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Biomedical subjects

Juan Carlos Kaski

Publications and source records attributed to Juan Carlos Kaski.

At least 19 recordsLinked to original sources
PubMed2004

Markers of inflammation and rapid coronary artery disease progression in patients with stable angina pectoris.

BACKGROUND: Both endothelial cell activation and macrophage activation play a significant role in atherogenesis and atheromatous plaque vulnerability and may determine rapid coronary artery disease (CAD) progression. We sought to assess the association between serum inflammatory markers and rapid CAD progression in patients with chronic stable angina pectoris. METHODS AND RESULTS: We studied 124 chronic stable angina pectoris patients (84 men; mean age, 61+/-10 years) who were on a waiting list for coronary angioplasty for a mean time of 4.8+/-2.4 months. CAD progression was defined as > or =10% diameter reduction of a pre-existing stenosis > or =50%, > or =30% diameter reduction of a stenosis <50%, development of a new stenosis > or =30% in a previously normal segment, or progression of any stenosis to total occlusion. CAD progression occurred in 35 patients (28%). After adjustment with binary logistic regression, neopterin (P<0.001), high-sensitivity C-reactive protein (P=0.017), matrix metalloproteinase-9 (P=0.002), soluble intercellular adhesion molecule 1 (P<0.001), and previous history of unstable angina (P=0.01) were independent predictors of rapid CAD progression. The association between rapid disease progression and inflammatory markers remained significant even when presence of complex lesions was introduced into the multivariate model. CONCLUSIONS: Rapid CAD progression in patients with stable angina pectoris is associated with increased C-reactive protein levels and raised concentrations of biochemical markers of endothelial and macrophage activation.

Aged↗
PubMed2004

Ischemia-modified albumin concentrations in patients with peripheral vascular disease and exercise-induced skeletal muscle ischemia.

BACKGROUND: Ischemia-modified albumin (IMA) is a new marker of myocardial ischemia, there is concern that IMA concentrations may be affected by ischemia occurring in tissues other than the myocardium. METHODS: We assessed 23 consecutive patients (15 males; mean age, 67 years) with typical leg claudication and documented peripheral vascular disease (PVD). All patients underwent both treadmill-exercise stress testing to induce leg ischemia and dobutamine stress echocardiography 1 week apart for the assessment of myocardial ischemia. Blood samples for IMA measurements were obtained at baseline, immediately after peak exercise/stress, and 1 h after exercise/stress. Statistical analysis was performed with the ANOVA repeated-measures test. RESULTS: Compared with baseline, mean (SD) IMA was significantly lower after the induction of skeletal muscle ischemia and returned to baseline values at 1 h: baseline, 74.6 (15.6) kilounits/L; peak stress, 69.5 (14.0) kilounits/L (P <0.0001 vs baseline); 1 h after stress, 75.9 (15.7) kilounits/L (P <0.0001 vs peak stress; P = 0.3 vs baseline). Baseline, peak stress, and 1-h poststress IMA concentrations were inversely correlated with the ankle-brachial index after exercise (r = -0.4; P <0.05). None of the patients showed regional wall motion abnormalities during dobutamine stress echocardiography, and IMA concentrations remained unchanged from baseline. There were no differences in baseline [74.6 (15.6) vs 72.7 (11.5) kilounits/L; P = 0.6], peak stress, or poststress IMA concentrations when exercise testing and dobutamine stress echocardiography values were compared. CONCLUSIONS: The relationship between disease severity (of a noncardiac origin) and baseline IMA values is an important and novel finding. IMA is significantly lower immediately after exercise-induced leg ischemia in patients with PVD and is related to disease severity. IMA concentrations can therefore be affected by the development of skeletal muscle ischemia, and this may have implications regarding the ability of IMA to detect myocardial ischemia in PVD patients.

Aged↗
PubMed2004

Effects of rosiglitazone on endothelial function in men with coronary artery disease without diabetes mellitus.

Recent data have shown that peroxisome proliferator-activated receptor-gamma agonists may exert protective effects on the vascular endothelium by amelioration of insulin resistance and through direct anti-inflammatory effects. In this study we assessed the effect of rosiglitazone on biochemical and biophysical indexes of endothelial function in male, nondiabetic patients with coronary artery disease. Consecutive male subjects (n = 71) with clinically stable, angiographically documented coronary artery disease and without diabetes mellitus were investigated. Patients were randomized in a double-blind manner to placebo or rosiglitazone for a total of 24 weeks. Flow-mediated dilation (FMD) of the brachial artery, C-reactive protein, von Willebrand factor, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels, and parameters of glucose and lipid metabolism were measured at baseline and after 12 and 24 weeks of treatment. Rosiglitazone treatment significantly reduced C-reactive protein (median 0.56 mg/L [interquartile range 0.33 to 1.02] to 0.33 mg/L [interquartile range 0.26 to 0.40], p <0.01), von Willebrand factor (139 +/- 47 to 132 +/- 44 IU/dl, p = 0.02), insulin resistance index (p = 0.05), and mean low-density lipoprotein (LDL) density (p <0.001) compared with placebo. However, no significant differences were seen between the rosiglitazone and placebo groups with regard to brachial artery FMD, intercellular adhesion molecule-1, or vascular cell adhesion molecule-1 levels. Rosiglitazone treatment significantly increased LDL (2.62 +/- 0.72 to 2.95 +/- 0.84 mmol/L, p = 0.03) and triglyceride (1.23 +/- 0.63 to 1.56 +/- 0.98 mmol/L, p = 0.04) levels. Thus, rosiglitazone reduced markers of inflammation and endothelial activation, but this did not translate into an improvement in FMD. Increased LDL and triglyceride levels may have played a role.

Aged↗
PubMed2004

Effect of radiofrequency catheter ablation on the biochemical marker ischemia modified albumin.

Ischemia-modified albumin (IMA) levels were measured after radiofrequency (RF) catheter ablation to evaluate the effect of direct myocardial necrosis on IMA formation. IMA levels have been shown to increase in patients after RF catheter ablation compared with those who undergo diagnostic electrophysiologic studies. The results of this study suggest that IMA may be a marker of myocardial injury.

Adult↗
PubMed2004

Pregnancy-associated plasma protein A and its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), are related to complex stenosis morphology in patients with stable angina pectoris.

BACKGROUND: The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) has been implicated in coronary plaque disruption. Its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), may also play a role in this process. Atheromatous plaque disruption often presents as complex angiographic lesions. We sought to assess whether PAPP-A, proMBP, and PAPP-A/ProMBP ratio are markers of angiographic plaque complexity in patients with chronic stable angina. METHODS AND RESULTS: We studied 396 stable angina patients (age 63+/-10 years, 230 men) of whom 289 had angiographically documented coronary artery disease (> or =75% stenosis). All coronary stenoses > or =30% diameter reduction (n =531 in 322 patients) were assessed and classified as complex (n =228) or smooth (n =303) by previously validated criteria. PAPP-A, proMBP, and C-reactive protein (hs-CRP) serum levels were measured by ELISA. Patients with complex coronary stenoses had a significantly (P<0.001) higher PAPP-A/proMBP ratio (3.1+/-1.2 versus 2.7+/-0.8x10(-3)) and PAPP-A levels (5.9+/-1.6 versus 5.1+/-1.4 mIU/L) than those without. On univariate analysis, male gender (P<0.001), age (P<0.001), previous history of myocardial infarction (P=0.013), reduced ejection fraction (P<0.001), severe coronary artery disease (P<0.001), aspirin treatment (P<0.001), PAPP-A levels (P<0.001), and PAPP-A/proMBP ratio (P<0.001) were correlated with the number of complex stenoses. Multiple regression analysis showed that male gender, age, severe coronary artery disease, and PAPP-A/proMBP ratio were independent predictors of the number of angiographically complex stenoses. CONCLUSIONS: In patients with stable angina, PAPP-A and PAPP-A/proMBP ratio are associated with angiographic plaque complexity.

Aged↗
PubMed2004

Effect of rosiglitazone on common carotid intima-media thickness progression in coronary artery disease patients without diabetes mellitus.

OBJECTIVE: Thiazolidinediones, such as rosiglitazone, have been shown to retard atherosclerosis disease progression in diabetic subjects. These agents may have anti-atherosclerotic effects through direct inhibition of inflammatory processes in the vessel wall, and so their benefit may extend to patients with atherosclerotic disease, even in the absence of diabetes. In this study, we assessed the effect of rosiglitazone on common carotid intima-media thickness (IMT) progression in nondiabetic coronary artery disease (CAD) patients. METHODS AND RESULTS: Consecutive subjects (n=92) with clinically stable, angiographically documented CAD and without diabetes mellitus were randomized in a double-blind manner to receive placebo or rosiglitazone for 48 weeks. They received single-dose placebo and rosiglitazone 4 mg daily for the initial 8 weeks, and the doses were doubled for the remainder of the study. Common carotid IMT together with fasting glucose, insulin, and lipid profile were measured at baseline and repeated after 24 and 48 weeks. Rosiglitazone-treated patients showed reduced IMT progression compared with the placebo group, -0.012 mm/48 weeks versus 0.031 mm/48 weeks (P=0.03). Rosiglitazone treatment significantly reduced insulin resistance, estimated by homeostasis model of insulin resistance index, compared with placebo (P=0.01). CONCLUSIONS: Rosiglitazone reduces common carotid IMT progression in nondiabetic CAD patients, and insulin-sensitization may be one contributory mechanism.

Adrenergic beta-Antagonists↗
PubMed2004

Prognostic value of neopterin levels in treated patients with hypertension and chest pain but without obstructive coronary artery disease.

We sought to assess the relation between circulating levels of inflammation markers, such as neopterin and C-reactive protein, and the development of adverse cardiovascular events in patients with hypertension but without obstructive coronary artery disease. We observed that patients who developed adverse events during follow-up had significantly higher neopterin levels compared with patients without events.

Aged↗
PubMed2004

Heat-shock protein 60-reactive CD4+CD28null T cells in patients with acute coronary syndromes.

BACKGROUND: CD4+CD28null T cells are present in increased numbers in the peripheral blood of patients with acute coronary syndrome (ACS) compared with patients with chronic stable angina (CSA). The triggers of activation and expansion of these cells to date remain unclear. METHODS AND RESULTS: Twenty-one patients with ACS and 12 CSA patients with angiographically confirmed coronary artery disease and 9 healthy volunteers were investigated. Peripheral blood leukocytes were stimulated with human cytomegalovirus (HCMV), Chlamydia pneumoniae, human heat-shock protein 60 (hHSP60), or oxidized LDL (ox-LDL). CD4+CD28null cells were separated by flow cytometry and assessed for antigen recognition using upregulation of interferon-gamma and perforin mRNA transcription as criteria for activation. CD4+CD28null cells from 12 of 21 patients with ACS reacted with hHSP60. No response was detected to HCMV, C pneumoniae, or ox-LDL. Incubation of the cells with anti-MHC class II and anti-CD4 antibodies but not anti-class I antibodies blocked antigen presentation, confirming recognition of the hHSP60 to be via the MHC class II pathway. Patients with CSA had low numbers of CD4+CD28null cells. These cells were nonreactive to any of the antigens used. Circulating CD4+CD28null cells were present in 5 of the 9 healthy controls. None reacted with hHSP60. CONCLUSIONS: We have shown that hHSP60 is an antigen recognized by CD4+CD28null T cells of ACS patients. Endothelial cells express hHSP60 either constitutively or under stress conditions. Circulating hHSP60-specific CD4+CD28null cells may, along other inflammatory mechanisms, contribute to vascular damage in these patients.

Acute Disease↗
PubMed2004

Effect of direct-current cardioversion on ischemia-modified albumin levels in patients with atrial fibrillation.

Ischemia-modified albumin (IMA), measured with the albumin cobalt binding test, is a marker of myocardial ischemia. We measured IMA concentrations after elective direct-current cardioversion for atrial fibrillation to determine whether transient myocardial ischemia occurs. Patients with electrocardiographic changes after cardioversion (ST-depression and/or T-wave inversion) had significantly higher IMA levels than those without these changes. Thus, elevated levels of IMA after cardioversion may reflect transient myocardial ischemia.

Aged↗
PubMed2004

Multiple complex stenoses, high neutrophil count and C-reactive protein levels in patients with chronic stable angina.

UNLABELLED: Inflammation plays an important role in atherosclerosis and the genesis of acute coronary syndromes, i.e., atheromatous plaque disruption. Neutrophil count and C-reactive protein (CRP) levels are markers of ongoing inflammation and predictors of cardiovascular risk. We sought to assess whether these inflammatory markers are associated with the presence of multiple complex stenoses in patients with chronic stable angina. METHODS AND RESULTS: We assessed 150 patients with chronic stable angina, 121 with significant coronary artery stenosis (> or =50% diameter reduction) and 29 without. CRP levels and neutrophil count were assessed at study entry. Stenoses were classified as "complex" (irregular or scalloped borders, ulceration or filling defects) or "smooth" (absence of complex features). Eighty-eight percent of the complex lesions were of type C according to AHA/ACC classification whereas the rest were type B. Patients with > or =3 complex lesions were considered to have multiple complex stenoses. Extent of coronary artery disease was assessed using a validated score. Baseline neutrophil count (4.39 x 10(9) L (-1) +/- 28 versus 3.82 x 10(9) L (-1) +/- 0.77; P = 0.004) and CRP levels (2.15 mg/L (4.6-1) versus 0.39 mg/L (0.69-0.23); P < 0.0001) were higher in patients with significant stenoses compared to patients without. No association was found between disease extent and CRP levels or neutrophil count. Neutrophil count, however (but not CRP) correlated with stenosis complexity (r = 0.28; P = 0.002 ) and was also an independent predictor of the presence of multiple complex stenoses (OR: 4.05; CI 95% (1.9-10.4); P = 0.038). CONCLUSIONS: CRP levels and neutrophil count are higher in angina patients with coronary stenoses compared to those without. Neutrophil count, but not CRP levels, correlates with angiographic stenosis complexity.

Aged↗
PubMed2004

C-reactive protein elevation and disease activity in patients with coronary artery disease.

AIMS: We sought to assess (1) whether C-reactive protein (CRP) is an independent predictor of future cardiovascular events after adjustment for coronary artery disease (CAD) severity and (2) whether CRP levels correlate with number of angiographically complex coronary artery stenosis. METHODS AND RESULTS: We studied 825 consecutive angina patients (mean age 63+/-10 years, 74% men), 700 with chronic stable angina (CSA) and 125 with acute coronary syndromes without ST-segment elevation (ACS). The composite endpoint of non-fatal acute myocardial infarction, hospital admission with class IIIb unstable angina and cardiac death was assessed at one year follow-up. Hs-CRP level was higher in CSA patients with the combined end-point (P=0.03) after adjustment for number of diseased coronary arteries. Hs-CRP was also significantly higher in patients with ACS compared to CSA ( P=0.004) and correlated with number of complex angiographic stenoses (r=0.36, P=0.01). Hs-CRP was also increased in patients with NYHA functional class III or IV compared to those in class I or II (p<0.0001). CONCLUSIONS: CRP levels predict future cardiovascular events independently of CAD severity and correlate with number of angiographically complex coronary artery stenosis in patients with ACS. Thus, CRP levels are a marker of atheromatous plaque vulnerability and CAD activity.

Angina Pectoris↗
PubMed2004

S100 protein and its relation to cerebral microemboli in on-pump and off-pump coronary artery bypass surgery.

OBJECTIVES: S100 protein has been used as a marker for cerebral injury. Studies have reported lower levels in off-pump coronary artery surgery (CABG) compared to on-pump surgery. However, most of these are flawed as S100 from extracerebral sources was included (e.g. blood from cardiotomy suckers). Microemboli (high-intensity transient signals or HITS) during CABG have been implicated as a cause of postoperative neurocognitive dysfunction. The aim of this study was to compare the number of HITS during on-pump and off-pump CABG, measure S100 accurately by excluding extracerebral sources, and assess whether any changes in S100 were related to HITS. METHODS: Thirty-five patients admitted for CABG were randomised to on-pump (n=20) or off-pump (n=15) surgery. Bilateral transcranial Doppler ultrasonography was performed on the middle cerebral artery to detect HITS. S100 was measured preoperatively, at termination of bypass in on-pump surgery, at completion of anastomoses in off-pump surgery, and 48 h postoperatively. A cell saver was used instead of cardiotomy suction in the on-pump group in order to limit extracerebral contamination of the S100 assay. RESULTS: The number of HITS was 2016+/-1897 during on-pump and 16+/-21 during off-pump surgery (P<0.0001). In on-pump surgery S100 increased from 0.05+/-0.03 to 0.50+/-0.28 microg/l (P<0.0001) at termination of bypass. In off-pump surgery S100 increased from 0.08+/-0.05 to 0.35+/-0.20 microg/l (P<0.0001) at completion of anastomoses. The mean intraoperative S100 in the on-pump group was 1.6 times greater compared to that in the off-pump group (95% CI 0.88-2.8; P=0.01). There was no evidence of a relationship between S100 and HITS in both groups. By 48 h S100 decreased to 0.22+/-0.14 microg/l in the on-pump and 0.21+/-0.09 microg/l in the off-pump group (P<0.0001, compared to the preoperative value). CONCLUSIONS: We have demonstrated a significantly higher number of cerebral microemboli in patients undergoing on-pump compared to off-pump CABG. By limiting contamination from extracerebral sources, we have shown S100 beta levels during on-pump CABG one and a half times greater than that in off-pump, although this did not reach statistical significance. In addition, we have shown no correlation between S100 beta and the total microemboli count, possibly because of the small numbers in this study.

Aged↗
PubMed2004

Ischemia Modified Albumin for the assessment of patients presenting to the emergency department with acute chest pain but normal or non-diagnostic 12-lead electrocardiograms and negative cardiac troponin T.

BACKGROUND: The diagnosis of myocardial ischemia in patients with acute chest pain at rest but non-diagnostic electrocardiograms (ECG) is problematic. Ischemia Modified Albumin (IMA) is a new biochemical marker of ischemia, which may be useful to characterise acute coronary syndrome (ACS) patients. METHODS: We studied 131 patients (mean age 58.5 years; 95 male) presenting to the emergency department with symptoms suggestive of ACS but with normal or non-diagnostic ECGs. Cardiac troponin T (cTnT) and IMA were measured within 3 h of last chest pain episode. Based on hospital diagnostic test results, patients were classified as having ACS or non-ischemic chest pain (NICP), by two independent cardiologists unaware of IMA results. RESULTS: Mean IMA levels (U/ml) were higher in patients with ACS (98.3+/-11) compared to patients with NICP (85.5+/-15); p<0.0001. IMA levels >93.5 U/ml demonstrated a sensitivity and specificity of 75% for the diagnosis of ACS; area under the receiver operator characteristic curve 0.78 (95% CI: 0.70-0.85). If we applied the manufacturer cutoff point of 85 U/ml, the sensitivity of IMA increased to 90.6% with a specificity of 49.3% (negative predictive value=84.6%). In combination with cTnT (6-12 h) (>0.05 ng/ml), the sensitivity increased to 92.2%. After multivariate analysis, IMA levels >85 U/ml (odds ratio=14.6 [95% CI 4.4-48.4]; p<0.0001), age and prior myocardial infarction were independent predictors of ACS. CONCLUSION: IMA may be a useful biomarker for the identification of ACS in patients presenting with typical acute chest pain but normal or non-diagnostic ECGs.

Adult↗
PubMed2004

Cardiac syndrome X. Diagnosis, pathogenesis and management.

Patients with cardiac syndrome X (typical chest pain and normal coronary arteriograms) represent a heterogeneous syndrome, which encompasses different pathogenic mechanisms. Although symptoms in most patients with cardiac syndrome X are non-cardiac, a sizable proportion of them have angina pectoris due to transient myocardial ischemia. Thus radionuclide myocardial perfusion defects, coronary sinus oxygen saturation abnormalities and pH changes, myocardial lactate production and stress-induced alterations of cardiac high energy phosphate suggest an ischemic origin of symptoms in at least a proportion of patients with cardiac syndrome X. Microvascular abnormalities, caused by endothelial dysfunction, appear to be responsible for myocardial ischemia in patients with cardiac syndrome X. Endothelial dysfunction is likely to be multifactorial in these patients and it is conceivable that risk factors such as hypertension, hypercholesterolemia, diabetes mellitus and smoking can contribute to its development. Most patients with cardiac syndrome X are postmenopausal women and estrogen deficiency has been therefore proposed as a pathogenic factor in female patients. Additional factors such as abnormal pain perception may contribute to the pathogenesis of chest pain in patients with angina pectoris and normal coronary angiograms. Although prognosis is good regarding survival, patients with cardiac syndrome X have an impaired quality of life. Management of this syndrome represents a major challenge to the treating physician. Understanding the mechanism underlying the condition is of vital importance for patient management. Thus diagnostic tests should aim at identifying the cause of the symptoms in the individual patient, i.e. myocardial ischemia, increased pain perception, abnormalities of adrenergic tone, non-cardiac mechanisms, etc. Moreover, it is important to bear in mind that treatment of cardiac syndrome X should be mainly directed towards improving quality of life, as prognosis is usually good in these patients. Conventional antianginal agents such nitrates, calcium channel antagonists, beta-adrenoceptor antagonists and nicorandil are effective particularly in patients in whom chest pain and ECG changes are clearly suggestive of myocardial ischemia and in those with objective documentation of ischemia. Angiotensin-converting enzyme inhibitors have been shown to be useful in syndrome X patients with increased adrenergic tone, borderline systemic hypertension, and those with documented endothelial dysfunction. Analgesic interventions of different sorts have been proposed based on the hypothesis that somatic and visceral perception of pain is altered in cardiac syndrome X patients. Pharmacological agents such as imipramine and aminophylline, and neural electrical stimulation techniques have been assessed in recent years with encouraging results. Psychological treatment, particularly cognitive therapy, appears to be useful in defined patient subsets. Relaxation techniques such as transcendental meditation have been successfully used in small studies and shown to improve not only chest pain but also exercise-induced ST segment changes. Reports indicate that these techniques improve quality of life.

Disease Management↗
PubMed2003

Placental infection with Chlamydia pneumoniae and intrauterine growth restriction.

BACKGROUND: The concept that low birth weight infants are more predisposed to coronary artery disease (CAD) in adulthood has been studied extensively. Although many infectious agents have been associated with intrauterine growth restriction (IUGR), Chlamydia pneumoniae an organism implicated in CAD has not been investigated. It was our aim to assess whether C. pneumoniae DNA is present in placental tissue and whether its detection is associated with IUGR. METHODS: Fifty-nine pregnant women were studied: 32 women had an uncomplicated pregnancy with no antenatal or post-natal evidence of IUGR. Twenty-seven women had pregnancies with ultrasonographically demonstrated IUGR, defined as foetal abdominal circumference measuring less than 2 S.D.s from the mean for gestational age. At the time of delivery, maternal blood and placental tissue samples were obtained. Placental samples were taken from four sites centrally and peripherally on the maternal and foetal side of the placentas and tested by nested polymerase chain reaction for C. pneumoniae DNA. IgG antibodies to C. pneumoniae were measured using microimmunfluorescence. RESULTS: C. pneumoniae DNA was detected in 44% of the placental tissue but there was no difference in the prevalence of bacterial DNA between the control and the low birth weight group (P=0.58). Additionally C. pneumoniae seropositivity did not differ between the index and control groups (78 vs. 70%, P=0.44). CONCLUSIONS: C. pneumoniae is present in placental tissue. Its presence however does not correlate with IUGR. Similarly, maternal C. pneumoniae seropositivity is not related to low birth weight. Thus C. pneumoniae infection is unlikely to play a role in the pathogenesis of IUGR.

Adult↗