Low-density Lipoprotein Reduction Research Articles

Integration of Personalized Health Planning and Shared Medical Appointments for Patients with Type 2 Diabetes Mellitus.

This study describes the feasibility of implementing personalized health planning (PHP) within shared medical appointments (SMAs) for patients with type 2 diabetes mellitus. The PHP-SMA approach was designed to synergize the benefits of SMAs with those of PHP, enabling greater patient engagement focused on meeting individualized therapeutic goals in a group setting. Patients were assigned randomly to a PHP-SMA or a standard eight-session SMA series. Standard SMAs included an interactive educational curriculum delivered in group medical encounters. The PHP-SMA included the addition of a patient self-assessment, health risk assessment, shared patient-provider goal setting, creation of a personal health plan, and follow-up on clinical progress. Clinical and patient-reported outcomes and qualitative data from focus groups with patients, providers, and administrative staff were used for evaluation. Qualitative data explored facilitators and barriers to implementation of the PHP-SMA. The Consolidated Framework for Implementation Research was used to provide insight into implementation factors. PHP was successfully integrated into SMAs in a primary care setting. Patients in the PHP-SMA (n = 12) were more likely to attend ≥5 sessions than patients assigned to the standard SMA (n = 7; 58% PHP, 28.5% control). Qualitative data evaluation described the advantages and barriers to PHP, the team-based approach to care, and patient participation. The PHP-SMA group experienced reductions in hemoglobin A1c, low-density lipoprotein, blood pressure, and body mass index, as well as successful attainment of health goals. The PHP-SMA is a proactive and participatory approach to chronic care delivery that synergizes the benefits of PHP within SMAs. This study describes the components of this intervention; collects evidence on feasibility, acceptability, and clinical outcomes; and identifies implementation barriers and facilitators. The PHP-SMA warrants further evaluation as an approach to improve health outcomes in patients with common chronic conditions.

Preclinical discovery and development of colesevelam for the treatment of type 2 diabetes

ABSTRACTIntroduction: Type 2 diabetes (T2D) is a major global health challenge associated with increased cardiovascular morbidity and mortality. Intervention strategies managing multiple risk factors (hyperglycemia, hypertension and dyslipidemia) in patients with T2D can reduce the risk of cardiovascular disease by ~50%.Areas covered: Herein, the authors provide an update on the development and clinical potential of colesevelam as a glucose-lowering drug in T2D. Furthermore, they outline the pharmacokinetics, pharmacodynamics, and the clinical efficacy and safety data from the studies carried out to obtain market authorization for colesevelam.Expert opinion: Four phase III clinical trials provide evidence that colesevelam, as a monotherapy and add-on to various background glucose-lowering treatments, confers placebo-corrected reductions in HbA1c of ~5 mmol/mol. In addition, colesevelam reduces low-density lipoprotein (LDL) cholesterol and total cholesterol. Some antidiabetic agents seem superior to colesevelam in terms of clinical efficiency (HbA1c lowering), tolerability/convenience, and price. Nonetheless, colesevelam offers a clinically relevant combination of HbA1c- and LDL-lowering that in selected patients could be relevant as add-on treatment to other glucose-lowering drugs and a statin. Potential patients include those with renal impairment, and patients that are close to reaching their lipid and glycemic treatment goals but need further LDL and HbA1c reductions.

Nutraceuticals from barley flour, flaxseed and rice bran oil-Extraction, chromatographic analysis, microbiological analysis and pesticide estimation

In the present study, barley flour, flaxseed and rice bran oil were utilized for the extraction of pivotal nutraceuticals like beta-glucans, lignans and gamma oryzanol concentrate, respectively, followed by their characterization on several parameters. Beta-glucan fibres isolated from six-rowed hull-less barley variety (HBL-276) by alkaline treatment followed by precipitation with ethanol revealed high beta-glucan content (65.74 ± 1.02/100 g). The flaxseed lignan concentrate and gamma oryzanol concentrate upon chromatographic analysis yielded high secoisolariciresinol diglucoside content (30 mg/g) and detected four major components of oryzanol (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, campesteryl ferulate and β-sitosteryl ferulate), respectively. The GC/MS analysis for pesticide estimation in raw materials did not show the presence of any pesticide which led to the safe utilization of these raw materials for extraction. In microbiological analysis of the three isolates, gamma oryzanol concentrate revealed the lowest total plate count, yeast and mould count and coliform count as well. Practical applications The nutraceuticals selected in this study have tremendous health as well as medicinal benefits. These impart immense protection against chronic and degenerative diseases like cardiovascular diseases and cancer. Incorporation of these isolated ingredients having health and nutritional properties into various food formulations can impart significant health benefits primarily reduction in blood serum low-density lipoprotein (LDL) cholesterol level, prevention in diseases like diabetes and cardiovascular diseases, minimizing atherosclerosis, etc. These isolates exhibited fairly less contamination with respect to microbiological analysis. Hence, including these isolated nutraceuticals into food products can be one of significant attempts towards the development of safe functional foods.

Guidelines, Clinical Evidence, and Real-Life Practice: How to Find Your Way in Managing Hypercholesterolaemia

Prof Masana presented evidence that low-density lipoprotein (LDL) cholesterol is a causal factor for atherosclerosis and that cardiovascular disease (CVD)-relative risk (RR) is reduced proportionally to LDL reductions, regardless of the type of monotherapy used. Combination therapy offers the advantage of increased lipid-lowering efficacy and a reduction in the side effects associated with high-intensity statins. The rationale thus exists for replacing high-intensity statin therapy with high-intensity cholesterol-lowering therapy. Prof Farnier gave an in-depth description of the results of the IMPROVE-IT, FOURIER, and ODYSSEY-Outcomes trials, demonstrating that the magnitude of clinical benefit is independent of whether it is achieved by statins, ezetimibe, or PCSK9 inhibitors. The IMPROVE-IT study also showed that the magnitude of benefit is proportionate to the absolute decrease in LDL cholesterol. This is consistent with the conclusions of a meta-analysis of randomised controlled statin trials, showing that patients achieving very low LDL cholesterol levels have a reduced risk of major cardiovascular (CV) events compared with those achieving moderately low levels. The greatest benefits for reductions in major adverse CV events from lowering LDL cholesterol occur in patients with diabetes. The above studies have led the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) taskforce on PCSK9 inhibitors to outline a strategy for additional treatment, with patients on maximally-tolerated statin doses failing to achieve LDL cholesterol goals at 4 weeks being considered for ezetimibe treatment, and those failing to achieve goals after a further 4 weeks being considered for PCSK9 inhibitors. Votes from the audience, collected at the start and end of each presentation, showed that the speakers convinced delegates that the lower the LDL cholesterol level achieved the better the outcome for patients would be, that combination therapy is as effective as single dose high-intensity statins, and that statins plus ezetimibe should be considered as standard treatment in high-risk patients, particularly in Type II diabetes mellitus (T2DM) patients.

General practice preventive health care in non-obstructive coronary artery disease determined by coronary computed tomography angiography

BackgroundThe aim of this study was to compare changes in health service utilization, preventive medical management, and cholesterol levels in patients without coronary artery disease (CAD) or with non-obstructive CAD as determined by coronary computed tomography angiography (CTA). MethodsSingle-center five-year observational registry-based cohort study of consecutive patients with chest pain undergoing coronary CTA with subsequent 12 months follow-up in general practice. ResultsWe included 3032 patients with a normal test result (n = 2179) or a diagnosis of non-obstructive CAD (n = 853) by coronary CTA. Median age was 55 (interquartile range: 47–63) years and 44% were males. After coronary CTA, the probability of a decrease in consultations with general practitioner was higher in patients with no CAD compared to patients with non-obstructive CAD (adjusted OR = 0.81 [95% CI: 0.68–0.96], P = 0.016). Accordingly, patients with non-obstructive CAD more frequently received prescriptions on lipid-lowering medical therapy (adjusted OR = 4.50 [95% CI: 3.31–6.12], P < 0.001) than patients with no CAD after coronary CTA. In patients with non-obstructive CAD, mean total-cholesterol reduction was 0.51 (P < 0.001) compared to 0.13 mmol/L (P < 0.001) in patients without non-obstructive CAD. The relative reduction in low-density lipoprotein was 14% higher (P < 0.001) in patients with compared to patients without non-obstructive CAD after coronary CTA. ConclusionsCoronary CTA with subsequent follow-up in general practice has the potential to align health service utilization that prioritizes high-risk patients and facilitate optimized preventive management.

Effect of cationic lipid type in cationic liposomes for siRNA delivery into the liver by sequential injection of chondroitin sulfate and cationic lipoplex

Previously, we reported that intravenous injection of chondroitin sulfate (CS), followed by intravenous injection of cationic liposome/siRNA complex (cationic lipoplex) could deliver siRNA into the liver. In this study, we examined the effects of the type of cationic lipid in the liposome on siRNA delivery into the liver. We used 6 types of cationic cholesterol derivatives and 11 types of dialkyl or trialkyl cationic lipids, and prepared 17 types of cationic liposomes to evaluate the gene-silencing effect of siRNA in mouse liver following sequential injection of CS plus cationic lipoplex. In 14 types of cationic liposomes, siRNA was accumulated in the liver when cationic lipoplexes were injected immediately after CS. However, suppression of apolipoprotein B (ApoB) mRNA expression in the liver and reduction of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol level in the serum were observed only after sequential injection of CS plus ApoB siRNA lipoplex with cationic liposomes composed of N-hexadecyl-N,N-dimethylhexadecan-1-aminium bromide (DC-1-16)/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and N,N-dimethyl-N-octadecyloctadecan-1-aminium bromide (DC-1-18)/DOPE. Based on these findings, the type of cationic lipid strongly affected the gene-silencing effect of siRNA in the liver by sequential injection of CS plus cationic lipoplex.

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism.

Thyroid dysfunction, manifesting as either overt or subclinical hypothyroidism, negatively affects lipid metabolism: this leads to hypercholesterolemia which progressively increases the risk for cardiovascular disease and, potentially, mortality. Hypercholesterolemia in hypothyroidism is mainly due to a reduction in low-density lipoprotein (LDL) receptor activity, this accompanied by concomitant diminishing control by triiodothyronine (T3) of sterol regulatory element-binding protein 2 (SREBP-2), which modulates cholesterol biosynthesis by regulating rate-limit degrading enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity. Recently, 3,5-diiodothyronine (T2), a natural thyroid hormone derivative, was found to repress the transcription factor carbohydrate-response element-binding protein (ChREBP) and also to be involved in lipid catabolism and lipogenesis, though via a different pathway than that of T3. While thyroid hormone could therapeutically reverse the dyslipidemic profile commonly occurring in hypothyroidism, it should be borne in mind that the potency of the effects may be age-and sex-dependent. Thyroid hormone administration possibly also sustains and enhances the efficacy of hypolipidemic drugs, such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9), in patients with dyslipidemia and hypothyroidism.

Effects of Glycemic Index and Intake of Dietary Fiber on Serum HDL-Cholesterol Levels

We previously studied effects of glycemic index (GI) and intake of dietary fiber on serum high-density lipoprotein (HDL)-C levels to make “Dietary Reference Intakes for Japanese 2015”, by using data obtained by clinical trials which evaluated effects of GI and intake of dietary fiber on HDL-C in Asian populations. We found that low GI and an increased intake of dietary fiber may be beneficially associated with HDL metabolism. Here we review meta-analyses on the effects of GI and intake of dietary fiber on serum HDL-C levels, to make “Dietary Reference Intake for Japanese 2020”. A search was conducted by using PubMed, Embase and Google Scholar, and the search period was comprised up to May 2018. In spite of significant associations of low GI and dietary fiber intake with reduction of low-density lipoprotein (LDL)-C, we could not observe any significant influences of low GI and dietary fiber intake on HDL metabolism. J Endocrinol Metab. 2018;8(4):57-61 doi: https://doi.org/10.14740/jem514w

Heparanase inhibition attenuates atherosclerosis progression and liver steatosis in E0 mice

Background and aimsIncreased oxidative stress is associated with accelerated atherosclerosis. Emerging evidence highlights the role of heparanase in atherogenesis, where heparanase inhibitor PG545 reduces oxidative stress in apolipoprotein E deficient mice (E0 mice). Herein, we studied the effects of PG545 on atherosclerosis progression in E0 mice. MethodsMale E0 mice fed a high-fat diet (n = 20) were divided into 3 groups treated with weekly intraperitoneal injections of either low (0.2 mg/mouse) or high dose (0.4 mg/mouse)PG545 or normal saline (controls) for twelve weeks. Body weight and food intake were measured weekly. At the end of the treatment period, blood pressure was measured, animals were sacrificed and serum samples were collected and assessed for biochemical parameters and oxidative stress. Aortic vessels and livers were collected for atherosclerotic plaques and histopathological analysis, respectively. ResultsBlood pressure decreased in mice treated with low, but not high dose of PG545. In addition, heparanase inhibition caused a dose-dependent reduction in serum oxidative stress, total cholesterol, low-density lipoproteins, triglycerides, high-density lipoproteins, and aryl esterase activity. Although food intake was not reduced by PG545, body weight gain was significantly attenuated in PG545 treated groups. Both doses of PG545 caused a marked reduction in aortic wall thickness and atherosclerosis development, and liver steatosis. Liver enzymes and serum creatinine were not affected by PG545. ConclusionsHeparanase inhibition by PG545 caused a significant reduction in lipid profile and serum oxidative stress along with attenuation of atherosclerosis, aortic wall thickness, and liver steatosis. Moreover, PG545 attenuated weight gain without reducing food intake. Collectively, these findings suggest that heparanase blockade is highly effective in slowing atherosclerosis formation and progression, and decreasing liver steatosis.

Intermittent Fasting: The Choice for a Healthier Lifestyle.

Obesity is a worldwide epidemic due to the availability of many unhealthy food options and limited physical exercise. Restriction of the daily food intake results in weight loss, which is also associated with better health outcomes including triglycerides, total cholesterol, low-density lipoprotein cholesterol, blood pressure, glucose, insulin, and C-reactive protein. Our aim is to briefly discuss the effects of intermittent fasting on weight and other biochemical markers mentioned previously. The study is designed as a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. To assess the effectiveness of intermittent fasting, related studies were reviewed between 2000 and 2018 and 815 studies were identified. Only four articles met the preset inclusion and exclusion criteria. All four studies have shown a significant decrease in fat mass with P-values <0.01. It was also noted that some biochemical markers were significantly reduced such as the reduction in low-density lipoprotein and triglyceride with P-values < 0.05. Other biochemical markers had inconsistent results. Based on the qualitative analysis, intermittent fasting was found to be efficient in reducing weight, irrespective of the body mass index. Further studies are needed to assess the ability to maintain the lost weight without regaining it and the long-term effects of such dietary changes.

Atherosclerosis and inflammation: overview and updates.

The concept that inflammation participates pivotally in the pathogenesis of atherosclerosis and its complications has gained considerable attention, but has not yet entered clinical practice. Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. The recognition of atherogenesis as an active process rather than a cholesterol storage disease or a repository of calcium has highlighted some key inflammatory mechanisms. For example, mononuclear phagocytes contribute to all stages of this disease, illustrating the link between inflammation and atherosclerosis. From a clinical perspective, harnessing inflammation may now help target therapeutics, change guidelines, and enter daily practice. Multiple lines of incontrovertible evidence have proven a causal role for low-density lipoprotein (LDL) cholesterol in atherosclerosis, and we have highly effective tools for lowering LDL, consequently reducing events. Yet, even with intense LDL reduction, events still occur. Inflammation can explain some of this residual risk. An anti-inflammatory intervention has now proven capable of improving outcomes in individuals well treated with LDL-lowering agents. A suite of trials are now pursuing anti-inflammatory therapies in this context. Assessment and treatment of residual inflammatory risk are poised to provide new inroads into preventive cardiology. This brief review aims to explore the potential mechanisms underlying the association of inflammation and atherogenesis, and their clinical consequences.

Hypoxis hemerocallidea alters metabolic parameters and hepatic histomorphology in streptozotocin-nicotinamide-induced diabetic male rats under antiretroviral therapy.

IntroductionHighly active antiretroviral therapy (HAART) and HIV/AIDS have been demonstrated to induce endocrine/metabolic dysfunction with a consequential increase in morbidity/mortality due to organ toxicities. This study aimed at investigating the possible protective effect of Hypoxis hemerocallidea (HH) against metabolic and hepatic histomorphology of diabetic rats under HAART.Material and methodsSixty-two adult male Sprague-Dawley rats were divided into a normoglycemic group A (n = 6) and 7 diabetic (110 mg/kg nicotinamide + 45 mg/kg streptozotocin) groups (B–H) (n = 8) and treated according to protocols. Concomitant treatment with adjuvant HH and HAART resulted in the least %body weight gain as the liver weight decreased in all treated animals.ResultsSignificant changes in serum lipids were aggravated by treatment with HH and HAART, triglycerides and total cholesterol levels were elevated (p < 0.001/0.05), but changes in high-density lipoprotein (HDL) and total protein levels were insignificant. While artherosclerotic and cardiopulmonary indexes remained insignificant, concomitant use of HH with HAART in diabetes resulted in reduction of low-density lipoprotein (LDL) (p < 0.001), and increased triglyceride (p < 0.05) and total cholesterol (p < 0.001). The parameters of liver injury showed a significant (p < 0.05) increase in ALT of animals treated with HH alone, HAART + HH and melatonin; however, an insignificant decline in AST level was recorded. Treatment with adjuvant HAART, HH and melatonin resulted in significant (p < 0.005/0.0001) up-regulation of ALP and total bilirubin levels. Histopathology derangement ranged from severe hepatocellular distortions, necrosis with reduced glycogen expression following co-treatment of HAART+melatonin, HH and HAART alone in diabetes.ConclusionsPresumptive hypoglycemic use of HH with HAART by people living with HIV/AIDS requires caution as implications for hepatocellular injuries are suspected with further uncontrolled metabolic disorder.

The Pharmacologic Role and Clinical Utility of PCSK9 Inhibitors for the Treatment of Hypercholesterolemia

In addition to monoclonal antibodies against proprotein convertase subtilisin-kexin type 9 (PCSK9), vaccines against PCSK9 and smaller molecule inhibitors as well as RNA inhibitors of PCSK9 production have been created. The monoclonal antibodies against PCSK9 and the PCSK9 RNA inhibitors can reduce low-density lipoproteins (LDLs) by over 50%, non-high-density lipoprotein (HDL) cholesterol and triglycerides, and increasing HDL. Although effective in several homozygous familial hypercholesterolemia patient types, PCSK9 inhibitors does not work in all patient types. Outcome trials show no effects on mortality but do show reductions in atherosclerotic events such as myocardial infarctions, strokes, and need for coronary revascularization. PCSK9 inhibitors have a very attractive safety profile with no significant elevations in measures of muscle or liver damage. The current and more advanced experimental agents all require subcutaneous dosing, and injection site reactions are among the most common adverse events. Therapy for the Food and Drug Administration(FDA) approved agents is markedly expensive, and this is the primary barrier to utilization. However, it is possible to identify patients with a number needed to treat to prevent an atherosclerotic event low enough to render it cost-effective and one such factor is whether or not you require a 50% reduction in LDL in order to achieve your LDL goal.

Assessment of Antihyperlipidemic and Antitumor Effect of Isolated Active Phytoconstituents from Apium graveolens L. through Bioassay-Guided Procedures

ABSTRACTThe seeds of A. graveolens yielded coumarin derivatives such as seselin, methoxsalen, and 3H-isobenzofuran-1-one through chromatographic separation techniques. The structure of the components has been established on the basis of spectral data analysis. The present study was undertaken to explore the antihyperlipidemic and antitumor effects of ethanolic extract and phytoconstituents of A. graveolens in rodents. Albino rats were administered intraperitoneal (i.p.) injection of Triton WR 1339 for the induction of hyperlipidemia at a dose of 400 mg/kg body weight. After 24 h of Triton administration, the test drugs were administered orally at dose of 50 mg/kg body weight in rats. The extract and isolated components were further investigated for the tumor take inhibitory activity in hybrid mice (of C57BL strain + Swiss albino strain). Preventive group animals were injected daily with the extract and isolated components at a dose of 50 mg/kg body weight i.p. for 10 consecutive days. The animals were observed for the growth of tumor after injection of B16F10 melanoma cells into the dorsal skin of mice. The study showed significant reduction in total cholesterol (p < .001), triglycerides (p < .001) and low-density lipoprotein (LDL) level (bp < .01) and significantly increased high density lipoprotein (HDL) level (p < .01) after the treatment. Pretreatment showed delay in tumor growth by increasing the volume-doubling time (p < .01), growth delay (p < .01), and mean survival time (p < .001). Acute treatment caused stimulatory effect on HDL level and inhibition in total cholesterol (TC) and triglyceride (TG) elevation induced by Triton. Tumor regression studies showed a regression response for tumor growth in vivo of murine mouse melanoma tumor cell lines.

Effect of cardiac rehabilitation on cardiovascular risk factors in chronic heart failure patients.

IntroductionCardiac rehabilitation improves disease-related symptoms, quality of life, and clinical outcomes. This study was done to evaluate the effect of cardiac rehabilitation program on cardiovascular risk factors in chronic heart failure patients as well as functional capacity and health related quality of life.MethodsThe study was conducted on 80 Patients with chronic stable heart failure. All patients had full history and thorough physical examination. Body mass index (BMI), waist circumference, glycated hemoglobin (HbA1c), lipid profile, and echocardiography, all of which were done before and after recruitment in a 2 months cardiac rehabilitation program (through prescribed exercise training, 2 sessions/week for 2 months). The changes in functional capacity were evaluated by 6-min walk test (6MWT) and the changes in the health related quality of life were measured by Minnesota living with heart failure questionnaire (MLHFQ), both were done before and after the rehabilitation program.ResultsThere was a highly significant reduction in the blood pressure, heart rate, BMI, waist circumference, the smokers’ number and the glycated hemoglobin (HbA1c) (P < 0.01). However, there was no statistically significant reductions in low density lipoproteins (LDL), Triglycerides (P > 0.05). Highly significant improvements were noted in the functional capacity and the health related quality of life as evidenced by improvement in the 6MWT and the MLHFQ scores (total score, physical and psychological domains, P < 0.01).ConclusionCardiac rehabilitation had a significant improvement of cardiovascular risk factors, functional capacity and Health related quality of life in patients with chronic heart failure.

Improved endothelial function after short-term therapy with evolocumab

The reduction of cholesterol levels with cholesterol-lowering therapy may improve endothelial function. Lipid-lowering therapy has been greatly enhanced by the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies. Less is known of the effect of PCSK9 inhibitors on endothelial function of subjects with hypercholesterolemia. To assess whether treatment with PCSK9 inhibitors may improve endothelial function evaluated by brachial artery vasoreactivity test. Brachial artery vasoreactivity test was performed in 14 consecutive patients with previous myocardial infarction before and after 2months of therapy with evolocumab 140mg twice in a month. Mean brachial artery diameter, velocity time integral, flow-mediated dilation (FMD) and low-density lipoprotein (LDL) cholesterol levels were also evaluated. After 2months of treatment with evolocumab, mean total cholesterol levels decreased from 245±41 to 128±30mg/dL (P<.001, -48%), and LDL levels from 176±43 to 71±26mg/dL (P=.001, -59%); FMD conversely increased from 6.3±4.1% to 8.8±6.3% (P=.004,+40%). Improvement in FMD was proportional to reduction of LDL levels (r=0.69, P=.006). Therapy with evolocumab increased brachial artery diameter during vasoreactivity test (peak values 0.39±0.09 vs 0.36±0.11cm, P=.010; final values 0.36±0.10 vs 0.34±0.10cm, P=.001), and velocity time integral (peak levels 96±1 vs 85±9cm, P=.045). Two months of treatment with evolocumab 140mg may improve endothelial function in subjects with increased cardiovascular risk. The improvement in endothelial function is proportional to LDL reduction.

Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome: Quantity vs quality over time and implication of CETP

Statins impact the metabolism, concentrations, composition, and function of circulating lipoproteins. We evaluated time course relationships between statin-mediated reduction in atherogenic apolipoprotein B (ApoB)-containing particles and dynamic intravascular remodeling of ApoAI-containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome. Insulin-resistant, hypertriglyceridemic, hypercholesterolemic, obese males (n=12) were treated with pitavastatin (4mg/d) and response evaluated at 6, 42, and 180days. Reduction in low-density lipoprotein (LDL) cholesterol, ApoB, and triglycerides (TGs) was essentially complete at 42days (-38%, -32%, and -35%, respectively); rapid reduction equally occurred in remnant cholesterol, ApoCII, CIII, and E levels (day 6; -35%, -50%, -23%, and -26%, respectively). Small dense LDLs (LDL4 and LDL5 subpopulations) predominated at baseline and were markedly reduced on treatment (-29% vs total LDL mass). Cholesteryl ester (CE) transfer protein activity and mass decreased progressively (-18% and -16%, respectively); concomitantly, TG depletion (up to -49%) and CE enrichment occurred in all high-density lipoprotein (HDL) particle subpopulations with normalization of CE/TG mass ratio at 180days. ApoAI was redistributed from LpAI to LpAI:AII particles in HDL2a and HDL3a subpopulations; ApoCIII was preferentially depleted from LpAI:AII-rich particles on treatment. Overall, statin action exhibits duality in mixed dyslipidemia, as CE transfer protein-mediated normalization of the HDL CE/TG core lags markedly behind subacute reduction in elevated levels of atherogenic ApoB-containing lipoproteins. Normalization of the HDL neutral lipid core is consistent with enhanced atheroprotective function. The HDL CE/TG ratio constitutes a metabolomic marker of perturbed HDL metabolism in insulin-resistant states, equally allowing monitoring of statin impact on HDL metabolism, structure, and function.

Ameliorative Effect of Epigallocatechin Gallate on Cardiac Hypertrophy and Fibrosis in Aged Rats.

The objective of the present study is to evaluate the effect of epigallocatechin gallate (EGCG) on aging-mediated cardiac hypertrophy, fibrosis, and apoptosis. The Wistar albino rats were divided into 4 groups (n = 18). Group I: young (3 months), group II: aged (24-26 months), group III: aged + EGCG (200 mg/kg for 30 days), and group IV: young + EGCG. At the end of 30 days, EGCG administration to the aged animals showed significant (P < 0.001) reduction of low-density lipoprotein, very low-density lipoprotein, triglyceride, total cholesterol with concomitant increase of high-density lipoprotein (P < 0.001) when compared with aged rats. Increased (P < 0.001) heart volume, weight with concomitant increase of left ventricular wall thickness, and reduced ventricular cavity were observed in aged rats supplemented with EGCG compared with aged animals. Histology and histomorphometry study of aged animals treated with EGCG showed marked increases in the diameter and volume of cardiomyocytes with concomitant reduction of numerical density when compared with aged animals. Reduced reactive oxygen species (P < 0.001) production with association of increased antioxidant defense system (P < 0.001) in aged hearts supplemented with EGCG when compared with aged animals. TUNEL staining and fibrosis showed a marked increase in apoptotic cell death (P < 0.001) and collagen deposition (P < 0.001) in aged animals treated with EGCG when compared with aged animals. Aged animals treated with EGCG showed a marked increase in protein expression of TGFβ, TNFα, and nuclear factor kappa B (NF-κB) and significant (P < 0.001) alteration in the gene expression of TGFβ, TNFα, NF-κB, α-SMA, and Nrf2 when compared with aged animals. Taken together, it is evident that EGCG may potentially inhibit aging-induced cardiac hypertrophy, fibrosis, and apoptosis, thereby preserving cardiac function. The proposed mechanism would be inhibition of reactive oxygen species-dependent activation of TGFβ1, TNFα, and NF-κB signaling pathway. Hence, the present study suggests that EGCG can be useful to fight against aging-induced cardiac hypertrophy, fibrosis, and apoptosis.

Effect of telemedicine messages integrated with peer group support on glycemic control in type 2 diabetics, Kingdom of Saudi Arabia

To test the effectiveness, feasibility, and acceptability of the Jizan Integrated Life Style Education (JILSE) program. Type 2 diabetes mellitus and its management is challenging in the Kingdom of Saudi Arabia. Audio-visual messages via mobile phone integrated with peer group support were used for diabetic patient empowerment. A quasi-experimental two-group pre- and post-evaluation study design was used. Newly diagnosed diabetes mellitus patients (200) were divided into intervention and control group with equal weightage to gender. Intervention group was divided into peer groups as “Diabetes Cluster” with 25 participants each and monthly meetings, periodic messages, and peer group interactions were encouraged for 6 months. Age, education level, height, weight, smoking habits, physical activity and exercise, duration of disease, type of treatment, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), glycosylated hemoglobin (HbA1C), and diabetic knowledge were measured and compared before and after the intervention. There was statistically significant reduction in intervention group compared to control group. The excess reduction in mean HbA1C was 16.87%. Fasting blood sugar was reduced by 6.17% and systolic and diastolic blood pressure by 6.07 and 0.75%. There was 9.97% reduction in total cholesterol value. The reduction in triglycerides, LDL, HDL, smoking habits, and physical exercise was not statistically significant (p > 0.05). The diabetic knowledge level was significantly improved after JILSE program. This study demonstrated that JILSE program is effective, feasible, and acceptable to Saudi diabetic patients. Diabetic patient peer group networks with periodic health education messages and motivation from specialists can decrease the blood glucose level, systolic and diastolic blood pressure, and BMI among diabetes type 2 patients.

High-Intensity Statin Therapy Is “Too Much,” Thus Not Indicated for Very Elderly Patients

Purpose: Although moderate- to high-intensity statin therapy is increasingly recommended in cardiovascular disease patients, the efficacy and safety in elderly patients have not been proven clearly. Here, we compare the effect of various-intensity statins between elderly and very elderly patients. Methods: 43,870 patients over 65 years old who were treated with statins were screened using electronic medical record data. Results: We evaluated 451 patients in the elderly group aged 65–74 years and 159 patients in the very elderly group over 75 years old. Baseline cholesterol profiles were similar between the 2 groups, but the 10-year atherosclerotic cardiovascular disease (ASCVD) risk was significantly higher in the very elderly (20.9 ± 11.5% vs. 37.2 ± 13.6%, p < 0.001). The reduction rate of low-density lipoprotein (LDL) (–40.2 ± 21.3% vs. –39.3 ± 21.0%, p = 0.634) and the ratio of target LDL attainment (74.2 vs. 79.2%, p = 0.252) were similar between the 2 groups. Low-intensity statins showed comparable LDL cholesterol reduction with moderate-intensity statins both in the elderly and the very elderly groups. The 10-year ASCVD risk reduction was similar between the 2 groups (–3.5 ± 4.9% vs. –3.0 ± 8.4%, p = 0.480), but in the very elderly group, no different ASCVD reduction rate was shown in low- to high-intensity statins (p = 0.784). Only the elderly group showed a significant correlation (r = 0.112, p = 0.017) with LDL reduction and 10-year ASCVD risk. Interestingly, the incidence of adverse drug reaction (ADR) was higher in the very elderly group (4.4%) than in the elderly group (2.7%) and was more frequent in high-intensity statin therapy. Conclusion: The efficacy of statins in LDL reduction was similar between the elderly and very elderly population. However, the benefit of moderate- to high-intensity statins is limited considering potential ADR. Therefore, the stepwise intensification of statin therapy might be necessary for the very elderly in spite of the higher cardiovascular risk.