脑钠肽在儿童心血管病中的研究进展

脑钠肽（brain natriuretic peptide,BNP）又称B型利钠肽（B-type natriuretic peptide,BNP）,是利钠肽家族之一,具有利钠、利尿及扩血管作用,其浓度与心室压力呈正相关,是成人心力衰竭（heart failure,HF）诊断和预后的生物标记物[1].近年发现BNP以及氨基末端脑钠肽原（amino-N-terminal-proBNP,NT-proBNP）的浓度测定在儿童各类心血管病中亦有广泛应用,其人工合成产品也应用于治疗,笔者就近年脑钠肽在儿科心血管领域的研究新进展作一综述.

心型脂肪酸结合蛋白对老年患者开胸术后心血管事件的预测价值

目的 探讨心型脂肪酸结合蛋白（H-FABP）对老年患者非心脏开胸术后心血管事件（PCE）的预测价值.方法 前瞻性选取2012年2月至2014年8月本院接受开胸手术的＞60岁的患者68例,对患者一般资料、术前术后H-FABP水平及PCE发生情况进行记录和分析.绘制H-FABP预测发生PCE的接受者操作特征曲线（ROC曲线）,评价其相关性.结果 共有18例患者发生PCE.心血管事件组术后H-FABP水平明显高于非心血管事件组（P＜0.05）,两组术前H-FABP水平差异无统计学意义（P＞0.05）.术后H-FABP和术前氮端脑钠肽前体（NT-proBNP）水平是开胸术后发生PCE的独立危险因素.术后H-FABP水平预测发生PCE曲线下面积为0.840（95％ CI：0.716～0.964,P＜0.01）,预测心血管事件发生的最佳界值为5.26 μg/L（OR 15.944,95％ CI：4.239～ 59.978,P＜0.01）,此时灵敏度77.8％,特异度84.0％.结论 术后H-FABP水平是老年开胸非心脏手术后PCE的独立危险因素,对PCE的发生具有较好的预测价值.

Pediatric nonalcoholic fatty liver disease,metabolic syndrome and cardiovascular risk

Nonalcoholic fatty liver disease(NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use.The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes.A more advanced form of NAFLD,nonalcoholic steatohepatitis,includes inflammation and liver cell injury,progressive to cryptogenic cirrhosis.NAFLD has become the most common cause of chronic liver disease in children and adolescents.The recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide.NAFLD is strongly associated with abdominal obesity,type 2 diabetes,and dyslipidemia,and most patients have evidence of insulin resistance.Thus,NAFLD shares many features of the metabolic syndrome(MetS),a highly atherogenic condition,and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis.Accumulating evidence suggests thatNAFLD is associated with a significantly greater overall mortality than in the general population,as well as with increased prevalence of cardiovascular disease(CVD),independently of classical atherosclerotic risk factors.Yet,several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS.Therefore,the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes.In children,the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively.Therapeutic goals for NAFLD should address nutrition,physical activity,and avoidance of smoking to prevent not only end-stage liver disease but also CVD.

Metabolic syndrome and chronic kidney disease:Current status and future directions

Metabolic syndrome(Met S) is a term used to denote a combination of selected,widely prevalent cardiovascular disease(CVD)-related risk factors.Despite the ambiguous definition of Met S,it has been clearly associated with chronic kidney disease markers including reduced glomerular filtration rate,proteinuria and/or microalbuminuria,and histopathological markers such as tubular atrophy and interstitial fibrosis.However,the etiological role of Met S in chronic kidney disease(CKD) is less clear.The relationship between MetS and CKD is complex and bidirectional,and so is best understood when CKD is viewed as a common progressive illness along the course of which MetS,another common disease,may intervene and contribute.Possible mechanisms of renal injury include insulin resistance and oxidative stress,increased proinflammatory cytokine production,increased connective tissue growth and profibrotic factor production,increased microvascular injury,and renal ischemia.MetS also portends a higher CVD risk at all stages of CKD from early renal insufficiency to end-stage renal disease.Clinical interventions for MetS in the presence of CKD should include a combination of weight reduction,appropriate dietary modification and increase physical activity,plus targeting of individual CVD-related risk factors such as dysglycemia,hypertension,and dyslipidemia while conforming to relevant national societal guidelines.

Metabolic syndrome vs. its components for prediction of cardiovascular mortality： A cohort study in Chinese elderly adults

Objective The predictive value of the metabolic syndrome （MetS） for mortality from all-cause and cardiovascular disease （CVD） in the Chinese population is unclear. The aim of this present study was to compare MetS with its individual components as predictors of mortality in Chinese elderly adults. Methods A cohort of 1,535 subjects （994 men and 541 women） aged 50 years or older was selected from employees of a machinery factory in 1994 and followed until 2009. Cox models were used to estimate the hazard ratios （HRs） predicted by MetS according to the harmonized defmition and by its individual components. Results The baseline prevalence of MetS was 28.0% in men and 48.4% in women. During a median follow-up of 15 years, 414 deaths occurred, of these, 153 participants died from CVD. Adjusted for age and gender, the HRs of mortality from all-cause and CVD in participants with MetS were 1.47 （95% confidence interval （CI）： 1.20-1.80） and 1.96 （95%CI： 1.42-2.72）, respectively, compared with those without MetS. Non-significant higher risk of CVD mortality was seen in those with one or two individual components （HR = 1.22, 95%CI： 0.59-2.50; fir = 1.82, 95%CI： 0.91-3.64, respectively）, while a substantially higher risk of CVD mortality only appeared in those with 3, 4, or 5 components （H_R = 2.81-3.72）, compared with those with no components. On evaluating the MetS components individually, we found that, independent of MetS, only hypertension and impaired glucose predicted higher mortality. Conclusions The number of positive MetS components seems no more informative than classifying （dichotomous） MetS for CVD risks assessment in this Chinese cohort.

Prevalence of Metabolic Syndrome and Its Associations with Other Metabolic Disorders and Cardiovascular Changes in Health Examination Population in Beijing

Objective To investigate the prevalence of metabolic syndrome(MS) and its associations with other metabolic disorders and cardiovascular changes in health examination population in Beijing.Methods Totally,10 916 individuals who received health examination in Health Examination Center of Peking Union Medical College Hospital were enrolled.The height,weight,blood pressure,serum levels of triglyceride,high-density lipoprotein cholesterol(HDL-C),and fasting blood glucose were recorded.MS was diagnosed based on the working criteria of Chinese Diabetes Society 2004(CDS2004).Meanwhile,other metabolic disorders,including fatty liver and hyperuricemia,were recorded.The cardiovascular changes were reflected by the reports of electrocardiogram(ECG) ST-T changes and atherosclerosis of retinal arteries.Results The overall prevalence rate of MS was 6.1%(666/10 916) in the population.The prevalence rate of MS in male was much higher than that in female(9.0% vs.2.7%,P=0.000).For individuals with MS,the prevalence rates of fatty liver and hyperuricemia were significantly higher than those without MS,respectively(70.4% vs.35.4%,P=0.000;29.9% vs.17.7%,P=0.000).As for cardiovascular changes,the prevalence rates of ECG ST-T changes and atherosclerosis of retinal arteries were significantly higher in individuals with MS than those without MS,respectively(13.8% vs.11.7%,P=0.012;12.0% vs.6.8%,P=0.000).Conclusions The prevalence of MS in Beijing population is high.The individuals with MS have a higher risk for other metabolic disorders and cardiovascular changes.

High prevalence of aspirin resistance in elderly patients with cardiovascular disease and metabolic syndrome

Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease （CVD）. Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome （control group） received daily aspirin therapy （〉 75 mg） over one month. Platelet aggregation was measured by light transmission aggregometry （LTA）. Aspirin resistance was defined as 〉 20% arachidonic acid （AA）- and 〉 70% adenosine diphosphate （ADP）-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one （but not both） of these criteria. Results By LTA, 38 of 469 （8.1%） patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio （OR） = 2.039; 95% confidence interval （CI）： 1.047-3.973]. In the multivariate logistic regression analysis, metabolic syndrome （OR = 4.951, 95% CI： 1.440-17.019, P = 0.011） was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.

Women and exercise in aging

Aging is associated with physiological declines, notably a decrease in bone mineral density （BMD） and lean body mass, with a concurrent increase in body fat and central adiposity. Interest in women and aging is of particular interest partly as a result of gender specific responses to aging, particularly as a result of menopause. It is possible that the onset of menopause may augment the physiological decline associated with aging and inactivity. More so, a higher incidence of metabolic syndrome （an accumulation of cardiovascular disease risk factors including obesity, low-density lipoprotein cholesterol, high blood pressure, and high fasting glucose） has been shown in middle-aged women during the postmenopausal period. This is due in part to the drastic changes in body composition, as previously discussed, but also a change in physical activity （PA） levels. Sarcopenia is an age related decrease in the cross-sectional area of skeletal muscle fibers that consequently leads to a decline in physical function, gait speed, balance, coordination, decreased BMD, and quality of life. PA plays an essential role in combating physiological decline associated with aging. Maintenance of adequate levels of PA can result in increased longevity and a reduced risk for metabolic disease along with other chronic diseases. The aim of this paper is to review relevant literature, examine current PA guidelines, and provide recom- mendations specific to women based on current research.

Clopidogrel and proton pump inhibitors-where do we stand in 2012?

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

Hepatitis C comorbidities affecting the course and response to therapy

Several studies have demonstrated that the outcome of chronic hepatitis C (CHC) infection is profoundly influenced by a variety of comorbidities. Many of these comorbidities have a significant influence on the response to antiviral therapy. These comorbidities negatively affect the course and outcome of liver disease, often reducing the chance of achieving a sustained virological response with PEGylated interferon and ribavirin treatments. Comorbidities affecting response to antiviral therapy reduce compliance and adherence to inadequate doses of therapy. The most important comorbidities affecting the course of CHC include hepatitis B virus coinfection, metabolic syndrome, and intestinal bacterial overgrowth. Comorbidities affecting the course and response to therapy include schistosomiasis, iron overload, alcohol abuse, and excessive smoking. Comorbidities affecting response to antiviral therapy include depression, anemia, cardiovascular disease, and renal failure.

Analysis and clinical applications of metabolic syndrome risk factors for cardiovascular

Metabolic syndrome had many different names, including syndrome X, insulin resistance syndrome. At present the cause of metabolic syndrome is unclear, it may come from two aspects： First, acquired, including being overweight or obese, reduced physical activity and excessive carbohydrate diet; Second, genetic factors, involving multiple genes, not yet fully elucidated. The syndrome is generally believed to be the collection of a variety of cardiovascular risk factors caused by poor lifestyle under the genetic background, including hypertension, dyslipidemia, abdominal obesity, hyperinsulinemia, microalbuminuria, hypercoagulable state, hyperhomocysteinemia and so on. Hyperinsulinemia and insulin resistance is the central link, which is closely related to dyslipidemia, impaired glucose tolerance, and abdominal obesity. Metabolic syndrome may eventually lead to atherosclerosis： coronary artery disease, myocardial infarction, stroke, peripheral vascular disease and endothelial dysfunction. In 1999, the working definition of World Health Organization （WHO） to the metabolic syndrome is： glucose regulation impairment or diabetes, and / or insulin resistance, accompanied by the other two items or more ingredients, such as hypertension, high triglycerides esters hyperlipidemia and / or low HDL cholesterol, central obesity or microalbuminuria.

慢性肾衰竭患者载脂蛋白与心脑血管并发症的相关性

目的:观察维持性血液透析(MHD)对载脂蛋白(Apo)及其比值的影响,探讨慢性肾衰竭(CRF)Apo与心脑血管并发症的相关性。方法:CRF肾衰竭期或终末期患者65名,分为CRF组及MHD组,每组以是否合并心脑血管并发症再分为并发症亚组及无并发症亚组,对照组21例,观察各组ApoB、ApoA1、ApoB/ApoA1,血浆白蛋白(Alb)水平。结果:与对照组相比,CRF组ApoB、ApoB/ApoA1升高(P<0.05),而MHD组上述指标得到改善;两并发症亚组的ApoB及ApoB/ApoA1均值较相对应的无并发症亚组升高,但无统计学意义。结论:MHD可以降低ApoB及ApoB/ApoA1,但其对CRF患者心脑血管并发症的预测意义尚不确定。

Cidea controls lipid droplet fusion and lipid storage in brown and white adipose tissue

Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes,fatty liver and cardiovascular diseases.The lipid droplet(LD)is an important subcellular organelle responsible for lipid storage.We previously observed that Fsp27,a member of the CIDE family proteins,is localized to LD-contact sites and promotes atypical LD fusion and growth.Cidea,a close homolog of Fsp27,is expressed at high levels in brown adipose tissue.However,the exact role of Cidea in promoting LD fusion and lipid storage in adipose tissue remains unknown.Here,we expressed Cidea in Fsp27-knockdown adipocytes and observed that Cidea has similar activity to Fsp27 in promoting lipid storage and LD fusion and growth.Next,we generated Cidea and Fsp27 double-deficient mice and observed that these animals had drastically reduced adipose tissue mass and a strong lean phenotype.In addition,Cidea/Fsp27 double-deficient mice had improved insulin sensitivity and were intolerant to cold.Furthermore,we observed that the brown and white adipose tissues of Cidea/Fsp27double-deficient mice had significantly reduced lipid storage and contained smaller LDs compared to those of Cidea or Fsp27single deficient mice.Overall,these data reveal an important role of Cidea in controlling lipid droplet fusion,lipid storage in brown and white adipose tissue,and the development of obesity.

Tea and human health: biomedical functions of tea active components and current issues

Originating in China, tea and tea planting have spread throughout the world since the middle of the Tang dynasty. Now people from 160 countries in the world are accustomed to tea drinking. A brief history of tea＇s medicinal role in China and its spread to the world are introduced. The effectiveness of tea active components and tea drinking on major human diseases, including cancer, metabolic syndrome, cardiovascular disease, and neurodegenerative diseases, is discussed. Also presented are some related issues, such as the bioavailability of tea active components, the new formulations of tea polyphenols, and the safety for consumers of dietary supplements containing tea polyphenols.