Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol and APOE ε4 allele

BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection.The relationship between cholesterol,APOE alleles,and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIM To investigate the role of APOE-ε2,-ε3,and-ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODS A total of 299 treatment-na?ve HCV patients were included in this retrospective study.Patients were stratified in chronic hepatitis C(CHC)(n=206)and spontaneous clearance(SC)(n=93).A clinical record was registered.Biochemical tests were assessed by dry chemistry assay.APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTS Total cholesterol,low-density lipoprotein cholesterol(LDL-c),triglycerides,and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOEε4 allele(12.4%vs 7.3%).SC patients were overweight(54.8%).Theε4 allele was associated with SC(OR=0.55,95%CI:0.31-0.98,P=0.042)and mild fibrosis(F1-F2)in CHC patients(OR 0.091,95%CI 0.01-0.75,P=0.020).LDL-c≥101.5 mg/dL(OR=0.20,95%CI:0.10-0.41,P<0.001)and BMI≥26.6 kg/m2(OR=0.37,95%CI:0.18-0.76,P<0.001)were associated with SC status;while ALT≥50.5 IU/L was negatively associated(OR=5.67,95%CI:2.69-11.97,P<0.001).CONCLUSION In SC patients,the APOEε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.

Intensive lipid-lowering therapy,time to think beyond low-density lipoprotein cholesterol

Statins have been shown to be effective in reducing cardiovascular events.Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol(LDL-c).Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have further improved clinical outcomes.Unselective application of these treatments is undesirable and unaffordable and,therefore,has been guided by LDL-c level.Nonetheless,the residual risk in the post-statin era is markedly heterogeneous,including thrombosis and inflammation risks.Moreover,the lipoprotein related risk is increasingly recognised to be related to other non-LDL-c markers such as Lp(a).Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease,post coronary artery bypass graft and diabetes.Notably,these clinical entities share similar phenotype of large burden of atherosclerotic plaques.Novel plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular sites.Those patients may be suitable candidates for intensive lipid lowering treatment.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

The rate of patients at high risk for cardiovascular disease with an optimal low-density cholesterol level: a multicenter study from Thailand

Background Hypercholesterolemia is a major risk factor for cardiovascular events in patients with established atherosclerotic disease (EAD) and in those with multiple risk factors (MRFs). This study aimed to investigate the rate of optimal low-density lipoprotein (LDL) cholesterol level in a multicenter registry of patients at high risk for cardiovascular events. Methods A multicenter registry of EAD and MRF patients was conducted. Demographic data,medical history,cardiovascular risk factors,anthropometric data,laboratory data,and medications were recorded and analyzed. We classified patients according to target LDL levels based on recommendation by the European Society of Cardiology (ESC) 2011 into Group 1 which is EAD and diabetes or chronic kidney disease (CKD)–target LDL below 70 mg/dL,and Group 2 which is MRF without diabetes or CKD–target LDL below 100 mg/dL. The rate of optimal LDL level in patients with Group 1 and Group 2 was analyzed and stratified according to the treatment pattern of lipid-lowering medications. Results A total of 3100 patients were included. Of those,51.7% were male. Average age was 65.8 ± 9.7 years. Average LDL level was 96.3 ± 32.6 mg/dL. A vast majority (92.7%) received statin and 9.3% received ezetimibe. Optimal LDL level was achieved in 20.3% of patients in Group 1 (LDL < 70 mg/dL),and in 46.6% in Group 2 (LDL < 100 mg/dL). The overall rate of optimal LDL control was 23% since 89.6% of study population belongs to Group 1. The rate of optimal LDL was not different between high and low potency statin. Factors that were associated with optimal LDL control were older age,the presence of coronary artery disease or peripheral artery disease. Conclusions The rates of optimal LDL level were unacceptably low in this study population. As such,a strategy to improve LDL control in high-risk population should be implemented.

Hepatitis C virus G1b infection decreases the number of small low-density lipoprotein particles

AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P &#x0003c; 0.001), as was that of high-density lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P &#x0003c; 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P &#x0003c; 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P &#x0003c; 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1b infection decreases the numbers of medium, small, and very small LDL particles.

Homozygous phytosterolemia and a literature review:A case report

BACKGROUND Phytosterolemia,also known as sitosterolemia,is a rare autosomal recessive disease characterized by elevated plasma plant sterol levels and xanthomata,which is easily misdiagnosed as familial hypercholesterolemia.Patients with homozygous phytosterolemia often have severe clinical manifestations,with xanthomata in childhood and premature atherosclerosis.Our patient had a milder clinical phenotype.CASE SUMMARY This report describes a patient with homozygous phytosterolemia who presented with only elevated cholesterol and low-density lipoprotein cholesterol(LDL-C)without xanthomata,arteriosclerosis,or hematological abnormalities.Homozygous mutation of ABCG5 which encodes an ATP-binding cassette transporter,was detected by whole exome sequencing and diagnosed as phytosterolemia.Measurement of the patient’s plasma plant sterol levels detected significant elevations in stigmasterol,rapeseed oil-derived plant sterol,andβ-glutaminol levels.Ezetimibe was started and a low plant sterol diet was recommended.The patient’s blood lipid profile was reexamined one month later and showed significant decreases in total cholesterol and LDL-C levels.Phytosterolemia has similar clinical features as familial hypercholesterolemia,is highly susceptible to misdiagnosis,and has a very low incidence,and therefore clinicians need to consider a genetic diagnosis of a definitively hyperlipidemic disorder when statin drugs fail to lower lipid levels.CONCLUSION Phytosterolemia is easily misdiagnosed as familial hypercholesterolaemia and can be treated by dietary modification and cholesterol absorption inhibitors to lower blood lipids.

Association and its population heterogeneities between low-density lipoprotein cholesterol and all-cause and cardiovascular mortality:A population-based cohort study

Background:The association and its population heterogeneities between low-density lipoprotein cholesterol(LDL-C)and all-cause and cardiovascular mortality remain unknown.We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease(CVD)mortality and heterogeneities in the associations among different population subgroups.Methods:A total of 2,968,462 participants aged 35-75 years from China Health Evaluation And risk Reduction through nationwide Teamwork(ChinaHEART)(2014-2019)were included.Cox proportional hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between LDL-C categories(<70.0,70.0-99.9,100.0-129.9[reference group],130.0-159.9,160.0-189.9,and≥190.0 mg/dL)and all-cause and cause-specific mortality.Results:During a median follow-up of 3.7 years,57,391 and 23,241 deaths from all-cause and overall CVD were documented.We observed J-shaped associations between LDL-C and death from all-cause,overall CVD,coronary heart disease(CHD),and ischemic stroke,and an L-shaped association between LDL-C and hemorrhagic stroke(HS)mortality(P for non-linearity<0.001).Compared with the reference group(100.0-129.9 mg/dL),very low LDL-C levels(<70.0 mg/dL)were significantly associated with increased risk of overall CVD(hazard ratio[HR]:1.10,95%confidence interval[CI]:1.06-1.14)and HS mortality(HR:1.37,95%CI:1.29-1.45).Very high LDL-C levels(≥190.0 mg/dL)were associated with increased risk of overall CVD(HR:1.51,95%CI:1.40-1.62)and CHD mortality(HR:2.08,95%CI:1.92-2.24).The stronger associations of very low LDL-C with risk of CVD mortality were observed in individuals with older age,low or normal body mass index,low or moderate 10-year atherosclerotic CVD risk,and those without diagnosed CVD or taking statins.Stronger associations between very high LDL-C levels and all-cause and CVD mortality were observed in younger people.Conclusions:People with very low LDL-C had a higher risk of all-cause,CVD,and HS mortality;those with very high LDL-C had a higher risk of all-cause,CVD,and CHD mortality.On the basis of our findings,comprehensive health assessment is needed to evaluate cardiovascular risk and implement appropriate lipid-lowering therapy for people with very low LDL-C.

Editorial on hemoglobin A1c, blood pressure, and lowdensity lipoprotein cholesterol goals in diabetics

The American Diabetes Association (ADA) 2013 guidelines state that a reasonable hemoglobin A1c goal for many nonpregnant adults with diabetes is less than 7.0% a hemoglobin A1c level of less than 6.5% may be considered in adults with short duration of diabetes, long life expectancy, and no significant cardiovascular disease if this can be achieved without significant hypoglycemia or other adverse effects of treatment. A hemoglobin A1c level less than 8.0% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced macrovascular and microvascular complications, extensive comorbidities, and long-standing diabetes in whom the hemoglobin A1c goal is difficult to attain despite multiple glucoselowering drugs including insulin. The ADA 2013 guidelines recommend that the systolic blood pressure in most diabetics with hypertension should be reduced to less than 140 mmHg. These guidelines also recommend use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in the treatment of hypertension in diabetics unless they are pregnant. Diabetics at high risk for cardiovascular events should have theirserum low-density lipoprotein (LDL) cholesterol lowered to less than 70 mg/dL with statins. Lower-risk diabetics should have their serum LDL cholesterol reduced to less than 100 mg/dL. Combination therapy of a statin with either a fibrate or niacin has not been shown to provide additional cardiovascular benefit above statin therapy alone and is not recommended. Hypertriglyceridemia should be treated with dietary and lifestyle changes. Severe hypertriglyceridemia should be treated with drug therapy to reduce the risk of acute pancreatitis.

Lower Baseline LDL Cholesterol Affects All-cause Mortality in Patients with First Percutaneous Coronary Intervention

Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. This study aimed to examine whether the “cholesterol paradox” also exists in the Chinese population.Methods A total of 2,056 patients who underwent the first percutaneous coronary intervention(PCI)between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L(100 mg/d L). The outcomes of interest included major adverse cardiovascular events(MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.Results All-cause mortality occurred in 8 patients(0.7%) from the low-LDL-C group and 12 patients(2.4%) in the high-LDL-C group, with a significant difference between the two groups(adjusted hazard ratio: 4.030, 95% confidence interval: 1.088–14.934;P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.Conclusion In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the “cholesterol paradox” may be inapplicable to Chinese populations.

EFFECTS OF RAPAMYCIN ON INTRACELLULAR CHOLESTEROL HOMEOSTASIS OF GLOMERULAR MESANGIAL CELL IN THE PRESENCE OF INTERLEUKIN-1β

Objective To investigate the effects of rapamycin on cholesterol homeostasis of glomerular mesangial cells and the underlying mechanisms. Methods Intracellular cholesterol accumulation was measured by Oil Red O staining and high performance liquid chromatography. The effects of rapamycin on interleukin-1β（1L-1β）-induced mRNA and protein changes of low-density lipoprotein receptor （LDLR） and ATP-binding cassette transporter Al （ABCAl） were assayed by quantitative real-time PCR and Western blot. Transient expressions of 3 types of mammalian target of rapamycin （mTOR）, including mTOR-WT （wild type）, mTOR-RR （rapamycin resistant, with kinase activity）, and mTOR-RR-KD （rapamycin resistant, without kinase activity）, were obtained by plasmid transfection. Results Rapamycin had no significant influence on intracellular cholesterol concentration trader normal condition, but it significantly decreased the intracellular cholesterol concentration in the presence of IL-1β. Rapamycin dose-dependently suppressed the increased expression of LDLR induced by IL-1β and up-regulated the suppressed expression of ABCAl caused by IL-1β Transient expression of 3 types of mTOR all reduced ABCAl mRNA expression significantly, which all could be overroded by rapamycin. Conclusions Rapamycin may contribute to the maintaining of glomerular mesangial cell intracellular cholesterol homeostasis under inflammatory state by both reducing cholesterol uptake and increasing cholesterol effiux. And the effect may be not completely mediiated by mTOR.

Lipoprotein in cholesterol transport: Highlights and recent insights into its structural basis and functional mechanism

Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease （CVD）. The highly dynamic lipoprotein molecules are capable of adopting an array of conformations that is crucial to lipid transport along the cholesterol transport pathway, among which high-density lipopro- tein （HDL） and low-density lipoprotein （LDL） are major players in plasma cholesterol metabolism. For a more detailed illustration of cholesterol transport process, as well as the development of therapies to prevent CVD, here we review the functional mechanism and structural basis of lipoproteins in cholesterol transport, as well as their structural dynamics in the plasma lipoprotein （HDL and LDL） elevations, in order to obtain better quantitative understandings on structure-function relationship of lipoproteins. Finally, we also provide an approach for further research on the lipoprotein in cholesterol transport.

Situational Analysis of Low-density Lipoprotein Cholesterol Control and the Use of Statin Therapy in Diabetes Patients Treated in Community Hospitals in Nanjing, China

Background：Comprehensive management of diabetes should include management of its comorbid conditions,especially cardiovascular complications,which are the leading cause of morbidity and mortality among patients with diabetes.Dyslipidemia is a comorbid condition of diabetes and a risk factor for cardiovascular complications.Therefore,lipid level management is a key of managing patients with diabetes successfully.However,it is not clear that how well dyslipidemia is managed in patients with diabetes in local Chinese health-care communities.This study aimed to assess how well low-density lipoprotein cholesterol （LDL-C） was managed in Nanjing community hospitals,China.Methods：We reviewed clinical records of 7364 diabetic patients who were treated in eleven community hospitals in Nanjing from October 2005 to October 2014.Information regarding LDL-C level,cardiovascular risk factors,and use of lipid-lowering agents were collected.Results：In patients without history of cardiovascular disease （CVD）,92.1% had one or more CVD risk factors,and the most common CVD risk factor was dyslipidemia.The overall average LDL-C level was 2.80 ± 0.88 mmol/L,which was 2.62 ± 0.90 mmol/L and 2.82 ± 0.87 mmol/L in patients with and without CVD history respectively.Only 38% of all patients met the target goal and 37.3% of patients who took lipid-lowering agents met target goal.Overall,24.5% of all patients were on lipid-lowering medication,and 36.3% of patients with a CVD history and 20.9% of patients without CVD history took statins for LDL-C management.The mean statin dosage was 13.9 ± 8.9 mg.Conclusions：Only a small portion of patients achieved target LDL-C level,and the rate of using statins to control LDL-C was low.Managing LDL-C with statins in patients with diabetes should be promoted,especially in patients without a CVD history and with one or more CVD risk factors.

Low levels of low-density lipoprotein cholesterol and cognitive decline

The relationship between low levels of serum low-density lipoprotein cholesterol(LDL-C)and subsequent cognitive decline remains unclear.The present study aimed to evaluate the longitudinal association between low LDL-C levels and cognition decline in the context of the current aggressive guideline-recommended targets(LDL-C levels less than 55 mg/dL for individuals at very high risk of cardiovascular events,and less than 70 mg/dL for high risk individuals).Data from wave 13(2016)to wave 14(2018)of the Health and Retirement Study(HRS)were utilized.LDL-C concentrations measured at wave 13 were categorized into 5 levels,reflecting currently recommended values for lipid lowering treatment.Of 7129 included participants(mean age:69.0±9.9 years,60.3%female),we found that compared to participants with LDL-C levels of 70.0-99.9 mg/dL,those with LDL-C levels of<55 mg/dL had significantly slower 2-year decline rates in global cognitive function(0.244 point/year;95%confidence interval(CI):0.065-0.422;P=0.008),working memory(0.068 point/year;95%CI:0.004-0.133;P=0.038),and borderline significantly in episodic memory(0.155 point/year;95%CI:-0.004-0.315;P=0.057).Similarly,significantly slower decline rates were observed in those with LDL-C levels of 55.0-69.9 mg/dL.The present study demonstrated that compared with LDL-C levels 70.0-99.9 mg/dL,low LDL-C levels(<70 mg/dL,especially<55 mg/dL)were associated with significantly slower cognitive decline in population-based setting.Future randomized controlled trials are warranted to ascertain the safety and benefit of current aggressive guideline-recommended targets on cognitive function.

Linkage of the cholesterol 7α-hydroxylase gene and low-density lipoprotein cholesterol conditional on apolipoprotein E association: the National Heart, Lung, and Blood Institute Family Heart Study

Background Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7α-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism. Methods Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used. Results The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.Conclusion Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.

Lowering low-density lipoprotein cholesterol: from mechanisms to therapies

Low-density lipoprotein(LDL)is the main carrier of cholesterol and cholesteryl ester in circulation.High plasma levels of LDL cholesterol(LDL-C)are a major risk factor of atherosclerotic cardiovascular disease(ASCVD).LDL-C lowering is recommended by many guidelines for the prevention and treatment of ASCVD.Statins,ezetimibe,and proprotein convertase subtilisin/kexin type 9 inhibitors are the mainstay of LDL-C-lowering therapy.Novel therapies are also emerging for patients who are intolerant to statins or respond poorly to standard treatments.Here,we review the most recent advances on LDL-C-lowering drugs,focusing on the mechanisms by which they act to reduce LDL-C levels.The article starts with the cornerstone therapies applicable to most patients at risk for ASCVD.Special treatments for those with little or no LDL receptor function then follow.The inhibitors of ATP-citrate lyase and cholesteryl ester transfer protein,which are recently approved and still under investigation for LDL-C lowering,respectively,are also included.Strategies targeting the stability of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol catabolism can be novel regimens to reduce LDL-C levels and cardiovascular risk.

非高密度脂蛋白胆固醇在冠心病危险性评估中的作用

目的探讨非高密度脂蛋白胆固醇（non-HDL-C）在冠心病危险性评估中的作用。方法对453例冠心病患者和336例健康对照血脂资料进行分析,比较non-HDL-C与其他血脂数据两组间差异的显著性,以及non-HDL-C和低密度脂蛋白胆固醇（LDL-C）的相关性。结果冠心病组non-HDL-C值[（4.02±1.20）mmol/L]明显高于健康对照组[（3.30±0.58）mmol/L],差异有统计学意义（t=10.132,P〈0.001）。non-HDL-C在冠心病组和健康对照组间差异的显著性高于LDL-C和总胆固醇（TC）及三酰甘油（TG）。随着TG水平增高,non-HDL-C与LDL-C相关性下降。结论non-HDL-C对冠心病危险性评估作用优于LDL-C,而且方法简便易行,适合临床推广应用。

脂蛋白血管外循环与胆固醇逆向转运

胆固醇逆向转运是机体周围组织细胞胆固醇转运至肝脏转化排泄的重要生理过程，它在维持机体胆固醇平衡和防止动脉粥样硬化的发生和发展过程中起着重要的作用。脂蛋白是胆固醇的载体，血浆脂蛋白可以透过血管壁进入间质组织，通过与组织细胞直接接触接受细胞释出的胆固醇，再经淋巴液或直接返回血浆，并运至肝脏代谢。因此，脂蛋白血管外循环是胆固醇逆向转运重要组成部分。研究脂蛋白血管外循环的过程、特征以及代谢变化的规律，对心血管病的防治具有重要的理论和实践价值。

Influences of blood lipids on the occurrence and prognosis of hemorrhagic transformation after acute cerebral infarction: a case-control study of 732 patients

Background: To study the influence of blood lipid levels on hemorrhagic transformation(HT) and prognosis after acute cerebral infarction(ACI).Methods: Patients with ACI within 72 h of symptoms onset between January 1 st, 2015, and December 31 st, 2016, were retrospectively analyzed. Patients were divided into group A(without HT) and group B(HT). The outcomes were assessed after 3 months of disease onset using the modified Rankin Scale(m RS). An m RS score of 0–2 points indicated excellent prognosis, and an m RS score of 3–6 points indicated poor prognosis.Results: A total of 732 patients conformed to the inclusion criteria, including 628 in group A and 104 in group B. The incidence of HT was 14.2%, and the median onset time was 2 d(interquartile range, 1–7 d). The percentages of patients with large infarct size and cortex involvement in group B were 80.8% and 79.8%, respectively, which were both significantly higher than those in group A(28.7 and 33.4%, respectively). The incidence rate of atrial fibrillation(AF) in group B was significantly higher than that in group A(39.4% vs. 13.9%, P<0.001). The adjusted multivariate analysis results showed that large infarct size, cortex involvement and AF were independent risk factors of HT, while total cholesterol(TC) was a protective factor of HT(OR=0.359, 95% CI 0.136–0.944, P=0.038). With every 1 mmol/L reduction in normal TC levels, the risk of HT increased by 64.1%. The mortality and morbidity at 3 months in group B(21.2% and 76.7%, respectively) were both significantly higher than those in group A(8.0% and 42.8%, respectively). The adjusted multivariate analysis results showed that large infarct size(OR=12.178, 95% CI 5.390–27.516, P<0.001) was an independent risk factor of long-term unfavorable outcomes, whereas low-density lipoprotein cholesterol(LDL-C) was a protective factor(OR=0.538, 95% CI 0.300–0.964, P=0.037). With every 1 mmol/L reduction in normal LDL-C levels, the risk of an unfavorable outcome increased by 46.2%. Major therapies, including intravenous recombinant human tissue plasminogen activator(r TPA), intensive lipid-lowering statins and anti-platelets, were not significantly related to either HT or long-term, post-ACI poor prognosis.Conclusions: For patients with large infarct sizes, especially those with cortex involvement, AF, or lower levels of TC, the risk of HT might increase after ACI. The risk of a long-term unfavorable outcome in these patients might increase with a reduction in LDL-C.

Anti-inflammatory and anti-thrombogenic effects of atorvastatin in acute ischemic stroke

Atorvastatin decreases inflammation and thrombogenesis in patients with carotid artery plaque. Atorvastatin is administered to lower lipid levels, but its anti-inflammatory and anti-thrombogenic effects remain unclear. Eighty-nine patients from northeastern China with acute ischemic stroke caused by large-artery atherosclerosis were randomly divided into the study and control groups. All patients received routine treatment, including antiplatelet therapy, circulatory support, and symp- tomatic treatment. The study group （n = 43） also received daily atorvastatin 20 mg/d, and the control group （n = 46） received daily placebo pills containing glucose. After 4 weeks, the levels of C-reactive protein, fibrinogen, and D-dimer were significantly lower in the study group than in the control group. Decreases in the levels of C-reactive protein, fibrinogen, and D-dimer were not associated with de- creases in the levels of triacylglycerol and low-density lipoprotein cholesterol. These results suggest that atorvastatin reduces inflammation and thrombogenesis independent of its lipid-lowering effects in patients with acute ischemic stroke caused by large-artery atherosclerosis.

Attainment of multifactorial treatment targets among the elderly in a lipid clinic

Objective To examine target attainment of lipid-lowering, antihypenensive and antidiabetic treatment in the elderly in a specialist set- ting of a University Hospital in Greece. Methods This was a retrospective study including consecutive subjects 〉 65 years old （n = 465） with a follow-up 〉 3 years. Low-density lipoprotein cholesterol （LDL-C）, blood pressure （BP） and glycated hemoglobin （HbAlc） goal achievement were recorded according to European Society of Cardiology/European Atherosclerosis Society （ESC/EAS）, European Society of Hypertension （ESH）/ESC and European Association for the Study of Diabetes （EASD） guidelines. Results The LDL-C targets were attained by 27~,4, 48% and 62% of very high, high and moderate risk patients, respectively. Those receiving statin ＋ ezetimibe achieved higher rates of LDL-C goal achievement compared with those receiving statin monotherapy （48% vs. 33%, P 〈 0.05）. Of the diabetic sub- jects, 71% had BP 〈 140/85 mmHg, while 78% of those without diabetes had BP 〈 140/90 mmHg. A higher proportion of the non-diabetic individuals （86%） had BP 〈 150/90 mmHg. Also, a higher proportion of those with diabetes had HbAlc 〈 8% rather than 〈 7% （88% and 47%, respectively）. Of note, almost one out of three non-diabetic individuals and one out of ten diabetic individuals had achieved all three treatment targets. Conclusions Even in a specialist setting of a University Hospital, a high proportion of the elderly remain at suboptimal LDL-C, BP and HbAlc levels. The use of drug combinations could improve multifactorial treatment target attainment, while less strict tar- gets could be more easily achieved in this population.