Atheromatous plaque location and arterial remodelling.
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Biomedical subjects
Publications and source records attributed to J C Kaski.
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BACKGROUND: Proinflammatory cytokines play a role in acute coronary events. However, the potential role of antiinflammatory cytokines in the modulation of the atherosclerotic process remains unknown. Interleukin (IL)-10, which is expressed in human atherosclerotic plaques, has potent deactivating properties in macrophages and T cells. The aim of this study was to assess whether serum concentrations of IL-10 differed between patients with unstable and stable angina pectoris. METHODS AND RESULTS: A total of 95 patients with angina pectoris and angiographically documented coronary artery disease were studied. Of these, 50 patients had chronic stable angina (with stable symptoms over 3 months), and 45 patients had Braunwald class IIIB unstable angina with ST-segment changes. Serum IL-10 and IL-6 concentrations were measured on admission using commercially available immunoassays. Serum IL-10 concentrations were lower in unstable angina patients compared with those who had chronic stable angina (28.4 versus 14.0 pg/mL; 95% CI, 9.8 to 19.0; P<0.0001), even after adjustment for variables that were significantly different on univariate analysis. IL-6 concentrations were higher in the unstable angina group (20.9 versus 11.4 pg/mL; 95% CI, 1.0 to 12.6; P=0.04). CONCLUSIONS: Patients with unstable angina had significantly lower serum IL-10 concentrations than did patients with chronic stable angina. This important finding is in keeping with previous data from animal model studies that suggest that IL-10 has a protective role in atherosclerosis.
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BACKGROUND: Plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) mediators of leukocyte adhesion to vascular endothelium may implicate in the pathogenesis of the syndrome of chest pain with normal coronary arteries. HYPOTHESIS: We attempted to determine whether markers of endothelial activation are raised in patients with chest pain and normal coronary arteries. METHODS: We measured plasma VCAM-1, ICAM-1 (ng/ ml) in 36 patients (34 men, 2 women, aged 62 +/- 9 years) with stable angina, coronary artery disease (CAD), and a positive response to exercise test; in 21 patients (6 men, 15 women, aged 56 +/- 9 years) with chest pain and normal coronary arteriograms (syndrome X); and in 11 healthy control subjects (8 men, 3 women, aged 49 +/- 14 years). RESULTS: Plasma ICAM-1 levels were significantly higher both in patients with CAD (mean +/- standard error of the mean) (328 +/- 26, p < 0.05), and in syndrome X (362 +/- 22, p < 0.01) than in controls (225 +/- 29). VCAM-1 levels were also higher in syndrome X (656 +/- 42 ng/ml) and in patients with CAD (626 +/- 42 ng/ml) than in controls (551 +/- 60, p = 0.09). CONCLUSIONS: ICAM-1 and VCAM-1 levels are increased both in patients with CAD and with syndrome X compared with control individuals. These findings may suggest the presence of chronic inflammation with involvement of the endothelium in patients with anginal chest pain and normal coronary angiograms.
OBJECTIVES: We sought to compare QT dispersion in patients presenting with Prinzmetal's variant angina complicated by cardiac arrest or syncope and patients with uncomplicated variant angina. BACKGROUND: Despite the usually benign course of treated Prinzmetal's variant angina, a proportion of vasospastic angina patients develop ventricular arrhythmias and sudden death in association with coronary spasm. Increased QT dispersion has been suggested to increase susceptibility to ventricular arrhythmias in patients with coronary artery spasm. METHODS: We studied 25 consecutive patients (mean age 58 years; 14 men) with classical Prinzmetal's variant angina and documented coronary artery spasm. None of the patients had coronary artery stenoses < or =40%. Five patients had suffered a documented cardiac arrest, two had recurrent syncope and 18 had no arrhythmic events or syncopal episodes. In all patients QT dispersion (QT maximum-QT minimum in every ECG lead) was measured on the baseline 12-lead electrocardiogram at study entry using a digitising board. RESULTS: Mean (+/-S.D.) QT dispersion of study patients was 62.3+/-19.5 ms. QT dispersion in patients with cardiac arrest and syncope (79.4+/-17.3 ms) was significantly higher compared to patients with no such events (56.3+/-16.9 ms), (95% CI 7.5-38.8, P=0.005). No significant clinical, biochemical or angiographic differences were found between patients with and those without cardiac arrest or syncope. CONCLUSION: QT dispersion is increased in patients with Prinzmetal's variant angina complicated by cardiac arrest and syncope compared to patients without such events. Increased QT dispersion may be both a substrate for sudden cardiac death and a marker of risk in patients with Prinzmetal's variant angina.
The endothelium plays a crucial role in the maintenance of vascular homeostasis; endothelial cells produce a series of molecules that determine vascular tone and modulate the interactions between the arterial wall components and the circulating blood. Endothelial dysfunction (ED) thus results in significantly impaired physiological responses that often lead to atheroma formation. Recent studies suggest that endothelial dysfunction as assessed invasively during coronary angiography is a prognostic marker. Recently, a non-invasive ultrasound technique has been developed which may allow screening of ED in both patients and healthy subjects. This article reviews current knowledge regarding non-invasive assessment of endothelial dysfunction and proposes potential uses of a promising ultrasound technique.
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AIMS: Patients with arterial hypertension often have a reduction in capillary density (rarefaction) and a reduction in coronary flow reserve because of functional and structural alterations of the coronary microcirculation. Patients with chest pain and normal coronary arteriograms may have coronary microvascular dysfunction, but it is not known whether capillary rarefaction plays a role in the pathogenesis of this syndrome. The aim of this study was to compare capillary density in hypertensive and normotensive subjects with anginal chest pain and normal coronary arteriograms vs asymptomatic hypertensives and healthy controls. METHODS AND RESULTS: We studied 49 patients with typical anginal chest pain, positive exercise testing and normal coronary arteriograms; 22 were hypertensive and 27 were normotensive. We used intra-vital video-microscopy to examine the skin of the dorsum of the middle finger of the non-dominant hand before and after maximization of perfused capillaries with venous congestion. Mean capillary density was significantly lower in patients with chest pain and normal coronary arteriograms independent of their blood pressure level, compared to normotensive healthy controls. Differences were found both at baseline [51+/-2 (hypertensive) and 52+/-2 (normotensive) vs 65+/-2 (controls) per 0.56 mm(2) respectively], (P<0.0001) and after maximization [57+/-3 (hypertensive) and 59+/-2 (normotensive) versus 75+/-3 (controls) respectively] (P<0.0001). CONCLUSIONS: Skin capillary density is significantly lower in patients with chest pain and normal coronary arteriograms compared to normotensive controls. The pathophysiological importance of capillary rarefaction in patients with chest pain and normal coronary arteriograms remains unknown. Further studies are needed to determine whether the abnormality is associated with myocardial flow disturbances such that the findings can be extended to the heart.
AIMS: To investigate the association between plasma endothelin levels and rapid coronary artery disease progression, as assessed by quantitative angiography. METHODS AND RESULTS: Changes in diameter were assessed in 224 coronary stenoses of 92 consecutive patients (62 men) with chronic stable angina pectoris who were on a waiting list for routine coronary angioplasty and underwent coronary angiography on two occasions: the first (diagnostic) angiogram was carried out at study entry and the second 5.5+/-3.0 months later, immediately prior to coronary angioplasty. A digital quantitative angiographic analysis system was used to assess differences in stenosis diameter between the first and second angiogram. Plasma immunoreactive endothelin levels were estimated by radioimmunoassay at study entry. Rapid coronary artery disease progression occurred in 29 (31.5%) patients according to pre-established criteria: 12 (41%) had a > or =10% diameter reduction of at least one pre-existing stenosis > or =50%, 10 (34%) had a > or =30% diameter reduction of a pre-existing stenosis <50%, 5 (17%) patients developed a new stenosis and 2 (7%) had progression of a lesion to total occlusion by the second angiogram. Baseline demographic, clinical and angiographic data were similar in patients with and without stenosis progression. Plasma endothelin levels were significantly higher in patients with rapid disease progression than in those without (5.7+/-2.0 pg. ml(-1)vs 3.9+/-1.6 pg. ml(-1), P<0.001). Multiple logistic regression analysis revealed that endothelin was an independent predictor of disease progression (P=0.001). Moreover, endothelin levels above 4.26 pg. ml(-1)(the median of the total endothelin concentrations) were associated with a sixfold increase in the risk of developing rapid stenosis progression. CONCLUSIONS: Plasma endothelin is raised in patients with coronary artery disease progression and may be a marker of risk of rapid stenosis progression. Endothelin may also play a pathogenic role in this process.
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OBJECTIVES: We sought to assess the relation between serum neopterin concentration and complex coronary artery stenosis in patients with unstable angina. BACKGROUND: Monocyte activation is associated with acute atheromatous plaque disruption and acute coronary syndromes. Angiographically demonstrated complex coronary stenosis is often an expression of plaque disruption. Increased serum concentration of neopterin, a pterydine derivative secreted by macrophages after stimulation by interferon-gamma, has been observed in patients with acute coronary syndromes as compared with control subjects and patients with stable angina pectoris. METHODS: We studied 50 patients with unstable angina (32 men) who underwent coronary angiography after hospital admission. All coronary stenoses with > or =30% diameter reduction were assessed and classified as "complex" (irregular or scalloped borders, ulceration or filling defects suggesting thrombi) or "smooth" (absence of complex features). Serum neopterin levels were assessed within 24 h of hospital admission using a commercially available immunoassay (enzyme-linked immunosorbent assay kit, IBL, Hamburg, Germany). RESULTS: Thirty-nine patients were classified in Braunwald class IIIb, four in class IIb and seven in class Ib. The number of complex lesions per patient was 2.6+/-1.8 (mean +/- SD). The mean neopterin concentration was 7.76+/-3.62 nmol/liter. A significant correlation was observed between neopterin serum concentration and the presence of complex coronary stenoses (r = 0.35, p = 0.015). Multiple regression analysis showed that serum neopterin (p < 0.0001) was independently associated with the number of complex lesions. Other variables associated with complex lesions were the number of vessels with > or =75% stenosis (p < 0.0001), plasma creatinine (p = 0.003), triglycerides (p = 0.014) and a history of unstable angina (p = 0.032). CONCLUSIONS: Serum neopterin concentration is associated with the presence of angiographically demonstrated complex lesions in patients with unstable angina and may represent a marker of coronary disease activity.