评价烟酸缓释片治疗混合性高脂血症的疗效及安全性

目的探讨烟酸缓释片治疗混合性高脂血症的临床疗效及安全性。方法85例高脂血症患者,随机分为阿伐他汀组(n=42,10 mg·d-1)和烟酸缓释片组(n=43,500 mg·d-1),疗程均为4 wk,观察治疗前后主要血脂参数(TC、TC、LDL-C、HDL- C、α-脂蛋白)的变化率、达标率及不良反应。结果在降低TG、α-脂蛋白,升高HDL-C方面,烟酸缓释片优于他汀类药物。在不良反应和安全性方面,烟酸缓释片组有较高比例患者出现皮肤潮红和瘙痒,但对肝、肾功能影响无统计学意义。结论烟酸缓释片(500 mg·d-1)可以更全面地改善混合性高脂血症患者的血脂异常,尤其是升高HDL-C、降低TG和α-脂蛋白方面,安全性好,但其耐受性和依从性方面较阿伐他汀差。     

Higher Dietary Inflammation in Patients with Schizophrenia: A Case-Control Study in Korea

Inflammation is a risk factor for the onset and progression of schizophrenia, and dietary factors are related to chronic inflammation. We investigated whether the dietary inflammatory index (DII) is associated with schizophrenia in the Korean population. Of the 256 subjects who responded to the questionnaire, 184 subjects (117 controls; 67 individuals with schizophrenia) were included in this case-control study. A semi-quantitative food frequency questionnaire was used to evaluate the dietary intakes of the study participants. The energy-adjusted DII (E-DII) was used to assess the inflammatory potential of the participants’ diets. Dietary intakes of vitamin C, niacin, and folate were significantly reduced in the patients with schizophrenia. The patients with schizophrenia had higher E-DII scores than the controls (p = 0.011). E-DII was positively associated with schizophrenia (odds ratio = 1.254, p = 0.010). The additional analysis confirmed that E-DII was significantly associated with schizophrenia, especially in the third tertile group of E-DII scores (odds ratio = 2.731, p = 0.016). Our findings suggest that patients with schizophrenia have more pro-inflammatory diets.     

Lowering the cost of lowering the cholesterol

Objectives:To describe a medical center policy designed to contain the cost of using the lipid-lowering drug lovastatin in a primary care setting, to examine the effect of the policy on cost containment, and to examine physician acceptance of the policy. Setting:A Veterans Affairs medical center. Interventions:The policy made lovastatin available to physicians when failure of therapy with diet and two first-line drugs was documented on an order form. The form also contained educational information including prices and recommended niacin as the drug treatment of first choice for most patients. Design:To evaluate the effect of the policy, lipid-lowering drug use at the medical center was compared with that at a similar center that did not restrict lovastatin use, and with lipid-lowering drug use in the United States as a whole. A written questionnaire was used to survey physician reaction to the policy. Results:The use of lovastatin as a percentage of total lipid-lowering drug use at the center with the lovastatin policy was one-fourth that at the other center or nationwide, and the use of niacin was four times greater (p<0.0001). The estimated savings in drug costs to the center with the lovastatin policy due to these differences was more than $30,000 per year. In the survey of physicians affected by the policy (n=78, response rate =100%), less than one-fourth viewed it unfavorably, and 90% favored this policy over restricting the drug to a subspecialty clinic. Conclusion:The authors’ experience indicates that a formulary policy that permits limited use of an expensive drug in a primary care setting can contain costs in a way that is acceptable to physicians. A policy of this type could be useful to the increasing number of health care provider organizations that cover the cost of outpatient medications. Presented at the annual meeting of the Society of General Internal Medicine, May 3, 1990, Washington, D.C.     

Short-Term Effects of Extended-Release Niacin With and Without the Addition of Laropiprant on Endothelial Function in Individuals With Low HDL-C: A Randomized,Controlled Crossover Trial

Background

Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation.

Objective

This study investigated the short-term effects of extended-release niacin (ERN) administered with or without the prostaglandin D2 receptor antagonist laropiprant on endothelial function in patients with low HDL-C.

Methods

Asymptomatic men and women aged between 20 and 60 years who had plasma HDL-C levels <40 mg/dL were treated with ERN monotherapy 1 g/d or ERN/laropiprant 1 g/20 mg (ERN/LRP) in a crossover study design. The sequence of treatments was decided by simple randomization. Plasma samples and flow-mediated dilation (FMD) of the brachial artery were obtained at baseline, day 7 of treatment period 1, day 7 of washout, and day 7 of treatment period 2.

Results

Eighteen patients were enrolled (mean [SD] age, 42 [17] years; 11 men). Triglyceride levels decreased by 4% and 3%, and HDL size decreased by 5.8% and 6.2%, with ERN and ERN/LRP, respectively (both, P < 0.05). There were no changes in HDL-C levels or in cholesteryl esterase transfer protein activity with either treatment. The median increases in FMD were 4.5% and 4.1% with ERN and ERN/LRP, which receded after washout. On intergroup analysis, there were no differences with respect to variation in plasma HDL-C, triglycerides, C-reactive protein, direct bilirubin, or FMD.

Conclusions

In these patients, the addition of laropiprant did not influence the effects of niacin on endothelial function. Based on these findings, short-term niacin treatment might improve endothelial function in patients with low HDL-C levels. ClinicalTrials.gov identifier: NCT01942291.     

Nicotinic acid/laropiprant reduces platelet count but increases mean platelet volume in patients with primary dyslipidemia

Introduction

Nicotinic acid (NA) has been associated with reduced cardiovascular morbidity and mortality. Of note, beyond its lipid-modifying actions, NA possesses a number of not yet thoroughly defined pleiotropic actions including anti-inflammatory and antithrombotic effects. As a growing body of evidence points towards mean platelet volume (MPV) and platelet distribution width (PDW) as independent risk factors for cardiovascular disease, it would be interesting to evaluate the effect of NA on these platelet indices.

Material and methods

We recruited 50 consecutive patients with dyslipidemia who were treated with a conventional statin dose (10–40 mg simvastatin or 10–20 mg atorvastatin or 5–20 mg rosuvastatin) and had not achieved the low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) goal. Add-on-statin treatment with extended release (ER) NA/laropiprant (1,000/20 mg/day for the first 4 weeks followed by 2,000/40 mg/day for the next 8 weeks) was given to all patients for 3 months.

Results

The ER-NA/laropiprant resulted in a 20% reduction in platelet count (from 277,150/µl (min: 163,000/µl – max: 223,400/µl) to 220,480/µl (min: 141,000/µl – max: 319,000/µl), p < 0.001), while it increased MPV by 3.5% (from 11.4 fl (min: 9.2 fl – max: 13.6 fl) to 11.8 fl (min: 9.5 fl – max: 14.1 fl), p = 0.01), without affecting PDW significantly (from 14.6 fl (min: 10.5 fl – max: 19.3 fl) to 14.5 fl (min: 11 fl – max: 21.1 fl), p = NS).

Conclusions

The NA is associated with reduced platelet count but with increased MPV, thereby raising questions regarding NA''s antithrombotic and vasculoprotective properties.     

Pellagra‐like condition is xeroderma pigmentosum/Cockayne syndrome complex and niacin confers clinical benefit

An extremely rare pellagra‐like condition has been described, which was partially responsive to niacin and associated with a multisystem involvement. The condition was proposed to represent a novel autosomal recessive entity but the underlying mutation remained unknown for almost three decades. The objective of this study was to identify the causal mutation in the pellagra‐like condition and investigate the mechanism by which niacin confers clinical benefit. Autozygosity mapping and exome sequencing were used to identify the causal mutation, and comet assay on patient fibroblasts before and after niacin treatment to assess its effect on DNA damage. We identified a single disease locus that harbors a novel mutation in ERCC5, thus confirming that the condition is in fact xeroderma pigmentosum/Cockayne syndrome (XP/CS) complex. Importantly, we also show that the previously described dermatological response to niacin is consistent with a dramatic protective effect against ultraviolet‐induced DNA damage in patient fibroblasts conferred by niacin treatment. Our findings show the power of exome sequencing in reassigning previously described novel clinical entities, and suggest a mechanism for the dermatological response to niacin in patients with XP/CS complex. This raises interesting possibilities about the potential therapeutic use of niacin in XP.     

The pharmacology of fluvastatin,a new HMG-CoA reductase inhibitor

As a therapeutic class, the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors are highly effective at lowering low-density lipoprotein cholesterol (LDL-C) levels. In addition, they are well tolerated and well suited to a broad range of patients with primary (type IIa or IIb) hypercholesterolemia. The most recently approved HMG-CoA reductase inhibitor, fluvastatin sodium (Lescol®, Sandoz Pharmaceuticals Corp.), is the only entirely synthetic agent in this class. This agent has a distinct biopharmaceutic profile that may be responsible for certain safety benefits. Fluvastatin exhibits a favorable drug-interaction profile when used in combination with cyclosporine, fibric acids, erythromycin, or niacin. To date, no case of drug-related myopathy or rhabdomyolysis has been documented in any patient receiving fluvastatin. The hepatotoxicity profile of fluvastatin is also favorable; liver-enzyme testing—required with all HMG-CoA reductase inhibitors—is recommended less frequently during the first year of therapy with this agent than with the other HMG-CoA reductase inhibitors. Both its favorable safety profile and its cost effectiveness render fluvastatin a highly attractive option when therapy calls for moderate reductions in cholesterol levels.