Angiogenesis, thrombogenesis, endothelial dysfunction and angiographic severity of coronary artery disease.

Background: Thrombogenesis, angiogenesis, and endothelial damage/dysfunction are components in the pathogenesis of atherosclerosis.

Objective: To investigate the relation of these variables to atherosclerotic disease severity and the possible interrelations between the three.

Methods: 111 patients attending for coronary angiography were studied (85 male, 26 female; mean (SD) age, 61.

Is the hypercoagulable state in atrial fibrillation mediated by vascular endothelial growth factor?

Background And Purpose: Tissue factor (TF; an initiator of coagulation) and vascular endothelial growth factor (VEGF; a marker of angiogenesis) are involved in the hypercoagulable state associated with malignancy. We investigated their roles in chronic atrial fibrillation (AF), a condition also associated with increased risk of stroke and thromboembolism, as well as a prothrombotic or hypercoagulable state.

Methods: We studied 25 patients with AF (20 men; mean+/-SD age, 62+/-13 years) who were compared with 2 control groups in sinus rhythm: 30 healthy control subjects (17 men; mean age, 60+/-9 years) and 35 patient control subjects with coronary artery disease (CAD; 27 men; mean age, 60+/-12 years).

Effects of enalapril and losartan on circulating adhesion molecules and monocyte chemotactic protein-1.

At least four independent studies in different clinical settings showed that angiotensin-converting enzyme inhibitors (ACE-Is) such as enalapril effectively decrease plasma levels of circulating adhesion molecules (cAMs). To examine whether this effect may be mediated by the decreased action of angiotensin, we compared the effects of enalapril with the direct angiotensin-II antagonist, losartan, on plasma levels of cAMs, and monocyte chemotactic protein-1 (MCP-1). In a randomized trial, we recruited 32 untreated patients (19 male, aged 59+/-13 years) with hypertension, who received either enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day) at equipotent doses.

Abnormal low-density lipoprotein subfraction profile in patients with untreated hypertension.

Background: Low-density lipoprotein (LDL) consists of a heterogeneous group of particles of varying size and electrophoretic mobility. A predominance of small, more mobile particles is a risk factor for cardiovascular disease.

Aim: To investigate the hypothesis that untreated patients with essential hypertension in the absence of vascular disease may exhibit abnormalities of LDL subfractions.

Plasma von Willebrand factor, fibrinogen and soluble P-selectin levels in paroxysmal, persistent and permanent atrial fibrillation. Effects of cardioversion and return of left atrial function.

Background: Atrial fibrillation is associated with increased risk of stroke and thromboembolism, possibly by conferring a prothrombotic or hypercoagulable state. However, it is unclear whether or not this differs in the clinical subgroups of chronic atrial fibrillation patients, that is, in those with paroxysmal, persistent or permanent atrial fibrillation. We therefore hypothesized that: (i) there are differences in the prothrombotic state between these patients; and (ii) reduction in indices of hypercoagulability would follow elective electrical cardioversion of persistent atrial fibrillation and the return of left atrial function.

Dyslipidaemia in patients with malignant-phase hypertension.

Low-density lipoprotein (LDL) consists of a heterogeneous group of particles of differing size, density and electrophoretic mobility, smaller particles being more atherogenic. A high proportion of small LDL particles is an independent risk factor for cardiovascular disease. We hypothesized that patients with malignant phase hypertension (MHT), the most severe form of hypertension, would demonstrate a more atherogenic LDL subfraction profile than either non-malignant hypertension (NMHT) or normotensive controls.

Effect of antihypertensive therapy using enalapril or losartan on haemostatic markers in essential hypertension: a pilot prospective randomised double-blind parallel group trial.

To test the hypothesis that the hypercoagulable state in hypertension is significantly altered by anti-hypertensive therapy, we conducted a pilot prospective randomised double-blind trial of 40 untreated hypertensive patients (30 males, mean age 59 years) who were treated with either enalapril (10-20 mg per day) or losartan (50-100 mg per day) for 8 weeks. Thrombogenicity was assessed by measurement of plasma fibrinogen, soluble P-selectin (an index of platelet activation), plasminogen activator inhibitor 1 (PAI-1, an index of fibrinolysis) and von Willebrand factor (an index of endothelial dysfunction). Baseline von Willebrand factor alone was significantly higher in untreated hypertensive patients compared to controls (P<0.

Effect of acute exercise on the raised plasma fibrinogen, soluble P-selectin and von Willebrand factor levels in chronic atrial fibrillation.

Background: There is increasing evidence that chronic atrial fibrillation (AF) is associated with a prothrombotic or hypercoagulable state.

Hypothesis: This study was undertaken to determine whether short-term exercise in patients with chronic AF would shift the overall hemostatic balance toward a more prothrombotic state with a reduction in fibrinolytic potential.

Methods: We recruited 20 patients (13 men; mean age 65 years +/- 11 standard deviation [SD]) with chronic AF who were not treated with antithrombotic therapy and exercised them to exhaustion using a multistage treadmill exercise (standard Bruce) protocol.

Plasma levels of vascular endothelial growth factor and its soluble receptor (SFlt-1) in essential hypertension.

In this study of 27 untreated patients with uncomplicated essential hypertension, we report on elevated plasma levels of vascular endothelial growth factor and its soluble receptor Flt-1 compared with healthy controls; these increased levels are reduced by the treatment of hypertension. This raises the possibility that abnormal angiogenesis may contribute to the pathogenesis of complications related to hypertension and merits exploration in larger studies.

Effects of fixed low-dose warfarin, aspirin-warfarin combination therapy, and dose-adjusted warfarin on thrombogenesis in chronic atrial fibrillation.

Background And Purpose: Recent clinical trials have established that adjusted-dose warfarin (international normalized ratio [INR] 2.0 to 3.0) is highly effective in the reduction of ischemic stroke in patients with nonvalvular atrial fibrillation (AF).

Matrix metalloproteinase-9 and tissue inhibitor metalloproteinase-1 levels in essential hypertension. Relationship to left ventricular mass and anti-hypertensive therapy.

To test the hypothesis that the activity of enzymes degrading the extracellular matrix in hypertensive patients are abnormal, and that the treatment of hypertension will normalise these abnormalities, we measured the serum levels of metalloproteinase MMP-9, and its inhibitor, tissue metalloproteinase inhibitor (TIMP-1). Thirty-two patients with untreated hypertension (BP 168/96) had significantly lower levels of both MMP-9 and TIMP-1 when compared to 24 matched normotensive controls (BP 123/80) (P<0.001).

Effect of degree of blood pressure on the hypercoagulable state in chronic atrial fibrillation.

To investigate the hypothesis that higher levels of blood pressure would further promote the hypercoagulable state in atrial fibrillation (AF) by increasing the degree of hemostatic abnormalities, we studied 82 consecutive patients with chronic nonvalvular AF who were not taking antithrombotic therapy. Patients with AF had higher levels of plasma fibrin D-dimer, von Willebrand factor, and fibrinogen than controls in sinus rhythm, and no differences between tertiles of either systolic, diastolic, or mean blood pressure were found, suggesting other mechanisms may be contributing to the hypercoagulable state in AF.

A cross-sectional and diurnal study of thrombogenesis among patients with chronic atrial fibrillation.

Objectives: First, we sought to determine whether there is diurnal variation in hemostatic factors related to thrombogenesis and hypercoagulability among patients with chronic atrial fibrillation (AF). Second, we sought to determine whether levels of soluble thrombomodulin (sTM), a marker of endothelial function, or soluble P-selectin (sP-sel), an index of platelet activation, are altered in patients with AF as compared with subjects in sinus rhythm.

Background: Atrial fibrillation is associated with an increased risk of stroke and thromboembolism and is known to confer a hypercoagulable state, with abnormalities of thrombosis, platelet activation and endothelial cell function.

Atrial fibrillation, thromboembolism and antithrombotic therapy.

Atrial fibrillation is the commonest sustained disorder of cardiac rhythm and is associated with increased risk of stroke and thromboembolic events. Warfarin (dose-adjusted to a target INR of 2.0-3.

Indexes of hypercoagulability measured in peripheral blood reflect levels in intracardiac blood in patients with atrial fibrillation secondary to mitral stenosis.

Systemic thromboembolism is a major complication in patients with mitral stenosis, especially in those who have atrial fibrillation (AF). It has been suggested that there may be increased regional left atrial coagulation activity in such patients, despite normal systemic coagulation activity on peripheral blood sampling. Our aim was to investigate whether there were significant differences between intracardiac versus peripheral indexes of hypercoagulability in 25 patients (5 men; mean age 60 years) with mitral stenosis who were undergoing percutaneous balloon mitral valvuloplasty and who were all in chronic AF.

Does hypertension confer a hypercoagulable state?

Although the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke and myocardial infarction) are paradoxically thrombotic rather than haemorrhagic. In keeping with Virchow's triad, patients with hypertension do demonstrate abnormalities of vessel wall (endothelial dysfunction or damage), blood constituents (abnormal levels of haemostatic factors, platelet activation and fibrinolysis) and blood flow (rheology and flow reserve), suggesting that hypertension does confer a prothrombotic or hypercoagulable state. These abnormalities appear to be related to target organ damage and long-term prognosis and are altered by treatment.

Case report: fatal verapamil overdosage despite intensive therapy and use of high dose intravenous calcium.

Although the initial treatment of choice in calcium antagonist poisoning is calcium, there has been controversy over the optimal regime of its administration. The administration of prolonged or regular, high doses of calcium has been suggested. We report a fatal case of verapamil overdosage which did not respond to intensive therapy and very high doses of intravenous calcium, despite achieving extremely high serum calcium levels.