PubMed Health⌕ Search

Biomedical subjects

Juan Carlos Kaski

Publications and source records attributed to Juan Carlos Kaski.

At least 19 recordsLinked to original sources
PubMed2006

Role of trimetazidine in management of ischemic cardiomyopathy.

Despite treatment with conventional agents, a high proportion of patients with ischemic cardiomyopathy continue to have symptoms. Moreover, a substantial proportion shows progressive contractile dysfunction leading to left ventricular (LV) enlargement and heart failure. Therefore, a need exists for new treatments for ischemic cardiomyopathy that tackle mechanisms other than those already addressed by conventional agents. Emerging evidence suggests that in patients with ischemic cardiomyopathy, LV dysfunction develops as a result of alterations in substrate metabolism, which contribute to contractile dysfunction and the progression of LV remodeling. Trimetazidine, a novel pharmacologic agent that acts on myocardial metabolic pathways, appears to protect the heart from the deleterious effects of ischemia, and it has been shown to enhance LV contractility in patients with stunned or hibernating myocardium. This article reviews recent clinical trials that have assessed the therapeutic role of trimetazidine in patients with ischemic cardiomyopathy. Trimetazidine has been shown to improve symptoms and LV ejection fraction and to have a beneficial effect on the inflammatory profile and endothelial function in these patients. These results suggest that trimetazidine is a useful adjunct to our current armamentarium for the treatment of patients with ischemic cardiomyopathy.

Humans↗
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↗
PubMed2006

Health-related quality of life outcome after on-pump versus off-pump coronary artery bypass graft surgery: a prospective randomized study.

BACKGROUND: The clinical benefit of off-pump coronary artery bypass graft surgery over on-pump surgery is a matter of controversy. The aim of this study was to assess quality of life in patients after on-pump and off-pump coronary artery bypass graft surgery, and compare the data with an age-matched and sex-matched standard population. METHODS: Two hundred twelve patients admitted for elective coronary artery bypass graft surgery were randomized to on-pump (n = 104) and off-pump (n = 108) surgery. Quality-of-life assessments were made 6 and 18 months postoperatively using the standard form of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36, version 2). The questionnaire yields eight subscores of functional health and well being. The eight SF-36 raw scores were standardized using means and standard deviations from a random sample of adults in Great Britain. Mean on-pump and off-pump SF-36 scores were compared using two-sample Student's t tests. RESULTS: Questionnaires were completed for 72% (154 of 212) and 46% (98 of 212) of patients at the 6- and 18-month follow-up, respectively. There were no significant differences between on-pump and off-pump patients in any of the eight subscales at both stages. Fifty-six (72%) on-pump and 59 (75%) off-pump patients reported a better health status compared with the 6-month period before surgery (not significant). CONCLUSIONS: Patients who have undergone off-pump coronary artery bypass graft surgery have a similar quality of life to on-pump patients at 6 and 18 months after surgery. For both groups, the majority of patients reported improved health after coronary artery bypass graft surgery compared with their preoperative status.

Aged↗
PubMed2006

Peroxisome proliferator-activated receptor-gamma agonists for management and prevention of vascular disease in patients with and without diabetes mellitus.

Inflammation is known to have a pathogenic role in atherosclerosis and the genesis of acute coronary syndromes. The peroxisome proliferator-activated receptor (PPAR)-gamma, which is expressed in many constituent cells of atheromatous plaques, inhibits the activation of several proinflammatory genes responsible for atheromatous plaque development and maturation. Agonists of this receptor, such as rosiglitazone and pioglitazone, are currently available for the treatment of type 2 diabetes mellitus, and several lines of evidence have shown that these drugs have antiatherogenic effects. Insulin resistance is associated with inflammation and has a key role in atherogenesis. The antiatherogenic and insulin sensitizing effects of the thiazolidinediones in patients with type 2 diabetes mellitus may be associated with this action. However, in recent years there has been growing evidence that the antiatherogenic effects of PPAR-gamma agonists are not confined to patients with diabetes mellitus. PPAR-gamma agonists have been shown to downregulate the expression of endothelial activation markers, reduce circulating platelet activity, improve flow-mediated dilatation and attenuate atheromatous plaque progression in patients without diabetes mellitus. These effects of PPAR-gamma agonists appear to result from both insulin sensitization and a direct modulation of transcriptional activity in the vessel wall. This review summarizes the current understanding of the role of PPAR-gamma agonists in atherogenesis and discusses their potential role in the treatment of coronary artery disease in patients with type 2 diabetes mellitus and in nondiabetic patients.

Atherosclerosis↗
PubMed2006

[Inflammation, atherosclerosis and cardiovascular disease risk: PAPP-A, Lp-PLA2 and cystatin C. New insights or redundant information?].

It is well-known that inflammation plays a role in atherogenesis, atherosclerotic plaque progression, and acute coronary syndrome. Inflammatory cells, and cytokines and other biomolecules are implicated in these processes, and have, therefore, been investigated as potential markers of atherosclerotic plaque progression and cardiovascular disease risk. The best characterized and most widely studied is C-reactive protein. However, its role in the clinical setting is still debated. Emerging novel biomarkers that may provide information complementary to that derived from C-reactive protein include pregnancy-associated plasma protein A, lipoprotein-associated phospholipase A2, and cystatin C. This article focuses on the potential value of these three new markers in patients with coronary heart disease, and their use as markers of disease risk in apparently healthy individuals.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Relation of circulating C-reactive protein to progression of aortic valve stenosis.

C-reactive protein (CRP) is a marker of inflammation and predicts outcome in apparently healthy subjects and patients with coronary artery disease. Systemic inflammation is present in patients with aortic valve stenosis (AS). The aim of this prospective study was to assess whether CRP levels predict the progression of AS severity. Blood samples for high-sensitivity CRP measurements and echocardiographic data were obtained in 43 patients (70% men; mean age 73 +/- 8 years) with asymptomatic degenerative AS at study entry. On the basis of repeat echocardiographic assessment at 6 months, patients were grouped as (1) slow progressors (a decrease in aortic valve area [AVA] <0.05 cm2 and/or an increase in aortic peak velocity <0.15 m/s) and (2) rapid progressors (a decrease in AVA > or =0.05 cm2 and/or an increase in aortic peak velocity > or =0.15 m/s). Plasma CRP levels were significantly higher in rapid progressors than slow progressors (median 5.1 [range 2.3 to 11.3] vs 2.1 [range 1.0 to 3.1] mg/L, p = 0.007). In multivariate analysis, CRP levels >3 mg/L were independently associated with rapid AS progression (odds ratio 9.1, 95% confidence interval 2.2 to 37.3). In conclusion, CRP levels are higher in patients with degenerative AS who show rapid valve disease progression. These findings suggest that inflammation may have a pathogenic role in degenerative AS.

Aged↗
PubMed2005

Relation of nocturnal melatonin levels to C-reactive protein concentration in patients with ST-segment elevation myocardial infarction.

C-reactive protein, a marker of inflammation, is increasingly measured to stratify risk for coronary artery disease and guide clinical management. Likewise, a relation has been suggested between decreased nocturnal melatonin levels and coronary artery disease. However, little is known about the association between melatonin and C-reactive protein in patients with ischemic heart disease.

C-Reactive Protein↗
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

Relationship among pregnancy associated plasma protein-A levels, clinical characteristics, and coronary artery disease extent in patients with chronic stable angina pectoris.

AIMS: To assess, in chronic stable angina (CSA) patients, the relationship among clinical characteristics and cardiovascular risk factors, extent of coronary artery disease (CAD), and pregnancy-associated plasma protein-A (PAPP-A) levels. METHODS AND RESULTS: We studied 643 CSA patients (63+/-10 years, 482 men) undergoing diagnostic coronary angiography; 97 with angiographically normal coronary arteries or <50% stenosis, 127 with single vessel disease (VD), and 419 with multi-VD. Patients' age, gender, cardiovascular risk factors, body mass index, history of previous myocardial infarction, angina class, left ventricular ejection fraction (LVEF), and treatment were assessed at study entry. PAPP-A levels (mIU/L) were higher in men than in women (6.2+/-2.4 vs. 5.2+/-1.8; P<0.001) and in hypertensive vs. normotensive patients (6.4+/-2.8 vs. 5.8+/-2.1; P=0.01). PAPP-A correlated directly with age (r=0.19, P<0.001) and inversely with LVEF (r=-0.11, P=0.01). Patients with multivessel disease (VD) had higher PAPP-A levels (6.45+/-2.58) than those with single-VD (5.49+/-1.54, P<0.001) or normal coronaries (4.62+/-1.17, P<0.001). Male gender, age, history of a previous MI, hypercholesterolaemia, and PAPP-A levels were independent predictors for the presence of CAD. CONCLUSION: In CSA patients PAPP-A levels correlate with age, male gender, hypertension, and CAD extent. In the present study, PAPP-A was an independent predictor for the presence and extent of CAD.

Angina Pectoris↗
PubMed2005

A comparative study of markers of inflammation for the assessment of cardiovascular risk in patients presenting to the emergency department with acute chest pain suggestive of acute coronary syndrome.

BACKGROUND: The role of inflammation in the pathogenesis of acute coronary syndrome (ACS) is established. Little is known however, regarding the use of inflammatory markers as predictors of future cardiovascular events in patients presenting to the emergency department (ED) with suspected ACS. HYPOTHESIS: To assess whether biomarkers that predict cardiovascular risk in apparently healthy individuals and coronary artery disease patients are useful predictors of future cardiovascular events in patients presenting to the ED with chest pain suggestive of ACS. METHODS: We compared the abilities of serum C-reactive protein (hs-CRP), albumin and leukocyte count to identify subjects with ACS and those who are at high risk of developing events during a 30-day follow-up. RESULTS: 144 patients (mean age 62+/-13 years, 45 female) presenting to the ED <3 h after the onset of symptoms suggestive of ACS were evaluated. Final hospital diagnoses were non-ischemic chest pain in 43 (30%) and ACS in 101 (70%) patients. Patients with ACS had significantly higher leukocyte count (p<0.0001) and hs-CRP levels (p<0.02) and lower albumin concentrations, compared to patients with NICP (p<0.0001). Lower albumin concentrations (p=0.03) and hs-CRP (p=0.049) were predictors of recurrent events at 30 days. On multivariate analysis, however, only leukocyte count was a predictor of ACS (OR 20.9; 95% CI: 3.7-19.5; p=0.01) and high hs-CRP levels were a predictor of clinical outcome (OR 2.8; 95% CI: 1.5-5.2; p=0.001). CONCLUSIONS: Leukocyte count is an independent predictor of ACS in patients presenting to the ED with chest pain suggestive of ACS and high hs-CRP levels are an independent predictor of clinical outcome in ACS patients.

Acute Disease↗
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

Brachial artery flow-mediated dilation and myocardial perfusion in patients with cardiac syndrome X.

We assessed the relation between systemic endothelial dysfunction abnormalities (brachial artery flow-mediated dilation) and myocardial perfusion abnormalities (single-photon emission computed tomography) in 41 patients who had cardiac syndrome X. Eighteen patients had normal perfusion scans and 18 had transient perfusion defects. Reverse redistribution was found in 5 patients. Patients who had myocardial perfusion defects had significantly lower flow-mediated dilation values (1.8%) than patients who had normal single-photon emission computed tomograms (3.9%, p = 0.012). Preserved systemic endothelial function appears to rule out the occurrence of transient single-photon emission computed tomographic defects in patients who have cardiac syndrome X.

Brachial Artery↗
PubMed2005

A protective contribution of the Q allele of the R353Q polymorphism of the Factor VII gene in individuals with chronic stable angina?

BACKGROUND: Factor VII polymorphisms have been suggested in some studies to show an association with some aspects of coronary disease, and there is a known association between FVII levels and polymorphic variants in the gene. The aim of the study was to assess whether Factor VII polymorphism R353Q is associated with the extent of coronary artery disease in patients with chronic stable angina. METHODS AND RESULTS: There is evidence that Factor VII polymorphisms are markers of susceptibility to coronary artery disease (CAD), but two studies have suggested that there is no association between the degree of vessel disease and these polymorphisms. One of these studies did not exclude patients with unstable angina or MI. We therefore set up a prospective cohort study to determine Factor VIIa, VIIc and VIIAg levels, genotype for R353Q, lipid status, smoking history and the degree of vessel disease, in patients attending the hospital for routine day case angiography over a 20 month period. From 519 cases, 400 had no previous MI or revascularisation, including 153 with zero vessel disease, and were successfully genotyped: 9 (2%) QQ, 78 (20%) RQ and 313 (78%) RR. Compared with RR subjects, heterozygotes were 2.7 years older (95% CI: 0.3, 5.0; p=0.027), but were not significantly different regarding gender, cholesterol, extent of vessel disease or smoking history. If those with vessel disease were considered, then the heterozygotes were 3.5 years older than the RR homozygotes (95% CI: 0.6-6.4, p=0.016). There was a significant association between all measures of Factor VII and the R353Q polymorphism, with the Q allele associating with lower levels. There was no significant association between the degree of vessel disease and genotype. CONCLUSIONS: The degree of vessel disease as seen at day case angiography is independent of polymorphism status, but there appears nonetheless to be a moderate protective effect of the Q allele against stable angina, in that angiographic investigation occurs a few years later for RQ heterozygotes than RR homozygotes. The effect may be mediated by reduced levels of Factor VII.

Alleles↗