Elevation of asymmetric dimethylarginine in patients with unstable angina and recurrent cardiovascular events.

AIMS: We investigated the role of asymmetric dimethylarginine (ADMA) for clinical outcome of patients with unstable angina. METHODS AND RESULTS: Forty-five patients with stable angina, 36 patients with unstable angina, and 40 healthy controls were included in this study. Coronary artery disease (CAD) patients were prospectively followed for 1 year. ADMA levels were measured at baseline and after 6 weeks using a validated ELISA. Baseline ADMA concentration in controls was significantly lower than in patients with CAD (0.59+/-0.23 vs. 0.76+/-0.17 micromol/L; P<0.001). Patients with unstable angina had significantly higher baseline ADMA levels than patients with stable angina (0.82+/-0.18 vs. 0.73+/-0.15 micromol/L; P=0.01). There was a significant reduction of ADMA levels at 6 weeks after percutaneous coronary intervention (PCI) in patients with unstable angina who experienced no recurrent cardiovascular event (from 0.81+/-0.14 to 0.73+/-0.19 micromol/L; P<0.05). In contrast, patients with unstable angina who had an event showed no significant decrease in ADMA at 6 weeks. Actuarial survival analysis showed a significantly higher event rate in patients with persistently elevated ADMA plasma concentrations. CONCLUSION: ADMA is significantly elevated in patients with unstable angina. A reduced ADMA level at 6 weeks after PCI may indicate a decreased risk of recurrent cardiovascular events.     

Coronary atherosclerosis and oxidative stress as reflected by autoantibodies against oxidized low-density lipoprotein and oxysterols

Clinical studies and animal experiments have demonstrated that oxidized low-density lipoprotein (oxLDL) and oxysterols play important roles in atherogenesis. OxLDL is immunogenic, and autoantibodies (Ab) against oxLDL are detectable in serum. We investigated the relevance of oxysterols and Ab against-oxLDL to coronary artery disease (CAD) in 183 patients undergoing coronary angiography. Patient groups included angiographically normal subjects (< 75% stenosis), others with spasm (> 75% narrowing in response to acetylcholine), and some others with fixed stenosis (> 75%). The group with stenosis was subdivided into patients with stable and unstable angina. Serum concentrations of autoantibodies and 25-, 27-, and 7-beta-hydroxycholesterols were significantly higher in the stenotic group than in the normal group (P < 0.01, P < 0.05, P < 0.05, and P < 0.05, respectively). Antibodies, but not oxysterol concentrations, were significantly greater in subjects with unstable than with stable angina (P < 0.01). We conclude that anti-oxLDL antibody and oxysterol concentrations are associated with coronary artery stenosis, and that oxidative stress may be greatly increased in unstable angina.     

Lipoprotein (a) is increased in acute coronary syndromes (unstable angina pectoris and myocardial infarction), but it is not predictive of the severity of coronary lesions

Lipoprotein (a) [Lp(a)] concentrations were determined in 365 patients undergoing coronary angiography for stable angina (n = 159), unstable angina (n = 99), recent myocardial infarction (n = 45), and nonischemic heart disease (cardiomyopathy or valvular disease, n = 62, non-IHD). Mean ± SD and median Lp(a) concentrations in stable angina (29.9 ± 29.2; 22 mg/dl) did not differ from those in non-IHD (26.9 ± 26.3; 17), but were significantly lower than in patients with unstable angina (52.7 ± 36.6; 58) and myocardial infarction (44.8 ± 36.4; 34) (p < 0.01). Coronary angiography revealed that 261 patients, including 4 patients in the non-IHD group, had significant (≥ 50%) coronary lesions. Lp(a) was higher in patients with (41 ± 35; 32) than in those without (28 ± 27; 19) angiographic evidence of significant coronary stenosis (p < 0.05) and showed a weak univariate correlation with the angiographic index (Total Score) of the severity of the disease (r = 0.106; p < 0.05). However, in the subgroup of 303 patients with stable/unstable angina or myocardial infarction, Lp(a) was predictive neither of angiographic presence nor of severity of coronary disease. Patients were then ranked according to the Total Score values. Among patients with comparable angiographic severity of coronary artery disease, Lp(a) appeared to be remarkably higher in patients with acute ischemic syndromes (unstable angina, myocardial infarction) than in patients with stable angina. In conclusion, Lp(a) was roughly twice as high in acute (unstable angina, myocardial infarction) than in chronic (stable angina) ischemic syndromes, but there was no difference between chronic stable angina and non-IHD. Serum level determination of Lp(a) made a poor contribution in predicting the extent of coronary artery disease.     

Prospective comparison of coronary artery remodeling between acute coronary syndrome and stable angina in single-vessel disease: correlation between C-reactive protein and extent of arterial remodeling

BACKGROUND: Retrospective intravascular ultrasound (IVUS) studies showed that positive remodeling of coronary artery was associated with unstable clinical presentation. However, no prospective IVUS study has been performed to demonstrate such relationship. The relationship between C-reactive protein (CRP) and coronary artery remodeling is unknown. HYPOTHESIS: Positive remodeling might be related with acute coronary syndrome in the prospective IVUS study. C-reactive protein levels might be associated with coronary artery remodeling. METHODS: Preintervention IVUS images were prospectively obtained in 93 patients with single-vessel disease (30 for acute coronary syndrome and 63 for stable angina). Serum sample for CRP measurement was collected 24 h prior to coronary intervention. The remodeling index was defined as a ratio of (lesion/average reference) external elastic membrane area. Positive remodeling was defined as a remodeling index > 1.05 and negative remodeling as a remodeling index < 0.95. RESULTS: The remodeling index was 0.99 +/- 0.13 in acute coronary syndrome versus 0.95 +/- 0.12 in stable angina (p = 0.048). Positive remodeling was associated with acute coronary syndrome (43 vs. 19%), whereas negative remodeling was more frequent in stable angina (49 vs. 33%) (p = 0.047). C-reactive protein levels were significantly higher in acute coronary syndrome than in stable angina (1.4 +/- 2.0 vs. 0.5 +/- 0.6 mg/dl, respectively, p = 0.002). However, there was no significant correlation between CRP levels and remodeling index (r = 0.078, p = 0.475). CONCLUSIONS: Positive remodeling may be related with acute coronary syndrome in the prospective IVUS analysis. C-reactive protein levels may not predict the extent of arterial remodeling.     

Interleukin-18: a strong predictor of the extent of coronary artery disease in patients with unstable angina

The aim of this study was to confirm that plasma interleukin (IL)-18 level is associated with the extent of coronary artery disease in unstable angina patients. Previous studies have shown that patients with unstable angina have significantly higher plasma IL-18 levels than healthy volunteers. However, the association between IL-18 and the extent of coronary artery atherosclerosis in patients with unstable angina remains unclear. Plasma concentrations of IL-18 and high-sensitivity C-reactive protein (hs-CRP) were measured in 166 consecutive patients admitted for coronary arteriography. One hundred and eighteen patients with unstable angina had coronary artery disease (coronary artery disease group; severity score: 2.32 ± 1.47; Gensini score: 31.3 ± 25.9), and 48 patients with coronary risk factors and without coronary artery lesions served as the risk control group. Plasma levels of IL-18 were higher in the coronary artery disease group than in the risk control group (P = 0.062). Additionally, plasma levels of IL-18 were significantly higher in 77 coronary artery disease patients with severity score ≥2 than in the risk control group (242.3 ± 110.6 vs 209.8 ± 120.3 pg/ml, P = 0.016). By univariate analysis, log-transformed plasma IL-18 concentration was positively correlated with coronary artery disease severity score (r = 0.244, P = 0.009). By multiple regression analyses, the association between coronary artery disease severity score and IL-18 remained significant (β = 0.733, P = 0.017) when controlling for age, diabetes mellitus and left ventricular ejection fraction. Additionally, coronary artery disease severity score was greater in the highest tertile (>246 pg/ml) of plasma IL-18 levels than in the middle (176–246 pg/ml) and the lowest (<176 pg/ml) tertiles (2.79 ± 1.52 vs 2.05 ± 1.08 vs 2.13 ± 1.66, P = 0.028). Of note, plasma hs-CRP level had no significant correlation with coronary artery severity. Plasma IL-18 level is associated with the extent of coronary artery disease in unstable angina patients, suggesting the link between IL-18 and coronary artery atherosclerosis in these patients.     

Inflammatory status as a main determinant of outcome in patients with unstable angina, independent of coagulation activation and endothelial cell function.

AIMS: Inflammation, endothelial cell function and the coagulation system have been demonstrated to be involved in the onset and course of unstable angina. Whether a proinflammatory state independently determines outcome is unknown and has not been determined yet in a clinically well defined study population of consecutive patients admitted with unstable angina. METHODS AND RESULTS: Markers of inflammation, coagulation activation and endothelial cell function were determined on admission in blood of 211 consecutive patients with severe unstable angina and were related to the in-hospital course. Refractory unstable angina occurred in 76 patients (36%) during their hospital stay. In a univariate analysis, C-reactive protein (P = 0.03), fibrinogen (P < 0.001) and erythrocyte sedimentation rate (P = 0.001) levels were significantly higher in patients with refractory unstable angina, when compared with patients who had an uneventful clinical course. The odds ratios (95% CI) adjusted for age, sex, body mass index, smoking behaviour and cholesterol levels of the occurrence of refractory unstable angina for patients in the highest quartile compared with patients in the lowest quartile of inflammatory markers were 2.19 (0.94-5.11) for C-reactive protein, 2.83 (1.13-7.10) for fibrinogen and 4.72 (1.70-13.09) for the erythrocyte sedimentation rate. The findings were not affected by the presence or absence of myocardial necrosis or the interval between onset of angina and blood collection. No association was found between markers of coagulation activation or markers of endothelial cell function, and in-hospital outcome. CONCLUSION: We found that in a clinically well-defined study population of patients with severe unstable angina, a proinflammatory state is an important and independent determinant of short-term outcome. The data strengthen the importance of inflammation in this syndrome.     

心绞痛患者冠状动脉内皮损伤及意义

目的　探讨冠心病患者冠状动脉 (冠脉 )内皮细胞损伤及在冠心病发生、发展过程中的临床意义。方法　 37例心绞痛患者均经冠脉造影证实有明显冠脉狭窄 ,测定其冠状窦和外周血中一氧化氮 (NO)、内皮素 (ET)含量和循环内皮细胞 (CEC)数量 ,比较不稳定性心绞痛、稳定型心绞痛和对照组间相同和不同部位之间指标的差异。结果　不稳定性心绞痛、稳定型心绞痛患者冠状窦和外周血中NO含量较对照组均明显降低 (P <0 0 1或P <0 0 5 ) ,ET含量和CEC数量均明显增高 (P <0 0 1或P <0 0 5 ) ,不稳定性心绞痛组NO含量较稳定型心绞痛组明显降低 (P <0 0 5 ) ,ET含量和CEC数量均明显增高 (P <0 0 1) ,不稳定性心绞痛和稳定型心绞痛患者冠状窦血中NO含量均明显低于外周血 (P <0 0 5 ) ,ET含量和CEC数量均明显高于外周血 (P <0 0 1或P <0 0 5 ) ,对照组冠状窦与外周血相比三项指标均未见明显差别 (P >0 0 5 )。结论　心绞痛患者冠脉局部内皮受损及功能紊乱与病情严重程度相一致 ,内皮损伤的加重可能是病情恶化以及急性冠脉事件发生的病理生理基础。     

不稳定型心绞痛患者冠状动脉局部炎性细胞因子的变化及临床意义

目的　研究不稳定型心绞痛 (USA)时炎性细胞因子在冠状动脉局部的变化及其临床意义。方法　测定 USA、稳定性心绞痛 (SA)及正常对照组患者右心房、外周静脉中的血浆血小板 α-颗粒膜蛋白 14 0 (GMP-14 0 )含量及中性粒细胞 (PMN)活性。结果　 U SA组冠状动脉局部表现为血小板高度活化、PMN活性明显增强 ,与外周血相比 ,GMP- 14 0含量、PMN活性均存在显著差异 (P <0 .0 5 ,P <0 .0 1) ;与 SA组及正常对照组比较 ,U SA组冠状动脉局部及外周血炎性细胞因子活性均明显增强。结论　 USA患者的冠状动脉局部存在急性炎症过程 ,炎症反应激活可诱导血管收缩、血栓形成 ,加重心肌损害     

Inflammatory markers and coronary interventions: a potentially useful follow-up modality after stenting.

Periprocedural levels of various inflammatory markers have been correlated with prognosis in patients undergoing percutaneous coronary interventions. However, long-term variations of interleukin-1 receptor antagonist (IL-1Ra) or C-reactive protein (CRP) during follow-up after coronary interventions were not previously investigated. The aim of our study was to perform serial evaluations of these markers before and after coronary stenting and to correlate them with clinical status. Plasma levels of IL-1Ra and CRP were measured at baseline and 3 and 6 months after the procedure in 31 patients with symptomatic coronary artery disease undergoing stent implantation, who had no evidence of myocardial ischemia at 6-month follow-up. While at 3 months there were no significant variations of baseline values, 6 months after the procedure a significant decrease from baseline was observed both in IL-1Ra and CRP levels (median -24 pg/ml, P = 0.048, and -0.13 mg/dl, P = 0.017, respectively). Six-month reduction in both IL-1Ra and CRP levels was significant in patients with unstable angina (n = 18; IL-1Ra: from 175 to 119 pg/ml, P = 0.001; CRP: from 0.52 to 0.18 mg/dl, P = 0.002) and nonsignificant in those with stable angina (n = 13) on admission (IL-1Ra: from 123 to 158 pg/ml, P = 0.22; CRP: from 0.19 to 0.10 mg/dl, P = 0.44). In conclusion, a significant reduction of IL-1Ra and CRP levels is observed 6 months after stent implantation in patients with preprocedural unstable angina who remain free of ischemia. This decrease suggests a stabilization of the inflammatory process and may be associated with a favorable prognosis after coronary interventions.     

Increased serum neopterin: a marker of coronary artery disease activity in women

OBJECTIVE: To assess whether neopterin concentrations in women with unstable angina differ from those in women with chronic stable angina. DESIGN: Prospective cohort study. SETTING: University hospital in south west London. PATIENTS: 114 consecutive women with angina were studied: 82 had chronic stable angina (typical exertional chest pain, positive exercise ECG testing, and/or abnormal myocardial scintigraphy; symptoms stable for at least three months), and 32 had unstable angina (Braunwald class III). All patients with chronic stable angina (100%) and 18 with unstable angina (56.3%) underwent digital coronary angiography; neopterin concentrations were determined using a commercially available immunoassay. MAIN OUTCOME MEASURES: Major clinical events during one year follow up were readmission with Braunwald's class IIIb unstable angina, non-fatal myocardial infarction, and cardiac death. RESULTS: Major events occurred in 12 women with chronic stable angina (14.6%) and nine women with unstable angina (28.1%). Mean (range) neopterin concentrations were significantly higher in women with unstable angina than in those with chronic stable angina (7.6 (5.1-11.5) nmol/l v 5.9 (4.4-7.5) nmol/l; p = 0.003), even after adjustment for variables which were significantly different on univariate analysis. In women with chronic stable angina, baseline neopterin concentrations were higher in those with cardiac events than in those without events (7.1 (5.9-9.1) nmol/l v 5.7 (3.9-7.3 nmol/l); p = 0.010), even after adjustment for variables with significant differences between both groups on univariate analysis. CONCLUSIONS: On average, women with unstable angina had significantly higher neopterin concentrations than women with chronic stable angina. Women with chronic stable angina with events during follow up had higher neopterin concentrations than those without events. Neopterin concentrations were similar in patients with unstable angina and women with chronic stable angina who developed events. Neopterin concentrations may therefore be a marker of risk in women with coronary artery disease.     

Expansion of peripheral CD8+ T cells in patients with coronary artery disease: relation to cytomegalovirus infection

OBJECTIVES: The nature of the immune response in coronary artery disease (CAD) is not fully defined. One pathogen that has been linked to atherogenesis, cytomegalovirus (CMV), is known to exert strong and long-lasting effects on peripheral T cells. In the present study, we investigated the effect of prior CMV infection on the immune system in CAD patients. SUBJECTS: Patients with stable angina and angiographically verified CAD (n=43) and clinically healthy controls (n=69) were included. METHODS: The expression of CD57 and CD28 on peripheral CD4+ and CD8+ T cells was evaluated with three-colour flow cytometry. The findings were related to serological markers of inflammation, T-cell activation and CMV seropositivity. RESULTS: An expansion of CD8+ T cells expressing CD57 but lacking CD28 was seen in the patient group. The numbers of CD8+ CD57+ and CD8+ CD28-T-cell subsets were independently related to CMV seropositivity (P<0.001) but also to CAD per se (P<0.05). Serum concentrations of C-reactive protein (CRP) and soluble interleukin-2 receptor (sIL-2R) were elevated in the patients but not related to CMV or CD8+ T-cell subsets. CONCLUSION: A pronounced shift in peripheral T-cell homeostasis was observed in CAD patients. Primarily CMV infection but also CAD per se contributed to the expansion of CD8+ T-cell subsets. The T-cell changes were not related to a systemic inflammatory response but should rather be considered as markers of a chronic antigen exposure and/or immunosenescence in CAD.     

冠心病患者单核细胞组织因子的表达

目的：测定冠心病患单核组织因子的表达,并评价它与冠心病活动性之间的关系。方法：用免疫荧光技术和流式细胞术,测定稳定型心绞（ＳＡＰ组）,不稳定型心绞痛（ＵＡＰ组）,急性心肌梗死（ＡＭＩ组）患和健康受定（对照组）循环中单细胞组织因子的表达。结果：ＳＡＰ试（对照组）和ＡＭＩ组单核细胞组织因子的表达均高于对照组,组织因子的表达与冠心病的活动性显相关。结论：冠心病患循环中,单核细胞组织因子的表达增强与冠心病的心病患血液呈血液呈高凝状态的原因之一。     

Residual high-grade angina after enhanced external counterpulsation therapy

OBJECTIVE: We evaluated the degree of residual angina on the outcomes of enhanced external counterpulsation (EECP) therapy for chronic stable angina. BACKGROUND: Angina refractory to medical therapy is common in the pool of patients who are not completely revascularized by angioplasty or bypass surgery. METHODS: We examined 902 patients enrolled from 1998 to 2001 in the Second International Enhanced External Counterpulsation Patient Registry. Baseline and outcome variables were stratified by the last recorded Canadian Cardiovascular Society class. RESULTS: Residual Class 3 (12.1%) or 4 (2.3%) angina was uncommon among patients with severe coronary artery disease after treatment with EECP. Prevalence of diabetes, hypertension, dyslipidemia, and heart failure was similar among the anginal post-EECP anginal classes. Multivessel coronary disease was more common in those with higher-grade angina at completion. More frequent and severe angina at entry was more common in those with the higher anginal classes at EECP (P<.001). There were no differences in the rates of chronic medications utilized or prior revascularization. At 3-year follow-up, rates of death, myocardial infarction, percutaneous coronary intervention, and coronary artery bypass surgery tended to be higher across increasing residual angina classes. The composite cardiac event rates were 34%, 33%, and 44% for those with Class 0, Class 1/2, and Class 3/4 angina at EECP completion (P=.01), respectively. Multivariate analysis for the composite endpoint found residual Class 3/4 angina (OR=1.59, 95% CI=1.19-2.17, P=.002), diabetes (OR=1.57, 95% CI=1.23-2.01, P=.0003), age (per decile OR=1.17, 95% CI=1.04-1.31, P=.007), and greater EECP augmentation (OR=0.79, 95% CI=0.65-0.96, P=.02) as significant predictors. CONCLUSIONS: Residual high-grade angina after EECP occurs in those with more severe angina and multivessel disease at baseline and is associated with cardiac events over the next 3 years. These data suggest that close clinical observation and intensive management of those with high-grade angina post-EECP are warranted.     

Short and long term outcome of percutaneous transluminal coronary angioplasty in unstable versus stable angina pectoris: A report of the 1985–1986 nhlbi ptca registry

In a cohort of 1,720 consecutive patients from the National Heart, Lung, and Blood Institute, Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry (August 1985–May 1986), we compared 768 patients (45%) with stable angina and 952 patients (55%) with unstable angina pectoris. Unstable angina patients exhibited at least one of the following characteristics: new onset angina, rapidly progressing angina, angina at rest, angina refractory to medication, variant angina, acute coronary insufficiency, or angina recurring shortly after an acute myocardial infarct. The distribution of single- and multi-vessel disease was similar among stable and unstable angina patients; multi-vessel disease predominated. Average severity of stenosis and incidence of tubular and diffuse stenosis morphology were higher among patients with unstable angina (both p<0.001). Patient success rates were similar in stable and unstable patients. However, on a per lesion basis, overall angiographic success rate and average reduction of severity of stenosis in successfully dilated lesions were significantly higher among patients with unstable angina (both p<0.001). Incidence of major patient complications (p<0.01) and of emergency coronary bypass surgery (p<0.05) were also higher in patients with unstable angina but consistent with their more precarious clinical condition and stenosis morphology. During a two year follow-up, the cumulative distributions of death, myocardial infarct, repeat PTCA, and coronary bypass surgery were not significantly different in patients with stable angina compared to patients with unstable angina. Comparison of the current PTCA Registry cohort with the cases reported in the 1979–1982 Registry revealed a 19% higher success rate for both stable and unstable angina patients. Major complication rates decreased between time periods for stable but not for unstable angina patients. Incidence of emergency bypass surgery decreased more for stable than for unstable angina patients. Coronary angioplasty is indicated in properly selected patients with unstable angina and both single-and-multi-vessel coronary disease.     

Increased plasma levels of soluble selectins in patients with unstable angina

BACKGROUND: Inflammation plays an important role in the pathogenesis of unstable angina. Adhesion molecules, such as selectins, mediate the interactions between leukocytes, platelets and endothelial cells during inflammation and thrombogenesis. HYPOTHESIS: The purpose of this study was to determine whether soluble E-selectin, P-selectin and L-selectin levels are increased in patients with unstable angina (UA). METHODS: Soluble E-, P- and L-selectin levels were measured by enzyme-linked immunoassay in the peripheral blood of 23 patients with UA, 26 patients with stable angina (SA) and 15 control patients with angiographically normal coronary arteries. RESULTS: Soluble E-selectin levels were significantly higher in patients with UA (45+/-11 ng/ml) than in controls (30+/-8 ng/ml, P<0.001), or patients with SA (34+/-8 ng/ml, P=0.001). Similarly, plasma levels of P- and L-selectin were significantly higher in patients with UA (427+/-144 and 772+/-160 ng/ml, respectively) than in patients with SA (278+/-79 and 643+/-94 ng/ml, respectively, P<0.005 vs. UA for both), or control patients (189+/-43 and 601+/-126 ng/ml, respectively, P=0.001 vs. UA for both). CONCLUSIONS: Plasma levels of soluble selectins were increased in patients with UA compared with patients with SA or patients without angiographically visible coronary artery disease. Measurements of these adhesion molecules may be helpful as non-invasive markers of coronary plaque destabilization in UA.     

Interleukin-1 Receptor Antagonist: A Sensitive Marker of Instability in Patients with Coronary Artery Disease

Background: Increased plasma levels of acute phase reactants are correlated with acute coronary syndromes and increased risk of in-hospital events. Interleukin-1 receptor antagonist (IL-1Ra) modulates the activity of IL-1, a cytokine associated with inflammatory response; we have prospectively investigated whether detection of increased levels of IL-1Ra in patients may be useful in the characterization of coronary syndromes. Methods: Plasma levels of IL-1Ra were measured in 118 consecutive patients undergoing coronary angiography with a clinical diagnosis of recent unstable angina (N = 57), chronic stable angina (N = 49) or atypical chest pain (N = 12). Results: Angiography showed significant coronary disease in the first two groups and was normal in the latter group. Patients with unstable angina had significantly higher levels of IL-1Ra than stable patients [158 (110–224) vs 108 (95–154) pg/ml, P = 0.002] and individuals with chest pain and normal coronary angiogram [110 (97–123) pg/ml, P: = 0.038]. In contrast, while C-reactive protein levels were significantly higher in patients with stable and unstable angina vs those without coronary disease (0.29 vs 0.06 mg/dl, P: = 0.022), they did not discriminate between stable and unstable angina patients (0.22 vs 0.32 mg/dl, P: = 0.66). Conclusions: These results indicate that IL-1Ra may be a sensitive marker of clinical instability in patients with coronary artery disease.     

Safety and prognostic value of early dobutamine-atropine stress echocardiography in patients with spontaneous chest pain and a non-diagnostic electrocardiogram.

AIMS: To risk stratify and shorten hospital stay in patients with spontaneous (resting) chest pain and a non-diagnostic electrocardiogram (ECG). METHODS AND RESULTS: The study comprised 102 patients (mean age 58+/-12 years, 67 men) with spontaneous chest pain and a non-diagnostic ECG. Forty-three patients had suspected coronary artery disease and 59 had known (but of unknown actual significance) coronary artery disease. All patients underwent serial creatine kinase enzyme measurements, continuous ECG monitoring for at least 12 h and early dobutamine-atropine stress echocardiography in patients with negative creatine kinase enzymes and normal findings at ECG monitoring. Dobutamine-atropine stress echocardiography was considered positive in patients with new or worsening wall thickening abnormalities. Patients with negative dobutamine-atropine stress echocardiography were discharged after the test. In-hospital and 6 month follow-up events noted were cardiac death, non-fatal myocardial infarction, unstable angina, and coronary artery bypass surgery or angioplasty. Thirteen patients had evidence of evolving myocardial infarction by elevated creatine kinase enzymes, or unstable angina by ECG monitoring. In the remaining 89 patients, dobutamine-atropine stress echocardiography was performed after a median observation period of 31 h (range 12-68 h). During dobutamine-atropine stress echocardiography no serious complications (death, non-fatal myocardial infarction, sustained ventricular tachycardia or ventricular fibrillation) occurred. Dobutamine-atropine stress echocardiography results were of poor quality in three, non-diagnostic in six, negative in 44 and positive in 36 patients. In the 80 patients with diagnostic dobutamine-atropine stress echocardiography, variables associated with in-hospital events (n=7) were history of exertional angina (P<0. 005), chest pain score (P<0.005), stress-induced angina (P<0.001) and positive dobutamine-atropine stress echocardiography (P<0.005). Variables associated with follow-up events (n=11) were history of exertional angina (P<0.05), chest pain score (P<0.001), stress-induced angina (P<0.01) and positive dobutamine-atropine stress echocardiography (P<0.01). At multivariate analysis the only significant predictor of events was positive dobutamine-atropine stress echocardiography (P<0.01). CONCLUSION: Early dobutamine-atropine stress echocardiography may safely distinguish between low- and high-risk subsets for subsequent cardiac events in patients with spontaneous chest pain and a non-diagnostic ECG.     

Marked elevation of vascular endothelial growth factor and basic fibroblast growth factor in pericardial fluid of patients with angina pectoris

Although we reported that basic fibroblast growth factor (bFGF) levels in pericardial fluid of patients with unstable angina are apparently increased, it was unclear whether vascular endothelial growth factor (VEGF) is also increased in patients with myocardial ischemia. Using an enzyme-linked immunosorbent assay, we measured the concentrations of VEGF and bFGF in pericardial fluid of 51 patients with open heart surgery. Patients were divided into group A (n=10) with class III unstable angina (Braunwald's classification), group B (n=24) with class I or II unstable angina or stable angina and group C (n=17) with non-ischemic heart disease. The VEGF level in pericardial fluid in group A was 83±7 pg/ml, being significantly (p<0.001) higher than the 27±3 pg/ml in group B and the 28±5 pg/ml in group C. The concentrations of bFGF in pericardial fluid in groups A and B were 1461±579 and 1224±161 pg/ml, respectively, significantly (p<0.05) higher than the 292±97 pg/ml in group C. The level of VEGF in pericardial fluid was increased only in patients with severe rest angina within 2 days before emergency coronary artery bypass graft surgery (CABG), while bFGF was increased in all patients undergoing CABG for coronary artery disease. Thus VEGF and bFGF may play important roles in mediating collateral growth in humans.     

Renal artery stenosis presenting as crescendo angina pectoris

The coexistence of different clinical syndromes due to atherosclerosis in different organs is not rare and emphasizes the diffuse nature of this vascular process. Although renovascular disease may cause hypertension and/or renal insufficiency, it may also occur in the absence of the usual clinical markers that suggest renovascular hypertension. We report a patient with stable coronary anatomy who presented with crescendo angina pectoris. Diagnosis of renovascular hypertension was made by screening renal angiography at the time of the cardiac catheterization. Renal artery stenting resulted in stabilization of the coronary syndrome and obviated the need for further coronary intervention. To our knowledge, this is the first case of renovascular hypertension precipitating an unstable coronary syndrome in a patient with documented stable coronary anatomy. Review of the literature supports that patients undergoing cardiac catheterization are a high risk population for renovascular disease, particularly in the presence of other predictive factors such as documented coronary artery disease, older age, female gender, congestive heart failure, peripheral vascular disease, renal insufficiency, and smoking. Firm recommendations for routine screening renal angiography in patients undergoing peripheral or coronary angiography will need further studies. © 1995 Wiley-Liss, Inc.     

Platelet bound oxLDL shows an inverse correlation with plasma anaphylatoxin C5a in patients with coronary artery disease

Both oxidized lipids as well as the complement system contribute to atherothrombosis. The expression of complement receptors correlates with the expression of platelet activation markers, and platelet bound oxidized low-density lipoprotein (oxLDL) modulates platelet function. In the present study, we investigated the relationship of markers of complement activation, the anaphylatoxins C5a and C3a, and oxidized low-density lipoprotein.

Two hundred and seven patients with coronary artery disease (CAD) were analyzed in this study. Using enzyme-linked immunosorbent assays, plasma levels of oxLDL, C3a, and C5a were measured. Moreover, we assessed platelet bound oxLDL by flow cytometry. The overall level of C5a in the troponin negative group (stable angina (SA) and unstable angina (UA)) compared to the troponin positive group (non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI)) did not differ significantly (62.7 ± 32.4 ng/ml versus 65.8 ± 40.3 ng/ml). While C5a and C3a showed a significant correlation with each other (r = 0.25, p < 0.001), there was no statistically significant relationship between C3a and platelet bound oxLDL (r = 0.06, p = 0.37). Furthermore, plasma oxLDL did not correlate with either C3a or C5a. However, we observed a moderate, yet significant negative correlation between plasma C5a and platelet bound oxLDL (r = ?0.15, p = 0.04). Partial correlation analysis correcting for the presence of acute coronary syndrome (ACS), troponin status or the subgroups SA, UA, NSTEMI, or STEMI did not alter this correlation substantially. Interestingly, flow cytometric analysis of human platelets showed increased expression of C5aR and P-selectin after in vitro stimulation with oxLDL.

In conclusion, the complement anaphylatoxin C5a shows an inverse correlation with platelet bound oxLDL. The relationship of oxidized lipids to particular complement components may add to the platelet–lipid interplay in atherogenesis and trigger future clinical and mechanistic studies.