Clinical articles

The major objective for the diagnosis and treatment of hypertension should be the detection of those at increased risk of coronary heart disease (CHD) and stroke, and the reduction of this risk.

We examined the workload implications of the National Service Framework for Coronary Heart Disease and the 1999 British Hypertension Society guidelines for the management of hypertension in clinical practice. The 1998 Health Survey for England was used to estimate the proportion of the English population aged 35 to 74 years that may require antihypertensive therapy. Of 8,154 subjects with blood pressure measurements, 400 (4.9%; 95% CI 4.4 to 5.4%) with cardiovascular disease were taking antihypertensive drugs and a further 100 (1.2%; 1.0 to 1.5%) were at treatment thresholds for secondary prevention of cardiovascular disease. There were 848 (10.4%; 9.7 to 11.1%) subjects free of cardiovascular disease on antihypertensive therapy and an additional 1,083 (13.3%; 12.5 to 14.0%) were identified for treatment. We estimate that 29.8% (28.8 to 30.8%) of the English population aged 35 to 74 years were candidates for antihypertensive therapy, of which 15.3% (14.5 to 16.1%) were already being treated but only 5.4% (4.9 to 5.9%) had their blood pressure controlled. An additional 14.5% of the English population will need antihypertensive therapy and an extra 9.9 % will need to have their treatment intensified to attain the blood pressure targets set by the British Hypertension Society guidelines.

Heart transplantation is an accepted therapeutic option in selected patients with end-stage heart failure. Up to 10% of patients develop renal failure while on the waiting list for heart transplantation. Renal dysfunction is a relative contraindication to heart transplantation. In order to establish current practice in UK heart transplant centres and overall surgical outcomes for combined heart and kidney transplantation, we surveyed the eight units currently responsible for heart transplantation, all but one of which had carried out at least one combined heart and kidney transplant. We obtained outcome data from the United Kingdom Transplant organisation. We found a wide variability in the level of renal function considered a contraindication to heart transplantation, and no consensus on the criteria for combined heart and kidney transplantation. The 30-day mortality was 14% (4/28) and survival at one, three, five and 10 years was 66.5 (95% confidence interval 57.3–75.7), 50.2 (40.3–60.1), 45.6 (35.6–55.7), and 30.8 (19.2–42.4) respectively, with significant variability between centres.
A prospective, controlled trial is needed to address these issues, but such a study remains extremely unlikely in the context of the increasing scarcity of organ donors.

This study looks at how well cardiovascular risk factors were being controlled in a high-risk group of patients awaiting coronary artery bypass surgery. It shows significant short falls in the implementation of currently advocated strategies.

This article explains how general practitioners can diagnose and treat heart failure in primary care. Diagnosis is difficult and four diagnostic tests – the electrocardiogram, chest x-ray, blood test for natriuretic peptides and echocardiography – are recommended as being of particular value in confirming the diagnosis in primary care.
A six-step treatment strategy is then given advising i) confirming the diagnosis, ii) excluding other treatable causes of heart failure, iii) giving general advice to the patient, iv) starting treatment with a diuretic, v) then adding an angiotensin-converting enzyme inhibitor, and, vi) finally adding a beta blocker. A 10-point plan explaining in detail how to start beta blockers in primary care concludes the article.

Pleuritic chest pain and hypoxia – a diagnostic dilemma Sanjiv Mahadeva, Pulak Sahay, Richard V Lewis Pulmonary thromboembolism (PE) is notoriously difficult to diagnose since it commonly presents in a non-specific manner. Only 15–30% of the patients identified at post-mortem as having a massive PE have been diagnosed correctly prior to death.1,2 However, large studies have shown that certain clinical symptoms and features such as dyspnoea, tachypnoea, pleuritic chest pain with a normal chest radiograph and a low PaO2 are present in more than 90% of patients with PE.2 Clinicians in a district hospital setting have to rely on these features, especially when facilities for detailed imaging such as computerised tomography (CT) or pulmonary angiography are not available. Occasionally, certain other diseases can mimic the clinical picture of PE and lead to delay in instituting appropriate treatment. We present two patients with symptoms and clinical investigations which were highly suggestive of acute PE but who turned out to have very different diagnoses in the end.

Rapid appraisal of clinicians’ reactions to guidance from the National Institute of Clinical Excellence on use of glycoprotein IIb/IIIa antagonists for acute coronary syndromes Khaled Alfakih, Alistair Hall, Mike Robinson We conducted a postal survey of UK consultant cardiologists to assess reaction to the guidance issued by the National Institute of Clinical Excellence (NICE) on the use of glycoprotein IIb/IIIa antagonists (GPAs) for acute coronary syndromes.

A new extended-release (XL) formulation of fluvastatin has been developed for once daily treatment of primary hypercholesterolaemia. This study was designed to determine the safety and effect of fluvastatin XL 80 mg on a range of lipid parameters compared with the immediate-release (IR) formulation of fluvastatin 40 mg.
In a multicentre, double-blind study, 555 patients with primary hypercholesterolaemia (Fredrickson types IIa or IIb) were randomised to 24 weeks treatment with fluvastatin XL 80 mg or IR 40 mg, each given once daily at bedtime. The study found the least square mean reduction in LDL-C after 24 weeks treatment was 32.6% in the fluvastatin XL 80 mg group (n=312) and 23.9% in the fluvastatin IR 40 mg group (n=165), an 8.7% between-treatment difference (95% confidence interval: 6.5%, 10.9%) in favour of the XL formulation (p<0.001). A higher proportion of patients in the fluvastatin XL 80 mg group achieved ≥ 35% reductions in low-density lipoprotein cholesterol (42.3% vs. 13.3%). High-density lipoprotein cholesterol levels were increased by 9.1% and 7.0%, respectively in the XL and IR groups; median triglyceride levels fell by 19% and 13%, respectively. Tolerability was comparable in the two groups, and there were no laboratory safety concerns.
The study concluded that fluvastatin XL 80 mg once daily is safe as a starting dose and effectively lowers low-density lipoprotein cholesterol and triglyceride levels in patients with primary hypercholesterolaemia.

This study investigated the effect of orlistat on weight loss and serum lipid parameters in obese patients with hypercholesterolaemia. A total of 215 adult obese patients (body mass index ≥30 kg/m2) with hypercholesterolaemia (total plasma cholesterol ≥6.5 mmol/L or plasma low density lipoprotein cholesterol ≥4.2 mmol/L) were recruited for screening at 12 out-patient clinics in the UK. Of these, 142 patients were randomised to receive double-blind treatment for 24 weeks with orlistat 120 mg (n=71) or placebo (n=71) three times daily in combination with a mildly hypocaloric diet. Patients completing the double-blind phase (orlistat n=42, placebo n=55) were eligible to enter a further 28-week open-label phase and received orlistat 120 mg three times daily in combination with the hypocaloric diet.
Mean weight loss after 24 weeks was 4.4 kg (4.4%) in the orlistat group vs. 2.6 kg (2.5%) with placebo (p<0.01). At the end of the double-blind phase, 44.0% of orlistat-treated patients vs. 18.0% of placebo recipients had lost ≥5% of their initial body weight (p<0.001), and 7.6% vs. 4.2% had lost ≥10% (p=NS). Patients who continued on orlistat during the open-label phase had a mean weight loss of 4.97 kg (4.86%) after 52 weeks. Patients who switched to orlistat had a mean weight loss of 4.28 kg (4.23%). Orlistat was associated with significantly greater reductions than placebo in plasma total cholesterol (-10.88 + 1.36% vs. -3.25 + 1.33%; p<0.001) and LDL-cholesterol (-14.14 + 2.68% vs. -3.68 + 3.61%; p<0.05) during the double-blind phase. Despite similar weight loss at the end of the 52-week period, patients who remained on orlistat throughout the study had greater improvements in plasma lipid concentrations than patients who switched to orlistat after 24 weeks.
Orlistat, in combination with a mildly hypocaloric diet, promotes clinically meaningful weight loss and improvements in lipid concentrations in obese patients with hypercholesterolaemia.

Hypertrophic cardiomyopathy (HCM) is the commonest inherited cardiovascular disorder with a prevalence of one in 500 in the general population. It is believed to be a disease of the cardiac sarcomere and is caused by a variety of mutations in genes responsible for sarcomeric contractile proteins. It is characterised macroscopically by myocardial hypertrophy and microscopically by myocyte fibrosis and disarray. Most patients tend to present with functional limitation and symptoms such as palpitation, chest pain or syncope. The underlying mechanisms involved are complex, multiple and not yet fully understood. Further clarification of these mechanisms may enable improvements in current symptom control or the development of new avenues of therapy. A small but significant proportion of patients suffer sudden cardiac death and this can be the initial presentation of the condition. In fact, HCM is the commonest cause of sudden death among individuals below the age of 30 years. The identification of this high-risk cohort remains the most important aspect of HCM management, particularly in light of growing evidence of the effectiveness of prophylactic strategies.