Clinical articles

The efficacy and safety of once- or twice-daily immediate-release (IR) fluvastatin 40 mg were compared with those of the extended-release (XL) formulation of fluvastatin 80 mg every night (qpm), which facilitates sustained drug delivery. Patients (n=442) with primary hypercholesterolaemia (Fredrickson types IIa and IIb) were randomised to the three treatment groups in the ratio 1:1:1. Active treatment was administered for 24 weeks, following a four-week placebo/dietary lead-in period.
At week 24, the mean reduction in low density lipoprotein cholesterol levels in patients treated with fluvastatin XL 80 mg every night (qpm) (-33.5%) was significantly greater than in the fluvastatin IR 40 mg every night (qpm) group (-23.2%; p<0.001), and similar to the reduction for patients treated with fluvastatin IR 40 mg twice-daily (bid) (-31.4%). Significant and dose-related alterations in other lipid variables were also apparent, particularly for high density lipoprotein cholesterol (10.2% increase) and apolipoprotein A1 and B levels (+11.5% and -24.2%, respectively) in the fluvastatin XL 80 mg qpm group compared with the fluvastatin IR 40 mg qpm group (all p<0.001). Mean triglyceride levels decreased by 14.6% in the fluvastatin XL 80 mg qpm group. Adverse events were generally mild, with no differences in frequency across the groups. Fluvastatin XL 80 mg qpm is a safe and effective lipid-lowering treatment for patients with type II hypercholesterolaemia.

One of the main targets of current research in cardiology is a diagnostic modality able not only to identify vulnerable atherosclerotic lesions but also to monitor the effects of therapeutic interventions on plaque composition. Most of the currently available techniques identify luminal diameter or stenosis, wall thickness or plaque volume, but are not capable of recognising vulnerable plaques that are prone to rupture. Thermography is a new technique which provides insight into the local inflammatory process within the atherosclerotic plaque. In this review we will present in detail the developments and the clinical implications of thermography in the human arterial system.

The prevalence of type 2 diabetes is set to double over the next 25 years, leading to substantial morbidity and mortality, particularly from macrovascular diabetic complications. Pre-diabetic dysglycaemia, characterised by impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), is associated with an increased risk of developing both type 2 diabetes and cardiovascular disease. IGT and IFG appear well before type 2 diabetes is diagnosed, thereby presenting an opportunity for intervention to reduce the future burden of diabetes and cardiovascular disease. Intensive lifestyle interventions are effective in preventing or delaying diabetes but are difficult to sustain long term. Intervention trials with pharmacological agents, e.g. the Diabetes Prevention Program (DPP) with metformin, and the STOP-NIDDM study with acarbose, have demonstrated significant decreases in the risk of progression to type 2 diabetes in populations with IGT. Moreover, preliminary evidence with these agents supports a possible beneficial effect on cardiovascular outcomes.

Recent trials have broadened the evidence base for statin use. It has now been documented that these drugs are effective agents not only in the general at-risk population, but also in the primary and secondary prevention of coronary heart disease in type 2 diabetics and in the elderly. The Heart Protection Study demonstrated the benefits of statin therapy in diabetics free of vascular disease, regardless of initial low-density lipoprotein (LDL) cholesterol level. Age is no longer a barrier to treatment, as revealed in the Prospective Study of Pravastatin in the Elderly at Risk, a trial which found that even a relatively brief period of statin therapy in elderly patients can result in a 19% reduction in the risk of a coronary event.
Statins have the ability to lower the plasma concentration of all apoB-containing lipoproteins. This may help explain their clinical efficacy in diabetics who generally have unremarkable LDL-cholesterol levels. Most currently available statins are also able to induce a modest (5% to 10%) rise in high-density lipoprotein cholesterol, an effect that appears distinct from LDL lowering. This broadens their use to subjects with a variety of problems such as the metabolic syndrome and insulin resistance.
The success of large-scale trials in coronary heart disease contrasts with the abundant evidence of under-treatment, even in high-risk groups. Thus the greatest need, at present, is to close the gap between the principles and practice of coronary disease prevention.

Treatment to reduce blood pressure is effective in preventing and slowing the progression of the vascular complications of diabetes. Recent studies have suggested that use of antihypertensives that inhibit the renin-angiotensin system may have particular benefit in patients with type 2 diabetes in terms of cardiovascular and renal protection. Present practice is to use angiotensin-converting enzyme (ACE) inhibitors as first-line agents, with angiotensin II receptor antagonists (AIIAs) as back-up drugs in the event of side effects or intolerance. The findings of recent trials with AIIAs, however, suggest that they are an equivalent class of drugs to the ACE inhibitors from the point of view of renal profile and that their better side-effect profile could also make them suitable first-line drugs for patients with microalbuminuria and overt nephropathy.

The British Hypertension Society (BHS) has recently published its latest guidance for the management of hypertension, BHS-IV.1,2 This article summarises these recommendations and discusses the main features of the new guidance.

Percutaneous treatment of bifurcation coronary lesions is less successful than treatment of non-bifurcation lesions, with a higher incidence of side branch occlusion and restenosis.
The ‘crush technique’ was developed to ensure complete coverage of the ostium of the side branch, where restenosis frequently occurs. Drug-eluting stents are deployed in both side and main branches. The main branch stent crushes the side branch stent against the wall of the main vessel. The ‘reversed crush’ is used when the side branch result is unsatisfactory following stenting of the main branch, or when a 6F guiding catheter is needed.
The ‘skirt technique’ was designed to treat pseudobifurcation lesions (lesions in the main branch which are immediately proximal to a bifurcation). It involves sandwiching two balloons in one stent.
Preliminary results using the crush technique in 35 patients show angiographic success in all lesions.

Echocardiography remains the ‘gold standard’ for the objective assessment of left ventricular systolic function. Even with the high prevalence of left ventricular systolic dysfunction, echocardiography is not universally available within UK primary care, despite the fact that the condition is predominantly managed within this arena.
We describe a service within one Primary Care Trust, where general practitioners and nurses refer patients who are suspected of having, or who are at high risk of developing heart failure, for a clinical assessment and an echocardiogram. Following this, a treatment plan is formulated and those with systolic dysfunction are followed up by a heart failure nurse. She ensures that the treatment regimen is adhered to and that the correct physiological and biochemical monitoring takes place.
In our study we found that of those referred, only 33% had evidence of left ventricular systolic dysfunction, with 62% showing normal function. Of those patients with left ventricular systolic dysfunction, 86% required a significant change in their medication. Three months after the assessment, using the ‘Minnesota Living with Heart Failure Questionnaire’, considerable improvement was noted in the quality of life of patients with left ventricular systolic dysfunction. This paper suggests that there is considerable scope for improvement in the management of chronic heart failure.

The secondary prevention of coronary heart disease (CHD) is a recognised priority for primary care and is a fundamental part of the published National Service Framework (NSF). The majority of patients receive statins to reduce their total cholesterol (TC) and low-density lipoprotein chol-esterol (LDL-C) levels. The NSF set out targets for both TC and LDL-C. This study was designed to investigate the applicability of these targets in a real-life setting. One hundred and ten patients aged under 75 with established CHD were screened and their lipids measured. Eighty (73%) were on a statin. Mean TC was 6.3 mmol/L before treatment and 4.8 mmol/L after. Of these 80 patients, 46 (58%) had a TC below 5.0 mmol/L. Only 39% of patients met the stricter criterion of less than 5.0 mmol/L and a 25% fall in TC. No patient whose pre-treatment TC was below 5.0 mmol/L had reached a 25% reduction as well. The use of a threshold and a percentage may be potentially confusing to GPs and reduce the implementation of these targets.

In patients presenting with persistent hoarseness due to left recurrent laryngeal nerve (LRLN) palsy and an abnormal left hilum on chest radiographs, a major cause is bronchogenic carcinoma. We describe two cases presenting with such a combination of symptoms and signs in whom a diagnosis of bronchogenic carcinoma was suspected. In each case, the LRLN palsy was in fact due to direct compression of the nerve by an aortic aneurysm.