Platelet aggregability to platelet activating factor at rest and after exercise in patients with coronary artery disease

The platelet response to the aggregatory effect of platelet-activatingfactor (PAF) in relation to blood PAF levels, serum PAF-acetylhydrolase(PAF-AH) activity and to their lipidoemic profile, was studiedin 44 patients with coronary artery disease undergoing exercisetests. The PAF EC₅₀ values in 21 patients with positive exercisetest results were found to be significantly decreased at restcompared with 21 normal subjects (126±3•9 nM and24•9±11•7 nM respectively) (P<0•0001).Moreover, the maximal percentage of aggregation to 50 nM PAFwas found to be significantly increased (20•0±4•3%vs 13•5±3•6% respectively) (P<0•0001).By contrast, the PAF EC₅₀ values and the maximal percentageof aggregation in 23 patients with negative exercise test resultswere not statistically significantly different from the controlgroup (25•2±11•4 nM and 14•1±4•7%,respectively). At the end of exercise, the PAF EC₅₀ values and the maximalpercentage of aggregation did not change in any group, and therewere no significant differences in the whole-blood PAF levelseither at rest or at the end of exercise. In patients with positiveexercise test results, the PAF-AH activity at rest was significantlyhigher compared with the control group (37•2±8•0nmol. ml^–1. min^–1 vs 32•4±4•3 nmol.ml^–1. min^–1), (P<0•03), whereas the enzymeactivity did not differ in patients with negative exercise testresults compared to controls (33•6±6•1 nmol.ml^–1. min^–1). There was no change in PAF-AH activity during exercise in anygroup. The enzyme activity was positively correlated to theserum total and low density lipoprotein (LDL) cholesterol levelsin the control group and in patients with negative exercisetest results, whereas no correlation was found between PAF-AHactivity and total or LDL cholesterol levels in patients withpositive exercise test results. Our results suggest that platelethyper-reactivity to PAF may play a pathophysiological role inmyocardial ischaemia observed during exercise in coronary arterydisease patients.     

Heparin-releasable platelet factor 4 in patients with coronary artery disease.

Recently, platelet factor 4 (PF4) release by heparin (heparin-releasable PF4) has been examined as a useful marker of the interaction between the substances liberated from circulating platelets and the vascular endothelium. We compared the plasma levels of PF4 and beta-thromboglobulin (beta-TG) after intravenous heparin injection in patients with coronary artery disease (CAD) and normal control subjects. We also studied the effects of low-dose aspirin (81 mg/day) on the plasma level of heparin-releasable PF4 in the CAD patients. Blood samples were obtained before and 5 min after the intravenous injection of heparin (1,000 IU) from 23 patients with CAD and 15 normal control subjects. Although the plasma beta-TG level remained unchanged after heparin injection, the plasma PF4 level markedly increased in both groups. There was a significant difference in plasma PF4 levels at 5 min after heparin injection between the CAD group (100.1 +/- 38.1) and the control group (61.0 +/- 24.0) (p less than 0.01). The PF4/beta-TG ratio after heparin injection was also higher in the CAD group than in the control group (p less than 0.01). There was a correlation between the PF4/beta-TG ratio after heparin and the Gensini CAD score, which defines the severity of coronary atherosclerosis (r = 0.489, n = 23, p less than 0.01). Low-dose aspirin was administered to 11 CAD patients for 246.0 +/- 28.8 days. Blood samples for the assay of PF4 and beta-TG were obtained as stated above, and platelet aggregation, thromboxane B2 (TxB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) levels were also measured before and during aspirin administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet counts and aggregates in coronary artery disease

Platelet counts and aggregates have been measured in arterial,coronary sinus and peripheral venous blood in groups of patientswith and without coronary artery disease, and under variousconditions associated with myocardial ischaemia. No changesin platelet counts were observed. An increase in platelet aggregatesacross the coronary vascular bed was observed during spontaneousor ergometrine-induced ischaemia, but not with pacing-inducedangina nor at the onset of coronary occlusion causing infarction.Platelet aggregates were high in systemic blood samples frompatients with frequent episodes of spontaneous angina but notin samples from patients with stable effort angina, nor werethey increased with exercise-induced angina or after myocardialinfarction. The findings suggest that platelet aggregates arefound in coronary sinus blood when there is very severe proximalnarrowing (but not complete occlusion) of a coronary arterysufficient to cause cardiac pain at rest, but not when proximalconstriction is less severe and the ischaemia is pacing-induced.Increased platelet aggregates in systemic blood samples maybe a marker of recent episodes of rest pain.     

冠心病患者纤溶活性、血小板功能及内皮素在运动前后的变化及其临床意义

目的研究冠心病患者在运动前后纤溶活性、血小板活化状态及血管内皮功能的变化。方法根据冠状动脉造影结果，选择冠心病患者（ＣＨＤ组）３７例，分为单支及多支病变组；另选健康人２７例为对照组（Ｃ组）。采用次极量运动试验观察上述部分指标在运动前后的变化。结果（１）运动前，组织型纤溶酶原激活剂（ｔＰＡ）、纤溶酶原激活剂抑制因子１（ＰＡＩ１）活性、血浆５羟色胺（５ＨＴ）水平及血小板５ＨＴ２Ａ受体密度，ＣＨＤ组均高于Ｃ组（Ｐ＜０．０５）；血浆内皮素（ＥＴ）１浓度两组差异无显著性（Ｐ＞０．０５）。（２）运动后，ＣＨＤ组ｔＰＡ活性下降（Ｐ＜０．０５），ＰＡＩ１活性上升（Ｐ＜０．０２５）；血浆５ＨＴ水平及血小板５ＨＴ２Ａ受体密度增加（Ｐ＜０．０５）；血浆ＥＴ１浓度上升，与Ｃ组比较差异有显著性（Ｐ＜０．０５）。上述各指标的增高，多支病变组较单支病变组明显（Ｐ＜０．０１～０．００５）。（３）运动前仅ＰＡＩ１活性与心肌缺血面积呈正相关（ｒ＝０．４５２，Ｐ＜０．００５）。结论冠心病患者纤溶活性下降，血小板激活，血管内皮受损，使冠心病患者易发生冠状动脉痉挛及血栓形成。次极量运动使之进一步加重而易诱发冠心病事件。     

Clopidogrel-mediated reduction of circulating tissue factor in patients with stable coronary artery disease

BACKGROUND: Tissue factor (TF), the initiator of coagulation, circulates in blood and contributes to thrombosis in patients with coronary artery disease (CAD). TF is present in the alpha-granules of platelets. Therapy with clopidogrel results in inhibition of platelet degranulation. Whether clopidogrel affects circulating TF is unknown. This study examined the effect of clopidogrel on TF level in the blood of patients with stable CAD and ST-elevation myocardial infarction (STEMI) as well as healthy controls. METHODS: Thirty-three patients with CAD and twenty with STEMI were studied pre and post clopidogrel therapy (loading dose 300 mg, then 75 mg daily). All were treated with aspirin 100 mg/d. The control groups consisted of thirty healthy male volunteers also treated with clopidogrel and ten patients with CAD treated with aspirin only. TF concentration in blood drawn pre and 96 h post clopidogrel administration was measured by enzyme-linked immunosorbent assay. RESULTS: Patients with CAD and STEMI had significantly more TF in blood than healthy controls. Clopidogrel reduced TF in stable CAD patients to levels seen in healthy controls. No alterations in TF were found in controls and patients with STEMI post clopidogrel therapy. Clopidogrel reduced sCD40L level in stable CAD patients, but not in STEMI patients. A correlation between TF and sCD40L was found for the combined CAD and control, but not STEMI group. CONCLUSION: Clopidogrel leads to a reduction of not only sCD40L but also TF in stable CAD. The reduction of TF may lead to a reduced thrombogenicity, contributing to the benefits of clopidogrel therapy.     

Evaluation of patients with coronary artery disease during exercise: The relation between extent of disease and perfusion deficit

The purpose of this study was to assess the relation between the extent of coronary artery disease (CAD) and size of exercise-induced myocardial hypoperfusion in 79 patients with angiographically documented CAD. None of the patients had Q-wave myocardial infarction. Fifty patients had one-vessel disease, ten had two-vessel disease, and 19 patients had three-vessel or left main disease. From a scintigraphic functional standpoint, patients were classified into two groups: 28 patients (35%) had large perfusion defects and 51 patients (65%) had small defects. The size of the thallium-201 perfusion defect during exercise was assessed as the perimeter of the defect in each projection expressed as a percentage abnormality of the total left ventricular perimeter in that projection. The average abnormality from the three projections was used in the final analysis. Eleven patients with large defects (39%) had one-vessel disease and 12 patients with small defects (24%) had multivessel disease. Stepwise multivariate discriminate analysis identified the number of diseased vessels (F = 13.9), the change in systolic blood pressure from rest to exercise (F = 10.8), the exercise heart rate (F = 9.1), and exercise electrocardiographic response (F = 7.8) as significant associates of the size of the perfusion defect (predictive accuracy = 70%). We conclude that the size of hypoperfused myocardium during exercise is variable in patients with CAD. Discriminate analysis identified the extent of CAD, exercise heart rate, change in systolic pressure from rest to exercise, and exercise electrocardiographic response as significant associates of the size of the defect.     

A clinical approach to exercise tolerance testing in coronary artery disease

Data from exercise tolerance testing should be incorporated into clinical decision making. A strategy for stratification of individual patients into high, indeterminate, and low-risk categories using Bruce protocol exercise testing is outlined. This approach will help to ensure further evaluation of high-risk individuals without excessive testing of patients having excellent long-term prognoses.     

Thrombopoietin and mean platelet volume in coronary artery disease

BACKGROUND: Large platelets are shown to be hemostatically more active. It has been suggested that mean platelet volume (MPV) is increased during acute myocardial infarction (AMI) and unstable angina pectoris (USAP). However, the underlying mechanism of the phenomenon remains unclear. HYPOTHESIS: In this study, platelets, MPV, and thrombopoietin (TP) levels were investigated in patients with coronary artery disease (CAD) and healthy controls. METHODS: Twenty patients with AMI and 20 patients with USAP were included in this study. Seventeen healthy adult subjects served as controls. Venous blood samples of the subjects were drawn within 12 h after admission. Thrombopoietin levels were measured by ELISA and platelet counts and MPV were assayed by autoanalyzer. RESULTS: Patients with AMI and USAP had higher platelet counts than those in the control group. Although the platelet counts were slightly higher in AMI than in USAP, this did not reach statistical significance. Mean platelet volume and levels of TP were found to be elevated in patients with AMI and USAP compared with control subjects (p < 0.001). Thrombopoietin levels were higher in AMI than USAP, but this was not statistically significant. There was a positive correlation between TP levels and MPV values (p < 0.05). CONCLUSION: Increased TP levels may increase both platelet counts and platelet size, resulting in hemostatically more active platelets, which may contribute to the development and progression of CAD.     

Haemodynamic effects of intravenous diltiazem at rest and exercise in patients with coronary artery disease

The acute effects of intravenous diltiazem on exercise performancewere studied in 10 patients with coronary artery disease. Haemodynamicmeasurements were made at rest and during exercise before andafter 0-5 mgkg^–1 of diltiazem. Diltiazem prolonged theduration of exercise (+2.85 min, P>0.001) and delayed theonset of ischaemic ST depression or angina in all patients.The highest tolerated heart rate and pressure rate product wereincreased in all but one patient after diltiazem. At rest diltiazem decreased mean arterial pressure (–10.8%,P>0.005), systemic vascular resistance (SVR) (-11.8%, P>005)and left ventricular stroke work index (SWI) (–14.1%,P>0.005). During exercise under diltiazem therapy, at the level achievedbefore the drug, the pulmonary capillary wedge pressure (-30%,P>0005) and the SVR (–13.6%, P>0.02) were lowered,the SWI (+13%, P>0.01) was increased: at the end of exerciseonly the SVR (14%, P>0.05) was reduced. Two patients experiencedangina on lying down and one had orthostatic hypotension afterexercise with diltiazem. This study indicates that intravenousdiltiazem is a potentially useful agent for the treatment ofangina by reducing myocardial oxygen demand at rest and by improvingleft ventricular performances on exercise.     

Arm exercise testing for coronary artery disease in patients with peripheral vascular disease

We evaluated 74 peripheral vascular disease (PVD) patients (54 men, age 61 +/- 7 years and 17 women, age 63 +/- 7 years) for potential coronary heart disease (CAD) using an arm exercise test (AET) protocol. All patients performed upright two-arm cranking using discontinuous stages of 2 minutes of exercise separated by 2 minutes of rest. Exercise intensity was increased by +100 or 200 kpm (kilopond meters) with each stage. ECG was monitored continuously and blood pressure and 12-lead ECG tracings were obtained at the end of each exercise stage. All patients reached an endpoint of subjective exhaustion. Men achieved 91 +/- 14% of age-predicted heart rate at 597 +/- 167 kpm, while women achieved 86 +/- 14% of age-predicted heart rate at 335 +/- 117 kpm. Ischemic ECG responses (+AET) defined as new or additional ST depression greater than 1.0 mm X 80 ms, occurred in 35 men (65%) and 7 women (42%). Coronary angiography was performed in a subset of 22 patients (15 males and 7 females). CAD (greater than 70% stenosis) was found in 11 of 12 men and 4 of 5 women who showed positive or strongly positive AET responses (overall predictive value for AET = 88%). We conclude that arm exercise stress testing is safely performed in PVD patients who cannot complete treadmill exercise. In this limited series of PVD patients, the predictive value of a +AET response for diagnosis of CAD is similar to established values for treadmill exercise.     

Noninvasive detection of coronary artery disease by assessing diastolic abnormalities during low isometric exercise

The handgrip-apexcardiographic test (HAT) is a simple low-level (40% of maximal voluntary handgrip during 2 min) stress test which can detect left ventricular (LV) diastolic abnormalities. To determine whether it contributes to the diagnosis of coronary artery disease (CAD), HAT was obtained in 68 patients–47 with and 21 without angina pectoris–who prospectively underwent coronary arteriography. According to the highest or lowest individual values of diastolic apexcardiographic indices in 255 healthy volunteers, a pathologic or positive HAT was defined by the presence of at least one of the following new criteria: (1) A wave relative to total height of apexcardiogram during and/or after handgrip>21%, (2) total apexcardiographic relaxation time (TART) during handgrip>TART at rest > 143 ms and/or TART corrected for the duration of diastole (TARTT) during handgrip <0.14, or (3) diastolic amplitude time index (DATI), given by dividing TAR-TI and A wave relative to total diastolic amplitude of apex tracing during handgrip<0.27. HAT was positive in 20 of 21 patients with single-vessel disease (sensitivity 95%), 21 of 24 patients with double-vessel disease (sensitivity 88%), and in 22 of 23 patients with triple-vessel disease (sensitivity 96%). Furthermore, HAT was positive in 20 of 21 (95%) patients without symptoms. Thus, the overall sensitivity of HAT for detecting CAD was 93%. This study is the first to demonstrate the high sensitivity of HAT in identifying patients with CAD with or without symptoms by assessing diastolic apexcardiographic abnormalities during low-level isometric stress. Thus, HAT potentially could become an additional simple diagnostic tool for noninvasive detection of patients with CAD.     

青年冠心病患者冠状动脉病变特点及相关危险因素分析

目的探讨冠状动脉粥样硬化性心脏病(冠心病)的临床特点在青年与老年患者间的差异。方法回顾性分析48例青年冠心病患者与156例老年冠心病患者的临床资料,着重分析比较两组的危险因素及冠状动脉造影结果。结果青年组冠心病患者女性比例占6.25%(3/48),明显低于老年组的33.33%(52/156),差异有统计学意义(P0.01)。青年组体质量指数明显高于老年组,差异有统计学意义[(27.03±2.73)kg/m2vs.(25.16±3.05)kg/m2,P0.01]。青年组大量吸烟的比例也远高于老年组,差异有统计学意义[75.00%(36/48)vs.36.54%(57/156),P0.01]。老年组合并原发性高血压、糖尿病的发生率高于青年组,差异有统计学意义[51.28%(80/156)vs.16.67%(8/48),P0.01;30.77%(48/156)vs.6.25%(3/48),P0.01]。青年组血浆总胆固醇,低密度脂蛋白胆固醇及三酰甘油浓度与老年组比较,差异无统计学意义(P0.05)。青年组高密度脂蛋白胆固醇浓度低于老年组,差异有统计学意义[(0.85±1.80)mmol/Lvs.(1.08±0.23)mmol/L,P0.01]。青年组血浆尿酸浓度高于老年组,差异有统计学意义[(349.10±67.02)mmol/lvs.(323.77±73.82)mmol/L,P0.01]。青年组冠状动脉病变以单支病变为主,且左前降支病变发生率最高。结论男性、肥胖、大量吸烟为青年冠心病主要发病危险因素,低高密度脂蛋白胆固醇浓度和高尿酸浓度也可能为青年冠心病的危险因素;青年冠状动脉病变轻,以单支病变为主。     

Radionuclide assessment of left ventricular function during dobutamine infusion in patients with coronary artery disease: comparison with ergometer exercise

The effects of dobutamine on left ventricular function were assessed employing radionuclide ventriculography (RNV) in 7 normal subjects (Group 1) and 21 patients with coronary artery disease (Group 2). After routine bicycle ergometer exercise RNV, dobutamine infusion was started at 5 micrograms/kg/min and the dosage was increased by 5 micrograms/kg/min every 4 minutes to a total of 15 micrograms/kg/min. In Group 1, left ventricular ejection fraction (LVEF) increased by both ergometer exercise and dobutamine infusion. In Group 2, LVEF did not increase during exercise, but increased during dobutamine infusion without evidence of significant myocardial ischemia. Only 2 patients in Group 2 had new regional wall motion abnormality. Left ventricular end-diastolic volume (LVEDV) in Group 2 increased from 191 +/- 19 to 210 +/- 18 ml during ergometer exercise, but decreased from 193 +/- 18 to 153 +/- 19 ml during dobutamine infusion. Short-term low-dose infusion of dobutamine may be used in patients without evidence of significant myocardial ischemia, but probably cannot be substituted for exercise testing in patients with mild to moderate coronary artery disease.     

QT离散度在冠心病患者运动试验中的意义

目的探讨平板运动试验中冠心病患者与冠状动脉正常者ＱＴ离散度（ＱＴｄ）变化的意义。方法分析经冠状脉动（冠脉）造影证实的１３例冠心病患者与１７例冠脉造影正常者平板运动试验前、试验中ＳＴ段下移０１ｍＶ以上或出现典型心绞痛症状或达亚极量心率时以及运动后体表１２导联心电图ＱＴｄ变化。结果运动前、中、后冠心病组ＱＴｄ分别为４６２±２０１ｍｓ，７１９±２０．４ｍｓ及５１．２±１４．５ｍｓ；而冠状动脉正常组分别为３２．３±６．６ｍｓ，３０．９±９．２ｍｓ与２９．４±８．５ｍｓ，两组相比Ｐ均＜０．０１；冠心病组ＱＴｄ运动中与运动前后相比Ｐ均＜０．０１，而冠脉正常组差异无显著性；以运动中ＱＴｄ≥６０ｍｓ判为异常，诊断冠心病的敏感性为９２．３％，特异性１００％，准确性９６．７％。结论冠心病患者运动试验中ＱＴｄ进一步显著增加，ＱＴｄ是运动试验中诊断冠心病心肌缺血敏感而特异的指标。     

冠心病患者平板运动试验中QT离散度变异的临床意义

目的 :探讨平板运动试验中冠心病患者 QT离散度 （QTd）变化的意义。方法 :经冠状动脉造影术证实的 14例冠心病患者与 16例冠脉造影正常者平板运动试验前、中、后体表心电图 QTd变化。结果 :运动前、中、后冠心病组QTd分别为 4 3± 16 ,70± 18及 4 8± 11ms,而冠状动脉正常组分别为 2 9± 4 ,2 9± 6及 2 7± 8ms。两组均 P<0 .0 1;冠心病组 QTd运动中与运动前后相比均 P<0 .0 1,而冠脉正常者差异并无显著性 ;以运动中 QTd≥ 6 0 m s判为异常 ,诊断冠心病的敏感性为 86 % ,特异性为 92 %。结论 :在平板运动试验中冠心病患者 QTd显著增大 ,它是运动试验中诊断冠心病的特异指标     

平板运动试验假阳性相关因素的分析

目的 探讨活动平板运动试验假阳性相关影响因素,调整观察参数,提高心电图活动平板运动试验评估冠脉病变的价值.方法 收集整理2012年1月至2014年6月因疑似冠心病在苏州九龙医院心脏中心接受活动平板运动试验、结果阳性的94例患者,所有患者均在平板运动试验后1w内行冠脉造影检查.根据造影结果将其分为真阳性组(A组)和假阳性组(B组),对比分析两组各项临床资料及活动平板试验数据.结果 真阳性组和假阳性组在性别、最大运动耐量(Mets)、运动峰值、心率收缩压乘积方面有显著差异(p＜0.05),A组平板运动试验中最大心率与运动终止后2 min心率的差值显著低于B组;A组平板运动试验终止后3 min收缩压与运动终止1 min收缩压的比值、包含2个以上冠心病危险因子的例数明显大于B组(p＜0.05).结论 活动平板试验参数结合相关的临床资料、血流动力学相关参数,能提高冠脉病变的诊断准确性,对临床诊断冠心病、评估治疗效果和预后等方面可提供有价值的参考.     

Diagnosing coronary artery disease in diabetic patients

Although several diagnostic modalities are available to the clinician interested in diagnosing coronary artery disease, very few have been validated in diabetic populations. This review discusses the non-invasive diagnosis of coronary disease in diabetic patients. Evidence regarding the prevalence and prognostic significance of silent ischemia is reviewed and the potential impact of silent ischemia on the diagnostic characteristics of the exercise treadmill test discussed. Other diagnostic tools are considered, and recommendations are made with respect to screening asymptomatic diabetic patients for coronary artery disease.     

Variable neurohumoral and hemodynamic responses to exercise in patients with exertional angina: influence of the severity of coronary artery disease

To assess neurohumoral and hemodynamic responses to exercise in patients with exertional angina, we measured plasma norepinephrine (NE) concentrations in 23 patients with exertional angina (with no heart failure) and compared the results with their coronary arteriographic findings. The 23 patients were divided into two groups: 14 cases with multiple vessel disease (MVD) and 9 cases with one-vessel disease. At resting state there were no significant differences between the two groups in levels of NE. At maximal exercise there were no significant differences between the groups in increases of heart rate, blood pressure, and rate-pressure product, but exercise-induced increase of plasma NE (%) was significantly larger in MVD (131.6 +/- 95.4%) (mean +/- SD) than in one-vessel disease (69.0 +/- 45.3%) (p less than 0.01). In conclusion, plasma NE responses to exercise differ between patients with multiple vessel disease and patients with one-vessel disease.     

Identification of patients with coronary artery disease by assessing diastolic abnormalities during isometric exercise.

BACKGROUND: Previous clinical studies using invasive and noninvasive methods have shown handgrip-induced diastolic abnormalities in patients with coronary artery disease (CAD). HYPOTHESIS: The study was undertaken to determine the utility of Doppler echo- and pressocardiography during hand-grip in discriminating patients with coronary artery disease (CAD) and in those with normal coronary arteries. METHODS: Both methods were obtained in 96 patients with suspected CAD within 24 h before coronary angiography. An abnormal handgrip-Doppler was defined by an early (E) to late (A) transmitral flow velocities ratio (E/A) < 1 during handgrip and a positive handgrip pressocardiographic test (HAT) by an abnormal increase in the A wave/total excursion or prolongation of the absolute or relative (heart-rate corrected) total relaxation time during isometric exercise. RESULTS: Of the 96 patients studied, 23 had normal coronary arteries and 73 showed CAD. In patients with normal coronary arteries, handgrip-Doppler showed an abnormal average E/A at rest and during handgrip, whereas all variables of HAT were within normal limits. In patients with CAD, handgrip-Doppler showed only a moderate handgrip-induced increase in average A (+ 19%, p < 0.001), whereas HAT showed a significant (p < 0.001) increase in mean A wave/total excursion (+ 60%) and decrease in the relative total relaxation time (- 17%). Furthermore, handgrip-Doppler and HAT were abnormal in 15 of 23 (65%, specificity 35%) and the HAT in 5 of 23 (22%, specificity 78%) patients with normal coronary arteries, as well as in 57 of 73 (sensitivity 78%) and 69 of 73 (95%) patients with CAD. CONCLUSIONS: Our study demonstrates that these noninvasive stress tests can become a useful new diagnostic modality for detecting patients with unknown or suspected CAD.