Salt and cardiovascular disease: clinical and epidemiological evidence.
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Biomedical subjects
Publications and source records attributed to C R Gibbs.
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It is well-recognized that patients with congestive heart failure are at an increased risk of stroke and venous thromboembolism. Nevertheless, stroke, thromboembolism and myocardial infarction have generally been regarded to be end points of secondary importance in large heart failure trials, when compared with mortality or hospital readmissions. It may well have been that the incidence of thrombotic events are underestimated. The problem of thrombus formation (thrombogenesis) in heart failure may therefore be a much more significant problem than is currently recognized. The pathophysiology of thrombogenesis in heart failure could well be explained in the context of Virchow's original triad. In addition to "abnormal flow" through low cardiac output, dilated cardiac chambers and poor contractility, patients with heart failure also demonstrate abnormalities of hemostasis and platelets (that is "abnormal blood constituents") and endothelial dysfunction ("vessel wall abnormalities"). These abnormalities contribute to a prothrombotic or hypercoagulable state, which increases the risk of thrombosis in heart failure and impaired left ventricular systolic function. Some observational data are available on the role of anticoagulants in heart failure, and there is sound evidence to support the use of antithrombotic therapy in patients with heart failure and atrial fibrillation. However, there are no large-scale prospective randomized controlled trials of antithrombotic therapy in patients with heart failure who remain in sinus rhythm, although important studies are in progress. Although the results of these studies are awaited, measurement of suitable markers of thrombogenesis might prove to be valuable in identifying "high risk" patients and in determining the nature, duration and intensity of such treatment. Further information is also needed on the predictive value of various markers of hypercoagulability in patients with heart failure, the association between hemostatic variables and the severity of heart failure, and the effects of different treatments.
AIMS: To determine patterns in presentation, risk factors, management and outcome of patients with ACE inhibitor associated angioedema in one British teaching hospital. METHODS: Cases of ACE inhibitor associated angioedema in patients presenting to the City Hospital, Birmingham between 1993 and 1999 were collected and entered prospectively onto a computerised register. RESULTS: A total of 20 cases (mean age 60 years, range 42-82 years) of ACE inhibitor associated angioedema were reported (11 female and 9 male) with 65% (n=13) of patients being black/Afro-Caribbean. In 70% of cases (n=14), angioedema occurred within 4 weeks of starting therapy, although three patients presented following long-term treatment (24-48 months). ACE inhibitors were continued in 50% (n=10) patients, despite at least one documented episode of angioedema. Admission to hospital was necessary in 40% (n=8) patients, with three of these admitted to the intensive care unit, and one of these died as a result of severe laryngeal obstruction. CONCLUSIONS: ACE inhibitor related angioedema is a serious and potentially fatal complication which is relatively rare in the general population, but is more common amongst black/Afro-Caribbean patients. ACE inhibitors are frequently continued following an episode of angioedema and it is important that these episodes are minimised by prompt cessation of the drug, careful patient counselling and heightened awareness in all clinicians who prescribe this common group of drugs.
The ethnic differences in the incidence, pathophysiology and management of hypertensive disease, are particularly pertinent to the Black or Afro-Caribbean populations, who have a high prevalence of hypertension and associated complications, such as strokes and renal impairment. Our understanding of the underlying pathophysiology of hypertensive disease and the optimal treatment of hypertension in Black patients continues to evolve, especially with the introduction of new drugs and the need for prognostic data in this ethnic population. We review the management of hypertensive disease in the black population, emphasizing race-related differences in the pathophysiology of hypertension and the importance of tailored management in this group of patients, including sensible application of non-pharmacological measures with effective antihypertensive agents. For example, diuretics and calcium antagonists are suitable first-line agents in black hypertensives, whilst beta-blockers and the ACE inhibitors tend to be less effective at lowering blood pressure, due to the low renin state in these patients.
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There is limited evidence that dipyridamole is generally an effective antithrombotic agent when used alone, nor is there convincing evidence that the combination of aspirin and dipyridamole is more effective than aspirin alone, except perhaps in cerebrovascular disease. There is no consistent evidence to support the routine use of dipyridamole after coronary artery bypass grafting and in patients with occlusive peripheral vascular disease, although these remain common reasons for its use. Dipyridamole is a useful agent in 'pharmacological stress' testing in nuclear cardiology imaging and may be valuable when combined with warfarin in certain patient groups, such as those with prosthetic heart valves. When combined with aspirin, dipyridamole may be of value in the secondary prophylaxis of cerebrovascular disease, although further studies are clearly needed. In a significant proportion of cases, evidence-based medicine cannot support the current widespread continued prescription of dipyridamole in cardiological practice, but the jury is still out on cerebrovascular disease.
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