Search

Objective: Accelerated atherosclerosis in diabetes constitutes an ongoing challenge despite optimal medical therapies. This study aimed to identify evolutionarily conserved lesion-based regulatory signaling networks in diabetic versus nondiabetic conditions during the development of atherosclerosis in an initial translational effort to provide insights for targets. Approach and Results: Serial 3-mm coronary artery segments of hypercholesterolemic Yorkshire swine and diabetic-hypercholesterolemic swine were characterized as mild, moderate, or severe phenotypic manifestations of coronary atherosclerosis based on histopathologic examination. Lesional RNA sequencing was performed (n=3–8 lesions per group) corresponding to increasing phenotypic severity. Differentially expressed genes, transcription factors, upstream regulators, and hubs were validated using the NanoString technology and a human atherosclerotic specimen cohort. Despite similar stage histopathologic characterization of lesions, genome-wide transcriptomics revealed gene sets and nodal signaling pathways uniquely expressed in diabetic lesions including signaling pathways for Th17, IL (interleukin)-17F, TWEAK (TNF [tumor necrosis factor]-related weak inducer of apoptosis), CD27, and PI3K/Akt. In contrast, pathways of nondiabetic lesions involved TREM-1 and Th1 and Th2 responses during the initiation stage, whereas networks for mitochondrial dysfunction, oxidative phosphorylation, and lipid metabolism emerged with progression. RNA sequencing data were validated in a human atherosclerosis specimen cohort using machine learning algorithms. F8 , MAPKAPK3 , and ITGB1 emerged as powerful genes for clustering diabetic versus nondiabetic lesions and for separating different degrees of atherosclerosis progression. Conclusions: This study identifies evolutionarily conserved gene signatures and signaling pathways in a stage-specific manner that successfully distinguishes diabetes- and non–diabetes-associated atherosclerosis. These findings establish new molecular insights and therapeutic opportunities to address accelerated atherosclerotic lesion formation in diabetes.

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.

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, n = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants &gt, 65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis, in age &gt, 65 years, Hazard Ratio (HR)(2nd vs. 1st SMI tertile) = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR(2nd vs. 1st SMI tertile) = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass.

The natural history of coronary atherosclerosis is complex and atherosclerotic plaques exhibit large morphologic and functional variability within the same individual as well as over time. The purpose of this article is to review the role of blood flow patterns and shear stress on the development of microvascular and epicardial endothelial dysfunction and atherosclerosis progression.Recent breakthroughs in cardiovascular imaging have facilitated in-vivo characterization of the anatomic and functional characteristics of atherosclerotic plaques and have highlighted the role of endothelial shear stress and epicardial and microvascular endothelial dysfunction in the natural history of coronary atherosclerosis.There is an important need to identify individual lesions which may progress to vulnerable plaque in order to provide early therapeutic management. Evaluation of endothelial shear stress, local blood flow patterns, epicardial and microvascular endothelial dysfunction, as well as their complex associations might indicate those patients who have microvascular endothelial dysfunction and increased risk for upstream epicardial endothelial dysfunction and plaque progression. Such high-risk patients could potentially be targeted for more intensive therapeutic strategies to prevent the progression of both microvascular and epicardial atherosclerotic manifestations.

Objectives This study sought to determine whether low endothelial shear stress (ESS) adds independent prognostication for future major adverse cardiac events (MACE) in coronary lesions in patients with high-risk acute coronary syndrome (ACS) from the United States and Europe. Background Low ESS is a proinflammatory, proatherogenic stimulus associated with coronary plaque development, progression, and destabilization in human-like animal models and in humans. Previous natural history studies including baseline ESS characterization investigated low-risk patients. Methods In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of MACE attributable to untreated nonculprit (nc) coronary lesions during 3.4-year follow-up were large plaque burden (PB), small minimum lumen area (MLA), and thin-cap fibroatheroma (TCFA) morphology. In this analysis, baseline ESS of nc lesions leading to new MACE (nc-MACE lesions) and randomly selected control nc lesions without MACE (nc-non-MACE lesions) were calculated. A propensity score for ESS was constructed for each lesion, and the relationship between ESS and subsequent nc-MACE was examined. Results A total of 145 lesions were analyzed in 97 patients: 23 nc-MACE lesions (13 TCFAs, 10 thick-cap fibroatheromas [ThCFAs]), and 122 nc-non-MACE lesions (63 TCFAs, 59 ThCFAs). Low local ESS ( Conclusions Local low ESS provides incremental risk stratification of untreated coronary lesions in high-risk patients, beyond measures of PB, MLA, and morphology.

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.

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 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.

Background: Patients with type 2 diabetes mellitus (DM2) exert a higher risk for thrombotic events. Platelet reactivity may be used to assess prothrombotic state in patients with cardiovascular disease. We aimed to investigate whether the administration of novel antiglycemic agents may influence platelet reactivity in these patients. Methods: We enrolled 99 patients (male=63.3%) receiving metformin for DM2 who did not achieve therapeutic targets under current treatment. Subjects were assigned to age and sex matched groups (n=33 per group) of an additional antiglycemic agent; either DPP-4 inhibitor, SGLT2 inhibitor or a GLP-1 agonist. Platelet reactivity was measured with PFA-200 assay; collagen/epinephrine (CEPI) and collagen/ADP closure time (CADP) were calculated in seconds and HbA1c at baseline and at 3 months. Results: There was no difference for male gender (p=0.10) or age (64.92 ± 8.30 years, p=0.27) between the study groups. All patients achieved better glycemic control in terms of HbA1c values between baseline and follow-up (7.78% vs. 6.92% for DPP-4, 7.52% vs. 6.73% for SGLT2 and 8.19% vs. 6.85% for GLP-1, p Conclusion: The addition of DPP-4 or GLP-1 to metformin influences platelet reactivity and achieves better glycemic control in DM2 patients, providing further insights in the pathophysiology of DM2. Disclosure G. Siasos: None. E. Bletsa: None. P.K. Stampouloglou: None. K. Batzias: None. A. Antonopoulos: None. S.A. Paschou: None. V. Tsigkou: None. N. Gouliopoulos: None. S. Mazaris: None. G. Vogiatzi: None. S. Tsalamandris: None. E. Oikonomou: None. M. Zaromytidou: None. M. Politou: None. A. Vryonidou: None. A. Thanopoulou: None. N. Tentolouris: None. D. Tousoulis: None.

Background: Arterial stiffness is a prominent macrovascular complication in patients with type 2 diabetes mellitus (DM2). Antiplatelet therapy is the cornerstone of CVD therapy. There is little evidence about the influence of antiglycemic agents on arterial wall properties and prothrombotic state. Methods: We enrolled 80 consecutive patients (males=64.4%), aged 64.19 ± 8.82 years receiving either metformin plus another antiglycemic agent such as sulphonylureas, DPP-4i, GLP-1 agonists, insulin, or metformin alone (n=16 per group). Applanation tonometry was used to assess aortic pulse wave velocity (PWV) as a measure of arterial stiffness. Platelet reactivity was measured with PFA-200, collagen/epinephrine (CEPI) and PFA-200 collagen/ADP closure time (CADP). Results: There was no difference between the study groups regarding gender, age, hypertension, dyslipidemia, smoking, PWV, CADP or CEPI (p=NS for all). When conducting a separate analysis between patients receiving aspirin (AS), dual antiplatelet therapy (DAPT) and those without antiplatelet therapy (nAPT), we observed that nAPT patients exerted significantly lower CEPI values (134.42 ± 40 s for nAPT vs. 170.36 ± 64 s for AS vs. 178.90 ± 74 s for DAPT, p=0.03). PWV was 10.96 ± 2.54 m/s for nAPT vs. 11.20 ± 2.88 m/s for AS vs. 10.82 ± 2.76 m/s for DAPT (p=0.9). Within-group analysis showed that CEPI values were significantly reduced in nAPT under sulphonylureas (121 s vs. 243 s vs. 262 s for nAPT, AS and DAPT respectively, p=0.02) or GLP-1 (138 s vs. 203 s vs. 168 s for nAPT, AS and DAPT respectively, p=0.05). Additionally, we found an inverse, linear association between CEPI and PWV (rho= -0.45, p=0.02) and CADP and PWV (rho= -0.04, p=0.05) in nAPT patients alone. Conclusion: Increased prothrombotic state is associated with impaired arterial wall elastic properties. Antidiabetic and antiplatelet treatment interactions may regulate the relationship between arterial stiffness and thrombosis in patients with DM2. Disclosure G. Siasos: None. P.K. Stampouloglou: None. K. Batzias: None. S.A. Paschou: None. A. Antonopoulos: None. V. Tsigkou: None. N. Gouliopoulos: None. M. Zaromytidou: None. S. Mazaris: None. E. Oikonomou: None. S. Tsalamandris: None. G. Vogiatzi: None. A. Thanopoulou: None. A. Vryonidou: None. M. Politou: None. D. Tousoulis: None. N. Tentolouris: None.

Intracoronary hemodynamics play a pivotal role in the initiation and progression of the atherosclerotic process. Low pro-inflammatory endothelial shear stress impacts vascular physiology and leads to the occurrence of coronary artery disease and its implications.

Patients with type 2 diabetes (T2D) are at high risk for thrombotic events. Platelet reactivity may be used to assess prothrombotic status. We investigated whether administration of novel antidiabetic agents may alter platelet reactivity in patients with T2D. We enrolled 54 consecutive male

Transplant (tplant) coronary artery disease (TCAD) is an immunologic phenomenon and a major cause of morbidity/mortality after heart tplant. Low ESS drives plaque behavior in native CAD, but its role in TCAD, with its prominent immunologic environment, has not been studied. We studied 21 pts (av

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 P =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; P =0.04). Lipid arc widened only in plaques with low ESS (126.4±15.2° to 141.1±14.0°; P =0.01). After adjustment, baseline ESS was associated with fibrous cap thickness (β, 9.089; 95% confidence interval, 2.539–15.640; P =0.007) and lipid arc (β, −4.381; 95% confidence interval, −6.946 to −1.815; P =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.

Arterial stiffness is considered a surrogate marker of arterial dysfunction in type 2 diabetes mellitus (DM2). Antiplatelet therapy is the cornerstone of cardiovascular disease therapy. There exists little evidence about the influence of antiglycemic agents on arterial wall properties and

Despite the important progress in identifying high-risk atherosclerotic plaques, many key elements are elusive. Advanced imaging modalities provide valuable information about the anatomic and functional plaque characteristics and underscore the presence of multiple plaque morphologies. However, how the heterogeneity of atherosclerotic plaque can alter our current understanding of coronary artery disease is not fully understood. Along the length of an individual plaque, the morphology patterns display marked heterogeneity. Contrary to previous beliefs, plaque morphology is also highly dynamic over time, with the vast majority of high-risk plaques becoming quiescent and mild plaques becoming severely obstructive in a short period of time. Endothelial shear stress, a local hemodynamic factor known for its critical effects in plaque initiation and progression, also displays longitudinal heterogeneity contributing to the arterial wall response in all time points. Risk stratification of plaques based on the morphological characteristics at one region of the plaque, usually the minimal lumen diameter, and at one point in time may be misleading. The evaluation of both morphological and hemodynamic characteristics along the length of a plaque will improve the risk assessment of individual plaques.

This study sought to determine whether low endothelial shear stress (ESS) adds independent prognostication for future major adverse cardiac events (MACE) in coronary lesions in patients with high-risk acute coronary syndrome (ACS) from the United States and Europe.Low ESS is a proinflammatory, proatherogenic stimulus associated with coronary plaque development, progression, and destabilization in human-like animal models and in humans. Previous natural history studies including baseline ESS characterization investigated low-risk patients.In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of MACE attributable to untreated nonculprit (nc) coronary lesions during 3.4-year follow-up were large plaque burden (PB), small minimum lumen area (MLA), and thin-cap fibroatheroma (TCFA) morphology. In this analysis, baseline ESS of nc lesions leading to new MACE (nc-MACE lesions) and randomly selected control nc lesions without MACE (nc-non-MACE lesions) were calculated. A propensity score for ESS was constructed for each lesion, and the relationship between ESS and subsequent nc-MACE was examined.A total of 145 lesions were analyzed in 97 patients: 23 nc-MACE lesions (13 TCFAs, 10 thick-cap fibroatheromas [ThCFAs]), and 122 nc-non-MACE lesions (63 TCFAs, 59 ThCFAs). Low local ESS (1.3 Pa) was strongly associated with subsequent nc-MACE compared with physiological/high ESS (≥1.3 Pa) (23 of 101 [22.8%]) versus (0 of 44 [0%]). In propensity-adjusted Cox regression, low ESS was strongly associated with MACE (hazard ratio: 4.34; 95% confidence interval: 1.89 to 10.00; p 0.001). Categorizing plaques by anatomic risk (high risk: ≥2 high-risk characteristics PB ≥70%, MLA ≤4 mmLocal low ESS provides incremental risk stratification of untreated coronary lesions in high-risk patients, beyond measures of PB, MLA, and morphology.

[1] Gibson CM, Cannon CP, DaleyWL, et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation 1996;93:879–88. [2] Kunadian V, Harrigan C, Zorkun C, et al. Use of the TIMI frame count in the assessment of coronary artery blood flow andmicrovascular function over the past 15 years. J Thromb Thrombolysis 2009;27:316–28. [3] Porto I, Hamilton-Craig C, Brancati M, Burzotta F, Galiuto L, Crea F. Angiographic assessment of microvascular perfusion–myocardial blush in clinical practice. Am Heart J 2010;160:1015–22. [4] Korosoglou G, Haars A, Michael G, et al. Quantitative evaluation of myocardial blush to assess tissue level reperfusion in patients with acute ST-elevation myocardial infarction: incremental prognostic value compared with visual assessment. Am Heart J 2007;153:612–20. [5] Haeck JD, Gu YL, Vogelzang M, et al. Feasibility and applicability of computerassisted myocardial blush quantification after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Catheter Cardiovasc Interv 2010;75:701–6. [6] Ungi T, Ungi I, Jonas Z, et al. Myocardium selective densitometric perfusion assessment after acute myocardial infarction. Cardiovasc Revasc Med 2009;10:49–54. [7] Ungi T, Zimmermann Z, Balazs E, et al. Vessel masking improves densitometric myocardial perfusion assessment. Int J Cardiovasc Imaging 2009;25:229–36. [8] Vijayalakshmi K, Ashton VJ, Wright RA, et al. Corrected TIMI frame count: applicability in modern digital catheter laboratories when different frame acquisition rates are used. Catheter Cardiovasc Interv 2004;63:426–32. [9] Gibson CM, Cannon CP,Murphy SA, et al. Relationship of TIMImyocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 2000;101:125–30. [10] Spaan J, Kolyva C, van den Wijngaard J, et al. Coronary structure and perfusion in health and disease. Philos Transact A Math Phys Eng Sci 2008;366:3137–53. [11] Cannon III RO. Microvascular angina and the continuing dilemma of chest pain with normal coronary angiograms. J Am Coll Cardiol 2009;54:877–85. [12] Miller JM, Rochitte CE, Dewey M, et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 2008;359:2324–36. [13] Wijns W, De Bruyne B, Vanhoenacker PK. What does the clinical cardiologist need from noninvasive cardiac imaging: is it time to adjust practices to meet evolving demands? J Nucl Cardiol 2007;14:366–70.

BACKGROUND: Multifocal atrial tachycardias confer an adverse prognosis in hospitalized patients. We assessed the prognostic impact of multifocal atrial rhythms (MARs—either chaotic atrial rhythm or multifocal atrial tachycardia/bradycardia) in very elderly outpatients. METHODS: One 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. RESULTS: A high prevalence of MARs was detected in the study population (namely, 6%), which in subjects >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). CONCLUSIONS: Contrary to hospitalized individuals with multifocal atrial tachycardias, MARs were not associated with increased mortality in elderly outpatients in this study.

In patients with coarctation of aorta (CoA) aortic remodelling may alter the elastic properties of large arteries, but the role of stiffness indices, such as pulse wave velocity (PWV) and augmentation index (AIx), in CoA remains unclear. We studied the association between CoA, arterial stiffness and

Low endothelial shear stress (ESS) is pro-inflammatory, and was an independent predictor of MACE in the PROSPECT study. The site of low ESS along the lesion course is unknown and may have important implications for evaluation of high-risk lesions. Baseline untreated non-culprit (nc) lesions in

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 ( versus , ). 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 ). 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) (, 95% CI: 0.19, 0.61), after controlling for several cofounders.Conclusion. Frequent fish consumption in elderly seems to moderate depression mood.

Clopidogrel, an antiplatelet agent, prevents platelet aggregation by inhibiting the adenosine disphosphate (ADP) P2Y12 receptor, which is located on the platelet surface. Although dual antiplatelet therapy appears to be efficient, a considerable number of patients continue to experience adverse cardiovascular events, such as stent thrombosis. The percentage of low response to antiplatelet therapy varies from 4% to 30% of patients depending on the cut-off values. In addition, several factors such as poor absorption, drug-to-drug interactions, inadequate dosing, elevated body mass index, insulin resistance and the nature of acute coronary syndromes have been implicated in low clopidogrel response. Recently, studies have focused on the role of genetic polymorphisms encoding enzymes that participate in clopidogrel hepatic metabolism or receptors involved in intestinal absorption and ADP induced platelet aggregation, which may affect the percentage of platelet inhibition after clopidogrel administration. The management of clopidogrel resistance remains a controversial issue and additional studies are required to evaluate the safety and efficacy of increased loading of clopidogrel or replacement with other new antiplatelet agents such as prasugrel.

Objectives: Metabolic syndrome (MetS) shows increased prevalence in elderly population, and confers further to cardiovascular wear and total mortality. Recently, Ikaria island inhabitants, an isolated rural group with lifelong characteristics, have been recognized as having among the highest longevity rates universally with high percentage of healthy aging, despite the considerable prevalence of cardiovascular disease risk factors. Aim of this work was to evaluate the relationship between total serum testosterone levels with metabolic syndrome (MetS) and its components. Methods: The working sample consisted of in 467 elderly individuals (mean age 75±6 years old, n=220 men); MetS was defined according to NCEP ATPIII criteria. Results: MetS prevalence was 52% in men and 64% in women. In men, age-adjusted analysis showed that serum testosterone levels were inversely associated with the likelihood of having MetS; while, in women no such association was observed. Those with MetS had lower testosterone levels; i.e., 10 ng/dl increase of testosterone was associated with 3% lower odds of having MetS in men (95% CI: 0.95-0.99), but not in women, after various adjustments, including daily hours of sleep. Testosterone was inversely associated with abnormal waist circumference, hs-CRP, insulin, HDL-cholesterol levels, only in men. When categories of lipids, hs-CRP, BMI and insulin resistance levels were taken into account, testosterone lost its significance in predicting MetS (p>0.20), suggesting a mediating effect of these markers. Conclusion: Low serum testosterone was associated with MetS, in elderly men; while, lipids, BMI, inflammation and insulin resistance markers levels seems to explain this relationship, suggesting a potential mediating effect. This finding may support a research hypothesis relating serum testosterone with cardiovascular disease.