Dennis V Cokkinos

Biomedical Research Foundation, Athínai, Attica, Greece

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Publications (511)1952.89 Total impact

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    ABSTRACT: Background: Calcific aortic valve stenosis (CAVS) is seen in a large proportion of individuals over 60 years. It is an active process, influenced by lipid accumulation, mechanical stress, inflammation, and abnormal extracellular matrix turnover. Various biomarkers (BMs) are studied, as regards mechanisms, diagnosis and prognosis. Methods: In the calcified valves calcium deposition, elastin fragmentation and disorganization of cellular matrix were assessed, together with expression of OPN, OPG, osteocalcin (OCN) and RL2. We prospectively studied the following serum BMs in 60 patients with CAVS and compared them to 20 healthy controls, free from any cardiac disease: Matrix metalloproteinases (MMP) 2 and 9 and tissue inhibitor of metalloproteinase 1 (TIMP1), which regulate collagen turnover, inflammatory factors, i.e. tumor necrosis factor a (TNFa), interleukin 2 (IL2), transforming growth factor β1 (TGF-β1) which regulates fibrosis, fetuin-A (fet-A), osteopontin (OPN), osteoprotegerin (OPG), sclerostin (SOST), and relaxin-2 (RL2) which positively or negatively regulate calcification. Monocyte chemoattractant protein 1 (MCP-1) which regulates migration and infiltration of monocytes/macrophages was also studied as well as malondialdehyde (MDA) an oxidative marker. Results: Extent of tissue valve calcification (Alizarin Red stain) was negatively correlated with tissue elastin, and RL2, and positively correlated with tissue OCN and serum TIMP1 and MCP-1 and negatively with MMP9. Tissue OCN was positively correlated with OPN and negatively with the elastin. Tissue OPN was negatively correlated with elastin and OPG. Tissue OPN OPG and RL2 were not correlated with serum levels In the serum we found in patients statistically lower TIMP1, fet-A and RL2 levels, while all other BMs were higher compared to the healthy group. Positive correlations between SOST and IL2, OPG and MDA but negative with TNFa and OPN were found; also MMP9 was negatively correlated with TNFa and MCP-1 was negatively correlated with TIMP1. Conclusion: We found that many BMs expressing calcification, collagen breakdown, or formation, and inflammation are increased in the valve tissue and in the serum of patients with CAVS as compared with healthy group. Our findings may give new insights towards diagnosis but also therapy. Thus antisclerostin, and antiflammatory agents could be tried for preventing aortic calcification progression.
    Full-text · Article · Sep 2015
  • Despina Sanoudou · Dimitris Tousoulis · Dennis V. Cokkinos
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    ABSTRACT: MicroRNAs were discovered approximately two decades ago, and have dramatically changed our understanding of physiological and pathological functions since. These small (≈22 nucleotides in length) non-coding RNAs, have the ability to silence the expression of various genes either through mRNA degradation or prevention of mRNA translation to proteins. They have been associated with cardiac development, structure and function but also with every aspect of cardiovascular disease. They can be detected in organs but also in the circulation. A constantly expanding number is shown to have diagnostic or prognostic value. Finally, they are already serving as novel therapeutic targets and/or tools, through a broad range of approaches.
    No preview · Article · Jan 2015

  • No preview · Article · Sep 2014 · Archives of Hellenic Medicine

  • No preview · Article · May 2014 · Resuscitation
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    ABSTRACT: Objective. To evaluate the association of BNP and CRP with the development of postoperative atrial fibrillation following coronary artery bypass grafting surgery. Methods. The series consists of 125 patients (aged 65 ± 9 years), who underwent isolated CABG-surgery. BNP and CRP levels were measured pre- and 24 hours postoperatively and their correlation to the development of postoperative AF was analyzed. Results. Forty-four patients (35%) developed AF postoperatively. They were significantly older (68 ± 8 versus 63 ± 9, P = 0.01) and predominantly nonsmokers (18% versus 46%, P = 0.004), compared to the non-AF cases. In addition they showed significant higher preoperative mean BNP levels of 629 versus 373 pg/mL (P = 0.019). Postoperative BNP levels were significantly higher in both groups (AF-group: 1032 pg/mL versus non-AF group: 705 pg/mL; P < 0.001), while there was a trend of more increased postoperative levels in AF-cases (P = 0.065). AF-episodes appeared significantly more frequent in the two highest quartiles of BNP levels with 44% (P = 0.035). On the contrary pre- and postoperative CRP levels were not associated with AF. Multivariable analysis revealed only increased preoperative BNP levels as independent predictor for postoperative AF (P = 0.036). Conclusion. Elevated preoperative BNP serum levels are associated with the development of post-CABG AF, while CRP does not seem to be influential.
    Full-text · Article · Dec 2013
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    ABSTRACT: Early statin treatment has beneficial effects on the prognosis after acute coronary syndromes. We investigated the impact of prior statin treatment on the outcome of patients without a prior history of coronary artery disease (CAD) who presented with ST-elevation myocardial infarction (STEMI) and were treated with thrombolysis. The study enrolled 1032 consecutive patients who satisfied the above criteria. They were categorized into two groups, based on their prior statin treatment for at least 3 months before admission: the statinpretreatment group (n=124) and the statin-naïve group (n=908). All patients received high-dose statins during hospitalization and were prescribed statins after discharge. The primary outcome was the incidence of successful thrombolysis, as expressed by the percentage of patients with 50% ST-segment resolution and complete retrosternal pain resolution at 90 minutes. Secondary outcomes included reduction in highsensitivity C-reactive protein (hs-CRP) and CK-MB levels, and in-hospital, short- and long-term cardiovascular mortality. ST-segment resolution 50% was observed in 63.7% of the statin-pretreatment group and in 49.1% of statin-naïve patients (p<0.01). Statin pretreatment was associated with lower hs-CRP and peak CK-MB levels (p<0.001). The statin-pretreatment group had lower 30-day mortality (5.6% vs. 12.3%, p<0.05), whereas no significant differences were detected in in-hospital or 3-year mortality. Prior statin treatment in patients without a history of CAD who present with STEMI is associated with successful thrombolysis, decreased systemic inflammation, a lesser degree of myocardial damage, and a possible reduction in short-term mortality.
    No preview · Article · Nov 2013
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    ABSTRACT: Introduction: Early statin treatment has beneficial effects on the prognosis after acute coronary syndromes. We investigated the impact of prior statin treatment on the outcome of patients without a prior history of coronary artery disease (CAD) who presented with ST-elevation myocardial infarction (STEMI) and were treated with thrombolysis. Methods: The study enrolled 1032 consecutive patients who satisfied the above criteria. They were categorized into two groups, based on their prior statin treatment for at least 3 months before admission: the statinpretreatment group (n=124) and the statin-naïve group (n=908). All patients received high-dose statins during hospitalization and were prescribed statins after discharge. The primary outcome was the incidence of successful thrombolysis, as expressed by the percentage of patients with ≥50% ST-segment resolution and complete retrosternal pain resolution at 90 minutes. Secondary outcomes included reduction in highsensitivity C-reactive protein (hs-CRP) and CK-MB levels, and in-hospital, short- and long-term cardiovascular mortality. Results: ST-segment resolution ≥50% was observed in 63.7% of the statin-pretreatment group and in 49.1% of statin-naïve patients (p<0.01). Statin pretreatment was associated with lower hs-CRP and peak CK-MB levels (p<0.001). The statin-pretreatment group had lower 30-day mortality (5.6% vs. 12.3%, p<0.05), whereas no significant differences were detected in in-hospital or 3-year mortality. Conclusions: Prior statin treatment in patients without a history of CAD who present with STEMI is associated with successful thrombolysis, decreased systemic inflammation, a lesser degree of myocardial damage, and a possible reduction in short-term mortality.
    Full-text · Article · Nov 2013 · Hellenic journal of cardiology: HJC = Hellēnikē kardiologikē epitheōrēsē
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    ABSTRACT: OBJECTIVES The present study investigated the potential of the failing myocardium of patients with ventricular assist devices (VAD) to respond to physiological growth stimuli, such as exercise, by activating growth signalling pathways. This may be of therapeutic relevance in identifying novel pharmacological targets for therapies that could facilitate recovery after VAD implantation.METHODS Twenty-two patients bridged to heart transplantation (HTx) with VAD were included in the study. A group of patients underwent moderate intensity aerobic exercise (GT), while another group of patients did not receive exercise training (CG). Thyroid hormone receptor alpha1 (TRα1) protein and total (t) and phosphorylated (p) protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) kinase signalling were measured in myocardial tissue by western blotting at pre-VAD and pre-HTx period. In addition, Thyroid hormone (TH) levels were measured in plasma.RESULTSPeak oxygen consumption (VO2) at pre-HTx period was higher in patients subjected to training protocol [18.0 (0.8) for GT when compared with 13.7 (0.7) for CG group, P = 0.002]. N-terminal-prohormone of brain natriuretic peptide (NT-proBNP) levels were 1068 (148) for CG vs 626 (115) for GT group, P = 0.035. A switch towards up-regulation of physiological growth signalling was observed: the ratio of p-Akt/t-Akt was 2-fold higher in GT vs CG, P < 0.05 while p-JNK/t-JNK was 2.5-fold lower (P < 0.05) in GT vs CG, in pre-HTx samples. This response was accompanied by a 2.0-fold increase in TRα1 expression in pre-HTx samples with concomitant increase in circulating T3 in GT vs CG, P < 0.05. No differences in peak VO2, NT-proBNP, T3, TRα1, p/t-AKT and p/t-JNK were found between groups in the pre-VAD period.CONCLUSIONS The unloaded failing myocardium responded to physical training by enhancing thyroid hormone signalling. This response was associated with an up-regulation of Akt and suppression of JNK activation.
    Preview · Article · Jul 2013 · Interactive Cardiovascular and Thoracic Surgery
  • Alkistis Kapelouzou · Dennis Cokkinos

    No preview · Article · Jul 2013 · Hellenic journal of cardiology: HJC = Hellēnikē kardiologikē epitheōrēsē
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    ABSTRACT: We evaluated nuclear factor kappa B {NFkB, rs28362491 [-94ins/delATTG (W/D)]} and angiotensin converting enzyme {ACE; rs1799752 [Ins(I)/Del(D)]} gene polymorphisms and their correlation with thyroid function in patients with heart failure (HF). Peak oxygen uptake (VO2) was evaluated (by Weber classification) during a symptom-limited cardiopulmonary exercise test in 194 patients. Thyroid-stimulating hormone, triiodothyronine (T3), thyroxine (T4), and free (F) T3 and FT4 were also measured. According to their cardiovascular (CV) capacity, patients were subdivided into four groups: group A included patients with peak VO2 >20 ml/kg/min, group B 16-20 ml/kg/min, group C 10-16 ml/kg/min, and group D 6-10 ml/kg/min. Patients were also genotyped for NFkB and ACE genetic variants. T3 was increased and FT3 was decreased for every raise in Weber's classification (p = 0.007 and p = 0.012, respectively). Del carriers had elevated FT3 levels compared with Ins carriers (p = 0.021). Patients with II genotype had elevated T4 levels compared with ID genotype (p = 0.044). Both T4 and FT4 were decreased in D allele carriers (p = 0.007 and p = 0.045, respectively). Thyroid hormones correlated with CV capacity. Associations between the NFkB and ACE gene polymorphisms and thyroid hormones levels were also observed. Further larger studies are required to clarify genes contribution in HF.
    No preview · Article · Mar 2013 · Endocrine
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    Preview · Article · Mar 2013 · Journal of the American College of Cardiology
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    Full-text · Article · Jan 2013 · Archives of Cardiovascular Diseases Supplements
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    ABSTRACT: Background: Arterial hypertension (AH), metabolic syndrome (MS) and diabetes mellitus type 2 (DM2) are interrelated metabolic disorders. The aim of our study was to evaluate how the coexistence of MS or DM2 with AH influences arterial reactivity during cold pressor test (CPT). Methods: We studied 102 patients, 32 with AH (Group A), 38 with AH and MS (Group B) and 32 with AH and DM2 (Group C). All patients underwent full laboratory evaluation and measurement of systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) and carotid-femoral pulse wave velocity (PWVc-f) before and during CPT. Results: During CPT PWVc-f, SBP, DBP and HR were increased significantly in all studied groups, but the change of PWVc-f and HR during CPT was significantly greater in group A compared to group C. On the contrary, the coexistence of MS or DM2 with AH does not alter the response of BP to CPT. Conclusion: The increase of CV risk resulting from the coexistence of MS or DM2 with AH, is best expressed by PWVc-f, while the change of the former and HR during CPT possibly reflects dysfunction of the autonomic nervous system.
    No preview · Article · Dec 2012
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    ABSTRACT: It has been reported that increased levels of C-reactive protein are related to adverse long-term prognosis in the setting of ST-segment elevation acute myocardial infarction (MI). In previous studies, the timing of C-reactive protein determination has varied widely. In the present study, serial high-sensitivity C-reactive protein (hsCRP) measurements were performed to investigate if any of the measurements is superior regarding long-term prognosis. A total of 861 consecutive patients admitted for ST-segment elevation MI and treated with intravenous thrombolysis within the first 6 hours from the index pain were included. HsCRP levels were determined at presentation and at 24, 48, and 72 hours. The median follow-up time was 3.5 years. New nonfatal MI and cardiac death were the study end points. By the end of follow-up, cardiac death was observed in 22.4% and nonfatal MI in 16.1% of the patients. HsCRP levels were found to be increasing during the first 72 hours. Multivariate Cox regression analysis demonstrated that hsCRP levels at presentation were an independent predictor of the 2 end points (relative risk [RR] 2.8, p = 0.002, and RR 2.1, p = 0.03, for MI and cardiac death, respectively), while hsCRP levels at 24 hours did not yield statistically significant results (RR 1.4, p = 0.40, and RR 1.1, p = 0.80, for MI and cardiac death, respectively). The corresponding RRs at 48 hours were 1.2 (p = 0.5) for MI and 3.2 (p = 0.007) for cardiac death and at 72 hours were 1.6 (p = 0.30) for MI and 3.9 (p <0.001) for cardiac death. In conclusion, hsCRP levels at presentation represent an independent predictor for fatal and nonfatal events during long-term follow-up. HsCRP levels at 48 and 72 hours, which are close to peak hsCRP levels, independently predict only cardiac death.
    No preview · Article · Oct 2012 · The American journal of cardiology

  • No preview · Article · Oct 2012 · Resuscitation
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    ABSTRACT: The aim of this study was to estimate the total annual cost of patients with or at risk for atherothrombosis in Greece. A multicentre, cost-of-illness study was conducted between January 2007 and December 2009. In the study, 800 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease (PAD) or multiple cardiovascular risk factors (MRF) were recruited. Direct and indirect cost data were assessed at patients' enrolment in the study, and at 6 and 12 months of follow-up. The annual total cost was 6,017/patient. This cost ranged from 10,098/patient with PAD to 1,813/patient with MRF. The annual direct health-care cost was 5,056/patient. This cost escalates from 1,623/patient with MRF to 8,697/patient with PAD. The total annual expenditures related to atherothrombosis, in Greece, were estimated to be 7.5 billion at the national level. The findings of the current study indicate the high economic burden of atherothrombosis in Greece.
    No preview · Article · Jul 2012 · The European Journal of Health Economics
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    Constantinos Pantos · Iordanis Mourouzis · Dennis V Cokkinos
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    ABSTRACT: Nature's models of repair and (or) regeneration provide substantial evidence that a natural healing process may exist in the heart. The potential for repair and (or) regeneration has been evolutionarily conserved in mammals, and seems to be restricted to the early developmental stages. This window of regeneration is reactivated during the disease state in which fetal gene reprogramming occurs in response to stress. Analogies exist between the damaged and developing heart, indicating that a regulatory network that drives embryonic heart development may control aspects of heart repair and (or) regeneration. In this context, thyroid hormone (TH), which is a critical regulator of the maturation of the myocardium, appears to have a reparative role later in adult life. Changes in TH - thyroid hormone receptor (TR) homeostasis govern the return of the injured myocardium to the fetal phenotype. Accordingly, TH can induce cardiac repair and (or) regeneration by reactivating developmental gene programming. As a proof of concept in humans, TH is found to be an independent determinant of functional recovery and mortality after myocardial infarction. The potential of TH to regenerate and (or) repair the ischemic myocardium is now awaited to be tested in clinical trials.
    Full-text · Article · Jul 2012 · Canadian Journal of Physiology and Pharmacology
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    ABSTRACT: Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients.
    Full-text · Article · Jun 2012 · Expert Review of Cardiovascular Therapy
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    ABSTRACT: Background: We hypothesised that combined aerobic training (AT) with resistance training (RT) and inspiratory muscle training (IMT) could result in additional benefits over AT alone in patients with chronic heart failure (CHF). Methods: Twenty-seven patients, age 58 ± 9 years, NYHA II/III and LVEF 29 ± 7% were randomly assigned to a 12-week AT (n=14) or a combined AT/RT/IMT (ARIS) (n=13) exercise program. AT consisted of bike exercise at 70-80% of max heart rate. ARIS training consisted of AT with RT of the quadriceps at 50% of 1 repetition maximum (1RM) and upper limb exercises using dumbbells of 1-2 kg as well as IMT at 60% of sustained maximal inspiratory pressure (SPI(max)). At baseline and after intervention patients underwent cardiopulmonary exercise testing, echocardiography, evaluation of dyspnea, muscle function and quality of life (QoL) scores. Results: The ARIS program as compared to AT alone, resulted in additional improvement in quadriceps muscle strength (1RM, p=0.005) and endurance (50%1 RM × number of max repetitions, p=0.01), SPI(max) (p<0.001), exercise time (p=0.01), circulatory power (peak oxygen consumption × peak systolic blood pressure, p=0.05), dyspnea (p=0.03) and QoL (p=0.03). Conclusions: ARIS training was safe and resulted in incremental benefits in both peripheral and respiratory muscle weakness, cardiopulmonary function and QoL compared to that of AT. The present findings may add a new prospective to cardiac rehabilitation programs of heart failure patients whilst the clinical significance of these outcomes need to be addressed in larger randomised studies.
    No preview · Article · May 2012 · International journal of cardiology
  • Dennis V Cokkinos · Christos Belogianneas
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    ABSTRACT: No abstract available.
    No preview · Article · Apr 2012 · Cardiology

Publication Stats

8k Citations
1,952.89 Total Impact Points

Institutions

  • 2011-2015
    • Biomedical Research Foundation
      • • Centre of Experimental Surgery
      • • Division of Nuclear Medicine
      Athínai, Attica, Greece
  • 2009-2013
    • Academy of Athens
      Athínai, Attica, Greece
  • 1995-2013
    • Onassis Cardiac Surgery Center
      • Department of Cardiology
      Kallithea, Attica, Greece
  • 2008
    • National Cardiology Hospital, Bulgaria
      Ulpia Serdica, Sofia-Capital, Bulgaria
  • 2001-2008
    • National and Kapodistrian University of Athens
      • • Department of Medicine
      • • Division of Pharmacology
      Athínai, Attica, Greece
  • 2000-2008
    • Hippokration General Hospital, Athens
      Athínai, Attica, Greece
  • 2007
    • Fourth Military Medical University
      Xi’an, Liaoning, China
  • 2003-2006
    • Harokopion University of Athens
      Athínai, Attica, Greece
  • 1999-2006
    • University of Patras
      • School of Medicine
      Rhion, West Greece, Greece
  • 1998
    • University of Utah
      • School of Medicine
      Salt Lake City, Utah, United States
  • 1994
    • Πανεπιστημιακό Γενικό Νοσοκομείο Πατρών
      Pátra, West Greece, Greece
  • 1992-1994
    • Tzaneio General Hospital of Piraeus
      Le Pirée, Attica, Greece