Carmine Pizzi

Endothelial Function Predicts Future Development of Coronary Artery Disease A Study of Women With Chest Pain and Normal Coronary Angiograms

Background—The prognosis for women with chest pain and angiographically normal coronary arteries is believed to be totally benign. Previous studies, however, did not account for the delay of a decade or so in the development of coronary artery disease that women may experience. Methods and Results—This study assessed long-term follow-up of 42 women with de novo angina, evidence of reversible myocardial perfusion defects on SPECT, and normal coronary angiograms. At recruitment, all women underwent endothelial function testing (intracoronary acetylcholine) during catheterization. Patients were followed up for >10 years. Angiography was repeated at the end of the follow-up in 37 patients. At recruitment, 22 patients developed diffuse vasoconstriction during acetylcholine in the absence of identifiable focal coronary spasm (acetylcholine-positive group). The remaining 20 patients showed vasodilation (acetylcholine-negative group). At the end of follow-up, in the acetylcholine-positive group, 1 patient developed cardiac death, 13 still complained of chest pain, and 8 had remission of symptoms. In the acetylcholine-negative group, all patients showed complete resolution of chest pain beginning 6 to 36 months after baseline assessment. Angiography showed development of coronary artery disease in the 13 symptomatic patients in the acetylcholine-positive group. Conclusions—In women with angiographically normal-appearing coronary arteries, persistence of chest pain over the years often relates to development of coronary artery disease. Endothelial dysfunction in a setting of normal coronary arteries is a sign of future development of atherosclerosis.

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

OBJECTIVESnWe 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).nnnBACKGROUNDnPatients 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.nnnMETHODSnWe 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.nnnRESULTSnC-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).nnnCONCLUSIONSnThe 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 u200a=u200a 0.36, p u200a=u200a 0.007), CRP concentration (r u200a=u200a 0.33, p u200a=u200a 0.02), and neopterin concentration (r u200a=u200a 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 u200a=u200a 0.02), CRP concentration (log transformed) (1.08 (0.63) v 0.6 (0.6), p u200a=u200a 0.03), and neopterin concentration (log transformed) (0.94 (0.18) v 0.79 (0.15), p u200a=u200a 0.002). Multiple regression analysis showed that neopterin concentration (B u200a=u200a 4.8, 95% confidence interval (CI) 1.9 to 7.7, p u200a=u200a 0.002) and extent of coronary artery disease (B u200a=u200a 0.6, 95% CI 0.03 to 1.2, p u200a=u200a 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.

Angiotensin-Converting Enzyme Inhibitors and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Cardiac Syndrome X. Role of Superoxide Dismutase Activity

Background—Morbidity of patients with Syndrome X (SX; chest pain and normal coronary angiograms) is high and is associated with continuing episodes of chest pain and hospitalization. Impairment of microvascular endothelial function caused by increased oxidative stress has been suggested to be a mechanism of the disease. Superoxide dismutase (SOD) is the major antioxidant enzyme system of the vascular wall. This study sought to establish whether combination treatment with ACE inhibitors and statins reduces oxidative stress and improves quality of life of patients with cardiac SX. Methods and Results—Forty-five patients with SX were randomly assigned to receive either a combination of ramipril (10 mg/d) and atorvastatin (40 mg/d) or placebo for 6 months. We determined the activity of extracellular SOD and its relation to flow-dependent endothelium-mediated dilation (FMD) and quality of life (exercise capacity and score with Seattle Angina Questionnaire [SAQ]) before and after treatment. After 6 months, patients with SX who received atorvastatin and ramipril had significantly reduced (P =0.001) SOD levels (188.1±29.6 U/mL). No significant changes were seen on placebo (262.9±48.8 U/mL). Reduction of SOD after therapy was negatively correlated with FMD (r =0.38; P =0.01) and positively with total cholesterol (r =−0.56; P <0.001). At follow-up, patients taking atorvastatin and ramipril improved their quality of life both in terms of exercise duration (by 23.46%) and SAQ (by 64.1%). Conclusions—Six months of therapy with atorvastatin and ramipril improves endothelial function and quality of life of patients with SX. Reduced SOD activity may reflect low superoxide anion production. Benefits of these drugs may be related to reduction of oxidative stress.