Hypertriglyceridemic Patients Research Articles

Prognostic Significance of Hypertriglyceridemia in Patients at High and Very High Cardiovascular Risk Depending on the Concentration of Highsensitivity C-reactive Protein.

It has been established that an increase in triglyceride-rich lipoprotein levels is associated with the development of systemic low-grade inflammation. Data on the prognostic role of hypertriglyceridemia (HTG) dependent on the state of low-grade inflammation are limited. The study's objective was to evaluate the predictive value of mild-to-moderate HTG (2.3- 11.2 mmol/L) regarding the development of cardiovascular events in patients at high and very high cardiovascular risk (CVR), depending on the high-sensitivity C-reactive protein (hsCRP) values. The study included 185 patients with high and very high CVR. The concentration of hsCRP in blood serum was measured using an enzyme-linked immunosorbent assay kit. The combined endpoint was cardiovascular death, nonfatal myocardial infarction or unstable angina (which required hospitalization), nonfatal stroke, and coronary revascularization. HTG was revealed in 17.3% of the patients. An increase in hsCRP ≥2.0 mg/L was observed in 51.9% of the patients. The event-free survival of patients with HTG was not statistically different from that in patients with TG <2.3 mmol/L (RR 1.61; 95% CI 0.86-3.00; p=0.133). In the subgroup of patients with hsCRP <2.0 mg/L, patients with HTG were not significantly different from patients without HTG. In the subgroup of patients with hsCRP≥2.0 mg/L, the presence of HTG was associated with a 4.63 times increase in the RR of adverse cardiovascular events (95% CI 1.35-15.8; p=0.015) after adjusting for potential confounders. In patients with high and very high CVR, an increase in TG ≥2.3 mmol/L was associated with the development of adverse cardiovascular events only in the subgroup of patients with an increase in hsCRP ≥2.0 mg/L. The presence of HTG was associated with a 4.63 times increase in RR of adverse cardiovascular events (95% CI 1.35-15.8; p=0.015).

The Relation between Resistin (−420C/G) Single Nucleotide Variant, Resistin Serum Concentration, Carbohydrate, and Lipid Parameters and Fried Food Taste Preference in Patients with Hypertriglyceridemia

Resistin is a proinflammatory adipokine involved in metabolic disorders. Its interplay with hypertriglyceridemia remains to be elucidated. We aimed to evaluate the relationship between resistin (-420C/G) single nucleotide variant (SNV) and metabolic parameters and preference for fried food consumption in hypertriglyceridemia. The study enrolled 179 hypertriglyceridemic (HTG) and 182 normotriglyceridemic (NTG) patients. Anthropometric measurements, serum resistin, insulin and fasting glucose concentration, a homeostatic model assessment-insulin resistance (HOMA-IR), triglycerides (TG), cholesterol concentration, and fried food taste preference (FP) or other cooking methods preference (OP) were assessed in the study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. HTG and NTG groups did not differ significantly in serum resistin concentration; HTG individuals demonstrated significantly increased serum levels of TG, glucose, total cholesterol (TCH), and HOMA-IR and decreased HDL cholesterol. Resistin, insulin, glucose, HOMA-IR, and cholesterol fractions were similar among particular resistin genotypes in HTG, NTG, FP, or OP groups. TG and TCH concentrations differ significantly among CG and CC genotypes in the FP group. Considering the FP group, GG and CG genotypes appeared more frequently in hyperlipidemic (OR 2.6 95% CI; 1.16-5.82; p = 0.01; significant after Bonferroni correction) than in NTG patients. Multivariable logistic regression models showed that the G allele and CG genotype of SNV (-420C/G), adjusted for selected confounders such as fried food preference, increased the odds of hypertriglyceridemia about twofold. Allele G and CG genotype of resistin SNV (-420C/G) are linked with the preference for fried food taste in hypertriglyceridemic patients.

Treatment of hypertriglyceridaemia with icosapent ethyl in patients with high/very high cardiovascular risk. Consensus document of the Sociedad Española de Cardiología [Spanish Society of Cardiology] and the Sociedad Española de Diabetes [Spanish Diabetes Society

The Working Groups of Cardiovascular Pharmacotherapy of the Sociedad Española de Cardiología and Cardiovascular Disease of the Sociedad Española de Diabetes have prepared a consensus document on the treatment of hypertriglyceridaemia in patients with high/very-high-cardiovascular risk with icosapent ethyl, a highly purified and stable eicosapentaenoic acid ethyl ester. This document is necessary since there are differences among the three main omega-3 fatty acids and there is large-scale clinical evidence with icosapent ethyl that demonstrates that in addition to its efficacy in lowering triglyceridaemia, it reduces the risk of cardiovascular events in both patients with atherosclerotic cardiovascular disease and in those with type 2 diabetes, with a good safety profile. The number needed to treat to avoid a major cardiovascular event is analysed, comparing it with other pivotal studies of pharmacological intervention in cardiovascular prevention, and an estimate of the Spanish population likely to be treated with ethyl icosapent is carried out. These recommendations are of interest to all clinicians who manage patients with lipid metabolism disorders, cardiovascular disease and diabetes.

Elevated serum triglyceride levels may be a key independent predicting factor for gallbladder cancer risk in gallbladder stone disease patients: a case–control study

BackgroundGallbladder stone diseases (GSD) is a main risk factor of gallbladder cancer (GBC). This study aimed to reveal their bridge to metabolic syndrome.Material/methodThe clinical and experimental data of 2210 GBC patients, from 3524 Chinese patients, in our hospital from Jan. 2009 to Dec. 2020 were summarized. The metabolic syndrome indexes, influencing factors for both GBC and GSD, were analyzed by unconditional logistic regression in this case–control study.ResultThere were significantly higher morbidity of GBC in the overall, GSD and non-GSD with hypertriglyceridemia patients versus non-hypertriglyceridemia ones (P < 0.001, all). In GSD patients, univariate regression showed a significantly positive correlation between serum triglyceride (TG), low density lipoprotein cholesterol (LDL-c), fasting insulin (FINS) levels, Homeostasis model assessment-insulin resistance (HOMA-IR), female being, body mass index, hypertriglyceridemia and hazard of GBC with GSD (P < 0.001, all), and a significantly negative correlation to systolic pressure (SBP), diastolic pressure (DBP), hypertension and high-density lipoprotein cholesterol (HDL-c), fasting blood glucose (FBG) (P < 0.05, all); multivariate regression showed that serum triglyceride was the most significantly positive factor associated to GBC (P < 0.001, all) among the hazard factors including serum TG, LDL-c levels, HOMA-IR. In non-GSD ones, multivariate regression showed that HOMA-IR was the most significantly positive factor associated to GBC among the hazard factors including serum TG, LDL-c levels, HOMA-IR, female being, while DM had a significantly inversion negative association (P < 0.001).ConclusionWe found initially that elevated serum TG levels could be the most remarkable independent predicting factor for GBC risk with GSD, while insulin resistance might act as the first one in non-GSD. More importantly, we advocated initially the sharp rise of serum TG levels as the potential of a candidate diagnostic or prognostic biomarker of GBC with GSD.Trial registrationThe study may be performed in accordance with the ethical standards provided by the responsible committee of our institution (First Affiliated Hospital of Xi’an Jiaotong University. XJTU1AF2020LSK-160) at which the work was carried out an in accordance with the Declaration of Helsinki. The ethics committee of our institution strictly comply with the requirements of ICH-GCP、GCP and relevant regulations to construct, operate and implement operating procedures.

Observational study of post prandial hypertriglyceridemia is a reliable predictor for coronary artery disease

Introduction: Hypertriglyceridemia is recognized as a high-risk factor for coronary artery disease. It remains unclear whether fasting or postprandial hypertriglyceridemia is more informative for predicting the risk of coronary artery disease. Recent studies recommended postprandial Hypertriglyceridemia as a useful predictor of cardiovascular disease risk. This study was conducted to find the correlation between postprandial Hypertriglyceridemia in patients with coronary artery disease. Materials and Methods: This was an observational study on 100 patients diagnosed with coronary artery disease from 14/10/2017 to 10/09/2018. In patients diagnosed with coronary artery disease based on ECG changes or TMT, changes were included in the study. Fasting lipid profile, FBS, and 2-hour postprandial Triglyceride were done. All statistical data were analyzed using frequency, percentages, and ratios. A chi-square test is used to study the associations among different variables. Results: Among the 100 cases included in the study, 68 were males, and 32 were females. Postprandial Hypertriglyceridemia was found in 71% of patients, 48% had high BMI, 80% of Patients had high Waist Hip ratio, and 64 % of patients had diabetes mellitus. There is a statistically significant correlation between postprandial Triglyceride and coronary artery disease with a relative risk of 1.45.

Long-term safety and efficacy of MND-2119 (self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester) in patients with hypertriglyceridemia: Results from a multicenter, 52-week, open-label study

BackgroundIn Japan, eicosapentaenoic acid ethyl ester (EPA-E) is administered twice-daily or three-times-daily for dyslipidemia. We have developed MND-2119, a novel self-emulsifying formulation of highly purified EPA-E which can be administered once-daily. ObjectiveThe objective of this study was to investigate the safety and efficacy of long-term administration of MND-2119 in hypertriglyceridemia patients. MethodsIn this multicenter, 52-week, open-label study, patients with high triglyceride (TG) (TG levels between ≥ 150 and < 500 mg/dL) undergoing lifestyle modification were randomized to MND-2119 2 g/day (n=61) or MND-2119 4 g/day (n=61). ResultsThe incidence of adverse events in MND-2119 2 g/day and MND-2119 4 g/day was 70.5% and 62.3%, respectively, and the incidence of adverse drug reactions was 9.8% and 8.2%, respectively. There were no notable problems in the safety assessments of both treatment groups. By Week 4, TG levels had decreased from baseline in both groups, and the TG reducing effect continued up to Week 52 (mean percentage change from baseline in TG at Week 52 [two-sided 95% confidence interval]: MND-2119 2 g/day: -16.71% [-26.61, -6.81], MND-2119 4 g/day: -21.01% [-27.86, -14.16]). In both groups, plasma EPA concentration at Week 4 was maintained up until Week 52 and the plasma EPA concentration at Week 52 was 200.5 ± 54.7 μg/mL in MND-2119 2 g/day and 308.6 ± 98.6 μg/mL in MND-2119 4 g/day. ConclusionLong-term administration of MND-2119 was not associated with any safety-related problems. TG levels decreased by Week 4, and the TG reducing effect continued up to Week 52.

Use of Digital Technology Tools to Characterize Adherence to Prescription-Grade Omega-3 Polyunsaturated Fatty Acid Therapy in Postmyocardial or Hypertriglyceridemic Patients in the DIAPAsOn Study: Prospective Observational Study.

BackgroundMaintaining sustained adherence to medication for optimal management of chronic noninfectious diseases, such as atherosclerotic vascular disease, is a well-documented therapeutic challenge.ObjectiveThe DIAPAsOn study was a 6-month, multicenter prospective observational study in the Russian Federation that examined adherence to a preparation of highly purified omega-3 polyunsaturated fatty acids (Omacor) in 2167 adult patients with a history of recent myocardial infarction or endogenous hypertriglyceridemia.MethodsA feature of DIAPAsOn was the use of a bespoke electronic patient engagement and data collection system to monitor adherence. Adherence was also monitored by enquiry at clinic visits. A full description of the study’s aims and methods has appeared in JMIR Research Protocols.ResultsThe net average reduction from baseline in both total and low-density lipoprotein cholesterol was approximately 1 mmol/L and the net average increase in high-density lipoprotein cholesterol was 0.2 (SD 0.53) mmol/L (P<.001 for all outcomes vs baseline). The mean triglyceride level was 3.0 (SD 1.3) mmol/L at visit 1, 2.0 (SD 0.9) mmol/L at visit 2, and 1.7 (SD 0.7) mmol/L at visit 3 (P<.001 for later visits vs visit 1). The percentage of patients with a triglyceride level <1.7 mmol/L rose from 13.1% (282/2151) at baseline to 54% (1028/1905) at the end of the study. Digital reporting of adherence was registered by 8.3% (180/2167) of patients; average scores indicted poor adherence. However, a clinic-based enquiry suggested high levels of adherence. Data on health-related quality of life accrued from digitally engaged patients identified improvements among patients reporting high adherence to study treatment, but patient numbers were small.ConclusionsThe lipid and lipoprotein findings indicate that Omacor had nominally favorable effects on the blood lipid profile. Less than 10% of patients enrolled in DIAPAsOn used the bespoke digital platform piloted in the study, and the level of self-reported adherence to medication by these patients was also low. Reasons for this low uptake and adherence are unclear. Better adherence was recorded in clinical reports.Trial RegistrationClinicalTrials.gov NCT03415152; https://clinicaltrials.gov/ct2/show/NCT03415152

Observational study of post prandial hypertriglyceridemia is a reliable predictor for coronary artery disease

Introduction: Hypertriglyceridemia is recognized as a high-risk factor for coronary artery disease. It remains unclear whether fasting or postprandial hypertriglyceridemia is more informative for predicting the risk of coronary artery disease. Recent studies recommended postprandial Hypertriglyceridemia as a useful predictor of cardiovascular disease risk. This study was conducted to find the correlation between postprandial Hypertriglyceridemia in patients with coronary artery disease. Materials and Methods: This was an observational study on 100 patients diagnosed with coronary artery disease from 14/10/2017 to 10/09/2018. In patients diagnosed with coronary artery disease based on ECG changes or TMT, changes were included in the study. Fasting lipid profile, FBS, and 2-hour postprandial Triglyceride were done. All statistical data were analyzed using frequency, percentages, and ratios. A chi-square test is used to study the associations among different variables. Results: Among the 100 cases included in the study, 68 were males, and 32 were females. Postprandial Hypertriglyceridemia was found in 71% of patients, 48% had high BMI, 80% of Patients had high Waist Hip ratio, and 64 % of patients had diabetes mellitus. There is a statistically significant correlation between postprandial Triglyceride and coronary artery disease with a relative risk of 1.45.

Tratamiento de la hipertrigliceridemia con icosapento de etilo en pacientes de alto/muy alto riesgo cardiovascular. Documento de consenso de la Sociedad Española de Cardiología y Sociedad Española de Diabetes

The Working Groups of Cardiovascular Pharmacotherapy of the Sociedad Española de Cardiología and Cardiovascular Disease of the Sociedad Española de Diabetes have prepared a consensus document on the treatment of hypertriglyceridaemia in patients with high/very-high-cardiovascular risk with icosapent ethyl, a highly purified and stable eicosapentaenoic acid ethyl ester. This document is necessary since there are differences among the three main omega-3 fatty acids and there is large-scale clinical evidence with icosapent ethyl that demonstrates that in addition to its efficacy in lowering triglyceridaemia, it reduces the risk of cardiovascular events in both patients with atherosclerotic cardiovascular disease and in those with type 2 diabetes, with a good safety profile. The number needed to treat to avoid a major cardiovascular event is analysed, comparing it with other pivotal studies of pharmacological intervention in cardiovascular prevention, and an estimate of the Spanish population likely to be treated with ethyl icosapent is carried out. These recommendations are of interest to all clinicians who manage patients with lipid metabolism disorders, cardiovascular disease and diabetes.

Palmar Striated Xanthomas in Clinical Practice.

Context Palmar striated xanthomas (PSX) are macular subcutaneous lesions conferring a yellow-to-orange coloration of palmar and finger creases that characterize dysbetalipoproteinemia, a disease associated with sustained plasma accumulation of triglyceride-rich lipoprotein remnants. Although remnants accumulation may occur in any condition interfering with triglyceride-rich lipoprotein hydrolysis or clearance, the presence of PSX has not been systematically assessed across the spectrum of lipid disorders potentially associated with sustained or recurrent remnants accumulation.ObjectiveThe aim of this study was to assess the occurrence of (PSX) in a wide spectrum of lipid disorders ranging from very severe hypercholesterolemia (homozygous familial hypercholesterolemia) to very severe hypertriglyceridemia (chylomicronemia).MethodsThis study involved 3382 dyslipidemic White adult patients (1856 men and 1526 women) seen at the Chicoutimi Hospital Lipid Clinic (Quebec, Canada), covering a wide range of lipid disorders, from severe hypertriglyceridemia to severe hypercholesterolemia. Categorical variables were compared using the Pearson χ 2 statistic, whereas univariate analysis of variance or nonparametric Kruskal-Wallis was used for continuous variables.ResultsA total of 5.1% (173/3382) of the studied patients presented PSX, a majority of them (67.1%) being women. PSX were observed in 18.8% of patients with dysbetalipoproteinemia and also among 14.1% of hypertriglyceridemic patients with partial lipoprotein lipase deficiency, 3.7% of patients with chylomicronemia, and in all those with homozygous familial hypercholesterolemia. Overall, 10.7% of patients with PSX did not meet dysbetalipoproteinemia diagnosis criteria.ConclusionAccording to our study, the PSX prevalence estimate among patients without dysbetalipoproteinemia would be around 10% and they could be observed in a wide spectrum of lipid disorders associated with recurrent or sustained remnant lipoprotein accumulation.

Prospective Validation of a Machine Learning Model for Low-Density Lipoprotein Cholesterol Estimation.

We aim to prospectively validate a previously developed machine learning algorithm for low-density lipoprotein cholesterol (LDL-C) estimation. We retrospectively and prospectively evaluated a machine learning algorithm based on k-nearest neighbors (KNN) according to age, sex, healthcare setting, and triglyceridemia against a direct LDL-C assay. The agreement of low-density lipoprotein-k-nearest neighbors (LDL-KNN) with the direct measurement was assessed using intraclass correlation coefficient (ICC). The analysis comprised 31,853 retrospective and 6599 prospective observations, with a mean age of 54.2 ± 17.2 years. LDL-KNN exhibited an ICC greater than 0.9 independently of age, sex, and disease status. LDL-KNN was in satisfactory agreement with direct LDL-C in observations with normal triglyceridemia and mild hypertriglyceridemia but displayed an ICC slightly below 0.9 in severely hypertriglyceridemic patients and lower in very low LDL-C observations. LDL-KNN performs robustly across ages, genders, healthcare settings, and triglyceridemia. Further algorithm development is needed for very low LDL-C observations.

Clinical features and functions of a novel Lpl mutation C.986A>C (p.Y329S) in patient with hypertriglyceridemia

ObjectiveTo investigate and assess the clinical features and functions of a new lipoprotein lipase (Lpl) gene mutation c.986A>C (p.Y329S) found in hypertriglyceridemia(HTG) patients from a Chinese family. MethodsFive members of a family with the proband were diagnosed with HTG were investigated, and fasting peripheral blood was collected . The plasma was then used to measure triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein cholesterol (HDL-C), free fatty acids (FFA), and glucose tolerance. Following that, genomic deoxyribonucleic acid (DNA) was extracted from whole-blood samples using the QIAamp whole-blood DNA kit, and the coding exon regions and flanking regions of 95 dyslipidemia-related genes were captured using GenCap liquid-phase target gene capture technology. The activity of LPL and its mutation were then determined using cell assays, and the newly discovered LPL mutant was functionally analyzed. The binding site of fenofibrate and LPL, as well as the mutation, were subjected to predictive analysis. ResultsThe LPL gene's c.986A>C (p.Y329S) heterozygous mutation was discovered, and patients with the mutation had the typical phenotype of LPL deficiency and weakened LPL activity. Furthermore, this mutant has been treated with fenofibrate, and its triglyceride level is perfectly controlled and stable. The prediction analysis of the fenofibrate and LPL binding sites reveals that the wild-type system, Phe378 contributes most to the binding energy of fenofibrate. In the mutant system, Tyr394, which contributes the most to the binding energy of fenofibrate, the contribution of S329 is greater than that of Y329 (0.9∼0.7 kal/mol) . After Y329 is mutated, the hydrogen bond data of fenofibrate and LPL will also increase to quote H-bond diagrams. ConclusionsA heterozygous mutation c.986A>C (p.Y329S) in exon 6 of Lpl gene occurs in the proband with familial HTG. Lpl c.986A>C (p.Y329S) mutation weakens the activity of the LPL, which may be the pathogenic mutation of HTG. In addition, The proband has been treated with fenofibrate and the triglyceride level is ideally controlled and stable. The prediction analysis of the fenofibrate and LPL binding site shows that the wild-type system, Phe378 contributes most to the binding energy of fenofibrate. In the mutant system, Tyr394, which contributes the most to the binding energy of fenofibrate, the contribution of S329 is greater than that of Y329 (0.9∼0.7 kal/mol). After Y329 is mutated, the hydrogen bond data of fenofibrate and LPL will also increase, which may be one of the reasons why the mutation has no effect on the therapeutic effect of fenofibrate.

Mitochondrial Homeostasis in Obesity-related Hypertriglyceridemia.

ContextThe prevalence of obesity and hypertriglyceridemia is an alarming worldwide health issue. Mitochondria play a central role in these disorders as they control cell metabolism.ObjectiveThe aim of the present study was to characterize mitochondrial homeostasis in subcutaneous and visceral adipose tissue (SAT and VAT) in grade III obese patients with and without hypertriglyceridemia. Moreover, this study presents the evaluation of mitochondrial fitness as a marker for hypertriglyceridemia improvement.PatientsEight control and 12 hypertriglyceridemic (HTG) grade III obese subjects undergoing bariatric surgery were included.Main Outcome MeasuresAnthropometric and biochemical data were obtained before and 3 months after surgery. Mitochondrial homeostasis was evaluated by mitochondrial DNA (mtDNA), gene expression and protein abundance in SAT and VAT.ResultsMitophagy-related gene expression was increased in HTG SAT and VAT, while mitochondrial marker gene expression and mtDNA were decreased, indicating an altered mitochondrial homeostasis in HTG. Mitophagy protein abundance was increased in VAT of those subjects that did not improve their levels of triglycerides after bariatric surgery, whereas mitochondrial protein was decreased in the same tissue. Indeed, triglyceride levels positively correlated with mitophagy-related genes and negatively with mitochondrial content markers. Moreover, mitochondria content and mitophagy markers seem to be significant predictors of hypertriglyceridemia and hypertriglyceridemia remission.ConclusionsMitochondrial homeostasis of adipose tissue is altered in hypertriglyceridemic patients. At the protein level, mitochondria content and mitophagy are potential markers of hypertriglyceridemia remission in obese patients after bariatric surgery. These results may contribute to the implementation of a clinical approach for personalized medicine.

Saroglitazar is noninferior to fenofibrate in reducing triglyceride levels in hypertriglyceridemic patients in a randomized clinical trial

Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500–1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = −55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = −41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated.

Hypertriglyceridemia Impairs Urethral Spontaneous Tone Through Down-regulation of ANO1 in Mouse Urethral Smooth Muscle Cells

ObjectiveTo investigate the effect of hypertriglyceridemia (HTG) on the Anoctamin 1 (ANO1)-centered signal on urinary incontinence. MethodsFemale mice were fed with high fat diet to set up HTG mice model. ANO1 expression in urethrae were detected by Flow Cytometry and Western Blotting. The habit of micturition was recorded through urine spot test. Urethral Smooth Muscle Myography was used to record the urethral spontaneous tone (STT) and contraction. Patch-clamp Recording confirmed the currents of ANO1 in urethral smooth muscle cells. ResultsHTG mice showed almost abolished STT and significantly decreased contraction induced by EACT. Meanwhile, a change in urination habits was detected in HTG mice which suggested that mice could not hold the urethral pressure. Furthermore, ANO1 expression in single urethral smooth muscle cells from HTG mice decreased almost 30% than that found in cells from normal group. Moreover, EACT (an N-aroylaminothiazole, ANO1 activator) induced decreased intracellular calcium ([Ca2+]i) and currents in single urethral smooth muscle cells from HTG mice. ConclusionThese results suggested that hypertriglyceridemia decreased the STT on urethral motility by down-regulating the expression of ANO1 in urethral smooth muscles. These findings provide a new perspective on the mechanism of urinary incontinence which is common in HTG patients.

Integrated omics analysis revealed the Tinospora cordifolia intervention modulated multiple signaling pathways in hypertriglyceridemia patients-a pilot clinical trial.

Hypertriglyceridemia (HTG) is strongly associated with the various types of disease conditions and evolving as epidemics. Hence, it is important to identify molecules that lower the triglyceride and chylomicron levels. Tinospora cordifolia is an illustrious Ayurveda drug, has proved juvenile and immunomodulatory properties. Twenty four (24) patients having >499mg/dL TG and 130-230mg/dL of cholesterol were randomized and given 100mL/day (~3.0g) water extract of T. cordifolia (TCE) for 14days. Basal parameters were analyzed before and after TC intervention to analyzed primary outcomes. Further, unbiased metabolomics and proteomics profiling was explored to assess the efficacy of TCE in HTG patients. TCE intervention decreased the levels of triglycerides, and VLDL to 380.45 ± 17.44, and 31.85 ± 5.88, and increased the HDL levels to 47.50 ± 9.05mg/dL significantly (p < 0.05). Metabolomics analysis identified the significant alteration in 69 metabolites and 72 proteins in plasma of HTG patients. TCE intervention reduced the level of isoprostanes, ROS, BCAA, and fatty acid derivatives, significantly. The annotation databases, Metboanalyst predicted Akt and Rap1 signaling, and ECM-receptor interaction is the most affected in HTG patients. TCE intervention normalized these events by increasing the peroxisome biogenesis and modulating Akt and Rap1 signaling pathway. T. cordifolia intervention suppresses the baseline in HTG patients. Omics analysis showed that TCE intervention modulates the Akt and Rap signaling, and peroxisome biogenesis to control the cellular switches and signaling pathways. Hence, TCE can be used as a supplement or alternate of standard drugs being used in the management of HTG. The online version contains supplementary material available at 10.1007/s40200-022-00985-6.

Identification of Key LncRNAs and Pathways in Prediabetes and Type 2 Diabetes Mellitus for Hypertriglyceridemia Patients Based on Weighted Gene Co-Expression Network Analysis.

AimsPrevalence of prediabetes and type 2 diabetes mellitus(T2DM) are increasing worldwide. Key lncRNAs were detected to provide a reference for searching potential biomarkers of prediabetes and T2DM in hypertriglyceridemia patients.MethodsThe study included 18 hypertriglyceridemia patients: 6 newly diagnosed type 2 diabetes patients, 6 samples with prediabetes and 6 samples with normal blood glucose. Weighted gene co-expression network analysis (WGCNA) was conducted to construct co‐expression network and obtain modules related to blood glucose, thus detecting key lncRNAs.ResultsThe green, yellow and yellow module was significantly related to blood glucose in T2DM versus normal controls, T2DM versus prediabetes, prediabetes versus normal controls, respectively. ENST00000503273, ENST00000462720, ENST00000480633 and ENST00000485392 were detected as key lncRNAs for the above three groups, respectively.ConclusionsFor hypertriglyceridemia patients with different blood glucose levels, ENST00000503273, ENST00000462720 and ENST00000480633 could be potential biomarkers of T2DM.

DNA methylation pattern of hypertriglyceridemic subjects

BackgroundChylomicronemias are generally diagnosed genetically by genomic sequencing or screening for mutations in causal genes with a large phenotypic effect. This strategy has allowed to improve the characterization of these patients, but we still have 30% of the patients without a conclusive genetic diagnosis. This is why we hypothesize that by adding the epigenetic component we can improve the genetic diagnosis, and for this we have explored the degree of methylation in the DNA of hypertriglyceridemic patients. MethodologyBlood cell DNA was obtained from 16 hypertriglyceridemic patients and from 16 age- and sex-matched control subjects. The degree of methylation in genome-wide DNA was determined using the Illumina Infinium Methylation EPIC Array Analysis. ResultsWe identified 31 differentially methylated cytosines by comparing the methylation patterns presented by hypertriglyceridemic patients vs control subjects. The cg03636183 in the F2RL3 gene was 10% hypomethylated in hypertriglyceridemic patients, and has previously been associated with an increased cardiovascular risk. Cg13824500 is 10% hypomethylated in hypertriglyceridemic patients and is located in VTI1A, which is a limiting gene in the transit of chylomicrons in the enterocyte through the endoplasmic reticulum and the Golgi apparatus. Cg26468118 in the RAB20 gene (13% hypomethylated) and cg21560722 in the SBF2 gene (33% hypermethylated) are involved in the regulation of Golgi apparatus vesicles. ConclusionsOur results suggest that there are differentially methylated regions related to the formation of chylomicrons in hypertriglyceridemic patients.

Effect of Pemafibrate on Serum Creatinine in Patients with Chronic Kidney Disease.

Introduction: Fibrates are recommended not to be used for the treatment of hypertriglyceridemia in patients with chronic kidney disease (CKD) based on clinical practice guidelines. The major reason for the negative suggestion is the elevation of serum creatinine and rhabdomyolysis by fibrates. This may cause clinical inertia for the treatment of hypertriglyceridemia using fibrate in patients with CKD, who are associated with an increasing risk of cardiovascular disease. Methods: We retrospectively studied the change of serum creatinine via the treatment of pemafibrate. Results: A total of 39 patients with CKD were treated with 0.2 mg of pemafibrate. Serum triglyceride was decreased in 23 fibrate-naïve patients from 380 [308, 455] mg/dL to 180 [152, 215] mg/dL via treatment with pemafibrate (p = 0.00003). Serum creatinine and eGFR were not changed from 1.22 ± 0.29 mg/dL to 1.21 ± 0.28 mg/dL (p = 0.70) and from 45.7 ± 10.9 mL/min/1.73 m2 to 46.2 ± 12.0 mL/min/1.73 m2 (p = 0.67) via treatment with pemafibrate, respectively. In 16 patients, with a change of treatment from fenofibrate or bezafibrate to pemafibrate, serum creatinine was significantly decreased from 1.32 ± 0.36 mg/dL to 1.17 ± 0.24 mg/dL (p = 0.003). eGFR was significantly increased from 45.2 ± 9.9 mL/min/1.73 m2 to 50.1 ± 8.6 mL/min/1.73 m2 (p = 0.001). Conclusions: These results suggest that treatment with pemafibrate does not affect the serum creatinine level and is suitable for use in patients with CKD for the treatment of hypertriglyceridemia.

Concordance of apolipoprotein B concentration with the Friedewald, Martin-Hopkins, and Sampson formulas for calculating LDL cholesterol.

IntroductionTwo new formulas, the Martin-Hopkins and the Sampson formula, were recently developed to overcome shortcomings of the Friedewald formula for calculating LDL-cholesterol. We aimed to compare the concordance of the two formulas with apolipoprotein B (apoB), a surrogate marker of the number of LDL particles.Materials and methodsIn a study of serum lipid data of 1179 patients who consulted the AZ St-Jan Hospital Bruges for cardiovascular risk assessment, the correlation and concordance of the Friedewald, Martin-Hopkins and Sampson formulas with apoB concentration, measured by immunonephelometry, were determined and compared.ResultsThe Martin-Hopkins formula showed significantly higher correlation coefficient than the Friedewald formula with apoB in the entire dataset and in patients with low LDL-cholesterol < 1.8 mmol/L. Both Martin-Hopkins and Sampson formulas yielded > 70% concordance of LDL-cholesterol with regard to treatment group classification based on population-equivalent thresholds of apoB in hypertriglyceridemic patients (2-4.5 mmol/L), with the highest concordance (75.6%) obtained using Martin-Hopkins formula vs. 60.5% with Friedewald formula.ConclusionThe Martin-Hopkins (and, to a lesser extent, Sampson) formula is more closely associated with the number of LDL particles than Friedewald formula. This, in combination with literature evidence of lesser accuracy of the Friedewald formula, is an argument to switch from Friedewald to a modified, improved formula.