氨氯地平对阿托伐他汀调脂作用的影响

目的观察氨氯地平对高血压合并冠心病患者阿托伐他汀调脂作用的影响。方法选择高血压合并冠心病患者174例,根据用药情况将患者分为2组,A组86例,以氨氯地平为基础的降压方案+阿托伐他汀;B组88例,无氨氯地平的降压方案+阿托伐他汀。分别观察2组在治疗前,治疗后2、4、8周时血脂、肝功、肌酸激酶等变化及不良反应发生情况。结果 A组与B组患者治疗前血清TC、TG、LDL-C、HDL-C水平差异无统计学意义(P0.05)。与治疗前比较,A组和B组患者治疗后2、4、8周血清TC、LDL-C水平明显降低,差异有统计学意义(P0.05);A组患者治疗后4、8周血清HDL-C水平明显升高,8周血清TG水平明显降低,差异有统计学意义(P0.05);B组患者治疗后2、4、8周血清HDL-C水平虽有升高趋势,TG水平虽有下降趋势,但差异无统计学意义(P0.05)。与B组比较,A组患者治疗后4、8周血清TC、LDL-C水平明显下降;治疗后8周血清HDL-C水平明显升高,差异有统计学意义(P0.05)。结论氨氯地平可能加强高血压合并冠心病患者阿托伐他汀的调脂作用,合用无明显不良反应。     

Impact of interferon-free antivirus therapy on lipid profiles in patients with chronic hepatitis C genotype 1b

AIM To investigate the influence of interferon-free antivirus therapy on lipid profiles in chronic hepatitis C virus genotype 1b(HCV1b) infection.METHODS Interferon-free antiviral agents were used to treat 276 patients with chronic HCV1 b infection, and changes in serum lipids of those who achieved sustained virologic response(SVR) were examined. The treatment regimen included 24 wk of daclatasvir plus asunaprevir(DCV + ASV) or 12 wk of sofosbuvir plus ledipasvir(SOF + LDV). SVR was achieved in 121(85.8%) of 141 patients treated with DCV + ASV and 132(97.8%) of 135 patients treated with SOF + LDV. In the two patient groups(DCV + ASV-SVR and SOF + LDV-SVR), serum total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), and triglycerides were measured at baseline during treatment and at 4 and 12 wk after treatment. Then, longitudinal changes in lipid profiles were analyzed.RESULTS Serum levels of TC, LDL-C, and HDL-C were significantly increased throughout the observation period in both the DCV + ASV-SVR and SOF + LDV-SVR groups. During antivirus treatment, the increases in TC and LDL-C were significantly greater in the SOF + LDVSVR group than in the DCV + ASV-SVR group(P 0.001). At 4 and 12 wk after the therapy, serum levels of TC and LDL-C were similar between the two groups and were significantly greater than those at baseline. Approximately 75%-80% of the increase in TC was derived from an increased LDL-C. In multiple regression analysis, the difference in therapy protocol(DCA + ASV or SOF + LDV) was an independent predictor that was significantly associated with the increase in TC and LDL-C at 4 wk of therapy.CONCLUSION Serum cholesterol significantly increased during SOF + LDV treatment. After treatment, HCV elimination was associated with a similar increase in cholesterol regardless of the therapy protocol.     

Serum lipid comparison in patients treated by statins or fibrates: existence of bad HDL-C responders to statins

INTRODUCTION: Major cardiac events are strongly associated with high levels of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C). The HDL-C target level (40 mg/dl) is often not achieved with statins. The aim of this study was to compare the proportions of patients achieving the HDL-C target levels after one year of treatment with statins or fibrates. Furthermore, a subgroup with low HDL-C levels during statin treatment was investigated and suggestions are made for a better management of these patients. METHODS: A survey of lipid levels, cardiovascular disease and risk factors in 120 outpatients treated with a statin or a fibrate for hyperlipidaemia (total cholesterol (TC) > 250 mg/dl or triglycerides (TG) > 200 mg/dl after diet). After one year of treatment the proportions of patients achieving the target levels for TC, LDL-C, HDL-C,TG,TC/HDL-C and LDL-C/HDL-C are compared for statins and fibrates. RESULTS: The proportions of patients achieving the target lipid levels with statins or fibrates are comparable except for HDL-C. Compared to the baseline, the proportion of patients achieving the HDL-C target level of 40 mg/dl increases only by 8.3% for statins and by 42.9% for fibrates. In total, 38.5% of the statin group had low HDL-C-levels after one year of treatment. Among these patients, eight were treated with a fibrate before the statin and six were treated with a fibrate afterwards. In those 14 patients, mean HDL-C increased during fibrate treatment by 48.5% and TC/HDL-C and LDL-C/HDL-C decreased by 25.7 and 26.5%, respectively as compared with statins. CONCLUSIONS: Patients with low levels of HDL-C during statin treatment had far better levels of HDL-C, TC/HDL-C and LDL-C/HDL-C with fibrates. A randomised double-blind crossover trial with simvastatin and fenofibrate has been initiated to corroborate these findings.     

Cholesterol levels after 3 days of high-dose simvastatin in patients at moderate to high risk for coronary events

BACKGROUND: Elevated levels of low-density lipoprotein cholesterol (LDL-C) impair vascular function by a variety of mechanisms. HMG CoA reductase inhibitors (statins) improve endothelial function by lowering LDL-C and possibly by other "pleiotropic" effects. How rapidly statins can lower LDL-C has not been thoroughly studied. METHODS: We examined the lipid response to 3 days of high-dose simvastatin in a randomized prospective double-blind placebo-controlled crossover study. Twenty-seven subjects at moderate to high risk for coronary heart disease (CHD) received either simvastatin 80 mg/day for 3 days followed by placebo for 3 days or placebo followed by simvastatin. After a washout period of 10 to 14 days, subjects received the opposite treatment. Nonfasting blood lipid levels, including total cholesterol, direct LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides, were obtained before randomization and after each 3-day treatment period. RESULTS: The mean LDL-C level at baseline was 107 mg/dl and decreased 24% in patients receiving simvastatin and 5.6% in patients receiving placebo (P < 0.001). Statistically significant reductions were also achieved in the total cholesterol and cholesterol/HDL-C ratio: 14% and 12%, respectively. Changes in HDL-C and triglyceride levels were not significant. CONCLUSION: Treatment with simvastatin for only 3 days results in a 24% drop in the LDL-C level. As defined by ATPIII, this decrease is comparable to that necessary to lower the LDL-C from one risk level to a lower one and is, therefore, both clinically and statistically significant.     

三磷酸腺苷结合盒转运体A1基因多态性与辛伐他汀调脂的关系

目的：研究三磷酸腺苷结合盒转运体A1（ABCA1）基因R219K多态性对血脂水平及辛伐他汀调脂治疗的影响。方法：原发性高脂血症患者80例,给予辛伐他汀20mg／d,治疗8周,治疗前后测定患者血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）及高密度脂蛋白胆固醇（HDL-C）浓度,治疗期间进行不良反应的监测。使用TaqMan荧光探针技术测定患者ABCA1基因R219K多态性。根据不同的基因型分组,比较不同基因型之间血脂水平变化的差异。进而判定不同基因型对血脂水平及辛伐他汀疗效的影响。结果：ABCA1 R219K基因存在三种基因型,即RR、RK和KK基因型。辛伐他汀治疗前RR基因型和RK基因型HDL—C水平明显低于KK基因型（P〈0．05）。辛伐他汀治疗8周后,三种基因型TC、TG、LDL-C水平均较前降低,HDL—C水平均较前升高;治疗后RR及RK基因型HDL—C水平仍低于KK型（P〈O．05）;但TC、TG、LDL—C和HDL—C水平的变化在不同基因型组之间无显著差异（P〉0．05）。结论：ABCA1基因R219K单核苷酸多态性可影响HDL—C水平,K等位基因与高HDL-C水平相关,但与辛伐他汀治疗的个体差异性无关。     

The long-term effects of rosiglitazone on serum lipid concentrations and body weight

OBJECTIVE: Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentrations and low density lipoprotein (LDL) particle size, it has unwanted effects on total cholesterol (TC) and LDL cholesterol (LDL-C) concentrations and body weight in some short-term studies. The aim of this study was to evaluate the long-term effects of rosiglitazone on serum lipid levels and body weight. DESIGN: Open labelled clinical study. PATIENTS AND MEASUREMENTS: We prospectively evaluated fasting serum glucose, haemoglobin A(1c) (HbA(1c)), lipid profiles and body weight at baseline and every 3 months after the use of rosiglitazone (4 mg/day) for 18 months in 202 type 2 diabetic patients. RESULTS: TC levels increased maximally at 3 months and decreased thereafter. However, overall, TC levels remained significantly higher at 18 months than those at baseline. LDL-C levels from the 3-month to the 12-month timepoint were significantly higher than those at baseline. However, after 15 months, LDL-C concentrations were not significantly different from basal LDL-C concentrations. HDL-C levels increased after the first 3 months and these levels were maintained. The increment of change in HDL-C was more prominent in patients with low basal HDL-C concentrations than in patients with high basal HDL-C concentrations. Body weight increased after the first 3 months and these levels were maintained. CONCLUSIONS: HDL-C and body weight increased and remained elevated for the duration of the study. There was an initial increase in LDL-C but this attenuated and by the end of the study was not significantly elevated above baseline levels.     

Modification of liver fibrosis,glucose and lipid profile after hepatitis C virus clearance with direct-acting antiviral agents

IntroductionThere is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels.Methods445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48).ResultsThe SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3–14.3) kPa at baseline to 6.4 (IQR 4.9–8.9) at SVR48 (p < 0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1–3.3) to 1.3 (IQR 0.9–2.0) (p < 0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5–1.7) to 0.3 (IQR 0.2–0.4) and from 6.2 (5.0–7.5) to 4.9 (IQR 3.8–5.9) (p < 0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172 mg/dL and 101.5 mg/dL to 191 mg/dL and 117.5 mg/dL (p < 0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7 mg/dL at baseline to 127.2 mg/dL at SVR48 (p < 0.001).DiscussionSVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48.     

Effects of vitamin D supplementation along with endurance physical activity on lipid profile in metabolic syndrome patients: A randomized controlled trial

Background and objectivesThis study was conducted to determine the effects of vitamin D supplementation along with endurance physical activity on lipid profile among metabolic syndrome patients.Materials and methodsIn a parallel randomized placebo controlled trial, 70 metabolic syndrome patients, were randomly assigned into three groups. Biochemical tests were assessed as baseline and after 12 weeks of intervention. Statistical analysis was performed using SPSS version 20.ResultsThe mean vitamin D levels was increased significantly in both vitamin D and vitamin D plus physical activity groups (P value < 0.05). No significant change was observed in the placebo group. Additionally, there was a significant decrease in total cholesterol and LDL-C in vitamin D plus physical activity group (P value < 0.05). No significant differences in changes of triglycerides and HDL-C among the three groups (P value > 0.05). While, in vitamin D group a decreased in total cholesterol, HDL-C, LDL-C and increase in triglycerides were observed, but did not reach a statistically significant.ConclusionDaily supplementation of vitamin D for 12 weeks, along with moderate endurance physical activity, significantly increase vitamin D concentration and induce a significant reduction in lipid profile in metabolic syndrome patients.     

阿托伐他汀联合非诺贝特对冠心病并糖尿病患者的疗效与安全性

目的：探讨阿托伐他汀联合非诺贝特治疗冠心病合并糖尿病患者的调脂疗效与安全性。方法：选择100例确诊冠心病合并糖尿病的患者为研究对象,在常规治疗基础上按1∶1随机分为两组：（1）他汀组（50例,给予阿托伐他汀20mg,每晚1次）;（2）联合治疗组（50例,给予阿托伐他汀20mg 每晚1次,非诺贝特200mg 每日1次治疗）。分别于治疗前、治疗6周和12周后检测血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平,观察治疗前后上述血脂水平的变化、达标率,并记录不良反应及临床事件。结果：治疗6周后,两组血清 TC、TG、LDL-C 水平均明显低于用药前,治疗12周后降低更为明显（P ＜0.05～＜0.01）,且12周后与他汀组比较,联合治疗组 TC [（4.35±0.71）mmol/L 比（4.09±0.56）mmol/L],TG [（2.35±0.62）mmol/L 比（1.65±0.49）mmol/L]和 LDL-C 水平[（2.01±0.39）mmol/L 比（1.85±0.22）mmol/L]降低更显著（P＜0.05或＜0.01）;两组治疗后 HDL-C 水平均升高,12周后升高更明显但两组比较无统计学差异（P ＞0.05）。治疗12周后,联合治疗组 LDL-C、TG、HDL-C 各项指标达标率、3项血脂指标均达标和非 HDL-C 的达标率（分别为70％、68％、80％、58％、70％）均明显高于他汀组（分别为50％、46％、48％、10％、48％）（P ＜0.05或＜0.01）。治疗期间两组均未观察到严重不良反应。结论：阿托伐他汀联合非诺贝特治疗冠心病合并糖尿病患者较单用阿托伐他汀更有效,能更全面地改善各项血脂水平,有助于血脂的全面达标,且具有更良好的安全性和耐受性。     

Treatment of hepatitis C virus with peg-interferon and ribavirin combination therapy significantly affects lipid metabolism

Aim:  We investigated lipid metabolism in patients with chronic hepatitis C virus (HCV), serotype 1, undergoing combination therapy with PEG-IFN α-2b (PEG-IFN) and ribavirin (RBV).
Methods:  A total of 185 patients with chronic HCV (HCV serotype 1; HCV RNA levels ≥ 100 KIU/mL) who received a combination of PEG-IFN and RBV were enrolled.
Results:  Sustained virological response (SVR) was obtained in 82 cases (44.3%). The median age, red blood cell and platelet counts differed significantly between the SVR and non-SVR groups before treatment. However there was no significant difference between total cholesterol (TC), LDL-cholesterol (LDL-C) and triglyceride (TG) levels before treatment. TC and LDL-C levels decreased during the treatment in both groups. In the SVR group, TC and LDL-C levels increased quickly after the end of the treatment and were higher than those before treatment. On the other hand, TC and LDL-C levels returned to pretreatment levels in the non-SVR group and were significantly lower than in the SVR group. TG levels were elevated in both groups after the beginning of treatment. After the end of treatment, this elevation persisted in the SVR group, while TG levels returned to pre-treatment levels in the non-SVR group. There was a significant difference in TG levels at 24 weeks after the end of the treatment between the 2 groups. In the non-SVR group some patients achieved normalization of ALT (alanine aminotransferase) but persistence of normal ALT levels did not contribute to the increase of TC and TG.
Conclusion:  TC, LDL-C and TG levels increase only in patients with HCV, serotype 1, undergoing combination therapy when a SVR is achieved.     

Sustained improvement of dyslipidaemia in HAART-treated patients replacing stavudine with tenofovir

OBJECTIVE: To describe the 12-month evolution of lipid profile in HIV-infected virologically suppressed patients substituting tenofovir for stavudine. DESIGN AND METHODS: 'Recover' was a prospective, multicenter, switch study conducted at 120 HIV units across Spain designed to identify single nucleoside analogue substitution due to adverse events in real practice. Tenofovir substituted stavudine in 873 adult patients. No other substitutions were allowed. This lipid sub-study included 352 randomly recruited patients with complete follow-up and lipid parameters. MAIN OUTCOME MEASURES: Changes in fasting levels of total cholesterol (TC), high and low-density lipoprotein cholesterol (HDL-C and LDL-C), and triglycerides (TG) at 48 weeks, and their cardiovascular risk (CVR) translation. RESULTS: At 48 weeks, there was a sustained reduction in median TC (-17.5 mg/dl; P < 0.001), LDL-C (-8.1 mg/dl; P < 0.001), and TG (-35 mg/dl; P < 0.001). HDL-C remained roughly unchanged (-0.8 mg/dl). Patients with baseline hyperlipidaemia showed greater reductions in LDL-C (-29 mg/dl; P < 0.001) and TG (-76 mg/dl; P < 0.001). The greatest TG reduction was observed in patients with severe hyper-TG (-266 mg/dl; P < 0.001). The estimated 10-year CVR decreased in all patients (P < 0.001), and to a higher extent in patients with baseline hyperlipidaemia. There was a trend towards reduction according to the use of lipid-lowering agents (11.6% to 9,9%; P = non-significant). CONCLUSIONS: The substitution of tenofovir for stavudine causes a sustained improvement of dyslipidaemia. The reduction, although modest, is robust and sustained over time, and significantly reduces the CVR. This switch strategy is safe and contributes to an improvement in the lipid profile, especially TG, in HAART-treated patients.     

杭州市部分职业人群血清非高密度脂蛋白胆固醇水平分析

低密度脂蛋白胆固醇（LDL-C）长期来被认为是致动脉粥样硬化（AS）的决定性因素和降脂治疗预防心血管疾病的首要目标。在低甘油三酯（TG）水平时,LDL-C含有大部分致AS的胆固醇;然而,当TG水平增高时,富含TG的脂蛋白、中低密度脂蛋白胆固醇（IDL-C）和极低密度脂蛋白胆固醇（VLDL-C）含有大量致AS的胆固醇,也应进行治疗。     

匹伐他汀对动脉粥样硬化患者脂蛋白颗粒和氧化型低密度脂蛋白的影响

目的探讨匹伐他汀对动脉粥样硬化(AS)患者脂蛋白颗粒和氧化型低密度脂蛋白(ox-LDL)的影响。方法连续入选未经降脂药物治疗的受试人群36例(AS患者18例,健康受试者18例),分为匹伐他汀组和对照组。Lipoprint脂蛋白分类检测仪分别对LDL和HDL颗粒进行分类。治疗8周后比较两组治疗前后脂蛋白颗粒和ox-LDL的变化。结果与治疗前相比,匹伐他汀治疗后低密度脂蛋白胆固醇(LDL-C),总胆固醇(TC),甘油三酯(TG)和载脂蛋白B的浓度显著降低(P<0.05),大颗粒、中等颗粒和小颗粒LDL-C的浓度及中等颗粒和小颗粒LDL的百分比也显著降低(P<0.05)。同时,高密度脂蛋白胆固醇(HDL-C)浓度显著增加(P<0.05),ox-LDL浓度显著降低(P<0.05)。结论匹伐他汀治疗8周可显著改善AS患者的血脂谱,并降低LDL-C和ox-LDL浓度,减少氧化应激反应。     

Statin therapy/lipid lowering therapy among Indian adults with first acute coronary event: The dyslipidemia Residual and Mixed Abnormalities IN spite of Statin therapy (REMAINS) study

ObjectiveThe primary objective was to evaluate the effect of statin therapy/lipid lowering therapy (LLT) on lipid profile, in adults presenting with first acute coronary event.Methods and materialA multicentre, observational, prospective cohort study of lipid profiles pre- and post-statin therapy/LLT, among adult patients with confirmed diagnosis of first acute coronary event. The primary outcome measures were low-density lipoprotein cholesterol (LDL-C) in mg/dl, high-density lipoprotein cholesterol (HDL-C) in mg/dl and triglycerides (TG) in mg/dl at baseline and end of study (EOS, 12 weeks [mean: 13.5 weeks]).ResultsTotally 474 patients completed the study. Number of patients with any LDL-C abnormality (LDL-C [all; LDL was abnormal, either alone or along with other lipid parameter(s)]) decreased from 118 (24.9%) to 27 (5.7%), and for LDL-C (only; only the LDL was abnormal), from 46 (9.7%) to 13 (2.7%), both from baseline to EOS. Of 118 patients with high LDL-C (all) at baseline, 91 (77.1%) had reduction in LDL-C to <100 mg/dl, of which 54 (45.8%) had LDL-C <70 mg/dl at EOS. The patients with LDL-C fraction abnormalities decreased, while HDL-C abnormalities increased at EOS from baseline. No major difference was observed at baseline and EOS in levels of TG (all [TG was abnormal, either alone or along with other lipid parameter(s)]) and TG (only [only the TG was abnormal]). Six (1.3%) had seven serious adverse events.ConclusionsThough statin therapy is effective in lowering LDL-C, there still remains residual dyslipidemia, which probably should be tackled with therapeutic and non-therapeutic options.     

载脂蛋白B/载脂蛋白A1及相关血脂指标对冠心病经皮冠状动脉介入治疗术预后的预测价值

目的探讨冠心病经皮冠状动脉介入治疗（percutaneous transluminal coronary, PCI）术后载脂蛋白B/载脂蛋白A1（ApoB/A1）比值及相关血脂指标的变化,及其对术后心脏事件的预测价值。 方法收集2013年5月至2014年8月在晋中市第一人民医院行PCI的老年患者117例,根据服用降脂药物的种类分为阿托伐他汀组（71例）、辛伐他汀组（46例）。观察比较两组患者术前及术后1、6、12个月的总胆固醇（TC）、LDL-C、HDL-C水平及ApoB/ApoA1、TC/HDL比值的变化情况,并分析其与12个月内发生心脏事件（再发心绞痛、心肌梗死、心源性猝死、再次血管重建术、死亡）的相关性。组间不同时点的比较以及趋势性和交互作用均采用重复测量方差分析,预后分析采用受试者工作特征曲线下面积（AUC）。 结果出院后1个月内不良事件发生率为4.3%（5/117）,出院后1～6个月不良事件发生率为6.0%（7/117）,出院后6～12个月不良事件发生率为12.0%（14/117）。两组患者LDL-C、HDL-C、TC水平及ApoB/ApoA1比值、TC/HDL-C比值的变化均为线性趋势（F=53.878、134、10.364、52.852、64.523,P<0.05或0.01）,而且随访期间两组患者LDL-C、HDL-C、TC水平均处于正常范围。术后1个月,各项血脂指标对于判断PCI术后预后的意义不大,但ApoB/ApoA1比值较其他血脂指标对术后预后判断价值更大（AUC=0.43,最接近0.05）;术后6、12个月ApoB/ApoA1比值较其他血脂指标对术后预后判断价值也更大（AUC=0.709、0.010,均P<0.05）。 结论PCI术后ApoB /ApoA1比值与心脏事件的发生相关,相对于其他血脂指标预测价值更大,而且随着时间的延长其预测性越来越准确。     

Niacin Administration Significantly Reduces Oxidative Stress in Patients With Hypercholesterolemia and Low Levels of High-Density Lipoprotein Cholesterol

Oxidative stress has been implicated in the pathogenesis of cardiovascular disorders, including atherosclerosis. In pharmacological doses, niacin (vitamin B₃) was proven to reduce total cholesterol, triglyceride, very-low-density lipoprotein, and low-density lipoprotein levels, and to increase high-density lipoprotein (HDL) levels. The aim of this study was to evaluate the effect of niacin treatment in patients with low levels of HDL cholesterol (HDL-C; <40 mg%) on their lipid profile and oxidative stress status. Seventeen patients with hypercholesterolemia and low HDL-C and 8 healthy control subjects were enrolled in the study. The patients were treated with niacin for 12 weeks. Lipid profile, oxidative stress and C-reactive protein (CRP) levels were determined at the time of enrollment, and 2 and 12 weeks after initiation of niacin treatment. Subjects with lower HDL-C levels exhibited higher oxidative stress compared with subjects with normal HDL-C levels. Niacin treatment in hypercholesterolemic patients caused a significant increase in HDL-C and apolipoprotein A1 levels, and a decrease in triglyceride levels. Niacin also significantly reduced oxidative stress, as measured by a significant decrease in the serum content of thiobarbituric acid reactive substances, lipid peroxides and paraoxonase activity, compared with the levels before treatment. Although serum CRP levels were not affected by niacin treatment, a correlation between CRP and HDL levels was obtained when computing the results. Niacin treatment in hypercholesterolemic patients with low HDL levels caused a significant decrease in their oxidative stress status. These results indicate an additional beneficial effect of niacin beyond its ability to affect the lipid profile.     

Usefulness of lipoprotein ratios in assessing carotid atherosclerosis in Japanese type 2 diabetic patients

ObjectiveIt is indicated that total/HDL cholesterol and LDL/HDL cholesterol ratios have more predictive power for cardiovascular disease compared to classic lipid parameters. However, there have been few reports about the usefulness of these indices for the assessment of early stage atherosclerosis in Japanese type 2 diabetic subjects.MethodsWe examined the relation between various lipid parameters and carotid atherosclerosis in 934 type 2 diabetic subjects without apparent atherosclerotic diseases (males, 71.7%; age, 59.6 ± 10.5 years (mean ± SD)). Serum concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride were measured. LDL cholesterol (LDL-C) level was calculated using the Friedewald formula. The presence of carotid plaque and intima-media thickness (IMT) were evaluated by ultrasonography.ResultsA stepwise multivariate regression analysis demonstrated that HDL-C (β = ?0.110, p < 0.001), TC/HDL-C (β = 0.132, p < 0.001) and LDL-C/HDL-C ratios (β = 0.132, p < 0.001) were independent determinants of IMT even after adjustment of other conventional risk factors. However, there was no significant correlation between IMT and TC, triglyceride, LDL-C, and non-HDL-C levels. TC/HDL-C and LDL-C/HDL-C ratios and non-HDL-C levels were significantly higher, but HDL-C levels were significantly lower in patients with carotid plaque than those without it (p < 0.05). There was no significant difference between the groups regarding TC, LDL-C, and triglyceride levels. Furthermore, TC/HDL-C (OR; 1.34, p < 0.001) and LDL-C/HDL-C (OR; 1.54, p < 0.001) ratios showed a positive and linear relationship with the prevalence of carotid plaque, whether covariates were adjusted or not.ConclusionsTC/HDL-C and LDL-C/HDL-C ratios are useful as a tool to assess the risk of early stage atherosclerosis in Japanese type 2 diabetic patients.     

Association between causative mutations and response to PCSK9 inhibitor therapy in subjects with familial hypercholesterolemia: A single center real-world study

Background and aimsFamilial hypercholesterolemia (FH) is an autosomal dominant disease that leads to cardiovascular (CV) disease. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-I) demonstrated efficacy in low-density lipoprotein cholesterol (LDL-C) reduction and in prevention of CV events. The aim of our study is to evaluate the relationship between LDL receptor (LDLR) mutations and response to PCSK9-I therapy.Methods and resultsWe evaluated total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in consecutive patients with FH before PCSK9-I treatment and after 12 (T12w) and 36 (T36w) weeks of treatment. We evaluated LDL-C target achievement according to different mutations in LDLR. Eighty FH subjects (mean age:54 ± 13.3 years), 39 heterozygous (He) with defective LDLR gene mutations, 30 He with null mutations and 11 compound-He or homozygous (Ho) were recruited. At baseline, 69 subjects were under maximal lipid lowering therapy (MLLT) and 11 subjects had statin-intolerance. From baseline to T36w we observed an overall 51% reduction in LDL-C. We found no difference in LDL-C changes between subjects with He-defective mutation and He-null mutations both at T12w (p = 1.00) and T36w (p = 0.538). At T36w, LDL-C target was achieved in 59% of He-defective mutations subjects and in 36% of He-null mutations subgroup (p = 0.069), whereas none of compound-He/Ho-FH achieved LDL-C target.ConclusionsAfter 36 weeks there were no differences in response to PCSK9-I therapy between different groups of He-FH subjects. Response to PCSK9-I was significantly lower in carriers of compound-He/Ho mutations.Registration number for clinical trials: NCT04313270 extension.     

Impact of HCV Eradication on Lipid Metabolism in HIV/HCV Coinfected Patients: Data from ICONA and HepaICONA Foundation Cohort Study

Objectives: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. Methods: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. Results: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p < 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). Conclusions: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.     

Major Lipids and Future Risk of Pneumonia: 20-Year Observation of the Atherosclerosis Risk in Communities (ARIC) Study Cohort

BackgroundCirculating lipids have been implicated as important modulators of immune response, and altered lipid levels correlate with the severity of infection. However, long-term prognostic implications of lipid levels regarding future infection risk remain unclear. The current project aims to explore whether baseline lipid levels are associated with risk of future serious infection, measured by hospitalization for pneumonia.MethodsA retrospective analysis was performed in 13,478 participants selected from the Atherosclerosis Risk in Communities (ARIC) study, a large community-based longitudinal cohort in the United States with a median follow-up time of >20 years. First incident of hospitalization for pneumonia was identified through hospital discharge records. Cox proportional hazard models were used to assess the association of baseline major lipid levels (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides) with time to first pneumonia hospitalization.ResultsA total of 1969 (14.61%) participants had a pneumonia hospitalization during a median follow-up time of 21.5 years. The hazard ratio (HR) for pneumonia hospitalization was 0.90 (95% confidence interval, 0.87-0.92) for every 10-mg/dL increase in baseline HDL-C, and 1.02 (95% confidence interval, 1.02-1.03) for every 10-mg/dL increase in baseline triglycerides. HDL-C and triglycerides both remained significant predictors of pneumonia hospitalization after multivariable adjustment. Such associations were not seen with baseline LDL-C or total cholesterol levels.ConclusionLower baseline HDL-C and higher triglyceride levels were strongly associated with increased risk of long-term pneumonia hospitalization in a large longitudinal US cohort.