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The combination of an anticoagulant and a hypolipidemic agent is commonly used in patients at risk for stroke because it controls thrombosis and lowers cholesterol levels. However, the use of anticoagulants carries a high risk of life-threatening bleeding. To address the need for personalized clinical monitoring and risk management, we developed a rapid and sensitive HPLC method with a streamlined sample preparation process. This method enables the simultaneous determination of concentrations for two commonly used anticoagulant drugs (apixaban and rivaroxaban) and three hypolipidemic drugs (rosuvastatin, atorvastatin calcium, and simvastatin). The chromatographic conditions and sample preparation methods were optimized. The drugs were well separated by the gradient elution of phosphoric acid (0.01%, v/v) and acetonitrile at a flow rate of 1.0 mL/min within 40 min on an Athena C18-WP column (4.6 × 150 mm, 5-μm particle size). The proposed method was linear (r2 ≥ 0.994) within the concentration ranges of 0.22–20 μg·mL−1 for the five analytes, including the expected range of therapeutic concentrations. This method enables simultaneous monitoring of the levels of the mentioned drugs in clinical practice. Furthermore, the chromatographic conditions were simple and feasible, making them highly suitable for emergency clinical medication monitoring in basic medical institutions. [ABSTRACT FROM AUTHOR]

Background: Remnant cholesterol (RC) is an emerging factor contributing to residual risk for the development of atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of RC with ASCVD in high ASCVD risk patients. Methods: RC was calculated in 906 participants (178 low/moderate-risk and 728 high-risk) consecutively recruited from a vascular registry. Subclinical carotid atherosclerosis was assessed by B-mode carotid ultrasonography. Maximal carotid wall thickness (maxWT) and carotid atherosclerotic burden (n ≥ 2 atherosclerotic plaques) were set as the vascular outcomes. An independent cohort of 87 consecutively recruited high-risk patients who were followed for their lipid profile for 3 months was also analyzed. Results: RC was increased in the high-risk group as compared to controls (26 ± 17 vs. 21 ± 11 mg/dl, respectively, p

The aim of the study is to study the regional hypolipidemic drugs market, external and internal factors affecting their level of consumption, including the information awareness of the final customers about this pharmacotherapeutic group and the adherence to treatment with these drugs.Materials and methods. The study was carried out using the methods of SWOT and STEP-analyses to assess the factors affecting the consumption of the studied group of drugs, as well as the questionnaire method of final customers and assessing their compliance using the Morisky-Green questionnaire.Results. The influence of environmental and internal factors on the level and structure of the consumption of hypolipidemic drugs has been studied, hereby, the problems of the group and ways to solve them have been outlined, and an increase or decrease in the need for hypolipidemic drugs at the regional level, have been predicted. The assessment of the information awareness and preferences of the final customers of hypolipidemic drugs has been carried out, and insufficient awareness of patients about the drugs under study, has been revealed. The compliance of the final customers has been studied. A low level of the compliance of the patients to the prescribed hypolipidemic therapy has been established.Conclusion. Modern advances in the treatment of cardiovascular diseases, based on fundamental achievements of science and practice, have created a high evidence base for the choice of strategies for pharmacotherapy with hypolipidemic drugs. The main ways to increase information awareness and compliance of the final customers are: development and intensification of educational programs to increase the level of knowledge and information awareness of doctors and pharmaceutical professionals, establishing the Doctor-Patient partnering relationships, increasing the trust level to the doctor and, as a result, the level of the patient compliance уровень; the development of materials for increasing the information awareness among the final customers about hypolipidemic drugs and hypolipidemic therapy in general.

Aim. To study structure of medical purposes of anti-anginal, antiplatelet and hypolipidemic means at coronary heart disease patients in ambulatory practice of Kursk (Russian Federation) and Chisinau (Republic of Moldova). Materials and methods. During the period from October, 2017 to January, 2018 as a one-stage descriptive research, questioning of doctors of the medical organizations of Kursk and Chisinau was carried out. Questionnaires included questions on pharmacoepidemiological aspects of purpose of antianginal, antiplatelet and hypolipidemic means. Total number of respondents was 132, of them 66 (2 cardiologists and 64 therapists) - in Kursk and 66 (10 cardiologists and 56 therapists) - in Chisinau. Results. Doctors of Kursk and Chisinau have no statistically significant differences in structure of appointments of the main groups of anti-anginal means, antiplatelet and hypolipidemic drugs. The tendency to more frequent use of blockers of calcium channels and nitrovazodilatator among doctors of Chisinau while in structure of appointments of doctors of Kursk some prevalence of a trimetazidin, antiagregants and statines was noted was noted (p>0.05). Leaders in group of beta blockers were bisoprolol and metoprolol in the conditions of the pharmaceutical market of Kursk and Chisinau. Priority of the choice of blockers of calcium channels authentically differed in the considered regions only on a felodipin - in Kursk appointed it to a thicket (p

After training as a gastroenterologist in the UK, the author became interested in lipidology while he was a research fellow in the USA and switched careers after returning home. Together with Nick Myant, he introduced the use of plasma exchange to treat familial hypercholesterolemia (FH) homozygotes and undertook non-steady state studies of LDL kinetics, which showed that the fractional catabolic rate of LDL remained constant irrespective of pool size. Subsequent steady-state turnover studies showed that FH homozygotes had an almost complete lack of receptor-mediated LDL catabolism, providing in vivo confirmation of the Nobel Prize-winning discovery by Goldstein and Brown that LDL receptor dysfunction was the cause of FH. Further investigation of metabolic defects in FH revealed that a significant proportion of LDL in homozygotes and heterozygotes was produced directly via a VLDL-independent pathway. Management of heterozygous FH has been greatly facilitated by statins and proprotein convertase subtilisin/kexin type 9 inhibitors but remains dependent upon lipoprotein apheresis in homozygotes. In a recent analysis of a large cohort treated with a combination of lipid-lowering measures, survival was markedly enhanced in homozygotes in the lowest quartile of on-treatment serum cholesterol. Emerging therapies could further improve the prognosis of homozygous FH; whereas in heterozygotes, the current need is better detection.

Obesity and its associated metabolic dysfunction and cardiovascular disease risk represent a leading cause of adult morbidity worldwide. Currently available pharmacological therapies for obesity have had limited success in reversing existing obesity and metabolic dysregulation. Previous prevention studies demonstrated that the citrus flavonoids, naringenin and nobiletin, protect against obesity and metabolic dysfunction in Ldlr−/− mice fed a high-fat cholesterol-containing (HFHC) diet. However, their effects in an intervention model are unknown. In this report, we show that, in Ldlr−/− mice with diet-induced obesity, citrus flavonoid supplementation to a HFHC diet reversed existing obesity and adipocyte size and number through enhanced energy expenditure and increased hepatic fatty acid oxidation. Caloric intake was unaffected and no evidence of white adipose tissue browning was observed. Reversal of adiposity was accompanied by improvements in hyperlipidemia, insulin sensitivity, hepatic steatosis, and a modest reduction in blood monocytes. Together, this resulted in atherosclerotic lesions that were unchanged in size, but characterized by reduced macrophage content, consistent with a more stable plaque phenotype. These studies further suggest potential therapeutic utility of citrus flavonoids, especially in the context of existing obesity, metabolic dysfunction, and cardiovascular disease.

Objectives: Aiming to reduce the occurrence of cardiovascular disease (CVD), Taiwan’s National Health Insurance (NHI) Administration expanded coverage for hypolipidemic drugs for high-risk patients, including patients with a history of CVD or diabetes in 2013. This study intended to evaluate the impact of this policy. Methods: Patients with diabetes but without a history of CVD (118,912 subjects) were selected as the study group, and patients with hypertension but without a history of CVD or diabetes (150,930 subjects) were the comparison group. Using August 1, 2013, as the cut-off point we defined 3 years each in the pre- and postpolicy periods. Generalized estimation equation (GEE) models with a difference-in-differences analysis were used to estimate the effects of the new policy in 2010 and 2016. Outcome variables included the likelihood of receiving hypolipidemic drugs, occurrence of CVD (acute myocardial infarction and ischemic stroke), and expenses for drugs and CVD. Results: After introduction of the policy, subjects in the study group were more likely to receive hypolipidemic drugs (OR=1.095, p<0.001), and less likely to have CVD (OR=0.914, p=0.0046) than subjects in the comparison group. The subjects in the study group also had lower expenses for hypolipidemic drugs (β=-0.016, p=0.0019), but the lower expenses for CVD did not reach the significance level (β=-0.087, p=0.1504). Conclusions: The expanded coverage for hypolipidemic drugs significantly increased the use of medications for high-risk patients, and reduced the occurrence of CVD in Taiwan. Long-tern evaluation of this medication policy is recommended. [ABSTRACT FROM AUTHOR]

Familial dysbetalipoproteinemia (FD) is a genetic disorder associated with impaired postprandial lipid clearance. The effect of adding bezafibrate to standard lipid-lowering therapy on postprandial and fasting lipid levels in patients with FD is unknown. In this randomized placebo-controlled double-blind crossover trial, 15 patients with FD received bezafibrate and placebo for 6 weeks in randomized order in addition to standard lipid-lowering therapy (statin, ezetimibe, and/or lifestyle). We assessed post-fat load lipids, expressed as incremental area under the curve (iAUC) and area under the curve (AUC), as well as fasting levels and safety, and found that adding bezafibrate did not reduce post-fat load non-HDL-cholesterol (non-HDL-C) iAUC (1.78 ± 4.49 mmol·h/l vs. 1.03 ± 2.13 mmol·h/l, P = 0.57), but did reduce post-fat load triglyceride (TG) iAUC (8.05 ± 3.32 mmol·h/l vs. 10.61 ± 5.92 mmol·h/l, P = 0.03) and apoB (0.64 ± 0.62 g·h/l vs. 0.93 ± 0.71 g·h/l, P = 0.01). Furthermore, bezafibrate significantly improved AUC and fasting levels of non-HDL-C, TG, total cholesterol, HDL-C, and apoB. Bezafibrate was associated with lower estimated glomerular filtration rate (78.4 ± 11.4 ml/min/1.73 m2 vs. 86.1 ± 5.85 ml/min/1.73 m2, P = 0.002). In conclusion, in patients with FD, the addition of bezafibrate to standard lipid-lowering therapy resulted in improved post-fat load and fasting plasma lipids. Combination therapy of statin/fibrate could be considered as standard lipid-lowering treatment in FD.

Though cardioprotective, niacin monotherapy is limited by unpleasant cutaneous symptoms mimicking dermatitis: niacin-associated skin toxicity (NASTy). Niacin is prototypical of several emerging drugs suffering off-target rubefacient properties whereby agonizing the GPR109A receptor on cutaneous immune cells provokes vasodilation, prompting skin plethora and rubor, as well as dolor, tumor, and calor, and systemically, heat loss, frigor, chills, and rigors. Typically, NASTy effects are described by subjective patient-reported perception, at best semi-quantitative and bias-prone. Conversely, objective, quantitative, and unbiased methods measuring NASTy stigmata would facilitate research to abolish them, motivating development of several objective methods. In early drug development, such methods might better predict clinical tolerability in larger clinical trials. Measuring cutaneous stigmata may also aid investigations of vasospastic, ischemic, and inflammatory skin conditions. We present methods to measure NASTy physical stigmata to facilitate research into novel niacin mimetics/analogs, detailing characteristics of each technique following niacin, and how NASTy stigmata relate to symptom perception. We gave niacin orally and measured rubor by colorimetry and white-light spectroscopy, plethora by laser Doppler flowmetry, and calor/frigor by thermometry. Surprisingly, each stigma's abruptness predicted symptom perception, whereas peak intensity did not. These methods are adaptable to study other rubefacient drugs or dermatologic and vascular disorders.

This article is devoted to contemporary approaches on statins and non-statin lipid-lowering drugs using according to authoritative Recommendations 2015-2016. Both approaches for cardiovascular risk levels estimation with life-style changes intervention, target level of lipid profile’s parameters and characteristics of statins and non-statin hypolipidemic drugs using for dyslipidemia control in different patient’s categories including children, women, oldest, patients with diabetes mellitus, chronic kidney disease, acute coronary syndrome and post- invasive intracoronary procedures, atherosclerosis-associated peripheral arteries disease are presented. The system literature search is performed on Scopus databases, Web of Science, MedLine, elibrary, RISC and other.

Background and objective The hypolipidemic statins have been associated with various side effects, and in some cases, adverse reactions in humans and experimental animals, such as myotoxicity, neurobehavioral toxicity, as well as liver and kidney injuries. The purpose of the present study was to examine the possibility of the induction of oxidative stress in the brain and plasma of mice dosed with single or repetitive doses of three statins (atorvastatin, simvastatin, and rosuvastatin). Methods Male Swiss-origin mice were dosed orally with single doses of each of the three statins at 500 or 1000 mg/kg of body weight. Other groups of mice were dosed orally with repeated daily doses of each of the statins at 200 mg/kg of body weight/day for 14 or 28 consecutive days. These doses of statins were chosen to not produce overt toxicity in mice within the time frame allocated for each experiment. Brain and plasma glutathione (GSH) and malondialdehyde (MDA) levels, as well as liver enzymes activities alanine transaminase (ALT) and aspartate transaminase (AST), were determined using commercial kits. Results Single-dose treatments of the mice with the statins at either 500 or 1000 mg/kg significantly and dose-dependently (p < 0.05) reduced the GSH level in the plasma and the whole brain when compared with respective control values. Atorvastatin was the least effective statin, as only the high dose achieved a significant reduction in brain GSH level in comparison with the respective control value. Repetitive administration of the three statins at 200 mg/kg of body weight/day for 14 or 28 consecutive days significantly and time-dependently reduced plasma and brain GSH levels in comparison with respective control values. The oxidative stress biomarker MDA level significantly increased in the plasma and brain of mice following single or repetitive treatments with the three statins, and the most effective one was rosuvastatin. In association with these changes, activities of the liver enzymes ALT and AST were also increased in the plasma with single and repetitive statin treatments, and the most effective one was rosuvastatin. Conclusion The data suggest an association of high doses of three statins (atorvastatin, simvastatin, and rosuvastatin) with the induction of oxidative stress manifested as GSH reduction and MDA elevation as adverse effects in the brain and plasma of mice, which suffered from the additional burden of liver injury. These effects could be the basis of an in-depth exploration of statin adverse effects in experimental animals and to find an animal model, probably the mice, for the induction of adverse effects of statins that target the brain, as well as to shed light on potential statin intolerance outcomes following single-dose treatments in this species., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Al-Shalchi et al.)

The article discusses prescribing pattern and rational use of hypolipidemic drugs to help physicians in controlling adverse drug reactions. It talks about observational study conducted in Jammu hospital where prescriptions of patients with atleast one hypolipidemic drug and prescription indicators were analysed. Results of the study are stated which include use of statins as a preventive measure for various diseases.

OBJECTIVE: To investigate the application status and the tendency of hypolipidemic drugs in Changshu Hospital Affiliated to Soochow University ( hereinafter referred to as “the hospital” ) during 2013-2015. METHODS： Statistical analysis was conducted on application data of hypolipidemic drugs in terms of consumption sum， defined daily dose system (DDDs) and defined daily cost (DDC)， etc. The synchronous correlation in application of the hypolipidemic drugs was evaluated by using the ratio of serial numbers. RESULTS： During 2013-2015， the consumption sum of the hypolipidemic drugs were respectively 1. 870 3 million yuan， 2. 894 4 million yuan and 3. 991 1 million yuan，and increased by 54. 75% and 37. 89% in 2014 and 2015 respectively. The consumption sum of western medicine were respectively 286. 433 4 million yuan，312. 4022 million yuan and 332. 937 5 million yuan， the ratio of consumption sum of hypolipidemic drugs versus the total consumption sum of western medicine were respectively 0. 65 % ，0. 93% and 1. 20%. The proportion of the consumption sum and DDDs of statin-related drugs in hypolipidemic drugs were in an increasing tendency year by year. The consumption sum and DDDs of rosuvastatin took the lead，and also in an increasing tendency with good synchronicity. CONCLUSIONS： Statins is the first choice of clinical drug application. The application of hypolipidemic drugs used in the hospital is basically rational and in line with the development trend of hypolipidemic drugs. [ABSTRACT FROM AUTHOR]

Background: Fibrates are widely used hypolipidemic drugs, which serve as ligand of peroxisome proliferatoractivated receptor α (PPARα). Recently, they have also been considered as potential anticancer agents. We studied effect of fibrates treatment on cell proliferation, expression of CYP2J2 and concomitant changes in expression of cell cycle regulatory proteins in three different human cell lines: HEK293, HepG2, and HT-29. Methods: We used WST-1 viability test, western blot and immunocytochemistry for detection of proteins of interests and analysis of cell cycle. Results: Our results showed that at lower concentrations of all tested fibrates, viability of all tested cell lines is increased, whereas at higher concentrations, repression is apparent. Unfortunately, the viability of tested cells is predominantly increased in a range of concentration which is reached in patient plasma. This phenomenon is accompanyed by elevation of CYP2J2, increased number of cyclin E-positive cells and decreased number of Cdc25Apositive cells in all tested cell lines, and elevated cyclin A expression in HepG2 and HT-29. These changes are concentration-dependent. We suppose that increased level of CYP2J2 could explain enhanced cell proliferation in lower concentration of fibrates. Conclusion: Based on our results, we suggested there is no anti-cancer effect of fibrates in tested carcinoma cell lines. [ABSTRACT FROM AUTHOR]

Microsomal triglyceride transfer protein (MTP) catalyzes the assembly of triglyceride (TG)-rich apolipoprotein B-containing liver (e.g., VLDL) and intestinal (e.g., chylomicron) lipoproteins. The human MTP gene promoter is reported here to associate in vivo with endogenous hepatocyte nuclear factor-4α (HNF-4α) and to be transactivated or transsuppressed by overexpressed or by dominant negative HNF-4α, respectively. Human MTP (hMTP) transactivation by HNF-4α is accounted for by the concerted activity of distal (−83/−70) and proximal (−50/−38) direct repeat 1 elements of the hMTP promoter that bind HNF-4α. Transactivation by HNF-4α is specifically antagonized by chicken ovalbumin upstream promoter. Transcriptional activation of hMTP by HNF-4α is mediated by HNF-4α domains engaged in ligand binding and ligand-driven transactivation and is further complemented by HNF-4α/HNF-1α synergism that involves the HNF-4α activation function 1 (AF-1) domain. hMTP transactivation by HNF-4α is specifically inhibited by β,β-tetramethyl-hexadecanedioic acid acting as an HNF-4α antagonist ligand.hMTP transactivation by HNF-4α may account for the activation or inhibition of MTP expression and the production of TG-rich lipoproteins by agonist (e.g., saturated fatty acids) or antagonist [e.g., (n-3) PUFA, hypolipidemic fibrates, or Methyl-substituted dicarboxylic acid (Medica) compounds] HNF-4α ligands.

The profile of liver acyl-CoAs induced by dietary fats of variable compositions or by xenobiotic hypolipidemic amphipathic carboxylates was evaluated in vivo using a novel electrospray ionization tandem mass spectrometry methodology of high resolution, sensitivity, and reliability. The composition of liver fatty acyl-CoAs was found to reflect the composition of dietary fat. Treatment with hypolipidemic carboxylates resulted in liver dominant abundance of their respective acyl-CoAs accompanied by an increase in liver fatty acyl-CoAs.Cellular effects exerted by dietary fatty acids and/or xenobiotic carboxylic drugs may be transduced in vivo by their respective acyl-CoAs.

Fibrates are widely used hypolipidemic drugs that regulate the expression of many genes involved in lipid metabolism by activating the peroxisome proliferator-activated receptor α (PPARα). The objective of this study was to investigate the mechanism of action of peroxisome proliferators and PPARα on the transcription of cholesterol 7α-hydroxylase, the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. When cotransfected with the expression vectors for PPARα and RXRα, Wy14,643 reduced human and rat cholesterol 7α-hydroxylase gene (CYP7A1)/luciferase reporter activities by 88% and 43%, respectively, in HepG2 cells, but not in CV-1 or CHO cells. We have mapped the peroxisome proliferator response element (PPRE) to a conserved sequence containing the canonical AGGTCA direct repeats separated by one nucleotide (DR1). This DR1 sequence was mapped previously as a binding site for the hepatocyte nuclear factor 4 (HNF-4) which stimulates CYP7A1 transcription. Electrophoretic mobility shift assay (EMSA) showed no direct binding of in vitro synthesized PPARα/RXRα heterodimer to the DR1 sequence. PPARα and Wy14,643 did not affect HNF-4 binding to the DR1. However, Wy14,643 and PPARα/RXRα significantly reduced HNF-4 expression in HepG2 cells. These results suggest that PPARα and agonist repress cholesterol 7α-hydroxylase activity by reducing the availability of HNF-4 for binding to the DR-1 sequence and therefore attenuates the transactivation of CYP7A1 by HNF-4.—Marrapodi, M., and J. Y. L. Chiang. Peroxisome proliferator-activated receptor α (PPARα) and agonist inhibit cholesterol 7α-hydroxylase gene (CYP7A1) transcription. J. Lipid Res. 2000. 41: 514–520.

Although pleiotropy, which is defined as multiple effects derived from a single gene, was recognized many years ago, and considerable progress has since been achieved in this field, it is not very clear how much this feature of a drug is clinically relevant. During the last decade, beneficial pleiotropic effects from hypolipidemic drugs (as in, effects that are different from the primary ones) have been associated with reduction of cardiovascular risk. As with statins, the agonists of peroxisome proliferator-activated receptors (PPARs), niacin and fibrates, have been suggested to exhibit pleiotropic activity that could significantly modify the outcome of a cardiovascular ailment. This review examines findings demonstrating the impacts of treatment with hypolipidemic drugs on cardiac response to ischemia in a setting of acute ischemia--reperfusion, in relation to PPAR activation. Specifically, it addresses the issue of susceptibility to ischemia, with particular regard to the preconditioning-like cardioprotection conferred by hypolipidemic drugs, as well as the potential molecular mechanisms behind this cardioprotection. Finally, the involvement of PPAR activation in the mechanisms of non-metabolic cardioprotective effects from hypolipidemic drugs, and their effects on normal and pathologically altered myocardium (in the hearts of hypertensive rats) is also discussed. [ABSTRACT FROM AUTHOR]

Introduction Hyperlipidemia is the most common form of dyslipidemia, which is the key risk factor for cardiovascular disease and stroke. The development of effective and safe drug treatments for hyperlipidemia has been proven challenging. Methods In this study, taking advantage of the transparency of larval zebrafish, we developed a zebrafish hyperlipidemia model for drug screening and efficacy assessment. Zebrafish at 5 d.p.f (days post fertilization) were fed with 0.1% egg yolk for 48 h (hours), followed by drug treatment for 24 h or 48 h. Tested drugs were administered into the zebrafish by direct soaking. Drug effect was evaluated based on quantitative analysis of Oil Red O (ORO) in zebrafish vena caudalis. Results All 5 human hypolipidemic drugs (simvastatin, lovastatin, ezetimibe, bezafibrate and hyodesoxycholic acid) showed significant hypolipidemic effects ( p < 0.01) in a dose-dependent manner in the zebrafish hyperlipidemia model. 'We also found a well-known Chinese tea Pu-erh tea significantly reduced lipids in this model ( p < 0.001 and p < 0.01). Discussion Our results demonstrate that the zebrafish hyperlipidemia model developed and validated in this study could be used for in vivo hyperlipidemia studies and drug screening and for assessing hypolipidemic drugs with different mechanisms. [ABSTRACT FROM AUTHOR]

Hyperlipidemia is a major cause of cardiovascular disease despite the availability of first-line cholesterol lowering agents such as statins. Although statin therapy is very efficient to reduce cholesterol, nearly 10-20% of individuals on statins, experience side effects, such myopathy, which hinder the drugs ability to achieve target low-density lipoprotein (LDL) cholesterol (LDL-C) levels. Statin-intolerant patients require more effective therapies for lowering LDL-C. As proprotein convertase subtilisin kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLR) and prevents it from recycling to the membrane, a new therapeutic approach to lowering LDL-C acts by blocking LDL-receptor degradation by serum PCSK9. Humanized monoclonal antibodies which target PCSK9 and its interaction with the LDL receptor (REGN727/SAR23653, AMG145, and RN316), as well as agents that inhibit PCSK9 synthesis, such as ALN-PCS, are now in clinical trials. The latter is a small interfering RNA (siRNA) that directs sequence-specific messenger RNA for PCSK9 leading to reduced hepatocyte-specific synthesis of PCSK9. Ongoing phase III trials' results are awaited with great interest in order to define these agents' long-term safety, tolerability and efficacy for reducing cardiovascular events. [ABSTRACT FROM AUTHOR]

Stroke is the second most common cause of mortality worldwide and the third most common cause of disability. Arterial hypertension is the most prevalent risk factor for stroke. A precise management of arterial hypertension prevents the first episode of stroke and the recurrence. Blood pressure must be decreased carefully and not very vigorously in the acute phase of the stroke. Recommended blood pressure goals in chronic tratment are at least 140 / 90 mm Hg and lower if tolerated. ACE inhibitors or angiotensin receptor blockers in combination with calcium channel blockers or indapamide are favorable antihypertensive drugs. Dyslipidemia is also a strong risk factor for ischaemic stroke and has no relatioship to the other etiologies of stroke. The cardiovascular risk in patients after a stroke is very high. An intensive hypolipidemic treatment by statins, ezetimibe and PCSK9i to LDL-cholesterol goals &lt; 1,4 mmol/l and a 50% decrease was proved to decrease the incidence of recurrent stroke.

Background: Liver is the main organ for metabolism of drugs and hepatotoxicity is a potential adverse effect for most drugs.Aims: This study was to study the frequency of drug-induced hepatotoxicity and to find the common drugs causing hepatotoxicity. Materials and Methods: The study was conducted at a tertiary care hospital in rural India. It is a study based on case series analysis. All patients with an abnormal liver function report, between July 2006 and July 2007, were included in the study. Results: The study included 411 patients. Among them 141 patients were females and 270 males. The common cause for abnormal liver function was alcoholic liver disease (30.4%) followed by drug-induced hepatotoxicity (15.8%) and malaria (15.3%). Drug-induced hepatotoxicity was seen in 65 patients. It was common in males (55%) compared to females (44%). The mean age of the patients with drug-induced hepatotoxicity was 43±15.9. Antitubercular drugs were the commonly encountered drugs (44%) causing hepatotoxicity followed by lipid lowering agents (41%). The others drugs included antiretroviral drugs (6%),steroids (5%) and chlorpromazine (2%). Conclusion: A thorough history of drug intake must be taken in all patients presenting with abnormal hepatic function. [ABSTRACT FROM AUTHOR]

Almost two thirds of major coronary events take place in subjects over 65 years of age. Old (65-75 years), very old (75-85 years), and oldest old (85+ years) individuals should be considered separately when addressing cardiovascular (CV) risk. Several observational investigations have shown that the relationship between plasma cholesterol and CV events is less stringent with advancing age, especially in the very old and oldest old subject. In this context, both a decrease in total cholesterol and low HDL-C levels may be linked to coronary morbidity and total mortality through an independent association with disability and frailty. On the other hand, although elevated plasma LDL-C might still represent a CV risk factor in older people, the potential benefits originating from its reduction may exceed those obtained in younger ages, given the higher prevalence of CV disease in late life. At present statins, which represent the most effective hypocholesterolemic drugs, have been shown to signiicantly reduce CV events up to 82 years of age in randomized controlled trials and epidemiological surveys. The occurrence of multiple chronic conditions (comorbidity), decreased life expectancy and polypharmacotherapy suggest the need for a careful assessment of indications for aggressive hypolipidemic treatment. Drug interactions and low-pharmacological adherence may concur, causing a failure of preventive measure or side effects. Specific guidelines do not always recommend special caution or prudence in the elderly, but the selection of older patients for hypolipidemic treatment requires a high grade of clinical judgment. [ABSTRACT FROM AUTHOR]

Abstract: Statins and fibrates can cause myopathy. To further understand the causes of the damage we performed a proteome analysis in fast-twitch skeletal muscle of rats chronically treated with different hypolipidemic drugs. The proteomic maps were obtained from extensor digitorum longus (EDL) muscles of rats treated for 2-months with 10mg/kg atorvastatin, 20mg/kg fluvastatin, 60mg/kg fenofibrate and control rats. The proteins differentially expressed were identified by mass spectrometry and further analyzed by immunoblot analysis. We found a significant modification in 40 out of 417 total spots analyzed in atorvastatin treated rats, 15 out of 436 total spots in fluvastatin treated rats and 21 out of 439 total spots in fenofibrate treated rats in comparison to controls. All treatments induced a general tendency to a down-regulation of protein expression; in particular, atorvastatin affected the protein pattern more extensively with respect to the other treatments. Energy production systems, both oxidative and glycolytic enzymes and creatine kinase, were down-regulated following atorvastatin administration, whereas fenofibrate determined mostly alterations in glycolytic enzymes and creatine kinase, oxidative enzymes being relatively spared. Additionally, all treatments resulted in some modifications of proteins involved in cellular defenses against oxidative stress, such as heat shock proteins, and of myofibrillar proteins. These results were confirmed by immunoblot analysis. In conclusions, the proteomic analysis showed that either statin or fibrate administration can modify the expression of proteins essential for skeletal muscle function suggesting potential mechanisms for statin myopathy. [Copyright &y& Elsevier]

Abstract: This review focuses on the non-statin strategies for the treatment of hyperlipidemias in humans. Even if statins remain the major hypolipidemic drugs at present, an increasing number of patients that are treated with statins raises as well the numbers of patients suffering from side effects or not responding well to the therapy. Thus, development of novel approaches to battle the world epidemics of hyperlipidemia remains relevant. The non-statin strategies include the decrease of cholesterol absorption from the diet, lowering the atherogenic lipoprotein release and increasing HDL levels, or increasing elimination of cholesterol by bile acid binding. Representative non-statin drugs that are on the market or are in development phases are described herein in comparison to statins. In addition to 3β-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), as the major regulatory enzyme of cholesterol synthesis that is the target of statins, some other enzymes of this multi-step pathway represent perspective targets for the development of novel hypolipidemics. None of these inhibitors are currently approved for use in humans. We describe the characteristics of the later enzymes of cholesterol synthesis, starting from the squalene synthase step. Inhibitors of these enzymes are critically evaluated, particularly concerning safety in humans (teratogenic potential, toxicity, and other side effects) and their hypolipidemic effects compared to the statins. Since only a limited number of publications discuss the non-statin approaches for the treatment of hyperlipidemias, this review represents a valuable up-to date summary, with a take-home message, that novel approaches deserve more attention in the future, irrespective of the success of statins. [Copyright &y& Elsevier]

Background and Purpose: Statins and fibrates can produce mild to life-threatening skeletal muscle damage. Resting chloride channel conductance (gCl), carried by the ClC-1 channel, is reduced in muscles of rats chronically treated with fluvastatin, atorvastatin or fenofibrate, along with increased resting cytosolic calcium in statin-treated rats. A high gCl, controlled by the Ca(2+)-dependent protein kinase C (PKC), maintains sarcolemma electrical stability and its reduction alters muscle function. Here, we investigated how statins and fenofibrate impaired gCl.Experimental Approach: In rats treated with fluvastatin, atorvastatin or fenofibrate, we examined the involvement of PKC in gCl reduction by the two intracellular microelectrodes technique and ClC-1 mRNA level by quantitative real time-polymerase chain reaction. Direct drug effects were tested by patch clamp analysis on human ClC-1 channels expressed in human embryonic kidney (HEK) 293 cells.Key Results: Chelerythrine, a PKC inhibitor, applied in vitro on muscle dissected from atorvastatin-treated rats fully restored gCl, suggesting the involvement of this enzyme in statin action. Chelerythrine partially restored gCl in muscles from fluvastatin-treated rats but not in those from fenofibrate-treated rats, implying additional mechanisms for gCl impairment. Accordingly, a decrease of ClC-1 channel mRNA was found in both fluvastatin- and fenofibrate-treated rat muscles. Fenofibric acid, the in vivo metabolite of fenofibrate, but not fluvastatin, rapidly reduced chloride currents in HEK 293 cells.Conclusions and Implications: Our data suggest multiple mechanisms underlie the effect of statins and fenofibrate on ClC-1 channel conductance. While statins promote Ca(2+)-mediated PKC activation, fenofibrate directly inhibits ClC-1 channels and both fluvastatin and fenofibrate impair expression of mRNA for ClC-1. [ABSTRACT FROM AUTHOR]

Background/Aims: Cardiovascular disease (CVD) is a major cause of mortality in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Dyslipidemia has been established as a well-known traditional risk factor for CVD in the general population and it is well known that patients with CKD exhibit significant alterations in lipoprotein metabolism. In this review the pathogenesis and treatment of renal dyslipidemia are discussed. Methods:Studies on lipid abnormalities in CKD stages 1–4, in nephrotic syndrome, and in hemodialysis and peritoneal dialysis patients are analyzed, as well as the lipid profile of kidney graft recipients. Also, the results of the effects of epoietin treatment and hypolipidemic drugs in CKD patients are reported. Results: Disturbances in lipoprotein metabolism are evident even at the early stages of CKD and usually follow a downhill course that parallels the decline of renal function. However, several intrinsic or exogenous factors can influence the phenotypic expression of these alterations. According to the literature, current evidence suggests that unlike dialysis patients, mild to moderate CKD patients could be benefit from the use of statins. Conclusion: The use of statins is indicated in patients with mild to moderate CKD, while in subjects with ESRD lipid-lowering therapy should be individualized. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background/aim: Hepatic bile acid synthesis is the main mechanism whereby the organism can degrade cholesterol. Plasma levels of 7α-hydroxy-4-cholesten-3-one have been reported to reflect bile acid synthesis and the expression or activity of the limiting enzyme of the main biosynthetic pathway, cholesterol 7α-hydroxylase. Aim of this study was to correlate the levels of this metabolite with the rates of cholesterol 7α-hydroxylation in vivo, a direct measurement of bile acid synthesis, in hyperlipidemic patients. Design: Concentrations of 7α-hydroxy-4-cholesten-3-one were assayed by gas–liquid chromatography: mass spectrometry in plasma samples obtained in 18 patients with primary hyperlipoproteinemia who previously underwent determination of cholesterol 7α-hydroxylation rates in vivo by tritium release analysis. Both determinations were performed in basal conditions and after treatment with hypolipidemic drugs (the fibric acid derivatives gemfibrozil and bezafibrate, cholestyramine alone or associated with simvastatin). Results: Changes in plasma 7α-hydroxy-4-cholesten-3-one profile closely reflected in vivo cholesterol 7α-hydroxylation rates during treatment with fibrates, cholestyramine and cholestyramine plus simvastatin. When plotting determinations from all studies (n =40), a very strict correlation was disclosed between plasma 7α-hydroxy-4-cholesten-3-one and cholesterol 7α-hydroxylation rates (r =0.81, P <0.001). Conclusions: Plasma 7α-hydroxy-4-cholesten-3-one closely mirrors measurements of cholesterol 7α-hydroxylation rates in vivo in hyperlipidemic subjects and therefore stands as a reliable marker of global bile acid synthesis. In view of the correlation observed, these data may help to interpret changes of plasma levels of this metabolite in terms of cholesterol balance quantification. [Copyright &y& Elsevier]

This review examines the various effects of Wy14,643, a hypolipidemic agent that activates peroxisome proliferator-activated receptor-α (PPARα), on the cardiovascular system. An emphasis has been placed on the specific cellular processes affected by Wy14,643 as they relate to vascular and cardiac function. Although the topic of this discussion is limited to vascular and cardiac tissues, the importance of circulating lipids on cardiovascular disease requires that a description of the indirect actions of this compound on liver metabolism also be included. Finally, the pharmacology of Wy14,643 is discussed within the context of PPARα-dependent and -independent mechanisms. [ABSTRACT FROM AUTHOR]