Increased HDL-C Levels Research Articles

Effect of polyphenol, flavonoid, and saponin fractions from Thymus atlanticus on acute and chronic hyperlipidemia in mice

BackgroundThymus atlanticus is an endemic plant of the Mediterranean region, which has been used in the Moroccan mountain area to treat several diseases. This study aimed to investigate the effect of polyphenol, flavonoid, and saponin fractions derived from this plant on acute and chronic hyperlipidemia in male albino mice.ResultsThe results indicated that the injection of Triton WR-1339 (20 mg/100 g body weight (B.wt.)) and 6-week administration of a high-fat diet (which is an 81.8% standard diet supplemented with 2% cholesterol, 16% lard, and 0.2% cholic acid) significantly increased plasma total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C), but did not affect high-density lipoprotein cholesterol (HDL-C) levels in mice. Administration of a single dose (2 mg/kg B.wt.) of polyphenol, flavonoid, or saponin fractions significantly suppressed the effect of Triton injection on plasma total cholesterol, triglycerides, and LDL-C. In addition, the supplementation of the high-fat diet with polyphenol fraction (2 mg/kg B.wt./day) prevented the increase of total cholesterol, triglycerides, and LDL-C, and effectively increased HDL-C level when compared to mice feeding only the high-fat diet.ConclusionIn conclusion, phenolic compounds from Thymus atlanticus possess a significant hypocholesterolemic and hypotriglyceridemic effects and, therefore, could have an important role in the management of dyslipidemia.

Effect of a 6-week and 12-week cardiac rehabilitation program on heart rate recovery

BackgroundCardiac rehabilitation has been shown to reduce cardiac mortality, improve quality of life, and reduce hospitalizations. Cardiac rehabilitation programs are usually performed over a 12-week period. Studies have shown that similar benefits could be achieved with shorter programs. Abnormal heart rate recovery after exercise has been associated with an increased risk of cardiovascular events and mortality. The main aim of this study was to compare the effect of a 6-week phase 2 cardiac rehabilitation program on heart rate recovery to a 12-week one in patients who had recovered from an anterior wall ST segment elevation myocardial infarction.ResultsThis prospective study included 60 patients enrolled in cardiac rehabilitation programs randomized into two equal groups: a 6-week and a 12-week program. Baseline patient demographics, lipid profile, and left ventricular ejection fraction (LVEF) were assessed. METs achieved, total exercise time, resting heart rate, peak heart rate, and heart rate recovery at 1 min were examined. These were re-assessed at the end of each program.Results showed no difference between both groups at the end of each program regarding lipid profile and LVEF. Patients enrolled in the 12-week cardiac rehabilitation program were able to achieve more METs, had a longer exercise time, a higher peak heart rate, and had a lower resting heart rate at the end of the program. Heart rate recovery was slightly higher in patients enrolled in the 6-week program 26.5 ± 6.78 versus 23.17 ± 6.12 bpm (p = 0.051).On comparing the magnitude of change between both programs, those in the 12-week program had more increase in HDL-C levels, METs achieved, and exercise time. Additionally, they had more reduction of resting heart rate. Heart rate recovery was more increased for those in the 6-week program.ConclusionAlthough heart rate recovery increases after completion of each of a 6-week and 12-week cardiac rehabilitation program compared to their baseline, there is no difference on comparing heart rate recovery between both programs at their end.Patients enrolled in a standard 12-week cardiac rehabilitation program achieve more METs, have a longer exercise time, a higher peak HR, and a lower resting HR at the end of the program compared to those in the 6-week program.

Hypolipidemic Effect of Avocado Peel (Persea americana Mill.) Extract in Rats with Dyslipidemia

Dyslipidemia is a disorder of lipid metabolism and one of the modifiable risk factors for cardiovascular disease. The prevalence of dyslipidemia based on raised total cholesterol in the world was 39%, of which 37% for men and 40% for women. Cholesterol-lowering drugs have been reported to have many side effects. One alternative medicine in reducing blood cholesterol levels by utilizing the potential of the avocado peel. This research was experimental with a pre-posttest control group design. This research was used 30 Sprague Dawley male rats divided into 6 groups, namely the normal control group (CG1), negative control (CG2), positive control (CG3) and 3 treatment groups (TG) who received avocado peel extract (APE) at 75, 150, and 300 mg/200gr bodyweight rats. Data were tested using a one-way ANOVA. The results showed that APE significantly reduced the levels of LDL-C (P<0.05) was 17.82±2.62, 29.62±2.00, and 36.33±4.47 mg/dl (TG1, TG2, TG3). Decreased triglycerides levels (P<0.05) of 1.62±4.17, 14.05±5.16, and 29.67±5.79 mg/dl (TG1, TG2, TG3). The increased levels of HDL-C (P<0.05) were 29.67±5.79, 22.63±4.82, and 34.35±2.72 mg/dl (TG1, TG2, TG3). Avocado peel (Persea americana Mill.) extract showed a hypolipidemic effect by reducing LDL-C, triglycerides, and increasing HDL-C levels in rats with dyslipidemia.

Trigonella foenum graecum derived mucilage supplementation in diet alleviates the progression of atherosclerosis in high cholesterol diet-fed rabbit model by regulating inflammation

Hypercholesterolemia is the risk factor that leads to atherosclerosis, which is the primary cause of mortality and morbidity in the developing and developed countries. This problem magnitude is profound as atherosclerosis claims more lives than all types of cancer combined, and the economic costs are considerable. Now, herbal medicine has grown in popularity all over the world. The present research work was undertaken to assess the effect of Trigonella foenum graecum (Fenugreek) mucilage (FGM) on inflammatory mediators and antioxidants in atherosclerotic progression. Male white rabbits of New Zealand strain were used in this study. Rabbits were grouped into three and fed with varying diets for 90 days: Group I - normal diet, Group II - high cholesterol diet (HCD), and Group III - HCD + FGM (75 mg/kg body weight). FGM supplementation decreased the total cholesterol (TC), LDL-C, triglycerides, and increased HDL-C levels significantly compared with HCD fed rabbits showing its atherogenicity. Administration of FGM significantly reduced the activities of inflammatory enzymes, inflammatory mediators, and acute-phase proteins which were elevated by HCD. The supplementation maintains the activities of antioxidant enzymes and paraoxonase 1 (PON1) that highlights its antioxidant role. The effect of FGM was further buttressed using the histopathological examination of the aorta. These findings indicated that FGM held promising potential to be further developed into a novel therapeutic agent for atherosclerosis.

Grape juice attenuates left ventricular hypertrophy in dyslipidemic mice.

ObjectiveWe evaluated the effects of grape juice (Vitis labrusca L.) on dyslipidemia, resistance to insulin, and left ventricular hypertrophy (LVH) in mice homozygous for the absence of the LDL receptor gene (LDLr -/-) under a hyperlipidemic diet.MethodologyWe divided 30 male mice (3 months old) into three groups (n = 10); the HL group was fed a high-fat diet, the HLU group received a high-fat diet and 2 g/kg/day of grape juice, and the HLS group was fed a high-fat diet and simvastatin (20 mg/kg/day). We assessed the blood pressure profile of the mice. We also determined the levels of C-reactive protein (CRP) and lipid profile, glycemic and insulinemic profiles, and calculated the HOMA-IR. Cardiomyocyte hypertrophy, interstitial collagen deposit, and the expression of CD40 ligand (CD40L) and metalloproteinases 2 and 9 were assessed immunohistologically.ResultsAfter 60 days, the mice treated with grape juice showed similar results as those of the group treated with simvastatin. The use of grape fruit attenuated dyslipidemia and insulin resistance and significantly increased the levels of high cholesterol density lipoproteins (HDLc). The antioxidant potential of phenolic compounds associated with the increase in HDLc levels in the mice of the HLU group prevented the development of LVH and arterial hypertension since it inhibited the inflammatory response induced by the CD40 pathway and its ligand CD40L. Consequently, there was a lower expression of MMP-2 and MMP-9 and lower serum levels of CRP.ConclusionGrape juice has a hypolipidemic and cardiac protective potential, presenting a similar effect as that of simvastatin through a direct antioxidant action of phenolic compounds, or indirectly, via antioxidant action and anti-inflammatory activity of the HDLc. These results suggest that grape juice is a functional food possessing a high potential to prevent cardiovascular diseases.

Evaluation of the Anti-Hypercholesterolemic and Antioxidant Activity of Mentha pulegium (L.) Aqueous Extract in Normal and Streptozotocin- Induced Diabetic Rats

Objective:Mentha pulegium L., an aromatic plant belonging to Lamiaceae family, is widely used by local population against diabetes, hypertension and cardiovascular disorders. The present study aimed to evaluate the in vivo antihypercholesterolemic effect of aerial parts aqueous extract (A.P.A.E) of Mentha pulegium (M. pulegium) in normal and streptozotocin-induced diabetic rat. Additionally, the in vitro antioxidant activity of M. pulegium A.P.A.E has been estimated.Methods:The effect of M. pulegium (L.) A.P.A.E (20 mg of lyophilized A.P.A.E per kg body weight) on plasma lipid profile was investigated in normal and streptozotocin (STZ) diabetic rats (n=6) treated for 15 days with M. pulegium (L.) A.P.A.E oral administration. The antioxidant activity was evaluated using DPPH (1-1-diphenyl 2-picryl hydrazyl) radical scavenging activity. Estimation of total polyphenol contents in A.P.A.E of M. pulegium was determined with the Folin- Ciocalteu reagent by the method using gallic acid as a standard phenolic compound. Also, flavonoids were estimated according to the method based on the formation of a complex flavonoidaluminium.Results:The results show that 15 days of M. pulegium A.P.A.E oral administration alleviated hyperlipidemia in diabetic rats by lowering significantly (p&lt;0.01) the plasma cholesterol levels without affecting the triglycerides (TG) levels significantly. However, no significant decrease in plasma cholesterol and plasma triglycerides has been shown in diabetic control rats. In addition, A.P.A.E oral administration has exerted some increasing activity on plasma HDL-c level (54.84 %), whereas the HDL-c level, in diabetic control rats, has significantly decreased (p&lt;0.05). On the other hand, M. pulegium A.P.A.E showed a high amount of flavonoid (83.07 ± 0.58 mg EQ / g of extract) and phenolic compounds (239.08 ± 35.40 mg EAG/g of extract). Also, according to the DPPH radical scavenging activity, this aqueous extract has demonstrated a significant antioxidant activity.Conclusion:We conclude that 15 days of M. pulegium A.P.A.E oral administration exhibited a significant antihypercholesterolemic effect and has also demonstrated a not negligent increase in HDL-c levels without affecting the triglycerides levels. Furthermore, A.P.A.E exhibited a potent antioxidant activity. Therefore, phytochemical compounds and antioxidant activity of M. pulegium A.P.A.E may be seemingly implicated in the antihypercholesterolemic effect demonstrated in this study.

Association of rs670 variant of APOA-1 gene with cardiometabolic markers after consuming sesame, canola and sesame-canola oils in adults with and without type 2 diabetes mellitus.

The inter-individual variations of the metabolic markers in response to dietary interventions may be mediated by genetic factors. We examined whether the type of dietary oils can modulate the effects of-75G/A polymorphism in APOA-1 gene on cardiometabolic markers. This study was a randomized, triple-blind, cross-over clinical trial. Participants with and without type 2 diabetes were randomly assigned to replace their regular oil with sesame oil, canola oil and sesame-canola oil for 9 weeks. Genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Ninety-five diabetes patients and 73 healthy individuals completed the study protocol. In patients with type 2 diabetes, the A allele carriers experienced greater decrease in systolic blood pressure compared with GG homozygotes following sesame-canola oil intake. Serum levels of HDL-C and TG: HDL ratio was increased and decreased following canola oil intake in patients carrying the A allele rather than non-A allele carriers, respectively. More reductions for risk of cardiovascular diseases and mortality, except risk of stroke were found in the A allele carriers compared with GG homozygotes after intakes of canola and sesame-canola oils, but not sesame oil. There was also a significant genotype effect as well as genotype-dietary oil interactions on cardiovascular risk scores. In healthy individuals, a considerable decrease in visceral fat was accompanied by a significant increase in HDL-C levels in the A allele carriers compared with non-A allele carriers after sesame oil intake. Patients with diabetes carrying the A allele might benefit from canola and sesame-canola oils intakes, and healthy A allele carriers from sesame and sesame-canola oils intakes as well. Future clinical trials are recommended to warrant current findings.

Glucocorticoids impair HDL-mediated cholesterol efflux besides increased HDL cholesterol concentration: a proof of concept.

Glucocorticoids (GC) are associated with increased cardiovascular morbidity despite increased HDL-C concentration. HDL-mediated cholesterol efflux, a major anti-atherogenic property of HDL particles, is negatively associated with CVD risk. We aimed to determine whether HDL-mediated cholesterol efflux was influenced by GC. Prospective, observational study. Lipid parameters, HDL composition, HDL-mediated cholesterol efflux, cholesteryl ester transfer protein, phospholipid transfer protein and lecithin cholesterol acyl-transferase (LCAT) activities were determined in ten patients with giant cell arteritis before and 3 months after GC introduction and in seven control subjects. HDL concentration and composition, HDL-mediated cholesterol efflux and LCAT activity were determined in GC-treated mice. In patients, HDL-C concentration was higher after than before treatment GC-treatment (P = 0.002), while HDL-mediated cholesterol efflux was decreased (P = 0.008) and negatively associated with the proportion of cholesteryl ester in HDL (P = 0.04), independently of CRP. As well, in mice, HDL-C level was increased after GC exposure (P = 0.04) and HDL-mediated cholesterol efflux decreased (P = 0.04). GC-treated patients had higher cholesteryl ester content in HDL, higher HDL2-to-HDL3 ratio and higher LCAT activity than before treatment (P = 0.008, P = 0.02 and P = 0.004, respectively). We report, for the first time, that in patients with giant cell arteritis and mice treated with GC, HDL-mediated cholesterol efflux was impaired by GC besides an increased HDL-C level. This impaired HDL functionality, possibly related to HDL enrichment in cholesteryl ester, could contribute to the increased CVD risk observed in GC-treated patients. Further studies are needed in larger populations, to further decipher the effect of GC on HDL.

The effects of exercise training on lipid metabolism and coronary heart disease.

Blood lipoproteins are formed by various amounts of cholesterol (C), triglycerides (TGs), phospholipids, and apolipoproteins (Apos). ApoA1 is the major structural protein of high-density lipoprotein (HDL), accounting for ~70% of HDL protein, and mediates many of the antiatherogenic functions of HDL. Conversely, ApoB is the predominant low-density lipoprotein (LDL) Apo and is an indicator of circulating LDL, associated with higher coronary heart disease (CHD) risk. Thus, the ratio of ApoB to ApoA1 (ApoB/ApoA1) is used as a surrogate marker of the risk of CHD related to lipoproteins. Elevated or abnormal levels of lipids and/or lipoproteins in the blood are a significant CHD risk factor, and several studies support the idea that aerobic exercise decreases CHD risk by partially lowering serum TG and LDL-cholesterol (LDL-C) levels and increasing HDL-C levels. Exercise also exerts an effect on HDL-C maturation and composition and on reverse C transport from peripheral cells to the liver to favor its catabolism and excretion. This process prevents atherosclerosis, and several studies showed that exercise training increases heart lipid metabolism and protects against cardiovascular disease. In these and other ways, it more and more appears that regular exercise, nutrition, and strategies to modulate lipid profile should be viewed as an integrated whole. The purpose of this review is to assess the effects of endurance training on the nontraditional lipid biomarkers, including ApoB, ApoA1, and ApoB/ApoA1, in CHD risk.

Systematic review and Meta-analysis on efficacy and safety of berberine for dyslipidemia

To evaluate the clinical efficacy and safety of berberine in the treatment of dyslipidemia. In this review, CNKI, WanFang, VIP, CBM, PubMed, Cochrane Library, EMbase, and Medline(OVID) were retrieved from database establishment to January, 2019 in any language. Randomized controlled trials(RCTs) of berberine with or without lipid-lowering drugs vs placebo, without drugs or lipid-lowering drugs only in treatment of dyslipidemia were collected. Data extraction and paper quality assessment were conducted according to the Cochrane Handbook. Then RevMan 5.3 software was used for Meta-analysis. A total of 25 trials were included, covering 3 042 cases, including 1 552 cases in the experimental group and 1 490 cases in the control group. The clinical heterogeneity of the included trials was relatively high, and the methodological quality of most trials was generally low, with bias in terms of random sequence generation, allocation hiding, blind method and result data. Interventions were divided into different subgroups for analysis. Meta-analysis suggested that use berberine alone or along with lipid lowing drugs could reduce TC, TG, LDL-C levels and increased HDL-C levels with statistically significant difference as compared with control group. As compared with control group, there was no statistically significant difference in the incidence of adverse events. No severe adverse effects were reported in all trials. Berberine has good efficacy and safety in the treatment of dyslipidemia. Due to the quality limitations of the included trials, the above conclusions need to be further verified by high-quality, large sample size and multi-center clinical trials.

Determinacion del efecto hipocolesterolemico y antiaterosclerotico de extracto acuoso de fruto Solanum Melongena “berenjena” en Rattus norvegicus var. Wistar con hiperlipemia experimental.

Se evaluó la actividad hipolipemiante del extracto acuoso de fruto de Solanum melongena “berenjena” en Rattus norvegicus variedad Wistar con hiperlipidemia experimental. Se llevó a cabo en el Laboratorio de Fisiología Animal de la Univerisdad Nacional de San Agustín y Bioterio de la Universidad Católica Santa María de 1 Junio al 31 Setiembre 2015. Se utilizaron 24 Rattus norvegicus variedad Wistar distribuidas en cuatro grupos de 6 ratas cada uno: un tratamiento control hipercolesterolémico y tres experimentales tratamiento de Solanum melongena a dosis de 0.5 g/kg/día, 1 g/kg/día y lovastatina a una dosis de 3 mg/kg. Se utilizó el método de Wiener en la determinación de Colesterol Total, Triglicéridos, HDL-colesterol y LDL-colesterol. Lahiperlipidemia se logró con una mezcla de 50 g de cerebro de res hervido con 50 g de conejina más 3 ml de manteca de cerdo por rata. Se observó disminución significativa (p&lt;0.01) en los niveles de colesterol, triglicéridos e índice aterogénico y aumento significativo en los niveles de HDL-C, en comparación al grupo control. Los resultados nos muestran que la administración de 0.5 y 1 g/kg/día de extracto acuoso de Solanum melongena “berenjena” disminuyen los niveles de colesterol total y triglicéridos en Rattus norvegicus variedad Wistar con hiperlipidemia experimental. Ademas no tiene efecto hepatotoxico y reduce las placas ateromatosas en aorta.

The cross-sectional study of hepatic lipase SNPs and plasma lipid levels.

By the combination of meta‐analysis, the data of the 1,000 Genomes Project Phase 3, and the promoter sequence of hepatic lipase (LIPC), we performed the cross‐sectional study to explore the associations of four variants (rs1077835; rs1077834; rs1800588 [C‐514T], and rs2070895 [G‐250A]) in LIPC promoter with plasma lipid levels. Our results indicate that the first and the next three of the four SNPs are, respectively, reported to be associated with the decreased and increased HDL‐c level. Meta‐analysis of 87 studies with 101,988 participants indicates that HDL‐c level in rs1800588 (C‐514T) (pooled mean difference = 0.03, 95%CI (0.03, 0.04), p < .001) and rs2070895 (G‐250A) (pooled mean difference = 0.07, 95%CI (0.05, 0.09), p < .001) is higher in allele T or A carriers. Similarly, LDL‐c, TC, TG, and BMI levels are generally increased in T or A alleles carriers. We failed to conduct the meta‐analysis of rs1077835 and rs1077834 due to the limited previous reports. Data from the 1,000 Genomes indicate that the allele frequencies of the four SNPs in total or subpopulations are almost equal to each other. The paired value r 2 and D' of the four SNPs are larger than 0.8, which indicate the linkage disequilibrium of the four variants. The analysis of LIPC promoter indicate that C‐514T and G‐250A are, respectively, located in transcriptional factor binding sites of USF1and Pbx1b, which may partly explain the effect of the two SNPs on the decreased LIPC activity in the alleles carriers and the corresponding increased plasma lipids hydrolyzed by LIPC. These results may help us to better understand the different effects of the four SNPs on the plasma lipid levels among subpopulations and offer clues for future clinical treatment of dyslipidemia‐related diseases.

Trends in Serum Lipid Levels of a 10- and 13-Year-Old Population in Fukuroi City, Japan (2007-2017).

BackgroundCurrent trends in serum lipid levels among children are likely to be important predictors of future cardiovascular disease prevalence. However, no studies have examined trends in low-density lipoprotein cholesterol (LDL-C) levels in Japanese children.MethodsWe investigated trends in LDL-C levels from 2008 through 2017 and HDL-C levels from 2007 through 2017 in a population of 10- and 13-year-old children in Fukuroi City, Japan. We analyzed 17,838 children, accounting for 93.8% of all fifth and eighth graders in the entire city. Adverse lipid levels were defined as follows: 130 mg/dL or higher for LDL-C, and lower than 40 mg/dL for HDL-C. The Jonckheere-Terpstra and Cochran-Armitage tests were used to evaluate secular trends in mean serum lipid levels and prevalence of dyslipidemia, respectively.ResultsThere were no significant trends in BMI during the study period. In children aged 10 years, serum levels of LDL-C and HDL-C showed significant positive associations with calendar year during the study period for both sexes. A significant increase in HDL-C levels was observed in girls aged 13 years. On the other hand, no significant trends were observed in the prevalence of high LDL-C or low HDL-C regardless of sex or age, while the prevalence of high non-HDL-C showed a significant increase in boys.ConclusionsIn the Fukuroi population, serum levels of LDL-C and HDL-C slightly increased in both boys and girls aged 10 years, and HDL-C levels slightly increased in girls aged 13 years, during the past decade.

Traditional Chinese patent medicine Zhixiong Capsule (ZXC) alleviated formed atherosclerotic plaque in rat thoracic artery and the mechanism investigation including blood-dissolved-component-based network pharmacology analysis and biochemical validation

Ethnopharmacological relevanceChinese patent medicine Zhixiong Capsule (ZXC) is the equal mixture of the extract of leech, Ligusticum chuanxiong Hort., Salvia miltiorrhiza Bunge, Leonurus japonicus Houtt., and Pueraria lobate (Willd.) Ohwi, which have been long used against inflammation, hyperlipidemia or blood stasis. In our previous study, ZXC showed good efficacy in preventing atherosclerosis (AS) plaque formation in rabbits. Aim of the studyIn actual clinic practice, patients are more likely to receive treatments after AS plaque formation. Therefore, the efficacy of ZXC on formed AS plaques and the underlying mechanisms were further investigated in this study. Materials and methodsSimvastatin (positive control) and ZXC (420 mg/kg and 840 mg/kg) were administrated to rats which first received long-term high fat diet administration (12 weeks). The blood lipid profiles of rats were monitored during the whole experiment, and the thoracic arteries were collected at the end of experiment for AS assessment (18th week). The blood-dissolved ZXC components were determined using an UPLC-QTOF-MS method, and the attained components were then used for network pharmacology analysis to predict the key ZXC components and targets. At last, the predicted targets were validated by ELISA and western blot methods. ResultsZXC administration showed good blood lipid-lowering effect by significantly reduced LDL-C and TC levels in rats while significantly increased HDL-C level. Compared with model group, simvastatin, low- and high-dose of ZXC administration decreased the ratio of intimal area and medial area by 81.1%, 71.1% and 71.4%, respectively (p < 0.01), and significantly alleviated collagen deposition and mineralization in rat arteries. It was found by network pharmacology analysis that leech and four components (namely daidzein, 4-methylenemiltirone, isorhamnetin and 2-isopropyl-8-methylphenanthrene-3,4-dione) are vital components for the anti-AS efficacy of ZXC. Combing the results from biochemical validation, IL-4, IL-13, MAPK1, MAPK14, JUN and P53 were confirmed as key targets of ZXC. ConclusionIt could be concluded that ZXC has value as an anti-AS agent in clinical treatment against formed AS plaque at the current application dosage.

Effect of a Dual PPAR \u03b1/\u03b3 agonist on Insulin Sensitivity in Patients of Type 2 Diabetes with Hypertriglyceridemia- Randomized double-blind placebo-controlled trial

Saroglitazar is a dual PPAR-α/γ agonist approved for the treatment of diabetic dyslipidemia. In addition to reduction in atherogenic lipids, it may also contribute to improvement in insulin sensitivity through PPAR-α/γ agonism, which remains unexplored. We conducted a randomized, double-blind, placebo-controlled trial in treatment-naive T2DM individuals with serum triglyceride >150 mg/dL. Participants were randomized to receive either saroglitazar 4 mg or placebo (1:1) daily for 4 months (n = 30). Insulin sensitivity (SIclamp) was studied using hyperinsulinemic-euglycemic clamp at baseline and at 4 months. We observed a significant reduction in TG (p = 0.001), HbA1c (p = 0.019) and fasting plasma glucose (p = 0.019) and significant increase in HDL-C levels (p < 0.01) with saroglitazar compared to placebo. Further, patients on saroglitazar had a greater improvement in SIclamp (p = 0.026) with the effect persisting despite adjusting for baseline weight, TG, HDL-C and HbA1c (p = 0.002). This was accompanied with significant increase in HOMA-β (p = 0.01) in the saroglitazar group and change in HOMA-β showed a trend towards significance with SIclamp (r = 0.503, p = 0.056). However, change in SIclamp did not significantly correlate with reduction in HbA1c and TG. We conclude that saroglitazar effectively reduces hypertriglyceridemia and improves insulin sensitivity along with β-cell function by reduction in gluco-lipotoxicity and possibly directly through PPAR-γ agonism in patients ofT2DM with hypertriglyceridemia.

Effects of Exercise Training and Statin Use in People Living with Human Immunodeficiency Virus with Dyslipidemia.

To evaluate the effects of the combination of exercise training (ET) and statins in people living with human immunodeficiency virus. This was a randomized, double-blind, placebo-controlled clinical trial. Eighty-three people living with human immunodeficiency virus were assigned to either placebo (PL), statins (STA), PL + ET (PLET) or STA + ET (STAET) groups. Volunteers assigned to STA and STAET groups were administered 10 mg of rosuvastatin, whereas the PL and PLET groups were administered a placebo. The PLET and STAET groups performed ET three times a week. Before and after the 12-wk follow-up, the volunteers underwent to anthropometric assessment and blood collection to evaluate lipid profile, cardiovascular markers, inflammatory profile; a Doppler ultrasound examination, muscle strength (MS) and cardiorespiratory fitness (CF) tests were performed. There was a decrease in total cholesterol, triglycerides, low-density lipoprotein, C-reactive protein, fibrinogen, interleukin (IL)-1β and right carotid intima-media thickness in the STA, PLET, and STAET groups compared with PL group (P < 0.001). Furthermore, there was a decrease in total cholesterol, triglycerides, low-density lipoprotein, IL-1β, IL-6, and IL-8 levels and in left and right carotid intima-media thickness and an increase in HDL-c levels in the STAET groups compared with the STA (P ≤ 0.001) and PLET groups (P ≤ 0.001). There was an increase in IL-10 levels, peak-systolic velocity, end-diastolic velocity, wall shear rate in the PLET and STAET groups compared with the PL (P ≤ 0.001) and STA groups (P ≤ 0.001). The PLET and STAET groups reduced body fat mass, body fat percentage and increased lean body mass, MS and CF compared with PL (P ≤ 0.001) and STA (P ≤ 0.001) groups. The combination of ET and statins is useful to enhance lipid and inflammatory profiles, reduce cardiovascular disease markers, and improve Doppler ultrasound findings, MS and CF in people living with HIV.

Efficacy and Safety of Pharmacological Combination Therapies for the Treatment of Type 2 Diabetes in China: A Systematic Review and Meta-Analysis

Background: Chinese guideline recommends using combination therapy of antidiabetic-drug plus metformin for type 2 diabetes (T2DM) patients failed to control glucose on metformin. Treatment effect varies between antidiabetic drugs, but there is no direct evidence on comparing the effect of each alternative drug plus metformin. This study aims to estimate and compare the efficacy and safety of seven classes of antidiabetic-drug added onto metformin for Chinese T2DM patients failed on metformin. Methods: Systematic review was performed by searching databases including CNKI, WanFang, CQVIP, PubMed, EMBASE, Web-of-Science, ScienceDirect, Cochrane-Library, to identify randomized controlled trials(1990-2016) comparing the treatment effect of 'antidiabetic-drug + metformin vs metformin' or 'metformin vs placebo/lifestyle-intervention' in Chinese T2DM patients. Based on Chinese guideline, three-line eight-class of antidiabetic-drugs were included: 1st-line-drug(metformin), 2nd-line-drug/oral-drug(α-glycosidase inhibitor, sulfonylurea, glinide, DPP-4 inhibitor, thiazolidinedione), 3rd-line-drug/injectable-drug(insulin, GLP-1 receptor agonist). Using metformin as common comparator, meta-analyses and indirect-treatment-comparisons were used to estimate the effect of 'antidiabetic-drug + metformin vs placebo/lifestyle-intervention'. Findings: 325 studies were finally included. Overall, compared with placebo/lifestyle-intervention, 'oral-drug + metformin' and 'injectable-drug + metformin' reduced HbA1c level by 1·89% and 2·28%, BMI level by 2·55kg/m2 and 3·10kg/m2, TC level by 1·03mmol/l and 1·50mmol/l, SBP level by 5·59mmHg and 8·51mmHg, while increased HDL-C level by 0·31mmol/l and 0·18mmol/l, respectively. In 'oral-drug + metformin', the top two treatments for reducing HbA1c level were 'glinide + metformin' (WMD:-2·03,95%CI[-2·70,-1·36]) and 'sulfonylurea + metformin' (WMD:-2·00,95%CI[-2·64,-1·36]); for reducing BMI level were 'glinide + metformin' (WMD:-4·25,95%CI[-5·70,-2·80]) and 'DPP-4 inhibitor + metformin' (WMD:-2·81,95%CI[-4·22,-1·40]); for reducing TC level were 'α-glycosidase inhibitor + metformin'(WMD:-1·41,95%CI[-2·15,-0·68]) and 'DPP-4 inhibitor + metformin' (WMD:-1·22,95%CI[-1·71,-0·73]); for increasing HDL-C level were 'α-glycosidase inhibitor + metformin'(WMD:0·51,95%CI[0·27,0·75]) and 'thiazolidinedione + metformin' (WMD:0·35,95%CI[0·10,0·60]). In 'injectable-drug + metformin', 'GLP-1 receptor agonist + metformin' was superior to 'insulin + metformin' in reducing HbA1c level (WMD:-2·42vs-2·04) and BMI level (WMD:-3·27vs-2·05), while inferior to 'insulin + metformin' in reducing TC level (WMD:-1·43vs-1·79). All combination therapies had no significant difference on risks of hypoglycemia or gastrointestinal-reaction vs placebo/lifestyle-intervention. Interpretation: Pharmacological combination therapies had better efficacy than placebo/lifestyle-intervention in Chinese T2DM patients. Funding: No funding was received. Declaration of Interest: There are no relevant conflicts of interest to disclose.

Optimizing Dyslipidemia Management for the Prevention of Cardiovascular Disease: a Focus on Risk Assessment and Therapeutic Options

Primary prevention of incident atherosclerotic cardiovascular disease (ASCVD) as well as decreasing the risk of future events in those with established atherosclerosis is critical from a public health perspective. Management of dyslipidemias constitutes a key target in decreasing the risk of developing ASCVD events. While there have been great strides in the treatment of dyslipidemia over the last three decades, there are important recent developments and ongoing research that will expand the available therapeutic options and enable further cardiovascular risk reduction. PURPOSE OF REVIEW: The purpose of this paper is to review new developments relating to the primary prevention and management of ASCVD with a specific focus on optimizing the treatment of dyslipidemias. RECENT FINDINGS: In the realm of ASCVD risk prediction, mounting evidence over the last decade has demonstrated that coronary artery calcium testing is superior to any serum biomarker in the prediction of future ASCVD events and in discriminating future cardiovascular risk. As such, it has been incorporated into the most recent ACC/AHA primary prevention guideline to help guide management decisions in select patients. In terms of the management of dyslipidemias, PCSK9 inhibitors lower LDL-C by 50-70% and provide an additional 15% reduction in key cardiovascular events in high-risk patients with known ASCVD, as demonstrated in the ODYSSEY and FOURIER trials. Cholesteryl ester transfer protein (CETP) inhibitors, which significantly increase HDL-C levels, demonstrated mixed results in large clinical trials and have helped reframe HDL-C as a risk marker rather than a modifiable risk factor. In regard to the management of triglycerides, the REDUCE-IT trial demonstrated a nearly 5% absolute reduction in key cardiovascular events with a highly purified fish-oil derivative named icosapent ethyl in high-risk patients already on statin therapy. Finally, in regard to lipoprotein(a)-which is a strong risk factor for ASCVD-there are exciting developments in the therapeutic pipeline which reduce circulating lipoprotein(a) levels by nearly 90%. The management of dyslipidemias continues to be an exciting field with several ongoing cardiovascular outcomes trials, improvement in risk prediction models, and new therapeutic agents in the pipeline that will further mitigate residual cardiovascular risk in both primary and secondary prevention patients.

Hypolipidemic effects of fucoidan fractions from Saccharina sculpera (Laminariales, Phaeophyceae)

Fucoidan is a kind of brown algae-derived macromolecule suggested to have hypolipidemic activity. Saccharina sculpera has attracted interest because it is rich in fucoidan. The monosaccharide composition and structural characteristics of isolated fractions (F1, F2 and F3) were determined using high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). The hypolipidemic effects of fucoidan fractions from Saccharina sculpera cultured in northern China were clarified by measuring cholesterol levels, antioxidative indicators and hepatic gene mRNA expression using an established hyperlipidemic Wistar rat model. The results showed that F1 is an acetylated galactofucan and that F2 consists of fucose, galactose, mannose and glucuronic acid. F3 is an acetylated galactofucan with high fucose. Fucoidan fractions from Saccharina sculpera could effectively reduce the level of lipids in serum by reducing the TG, TC, and LDL-C levels and increasing HDL-C levels and could effectively prevent lipid accumulation in the liver. The findings obtained from hepatic gene expression showed that fucoidan could inhibit cholesterol synthesis via downregulation of HMG-CoA-R and upregulation of LCAT, slow the synthesis of fatty acids via downregulation of SREBP-1c, and promote β-oxidation of fatty acids via upregulation of PPARα, PPARγ and LPL. These results demonstrated that the hypolipidemic activity of fucoidan was related to the inhibition of cholesterol synthesis and reverse transport, the regulation of fatty acid synthesis, and acceleration of mitochondrial β-oxidation.

Safety assessment and the effect of squalene isolated from schizochytrium mangrovei pq6 on serum hdl - cholesterol levels in animal models

In this paper, the acute and subchronic toxicity and the effect of squalene isolated from heterotrophic marine microalga Schizochytrium mangrovei PQ6 on the serum levels of HDL-C were investigated using animal models. The results of acute toxicity study showed that by oral administration of the squalene on albino mice at the highest dose of 58.25 g/kg of whole body of mice/day, the LD50 was not determined. Squalene at doses of 400 mg and 1,200 mg/kg/day for 60 consecutive days have allowed the normal behavior, body weight, hematological and biochemical parameters, liver and kidney functions, morphology of liver, kidney and spleen, total plasma cholesterol content, however, HDL-C level was higher in squalene treated mices compared to control group (p &lt; 0.05). In addition, at doses of 600 and 1,200 mg/kg/day for 60 continuous days, squalene treated mice showed the increase in HDL-C level and HDL-C/total cholesterol ratio and the decrease in the contents of LDL-C and VLDL-C without affecting the body and liver weights and levels of total cholesterol and triglyceride.