Christopher R. Gibbs

Abnormalities of Hemorheological, Endothelial, and Platelet Function in Patients With Chronic Heart Failure in Sinus Rhythm Effects of Angiotensin-Converting Enzyme Inhibitor and β-Blocker Therapy

BackgroundTo investigate the hypothesis that abnormalities of hemorheological (fibrinogen, plasma viscosity), endothelial (von Willebrand factor [vWF]), and platelet (soluble P-selectin) function would exist in patients with chronic heart failure (CHF) who are in sinus rhythm, we conducted a cross-sectional study of 120 patients with stable CHF (median ejection fraction 30%). We also hypothesized that ACE inhibitors and &bgr;-blockers would beneficially affect the measured indices. Methods and ResultsIn the cross-sectional analysis, plasma viscosity (P =0.001), fibrinogen (P =0.02), vWF (P <0.0001), and soluble P-selectin (P <0.001) levels were elevated in patients with CHF compared with healthy controls. Women demonstrated greater abnormalities of hemorheological indices and vWF than males (all P <0.05). Plasma viscosity (P =0.009) and fibrinogen (P =0.0014) levels were higher in patients with more severe symptoms (New York Heart Association [NYHA] class III–IV), but there was no relationship with left ventricular ejection fraction. When ACE inhibitors were introduced, there was a reduction in fibrinogen (repeated-measures ANOVA, P =0.016) and vWF (P =0.006) levels compared with baseline. There were no significant changes in hemorheological, endothelial, or platelet markers after the introduction of &bgr;-blocker therapy, apart from a rise in mean platelet count (P <0.001). ConclusionsAbnormal levels of soluble P-selectin, vWF, and hemorheological indices may contribute to a hypercoagulable state in CHF, especially in female patients and in those with more severe NYHA class. Treatment with ACE inhibitors improved the prothrombotic state in CHF, whereas the addition of &bgr;-blockers did not. These positive effects of ACE inhibitors may offer an explanation for the observed reduction in ischemic events in clinical trials.

Management of pericardial effusion by drainage: a survey of 10 years' experience in a city centre general hospital serving a multiracial population

The aim of the study was to determine the aetiology of large and symptomatic pericardial effusions and to review the management and subsequent outcome. A survey was done on a consecutive cases of patients who had undergone percutaneous pericardiocentesis over a 10 year period in a city centre general hospital serving a multiethnic catchment population. In all, 46 patients (24 male, 22 female; age range 16 to 90 years, mean 54 years) underwent a total of 51 pericardial drainage procedures (or attempted pericardiocentesis) between 1989 and 1998. Malignancy (44%), tuberculosis (26%), idiopathic (11%), and post-cardiac surgery (9%) were the most common causes of pericardial effusion. The most common presenting symptoms were breathlessness (90%), chest pain (74%), cough (70%), abdominal pain (61%) (presumed to be related to hepatic congestion), and unexplained fever (28%). In the 12 cases of tuberculous pericarditis, nine occurred in patients of Indo-Asian origin, and three in patients of Afro-Caribbean origin. Fever, night sweats, and weight loss were common among these patients, occurring in over 80% of cases of tuberculous pericarditis. Pulsus paradoxus was the most specific sign (100%) for the presence of echocardiographic features of tamponade, with strongest positive predictive value (100%). Although malignancy remains the most common cause in developed countries, tuberculous disease should be considered in patients from areas where tuberculosis is endemic. Percutaneous pericardiocentesis remains an effective measure for the immediate relief of symptoms in patients with cardiac tamponade, although its diagnostic yield in tuberculous pericarditis is relatively low.

Vascular endothelial growth factor and soluble P-selectin in acute and chronic congestive heart failure

Because congestive heart failure (CHF) is characterized clinically by tissue hypoxia, we hypothesized that there would be evidence of neovascularization, possibly resulting from this process. To test this, we measured levels of vascular endothelial growth factor (VEGF), associated with angiogenesis, in the plasma of patients with varying degrees of CHF (presenting acutely and in the chronic phase) and compared levels with those in healthy controls. To test the hypothesis of a link between VEGF and platelet activation and a tendency to hypercoagulability in CHF, 1,2 we also measured plasma levels of fibrinogen and soluble P-selectin, because these markers of coagulation and platelet activation have previously been shown to increase in patients with chronic CHF. 2 Our methods to testing these hypotheses were cross sectional (comparing patients with acute and chronic CHF with healthy controls), interventional (examining markers before and after successful treatment of acute CHF), and using a follow-up approach (at which time we questioned whether or not plasma markers could predict those at risk of mortality). ••• We recruited consecutive patients admitted with acute CHF secondary to impaired left ventricular systolic function, which was documented as an ejection fraction 40%, either by echocardiography, radionuclide imaging, or left ventriculography on admission, or within the previous 6 months. Patients were excluded from the study for the following criteria: concomitant acute coronary syndromes; infection or pyrexial illness; recent (3 months) myocardial infarction or stroke; unstable angina or ventricular arrhythmias; chronic and systemic illnesses including renal failure, hepatic impairment, cancer, and inflammatory connective tissue disease; and use of oral steroids or hormone replacement therapy. Baseline results from patients with acute CHF (i.e., subjects presenting acutely with severe symptomatic disease) were compared with 2 age- and gender-matched control groups; these were outpatients with chronic stable CHF in sinus rhythm (chronic CHF) and healthy control subjects recruited from among healthy hospital staff and from subjects attending the hospital for hernia repairs, varicose vein procedures, or other relatively minor operations. Subjects with CHF were classified according to the New York Heart Association (NYHA) criteria, with class I to II being no or mild symptoms and class III to IV being moderate to severe symptoms. Left ventricular ejection fraction was estimated using transthoracic M-mode echocardiography. All healthy controls had no clinical evidence of vascular, metabolic, neoplastic, diabetic, or in flammatory disease on careful history, examination, and routine laboratory tests. Blood tests were performed in patients with acute decompensated CHF between days 1 and 7 after hospital admission, and again at 3 months after standard treatment for heart failure according to local guidelines. 3 Patients were followed up for clinical end points that consisted of all-cause mortality and hospitalizations for stroke, myocardial infarction, thromboembolism, unstable angina, and revascularization for up to 6 months. Citrated plasma and serum were obtained from

Anti-oxidative properties of beta-blockers and angiotensin-converting enzyme inhibitors in congestive heart failure.

Chronic elevation of plasma catecholamines and sympathetic stimulation in chronic heart failure (CHF) leads to increased production of free radicals, and so possibly to endothelial damage/dysfunction and atheroma formation. Abnormal oxidative stress may therefore be related to some of the high mortality and morbidity in CHF. The objective of the present prospective open study was to compare the effects of β‐blockers and ACE inhibitors in relation to oxidative stress and endothelial damage in CHF.

Neither carvedilol nor bisoprolol in maximally tolerated doses has any specific advantage in lowering chronic heart failure oxidant stress: implications for β-blocker selection

We hypothesized that abnormal oxidative stress in chronic heart failure (CHF) could be related to endothelial damage and platelet activation, and that the vasodilating beta-blocker carvedilol would have beneficial effects on these processes compared with a selective non-vasodilating cardioselective beta-blocker, bisoprolol. We therefore assessed the effects of introducing carvedilol and bisoprolol in a prospective manner on indices of oxidative stress [lipid hydroperoxides (LHP)], endothelial damage [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and coagulation (fibrinogen) and their inter-relationships in stable outpatients with CHF in sinus rhythm. We recruited 46 patients [23 male; age 64 +/- 13 years (mean +/- S.D.); range 38-85 years] with CHF. Baseline levels of serum LHP (P<0.002), plasma vWf (P<0.001) and soluble P-selectin (P=0.02), but not fibrinogen (P=0.16), were higher in CHF patients compared with 22 age- and sex-matched healthy controls. After treatment for 2 months, systolic blood pressure fell in both arms of the study (both P<0.01), but there were no statistically significant (defined as P<0.01) decreases in LHP, vWf, fibrinogen or soluble P-selectin levels with either carvedilol or bisoprolol. In conclusion, patients with CHF have increased levels of plasma LHP and vWf, indicating increased oxidative stress and endothelial damage respectively. Contrary to the proposed antioxidative effects of carvedilol, initiating and titrating such therapy did not result in a reduction in levels of LHP in CHF.

Salt and cardiovascular disease: clinical and epidemiological evidence.

In particular, there is now a mass of evidence linking dietary intake of salt and blood pressure. The influence of dietary intake of salt on blood pressure has been studied extensively for animal experimental models, in epidemiological studies, in controlled clinical intervention trials and in population studies on restriction of sodium intake. Indeed, restriction of salt intake is a simple, easy, non-pharmacological way to reduce blood pressure, which is additive to drug treatment. In this review, we will examine the clinical evidence linking salt to blood pressure and the possible direct effects of salt on the cardiovascular system.

Ambulatory Blood Pressure Monitoring and Stroke More Questions Than Answers

The increasing use of ambulatory blood pressure monitoring (ABPM) devices in the investigation of hypertension has allowed detailed study of the circadian rhythm of blood pressure variability, the assessment of resistant hypertension, and the syndrome of “white coat” hypertension. The relevance of ABPM to target-organ damage and the complications of hypertension, such as heart attacks and strokes, has only recently gained prominence. There are more than 30 cross-sectional studies that have linked ABPM to hypertensive target-organ damage, including left ventricular hypertrophy (LVH),1 2 microalbuminuria,3 hypertensive retinal changes, and cerebrovascular disease.4 The majority of these studies have consistently reported that patients with an absent or reduced fall in blood pressure at night (referred to as “nondippers”) have more severe target-organ damage, including LVH5 and cerebrovascular disease,4 6 when compared with patients who demonstrate a normal nocturnal fall in blood pressure. For example, Verdecchia et al,7 in a prospective cohort of over 1100 hypertensive patients, reported higher mortality rates both in nondippers and “reverse dippers” and higher cardiovascular morbidity rates in female nondippers compared with dippers.8 In addition, Yamamoto et al9 recently reported that progressive cerebrovascular disease, including silent ischemic lesions and symptomatic stroke, was associated with a reduced nocturnal blood pressure fall in patients with a history of lacunar infarction. In a cross-sectional study of patients admitted with acute stroke (ictus <12 hours), Lip at al10 reported that such patients could generally be classed as nondippers, with higher blood pressures recorded using ABPM (but not using casual manual measurements) in black/Afro-Caribbean patients and also in patients with hemorrhagic stroke. These studies therefore suggest the potential usefulness of ABPM in epidemiological, cohort, or cross-sectional studies and the assessment of ethnic differences, stroke subtypes, and prognosis. A nondipper status …