 different types of B-cell disorders suggests that IL-10 and low HDL-C could be useful biomarkers of disease activity in these conditions. Finally, future research focusing on strategies to alter lipoprotein levels by modulating circulating IL-10 levels or its signaling pathways may be useful for developing novel targeted therapies.*Ref: Severe acquired (secondary) high-density lipoprotein deficiency. Goldberg RB, Mendez AJ. J Clin Lipidol. 2007;1:41-56**Ref: Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Price S, Shaw PA, Seitz A et al. Blood. 2014 Mar 27;123(13):1989-99. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Serum amylase levels are decreased in Chinese non-alcoholic fatty liver disease patients.

BackgroundLow serum amylase levels have been reported in patients with metabolic syndrome (MS), diabetes, and asymptomatic non-alcoholic fatty liver disease (NAFLD). However, no study has yet indicated the serum amylase levels in NAFLD with MS. The aim of the present study was to evaluate serum amylase levels in NAFLD patients with and without MS, and to explore a possible association between serum amylase levels with the components of MS and the degree of hepatic fibrosis in NAFLD patients.MethodsOur study included 713 NAFLD participants (180 females and 533 males) and 304 healthy control participants (110 females and 194 males). The diagnosis of NAFLD was based on ultrasonography, and advanced fibrosis was assessed by the FIB-4 index.ResultsSerum amylase levels were significantly lower in NAFLD patients with MS compared with NAFLD patients without MS and healthy controls (42, 45, and 53 IU/L, respectively). The serum amylase levels of patients with elevated glucose, elevated triglycerides, and low high density lipoprotein cholesterol patients were significantly lower than in case of normal parameters (both p < 0.05). Multivariate logistic regression analysis showed that a relative serum amylase level increase was an independent factor predicting advanced fibrosis (FIB-4 ≥1.3) in NAFLD participants (OR: 1.840, 95% CI: 1.117-3.030, p=0.017).ConclusionsCompared with NAFLD patients without MS and healthy controls, serum amylase levels were significantly lower in NAFLD patients with MS. Moreover, a relative serum amylase increase may be an independent factor of more advanced hepatic fibrosis.

Changes in high-density-lipoprotein cholesterol upon statin treatment in type 2 diabetic patients: A meta-analysis

Background and aimTo investigate the diversity of change in high-density-lipoprote in cholesterol (HDL-C) after statin treatment in patients with type 2 diabetes mellitus (T2DM). Methods and resultsA systemic review searched for trials that reported a serum change in HDL-C in patients with T2DM after statin treatment, and extracted data for meta-analysis. Of 6709 articles surveyed, 160 articles were identified as eligible articles. In the analysis of simvastatin, serum HDL-C was increased in Non-Asian and Asian patients with T2DM by 2.17 mg/dl (95% CI 1.43 ∼ 2.90 mg/dl, p < 0.001) and 2.31 mg/dl (95% CI 1.37 ∼ 3.25 mg/dl, p < 0.001), respectively. In the analysis of atorvastatin, although significant, serum HDL-C was subtly increased in Non-Asian patients with T2DM by 1.14 mg/dl (95% CI 0.28 ∼ 2.01 mg/dl, p = 0.010) mg/dl; however, atorvastatin treatment did not significantly change the serum HDL-C by 0.12 mg/dl (95% CI −1.04 ∼ 1.27 mg/dl, p = 0.839) mg/dl in Asian patients with T2DM. According to meta-regression analysis, the baseline HDL-C did not affect the change in serum HDL-C in Asian patients with T2DM after either simvastatin or atorvastatin treatment. However, contrary to simvastatin, the coefficient of regression (r) showed a significant negative association (r = −0.18; 95% CI −0.32 to −0.04; p = 0.01) between baseline HDL-C and the change of HDL-C in non-Asian patients with T2DM after atorvastatin treatment. ConclusionWe have demonstrated for the first time that there may be a discrepancy in the change of serum HDL-C in Asian patients with T2DM after atorvastatin treatment.

Correlation between tongue manifestations and glucose, total cholesterol, and high-density lipoprotein cholesterol in patients with acute cerebral infarction

ObjectiveTo analyze the association between tongue manifestations and the levels of glucose (GLU), total cholesterol (TCH), and high-density lipoprotein cholesterol (HDL-C) in subjects with acute cerebral infarction. MethodsHospitalized patients with first unilateral cerebral infarction in the Neurological Department of Xuanwu Hospital were included and the correlation between tongue fur color, fur nature, and the levels of GLU, TCH, HDL-C were analyzed. ResultsHDL level in the thin fur group was higher than that in the thick fur group (P=0.02). The difference in the levels of GLU, TCH, and HDL-C among the groups was significant (P<0.05), classified in terms of slippery, moist, and dry fur. Further comparison between the groups by Student-Newman-Keuls test showed that GLU level in the dry fur group was the highest. Moreover, the TCH level in the slippery fur group was higher than the other two groups. ConclusionA correlation between tongue manifestations and GLU, TCH, HDL-C was identified in the patients with acute cerebral infarction.

Plasma Antimicrobial Peptide LL-37 Level Is Inversely Associated with HDL Cholesterol Level in Patients with Type 2 Diabetes Mellitus.

Introduction. Relation between atherosclerosis and innate immunity has attracted attention. As the antimicrobial peptide, LL-37, could have an important role in atherosclerosis, we supposed that there could be a meaningful association of plasma LL-37 level with risk factors for cardiovascular disease in subjects with type 2 diabetes mellitus. Materials and Methods. We evaluated plasma LL-37 level and other clinical markers in Japanese subjects with type 2 diabetes mellitus (n = 133, 115 men and 18 women; age 64.7 ± 11.5 years; HbA1c 8.1 ± 1.6%). Plasma level of LL-37 was measured by ELISA. Results. Mean plasma LL-37 level was 71.2 ± 22.3 ng/mL. Plasma LL-37 level showed significant correlations with HDL cholesterol (r = −0.450, P < 0.01), triglyceride (r = 0.445, P < 0.01), and high sensitive C-reactive protein (r = 0.316, P < 0.01) but no significant correlation with age, body mass index, HbA1c, estimated glomerular filtration rate, 25-hydroxyvitamin D, or vitamin D binding protein. Multiple linear regression analysis showed significant correlations of plasma LL-37 level with HDL cholesterol (β = −0.411, P < 0.01) and high sensitive C-reactive protein (β = 0.193, P < 0.05). Conclusion. Plasma LL-37 level was positively correlated with inflammatory markers and negatively correlated with HDL cholesterol in patients with type 2 diabetes mellitus.

Study of Cholesteryl Ester Transfer Protein (CETP) I405v Genotype and Its Association with Lipid Fractions in Myocardial Infarction Patients: A Case Control Study.

We determine the significant relation of HDL cholesterol and total cholesterol/HDL cholesterol between CETP I405V genotypes and activity of CETP. CETP is an essential for transfer of cholesterol ester to the liver from peripheral tissues which facilitating its transfer to TG rich VLDL. Reduction activity of CETP I405V may associate with genotypes of CETP I405V. This study is undertaken to assess the presence and impact of CETP I405V genotype in our population. In this study 100 acute myocardial infarction patients and 100 normal age & sex matched healthy individuals were included. Serum Lipid profile was estimated by using universal standard methods whereas CETP I405V genotype was studied by ARMS PCR. There is presence of CETP 405Val genotype both in patient as well as in control group. RESULTs show that HDL cholesterol (p<0.0001) and ratio of total cholesterol/HDL cholesterol are significantly (p<0.0043) associated with Val/Val genotype. In addition to that the CETP I405V genotype is associated with inhibition of CETP activity with higher HDL-C level and decreased total cholesterol/HDL cholesterol ratio. Our results show that the CETP I405V genotypes are very much significantly determinant of HDL cholesterol in patients with CHD.

Metabolic Syndrome in Children with Chronic Kidney Disease: PON1 and Treatment Modality

We undertook this study to evaluate the relationship between PON1, SOD and metabolic syndrome (MetS) in pediatric patients undergoing peritoneal dialysis, hemodialysis and patients in early stages of CKD. We carried out an analytical cross-sectional study of 134 children 6-17 years old. We registered anthropometric variables, vital signs, basic biochemical parameters, intact PTH (iPTH), high sensitivity CRP (hs-CRP), paraoxonase-1; SOD; PON1/HDL-cholesterol and homocysteine. For statistical analyses we used t test, Mann Whitney U test, χ(2), Fisher exact test, linear or logistic regression models, using SPSS v.16.0. p values <0.05 were considered as significant. There were 66 (49.3%) females; 39 (29.1%) had CKD stages 2-4 (predialysis), 42 (31.3%) on hemodialysis (HD) and 53 (39.6%) on automated peritoneal dialysis (PD). Time from diagnosis was 26 months. Significant differences were observed in mean, systolic and diastolic blood pressure, C-peptide, triglycerides, and HDL-cholesterol as well as PON1/HDL-cholesterol ratio and SOD. This study demonstrates that PON1 and SOD may be predictors for the presence of MetS in pediatric patients under treatment with peritoneal dialysis. The positive correlation observed in PON1/HDL-cholesterol ratio may reflect the protector effect of HDL-cholesterol in patients with CKD according with the modality of treatment.

Low level of high-density lipoprotein cholesterol correlates with poor prognosis in extranodal natural killer/T cell lymphoma

Studies have found that lymphoma patients often exhibit abnormal lipid metabolism, and a decrease in serum high-density lipoprotein cholesterol (HDL-C) may occur during lymphomagenesis and tumor growth. However, no literatures have investigated the role of HDL-C in patients with extranodal natural killer/T cell lymphoma (ENKTL). In this study, we retrospectively reviewed the HDL-C level in 107 patients newly diagnosed with ENKTL that received either l-asparaginase-based regimen or EPOCH regimen as induction chemotherapy, and evaluated its prognostic value. The mean level of HDL-C was 1.10 mmol/L (range, 0.15–2.63), and the HDL-C level was significantly lower in patients with elevated LDH and beta 2-microglobulin (β2-MG) (p = 0.017 and 0.001, respectively) and those who underwent disease progression and died (p = 0.031 and 0.007, respectively). In univariate survival analysis, higher Eastern Cooperative Oncology Group performance status score (≥1), Ann Arbor stage III–IV, elevated LDH, higher international prognostic index (IPI) score (≥2 vs. 1 vs. 0), decreased HDL-C level (<40 mg/dL), elevated β2-MG level, and response status after induction chemotherapy correlated significantly with poor progression-free survival (PFS) and overall survival (OS) (p < 0.05). In a multivariate Cox regression model that included IPI score, HDL-C level, β2-MG level, and response status after induction chemotherapy, it was found that HDL-C level and response status after chemotherapy were independent prognostic factors for OS (p = 0.014 and 0.010, respectively) and PFS (p = 0.016 and 0.020, respectively). In conclusion, HDL-C was found to be a valuable independent prognostic factor in ENKTL, and the mechanism needs to be further investigated, which may offer the possibility of therapeutic targets.

Serum amyloid A is independently related to apolipoprotein A-I but not to HDL-cholesterol in patients with angina pectoris

BackgroundInflammation processes are considered important links between classical lipid risk factors and the progression of atherosclerosis. The interrelationship of high density lipoproteins (HDL) and apolipoprotein apoA-1 with acute phase proteins and cytokines was examined in a clinical setting of patients with angina pectoris. MethodsOn exclusion criteria (myocardial infarction, heart failure, CHD>2years, anticoagulant therapy), 198 patients were recruited and were subdivided according to angiographically documented stenosis, no stenosis vs. =50% stenosis, in accordance with CASS guidelines. Lipids, apoA-1 and apoB, C-reactive protein (hs-CRP), fibrinogen, serum amyloid A (SAA) and cytokines (IL-6, IL-8, IL-10, IL2R, TNFα) were measured. ResultsLow HDL-C (and apoA-I) is associated with advanced coronary stenosis (=50%) and with the number of diseased vessels, independent of age, gender, diabetes, smoking and lipid-lowering therapy. In contrast to hs-CRP and fibrinogen, SAA as well as cytokine levels were not significantly associated with stenosis. SAA (P=0.0003) and diabetes (P=0.0002) were strong predictors of apoA-I concentration independent of age, gender, BMI, smoking, CRP, as well as IL-6 in a multiple regression model. High SAA (P=0.0067) and TG (P=0.0123) were significant predictors of apoA-I/HDL-C ratio. However, SAA was not independently related to HDL-C. ConclusionsSAA is independently and inversely related to apoA-I but not to HDL-C in patients with angina pectoris, reflecting the effect of SAA on the quality of HDL particles. However, HDL-c but not SAA is inversely related to the degree of coronary artery stenosis.

GW24-e2194 Low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio on admission is associated with clinical outcome in patients with ST segment elevation myocardial infarction undergoing urgent percutaneous coronary intervention

ObjectivesTo analyse the relationship between low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio on admission and cardiovascular events in patients with ST segment elevation myocardial infarction (STEMI) undergoing urgent percutaneous...

High-density lipoprotein cholesterol raising

Cardiovascular disease (CVD) is the leading cause of morbidity and premature mortality in Europe and the United States, and is increasingly common in developing countries. High-density lipoprotein cholesterol (HDL-C) is an independent risk factor for CVD and is superior to low-density lipoprotein cholesterol (LDL-C) as a predictor of cardiovascular events. The residual risk conferred by low HDL-C in patients with a satisfactory LDL-C was recently highlighted by the European Atherosclerosis Society. Despite the lack of randomized controlled trials, it has been suggested that raising the level of HDL-C should be considered as a therapeutic strategy in high-risk patients because of the strong epidemiological evidence, compelling biological plausibility, and both experimental and clinical research supporting its cardioprotective effects. Three recent large randomized clinical trials investigating the effect of HDL-C raising with niacin and dalcetrapib in statin-treated patients failed to demonstrate an improvement in cardiovascular outcomes. There is evidence to support the view that HDL functionality and the mechanism by which a therapeutic agent raises HDL-C are more important than plasma HDL-C levels. Future therapeutic agents will be required to improve this functionality rather than simply raising the cholesterol cargo.

Susceptibility gene for stroke or cerebral infarction in the Han population in Hunan Province of China.

The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistance, coronary artery disease and familial hyperlipidemia. In this study, the scavenger receptor class B type I gene exon 1 G4A gene polymorphism in atherosclerotic cerebral infarction patients, cerebral hemorrhage patients and normal controls was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that the GA + AA genotype frequency of scavenger receptor class B type I gene G4A in atherosclerotic cerebral infarction patients was similar to that in cerebral hemorrhage patients and normal controls; however, the A allele frequency was significantly lower than that in normal controls. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA + AA genotype was significantly higher, while the serum level of low-density lipoprotein cholesterol was significantly lower than that in patients with the GG genotype, in both the atherosclerotic cerebral infarction and cerebral hemorrhage groups. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA + AA genotype was significantly higher, while the serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly lower than those in normal controls with the GG genotype. Our experimental results suggest that the G4A polymorphism of the scavenger receptor class B type I gene is a possible predisposing risk factor for atherosclerotic cerebral infarction, and that it has no association with cerebral hemorrhage in the Han population in Hunan province of China. The A allele is possibly associated with the metabolism of high-density and low-density lipoprotein cholesterol.

Lack of protective role of HDL-C in patients with coronary artery disease undergoing elective coronary artery bypass grafting

Primary prevention studies have confirmed that high-density lipoprotein cholesterol (HDL-C) levels are strongly associated with reduced cardiovascular events. However, recent evidence suggests that HDL-C functionality may be impaired under certain conditions. In the present study, we hypothesize that HDL-C may lose their protective role in the secondary prevention of coronary artery disease (CAD). A consecutive series of 1548 patients undergoing isolated first-time elective CABG at one institution between 2004 and 2009 was studied. According to the ATPIII criteria, pre-operative HDL-C values were used to identify patients with high (Group A) vs. low HDL-C (Group B). To eliminate biased estimates, a propensity score model was built and two cohorts of 1:1 optimally matched patients were obtained. Cumulative survival and major adverse cardiovascular events (MACE) were analysed by means of Kaplan-Meier method. Cox proportional-hazards regression models were used to identify independent predictors of MACE and death. Propensity matching identified two cohorts of 502 patients each. At a median follow-up time of 32 months, there were 44 out of 502 (8.8%) deaths in Group A and 36 out of 502 deaths in Group B (7.2%, HR 1.19; P = 0.42). MACE occurred in 165 out of 502 (32.9%) in Group A and 120 out of 502 (23.9%) in Group B (P = 0.04). Regression analysis showed that pre-operative HDL-C levels were not associated with reduced but rather increased MACE occurrence during follow-up (HR 1.43, P = 0.11). Higher HDL-C levels are not associated with reduced risk of vascular events in CAD patients undergoing CABG. Our findings may support efforts to improve HDL-C functionality instead of increasing their levels.

A Review of Currently Available Fenofibrate and Fenofibric Acid Formulations

Fenofibrate is a third-generation fibric acid derivative indicated as a monotherapy to reduce elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, and apolipoprotein B; to increase high-density lipoprotein cholesterol in patients with primary hyperlipidemia or mixed dyslipidemia; and to reduce triglycerides in patients with severe hypertriglyceridemia. In this review, the key characteristics of available fenofibrate formulations are examined. A literature search was conducted, focusing on comparative studies examining bioavailability, food effects, absorption, and lipid efficacy. Fenofibrate is highly lipophilic, virtually insoluble in water, and poorly absorbed. Coadministration with meals was necessary to maximize bioavailability of early formulations. Micronized and nanoparticle formulations of fenofibrate with reduced particle sizes were developed, resulting in greater solubility, improved bioavailability, and in some cases, the ability to be given irrespective of food. A recently introduced hydrophilic choline salt of fenofibric acid also can be taken without regard to meals, is absorbed throughout the gastrointestinal tract, has the highest bioavailability among marketed formulations, and is approved for coadministration with a statin. Differences in bioavailability of fenofibrate formulations have resulted in low-dose (40 - 67) mg and standard-dose (120 - 200 mg) formulations. Different formulations are not equivalent on a milligram-to-milligram basis. In order to prevent medication errors, resulting in underdosing or overdosing with attendant consequences, it is important for healthcare providers to recognize that the formulations of fenofibrate and fenofibric acid that are currently available vary substantially in relation to food effect, equivalency on a milligram-to-milligram basis, and indication to be coadministered with a statin. doi: http://dx.doi.org/10.4021/cr270w

Low levels of high-density lipoprotein cholesterol in patients with atherosclerotic stroke: A prospective cohort study

ObjectiveThe purpose of this study was to evaluate the influence of baseline high-density lipoprotein cholesterol (HDL-C) on initial stroke severity and clinical outcomes in acute ischemic stroke. MethodsFrom August 2006 through December 2011, patients with acute atherosclerotic ischemic stroke were included. Total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and HDL-C were checked and National Institutes of Health Stroke Scale (NIHSS) scores were obtained at admission. The primary outcomes were a composite end point of all-cause mortality, recurrent stroke, or occurrence of ischemic heart disease during follow-up. ResultsOverall, 3093 subjects (mean age 66.8 years) were included and 675 patients (22%) had low HDL-C (≤35 mg/dL) at admission. These patients had higher NIHSS scores. After adjusting for all clinical factors in multivariate logistic analysis, low HDL-C at admission (OR, 1.79, 95% CI, 1.40–2.29) was significantly associated with higher stroke severity (NIHSS score > 6). During the follow-up period, 280 patients (9%) developed one of the components of the composite end point, including 76 (11.3%) in patients with low HDL-C and 204 (8.4%) in patients with normal HDL-C at admission (p < 0.001). In multivariate Cox regression analysis, after adjusting for all clinical factors, low HDL-C at admission (HR, 1.41, 95% CI, 1.02–1.95) was a significant independent predictor of the composite end point. ConclusionsLow baseline HDL-C (≤35 mg/dL) at admission was associated with higher stroke severity and poor clinical outcome during follow-up in patients with atherosclerotic ischemic stroke.

Triglyceride-rich lipoproteins and HDL: What do recent trials tell us?

Cardiometabolic disease is the leading, preventable cause of death worldwide. Elevated triglycerides, a marker of triglyceride-rich lipoproteins (TRL), with or without low plasma concentration of high-density lipoprotein (HDL) cholesterol, is a key driver of atherogenic risk associated with cardiometabolic disease. The European Atherosclerosis Society (EAS) Consensus Panel has highlighted this association in a recent position paper [ [1] Chapman M.J. Ginsberg H.N. Amarenco P. et al. European Atherosclerosis Society Consensus PanelTriglyceride-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: 1345-1361 Crossref PubMed Scopus (905) Google Scholar ]. However, in the light of recent developments there has been confusion about the relevance of each factor to this increased cardiovascular risk.

Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: Further evidence for a unique form of Metabolic Syndrome in HIV patients

IntroductionPlasma triglycerides (TG) and HDL-C are inversely related in Metabolic Syndrome (MetS), due to exchange of VLDL-TG for HDL-cholesteryl esters catalyzed by cholesteryl ester transfer protein (CETP). We investigated the relationship of TG to HDL-C in highly-active antiretroviral drug (HAART)-treated HIV patients. MethodsFasting plasma TG and HDL-C levels were compared in 179 hypertriglyceridemic HIV/HAART patients and 71 HIV-negative persons (31 normotriglyceridemic (NL) and 40 hypertriglyceridemic due to type IV hyperlipidemia (HTG)). CETP mass and activity were compared in 19 NL and 87 HIV/HAART subjects. ResultsAmong the three groups, a plot of HDL-C vs. TG gave similar slopes but significantly different y-intercepts (9.24±0.45, 8.16±0.54, 6.70±0.65, sqrt(HDL-C) for NL, HIV and HTG respectively; P<0.001); this difference persisted after adjusting HDL-C for TG, age, BMI, gender, glucose, CD4 count, viral load and HAART strata (7.18±0.20, 6.20±0.05 and 4.55±0.15 sqrt(HDL-C) for NL, HIV and HTG, respectively, P<0.001). CETP activity was not different between NL and HIV, but CETP mass was significantly higher in HIV (1.47±0.53 compared to 0.93±0.27μg/mL, P<0.0001), hence CETP specific activity was lower in HIV (22.67±13.46 compared to 28.46±8.24nmol/μg/h, P=0.001). ConclusionsDyslipidemic HIV/HAART patients have a distinctive HDL-C plasma concentration adjusted for TG. The weak inverse relationship between HDL-C and TG is not explained by altered total CETP activity; it could result from a non-CETP-dependent mechanism or a decrease in CETP function due to inhibitors of CETP activity in HIV patients’ plasma.

Adverse events following statin–fenofibrate therapy versus statin alone: A meta‐analysis of randomized controlled trials

The combination of fenofibrate with statins is a beneficial therapeutic option for patients with mixed dyslipidaemia, but concerns about adverse events (AEs) make physicians reluctant to use this combination therapy. Medline, Embase and the Cochrane Library were searched to identify 13 randomized controlled trials, involving 7712 patients, of statin-fenofibrate therapy versus statin alone for review. There were significant decreases in low-density lipoprotein-cholesterol, triglycerides and total cholesterol and increases in high-density lipoprotein-cholesterol in patients receiving combination therapy compared with statin therapy alone. The incidence of aminotransferase elevations in the fenofibrate-statin therapy group was significantly higher than in the statin monotherapy group (odds ratio (OR), 1.66; 95% confidence interval (CI) 1.17-2.37; P < 0.05). The incidence of elevated creatine kinase levels (OR 0.88; 95% CI 0.63-1.23; P > 0.05), muscle-associated AEs (OR 0.98; 95% CI 0.88-1.09; P > 0.05) and withdrawals attributed to liver and muscle dysfunction did not differ significantly between the two groups. The efficacy of fenofibrate + standard-dose statin and incidence of AEs in the fenofibrate + standard-dose statin group were almost identical to those in the fenofibrate-statin group. In conclusion, combination therapy improves the blood lipid profile of patients. Fenofibrate-statin combination therapy appears to be as well tolerated as statin monotherapy. Physicians should consider fenofibrate-statin combination therapy in patients but monitor aminotransferase levels to avoid hepatic complications.