Relación entre niveles de vitamina D y perfil lipídico en embarazadas de alto riesgo / Relationship between level of vitamin D and lipid profile in high risk pregnant women

En la Argentina, las embarazadas presentan alta prevalencia (80%) de hipovitaminosis D y de sobrepeso u obesidad (27,4%). Ambas condiciones pueden aumentar la morbimortalidad materno-fetal. Bajos niveles de vitamina D se han relacionado con aumento del colesterol total, LDL, triglicéridos (Tg) y descenso de HDL. Objetivo: evaluar los niveles de 25-hidroxivitamina D (25OHD) y su relación con el perfil lipídico en pacientes embarazadas de alto riesgo. Materiales y métodos: estudio de corte transversal entre septiembre de 2016 y abril de 2017. Se excluyeron pacientes que recibieron suplementos de vitamina D, con disfunción tiroidea no compensada, malabsorción, insuficiencia cardíaca, renal o hepática y dislipidemia familiar. Niveles circulantes de 25OHD < 30 ng/ml se consideraron hipovitaminosis. Resultados: se evaluaron 86 embarazadas de 29,3 ± 7,1 años durante la semana 28 ± 6,5. El IMC pregestacional fue 28,3 ± 6,5 kg/m2 y la ganancia de peso 7 ± 4,3 kg. Perfil lipídico: colesterol total 240 ± 54 mg/dl; LDL 156 ± 54 mg/dl; HDL 66 ± 15 mg/dl; Tg 204 ± 80 mg/dl. La media de 25OHD fue de 23,8 ± 9 ng/ml, con una prevalencia de hipovitaminosis D de 77,9 %. Las pacientes con hipovitaminosis D presentaron mayores valores de colesterol total y LDL (p < 0,05), con tendencia no significativa a presentar mayores valores de Tg. Conclusión: en embarazadas de alto riesgo se observó una alta prevalencia de hipovitaminosis D, asociada con mayores concentraciones de colesterol total y LDL. (AU)

In Argentina, pregnant women have a high prevalence (80 %) of hypovitaminosis D and verweight/obesity (27.4%), conditions that can increase maternal-fetal morbidity and mortality. Low levels of 25-hydroxyvitamin D (25OHD) have been linked to an increase in total cholesterol, LDL cholesterol, triglycerides (TG) and a decrease in HDL cholesterol. Objective: to evaluate the levels of vitamin D and its relationship with the lipid profile in high risk pregnant patients. Materials and methods: cross-sectional study between September 2016 and April 2017. Patients who received vitamin D supplements or had non-compensated thyroid dysfunction, malabsorption, heart failure, renal or hepatic failure, or familial dyslipidemia were excluded. Hypovitaminosis D was defined as a circulating level of 25OHD < 30 ng/ml. Results: We assessed 86 women of 29.3 ± 7.1 years during pregnancy week 28 ± 6.5. Pre-gestational BMI was 28.3 ± 6.5 kg/m2. Their weight gain was 7 ± 4.3 kg. Lipid profile: total cholesterol 240 ± 54 mg/dl; LDL cholesterol 156 ± 54 mg/dl; HDL cholesterol 66 ± 15 mg/dL; TG 204 ± 80 mg/dl. The mean 25OHD level was 23.8 ± 9 ng/ml, with a 77.9 % prevalence of hypovitaminosis D. Patients with hypovitaminosis D had higher values of total cholesterol and LDL cholesterol (p<0.05), and a non-significant trend toward higher triglyceridemia. Conclusion: A high prevalence of hypovitaminosis D, associated with high total and LDL cholesterol was found in high risk pregnant women. (AU)

From clinical appearance to accurate management in acute ischemic stroke patients: With the guidance of innovative traditional Chinese medicine diagnosis.

OBJECTIVE: To investigate the correlation between simplified classification and laboratory indicators in patients with acute ischemic stroke, also provide accurate evidences for simplified classification and guide clinical interventions and treatment. METHODS: Two hundred patients with acute ischemic stroke were classified into four types according to the characteristics of Traditional Chinese Medicine syndrome: phlegm-heat syndrome, phlegm-dampness syndrome, qi deficiency syndrome, and yin deficiency syndrome. The differences between the types of syndromes and the correlation between laboratory indicators and syndromes were analyzed. RESULTS: Among the 200 patients with acute ischemic stroke, there were significant differences in the level of low-density lipoprotein (LDL-C) (p < .05) between patients with phlegm-heat syndrome and other three types. There were significant differences in the levels of homocysteine (HCY) and fibrinogen (Fib) between patients with yin deficiency syndrome and other three types (p < .05). In addition, there were statistically significant differences in blood glucose (Glu), glycosylated hemoglobin (HBA1c), and total cholesterol (CHO) between phlegm-heat syndrome and qi deficiency syndrome (p < .05). There were significant differences in the levels of Glu, HBA1c, D-2 polymer (D-D), and C-reactive protein (CRP)s between patients with phlegm-heat syndrome and phlegm-dampness syndrome (p < .05). There were statistically significant differences in the levels of CRP and urea nitrogen between patients with yin deficiency syndrome and phlegm-dampness syndrome and qi deficiency syndrome (p < .05). CONCLUSIONS: The four-type simplified classification of Integrated TCM and Western medicine in acute ischemic stroke has specific laboratory data to support. Simplified classification with TCM treatment and intervention of different patients improves the survival and treatment, which is an innovative, easy-to-master clinical diagnosis and treatment model.

Hypolipidemic effect of steroid compound from Cestrum diurnum (Solanaceae: Solanales) in normocholesterolemic albino rat.

The present study was carried out to establish the hypolipidemic effect of a phyto-steroid compound isolated from the chloroform: methanol extract of fresh mature leaves of the plant Cestrum diurnum (Solanaceae: Solanales). Change in the haematological parameters was studied in normocholesterolemic albino rats after oral administration of single dose of isolated phytosteroid (2 mg/ day) up to 15 days and compared with control rats. Application of phytosteroid fraction resulted in a significant reduction in total plasma cholesterol and free cholesterol levels. The plasma triglyceride levels also decreased significantly. A sharp increase in the HDL cholesterol level and a significant decrease in the LDL and VLDL amount were also documented. Free fatty acid level was significantly low in treated rats.

Dietary supplementation with L-lysine affects body weight and blood hematological and biochemical parameters in rats.

L-Lysine (Lys) is a popular additive in foods, but the physiological effects of excess Lys supplementation are poorly understood and upper limits of safe intake have not been established. The objectives of this study were to examine the effects of dietary supplementation with increasing amounts of Lys on body weight (BW), food intake, and various blood hematological and biochemical parameters in rats. Male Sprague-Dawley rats at 10 weeks of age were assigned to ten diet groups (eight rats/group) and fed diets containing either 7% or 20% casein and supplemented with either 0% (Control), 1.5%, 3%, 6% Lys, or 6% Lys + 3% arginine for 1 week. Rats fed 7% casein with ≥ 1.5% Lys supplementation had lower serum albumin and leptin and higher LDL cholesterol (LDLC), ratios of total cholesterol (TC):HDL cholesterol (HDLC) and LDLC:HDLC than those fed 7% casein Control diet (P < 0.05). Rats fed 7% casein diet supplemented with 3% Lys diet had lower BW gain, food intake, serum alkaline phosphatase activity, and increased mean corpuscular hemoglobin concentration, blood urea nitrogen and serum pancreatic polypeptide compared to rats fed the Control diet (P < 0.05). Addition of 6% Lys in 7% casein caused significant BW loss (P < 0.001) and altered additional parameters. Addition of 6% Lys in a 20% casein diet reduced BW gain and food intake and altered numerous parameters. Arg supplementation normalized many of the endpoints changed by Lys. Collectively, these results show that Lys supplementation affects BW, food intake and a number of hematological and biochemical parameters. These effects of Lys supplementation were confined primarily in diets with lower levels of dietary protein. In the context of a low protein diet (7% casein), levels of Lys supplementation ≥ 1.5% may exert adverse health effects in rats.

Usefulness of compounds with monacolin K in a case of statins intolerance / Utilidad de los compuestos con monacolina K en un caso de intolerancia a estatinas

Many patients with familial hypercholesterolaemia (FH) or in secondary prevention situations and with statin intolerance do not achieve LDL-C targets, and require treatment with PCSK9 inhibitors (iPCSK9) and ezetimibe. The case is presented on a patient with FH and total intolerance to statins. Treatment with iPCSK9 and ezetimibe failed to achieve her LDL-C target. A compound with red yeast rice derivatives containing 3mg of monacolin K was added, with good therapeutic compliance, and a very good control of LDL-C. The addition of red yeast rice derivatives containing low doses of monacolin K, together with IPCSK9 in patients with total intolerance to statins, may open a new path to obtain LDL-C targets in patients with high/very high cardiovascular risk

Muchos pacientes con hipercolesterolemia familiar (HF) o en situaciones de prevención secundaria con intolerancia a estatinas no logran objetivos a pesar del tratamiento con inhibidores de PCSK9 (iPCSK9) y ezetimiba. Presentamos el caso de un paciente con HF e intolerancia total a las estatinas. El tratamiento con iPCSK9 y ezetimiba no logró el objetivo lipídico. Se añadió un compuesto derivado de la levadura roja del arroz, que contenía 3mg de monacolina K con una excelente tolerancia, lográndose un muy buen control de los objetivos de cLDL. La suma al tratamiento de IPCSK9 de un compuesto derivado de la levadura roja del arroz, con bajas dosis de monacolina K, abre una nueva puerta para lograr los objetivos de cLDL en pacientes de muy alto riesgo cardiovascular

Comparison of efficacy and safety of combination therapy with statins and omega-3 fatty acids versus statin monotherapy in patients with dyslipidemia: A systematic review and meta-analysis.

OBJECTIVE: Dyslipidemia is a major risk factor for the development of cardiovascular disease. Both statins and omega-3 fatty acids demonstrate beneficial effects on lipid concentrations. The goal was to evaluate the safety and efficacy of combination therapy with statins and omega-3 fatty acids. METHODS: We performed a systematic review and meta-analysis of published data to compare the safety and efficacy of combination therapy with statins and omega-3 fatty acids versus statin monotherapy in patients with dyslipidemia. Six articles were assessed in the present meta-analysis (quantitative assessment) and qualitative assessment. RESULTS: In terms of efficacy, the combination treatment afforded a significantly greater reduction in total cholesterol/high-density lipoprotein cholesterol than statin alone did [standard difference in means = -0.215; 95% confidence interval (CI) -0.359--0.071]. However, there was no significant difference in low-density lipoprotein (LDL) cholesterol between the 2 groups. Qualitative assessment of other lipid parameters was performed. Combination therapy with statins and omega-3 fatty acids was generally more effective on lipid concentration than statin monotherapy. In terms of safety, there were no significant differences in total adverse events between the 2 groups. Gastrointestinal adverse events were found to be significantly increased in patients receiving combination therapy using the fixed-effects model (relative risk = 0.547; 95% CI 0.368-0.812). CONCLUSIONS: We suggest that combination therapy with statins and omega-3 fatty acids enhances lipid profile, except LDL cholesterol, compared with statin monotherapy. Nevertheless, statin and omega-3 fatty acid combination should be cautiously recommended, taking into account the clinical importance of LDL cholesterol and safety issues associated with their concomitant use.

Aortic Calcification Progression in Heterozygote Familial Hypercholesterolemia.

BACKGROUND: Patients with homozygous and heterozygous familial hypercholesterolemia (HeFH) develop severe aortic calcifications in an age- and gene dosage-dependent manner. The purpose of this study was to determine the rate of progression of aortic calcification in patients with HeFH. METHODS: We performed thoracoabdominal computed tomography scans and quantified aortic calcium (AoCa) score in 16 HeFH patients, all with the null low-density lipoprotein (LDL) receptor DEL15Kb mutation. Patients (12 men, 4 women) were rescanned an average of 8.2 ± 0.8 years after the first scan. RESULTS: Mean LDL cholesterol (LDL-C) during treatment was 2.53 mmol/L; all patients were receiving high-dose statin/ezetimibe; 5 of 16 were receiving evolocumab. Baseline LDL-C was 7.6 ± 1.3 mmol/L. Aortic calcifications increased in all patients in an exponential fashion with respect to age. Age was the strongest correlate of AoCa score. Cholesterol, LDL-C, or age × cholesterol did not correlate with AoCa score or its progression. Control patients (n = 31; 8 male, 23 female; mean age 61 ± 11 years) who underwent virtual colonoscopy were rescanned over the same period and showed an abdominal AoCa score of 1472 ± 2489 compared with 7916 ± 7060 Agatston U (P < 0.001) in patients with HeFH during treatment (mean age, 60 ± 14 years). The rate of progression was 159 vs 312 Agatston U/y in control participants vs those with HeFH. CONCLUSIONS: HeFH patients exhibit accelerated aortic calcification that increases exponentially with age. LDL-C at baseline or during treatment seems to have little effect on the rate of progression of AoCa score. Strategies to prevent aortic calcifications with statins have not met with clinical success and novel approaches are required; statins might also contribute to the process of arterial calcification.

Abordagem das hipertrigliceridemias graves / Management to severe hypertriglyceridemia

Os níveis de triglicérides plasmáticos são biomarcadores das lipoproteínas ricas em triglicérides circulantes e de seus remanescentes. Formas leves a moderadas de hipertrigliceridemia podem ser secundárias a outras desordens metabólicas, fatores ambientais ou medicamentos, ou ainda poligênicas. Já as formas mais graves são, em geral, monogênicas e resultam de alterações em seis genes. Fatores não genéticos podem exacerbar as hipertrigliceridemias. As hipertrigliceridemias classificam-se quanto à gravidade em leves a moderadas (triglicérides > 200-499 mg/dL) e graves (acima de 500 mg/dL) ou muito graves (> 885 mg/dL, ou > 1000 mg/dL). Quando a hipertrigliceridemia se associa à elevação do LDL-colesterol e/ou à redução do HDL-colesterol, existe risco aumentado de eventos cardiovasculares. No entanto, nas formas graves de hipertrigliceridemia, a pancreatite e as dores abdominais recorrentes são as principais complicações. Estudos prospectivos observacionais, de randomização mendeliana e de intervenção terapêutica mostram não apenas a associação entre marcadores lipídicos e risco de doença cardiovascular, mas podem também evidenciar moléculas que sejam alvos terapêuticos no tratamento de dislipidemias e na redução do risco de eventos cardiovasculares. O tratamento das hipertrigliceridemias tem como objetivos a redução imediata do risco de pancreatite em pacientes com hipertrigliceridemias graves (> 1000 mg/dL) e redução do risco cardiovascular global nas formas leves a moderadas. Dieta restrita em gorduras e carboidratos simples, restrição de álcool, e o uso de fibratos isolados ou associados a ácidos graxos ômega-3 e ácido nicotínico são as principais opções terapêuticas. No entanto, as formas genéticas, que incluem as quilomicronemias familiares, são pouco responsivas à associação de fármacos, havendo necessidade de novas terapias para seu controle

Plasma concentrations of triglycerides are considered biomarkers of circulating triglyceride-rich lipoproteins and their remnants. Mild to moderate hypertriglyceridemia may be secondary to other metabolic disorders, environmental factors, drugs, or polygenic factors. On the other hand, severe forms of hypertriglyceridemia are generally monogenic and the result of six defective genes. Hypertriglyceridemia can be exacerbated by non-genetic factors. It can be classified, according to severity, as mild to moderate (triglycerides >200-499 mg/dL), severe (> 500 mg/dL) or very severe (> 885 mg/dL, or > 1000 mg/dL). When hypertriglyceridemia is associated with LDL-cholesterol elevation and/or a reduction in HDL-cholesterol, there is an increased risk of cardiovascular events. However, in severe forms of hypertriglyceridemia, pancreatitis and recurrent abdominal pain are the main complications. Prospective observational studies, Mendelian randomization studies and intervention studies have not only demonstrated the association between lipid markers and cardiovascular risk, but can also identify molecules as therapeutic targets in the treatment of dyslipidemias and reduction of pancreatitis and cardiovascular risk. Treatment of hypertriglyceridemia has two main objectives: to immediately reduce the risk of pancreatitis in patients with severe hypertriglyceridemia (> 1000 mg/dL), and to reduce global cardiovascular risk in mild to moderate forms. A diet that is low in fat and simple carbohydrates, with alcohol intake, and the use of fibrates, either alone or combined with omega-3 fatty acids, and niacin are the best therapeutic options. However, severe genetic hypertriglyceridemia, including familial chylomicronemia, are less responsive to drug therapy, even in combination, and require new strategies for control of dyslipidemia

Terapêutica hipolipemiante na hipercolesterolemia familiar / Lipid-lowering therapy in familial hypercholesterolemia

A hipercolesterolemia familiar (HF) é doença metabólica muito comum, mas não reconhecida e tratada adequadamente. Sua forma homozigótica, mais rara, leva a aumentos muito importantes do LDL-colesterol e à evolução dramática da aterosclerose e suas complicações em fases muito precoces da vida. Na sua forma mais branda, muito mais comum, a heterozigótica, o aparecimento de manifestações ateroscleróticas costuma ser mais tardio, dependendo da intensidade das alterações do perfil lipídico e dos outros fatores de risco eventualmente presentes. Os recursos terapêuticos para controle da HF vão desde as mudanças do estilo de vida até os medicamentos de uso comum como estatinas potentes em altas doses, na maioria das vezes combinadas à ezetimiba e/ou resina, niacina e fibratos. Novos produtos foram aprovados para uso em outros países, como a lomitapida e o mipomersen, mas apenas para a HF na forma homozigótica. Os inibidores da PCSK9 são importante esperança no controle desses pacientes. As pesquisas com os inibidores da CETP têm sido marcadas por decepções, mas um estudo clínico envolvendo um deles ainda está em andamento. Nosso país não dispõe da LDL-aférese, recurso que se tem mostrado fundamental para a melhora do prognóstico dos portadores das formas graves da HF

Familial hypercholesterolemia (FH) is a common metabolic disease, although not adequately recognized and treated. Its rarer, homozygous form leads to a significant increase in LDL-cholesterol and marked development of atherosclerosis and its complications in very early phases of life. In its milder, much more common, heterozygous form, the appearance of clinical manifestations usually occurs later, depending on the intensity of the changes in lipid profile and the presence of other risk factors. Therapeutic resources for FH control range from changes in lifestyle to medications commonly used as high potency statins in high dosages, in most cases combined with ezetimibe and/or resins, niacin and fibrates. New products have recently been approved for use in other countries such as lomitapide and mipomersen, but only for homozygous FH. PCSK9 inhibitors are an important hope for the control of these patients.Research with CETP inhibitors has failed to demonstrate clinical benefits to date, but a clinical study evaluating one of them is still ongoing. Our country does not have availability of LDL-apheresis, a resource that has proven fundamental for improving the prognosis of patients with more severe forms of FH

[Chemical Constituents of Lowering LDL-C in Effective Part of Oroxylum indicum].

Objective: To investigate the chemical constituents of effective part of Oroxylum indicum which related to lowering LDLC action. Methods: The compounds were isolated with chromatography methods such as silica gel,polyamide and Sephadex LH-20. The structures were identified by physiochemical properties and spectral analysis. Results: 14 compounds were isolated from 95% alcohol extract and elucidated as ß-sitosterol( 1), hexadecanoic acid( 2), oroxin A( 3), oroxin B( 4), chrysin( 5), quercetin( 6),quercetin-3-Orutinoside( 7),5,4'-dihydroxy-3,6,7-trimethoxyflavone( 8), diosmetin( 9), geniposide( 10),isoorientin( 11), quercitroside( 12), apigenin( 13) and gallicacid( 14). Conclusion: Compounds 2,7 ~ 12 and 14 are reported from this plants for the first time.

HDL protein composition alters from proatherogenic into less atherogenic and proinflammatory in rheumatoid arthritis patients responding to rituximab.

OBJECTIVE: An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid profile are limited. Therefore, changes in lipids in RTX treated RA patients were evaluated. METHODS: In 49 consecutive RTX treated RA patients, serum and EDTA plasma samples were collected at baseline, 1, 3 and 6 months. In these samples, lipid and levels were assessed to determine changes in time. Surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) MS analysis was performed in six good and six non-responding RA patients to study functional high density lipoprotein (HDL) protein composition changes in time. RESULTS: In the total group (n=49), the atherogenic index decreased from 4.3 to 3.9 (∼9%) after 6 months. Testing for effect modification revealed a difference in the effect on lipid levels between responders and non-responders upon RTX (p<0.001). ApoB to ApoA-I ratios decreased significantly (∼9%) in good responding (n=32) patients. SELDI-TOF MS analysis revealed a significant decrease in density of mass charge (m/z) marker 11743, representing a decrease in serum amyloid A, in good responding patients. CONCLUSION: This study indicates beneficial effects on cholesterol profile upon RTX treatment along with improvement of disease activity. Proteomic analysis of the HDL particle reveals composition changes from proatherogenic to a less proatherogenic composition during 6 months RTX treatment. Whether these HDL particle alterations during immunotherapies result in a lower CV event rate remains to be established.

Cost-effectiveness of a multicondition collaborative care intervention: a randomized controlled trial.

CONTEXT: Patients with depression and poorly controlled diabetes mellitus, coronary heart disease (CHD), or both have higher medical complication rates and higher health care costs, suggesting that more effective care management of psychiatric and medical disease control might also reduce medical service use and enhance quality of life. OBJECTIVE: To evaluate the cost-effectiveness of a multicondition collaborative treatment program (TEAMcare) compared with usual primary care (UC) in outpatients with depression and poorly controlled diabetes or CHD. DESIGN: Randomized controlled trial of a systematic care management program aimed at improving depression scores and hemoglobin A(1c) (HbA(1c)), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) levels. SETTING: Fourteen primary care clinics of an integrated health care system. PATIENTS: Population-based screening identified 214 adults with depressive disorder and poorly controlled diabetes or CHD. INTERVENTION: Physician-supervised nurses collaborated with primary care physicians to provide treatment of multiple disease risk factors. MAIN OUTCOME MEASURES: Blinded assessments evaluated depressive symptoms, SBP, and HbA(1c) at baseline and at 6, 12, 18, and 24 months. Fasting LDL-C concentration was assessed at baseline and at 12 and 24 months. Health plan accounting records were used to assess medical service costs. Quality-adjusted life-years (QALYs) were assessed using a previously developed regression model based on intervention vs UC differences in HbA(1c), LDL-C, and SBP levels over 24 months. RESULTS: Over 24 months, compared with UC controls, intervention patients had a mean of 114 (95% CI, 79 to 149) additional depression-free days and an estimated 0.335 (95% CI, -0.18 to 0.85) additional QALYs. Intervention patients also had lower mean outpatient health costs of $594 per patient (95% CI, -$3241 to $2053) relative to UC patients. CONCLUSIONS: For adults with depression and poorly controlled diabetes, CHD, or both, a systematic intervention program aimed at improving depression scores and HbA(1c), SBP, and LDL-C levels seemed to be a high-value program that for no or modest additional cost markedly improved QALYs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00468676

Water extracts of cinnamon and clove exhibits potent inhibition of protein glycation and anti-atherosclerotic activity in vitro and in vivo hypolipidemic activity in zebrafish.

Advanced glycation end products contribute to the pathogenesis of diabetic complications and atherosclerosis. Aqueous extracts of ground pepper, cinnamon, rosemary, ginger, and clove were analyzed and tested for anti-atherosclerotic activity in vitro and in vivo using hypercholesterolemic zebrafish. Cinnamon and clove extracts (at final 10 µg/mL) had the strongest anti-glycation and antioxidant activity in this study. Cinnamon and clove had the strongest inhibition of activity against copper-mediated low-density lipoprotein (LDL) oxidation and LDL phagocytosis by macrophages. Cinnamon or clove extracts had potent cholesteryl ester transfer protein (CETP) inhibitory activity in a concentration-dependent manner. They exhibited hypolipidemic activity in a hypercholesterolemic zebrafish model; the clove extract-treated group had a 68% and 80% decrease in serum cholesterol and TG levels, respectively. The clove extract-fed group had the smallest increase in body weight and height and the strongest antioxidant activity following a 5-week high cholesterol diet. Hydrophilic ingredients of cinnamon and clove showed potent activities to suppress the incidence of atherosclerosis and diabetes via strong antioxidant potential, prevention of apoA-I glycation and LDL-phagocytosis, inhibition of CETP, and hypolipidemic activity. These results suggest the potential to develop a new functional dietary agent to treat chronic metabolic diseases, such as hyperlipidemia and diabetes.

Impact of adding a single allele in the 9p21 locus to traditional risk factors on reclassification of coronary heart disease risk and implications for lipid-modifying therapy in the Atherosclerosis Risk in Communities study.

BACKGROUND: A single-nucleotide polymorphism on chromosome 9p21, rs10757274 (9p21 allele), has been shown to predict coronary heart disease (CHD) in whites. We evaluated whether adding the 9p21 allele to traditional risk factors (RFs) improved CHD risk prediction in whites from the Atherosclerosis Risk in Communities study and whether changes in risk prediction would modify lipid therapy recommendations. METHODS AND RESULTS: Whites (n=9998) in the Atherosclerosis Risk in Communities study for whom the 9p21 genotype and traditional RF information was available were included. Using Cox proportional hazards models, the Atherosclerosis Risk in Communities Cardiovascular Risk Score, which is based on traditional RFs, was determined. A total of 1349 individuals (13.5%) developed incident CHD events during a period of 14.6 years. Adding the 9p21 allele to traditional RFs was associated with a hazard ratio of incident CHD of 1.2 per allele (P<0.000003) and a significant increase in the area under the curve of the receiver operating characteristic from 0.782 to 0.786 (95% CI, 0.001, 0.007). The 9p21 allele's greatest influence to the Atherosclerosis Risk in Communities Cardiovascular Risk Score was observed in the intermediate-low (>5% to 10% to 100 mg/dL. CONCLUSIONS: Adding the 9p21 allele to traditional RFs in whites in the Atherosclerosis Risk in Communities study modestly improved CHD risk prediction in the intermediate categories.

Dietary fenugreek seed regresses preestablished cholesterol gallstones in mice.

An animal study was carried out to evaluate the influence of dietary fenugreek seeds on regression of preestablished cholesterol gallstones (CGS). CGS was induced by feeding a high-cholesterol diet for 10 weeks. After CGS induction, the animals were maintained for a further 10 weeks on experimental diets of high cholesterol, 6% fenugreek powder, 12% fenugreek powder, or basal control. Incidence of CGS and its severity were evaluated at the end of this feeding regimen. The incidence of CGS was significantly lowered as a result of dietary fenugreek seeds, the extent of regression being 61% and 64% in the low and high dose groups compared with 10% regression in the basal control group. The antilithogenic influence of dietary fenugreek was accompanied by significant reductions of more than 35% in serum cholesterol concentration. Hepatic cholesterol concentration was also profoundly lowered by dietary fenugreek, being 53%-63% lower than that of the basal control diet. Biliary cholesterol concentration was significantly lower as a result of dietary fenugreek during the post-CGS induction period, resulting in a decreased cholesterol:phospholipid ratio (0.44 and 0.40 compared with 0.79 in the basal control group). Biliary cholesterol : bile acid ratio was lowered by 67% and 73% upon feeding fenugreek, significantly lower than that in the basal control group. The cholesterol saturation index in the bile was also beneficially lowered by fenugreek treatment during the post-CGS induction period (the index was 0.90 and 0.42 compared with 1.86 in the basal control group). The present study provides evidence of the potency of hypolipidemic fenugreek seeds in regressing preestablished CGS, and this beneficial antilithogenic effect is attributable to its primary influence on cholesterol levels. This finding is significant in the context of evolving a dietary strategy to address CGS, which could help in preventing the incidence and regression of existing CGS and controlling possible recurrence.

Anodic porous alumina as mechanical stability enhancer for LDL-cholesterol sensitive electrodes.

In this work, to improve the mechanical stability of electrodes based on P450scc for LDL-cholesterol detection and measure, anodic porous alumina (APA) was used. This inorganic matrix, which pores can be tuned in diameter modifying the synthesis parameters, was realized with cavities 275 nm wide and 160 microm deep (as demonstrated with AFM and SEM measurement), to allow the immobilization of P450scc macromolecules preserving their electronic sensitivity to its native substrate, cholesterol. Even if the sensitivity of the APA+P450scc system was slightly reduced with respect to the pure P450scc system, the readout was stable for a much longer period of time, and the measures remained reproducible inside a proper confidentiality band, as demonstrated with several cyclic voltammetry measures. To optimize the adhesion of P450scc to APA, a layer of poly-L-lysine, a poly-cathion, was successfully implemented as intermediate organic structure.

Safety and efficacy of Atorvastatin-induced very low-density lipoprotein cholesterol levels in Patients with coronary heart disease (a post hoc analysis of the treating to new targets [TNT] study).

High-dose statin therapy has been demonstrated to provide incremental benefit when low-density lipoprotein (LDL) cholesterol concentrations are lowered well below recommended target levels. This secondary analysis of the Treating to New Targets (TNT) study was conducted to investigate whether the attainment of very low LDL cholesterol levels was associated with a further reduction in major cardiovascular events compared with higher LDL cholesterol concentrations and whether any incremental benefit was achieved without additional safety risk. Patients with coronary heart disease and LDL cholesterol levels <130 mg/dl (3.4 mmol/L) were randomized to therapy with atorvastatin 10 mg/day (n = 5,006) or 80 mg/day (n = 4,995). The primary end point was the occurrence of a first major cardiovascular event. Clinical outcomes and safety data were compared across on-treatment LDL cholesterol quintiles. There was a highly significant reduction in the rate of major cardiovascular events with descending achieved levels of on-treatment LDL cholesterol (p <0.0001 for trend across LDL cholesterol). Analysis of individual components of the primary end point demonstrated similar results. Death from any cause and from noncardiovascular causes was lowest in patients with the lowest on-treatment LDL cholesterol levels. Cardiovascular deaths were also reduced with lower levels of on-treatment LDL cholesterol. There were no clinically important differences in adverse event rates across quintiles. Specifically, no increase in muscle complaints, suicide, hemorrhagic stroke, or cancer deaths was observed at the lowest LDL cholesterol levels. In conclusion, the present analysis adds support to the concept that for patients with established atherosclerotic cardiovascular disease, a further risk reduction without sacrifice of safety can be achieved by reducing LDL cholesterol to very low levels.

Effect of red mold rice supplements on serum and meat cholesterol levels of broilers chicken.

Monacolin K is a secondary metabolite produced by Monascus species. It was found that it is able to decrease cholesterol levels. In this study, red mold rice (RMR) was added to the diet of Arbor Acres broiler chickens, and the cholesterol level in meat, as well as the concentration of triglyceride, the high-density lipoprotein cholesterol (HDL-C), and the low-density lipoprotein cholesterol (LDL-C) in the serum were evaluated. Four-week-old broilers are studied and divided into four groups in that each group contains 15 subjects. A 3-week experimental feeding trial was conducted in which three groups of broilers were fed 2.0, 5.0, and 8.0% of RMR (RMR groups) within their diet, respectively, and the result was compared to the control group. The results indicated that for each RMR group, the cholesterol content was significantly lower than that of the control group; in addition, their meat products contain higher level of unsaturated fatty acids. Triglyceride and cholesterol concentration in serum was also found to be considerably lower in RMR groups when compared to control group. Finally, in RMR groups, HDL-C/LDL-C and HDL-C/cholesterol ratios were all higher than those of the control group. In short, the results demonstrated that the cholesterol levels could be lowered by adding RMR to the diet of chickens.

Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa rats.

Hepatic steatosis is commonly present during the development of insulin resistance, and it is a clear sign of lipotoxicity attributable in part to an accelerated lipogenesis. There is evidence that a soy protein diet prevents the overexpression of hepatic sterol-regulatory element binding protein-1 (SREBP-1), decreasing lipid accumulation. Therefore, the aim of the present work was to study whether a soy protein diet may prevent the development of fatty liver through the regulation of transcription factors involved in lipid metabolism in hyperinsulinemic and hyperleptinemic Zucker obese fa/fa rats. Serum and hepatic cholesterol and triglyceride levels, as well as VLDL-triglyceride and LDL-cholesterol, were significantly lower in rats fed soy protein than in rats fed a casein diet for 160 days. The reduction in hepatic cholesterol was associated with a low expression of liver X receptor-alpha and its target genes, 7-alpha hydroxylase and ABCA1. Soy protein also decreased the expression of SREBP-1 and several of its target genes, FAS, stearoyl-CoA desaturase-1, and delta5 and delta6 desaturases, decreasing lipogenesis even in the presence of hyperinsulinemia. Reduction in SREBP-1 was not associated with the presence of soy isoflavones. Finally, soy protein reduced SREBP-1 expression in adipocytes, preventing hypertrophy, which also helps prevent the development of hepatic lipotoxicity.