Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5±10 years old, 117 men and 14 women) with left ventricular ejection fraction of 50.7±9.2% and low logistic EuroScore (3.5±3.2%) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11–24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), p=0.007]. OPN levels were positively related to EuroScore (r=0.2, p=0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p=0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43–4.99), p=0.527]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p=0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome

The pathophysiological relationship and clinical significance of left atrial function and left ventricular diastolic dysfunction in beta-thalassemia major

Iron deposition in combination with inflammatory and immunogenetic factors is involved in the pathophysiology of cardiac dysfunction in -thalassemia major. We investigated the mechanical and endocrine function of the left atrium and ventricle to identify early signs of dysfunction. We studied 90 patients (mean age: 29 +/- 11 years) with -thalassemia and normal left ventricular function and 90 age and sex-matched healthy controls. Patients and controls underwent a thorough cardiac echocardiographic study and measurements of the b-type (NT-proBNP) and atrial natriuretic peptides (proANP). Patients underwent 24-hr Holter recordings for arrhythmia monitoring. In the patient group, atria were affected early during the course of the disease, prior to diastolic and systolic left ventricular dysfunction. The E/Eratio (E Doppler mitral fast inflow to the corresponding tissue Doppler E) continually increased with age (P<0.05) and reached levels indicating left ventricular diastolic dysfunction (E/E>15) in the third decade whereas indexes of active and passive atrial function decreased gradually throughout life. In controls, the E/E ratio continually increased with age but with later (fifth decade) appearance of diastolic dysfunction and a compensatory increase in atrial active function. Both natriuretic peptides were significantly increased in patients compared to controls (558 +/- 141 and 2,580 +/- 1,830 fmol/mL for NT-proBNP and proANP versus 332 +/- 106 and 1,331 +/- 1,134 fmol/mL, respectively). Atrial fibrillation was found in a subgroup of 23 (26%) patients, older in age with mild diastolic function and enlarged, depressed atria. In conclusion, atrial mechanical depression seems to be a very early sign of cardiac damage. It may become echocardiographically evident even before diastolic and systolic dysfunction and is associated to supraventricular arrhythmias. Am. J. Hematol. 89:13-18, 2014. (c) 2013 Wiley Periodicals, Inc

The Association Between a Common FCGR2A Polymorphism and C-Reactive Protein and Coronary Artery Disease Revisited

Introduction: The Fc gamma RIIa receptor is responsible for the clearance of large immune complexes and recently has been proved to be a C-reactive protein (CRP) receptor as well. A polymorphism in the corresponding FCG2RA gene resulting in an amino acid change (R131H) has been implicated, with conflicting results in the pathogenesis of various autoimmune or inflammatory disorders (e. g., atherosclerosis and coronary artery disease [CAD]). Methods: We recently developed a real-time polymerase chain reaction and melting curve analysis method for the genotyping of the above polymorphism. We further looked at its validity with bioinformatics study and DNA sequencing. Then we genotyped 134 CAD patients and 45 angiographically normal controls and determined serum high-sensitivity CRP by nephelometry (Dade-Behring). Also, we used apparently healthy platelet donors (n = 206) as a larger control group. Results: Our method is accurate and devoid of problems with homologs and copy number variants. The need for reference materials is stressed. There were statistically significant differences (p < 0.05) between the CAD patients and each of the two other control groups, with the percentage of RR genotype rising from 6.5% and 11% in the control groups to an average of 19% in all CAD patients (17%, 24%, and 18.5% in stable angina, unstable angina, and myocardial infarction, respectively). In a logistic regression model that included known risk factors for CAD including CRP, the RR genotype remained a significant predictor for CAD (odds ratio: 6.3 [1.1-36.3]). Also after linear regression analysis, CRP levels were reduced in the RR carriers (vs. HH + HR), controlling for age, sex, and disease (marginal p = 0.07). Conclusions: With our accurate genotyping method, the RR genotype was correlated with atherothrombotic CAD events. The inverse correlation found between CRP levels and genotype supports the in vitro data of RR cells binding CRP stronger than HH

TLR-4 and CD14 Genotypes and Soluble CD14: Could They Predispose to Coronary Atherosclerosis?

Background: Inflammatory mechanisms are key to the pathogenesis of atherosclerosis. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14 promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in subjects with Coronary Artery Disease (CAD). Methods: DNA was obtained from 100 human paraffin-embedded aortic specimens, from cadavers with known coronary atheromatosis (Group A) and 100 blood samples from patients with CAD, as detected by cardiac Multi-Detector-row-Computed-Tomography (MDCT) (Group B). Our control group consisted of 100 healthy individuals (Group C). Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR). Plasma levels of sCD14 were measured with ELISA. Results: For TLR-4 Asp299Gly and Thr399Ile polymorphisms, no statistically significant differences were observed. Regarding the C260T polymorphism, frequencies of T allele were significantly higher in the control group compared to the case group (p = 0.05). The Odds Ratio (OR) showed statistically significant association of TT genotype with healthy individuals (OR 0.25, 95% Confidence Interval CI 0.10–0.62, p = 0.0017). Plasma levels of sCD14 in patients with CAD (mean value = 1.35 μg/mL) were reduced when compared to reference value. Conclusions: The studied polymorphisms ofTLR-4 showed no association with CAD. Conversely, the functional polymorphism of CD14 has a statistically significant difference in expression between healthy and affected by CAD individuals