Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study

OBJECTIVE: To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis. METHODS: One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (A/V ratio) was calculated. MAIN OUTCOME MEASURES: Retinal vascular abnormalities, mean arteriolar blood pressure (MABP). RESULTS: Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0.10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher blood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1.34), and retinopathy had an OR of 1.25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89. CONCLUSION: Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors.     

Modification of low density lipoprotein potentiates its inhibitory effect on catecholamine secretion in cultured bovine adrenal medullary cells

Low density lipoprotein (LDL) and lipoprotein(a) suppress catecholamine secretion in cultured adrenal medullary cells. Modification of LDL by oxidation or acetylation potentiates various atherogenic actions of LDL. In the present study, we investigated whether the modification of LDL influences catecholamine secretion in cultured bovine adrenal medullary cells. The exposure of LDL to CuSO₄ caused a time-dependent oxidation of LDL. Maximal oxidation of LDL was observed after exposure to CuSO₄ for 24 h. Native LDL inhibited catecholamine secretion induced by carbachol to 68.5% of control. Oxidized LDL caused further inhibition of carbachol-evoked secretion to 37.6% of control. Acetylated LDL inhibited it to 41.0% of control. There was a good correlation between the extent of LDL oxidation and the inhibition of catecholamine secretion. These results suggest that oxidation or acetylation of LDL augments its inhibitory effect on the secretion of catecholamines. Since catecholamines are a risk factor of atherosclerosis, the inhibitory effect by such modified LDL may be a mechanism inhibiting atherosclerotic progression. Received: 29 January 1999 / Accepted: 19 April 1999 / Published online: 22 June 1999     

Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental arterial wall injury

To test iodine-125 labelled low-density lipoprotein (¹²⁵I-LDL), polyclonal indium-111 labelled immunoglobulin G (¹¹¹In-IgG) and iodine-125 labelled endothelin-1 uptake in metabolically active atheromatous plaques after arterial wall injury, we performed balloon de-endothelialization of carotid arteries or abdominal aortas in 24 New Zealand male rabbits which were fed with a normal diet (n=14) or a hypercholesterolaemic diet (n=10) after surgery. Six weeks later the animals were injected with 200 Ci of (¹²⁵I-LDL), and/or with 100 Ci of ¹¹¹In-IgG or with 9 Ci of ¹²⁵I-endothelin-1. Forty-eight hours later the animals were sacrificed. Carotid arteries and aortas were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral carotid arteries and thoracic aortas served as controls.Significant ¹¹¹In-IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting. The percentage of the injected dose per gram (%D.inj/g) was 0.0188±0.06 versus 0.0059±0.003 in controls (P< 0.05). There was no difference in ¹¹¹In-IgG uptake between arteries with injury alone and those with active atheroma formation at the site of the injury. Significant (¹²⁵I-LDL), uptake was observed only when lipid deposition was present at light microscopy (%D.inj/g of 0.0024±0.0005 vs 0.0010±0.0003 in controls, P < 0.05). ¹²⁵I-endothelin-1 accumulation was observed in four of five injured aortas both at autoradiography, with diffuse localization, and at well counting (%D.inj/g of 0.0012±0.0004 in the abdominal aortas vs 0.0008±0.0003 in the thoracic aortas).Polyclonal IgG may accumulate in injured arteries without active atheroma formation. Inflammatory reaction at the site of the injury may cause ¹¹¹In-IgG uptake independently of atheromatous plaque formation. LDL accumulation takes place only with active atheroma formation at the site of the injury. Use of labelled peptides such as endothelin-1 may provide further insight into the mechanisms of atheromatous plaque formation.     

Concept of an antiatherosclerotic efficacy of calcium entry blockers

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers.INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CHAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031).     

颈总动脉超声检查对预测冠心病的价值

目的 探讨颈总动脉超声检查预诊冠心病的价值，寻找一个较理想的早期预测动脉粥样硬化的指标。方法 用超声观察临床确诊的冠心病患者的双侧颈总动脉(CCA)及球部，并与部分冠脉造影对照。观察动脉内径、内-中膜厚度(IMT)、有无斑块及数量、是否钙化、彩色血流、血流速度、搏动指数、阻力指数(RI)，计算颈总动脉内一中膜横切面面积(IMCSA)。结果 本研究显示，动脉粥样硬化的表现多为动脉内径增大、IMT增厚、IMCSA增大、血流速度(舒张期和平均血流速度)减慢、PI和RI增加。本研究还显示，斑块形成以心绞痛组发生率最高，高血压组和心肌梗死组次之，以软性斑快为主，多在双侧CCA及分叉处。结论颈总动脉尤其分叉处的IMT增加或内-中膜精糙，回声增强，是动脉粥样硬化的早期表现，对预测冠心病具有一定的应用价值。     

脑梗塞患者血清肺炎衣原体特异性抗体的检测

目的探讨肺炎衣原体(CPn)感染与动脉血栓性脑梗塞的关系.方法用酶联免疫吸附试验(ELISA)法测定了112例脑梗塞患者和50例其他疾病患者的血清肺炎衣原体特异性IgG抗体及IgM抗体.结果肺炎衣原体慢性感染率分别为脑梗塞组的85.71%(96/112)和对照组48.00%(24/50),脑梗塞患者肺炎衣原体慢性感染率均明显高于对照组,肺炎衣原体IgG阳性病例血清TG浓度明显高于肺炎衣原体IgG阴性的病例(P＜0.05);HDL-C则明显低于阴性组.结论脑梗塞患者肺炎衣原体感染率明显增高,提示肺炎衣原体感染可能与脑梗塞有关.其可能的机制是肺炎衣原体感染后形成免疫复合物沉积在血管壁,引起血管局部损伤;并改变了血脂浓度,增加了脑血管病发生的危险性.     

新疆维吾尔族、汉族2型糖尿病住院患者颈动脉粥样硬化及危险因素的对比研究

目的比较维吾尔族和汉族2型糖尿病住院患者颈动脉粥样硬化的检出率及相关的危险因素。方法136例维吾尔族和158例汉族2型糖尿病住院患者进行颈动脉B超检查,记录临床资料,测量收缩压(SBP)、舒张压(DBP)、计算体质指数(BMI),检测糖化血红蛋白(HbA1C)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、脂蛋白a(LP(a))、凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fg)。结果维吾尔族和汉族2型糖尿病患者颈动脉粥样硬化检出率分别为38.2%,51.8%,维吾尔族患者高于汉族(P<0.05)。维吾尔族患者BMI、LDL-C和病程分别为(28.67±3.02)kg/m2(、3.29±0.53)mmol/L(、5.42±0.58)a,BMI、LDL-C高于汉族患者,差别有统计学意义(P<0.05),而病程明显短于汉族患者(P<0.05)。结论维吾尔族2型糖尿病住院患者颈动脉粥样硬化的检出率显著高于汉族患者并有早发倾向,这可能与维吾尔族患者的BMI和LDL-C水平高于汉族患者有关。     

超声检测颈动脉对冠心病的预诊断价值

目的探讨颈动脉粥样硬化与冠心病的关系。方法对91例冠心病的患者行冠状动脉造影和颈动脉超声检查。分为对照(CON)组、稳定型心绞痛(SAP)组和不稳定型心绞痛(UAP)组。结果SAP组和UAP组的IMT值、颈动脉硬化和斑块形成的阳性率均明显高于CON组(P<0.01);冠脉单支和多支病变组与CON组比较上述指标亦有明显增高(P<0.01);UAP组不稳定型斑块比例显著高于SAP组(P<0.01)。比较两者的检出率,颈动脉硬化具有较高的敏感度,特异性偏低;而粥样斑块形成则有较高的特异性,敏感度较低,阳性似然比、阴性似然比均高于颈动脉硬化。结论测定颈动脉壁厚度、粥样斑块及其性质,对冠心病的预测具有临床意义。     

血清胆红素与冠心病的关系

目的探讨血清总胆红素与冠心病的关系。方法对120例冠心病患者与120例健康者作对照,用改良J-G法检测血清总胆红素;用胆固醇氧化酶法(CHOD-PAP)检测总胆固醇(TC);用磷酸甘油氧化酶法(GPO-PAP)检测甘油三酯(TG);用直接匀相测定法检测高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),进行两组比较。结果冠心病组的总胆红素明显低于对照组(P<0.05)。结论血清胆红素的降低,可导致冠心病的发生。     

Outcomes of Carotid Revascularization in Patients with Contralateral Carotid Artery Occlusion

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