High-density Lipoprotein Cholesterol Concentrations Research Articles

#1672 High level of HDL-C is associated with a higher risk of ESRD and all-cause mortality in patients with DM and CKD

Abstract Background and Aims Previous studies have regarded high-density lipoprotein cholesterol (HDL-C) as ‘good cholesterol’; however, recent research has unveiled a higher incidence of adverse events among individuals with extremely elevated HDL-C levels. Method Two cohorts of subjects were analyzed in this study. In the first cohort, a total of 375 participants with DKD who underwent renal-biopsy between January 2008 and September 2020, from West China Hospital T2DM-DKD cohort, were enrolled for the longitudinal observational study. Additionally, 3,262 participants with DM and chronic kidney disease (CKD) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the association between HDL-C concentration and the incidence of end-stage renal disease (ESRD) as well as all-cause mortality. Results Patients were divided into three groups based on HDL-C levels. After a median follow-up of 36 months, 44% of the patients developed ESRD in T2DM-DKD cohort. Patients in Group 3 (HDL-C ≥1.55 mmol/L) exhibited a higher risk of ESRD compared to Group 1 (HDL-C <1.03 mmol/L). After adjusting for confounders, Group 3 patients still had a significantly higher risk of ESRD (adjusted HR: 1.68, 95% CI: 1.03, 2.71). Analysis of HDL subfractions revealed that a higher HDL3/HDL2 ratio was associated with a lower risk of ESRD. Furthermore, in the NHANES cohort, higher HDL-C levels were linked to a higher risk of all-cause mortality during a median follow-up of 75 months as the result of the weighted Kaplan-Meier curves (p = 0.02). Notably, in patients with CKD stages 1-2, Group 3 participants had a significantly higher hazard ratio (HR: 1.61, 95% CI: 1.19, 2.19) after adjusting for confounders. Conclusion This study challenges the notion of HDL-C as ‘good cholesterol’ in patients with DKD, as higher HDL-C levels were associated with increased risks of ESRD and all-cause mortality. Additionally, the study highlights the potential protective effect of a higher HDL3/HDL2 ratio against ESRD. These findings contribute to reevaluating the role of HDL-C and its subfractions in DKD patients.

Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction

This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96–0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96–1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P < 0.05). AIP levels were not independently associated with the risk of composite outcomes in both patients with non-AMI and AMI. In conclusion, an inverse association between AIP and the risk of HPR was observed in patients with non-AMI. This suggests that the association between plasma atherogenicity and platelet reactivity may play a substantial role in the development of AMI.Trial registration: NCT04734028.

Biomarker signatures associated with ageing free of major chronic diseases: results from a population-based sample of the EPIC-Potsdam cohort.

A number of biomarkers denoting various pathophysiological pathways have been implicated in the aetiology and risk of age-related diseases. Hence, the combined impact of multiple biomarkers in relation to ageing free of major chronic diseases, such as cancer, cardiovascular disease and type 2 diabetes, has not been sufficiently explored. We measured concentrations of 13 biomarkers in a random subcohort of 2,500 participants in the European Prospective Investigation into Cancer and Nutrition Potsdam study. Chronic disease-free ageing was defined as reaching the age of 70years within study follow-up without major chronic diseases, including cardiovascular disease, type 2 diabetes or cancer. Using a novel machine-learning technique, we aimed to identify biomarker clusters and explore their association with chronic disease-free ageing in multivariable-adjusted logistic regression analysis taking socio-demographic, lifestyle and anthropometric factors into account. Of the participants who reached the age of 70years, 321 met our criteria for chronic-disease free ageing. Machine learning analysis identified three distinct biomarker clusters, among which a signature characterised by high concentrations of high-density lipoprotein cholesterol, adiponectin and insulin-like growth factor-binding protein 2 and low concentrations of triglycerides was associated with highest odds for ageing free of major chronic diseases. After multivariable adjustment, the association was attenuated by socio-demographic, lifestyle and adiposity indicators, pointing to the relative importance of these factors as determinants of healthy ageing. These data underline the importance of exploring combinations of biomarkers rather than single molecules in understanding complex biological pathways underpinning healthy ageing.

Response of laying hens fed diet supplemented with a mixture of olive, laurel, and rosemary leaf powders: Metabolic profile, oxidative status, intestinal histomorphology, and egg quality

This study aimed to evaluate the effects of a mixture of olive, laurel, and rosemary leaf powders, on the oxidative state, biochemical, immune, intestinal morphophysiological parameters, and egg quality of laying hens. One hundred Lohmann Brown hens (28 weeks old) were equally assigned to two groups (n. 50) corresponding to a basal control diet (CON) or the diet supplemented with 6 g/kg feed of leaf powder mixture (LPM) containing olive, laurel, and rosemary leaves (1:1:1), for 60 days. Oxidative status, biochemical indices, immune response, cecal short chain fatty acids (SCFAs), intestinal morphological characteristics, and some egg traits were evaluated at the end of the experiment. The results indicated that LPM improved (P < 0.05) the oxidative status (TOS, ROMs), the immune system (IL-6, IL-1β, and TNF-α), the total protein and HDL cholesterol content, whereas it decreased (P < 0.05) total cholesterol and LDL cholesterol. Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase were significantly (P < 0.05) lower in the LPM than in the CON group. A significant increase (P < 0.05) in SCFA content in the caecum, as well as in villi height and crypt depth in both duodenum and ileum of LPM-treated hens, was observed. Egg quality parameters were not influenced (P > 0.05) by LPM. These findings indicate that LPM can be considered a candidate as an antioxidant ingredient for functional food in laying hens.

Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials.

Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

Association between HDL cholesterol with diabetic retinopathy in diabetic patients: a cross-sectional retrospective study

ObjectiveDiabetic patients are often comorbid with dyslipidemia, however, the relationship between high-density lipoprotein cholesterol(HDL-C) and diabetic retinopathy (DR) in the adult diabetic population remains to be fully elucidated.The aim of this study is to evaluate the associations between HDL-C and DR in the United States adults with diabetes.MethodsA total of 1708 participants from the National Health and Nutrition Examination Survey (NHANES) 2005–2008 were enrolled in the present study. Fundus images of all study subjects were captured and evaluated using a digital camera and an ophthalmic digital imaging system, and the diagnosis of DR was made by the severity scale of the Early Treatment Diabetic Retinopathy Study (ETDRS).Roche Diagnostics were used to measure serum HDL-C concentration. The relationship of DR with HDL-C was investigated using multivariable logistic regression. The potential non-line correlation was explored with smooth curve fitting approach.ResultsThe fully-adjusted model showed that HDL-C positively correlated with DR(OR:1.69, 95%CI: 1.25–2.31).However, an inverted U-shaped association between them was observed by applying the smooth curve fitted method. The inflection point of HDL-C(1.99mmol/l) was calculated by utilizing the two-piecewise logistic regression model. In the subgroup analysis, the inverted U-shaped nonlinear correlation between HDL-C and DR was also found in female, Non-Hispanic White, and lower age groups.ConclusionOur study revealed an inverted U-shaped positive relationship between HDL-C and DR.The findings may provide us with a more comprehensive understanding of the association between HDL-C and DR.

Guiding Dyslipidemia Treatment: A Population Pharmacokinetic-Pharmacodynamic Framework for Obicetrapib.

Obicetrapib is a selective inhibitor of cholesteryl ester transfer protein that is currently in phase 3 of development for the treatment of dyslipidemia as adjunct therapy. The purpose of this study was to comprehensively characterize the pharmacokinetic (PK) and pharmacodynamic (PD) disposition of obicetrapib. Data from 7 clinical trials conducted in healthy adults and those with varying degrees of dyslipidemia were included for model development. The structural model that best described obicetrapib PK was a 3-compartment model with 4-compartment transit absorption and first-order elimination. Body weight was the only covariate found to significantly explain observed variability and was therefore included using allometric scaling on all disposition parameters. For a typical patient weighing 75 kg, the estimated apparent total body clearance and apparent volume of distribution of the central compartment was 0.81 L/h and 36.1 L, respectively. The final PK model parameters were estimated with good precision and were ultimately leveraged to sequentially inform 2 turnover models that describe obicetrapib's effect on low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) concentrations. The maximum stimulatory effect of obicetrapib on LDL-C loss was estimated to be 1.046, while the maximum inhibitory effect of obicetrapib on HDL-C loss was 0.691. This corresponds to a predicted typical maximum percent change from baseline LDL-C and HDL-C of 51.1% and 224%, respectively. The final sequential model described obicetrapib PKPD well and was ultimately able to both demonstrate evidence of internal consistency and support decision-making throughout the development lifecycle.

The Association of Dyslipidemias with Cholelithiasis: A Case-Control Study Conducted at Pakistan Institute of Medical Sciences (PIMS), Islamabad

Objective: To find the association of lipid profile with early sign of cholecystitis (gall stones formation). Study Design: Case control study. Place and Duration of Study Methodology: The study recruited cholecystitis patients from 1st April 2022 to 30th September 2022 at Pathology Department, Pakistan Institute of Medical Sciences, Islamabad. Those patients having an age above 40 years and clinically diagnosed with gall bladder stone, went under ultrasonography examination, were included in the study. A total of 100 cases were compared with 100 controls in a case control study design. The lipid profile included serum concentrations of HDL cholesterol, Total Cholesterol, triglyceride, LDL cholesterol levels. Other tests as fasting blood glucose (FBG), total bilirubin (T-bil), alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cr), uric acid (UA), and urea nitrogen (UN) were also conducted. Results: The mean age of the gall stone patients and of normal controls was 51.71±13.48 and 42.00±13.14 years respectively. There was no variance in the BMI of both groups. The incidence of kidney stones was higher in the cases than controls while hypertension was more commonly reported in the 36% of the cases in comparison to the 19% of the controls. The logistic regression analysis presented a data where significant difference within lipid profile values of cases and controls could be seen having high values reported in cases than controls. The multivariant analysis of the lipid profile analyzed values presented a significant variance in the odds ration of high-density lipoprotein cholesterol levels and triglycerides of cases and controls. Conclusion: Low levels of high-density lipoprotein cholesterol and high levels of triglycerides are associated with the risk of gall bladder formation.

Association of High-Density Lipoprotein Parameters and Risk of HeartFailure: A Multicohort Analysis.

High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease. The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes. Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection fraction were assessed using adjusted Cox models. Among 16,925 participants (53.5% women; 21.8% Black), there were 612 incident HF events (3.6%) (HF with reduced ejection fraction, 309 [50.5%]; HF preserved ejection fraction, 303 [49.5%]) over median follow-up of 11.4 years. In adjusted models, higher HDL-P was significantly associated with lower HF risk (HR of highest vs lowest tertile of HDL-P: 0.76 [95%CI: 0.62-0.93]). Larger HDL-size was significantly associated with higher overall HF risk (HR of largest vs smallest tertile of HDL-size: 1.27 [95%CI: 1.03-1.58]). HF risk associated with HDL-P and HDL-size was similar for HF subtypes. In adjusted analyses, there was no significant association between HDL-C and HF risk. Higher HDL-C/HDL-P was significantly associated with higher overall HF risk (HR of highest vs lowest tertile of HDL-C/HDL-P: 1.29 [95%CI: 1.04-1.60]). Higher HDL-P was associated with a lower risk of HF. In contrast, larger HDL-size was associated with higher risk of HF and there was no significant association observed between HDL-C and HF risk after accounting for cardiovascular risk factors.

Weight loss benefits on HDL cholesterol persist even after weight regaining.

Obesity-related comorbidities may relapse in patients with weight regain after bariatric surgery. However, HDL cholesterol (HDLc) levels increase after surgery and seem to remain stable despite a gradual increase in BMI. The aim of this study is to analyze the effects of weight regain after bariatric surgery on HDL cholesterol. This is a retrospective, observational, cohort study in patients who underwent bariatric surgery in the Hospital de la Santa Creu i Sant Pau (Barcelona) between 2007 and 2015. Patients without at least 5 years of follow-up after surgery, under fibrate treatment, and those who required revisional surgery were excluded from the analysis. Data were collected at baseline, 3 and 6 months after surgery, and then annually until 5 years post-surgery. One hundred fifty patients were analyzed. 93.3% of patients reached > 20% of total weight loss after surgery. At 5th year, 37% of patients had regained > 15% of nadir weight, 60% had regained > 10%, and 22% had regained < 5% of nadir weight. No differences were found in HDLc levels between the different groups of weight regain, nor in the % of change in HDLc levels between nadir weight and 5 years, or in the proportion of patients with normal HDLc concentrations either. HDLc remains stable regardless of weight regain after bariatric surgery.

Effect of moxibustion on the SIRT1/FOXO3a signaling pathway in ApoE-/- mice with atherosclerosis.

To observe the effects of moxibustion on blood lipid metabolism, pathological morphology of thoracic aorta, and the expression of silent information regulator 1 (SIRT1) and forkhead box transcription factor O3a (FOXO3a) in ApoE-/- atherosclerosis (AS) mice, so as to explore the potential mechanism of moxibustion in preventing and treating AS. Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, simvastatin group, and moxibustion group, with 10 mice in each group. From the first day of modeling, mice in the moxibustion group received mild moxibustion treatment at "Shenque"(CV8), "Yinlingquan"(SP9), bilateral "Neiguan"(PC6) and "Xuehai"(SP10) for 30 min per time；the mice in the simvastatin group were given simvastatin orally (2.5 mg·kg-1·d-1), with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. The body weight and general condition of the mice were observed and recorded during the intervention period. After the intervention, the contents of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemistry analyzer. Hematoxylin eosin (HE) staining was used to observe the pathological morphology of the thoracic aorta. ELISA was used to measure the contents of serum oxidized low-density lipoprotein (ox-LDL) and superoxide dismutase (SOD) activity. Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta. Compared with the control group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of the model group mice were significantly increased(P<0.05, P<0.01), while the HDL-C contents, SOD activity, and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05, P<0.01). HE staining showed thickening of the aortic intima, endothelial cell degeneration, swelling, and shedding. Compared with the model group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01), while the serum SOD activity, expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01). The HDL-C contents were significantly increased in the simvastatin group(P<0.05). The thoracic aortic structure was more intact in both groups, with a more regular lumen and orderly arrangement of the elastic membrane in the media, and a slight amount of endothelial cell degeneration and swelling in the intima. There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups. Moxibustion can reduce the body weight of AS model mice, regulate lipid levels, repair vascular intima, and alleviate endothelial damage. Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.

The association of the platelet/high-density lipoprotein cholesterol ratio with self-reported stroke and cardiovascular mortality: a population-based observational study

BackgroundPrevious studies have shown that the relationship between high-density lipoprotein cholesterol (HDL-C) and stroke is controversial, and the association between the platelet/high-density lipoprotein cholesterol ratio (PHR), a novel marker for inflammation and hypercoagulability states, and stroke has not been established.MethodsThis study presents an analysis of cross-sectional data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES). Stroke history, HDL-C levels, and platelet counts were obtained during cross-sectional surveys. The PHR was calculated as the ratio of the number of platelets to HDL-C concentration. Weighted logistic regression was used to assess the associations of HDL-C and the PHR with stroke. Nonlinearity of this relationship was determined through restricted cubic splines (RCSs) and two-piecewise linear regression for identifying inflection points. Furthermore, Cox regression was utilized to prospectively analyze the associations of the PHR and HDL-C concentration with cardiovascular disease (CVD) mortality in stroke survivors.ResultsA total of 27,301 eligible participants were included in the study; mean age, 47.28 years and 50.57% were female, among whom 1,040 had a history of stroke. After full adjustment, the odds ratio (OR) of stroke associated with a per standard deviation (SD) increase in the PHR was estimated at 1.13 (95% confidence interval (CI): 1.03 − 1.24, P = 0.01), and the OR of stroke associated with a per SD increase in HDL-C was 0.95 (95% CI: 0.86–1.05, P = 0.30). The RCS indicated a nonlinear relationship for both variables (PPHR = 0.018 and PHDL-C = 0.003), and further piecewise linear regression identified inflection points at PHR = 223.684 and HDL-C = 1.4 mmol/L. Segmental regression indicated that in the PHR ≥ 223.684 segment, the estimated OR of stroke associated with a per-SD increase in the PHR was 1.20 (95% CI: 1.09 − 1.31, P < 0.001), while the association of stroke with HDL-C was not significant before or after the inflection point (P > 0.05). Furthermore, Cox regression and RCS showed that a per-SD increase in the PHR was linearly associated with a greater risk of CVD mortality among stroke survivors (HR: 1.14, 95% CI: 1.06 − 1.22, P < 0.001; nonlinear, P = 0.956), while HDL-C was not significantly associated with CVD mortality.ConclusionThe association between the PHR and stroke incidence exhibited a significant threshold effect, with an inflection point at 223.684. A PHR exceeding 223.684 was positively associated with stroke, while the association between HDL-C and stroke was not significant. Additionally, the PHR was positively and linearly associated with CVD mortality among stroke survivors.

Dietary Lysophosphatidylcholine Improves the Uptake of Astaxanthin and Modulates Cholesterol Transport in Pacific White Shrimp Litopenaeus vannamei.

Astaxanthin (AST), functioning as an efficient antioxidant and pigment, is one of the most expensive additives in shrimp feeds. How to improve the uptake efficiency of dietary astaxanthin into farmed shrimp is of significance. The present study investigated the effects of lysophosphatidylcholine (LPC), an emulsifier, on dietary astaxanthin efficiency, growth performance, body color, body composition, as well as lipid metabolism of juvenile Pacific white shrimp (average initial body weight: 2.4 g). Three diets were prepared: control group, the AST group (supplemented with 0.02% AST), and the AST + LPC group (supplemented with 0.02% AST and 0.1% LPC). Each diet was fed to triplicate tanks, and each tank was stocked with 30 shrimp. The shrimp were fed four times daily for eight weeks. The AST supplementation improved the growth of white shrimp, while LPC further promoted the final weight of shrimp, but the whole-shrimp proximate composition and fatty acid composition were only slightly affected by AST and LPC. The LPC supplementation significantly increased the astaxanthin deposition in the muscle. The LPC supplementation significantly increased the shell yellowness of both raw and cooked shrimp compared to the AST group. Moreover, the dietary LPC increased the high-density lipoprotein-cholesterol content but decreased the low-density lipoprotein-cholesterol content in the serum, indicating the possible regulation of lipid and cholesterol transport. The addition of astaxanthin significantly up-regulated the expression of npc2 in the hepatopancreas compared to the control group, while the addition of LPC down-regulated the expression of mttp compared to the AST group. In conclusion, the LPC supplementation could facilitate the deposition of dietary astaxanthin into farmed shrimp and further enlarge the beneficial effects of dietary astaxanthin. LPC may also independently regulate shrimp body color and cholesterol transportation. This was the first investigation of the promoting effects of LPC on dietary astaxanthin efficiency.

No effect of liraglutide on high density lipoprotein apolipoprotein AI kinetics in patients with type 2 diabetes

AimThe catabolism of high density lipoprotein (HDL) apolipoprotein AI (apoAI) is accelerated in patients with type 2 diabetes (T2D), related to hypertriglyceridemia, insulin resistance and low plasma adiponectin levels. Since liraglutide is likely to partly correct these abnormalities, we hypothesized that it might have a beneficial effect on HDL apoAI kinetics in patients with T2D. MethodsAn in vivo kinetic study of HDL apoAI was performed in 10 patients with T2D before and after 6 months of treatment with 1.2 mg/day of liraglutide, using a bolus of l-[1–13C]leucine followed by a 16-hour constant infusion. ResultsLiraglutide reduced BMI (34.9 ± 4.7 vs 36.6 ± 4.9 kg/m2, P = 0.012), HbA1c (7.1 ± 1.1 vs 9.6 ± 2.6%, P = 0.003), HOMA-IR (5.5 ± 1.9 vs 11.6 ± 11.2, P = 0.003), fasting triglycerides (1.76 ± 0.37 vs 2.48 ± 0.69 mmol/l, P < 0.001) and triglycerides during kinetics (2.34 ± 0.81 vs 2.66 ± 0.65 mmol/l, P = 0.053). Plasma HDL cholesterol and adiponectin concentrations were unchanged (respectively 0.97 ± 0.26 vs 0.97 ± 0.19 mmol/l, P = 1; 3169 ± 1561 vs 2618 ± 1651 µg/l, P = 0.160), similar to triglyceride content in HDL (5.13 ± 1.73 vs 5.39 ± 1.07%, P = 0.386). Liraglutide modified neither HDL apoAI fractional catabolic rate (0.35 ± 0.11 vs 0.38 ± 0.11 pool/day, P = 0.375), nor its production rate (0.44 ± 0.13 vs 0.49 ± 0.15 g/l/day, P = 0.375), nor its plasma concentration (1.26 ± 0.19 vs 1.29 ± 0.14 g/l, P = 0.386). ConclusionSix months of treatment with 1.2 mg/day of liraglutide had no effect on the kinetics of HDL apoAI in patients with T2D. The lack of decrease in triglyceride content in HDL related to an only moderate decrease in triglyceridemia, probably greatly explains these results. Insufficient improvement of insulin sensitivity and adiponectinemia may also be implied.

Metabolic effects of testosterone added to intensive lifestyle intervention in older men with obesity and hypogonadism.

Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear. To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism. Secondary analysis of a randomized, double-blind, placebo-controlled trial. Veterans Affairs Medical Center. 83 older (age ≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and persistently low AM testosterone (< 10.4 nmol/L) associated with frailty. LT (weight management and exercise training) plus either testosterone (LT+TRT) or placebo (LT+Pbo) for six months. Primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure, and metabolic syndrome score. HbA1c decreased similarly in LT+TRT and LT+Pbo groups (-0.5% vs. -0.6%, respectively; p= 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in LT+Pbo group vs. 0.2 ± 1.1 mg/dL in LT+TRT group, p= 0.01) and adiponectin levels (-408 ± 489 ng/mL in TRT+LT group vs 1832 ± 468 ng/mL in LT+Pbo group, p= 0.02). In older men with obesity and hypogonadism, adding TRT for six months to LT does not result in further improved cardiometabolic profiles, and could potentially blunt some of the metabolic benefits induced by LT.

The high-density lipoprotein cholesterol (HDL-C)-concentration-dependent association between anti-inflammatory capacity and sepsis: A single-center cross-sectional study.

Known to have pleiotropic functions, high-density lipoprotein (HDL) helps to regulate systemic inflammation during sepsis. As preserving HDL-C level is a promising therapeutic strategy for sepsis, the interaction between HDL and sepsis worth further investigation. This study aimed to determine the impact of sepsis on HDL's anti-inflammatory capacity and explore its correlations with disease severity and laboratory parameters. We enrolled 80 septic subjects admitted to the intensive care unit and 50 controls admitted for scheduled coronary angiography in this cross-sectional study. We used apolipoprotein-B depleted (apoB-depleted) plasma to measure the anti-inflammatory capacity of HDL-C. ApoB-depleted plasma's anti-inflammatory capacity is defined as its ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical-vein endothelial cells. A subgroup analysis was conducted to investigate in septic subjects according to disease severity. ApoB-depleted plasma's anti-inflammatory capacity was reduced in septic subjects relative to controls (VCAM-1 mRNA fold change: 50.1% vs. 35.5%; p < 0.0001). The impairment was more pronounced in septic subjects with than in those without septic shock (55.8% vs. 45.3%, p = 0.0022). Both associations were rendered non-significant with the adjustment for the HDL-C level. In sepsis patients, VCAM-1 mRNA fold change correlated with the SOFA score (Spearman's r = 0.231, p = 0.039), lactate level (r = 0.297, p = 0.0074), HDL-C level (r = -0.370, p = 0.0007), and inflammatory markers (C-reactive protein level: r = 0.441, p <0.0001; white blood cell: r = 0.353, p = 0.0013). ApoB-depleted plasma's anti-inflammatory capacity is reduced in sepsis patients and this association depends of HDL-C concentration. In sepsis patients, this capacity correlates with disease severity and inflammatory markers. These findings explain the prognostic role of the HDL-C level in sepsis and indirectly support the rationale for targeting HDL-C as sepsis treatment.

Predictors of visceral obesity among patients with pathology of the gastrointestinal tract

Background. In Ukraine, metabolic syndrome remains one of the most important problems of family medicine, it contributes to an increase in the prevalence of digestive diseases. Among the components of metabolic syndrome, researchers consider visceral obesity to be the most prognostically unfavo­rable. The purpose is to optimize diagnostic approaches to the formation of a risk group for the detection of visceral obesity in gastroenterology patients. Materials and methods. Eighty patients with gastrointestinal diseases were examined, 56 men (70.0 %) and 24 women (30.0 %). The age of the patients ranged from 18 to 66 years, with an average of (39.04 ± 1.03) years. TANITA MC-780MA body composition analyzer scales (Japan) were used to assess body structure. In all patients, serum levels of glucose, insulin, leptin, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) were determined, as well as low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), atherogenicity coefficient (AC) and homeostasis model assessment of insulin resistance (HOMA-IR). Results. Gastroenterological patients with visce­ral obesity had more pronounced changes in lipid and carbohydrate metabolism, which were characterized by a decrease in the content of HDL-C by 16.3 % (p &lt; 0.05), an increase in TG by 41.9 % (p &lt; 0.001), VLDL-C by 41.7 % (p &lt; 0.01), AС by 41.6 % (p &lt; 0.01), HOMA-IR by 28.0 % (p &lt; 0.01) compared to patients without visceral obesity. According to the results of the correlation analysis, functional relationships were found between the amount of visceral fat and the level of leptin (r = 0.37; р = 0.0008), insulin (r = 0.41; р = 0.001), HOMA-IR (r = 0.48; р = 0.00001), TG (r = 0.452; р = 0.017), LDL-C (r = 0.383; р = 0.016), AС (r = 0.566; p &lt; 0.001), TG/glucose ratio (r = 0.27; p = 0.0181), HDL-C (r = –0.448; p = 0.004). Determined predictors for the development of visceral obesity were as follows: triglycerides/high-density lipoprotein ratio (odds ratio (OR) 1.32; p = 0.0001), triglycerides/glucose ratio (OR 1.17; p = 0.0014), HOMA-IR (OR 1.26; p = 0.0013), atherogenicity coefficient (OR 1.13; p = 0.0001), leptin/triglycerides ratio (OR 1.35; p = 0.0014). Conclusions. The formation of a risk group for the detection of visceral obesity with the help of defined diagnostic criteria will allow to personalize the management of gastroenterology patients already at the primary level of medical care.

Metabolic abnormalities in patients with non-alcoholic fatty liver disease with immune response to SARS-CoV-2

Background. It is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect hepatocytes. At the same time, overweight and obesity are surrogate markers of the adverse effects of coronavirus disease 2019 (COVID-19). The purpose of the study: to evaluate changes in lipid and carbohydrate metabolism and their indices in the serum of patients with non-alcoholic fatty liver disease (NAFLD) with an immune response to SARS-CoV-2. Materials and methods. We studied 37 patients with NAFLD who had IgG to SARS-CoV-2. All patients were divided into two groups: group I consisted of 19 participants who were PCR-negative for SARS-CoV-2, group II included 18 patients who had COVID-19, as confirmed by PCR testing. The content of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), glucose, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol (VLDL-C), atherogenicity coefficient, insulin resistance indices (HOMA-IR), TG to glucose (TG/Gly) and TG to HDL-C (TG/HDL-C) ratio were assessed in all patients. Results. Among patients with NAFLD with an immune response to SARS-CoV-2, dyslipidemia manifested by a probable increase in the median TG content in groups I and II by 2.5 and 3.4 times (р = 0.0001), respectively; TC — by 1.2 times (р = 0.0425) in both groups, with a tendency to increase; VLDL-C — by 1.8 (р = 0.010) and 2.5 times (р = 0.0022), respectively, and a decrease in the median content of HDL-C by 1.7 (р = 0.0016) and 1.9 times (р = 0.0008), respectively, in blood serum. The identified changes led to a statistically significant increase in the median atherogenicity coefficient in groups I and II — by 2.2 (р = 0.0036) and 2.5 times (р = 0.007). An increase in the HOMA-IR did not have a statistically significant difference between the groups: in group I, this index increased by 3.1 times (p &lt; 0.05) compared with the controls, in group II — by 3 times (p &lt; 0.05). In addition, patients in both groups had a statistically significant increase in TG/Gly and TG/HDL-C ratio compared to controls. However, the detected changes were more pronounced in group II, where TG/Gly and TG/HDL-C levels were 1.5 (р = 0.038) and 1.9 times (р = 0.035), respectively, higher than in group I. Conclusions. Patients with an immune response to SARS-CoV-2 with NAFLD have disorders of lipid and carbohydrate metabolism. At the same time, the signs of dyslipidemia were more pronounced in participants with a history of SARS-CoV-2. TG/Gly and TG/HDL-C ratio should be included in the diagnostic algorithm for assessing insulin resistance in patients with COVID-19 who are overweight or obese.

Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

Effects of sleep-disordered breathing on serum lipid levels in children:a case control study

BackgroundSleep-disordered breathing (SDB) during childhood is common and includes a range of breathing abnormalities that range from primary snoring (PS) to obstructive sleep apnea syndrome (OSAS).Studies have shown that not only OSAS, but also PS, which is originally considered harmless, could cause cardiovascular, cognitive, behavioral, and psychosocial problems. Many researches are focused on the relation of OSA and serum lipid levels. However, little studies are focused on PS and serum lipid levels in children.We evaluated whether serum lipid (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)) concentrations were associated with specific components of SDB, including indices of oxygen reduction index, lowest oxygen saturation, mean oxygen saturation. And we explored whether serum lipid levels were associated with different degree sleep disordered (PS and OSA group) and obese.MethodsThis was a cross-sectional study. Children who were complained by their guardians with habitual snoring and(or) mouth breathing were collected in the SDB group. Normal children without sleep problem were matched in the control group. Subjects in the SDB group underwent polysomnography. The serum lipid profiles of all the children included TC, TG, HDL-C and LDL-C concentrations were measured by appropriate enzymatic assays.ResultsA total of 241 with Apnea/Hypopnea Index ≥ 5 (AHI) were assigned to the OSAS group and the remaining 155 with normal AHI were assigned to the PS group. The values of TC, TG, LDL-C and LDL/HDL were significantly higher in the OSAS group than in the PS group, and the values in the PS group were significantly higher than the control group. Multiple regression analysis revealed serum TG only correlated negatively with lowest oxygen saturation. Body mass index-z score has a positive effect on TG in all the 1310 children (P = 0.031) and in SDB 396 children(P = 0.012). The level of serum TG in obese group was significantly higher than that in non-obese group.ConclusionsSDB had a very obvious effect on blood lipids, whereas PS without apnea and hypoxia. Obese only affects the aggregation of TG.Trial registrationChiCTR1900026807(2019.10.23).