Elevated Low-density Lipoprotein Levels Research Articles

Atorvastatin in nano-particulate formulation abates muscle and liver affliction when coalesced with coenzyme Q10 and/or vitamin E in hyperlipidemic rats

AimsStatins are the most widely used to lower elevated low-density lipoprotein levels and preventing cardiovascular diseases in humans. However, about 20% of patients treated with this medication suffer from statin-related myalgia. To this end, this study investigated the potential effect of nano-particulate formulation in alleviating the muscles and liver damage either alone or when co-administered with nano coenzyme Q10 and nano vitamin E. Materials and methodsMale Wistar rats were fed normal diet or high-fat diet for 12 weeks, following which rats were treated with either (i) atorvastatin (5 or 20 mg/kg/day, p.o.) or (ii) atorvastatin with CoQ10 (10 mg/kg/day, p.o.) (iii) and/or vitamin E (30 mg/kg/day, p.o.) in free particle or nanoparticle forms for another 4 weeks. In all rats, serum total cholesterol (CH), triglycerides (TGs), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), creatine kinase (CK), albumin (ALB), as well as hepatic malondialdehyde (MDA) and antioxidants “reduced glutathione (GSH) and superoxide dismutase (SOD)” were measured. Additionally quadriceps muscles and liver tissues were used for histopathological examination. Key findingsThe antihyperlipidemic effect of statins was not altered when formulated as nanoparticles; albeit the former showed a prominent reduction in the liver and muscle enzymes and histopathological alterations together with a marked decline in the oxidative stress as compared to the free particulate form. These results were augmented when atorvastatin was combined with CoQ10 and/or Vit.E. SignificanceNanoparticulate formulation alleviated the statins induced liver and muscle damage especially when combined with CoQ10 and/or Vit.E.

Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model.

Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model. Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining. Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment. Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.

Polypill Variants (Quarter Pill Trials).

The cardiovascular polypill or fixed-dose combination pill, consisting of 3, 4, or more drugs in a single tablet (or capsule), has been proposed as an effective and convenient therapy in both secondary and primary prevention of cardiovascular disease (CVD). Each of the drugs in the combination has a documented ability to prevent CVD events. The combined effect has been estimated to reduce risk by 75% to 80%. Since the concept was introduced 15 years ago, several polypills are available and their effects on risk factors evaluated. Their effects on individual risk factors, such as hypertension and elevated low-density lipoprotein levels, are similar to the individual drugs separately. Enhancement of adherence of the polypill has also been shown compared to individual drugs given separately. Based on the reductions on the individual risk factors, the reductions in risk are estimated to be substantial. A few large long-term randomized controlled trials are ongoing and will be completed in the next 2 years. If the effects on CVD outcomes are as predicted, this would help the many millions of individuals who are currently not adequately treated or not treated at all. There are however considerable challenges in development and acceptance of the polypill. These include regulatory issues; intellectual property; perception by the public, patients, and physicians; and the role of health systems and societal approach to disease prevention. For the polypill to be accepted and achieve even a part of its potential, multiple barriers outlined in this review have to be overcome.

Effects of Herbal-cake-separated Moxibustion on Blood Lipid Protein Levels and Expression of Toll-like Receptor and Nuclear Factor Genes in Atherosclerotic Plaques in Hyperglycemia Rabbits

To observe the effect of herbal cake-separated moxibustion on blood lipid-apoprotein levels and the expression of Toll-like receptor 2 (TLR 2), TLR 4 and nuclear factor kappa B(NF-κB) mRNAs in atherosclerotic (AS) vulnerable plaques of hyperglycemia rabbits, so as to explore its mechanism underlying improvement of atherosclerosis. Sixty New Zealand rabbits were randomly divided into 5 groups: control, model, direct moxibustion, herbal-cake-separated moxibustion and medication groups(n＝12 rabbits in each group). The AS vulnerable plaque model was established by high-fat forage feeding plus balloon-induced abdominal aorta injury and gene transfection of Ad 5-p 53 recombinant vector. Direct moxibustion or herbal-cake-separated moxibustion was applied to "Juque" (CV 14) and bilateral "Tianshu" (ST 25), "Fenglong" (ST 40), or bilateral "Xinshu" (BL 15), "Pishu" (BL 20) and "Ganshu" (BL 18) for 15－20 min every time. The medication group was treated by feeding Atorvastatin. All the treatments were conducted once daily for 8 weeks. Plasma total cholesterol(TC) and triglyceri-de(TG) contents were detected by enzyme method, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) contents detected by colorimetric determination, and plasma apolipoprotein A(Apo-A) and apolipoprotein B(Apo-B) levels determined by electrophoretic method. The pathological changes of vulnerable plaque and the aortic intima and media thickness were observed under light microscope after H．E. staining. The expression levels of TLR 2, TLR 4 and NF-κB mRNAs in AS plaques were determined by quantitative real-time PCR. After modeling, the levels of plasma TC, TG, LDL and Apo-B in the model group were remarkably increased (P<0.01), and Apo-A and HDL/LDL were significantly decreased in comparison with the control group (P<0.01). Additionally, the aortic intima and media thickness and the expression levels of TLR 2, TLR 4 and NF-κB mRNAs in AS plaques were significantly increased (P<0.01). After the treatment, the elevated levels of plasma TC, TG, LDL and Apo-B, the aortic intima thickness and media thickness, and the expression levels of TLR 2, TLR 4 and NF-κB mRNAs in the 3 treatment groups were significantly down-regulated in comparison with the model group (P<0.05, P<0.01), while the decreased levels of Apo-A and HDL/LDL were considerably increased (P<0.01). Comparison among the 3 treatment groups showed that the therapeutic effects of the herbal-cake-separated moxibustion and medication were significantly superior to those of the direct moxibustion in down-regulating the levels of TC, TG, LDL, Apo-B, TLR 2 mRNA, TLR 4 mRNA and NF-κB mRNA, and reducing the thickness of the aortic intima and media, as well as in up-regulating the levels of Apo-A and HDL/LDL (P<0.05, P<0.01). No significant differences were found between the herbal-cake-separated moxibustion and medication groups in the above-mentioned indexes (P>0.05). Herbal-cake-separated moxibustion has a positive role in stabilizing AS vulnerable plaque in hyperglycemia rabbits, which may be associated with its effects in regulating blood lipid-apolipoprotein levels and inhibiting the expression of TLR 2, TLR 4 and NF-κB mRNAs in vulnerable plaques.

Dyslipidemia and Associated Cardiovascular Risk Factors among Young Nepalese University Students.

IntroductionCardiovascular diseases are one of the main causes of morbidity and mortality worldwide, atherosclerosis being the principal underlying cause of cardiovascular diseases. Early detection of dyslipidemia and long-term prevention of atherosclerosis by controlling risk factors should begin in young age. The purpose of this study was to assess dyslipidemia and associated cardiovascular risk factors among university students of Nepal.MethodsA sample of 280 students aged 17–24 years, were selected randomly from Institute of Medicine, Tribhuvan University. An interview-based questionnaire was designed and information was collected on the basis of age, gender, smoking and alcohol consumption. Body mass index and waist-to-hip ratio of all participants were calculated. Fasting blood samples were collected from all participants and assayed for fasting serum total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein.ResultsOverall, dyslipidemia was seen as hypercholesterolemia in 31 (11.1%), elevated low-density lipoprotein in 34 (12.1%), low high-density lipoprotein in 95 (33.9%) and hypertriglyceridemia in 39 (13.9%). Current smoking and binge drinking were significantly associated with hypercholesterolemia. Gender, binge drinking, and current smoking were found to be significantly associated with elevated low-density lipoprotein. All factors were significantly associated with hypertriglyceridemia. There was no statistically significant association between risk factors and the low high-density lipoprotein. Body mass index and waist-to-hip ratio were significantly higher in subjects with hypercholesterolemia, hypertriglyceridemia, and elevated low-density lipoprotein level.ConclusionsThe prevalence of dyslipidemia was high in young Nepalese university students. Screening the levels of lipids in youth, especially those at risk, and accurate follow-up of those with dyslipidemia can be done to reduce morbidity and mortality.

(Pro)renin Receptor Inhibition Reprograms Hepatic Lipid Metabolism and Protects Mice From Diet-Induced Obesity and Hepatosteatosis

An elevated level of plasma LDL (low-density lipoprotein) is an established risk factor for cardiovascular disease. Recently, we reported that the (pro)renin receptor ([P]RR) regulates LDL metabolism in vitro via the LDLR (LDL receptor) and SORT1 (sortilin-1), independently of the renin-angiotensin system. To investigate the physiological role of (P)RR in lipid metabolism in vivo. We used N-acetylgalactosamine modified antisense oligonucleotides to specifically inhibit hepatic (P)RR expression in C57BL/6 mice and studied the consequences this has on lipid metabolism. In line with our earlier report, hepatic (P)RR silencing increased plasma LDL-C (LDL cholesterol). Unexpectedly, this also resulted in markedly reduced plasma triglycerides in a SORT1-independent manner in C57BL/6 mice fed a normal- or high-fat diet. In LDLR-deficient mice, hepatic (P)RR inhibition reduced both plasma cholesterol and triglycerides, in a diet-independent manner. Mechanistically, we found that (P)RR inhibition decreased protein abundance of ACC (acetyl-CoA carboxylase) and PDH (pyruvate dehydrogenase). This alteration reprograms hepatic metabolism, leading to reduced lipid synthesis and increased fatty acid oxidation. As a result, hepatic (P)RR inhibition attenuated diet-induced obesity and hepatosteatosis. Collectively, our study suggests that (P)RR plays a key role in energy homeostasis and regulation of plasma lipids by integrating hepatic glucose and lipid metabolism.

English

Tumor necrosis factor-&alpha; (TNF-&alpha;) is an adipokine produced in adipocytes which acts as a marker of inflammation. Increased levels of TNF-&alpha; have been associated with obesity and abnormal lipid profile. This study aimed to examine the relationship between polymorphism in -308 G/A TNF-&alpha; with concentrations of TNF-&alpha;, lipid profile and obesity in a Javanese population. The study consisted of 200 participants (98 controls and 102 obese) from a Javanese sample population. All subjects were measured for anthropometry, high-density lipoprotein (HDL)-C, low-density lipoprotein (LDL)-C, triglyceride, cholesterol, and TNF-&alpha; levels. Lipid profile were measured using the enzymatic colorimetric method, TNF-&alpha; level was measured with enzyme-linked immunosorbent assay (ELISA) and -308 G/A TNF-&alpha; polymorphism was detected using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Results showed that the GA genotype have LDL-C, triglyceride, cholesterol and TNF-&alpha; levels higher than the GG genotype. The findings demonstrate that 308 G/A TNF-&alpha; gene polymorphism plays a role in increasing the risk of obesity with odds ratio for A to G allele 1.96 (95% CI = 1.60-2.40) and odds ratio for GA to GG genotype 3.52 (95% CI = 2.84-4.36). TNF-&alpha; polymorphism (-308G/A) contributed to increased body mass index and elevated levels of LDL, triglyceride, cholesterol and TNF-&alpha; in obese Javanese population. This polymorphism may be used as a marker in the development of metabolic diseases and the identification of risk of obesity. Multifactorial analysis in the future may reveal basic genotypic differences between ethnic groups and demonstrate evidence for other environmental factors. Key words: Adipokines, lipid profile, obese, polymorphism, populations, tumor necrosis factor-&alpha; (TNF-&alpha;).

Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease

BackgroundLoss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease.MethodsWe sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study. We performed tests of association for loss-of-function variants in ANGPTL3 with lipid levels and with coronary artery disease in 13,102 case patients and 40,430 controls from the DiscovEHR study, with follow-up studies involving 23,317 case patients and 107,166 controls from four population studies. We also tested the effects of a human monoclonal antibody, evinacumab, against Angptl3 in dyslipidemic mice and against ANGPTL3 in healthy human volunteers with elevated levels of triglycerides or LDL cholesterol.ResultsIn the DiscovEHR study, participants with heterozygous loss-of-function variants in ANGPTL3 had significantly lower serum levels of triglycerides, HDL cholesterol, and LDL cholesterol than participants without these variants. Loss-of-function variants were found in 0.33% of case patients with coronary artery disease and in 0.45% of controls (adjusted odds ratio, 0.59; 95% confidence interval, 0.41 to 0.85; P=0.004). These results were confirmed in the follow-up studies. In dyslipidemic mice, inhibition of Angptl3 with evinacumab resulted in a greater decrease in atherosclerotic lesion area and necrotic content than a control antibody. In humans, evinacumab caused a dose-dependent placebo-adjusted reduction in fasting triglyceride levels of up to 76% and LDL cholesterol levels of up to 23%.ConclusionsGenetic and therapeutic antagonism of ANGPTL3 in humans and of Angptl3 in mice was associated with decreased levels of all three major lipid fractions and decreased odds of atherosclerotic cardiovascular disease. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT01749878.)

Genetic variation in the microsomal triglyceride transfer protein (\u2212493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus

BackgroundIn chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment. Among the associated metabolic factors, hepatic steatosis is characterized by an accumulation of triglycerides in hepatocytes. In the host, genetic determinants of hepatic steatosis are observed, such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene. The MTTP -493G/T SNP appears to play an important role in the regulation of gene expression and influences the plasma concentration of circulating low-density lipoprotein (LDL). The present study investigated the influence of this SNP in the development of hepatic steatosis in patients with chronic hepatitis C and evaluated the association of hepatic steatosis with certain characteristics of these patients and the hepatitis C virus (HCV).MethodsTwo hundred thirty-nine patients with chronic hepatitis C were genotyped for the MTTP -493G⁄T SNP by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The association between hepatic steatosis and selected characteristics of the patient and virus was evaluated using bivariate and multivariate analyses.ResultsThe most prevalent MTTP -493G/T genotype was GG (46%) followed by GT (43.5%) and TT (10.5%). Multivariate analysis of the total cohort revealed associations between the presence of hepatic steatosis and inflammatory activity of moderate to high intensity (P < 0.001), advanced age (P = 0.010), elevated gamma glutamyl transpeptidase (GGT) levels (P = 0.010) and low LDL levels (P = 0.022). Hepatic steatosis was also associated with the TT/GT genotype of the MTTP -493G⁄T SNP in patients infected with HCV genotype 3 (P < 0.001).ConclusionsIn chronic hepatitis C patients infected with HCV genotype 3 and with the TT/GT genotype of the MTTP -493G/T SNP, a significant increase in hepatic steatosis was observed, which may indicate that this SNP has a significant influence on the accumulation of triglycerides in hepatocytes. Furthermore, associations were observed between hepatic steatosis and inflammatory activity of moderate to high intensity, advanced age, elevated GGT and low LDL levels.

HYPOLIPIDEMIC POTENTIAL OF METHANOLIC EXTRACT OF GRACILARIA CORTICATA ON STREPTOZOTOCIN-INDUCED DIABETIC RATS

ABSTRACTObjectives: Diabetes mellitus is associated with profound alterations in the levels of plasma lipids and the lipoprotein profile. Herbs and herbal drugpreparations find wide use in alleviating the complications of uncontrolled diabetes owing to their low cost and lesser side effects. This study wasaimed at establishing the hypolipidemic effect of methanolic extract of sea weed Gracilaria corticata on streptozotocin (STZ)-induced diabetic rats.Methods: STZ-induced Wistar male albino rats were administered with methanolic extract of Gracilaria corticata (MGC) at a dosage of 100 mg/kgBW/day per orally for 45 days. Glibenclamide (600 μg/kg BW/day) administered rats served as standard drug control. Animals were sacrificed on46th day, biochemical parameters associated with lipid metabolism were analyzed in blood and tissue samples, statistical significance determined.Results: Elevated levels of total cholesterol, triglycerides, and free fatty acids were observed in the plasma and tissues of diabetic rats as compared toMGC and glibenclamide treated groups. The diabetic rats also had elevated levels of low-density lipoprotein (LDL-C) and very low-density lipoprotein(VLDL-C) and decreased levels of high-density lipoprotein (HDL-C) while the MGC and glibenclamide treated rats showed near normal levels of theseindices.Conclusion: This study establishes the hypolipidemic potential of MGC in STZ-induced diabetic rats.Keywords: Gracilaria corticata, Diabetes mellitus, Hypolipidemic, Streptozotocin.

Abstract P030: Long-term Pharmacotherapy for Elevated Low Density Lipoprotein Levels in Children: A Retrospective Analysis

Background: There is limited research detailing LDL trends over the long term in children on various lipid lowering medications. Objectives: This study sought to assess factors associated with stability of LDL levels in children on long-term pharmacotherapy and their ability to reach the current recommended LDL goal of 130 mg/dL or less while on pharmacotherapy. Methods: Medical records of children seen in a university pediatric cholesterol clinic between 1998 and 2012 who were treated with a statin, ezetimibe, or both were reviewed. Aggregate data were obtained to determine the number of children who were able to reach an LDL level of 130 mg/dL or less while on pharmacotherapy. Kaplan-Meier curve and proportional hazard regression analysis were used to examine the propensity for LDL levels to stabilize over time while on pharmacotherapy as well as factors affecting this propensity. Results: 76 patients who contributed 864 total visits met inclusion criteria. 56 of 76 patients developed a stable LDL with median time to stability of 28 months on pharmacotherapy. Younger age of first visit was associated with development of LDL stability (9.8 years for stable LDL vs. 13.3 years for nonstable LDL; p= 0.004). Titration to higher statin doses and/or higher potency statins was also associated with higher propensity for LDL stabilization. There was no significant difference between patients who were taking a statin, ezetimibe, or both in terms of their propensity to stabilize even when stratifying for presence of probable familial hypercholesterolemia (p=0.579). 36 of 76 patients were able to reach an LDL of 130 mg/dL or less, with only 11 of 38 patients with probable familial hypercholesterolemia (&gt;190 mg/dL baseline LDL) reaching this goal. Conclusion: A majority of children in a university pediatric cholesterol clinic were able to reach a stable LDL level on pharmacotherapy after a median 28 month interval. On the other hand, the majority of children had difficulty reaching the current recommended goal LDL of 130 mg/dL or less, even after aggressive titration of medication. This was specifically true for those with probable familial hypercholesterolemia. Further research is needed to assess the utility of goal-directed therapy in children with regards to cardiovascular outcomes.

The role of proprotein convertase subtilisin/kexin type 9 inhibitors in managing cardiovascular risk

Hypercholesterolaemia and dyslipidaemia, marked by decreased levels of high-density lipoprotein and elevated levels of lowdensity lipoprotein (LDL), increase the risk of cardiovascular disease. Familial hypercholesterolaemia (FH), diagnosed based on the clinical features seen in patients with a positive family history, constitutes a heritable disorder involving a single gene. FH can exist in either the heterozygous or homozygous form, and may be differentiated based on clinical features and genetic studies. A novel drug target, proprotein convertase subtilisin/kexin type 9 (PCSK9), has resulted in the development and subsequent approval of new, targeted monoclonal antibodies in the treatment of FH. Targeting PCSK9 with monoclonal antibodies, i.e. evolocumab and alirocumab, inhibits the degradation of LDL receptors, and against a background of optimised statin therapy, increases the life expectancy of patients with hypercholesterolaemia by reducing the incidence and severity of coronary artery disease.

Study of musculoskeletal disorders in a cohort of Egyptian diabetic patients and its relation to glycemic control

Background Diabetes mellitus (DM) affects the musculoskeletal (MSK) system, resulting in significant morbidity. These manifestations are unrecognized, though they are found in daily practice.Aim To study the effect of DM on the MSK system and the prevalence of these MSK disorders among Egyptians.Patients and methods In total, 100 patients with type 1 DM, 100 patients with type 2 DM, and 100 normal controls were examined for different types of MSK disorders. Fasting and postprandial blood glucose, glycosylated hemoglobin, and lipid profile testings were done for patients and controls. Plain radiography of the dorsolumbar region and ankle joint and nerve conduction study of the median nerve were done in some selected cases.Results These MSK manifestations were found in patients with types 1 and 2 DM, and their prevalence rates are as follows: carpal tunnel syndrome (14 and 5%, respectively), sclerodactyly (9 and 3%, respectively), Charcot joint (2 and 4%, respectively), limited joint mobility (2 and 6%, respectively), stenosing tenosynovitis (1 and 5%, respectively), shoulder capsulitis (1 and 10%, respectively), diffuse idiopathic skeletal hyperostosis (0 and 3%, respectively) and Dupuytren’s contracture (0 and 1%, respectively). MSK manifestations were more prevalent in patients with longer disease duration, poor glycemic control, and higher levels of lipid profile.Conclusion The result of this study emphasizes the importance of glycemic control and its relation to MSK manifestations, in addition to the new finding that elevated levels of low-density lipoprotein are significantly related to MSK manifestations.

Study of musculoskeletal disorders in a cohort of Egyptian diabetic patients and its relation to glycemic control

Background Diabetes mellitus (DM) affects the musculoskeletal (MSK) system, resulting in significant morbidity. These manifestations are unrecognized, though they are found in daily practice. Aim To study the effect of DM on the MSK system and the prevalence of these MSK disorders among Egyptians. Patients and methods In total, 100 patients with type 1 DM, 100 patients with type 2 DM, and 100 normal controls were examined for different types of MSK disorders. Fasting and postprandial blood glucose, glycosylated hemoglobin, and lipid profile testings were done for patients and controls. Plain radiography of the dorsolumbar region and ankle joint and nerve conduction study of the median nerve were done in some selected cases. Results These MSK manifestations were found in patients with types 1 and 2 DM, and their prevalence rates are as follows: carpal tunnel syndrome (14 and 5%, respectively), sclerodactyly (9 and 3%, respectively), Charcot joint (2 and 4%, respectively), limited joint mobility (2 and 6%, respectively), stenosing tenosynovitis (1 and 5%, respectively), shoulder capsulitis (1 and 10%, respectively), diffuse idiopathic skeletal hyperostosis (0 and 3%, respectively) and Dupuytren’s contracture (0 and 1%, respectively). MSK manifestations were more prevalent in patients with longer disease duration, poor glycemic control, and higher levels of lipid profile. Conclusion The result of this study emphasizes the importance of glycemic control and its relation to MSK manifestations, in addition to the new finding that elevated levels of low-density lipoprotein are significantly related to MSK manifestations.

Early Cardiac Rehabilitation in a 14 year Old Male with Familial Hypercholesterolemia Post Coronary Artery Bypass Graft Surgery-a Case Report

Familial Hypercholesterolemia is a genetic disorder caused by mutations in the genes encoding the low density lipoprotein (LDL) receptor consequently which results in elevated plasma levels of LDL. We report a case of a fourteen year old male with homozygous familial hypercholesterolemia who underwent coronary artery bypass surgery and later underwent a phase one cardiac rehabilitation program. The program consisted of early post surgical respiratory care with bronchial hygiene therapy and a submaximal exercise stress test done at the end of first phase of cardiac rehabilitation.

Familial Hypercholesterolemia and Pregnancy: Risk and Management

Familial hypercholesterolemia (FH) is a dominantly inherited disorder present from birth with elevated levels of low-density lipoprotein (LDL) cholesterol and increased risk for premature coronary heart disease (CHD) with clinical manifestation between the first and the fourth decades of life. Although statins are the most effective therapy for individuals with FH the use of statins is contraindicated during pregnancy. For this reason, before of a pregnancy the lipid-lowering drugs are discontinued because of possible teratogenic effects with modifications in estrogen and progesterone levels that negatively influence the lipid metabolism. Pregnancy in women affected by FH is rare and might be a critical challenge for both mother and fetus. There are limited therapeutic options available to treat pregnant women with FH and the potential risks to mother and fetus related to elevated cholesterol levels are a certainty. Regarding how to treat these women during pregnancy remains a challenge.

Long-term pharmacotherapy for elevated low density lipoprotein levels in children: A retrospective analysis

There is limited research detailing low-density lipoprotein cholesterol (LDL-C) trends over the long term in children on various lipid-lowering medications. This study sought to assess factors associated with stability of LDL-C levels in children on long-term pharmacotherapy and their ability to reach the LDL-C goal of ≤130 mg/dL while on pharmacotherapy. Medical records of children seen in a university pediatric cholesterol clinic between 1998 and 2012 treated with a statin, ezetimibe, or both were reviewed. Aggregate data were obtained to determine the number of children able to reach an LDL-C level of ≤130 mg/dL while on pharmacotherapy. Kaplan-Meier curve and proportional hazard regression analysis were used to examine the propensity for LDL-C levels to stabilize over time while on pharmacotherapy as well as factors affecting this propensity. Overall, 76 patients who contributed 864 total visits were included. Of the 76 patients, 56 developed a stable LDL-C with median time to stability of 28 months on pharmacotherapy. Younger age at first visit and higher medication potencies/doses were associated with an increased propensity to stabilize. Only 36 patients were able to reach an LDL-C of ≤130 mg/dL, with only 11 of 38 patients with probable familial hypercholesterolemia reaching this goal. Most children reached LDL-C stability on pharmacotherapy after a median 28-month interval. However, most children had difficulty in reaching the LDL-C goal of ≤130 mg/dL even with aggressive medication titration. This was specifically true for those with probable familial hypercholesterolemia.

Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet.

Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low-density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium-dependent relaxations in cholesterol-fed rats. For this purpose, rats were fed by 2% cholesterol-enriched or standard chow for 8 weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100 mg/kg/day. Atorvastatin at dose of 20 mg/kg of body weight daily was also given as positive control. After 8 weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium-dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL-cholesterol levels were found to be increased in cholesterol-fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis.

Marcadores genéticos relacionados con el desarrollo de síndrome metabólico y riesgo de enfermedad coronaria cardiaca

Variantes genéticas se han relacionado con enfermedades de rasgos complejos y factores de riesgo asociados a éstas. El propósito de este estudio fue evaluar la asociación entre diversos polimorfismos de un solo nucleótido (SNP, por sus siglas en inglés) con el síndrome metabólico (SM) y con el índice aterogénico de plasma (IAP). Se estudiaron mujeres guerrerenses, a quienes se les realizaron mediciones somatométricas, biomarcadores sanguíneos y se identificaron SNP en siete genes por reacción en cadena de la polimerasa (PCR, por sus siglas en inglés) en tiempo real. Se observó disminución de adiponectina en mujeres con SM y con el mayor riesgo aterogénico, y se encontraron asociaciones entre apoproteina E (APOE) con niveles elevados de lipoproteínas de baja densidad (LDL, por sus siglas en inglés) y triglicéridos, del SNP rs1501299 con el IAP, de los genotipos AA/rs708272 y GG/rs1884051, con los niveles altos de LDL, y del genotipo AA/rs854560 con LDL y con la actividad paraoxonasa. Los resultados indican que biomarcadores sanguíneos y genéticos pudiesen estar implicados en alteraciones metabólicas y, por tanto, incrementar el riesgo individual del desarrollo de enfermedades.

Clinical Assessment of Lipid Profiles in Live Kidney Donors

BackgroundAbnormal serum lipid profiles are an issue in chronic kidney disease (CKD), but the clinical ramifications of dyslipidemia in live kidney donors are unclear. Thus, we explored the relationship between serum lipids and residual renal function in living donors post-nephrectomy. MethodsCharts of living donors who underwent nephrectomy between January 2010 and March 2013 were reviewed, targeting those with 6-month follow-up examinations at minimum. Altogether, 282 donors were studied, examining total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels assayed before donation by standard techniques. Median follow-up time was 14 months. The relationship between postoperative renal function and allograft biopsy results was assessed. Recursive partitioning was applied to identify optimal cut-off points for each parameter. ResultsMedian (interquartile range) serum TC, TG, LDL, and HDL levels were 183 (161–205) mg/dL, 86 (63–131) mg/dL, 108 (92–128) mg/dL, and 53 (44–62) mg/dL, respectively. The glomerular filtration rate at last follow-up was associated with TC (r = −0.187; P = .002) and LDL (r = −0.172; P = .005) levels, but showed no correlation with TG and HDL. Root nodes of TC and LDL determinations in recursive partitioning were 170.5 mg/dL and 80.5 mg/dL, respectively, serving as thresholds for further evaluation. On logistic regression analysis, the likelihood of CKD (glomerular filtration rate < 60 mL/min/1.73 m2) at last follow-up was greater in donors with elevated TC and LDL levels (odds ratio = 1.96 and 3.33; P = .021 and .029, respectively). ConclusionKidney donors with serum TC and LDL elevations require close observation, given their demonstrable predisposition to CKD after donation.