Higher Baseline Triglycerides Research Articles

Development and Progression of Polyneuropathy Over 5 Years in Patients With Type 2 Diabetes.

There is a need for knowledge regarding the natural course of diabetic polyneuropathy (DPN), a complication in type 2 diabetes (T2D). The aim of this study was to examine the development of DPN over time. Patients with newly diagnosed T2D, recruited from a national cohort, and controls without diabetes of similar age and sex, underwent sensory phenotyping in 2016-2018. The Toronto consensus criteria were used to classify patients into possible, probable, and confirmed DPN. For this 5-year, observational, follow-up, cohort study, all participants were invited to a reexamination combining bedside sensory examination, quantitative sensory testing (QST), nerve conduction studies (NCSs), and skin biopsies measuring intraepidermal nerve fiber density (IENFD) in order to compare phenotypic and diagnostic changes over time. Of the baseline 389 patients and 97 controls, 184 patients (median [interquartile range] diabetes duration 5.9 [4.1-7.4] years, mean hemoglobin A1c [HbA1c] 51 ± 11 mmol/mol at baseline) and 43 controls completed follow-up (46.9%). Confirmed DPN was present in 35.8% and 50.3%, probable DPN in 27.2% and 14.6%, possible DPN in 17.2% and 16.6%, and no DPN in 15.2% and 17.9% at baseline and follow-up, respectively. The estimated prevalence (95% CI) of confirmed DPN was 33.5% (24.9-42.1) compared with 22.7% (17.5-28.0) at baseline. During the follow-up period, 43.9% of patients with probable DPN developed confirmed DPN. Progression of neuropathy occurred in 16.5% and 24.7% and regression in 5.9% and 18.6% of patients based on NCS and IENFD, respectively. Progression based on NCS and/or IENFD was associated with higher baseline waist circumference and triglycerides, and regression with lower baseline HbA1c. Patients with at least probable DPN at baseline but neither patients without DPN nor controls developed increased spread of hyposensitivity, more hyposensitivity on QST and lower NCS z-scores at follow-up, and worsening of nerve parameters at follow-up correlated with higher baseline triglycerides. In patients with well-regulated T2D, the proportion of patients with confirmed DPN increased over 5 years driven by progression from probable DPN. A large proportion of patients progressed, and a smaller proportion regressed on nerve parameters. Higher triglycerides correlated with this progression and may constitute a risk factor.

Genetic and biomarker modulation of arterial stiffness change in the SardiNIA population cohort.

Arterial stiffness (AS), quantified by pulse wave velocity (PWV), arises due to impaired arterial elastic tissue and smooth muscle dysfunction. We aimed to examine the longitudinal association of genetic, lipid and inflammation biomarkers with PWV and how these associations may change with aging. We utilized genotype and four time-point biomarker data from the SardiNIA cohort [n = 6,301; mean baseline age 43.3 (SD 17.3); 58% females]. To investigate the association of PWV with genetic variants, lipid, and inflammation biomarkers, we employed linear mixed modeling, using age as the time scale. Biomarkers exhibiting significant longitudinal associations were categorized into tertiles and individuals within the second tertile or those with heterozygous alleles were excluded, leaving a cohort of 2,000 individuals. This cohort was further divided into four risk groups: low genetic and low biomarker (L-L), low genetic and high biomarker (L-H), high genetic and low biomarker (H-L), and high genetic and high biomarker risk (H-H). Subsequent analyses focused on these risk groups to assess their association to PWV with time. Using the complete dataset, we found a significant longitudinal association of total cholesterol (TC), triglycerides (TG), fibrinogen (FGN), and total white blood cell count (TWBC) with PWV, all with p < 3.33 × 10-3. After grouping, individuals with homogeneous risk alleles of SNP rs3742207 and high baseline TG levels (H-H group) exhibited a 1.39-fold higher PWV (m/s) (95% CI, 1.17-1.64, p = 1.21 × 10-4) compared to the L-L group. Similarly, individuals in the H-H group of rs3742207-TWBC combination showed 1.75 times higher PWV (95% CI, 1.48-0.2.07, p = 1.01 × 10-10) compared to the L-L group. Similar patterns were observed for groups based on SNP rs7152623-TWBC risk. Furthermore, these associations became more pronounced with increasing age (p < 3.33 × 10-3). The longitudinal association of TG and TWBC biomarkers with PWV varied by SNPs rs3742207 and rs7152623 genotype. Further studies are warranted to investigate the function of genetics, lipids, and inflammation biomarkers on PWV change.

1247-P: Mildly Elevated Triglyceride Levels Are Associated with Increased Risk for Major Adverse Cardiovascular Events in Statin-Naïve Rheumatoid Arthritis Patients—A Nationwide Cohort Study

Objectives: To investigate the association between the four components of the lipid profile at baseline and major adverse cardiovascular events (MACEs) in statin-naïve rheumatoid arthritis (RA) patients with no previous history of cardiovascular events compared to non-RA controls. Methods: This nationwide population-based cohort study was performed on a total of 15,216 statin-naïve RA patients and 60,864 non-RA controls. The end point was a composite of clinical events, including myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death. We compared the incidence of and risk for clinical events according to each lipid variable. Results: During follow-up (median 4.70 years in RA group and 5.05 years in non-RA group), the incidence of MACE per 1000 person-years was 7.27 in the RA group and 7.16 in the non-RA group. Among the four lipid components, only higher baseline triglyceride (TG) levels were significantly associated with increased risk for MACE in the RA group. The risk for MACE was significantly higher in the third (adjusted hazard ratio (HR), 1.31 [95% confidence interval (CI), 1.00-1.71]) and highest quartiles (adjusted HR, 1.71 [95%CI, 1.30-2.23]) of baseline TG level versus the lowest quartile. In contrast, higher baseline total cholesterol, TG, and low-density lipoprotein cholesterol, and lower high-density lipoprotein cholesterol levels were significantly associated with increased MACE risk in the propensity score-matched non-RA group. Conclusions: In statin-naïve RA patients, increased TG level is associated with increased risk for MACE. Therefore, screening and intervention for increased TG level may be clinically beneficial in this population. Disclosure W.Choi: None. J.Kang: None. J.Park: None. A.Hong: None. J.Yoon: None. H.Kim: None. H.Kang: None. Funding National Research Foundation of Korea (2022R1C1C1006021)

Higher serum triglyceride can predict recurrent coronary revascularization events in patients undergoing percutaneous coronary intervention with baseline LDL-C

Patients with low baseline low-density lipoprotein cholesterol (LDL-C) but experiencing recurrent coronary revascularization events have been rarely investigated. In this retrospective cohort study, we enrolled patients undergoing percutaneous coronary intervention...

Genetic European Ancestry and Incident Diabetes in Black Individuals: Insights From the SPRINT Trial.

Black individuals have high incident diabetes risk, despite having paradoxically lower triglyceride and higher HDL (high-density lipoprotein) cholesterol levels. The basis of this is poorly understood. We evaluated the participants of SPRINT (Systolic Blood Pressure Intervention Trial) to assess the association of estimated European genetic ancestry with the risk of incident diabetes in self-identified Black individuals. Self-identified non-Hispanic Black SPRINT participants free of diabetes at baseline were included. Black participants were stratified into tertiles (T1-T3) of European ancestry proportions estimated using 106 biallelic ancestry informative genetic markers. The multivariable-adjusted association of European ancestry proportion with indices of baseline metabolic syndrome (ie, fasting plasma glucose, triglycerides, HDL cholesterol, body mass index, and blood pressure) was assessed. Multivariable-adjusted Cox regression determined the risk of incident diabetes (fasting plasma glucose ≥126 mg/dL or self-reported diabetes treatment) across tertiles of European ancestry proportion. Among 2466 Black SPRINT participants, a higher European ancestry proportion was independently associated with higher baseline triglyceride and lower HDL cholesterol levels (P<0.001 for both). European ancestry proportion was not associated with baseline fasting plasma glucose, body mass index, and blood pressure (P>0.05). Compared with the first tertile, those in the second (hazard ratio, 0.64 [95% CI, 0.45-0.90]) and third tertiles (hazard ratio, 0.61 [95% CI, 0.44-0.89]) of the European ancestry proportion had a lower risk of incident diabetes. A 5% point higher European ancestry was associated with a 29% lower risk of incident diabetes (hazard ratio, 0.71 [95% CI, 0.55-0.93]). There was no evidence of a differential association between the European ancestry proportion tertiles and incident diabetes between those randomized to intensive versus standard blood pressure treatment. The higher risk of incident diabetes in Black individuals may have genetic determinants in addition to adverse social factors. Further research may help understand the interplay between biological and social determinants of cardiometabolic health in Black individuals. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

The Effects and Safety of Chinese Herbal Medicine on Blood Lipid Profiles in Placebo-Controlled Weight-Loss Trials: A Systematic Review and Meta-Analysis

This study was conducted to assess the effects and safety of Chinese herbal medicine (CHM) on blood lipids among adults with overweight or obesity. Fourteen bibliographic databases were comprehensively searched, from their respective inceptions up to April 2021, for randomised placebo-controlled weight-loss trials using CHM formulation on total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol over ≥4 weeks. Data collection, risk of bias assessment, and statistical analyses were guided by the Cochrane Handbook (v6.1). Continuous outcomes were expressed as the mean difference with 95% confidence intervals, and categorical outcomes were expressed as a risk ratio with 95% confidence intervals. All analyses were two-tailed with a statistical significance of p < 0.05. Fifteen eligible studies with 1,533 participants were included in this meta-analysis. Findings from meta-analyses indicated that CHM interventions, compared to placebo, reduced triglyceride (MD −0.21 mmol/L, 95% CI −0.41 to −0.02, I2 = 81%) and increased HDL cholesterol (MD 0.16 mmol/L, 95% CI 0.04 to 0.27, I2 = 94%) over a median of 12 weeks. The reduction in total cholesterol and LDL cholesterol were not statistically significant. Furthermore, the tendency of reduced triglycerides was identified among overweight participants with high baseline triglycerides. Attrition rates and frequency of adverse events were indifferent between the two groups. CHM may provide lipid-modulating benefits on triglycerides and HDL cholesterol among participants with overweight/obesity, with the tendency for significant triglyceride reduction observed among overweight participants with high baseline triglycerides. However, rigorously conducted randomised controlled trials with larger sample sizes are required to validate these findings.

794-P: Predictors of Hemoglobin (Hb) and Its Changes Focusing on Anemia and Polycythemia after Administration of the SGLT2 Inhibitor Tofogliflozin

SGLT2 inhibitors (SGLT2is) increase hematocrit (Ht) and Hb, which may contribute to correcting anemia but also might cause secondary polycythemia. We investigated predictors of Hb after short- and long-term therapy with tofogliflozin (TOFO), a SGLT2i, and explored its impact on Hb in relation to anemia and polycythemia in type 2 diabetes mellitus (T2DM). Analyzed were 774 T2DM patients (66% male) who received TOFO for 52 weeks in two phase 3 studies. Mean baseline characteristics were age 59 y, HbA1c 8%, BMI 26 kg/m2, hemoglobin 15 g/dL and eGFR 84 mL/min/1.73m2. Participants were divided into the Anemia group (baseline Hb &amp;lt;13 g/dL in men and &amp;lt;12 g/dL in women, mean baseline Hb 11.8 g/dL) and Polycythemia group (&amp;gt;16.5 g/dL in men and &amp;gt;16 g/dL in women, mean baseline Hb 17.2 g/dL). Paired t-tests analyzed differences from baseline to weeks 4 and 52. Generalized linear model explored predictors of Hb at weeks 4 and 52. Correlation analysis was performed by Spearman’s product-moment correlation coefficients. Hb was significantly increased at week 4 [mean, +0.14g/dL*; *p&amp;lt;0.05 vs. baseline] and week 52 (+0.34g/dL*). Higher baseline brain natriuretic peptide and lower Ht and triglycerides (TG) were independently correlated with greater increases in Hb at week 4. Lower baseline Hb and TG were significantly correlated with greater increases in Hb at week 52. Higher baseline TG levels and proportion of fatty liver as a comorbidity were observed with higher baseline Hb values. Hb had significantly changed at week 52 in Anemia (+0.94*) and Polythycemia groups (-0.29*). Change in Hb was significantly correlated with change in TG at week 52 (Rho=0.42, p&amp;lt;0.05) in Polycythemia but not Anemia. Increased Hb after short-term TOFO therapy may be due to hemoconcentration while Hb may be corrected according to baseline Hb levels after long-term TOFO therapy. Lower TG in relation to improved fatty liver may be related to correction of higher Hb levels. Disclosure Y. Matsubayashi: None. A. Yoshida: Employee; Self; Kowa Company, Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd. K. Kaku: Advisory Panel; Self; Novo Nordisk Pharma Ltd., Consultant; Self; Sanwa Kagaku Kenkyusho, Research Support; Self; Taisho Pharmaceutical Co., Ltd., Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Eli Lilly Japan K. K., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

Pemafibrate decreases triglycerides and small, dense LDL, but increases LDL-C depending on baseline triglycerides and LDL-C in type 2 diabetes patients with hypertriglyceridemia: an observational study

BackgroundPemafibrate, a selective PPARα modulator, has the beneficial effects on serum triglycerides (TGs) and very low density lipoprotein (VLDL), especially in patients with diabetes mellitus or metabolic syndrome. However, its effect on the low density lipoprotein cholesterol (LDL-C) levels is still undefined. LDL-C increased in some cases together with a decrease in TGs, and the profile of lipids, especially LDL-C, during pemafibrate administration was evaluated.MethodsPemafibrate was administered to type 2 diabetes patients with hypertriglyceridemia. Fifty-one type 2 diabetes patients (mean age 62 ± 13 years) with a high rate of hypertension and no renal insufficiency were analyzed. Pemafibrate 0.2 mg (0.1 mg twice daily) was administered, and serum lipids were monitored every 4–8 weeks from 8 weeks before administration to 24 weeks after administration. LDL-C was measured by the direct method. Lipoprotein fractions were measured by electrophoresis (polyacrylamide gel, PAG), and LDL-migration index (LDL-MI) was calculated to estimate small, dense LDL.ResultsPemafibrate reduced serum TGs, midband and VLDL fractions by PAG. Pemafibrate increased LDL-C levels from baseline by 5.3% (− 3.8–19.1, IQR). Patients were divided into 2 groups: LDL-C increase of > 5.3% (group I, n = 25) and < 5.3% (group NI, n = 26) after pemafibrate. Compared to group NI, group I had lower LDL-C (2.53 [1.96–3.26] vs. 3.36 [3.05–3.72] mmol/L, P = 0.0009), higher TGs (3.71 [2.62–6.69] vs. 3.25 [2.64–3.80] mmol/L), lower LDL by PAG (34.2 [14.5, SD] vs. 46.4% [6.5], P = 0.0011), higher VLDL by PAG (28.2 [10.8] vs. 22.0% [5.2], P = 0.0234), and higher LDL-MI (0.421 [0.391–0.450] vs. 0.354 [0.341–0.396], P < 0.0001) at baseline. Pemafibrate decreased LDL-MI in group I, and the differences between the groups disappeared. These results showed contradictory effects of pemafibrate on LDL-C levels, and these effects were dependent on the baseline levels of LDL-C and TGs.ConclusionsPemafibrate significantly reduced TGs, VLDL, midband, and small, dense LDL, but increased LDL-C in diabetes patients with higher baseline TGs and lower baseline LDL-C. Even if pre-dose LDL-C remains in the normal range, pemafibrate improves LDL composition and may reduce cardiovascular disease risk.

Characteristics and Outcomes of Patients Treated With Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (The Mayo Clinic Experience)

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors represent a novel addition to the lipid-lowering armamentarium. We attempted to characterize a real-world group of patients with a clinical indication for PCSK9 inhibitors and describe their clinical outcomes and adverse effect profile. A retrospective chart review was conducted, evaluating all patients referred to preventive cardiology at the Mayo Clinic (Minnesota) between September, 2015 and December, 2018 for management of severe dyslipidemia. A total of 222 patients were referred and a recommendation to start a PCSK9 inhibitor was given to 164 patients (73.9%). Of these, 28 patients (17.1%) declined the use of a PCSK9 inhibitor. A total of 136 previous authorizations were submitted. Of these applications, 96 (70.6%) were approved and 17 (12.5%) were rejected. The cohort's mean age was 64.1 years (range 39 to 91). High-intensity statins and ezetimibe were used in 50 (52.1%) and 80 (83.3%) of the treated patients. Mean pretreatment low-density lipoprotein cholesterol was 167.9 mg/dl. At a median follow-up of 19.0 months, the mean low-density lipoprotein reduction was 60.9% (range 0 to 90.3%). Higher low-density lipoprotein cholesterol percent reductions were seen in younger patients (p value 0.048), patients on high-intensity statins (p value 0.027), those with statin intolerance (p value 0.046), and individuals with a higher baseline triglycerides (p value 0.047). Two (2.1%) patients underwent coronary revascularization, and 1 (1.0%) patient was hospitalized for unstable angina. No cardiovascular deaths occurred. Adverse events were reported in 12 (12.5%) patients, and were all minor (injection site reactions, myalgias, and flu-like illness). In conclusion, our study shows an efficacy and safety profile that is concordant with previous investigations. The use of a standardized application form was associated with a high insurance approval rate.

Genetic variants in the LPL and GPIHBP1 genes, in patients with severe hypertriglyceridaemia, detected with high resolution melting analysis

IntroductionPathogenic variants in lipoprotein lipase (LPL) and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) have been described in patients with severe hypertriglyceridaemia. We aimed to optimise high resolution melting (HRM) assays to detect the presence of functional variants in these genes. MethodsOne hundred and sixteen patients with severe hypertriglyceridaemia were studied. HRM assays were optimised to scan exons and splice junctions in LPL and GPIHBP1. Sanger sequencing was the reference method. Next-generation-sequencing (NGS) was performed in five patients, including one with Familial Chylomicronemia syndrome (FCS). ResultsWe identified 15 different variants in LPL and 6 in GPIHBP1. The variants revealed with NGS were also detected with HRM, including a rare premature stop codon in LPL (p.Trp421*) and two LPL pathogenic variants in the patient with FCS (p.His80Arg + p.Gly215Glu). Having multiple functional variant alleles was associated with pancreatitis onset at younger ages and higher baseline triglycerides. ConclusionsOur HRM assays detected the presence of functional gene variants that were confirmed with Sanger and NGS sequencing. The presence of multiple functional variant alleles was associated with differences in the clinical profile. Therefore, these assays represent a reliable, cost-effective tool that can be used to complement the NGS approach for gene scanning.

Lipid profile and renal safety of tenofovir disoproxil fumarate-based anti-retroviral therapy in HIV-infected Chinese patients

BackgroundTenofovir disoproxil fumarate (TDF) is an important component of antiretroviral therapy (ART) that has been widely used. The aim of this study was to observe the long-term impact of TDF-based ART on lipid metabolism profiles and renal functions in Chinese patients. Methods414 and 124 HIV-infected, ART-naïve patients who initiated TDF-based regimens and non-TDF regimens respectively were retrospectively included. Demographic characteristics and clinical information of each patient was collected. Changes of lipid profiles and renal function, as well as the risk factors of hyperlipidemia and renal dysfunction were analyzed. ResultsAfter 96 weeks of ART, HIV viral loads were undetectable in 97.34% (403/414) of patients exposed to TDF. The plasma total cholesterol (TCH) increased from 3.97 ± 0.83 mmol/L to 4.53 ± 0.87 mmol/L (P < 0.001), which did not show a significant difference comparing with non-TDF exposed group. By contrast, the plasma triglyceride (TG) levels increased, but were still lower than that in the non-TDF exposed group (0.26 ± 1.24 vs. 0.89 ± 1.78, P < 0.001). The mean estimated glomerular filtration rate (eGFR) decreased from 127.29 ± 24.04ml∙min−1∙1.73 m−2 at baseline to 118.84 ± 22.74 ml∙min−1∙1.73 m−2(P < 0.001) in the TDF exposed group, while it increased in the non-TDF exposed group. In the TDF group, high body mass index (BMI) (OR = 1.13, P = 0.01), high baseline TG (OR = 2.33, P<0.001) and receiving protease inhibitors (PIs) (OR = 7.58, P < 0.001) were associated with hypertriglyceridemia after ART, while high baseline TCH predicted hypercholesterolemia (OR = 3.58, P < 0.001). MSM (OR = 0.22, P = 0.02) and baseline eGFR (OR = 0.90, P < 0.001) was associated with renal dysfunction after ART. ConclusionsTDF-based regimens are of good therapeutic effect among Chinese people. These regimens showed a better plasma lipid profile but mild renal dysfunction as compared to non-TDF based regimens. Patients with high BMI, high baseline TG, high baseline TCH and low baseline eGFR should be closely monitored when using TDF-based ART.

Study on the Prevalence of Vascular Calcification in Different Types of Arteries and Influencing Factors in Maintenance Peritoneal Dialysis Patients

Objective: To investigate the occurrence of vascular calcification (VC) in different types of arteries in patients with maintenance peritoneal dialysis (PD) patients and its influencing factors. Methods: This study enrolled PD patients with stable status who has received PD treatment for more than 6 months in Peking University People’s Hospital. We used plain X-ray films of abdomen, pelvis, and hands to quantitatively evaluate VC of large artery (abdominal aorta, iliac artery), medium artery (femoral artery, radial artery), and small artery (finger arteries). Two radiologists read and scored radiographs blindly. Demographic data, clinical characteristics, Charlson comorbidity index (CCI), baseline and time-average laboratory indices including parameters of calcium phosphorus metabolism, serum albumin, PD adequacy were collected. A logistic regression model was used to estimate the influencing factors of different sites of VC. Results: (1) 154 PD patients were enrolled in this study: seventy-eight males, mean age was 60.4 ± 13.9 years, and median PD duration was 24 (16.39) months. The major primary disease was diabetic nephropathy (39%). (2) Among the 154 PD patients, the proportion of calcification of large artery was the highest (found in 100 patients, accounting for 64.9%); then the medium artery (66, 42.9%); and 15 of small artery, accounting for 9.7%. (3) Logistic regression showed that older age, longer dialysis duration, lower baseline serum intact parathyroid hormone (iPTH), and higher CCI scores were independent risk factors of large artery calcification (p < 0.05), and higher CCI scores, higher baseline serum triglycerides (TG), lower baseline serum iPTH, and time-average iPTH were independent risk factors of medium and small arteries. Conclusions: In PD patients, the occurrence of large artery calcification was higher than others. Among different sites of VC, the abdominal aortic calcification was most likely to occur, and the proportion of small artery calcification was low. Calcification of medium and small arteries can exist alone without calcification of large artery. Large artery calcification was more likely to occur in patients with older age, longer dialysis duration, lower baseline serum iPTH levels and higher CCI scores. Patients with higher CCI scores, higher baseline TG and lower baseline iPTH, and time-average iPTH were more likely to develop small and medium artery calcification.

Sex Effect on Obesity Indices and Metabolic Outcomes in Patients with Obese Obstructive Sleep Apnea and Type 2 Diabetes After Laparoscopic Roux-en-Y Gastric Bypass Surgery: a Preliminary Study.

Roux-en-Y gastric bypass (RYGB) surgery is an effective therapy for obstructive sleep apnea (OSA). However, little attention has been paid to the treatment goals systematically stratified by sex. The objective of this study was to assess how sex differences affect obesity indices and metabolic outcomes after RYGB surgery. A sleep questionnaire was conducted and medical histories were taken. Full-night polysomnography (PSG), anthropometric variables, and blood samples were collected. Thirty-five consecutive patients with OSA who underwent laparoscopic RYGB surgery were prospectively examined for at least 6months were included in the study. Significant improvements (p < 0.01) in sleep parameters (except for micro-arousal), obesity indices, and metabolic outcomes [except low-density lipoprotein in men and high-density lipoprotein (HDL) in women] were obtained in men and women with OSA. Men had higher baseline triglyceride (TG) (p < 0.01) and lower HDL levels (p < 0.01) but a larger neck circumference (NC) (p = 0.03) at follow-up than did women. However, only TG in men improved more than in women (p = 0.02). Sleep parameters, obesity indices, and metabolic outcomes after RYGB surgery were of similar magnitude in women and men with OSA. Alleviating sleep and obesity problems was correlated with metabolic outcomes in men and women.

Abstract 16803: Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester): Effects on Remnant-Like Particle Cholesterol From the MARINE and ANCHOR Studies

Background: Remnant-like particle cholesterol (RLP-C) represents the cholesterol carried by partially catabolized triglyceride (TG)-rich lipoproteins such as very-low-density lipoproteins (VLDL) in the fasted state and chylomicron remnants in the post-prandial state. Increased RLP-C levels are atherogenic and may increase the risk of atherosclerotic cardiovascular disease. Long-chain polyunsaturated omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid reduce RLP-C levels. Icosapent ethyl (IPE) is a high-purity prescription form of EPA ethyl ester approved to reduce TG levels in patients with severe (&gt;=500 mg/dL) hypertriglyceridemia. Objective: To evaluate the effects of IPE on RLP-C levels in patients from the MARINE and ANCHOR studies. Methods: MARINE (TG &gt;=500 and &lt;=2000 mg/dL; N=229) and ANCHOR (TG &gt;=200 and &lt;500 mg/dL despite statin control of low-density lipoprotein cholesterol; N=702) were both 12-week, phase 3, double-blind studies that randomized patients to IPE 4 g/day, 2 g/day, or placebo. This analysis assessed the median percentage change from baseline to study end in RLP-C levels compared with placebo. Serum RLP-C was measured with an immunoseparation assay (Polymedco). Results: In both the MARINE (n=218 with RLP-C data) and ANCHOR (n=252 with RLP-C data) studies, compared with placebo, IPE 4 g/day (Table) and 2 g/day reduced RLP-C levels. Compared with placebo, the approved IPE dose of 4 g/day also reduced RLP-C to a greater extent in subgroups with higher baseline TG levels, reduced RLP-C in statin-treated patients in the MARINE study, and reduced RLP-C in patients receiving moderate- to high-intensity statins in the ANCHOR study. Conclusions: Compared with placebo, IPE reduced RLP-C levels in patients in the MARINE and ANCHOR studies, including significant reductions in RLP-C in hypertriglyceridemic patients with TG &gt;=200 mg/dL or &gt;=500 mg/dL receiving statin therapy.

Effect of sitagliptin on lipid profile in patients with type 2 diabetes mellitus.

BackgroundAnimal studies have demonstrated that an inhibition of DPP-4 has an impact on the secretion of cholesterol and apoB by the small intestine. However, there is no consensus about the changes of the lipid profile following administration of sitagliptin.MethodsAccordingly, we treated patients who had type 2 diabetes complicated by dyslipidemia with sitagliptin and evaluated its effects on the profile of lipid parameters. A total of 248 outpatients with type 2 diabetes complicated by dyslipidemia were treated with sitagliptin at a daily dose of 50 mg. The levels and percent changes of lipid and glucose metabolism markers were measured at baseline and at 12 weeks after the initiation of treatment.ResultsBoth plasma glucose and HbA1c were significantly decreased. Among the lipid parameters, total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) showed a significant decrease (TC 3.6±15.6%, non-HDL-C 2.9±19.7%; P < 0.05). Stratified analysis revealed a significant decrease of TC, low-density lipoprotein cholesterol (LDL-C) and non-HDL-C in the high triglyceride (TG) group (≥ 150 mg/dL) (P < 0.05). Analysis stratified by demographic factors demonstrated significant differences in the changes of TC, LDL-C and non-HDL-C. Multivariate analysis showed a significant decrease of the TC, LDL-C and non-HDL-C levels in the high TG group (≥ 150 mg/dL), as well as a significant decrease of TC and LDL-C in patients using strong statins.ConclusionsThe results suggested that sitagliptin caused a significant decrease of TC, LDL-C and non-HDL-C, particularly in patients with high baseline TG levels and those using strong statins.

Possible effects of some antipsychotic drugs on C-reactive protein in a drug-naïve psychotic sample

Antipsychotic effects on C-reactive protein (CRP) have received little attention. This randomized open-label study investigated the possible effects of antipsychotics on CRP levels after 3 and 12 months of treatment in a Spanish drug-naïve sample taking haloperidol (N = 36 after 3 months), olanzapine (N = 36 after 3 months) or risperidone (N = 39 after 3 months). After 3 months and adjusting for differences in baseline CRP levels, baseline smoking and high baseline triglyceride levels, patients on haloperidol treatment had CRP levels that were 92.7% higher than those of patients on risperidone treatment (p = 0.009). After 12 months, only smoking was associated with increased CRP levels. Future studies need to verify that different antipsychotics may have differential effects on CRP levels, particularly after 3 months of treatment.

Effects of combination lipid therapy in type 2 diabetes mellitus.

We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease. We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P=0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P=0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P=0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P=0.057 for interaction). The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

Relationships Between Metabolic Syndrome and Other Baseline Factors and the Efficacy of Ezetimibe/Simvastatin and Atorvastatin in Patients With Type 2 Diabetes and Hypercholesterolemia

OBJECTIVETo investigate relationships between baseline factors and treatment-associated efficacy changes in type 2 diabetes.RESEARCH DESIGN AND METHODSMultivariable analyses of treatment response in 1,229 type 2 diabetic patients with hypercholesterolemia who received ezetimibe/simvastatin or atorvastatin in a randomized double-blind 6-week study.RESULTSIncreasing age was related to improvements in all lipid assessments. Men had greater triglyceride and non-HDL cholesterol reductions than women, and black/Hispanic patients had less favorable lipid effects than other races/ethnicities. Increasing baseline LDL cholesterol was associated with improvements in most lipids; higher baseline non-HDL cholesterol with improved HDL cholesterol and triglycerides; higher baseline HDL cholesterol with greater non-HDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) reductions; and higher baseline hs-CRP with smaller LDL cholesterol, non-HDL cholesterol, and apolipoprotein B reductions. Patients with high baseline non-HDL cholesterol or triglycerides less frequently attained LDL cholesterol targets. Obesity was inversely related to HDL cholesterol and hs-CRP changes, and higher baseline A1C to smaller apolipoprotein B reductions. Metabolic syndrome was not a significant predictor.CONCLUSIONSTreatment responses in type 2 diabetic patients were related to baseline factors, although treatment effects (ezetimibe/simvastatin being more effective than atorvastatin) remained consistent. The presence of predictive factors should be considered in planning lipid-altering therapy.

Association of Single‐Nucleotide Polymorphism 3 and c.553G&gt;T ofAPOA5with Hypertriglyceridemia after Treatment with Highly Active Antiretroviral Therapy Containing Protease Inhibitors in HIV‐Infected Individuals in Taiwan

We investigated the relationship between hypertriglyceridemia and the single-nucleotide polymorphisms (SNPs) on APOA5 in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) in Taiwan. Receipt of protease inhibitor-based HAART, high baseline triglyceride levels, and carriage of APOA5 SNP3 or c.553G>T variants or APOA5 SNP1T/SNP2G/SNP3C/c.553T haplotype were statistically significantly associated with development of extreme hypertriglyceridemia (triglyceride level, >500 mg/dL).

Cardiovascular risk score change in HIV‐1‐infected patients switched to an atazanavir‐based combination antiretroviral regimen

We aimed to establish whether the limited impact of atazanavir on the plasma lipid profile could translate into a reduction in the predicted cardiovascular risk in antiretroviral (ARV)-experienced patients switching to an atazanavir-containing regimen. HIV-1-infected treatment-experienced patients, switched to atazanavir for whatever reason and without prior major cardiovascular events, were selected and followed for at least 1 month. An individual cardiovascular risk score (10-year risk of major cardiovascular events) based on validated events and measurable risk factors in Italian cardiovascular cohorts was calculated using software available online. A total of 197 patients were selected for inclusion in the study. After switching to atazanavir, the mean changes from pre-switch to last available measurement were -6.5% (P<0.001) for total cholesterol, -1.7% (P=0.029) for high-density lipoprotein (HDL) cholesterol, -11.3% (P<0.001) for non-HDL cholesterol and -8.6% (P<0.001) for triglycerides. The crude cardiovascular risk score was reduced from 3.43 to 3.38% (P=0.51); the analysis normalized by age showed a reduction from 3.43 to 3.14% (P<0.001). Subsets of patients with high baseline total cholesterol or triglycerides showed more marked reductions. A treatment switch to atazanavir caused significant reductions in plasma lipids and a modest but significant reduction in the normalized-for-age cardiovascular risk score. Efforts should be made to concomitantly reduce the other preventable cardiovascular risk factors.