John Zarifis

Fibrin d-Dimer and β-Thromboglobulin as Markers of Thrombogenesis and Platelet Activation in Atrial Fibrillation Effects of Introducing Ultra–Low-Dose Warfarin and Aspirin

BACKGROUND Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoagulable or prothrombotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional warfarin, and aspirin. (300 mg) therapy on thrombogenesis and platelet activation in AF. METHODS AND RESULTS We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomization to either 1 mg warfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) with samples taken 2 and 6 weeks later. Pretreatment results were compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-TG and D-dimer levels in patients with AF were elevated compared with those of control subjects (P < .001). In phase 1, there were no significant changes in median levels of fibrin D-dimer or beta-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median beta-TG at 6 weeks (P = .025) and a sequential reduction in median D-dimer levels at 2 (P = .001) and 6 (P < .001) weeks compared with baseline levels. CONCLUSIONS Patients with AF have increased intravascular thrombogenesis and platelet activation compared with patients in sinus rhythm. Introduction of ultra-low-dose warfarin (1 mg) or aspirin 300 mg does not significantly alter these markers, although conventional warfarin therapy reduces beta-TG and fibrin D-dimer levels. This is consistent with the beneficial effect of full-dose warfarin in preventing stroke and thromboembolism in AF and suggests that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.

Ambulatory Blood Pressure Monitoring in Atrial Fibrillation

Ambulatory blood pressure monitoring (ABPM) devices are increasingly used in the assessment of hypertension, but patients with atrial fibrillation are usually excluded because device accuracy in this patient group is unproved. The present study investigates the clinical use of the Spacelabs 90207 oscillometric ABPM device in outpatients with chronic atrial fibrillation and suggests that such devices can be used in clinical practice to assess blood pressure in stable outpatients with chronic atrial fibrillation.

An 8-year follow-up study of acute admissions with heart failure in a multiethnic population

In 1994, we reported a cross‐sectional survey of acute heart failure admissions to a city centre hospital serving a multiethnic population and found ethnic differences in aetiological factors and short‐term (in‐patient) mortality. We analysed long‐term mortality data for this original survey cohort after 8 years’ follow‐up. At 8 years’ follow‐up, the total mortality was 90.5% amongst Europeans and 87.0% amongst non‐Europeans (log rank test, P=0.0705). The non‐European patients had significantly better survival at all time points until 6 years, after which the survival curves start to converge. In univariate analysis, age <75.6 years (that is, the median age of the whole cohort), use of beta‐blockers, use of ACE inhibitors, and absence of atrial fibrillation were significantly associated with increased survival. In addition, patients who had had an echocardiographic examination had significantly prolonged survival when compared to those who did not. Using a Cox multiple regression analysis, age, renal impairment, atrial fibrillation, absence of echocardiography, absence of beta‐blockers or ACE inhibitor use (and not ethnicity) remained significant predictors of mortality at 8 years. While this follow‐up study has suggested that survival following admission for acutely decompensated heart failure is not different between different ethnic groups when corrected for age, it is clear from the younger age of heart failure patients from ethnic minority groups and the relatively high prevalence, that the burden of heart failure is greater in these populations. Future observational and therapeutic trials in heart failure should include sufficient numbers of participants from ethnic minority groups to ensure that the results can be applied to the population at risk.

Hormone replacement therapy and cardiovascular risk : the cardiovascular physicians' viewpoint

Abstract. Sufficient evidence has accumulated showing that hormone replacement therapy (HRT) does protect against cardiovascular disease in women, although data regarding the true magnitude of that protection remains incomplete. There is no evidence that HRT increases the risk of hypertension or thromboembolism, and beneficial effects have been found for plasma lipids, clotting factors and cardiovascular haemodynamics. However, the evidence is not convincing of any beneficial effect of HRT in preventing strokes, and concerns about the risk of cancer with HRT remain.

Malignant Hypertension in Association with Primary Aldosteronism

Primary aldosteronism is associated with low plasma renin levels, whilst malignant phase hypertension is generally associated with raised renin activity. These two conditions are therefore at opposite ends of the renin spectrum, so in theory their co-existence would be unusual. We describe in detail 3 cases of primary hyperaldosteronism from a disease register of 315 cases of malignant hypertension seen in one medical centre over 29 years.

Open access echocardiography. Hospital patients need open access echocardiography.

EDITOR,--We agree with C M Francis and colleagues that echocardiography is useful in patients with heart failure and that an open access service may be used successfully by general practitioners.1 Heart failure is also common among patients admitted to hospital,2 but we have noted a reluctance to use echocardiography in such patients. To investigate this further we recently …

Atrial fibrillation and stroke in patients admitted to a city centre hospital serving a multiethnic community

We read with great interest the paper by Arboix et been based in caucasian populations, and there is al. [1], who describe the clinical presentation of little or no data on AF, especially in the context of cardioembolic versus atherothrombotic cerebral inassociated stroke, in patients with AF from Afrofarction in patients with atrial fibrillation (AF) admitCaribbean or Indo-Asian populations [5]. In our ted to their hospital. survey of patients AF amongst acute medical admisMore information on patients admitted with AF sions to our city centre hospital serving a multiethnic and stroke is needed in view of the higher morbidity population of 300 000 where the ethnic mix is 25% and in-hospital mortality amongst patients with AF Indo-Asian and 11% Afro-Caribbean, 203 patients and stroke, which (as the authors point out) has with AF were admitted over a 6-month period [6]. Of previously been noted in previous studies [2,3]. these, 59 patients had a history of stroke (with 31 Nevertheless, it is often difficult to distinguish bepresenting with new-onset stroke as the main presenttween patients with preexisting AF who then have a ing symptom). Demographic information, past medistroke, or patients who develop AF de novo as a cal history and risk factors for cardiovascular events consequence of the acute event – the study by Arboix are summarised in Table 1. et al. [1] is less clear on this distinction. Furthermore, Associated cardiovascular risk factors were broadly it should not be presumed that all strokes in patient similar in both groups (Table 1); however, the with AF are cardioembolic, as some are atherothrompredominant aetiological factor for AF amongst Afrobotic (as in the study by Arboix et al. [1]) and Caribbean patients was hypertension, whilst the main importantly, some strokes are also haemorrhagic. aetiological factor for AF amongst Indo-Asian paIndeed, in the Oxfordshire Community Stroke Study, tients was ischaemic heart disease [6], in keeping AF was present in 11% of haemorrhagic strokes [4]. with known ethnic differences in cardiovascular Clearly, anticoagulant therapy in the latter group of disease patterns in the United Kingdom [7]. Apart patients would be disastrous. from age ( p50.017), there were no statistically Finally, most of the world literature on AF has significant differences between patients with AF with a stroke compared to those who did not have a stroke. Nevertheless, there was a trend towards fewer non*Corresponding author: Tel.: 144-121-507-5080; fax: 144-121-554caucasian patients ( p50.13) amongst the patients 4083. E-mail address: g.y.h.lip@bham.ac.uk (G.Y.H. Lip). with AF and stroke.