Coronary Flow Velocity Reserve and Carotid Intima Media Thickness in Patients with Autosomal Dominant Polycystic Kidney Disease: From Impaired Tubules to Impaired Carotid and Coronary Arteries

Background and objectives: Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease. Endothelial dysfunction, an early and reversible feature in the pathogenesis of atherosclerosis, is associated with increased vascular smooth muscle tone, arterial stiffening, and increased intima-media thickness. Coronary flow velocity reserve is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. The aim of the study was to investigate the carotid intima-media thickness and coronary flow velocity reserve in patients with autosomal dominant polycystic kidney disease.Design, setting, participants, & measurements: Thirty normotensive patients with autosomal dominant polycystic kidney disease (10 male, 20 female) with well-preserved renal function and 30 healthy subjects (12 male, 18 female) were included in the study. Coronary flow velocity reserve was measured at baseline and after dipyridamole infusion by echocardiography. Coronary flow velocity reserve was calculated as the ratio of hyperemic to baseline diastolic peak velocities.Results: Carotid intima-media thickness was significantly higher in patients than in control subjects (0.80 ± 0.29 versus 0.54 ± 0.14 mm, respectively; P < 0.001). Moreover, coronary flow velocity reserve was significantly lower in patients than in control subjects (1.84 ± 0.39 versus 2.65 ± 0.68, respectively; P < 0.001).Conclusions: Normotensive patients with autosomal dominant polycystic kidney disease with well-preserved renal function have significantly increased carotid intima-media thickness and significantly decreased coronary flow velocity reserve compared with healthy subjects. These findings suggest that atherosclerosis starts at an early stage in the course of their disease in patients with autosomal dominant polycystic kidney disease.Autosomal-dominant polycystic kidney disease (ADPKD) is a hereditary renal disease that occurs in 1 of 400 to 1000 individuals (1,2). Cardiovascular problems are a major cause of morbidity and mortality in patients with ADPKD (3). Hypertension, a common finding in patients with ADPKD, often occurs before the onset of renal insufficiency and is associated with faster progression to ESRD and increased cardiovascular mortality (4,5). Activation of the renin-angiotensin-aldosterone system (RAAS) caused by cyst expansion and local ischemia has been proposed to play an important role in the development of hypertension in ADPKD (6). The RAAS is stimulated at an early stage of ADPKD, even before the onset of hypertension and clinical findings (7,8). Likewise, increased left ventricular mass indexes and biventricular diastolic dysfunction have been reported before the development of hypertension in patients with ADPKD with well-preserved renal function (9–16). Moreover, endothelial dysfunction (ED), which is an early manifestation of vascular injury, occurs in both normotensive and hypertensive patients with ADPKD, before the onset of renal failure (17).Coronary flow velocity reserve (CFVR) represents the capacity of the coronary circulation to dilate after an increase in myocardial metabolic demands (18). Although CFVR was measured invasively until recently, it can be evaluated noninvasively by using Doppler and vasodilator stress, such as dipyridamole or adenosine (19). By using this method, impairment of CFVR can be assessed before development of angiographically detectable stenosis in epicardial coronary arteries. The aim of this study was to investigate the CFVR in patients with ADPKD, with well-preserved renal function.     

舒降之、普罗布考和开搏通对颈动脉和股动脉内膜中膜厚度的影响

应用高频超声显像技术探讨舒降之、普罗布考和开搏通对动脉粥样硬化患者颈动脉和股动脉内膜中膜厚度的影响。在 10 2例患者中 ,应用高频超声技术测量颈动脉和股动脉后壁内膜中膜的正常厚度、最大厚度、四条动脉最大厚度的平均值和四条动脉中单个最大厚度 ,同时测量管壁的僵硬度 β。然后分别服用舒降之、普罗布考、开搏通三年后复查。结果发现 ,各组治疗前后斑块部位内膜中膜厚度均增加 (P均 <0 .0 5 )。对照组正常厚度的变化值 (0 .0 4± 0 .12mm)均显著高于普罗布考组的右颈动脉 (0 .0 4± 0 .12mm)和舒降之组左颈动脉 (0 .0 4± 0 .2 6mm)及右股动脉 (0 .0 3± 0 .2 3mm) (P <0 .0 5 )。舒降之组最大厚度、四条动脉最大厚度的平均值和各治疗组右侧股动脉最大厚度的变化值显著低于对照组 (P <0 .0 5 )。舒降之组 (0 .17± 0 .12mm)和开搏通组 (0 .2 1± 0 .15mm)四条动脉最大厚度的平均值的变化率显著低于对照组 (0 .2 5± 0 .2 0mm) (P均 <0 .0 1)。各组四条动脉中单个最大厚度的变化值及变化率显著低于对照组 (P均 <0 .0 5 )。本研究结果表明 ,动脉粥样硬化斑块较正常内膜—中膜厚度进展较快 ,药物治疗延缓动脉粥样硬化的进展 ,以舒降之作用最佳。高频超声技术能够可靠的观察颈动脉和股动脉动脉粥样     

Carotid Intima Media Thickness in Patients with Obstructive Sleep Apnea: Comparison with a Community-Based Cohort

Background

The impact of obstructive sleep apnea (OSA) on the development of atherosclerotic cardiovascular disease (CVD) in the absence of overt CVD or risk factors is unclear. Our purpose was to assess whether patients with OSA without overt CVD or risk factors have subclinical atherosclerosis as evaluated by carotid intima medial thickness (CIMT) compared to matched controls.

Methods

We measured CIMT in patients >40 years old, who underwent polysomnography for suspected OSA and did not have a history of CVD or risk factors (smoking, hypertension, diabetes, hyperlipidemia). OSA severity was classified according to apnea–hypopnea index. Serum levels of high-sensitivity C-reactive protein, fibrinogen, and lipids were assessed and relationships with OSA severity explored. CIMT measurements from patients with OSA were compared those of to age-, gender-, and BMI-matched controls from a community-based cohort without known CVD or OSA.

Results

Fifty-one patients were studied. Of these, patients with severe OSA had an increased CIMT compared to patients without OSA, but the relationship was not significant after controlling for age (p = 0.10). However, 37 patients had OSA and were matched to 105 controls. CIMT was significantly increased in OSA patients versus controls (0.77 vs. 0.68 mm, p = 0.03). The difference between patients and controls was greater for patients with severe OSA (0.83 vs. 0.71 mm) than for patients with mild-to-moderate OSA (0.71 vs. 0.67 mm).

Conclusions

Patients with OSA but without a history of or risk factors for CVD have increased CIMT compared to a BMI-, age-, and gender-matched cohort. This provides evidence that OSA is an independent risk factor for the development of CVD.     

早发冠心病患者颈总动脉内膜—中层厚度与载脂蛋白E基因型的关系

探讨早发冠心病患者颈总动脉内膜-中层厚度与载脂蛋白E基因型关系.用超声检测85例早发冠心病患者颈总动脉内膜-中层厚度,同时运用聚合酶链反应及限制性片段长度多肽性方法分析其载脂蛋白 E基因型及等位基因频率分布.结果发现,病例组载脂蛋白 E基因型共有5种,主要基因型按频率高低为载脂蛋白E3/3>E3/4>E2/3,载脂蛋白E2/4和E4/4为少见基因型;载脂蛋白 E等位基因频率为ε3>ε4>ε2.载脂蛋白E3/4基因型组总胆固醇和低密度脂蛋白胆固醇高于载脂蛋白E2/3组, 高密度脂蛋白胆固醇低于载脂蛋白E2/3组(P均<0.05);载脂蛋白E3/4基因型组内膜-中层厚度高于载脂蛋白E2/3组(P<0.05).内膜-中层厚度与总胆固醇(r=0.401,P<0.01)和低密度脂蛋白胆固醇(r=0.376,P<0.01)呈正相关.以上提示,早发冠心病患者颈总动脉内膜-中层厚度与载脂蛋白E基因型密切相关,载脂蛋白E基因型通过调节脂质代谢影响内膜-中层厚度.     

2型糖尿病患者心率变异与颈动脉内膜增厚

目的 探讨2型糖尿病患者心率变异(HRV)与颈动脉内膜增厚的关系及其临床意义.方法 2型糖尿病患者132例按颈动脉内膜一中膜厚度(IMT)分T1组(36例,IMT＜1.0 mm),T2组(54例,IMT 1.1～1.3 ram),T3组(42例,IMT≥1.3 mm)及30例正常对照者(TO组)作为研究对象.Holter HRV时域、频域指标评估心脏自主神经调节功能.结果 1)2型糖尿病有或无颈动脉内膜增厚组各HRV指标(SDNN,SDANN,RMSSD,PNN50,SDNN指数)均较正常对照组低(P＜0.05或P＜0.01).2)2型糖尿病合并颈动脉内膜增厚者HRV指数较无病变者有进一步的下降,而且HRV指数与IMT呈负相关.结论 HRV是2型糖尿病颈动脉粥样硬化的独立相关因素,可对大血管并发症作出早期的诊断,改善预后.     

2型糖尿病患者心率变异与颈动脉内膜增厚

目的探讨2型糖尿病患者心率变异(HRV)与颈动脉内膜增厚的关系及其临床意义。方法2型糖尿病患者132例按颈动脉内膜-中膜厚度(IMT)分T1组(36例,IMT<1·0mm),T2组(54例,IMT1·1～1·3mm),T3组(42例,IMT≥1·3mm)及30例正常对照者(T0组)作为研究对象。HolterHRV时域、频域指标评估心脏自主神经调节功能。结果1)2型糖尿病有或无颈动脉内膜增厚组各HRV指标(SDNN,SDANN,RMSSD,PNN50,SDNN指数)均较正常对照组低(P<0·05或P<0·01)。2)2型糖尿病合并颈动脉内膜增厚者HRV指数较无病变者有进一步的下降,而且HRV指数与IMT呈负相关。结论HRV是2型糖尿病颈动脉粥样硬化的独立相关因素,可对大血管并发症作出早期的诊断,改善预后。     

老老年高血压病患者昼夜血压节律对颈动脉硬化的影响

目的探讨老老年高血压病患者昼夜血压节律对颈动脉硬化的影响。方法应用24h动态血压监测仪监测82例年龄≥80岁的高血压病患者血压水平,根据夜间血压下降率将患者分为非杓型组和杓型组。测定两组患者颈动脉内膜中层厚度(IMT)。结果非杓型组与杓型组的IMT分别为(0.17±0.08)cm、(0.14±0.04)cm,差异有统计学意义(P<0.01)。结论昼夜血压节律异常的老老年高血压病患者颈动脉硬化更明显。     

颈动脉超声在颈动脉疾病中的临床应用进展

颈动脉超声检查具有无创伤性、可重复性、可进行血流动力学评价,而且检查费用低廉,对颈动脉疾病的早期诊断具有重要价值。文章介绍了超声对颈动脉粥样硬化斑块的形态学评价、各种超声检查方法在颈动脉狭窄评价中的应用及优缺点,强调综合应用各种检查方法和参数指标在提高颈动脉狭窄诊断准确率中的重要性。     

超声测量颈动脉内膜中层厚度与颈动脉斑块的关系

为了探讨颈动脉内膜中层厚度与局限性颈动脉斑块的联系 ,对 91名受试对象的颈总动脉内膜中层厚度及颈内动脉和颈动脉分叉处的斑块进行超声检测 ,并将颈动脉内膜中层厚度进行分级。结果观察到有斑块者较无斑块者其颈动脉内膜中层厚度明显增加 ( 0 .83± 0 .16mm比 0 .6 4± 0 .12mm ,P <0 .0 1) ,且随斑块的严重程度增加 ,其内膜中层厚度呈增厚趋势。该结果支持颈总动脉内膜中层厚度与颈动脉局限性动脉粥样硬化斑块明显相关 ,提示颈动脉内膜中层厚度增厚可能是颈动脉粥样硬化的早期表现     

Effect of Probucol and/or Cilostazol on Carotid Intima Media Thickness in Patients with Coronary Heart Disease: A Randomized,Multicenter, Multinational Study

Aim: In a prospective randomized multinational open blinded endpoint study, the long-term effects of probucol or probucol and cilostazol with statin on carotid mean intima media thickness (IMT) were evaluated for the first time.Methods: Hypercholesterolemic patients with coronary artery disease were randomized to three groups and received study drugs for 3 years: the control with statin alone; the probucol group with statin and probucol; and the combo group with statin, probucol, and cilostazol. Primary efficacy endpoint was changes of mean carotid IMT at 3 years. Biomarkers, major adverse cerebro-cardiovascular events (MACCEs) and safety were secondary endpoints.Results: Two hundred eighty-one patients were randomized into three groups. All three groups showed significant regression of carotid IMT at 3 years compared with baseline. Decrease in mean carotid IMT was significantly greater in the combo group than in the control group at 1 year. However, there were no significant differences in changes of mean carotid IMT between groups at 3 years (control; −0.12 ± 0.36 mm vs. probucol; −0.11 ± 0.32 mm vs. combo; −0.16 ± 0.38 mm). MACCEs were frequent in the control group, but the difference was not significant (control; 10.8% vs. probucol; 4.4% vs. combo; 6.9%, p = 0.35). Probucol and cilostazol were well tolerated in long-term treatment without serious drug-related adverse reactions.Conclusion: Probucol or probucol and cilostazol with statin did not reduce carotid IMT in comparison with statin alone in this study. However, the clinical outcome of probucol-based treatment with current standard statin treatment may need further studies.     

慢性阻塞性肺疾病患者代谢综合征与颈动脉内膜中膜厚度的相关性研究

目的探讨慢性阻塞性肺疾病(COPD)患者代谢综合征与颈动脉内膜中膜厚度(IMT)的相关性。方法选取2013—2014年就诊于西安市第一医院的60例COPD患者作为COPD组,另选取同期在西安市第一医院体检中心进行体检的无COPD病史的健康者60例作为对照组。所有受试者在入组时记录人口学信息及既往病史,采集空腹静脉血检测空腹血糖(FPG)、三酰甘油(TG)及高密度脂蛋白胆固醇(HDL-C)水平;采用颈动脉超声检查仪检查颈动脉IMT;对颈动脉IMT的相关因素进行多元逐步线性回归分析。结果 COPD组患者代谢综合征发生率为51.7%,高于对照组的30.0%(P0.05);COPD组患者颈动脉IMT为(1.07±0.25)mm,高于对照组的(0.86±0.18)mm(P0.05)。多元线性回归分析结果显示,COPD发生率(β=0.24,P=0.00)、年龄(β=0.18,P=0.01)及BMI(β=0.18,P=0.03)与颈动脉IMT呈线性相关,而代谢综合征发生率与颈动脉IMT无直线相关性(β=0.10,P=0.26)。结论 COPD患者代谢综合征发生率及颈动脉IMT明显增高,但代谢综合征与颈动脉IMT无直线相关性。     

超声在糖尿病合并颈动脉粥样硬化诊断中的临床价值

目的探讨超声在糖尿病合并颈动脉粥样硬化诊断中的临床价值。方法收集应用超声检测的100例门诊和住院的临床诊断为糖尿病合并高血压、冠心病和(或)脑梗死患者为研究对象,应用彩色超声诊断仪检查患者的颈总动脉、颈内动脉和颈外动脉的内径、颈动脉内膜-中层厚度和血流以及粥样斑块位置、大小、内部回声情况,评价超声诊断的临床价值。结果该组患者均有颈动脉内膜-中层的增厚,内膜面毛糙、高低不平。18例患者一处或多处斑块形成,其中斑块表现为弱回声及等回声、强回声本别有3例和15例患者。12例患者位于颈总动脉及分叉处,6例患者位于颈内动脉及起始段。12例患者双侧对称出现,6例患者单侧出现。确诊的35例患者均出现血流信号。在未形成斑块的轻度颈动脉粥样硬化的18例糖尿病患者中,为正常层流,其中充满整个管腔者有8例,血流呈现偏黯淡颜色者9例。形成斑块的17例患者中,均在病变处见到血流充盈缺损,病变处血流明显变细呈五彩镶嵌者有4例。频谱多普勒扫查未见异常改变的患者为7例;狭窄处频带和峰值流速分别轻度增宽和加快的患者为11例;血流速度偏低,波峰圆钝且收缩期峰值后移的患者为13例;4例患者狭窄处频谱充填且远端低平,峰值于舒张末期加快,峰值流速和加速时间分别得到降低和延长,轻度提高了对侧颈动脉流速。结论超声在糖尿病合并颈动脉粥样硬化诊断中具有一定的临床价值。     

体表超声检测颈动脉粥样硬化与冠心病相关性研究进展

体表超声检测颈动脉粥样硬化与冠心病之间关系密切，可反映冠状动脉粥样硬化及其程度．已广泛用于临床及流行病学的检查。     

开滦集团职工中老年人群心血管健康行为和因素对颈动脉内膜中膜厚度的影响

目的探讨中老年人群心血管健康行为和因素对颈动脉内膜中膜厚度的影响。方法采用横断面研究方法,随机分层抽取唐山开滦(集团)有限责任公司在职及离退休职工中年龄≥40岁,排除既往心肌梗死、缺血性脑卒中(不包括腔隙性脑梗死)及相关研究资料缺失者,最终纳入统计分析的共5353例,进行统一问卷调查、血液生物化学指标检测及颈动脉超声检测,采用多元线性回归分析心血管健康评分对颈动脉内膜中膜厚度的影响,采用多因素Logistic回归分析心血管健康行为和因素对颈动脉硬化的影响。结果本研究人群共5353例,年龄40~94(55.1±11.8)岁,其中男性3209例,占59.9%。1具备≤1项、2项、3项、4项、5项以及≥6项理想心血管健康行为和因素的研究人群颈动脉内膜中膜厚度分别为0.89±0.19 mm、0.88±0.19 mm、0.85±0.19 mm、0.82±0.18 mm、0.80±0.18 mm、0.76±0.15 mm,各组颈动脉硬化检出率分别为32.6%、31.4%、24.7%、20.3%、15.9%、9.5%。2影响颈动脉内膜中膜厚度的多元线性回归模型校正年龄、性别、甘油三酯、高密度脂蛋白、低密度脂蛋白等因素后,心血管健康评分与颈动脉内膜中膜厚度呈线性负相关(B=-0.012,95%CI:-0.014~-0.011,P0.001);影响颈动脉硬化的多因素Logistic回归模型校正年龄、性别、甘油三酯、高密度脂蛋白、低密度脂蛋白等因素后,与具有≤1项理想心血管健康行为和因素的研究人群比较,具有3项、4项、5项以及≥6项理想心血管健康行为和因素的研究人群发生颈动脉硬化的风险值(OR)分别为0.62、0.40、0.31、0.18。结论中老年人群理想心血管健康行为和因素是颈动脉内膜中膜厚度的保护性因素,随着理想心血管健康行为和因素项数及其评分的增加,颈动脉内膜中膜厚度和颈动脉硬化检出率均降低。     

Biology of Calcification in Vascular Cells: Intima versus Media

Background: Vascular calcification occurs at two distinct sites within the vessel wall: the intima and the media. Intimal calcification occurs in the context of atherosclerosis, associated with lipid, macrophages and vascular smooth muscle cells, whereas medial calcification can exist independently of atherosclerosis and is associate with elastin and vascular smooth muscle cells. Pathogenesis: In this review we compare intimal and medial calcification, particularly discussing the mechanisms which may be responsible for each type of calcification. Similar mechanisms probably initiate and regulate both forms of calcification including the generation of matrix vesicles/apoptotic bodies and local expression of mineralization-regulating proteins. However, since different modifying agents such as lipids in the intima and elastin in the media are present at the sites of calcification and are associated with particular diseases, this implies that the etiologies of these processes differ. For example, intimal calcification is associated with atherosclerosis while medial calcification occurs commonly in the diabetic neuropathic leg. Clinical Importance: Since both types of calcification correlate with significant morbidity and mortality, we discuss the different types of calcification in terms of their clinical importance. Hintergrund: Die Kalzifizierung der arteriellen Gefäßwand kann mit unterschiedlicher Lokalisation in der Intima oder aber der Media stattfinden. Die Kalzifizierung der Intima verläuft im Zusammenhang mit atherosklerotischer Plaquebildung und ist mit Lipidakkumulation, Makrophagen und glatten Muskelzellen assoziiert. Die Kalzifizierung der Media kann unabhängig von Atherosklerose vorkommen und ist mit Elastin und glatten Muskelzellen assoziiert. Pathogenese: In der vorliegenden Übersicht vergleichen wir die Kalzifizierung von Intima und Media besonders bezüglich der jeweils zugrunde liegenden Mechanismen. Beide Formen der Gefäßkalzifizierung werden vermutlich durch ähnliche Mechanismen initiiert und reguliert. Dabei spielen die Bildung von Matrixvesikeln bzw. Apoptose ebenso wie die lokale Expression von mineralisationsregulierenden Proteinen eine Rolle. Der Nachweis unterschiedlicher modifizierender Faktoren allerdings, die mit den beiden Formen der Kalzifizierung einhergehen, nämlich Lipide in der Intima und Elastin in der Media, weist auf eine unterschiedliche Erkrankungsätiologie hin. So ist die Kalzifizierung der Intima ein Ausdruck der atherosklerotischen Plaquebildung, während die Kalzifizierung der Media häufig in den Beinarterien bei der peripheren diabetischen Neuropathie gefunden wird. Klinik: Beide Formen der Kalzifizierung der Gefäßwand gehen mit erheblicher Morbidität und Mortalität einher. In der vorliegenden Arbeit werden diese Erkrankungen deshalb im Hinblick auf ihre klinische Bedeutung vorgestellt.