Mitral and aortic annular calcifications and cerebrovascular ischemic episodes in patients with coronary artery disease.

INTRODUCTION:  Atherosclerosis is a systemic pathological process involving the whole arterial bed. Valvular calcifications are associated with cardiovascular risk factors. Significant carotid stenosis accounts for approximately 20% of cerebrovascular ischemic episodes.  OBJECTIVES:  The aim of the study was to assess the relationship between mitral and aortic annular calcifications, increased carotid intima-media thickness (CIMT), and incidence of cerebrovascular ischemic episodes. PATIENTS AND METHODS:  A total of 127 patients with angiographically confirmed coronary artery disease (68 men and 59 women; aged 74 (33-87) years) were divided into 4 groups: with aortic valve calcifications (AVCs), mitral annular calcifications (MACs), both aortic valve and mitral annular calcifications (AMVCs), and no valvular calcifications (no-VCs), based on the echocardiographic assessment of the mitral and aortic valves. CIMT and the presence of atherosclerotic plaques were evaluated by carotid ultrasonography. A history of cerebrovascular ischemic episodes was obtained.  RESULTS:  The combined prevalence of mitral or aortic valve calcifications in the study population was 59% (AVCs, 55%; MACs, 24%; and AMVCs, 21%). CIMT was significantly increased in the MAC and AMVC groups (P <0.05 for MACs; P <0.01 for AMVCs). Ischemic stroke was more common in the AVC group (P <0.05), while the MAC group had a higher incidence of carotid plaques (P <0.05), transient ischemic attacks (TIA; P <0.05), and strokes (P <0.05) as compared with the no-VC group. In multivariate analysis, only MACs remained independently associated with increased CIMT. CONCLUSIONS:  In patients with coronary artery disease, MACs are independently associated with increased CIMT but not with TIA or stroke. There is no relationship between the concomitant presence of mitral and aortic calcifications and carotid atherosclerosis.  

Serum biomarkers and clinical outcomes in heart failure patients treated de novo with carvedilol.

BACKGROUND: The role of inflammatory and hemodynamic stress biomarkers in heart failure (HF) patients treated de novo with beta-blockers has been poorly studied. METHODS: A total of 86 patients (age 56 ± 9 years, 81 men) with left ventricular ejection fraction (LVEF) < 40% and previously not treated with beta-blockers were initiated on carvedilol. At baseline and 12 months later we performed echocardiography, cardiopulmonary exercise testing, and determined serum levels of B-type natriuretic peptide (BNP), endothelin-1 (ET-1), C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha (TNF -a). Patients were followed up over a total period of 9 ± 3 years from baseline. RESULTS: Increased baseline CRP and its on-treatment decrease were associated with improvement of LVEF (est. coefficient per one SD: 1.6; 95% CI: -0.05,3.28; p = 0.056, and -1.80; -3.43, -0.18; p = 0.030, respectively) and diminishing of LV end-systolic volume index [mL/m2] (-6.83; -11.32; -2.34; p = 0.003, and 5.85; 1.23; -10.46; p = 0.014, respectively). Higher baseline ET-1 and on-treatment increase in TNF-a predicted frequent admissions (> 1) for cardiac complications (odds ratio per one SD: 1.98; 95% CI: 1.09-3.59; p = 0.025, and 2.07, 1.12-3.84, p = 0.021, respectively) whereas higher baseline BNP was associated with increased mortality (hazard ratio per one SD: 2.09, 95% CI: 1.26-3.45; p = 0.004). CONCLUSIONS: Serum biomarkers may have different roles in prediction of clinical outcomes among HF patients treated de novo with carvedilol.

Active tissue factor and activated factor XI in circulating blood of patients with systolic heart failure due to ischemic cardiomyopathy.

INTRODUCTION: Elevated clotting factors and thrombin generation have been reported to occur in patients with heart failure (HF). Circulating activated factor XI (FXIa) and active tissue factor (TF) can be detected in acute coronary syndromes and stable angina. OBJECTIVES: We investigated circulating FXIa and active TF and their associations in patients with systolic HF due to ischemic cardiomyopathy. PATIENTS AND METHODS: In an observational study, we assessed 53 consecutive patients, aged below 75 years, with stable HF associated with documented coronary artery disease (CAD). Atrial fibrillation, recent thromboembolic events, and current anticoagulant therapy were the exclusion criteria. Plasma TF and FXIa activity was determined in clotting assays by measuring the response to inhibitory monoclonal antibodies. RESULTS: Coagulant TF activity was detected in 20 patients (37.7%), and FXIa in 22 patients (41.5%). Patients with detectable TF activity and/or FXIa were younger, had a history of myocardial infarction more frequently, significantly higher F1+2 prothrombin fragments, larger left atrium (LA) and right ventricular diastolic diameter, and higher right ventricular systolic pressure than the remaining subjects (P ≤ 0.01 for all). Circulating FXIa was positively correlated with F1+2 levels (r = 0.69; P < 0.001). CONCLUSIONS: Circulating active TF and FXIa occurred in about 40% of patients with systolic HF due to ischemic cardiomyopathy. The presence of these factors was associated with enhanced thrombin formation. Associations between both factors and LA diameter and right ventricular parameters might suggest that TF and FXIa predispose to thromboembolic complications of HF.

Altered fibrin clot properties in patients with chronic heart failure and sinus rhythm: a novel prothrombotic mechanism.

BACKGROUND: Thromboembolic complications occur more frequently in patients with chronic heart failure (CHF) than in the general population. Formation of a compact fibrin clot resistant to lysis has been shown in arterial and venous thrombosis. OBJECTIVE: To investigate fibrin clot properties in patients with CHF. METHOD: Plasma clot permeability, compaction, turbidity and fibrinolysis were assessed in 36 consecutive patients with stable CHF (30M, 6F; aged 64+/-10 years, left ventricular ejection fraction (LVEF) 34.9+/-6.7%) and 36 controls matched for age, sex, cardiovascular risk factors and medication. Exclusion criteria were LVEF >40%, anticoagulant therapy, previous thromboembolic events, atrial fibrillation. RESULTS: Clots obtained from plasma of patients with CHF had 23% lower clot permeability (p<0.0001), 13% less clot compaction (p<0.001), 15% faster fibrin polymerisation (p<0.0001) and tended to have prolonged fibrinolysis time (p=0.1) compared with controls. C-reactive protein and fibrinogen were associated inversely with clot permeability (R(2)=0.84, p<0.0001 and R(2)=0.79, p<0.0001, respectively) and positively with fibrinolysis time (R(2)=0.88, p<0.0001 and R(2)=0.80, p<0.0001, respectively) in patients with CHF. Plasma thrombin-antithrombin complex concentrations were inversely correlated with clot permeability (R(2)=0.88, p<0.0001) and positively with fibrinolysis time (R(2)=0.91, p<0.0001). Left atrium diameter, but not LVEF, correlated with fibrinolysis time (R(2)=0.61, p=0.027). CONCLUSIONS: Patients with CHF with sinus rhythm are characterised by faster formation of compact plasma fibrin clots, which might predispose to thromboembolic complications.

Comparison of aortic pulse wave velocity measured by three techniques: Complior, SphygmoCor and Arteriograph.

BACKGROUND: New 2007 European Society of Hypertension guidelines recommend measuring arterial stiffness in patients with arterial hypertension, suggesting a carotid-femoral pulse wave velocity over 12 m/s as an estimate of subclinical organ damage. Considering this cutoff point, it is worth exploring whether or not there are significant differences in results obtained using various techniques for measuring aortic pulse wave velocity. The aim of the study was to compare aortic pulse wave velocity measurements using Complior, SphygmoCor, and Arteriograph devices, and to assess the effect of pulse wave transit time and traveled distance on pulse wave velocity values. METHODS: Aortic pulse wave velocity was measured on a single visit, using these devices, in randomized order, in a group of 64 patients with grade 1 or 2 arterial hypertension. RESULTS: Aortic pulse wave velocity measured using Complior (10.1 +/- 1.7 m/s) was significantly higher than that obtained using SphygmoCor (8.1 +/- 1.1 m/s) or Arteriograph (8.6 +/- 1.3 m/s). No differences were noted between pulse wave velocity measurements using SphygmoCor and Arteriograph. Between-method comparison revealed that differences in traveled distance were significant: Complior versus Arteriograph [0.09 m, Confidence interval (CI): 0.08-0.12 m, P < 0.05], Complior versus SphygmoCor (0.15 m, CI: 0.13-0.16 m, P < 0.05), Arteriograph versus SphygmoCor (0.05 m, CI: 0.03-0.07 m, P < 0.05). No between-method differences were found for transit times. CONCLUSION: Differences in pulse wave velocity obtained by compared devices resulted primarily from using various methods for measuring traveled distance. It appears reasonable to establish uniform principles for the measurement of traveled distance. Because a large number of prognosis/survival studies used direct distance between carotid and femoral sites of pulse wave recording, this distance should be mostly recommended.