Arterial aging mediates the effect of TNF-α and ACE polymorphisms on mental health in elderly individuals: insights from IKARIA study.

BACKGROUND: Aging is characterized by an insidious decline in cognitive function. Several genetic and lifestyle factors have been implicated in the increased risk or early onset of dementia. AIM: We sought to assess the role of tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) polymorphisms on the development of impaired mental health in respect to indices of arterial aging in nonagenarian individuals. DESIGN: 178 consecutive subjects above 75 years that permanently inhabit in the island of IKARIA, Greece were recruited. METHODS: Aortic distensibility (AoD) was calculated and genetic evaluation was performed on the ACE Insertion/Deletion gene polymorphism (intron 16) and the G/A transition (position -308) of the TNF gene. Cognitive function was evaluated using the Mini-mental State Examination (MMSE). RESULTS: The DD genotype for ACE was independently associated ( b = -0.44, P = 0.007) with AD while AoD remained an independent determinant of mental status (OR = 1.82, P = 0.036). Interestingly though, when a combined genetic index (GI) was calculated for both genes (ACE and TNF), subjects being double homozygous (DD for ACE and GG for TNF) for these loci presented significantly decreased MMSE (adjusted OR = 0.259, P = 0.033). This GI independently associated with AD (beta coefficient = -0.785, P = 0.002). When AoD was included, GI lost its predictive role (OR = 0.784, P = 0.783) towards MMSE. AoD has marginal indirect mediating effect in the association of the GI with MMSE ( P = 0.07). CONCLUSION: Vascular aging may modulates the genetic substrate of elderly subjects on the risk for developing dementia.

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 study's 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.

Renal function, cardiovascular disease risk factors' prevalence and 5-year disease incidence; the role of diet, exercise, lipids and inflammation markers: the ATTICA study.

BACKGROUND: We aimed to evaluate the association between renal function and various cardiovascular disease (CVD) risk factors, as well as 5-year incidence of CVD, in a sample of CVD free adults. METHODS: (i) Cross-sectional information from n = 1975. Greek men and women (>18 years) without CVD and hypertension at baseline examination and (ii) 5-year (2001-06) survival data from n = 2101 individuals without CVD at baseline, all participants in the ATTICA study, were analysed in this work. Kidney function was quantified by the baseline estimated creatinine clearance rate (C(cr)), using the Cockcroft-Gault formula and the National Kidney Foundation recommendations. Outcome of interest was the development of CVD that was defined according to WHO-ICD-10 criteria. RESULTS: At baseline, the prevalence of moderate-to-severe renal dysfunction (i.e. C(cr) < 60) was 2.8% in males and 7.7% in females. Physical activity status, cigarette smoking, hypercholesterolemia and homocysteine levels and greater adherence to the Mediterranean diet were inversely associated with C(cr) rate (P < 0.05), while no association was found with history of diabetes. During the 5-year follow-up, people with moderate-to-severe renal dysfunction as compared with normal, had 3.21 times higher CVD risk [95% confidence interval (CI) 1.98-5.19], after adjusting for history of hypertension (hazard ratio = 2.15, 95% CI 1.48-3.11), hypercholesterolemia (1.37, 0.98-1.98), diabetes (3.28, 2.15-5.00), smoking habits (0.89, 0.60-1.32) and physical activity status (0.86, 0.56-1.21). CONCLUSION: Renal function seems to be associated with the levels of lifestyle and bio-clinical CVD risk factors and contribute to the long-term incidence of cardiac events. Public health care practitioners should take into account renal function in better preventing the burden of CVD at individual, and population level, as well.

Resistance exercise plus to aerobic activities is associated with better lipids' profile among healthy individuals: the ATTICA study.

BACKGROUND: The influence of different types of exercise on risk factors for cardiovascular diseases has rarely been investigated. The aim of the present work was to evaluate the effect of adding resistance exercise to aerobic activities on lipid-lipoprotein profile, in a representative sample of men and women from the province of Attica, Greece. METHODS: We randomly enrolled 1514 and 1528 healthy men and women, respectively, stratified by city, age and gender distribution. Participants were classified as inactive (INA), sufficiently active (SA) and highly active for either aerobic activities (HAA) alone or a combination of aerobic plus resistance exercise (HAC). The main outcome measures are lipid-lipoprotein profile [total, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein-A1, apolipoprotein-B] and anthropometric indices. RESULTS: From those participating in aerobic activities, 480 (31.7%) men and 502 (32.9%) women were classified as SA, 100 men (6.6%) and 93 women (6.1%) as HAA and 90 men (5.9%) and 49 women (3.2%) as HAC. After various adjustments were made, men from the HAC group had an average of 23% lower plasma triacylglycerol concentration (P = 0.04) and 10% lower LDL-cholesterol (P = 0.01) when compared with the HAA group. Moreover, women from the HAC group had 13% lower LDL-cholesterol when compared with HAA group (P = 0.051). CONCLUSION: These data suggest that combining aerobic and resistance-type activities may confer a better effect on lipoprotein profile in healthy individuals than aerobic activities alone.

Apolipoprotein E polymorphism is not associated with lipid levels and coronary artery disease in Greek patients with familial hypercholesterolaemia.

Familial hypercholesterolaemia is a genetic disorder characterised by high low-density lipoprotein (LDL) cholesterol concentrations, which frequently gives rise to premature coronary artery disease (CAD). The clinical expression of familial hypercholesterolaemia is highly variable even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental and other genetic factors. Apolipoprotein E (Apo-E) has been extensively studied for its effects on the phenotype of familial hypercholesterolaemia. In this study we examined the influence of Apo-E genotype on lipid parameters and the incidence of CAD in 93 Greek patients with familial hypercholesterolaemia. Apo-E E2, E3 and E4 allele frequencies were 0.06, 0.86 and 0.09 respectively. The levels of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoproteins A and B and lipoprotein alpha did not differ significantly among carriers and non-carriers of the E4 allele. The prevalence of CAD and hypertension did not differ either. Our results suggest that the E4 allele is not associated with lipid levels or with the prevalence of CAD among familial hypercholesterolaemia patients of the Greek population.

FH clinical phenotype in Greek patients with LDL-R defective vs. negative mutations.

BACKGROUND: Familial hypercholesterolaemia (FH) is caused by mutations in the low-density lipoprotein receptor gene and the gene encoding apolipoprotein B-100, affecting one in 500 individuals. METHODS: One hundred and eighty-three Greek FH patients were screened for mutations on the LDLR and ApoB genes. RESULTS: We identified mutations in 67 probands and 11 relatives. Sixteen mutations located in eight different exons and the promoter of the LDLR were discovered. Among them 10 were missense mutations (C6W, S265R, A370T, Q363P, D365E, V408M, A410T, A517T, G528D, G571E), two were nonsense mutations (Q363X and C660X), three were splice defects (2140 + 5G-->A and 2140 + 9C-->T, 1706 - 10G-->A), and one was a nucleotide substitution (- 45delT) on the promoter. None of the subjects carried any apoB mutation. The detection rate of mutations in this study was 43%. From the above mutations, A410T, A519T and the splice site defects 2140 + 9C-->T were detected for the first time in the Greek population. Among them V408M, G528D, C6W and S265R account for 73% of heterozygous FH probands. V408M mutation is more common in Central West, while C6W is more common in Central East. Separating the patients into two groups (receptor defective and receptor negative) we found that the receptor negative group had higher levels of total cholesterol, low-density lipoprotein cholesterol and higher prevalence of tendon xanthomas compared with the receptor-defective group. DISCUSSION: The homogenous molecular basis of familial hypercholesterolaemia in Greece facilitates the application of a DNA diagnostic strategy based on the origin of the patient. The early mutation analysis would add valuable information on the severity of the disease.

FH-Pyrgos: a novel mutation in the promoter (-45delT) of the low-density lipoprotein receptor gene associated with familial hypercholesterolemia.

In a patient with familial hypercholesterolemia (FH), we have identified a new mutation (-45delT) in repeat 3 of the low-density lipoprotein receptor (LDLR) gene promoter. Analysis of a neutral polymorphism in the LDLR mRNA from the patient's white blood cells showed that the expression of one allele was significantly reduced, and cells have only 24% of LDLR activity by binding and uptake of DiI-LDL. Transient transfection studies using a luciferase gene reporter revealed that the -45delT mutation considerably reduces the transcriptional activity of the LDLR promoter and strongly suggest that the mutation is the cause of the FH phenotype.

Association between exposure to environmental tobacco smoke and the development of acute coronary syndromes: the CARDIO2000 case-control study.

OBJECTIVE: To investigate the association between environmental tobacco smoke (ETS) exposure (at least 30 minutes a day) and the risk of developing acute coronary syndromes (ACS). DESIGN AND SETTING: The CARDIO2000 is a case-control study which was conducted in Greece from 2000 to 2001. Cases included 847 individuals with a first event of ACS and 1078 cardiovascular disease-free controls. Cases and controls were frequency matched on age (within three years of age), sex, and region. MAIN OUTCOME MEASURES: ACS was defined as a diagnosis of first acute myocardial infarction or unstable angina. Main independent variable: Exposure to ETS was measured by self report as follows: after the second day of hospitalisation for the cases, and at the entry for the controls, participants were asked whether they were currently exposed to tobacco smoke from other people (home and/or work) for more than 30 minutes a day. The responses were categorised into three levels: no exposure, occasional exposure (< 3 times per week), and regular exposure. In addition participants were asked how many years they had been exposed. Because these were self reported assessments and prone to bias, the results were compared to reports obtained from subjects' relatives or friends, using the Kendal's tau coefficient that showed high agreement. RESULTS: 731 (86%) of the patients and 605 (56%) of the controls reported current exposure of 30 minutes per day or more to ETS. Among current non-smokers, cases were 47% more likely to report regular exposure to ETS (odds ratio (OR) 1.47, 95% confidence interval (CI) 1.26 to 1.80) compared to controls. Exposure to ETS at work was associated with a greater risk of ACS compared to home exposure (+97% v +33%). The risk of ACS was also raised in active smokers (OR 2.83, 95% CI 2.07 to 3.31) regularly exposed to ETS. CONCLUSIONS: This study supports the hypothesis that exposure to ETS increases the risk of developing ACS. The consistency of these findings with the existing totality of evidence presented in the literature supports the role of ETS in the aetiology of ACS.

The effect of the combination of Mediterranean diet and leisure time physical activity on the risk of developing acute coronary syndromes, in hypertensive subjects.

The World Health Organization reports that the number of hypertensives, worldwide, is estimated to be 600 million people. In addition a considerable proportion of hypertensive subjects remains untreated or uncontrolled. In this work we investigated the combined effect of physical activity and Mediterranean diet on coronary risk, in hypertensives. Thus we randomly selected, from all Greek regions, 848 hospitalised patients (695 males, 58 +/- 10 years old and 153 females, 65 +/- 9 years old) with a first event of coronary heart disease (CHD) and 1078 paired, by sex, age, region controls, without any suspicions for CHD. Physically active were those who reported non-occupational physical activity more than once per week. Subjects 'closer' to the Mediterranean diet were assessed through a special nutrient questionnaire. A total of 418 (49%) of the patients and 303 (28%) of the controls were hypertensive. Of these, 115 (27%) patients and 70 (23%) controls were untreated, 148 (35%)-111 (36%) were uncontrolled and 155 (38%)-122 (41%) were controlled (P-value <0.01). One hundred and sixty-two (19%) of the patients and 265 (25%) of the controls (P < 0.01) were 'closer' to the combination of Mediterranean type of diet and physical activity. The analysis showed that the previous combination is related to a 25% reduction of the coronary risk in controlled hypertensive subjects (OR = 0.75, P < 0.01), a 11% reduction in untreated (OR = 0.89, P < 0.05) and 17% reduction (OR = 0.83, P < 0.05) in uncontrolled, after adjusting for age, sex, educational and financial level and the conventional cardiovascular risk factors. Consequently, the adoption of Mediterranean diet by physically active subjects seems to reduce significantly the coronary risk and prevent, approximately, the one-third of acute CHD, in controlled hypertensive subjects.

Influence of biological factors on lipid and fibrinogen measurements in young men. An epidemiological study in 2009 recruits.

AIMS: The aim of the present study was to detect significant relationships between lipid and fibrinogen measurements and several biological factors in young men. METHODS AND RESULTS: Medical history was obtained, and plasma lipids, lipoprotein (a) and fibrinogen levels were measured in 2009 male Greek army recruits (mean age 22.37+/-3.03 years) not taking any drugs. Plasma levels were as follows: total cholesterol, 171+/-34 mg x dl(-1), low density lipoprotein (LDL) cholesterol, 111+/-34 mg x dl(-1), high density lipoprotein (HDL) cholesterol, 45+/-10 mg x dl(1), and triglycerides, 74+/-32 mg x dl(-1). Lipoprotein (a) and fibrinogen were 18+/-13 and 278+/-67 mg x dl(-1). The atherosclerotic index, calculated as the ratio of total cholesterol/HDL, was 4+/-1. Analysis of multivariate models that included potentially confounding factors revealed the following: body mass index, season of year during which blood examinations were performed, alcohol consumption, and place of residence were found to be significantly associated with plasma levels of total cholesterol, LDL-cholesterol, fibrinogen and the atherosclerotic index in the pooled population. Season and physical activity were significantly associated with HDL-cholesterol, whereas season and family history of acute myocardial infarction were associated with triglycerides levels. Body mass index, family history of myocardial infarction and physical activity were associated with lipoprotein (a). CONCLUSION: Body mass index, season, alcohol consumption and place of residence are markers of plasma lipid profile and fibrinogen in young men. A family history of acute myocardial infarction and physical activity are related to lipoprotein (a).

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.

Differentiation of beta-blocker effects on serum lipids and apolipoproteins in hypertensive patients with normolipidaemic or dyslipidaemic profiles.

To evaluate the differential effects of beta-blockers on serum lipids and apolipoproteins in normolipidaemic and dyslipidaemic hypertensives, 330 patients with mild to moderate essential hypertension were studied 1 month after placebo therapy and 6 months after monotherapy with propranolol (n = 53), atenolol (n = 66), metoprolol (n = 58), pindolol (n = 53), or celiprolol (n = 100). Serum total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), and apolipoproteins (Apo) A1 and B were measured at baseline and study end. A total of 136 (41.2%) patients were considered normolipidaemic (pretreatment LDL-C < 160 mg.dl-1) and 194 (58.8%) were considered dyslipidaemic (LDL-C > 160 mg.dl-1). Changes in total cholesterol differed between normolipidaemics and dyslipidaemics with propranolol (+13% in normolipidaemics vs -0.5% in dyslipidaemics, P < 0.001), atenolol (+7% vs -2%, P = 0.01), metoprolol (+9% vs -4%, P0.0006), pindolol (+8% vs -9%, P < 0.001), and celiprolol (-1% vs -13%, P = 0.002). HDL-C differed less, with propranolol (-18% vs -13%), atenolol (-6% vs -2%), metoprolol (-2% vs -6%), pindolol (+4% vs +1%), and celiprolol (+9% vs +4%); none of these changes between normolipidaemic and dyslipidaemic patients were statistically significant. LDL-C changes differed the most, with propranolol (+35% vs -1%, P < 0.0001), atenolol (+15% vs -4%, P = 0.001), metoprolol (+12% vs -6%, P = 0.004), pindolol (+12% vs -13%, P < 0.0001), and celiprolol (+3% vs -16%, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of arterial hypertension on coronary collateral circulation development and left ventricular function in coronary artery disease.

To assess the role of arterial hypertension in the development of coronary collateral circulation in relation to coronary artery disease, severity and left ventricular function, we studied 433 men with angiographically documented coronary artery disease. Of these, 122 showed disease in one vessel, 157 showed disease in two vessels and 159 patients showed disease in three vessels; 153 (35.3%) patients had arterial hypertension. The hypertensive patients had a similar distribution of diseased coronary vessels and similar coronary obstruction scores according to Gensini compared with the normotensive patients (64 versus 62, NS), but they had higher left ventricular ejection fraction values (51.5 versus 46.8%, P = 0.002). Coronary collateral circulation was more often seen in hypertensives (70.6 versus 57.1%, P = 0.006), especially high-grade coronary collateral circulation (27 versus 15%, P = 0.001). However, patients with coronary collateral circulation had more severe coronary artery disease, whether they had arterial hypertension (71 versus 46, P = 0.00008) or not (76 versus 43, P less than 0.00001). Thus, for a similar severity of coronary artery disease, patients with arterial hypertension and also coronary collateral circulation had higher ejection fraction values (52.6 versus 46.1%, P = 0.0006). This was more readily observed in those patients with disease in three vessels and coronary collateral circulation (52 versus 42.8%, P = 0.002). Patients without coronary collateral circulation had similar ejection fraction and coronary obstruction score values, irrespective of arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)