Christina Chrysohoou

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.

Air pollution and inflammation (interleukin-6, C-reactive protein, fibrinogen) in myocardial infarction survivors.

Background Numerous studies have found that ambient air pollution has been associated with cardiovascular disease exacerbation. Objectives Given previous findings, we hypothesized that particulate air pollution might induce systemic inflammation in myocardial infarction (MI) survivors, contributing to an increased vulnerability to elevated concentrations of ambient particles. Methods A prospective longitudinal study of 1,003 MI survivors was performed in six European cities between May 2003 and July 2004. We compared repeated measurements of interleukin 6 (IL-6), fibrinogen, and C-reactive protein (CRP) with concurrent levels of air pollution. We collected hourly data on particle number concentrations (PNC), mass concentrations of particulate matter (PM) < 10 μm (PM10) and < 2.5 μm (PM2.5), gaseous pollutants, and meteorologic data at central monitoring sites in each city. City-specific confounder models were built for each blood marker separately, adjusting for meteorology and time-varying and time-invariant covariates. Data were analyzed with mixed-effects models. Results Pooled results show an increase in IL-6 when concentrations of PNC were elevated 12–17 hr before blood withdrawal [percent change of geometric mean, 2.7; 95% confidence interval (CI), 1.0–4.6]. Five day cumulative exposure to PM10 was associated with increased fibrinogen concentrations (percent change of arithmetic mean, 0.6; 95% CI, 0.1–1.1). Results remained stable for smokers, diabetics, and patients with heart failure. No consistent associations were found for CRP. Conclusions Results indicate an immediate response to PNC on the IL-6 level, possibly leading to the production of acute-phase proteins, as seen in increased fibrinogen levels. This might provide a link between air pollution and adverse cardiac events.

Adherence to the Mediterranean diet is associated with total antioxidant capacity in healthy adults: the ATTICA study

BACKGROUND Greater adherence to the Mediterranean diet has been associated with a lower incidence of cardiovascular disease and cancer. OBJECTIVE We studied the effect of the Mediterranean diet on total antioxidant capacity (TAC) in 3042 participants who had no clinical evidence of cardiovascular disease. DESIGN During 2001-2002, a random sample of 1514 men and 1528 women aged 18-89 y from the Attica area of Greece was selected. TAC was measured with an immune-diagnostic assay. Food consumption was evaluated with a validated food-frequency questionnaire, and adherence to the Mediterranean diet was assessed on the basis of a diet score that incorporated the inherent characteristics of this diet. RESULTS TAC was positively correlated with diet score. The participants in the highest tertile of the diet score had, on average, 11% higher TAC levels than did the participants in the lowest tertile, even after adjustment for relevant confounders (P < 0.01). On the other hand, the participants in the highest tertile of the diet score had, on average, 19% lower oxidized LDL-cholesterol concentrations than did the participants in the lowest tertile (P < 0.01). An additional analysis showed that TAC was positively correlated with the consumption of olive oil (rho = 0.54, P = 0.002) and of fruit and vegetables (rho = 0.34 and rho = 0.31, respectively; P < 0.001 for both), whereas it was inversely associated with the consumption of red meat (rho = -0.35, P = 0.02). CONCLUSION Greater adherence to the Mediterranean diet is associated with elevated TAC levels and low oxidized LDL-cholesterol concentrations, which may explain the beneficial role of this diet on the cardiovascular system.

Unsaturated fatty acids are inversely associated and n-6/n-3 ratios are positively related to inflammation and coagulation markers in plasma of apparently healthy adults.

BACKGROUND Blood lipids and inflammatory markers levels have been associated with the development and progression of atherosclerosis. As the association of inflammatory markers with plasma fatty acids has not been extensively evaluated and understood, we sought to investigate the associations between dietary and plasma fatty acids with various inflammation and coagulation markers. METHODS High sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), fibrinogen, and homocysteine were measured in serum of 374 free-living, healthy men and women, randomly selected from the ATTICAs study database. Total plasma fatty acids were determined by gas chromatography. Dietary fatty acids were assessed through a semi-quantitative FFQ. RESULTS Multi-adjusted regression analyses revealed that plasma n-3 fatty acids were inversely associated with CRP, IL-6 and TNF-alpha; plasma n-6 fatty acids were inversely associated with CRP, IL-6 and fibrinogen; monounsaturated fatty acids were inversely associated with CRP and IL-6 (all p-values<0.05). Interestingly, the n-6/n-3 ratios exhibited the strongest positive correlations with all the markers studied. No associations were observed between dietary fatty acids and the investigated markers. CONCLUSIONS Measurements of total plasma fatty acids could provide insights into the relationships between diet and atherosclerotic disease. Moreover, the n-6/n-3 ratio may constitute a predictor of low-grade inflammation and coagulation.

Association of Leisure-Time Physical Activity on Inflammation Markers (C-Reactive Protein, White Cell Blood Count, Serum Amyloid A, and Fibrinogen) in Healthy Subjects (from the ATTICA Study)

T the 20th century, many researchers focused their interest on prevention and therapy of cardiovascular diseases. Among the factors that may influence the occurrence of disease is the beneficial effect of physical activity, which has been discussed in several studies.1–3 In addition, recent studies have provided evidence that inflammation plays a role in the pathogenesis of cardiovascular disease.4,5 Several investigators have addressed the association between fitness and the inflammation process,6–9 but the strength of this relation has not been fully investigated. The aim of this study is to evaluate the effect of various levels of leisure-time physical activity on inflammation markers, such as high-sensitivity C-reactive protein (CRP), fibrinogen, amyloid A, and white blood cell (WBC) counts, in a population-based sample of healthy adults. • • • The ATTICA study is a health and nutrition crosssectional survey that was carried out in the province of Attica from 2001 to 2002. A sample of 891 men and 965 women, aged 18 years old, was drawn from the general population, which excluded persons living in institutions, or subjects with mobility problems or who had chronic disease that could restrict their physical activity status (e.g., arthritis). Also, all subjects entered into this study were without any clinical evidence of coronary heart disease, stroke, or any atherosclerotic disease according to a detailed medical history, a physical examination, and electrocardiography as performed by a cardiologist. The stratification was random and based on the age/gender/city distribution of the Attica area (census of 2001). The study’s design anticipated enrolling only 1 participant per household (78% of the selected subjects participated). The number of the participants was determined by power analysis. All participants were interviewed by trained personnel who used a standard questionnaire. Physical activity was defined as any type of nonoccupational physical exercise 1 time per week, during the past year. A self-reported questionnaire was applied that was based on a special questionnaire for the assessment of leisure-time physical activity.10 Physical activity was graded in qualitative terms as follows: light (expended calories 4 kcal/min, i.e., walking slowly, stationary cycling, light stretching, and so forth), moderate (expended calories 4 to 7 kcal/min, i.e., walking briskly, cycling outdoors, swimming with moderate effort, and so forth), and high (expended calories 7 kcal/min, i.e., walking briskly uphill, long distance running, cycling fast or racing, swimming fast crawl, and so forth). The remaining subjects were defined as physically inactive. The duration of physical activity, in years of exercise, was also taken into account. Venous blood samples were collected between 8 and 10 A.M., with patients seated after 12 hours of fasting and avoidance of alcohol. High-sensitivity CRP levels, as well as fibrinogen levels, were measured by BNII Dade Behring Inc. (Leiderbach, Germany) automatic nephelometry. For the determination of plasma fibrinogen, blood was anticoagulated with 3.8% trisodium citrate (9:1 volume/volume) and cooled on ice until centrifugation. The intraand interassay coefficients of variation of fibrinogen did not exceed 9%, total cholesterol 8%). All other biochemical examinations (uric acid, urea, creatinine, total cholesterol, low-density lipoprotein cholesterol, highdensity lipoprotein cholesterol, triglycerides) were measured using a chromatographic enzymatic method with a Technicon RA-1000 automatic analyzer (TexLab Inc., Houston, Texas). Blood pressure at rest was measured with subject sitting comfortably for 5 to 10 minutes and the cuff arm supported at the heart level. Hypertension was defined as systolic blood pressure 140 mm Hg, diastolic blood pressure 90 mm Hg, or the use of any antihypertensive medication. Hypercholesterolemia was defined as total cholesterol levels 220 mg/dl or the use of antilipidemic medication. Diabetes mellitus was defined as a fasting blood sugar 125 mg/dl or the use of antidiabetic medication. The questionnaire given to subjects included the following demographic characteristics: age, gender, financial status (classified as low, moderate, high, and very high), and educational level (as an index of social status) that was measured in years of schooling. DiFrom the Cardiology Clinic, School of Medicine, University of Athens; Hellenic Heart Foundation, Athens, Greece; and Cardiology Division, Georgetown University, Washington, DC. The ATTICA study is funded by research grants from the Hellenic Cardiological Society and the Hellenic Heart Foundation, Athens, Greece. Dr. Panagiotakos’ address is: 48-50 Chiou Str., Glyfada, 165 61, Attica, Greece. E-mail: D.b.Panagiotakos@usa.net. Manuscript received July 29, 2002; revised manuscript received and accepted September 24, 2002.

The associations between physical activity, inflammation, and coagulation markers, in people with metabolic syndrome: the ATTICA study:

Objective Metabolic syndrome is a condition that promotes atherosclerosis and increases the risk of cardiovascular mortality and morbidity. We evaluated whether leisure time physical activity is associated with the levels of inflammatory and coagulation markers, in people with metabolic syndrome. Methods From May 2001 to December 2002 we randomly enrolled 1514 men and 1528 women (>18 years old), without any clinical evidence of cardiovascular disease, stratified by age-gender (census 2001). The population of the study was divided into those who fulfilled the NCEP ATP III criteria for the metabolic syndrome (n = 701 or 33% men and 13% women) and the rest of the participants (n = 2341). We assessed the relationship between self-reported physical activity status and inflammatory, and coagulation markers [i.e., C-reactive protein (CRP), serum amyloid-A (SAA), interleukin (IL)-6, tumour necrosis factor (TNF)-α, white blood cell (WBC) counts, and fibrinogen (FIB)], after taking into account the effect of several confounders. Results Of the non-metabolic syndrome group, 56% of men and 58% of women were classified as sedentary, while of the metabolic syndrome group 58% men and 72% women were sedentary. After controlling for various potential confounders we found that physically active individuals with the metabolic syndrome had 36% lower levels of CRP, 15% lower levels of WBC, 19% lower levels of SAA, 15% lower levels of TNF-α, 30% lower levels of IL-6 and 15% lower levels of FIB, compared to sedentary (all P<0.05). Similar results were observed in the non-metabolic syndrome group. Conclusions The adoption of a physically active lifestyle is independently associated with lower levels of the investigated biomarkers in individuals with the metabolic syndrome. The latter may suggest a pathway for reducing cardiovascular events, even in high-risk people. Eur J Cardiovasc Prev Rehabil 12: 151–158

The Association between Adherence to the Mediterranean Diet and Fasting Indices of Glucose Homoeostasis: The ATTICA Study

Objective: We investigated the association between adherence to Mediterranean diet and fasting indices of glucose homoeostasis, in a Greek adult population. Methods: During 2001–2002 we randomly enrolled 1514 men and 1528 women (18–89 years old) without history of CVD, from the Attica area. Diabetes mellitus (type 2) and impaired fasting glucose (IFG) were defined according to the established ADA criteria. Insulin resistance was evaluated by HOMA-IR. Dietary habits were assessed through a validated food frequency questionnaire and a diet score (range 0–55) was developed (higher values means greater adherence to the Mediterranean diet). Results: The overall prevalence of diabetes type 2 was 7.9% in men and 6.0% in women (P = 0.05). Mean diet score was 26.3 ± 6.8 in normoglycemic, 25.7 ± 6.4 in IFG and 22.2 ± 5.8 in diabetic subjects (p < 0.001). In normoglycemic subjects who were in the upper tertile of the diet score we observed 7% lower glucose (p < 0.05), 5% lower insulin (p < 0.05) and 15% lower HOMA-IR (p < 0.01) levels compared to subjects in the lower tertile of the diet score. Additionally, in diabetic/IFG participants who where in the upper tertile of the diet score we observed 15% lower glucose (p < 0.05), 15% lower insulin (p < 0.05) and 27% lower HOMA-IR (p < 0.01) levels compared to those in the lower tertile. However, multiple regression analysis, adjusted for age, sex, BMI, waist-to-hip ratio, physical activity, smoking status, and presence of hypertension and hypercholesterolemia, confirmed the previous associations in normoglycemic, but not in diabetic/IFG people. Conclusion: An inverse association was observed between adherence to Mediterranean diet and indices of glucose homeostasis, only in normoglycemic people.

Relationship between meat intake and the development of acute coronary syndromes: the CARDIO2000 case-control study

Objective:The aim of the present study was to evaluate the association between meat consumption and the prevalence of a first, non-fatal event of an acute coronary syndrome (ACS), in a Greek sample.Design:Randomized, case–control study.Setting:Tertiary care.Subjects:A total of 848 out of 956 patients who had been randomly selected from hospitals with first event of an ACS and 1078 population-based controls, age and sex matched.Interventions:Detailed information regarding their medical records, alcohol intake, physical activity and smoking habits was recorded. Nutritional habits were evaluated with a semiquantitative food-frequency questionnaire. Multiple logistic regression analysis estimated the odds ratio of having ACS by level of meat intake, after taking into account several confounders.Results:Patients consumed higher quantities of meat compared with controls (6.5±2.9 vs 4.9±2.1 portions per month, P<0.001). Food-specific analysis showed that red meat consumption was strongly associated with 52% increased odds of ACS (95% confidence interval (CI) 1.47–1.58). On the contrary, white meat consumption seems to be associated with only 18% likelihood of having cardiac events (95% CI 1.11–1.26). Participants who consumed >8 portions red meat and >12 portions white meat per month had 4.9 times and 3.7 higher odds of having ACS, respectively (P<0.001), compared with low meat intake (<4 portions and <8 portions per month, respectively).Conclusions:Increased red meat consumption showed a strong positive association with cardiac disease risk, whereas white meat consumption showed less prominent results, after controlling for several potential confounding factors.

Temperature differences are associated with malignancy on lung lesions: a clinical study

BackgroundAlthough new endoscopic techniques can enhance the ability to detect a suspicious lung lesion, the primary diagnosis still depends on subjective visual assessment. We evaluated whether thermal heterogeneity of solid tumors, in bronchial epithelium, constitutes an additional marker for the diagnosis of benign and malignant lesions.MethodsA new method, developed in our institute, is introduced in order to detect temperature in human pulmonary epithelium, in vivo. This method is based on a thermography catheter, which passes the biopsy channel of the fiber optic bronchoscope. We calculated the temperature differences (ΔT) between the lesion and a normal bronchial epithelium area on 22 lesions of 20 subjects, 50 – 65 years old.ResultsEleven lesions were benign and 11 were malignant, according to the biopsy histology followed the thermography procedure. We found significant differences of ÄT between patients with benign and malignant tumor (0.71 ± 0.6 vs. 1.23 ± 0.4°C, p < 0.05). Logistic regression analysis showed that 1-Celsius degree differences between normal tissue and suspicious lesion six-fold the probability of malignancy (odds ratio = 6.18, 95% CI 0.89 – 42.7). Also, ΔT values greater than 1.05°C, constitutes a crucial point for the discrimination of malignancy, in bronchial epithelium, with sensitivity (64%) and specificity (91%).ConclusionThese findings suggest that the calculated ΔT between normal tissue and a neoplastic area could be a useful criterion for the diagnosis of malignancy in tumors of lung lesions.

The associations between smoking, physical activity, dietary habits and plasma homocysteine levels in cardiovascular disease-free people: the ‘ATTICA’ study

Homocysteine levels are considered, by some investigators, as an independent factor of cardiovascular disease; however, others suggest that there is not a causal relationship. The aim of this work was to investigate the associations between homocysteine levels and several lifestyle-related factors. The ATTICA study is a population-based cohort that has randomly enrolled 1128 adult men and 1154 women, stratified by age and gender, from the greater area of Athens, during 2001 2002. Among several demographic, lifestyle, clinical and biochemical characteristics, we measured total plasma homocysteine levels. For the present analysis, we excluded people who had a history of cardiovascular disease. The factors that showed the strongest relationship with homocysteine levels, in both genders, even after adjusting for several potential confounders were: cigarette smoking (p=0.03), endurance exercise (inverse, p<0.05), fruit (inverse, p=0.01) and vegetable intake (inverse, p=0.04), and alcohol (p=0.04) and coffee intake (p=0.04). In conclusion, several lifestyle-related factors seem to be associated with homocysteine levels. However, the vast majority of the associations were weak when we adjusted for other co-factors. The latter may indicate the mutual confounding effect of various socio-demographic, anthropometric and other clinical characteristics on the relationship between homocysteine and cardiovascular risk.