Hypertriglyceridemic Subjects Research Articles

A stronger association of depression with rheumatoid arthritis in presence of obesity and hypertriglyceridemia.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic and systemic inflammation. Recent research underscores the role of chronic inflammation in multiple common RA comorbidities such as depression, obesity, and cardiovascular diseases (CVDs), suggesting a potential overlap of the pathogenic mechanisms for RA. However, it is not well understood how the coexistence of these comorbid conditions impacts the risk of RA and whether any such association relates to body's inflammatory state. We used data from the 2007-2010 United States National Health and Nutrition Examination Survey (NHANES) database and compared RA prevalence between subsamples with the presence of any two conditions among depression, obesity, and hypertriglyceridemia (HTG). Each subsample was further divided into three categories based on the serum level of the inflammatory marker C-reactive protein (CRP) and analyzed for statistically significant differences using three-way χ2 tests of independence. The study was conducted on 4,136 patients who fulfilled the inclusion criteria (representing 163,540,241 individuals after adjustment for sampling weights). Rates of depression, obesity, and HTG were found to be significantly higher (P < 0.001) among the subjects with RA compared with the control population with no arthritis. The presence of depression along with obesity or HTG showed a noticeably higher RA prevalence but such an association was not observed for the combination of obesity and HTG. The synergistic effect of HTG with depression was found to be most prominent at a medium CRP level (1-3 mg/L), while for obesity, the effect was observed across all CRP levels examined. These findings were further confirmed by the three-way χ2 test for independence. The presence of obesity or HTG in subjects suffering from depression might pose an increased risk of RA. Inflammatory mechanisms potentially play an important underlying role as suggested by the strong dependency of the association to CRP level. Identification of synergistic associations between RA risk conditions could provide useful information to predict the development and progress of RA.

Prediction of LDL in hypertriglyceridemic subjects using an innovative ensemble machine learning technique

Abstract Objectives Determining low-density lipoprotein (LDL) is a costly and time-consuming operation, but triglyceride value above 400 (TG&gt;400) always requires LDL measurement. Obtaining a fast LDL forecast by accurate prediction can be valuable to experts. However, if a high error margin exists, LDL prediction can be critical and unusable. Our objective is LDL value and level prediction with an error less than low total acceptable error rate (% TEa). Methods Our present work used 6392 lab records to predict the patient LDL value using state-of-the-art Artificial Intelligence methods. The designed model, p-LDL-M, predicts LDL value and class with an overall average test score of 98.70 %, using custom, hyper-parameter-tuned Ensemble Machine Learning algorithm. Results The results show that using our innovative p-LDL-M is advisable for subjects with critical TG&gt;400. Analysis proved that our model is positively affected by the Hopkins and Friedewald equations normally used for (TG≤400). The conclusion follows that the test score performance of p-LDL-M using only (TG&gt;400) is 7.72 % inferior to the same p-LDL-M, using Hopkins and Friedewald supported data. In addition, the test score performance of the NIH-Equ-2 for (TG&gt;400) is much inferior to p-LDL-M prediction results. Conclusions In conclusion, obtaining an accurate and fast LDL value and level forecast for people with (TG&gt;400) using our innovative p-LDL-M is highly recommendable.

Abstract TP174: The Impact Of Serum Triglycerides On Stroke Severity And Prognosis. Analysis In 6558 Patients (2014-2022)

Hypothesis: Hypertriglyceridemia (HT) may increase the risk of stroke. Limited studies have shown that stroke severity and infarction size are smaller with HT. We explored the relationship between triglyceride and stroke risk factors, severity and outcome in a large prospective database. Methods: We interrogated the Qatar Stroke Database in all patients admitted between 2014-2022 with acute ischemic stroke and evaluated the relationship between vascular risk factors, stroke severity (measured on NIHSS), stroke type (TOAST classification) and the short- (mRS at 90 days) and long-term outcomes (MACE at 1 year) in patients with and without HT. Results: 6558 patients with ischemic stroke [mean age 54.6 ± 12. 9; male 82.1%) with normal (&lt;1.7 mmol/L) in 4161 (63.4%) and high (≥1.7 mmol/L) in 2397 (36.6%) were analyzed. Patients with HT were younger (53.1 ±11.4 versus 55.4 ±13.6, p &lt;0.001), and had more diabetes, obesity, and active smoking. Stroke severity was higher with normal triglycerides (NIHSS: &lt;1.7 mmol/l - 5.5 ±5.6 vs. &gt;1.7 mmol/l - 4.4 ±4.6; p&lt;0.001). Lacunar stroke was more common with HT (53.4% vs. 45.7%, p&lt;0.001). mRS of 3-6 was more common with normal triglycerides (i.e. poorer outcome) at discharge (42% vs 35.5 p&lt;0.001) and 90-days (31.7% vs 25.5%, p&lt;0.001). Multivariate analysis showed that age, hypertension, HT, obesity, active smoking, and diabetes were independently associated with stroke severity. Conclusion: Onset of stroke occurs earlier in HT. The lower severity of symptoms and better prognosis evident with HT may in part be related to higher rates of lacunar stroke. Long-term MACE are however more frequently seen in HT subjects.

Sphingosine-1-phosphate: metabolism, transport, atheroprotection and effect of statin treatment.

To better define the metabolism of sphingosine-1-phosphate (S1P), its transport in plasma and its interactions with S1P receptors on vascular cells, and to evaluate the effect of statin treatment on the subnormal plasma levels of high-density lipoprotein (HDL)-bound S1P characteristic of the atherogenic dyslipidemia of metabolic syndrome (MetS). Neither clinical intervention trials targeted to raising high-density lipoprotein-cholesterol (HDL-C) levels nor human genome-wide association studies (GWAS) studies have provided evidence to support an atheroprotective role of HDL. Recently however a large monogenic univariable Mendelian randomization on the N396S mutation in the gene encoding endothelial lipase revealed a causal protective effect of elevated HDL-C on coronary artery disease conferred by reduced enzyme activity. Given the complexity of the HDL lipidome and proteome, components of HDL other than cholesterol may in all likelihood contribute to such a protective effect. Among HDL lipids, S1P is a bioactive sphingolipid present in a small proportion of HDL particles (about 5%); indeed, S1P is preferentially enriched in small dense HDL3. As S1P is bound to apolipoprotein (apo) M in HDL, such enrichment is consistent with the elevated apoM concentration in HDL3. When HDL/apoM-bound S1P acts on S1P1 or S1P3 receptors in endothelial cells, potent antiatherogenic and vasculoprotective effects are exerted; those exerted by albumin-bound S1P at these receptors are typically weaker. When HDL/apoM-bound S1P binds to S1P2 receptors, proatherogenic effects may potentially be induced. Subnormal plasma levels of HDL-associated S1P are typical of dyslipidemic individuals at high cardiovascular risk and in patients with coronary heart disease. International Guidelines recommend statin treatment as first-line lipid lowering therapy in these groups. The cardiovascular benefits of statin therapy are derived primarily from reduction in low-density lipoprotein (LDL)-cholesterol, although minor contributions from pleiotropic actions cannot be excluded. Might statin treatment therefore normalize, directly or indirectly, the subnormal levels of S1P in dyslipidemic subjects at high cardiovascular risk? Our unpublished findings in the CAPITAIN study (ClinicalTrials.gov: NCT01595828), involving a cohort of obese, hypertriglyceridemic subjects (n = 12) exhibiting the MetS, showed that pitavastatin calcium (4 mg/day) treatment for 180days was without effect on either total plasma or HDL-associated S1P levels, suggesting that statin-mediated improvement of endothelial function is not due to normalization of HDL-bound S1P. Statins may however induce the expression of S1P1 receptors in endothelial cells, thereby potentiating increase in endothelial nitric oxide synthase response to HDL-bound S1P, with beneficial downstream vasculoprotective effects. Current evidence indicates that S1P in small dense HDL3 containing apoM exerts antiatherogenic effects and that statins exert vasculoprotective effects through activation of endothelial cell S1P1 receptors in response to HDL/apoM-bound S1P.

A Head-to-Head Comparison of a Free Fatty Acid Formulation of Omega-3 Pentaenoic Acids Versus Icosapent Ethyl in Adults With Hypertriglyceridemia: The ENHANCE-IT Study.

BackgroundMAT9001 is an omega‐3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA‐ethyl esters [EE]), EPA+DPA‐FFA previously showed enhanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very–low fat diet. This trial compared pharmacodynamic responses and plasma omega‐3 levels following twice daily dosing, with meals, of EPA+DPA‐FFA and EPA‐EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet.Methods and ResultsThis open‐label, randomized, 2‐way crossover trial, with 28‐day treatment periods separated by ≥28‐day washout, was conducted at 8 US centers and included 100 subjects with fasting triglycerides 1.70 to 5.64 mmol/L (150–499 mg/dL) (median 2.31 mmol/L [204 mg/dL]; 57% women, average age 60.3 years). The primary end point was least squares geometric mean percent change from baseline plasma triglycerides. In the 94 subjects with analyzable data for both treatment periods, EPA+DPA‐FFA and EPA‐EE reduced least squares geometric mean triglycerides from baseline: 20.9% and 18.3%, respectively (P=not significant). EPA+DPA‐FFA reduced least squares geometric mean high‐sensitivity C‐reactive protein by 5.8%; EPA‐EE increased high‐sensitivity C‐reactive protein by 8.5% (P=0.034). EPA+DPA‐FFA increased least squares geometric mean plasma EPA, DPA, and total omega‐3 (EPA+docosahexaenoic acid+DPA) concentrations by 848%, 177%, and 205%, respectively, compared with corresponding changes with EPA‐EE of 692%, 140%, and 165% (all P<0.001). EPA+DPA‐FFA increased docosahexaenoic acid by 1.7%; EPA‐EE decreased docosahexaenoic acid by 3.3% (P=0.011). Lipoprotein cholesterol and apolipoprotein responses did not differ between treatments.ConclusionsEPA+DPA‐FFA raised plasma EPA, DPA, and total omega‐3 significantly more than did EPA‐EE. EPA+DPA‐FFA also reduced triglycerides and high‐sensitivity C‐reactive protein without increasing low‐density lipoprotein cholesterol.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT04177680.

Beyond predicting diagnosis: Is there a role for measuring biotinidase activity in liver glycogen storage diseases?

IntroductionBiotinidase synthesis is needed to recycle biotin for essential metabolic reactions. Biotinidase activity is lower than normal levels in advanced liver disease but is higher in hepatic glycogen storage disorders (GSDs), however the cause of this association remains unclear. MethodsIn this study, biotinidase activity was measured in plasma samples from 45 individuals with hepatic GSDs; GSDI (a, b; n = 25) and GSD III (a, b; n = 20), complemented by a chart review to associate biotinidase activity levels with clinical laboratory and imaging findings known to be implicated in these GSDs. ResultsOur findings showed variation in biotinidase activity levels among subjects with GSD I and III; biotinidase activity correlated positively with hypertriglyceridemia in subjects with GSD I (r = 0.47, P = 0.036) and GSD III (r = 0.58, P = 0.014), and correlated negatively with age (r = −0.50, P = 0.03) in patients with GSD III. Additionally, biotinidase activity was reduced, albeit within the normal range in subjects with evidence of fibrosis/cirrhosis, as compared to subjects with hepatomegaly with or without steatosis (P = 0.002). DiscussionsThese findings suggest that abnormal lipid metabolism in GSD I and III and progressive liver disease in GSD III may influence biotinidase activity levels. We suggest that a prospective, multi-center, longitudinal study designed to assess the significance of monitoring biotinidase activity in a larger cohort with hepatic GSDs is warranted to confirm this observation. Take-home messageAltered lipid metabolism and advancing liver fibrosis/cirrhosis may influence biotinidase activity levels in patients with hepatic glycogen storage disease. Thus, longitudinal monitoring of biotinidase activity, when combined with clinical and other biochemical findings may be informative.

An Open-label, Crossover Study Comparing EPA+DPA-Free Fatty Acids and EPA-Ethyl Esters in Adults with Elevated Triglycerides: ENHANCE-IT

<h3>Lead Author's Financial Disclosures</h3> K.C.M. has received consulting fees from Matinas BioPharma, Inc., Acasti Pharma, Inc., New Amsterdam Pharma, Pharmavite, and 89Bio. He has received research grant support from Matinas BioPharma, Inc, and Pharmavite. <h3>Study Funding</h3> Matinas BioPharma, Inc. <h3>Background/Synopsis</h3> Few head-to-head studies have directly compared the efficacy of prescription omega-3 fatty acid (OM-3) products. Both the degree of triglyceride (TG) lowering and the achieved blood levels of individual OM-3 fatty acids are important predictors of clinical efficacy. MAT9001 is a unique OM-3 free-fatty-acid (FFA) formulation, containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). A prior crossover study comparing EPA+DPA-FFA and icosapent ethyl (EPA-EE - an ethyl ester EPA formulation) showed enhanced TG lowering and higher EPA levels with EPA+DPA-FFA when both agents were administered with a very-low fat diet and once daily dosing. <h3>Objective/Purpose</h3> To compare pharmacodynamic responses and plasma OM-3 levels following 28-day twice daily treatment with EPA+DPA-FFA and EPA-EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet. <h3>Methods</h3> This open-label, 2-way crossover trial was conducted at 8 centers in the US and included 100 subjects with fasting TG 150-499 mg/dL (median 204 mg/dL; 57% female, average age 60.3 years). Participants were randomized to EPA+DPA-FFA or EPA-EE for 28 days, washed out for at least 28 days, and then crossed over to the other therapy. Both drugs were given as 2 g twice daily, with meals. The primary endpoint was least squares geometric mean (LSGM) % change from baseline in plasma TG. Additional measurements included other lipoprotein-related markers, high-sensitivity C-reactive protein (hs-CRP) and plasma levels of individual OM-3 fatty acids. <h3>Results</h3> Ninety-four subjects had analyzable data for both treatment periods. EPA+DPA-FFA and EPA-EE reduced TG from baseline: 20.9% and 18.3%, respectively (p=NS). EPA+DPA-FFA reduced hs-CRP by 5.8% compared with an increase of 8.5% with EPA-EE (p = 0.034). EPA+DPA-FFA increased LSGM plasma EPA, DPA, and total OM-3 concentrations by 848%, 692%, and 177% respectively, which were greater than corresponding changes with EPA-EE of 140%, 205%, and 165%, respectively (all p < 0.001). EPA+DPA-FFA increased docosahexaenoic acid (DHA) by 1.7%; EPA-EE decreased DHA by 3.3% (p = 0.011). Responses for lipoprotein cholesterol levels (total, VLDL, LDL, HDL) and apolipoprotein (A-1, B and C-3) did not differ between treatments. <h3>Conclusions</h3> These results demonstrate that a FFA formulation of EPA+DPA produced significantly higher plasma EPA, DPA and total OM-3 levels compared with an EE formulation of EPA, and support the

Heparin binding triggers human VLDL remodeling by circulating lipoprotein lipase: Relevance to VLDL functionality in health and disease

Hydrolysis of VLDL triacylglycerol (TG) by lipoprotein lipase (LpL) is a major step in energy metabolism and VLDL-to-LDL maturation. Most functional LpL is anchored to the vascular endothelium, yet a small amount circulates on TG-rich lipoproteins. As circulating LpL has low catalytic activity, its role in VLDL remodeling is unclear. We use pre-heparin plasma and heparin-sepharose affinity chromatography to isolate VLDL fractions from normolipidemic, hypertriglyceridemic, or type-2 diabetic subjects. LpL is detected only in the heparin-bound fraction. Transient binding to heparin activates this VLDL-associated LpL, which hydrolyses TG, leading to gradual VLDL remodeling into IDL/LDL and HDL-size particles. The products and the timeframe of this remodeling closely resemble VLDL-to-LDL maturation in vivo. Importantly, the VLDL fraction that does not bind heparin is not remodeled. This relatively inert LpL-free VLDL is rich in TG and apoC-III, poor in apoE and apoC-II, shows impaired functionality as a substrate for the exogenous LpL or CETP, and likely has prolonged residence time in blood, which is expected to promote atherogenesis. This non-bound VLDL fraction increases in hypertriglyceridemia and in type-2 diabetes but decreases upon diabetes treatment that restores the glycemic control. In stark contrast, heparin binding by LDL increases in type-2 diabetes triggering pro-atherogenic LDL modifications. Therefore, the effects of heparin binding are associated negatively with atherogenesis for VLDL but positively for LDL. Collectively, the results reveal that binding to glycosaminoglycans initiates VLDL remodeling by circulating LpL, and suggest heparin binding as a marker of VLDL functionality and a readout for treatment of metabolic disorders.

Effect of supplementation of Purslane (Portulacaoleracea) in hypertriglyceridemic subjects

Background: Portulacaoleraca (Purslane) has several health benefits. It is listed by the world health organisation as one of the most used medicinal plants and it has been given the term 'global panacea'. Many studies have demonstrated various pharmacological effects of this plant including hypoglycaemic, hypocholesterolemic, hypotriglyceridemic and antioxidant effects.Methods: A new product was developed using dried Portulacaoleraca leaves which was similar to spice powder/ chutney powder/karampodi and is used in South India as a food adjunct. The new product developed was used for supplementation studies for 90 days (3 months) among hyper triglyceridemic subjects after receiving a written informed consent. Biochemical parameters like lipid profile, i.e., total cholesterol, low density lipoprotein cholesterol, triglycerides, high density lipoprotein cholesterol, very low density lipoprotein cholesterol, kidney function test, liver function test were assessed. Baseline information, their medical history and 24 hr dietary recall was elicited from the subjects through a pretested schedule.Results: The results have shown that the triglyceride levels were significantly decreased. Total cholesterol and its fractions in the test groups showed significant decrease from pre- supplementation to during-supplementation and were stable at post-supplementation period.Conclusions: Our results indicated that the spice powder was rich in polyunsaturated fatty acids had a strong hypotriglyceridemic effect.

Apolipoprotein B48 metabolism in chylomicrons and very low-density lipoproteins and its role in triglyceride transport in normo- and hypertriglyceridemic human subjects.

Renewed interest in triglyceride-rich lipoproteins as causative agents in cardiovascular disease mandates further exploration of the integrated metabolism of chylomicrons and very low-density lipoproteins (VLDL). Novel tracer techniques and an integrated multi-compartmental model were used to determine the kinetics of apoB48- and apoB100-containing particles in the chylomicron and VLDL density intervals in 15 subjects with a wide range of plasma triglyceride levels. Following a fat-rich meal, apoB48 appeared in the chylomicron, VLDL1 and VLDL2 fractions in all subjects. Chylomicrons cleared rapidly from the circulation but apoB48-containing VLDL accumulated, and over the day were 3-fold higher in those with high versus low plasma triglyceride. ApoB48-containing particles were secreted directly into both the chylomicron and VLDL fractions at rates that were similar across the plasma triglyceride range studied. During fat absorption, whilst most triglyceride entered the circulation in chylomicrons, the majority of apoB48 particles were secreted into the VLDL density range. The intestine secretes apoB48-containing particles not only as chylomicrons but also directly into the VLDL1 and VLDL2 density ranges both in the basal state and during dietary lipid absorption. Over the day, apoB48-containing particles appear to comprise about 20-25% of circulating VLDL and, especially in those with elevated triglycerides, form part of a slowly cleared 'remnant' particle population, thereby potentially increasing CHD risk. These findings provide a metabolic understanding of the potential consequences for increased CHD risk when slowed lipolysis leads to the accumulation of remnants, especially in individuals with hypertriglyceridemia.

The spectrum of type III hyperlipoproteinemia

Type III hyperlipoproteinemia is a highly atherogenic dyslipoproteinemia characterized by hypercholesterolemia and hypertriglyceridemia due to markedly increased numbers of cholesterol-enriched chylomicron and very-low-density lipoprotein (VLDL) remnant lipoprotein particles. Type III can be distinguished from mixed hyperlipidemia based on a simple diagnostic algorithm, which involves total cholesterol, triglycerides, and apolipoprotein B (apoB). However, apoB is not measured routinely. The objective of the present study was to determine if patients with type III could be distinguished from mixed hyperlipidemia based on lipoprotein lipids. Classification was based first on total cholesterol and triglyceride and then on the apoB diagnostic algorithm using apoB plus total cholesterol plus triglycerides, and validated by sequential ultracentrifugation. Four hundred and forty normals, 637 patients with hypertriglyceridemia, and 714 with hypertriglyceridemia and hypercholesterolemia were studied. Plasma lipoproteins were separated by sequential ultracentrifugation and heparin-manganese precipitation. Cholesterol, triglyceride, and apoB were measured in plasma and isolated lipoprotein fractions. Of the 1351 patients with hypertriglyceridemia, 49 had type III hyperlipoproteinemia, as diagnosed by the apoB algorithm and validated by ultracentrifugation. Plasma triglycerides were higher in the type III subjects: 4.16mmol/L (3.35-6.08, 25th-75th percentile), but there was considerable overlap with the hypertriglyceridemic subjects 2.65mmol/L (1.91-4.20, 25th-75th percentile) and the combined hyperlipidemic subjects 3.02mmol/L (2.07-5.32, 25th-75th percentile). Similarly, total cholesterol was 4.79mmol/L (4.31-5.58, 25th-75th percentile) for type III vs 5.5 mmol/L (4.64-5.78, 25th-75th percentile) and 7.02 mmol/L (6.39-7.96, 25th-75th percentile), respectively. By contrast, as identified by the apoB algorithm, the VLDL-C/TG, VLDL-C/VLDL-TG, VLDL-C/VLDL apoB, and VLDL apoB/LDL apoB ratios were all higher in type III than in the other hypertriglyceridemic dyslipoproteinemias with the exception of type V as diagnosed by the apoB algorithm. Cholesterol and triglycerides cannot reliably distinguish type III hyperlipoproteinemia from mixed hyperlipidemia. Adding apoB and applying the apoB algorithm makes reliable diagnosis possible and easy. However, unless apoB is introduced into routine clinical care, type III hyperlipoproteinemia will often not be recognized. Given the cardiovascular risk associated with type III and its responsiveness to treatment, this should not be acceptable.

Relationship between GSTM1 and GSTT1 gene polymorphisms and plasma lipid and apolipoprotein levels in Chinese normalipidemic and endogenous hypertriglyceridemic subjects

To investigate effects of GSTM1 and GSTT1 gene polymorphisms on serum lipid and apopoprotein levels in healthy normolipidemic and endogenous hypertriglyceridemic subjects. Two hundred and thirty-seven healthy normolipidemic and 102 endogenous hypertriglyceridemic subjects from a population of Chinese Han nationality in Chengdu area were studied using the multiplex polymerase chain reaction (PCR). Serum lipids were measured by enzymatic kits and apolipoproteins AⅠ, AⅡ, B100, CⅡ, CⅢ and E were measured by the RID kits. The non-null and null genotype frequencies for GSTM1 site were 39.2% and 60.8% in the control group, respectively, and 47.6% and 52.4% in the HTG group, respectively. The non-null and null genotype frequencies for GSTT1 site were 51.5% and 48.5% in the control group, respectively, and 57.3% and 42.7% in the HTG group, respectively. The GSTM1 and GSTT1 genotype frequencies in HTG subjects were not different from those in the controls, respectively (P>0.05). However, in control group subjects with both null genotypes (GSTT1- and GSTM1-) showed the lowest plasma HDL-C levels (1.29±0.30 mmol/L), whereas those with each of the other three genotype combinations showed relatively higher HDL-C levels. There was significant difference of HDL-C levels between subjects with GSTT1-/GSTM1-and those with GSTT1+/GSTM1-(P<0.05). Similar result was not observed in HTG group. No significant changes of lipid and lipoprotein levels were observed in either GSTM1 or GSTT1 polymorphism alone in control or HTG group. The present study provides an evidence that the presence of double deletion genotypes is associated with low HDL-cholesterol levels in normal Chinese subjects. However, these polymorphisms are not associated with lipid levels in endogenous hypertriglyceridemia in Chinese population of Chengdu area.

The Lipid-lowering Effects and Associated Mechanisms of Dietary Phytosterol Supplementation.

Phytosterols (PS) are plant-based structural analogous of mammalian cholesterol that have been shown to lower blood cholesterol concentrations by ~10%, although inter-individual response to PS supplementation due to subject-specific metabolic and genetic factors is evident. Recent work further suggests that PS may act as effective triglyceride (TG)-lowering agents with maximal TG reductions observed in hypertriglyceridemic subjects. Although PS have been demonstrated to interfere with cholesterol and perhaps TG absorption within the intestine, they also have the capacity to modulate the expression of lipid regulatory genes through liver X receptor (LXR) activation. Identification of single-nucleotide polymorphisms (SNP) in key cholesterol and TG regulating genes, in particular adenosine triphosphate binding cassette G8 (ABCG8) and apolipoprotein E (apoE) have provided insight into the potential of utilizing genomic identifiers as an indicator of PS responsiveness. While PS supplementation is deemed safe, expanding research into the atherogenic potential of oxidized phytosterols (oxyphytosterols) has emerged with their identification in arterial lesions. This review will highlight the lipid-lowering utility and associated mechanisms of PS and discuss novel applications and future research priorities for PS pertaining to in utero PS exposure for long-term cardiovascular disease risk protection and combination therapies with lipidlowering drugs.

Hypertension and Lipid Profile of Patients of DG Khan District

During this study one hundred participants were enclosed with average age ± Coyote State of fifty 0 ± 5.91 years. The mean SBP and DBP were 137.5 ± 9.61 mmHg and ninety-four 5 ± 8.7 mmHg, severally. The mean TC, HDL, and low-density lipoprotein were lower for females as compared to males, that was statistically important (P and lt; 0.05). The mean age ± Coyote State of hypertensive patients and traditional were fifty 00 ± 4.06 and 35.4 ± 3.52 years, severally. Humour levels of TC, TG, and low-density lipoprotein were 238.3 ± 3.4, 178.3 ± 6.3, and 151.3 ± 7.8 mg/dL, severally, in hypertensive subjects whereas in traditional subjects, they were 187 ± 6.2, 141.5 ± 11.2, and 110.3 ± 6.3 mg/dL, severally, that were considerably higher in hypertensive patients (P and lt; 0.001). The humour HDL was considerably lower (P and lt; 0.001) in hypertensive patients (41.2 ± 3.2 mg/dL) than in normotensive subjects (44.3 ± 5.6 mg/dL). The mean SBPs of hypertensives and normotensives were 146.8 ± 8.5 mmHg versus 119.2 ± 9.3 mmHg, severally, and mean DBPs were ninety-eight 9 ± 7.3 mmHg versus eighty-four 9 ± 5.3 mmHg, severally. The mean SBP and DBP of hypertensives were beyond those of normotensives (P and lt; 0.001). Age, WC, and BMI showed important association with hypertensive patients (P and lt;0.001) however not with traditional subjects. This study was conducted in DG Khan patients showed that the foremost rife abnormality in adults, aged 20-69 years, was cholesterin below zero 9 mmol/L (46.2% for men and twenty-eight 7% for women). Hypertriglyceridemia (and gt; 2.26 mmol/L) was the second most rife abnormality (24.3%). Increased LDL (≥ 4.21 mmol/L) was ascertained in eleven 2% of the sample. Half the hyper triglyceridemic subjects had a mixed dyslipidemia or low cholesterin. Over five hundredth of the low HDL cases weren't involving hypertriglyceridemia. The Survey of HDL measured lipids and different vessel risk factors in non diabetic patients undergoing treatment for dyslipidemia in DG Khan and showed that diabetic patients had lower HDL (1.22 ± 0.37 mmol/L versus one.35 ± 0.44 mmol/L, and nbsp; P and lt;0.001) and better TG (2.32 ± 2.10 mmol/L versus one.85 ± 1.60 mmol/L, and nbsp; P and lt; 0.001) than nondiabetic patients. When a diabetic compared to nondiabetic patients had low HDL (45% versus half-hour, severally), high TG (≥ 1.7 mmol/L; fifty-seven versus forty-second, severally), or each (32% versus a hundred and ninetieth, severally). HDL and lt 0.9 mmol/L was found in eighteen of diabetic and 12-tone system of nondiabetic subjects. Previous studies showed the high rate of CVD mortality among South-East Asian compared to the remainder of the planet which majority of CVD deaths occur below the age of seventy and nbsp a good vary of risk factors for CVD has been studied in DG Khan, however few studies have measured the association of CVD risk with cardiovascular disease and macromolecule profile. A study in rural areas of DG Khan according that the prevalence of “high” TC concentration (and gt; 240 mg/dL or and gt; 6.2 mmol/L) is regarding 17 November, “high” LDL (≥ 160 mg/dL or ≥ 4.2 mmol/L) is regarding two%, and “low” HDL (and lt; 40 mg/dL or and lt; 1.04 mmol/L) is regarding sixty seven.

High frequency of type 2 diabetes and impaired glucose tolerance in Japanese subjects with the angiopoietin-like protein 8 R59W variant

Angiopoietin-like protein 8 (ANGPTL8) is considered to be metabolically multifunctional. One notable function still to be elucidated definitively is a betatrophic role in protecting and preserving pancreatic beta-cell function. There is, however, a paucity of data regarding the role of ANGPTL8 in the etiology of type 2 diabetes (T2D), but some findings of human research have suggested the potential for significant involvement. To examine the frequency of T2D and impaired glucose tolerance (IGT) in Japanese subjects with the ANGPTL8 R59W variant. ANGPTL8 R59W (Rs2278426, c.194C>T) was determined by polymerase chain reaction-restriction fragment length polymorphism using the restriction enzyme FokI in 797 consecutive Japanese individuals. Subjects with triglyceride levels greater than or equal to 150mg/dL were considered to be hypertriglyceridemic. Genotype frequencies of ANGPTL8 R59W were as follows: wild-type RR (C/C) 53.5%, RW (C/T) 36.6%, and WW (T/T) 9.9%. T2D and IGT were significantly prevalent in WW and RW subjects relative to RR among all 797 subjects (P=.0138) and also in hypertriglyceridemic subjects (P=.0015). In multiple logistic regression models for the existence of T2D and IGT in hypertriglyceridemic subjects, the odds ratio for heterozygote RW and homozygote WW genotypes to wild-type RR was 2.406 (P=.0017) after controlling the risk factors of age, gender, and body mass index as covariates. The frequency of ANGPTL8 R59W is significantly higher in Japanese subjects than in other ethnic groups. The rates of T2D and IGT were greater in subjects with the R59W variant. These findings indicate that ANGPTL8 is a participant in diabetes and a potential therapeutic target for T2D prevention, especially in East Asians.

Postprandial triglyceride responses and endothelial function in prediabetic first-degree relatives of patients with diabetes

Only a few studies have reported on postprandial lipid responses and endothelial function in prediabetic subjects. None of the study has compared role of familial predisposition in determining postprandial endothelial dysfunction and postprandial hypertriglyceridemia in subjects with prediabetes. The objective was to study the postprandial triglyceride (PPTG) responses and endothelial function in prediabetic first-degree relatives of patients with diabetes. Thirty-nine subjects were recruited on the basis of oral glucose tolerance test into 3 groups: group 1, prediabetic subjects who had a first-degree relative with diabetes; group 2, prediabetic subjects without family history of diabetes; and group 3, normal glucose tolerance subjects without family history of diabetes. Oral fat challenge test was performed in all study subjects and PPTG responses were measured up to 8hours. Postprandial endothelial function after 4hours of fat challenge was estimated by flow-mediated dilation. Postprandial endothelial dysfunction was greatest in group 1 and significantly higher in group 1 compared with group 2 (P<.001) and group 2 compared with group 3 (P<.001). PPTG responses (TG-AUC, TG-peak, TG-6hour, and TG-8hour) were significantly higher in group 1 compared with groups 2 and 3. However, they were similar between groups 2 and 3. Endothelial function showed significant negative correlation with TG-6hour and TG-8hour. Prediabetic subjects respond to fat challenge with a greater degree of TG response and endothelial dysfunction compared with normal glucose tolerance subjects especially if they have a first-degree relative with diabetes. This may contribute to enhanced cardiovascular risk reported in prediabetic individuals.

Lipid-lowering and anti-inflammatory effects of omega 3 ethyl esters and krill oil: a randomized, cross-over, clinical trial.

IntroductionPolyunsaturated fatty acids (PUFAs) derived from different sources could have different lipid-lowering effects in humans. The main aim of our study was to compare the short-term triglyceride-lowering efficacy of krill oil and purified omega 3 ethyl ester PUFAs in mildly overweight hypertriglyceridemic subjects.Material and methodsThis double-blind, randomized clinical trial was carried out in 25 moderately hypertriglyceridemic subjects (TG = 150–500 mg/dl). After a 4-week run-in, participants were allocated to treatment with similar pills containing omega 3 ethyl ester PUFAs 1000 mg twice a day vs. krill oil 500 mg twice a day. After 4 weeks of treatment, participants were asked to observe a 4-week wash-out period, and they were then assigned to the alternative treatment for a further period of 4 weeks.ResultsAlthough both PUFA sources were able to improve TG plasma levels, esterified omega 3 PUFAs were more efficacious than krill oil (p < 0.05). Nonetheless, only krill oil treatment was able to significantly improve high-density lipoprotein cholesterol and apolipoprotein AI levels, compared to both baseline (p < 0.05) and end of treatment with esterified omega 3 PUFAs (p < 0.05) values. Both treatments were able to significantly reduce high-sensitivity C-reactive protein (hs-CRP) levels from the baseline (p < 0.05), but krill oil improved it more efficaciously than esterified omega 3 PUFAs (p < 0.05).ConclusionsKrill oil has lipid-lowering effects comparable with those obtained through a 4-fold higher dose of purified omega 3 ethyl ester PUFAs in mildly overweight hypertriglyceridemic subjects, while more efficaciously reducing hs-CRP.

Association of NCOA3 polymorphisms with Dyslipidemia in the Chinese Han population.

BackgroundNuclear receptor coactivator-3 (NCOA3) is involved in various physiological processes. Emerging evidence from previous studies using animal models suggests that the NCOA3 gene (NCOA3) plays a critical role in lipid metabolism as well as adipogenesis and obesity. The present study aims to investigate the association between NCOA3 SNPs and dyslipidemia in the Chinese Han population.MethodsFive hundred and twenty-nine (529) Chinese Han subjects were recruited. Four tag SNPs (rs2425955G > T, rs6066394T > C, rs10485463C > G, and rs6094753G > A) in NCOA3, selected from the HapMap website, were genotyped using MALDI-TOF mass spectrometry. Data analysis was performed using SPSS 16.0, SNPStats and haploview 4.2.ResultsFour SNPs (rs2425955, rs6066394, rs10485463, and rs6094753) were associated with triglyceride levels. Except for SNP rs10485463, genotype distributions and allele frequencies of the other three NCOA3 SNPs (rs2425955, rs6066394, and rs6094753) were significantly different between hypertriglyceridemia subjects and normal group. Significant differences were also observed in allele frequencies and genotype distributions of SNP rs10485463 between low-HDL cholesterolemia subjects and normal group. Carriers of rs2425955 T allele had a lower risk of hypertriglyceridemia compared to GG genotype. Similar results were observed from rs6094753. Subjects with rs6066394 CT genotype had a lower risk of hypertriglyceridemia than those with the TT genotype; however, CC and TT genotypes showed no significant difference in the risk of hypertriglyceridemia. Similar results were found in the association between rs6066394 and hypercholesterolemia. The variant alleles of rs2425955, rs6066394 and rs6094753 were associated with a lower risk of hypertriglyceridemia compared with the wild-type alleles. The G allele of rs10485463 was associated with an increased risk of low-HDL cholesterolemia. In the log-additive model the association between rs2425955 and hypertriglyceridemia remained significant after Bonferroni correction, and genotypes with variant alleles were associated with a lower risk of hypertriglyceridemia.ConclusionsIn summary, this study demonstrated that variation in NCOA3 might influence the risk of dyslipidemia and serum lipid levels in Chinese Han population.

Hypertriglyceridemic subjects exhibit an accumulation of small dense chylomicron particles in the fasting state

AimNormocholesterolemic subjects with elevated fasting plasma triglycerides are at increased risk of atherosclerosis through mechanisms that are not yet delineated. We hypothesized that elevated plasma triglyceride is associated with increased vascular exposure to pro-atherogenic lipoprotein remnants. To test this hypothesis, the abundance, and size distribution of chylomicron particles were determined in individuals with and without hypertriglyceridemia. MethodsTwelve hypertriglyceridemic subjects (HTG group, triglyceride concentration ≥1.7 mmol/L) and twelve normotriglyceridemic subjects (NTG group) matched for age and gender were studied. The distribution of chylomicron particles was assessed by determining the fasting concentration of apo B-48 in serum lipoprotein fractions with Svedberg flotation rates of (Sf) > 400, Sf 20–400 and Sf < 20. ResultsThe total concentration of apo B-48 in subjects with HTG was almost twice that observed in NTG controls with ∼80% of the increase residing in the Sf < 20 fraction (HTG: 8.7 ± 1.0 μg/mL vs NTG: 5.0 ± 0.6 μg/mL; P = 0.016). Significantly greater concentrations of apo B-48 were also observed in the less dense Sf 20–400 (HTG: 1.1 ± 0.2 μg/mL vs NTG: 0.4 ± 0.07 μg/mL; P < 0.001) and the Sf > 400 (HTG: 1.1 ± 0.3 μg/mL vs NTG: 0.3 ± 0.04 μg/mL; P < 0.001) fractions. An accumulation of triglyceride was also observed across all lipoprotein fractions in HTG subjects compared to NTG (Sf 400 & Sf 20–400: P < 0.001 and Sf < 20: P = 0.013). ConclusionNormocholesterolemic, moderately hypertriglyceridemic subjects are at increased atherogenic risk due to greater apo B-48 concentration in the small, dense lipoprotein fraction.

Effect of DHA-rich fish oil on PPARγ target genes related to lipid metabolism in type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial

The beneficial effects of omega-3 polyunsaturated fatty acids on lipid levels are well documented. However, the related molecular mechanisms are widely unknown. Omega-3 polyunsaturated fatty acids are natural ligand for peroxisome proliferator-activated receptor γ (PPARγ). The aim of this study was to evaluate the effect of docosahexaenoic acid (DHA)-rich fish oil supplementation on modulation of some PPARγ-responsive genes related to lipid metabolism. Patients with type 2 diabetes were randomly assigned to consume either DHA-rich fish oil (containing 2400 mg/d fish oil; DHA: 1450 mg and eicosapentaenoic acid: 400 mg) or placebo for 8 weeks. Lipid profile and glycemic control parameters as well as the gene expression of PPARγ, liver x receptor-a, ATP-binding cassette A1, and CD36 in peripheral blood mononuclear cells were measured at baseline and after 8 weeks. DHA-rich fish oil supplementation resulted in decreased triglycerides (TG) level compared with placebo group, independently of the baseline value of TG (all patients (P = .003), hypertriglyceridemic subjects (P = .01), and normotriglyceridemic subjects (P = .02)). Moreover, a higher reduction in TG level was observed in hypertriglyceridemic subjects, comparing to normotriglyceridemic subjects with DHA-rich fish oil supplementation (P = .01). Other lipid parameters as well as the expression of PPARγ, liver x receptor-a, ATP-binding cassette A1, and CD36 were not affected by DHA-rich fish oil supplementation. Only in hypertriglyceridemic subjects, DHA-rich fish oil supplementation upregulated CD36 expression, compared with the placebo group (P = .01). DHA-rich fish oil supplementation for 8 weeks increased CD36 expression in hypertriglyceridemic subjects, which might result to higher reduction in TG level, comparing with normotriglyceridemic subjects. However, this finding should be investigated in further studies.