Pavlos Toutouzas

Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation

BACKGROUND The prolongation of intraatrial and interatrial conduction time and the inhomogeneous propagation of sinus impulses are well known electrophysiologic characteristics in patients with paroxysmal atrial fibrillation (PAF). METHODS To search for possible electrocardiographic markers that could serve as predictors of idiopathic PAF, we measured the maximum P-wave duration (P maximum) and the difference between the maximum and the minimum P-wave duration (P dispersion) from the 12-lead surface electrocardiogram of 60 patients with a history of idiopathic PAF and 40 age-matched healthy control subjects. RESULTS P maximum and P dispersion were found to be significantly higher in patients with idiopathic PAF than in control subjects. A P maximum value of 110 msec and a P dispersion value of 40 msec separated patients from control subjects, with a sensitivity of 88% and 83% and a specificity of 75% and 85%, respectively. CONCLUSIONS P maximum and P dispersion are simple electrocardiographic markers that could be used for the prediction of idiopathic PAF.

Vascular Factors and Risk of Dementia: Design of the Three-City Study and Baseline Characteristics of the Study Population

Objective: To describe the baseline characteristics of the participants in the Three-City (3C) Study, a study aiming to evaluate the risk of dementia and cognitive impairment attributable to vascular factors. Methods: Between 1999 and 2001, 9,693 persons aged 65 years and over, noninstitutionalized, were recruited from the electoral rolls of three French cities, i.e. Bordeaux, Dijon and Montpellier. Health-related data were collected during face-to-face interviews using standardized questionnaires. The baseline examination included cognitive testing and diagnosis of dementia, and assessment of vascular risk factors, including blood pressure measurements, ultrasound examination of the carotid arteries, and measurement of biological parameters (glycemia, total, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinemia); 3,442 magnetic resonance imaging (MRI) examinations were performed in subjects aged 65–79. Measurements of ultrasound, blood, and MRI parameters were centralized. Two follow-up examinations (at 2 and 4 years) were planned. Results: After exclusion of the participants who had subsequently refused the medical interview, the 3C Study sample consisted of 3,649 men (39.3%) and 5,645 women, mean age 74.4 years, with a relatively high level of education and income. Forty-two percent of the participants reported to be followed up for hypertension, about one third for hypercholesterolemia, and 8% for diabetes; 65% had elevated blood pressure measures (systolic blood pressure ≧140 or diastolic blood pressure ≧90). The proportion of Mini-Mental State Examination scores below 24 was 7% and dementia was diagnosed in 2.2% of the participants. Conclusion: Distribution of baseline characteristics of the 3C Study participants suggests that this study will provide a unique opportunity to estimate the risk of dementia attributable to vascular factors.

Thermal Heterogeneity Within Human Atherosclerotic Coronary Arteries Detected In Vivo A New Method of Detection by Application of a Special Thermography Catheter

BACKGROUND Activated macrophages play an important role in the pathogenesis of acute ischemic syndromes. It has been postulated that detection of heat released by activated inflammatory cells of atherosclerotic plaques may predict plaque rupture and thrombosis. Previous ex vivo studies have shown that there is thermal heterogeneity in human carotid atherosclerotic plaques. METHODS AND RESULTS To measure the temperature of human arteries in vivo, we developed a catheter-based technique. Ninety patients (45 with normal coronary arteries, 15 with stable angina [SA], 15 with unstable angina [UA], and 15 with acute myocardial infarction [AMI]) were studied. The thermistor of the thermography catheter has a temperature accuracy of 0.05 degrees C, a time constant of 300 ms, and a spatial resolution of 0.5 mm. Temperature was constant within the arteries of the control subjects, whereas most atherosclerotic plaques showed higher temperature compared with healthy vessel wall. Temperature differences between atherosclerotic plaque and healthy vessel wall increased progressively from SA to AMI patients (difference of plaque temperature from background temperature, 0. 106+/-0.110 degrees C in SA, 0.683+/-0.347 degrees C in UA, and 1. 472+/-0.691 degrees C in AMI). Heterogeneity within the plaque was shown in 20%, 40%, and 67% of the patients with SA, UA, and AMI, respectively, whereas no heterogeneity was shown in the control subjects. CONCLUSIONS Thermal heterogeneity within human atherosclerotic coronary arteries was shown in vivo by use of a special thermography catheter. This heterogeneity is larger in UA and AMI, suggesting that it may be related to the pathogenesis.

Impact of lifestyle habits on the prevalence of the metabolic syndrome among Greek adults from the ATTICA study

BACKGROUND Individuals with the metabolic syndrome (MS) are at high risk for coronary heart disease and may benefit from aggressive lifestyle modification. In this study, we evaluated the effect of leisure time physical activity (PA) and the Mediterranean diet (MD) on the prevalence of the MS. METHODS The ATTICA study is a health and nutritional survey. On the basis of a multistage, random sampling, 1128 men and 1154 women (>18 years old) without any evidence of cardiovascular disease or diabetes mellitus were enrolled from the greater Athens area during 2001 to 2002. The MS was defined according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. PA was determined from a detailed questionnaire and graded according to the kcal/min expanded. MD was assessed through a validated nutrient questionnaire. RESULTS The overall prevalence of the MS was 453 of 2282 subjects (19.8%). Of these subjects, 284 (25.2%) were men and 169 (14.6%) were women (P <.001). The prevalence of the MS increased accordingly to age (P for trend <.001). With multiple logistic regression analysis, the odds ratio of having the MS when the participant consumed the MD was 0.81 (95% CI, 0.68-0.976), and when even a little to moderate PA (<7 kcal/min)was reported, the odds ratio was 0.75 (95% CI, 0.65-0.86). The higher levels of inflammation and coagulation markers among participants with MS did not explain much of the aforementioned effect of lifestyle modification. CONCLUSION MS is common in Greece and is becoming even more common in the middle-aged population. The suggested therapeutic lifestyle approach may contribute to the reduction of the prevalence of the MS, beyond the levels of several lipid, inflammation, and coagulation markers.

Unfavorable Effect of Smoking on the Elastic Properties of the Human Aorta

BACKGROUND Smoking is a major risk factor for cardiovascular morbidity and mortality. Because previous studies have shown that smoking affects vasomotor response, we hypothesized that smoking may also acutely alter aortic elastic properties. METHODS AND RESULTS We studied 40 male current and long-term smokers who underwent diagnostic cardiac catheterization for chest-pain evaluation. Twenty subjects (age, 48 +/- 2 years, mean +/- SEM) were randomly assigned to smoking and 20 (age, 47 +/- 2 years) to sham smoking studies. Aortic elastic properties were studied with the determination of the aortic pressure-diameter relation before smoking, every minute for the first 5 minutes after the initiation of smoking or sham smoking, and every 5 minutes for the following 15 minutes. Instantaneous diameter of the thoracic aorta was measured with a special ultrasonic dimension catheter developed in our laboratory and previously validated. Instantaneous aortic pressure was measured at the same site as was diameter with a Millar micromanometer. Smoking was associated with significant changes in the aortic pressure-diameter relation that denote deterioration of the elastic properties and were maintained during the whole study period: the slope of the pressure-diameter loop became steeper (baseline, 35.43 +/- 1.38; minute 1, 45.26 +/- 1.65; peak at minute 10, 46.36 +/- 1.69 mm Hg/mm; P < .001) and aortic distensibility decreased (baseline, 2.08 +/- 0.12; minute 1, 1.60 +/- 0.08; nadir at minute 5, 1.54 +/- 0.07 x 10(-6) cm2.dyne-1; P < .001). In contrast, no changes in aortic elasticity indexes were observed with sham smoking. CONCLUSIONS Smoking is associated with an acute deterioration of aortic elastic properties. This effect of smoking may contribute to the unfavorable consequences of smoking on the cardiovascular system.

Effect of Vasa Vasorum Flow on Structure and Function of the Aorta in Experimental Animals

BACKGROUND It is known that vasa vasorum flow contributes substantially to the nutrition of the outer layers of the thoracic aorta. This investigation was undertaken to test the hypothesis that impairment of vasa vasorum flow would alter the structure of the aortic wall and change the elastic properties of the aorta. METHODS AND RESULTS The periaortic fat that contain the vasa vasorum for the ascending aorta was removed in seven anesthetized dogs, and the results were compared with those obtained from six weight-matched sham-operated control dogs. Aortic pressures, aortic diameters, and aortic distensibility were obtained before and 30 minutes and 15 days after removal of the periaortic vasa vasorum network. Aortic pressures were measured directly with a fluid-filled catheter. Aortic diameters were measured simultaneously with aortic pressures with an elastic, air-filled ring connected to a transducer. Aortic distensibility was calculated by the formula 2 x pulsatile change in aortic diameter/(diastolic aortic diameter x pulse pressure). Histology was performed in transverse blocks of aortic wall at the end of the experiment in both groups. The efficacy of the technique for the interruption of vasa vasorum blood supply to the aortic wall was demonstrated by histology in four additional animals that were killed without removal of vasa vasorum (two animals) and immediately after vasa vasorum removal (two animals). At baseline, heart rate, aortic pressures, aortic diameters, and aortic distensibility were similar in the two groups. A significant decrease in aortic distensibility was observed 30 minutes and 15 days after removal of the vasa vasorum in the experimental group (baseline, 3.453 +/- 1.023; 30 minutes, 2.521 +/- 0.760; 15 days, 1.586 +/- 0.488 10(-6).cm2.dyn-1; F = 9.532, P < .001). No changes were observed in aortic distensibility in the control group during the experiment. Histology of the aorta revealed medial necrosis, alterations of the elastin fibers, and a trend (P = .055) for altered collagen-to-elastin ratio in a region occupying more than the one (outer) half of the media of the experimental group animals. No changes were observed in the control group. CONCLUSIONS The findings of the present study demonstrated that interruption of vasa vasorum flow led to an acute decrease in the distensibility of the ascending aorta. Moreover, structural changes of the aortic wall and further deterioration of the elastic properties of the aorta occurred 15 days after vasa vasorum removal.

Increased local temperature in human coronary atherosclerotic plaques: an independent predictor of clinical outcome in patients undergoing a percutaneous coronary intervention☆

OBJECTIVES We investigated the midterm clinical significance of human coronary atherosclerotic plaques temperature after a successful percutaneous coronary intervention. BACKGROUND Previous studies have shown an increased temperature in human atherosclerotic plaques. However, the prognostic significance of atherosclerotic plaque temperature in patients undergoing a successful percutaneous intervention is unknown. METHODS We prospectively investigated the relation between the temperature difference (deltaT) between the atherosclerotic plaque and the healthy vessel wall and event-free survival among 86 patients undergoing a successful percutaneous intervention. Temperature was measured by a thermography catheter, as previously validated. The study group consisted of patients with effort angina (EA) (34.5%), unstable angina (UA) (34.5%) and acute myocardial infarction (AMI) (30%). RESULTS The deltaT increased progressively from EA to AMI (0.132 +/- 0.18 degrees C in EA, 0.637 +/- 0.26 degrees C in UA and 0.942 +/- 0.58 degrees C in AMI). The median clinical follow-up period was 17.88 +/- 7.16 months. The deltaT was greater in patients with adverse cardiac events than in patients without events (deltaT: 0.939 +/- 0.49 degrees C vs. 0.428 +/- 0.42 degrees C; p < 0.0001). The deltaT was a strong predictor of adverse cardiac events during the follow-up period (odds ratio 2.14, p = 0.043). The threshold of the deltaT value, above which the risk for an adverse cardiac event was significantly increased, was 0.5 degrees C. The incidence of adverse cardiac events in patients with deltaT > or = 0.5 degrees C was 41%, as compared with 7% in patients with deltaT < 0.5 degrees C (p < 0.001). CONCLUSIONS Increased local temperature in atherosclerotic plaques is a strong predictor of an unfavorable clinical outcome in patients with coronary artery disease undergoing percutaneous interventions.

Efficacy of antithrombotic therapy in chronic heart failure: The HELAS study

It is not clear if long‐term antithrombotic treatment has a beneficial effect on the incidence of thromboembolism in chronic heart failure (CHF). The HELAS study (Heart failure Long‐term Antithrombotic Study) is a multicentre, randomised, double‐blind, placebo‐controlled trial to evaluate antithrombotic treatment in patients with CHF.

Inflammatory and thrombotic mechanisms in coronary atherosclerosis

Many molecular and cellular mechanisms link inflammation and haemostatic mechanisms. Inflammation, and perhaps chronic infection, may play important roles in the initiation and progression of atherosclerosis. Atherosclerotic lesions are heavily infiltrated by cellular components associated with inflammation (macrophages and T lymphocytes), and acute plaque rupture is also associated with inflammatory components. Several markers of systemic inflammation may predict future cardiovascular events in apparently healthy subjects as well as in patients with chronic and acute syndromes. There may thus be therapeutic potential in modifying the atherosclerotic, vasomotor, and thrombotic components of ischaemic heart disease.

Carotid Artery Disease as a Marker for the Presence of Severe Coronary Artery Disease in Patients Evaluated for Chest Pain

BACKGROUND AND PURPOSE We sought in this study to elucidate whether carotid artery disease detected by ultrasonography can be a clinically useful marker for the presence of severe coronary artery disease (CAD) in patients evaluated for chest pain. METHODS Duplex ultrasonography and quantitative coronary angiography were used to assess carotid and coronary artery atherosclerosis in 225 consecutive patients (mean age, 58+/-9 years) with chest pain referred for cardiac catheterization. RESULTS CAD was present in 197 patients (88%). Fifty-seven patients (25%) had 1-vessel disease, 52 (23%) had 2-vessel disease, 53 (24%) had 3-vessel disease, and 35 (16%) had left main stem CAD (LMS-CAD). The incidence of severe CAD (3-vessel disease or LMS-CAD) was 24% and 63% in the normal and impaired ejection fraction (EF) subgroups, respectively (P<0.005). Carotid disease (lumen diameter stenosis of >/=50%) was present in 5.3%, 13.5%, 24.5%, and 40% of patients with 1-, 2-, and 3-vessel disease and LMS-CAD, respectively. Moreover, the incidence of carotid disease in patients with severe CAD was 31% in the entire study population and 46% and 5% in the subgroups with impaired and normal EF, respectively (P<0.005). In the entire study population, the presence of severe CAD was determined by age, male sex, and carotid disease; in the impaired EF group by age and carotid disease; and in the normal EF group only by age. Carotid disease has a high negative (92%) and a high positive (91%) predictive value for the presence of severe CAD in the subgroup with normal and impaired EF, respectively. CONCLUSIONS In patients evaluated for chest pain, carotid disease is significantly correlated with severe CAD. Furthermore, in patients with impaired left ventricular systolic performance the presence of carotid disease reflects the presence of severe CAD, while in patients with normal EF the absence of carotid disease reflects the absence of severe CAD.