Lower HDL-cholesterol Concentrations Research Articles

Low-Density Lipoprotein Cholesterol and the Risk of Rheumatoid Arthritis: A Prospective Study in a Chinese Cohort.

Objective: This study aimed to investigate whether low-density lipoprotein cholesterol (LDL-C) concentration was associated with the risk of rheumatoid arthritis (RA) in Chinese adults. Methods: The study included the 97,411 participants in the Kailuan Study without RA, with complete baseline LDL-C data, and who did not use lipid-lowering medications at baseline or during follow-up. We used Cox proportional hazards modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to baseline LDL-C tertiles, adjusting for age, sex, body mass index, HDL-C, triglycerides, diabetes, hypertension, alcohol consumption, and smoking. We also calculated the HR and 95% CI of RA using updated LDL-C measurements prior to the end of follow-up, adjusting for covariates. Results: We identified 97 incident RA cases between 2006 and 2018. After adjusting for potential confounders, updated LDL-C concentration—rather than baseline LDL-C—was inversely associated with RA risk. The adjusted HR of RA was 0.64 (95% CI: 0.38, 1.09; p-trend = 0.10) comparing the two extreme baseline LDL-C tertiles, and 0.38 (95% CI: 0.22, 0.64; p-trend < 0.01) comparing the two extreme tertiles of the updated LDL-C concentrations. Conclusions: In this prospective study, high LDL-C concentrations, when measured closest to RA diagnosis or the end of follow-up, were associated with a low risk of RA. These findings highlight the changes in LDL-C prior to RA diagnosis, and the importance of including lipid analyses into studies of the pathogenesis of RA.

Is there a role of lipid-lowering therapies in the management of fatty liver disease?

Atherogenic dyslipidemia is characterized by increased triglyceride-rich lipoproteins and low high-density lipoprotein cholesterol concentrations. It is highly prevalent in non-alcoholic fatty liver disease (NAFLD) and contributes to the increased cardiovascular risk associated with this condition. Alongside insulin resistance it plays an important pathogenetic role in NAFLD/non-alcoholic steatohepatitis (NASH) development and progression. It has been shown that cholesterol-lowering reduces cardiovascular risk more in NAFLD vs non-NAFLD high-risk individuals. This evidence highlights the importance of effective lipid modulation in NAFLD. In this narrative review the effects of the most commonly used lipid-lowering therapies on liver outcomes alongside their therapeutic implications in NAFLD/NASH are critically discussed. Preclinical and clinical evidence suggests that statins reduce hepatic steatosis, inflammation and fibrosis in patients with NAFLD/NASH. Most data are derived from observational and small prospective clinical studies using changes in liver enzyme activities, steatosis/fibrosis scores, and imaging evidence of steatosis as surrogates. Also, relevant histologic benefits were noted in small biopsy studies. Atorvastatin and rosuvastatin showed greater benefits, whereas data for other statins are scarce and sometimes conflicting. Similar studies to those of statins showed efficacy of ezetimibe against hepatic steatosis. However, no significant anti-inflammatory and anti-fibrotic actions of ezetimibe have been shown. Preclinical studies showed that fibrates through peroxisome proliferator-activated receptor (PPAR)α activation may have a role in NAFLD prevention and management. Nevertheless, no relevant benefits have been noted in human studies. Species-related differences in PPARα expression and its activation responsiveness may help explain this discrepancy. Omega-3 fatty acids reduced hepatic steatosis in numerous heterogeneous studies, but their benefits on hepatic inflammation and fibrosis have not been established. Promising preliminary data for the highly purified eicosapentaenoic acid require further confirmation. Observational studies suggest that proprotein convertase subtilisin/kexin9 inhibitors may also have a role in the management of NAFLD, though this needs to be established by future prospective studies.

Association of Dyslipidemia and Respiratory Resistance Assessed by the Forced Oscillation Technique in Asthmatic Children.

This study aimed to evaluate the associations between dyslipidemia and pulmonary function parameters assessed by spirometry and the forced oscillation technique in asthmatic children. Asthmatic children (5-18years old) had fasting serum lipid profiles including low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and C-reactive protein (CRP) measured. Pulmonary function tests were assessed by spirometry and the forced oscillation technique (FOT). One hundred forty-one asthmatic children were enrolled with a mean (SD) age of 11.82 (3.38) years. Eighty-eight (62.4%) children were boys, 64 (45.4%) had dyslipidemia, and 20 (14.2%) were obese. Among the children with dyslipidemia, a high LDL-C concentration (65.6%) was the most common form of dyslipidemia, followed by high TC (57.8%), high TG (35.9%), and low HDL-C concentrations (15.6%). Multivariable analysis showed significant associations between HDL-C concentrations and respiratory resistance at 5Hz (R5) and respiratory resistance at 20Hz (R20), and TC concentrations were modestly associated with reactance at 5Hz (X5), the frequency of resonance (Fres), and the area of reactance (ALX). Asthmatic children who had high LDL-C concentrations had a significantly higher expiratory phase R5, whole breath R20, and expiratory phase R20 than those in children with normal LDL-C concentrations. This study suggests an association of blood cholesterol, especially HDL-C and LDL-C, and respiratory resistance measured by the FOT, irrespective of the obesity status. An intervention for improving LDL-C and HDL-C concentrations may be beneficial on lung function parameters in asthmatic children. TCTR20200305005; date of registration: 03-04-2020 (retrospectively registered).

Lipid control in adult Chinese patients with type 2 diabetes: a retrospective analysis of time trends and geographic regional differences.

Lipid control in adult Chinese patients with type 2 diabetes: a retrospective analysis of time trends and geographic regional differences.

Dihydroartemisinin improves hypercholesterolemia in ovariectomized mice via enhancing vectorial transport of cholesterol and bile acids from blood to bile

The increase of concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the serum of postmenopausal women is the important risk factor of the high morbidity of cardiovascular diseases of old women worldwide. To test the anti-hypercholesterolemia function of dihydroartemisinin (DHA) in postmenopausal women, ovariectomized (OVX) mice were generated, and DHA were administrated to OVX mice for 4 weeks. The blood and liver tissues were collected for biochemical and histological tests respectively. The mRNA and protein expression levels of genes related to metabolism and transport of cholesterol, bile acid and fatty acid in the liver or ileum were checked through qPCR and western blot. DHA could significantly reduce the high concentrations of TC and LDL-C in the serum and the lipid accumulation in the liver of ovariectomized mice. The expression of ABCG5/8 was reduced in liver of OVX mice, and DHA could up-regulate the expression of them. Genes of transport proteins for bile salt transport from blood to bile, including Slc10a1, Slco1b2 and Abcb11, were also significantly up-regulated by DHA. DHA also down-regulated the expression of Slc10a2 in the ileum of OVX mice to reduce the absorption of bile salts. Genes required for fatty acid synthesis and uptake, such as Fasn and CD36, were reduced in the liver of OVX mice, and DHA administration could significantly up-regulate the expression of them. These results demonstrated that DHA could improve hypercholesterolemia in OVX mice through enhancing the vectorial transport of cholesterol and bile acid from blood to bile.

Association of Serum High-Density Lipoprotein Cholesterol with High Blood Pressures at Checkup: Results of Kanagawa Investigation of Total Checkup Data from the National Database-9 (KITCHEN-9).

Background: although high-density lipoprotein has cardioprotective effects, the association between serum high-density lipoprotein cholesterol (HDL-C) and hypertension is poorly understood. Therefore, we investigated whether high and low concentrations of HDL-C are associated with high blood pressure (HBP) using a large healthcare dataset. Methods: in a community-based cross-sectional study of 1,493,152 Japanese people (830,669 men and 662,483 women) aged 40–74 years who underwent a health checkup, blood pressures automatically measured at healthcare center were investigated in nine HDL-C groups (20–110 mg/dL or over). Results: crude U-shaped relationship were observed between the nine HDL-C and blood pressures in both men and women. Logistic regression analysis showed left-to-right inverted J-shaped relationships between HDL-C and odds ratios for HBP (≥140/90 mmHg and/or pharmacotherapy), with lower limits of 90–99 mg/dL in both sexes, which were unchanged after adjusting for confounding factors. However, further adjustment for body mass index and serum triglyceride concentration revealed positive linear associations between HDL-C and HBP, although blunt U-shaped associations remained in nonalcohol drinkers. Conclusion: both low and extremely high HDL-C concentrations are associated with HBP. The former association might be dependent on excess fat mass concomitant with low HDL-C, whereas the latter association may be largely dependent on frequent alcohol consumption.

Nut Consumption Is Associated with Lower Risk of Metabolic Syndrome and Its Components in Type 1 Diabetes

Although nut consumption has been associated with several health benefits, it has not been investigated in individuals with type 1 diabetes. Therefore, our aim was to assess nut consumption and its association with metabolic syndrome in adult individuals with type 1 diabetes taking part in the Finnish Diabetic Nephropathy Study. The nut intake of the 1058 participants was assessed from 3-day food records that were completed twice, and the number of weekly servings, assuming a serving size of 28.4 g, was calculated. Metabolic syndrome was defined as the presence of ≥3 of the cardiovascular risk factors: central obesity, high blood pressure (≥130/85 mmHg or use of antihypertensive medication), high triglyceride concentration (≥1.70 mmol/L or use of lipid-lowering medication), low HDL-cholesterol concentration (<1.00 mmol/L in men and <1.30 mmol/L in women or use of lipid-lowering medication), and hyperglycaemia. Overweight/obesity was defined as a BMI ≥25 kg/m2. HbA1c > 59 mmol/mol (>7.5%) was used as a criterion for suboptimal glycaemic control. Of the 1058 (mean age 46 years, 41.6% men) participants, 689 (54.1%) reported no nut intake. In the remaining sample, the median weekly nut intake was 40.8 g. In the adjusted models, higher nut intake, as the continuous number of weekly servings and the comparison of those with <2 and ≥2 weekly servings, was associated with lower metabolic syndrome score, waist circumference, HbA1c, and BMI. Nut consumption as a continuous variable was negatively associated with the presence of metabolic syndrome, its blood pressure, triglyceride, and HDL-cholesterol components, and suboptimal glycaemic control. Consumption of ≥2 weekly servings was associated with lower odds of suboptimal glycaemic control (by 51.5%), overweight/obesity (by 33.4%), and metabolic syndrome (by 51.8%) and meeting the waist (by 37.3%), blood pressure (by 44.5%), triglyceride (by 37.7%), and HDL-cholesterol (by 36.2%) components of the metabolic syndrome. In conclusion, a weekly nut intake of ≥2 servings was beneficially associated with all the components of the metabolic syndrome in type 1 diabetes. The causality of this association will need to be investigated.

Adeno-Associated Virus-Mediated Gain-of-Function mPCSK9 Expression in the Mouse Induces Hypercholesterolemia, Monocytosis, Neutrophilia, and a Hypercoagulative State.

Hypercholesterolemia has previously been induced in the mouse by a single intravenous injection of adeno-associated virus (AAV)-based vector harboring gain-of-function pro-protein convertase subtilisin/kexin type 9. Despite the recent emergence of the PCSK9-AAV model, the profile of hematological and coagulation parameters associated with it has yet to be characterized. We injected 1.0 × 1011 viral particles of mPCSK9-AAV or control AAV into juvenile male C57BL/6N mice and fed them with either a Western-type high-fat diet (HFD) or standard diet over the course of 3 weeks. mPCSK9-AAV mice on HFD exhibited greater plasma PCSK9 concentration and lower low-density lipoprotein levels, concomitant with increased total cholesterol and non-high-density lipoprotein (non-HDL)-cholesterol concentrations, and lower HDL-cholesterol concentrations than control mice. Furthermore, mPCSK9-AAV-injected mice on HFD exhibited no signs of atherosclerosis at 3 weeks after the AAV injection. Hypercholesterolemia was associated with a thromboinflammatory phenotype, as neutrophil levels, monocyte levels, and neutrophil-to-lymphocyte ratios were higher and activated partial thromboplastin times (aPTTs) was lower in HFD-fed mPCSK9-AAV mice. Therefore, the mPCSK9-AAV is a suitable model of hypercholesterolemia to examine the role of thromboinflammatory processes in the pathogenesis of cardiovascular and cerebrovascular diseases.

Postprandial dyslipidemia after a standardized high-fat meal in BMI-matched healthy individuals, and in subjects with prediabetes or type 2 diabetes

A relationship between postprandial hyperlipidemia and glucose homeostasis/cardiovascular diseases has been suggested. We investigated postprandial plasma lipid patterns after a standardized high-fat meal and their association with glucose homeostasis and subclinical atherosclerosis. Using matching by BMI, 32 healthy individuals with normal glucose tolerance (NGT), 21 subjects with impaired glucose tolerance (IGT), and 20 subjects with drug-naïve type 2 diabetes (T2D) were enrolled. Plasma concentrations of triglycerides (TGs), apolipoprotein-B (ApoB), ApoB48, ApoB100, glucose, and insulin at baseline and 1, 2, 3, 4, 5, 6, and 8h after a standardized meal (1041.03kcal with 70.99g of fat) were measured. Body composition, abdominal visceral fat area, and resting energy expenditure (REE) were measured using dual energy X-ray absorptiometry, computed tomography, and indirect calorimetry, respectively. The intima-media thickness (IMT) of the carotid artery and the ankle-brachial index (ABI) were used to detect subclinical atherosclerosis. Baseline data and area under the curve (AUC) of plasma concentrations of TGs, ApoB, and ApoB48 in the IGT and T2D groups were higher than in the NGT group. The peak TG concentrations after the meal was observed at 5h in subjects with IGT and T2D, while healthy subjects showed the highest concentrations at 4h. In multivariable analysis, high abdominal visceral fat area and low HDL-cholesterol concentrations were independently associated with the AUCTG and AUCApoB after adjusting for confounders including baseline TG and the REE. High LDL-cholesterol and high HbA1c concentrations were also associated with the AUCApoB. Furthermore, high AUCTG and AUCApoB values were independent factors for an increased carotid IMT and a low ABI after adjusting for relevant variables. Abdominal visceral obesity and low HDL-cholesterol concentrations were associated with increased post load excursions of TGs and ApoB in this series. These elevated concentrations of TGs and ApoB were linked with subclinical atherosclerosis.

Different associations between HDL cholesterol and cardiovascular diseases in people with diabetes mellitus and people without diabetes mellitus: a prospective community-based study

Experimental studies have found that the functionality of HDL cholesterol may be lost in the presence of diabetes mellitus (DM). We aimed to elucidate whether DM modified the association between HDL-cholesterol concentrations and cardiovascular disease (CVD) outcomes. Included were 91,354 Chinese adults (8244 participants with DM and 83,110 participants without DM) free of CVD or cancer at baseline (2006) and without use of lipid-lowering drugs at baseline and during follow-up. The primary endpoint of interest was a composite of CVDs (myocardial infarction, ischemic stroke, and hemorrhagic stroke). Cumulative average HDL-cholesterol concentrations were calculated from all available HDL-cholesterol measures at baseline (2006) and during the follow-up period (2008, 2010, 2012, and 2014). During a mean of 10.4 y of follow-up, there were 5076 CVD events identified. There was a significant interaction between DM and HDL-cholesterol concentrations on CVD risk (Pinteraction=0.003). The association between HDL-cholesterol concentrations and CVD followed a U-shaped curve in individuals without DM (Pnonlinearity<0.001). The adjusted HR of CVD was 1.26 (95% CI: 1.07, 1.48) for HDL-cholesterol concentrations<1.04 mmol/L and 1.76 (95% CI: 1.53, 2.03) for HDL-cholesterol concentrations>2.07 mmol/L, relative to the lowest-risk group (HDL-cholesterol concentrations of 1.30-1.42 mmol/L). In participants with DM, higher HDL-cholesterol concentrations were associated with a higher risk of CVD, in a dose-response manner (Pnonlinearity=0.44; Ptrend<0.001). The adjusted HR of CVD was 1.62 (95% CI: 1.19, 2.20) for HDL-cholesterol concentrations>2.07 mmol/L, relative to HDL-cholesterol concentrations of 1.30-1.42 mmol/L. High HDL-cholesterol concentrations were paradoxically associated with high risk of composite CVD outcomes in individuals with or without DM. However, low HDL-cholesterol concentrations failed to predict future CVD risk in individuals with DM.

Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat.

BackgroundBoth intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study.MethodsAll participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits.ResultsA total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm2 in men and 63.1±39.5 cm2 in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance.ConclusionThese results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

Lipoprotein(a) Concentrations Correlate With LDL-C in Children With Type 1 and 2 Diabetes.

ContextElevated levels of lipoprotein(a) (Lp[a]) is an independent risk factor for atherosclerotic cardiovascular disease especially in patients with diabetes. Adult levels of Lp(a) are thought to be is expressed by the second year of life.ObjectiveWe hypothesized that Lp(a) would be influenced by low density lipoprotein cholesterol (LDL-C), race, and HbA1C.MethodsRetrospective electronic medical record review of children and adolescents with type 1 diabetes (T1D) (n = 607) and type 2 diabetes (T2D) (n = 93).ResultsTotal of 700 subjects, ages 12-19 years with T1D (n = 607) and T2D (n = 93), 49% were male, mean age was 13.2 ± 3.08 years, and the median Lp(a) was 8.00 mg/dL, IQR 5.00-12.00. The Black subjects had an increased relative risk (RR) of higher Lp(a) compared with White subjects (RR 1.25, P < .0001). Among patients with T1D, Black people had an increased relative risk of higher Lp(a) than White people (RR 1.23, P = .0002). In T2D, Black subjects have 43% higher risk of having elevated Lp(a) than White subjects (RR 1.43, P = .268). In T1D, a 5 mg/dL increase in LDL-C results in 2% increase in Lp(a) (P < .0001). In T2D, a 5 mg/dL increase of LDL-C results in an increase of Lp(a) by 3%. LDL-C and BMI are independently associated with Lp(a) (RR = 1.02, P < .001; RR = 0.98, P < .001).ConclusionOur data suggest that Lp(a) is associated with LDL-C in children with diabetes. Lp(a) is differentially increased at higher concentrations of LDL-C. Black children with diabetes have a significant burden of Lp(a) concentrations compared with White children.

Compositional and functional properties of high-density lipoproteins in relation to coronary in-stent restenosis.

In-stent restenosis (ISR) is an unfavorable outcome that occurs in patients after coronary stenting. Use of drugs such as statins as well as drug-eluting stents has only been partially effective in reducing the rate of ISR. Since low high-density lipoprotein cholesterol (HDL-C) concentration is a pivotal cardiovascular disease risk factor, this study aimed to evaluate the compositional and functional alterations of HDL in individuals with ISR. This case-control study included 21 ISR, 26 non-ISR (NISR), 16 angiography-negative, and 18 healthy subjects. Serum HDL2 (d: 1.063-1.125 g/ml) and HDL3 (d: 1.125-1.210 g/ml) subfractions were extracted from each subject using sequential ultracentrifugation. The capacity of HDL to efflux cellular cholesterol from lipid-loaded macrophages as well as to take up free cholesterol (FC) from triglyceride-rich lipoproteins (TGRLs) during lipolysis was assessed. No difference was found in the HDL2 and HDL3 content of free cholesterol and total protein among the groups. The NISR group showed lower triglyceride content in HDL2 and higher phospholipid content in HDL3 relative to healthy subjects. Strong positive correlations were found between the cholesterol efflux capacity (CEC) of HDL2 and its phospholipid content in the healthy (r = 0.50), angiography-negative (r = 0.55) and ISR (r = 0.52) groups. The capacity of apolipoprotein B (apoB)-depleted serum to take up free cholesterol was not different among the groups. Despite some compositional alterations, the capacity of HDL to efflux cholesterol from lipid-loaded macrophages as well as to take up free cholesterol from TGRLs during lipolysis was not associated with ISR in this study.

Effect of high-density lipoproteins of patients with in-stent restenosis on the expression of adhesion molecules in endothelial cells.

Background and Aims: In-stent restenosis (ISR) as an important unfavorable outcome in patients who underwent stent implantation still remains a clinical challenge. Complex pathophysiological mechanisms, including chronic vascular inflammation are involved during the progression of restenosis. Low high-density lipoprotein cholesterol (HDL-C) concentration is also a pivotal risk factor for cardiovascular disease, though, recently, its anti-atherosclerotic function has been more considerable. Besides the key role in efflux of cholesterol from macrophages, HDL has additional properties like its ability to inhibit the cytokine-induced expression of vascular cell adhesion molecules in endothelial cells, that may also be anti-atherogenic.

A combination of single nucleotide polymorphisms is associated with the interindividual variability in the blood lipid response to dietary fatty acid consumption in a randomized clinical trial

Blood lipid concentrations display high interindividual variability in response to dietary interventions, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explain a limited fraction of the variability of these complex phenotypes. We aimed to identify combinations of SNPs associated with the variability in LDL cholesterol and triglyceride (TG) concentration changes following 5 dietary interventions. In a multicenter randomized crossover trial, 92 participants with elevated waist circumference and low HDL cholesterol concentrations consumed 5 isoenergetic diets for 4 wk: a diet rich in saturated fatty acids (SFAs) from cheese, SFA from butter, monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs), and a diet higher in carbohydrates (CHO). The association between 22 candidate SNPs in genes involved in lipid and bile acid metabolism and transport and changes in LDL cholesterol and TG concentrations was assessed with univariate statistics followed by partial least squares regression. Endpoint LDL cholesterol concentrations were significantly different (cheese: 3.18±0.04, butter: 3.31±0.04, MUFA: 3.00±0.04, PUFA: 2.81±0.04, CHO: 3.11±0.04 mmol/L; P<0.001) while endpoint TG concentrations were not (P=0.117). Both displayed consistently elevated interindividual variability following the dietary interventions (CVs of 34.5±2.2% and 55.8±1.8%, respectively). Among the 22 candidate SNPs, only ABCA1-rs2066714 and apolipoprotein E (APOE) isoforms exhibited consistent significant effects, namely on LDL cholesterol concentrations. However, several SNPs were significantly associated with changes in LDL cholesterol and TG concentrations in a diet-specific fashion. Generated multivariate models explained from 16.0 to 33.6% of the interindividual variability in LDL cholesterol concentration changes and from 17.5 to 32.0% of that in TG concentration changes. We report combinations of SNPs associated with a significant part of the variability in LDL cholesterol and TG concentrations following dietary interventions differing in their fatty acid profiles.

Prevalence of coronary calcium deposits in Sheehan's syndrome patients on long term replacement treatment.

Sheehan's Syndrome (SS) is one of the most important causes of hypopituitarism in developing countries with patients having varying degrees and severity of anterior pituitary hormone deficiency including growth hormone deficiency (GHD). SS is characterized by increased clustering of metabolic and proinflammatory risk factors predisposing them to increased cardiovascular morbidity and mortality. Coronary calcium deposits (CCD), a marker for significant coronary atherosclerosis, is used for evaluation in asymptomatic individuals of global cardiac risk to develop events related to coronary heart disease (CHD). This study therefore aimed to evaluate the prevalence of coronary artery disease in patients with SS appropriately replaced for pituitary hormone deficiencies but untreated for GHD. Thirty patients previously diagnosed with SS and stable on a conventional replacement treatment for at least 6months before the study and thirty age and Body Mass Index (BMI) matched controls were enrolled in this observational study. The subjects underwent detailed clinical, biochemical, and hormone analysis. Coronary multidetector computed tomography was performed in 19 SS patients and 19 healthy participants by a 16-row multislice scanner. Non contrast acquisitions were performed to detect coronary calcifications. Calcium was quantified by the Agatston score (AS) in all subjects. AS > 10 indicates increased CHD risk. The mean (± SD) age was 38.30 ± 10.73years and the diagnostic delay was 11.35 ± 4.74years. Patients with SS had significantly higher mean triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The prevalence of CCD was significantly higher in patients of SS compared to controls (42.1% vs. 5.3%; P = 0.023). The presence of CCD and AS > 10 were detected in 42.1% and 31.6% of patients respectively. The presence of significant calcification (Agatston score > 10) was documented in 75% of patients (6/8) of the SS patients with CCD compared to none in the control group (P = 0.019). (Left anteriordescending, 1; left circumflex, 2; right coronary artery, 2 and posterior descending, 1) CONCLUSION: Since coronary artery calcium is an independent predictor of CHD events, the presence of significant prevalence of CCD in patients with SS compared to healthy matched controls, undermines the importance of early risk stratification of SS individuals with plethora of conventional cardiovascular risk factors that are at relatively high risk to avoid the adverse vascular consequences.

Combined association of skeletal muscle mass and grip strength with cardiovascular diseases in patients with type 2 diabetes.

Appendicular skeletal muscle mass (ASM) and grip strength (GS) have been suggested to be related to cardiovascular diseases (CVDs), but their association with type 2 diabetes (T2D) remains unclear. Therefore, we examined the combined association of ASM and GS with the prevalence of CVD in patients with T2D. A total of 1230 patients with T2D were recruited and divided into four groups based on the sex-specific median values of ASM adjusted for body mass index (ASM/BMI; short: SM) and GS: high SM/high GS (HSM/HGS), high SM/low GS (HSM/LGS), low SM/high GS (LSM/HGS), and low SM/low GS (LSM/LGS). The LSM/LGS group was older and had higher values of systolic blood pressure, homeostasis model assessment of insulin resistance, waist circumference, and C-reactive protein but lower high-density lipoprotein cholesterol concentrations than the HSM/HGS group. After adjusting for potential confounders, the odds ratios (ORs) and 95% CIs for CVD, coronary heart disease (CHD), ischemic stroke, and peripheral arterial disease (PAD) in the LSM/LGS group were 2.90 (1.89-4.47), 2.39 (1.46-3.92), 1.77 (0.84-3.71), and 5.83 (1.58-21.48), respectively. After adjusting for variable confounders among patients with higher glycosylated hemoglobin (HbA1c) (≥7.1%), the ORs and 95% CIs for CVD and CHD in the LSM/LGS group were 7.27 (3.37-15.67) and 6.17 (2.65-14.37), respectively. The combination of low SM and GS was strongly associated with CVD, CHD, and PAD in patients with T2D, especially in those with higher HbA1c levels.

Association of muscle mass and fat mass on low-density-lipoprotein cholesterol and triglyceride plasma concentration in children and adolescents.

Obesity has often been associated with high low-density-lipoprotein cholesterol (LDL-C) and triglyceride plasma concentrations, known risk factors for diabetes mellitus and cardiovascular disease. Study objective was to evaluate the association of LDL-C and triglyceride plasma concentration with muscle and fat mass in children and adolescents. We analyzed data of the National Health and Nutrition Examination Survey (1999-2004) to estimate lean muscle and fat mass assessed by dual-energy X-ray absorptiometry (DXA) of participants whose lipid profiles had been examined. Fat mass was operationalized by DXA-determined fat mass index (FMI). Muscle mass was assessed by appendicular lean mass index (aLMI). High LDL-C and triglyceride concentration was defined as above 130mg/dL. For the evaluation of the association of LDL-C and triglyceride plasma concentration with LMI and FMI Z-scores, the data of 2,487 children and adolescents (age 8-19 years) (984 females) were eligible. High aLMI showed no association with LDL-C or triglyceride concentration, but high FMI showed significant association with LDL-C and triglyceride plasma concentration in the bivariate regression analysis. Isolated muscle mass increase may not be protective against high LDL-C and triglycerides plasma levels in children and adolescents. Thus, exercise may lead to risk factor reduction mainly through fat mass reduction.

High plasma concentration of non-esterified polyunsaturated fatty acids is a specific feature of severe COVID-19 pneumonia

COVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological (including plasma cytokines) features were assessed. Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response but higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels. NEFAs and PUFAs concentrations were negatively correlated with the number of ventilator-free days. Among hospitalized patients with severe pneumonia, COVID-19 is independently associated with higher NEFAs (mainly linoleic and arachidonic acids) and lower apolipoprotein E and HDL concentrations. These features might act as mediators in COVID-19 pathogenesis and emerge as new therapeutic targets. Further investigations are required to define the role of NEFAs in the pathogenesis and the dysregulated immune response associated with COVID-19.Trial registration: NCT04435223.

High Plasma Concentration of Non-Esterified Polyunsaturated Fatty Acids Is a Specific Feature of Severe COVID-19 Pneumonia

Background: The pathogenesis of severe COVID-19 is frequently associated with an uncontrolled inflammatory response. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status.Methods: Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological features were assessed.Findings: Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response with higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients, suggesting an increase in phospholipase A2 activity. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels.Trial Registration: NCT04435223Funding Statement: This study was supported by grant (MN) from the COVIDOLIP – AOIc2020 (Institutional grant), by the INSERM (Centre de Recherche UMR 1231) and the ANR Investissements d’Avenir Grant (ANR-11 LABX-0021-01, Labex Lipstic).Declaration of Interest: The authors declare no existing conflict of interest.Ethics Approval Statement: The study fulfilled legal and ethics requirements: Approval was obtained from the CPP (Comité de Protection des Personnes SUD MEDITERRANEE V; 2017-A03404-49) for the original study and an amendment was obtained to include supplementary patients with severe COVID-19. All subjects (or their legal representatives) received written information and provided their consent to participate.