John Skoumas

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.

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.

Aortic stiffness in young patients with heterozygous familial hypercholesterolemia.

BACKGROUND Dyslipidemia is a primary risk factor for the development of atherosclerosis. Aortic distensibility is an important determinant of left ventricular function and coronary blood flow whose possible alterations in patients with dyslipidemia have not been fully investigated. METHODS To assess the effect of dyslipidemia on the elastic properties of the aorta, we studied 60 patients (mean age 37+/-11 years) with heterozygous familial hypercholesterolemia and no manifest arterial disease and compared them with 20 of their normolipidemic siblings (mean age 34+/-10 years). Two indexes of the aortic elastic properties were measured: aortic distensibility was calculated by use of the formula: 2 x (AoS-AoD)/PP x AoD, and aortic stiffness index was calculated by use of the formula: In (SBP/DBP)/(AoS-AoD)/AoD, where AoS and AoD are aortic root end-systolic and end-diastolic diameters, respectively, SBP and DBP are systolic and diastolic arterial pressure, respectively, and PP is pulse pressure. Internal aortic root diameters were measured at 3 cm above the aortic valve by use of two-dimensional guided M-mode transthoracic echocardiography, and arterial pressure was measured simultaneously at the brachial artery by sphygmomanometry. RESULTS The mean aortic systolic and diastolic diameter index did not differ significantly between the two groups. In contrast, aortic distensibility was found to be significantly reduced in subjects with isolated familial hypercholesterolemia compared with that in the control group (2.15+/-1.72 cm2.dynes(-1).10(-6) vs 3.18+/-1.58 cm2.dynes(-1).10(-6), p < 0.02). In addition, the mean aortic stiffness index was double in patients with familial hypercholesterolemia compared with that in normolipidemic subjects. CONCLUSIONS Severe dyslipidemia does not overtly influence aortic dimensions but leads to impairment of aortic elastic properties before the occurrence of clinical manifestations of atherosclerotic disease.

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 effect of Mediterranean diet on the risk of the development of acute coronary syndromes in hypercholesterolemic people: a case-control study (CARDIO2000).

BackgroundHypercholesterolemia has been identified as a major risk factor for the development of coronary artery disease. The aim of this study was to assess the effect of a Mediterranean diet on the development of non-fatal acute coronary syndromes (ACS) in hypercholesterolemic people, with or without statin treatment. MethodsDuring 2000–2001, 848 randomly selected patients with a first event of coronary heart disease and 1078 cardiovascular disease-free people, matched to the patients by sex, age and region, were studied. Treatment of hypercholesterolemia with statin and the adoption of a Mediterranean diet were recorded. ResultsHypercholesterolemia was present in 534 (63%) out of 848 coronary patients and 399 (37%) out of 1078 control participants. One hundred and seventy-one (32%) of the hypercholesterolemic patients and 168 (42%) of the hypercholesterolemic control participants were treated with statins and also followed a Mediterranean diet. The analysis showed that the combination of a Mediterranean diet and statin medical therapy is associated with an additional reduction of the coronary risk (odds ratio = 0.57, P < 0.01), independently from cholesterol levels and the other cardiovascular factors. ConclusionThe adoption of a Mediterranean diet by hypercholesterolemic people seems to reinforce the benefits from statin treatment on lipid levels and reduces the risk of developing ACS. However, it is hard to claim that our findings suggest causal evidence, and in order to explain the potential common mechanism between diet and statin treatment much remains to be learned.

Physical activity, high density lipoprotein cholesterol and other lipids levels, in men and women from the ATTICA study.

BackgroundPhysical activity has long been associated with reduced risk of coronary heart disease (CHD). In this work we evaluated the effect of physical activity on lipid levels, in a sample of cardiovascular disease free people.MethodsThe ATTICA study is a population – based cohort that has randomly enrolled 2772 individuals, stratified by age – gender (according to the census 2001), from the greater area of Athens, during 2001–2002. Of them, 1376 were men (45 ± 12 years old, range: 18 – 86) and 1396 women (45 ± 13 years old, range: 18 – 88). We assessed the relationship between physical activity status (measured in kcal/min expended per day) and several lipids, after taking into account the effect of several characteristics of the participants.Results578 (42%) men and 584 (40%) women were classified as physically active. Compared to sedentary physically active women had significantly lower levels of total serum cholesterol (p < 0.05), LDL (p < 0.05) and oxidized LDL cholesterol (p < 0.05), triglycerides (p < 0.05), apolipoprotein B (p < 0.05), and higher levels of HDL cholesterol (p < 0.05) and apolipoprotein A1 (p < 0.05). Similar associations were observed in men, but the benefits did not reach statistical significance. However, when we adjusted for age, smoking habits and body mass index, physical activity was only significantly associated with higher HDL-cholesterol (p < 0.05) and apolipoprotein A1 (p < 0.05) levels, in women, but not in men.ConclusionsSubstantial independent increases in HDL-cholesterol and apolipoprotein A1 concentrations were observed in women, but not in men, in a Mediterranean cohort.

The association between secondhand smoke and the risk of developing acute coronary syndromes, among non-smokers, under the presence of several cardiovascular risk factors: The CARDIO2000 case-control study

BackgroundThe purpose of this study was to investigate the association between secondhand smoke and the risk of developing a first event of acute coronary syndromes (ACS), i.e. acute myocardial infarction or unstable angina, among non-smokers, in relation to the presence of several other cardiovascular risk factors.MethodsEight hundred and forty-eight patients with first event of ACS and 1078 cardiovascular disease-free matched controls completed a detailed questionnaire regarding their exposure to secondhand smoke, among other investigated parameters.ResultsTwo hundred and ninety–seven (35%) of the patients and 259 (24%) of the controls were defined as secondhand smokers. After controlling for several potential confounders, the results showed that non-smokers occasionally (< 3 time per week) exposed to cigarette smoke were associated with 26% higher risk of ACS (OR = 1.26, P-value < 0.01) compared to non-smokers not exposed to smoke, while regular exposure is associated with 99% higher risk of developing ACS (OR = 1.99, P-value < 0.001). Moreover, the previous risk increases progressively from 15% to 256% if one or more of the classical cardiovascular risk factors (i.e. hypertension, hypercholesterolemia, diabetes mellitus, sedentary life and family history of premature coronary heart disease) are present.ConclusionsConsequently, this study supports the hypothesis that even occasional secondhand smoke increases the risk of developing acute coronary syndromes, especially when other risk factors are present. Given the high prevalence of cigarette smoking, the public health consequences of passive smoking with regard to coronary heart disease are important.

Dietary antioxidant capacity is inversely associated with diabetes biomarkers: The ATTICA study

BACKGROUND AND AIMS Elevated dietary antioxidant activity has been regarded as providing potential benefits to health. The present work aimed at evaluating the association of glycemic indices with total dietary antioxidant capacity in healthy adults. METHODS AND RESULTS The ATTICA study consisted of men and women, randomly selected from all areas of Attica region in Greece. In this work, a random sub-sample from the ATTICA studys database was studied, consisting of 551 men (41 ± 11 years) and 467 women (38 ± 11 years), with complete nutritional and biochemical information. Dietary habits were evaluated using a validated food-frequency questionnaire. The dietary antioxidant capacity was based on published values for Italian foods measured by three different assays: ferric-reducing antioxidant power (FRAP), total radical-trapping antioxidant parameter (TRAP) and Trolox equivalent antioxidant capacity (TEAC). Inverse, age-energy adjusted correlations were observed between FRAP and log-glucose (r = -0.149, p = 0.001), log-insulin (r = -0.221, p = 0.001) and log-HOMA-IR (r = -0.186, p = 0.001) concentration, as well as with TRAP and TEAC. After controlling for age, gender, body mass index, physical activity status, smoking habits and energy intake, multi-adjusted analysis confirmed the previous relationships only among participants who were not on the Mediterranean dietary pattern. CONCLUSIONS Although more prospective studies are required, the data presented support the view that dietary modification towards higher consumption of antioxidants should be implemented in public health strategies, in order to better control glycemic markers in individuals, and prevent the development of diabetes at the population level.

Effects of chronic alcohol consumption on lipid levels, inflammatory and haemostatic factors in the general population: the ‘ATTICA’ Study:

Background Epidemiological studies suggest an unclear effect of alcohol consumption on cardiovascular risk. This ambiguity is likely related to the quantity of alcohol consumed in populations studied. The aim of this work was to evaluate the association between chronic alcohol consumption and several clinical and biochemical parameters related to coronary risk, in cardiovascular disease free men and women. Methods The ‘ATTICA’ study is a population-based cohort, which randomly enrolled 750 men and 883 women (18-88 years old) from area around Athens, during 2001-2002. We investigated the association between alcohol consumption and arterial blood pressure, fibrinogen levels, glucose concentration, total cholesterol, HDL and LDL, apolipoprotein A1 and B, Lp(a), uric acid, leucocyte count, triglycerides, C-reactive protein and homocysteine levels. Results Multivariate analysis, after controlling for several potential confounders, revealed a J-shaped association between alcohol intake (none, 1-2, 3-4, 5+ wine glasses/day) and uric acid, C-reactive protein, homocysteine, fibrinogen, triglycerides, apolipoproteins A1 and B, HDL and total cholesterols, blood glucose levels, leucocyte count and arterial blood pressure levels (only in males). The most beneficial values of all these biochemical and clinical parameters were found in alcohol intake of 100-200 ml (12% alcohol), even after adjustment for various potential confounders. Conclusions The controversial association between alcohol intake and cardiovascular disease seems to be partially explained by the J-shaped relation of several biochemical parameters related to atherosclerosis and the amount of alcoholic beverages consumed.

Importance of LDL/HDL cholesterol ratio as a predictor for coronary heart disease events in patients with heterozygous familial hypercholesterolaemia: a 15-year follow-up (1987-2002)

SUMMARY This study evaluated the prognostic significance of several risk factors on the outcome of coronary heart disease (CHD) in 639 cardiovascular disease-free subjects with heterozygous familial hypercholesterolaemia (FH). During the 15-year follow-up, 53 (18%) men and 34 (9.8%) women had a CHD event (men vs women, p < 0.001). The age-adjusted 15-year event rate was 3% (87 events/2915 person-years). Smoking increased the CHD risk (hazard ratio = 2.45, p < 0.001), women had a 74% lower risk of a vascular event, compared to men, after controlling for the post-menopausal status (hazard ratio = 0.26, p < 0.001). A one-unit difference in low density lipoprotein (LDL)/high density lipoprotein cholesterol (HDL) cholesterol ratio was associated with a 17% higher risk (hazard ratio = 1.17, p < 0.05); hypertension increased the risk for an adverse event (hazard ratio = 3.02, p < 0.05) and a 1 mg/dl increase in plasma fibrinogen level was associated with a 4% higher CHD risk (hazard ratio = 1.04, p < 0.05). With the power of the 15 years of prospective evaluation, the study shows that increased smoking, hypertension and LDL cholesterol levels eight times more than HDL cholesterol predicts an adverse CHD event, in patients with FH.