Pathophysiology of acute coronary syndromes

The natural history of coronary artery disease is punctuated by clinical manifestations of unstable angina, acute myocardial infarction, and ischemic sudden death. These acute coronary syndromes share common pathophysiologic mechanisms that include fissuring of a plaque followed by varying degrees of dynamic coronary obstruction, which is due to vasoconstriction and coronary thrombosis. The response to plaque fissure is likely to be modulated by local and/or systemic procoagulant and anticoagulant-fibrinolytic activities. The key role of coronary thrombosis in acute coronary syndromes has substantial implications for prevention and treatment of complications of coronary atherosclerosis.     

Hemorheological abnormalities in stable angina and acute coronary syndromes

The pathophysiological abnormalities of stable angina (SA) and acute coronary syndromes (ACS) may, in part, be promoted by fluid forces associated with local blood flow and hence by the rheological properties of blood. This study evaluated several hemorheological parameters in 16 healthy controls and in 16 SA, 18 unstable angina (UA) and 19 acute myocardial infarct (AMI) patients; all patients underwent diagnostic angiography following blood sampling. Rheological measurements included whole blood viscosity, plasma viscosity and RBC aggregation via erythrocyte sedimentation rate (ESR) and Myrenne aggregometer indices. Compared to controls, RBC aggregation was significantly elevated in all patient groups (p<0.001), with the rank being AMI>UA>SA. RBC aggregability as tested in 70 kDa dextran exceeded control in all patients. Blood viscosity values calculated at 40% Hct, plasma viscosity and yield shear stress values followed the same pattern (AMI>UA>SA>control); increases of inflammatory markers (i.e., WBC count, hs-CRP) were elevated in all patient groups in the order AMI>UA>SA. Our study thus indicates an association between hemorheological abnormalities and the severity of coronary artery disease, and suggests the merit of evaluating whether therapeutic interventions that normalize blood rheology may reduce the incidence and/or progression of coronary artery disease.     

Interleukin-6 and E-selectin in acute coronary syndromes and stable angina pectoris

Objectives

The purpose of the study was to compare the serum levels of interleukin-6 (IL-6), E-selectin, and trans-fatty acids (TFA) between those with stable and unstable angina pectoris.

Methods

From September 2008 to March 2009, a case?Ccontrol study was performed at two university hospitals. We included 89 patients with acute coronary syndrome (ACS) including patients with myocardial infarction and those with unstable angina pectoris (case group) and 93 patients with stable angina pectoris (control group). The two groups were matched with respect to demographic characteristics and risk factors of cardiovascular diseases. Serum levels of IL-6 and E-selectin were measured using the enzyme linked immunosorbent assay, while TFA and lipoproteins were measured using gas chromatography and enzymatic methods, respectively.

Results

No significant differences between baseline characteristics of the two study groups were observed. Patients with stable angina had significantly higher serum levels of total cholesterol (187.0?±?3.7 vs. 171.6?±?4.2?mg/dl; p?=?0.009), low density lipoproteins (104.8?±?2.4 vs. 95.4?±?2.7; p?=?0.017), and TFA (1.41?±?0.47 vs. 1.24?±?0.69?mg/dl; p?=?0.047) compared to those with ACS. Serum levels of IL-6 were found to be significantly higher in those with stable angina compared to those with ACS (102.4?±?1.9 vs. 224.6?±?3.6; p?=?0.007). However, patients with ACS had higher levels of E-selectin (53.5?±?25.7 vs. 49.2?±?23.5???g/dl; p?=?0.52), but the difference did not reach statistical significance.

Conclusion

In the current study, inflammation as measured by IL-6 and E-selectin was not found to play an important role in progression of ischemic heart disease from stable angina to unstable angina or myocardial infarction, which is contrary to previous studies.     

Unstable angina with coronary to pulmonary artery fistulae

Three patients presenting with chest pain were found at cardiac catheterization to have fistulae between the left anterior descending coronary and the main pulmonary artery. Two patients presented with unstable angina, the third with atypical chest pain. Of the two patients presenting with unstable angina both had concomitant coronary artery disease. One was successfully treated with percutaneous transluminal coronary angioplasty. The other underwent successful double aorto-coronary bypass grafting and fistulae ligation. The remaining patient's symptoms resolved after informing him that he did not have atheromatous coronary artery disease. In no patient was the presence of the fistula felt to be related to the patients presenting complaint. In the two patients with unstable angina, a coronary steal phenomenon was postulated as a possible contributing factor.     

急诊冠状动脉内支架置入治疗不稳定性心绞痛

目的　探讨在不稳定性心绞痛病人症状未缓解状态下行急诊冠状动脉内支架置入的疗效及安全性。方法　对53例不稳定性心绞痛病人在心绞痛反复发作时即行冠状动脉造影，明确病变后行冠状动脉支架置入术。结果　53处病变置入56个支架，术中无严重并发症，34例心绞痛消失；9例有不典型胸痛，症状在1～2天内消失，无急诊冠状动脉搭桥及死亡。随访3个月～3年,6例冠脉造影证实再狭窄，5例行再次PTCA术后症状消失，1例行PTCA后仍有症状行冠状动脉旁路移植术(CABG)，无死亡病例。结论　冠状动脉内支架置入治疗急性冠状动脉综合征近期及远期效果较好，治疗成功率及安全性较高。     

History of depression,angina, and quality of life after acute coronary syndromes

Background Depression has been associated with higher mortality and morbidity rates after acute coronary syndromes (ACS), but little is known about the association between depression, angina burden, and quality of life. We evaluated the association between a history of depression and patient-reported angina frequency, physical limitation, and quality of life 7 months after discharge from the hospital for ACS. Methods Patients were enrolled in the Department of Veterans Affairs Access to Cardiology Study, a cohort study of all patients with acute myocardial infarction or unstable angina who were discharged from 24 Veterans Affairs medical centers between March 1998 and February 1999. Data from 1957 patients who completed a 7-month postdischarge Seattle Angina Questionnaire were analyzed. Multivariate logistic regression was used to evaluate a history of depression as an independent predictor of angina frequency, physical limitation, and quality of life 7 months after ACS, as measured with the Seattle Angina Questionnaire. Results A total of 526 patients (26.7%) had a history of depression. After adjustment for a wide array of demographic, cardiac, and comorbid factors, a history of depression was significantly associated with more frequent angina (odds ratio [OR] 2.40, 95% CI 1.86-3.10, P < .001), greater physical limitation (OR 2.89, 95% CI 2.17-3.86, P < .001), and worse quality of life (OR 2.84, 95% CI 2.16-3.72, P < .001) after ACS. Conclusion We found a strong association between a history of depression and both heavier angina burden and worse health status after ACS. These findings further support the importance of depression as a risk marker for adverse outcomes after ACS. (Am Heart J 2003;145:493-9.)     

Platelet hyper-function in acute coronary syndromes.

Previous studies have demonstrated shortened bleeding times in patients with acute coronary syndromes, especially in myocardial infarction (MI). In this study we have investigated platelet hyper-function using the PFA-100 with collagen/adenosine diphosphate and collagen/epinephrine cartridges in 78 patients presenting with acute chest pain. Patients were classified into MI, unstable angina (UA) and non-specific chest pain. All patients received 300 mg aspirin (ASA) more than 2 h before blood samples were collected. Twenty healthy normal subjects were also tested before and 2 h after 300 mg ASA (n = 10). The collagen/adenosine diphosphate closure time was significantly shorter in MI patients (median, 71 s; P = 0.0237) but not in UA patients (median, 81 s; P > 0.05) compared with normal subjects (median, 92.5 s). The collagen/epinephrine closure times were significantly longer in UA patients (median, 233 s) than in untreated controls (median, 125 s; P < 0.0001), as expected, but there was no difference in MI patients (median, 149.24 s; P > 0.05), suggesting that the MI patients were not all responding to ASA. Analysis of a subset of the apparent ASA non-responders (n = 5) by platelet aggregation demonstrated that this was not related to failure of ASA to block cyclo-oxygenase activity. Von Willebrand factor levels were significantly elevated in both UA and MI patients compared with normal subjects (mean, 175.5 and 248.9 versus 89.1 s; P < 0.0001 and P < 0.0001, respectively) and were also significantly higher in the MI group compared with the UA group (P < 0.05). There is evidence for platelet hyper-function and elevated von Willebrand factor levels in the MI group that could explain their decreased responsiveness to ASA on the collagen/epinephrine cartridge.     

Unstable angina

Opinion Statement The recent availability of novel antiplatelet and antithrombin agents has revolutionized the therapeutic options for intermediate- and high-risk unstable angina (UA). Current guidelines recommend aspirin, unfractionated heparin (UFH), and antianginal therapy. Low-molecular-weight heparin (LMWH) and direct thrombin inhibitors have significant theoretical advantages and apparent clinical benefits compared with UFH and are good alternatives in selected patients. Glycoprotein (GP) IIb/IIIa receptor inhibition reduces the future risk of myocardial infarction (MI) and may reduce the incidence of death in patients with unstable angina. In particular, these drugs should be considered for use in combination with aspirin and UFH in patients undergoing an “early invasive” approach. Coronary revascularization plays an important role in high-risk patients and in those with refractory angina, but its routine application continues to be controversial. Issues regarding the use of LMWH in combination with GP IIb/IIIa inhibitors and during percutaneous transluminal coronary angioplasty (PTCA) are being addressed in clinical trials. Ideally, the incidence of serious cardiac events in patients with UA will continue to decrease with the ongoing search for potent drug combinations that achieve early control of intracoronary thrombosis.     

Unstable angina

Patients with unstable angina, defined as resting chest pain associated with transient repolarization changes on the electrocardiogram, represent a high risk subset among the clinical manifestations of ischemic heart disease. Pathogenetic mechanisms include coronary spasm and vasoconstriction, coronary thrombosis and platelet aggregation. Early prognosis is related to the degree of activity of the disease while long-term outcome depends on the extent of the coronary disease and the degree of left ventricular dysfunction. Medical treatment should include the combination of beta-blockers, nitrates and calcium antagonists as well as the use of heparin and aspirin. Despite such an aggressive treatment, attacks of resting chest pain persist in almost 30 per cent of patients. In these cases emergency revascularization may be achieved by either coronary angioplasty or bypass surgery. The latter operation may result in improved survival in patients with impaired left ventricular function and triple vessel disease.