Clinical articles

Modest elevations in plasma homocysteine from either genetic or acquired causes appear to relate to cardiovascular disease on the basis of strong epidemiological evidence. We know that homocysteine can be lowered with varying doses of folic acid, with or without vitamins B6 and B12, although we do not yet know the potential cardiovascular benefit of vitamin supplementation in these subjects. Several multicentre interventional trials are underway to address this question and, until these are complete, we recommend a healthy diet high in folate replete foodstuffs. We also recommend oral folic acid supplements in some subjects with cardiovascular disease and high homocysteine, mindful that definitive evidence of benefit is lacking.

The evidence for ambulatory blood pressure measurement (ABPM) as an indispensable investigation in clinical practice is now overwhelming. For years the argument against ABPM has been based on a lack of evidence showing the technique was superior to conventional measurement in predicting outcome. There is now ample evidence from longitudinal studies that ABPM is a much stronger predictor of cardiovascular morbidity and mortality than conventional measurement.1 Moreover, though the relevance of nocturnal hypertension has been a controversial topic, recent evidence has shown that a non-dipping nocturnal pattern is a strong independent risk for cardiovascular mortality.

The study aim was to compare clinic and 24-hour ambulatory blood pressure monitoring, and to determine the influence of the latter on the management of a group of patients with variable or uncontrolled blood pressure. A retrospective data analysis was carried out on patients selected from out-patient clinics at New Cross Hospital. One hundred and seventy-one patients with uncontrolled or variable blood pressure underwent 24-hour ambulatory blood pressure monitoring and 153 results were analysed.
Following ambulatory blood pressure monitoring, 56% of the patients had their treatment regimens either decreased, unaltered or did not require antihypertensive therapy. The study found 24-hour ambulatory blood pressure monitoring helps in the assessment of overall 24-hour blood pressure control of patients and may also help in the better management of difficult groups of patients.

Glucose-insulin-potassium (GIK) therapy addresses the metabolic changes of ischaemia secondary to acute myocardial infarction. These changes include elevated plasma free fatty acid concentration and glucose intolerance. A meta-analysis of trials from the pre-thrombolysis era showed a significant reduction in the number of deaths in the GIK group in comparison to placebo (16.1% vs. 21% respectively, p=0.004). High-dose GIK therapy was found to be of particular benefit.
Three randomised trials in the post-thrombolysis era have been published, with variable results. The DIGAMI study (in diabetics) and the ECLA pilot trial had positive results: in the latter there was a 60% reduction in in-hospital mortality in patients who received GIK therapy plus reperfusion. By contrast, the Pol-GIK trial was negative.
Outstanding questions include the usefulness of GIK therapy and beta blockade in the presence of thrombolysis or primary angioplasty. GIK therapy and beta blockade might act in complementary fashion to antagonise the metabolic changes of ischaemia while thrombolysis or angioplasty improve early reperfusion and limit infarct size. Patients with acute coronary syndrome might benefit more from GIK therapy since they have some coronary flow.

A significant left main coronary artery (LMCA) stenosis is an important predictor of survival in patients with coronary artery disease. In the past, percutaneous coronary intervention (PCI) was generally restricted to patients with protected left main disease; and >50% stenosis of the LMCA was a contraindication to balloon angioplasty.
In the pre-stent era, results of left main balloon angioplasty were poor. For example, in one series, in-hospital mortality was 9.1% in the elective group and 50% in the acute group. The development of coronary stenting and effective antiplatelet therapy in the 1990s stimulated renewed interest in PCI for LMCA disease. A number of studies reported good outcomes for protected LMCA lesions, though results in haemodynamically unstable patients remained poor.
The figures for a number of studies of elective PCI for unprotected left main stenosis are also described. The best documented outcomes so far are one-year actuarial survival of 89% in high-risk patients and 98% in low-risk patients.
If severe calcification is obvious on angiography or ultrasound then debulking seems sensible. The data suggest that directional coronary atherectomy alone or with stenting may be associated with reduced restenosis rates.
The use of glycoprotein IIb/IIIa inhibitors and drug-eluting stents may further improve the outlook for patients with LMCA stenosis.

The objective of this study was to describe the context, procedural outcome and long-term results of contemporary small vessel (SV) coronary artery stenting. It was set in a tertiary cardiology centre. The study was designed as a retrospective analysis of the procedural and long-term results in a consecutive series of patients undergoing implantation of an SV stent (defined as < 2.5 mm) in 1999–2000. Of the 1,130 percutaneous coronary interventions (PCIs) in the study period, 138 (12%) involved placement of SV stents. Of these interventions 58% consisted of SV stents as sole treatment. Some 69% of patients were male and their mean age was 58 years; 46% were hypertensive, 13% diabetic, 84% hypercholesterolaemic and 18% were smokers. Of these patients 54% were in anginal classes III and IV. Of the SV stents fitted, 94% were 2.5 mm and 6% were 2.0 mm. 75% of SV stents were implanted in main epicardial vessels. The mean follow-up for these patients was 17 months. Long-term symptomatic benefit was achieved in 76%. The major adverse cardiac events (MACE) rate was 15%, comprising 1% acute myocardial infarction (AMI) and 14% re-PCI. There were no deaths. In conclusion, SV stenting in the modern era, in an unselected series of patients, is performed in 12% of PCI procedures. It comprises the sole treatment in 58% of these interventions. The majority of SV stents are 2.5 mm and are placed in main coronary arteries. Procedural and long-term results are excellent. These data may inform the choice of treatment for patients with SV disease and may be useful in planning studies in stenting SVs.

The mode of action of non-steroidal anti-inflammatory drugs and the role of the cyclo-oxygenase enzymes COX1 and COX2 and their inhibitors is described. These can have potentially serious effects on the cardiovascular and renal system which are discussed.
The alternative, widely-prescribed analgesic, paracetamol, is also discussed, as are two theories ‘confounded by indication’ and ‘protopathic bias’ to help explain why paracetamol is sometimes described as being linked to asthma and upper gastro-intestinal damage, both effects not expected from a knowledge of its mode of action.

Amiodarone is a potentially hazardous drug indicated for atrial and ventricular arrhythmias. The purpose of the audit was to assess the risk associated with amiodarone therapy and identify measures to improve patient safety. The setting was a rural practice with 13,000 patients in Lanark, Scotland. A computer search identified 16 patients (11 male, five female) receiving amiodarone. The mean age was 74 years (range 61–89 years).
Action taken was raising doctor awareness and systematic biochemical and clinical review. Results showed that, in spite of substantial mortality and morbidity prior to the audit, there was no effective practice monitoring system for amiodarone therapy. The prevalence of clinical hypothyroidism and hyperthyroidism (29%) and ‘silent’ biochemical thyroid dysfunction (14%) exceeded published estimates (14–18% and 10% respectively). Although standards improved for biochemical monitoring, increasing awareness of the need for close surveillance did not appear to change the practice of some of the general practitioners (GPs), notably the clinical examination of pulse and blood pressure.
The audit demonstrates a need for a more systematic approach to amiodarone monitoring. Recommenda-tions include enhancements to the patient information leaflet, the development of local protocols and patient involvement in quality improvements including improved communication, patient-held record cards, better quality follow-up information, and more effective reporting systems.

There is strong evidence to support a causal relationship between the level of circulating plasma cholesterol and the risk of clinically overt coronary heart disease (CHD) events. Current UK guidelines recommend reductions of total cholesterol levels to below 5.0 mmol/L. Statins remain the drugs of first choice for reducing low-density lipoproteins (LDL). Rosuvastatin has already been approved in the Netherlands and is likely to become more widely available in the next year. It has a potent effect in lowering LDL and it also appears to raise high-density lipoproteins (HDL). It has a similar safety profile compared with other statins.
Cholesterol absorption inhibitors are a new treatment option for the management of hypercholesterolaemia. Ezetimibe, the first drug in this class, has recently been approved for use in the US and Germany. It selectively inhibits the uptake of dietary and biliary cholesterol at the level of the enterocyte. The site of action of ezetimibe may be the ‘sterol permease’ transport protein. As monotherapy, the role of ezetimibe appears limited at present. However, in combination with a low-dose statin, significant reductions in plasma LDL levels are seen. It may also be a useful agent for patients with homozygous familial hypercholesterolaemia.

The success of developments in heart transplantation has given women recipients the opportunity to have children. The first successful pregnancy in a patient who had received a heart transplant was reported by Lowenstein et al. in 1988.1 The cardiovascular effects of pregnancy demonstrate the durability of transplanted hearts. We report a successful pregnancy in a 20-year-old patient who had previously had a heart transplant; we also discuss the management of such patients.