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Dimitrios A Stakos

Publications and source records attributed to Dimitrios A Stakos.

10 recordsLinked to original sources
PubMed2006

Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a factor analysis approach.

BACKGROUND: Numerous inflammatory mediators such as C-reactive protein (CRP), fibrinogen, interleukin-18 (IL-18), and inter-cellular adhesion molecule-1 (ICAM-1) have been proposed for risk stratification in acute coronary syndrome (ACS) patients. However, interactions between these markers have made it difficult to assess their true role in risk prediction. Factor analysis is a multivariable statistical technique that reduces a large number of intercorrelated variables to a smaller set of independent clusters, underlining physiological relationships. The aim of this study was to investigate, using factor analysis, a clustering of pro-inflammatory markers, anti-inflammatory cytokines such as interleukin-10 (IL-10) and HDL cholesterol, and to determine their role in prediction of risk of recurrent coronary events in ACS patients. METHODS: We assessed 320 consecutive patients (236 men; 67 years; IQ 58-74 years) admitted with ACS. The composite of cardiac death and re-hospitalization with non-fatal myocardial infarction, or unstable angina, was the pre-specified study end-point. Serum CRP, fibrinogen, HDL cholesterol, IL-10, IL-18 and ICAM-1 levels were measured at study entry. We assessed independent predictors of the combined end-point during a 1-year follow-up using multiple logistic regression analysis. RESULTS: Factor analysis identified three clusters which were arbitrarily interpreted as (1) a "systemic inflammation" cluster with positive loadings of CRP and fibrinogen, (2) a "local inflammation-endothelial dysfunction" cluster with positive loadings of IL-18 and ICAM-1 and (3) an "anti-inflammation" cluster comprising IL-10 and HDL cholesterol. Only the "anti-inflammation" cluster was a significant predictor (OR 0.66, 95% CI: 0.49-0.89) of adverse cardiac events during a 1-year follow-up and remained significant (OR 0.65, 95% CI: 0.48-0.88) in a multivariate model that included all three factors. CONCLUSIONS: Although inflammatory markers such as CRP predict future cardiovascular events in ACS patients, when all inflammatory mediators are taken into account in a prospective analysis of risk, markers reflecting anti-inflammatory mechanisms are better prognostic markers.

Acute Disease↗
PubMed2006

Interleukin-18/interleukin-10 ratio is an independent predictor of recurrent coronary events during a 1-year follow-up in patients with acute coronary syndrome.

BACKGROUND: The pro-inflammatory cytokine IL-18 has been suggested to play a role in atherogenesis and atheromatous plaque rupture leading to the acute coronary syndrome (ACS). Conversely, the anti-inflammatory cytokine IL-10 seems to have an atheroprotective role. Patients with unstable coronary artery disease show an imbalance between serum levels of pro- and anti-inflammatory cytokines, and studies have shown that IL-18/IL-10 ratio is an independent predictor of adverse in-hospital events in patients with ACS. We assessed the long-term prognostic significance of admission interleukin-18 (IL-18)/interleukin-10 (IL-10) ratio for recurrent coronary events during a 1-year follow-up in patients presenting with an ACS. METHODS: We assessed independent predictors of the combined end-point using multiple logistic regression analysis, in 186 patients (138 men, 65+/-12 years) with ACS (75 STEMI, 65 NSTEMI and 46 unstable angina). The composite of cardiac death and re-hospitalization with non-fatal myocardial infarction, or unstable angina, was the pre-specified study end-point. Serum IL-10 and IL-18 levels were measured at study entry using commercially available ELISAs. RESULTS: During the 1-year follow-up, 48 (26%) patients had recurrent cardiac events and 138 (74%) were event-free. IL-18/IL-10 ratio predicted the occurrence of adverse cardiac events (OR 1.91, 95% CI 1.37-2.65, p<0.001), and was found to be an independent predictor among other established biochemical and clinical risk markers (OR 2.31, 95% CI 1.55-3.42, p<0.001). CONCLUSIONS: Serum IL-18/IL-10 ratio is an independent predictor of recurrent coronary events during long-term follow-up in patients presenting with ACS. Our study further supports the hypothesis that the balance between pro-inflammatory and anti-inflammatory cytokines may be an important determinant of patient outcome, suggesting a pathogenic role in plaque progression and instability.

Aged↗
PubMed2005

Comparison of levels of matrix metalloproteinase-2 and -3 in patients with ischemic cardiomyopathy versus nonischemic cardiomyopathy.

It has been reported that circulating matrix metalloproteinase (MMP) levels are upregulated in patients with chronic heart failure. However, experimental studies indicate that differences in the profiles of MMPs and tissue inhibitors of metalloproteinase (TIMPs) may exist in ischemic compared with nonischemic cardiomyopathy. This study examined whether circulating levels of MMPs and TIMP-1 are related to the pathogenesis of heart failure. Circulating levels of MMP-2, MMP-3, and TIMP-1 were assessed in 52 patients with compensated end-stage chronic heart failure, including 26 patients (mean 64 +/- 7 years; 10 men) with ischemic cardiomyopathy (IC) and 26 (mean age 66 +/- 6 years; 14 men) with idiopathic dilated cardiomyopathy (IDC). Serum MMP-2 (p <0.001) and MMP-3 (p <0.001) levels were higher in patients with IDC than in those with IC. Serum TIMP-1 levels were lower in patients with IDC (p = 0.011) than in those with IC. This study shows that in patients with compensated end-stage chronic heart failure, circulating levels of MMP-2, MMP-3, and TIMP-1 are associated with the pathogenesis of heart failure.

Aged↗
PubMed2005

Alteplase treatment affects circulating matrix metalloproteinase concentrations in patients with ST segment elevation acute myocardial infarction.

INTRODUCTION: Matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques. Acute coronary syndromes may be precipitated by MMPs through degradation of the fibrous cap and subsequent plaque disruption. Serine proteases such as plasmin activate MMPs and may contribute to plaque events. Thrombolysis with recombinant tissue plasminogen activator (rtPA) is widely used for treatment of acute ST segment elevation myocardial infarction (STEMI). In the present study we assessed whether thrombolytic therapy with rtPA in patients with STEMI influences serum levels of MMP-2 and MMP-9. METHODS: We recruited 108 patients (92 men, mean age 64 +/- 12 years) with STEMI, of whom 84 (78%) received thrombolytic treatment with rtPA and 24 (22%) did not. MMP-2 and MMP-9 levels were assessed at hospital admission (baseline), and at 24 and 72 h after admission, using a commercially available ELISA. RESULTS: Overall, MMP-9 levels were higher in the thrombolysis group compared to patients without thrombolysis (p < 0.001). Thrombolysis treatment significantly affected the change in MMP-9 levels during the 72-h study period (p < 0.001). CONCLUSIONS: The present study showed that thrombolysis could affect circulating levels of MMP-9 in STEMI patients. Whether this effect may lead to plaque instability deserves further investigation.

Aged↗
PubMed2005

N-terminal pro-B-type natriuretic peptide and matrix metalloproteinases in early and late left ventricular remodeling after acute myocardial infarction.

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a predictor of left ventricular remodeling. Matrix metalloproteinases (MMPs) contribute to collagen breakdown that is associated with ventricular remodeling after acute myocardial infarction (AMI). We assessed the association between circulating levels of NT-pro-BNP, MMP-2, and MMP-9 and their inhibitor (tissue inhibitor of metalloproteinase-1) early (24 and 72 hours) and late (7 and 30 days) after AMI in 108 patients who had ST-elevation AMI (90 men; mean age 60 years). Serum MMP-2 levels measured 24 and 72 hours after AMI were inversely associated with NT-pro-BNP levels, whereas MMP-9 serum levels were positively related. During late-stage remodeling after AMI, circulating concentrations of tissue inhibitor of metalloproteinase-1 were independently associated with NT-pro-BNP levels 7 and 30 days after AMI. This study shows that, in patients who have ST-elevation AMI, circulating levels of NT-pro-BNP are associated with MMPs in a species-specific and time-dependent manner.

Acute Disease↗
PubMed2005

Interleukin-18: interleukin-10 ratio and in-hospital adverse events in patients with acute coronary syndrome.

INTRODUCTION: Inflammatory mechanisms contribute to the development of acute coronary syndromes (ACS), and it has been suggested that an imbalance between pro- and anti-inflammatory responses may be an important determinant of recurrent cardiac events in this setting. Both increased serum levels of interleukin (IL)-18 and reduced concentrations of IL-10 have been shown to have prognostic significance in ACS. We sought to assess whether the ratio of serum IL-18/IL-10 levels has higher positive predictive value than the individual measurement of IL-10 and IL-18 in patients admitted to hospital with ACS. METHODS: We recruited 107 consecutive patients (79 men, mean age 65+/-12 years) with ACS (41 STEMI, 39 NSTEMI and 27 UA). The composite of cardiac death, recurrence of unstable angina, re-infarction, life threatening arrhythmias, and urgent revascularization during hospitalization was the pre-specified study end-point. We assessed independent predictors of the combined end-point using multiple logistic regression analysis. Serum IL-10 and IL-18 levels were measured at study entry using commercially available ELISAs. RESULTS: During hospitalization 44 patients (41%) had events and 63 (59%) had no events. Significantly higher odd ratios were found for IL-18/IL-10 ratio (1.74 95% CI 1.09-2.78) compared to individual IL-18 (1.46 95% CI 0.93-2.27) and 1/IL-10 (1.63 95% CI 1.04-2.56) measurements. CONCLUSION: Serum IL-18/IL-10 ratio is an independent predictor of in-hospital adverse events in patients with ACS. Our study strongly endorses the notion that an imbalance between pro and anti-inflammatory forces predisposes to plaque disruption and recurrent cardiovascular events.

Acute Disease↗
PubMed2005

Levosimendan use reduces matrix metalloproteinase-2 in patients with decompensated heart failure.

BACKGROUND: Extracellular matrix metabolism (ECM) has an important role in left ventricular (LV) remodeling in chronic heart failure (CHF). Matrix metalloproteinases (MMPs) are involved in the regulation of extracellular matrix (ECM) metabolism. We investigated the effect of levosimendan, a novel calcium sensitizer, on serum levels of MMP-2. METHODS: Our study population consisted of 60 consecutive patients with advanced heart failure who were admitted to hospital with an acute decompensation of their CHF. Patients were randomized to levosimendan (n = 30; 18 men, aged 65 +/- 3 years) or placebo (n = 30; 15 men, aged 67 +/- 4 years). Serum MMP-2 levels were assessed before and after treatment with levosimendan or placebo, using a commercially available ELISA. RESULTS: Serum levels of MMP-2 were reduced from 427 ng/ml 95%CI 372-484 to 371 ng/ml 95%CI 329-413 in the levosimendan treated group and from 433 ng/ml 95%CI 422-444 to 425 ng/ml 95%CI 414-436 in the placebo group. Repeated measurements ANOVA showed that treatment with levosimendan significantly affected levels of MMP-2 (p = 0.019). CONCLUSIONS: The present study showed that levosimendan may beneficially affect ECM remodeling in patients with acutely decompensated CHF. Whether these effects translate into added clinical benefits, as suggested by an improved ejection fraction in the levosimendan group, deserves further investigation.

Aged↗
PubMed2003

Long-term cardiovascular effects of insulin sensitizer troglitazone on non-diabetic individuals with insulin resistance: double blind, prospective randomized study.

OBJECTIVES: The study was undertaken to assess the long-term cardiovascular effects of troglitazone on non-diabetic individuals with insulin resistance. BACKGROUND: It has been suggested that treatment with troglitazone or similar insulin-sensitizing agents may prevent cardiovascular complications in non-diabetic individuals with insulin resistance. However, the long-term cardiovascular effects of these agents on non-diabetic individuals remain to be defined. METHODS: A total of 137 African-American offspring of type 2 diabetic parents, with normal glucose tolerance and insulin resistance, were randomly divided to receive troglitazone 200 mg/day (n = 40), or placebo (n = 97) for 24 months. Brachial artery blood pressure (sphygmomanometry); aortic pulse wave velocity (carotid to femoral artery, Doppler), left ventricular diameters and mass (echocardiography); ascending and abdominal aortic distensibility (echocardiography, blood pressure); and metabolic and lipid profile were assessed at baseline, 12, and 24 months after randomization (delta 12, delta 24 respectively). RESULTS: The pulse wave velocity increased significantly in the troglitazone group compared to placebo group (p < 0.05). Changes from baseline in the troglitazone group were significant (delta 12 = 1.09 +/- 0.36 m/sec, delta 24 = 2.08 +/- 0.45 m/sec, ANOVA p < 0.001), while pulse wave velocity remained unchanged in the placebo group. This increase in pulse wave velocity is consistent with a decrease in the elastic properties of the aorta. CONCLUSIONS: Long-term administration of troglitazone to non-diabetic African-Americans with insulin resistance was associated with a decrease in the elastic properties of the aorta. Long-term therapy with troglitazone or similar agents for the prevention of cardiovascular complications in non-diabetic individuals with insulin resistance has to be critically evaluated.

Adult↗
PubMedDate not supplied

Cardiovascular effects of type 1 diabetes mellitus in children.

Previous studies have shown that type 1 diabetes mellitus (DM) is associated with cardiovascular abnormalities. Early detection and treatment of these abnormalities may help to prevent the natural progression of the disease. The present study was undertaken to define early cardiovascular abnormalities in children with type 1 DM. Simultaneous evaluation of multiple cardiovascular parameters was performed in 14 children with type 1 DM and 14 age-and gender-matched normal subjects. Measurements of carotid artery intima-media thickness (cIMT, echocardiography), carotid and aortic (ascending and abdominal) distensibility (echocardiography, brachial artery blood pressure), aortic pulse wave velocity (carotid to femoral artery, Doppler), and left ventricular dimensions, mass, and function (echocardiography) were performed. Diabetic children demonstrated a greater cIMT (0.36 +/- 0.04 mm vs 0.31 +/- 0.03 mm, p = 0.002) and decreased carotid artery distensibility (4.4 +/- 1.6 cm(2) . dynes(-1) . 10(-6) vs 6.0 +/- 1.9 cm(2) . dynes(-1) .10(-6), p < 0.01) compared to control. Aortic pulse wave velocity was increased in DM (6.70 +/- 0.39 vs 6.30 +/- 0.31, p = 0.02) compared to control. Left ventricular diameters, mass, and systolic and diastolic function did not differ between the 2 groups. Simultaneous assessment of multiple cardiovascular parameters in children with type 1 DM revealed impaired carotid artery structure and function, and decreased elastic properties of the aorta, before demonstrable changes in left ventricular structure and function could be detected.

Adolescent↗