Juan Cosin-Sales

C-reactive protein, clinical presentation, and ischemic activity in patients with chest pain and normal coronary angiograms

OBJECTIVES We sought to investigate the relationship among C-reactive protein (hs-CRP), clinical characteristics, exercise stress test responses, and ST-segment changes during daily life in patients with typical chest pain and normal coronary angiograms (CPNCA). BACKGROUND Patients with CPNCA have coronary microvascular endothelial dysfunction and myocardial ischemia. Elevated hs-CRP levels have been related to atherogenesis and endothelial dysfunction. The relationship between hs-CRP and disease activity has not been previously investigated in CPNCA patients. METHODS We studied 137 consecutive CPNCA patients (mean age, 57 +/- 9; 33 men). All completed standardized angina questionnaires, underwent exercise stress testing, 24-h ambulatory electrocardiogram (ECG) monitoring (Holter), and hs-CRP measurements at study entry. RESULTS C-reactive protein levels (mg/l) were higher in patients with frequent (2.9 +/- 3.3) and prolonged (3.9 +/- 4.1) chest pain episodes, and in those with ST-segment depression on exercise testing (2.6 +/- 2.8) and Holter monitoring (3.4 +/- 3.1) compared with patients with occasional (1.3 +/- 1.2; p = 0.002) or shorter chest pain (1.5 +/- 1.3; p < 0.001) episodes, negative exercise stress testing (1.1 +/- 1.1; p < 0.001), and no ST-segment shifts on Holter monitoring (0.9 +/- 0.7; p < 0.001). Moreover, we found a correlation between hs-CRP concentration and number of ischemic episodes during Holter monitoring (r = 0.65; p < 0.001) and with the magnitude of ST-segment depression on exercise testing (r = -0.43; p < 0.001). The hs-CRP was the only independent variable (multivariate logistic regression) capable of predicting positive findings on Holter monitoring (odds ratio [OR], 3.8; confidence interval [CI], 2.3 to 6.2) and exercise testing (OR, 1.7; CI, 1.2 to 2.2). CONCLUSIONS The hs-CRP correlates with symptoms and ECG markers of myocardial ischemia in CPNCA patients. Whether hs-CRP is related to the pathogenesis of angina in these patients deserves further investigation.

Markers of inflammation and multiple complex stenoses (pancoronary plaque vulnerability) in patients with non-ST segment elevation acute coronary syndromes

Objective: To assess the relation between markers of inflammation and the presence of multiple vulnerable plaques in patients with non-ST segment elevation acute coronary syndromes. Design: Prospective cohort study of 55 patients with non-ST segment elevation acute coronary syndromes and angiographically documented coronary disease. Blood samples were obtained at study entry for the assessment of high sensitivity C reactive protein (CRP), neopterin, and neutrophil count. Coronary stenoses were assessed by quantitative computerised angiography and classified as “complex” (irregular borders, ulceration, or filling defects) or “smooth” (absence of complex features). Extent of disease was also assessed by a validated angiographic score. Results: Neutrophil count (r  =  0.36, p  =  0.007), CRP concentration (r  =  0.33, p  =  0.02), and neopterin concentration (r  =  0.45, p < 0.001) correlated with the number of complex stenoses. Patients with multiple (three or more) complex stenoses, but not patients with multiple smooth lesions, had a higher neutrophil count (5.9 (1.4) × 109/l v 4.8 (1.4) × 109/l, p  =  0.02), CRP concentration (log transformed) (1.08 (0.63) v 0.6 (0.6), p  =  0.03), and neopterin concentration (log transformed) (0.94 (0.18) v 0.79 (0.15), p  =  0.002). Multiple regression analysis showed that neopterin concentration (B  =  4.8, 95% confidence interval (CI) 1.9 to 7.7, p  =  0.002) and extent of coronary artery disease (B  =  0.6, 95% CI 0.03 to 1.2, p  =  0.04) were independently associated with the number of complex stenoses. Conclusions: Acute inflammatory markers such as high neutrophil count, CRP concentration, and neopterin concentration correlate with the presence of multiple angiographically complex coronary stenoses. Neopterin concentration was a stronger predictor of multiple complex plaques than were neutrophil count and CRP concentration. These findings suggest that a relation exists between inflammation and pancoronary plaque vulnerability.

Pregnancy-Associated Plasma Protein A and Its Endogenous Inhibitor, the Proform of Eosinophil Major Basic Protein (proMBP), Are Related to Complex Stenosis Morphology in Patients With Stable Angina Pectoris

Background—The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) has been implicated in coronary plaque disruption. Its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), may also play a role in this process. Atheromatous plaque disruption often presents as complex angiographic lesions. We sought to assess whether PAPP-A, proMBP, and PAPP-A/ProMBP ratio are markers of angiographic plaque complexity in patients with chronic stable angina. Methods and Results—We studied 396 stable angina patients (age 63±10 years, 230 men) of whom 289 had angiographically documented coronary artery disease (≥75% stenosis). All coronary stenoses ≥30% diameter reduction (n =531 in 322 patients) were assessed and classified as complex (n =228) or smooth (n =303) by previously validated criteria. PAPP-A, proMBP, and C-reactive protein (hs-CRP) serum levels were measured by ELISA. Patients with complex coronary stenoses had a significantly (P <0.001) higher PAPP-A/proMBP ratio (3.1±1.2 versus 2.7±0.8×10−3) and PAPP-A levels (5.9±1.6 versus 5.1±1.4 mIU/L) than those without. On univariate analysis, male gender (P <0.001), age (P <0.001), previous history of myocardial infarction (P <0.013), reduced ejection fraction (P <0.001), severe coronary artery disease (P <0.001), aspirin treatment (P <0.001), PAPP-A levels (P <0.001), and PAPP-A/proMBP ratio (P <0.001) were correlated with the number of complex stenoses. Multiple regression analysis showed that male gender, age, severe coronary artery disease, and PAPP-A/proMBP ratio were independent predictors of the number of angiographically complex stenoses. Conclusions—In patients with stable angina, PAPP-A and PAPP-A/proMBP ratio are associated with angiographic plaque complexity.

Cardiac Syndrome X

Patients with cardiac syndrome X (typical chest pain and normal coronary arteriograms) represent a heterogeneous syndrome, which encompasses different pathogenic mechanisms. Although symptoms in most patients with cardiac syndrome X are non-cardiac, a sizable proportion of them have angina pectoris due to transient myocardial ischemia. Thus radionuclide myocardial perfusion defects, coronary sinus oxygen saturation abnormalities and pH changes, myocardial lactate production and stress-induced alterations of cardiac high energy phosphate suggest an ischemic origin of symptoms in at least a proportion of patients with cardiac syndrome X. Microvascular abnormalities, caused by endothelial dysfunction, appear to be responsible for myocardial ischemia in patients with cardiac syndrome X. Endothelial dysfunction is likely to be multifactorial in these patients and it is conceivable that risk factors such as hypertension, hypercholesterolemia, diabetes mellitus and smoking can contribute to its development. Most patients with cardiac syndrome X are postmenopausal women and estrogen deficiency has been therefore proposed as a pathogenic factor in female patients. Additional factors such as abnormal pain perception may contribute to the pathogenesis of chest pain in patients with angina pectoris and normal coronary angiograms. Although prognosis is good regarding survival, patients with cardiac syndrome X have an impaired quality of life. Management of this syndrome represents a major challenge to the treating physician. Understanding the mechanism underlying the condition is of vital importance for patient management. Thus diagnostic tests should aim at identifying the cause of the symptoms in the individual patient, i.e. myocardial ischemia, increased pain perception, abnormalities of adrenergic tone, non-cardiac mechanisms, etc. Moreover, it is important to bear in mind that treatment of cardiac syndrome X should be mainly directed towards improving quality of life, as prognosis is usually good in these patients. Conventional antianginal agents such nitrates, calcium channel antagonists, β-adrenoceptor antagonists and nicorandil are effective particularly in patients in whom chest pain and ECG changes are clearly suggestive of myocardial ischemia and in those with objective documentation of ischemia. Angiotensin-converting enzyme inhibitors have been shown to be useful in syndrome X patients with increased adrenergic tone, borderline systemic hypertension, and those with documented endothelial dysfunction. Analgesic interventions of different sorts have been proposed based on the hypothesis that somatic and visceral perception of pain is altered in cardiac syndrome X patients. Pharmacological agents such as imipramine and aminophylline, and neural electrical stimulation techniques have been assessed in recent years with encouraging results. Psychological treatment, particularly cognitive therapy, appears to be useful in defined patient subsets. Relaxation techniques such as transcendental meditation have been successfully used in small studies and shown to improve not only chest pain but also exercise-induced ST segment changes. Reports indicate that these techniques improve quality of life.

Anticoagulation prescription in atrial fibrillation

Aims: We seek to assess the factors associated with the anticoagulation prescription in a cohort of patients with atrial fibrillation (AF) collected from out-patient clinics. Methods: A total of 1524 patients with a history of AF were collected from out-patients clinics. CHADS2, CHA2DS2-VASc and HAS-BLED scores were calculated in every patient. Variables associated with anticoagulant treatment prescription were analyzed in univariant and multivariant models. Results: Most patients received either anticoagulant (62%) or antiplatelet treatment (37%). Anticoagulation rates increased among higher CHADS2 and CHA2DS2-VASc score values. A logistic regression model was performed to assess the variables associated with the prescription of anticoagulant treatment; the variables with stronger association were the presence of arrhythmia at the current visit (odds ratio (OR) 33, 95% CI 27 – 40, p < 0.001) and lack of concomitant antiplatelet treatment (OR 0.17, 95% CI 0.14 – 0.21, p < 0.001). Conclusions: Although prognosis of patients with AF is mainly determined by the long-term thrombotic risk, the prescription of antithrombotic therapy depends more on the bleeding risk and the immediate thrombotic risk perception.