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Background: Atherosclerosis, a leading cause of mortality, necessitates effective management of hypercholesterolemia, specifically elevated low-density lipoprotein cholesterol (LDL-C). The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has revolutionised lipid-lowering. PCSK9i demonstrates substantial LDL-C reduction and cardiovascular benefits, particularly in statin-intolerant or nonresponsive individuals. However, the potential pleiotropic effects of PCSK9i, especially on arterial stiffness, remain a subject of investigation. This systematic review and meta-analysis seek to provide a nuanced understanding of the potential pleiotropic effects of PCSK9i, specifically on arterial health. The primary objective was to analyse the influence of PCSK9i on arterial stiffness, extending beyond traditional lipid-lowering metrics and contributing to a more comprehensive approach to cardiovascular risk reduction., Methods: A systematic search was conducted across major databases, clinical trial registries and grey literature. Inclusion criteria comprised adults in prospective cohort studies undergoing PCSK9i augmentation in lipid-lowering therapy, with a focus on arterial stiffness measured by pulse wave velocity (PWv). Random-effects meta-analyses, sensitivity analyses and meta-regression models were employed to assess the pooled effect of adding PCSK9i to lipid-lowering interventions on arterial stiffness., Results: Five studies (158 participants) met the inclusion criteria, demonstrating a significant reduction in PWv (mean difference: -2.61 m/s [95% CI: -3.70, -1.52]; ES: -1.62 [95% CI: -2.53, -.71]) upon adding PCSK9i to lipid-lowering interventions. Subgroup analysis and meta-regression models suggested potential sex-based and baseline PWv-dependent variations, emphasising patient-specific characteristics., Conclusion: The meta-analysis provides robust evidence that adding PCSK9i to lipid-lowering interventions significantly improves arterial stiffness, indicating broader vascular benefits beyond LDL-C reduction., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: The effectiveness of statin treatment to reduce coronary events and mortality has been hardly examined considering goals of LDL-C. We aimed to analyse such association in secondary cardiovascular prevention., Methods: Retrospective cohort analysis of electronic health records from the SIDIAP database, Catalonia-Spain. Recruitment period was from 2006 to 2017 and study period finished at the end of 2018. We included 54,175 people aged ≥35 years in cardiovascular secondary prevention starting statin treatment. We analysed the association of achieved LDL-C goals after statin initiation with coronary heart disease and all-cause mortality., Results: Mean age was 69 years and 20,146 (37.2%) were women. Coronary heart disease occurred in 5687 (10.5%) participants, and 10,676 (19.7%) persons passed away. Median follow-up lasted 5.7 years (interquartile range, 3.4-8.1). The coronary heart disease HRs (95% CI) for the LDL-C goals of 70-100, <70-55 and <55 mg/dL were .86 (.81-.92), .83 (.76-.9) and .8 (.72-.88), respectively. They were .89 (.83-.96) in the group with 30%-40% reduction and .86 (.8-.93) in the groups with 40%-50% and ≥50% reduction. We observed no association with mortality. We observed no relevant differences by sex or age., Conclusions: This population-level retrospective analysis of real-world data observed that treatment with statins is effective to achieve certain LDL-C goals and CHD reduction. The lack of significant difference between LDL-C goals needs confirmation in additional studies with real-world data. The LDL-C target should consider the magnitude of the decrease in coronary events., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs)., Methods: We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively., Results: A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG)., Conclusions: MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Randomized cardiovascular trials aimed to reduce the excessive residual risk in high-risk patients through a more aggressive low-density lipoprotein-cholesterol control or targeting triglycerides or high-density lipoprotein-cholesterol levels have shown a null or, at best, limited incremental benefit. In some cases, the treatment produced meaningful effects only in study subgroups. As a consequence, some compounds were withdrawn (e.g., nicotinic acid derivatives and cholesteryl ester transfer protein inhibitors), whereas others (fibrates) are utilized with reluctance due to the low level of evidence-based data. By reviewing these trials analytically, we identified a common feature that might explain their meager results: most of them involved patients generically at high cardiovascular risk with normal or near normal lipid levels and not patients with "true" dyslipidemia, who would receive the treatment if it were part of usual care. These observations may warrant re-examining a central criterion of pragmatism, eligibility, in the outline of forthcoming cardiovascular trials with novel lipid-modifying drugs., (© 2019 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The aims of this study were to evaluate the efficacy of corn silk decoction on lipid profile in patients with angina pectoris. PubMed, Cochrane, Embase, Google Scholar, Chongqing VIP Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, and Wanfang database were searched up to January 2019 for randomized controlled trials that assessed the impact of corn silk decoction on total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with angina pectoris. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using Review Manager (version 5.3) software. Random effects model was applied in this systematic review and meta-analysis to compensate for potential heterogeneity among the included studies. A total of four randomized controlled trials were eligible for meta-analysis. Pooled results of these studies indicated that corn silk decoction might improve high-density lipoprotein cholesterol and reduce total cholesterol, triglycerides, and low-density lipoprotein cholesterol in patients with angina pectoris. Subgroup analyses showed that corn silk decoction or modified corn silk decoction plus conventional pharmaceutical treatment could have favorable effects on blood lipids. However, the lack of blinding in most studies may have led to overestimation of these effects. Further studies with better design are needed to confirm these findings., (© 2019 John Wiley & Sons, Ltd.)

Objective: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients., Methods: A randomized, double-blind, placebo-controlled trial was designed to detect a 32% CVE risk reduction based on an estimated 1.6% per annum event rate with 80% power at P < 0.05. RA patients age >50 years or with a disease duration of >10 years who did not have clinical atherosclerosis, diabetes, or myopathy received atorvastatin 40 mg daily or matching placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary and tertiary end points included plasma lipids and safety., Results: A total of 3,002 patients (mean age 61 years; 74% female) were followed up for a median of 2.51 years (interquartile range [IQR] 1.90, 3.49 years) (7,827 patient-years). The study was terminated early due to a lower than expected event rate (0.70% per annum). Of the 1,504 patients receiving atorvastatin, 24 (1.6%) experienced a primary end point, compared with 36 (2.4%) of the 1,498 receiving placebo (hazard ratio [HR] 0.66 [95% confidence interval (95% CI) 0.39, 1.11]; P = 0.115 and adjusted HR 0.60 [95% CI 0.32, 1.15]; P = 0.127). At trial end, patients receiving atorvastatin had a mean ± SD low-density lipoprotein (LDL) cholesterol level 0.77 ± 0.04 mmoles/liter lower than those receiving placebo (P < 0.0001). C-reactive protein level was also significantly lower in the atorvastatin group than the placebo group (median 2.59 mg/liter [IQR 0.94, 6.08] versus 3.60 mg/liter [IQR 1.47, 7.49]; P < 0.0001). CVE risk reduction per mmole/liter reduction in LDL cholesterol was 42% (95% CI -14%, 70%). The rates of adverse events in the atorvastatin group (n = 298 [19.8%]) and placebo group (n = 292 [19.5%]) were similar., Conclusion: Atorvastatin 40 mg daily is safe and results in a significantly greater reduction of LDL cholesterol level than placebo in patients with RA. The 34% CVE risk reduction is consistent with the Cholesterol Treatment Trialists' Collaboration meta-analysis of statin effects in other populations., (© 2019, The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

In this paper, we propose a class of multivariate random effects models allowing for the inclusion of study-level covariates to carry out meta-analyses. As existing algorithms for computing maximum likelihood estimates often converge poorly or may not converge at all when the random effects are multi-dimensional, we develop an efficient expectation-maximization algorithm for fitting multi-dimensional random effects regression models. In addition, we also develop a new methodology for carrying out variable selection with study-level covariates. We examine the performance of the proposed methodology via a simulation study. We apply the proposed methodology to analyze metadata from 26 studies involving statins as a monotherapy and in combination with ezetimibe. In particular, we compare the low-density lipoprotein cholesterol-lowering efficacy of monotherapy and combination therapy on two patient populations (naïve and non-naïve patients to statin monotherapy at baseline), controlling for aggregate covariates. The proposed methodology is quite general and can be applied in any meta-analysis setting for a wide range of scientific applications and therefore offers new analytic methods of clinical importance., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background and Purpose: The most common prescribed antiepileptic drugs (AEDs), phenytoin and valproate, are potent enzyme inducers and inhibitors of the cytochrome P450 system, which interfere with lipid profile and glucose homeostasis. Studies on this topic have suffered from inadequate assessment of confounders and have rarely included glucose homeostasis and lipid profile as well as both enzyme inducers and inhibitors in the same study. We sought to determine whether these drugs had an effect on lipid profile and glucose homeostasis in Thai epileptic patients., Methods: We recruited 98 patients with epilepsy (45 taking phenytoin, 27 taking valproate, and 26 not taking any AED). Fasting blood samples were obtained to measure serum lipid, and glucose homeostasis was evaluated via the oral glucose tolerance test. We calculated the homeostasis model assessment index for each patient., Results: Our study revealed that CYP450 was induced by AEDs, and that patients on phenytoin had an increased mean value of serum total cholesterol, serum total triglycerides, and serum LDL cholesterol when compared with patients with epilepsy taking valproate and those taking no AEDs. No statistical significant difference was observed between patients taking valproate and patients taking no AEDs. In addition, patients with epilepsy taking phenytoin had higher fasting plasma glucose levels at fasting state than both those taking valproate and those taking no AEDs. Thirty percent of the patients taking phenytoin exhibited insulin resistance. We have found a negative correlation between log insulin sensitivity and log TG, but not high-density lipoprotein (HDL)., Conclusion: CYP450-induced phenytoin produces significant amelioration in several serologic markers of atherosclerosis. These findings suggest that phenytoin may substantially increase the risk of vascular events., (© 2012 The Author(s). European Journal of Neurology © 2012 EFNS.)

Purpose: Assessment of quality of cardiometabolic risk management in diabetes in primary care., Methods: In a descriptive cohort study including 95 Dutch general practices, we assessed medication treatment in relation to the level of control for HbA1c, systolic blood pressure (SBP) and LDL-cholesterol (LDL-c) in 2007. We also applied a prospective measure of treatment quality by assessing treatment modifications in not well-controlled patients. In a subpopulation of 23 practices, we studied trends in these quality indicators from 2004 (2059 patients) to 2007 (2929 patients)., Results: In 2007, averages for HbA1c, SBP and LDL-c were 6.9%, 142 mmHg and 2.3 mmol/l, respectively. Of the patients with an HbA1c >  8.5%, 16% were treated with one oral drug class and 50% used insulin. In 27% of these patients, therapy modification occurred subsequently. During the 4-year period, a slight decrease in average HbA1c was observed, but no changes in treatment level. In 2007, 56% of the patients had an SBP ≥ 140 mmHg, 19% of whom were not using antihypertensives. In the 13% with an SBP > 160 mmHg, 23% received a therapy modification. During the 4-year period, the average SBP decreased with 6 mmHg but the treatment level showed no substantial increase. In 2007, 39% had an LDL-c level ≥ 2.5 mmol/l, 49% of whom were not using statins. Of the patients with an LDL-c > 3.5 mmol/l, only 9% received a therapy modification., Conclusions: The decreasing population averages of HbA1c, SBP and LDL-c values suggest improvement in quality of care. However, the relatively few therapy modifications observed in insufficiently controlled patients show room for improvement., (Copyright © 2010 John Wiley & Sons, Ltd.)

Angiotensin-converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol impeding atherosclerosis. It is hypothesized that these medications may improve blood pressure and serum cholesterol by modifying the antioxidative status and energy metabolism of erythrocytes. In this study, the effects of 2 treatments are compared: lisinopril alone versus lisinopril + simvastatin, on erythrocyte antioxidant and energy metabolic enzymes. Patients with atherosclerosis and moderate hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher catalase activity and lower glutathione peroxidase activity are observed in 94% to 100% patients from both groups after 12 and 24 weeks of treatment. Superoxide dismutase activity is increased significantly only after 24 weeks. No changes of glutathione reductase, lactate dehydrogenase, and phosphofructokinase activities are found under any conditions indicated. Both treatments decrease systolic and diastolic blood pressure equally. Only lisinopril + simvastatin treatment decreases plasma total cholesterol and low-density lipoprotein cholesterol. The results show for the first time that lisinopril monotherapy and combined lisinopril + simvastatin therapy exhibit specific and pronounced effects on antioxidant and energy metabolic enzyme activities in erythrocytes of hypertensive patients.

The effects of demographic and clinical covariates on the apparent clearance (CL/F) of orally administered atorvastatin, with chronic dosing in a patient population that included the elderly, were studied in 143 patients (atorvastatin: 34 +/- 26 mg/day, mean +/- SD; men (n = 64), age 64.6 +/- 12.1 years, and women (n = 79), age 69.3 +/- 13 years). The time of dose administration had a strong influence on Ka (faster with morning dosing); the factors found to slow CL/F were coadministration of CYP3A inhibitors and advancing age--the latter factor was relevant only in the men, not in the women.

Background: Patients with metabolic syndrome (MS) and type 2 diabetes (T2DM) show increased risk for coronary artery disease. Lipoprotein metabolism is characterized by elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) and predominance of atherogenic small, dense low-density lipoprotein (sdLDL), while low-density lipoprotein (LDL) cholesterol is only slightly elevated., Methods: Multicentre, randomized, open-label cross-over study investigating the effect of combination of fluvastatin/fenofibrate (80/200 mg) (F&F) on LDL-subfractions compared with combination of simvastatin/ezetimibe (20/10 mg) (S&E) in patients with MS/T2DM., Results: Seventy-five patients were randomized, 69 completed the study and LDL-subfractions of 56 patients were analysed. Thirty-eight out of 56 patients (68%) showed a profile dominated by sdLDL. In these, TG and total cholesterol (TC) were elevated compared with non-sdLDL patients. In all patients, reduction of TC and LDL cholesterol (LDL-C) by S&E was stronger than by F&F. The increase of HDL-C was stronger with S&E in the non-sdLDL group, whereas in the sdLDL group, there was no difference between treatments. In non-sdLDL patients, there was no effect on TG or LDL-radius. However, in the sdLDL group, F&F was more effective in reducing TG and increased LDL radius, whereas S&E reduced LDL radius even further., Conclusions: S&E is more efficient in reducing TC and LDL-C. This is also true for HDL-C increase in non-sdLDL patients. However, in patients with sdLDL, F&F was more efficient in reducing TG and increasing LDL radius.

The aerial parts of Anethum graveolens (dillweed) are used in Iran as a hypolipidemic agent. The scientific basis for its use has yet to be established. In this study the hypolipidemic activity of dill powder and its essential oil (its most important fraction) were evaluated in male Wistar rats (180 +/- 20 g) fed a high cholesterol diet. Anethum graveolens essential oil (AGEO) was prepared by hydrodistillation and analysed using GC/MS. AGEO had a yield of 2% and GC/MS analysis showed that alpha-phellandrene (32%), limonene (28%) and carvone (28%) were its major components. Daily oral administration of AGEO to rats at doses of 45, 90 and 180 mg/kg for 2 weeks significantly and in a dose-dependent manner reduced total cholesterol, triglyceride and low density lipoprotein cholesterol (LDL-C). AGEO also increased significantly high density lipoprotein cholesterol (HDL-C). Anethum graveolens powder when added to the diet of animals showed similar effects on serum lipids. It is concluded that Anethum graveolens has significant lipid lowering effects and is a promising cardioprotective agent.

Objective: To evaluate the effects of soygerm isoflavones extracts on blood lipoproteins, antioxidative capacity and urinary estrogen metabolites in postmenopausal women who receive hormone therapy (HT)., Method: Thirty-nine volunteers receiving HT were recruited, and 33 completed the study. All subjects received 6 g of soygerm extracts per day for 4 weeks. Blood and urine samples were collected for study at the beginning and at the end of study., Result: Plasma HDL-C levels increased markedly with significant decreases of plasma LDL-C/HDL-C ratio and LDL-TG levels. The lag time of conjugated dienes formation prolonged for 9.9% and thiobarbituric acid reactive substances production in copper-catalyzed oxidation of LDL decreased. The differences were statistically significant. Urinary ratio of 2-OHE(1) to 16alpha-OHE(1) increased without statistical significance., Conclusion: Soygerm extracts may improve serum lipid profile in postmenopausal Taiwanese women who receive HT, and probably provide a favorable effect on estrogen metabolism.

Hyperlipidaemia, atherosclerosis and related diseases are becoming a major health problem in developing countries. Ocimum basilicum is one of the medicinal plants widely used in Morocco to reduce plasma cholesterol and to reduce the risk of atherosclerosis-related diseases. However, mechanisms underlying the reported hypolipidaemic effect of this plant have not been investigated. This study evaluates the lipid lowering effect of aqueous Ocimum basilicum extract in Triton WR-1339-induced hyperlipidaemic rats. Hyperlipidaemia was developed in animals by intraperitoneal injection of Triton (200 mg/kg). After injection of Triton the animals were divided into three treatment groups: hyperlipidaemic, hyperlipidaemic plus herb extract and hyperlipidaemic plus fenofibrate treated rats. At 7 h after the Triton injection, levels of plasma cholesterol, triglycerides and LDL-cholesterol in rats treated also with the Ocimum basilicum extract (0.5 g/100 g body weight) were, respectively, 50%, 83% and 79% lower than Triton-treated rats and HDL-cholesterol was 129% higher than in rats given Triton alone. At 24 h following Ocimum basilicum administration, total cholesterol, triglycerides and LDL-cholesterol levels decreased by 56%, 63% and 68%, respectively, in comparison with the Triton treated group and HDL-cholesterol was not increased significantly. The hypolipidaemic effect exerted by Ocimum basilicum extract was markedly stronger than the effect induced by fenofibrate treatments. Further it was demonstrated that Ocimum basilicum aqueous extract displayed a very high antioxidant power. These results indicate that Ocimum basilicum extract may contain hypolipidaemic and antioxidant substances and its use as a therapeutic tool in hyperlipidaemic subjects may be of benefit and encourage further investigation in this field.

Recent clinical trials confirm that aggressive lipid-lowering therapy with statins decreases low density lipoprotein (LDL) cholesterol to well below 100 mg/dL in high risk patients, and prevents cardiovascular events. Similarly, aggressive lipid lowering is being explored as a possible means of promoting regression of atherosclerosis and of affording greater protection from atherosclerotic events. A growing body of evidence indicates that intensive statin therapy, particularly in high risk patients, slows the rate of progression of atherosclerosis compared with moderate therapy, and that reductions of > or =40% in LDL cholesterol are necessary to achieve atherosclerosis regression. Questions remain regarding the extent of regression achieved with statin therapy and whether to dose statins to achieve a specific LDL-cholesterol level or a certain percent reduction; however, ongoing clinical trials may provide insight and guidance.

The role of natural products in preventing diseases, such as atherosclerosis, is being recognized increasingly. In this study, the in vitro antioxidant activity of the polar extract obtained from Alkanna albugam root, belonging to the Boraginaceae family, against LDL oxidation, was investigated and compared with the respective activity of Greek Mentha piperita, Rosmarinus officinalis and Sideritis clandestina, belonging to the Lamiaceae family. Of the extracts tested, only those from Alkanna albugam root and Mentha piperita exhibited statistically significant activity. Weaker activity was shown by the extracts obtained from Rosmarinus officinalis and Sideritis clandestina., (Copyright 2005 John Wiley & Sons, Ltd.)

Hwaotang (HOT), a traditional Korean medicinal formulation, is a dried decoctum of a mixture of seven herbal medicines, consisting of Angelica gigantis Radix, Rehmanniae Radix, Paeoniae Radix, Ciniamomi Cortex, Cnidii Rhizoma, Persicae Semen and Carthami Flos. In the present study, the inhibitory effects and anti thrombic properties of HOT on the progression of atherosclerotic lesions were studied using the spontaneous familial hypercholesterolemia (FH) model, Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits and rats. Changes in blood chemistry, pathology and low-density lipoprotein (LDL) oxidation were measured in a control and HOT group. In the control group, the area of atheromatous plaques of the aorta progressed between week 12 (36.65%) and week 14 (46.22%). This progression of atherosclerotic lesions did not occur in the HOT-treated group after 12 (24.24%) and 14 (23.34%) weeks. Antioxidative effects on LDL were seen in the HOT in weeks 12 and 14. HOT improved the hypercholesterolemia in the KHC rabbits. On the other hand, HOT and five of the seven herbs, except Cnidii Rhizoma and Carthami Flos, inhibited the endotoxin-induced hepatic venous thrombosis in high cholesterol diet-treated rats. However, Ciniamomi Cortex showed a very weak inhibitory effect on the endotoxin-induced hepatic venous thrombosis. The extract also inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In conclusion, these results suggest that HOT has inhibitory effects on the development of atheromatous plaque formation in spontaneous FH rabbits. It is also suggested that the antioxidative effects of HOT on LDL led to the beneficial effects observed in this study. The protection by HOT and its herbs on the artificially induced ischemic infarction might be related to their inhibitory effects on disseminated intravascular coagulation, platelet coagulation and thrombotic action., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

Background: Myopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle., Methods: Forty-eight patients with hypercholesterolemia (33 men and 15 women) were randomly assigned to receive 80 mg/d of simvastatin (n = 16), 40 mg/d of atorvastatin (n = 16), or placebo (n = 16) for 8 weeks. Plasma samples and muscle biopsy specimens were obtained at baseline and at the end of the follow-up., Results: The ratio of plasma lathosterol to cholesterol, a marker of endogenous cholesterol synthesis, decreased significantly by 66% in both statin groups. Muscle campesterol concentrations increased from 21.1 +/- 7.1 nmol/g to 41.2 +/- 27.0 nmol/g in the simvastatin group and from 22.6 +/- 8.6 nmol/g to 40.0 +/- 18.7 nmol/g in the atorvastatin group (P = .005, repeated-measurements ANOVA). The muscle ubiquinone concentration was reduced significantly from 39.7 +/- 13.6 nmol/g to 26.4 +/- 7.9 nmol/g (P = .031, repeated-measurements ANOVA) in the simvastatin group, but no reduction was observed in the atorvastatin or placebo group. Respiratory chain enzyme activities were assessed in 6 patients taking simvastatin with markedly reduced muscle ubiquinone and in matched subjects selected from the atorvastatin (n = 6) and placebo (n = 6) groups. Respiratory chain enzyme and citrate synthase activities were reduced in the patients taking simvastatin., Conclusions: High-dose statin treatment leads to changes in the skeletal muscle sterol metabolism. Furthermore, aggressive statin treatment may affect mitochondrial volume.

Several inflammatory diseases are thought to be related to oxidative injury and free oxygen radicals have been proposed as important causative agents of heart disease and aging. To investigate the effects of daily intake of medicinal plants on antioxidant enzymes, lipid peroxidation and lipid profiles in rat, 28 rats were randomly divided into four groups and administered with three plant extracts (0.2 g/kg body weight): Piper cubeba (fruit), Physalis angulata (flower), Rosa hybrida (flower) and with saline as a control. After 3 weeks, superoxide dismutase (SOD), catalase, thiobarbituric acid reactive substance (TBARS), triglyceride (TG) and cholesterol levels in plasma were measured. The SOD activity of the Piper cubeba group and the catalase activity of the Piper cubeba and Rosa hybrida groups were significantly increased compared with the control group, while the SOD and catalase activities of the Physalis angulata group were not significantly changed (p<0.05). TBARS, a marker of lipid peroxidation, was significantly lower in all experimental groups compeered with the control group. No significant changes occurred in the TG, total- and LDL-cholesterol of all groups, but the HDL-cholesterol of the Physalis angulata group was significantly increased. This study showed that the intake of medicinal plants in rats results in an increase in antioxidant enzyme activity and HDL-cholesterol, and a decrease in malondialdehyde, which may reduce the risk of inflammatory and heart disease., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

It has been estimated that 92% of individuals with type 2 diabetes, without cardiovascular disease (CVD), have a dyslipidaemic profile. Several guidelines on cardiovascular risk now recommend that patients with diabetes should be considered at high risk of CVD and should thus receive lipid-lowering therapy to reduce low-density lipoprotein cholesterol (LDL-C) to below 2.5 mmol/L. Since their introduction in 1987, statins have revolutionized the management of CVD. The most recent statin to be introduced, rosuvastatin, has been shown to be the most effective at lowering LDL-C, as well as consistently raising HDL-C across the 10-40 mg dose range. This has been confirmed by many studies, including the Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study in which rosuvastatin 10 mg was shown to be more effective than commonly used doses of other statins, both for LDL-C reduction and achieving treatment target goals. The effectiveness of rosuvastatin has also been studied in type 2 diabetes patients in three studies: the URANUS (Use of Rosuvastatin vs. Atorvastatin iN type 2 diabetes mellitUS), ANDROMEDA (A raNdomized, Double-blind study to compare Rosuvastatin [10 & 20 mg] and atOrvastatin [10 & 20 Mg] in patiEnts with type II DiAbetes) and CORALL (COmpare Rosuvastatin [10-40 mg] with Atorvastatin [20-80 mg] on apo B/apo A-1 ratio in patients with type 2 diabetes meLLitus and dyslipidaemia) studies. URANUS and ANDROMEDA showed rosuvastatin to be more effective than atorvastatin at reducing LDL-C and achieving treatment target goals. CORALL demonstrated rosuvastatin 10, 20 and 40 mg to be more effective at lowering LDL-C than 20, 40 and 80 mg of atorvastatin, respectively. Ongoing studies will evaluate whether these properties of rosuvastatin translate into beneficial effects on atherosclerosis and significant reductions in cardiovascular events.

Atherosclerosis is a multifactorial condition that can result in cardiovascular disease. Statin therapy is thought to mediate cardioprotective effects that influence endothelial function, inflammatory responses, plaque stability and thrombus formation, processes involved in atherosclerosis. Although reduction in low-density lipoprotein cholesterol (LDL-C) potentially plays a role in all of these effects, several lines of evidence also implicate nonlipidmediated 'pleiotropic' effects. For example, statin therapy confers a lower risk for coronary heart disease than placebo in patients with comparable serum cholesterol levels, and confers a greater magnitude of clinical benefit than expected based on LDL-C levels alone. Moreover, while nonstatin lipid-lowering therapy does not necessarily reduce stroke risk, statins have shown a significant reduction in stroke. Statins exert their pleiotropic effects, in part, by improving endothelial function via up-regulation of endothelial nitric oxide synthase enzyme activity. Markers of inflammation such as high sensitivity C-reactive protein have been also shown to add further prognostic information about patients at risk of cardiovascular disease who may benefit from statin therapy. Further studies are still needed to determine whether statins have direct effects on inflammatory pathways.

The antioxidant effect of three different extracts of Morus nigra fruit (fruit juice, hydroalcoholic and polyphenolic) on haemoglobin glycosylation, peroxidative damage to human erythrocytes, liver hepatooytes of rats and human low-density lipoprotein (LDL) were studied. The results show that all three extracts inhibited haemoglobin glycosylation induced by glucose to differing degrees. The haemolysis of human erythrocytes induced by hydrogen peroxide was also inhibited. The production of malondialdehyde (MDA) during peroxidative damage to plasma membranes of isolated rat hepatocytes induced by tert-butyl hydroperoxide (tBH) was also inhibited. Inhibition of lipid peroxidation of LDL induced by copper (II) ion was achieved during the study. The results suggest that Morus nigra fruit has a protective action against peroxidative damage to biomembranes and biomolecules., (Copyright 2004 John Wiley & Sons, Ltd.)

Background: Kliogest is commonly prescribed for the relief of acute postmenopausal symptoms and prevention of postmenopausal bone loss. However, there have been few data on its effect in Asian women., Methods: This 1-year, single-center, randomized, double-blind and placebo-controlled study evaluated the efficacy and safety of Kliogest in hormone replacement therapy (HRT)-naïve Thai women. The subjects were 120 healthy Thai women aged between 45 and 65 years, with intact uterus, and who had been amenorrheic for at least 1 year., Results: Kliogest increased spine (+ 6%, p < 0.01) and hip (+2%, p < 0.01) bone mineral density (BMD), and lowered plasma total cholesterol (TC) (-16%, p < 0.05) and low density lipoprotein cholesterol (LDL-C) (-16%, p < 0.05) concentrations. However, Kliogest also resulted in a decrease in high density lipoprotein cholesterol (HDL-C) concentration (-18%, p < 0.05). Compared to placebo, the reduction in menopausal symptoms by Kliogest was not statistically significant. The frequency and severity of treatment-related uterine bleeding decreased with the duration of Kliogest treatment. Furthermore, there was a fairly strong relationship between the change in serum estrone concentration and the average monthly weighted bleeding scores over the first 6 months (Spearman's correlation r = 0.54; p < 0.001), which became weaker over the entire treatment period (Spearman's correlation r = 0.27; p < 0.01). Although there was a small to moderate relationship between baseline estrone concentration and both lumbar (r = 0.23, p < 0.02) and hip (r = 0.20, p < 0.05) BMD, there was no significant relationship between Kliogest-induced change in estrone concentration and change in lumbar and hip BMD., Conclusions: Continuous treatment with Kliogest for 1 year reversed the potential postmenopausal bone loss in HRT-naïve Thai postmenopausal women. However, its effect on cardiovascular risk is uncertain. Furthermore, Kliogest is safe but appears to have no significant effect on climacteric symptoms in the patients in the present study.

Capsaicin (8-methyl-n-vanillyl-6-nonenamide), a pungent component found in red pepper can induce body heat and possibly enhance blood flow as well as increase energy expenditure, and prevent oxidative stress. Male Wistar rats were divided into vehicle, 1 mg/kg body weight capsaicin and 3 mg/kg body weight capsaicin groups. Samples were taken from the animals on day 1 of i.p. treatment with capsaicin and on 3 consecutive days of i.p. treatment with capsaicin. Our investigation demonstrated that blood flow measurements in rats was negatively correlated with LDL after treatment with capsaicin. Although capsaicin did not show a noticeable effect on the serum total cholesterol level, LDL decreased while HDL and triglyceride increased in rats treated with 3 mg/kg capsaicin for 3 days. The antioxidant effect of capsaicin was not shown when the rats were treated with 1 mg/kg body weight capsaicin. However, rats treated with 3 mg/kg body weight capsaicin for 3 days showed a reduction of oxidative stress measured as malondialdehyde in the liver, lung, kidney and muscle. Liver glycogen was found to decrease after 3 days treatment with 3 mg/kg body weight capsaicin. From this study, it is hypothesized that capsaicin can be a potent antioxidant and aid in lowering LDL even when consumed for a short period., (Copyright 2003 John Wiley & Sons, Ltd.)

The lipoidal matters of Corallina officinalis L. showed a seasonal nonsignificant quantitative variation. However, the fatty acids revealed a relative increase in the summer and winter, while unsaponifiable matter exhibited a slight increase in the spring. The GC/MS analysis of saponifiable and unsaponifiable matter of the algal samples collected in different seasons revealed that samples collected in the spring contained a low cholesterol content and high steroidal compounds as well as high polyunsaturated fatty acids. The alcohol extract, hexane extract and fatty acid fraction of this algal sample exhibited a significant hypolipidaemic activity. Also, two biologically active fractions of hydrocarbons were isolated by CC technique from the hexane fraction of C. officinalis L. and identified by GC/MS., (Copyright 2003 John Wiley & Sons, Ltd.)

Background and Objectives: Fibrates induce hepatic peroxisome proliferation and carcinogenesis in rodents by activating peroxisome proliferator-activated receptor alpha (PPAR(alpha)). There is no conclusive evidence that humans are unresponsive to peroxisome proliferation, and concern exists about the long-term safety of fibrate treatment., Methods: In a university hospital setting, 48 patients with uncomplicated gallstones and a serum level of low-density lipoprotein cholesterol greater than 130 mg/dL were randomly assigned to open-label treatment with bezafibrate (400 mg/d), fenofibrate (200 mg/d), gemfibrozil (900 mg/d), or placebo for 8 weeks before elective cholecystectomy. Serum samples for lipid determinations were obtained at baseline and before surgery. A liver specimen was obtained at operation, and the relative levels of messenger ribonucleic acid (mRNA) for the wild and truncated forms of PPAR(alpha), acyl coenzyme A oxidase, liver carnitine palmitoyltransferase I, apolipoprotein A-I, and stearoyl coenzyme A desaturase were determined., Results: Fenofibrate, bezafibrate, and gemfibrozil reduced plasma low-density lipoprotein cholesterol levels by 22% (P =.009), 14% (P =.042), and 11% (not significant), respectively. Plasma triglyceride levels decreased significantly (24%-36%; P <.05), whereas high-density lipoprotein cholesterol levels rose nonsignificantly after treatment with the 3 fibrates. Except for a 35% increase of apolipoprotein A-I mRNA after fenofibrate administration (P <.05), none of the individual fibrates induced significant changes in the mRNAs tested, although as a group they increased the mRNA for liver carnitine palmitoyltransferase I by 40%(P =.08; marginally significant)., Conclusions: Fibrate administration to humans at pharmacologic doses able to activate PPAR(alpha) and to induce a hypolipidemic effect does not increase the hepatic expression of acyl coenzyme A oxidase, a well-known marker of peroxisome proliferation in rodents.

Objectives: To compare tibolone therapy with four different estrogen replacement therapy protocols, with regard to the effects on plasma lipid profiles., Methods: The plasma lipid levels of 178 postmenopausal women in five different therapy groups were compared with each other as well as their baseline levels with 6-month intervals during 2-year follow-up. Student's t-test, paired t-test and Pearson correlation analysis were utilized for statistical analysis., Results: HDL cholesterol levels increased significantly from baseline in groups using oral estrogen (P<0.05) but a slight non-significant decrease was seen in tibolone therapy (P>0.05). LDL cholesterol levels significantly decreased at the end of the second year in oral estrogen and tibolone users (P<0.05). Triglyceride levels increased non-significantly with estrogen therapy (P>0.05), whilst decreased significantly in the tibolone group (P<0.05)., Conclusion: Tibolone may be a good alternative to estrogen replacement therapy in postmenopausal women, as it has beneficial effects on LDL cholesterol and triglyceride levels, which play important role in atherosclerosis.

An aqueous extract of Apocynum venetum leaves and its constituents inhibited thiobarbituric acid reactive substances (TBARS) and conjugated-diene formation in the Cu(2+)-induced oxidation of low density lipoprotein (LDL) in vitro. The TBARS formation was most strongly inhibited by chlorogenic acid with an IC(50) value of 1.9 microM, but other constituents were in a range of 2.3-23.3 microM. On the other hand, the lag time in the conjugated-diene formation was dose-dependently prolonged by addition of the aqueous extract. Catechin prolonged the lag time more than 300 min and other constituents such as chlorogenic acid, epicatechin, epigallocatechin, hyperoside and isoquercitrin led to no conjugated-diene formation within 700 min under the experimental conditions., (Copyright 2000 John Wiley & Sons, Ltd.)

To test the effects of fluvastatin on low-density lipoprotein (LDL) receptor activity in patients with heterozygous familial hypercholesterolemia, the authors measured LDL receptor activity in stimulated T-lymphocytes prepared from 34 patients before and after treatment with 40 mg fluvastatin daily for 12 weeks. Maximally induced pretreatment LDL receptor activities did not correlate with pretreatment plasma cholesterol levels or with changes in plasma cholesterol levels during treatment, and there were no significant changes in LDL receptor activity during treatment. Barring methodological problems, two explanations are possible. Insofar that LDL receptor activity in lymphocytes reflects LDL receptor activity in the liver, the results suggest that the primary response to treatment with fluvastatin in heterozygous familial hypercholesterolemia (FH) patients is not enhanced LDL receptor activity. Alternatively, fluvastatin increases LDL receptor activity in hepatocytes but has little effect on receptor-dependent lipoprotein catabolism in extrahepatic tissues in vivo.

Nonadherence to treatment is a common problem in the clinical management of hypercholesterolemic patients. This study was carried out with the aim of monitoring the daily compliance to a 6-month course of lipid-lowering therapy, using a microelectronic device, the Medication Event Monitoring System (MEMS), versus pill count. Forty men with primary hypercholesterolemia were prescribed fluvastatin 1 x 40 mg daily, provided in a MEMS package to record the date and time of each opening of the pillbox. Thirty-nine of 40 patients (98%) completed the study. Total cholesterol and LDL cholesterol levels decreased significantly (18% and 25%, p < 0.001) during the 6-month therapy period. A high mean rate of compliance was achieved by MEMS using the following three indexes--compliance to total prescribed dose (88.8% +/- 13.5%), compliance to prescribed days (82.4% +/- 19.5%), and compliance to prescribed time of day (81.86% +/- 19.5%)--and by pill count (93.4% +/- 9.5%). In addition, the MEMS provided some patterns of nonadherence to medication, undetectable by pill count alone, such as a drug holiday in 38% of cases, a drug omission for more than 7 consecutive days in 9% of cases, and, conversely, use of more than the one prescribed daily dose in 47% of cases. A significant correlation between the rate of compliance and the decrease in LDL cholesterol was observed only when the compliance was assessed by MEMS. The results indicate that MEMS is a useful tool for monitoring compliance in clinical practice and may possibly increase adherence to long-term lipid-lowering therapy.

This study investigates the hypothesis that lipid soluble antioxidants may increase the resistance of low-density lipoprotein (LDL) to oxidation and also enhance vascular endothelial responses in humans. In a double-blind parallel group study, 24 hypercholesterolaemic patients already on treatment with simvastatin (20 mg day-1), were randomized to supplementary treatment with probucol (500 mg bd), vitamin E (400 IU daily) or placebo for 8 weeks. Mean serum cholesterol before antioxidant treatment was 7.00 mmol l-1. Resistance of LDL to oxidation by copper was increased by 830% in the probucol group and by 30% in the vitamin E group. However, thiobarbituric acid reacting substances in whole serum were not altered by either antioxidant. Probucol lowered HDL- and LDL-cholesterol levels and increased the QT interval. Forearm vascular responses, as measured by venous occlusion plethysmography, to acetylcholine, glyceryl trinitrate and NG-monomethyl-L-arginine, were not significantly changed by antioxidant treatment. Probucol has a major, and vitamin E a minor, effect on LDL resistance to oxidation but neither compound appears to alter forearm vascular responses in vivo.

Apolipoprotein B XbaI polymorphism and apolipoprotein AI/CIII SstI polymorphism have been found to be associated with variations in serum lipoprotein levels. We investigated whether these gene polymorphisms are involved in determining the lipid-modulating action of gemfibrozil. Of the 221 male subjects with hyperlipidemia studied, 121 responded well to the treatment with more than a 25% reduction in the non-high-density lipoprotein cholesterol level, whereas 100 were nonresponders. Among responders, but not nonresponders, homozygosity for the apolipoprotein B X2 allele (XbaI site present) and heterozygosity for the apolipoprotein AI/CIII S2 allele (SstI site present) were associated with elevated baseline serum low-density lipoprotein cholesterol and triglyceride levels, respectively. However, the hypolipidemic effect of gemfibrozil among the responders was independent of these gene polymorphisms. These data indicate that common polymorphisms of the apolipoprotein B and apolipoprotein AI/CIII gene loci influence serum lipid levels by mechanisms that are amenable to an intervention with gemfibrozil.