New insights into the mechanisms of diastolic dysfunction in patients with type 2 diabetes.

BACKGROUND: Little is known about the role of advanced glycation end products (AGEs) and their receptor (RAGE) in diabetic cardiovascular complications. Therefore, we aimed to evaluate the association of serum soluble RAGE (sRAGE) levels and left ventricular (LV) diastolic dysfunction in patients with type 2 diabetes. METHODS: Our study consisted of 40 patients with type 2 diabetes and 40 age- and sex-matched healthy control group. Subjects with age ≥ 50 years old and any cardiovascular risk factors or conditions were excluded from the study. Serum sRAGE levels determined by enzyme-linked immunosorbent assay and LV diastolic dysfunction were evaluated according to current American Society of Echocardiography guidelines. RESULTS: Baseline characteristics were similar between groups except body mass index, waist-hip ratio, and fasting glucose levels. Serum sRAGE level was significantly lower in diabetic group compared with control group (676 ± 128 vs. 1044 ± 344, p < 0.05). Diastolic dysfunction was observed in 50% of diabetic patients (40% grade I and 10% grade II). Correlation analysis showed that serum sRAGE was negatively correlated with duration of diabetes, septal E'/A', lateral E'/A', and average E/E'. In multivariate regression analysis, serum sRAGE level was strongly associated with diastolic dysfunction in patients with type 2 diabetes. CONCLUSION: Our study showed that serum sRAGE level was significantly lower in type 2 diabetic patients aged < 50 years old. Also, sRAGE has negative correlation with the duration of diabetes and it was significantly associated with the presence of diastolic dysfunction in type 2 diabetes.

Pulmonary embolism presenting with evolving electrocardiographic abnormalities mimicking anteroseptal myocardial infarction: a case report.

OBJECTIVES: To report a case with dynamic ST segment elevation suggestive of anteroseptal acute myocardial infarction (AMI) that proved to be bilateral pulmonary thromboembolism (PTE). CLINICAL PRESENTATION AND INTERVENTION: A 50-year-old woman with syncope was transferred to the emergency department. Findings from the admission electrocardiogram were suggestive of anteroseptal AMI; however, coronary angiography revealed that the patient had normal coronary arteries. On further evaluation, the patient was found to have massive bilateral PTE. CONCLUSION: This report emphasizes the role of evolving electrocardiographic changes in the diagnosis of PTE, particularly in patients with chest pain and ST segment elevation suggestive of acute coronary syndrome.

Association of plasma osteopontin levels with coronary calcification evaluated by tomographic coronary calcium scoring.

Evidence indicates that proteins controlling bone mineralization are also involved in the regulation of coronary calcification. The aim of the present study is to evaluate the association between plasma osteopontin (OPN) levels and coronary calcification quantified by using tomographic coronary calcium scoring. Plasma OPN levels were measured from samples of 80 intermediate-risk asymptomatic patients (56 +/- 10 years) who underwent tomographic coronary calcium scoring via multislice computed tomography for incremental risk stratification. There was no significant difference regarding OPN levels between patients with and without coronary calcification in the whole study population. Of 49 patients not receiving renin-angiotensin system inhibitors and/or statins, plasma OPN levels of patients with coronary calcification (38.7%) were significantly higher than those without coronary calcification (61.3%) (8.88 +/- 2.85 vs. 6.79 +/- 2.41, P = 0.008, respectively). On a binary logistic regression model, only age and plasma OPN level were found to be significant independent associated variables for the presence of coronary calcification in patients not receiving these medications (odds ratio for age, 1.15, P = 0.017; for plasma OPN levels, 1.63, P = 0.014). Our results indicate that plasma OPN levels may be predictive of coronary calcification, suggesting an important role of OPN in the atherosclerotic calcification pathogenesis.

B-type natriuretic peptide (BNP) levels in female systemic lupus erythematosus patients: what is the clinical significance?

Cardiovascular disease is a major cause of death in patients with systemic lupus erythematosus (SLE) especially during the late phase of the disease. This study was conducted to evaluate B-type natriuretic peptide (BNP) levels in female SLE patients without cardiac symptoms and to investigate whether BNP levels correlated with echocardiographic findings. We studied 59 women with SLE and 33 healthy women. SLE patients with history of cardiac disease, diabetes mellitus, hypertension, and other inflammatory diseases were excluded from the study. All subjects had a complete history and physical examination. Overall disease activity assessment in SLE patients at the time of the study were derived by calculation of SLE disease activity index (SLEDAI). BNP levels were determined, and transthoracic echocardiography were performed in all subjects. There was no difference between SLE patients and controls in terms of age, blood pressure, smoking status, plasma glucose, creatinine levels, and lipid profiles. Nine patients had SLEDAI score greater than 5. All subjects had an EF greater than 55%. Diastolic dysfunction was more frequent in lupus patients than in controls (15 [25.4%] vs. 2 [6%]; p = 0.022). BNP levels of SLE patients were significantly higher than controls (median 17.9 range [5-211] pg/ml vs. median 14.7 range [5-39.7] pg/ml; p = 0.033). Twenty-seven of the SLE patients (46%) and seven of the controls (21%) had BNP levels greater than or equal to 20 pg/ml (p = 0.019). There were no differences in BNP levels of SLE patients with and without diastolic dysfunction (median 17.8 range [5-117] pg/ml vs. median 18.5 range [5-211] pg/mL; p = NS). BNP levels were positively correlated with left atrium diameter (r (2) = 0.39, p = 0.001). BNP levels did not correlate with erythrocyte sedimentation rate/C-reactive protein levels, SLEDAI scores, total steroid dosage used, or other echocardigraphic parameters. BNP levels were increased in female SLE patients without cardiac symptoms as compared to healthy controls. Although none of the SLE patients in our study had clinical signs of ischemic heart disease, increased levels of BNP in SLE patients might be a reflection of a ischemic myocardial tissue.

QT interval dispersion changes according to the vessel involved during percutaneous coronary angioplasty.

Increased QT dispersion (QTd) is a noninvasive marker of an electrophysiologic abnormality associated with high mortality in coronary artery disease. The purposes of this study were to measure changes in QTd and ST-segment changes immediately before, during and after intracoronary balloon inflation and to determine whether the coronary artery vessel involved and/or the duration of inflation affect(s) QTd. A total of 45 patients (32 men, 13 women, mean age 58 +/- 11 years) who were referred for elective percutaneous transluminal coronary angioplasty were included. The mean QT interval dispersions for all patients before the inflation, during the balloon inflation at 60 sec and after the balloon deflation at 5 min were 68 +/- 13 ms, 82 +/- 16 ms and 71 +/- 13 ms, respectively. There was no significant difference between baseline and 5 min after deflation. The increase in QTd during the balloon inflation was significant (p<0.01). There was no significant QTd change in patients with left circumflex artery (Cx) lesions during inflation and after deflation compared with baseline. The differences were statistically significant only in patients with left anterior descending (LAD) lesions and right coronary artery (RCA) lesions at 60 sec during balloon inflation (p=0.001 vs. p=0.04). Acute reversible myocardial ischemia induced by balloon inflation causes an increase in QTd limited to the LAD and RCA vessels. Therefore, when using QTd as a marker of myocardial repolarization abnormality due to acute reversible ischemia, the involved coronary artery vessel must be taken into account.

Plasma soluble osteopontin concentrations are increased in patients with rheumatic mitral stenosis and associated with the severity of mitral valve calcium.

Although the severity of valvular calcification is an important prognostic indicator, the cellular mechanisms of the calcification process are unknown. Osteopontin modulates inflammation and biomineralization, and increased osteopontin expression has been demonstrated in calcified degenerative or rheumatic cardiac valves. The present study evaluated soluble plasma osteopontin in 32 patients with echocardiographically determined rheumatic mitral stenosis and compared the results to those of a control group of 22 healthy patients. Patients were evaluated with routine echocardiographic techniques, Wilkins scoring, and 2-dimensional echocardiographic calcium scoring. Patients with rheumatic involvement other than in the mitral valve were excluded. Plasma osteopontin and high-sensitivity C-reactive protein levels in patients with mitral stenosis were significantly higher those of the control group (p = 0.006 and p = 0.0001, respectively). A significant correlation was found between plasma osteopontin levels and the severity of mitral valve calcification (p = 0.003) and also between high-sensitivity C-reactive protein levels and Wilkins score (p = 0.009). There was a stepwise and statistically significant increase in soluble plasma osteopontin levels in association with the severity of mitral valve calcification. In conclusion, increased osteopontin levels were correlated with the severity of mitral valve calcification in patients with rheumatic mitral stenosis, suggesting an important role of osteopontin in the modulation of valvular calcification. Elevated levels of high-sensitivity C-reactive protein concentrations suggest the presence of ongoing inflammation in those patients.

Plasma osteopontin levels are elevated in non-ST-segment elevation acute coronary syndromes.

BACKGROUND: The regions of ruptured atherosclerotic plaques have numerous macrophages. Osteopontin that modulates macrophage function has been shown in atherosclerotic plaques. We aimed to study the plasma levels of osteopontin in patients with unstable angina or non-ST-seg ment elevation myocardial infarction (NSTEMI) and the rela tionship between osteopontin and the extent of the coronary artery disease (CAD). METHODS: We studied 65 patients with unstable angina or NSTEMI, 25 patients with stable angina and 18 patients as the control group. The extent of coronary artery stenosis was determined by the number of vessels with >50% stenosis. Plasma osteopontin concentrations were measured from the blood samples that were drawn immediately after admission to the emergency department in unstable angina/NSTEMI patients and before the coronary angiograph in the stable angina and control groups. RESULTS: The plasma osteopontin concentration was (495 118 ng/ml) significantly higher in the patients with unstable angina/NSTEMI compared to the stable angina group (319 106 ng/ml) and control group (125+/-54 ng/ml) (p=0.0001 The plasma osteopontin levels were lower in the patients with stable angina pectoris who had one-vessel disease compared to those with two-vessel disease (p=0.01). How ever, in the unstable angina/NSTEMI group, the plasma osteopontin levels were statistically not different among the patients with one-vessel, and two-vessel and three-vessel disease (p=NS). There was no correlation between the plasma osteopontin levels and the extent of coronary stenosis. CONCLUSIONS: The plasma osteopontin levels are elevatedin patients with unstable angina/NSTEMI, but there appears to be no correlation with the extent of CAD. These results ma suggest that osteopontin may have a role in the pathobiology of ACS.

Simvastatin treatment improves endothelial function and increases fibrinolysis in patients with hypercholestrolemia.

OBJECTIVES: Statins reduce cardiovascular events by cholesterol-lowering as well as nonlipid-related actions. Thrombin activatable fibrinolysis inhibitor (TAFI) is a recently identified independent risk factor of thrombosis. Endothelial dysfunction is also a strong predictor of cardiovascular events. The aim of this study was to assess the effects of simvastatin treatment on circulating TAFI concentrations and endothelial function in patients with hypercholesterolemia. METHODS: Thirty-five patients (19 female, mean age 48 +/- 7 years) with hyperlipidemia were recruited into the study. Simvastatin was administered, 40 mg daily, for eight weeks to all subjects. Study subjects did not receive any medication except for lipid-lowering therapy during the follow-up period. Endothelial function was evaluated by flow-mediated dilation (FMD) from the brachial artery of the patients. Plasma lipid parameters, TAFI levels and endothelial function were measured before and after simvastatin treatment. RESULTS: Treatment with simvastatin showed a significant decrement in plasma total cholesterol, LDL cholesterol and triglyceride levels (p<0.05). Plasma TAFI levels were also significantly decreased after simvastatin treatment [median 17.0 (range 0.4-93.7) mcg/mL versus median 6.9 (range 0.8-63.0) mcg/mL, p<0.001]. Mean FMD was measured 7.7 +/- 2.5% at baseline and significantly improved after treatment (13.0 +/- 1.4%) (p=0.001). CONCLUSION: Our findings of decreased TAFI levels may reflect the beneficial effect of simvastatin treatment on fibrinolysis, and improved endothelial function may suggest the improved future cardiovascular events in hyperlipidemic patients.

Holter monitoring for 24 hours in patients with thromboembolic stroke and sinus rhythm diagnosed in the emergency department.

It is well known that patients with ischemic stroke show ST-T abnormalities and various rhythm abnormalities on an electrocardiogram (ECG). The most commonly encountered rhythm abnormality is atrial fibrillation. It was recently shown that paroxysmal atrial fibrillation (PAF) is an important causative factor in patients with stroke. Detection of PAF is important in identifying the cause, prognosis, and treatment in patients with thromboembolic stroke. Investigators in the present study followed patients with thromboembolic stroke who had been admitted to the emergency department in sinus rhythm; 24-h Holter monitoring was used, and patients were assessed at referral and every 6 h for 24 h with ECG, which was used to detect rhythm disturbances, especially PAF. In 26 patients with stroke who came to the emergency department, acute thromboembolic stroke was diagnosed on the basis of magnetic resonance imaging; no rhythm abnormalities were noted on Holter monitoring. Eighteen patients were male and 8 were female (mean age: 66+/-13 y). Arrhythmia was identified on ECG in 3 patients (11%) and on 24-h Holter monitoring in 24 patients (92%). PAF was diagnosed in 3 patients (11%) on ECG and in 11 patients (42%) on Holter monitoring. In 2 patients, nonsustained ventricular tachycardia was detected only on Holter monitoring, which was found to be significantly superior to ECG for the detection of arrhythmias (P<.001). Investigators found no significant relationship between PAF and variables such as hypertension, diabetes, coronary artery disease, history of myocardial infarction, ST-T changes, and elevations in cardiac markers. However, a significant relationship (P<.01) was seen between nonsustained ventricular tachycardia and a history of myocardial infarction. No relationship was discerned between arrhythmia and stroke localization. Study results suggested that (1) PAF is a commonly diagnosed rhythm abnormality, and (2) Holter monitoring is superior to routine ECG for the detection of arrhythmias such as PAF in patients anticipated to have thromboembolic stroke with sinus rhythm.

Right ventricular outflow tract thrombus in a case of Behcet's disease.

Behcet's disease is known as a chronic systemic vasculitic syndrome, the hallmark of which is recurrent oral aphthous and genital ulcerations and uveitis. Vascular involvement, mainly thrombosis, reportedly affects as many as one-third of patients. Cardiac involvement, however, is very rare. We present in this report a young female patient developing right ventricular thrombus while being treated medically.

Impaired fibrinolytic capacity in rheumatic mitral stenosis with or without atrial fibrillation and nonrheumatic atrial fibrillation.

Chronic atrial fibrillation (AF) has often been associated with systemic embolization, and patients with mitral stenosis (MS) have the highest thromboembolic risk. Increased risk of thromboembolism could be in part due to impaired fibrinolytic function. Global fibrinolytic capacity (GFC) is an innovative technique for evaluating the entire fibrinolytic system. The aim of our study was to evaluate fibrinolytic activity in patients with rheumatic and nonrheumatic chronic AE To investigate fibrinolytic activity, we assessed GFC in peripheral blood samples of 32 patients with nonrheumatic AF (14 women; mean age, 56 +/- 1 years), 30 patients with rheumatic MS and AF (23 women; mean age, 35 +/- 9 years), and 32 patients with rheumatic MS and sinus rhythm (24 women; mean age, 36 +/- 8 years). The control group comprised 30 healthy adult subjects in normal sinus rhythm. Patients with chronic AF (rheumatic and nonrheumatic) had lower GFC than did the controls (P = .0001). The rheumatic AF group also showed decreased levels of GFC compared with the nonrheumatic AF group, with the rheumatic MS and sinus rhythm group, and with controls (P = .03, P = .02, P = .0001, respectively). GFC was lower in patients with rheumatic MS and sinus rhythm than in controls (P = .003). Although there were correlations between GFC and mitral valve area, transmitral mean gradient, left atrial diameter, and mitral calcification in patients with rheumatic MS, multivariate analysis showed only transmitral gradient as an independent factor affecting GFC. Patients with AF have decreased GFC, a finding that suggests the presence of a hypofibrinolytic state. Fibrinolytic dysfunction was more pronounced in rheumatic MS patients with AF than in those with nonrheumatic AF. Moreover, patients with rheumatic MS and sinus rhythm had decreased global fibrinolytic activity. Hypofibrinolysis documented by decreased GFC can be one of the important causes of increased risk of embolism in patients with AF and rheumatic MS.

Effects of short-term atorvastatin treatment on global fibrinolytic capacity, and sL-selectin and sFas levels in hyperlipidemic patients with coronary artery disease.

BACKGROUND: The beneficial effects of HMG-CoA reductase inhibitors (statins) in patients with coronary artery disease (CAD) appear to be attributable not only to their lipid-lowering properties, but also to their therapeutic effects on the coagulation system, and anti-inflammatory effect. Furthermore, statins mitigate the apoptosis of vascular smooth muscle cells (VSMC) and macrophages in atherosclerotic plaques. HYPOTHESIS: The purpose of this study was to evaluate the effects of short-term atorvastatin treatment on the fibrinolytic system and systemic inflammatory status, and on apoptosis in hyperlipidemic patients with CAD. METHODS: The study population consisted of 36 hyperlipidemic patients (14 women and 22 men, mean age 53+/-9 years) with stable CAD, untreated with lipid-lowering medications. Serum lipoproteins, fibrinogen levels, sFas and sL-selectin, and global fibrinolytic capacity (GFC) were measured at baseline and after 12 weeks of treatment with atorvastatin, 10 mg/day. RESULTS: Atorvastatin treatment decreased serum low-density lipoprotein (-39%, P=0.0001), total cholesterol (-32%, P=0.0001), and triglycerides (-22%, P=0.0001), and increased high-density lipoprotein (+13%, P=0.0001) at 12 weeks compared to baseline. These effects were associated with a decrease in plasma fibrinogen from 331+/-73 to 298+/-58 mg/dl (P=0.0001), and sL-selectin levels from 666+/-201 to 584+/-162 ng/ml (P=0.0001). sFas levels and GFC increased from 3754+/-1264 to 4873+/-1835 pg/ml and from 3.5+/-2.4 to 5.6+/-2.9 microg/ml, respectively (both P=0.0001). CONCLUSIONS: These results suggest that lipid lowering with atorvastatin therapy significantly increases GFC, decreases fibrinogen levels, and causes leukocyte deactivation. Our findings also suggest that atorvastatin treatment mitigates apoptosis of VSMC in the atherosclerotic plaque. These effects of atorvastatin may, in part, explain the early decrease in cardiovascular events observed in clinical trials of statins.

Angiotensin-converting enzyme genotype predicts valve damage in acute rheumatic fever.

BACKGROUND AND AIM OF THE STUDY: The genetic basis for host susceptibility to subsequent valve damage and scarring is not well defined in patients with a history of acute rheumatic fever (ARF). A high angiotensin-converting enzyme (ACE) activity has been demonstrated in valve tissue; hence, the study aim was to determine whether the ACE-DD genotype was a predisposing factor to heart valve damage after ARF attack. METHODS: A total of 165 patients diagnosed previously (16 +/- 5 years ago) with ARF was evaluated. Diagnoses were conducted according to Jones' criteria, and all received similar treatment and remain on regular penicillin prophylaxis. The ACE genotype was determined using polymerase chain reaction methods. RESULTS: Echocardiography showed that 39 patients (11 males, 28 females; mean age 25 +/- 6 years) had completely normal valves, and 126 patients (38 males, 88 females; mean age 21 +/- 6 years) had valve disease. The mitral valve was involved in 93% of patients (stenosis 86%, regurgitation 69%), and the aortic valve in 50% (stenosis 19%, regurgitation 48%). The ACE-DD genotype is associated with a significantly greater risk of valve involvement (risk ratio 2.7, 95% CI 1.15-6.5, p = 0.02). The distribution of genotypes was similar between aortic and mitral valve involvement. CONCLUSION: In patients with acute rheumatic fever the ACE-DD genotype is associated with an increased risk of subsequent heart valve damage.

Detection of patients with hypertrophic cardiomyopathy at risk for paroxysmal atrial fibrillation during sinus rhythm by P-wave dispersion.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) in hypertrophic cardiomyopathy (HCM) is associated with poor prognosis. Previous studies have shown good correlation between P-wave dispersion (Pd) and occurrence of PAF. However, Pd in patients with HCM for predicting PAF has not been studied. HYPOTHESIS: The aim of the study was to determine whether Pd could identify patients with HCM who are likely to suffer from PAF. METHODS: Twenty-two patients with HCM with a history of PAF (Group 1) and 26 patients with HCM without a history of PAF (Group 2) were studied. Maximum (Pmax) and minimum (Pmin) P-wave durations, as well as P-wave dispersion (Pd = Pmax - Pmin) were calculated from 12-lead surface electrocardiograms (ECG). RESULTS: P-wave dispersion was significantly different between the groups (Group 1: 55 +/- 6 ms vs. Group 2: 37 +/- 8 ms; p<0.001), while Pmax (Group 1: 134 +/- 11 ms vs. Group 2: 128 +/- 13 ms; p = 0.06) and Pmin (Group 1: 78 +/- 9 ms vs. Group 2: 81 +/- 7 ms; p = 0.07) was not significantly different. Patients with a history of PAF had higher left atrial diameter than the patients without PAF (Group 1: 52 +/- 8 mm vs. Group 2: 48 +/- 10 mm; p = 0.02). A cut-off value of 46 ms for Pd had a sensitivity of 76% and a specificity of 82% in discriminating between patients with and without PAF. CONCLUSION: This study suggests that P-wave dispersion could identify patients with HCM who are likely to develop PAF.

Diminished global fibrinolytic capacity in patients with mitral valve prolapse is associated with transient ischemic attacks.

Although mitral valve prolapse (MVP) has shown to be associated with thromboembolic complications, the cause of thromboembolic events in those patients is still unknown. The purpose of this study was to evaluate the fibrinolytic activity in MVP patients. The study included 35 consecutive patients (25 women, mean age 25+/-11 years) with echocardiographically documented MVP and 25 age- and sex-matched subjects as a control group. Four of MVP patients have a history of transient ischemic attack (TIA). Global fibrinolytic capacity (GFC), a new technique that examines the effectiveness of the entire fibrinolytic system, was measured. Global fibrinolytic capacity was found to be nonsignificantly increased in MVP patients (3.14+/-1.42 microg/mL) compared to those in control subjects (2.36+/-1.33 microg/mL) (p>0.05). However, in four of these MVP patients who had a history of transient ischemic attack, the GFC level was significantly lower than in patients who have no history of transient ischemic attack (1.67+/-0.6 microg/mL vs 3.27+/-1.46 (microg/mL, p=0.003). Furthermore, the GFC levels of these four patients were less than those of controls (p=0.04). These results showed that global fibrinolytic activity was similar in MVP patients without a history of TIA and control subjects. However, MVP patients with a history of TIA had significantly decreased global fibrinolytic activity compared to controls and as well as MVP patients without a history of TIA.

Prevalence of coronary artery disease before valvular surgery in patients with rheumatic valvular disease.

BACKGROUND: Although many patients with valvular heart disease have concomitant coronary artery disease (CAD), there are limited data on the association between rheumatic valvular disease (RVD) and CAD. In this study, we aimed to investigate the prevalence of CAD in a group of patients with RVD and undergoing coronary angiography before valvular surgery. METHODS: In this retrospective analysis, we enrolled a total of 1075 patients (658 women, 61.2%; mean age: 53.2 ± 9.9 years) who underwent coronary angiography for the evaluation of CAD before valvular surgery between January 2003 and May 2010. RESULTS: The overall prevalence of significant CAD was 11.1%. Patients with significant CAD were older than patients without significant CAD (55.16 ± 10.4 vs. 51.45 ± 9.1; P<0.001). In addition, hypertension, smoking, diabetes mellitus, and dyslipidemia were more prevalent among patients with significant CAD (P<0.05). After adjustment for several risk factors, only aortic stenosis remained the predictor of significant CAD (odds ratio: 1.66; 95% confidence interval: 1.26-2.19; P<0.001). However, aortic regurgitation was inversely associated with the presence of CAD (odds ratio: 0.56; 95% confidence interval: 0.21-1.01; P<0.001). CONCLUSION: The overall prevalence of CAD in our population with RVD was low. Rheumatic aortic stenosis is associated with an increased prevalence of CAD, whereas the prevalence of CAD is lower in those patients with aortic regurgitation.