Baseline HDL-C Research Articles

Incidence of non-alcoholic fatty liver disease in antiretroviral therapy-naïve people with human immunodeficiency virus who start DTG/ABC/3TC compared to BIC/FTC/TAF at 48-week follow-up.

To determine the incidence of non-alcoholic fatty liver disease (NAFLD) by non-invasive methods in people living with HIV (PLWH). Prospective cohort, in PLWH naïve to antiretroviral therapy, starting bictegravir (BIC) or dolutegravir (DTG) at the Hospital de Infectología "La Raza", in Mexico City, from February 2021 to August 2023. We measured at baseline and 48weeks triglycerides and glucose index (TyG), fatty liver index (FLI), hepatic steatosis index (HSI) and liver ultrasonography; relative risk (RR) for developing NAFLD was determined. At 48weeks, TyG index in BIC-group 4.54 (IQR 4.36-4.75), in DTG-group 4.66 (IQR 4.49-4.80), p = .080; HSI in BIC-group 30.30 (IQR 28.12-33.70), in DTG-group 30.85 (IQR 28.02-34.50), p = .650; FLI in BIC-group 14.88 (IQR 7.91-31.80), in DTG-group 19.49 (IQR 8.49-32.28), p = .729; NAFLD was detected by US in 6 [10.3% (95%CI 4.8%-20.7%)] in BIC-group and, 7 [10.9% (95%CI 6.4%-20.9%)] in DTG-group, p = .916. Risk factors for NAFLD development were baseline BMI ≥25kg/m2, baseline HDL-c <40mg/dL, and FIB-4 >1.3 at 48weeks. There is a high incidence of NAFLD in PLWH who start a second generation INSTI at 48weeks; baseline overweight, low HDL-cholesterol and FIB-4 >1.3 at 48weeks of treatment were independent risk factors for NAFLD development.

Cognitive impairment and depression precede increased HDL-C levels in middle-aged and older Chinese adults: cross-lagged panel analyses

BackgroundHigh-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults.MethodsThe datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for.ResultsThe analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (β = − 0.036 and β = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (β = − 0.008 and β = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (β = − 0.026 and β = − 0.053, respectively, P < 0.05).ConclusionsCognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.

Association of thyroid peroxidase antibody positivity in the first trimester with gestational metabolic disorders: a retrospective study

Objective To investigate the association between thyroid peroxidase antibody (TPOAb) positivity in the first trimester and maternal metabolic syndrome in pregnancy. Methods The study retrospectively reviewed the medical records for 787 pregnant women. Serum-free thyroid hormone, thyroid stimulating hormone, and TPOAb levels were measured in early pregnancy (<13 weeks gestation). Baseline demographics, clinical characteristics, thyroid function, and pregnancy outcomes were compared between women who were TPOAb positive or TPOAb negative in the first trimester. Associations between TPOAb positivity in the first trimester and the occurrence of gestational diabetes mellitus, hypertensive disorders complicating pregnancy (HDCP), maternal metabolic syndrome in pregnancy, and adverse pregnancy outcomes were explored. Results Data for 787 women with a singleton pregnancy were included in the analyses. In women who were TPOAb positive compared to TPOAb negative in the first trimester, baseline HDL-C was significantly lower (1.51 [1.33, 1.81] vs. 1.62 [1.40, 1.87], p = 0.028), and there was a significantly higher incidence of HDCP (15.8% vs. 6%, p < 0.0001), maternal metabolic syndrome in pregnancy (18.8% vs 6.4%, p < 0.0001) or preeclampsia (7% vs, 2.5%, p = 0.024). There was a significant nonlinear association between TPOAb levels in the first trimester and the incidence of HDCP or maternal metabolic syndrome in pregnancy (both p < 0.001). The logit of the probability of having HDCP or maternal metabolic syndrome in pregnancy increased rapidly at TPOAb (log10) ≤ 1.5 (TPOAb (log10) = 1.07 as reference). After adjusting for confounders (maternal age, pre-pregnancy BMI, gravidity, parity and history of adverse events during pregnancy), there was a significantly higher risk of HDCP (odds ratio [OR], 3.029; 95% confidence interval [CI], 1.586, 5.622, p = 0.001), maternal metabolic syndrome in pregnancy (OR, 2.841; 95% CI, 1.473-5.260, p = 0.001), or preeclampsia (OR 3.315, 95% CI 1.305-7.788, p = 0.008) in women who were TPOAb positive compared to TPOAb negative in the first trimester. Conclusion TPOAb positivity in the first trimester may increase the risk of HDCP, maternal metabolic syndrome in pregnancy, and preeclampsia, emphasizing the need for universal screening for thyroid disorders and better diagnostic criteria and management strategies for metabolic disorders during pregnancy.

Clinical significance of the m6A methyltransferase METTL3 in peripheral blood of patients with coronary heart disease.

This study aims to explore the association of methyltransferase-like protein 3 (METTL3) expression with severity of coronary artery stenosis in patients with coronary heart disease (CHD). A total of 100 patients administrated in the Fourth Affiliated Hospital of China Medical University between October 2022 and June 2023 with primary symptoms of chest pain or tightness, or cardiac discomfort, and who underwent coronary angiography for a definitive diagnosis, were included in the study. The baseline characteristics, including TG, TC, LDL-C, HDL-C, uric acid and past history were recorded. Peripheral blood samples were collected to assess the expression levels of METTL3, YT521-B homology domains 1 (YTHDF1), YT521-B homology domains 2 (YTHDF2), and YT521-B homology domains 3 (YTHDF3) using the PCR method. Relative expression levels of METTL3 protein were determined by Western blotting. Correlation analysis were conducted to evaluate the relationship between METTL3/YTHDF1 gene expression and clinical data. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of METTL3 and YTHDF1 for CHD. Binary logistic regression was used to determine whether the expression of METTL3 and YTHDF1 in peripheral blood were risk factors for CHD. The study found no significant differences in baseline characteristics between CHD patients and controls, except for length of stay, Lymphocytes, Neutrophils, AST, HDL-C and modified Gensini score. The gene expression levels of METTL3 and YTHDF1 were significantly higher in CHD patients compared to controls (p < 0.05). Furthermore, METTL3 protein expression was also significantly elevated in the CHD group compared to the control group (p < 0.05). METTL3 gene expression correlated with HDL-C and Gensini score, while YTHDF1 gene expression correlated with Age, WBC, Neutrophils, RDW-CV, modified Gensini score. ROC curve analysis demonstrated an AUC of 0.692 for METTL3 in CHD, with a sensitivity of 66.7% and a specificity of 69.8% at a cut-off value of >0.052. The AUC for YTHDF1 in CHD was 0.623, with a sensitivity of 47.4% and a specificity of 74.4% at a cut-off value of >0.027. Binary logistic regression revealed that only increased METTL3 expression in peripheral blood was an independent risk factor for CHD (p < 0.05). The increased expression of METTL3 in peripheral blood may serve as a potential biomarker and predictive factor for CHD.

Changes in high-density lipoprotein cholesterol with risk of Cardiovascular Disease among initially high-density lipoprotein-high participants

BackgroundHigh-density lipoprotein cholesterol’s (HDL-C) long-held status as a cardiovascular disease (CVD) preventative has been called into question. Most of the evidence, however, focused on either the risk of death from CVD, or on single time point level of HDL-C. This study aimed to determine the association between changes in HDL-C levels and incident CVD in individuals with high baseline HDL-C levels (≥ 60 mg/dL).Methods77,134 people from the Korea National Health Insurance Service-Health Screening Cohort were followed for 517,515 person-years. Cox proportional hazards regression was used to evaluate the association between change in HDL-C levels and the risk of incident CVD. All participants were followed up until 31 December 2019, CVD, or death.ResultsParticipants with the greatest increase in their HDL-C levels had higher risks of CVD (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.05–1.25) and CHD (aHR 1.27, CI 1.11–1.46) after adjusting for age, sex, household income, body mass index, hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol consumption, moderate-to-vigorous physical activity, Charlson comorbidity index, and total cholesterol than those with the lowest increase in HDL-C levels. Such association remained significant even among participants with decreased low-density lipoprotein cholesterol (LDL-C) levels for CHD (aHR 1.26, CI 1.03–1.53).ConclusionsIn people with already high HDL-C levels, additional increases in HDL-C levels may be associated with an increased risk of CVD. This finding held true irrespective of the change in their LDL-C levels. Increasing HDL-C levels may lead to unintentionally elevated risk of CVD.

Abstract 12593: Type 2 Diabetes Mellitus Polygenic Score Predicts New Onset Diabetes in Patients With Established Atherosclerotic Cardiovascular Disease: A FOURIER Sub-Study

Introduction: Polygenic scores (PS) have been created to predict the risk of developing type 2 diabetes (T2D). We tested whether a contemporary T2D PS predicts new-onset T2D in individuals with established atherosclerotic cardiovascular disease (ACSVD) and across a range of HbA1c and BMI levels. Methods: We analyzed individuals without T2D at baseline with available genotyping data from the FOURIER trial. Genetic risk was characterized using a PS for T2D based on 554 previously identified genome-wide significant single nucleotide polymorphisms. PS was analyzed continuously and categorized as high (top 20%) vs. low (bottom 80%). New-onset T2D was pre-specified and adjudicated centrally according to the American Diabetes Association definitions. HRs were calculated and adjusted for baseline age, sex, BMI, HbA1c, SBP, DBP, HDL-C, and triglycerides. Results: The 9115 participants in this study had mean age of 63±9 yrs and 22.5% were women. Mean HbA1c and BMI were 5.6±0.4% and 28.7±5 kg/m 2 , respectively. A total of 641 new-onset diabetes cases occurred over a median of 2.3 years of follow up. T2D PS significantly predicted new-onset T2D (adjusted HR per 1-SD increase 1.13 95% CI 1.04-1.23, P=0.006). The rates of new-onset T2D in the high and low genetic risk categories were 10.8% vs. 6.6 %, respectively (adjusted HR 1.41 95% CI 1.18-1.69, P&lt;0.001, Panel A). The predictive strength of high genetic risk for T2D appeared strongest in those without key clinical risk factors, namely, those without pre-diabetes [HR 2.01 (1.03-3.89); Panel B] and those with normal weight [HR 2.77 (1.65-4.66); Panel C]. There was no treatment interaction with evolocumab for new-onset T2D. Conclusions: Within a relatively short follow up, we found that a contemporary T2D PS strongly predicted new-onset T2D in patients with established ASCVD. This genetic risk appeared more discriminatory in those lacking traditional clinical risk factors.

A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease

BackgroundCurrently, there is no approved medication for non-alcoholic fatty liver disease management. Pre-clinical and clinical studies showed that several bioactive molecules in plants or foods (i.e., curcumin complex, bergamot polyphenol fraction, artichoke leaf extract, black seed oil, concentrate fish oil, picroliv root, glutathione, S-adenosyl-l-methionine and other natural ingredients) have been associated with improved fatty liver disease. Starting from these evidences, our purpose was to evaluate the effects of a novel combination of abovementioned nutraceuticals as a treatment for adults with fatty liver disease.MethodsA total of 140 participants with liver steatosis were enrolled in a randomized, double-blind, placebo controlled clinical trial. The intervention group received six softgel capsules daily of a nutraceutical (namely Livogen Plus®) containing a combination of natural bioactive components for 12 weeks. The control group received six softgel capsules daily of a placebo containing maltodextrin for 12 weeks. The primary outcome measure was the change in liver fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, transaminases, and cytokines were measured at baseline and after intervention.ResultsAfter adjustment for confounding variables (i.e., CAP score and triglyceride at baseline, and changes of serum γGT, and vegetable and animal proteins, cholesterol intake at the follow-up), we found a greater CAP score reduction in the nutraceutical group rather than placebo (− 34 ± 5 dB/m vs. − 20 ± 5 dB/m, respectively; p = 0.045). The CAP score reduction (%) was even greater in those with aged 60 or less, low baseline HDL-C, AST reduction as well as in men.ConclusionOur results showed that a new combination of bioactive molecules as nutraceutical was safe and effective in reducing liver fat content over 12 weeks in individuals with hepatic steatosis.Trial registration ISRCTN, ISRCTN70887063. Registered 03 August 2021—retrospectively registered, https://doi.org/10.1186/ISRCTN70887063

803-P: Serum Adiponectin Level Is Reduced after Short-Term Intensive Insulin Therapy in Patients with Newly Diagnosed Type 2 Diabetes

Objective: Short-term intensive insulin therapy (SIIT) can induce remission of type 2 diabetes (T2D) , and the improvement of insulin sensitivity is considered essential. This study aimed to evaluate the role of adiponectin change during SIIT in patients with newly diagnosed T2D. Methods: SIIT was given to 42 patients with newly diagnosed T2D to normalize blood glucose (4.4-6.0 mmol/L for fasting blood glucose [FBG], 4.4-8.0 mmol/L for 2h-postprandial blood glucose [2hBG]) for two weeks. Serum lipids, adiponectin, and high-sensitive C reactive protein levels, insulin resistance and β-cell function were evaluated before and after SIIT. Results:After the therepy, FBG (11.8±2.9 mmol/L vs. 6.8±1.3mmol/L,P&amp;lt;0.001) and 2hPG (18.4mmol/L± 6.4mmol/L vs. 9.7±2.4mmol/L, P&amp;lt;0.001) were both significantly decreased, with β-cell function (measured by acute insulin response [AIR], HOM-B) and insulin sensitivity (measured by HOMA-IR) improved. Serum adiponectin raised from 2.9±1.2mg/L to 3.4±1.1mg/L (P&amp;lt;0.001) ,while serum triglyceride and LDL-C decreased significantly. Serum adiponectin after treatment was correlated with baseline triglyceride (r = -0.33, P = 0.04) , HDL-C (r = 0.34, P = 0.03) , LDL-C (r = -0.31, P = 0.05) and Hs-CRP (r = -0.33, P = 0.05) ; the change of adiponectin (Δadiponectin) after treatment were significantly correlated with the level of Δtriglyceride (r = 0.38, P = 0.03) . There was no notable correlation between adiponectin and β-cell function index or HOMA-IR. Adiponectin levels were similar between patients who obtained diabetes remission (defined as FBG&amp;lt; 7.0mmol/L, 2hBG&amp;lt;10.0mmol/L without hypoglycemic agents) and those who did not (baseline:3.0±1.5mg/L vs. 2.9±1.0 mg/L; after SIIT:3.4±1.0mg/L vs. 3.3±0.9 mg/L,both P&amp;gt;0.05) . Conclusion: Adiponectin level was significantly increased after SIIT in patients with newly diagnosed T2D. The change of adiponectin is related to the improvement of lipid metabolism and reduced inflammation. Disclosure L.Liu: None. W.Ke: n/a. J.Chen: None. Y.Li: None. Funding The National Key R&amp;D Program of China (2018YFC1314100) , the Key-Area Research and Development Program of Guangdong Province (2019B020230001) , the National Natural Science Fund of China (81800716) , the science and technology program of Guangzhou, 202002020053.

High S100B Levels Predict Antidepressant Response in Patients With Major Depression Even When Considering Inflammatory and Metabolic Markers.

BackgroundThe relationship between antidepressant response and glial, inflammatory, and metabolic markers is poorly understood in depression. This study assessed the ability of biological markers to predict antidepressant response in major depressive disorder (MDD).MethodsWe included 31 MDD outpatients treated with escitalopram or sertraline for 8 consecutive weeks. The Montgomery-Åsberg Depression Rating Scale (MADRS) was administered at baseline and at week 4 and 8 of treatment. Concomitantly, blood samples were collected for the determination of serum S100B, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL)-C levels. Treatment response was defined as ≥50% improvement in the MADRS score from baseline to either week 4 or 8. Variables associated with treatment response were included in a linear regression model as predictors of treatment response.ResultsTwenty-seven patients (87%) completed 8 weeks of treatment; 74% and 63% were responders at week 4 and 8, respectively. High S100B and low HDL-C levels at baseline were associated with better treatment response at both time points. Low CRP levels were correlated with better response at week 4. Multivariate analysis showed that high baseline S100B levels and low baseline HDL-C levels were good predictors of treatment response at week 4 (R2 = 0.457, P = .001), while S100B was at week 8 (R2 = 0.239, P = .011). Importantly, baseline S100B and HDL-C levels were not associated with depression severity and did not change over time with clinical improvement.ConclusionsSerum S100B levels appear to be a useful biomarker of antidepressant response in MDD even when considering inflammatory and metabolic markers.

Abstract 10357: ARO-APOC3, an Investigational RNAi Therapeutic, Shows Similar Efficacy and Safety in Genetically Confirmed FCS and Non-FCS Participants with Severe Hypertriglyceridemia

Background: Familial chylomicronemia syndrome (FCS) is an ultrarare condition caused by biallelic pathogenic DNA variants in lipolysis-associated genes, resulting in severe hypertriglyceridemia (HTG) and associated with high risk of acute pancreatitis with few therapeutic options. In a 16-week Phase 1 study (NCT03783377), subcutaneously administered ARO-APOC3 reduced serum apolipoprotein C3 (APOC3) and TG in healthy volunteers and participants (pts) with HTG and was well tolerated. Purpose: To report on the safety/pharmacodynamic (PD) effects of ARO-APOC3 in both FCS pts with biallelic pathogenic variants and pts with severely elevated TG at screening (&gt;880 mg/dL) but without biallelic pathogenic variants (chylomicronemia (MCM)). Methods: Four genetically confirmed FCS pts received 50 mg ARO-APOC3 and 26 MCM pts received 10, 25, 50, or 100 mg ARO-APOC3 on Days 1 and 29. Since similar PD responses were observed among MCM pts, results were pooled across dose levels. Safety and PD responses were examined. Maximal mean/median changes from baseline for APOC3, TG, non-HDL-C, and HDL-C were reported. Results: Baseline/demographics were comparable between groups, except for mean BMI (22.1 [FCS] and 30.5 [MCM] kg/m 2 ), and mean baseline HDL-C , which were lower in FCS pts (Table 1) (p&lt;0.0001 for both). Mean APOC3 was reduced by 98% and 96% in FCS and MCM pts, respectively. Both groups also showed similar maximum median reductions in TG of 91% and 90%, respectively. Similar to the full study, non-HDL-C was reduced and HDL-C increased with treatment in both groups (Table 1). AEs were similar between groups, suggesting a comparable safety profile. Conclusions: In patients with severe HTG, ARO-APOC3 was safe, and consistently decreased APOC3, TG, and non-HDL-C, and increased HDL-C, regardless of underlying genetic cause of HTG, and may represent a promising RNAi therapeutic for the treatment of severe HTG.

Abstract MP12: Proteomic Predictors Of High-density Lipoprotein Cholesterol Response To Regular Exercise

Introduction: Regular exercise beneficially increases plasma HDL-C levels at the group level. However, variation in individual HDL-C responses to exercise highlight a need for predictive biomarkers of exercise response. Hypothesis: We hypothesized that baseline abundance of circulating proteins is predictive of HDL-C response to exercise and that identified proteins are part of a complex biological network of exercise response. Methods: We measured over 5,000 circulating proteins using an aptamer-affinity based platform (SomaScan) in 667 black and white adults from the HERITAGE Family Study. Fasting plasma HDL-C was measured at baseline and following 20 weeks of supervised endurance exercise training. To predict exercise induced changes in HDL-C using baseline abundance of circulating proteins, models were created using LASSO regression and a 70/30 training test data split with 10-fold cross validation. Biological pathways, networks, and functions involving proteins identified in predictive modeling were investigated by ingenuity pathway analysis (IPA) and integrated molecular pathway level analysis (IMPaLA). Results: Regular exercise significantly increased HDL-C in the sample by 1.5 ± 4.6 mg/dL (p&lt;0.0001), however marked inter-individual differences in response were present (range: -19.5 to +17.4 mg/dL). LASSO regression of circulating proteins only yielded a model of 120 proteins with similar but stronger predictive power to a model of 19 clinical traits (root mean square error = 4.52 and 5.3 mg/dL respectively). LASSO regression of both clinical and proteomic predictors resulted in a final model of baseline HDL-C and 116 circulating proteins, with an improved root mean square error of 4.11 mg/dL. Furthermore, this panel of 116 proteins was able to explain 40.0% of the variance in exercise induced changes in plasma HDL-C, while clinical predictors alone (including baseline HDL-C) explained only 3.9%. Pathway analysis of these 116 proteins identified several biological processes including pathways involved in the progression towards atherosclerosis, angiogenesis, mTOR signaling, and mitochondrial fatty acid synthesis. Conclusions: Circulating proteins may allow for prediction of exercise induced changes in HDL-C. Additionally, proteins predictive of HDL-C response to exercise are associated with important biological pathways and may provide insights into the molecular mechanisms of the benefits of regular exercise.

Predictors of Normalization of Fasting Glucose in Patients With Prediabetes Using Remote Continuous Care Emphasizing Low Carbohydrate Intake

Background: Prediabetes phenotypes differ based on whether an individual exhibits impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or both. The traditional diabetes prevention approach focused on weight loss via fat/caloric restriction and exercise appears less effective in those with IFG. Given that even transient regression to normal glucose regulation is associated with reduced risk of progression to type 2 diabetes, interventions that elicit normal fasting glucose (NFG) may be beneficial. Here, we explored predictors of normalization of fasting glucose (FG) over one-year treatment with carbohydrate restricted nutrition therapy (Carb-R) delivered via a continuous remote care model. Methods: Data were obtained from medical records of adults with prediabetes who were treated at least one year at time of analysis. Of 738 patients with an antecedent prediabetes diagnosis, 460 had IFG (100mg/dL to 125mg/dL) at enrollment in the clinic and were included in this analysis. Patients were counseled on Carb-R targeting nutritional ketosis (NK) and reported fasting blood glucose, blood beta-hydroxybutyrate (BHB), and weight via an app facilitating remote monitoring and medical/coaching support. BHB ≥0.5 mM indicated NK. Cox proportional hazard regression was used to model time of first incidence of NFG at 3, 6, 9, and 12 months and to assess if normalization of fasting glucose was associated with baseline factors, weight change, metformin use, and degree or frequency of NK achieved, analyzed separately. Mean±SE is reported. Results: Patients with IFG were 53.9±0.4 years of age, 64.0% female, HbA1c 5.92±0.02%, and fasting glucose 114.5±0.8 mg/dL at enrollment. During treatment, 199 (43.3%) patients normalized FG at ≥1 time point with mean weight loss of 10.0±0.4 kg (-8.9%) at time of normalization, 192 (41.7%) did not, and 69 (15.0%) were missing glucose data. In an adjusted multivariate model, lower baseline HbA1c (HR 0.60, p=0.03), female sex (HR 1.39, p=0.04), and greater mean BHB value (HR 1.83, p<0.001) or higher proportion of days on which NK was reported (HR 3.23, p<0.001) were associated with reversion to NFG. Age, metformin use, weight change, and baseline fasting glucose, weight, triglycerides, HDL-C, and LDL-C were not associated with reversion to NFG (p>0.05). Conclusions: Greater adherence to Carb-R indicated by greater BHB values and a greater proportion of days in NK were strongly associated with normalization of FG in prediabetes patients with IFG. Weight loss, a common goal for diabetes prevention, was not associated with reversion to NFG. Future studies should assess the effects of Carb-R including NK in other prediabetes phenotypes and on progression to type 2 diabetes.

Association between apolipoprotein E-containing HDL-C and coronary heart disease risk: a community-based cohort study

Objective: To assess whether apolipoprotein E-containing HDL-C (APOE-HDL-C) is causally associated with coronary heart disease (CHD) risk. Methods: In total, 5 417 cardiovascular disease-free participants at baseline were followed up for up to 10 years in the Chinese Multi-provincial Cohort Study. APOE-HDL-C and HDL-C were measured in all participants. APOE-HDL-C/total HDL-C ratio was calculated. Multivariate Cox regression was employed to assess the association between HDL-C related biomarkers and 10-year CHD incident risk. Results: A total of 100 incident CHD events occurred during a mean 6.8 years follow-up. High levels of baseline HDL-C related biomarkers were significantly negatively associated with incident CHD risk. Comparison with participant with lowest level of APOE-HDL-C/total HDL-C ratio, those with highest level of APOE-HDL-C/total HDL-C ratio had 74% decreased risk of CHD (HR=0.26, 95%CI: 0.12-0.71). The individual with the highest level of APOE-HDL-C/total HDL-C ratio had the lowest absolute risk[0.48% (0.44%-0.52%)] of CHD, which was significantly lower than that [0.83% (0.78%-0.88%)] of the individual with the highest level of HDL-C. Conclusions: Our findings revealed that the APOE-HDL-C/total HDL-C ratio was significantly related to a 10-year increased risk of incident CHD, even beyond HDL-C. It seemed that APOE-HDL-C could serve as a new indicator of the anti-atherosclerotic function of HDL.

Major Lipids and Future Risk of Pneumonia: 20-Year Observation of the Atherosclerosis Risk in Communities (ARIC) Study Cohort

BackgroundCirculating lipids have been implicated as important modulators of immune response, and altered lipid levels correlate with the severity of infection. However, long-term prognostic implications of lipid levels regarding future infection risk remain unclear. The current project aims to explore whether baseline lipid levels are associated with risk of future serious infection, measured by hospitalization for pneumonia. MethodsA retrospective analysis was performed in 13,478 participants selected from the Atherosclerosis Risk in Communities (ARIC) study, a large community-based longitudinal cohort in the United States with a median follow-up time of >20 years. First incident of hospitalization for pneumonia was identified through hospital discharge records. Cox proportional hazard models were used to assess the association of baseline major lipid levels (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides) with time to first pneumonia hospitalization. ResultsA total of 1969 (14.61%) participants had a pneumonia hospitalization during a median follow-up time of 21.5 years. The hazard ratio (HR) for pneumonia hospitalization was 0.90 (95% confidence interval, 0.87-0.92) for every 10-mg/dL increase in baseline HDL-C, and 1.02 (95% confidence interval, 1.02-1.03) for every 10-mg/dL increase in baseline triglycerides. HDL-C and triglycerides both remained significant predictors of pneumonia hospitalization after multivariable adjustment. Such associations were not seen with baseline LDL-C or total cholesterol levels. ConclusionLower baseline HDL-C and higher triglyceride levels were strongly associated with increased risk of long-term pneumonia hospitalization in a large longitudinal US cohort.

P0260CLINICAL PROFILE OF PATIENTS INITIATING EVOLOCUMAB IN SPANISH NEPHROLOGY UNITS: A RESTROSPECTIVE, OBSERVATIONAL STUDY IN CLINICAL PRACTICE (RETOSS-NEPHRO)

Abstract Background and Aims Cardiovascular disease is the primary cause of morbidity and mortality in patients with chronic kidney disease (CKD). Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers serum low density lipoprotein cholesterol (LDL-C) levels. Evolocumab is indicated for adult patients with hypercholesterolaemia or mixed dyslipidaemia who are unable to reach LDL-C goals with the maximum tolerated dose of statin or are statin intolerant. This study was conducted to describe clinical characteristics, reasons for therapy initiation and treatment effects in patients treated with evolocumab in Spanish Nephrology units. Method Retrospective, observational, chart review of consecutive patients initiating evolocumab (Feb-2016 to Aug-2018) in 15 Spanish Nephrology Units. Patient characteristics, lipid modifying therapies and lipid profiles over time were retrospectively collected at 24 weeks pre- and 12±4 weeks post-evolocumab initiation. Results 60 patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years; mean (SD) body mass index, 28.0 (4.7) kg/m2; 45.0% had familial hypercholesterolemia (FH) (5.0% homozygous, 23.3% heterozygous, 16.7% undetermined FH); from the total population, 35% were in primary prevention and 65.0% started evolocumab after previous Atherosclerotic Cardiovascular Disease [ASCVD]. Regarding renal function, mean (SD) eGFR was 62.6 (30.0) ml/min/1.73m2; 51.7% of patients had eGFR &amp;lt;60 ml/min/1.73m2 (CKD stage&amp;gt;2), 50.0% had proteinuria (&amp;gt;300 mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%); 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-C at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-C≥160; 29.3% ≥190). Mean (SD) baseline HDL-C and total cholesterol were 48.5 (15.0) mg/dL and 273.1 (82.7) mg/dL, respectively. After 12 weeks, evolocumab resulted in LDL-C reductions of 60.1%, to a mean (SD) of 72.7 (80.3) mg/dL, with similar results observed in patients in primary/secondary prevention, with CKD stage &amp;gt;2/≤2 or with/without proteinuria. Conversely, patients with/without FH showed significant differences between their reductions (46.6% vs 76.6%, respectively, p=0.0276). At week 12, 90.0% of patients reached LDL-C levels &amp;lt;100 mg/dL, 70.0% &amp;lt;70 mg/dL, and 55.0% &amp;lt;55mg/dL, while eGFR levels and statin use remained stable. Conclusion In Spanish Nephrology Units, evolocumab was predominantly prescribed in patients with FH, ASCVD and/or CKD stage &amp;gt;2. Initial evolocumab use was aligned with ESC/EAS dyslipidaemia guidelines, but with higher baseline LDL-C levels than the recommended thresholds. After 12 weeks of evolocumab treatment, LDL–C levels were more than halved and the majority of patients achieved both the 2016 and 2019 EAS/ESC targets of LDL-C control.

Additive Value of High-Density Lipoprotein Cholesterol and C-Reactive Protein Level Assessment for Prediction of 2-year Mortality After Transcatheter Aortic Valve Implantation

Available prediction models are inaccurate in elderly who underwent transcatheter aortic valve implantation (TAVI). The aim of present study was to analyze the separate and combined prognostic values of baseline HDL-C and C-reactive protein (CRP) levels in patients treated successfully with TAVI who had complete 2-year follow-up. We analyzed 334 patients treated with TAVI from 01/2010 to 07/2017 who had measurements of HDL-C and CRP on admission or during qualification for the procedure. Baseline HDL-C ≤46 mg/dl (areas under the curve [AUC] = 0.657) and CRP ≥0.20 mg/dl (AUC = 0.634) were predictive of 2-year mortality. After stratification with both cutoffs, patients with low HDL-C and concomitant high CRP most often had LVEF ≤50% and were high risk as per EuroSCORE II. Those with isolated CRP elevation had the lowest frequency of LVEF ≤50%, but more sarcopenia (based on psoas muscle area). After adjustment in the multivariate analysis for other identified predictors including EuroSCORE II and statin therapy, isolated HDL-C ≤46 mg/dl (identified in 40 patients) and isolated CRP ≥0.20 mg/dl (n = 109) were both independent predictors of 2-year mortality (hazard ratio [HR] = 2.92 and HR = 2.42, respectively) compared with patients with both markers within established cutoffs (n = 105) who had the lowest 2-year mortality (9.5%). Patients with both markers exceeding cutoffs (n = 80) had the highest risk (HR = 4.53) with 2-year mortality of 42.5%. High CRP was associated with increased mortality within the first year of follow-up, whereas low HDL-C increased mortality in the second year. The combination of both markers with EuroSCORE II enhanced mortality prediction (AUC = 0.697). In conclusion, low baseline HDL-C and high CRP jointly contribute to the prediction of increased all-cause mortality after TAVI.

Effect of a Dual PPAR \u03b1/\u03b3 agonist on Insulin Sensitivity in Patients of Type 2 Diabetes with Hypertriglyceridemia- Randomized double-blind placebo-controlled trial

Saroglitazar is a dual PPAR-α/γ agonist approved for the treatment of diabetic dyslipidemia. In addition to reduction in atherogenic lipids, it may also contribute to improvement in insulin sensitivity through PPAR-α/γ agonism, which remains unexplored. We conducted a randomized, double-blind, placebo-controlled trial in treatment-naive T2DM individuals with serum triglyceride >150 mg/dL. Participants were randomized to receive either saroglitazar 4 mg or placebo (1:1) daily for 4 months (n = 30). Insulin sensitivity (SIclamp) was studied using hyperinsulinemic-euglycemic clamp at baseline and at 4 months. We observed a significant reduction in TG (p = 0.001), HbA1c (p = 0.019) and fasting plasma glucose (p = 0.019) and significant increase in HDL-C levels (p < 0.01) with saroglitazar compared to placebo. Further, patients on saroglitazar had a greater improvement in SIclamp (p = 0.026) with the effect persisting despite adjusting for baseline weight, TG, HDL-C and HbA1c (p = 0.002). This was accompanied with significant increase in HOMA-β (p = 0.01) in the saroglitazar group and change in HOMA-β showed a trend towards significance with SIclamp (r = 0.503, p = 0.056). However, change in SIclamp did not significantly correlate with reduction in HbA1c and TG. We conclude that saroglitazar effectively reduces hypertriglyceridemia and improves insulin sensitivity along with β-cell function by reduction in gluco-lipotoxicity and possibly directly through PPAR-γ agonism in patients ofT2DM with hypertriglyceridemia.

P1681Clinical profile of patients initiating evolocumab in Spanish Cardiology Units: A RETrospective, Observational Study of Real-World Clinical Practice (RETOSS-Cardio)

Abstract Background/Introduction Cardiovascular (CV) disease represents the leading cause of death and disability in developed countries with elevated LDL-C among the main risk factors for CV events. Purpose We conducted a study to describe the clinical profile of patients initiating evolocumab in real-world clinical practice, specifically hospital cardiology units in Spain. Methods Retrospective, observational, serial chart review of consecutive hyperlipidemic patients (≥18 years) who initiated evolocumab in 31 Spanish hospital cardiology units from February-2016 to May-2017. Relevant patients characteristics and clinical data were collected from medical records at 12 weeks pre- and 12±4 weeks post-evolocumab initiation. Baseline values correspond to data collected up to 12 weeks prior to initiation of evolocumab. Results 186 patients were enrolled: 72.0% men, mean (SD) age 60.3 (9.8) years, mean (SD) body mass index 28.5 (4.3) kg/m2. CV history and CV risk factors at evolocumab initiation are summarised below (Figure). Half of all patients were statin intolerant and almost all (94.1%) were secondary prevention. At baseline, half (51.1%) of all patients were receiving ezetimibe and 44.1% were receiving high-intensity statins. At baseline, mean (SD) LDL-C was 144.0 (49.0) mg/dL; 38.7% of patients had LDL-C 100-&lt;130 mg/dL, 28.0% had LDL-C 130-&lt;160 mg/dl, 12.4% had LDL-C ≥160 mg/dL, 12.9% had LDL-C ≥190 mg/dL. Mean (SD) baseline HDL-C was 47.7 (13.0) mg/dL. After 12 weeks of evolocumab treatment, mean (SD) LDL-C was reduced by 57.6% (21.6) to 62.2% (44.1) mg/dL (p&lt;0.0001; LDL-C reductions of 57.5% [23.2]/57.6% [21.6] in patients with/without FH and 46.0% [21.5]/58.5% [22.1] in primary/secondary prevention patients, respectively). At week 12, 64.9% patients reached LDL-C levels &lt;70 mg/dL, and 49.1% &lt;50 mg/dL, while statin use remained stable (data not shown). Only 3.2% (n=6) patients discontinued evolocumab (voluntary withdrawal, mostly). Baseline CV history and CV risk factors Conclusions In Spanish Cardiology Units, evolocumab was typically prescribed in patients with FH and/or atherosclerotic cardiovascular disease, aligned with 2016 ESC/EAS guidelines recommendation on PCSK9i usage. Patients tended to have LDL-C levels above the recommended thresholds with LDL- levels markedly reduced after 12 (± 4) weeks of evolocumab treatment. Acknowledgement/Funding This work was supported by Amgen.

Predictors of Cholesterol Lowering with Corn Oil Consumption: Results from a Pooled Analysis of Randomized, Free-living Feeding Trials (P08-112-19)

ObjectivesThis pooled analysis of data from two clinical trials was designed to evaluate potential predictors of lipid responses to corn oil consumption. MethodsFree-living subjects in two clinical feeding trials consumed study products made with corn oil (each 4 tablespoons per day) as part of their habitual diets for four weeks. Subjects were required to have fasting low-density lipoprotein (LDL-C) levels ≥115 and < 190 mg/dL and triglycerides (TG) < 375 mg/dL. Baseline, end of treatment and % changes from baseline in fasting LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) levels were analyzed in the per protocol samples for all subjects and according to the following subgroups: tertile of baseline LDL-C (< 122.5, 122.5–135.25 or > 135.25 mg/dL), median baseline saturated fatty acid intake (< or ≥ 11.9% of energy), median body mass index (BMI; < or ≥ 21.35 kg/m2), median age (< or ≥ 51 y), male or female and non-Hispanic white or other race/ethnicity. Within group p-values were generated using paired t-tests or, when the values were non-normally distributed, the Wilcoxon test. ResultsOverall (n = 42 subjects) median baseline LDL-C, non-HDL-C, total-C, HDL-C and TG concentrations were 139, 158, 208, 47 and 101 mg/dL, respectively, and the total-C: HDL-C ratio was 4.3. Changes from baseline in LDL-C and non-HDL-C levels during corn oil consumption in the overall sample were −4.3% and −3.5%, respectively. LDL-C and non-HDL-C responses were statistically significant for subjects in the highest baseline LDL-C tertile (−8.3%, P = 0.017 and −5.5%, P = 0.025, respectively) and for subjects with BMI below the median (−5.6%, P = 0.013 and −4.5%, P = 0.009, respectively). LDL-C and non-HDL-C responses did not reach statistical significance in any other subgroup. ConclusionsHigher baseline LDL-C and lower BMI were predictive of larger reductions in LDL-C and non-HDL-C, two major risk factors for cardiovascular disease, during corn oil consumption in a pooled analysis from two feeding studies. Funding SourcesACH Food Companies, Inc.

1219-P: Enhanced Response in Serum Ketone Level in Men Compared with Women by Administration of SGLT2 Inhibitor

SGLT2 inhibitors (SGLT2is) reduce hyperglycemia and insulin levels via increased urinary glucose excretion (UGE). Reduced insulin triggers decreased tissue glucose disposal and increased lipid use followed by ketone production. The metabolic response to starvation, the production of beta-hydroxybutyrate (BHB), was reported to be influenced by sex and menopausal status in healthy persons. However, little is known of sex- and menopausal status-specific effects of SGLT2is on BHB. This study investigated the effect of the SGLT2i tofogliflozin on BHB according to sex and menopausal status in type 2 diabetes mellitus (T2DM). Analyzed were 190 T2DM patients taking tofogliflozin as initial monotherapy in a Phase 3 study. Baseline characteristics were: men (66%); premenopausal (7%) and postmenopausal women (27%), age (mean 58y), and mean HbA1c (7.8%), BMI (26kg/m2), BHB (69µmol/L) and eGFR (83mL/min/1.73m2). Sex- and menopausal status-specific differences were analyzed by multivariate analysis. Longer duration of diabetes and lower baseline HDL-C and adiponectin were noted in men while age and HbA1c, BMI, BHB and eGFR were identical between sexes. Increases in BHB at weeks 4 and 52 were: men, median +128%* and +64*, respectively (+ p&amp;lt;0.01 vs. baseline); women, +48* and +58*, respectively. Mean increases in the fasting free fatty acid-to-insulin ratio (FIR) at week 52 were +88%* for men and +53* for women. Reductions in HbA1c and fasting insulin and increases in UGE and free fatty acids at week 52 were similar between sexes. Multivariate analyses showed a greater increase in BHB at week 52 in men than in women, especially postmenopausal women. Further, FIR increased greater in men than in women. Finally, premenopausal women had a greater increase in BHB than postmenopausal women. Results suggest that the different degrees of BHB elevation between sexes via tofogliflozin may provide clinical insights into sex- and menopause-specific metabolic responses to increased lipid use via SGLT2is in T2DM. Disclosure A. Yoshida: Employee; Self; Kowa Pharmaceutical Co. Ltd. Y. Matsubayashi: None. T. Nojima: Employee; Self; Kowa Co., Ltd. H. Suganami: Employee; Self; Kowa Co., Ltd. K. Kaku: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.