Fish Consumption Moderates Depressive Symptomatology in Elderly Men and Women from the IKARIA Study

Background. The aim was to examine the association of depressive symptoms with fish eating habits, in elderly individuals. Methods. From June to October of 2009, we studied 330 men and 343 women, aged 65 to 100 years, permanent inhabitants of Ikaria Island. Among several characteristics, depression was assessed with the Geriatric Depression scale (GDS range 0–15), while dietary habits through a valid semiquantitative food frequency questionnaire. Results. Women had significantly higher values of the GDS compared to men (4.8 ± 3.5 versus 3.3 ± 3.1, P = .001). Participants in the upper tertile of depression scale ate less frequent fish and consumed higher quantities of alcohol, compared to those in the lowest tertile (all P < .05). Regarding fish consumption, 50% of the individuals reported consuming 1-2 times weekly, 32% 3 to 5 times weekly, 11% 2-3 times monthly, while the rest reported rare (4.5%) and everyday (1.2%) consumption. Logistic regression showed that increased fish consumption (>3 times/week versus never/rare) was inversely associated with the odds of having GDS greater the median value (i.e., 4) (odds  ratio = 0.34, 95% CI: 0.19, 0.61), after controlling for several cofounders. Conclusion. Frequent fish consumption in elderly seems to moderate depression mood

Effects of CYP2C19 polymorphism on endothelial function, arterial stiffness and subclinical inflammation in patients with coronary artery disease

Background: Coronary artery disease( CAD) is one of the leading causes of death. Dual antiplatelet therapy with aspirin and clopidogrel is the gold standard treatment for CAD. However a significant percentage of patients respond poorly to clopidogrel treatment, a phenomenon known as clopidogrel resistance. The role of CYP2C19*2 polymorphism in plasma clopidogrel active drug metabolite concentrations, in platelet inhibition and in cardiovascular prognosis has been investigated in many studies.Purpose: The evaluation of the impact of functional genetic polymorphism CYP2C19*2 on arterial properties, inflammatory status and clopidogrel resistance in patients with CAD.Methods: We consecutively enrolled 353 patients with stable CAD receiving clopidogrel regimen (75mg/d), at least one month after percutaneous coronary intervention. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as an index of arterial wave reflections. CYP2C19*2 genotyping was performed by real-time polymerase chain reaction. Serum IL-6, TNF-a and ICAM-1was measured by ELISA. High on treatment platelet reactivity was evaluated using VerifyNow Assay.Results: From the study population 37.6% were carriers of at least one CYP2C19*2 reduced-function allele and 62.4% were non carriers. Importantly, there was no difference in FMD (4.72±2.32% vs. 4.65±2.21% vs. 5.18±2.43%, p=0.11), PWV (8.84±2.11m/sec vs. 8.62±2.24m/sec vs. 9.01±2.48m/sec, p=0.11) , AIx values (25.42±8.30% vs. 23.9±11.02% vs. 22.82±5.84, p=0.08) and ICAM-1(5.62±0.35ng/ml vs 5.55±0.48ng/ml, p=0.456), TNF-a (0.67±0.79 pg/ml vs 0.73±0.69 pg/ml vs 0.40±0.21 pg/ml, p=0.666), IL-6(1.04±0.91pg/ml vs 0.96±0.75pg/ml vs 1.01±0.87 pg/ml, p=0,816) between carriers and non carriers respectively. Patients with increased PRU demonstrated elevated values of PWV (8.81±2.25 m/sec vs. 7.69±1.95 m/sec, p=0.001), Aix (25.27±8.67 % vs. 20.87±10.57 %, p=0.04) and FMD (4.57± 1.97% vs 6.77±3,35%, p=0.005) . Finally, carriers of two CYP2C19*2 reduced-function allele had significantly increased PRU (292±53 vs. 198±83, p=0.007).Conclusion: The presence of CYP2C19*2 loss of action polymorphism displays no impact on arterial wall properties in patients with CAD treated with clopidogrel regimen. Both CYP2C19*2 and HPR are associated with recurrent cardiovascular events. Increased HPR is associated with impaired arterial stiffness and endothelial function in patients after percutaneous coronary intervention receiving clopidogrel treatment, highlighting another clinical factor implicated in individual platelet response to antiplatelet therapy.Η περίληψη να περιλαμβάνει τον στόχο, τη μεθοδολογία και τα αποτελέσματα - συμπεράσματα της διατριβής. Συστήνεται να είναι έως 2.500 χαρακτήρες μαζί με τα κενά ή ~450 λέξεις.Εισαγωγή: Η στεφανιαία νόσος (ΣΝ) είναι μία από τις πρώτες αιτίες θανάτου. H διπλή αντιαιμοπεταλιακή αγωγή με ασπιρίνη και κλοπιδογρέλη αποτελεί την θεραπεία εκλογής σε ασθενείς με ΣΝ. Ωστόσο, ένα σημαντικό ποσοστό των ασθενών θα ανταποκριθούν ανεπαρκώς στην χορήγηση κλοπιδογρέλης, ένα φαινόμενο γνωστό ως αντίσταση στην κλοπιδογρέλη. Η επίδραση του CYP2C19 * 2 πολυμορφισμού στα επίπεδα πλάσματος του ενεργού μεταβολίτη της κλοπιδογρέλης, στην αναστολή των αιμοπεταλίων και στην καρδιαγγειακή πρόγνωση αποτελεί αντικείμενο έντονης ερευνητικής δραστηριότητας τα τελευταία χρόνια.Σκοπός: Διερεύνηση της επίδρασης του γενετικού πολυμορφισμού CYP2C19*2 στην λειτουργικότητα των αγγείων, στην υποκλινική φλεγμονή και στην αντίσταση στην κλοπιδογρέλη σε στεφανιαίους ασθενείς.Υλικό και μέθοδος: Στην μελέτη συμμετείχαν 353 ασθενείς με σταθερή στεφανιαία νόσο που λαμβάνουν θεραπευτική αγωγή με κλοπιδογρέλη (75 mg / d), τουλάχιστον ένα μήνα μετά από διαδερμική στεφανιαία παρέμβαση. Η ενδοθηλιακή λειτουργία εκτιμήθηκε με την υπερηχογραφική μέτρηση της ενδοθηλιοεξαρτώμενης αγγειοδιαστολής (FMD) και η αρτηριακή σκληρία με τη μέτρηση της ταχύτητας του σφυγμικού κύματος (PWV) και το δείκτη ενίσχυσης των ανακλωμένων κυμάτων (AIx). Η ταυτοποίηση του CYP2C19*2 πολυμορφισμού πραγματοποιήθηκε με την αλυσιδωτή αντίδραση πολυμεράσης. Η μέτρηση των επιπέδων IL-6, TNF-a και ICAM-1 έγινε με την μέθοδο ELISA. Η αντίσταση στην κλοπιδογρέλη αξιολογήθηκε με την βοήθεια του αναλυτή VerifyNow.Αποτελέσματα: Από το δείγμα της μελέτης 37,6% ήταν φορείς τουλάχιστον ένα αλληλομόρφου του CYP2C19 * 2 με μειωμένη λειτουργικότητα και 62,4% ήταν φορείς του άγριου τύπου. Δεν σημειώθηκε στατιστικά σημαντική διαφορά των τιμών FMD (4.72±2.32% vs. 4.65±2.21% vs. 5.18±2.43%, p=0.11), PWV (8.84±2.11m/sec vs. 8.62±2.24m/sec vs. 9.01±2482m/sec, p=0.11), Aix (25.42±8.30% vs. 23.09±11.02% vs. 22.82±5.84, p=0.08) και των επιπέδων ICAM-1(5.62±0.35ng/ml vs 5.55±0.48ng/ml, p=0.456), TNF-a (0.67±0.79 pg/ml vs 0.73±0.69 pg/ml vs 0.40±0.21 pg/ml, p=0.666), και IL-6(1.04±0.91pg/ml vs 0.96±0.75pg/ml vs 1.01±0.87 pg/ml, p=0,816) μεταξύ φορέων και μη φορέων, αντίστοιχα. Οι ασθενείς με αυξημένες τιμές PRU εμφάνισαν αυξημένες τιμές των PWV (8,81 ± 2,25 m /sec έναντι 7,69 ± 1,95 m / sec, p = 0,001), Aix (25.27 ± 8.67% έναντι 20.87 ± 10.57%, p = 0,04 ) και FMD (4.57± 1.97% vs 6.77±3,35%, p=0.005). Τέλος, οι φορείς ομόζυγοι για τον CYP2C19*2 πολυμορφισμό είχαν σημαντικά αυξημένες τιμές PRU (292 ± 53 έναντι 198 ± 83, p = 0,007).Συμπέρασμα: Η παρουσία του CYP2C19 * 2 πολυμορφισμού δεν εμφανίζει καμία επίδραση στην λειτουργικότητα των μεγάλων αγγείων και στην υποκλινική φλεφμονή επηρεάζοντας παρόλα αυτά την κλινική έκβαση των ασθενών. Η αυξημένη αντιδραστικότητα των αιμοπεταλίων σχετίζεται με αυξημένη αρτηριακή σκληρία, ενδοθηλιακή δυσλειτουργία και αυξημένο καρδιαγγειακό κίνδυνο σε ασθενείς μετά από διαδερμική στεφανιαία παρέμβαση υπό θεραπεία με κλοπιδογρέλη

Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients

Background: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). Methods: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Results: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p&lt;0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p&lt;0.001), osteopontin (p&lt;0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p&lt;0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders Lb coefficient= 0.79, 95% CI (-1.54, -0.05), p=0.04]. Conclusion: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation

Low Endothelial Shear Stress Predicts Evolution to High-Risk Coronary Plaque Phenotype in the Future: A Serial Optical Coherence Tomography and Computational Fluid Dynamics Study.

BACKGROUND Low endothelial shear stress (ESS) is associated with plaque progression and vulnerability. To date, changes in plaque phenotype over time in relation to ESS have not been studied in humans. The aim of this study was to investigate whether local ESS can predict subsequent changes to plaque phenotype using optical coherence tomography. METHODS AND RESULTS A total of 25 coronary arteries from 20 patients who underwent baseline and 6-month follow-up optical coherence tomography were included. Arteries were divided into serial 3-mm segments, and plaque characteristics were evaluated in each segment. A total of 145 segments were divided into low-ESS group (ESS <1 Pa) and higher-ESS group (ESS ≥1 Pa) based on baseline computational flow dynamics analyses. At baseline, low-ESS segments had significantly thinner fibrous cap thickness compared with higher-ESS segments (128.2±12.3 versus 165.0±12.0 μm;=0.03), although lipid arc was similar. At follow-up, fibrous cap thickness remained thin in low-ESS segments, whereas it significantly increased in higher-ESS segments (165.0±12.0 to 182.2±14.1 μm;=0.04). Lipid arc widened only in plaques with low ESS (126.4±15.2° to 141.1±14.0°;=0.01). After adjustment, baseline ESS was associated with fibrous cap thickness (β, 9.089; 95% confidence interval, 2.539-15.640;=0.007) and lipid arc (β, -4.381; 95% confidence interval, -6.946 to -1.815;=0.001) at follow-up. CONCLUSIONS Low ESS is significantly associated with baseline high-risk plaque phenotype and progression to higher-risk phenotype at 6 months. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538

The Natural History of Multifocal Atrial Rhythms in Elderly Outpatients: Insights from the “Ikaria Study”

BackgroundMultifocal atrial tachycardias confer an adverse prognosis in hospitalized patients. We assessed the prognostic impact of multifocal atrial rhythms (MARseither chaotic atrial rhythm or multifocal atrial tachycardia/bradycardia) in very elderly outpatients. MethodsOne hundred ten subjects aged 60-74 years, 112 aged 75-89 years, and 61 over 90 years old, were enrolled and prospectively evaluated. Several demographic and clinical characteristic were recorded in all individuals. ResultsA high prevalence of MARs was detected in the study population (namely, 6%), which in subjects &gt;90 years was even higher (15%). Individuals with MARs were older, more often female and less active. In multivariate analysis, independent predictors of MARs were age (OR = 1.07, 95% CI: 1.02-1.13, P = 0.01) and female sex (OR = 4.77, 95% CI: 1.23-18.48, P = 0.02). The mortality rate during the follow-up period was 8.4% without differences between age groups (P = 0.209). In particular, mortality rate was 6% in individuals with MARs and 9% in those without (P = 0.72). Mortality was associated with age (OR 1.07, 95% CI: 1.02-1.12, P = 0.005) and history of cardiovascular disease at baseline (OR 4.57, 95% CI: 1.87-11.2 P = 0.001). ConclusionsContrary to hospitalized individuals with multifocal atrial tachycardias, MARs were not associated with increased mortality in elderly outpatients in this study

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