Adverse Events After Initiating Angiotensin-Converting Enzyme Inhibitor/Angiotensin II Receptor Blocker Therapy in Individuals with Heart Failure and Multimorbidity

BackgroundCurrent clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy. However, evidence is lacking on whether routine follow-up testing reduces therapy-related adverse events in adults with heart failure and if multimorbidity influences the association between laboratory testing and these adverse events.MethodsWe conducted a retrospective cohort study among adults with heart failure from 4 US integrated health care delivery systems. Multimorbidity was defined using counts of chronic conditions. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACEI or ARB therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression.ResultsWe identified 3629 matched adults with heart failure initiating ACEI or ARB therapy between January 1, 2005, and December 31, 2012. Follow-up testing was not significantly associated with 30-day all-cause mortality (adjusted hazard ratio [aHR] 0.45, 95% confidence interval [CI] 0.14; 1.39) and hospitalization with hyperkalemia (aHR 0.73, 95% CI, 0.33; 1.61). However, follow-up testing was significantly associated with hospitalization with acute kidney injury (aHR, 1.40, 95% CI, 1.01; 1.94). Interaction between multimorbidity burden and follow-up testing was not statistically significant in any of the outcome models examined.ConclusionsRoutine laboratory monitoring after ACEI or ARB therapy initiation was not associated with risk of 30-day all-cause mortality or hospitalization with hyperkalemia across the spectrum of multimorbidity burden in a cohort of patients with heart failure.     

Life-Course Implications of Pediatric Risk Factors for Cardiovascular Disease

The concept that origins of cardiovascular disease (CVD) begin in childhood is supported by substantial evidence. Prospective studies beginning in childhood report associations of childhood obesity, abnormal blood pressure (BP), dyslipidemia, diabetes, and tobacco use with intermediate CVD markers, including left ventricular hypertrophy and vascular stiffness in young adulthood. Trajectory analyses from longitudinal studies describe discrete BP pathways from childhood to young adult status of hypertension and prehypertension. Among individuals with familial hypercholesterolemia, abnormal low-density lipoprotein cholesterol levels are present in childhood. Some children are at risk for future CVD owing to hereditary factors, psychosocial stress, race, low birth weight, or other nonmodifiable exposures. Behavioural factors, including suboptimal diet, sedentary activity, and tobacco use, in childhood augment risk and can be modified to reduce risk. Pharmacologic treatments are reserved for those at high levels of the BP and cholesterol distributions and for those with diabetes and additional risk factors.     

WHO HEARTS: A Global Program to Reduce Cardiovascular Disease Burden: Experience Implementing in the Americas and Opportunities in Canada

Globally, cardiovascular diseases (CVDs) are the leading cause of death. Viewed as a threat to the global economy, the United Nations included reducing noncommunicable diseases, including CVDs, in the 2030 sustainable development goals, and the World Health Assembly agreed to a target to reduce noncommunicable diseases 25% by the year 2025. In response, the World Health Organisation led the development of HEARTS, a technical package to guide governments in strengthening primary care to reduce CVDs. HEARTS recommends a public health and health system approach to introduce highly simplified interventions done systematically at a primary health care level and has a focus on hypertension as a clinical entry point. The HEARTS modules include healthy lifestyle counselling, evidence-based treatment protocols, access to essential medicines and technology, CVD risk-based management, team-based care, systems for monitoring, and an implementation guide. There are early positive global experiences in implementing HEARTS. Led by the Pan American Health Organisation, many national governments in the Americas are adopting HEARTS and have shown early success. Unfortunately, in Canada hypertension control is declining in women since 2010-2011 and the dramatic reductions in rates of CVD seen before 2010 have flattened when age adjusted and increased for rates that are not age adjusted, and there are marked increases in absolute numbers of Canadians with adverse CVD outcomes. Several steps that Canada could take to enhance hypertension control are outlined, the core of which is to implement a strong governmental nongovernmental collaborative strategy to prevent and control CVDs, focusing on HEARTS.     

慢性肾炎患者外周血共刺激分子CD28和CD137水平变化研究

目的　研究慢性肾炎患者外周血共刺激分子CD2 8和CD1 37的表达特点及其在慢性肾炎免疫病理机制中的作用。方法　采用免疫荧光标记和流式细胞仪分析 ,对 5 2例慢性肾炎患者外周血共刺激分子CD2 8、CD1 37和T淋巴细胞亚群的表达进行检测。结果　慢性肾炎患者T细胞亚群明显失衡 ,表现为CD4减少 ,CD8增加 ,CD4 CD8比值显著降低。共刺激分子CD2 8表达显著低于正常对照组 (P <0 0 1) ,且CD+4 CD+2 8T细胞和CD+8CD+2 8T细胞均显著减少 (P <0 0 1)。共刺激分子CD1 37表达显著高于正常对照组 (P <0 0 1)。结论　慢性肾炎患者外周血T细胞亚群失衡和T细胞活化所必需的共刺激分子CD2 8、CD1 37异常表达 ,可能在慢性肾炎发生和病变进展中起着重要作用     

血清和尿Ⅳ型胶原、层粘连蛋白、Ⅲ型胶原测定在高血压性肾损害中的意义

目的　观察高血压病患者血清和尿中Ⅳ型胶原 (C Ⅳ )、层粘连蛋白 (LN )、Ⅲ型胶原(C Ⅲ )水平变化及与尿白蛋白、β2 微球蛋白排泄量间的关系 ,探讨其在高血压性肾损害发生发展中的作用及在早期诊断中的意义。方法　测定 5 7例常规检查尿蛋白阴性、肾功能正常的高血压患者高血压组血清和尿C Ⅳ、LN、C Ⅲ水平及晨尿白蛋白、β2 微球蛋白排泄量 ,并与 5 7名健康体检者(对照组 )比较 ,同时观察高血压组患者尿白蛋白、β2 微球蛋白与上述各指标间的相关关系。结果　高血压组患者血和尿C Ⅳ、LN及C Ⅲ水平均较对照组升高 ,除尿C Ⅳ外 ,均有显著性差异 (P <0 .0 5～ 0 .0 0 1) ;高血压组患者尿 β2 微球蛋白排泄量显著高于对照组 ,且与血、尿C Ⅲ水平呈显著正相关关系。结论　高血压患者在尚无肾脏损伤临床表现的早期 ,即可表现为血和尿C Ⅳ、LN及C Ⅲ水平的升高 ,尤其是血和尿C Ⅲ水平的升高 ,可能提示高血压早期肾小管间质损伤的存在     

尿毒症患者炎症反应与血脂的关系

目的　通过分析尿毒症患者慢性炎症指标与血脂的关系 ,探讨尿毒症的炎症反应影响心血管系统的途径。方法　测定 67例尿毒症患者慢性炎症指标血C 反应蛋白 (CRP)、白细胞介素 6(IL 6)、肿瘤坏死因子 α(TNF α)及血脂 ,并分析它们之间的关系。结果　 2 6.87%的尿毒症患者CRP超过正常参考值 ( 5mg/L) ,CRP升高组血清甘油三酯 (TG)、低密度脂蛋白胆固醇 (LDL C)、载脂蛋白B(ApoB)、载脂蛋白A1/载脂蛋白B(ApoA1/ApoB)、脂蛋白 (a) [Lp(a) ]高于CRP正常组 (P值均 <0 .0 5 ) ;血CRP与总胆固醇 (TC) (P <0 .0 5 )、TG、LDL C、ApoB、Lp(a)、血清肌酐 (Scr)、血尿素氮(BUN)呈正相关 (P值均 <0 .0 1) ,Logistic回归分析显示 ,CRP与TG、Lp(a)关系更为显著。结论　尿毒症患者存在慢性炎症状态 ,慢性炎症与脂代谢紊乱密切相关。     

糖尿病大鼠肾脏热休克蛋白70的表达及普罗布考干预的研究

目的 观察糖尿病大鼠肾脏中热休克蛋白70（HSP70）的表达并观察普罗布考对HSP70表达的影响. 方法 链脲佐菌素构建糖尿病大鼠模型50只,随机分为糖尿病（DM）组、普罗布考（PT）组,另设健康对照（NC）组.RT-PCR测定各组肾组织HSP70 mRNA的表达,免疫组织化学法观察HSP70的表达情况,Western blot测定HSP70蛋白的表达水平. 结果 DM组4、8及12周肾脏中HSP70 mRNA及蛋白的表达逐渐升高.同一时间的PT组肾脏HSP70 mRNA及蛋白的表达均较DM组减少（P＜0.05）. 结论 糖尿病大鼠肾脏中HSP70的表达升高,普罗布考可降低HSP70的表达,对肾脏起保护作用.     

大鼠慢性牙周炎与IgA肾病复合模型血清中MMP-3的表达及意义

目的：研究大鼠慢性牙周炎与IgA肾病（IgAN）复合模型血清中基质金属蛋白酶-3（MMP-3）的水平,探讨慢性牙周炎与IgAN之间的可能发病机制。方法：40只SD大鼠随机分成4组,每组10只,分别为空白对照组、慢性牙周炎组、IgAN组和慢性牙周炎＋IgAN复合组。第12周末处死动物分别检测血清中MMP-3、血肌酐（Scr）,24h尿蛋白,大鼠牙龈附着丧失（AL）及出血指数（SBI）结果,观察牙周和。肾脏组织病理学改变。结果：慢性牙周炎＋IgAN复合组分别与空白对照组、慢性牙周炎组、IgAN组相比,血清MMP-3、Scr含量均显著增高（P〈0．05）,血清MMP-3与24h尿蛋白定量、AL的多元线性回归方程：24h尿蛋白-1．822＋0．206×MMP-3,R2—0．691（P〈0．05）AL-26．316＋1．577×MMP-3,R2—0．549（P〈0．05）。结论：血清MMP-3的水平在慢性牙周炎与IgAN复合组中明显增加,可能与两种疾病存在一定的关系,为研究二者发病机制提供了一个方向。     

运用两种BSA剂量建立IgA肾病大鼠模型观察

目的:目前IgA肾病(IgAN)动物模型并无经典造模方法,本实验选择国内较常用方法建立大鼠IgAN模型,分两个时间点观察不同剂量牛血清白蛋白(bovine serum albumin,BSA)灌胃联合注射脂多糖(lipopolysaccharide,LPS)+四氯化碳(carbon terachloride,CCL4)方法建立IgA肾病模型效果。方法:将SPF级健康雄性SD大鼠60只(平均体重200～240g)随机分为3组,每组20只。低剂量组(A组):BSA400mg/kg(100g/L)隔天灌胃,持续12周;皮下注射蓖麻油0.3ml+CCL40.10ml,每周1次持续12周,第8周LPS0.05mg尾静脉注射。高剂量组(B组):BSA增加至600mg/kg(100g/L),余干预同低剂量组。对照组(C组)生理盐水4ml/kg灌胃,0.4ml皮下注射。建模后第8周、12周每组各处死10只大鼠,留取血、尿、肾组织标本检测。观察指标:一般情况、蛋白尿、血尿、肝肾功能、肾组织病理。结果:模型组大鼠血肌酐、尿素氮及尿蛋白均明显增高(P<0.05),高剂量组显著高于低剂量组(P<0.05),且肾组织病理8周后均出现轻中度系膜细胞及系膜基质的增生,12周末显著伴肾间质轻度纤维化,高剂量组病变较重;12周末均有荧光出现,均强于第8周,低剂量组荧光表达不典型,高剂量组表达强于低剂量组(P<0.05)。电镜报告与病理表现一致。结论:运用BSA+LPS+CCL4联合造模方法在12周左右可建立快速IgA肾病动物模型,而且高剂量BSA(600mg/kg)组肾组织病变更显著,模型更典型。此模型的建立及运用可以为IgA肾病临床及基础研究提供良好动物模型基础。