Effects of Elobixibat on Constipation and Lipid Metabolism in Patients With Moderate to End-Stage Chronic Kidney Disease

Objective:The aim of this study was to investigate the effects of elobixibat on constipation and lipid metabolism; and determine the factors associated with the effect of elobixibat on constipation in patients with moderate to end-stage chronic kidney disease (CKD).Methods:Stool frequency and serum lipid parameters were retrospectively analyzed before and after 4 weeks of elobixibat administration in 42 patients (CKD stage G3, 6; stage G4, 9; stage G5, 9; stage G5D, 18). Relationships between the change in stool frequency after initiation of elobixibat and various clinical parameters were analyzed by using linear regression analysis.Results:Elobixibat increased stool frequency from 0.5 ± 0.4 per day to 1.1 ± 0.6 per day (p < 0.001) regardless of whether patients were undergoing dialysis, on concomitant laxatives, or were administered elobixibat before or after breakfast. Elobixibat reduced low-density lipoprotein cholesterol concentration (from 90.9 ± 37.2 mg/dL to 77.5 ± 34.8 mg/dL, p < 0.05) and increased high-density lipoprotein cholesterol concentration (from 44.9 ± 14.3 mg/dL to 57.0 ± 25.8 mg/dL, p < 0.05), but did not change triglyceride concentration. Adverse effects were observed in two patients (nausea and diarrhea). Only phosphate concentration was correlated with the change in stool frequency after initiation of elobixibat (standard coefficient = 0.321, p = 0.043).Conclusions:Elobixibat improved constipation and lipid metabolism in patients with moderate to end-stage CKD, without serious adverse events.

The Independent Association Between Age and Serum Cholesterol Levels in Patients with Familial Hypercholesterolemia

(1) Background: Studies have suggested that age and the serum total cholesterol (TC) concentration are independent risk factors for cardiovascular disease (CVD) in patients with familial hypercholesterolemia (FH); however, the relationship between age and TC in patients with FH is unclear. We aimed to investigate the correlation between age and TC in patients with FH. (2) Methods: In this retrospective, controlled not matched analysis, a total of 103 patients with FH and 106 non-FH controls were recruited into the study from 2004 to 2017. Spearman and partial correlation analyses, as well as multiple regression analyses, were used to evaluate the relationship between TC and age. (3) Results: There were no significant differences in age, gender, or BMI between the FH group and the control group (p > 0.05). Family history of CVD, TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipoprotein (a) (Lp(a)) and non-HDL-C levels were significantly higher in patients with FH compared to the control (p < 0.01). Additionally, the serum TC levels for ages ≥ 50 years were significantly higher than those for ages < 50 years (p < 0.05) in FH patients. In both Spearman and partial correlation analyses, age was found to be significantly correlated with serum TC (p < 0.001) in the FH group but not in the control group, which was confirmed by further multiple linear regression analyses and logistic regression analyses. (4) Conclusions: Age is an independent factor influencing serum TC level in patients with FH, and it is necessary to conduct early screening and early intervention.

Liver Steatosis: Better Predictor of CKD in MAFLD Than Liver Fibrosis as Determined by Transient Elastography With Controlled Attenuation Parameter

Background: Changing the term/concept of the non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated fatty liver disease (MAFLD) may broaden the pathological definition that can include chronic renal involvement, and, possibly, changes chronic kidney disease's (CKD's) epidemiological association with liver disease, because CKD is associated with metabolic disorders and almost all patients with CKD present some form of an atherogenic dyslipidemia. Our study explores the relationship between MAFLD and CKD using Transient Elastography (TE) with a Controlled Attenuated Parameter (CAP).Methods: We evaluated 335 patients with diabetes with MAFLD and with high CKD risk using TE with CAP (FibroScan®). The CKD was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Logistic regression and stepwise multiple logistic regression were used to evaluate the factors associated with CKD. In addition, a receiver operating characteristic curve (ROC) analysis was used to assess the performance of CAP and TE in predicting CKD and its optimal threshold.Results: The prevalence of CKD in our group was 60.8%. Patients with CKD had higher mean liver stiffness measurements (LSM) and CAP values than those without CKD. We found that hepatic steatosis was a better predictor of CKD than fibrosis. Univariate regression showed that CAP values &gt;353 dB/m were predictive of CKD; while the multivariate regression analysis (after adjustment according to sex, body mass index (BMI), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and fasting glucose) showed that CAP values &gt;353 dB/m were more strongly associated with the presence of CKD compared to the LSM (fibrosis) values.Conclusion: In patients with MAFLD, CAP-assessed steatosis appears to be a better predictor of CKD compared to LSM-assessed hepatic fibrosis.

Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)‐Free Low‐Density Lipoprotein Cholesterol

Background Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]‐C) and its contribution to low‐density lipoprotein cholesterol (LDL‐C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)‐C from particle number using fixed conversion factors has been proposed (Lp[a]‐C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]‐C). The accuracy of this method, which theoretically can isolate “Lp(a)‐free LDL‐C,” has not been validated. Methods and Results In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)‐C and Lp(a)‐free LDL‐C with measured values and quantified absolute and percent error. We compared findings with an analogous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)‐C and Lp(a)‐free LDL‐C increased with higher Lp(a)‐C values. Median error for estimated Lp(a)‐C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased linearly, overestimating by +30.8 mg/dL (interquartile range, 26.1–36.5) for estimated Lp(a)‐C ≥50 mg/dL. This error relationship persisted after stratification by overall high‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)‐free LDL‐C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)‐C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)‐C≥50 mg/dL. Conclusions Lp(a)‐C estimations using fixed conversion factors overestimated Lp(a)‐C and subsequently underestimated Lp(a)‐free LDL‐C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)‐C estimations to correct LDL‐C may lead to undertreatment of high‐risk patients.

Executive functioning and serum lipid fractions in Parkinson’s disease—a possible sex-effect: the PACOS study

The association between dyslipidemia and cognitive performance in Parkinson’s disease (PD) patients still needs to be clarified. Aim of the study was to evaluate the presence of possible associations between serum lipids fractions and executive dysfunction also exploring the sex-specific contribute of lipids level on cognition. Patients from the PACOS cohort, who underwent a complete serum lipid profile measures (total cholesterol-TC, low-density lipoprotein cholesterol-LDL, high-density lipoprotein cholesterol-HDL and triglycerides-TG) were selected. Adult Treatment Panel III guidelines of the National Cholesterol Education Program were used to classify normal/abnormal lipid fractions. Executive functioning was assessed with the Frontal Assessment Battery (FAB). Logistic regression was performed to assess associations between lipids fractions and FAB score. Correlations between lipids fractions and FAB score were explored. Sex-stratified analysis was performed. Three hundred and forty-eight PD patients (148 women; age 66.5 ± 9.5 years; disease duration 3.9 ± 4.9 years) were enrolled. Women presented significantly higher TC, LDL and HDL than men. In the whole sample, any association between lipid profile measures and FAB score was found. Among women, a positive association between hypertriglyceridemia and FAB score under cutoff was found (OR 3.4; 95%CI 1.29–9.03; p value 0.013). A statistically significant negative correlation was found between the FAB score and triglyceride serum levels (r = − 0.226; p value 0.005). Differently, among men, a statistically significant negative association between hypercholesterolemia and FAB score under cutoff (OR 0.4; 95%CI 0.17–0.84; p value 0.018) and between high LDL levels and FAB score under cutoff (OR 0.4; 95%CI 0.18–0.90; p value 0.027) were found. Our data suggest a sex-specific different role of lipids in executive functioning.

Baseline Low-Density-Lipoprotein Cholesterol Modifies the Risk of All-Cause Death Associated With Elevated Lipoprotein(a) in Coronary Artery Disease Patients

Background: The prognostic value of elevated lipoprotein(a) [Lp(a)] in coronary artery disease (CAD) patients is inconsistent in previous studies, and whether such value changes at different low-density-lipoprotein cholesterol (LDL-C) levels is unclear.Methods and Findings: CAD patients treated with statin therapy from January 2007 to December 2018 in the Guangdong Provincial People's Hospital (NCT04407936) were consecutively enrolled. Individuals were categorized according to the baseline LDL-C at cut-off of 70 and 100 mg/dL. The primary outcome was 5-year all-cause death. Multivariate Cox proportional models and penalized spline analyses were used to evaluate the association between Lp(a) and all-cause mortality. Among 30,908 patients, the mean age was 63.1 ± 10.7 years, and 76.7% were men. A total of 2,383 (7.7%) patients died at 5-year follow-up. Compared with Lp(a) &lt;50 mg/dL, Lp(a) ≥ 50 mg/dL predicted higher all-cause mortality (multivariable adjusted HR = 1.19, 95% CI 1.07–1.31) in the total cohort. However, when analyzed within each LDL-C category, there was no significant association between Lp(a) ≥ 50 mg/dL and higher all-cause mortality unless the baseline LDL-C was ≥ 100 mg/dL (HR = 1.19, 95% CI 1.04–1.36). The results from penalized spline analyses were robust.Conclusions: In statin-treated CAD patients, elevated Lp(a) was associated with increased risks of all-cause death, and such an association was modified by the baseline LDL-C levels. Patients with Lp(a) ≥ 50 mg/dL had higher long-term risks of all-cause death compared with those with Lp(a) &lt;50 mg/dL only when their baseline LDL-C was ≥ 100 mg/dL.

Associations of polymorphisms of some genes with excessive weight in a population sample of young citizens of Novosibirsk

Aim of the study was to investigate the associations of polymorphisms of some genes with overweight and some anthropometric and biochemical indicators in a population sample of the young population of Novosibirsk. Material and methods. The study was carried out on a sample of young people aged 25–35 years, residents of Novosibirsk, selected by the method of random numbers (n = 319). During the survey, a questionnaire was filled out, anthropometric measurements, blood sampling, followed by biochemical and molecular genetic studies were carried out. Results. The odds ratio (OR) to detect a carrier of the AA rs9939609 genotype of the FTO gene in the group with an increased body mass index (BMI) compared to the group with a normal BMI is 2.1 times higher (95% confidence interval (95 % CI) 1.2– 3.8; p = 0.019 in the AA vs AT+TT model). In the Kruskal – Wallis test in the general group, differences were found in carriers of different rs9939609 genotypes of the FTO gene in the thickness of the skin fold in the middle third of the right shoulder (p = 0.0008) and under the right shoulder blade (p = 0.026). In carriers of the AA genotype, these indicators were noticeably higher compared to carriers of the AT and TT genotypes. Differences in high density lipoprotein cholesterol were found in women (p = 0.032; the lowest level in the AA genotype) and low density lipoprotein cholesterol (p = 0.027; the highest value in the AA genotype). In addition, female carriers of the TT rs7903146 genotype of the TCF7L2 gene had lower diastolic blood pressure than carriers of the CT and CC genotypes (p = 0.027). The probability of detecting a male carrier of the CT or TT genotypes of the TCF7L2 gene polymorphism rs7903146 in the obese group is 0.313 (95 % CI 0.102–0.955; p = 0.036 in the CC vs CT+TT model) compared with the group with excess BMI (25 ≤ BMI < 30 kg/m2 ). The probability of detecting the allele with rs10811661 of the CDKN2AB gene in the obese group is 2.2 times higher (95 % CI 1.1–4.5; p = 0.035) compared with the group with an excess BMI. Conclusion. The association of overweight in the population sample of the young population of Novosibirsk was confirmed with rs9939609 of the FTO gene, rs7903146 of the TCF7L2 gene, rs10811661 of the CDKN2AB gene. The association of rs2237892 of the KCNQ1 gene and rs1111875 of the HHEX gene with overweight was not found. Associations of the studied SNPs with some anthropometric and biochemical indicators were found.

The Ratio of Free Fatty Acids (Ffas) Divided By High-Density Lipoprotein Cholesterol (HDL-C) Is A Promising Pre-Treatment Biomarker For Predicting Worse Overall Survival (OS) of Neuroendocrine Tumours (Nets) In The Colorectum: A Retrospective Study.

Background: free fatty acids (FFAs) and high-density lipoprotein cholesterol (HDL-C) were associated with various malignancy. However, whether FFA, HDL-C and FFA/HDL-C can play a potiential role in predicting patients with colorectal neuroendocrine tumours (NETs) was unclear. Meanwhile, FFA/HDL-C has a superior prognosis ability was unknown, too.Methods: One hundred patients with pathologically diagnosed colorectal NETs in 2011-2017 were enrolled, and the levels of FFA, HDL-C, low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), cholesterol (CHOL), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) between colorectal NET patients and healthy controls matched by age and sex were compared. In addition, the association of clinicopathological characteristics and follow-up data with FFA, HDL-C and FFA/HDL-C was analysed.Results: FFA was overexpressed (0.55±0.23 vs. 0.48±0.11, P= 0.006), and HDL-C was underexpressed (1.31±0.41 vs. 1.41±0.29, P=0.046) in colorectal NETs. FFA ≥0.52 mmol/L predicted lymph node metastasis (LNM) (P=0.015), HDL-C ≤1.0 mmol/L predicted tumour size ≥2 cm (P=0.017), and FFA/HDL-C>0.75 predicted tumour grade (P=0.030), LNM (P=0.014), and tumour size(P=0.018). No significant association was found between FFA and tumour grade (P=0.613) or HDL-C and tumour grade (P=0.594) or FFA and tumour size (P=0.142) or HDL-C and LNM (P=0.443). FFA ≥0.52 mmol/L (P=0.014) and HDL-C ≤1.0 mmol/L predicted worse overall survival (OS) (P=0.019). FFA/HDL-C predicted an even worse prognosis in terms of OS (P<0.001).Conclusion: FFA ≥0.52 mmol/L HDL-C ≤1.0 mmol/L and FFA/HDL-C>0.75 were promising cut-off values in predicting LNM, tumour size and worse OS in colorectal NETs.

Lipid Metabolism Affects Fetal Fraction and Screen Failures in Non-invasive Prenatal Testing

Objective: To assess the association between lipid metabolism and fetal fraction, which is a critical factor in ensuring a highly accurate non-invasive prenatal testing (NIPT), and on the rate of screen failures or “no calls” in NIPT.Methods: A total of 4,514 pregnant women at 12–26 weeks of gestation underwent NIPT sequencing and serum lipid measurements. Univariate analysis and multivariate regression models were used to evaluate the associations of serum lipid concentrations with the fetal fraction and the rate of screen failures.Results: The fetal fraction decreased with increased low-density lipoprotein cholesterol and triglyceride (TG) levels, which were significant factors (standardized coefficient: −0.11). Conversely, high-density lipoprotein cholesterol and the interval between the two tests were positively correlated with the fetal fraction. The median fetal fraction was 10.88% (interquartile range, 8.28–13.89%) and this decreased with TG from 11.56% at ≤1.10 mmol/L to 9.51% at &gt;2.30 mmol/L. Meanwhile, multivariate logistic regression analysis revealed that increased TG levels were independently associated with the risk of screen failures. The rate of screen failures showed an increase with TG levels from 1.20% at ≤1.70 mmol/L to 2.41% at &gt;2.30 mmol/L.Conclusions: The fetal fraction and the rate of screen failures in NIPT are affected by TG levels. Meanwhile, in pregnant women with high TG levels, delaying the time between NIPT blood collections can significantly increase the fetal fraction.