Lipidic Profiles of Patients Starting Peritoneal Dialysis Suggest an Increased Cardiovascular Risk Beyond Classical Dyslipidemia Biomarkers

Background. Lipids are molecules that constitute a fundamental part of the plasma. Chronic kidney disease (CKD) produces profound changes in lipid metabolism, and associated lipid disorders, in turn, contribute to the progression of CKD. Patients on peritoneal dialysis (PD) have more atherogenic lipid profiles than non-dialysis-dependent CKD patients. Methods. Single-center prospective observational study of a cohort of CKD patients who started renal replacement therapy with continuous ambulatory peritoneal dialysis. The differences in the lipid profile and analytical variables before and six months after the start of peritoneal dialysis were analyzed. Samples were analyzed on an Ultra-Performance Liquid Chromatography system. Results. Thirty-nine patients were enrolled in this study. Their mean age was 57.9 ± 16.3 years. A total of 157 endogenous lipid species of 11 lipid subclasses were identified. There were significant increases in total free fatty acids (p< 0.05), diacylglycerides (p <0.01), triacylglycerides, (p <0.01), phosphatidylcholines (p <0.01), phosphatidylethanolamines (p <0.01), ceramides (p <0.01), sphingomyelins (p <0.01), and cholesterol esters (p<0.01) from baseline to 6 months. However, there were no differences in the classical lipid markers, neither lysophosphatidylcholines, monoacylglycerides, and sphingosine levels. Conclusions. Patients on PD present changes in the lipidomic profile beyond the classic markers of dyslipidemia, that suggest an increased cardiovascular risk in them.

Application of phytocomplex and nordic walking in dyslipidemia

The results of assessing the effectiveness of using the original phytocomplex in combination with physical training in the form of Nordic walking in 78 men with dyslipidemia are presented. It was found that in the main group (n=39), against the background of the use of phytocomplex and physical training, there is a decrease in the content of atherogenic lipid fractions and the atherogenic coefficient, an increase in physical performance, and an improvement in the indicators of the adaptive reserve of the cardiovascular system. In the control group (n=39), against the background of a hypolipidemic diet and climatotherapy, less significant dynamics of the parameters is noted.

Relationship between Serum Angiopoietin-like Proteins 3 and 8 and Atherogenic Lipid Biomarkers in Non-Diabetic Adults Depends on Gender and Obesity

Hypertriglyceridemia is an independent risk factor for coronary artery disease. Lipoprotein lipase (LPL) plays an essential role in the metabolism of triglyceride-rich lipoproteins (TRLs). Angiopoietin-like proteins ANGPTL3 and ANGPTL8 are shown to be important regulators of LPL activity. Increased concentrations of these proteins may reflect cardiovascular risk, and the treatment of patients with dyslipidemia with ANGPTLs inhibitors may decrease this risk. We assessed the gender-specific relationships of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and obesity in non-diabetic adults. The study comprised 238 participants aged 25–74 [122 with triglycerides (TG) <150 mg/dL (<1.7 mmol/L) and 116 with hypertriglyceridemia]. Total cholesterol, HDL-cholesterol, LDL-cholesterol, TG, C-reactive protein (CRP), glycated hemoglobin, apolipoprotein B, small dense LDL-C (sd-LDL-C), ANGPTL3, and ANGPTL8 were measured. Non-HDL-cholesterol, remnant cholesterol (remnant-C) concentrations, and body mass index (BMI) were calculated. Results: Women and men did not differ in terms of age, CRP levels, the percentage of obese subjects, and concentrations of atherogenic lipid biomarkers, except higher TG in males and higher ANGPTL3 concentrations in females. Positive correlations of both ANGPTLs with TG, remnant-C, and sdLDL-C levels were found in females. In males, only ANGPTL3 correlated positively with atherogenic biomarkers, but there were no correlations with ANGPTL8. Concentrations of ANGPTL3 were higher in obese men, whereas ANGPTL8 levels were higher in obese women. In women alone, ANGPTL8 showed very good discrimination power to identify subjects with hypertriglyceridemia (AUC = 0.83). Contrary to this, ANGPTL3 was a better discriminator of hypertriglyceridemia (AUC = 0.78) in male subjects. Regression models, adjusted for age, sex, and BMI showed a weak but significant effect of ANGPTL8 to increase the risk of hypertriglyceridemia. Conclusions: In females, ANGPTL8 is more strongly associated with TRLs metabolism, whereas in males, ANGPTL3 plays a more important role. We suggest sex differences be taken into consideration when applying new therapies with angiopoietin-like proteins inhibitors in the treatment of dyslipidemia.

Estimating causal effects of atherogenic lipid-related traits on COVID-19 susceptibility and severity using a two-sample Mendelian randomization approach

Background As the number of COVID-19 deaths continues to rise worldwide, the identification of risk factors for the disease is an urgent issue, and it remains controversial whether atherogenic lipid-related traits including serum apolipoprotein B, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels, are risk factors. The aim of this study was to estimate causal effects of lipid-related traits on COVID-19 risk in the European population using a two-sample Mendelian randomization (MR) approach. Methods We used summary statistics from a genome-wide association study (GWAS) that included 441,016 participants from the UK Biobank as the exposure dataset of lipid-related traits and from COVID-19 Host Genetics Initiative GWAS meta-analyses of European ancestry as the outcome dataset for COVID-19 susceptibility (32,494 cases and 1,316,207 controls), hospitalization (8316 cases and 1,549,095 controls), and severity (4792 cases and 1,054,664 controls). We performed two-sample MR analyses using the inverse variance weighted (IVW) method. As sensitivity analyses, the MR-Egger regression, weighted median, and weighted mode methods were conducted as were leave-one-out sensitivity analysis, the MR-PRESSO global test, PhenoScanner searches, and IVW multivariable MR analyses. A P value below 0.0055 with Bonferroni correction was considered statistically significant. Results This MR study suggested that serum apolipoprotein B or LDL-cholesterol levels were not significantly associated with COVID-19 risk. On the other hand, we inferred that higher serum triglyceride levels were suggestively associated with higher risks of COVID-19 susceptibility (odds ratio [OR] per standard deviation increase in lifelong triglyceride levels, 1.065; 95% confidence interval [CI], 1.001–1.13; P = 0.045) and hospitalization (OR, 1.174; 95% CI, 1.04–1.33; P = 0.012), and were significantly associated with COVID-19 severity (OR, 1.274; 95% CI, 1.08–1.50; P = 0.004). Sensitivity and bidirectional MR analyses suggested that horizontal pleiotropy and reverse causation were unlikely. Conclusions Our MR study indicates a causal effect of higher serum triglyceride levels on a greater risk of COVID-19 severity in the European population using the latest and largest GWAS datasets to date. However, as the underlying mechanisms remain unclear and our study might be still biased due to possible horizontal pleiotropy, further studies are warranted to validate our findings and investigate underlying mechanisms.

Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence

Senescence in placenta/fetal membranes is a normal phenomenon linked to term parturition. However, excessive senescence which may be induced by telomere attrition, has been associated with preeclampsia (PE). We hypothesized that the telomerase complex in peripheral blood mononuclear cells (PBMC) and circulating telomere associated senescence markers would be dysregulated in women with PE. We measured long non-coding (nc) RNA telomerase RNA component (TERC) and RNAs involved in the maturation of TERC in PBMC, and the expression of TERC and 5′–3′ Exoribonuclease 1 (XRN1) in extracellular vesicles at 22–24 weeks, 36–38 weeks and, 5-year follow-up in controls and PE. We also measured telomere length at 22–24 weeks and 5-year follow-up. The circulating senescence markers cathelicidin antimicrobial peptide (CAMP), β-galactosidase, stathmin 1 (STMN1) and chitotriosidase/CHIT1 were measured at 14–16, 22–24, 36–38 weeks and at 5-year follow-up in the STORK study and before delivery and 6 months post-partum in the ACUTE PE study. We found decreased expression of TERC in PBMC early in pregnant women who subsequently developed PE. XRN1 involved in the maturation of TERC was also reduced in pregnancy and 5-year follow-up. Further, we found that the senescence markers CAMP and β-galactosidase were increased in PE pregnancies, and CAMP remained higher at 5-year follow-up. β-galactosidase was associated with atherogenic lipid ratios during pregnancy and at 5-year follow-up, in PE particularly. This study suggests a potential involvement of dysfunctional telomerase biology in the pathophysiology of PE, which is not restricted to the placenta.

Hyperhomocysteinemia Is Associated With Lipid Profiles and Lipid Ratio in Patients With Coronary Artery Disease

Objective: This study aimed to investigate the correlation of Hyperhomocysteinemia (HHcy) or serum homocysteine (Hcy) levels with lipid levels and lipid ratios in individuals with coronary artery disease(CAD).Methods: A total of 1646 subjects with suspected CAD were divided into CAD or control groups. Serum Hcy, total cholesterol(TC), triglycerides(TGs), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), apolipoprotein(Apo)AI and ApoB concentrations were detected.Results: Serum TC, LDL-C and ApoB in control subjects with HHcy were lower than those in individuals with normal Hcy, and serum HDL-C and ApoAI in CAD subjects with HHcy were lower than those in individuals with normal Hcy(P < 0.05). The correlation analysis showed that serum TGs, LDL-C, ApoAI and HDL-C were correlated with Hcy(P <0.05). There are different HHcy trends affecting the ratios of TC/HDL-C and LDL/HDL-C between the CAD and controls(Pinteraction for TC/HDL-C=0.025; Pinteraction for LDL/HDL-C=0.033). CAD patients with HHcy had a higher ratio of TC/HDL-C(P=0.022) and LDL/HDL-C(P=0.045) than those with normal Hcy, but in the controls, the subjects with HHcy exhibited a trend toward a decreased ratio of TC/HDL-C(P=0.481) and LDL/HDL-C(P=0.303).Conclusion: HHcy was related to the atherogenic lipid profile in patients with CAD. The lipid ratio is more suitable for assessing the effect of HHcy on CAD.

Gender differences in lipid metabolism

The search for early markers of atherosclerosis is an effective method for providing personalized medicine allowing the prevention of the progression of this pathology. The aim of this study was the determination of the total indices of dyslipidemia and the identification of the gender indices of the extended lipid profile in the population of residents of the Southern and Central Federal Districts (Voronezh, Belgorod, Lipetsk, Kursk and Rostov regions) for the identification of early markers of atherogenicity. In a simultaneous clinical study, involving 339 patients (mean age 48 years), the concentrations of total cholesterol, triglycerides, LDL (low density lipoproteins), HDL (high density lipoproteins), apolipoproteins B and A1, the ApoB/ApoA1 ratio and the atherogenic coefficient were determined. For the identification of the relationship between changes in lipid profile indicators with cytolysis syndrome and indicators of carbohydrate metabolism, the activity of ALAT (alanine aminotransferase), GGTP (gamma-glutamyl transpeptidase) and glucose contentwere also studied. Analysis of the results of the lipid spectrum of the population sample of the middle age group revealed significant metabolic disorders of lipid metabolism with a predominance of atherogenic lipid fractions and a significant excess of indicators of atherogenic lipid fractions in middle-aged men in comparison with women. It has been shown that the apoB/apoA1 index can be used as an auxiliary marker for early assessment of the prevalence of atherogenic lipid fractions, allowing the identification of risk groups for the development of diseases associated with metabolic disorders

Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation

Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to systemic inflammasome activation, and elevated atherogenic lipid ratios have been shown to correlate with circulating levels of inflammatory biomarkers in SMI. It is, however, not yet known if increased systemic cholesterol load leads to inflammasome activation in these patients. Methods: We tested the hypothesis that patients with SCZ and BD display higher circulating levels compared to healthy individuals of key members of the IL-18 system using a large patient cohort (n=1632; including 737 SCZ and 895 BD), and healthy controls (CTRL; n=1070). In addition, we assessed associations with coronary artery disease risk factors in SMI, focusing on relevant inflammasome-related, neuroendocrine, and lipid markers. Results: We report higher baseline levels of circulating IL-18 system components (IL-18, IL-18BPA) as well as increased expression of inflammasome-related genes (NLRP3 and NLRC4) in the blood of patients relative to CTRL. We demonstrate a cholesterol dyslipidemia pattern in psychotic disorders, and report correlations between levels of blood cholesterol species and the expression of inflammasome system elements in SMI. Conclusions: Based on these results, we suggest a link between systemic inflammasome activation/dysregulation and cholesterol load in SMI. Our findings further the understanding of possible underlying inflammatory and metabolic mechanisms and may expose important therapeutic targets in SMI.

Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: An analysis from BANTING and BERSON

Background Atherogenic dyslipidemia (AD), characterized by increased concentrations of apolipoprotein B (ApoB)-containing particles, is often present in individuals with type 2 diabetes mellitus (T2DM). Non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol transported by apolipoprotein B (ApoB)-containing particles), and total apoB are considered secondary goals of lipid-lowering therapy to guide treatment of residual cardiovascular risk. The BANTING and BERSON studies demonstrated that evolocumab added to statin therapy reduced atherogenic lipid and lipoproteins concentrations in patients with T2DM. Methods This post-hoc analysis combined data from two randomized, placebo-controlled trials, BANTING and BERSON, to investigate the effect of evolocumab (140 mg every two weeks [Q2W] or 420 mg monthly [QM]) on atherogenic lipid (LDL-C, non-HDL-C, VLDL-C, remnant cholesterol) and lipoproteins (ApoB, lipoprotein(a) (Lp[a])), and achievement of 2019 European Society of Cardiology/European Atherosclerosis Society lipid treatment goals in individuals with and without AD. Results In individuals with high TGs with (n = 389) and without (n = 196) AD receiving background statin therapy, evolocumab, compared with placebo, substantially reduced the cholesterol levels from all ApoB atherogenic lipoproteins (least squares (LS) mean LDL-C by 66.7% to 74.3%, non-HDL-C by 53.4% to 65.8%, median remnant cholesterol by 28.9% to 34.2%, VLDL-C by 16.1% to 19.6%) and median TGs levels (by 17.5% to 19.6%) at the mean of weeks 10 and 12. LS mean ApoB was significantly reduced by 41.5% to 56.6% at week 12. Results were consistent in diabetic individuals with normal TGs (n = 519). Evolocumab was also associated with a significant reduction in median Lp(a) by 35.0% to 53.9% at the mean of weeks 10 and 12. A majority (74.7% to 79.8%) of evolocumab-treated individuals achieved the goal of both an LDL-C < 1.4 mmol/L and an LDL-C reduction of at least 50%, > 75% achieved non-HDL-C < 2.2 mmol/L at the mean of weeks 10 and 12, and > 67% achieved ApoB < 65 mg/dL at week 12. Conclusions Evolocumab effectively reduced LDL-C, non-HDL-C, ApoB, Lp(a), and remnant cholesterol in individuals with T2DM with and without AD. Evolocumab Q2W or QM enabled most individuals at high/very-high cardiovascular disease risk to achieve their LDL-C, non-HDL-C, and ApoB recommended goals.