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Recent papers on cardiovascular medicine

Dr Rubin Minhas gives a personal take on recent cardiovascular papers that have caught his eye

Dr Rubin Minhas gives a personal take on recent cardiovascular papers that have caught his eye

Is BMI or waist circumference a better MI predictor?

The paper:

Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet 2005; 366:1640-1649

Method:

This study followed the original INTERHEART study by the same research team led by Professor Salim Yusuf. Although there has been epidemiological data describing the significance of the various indices of body fat for many years, most studies have been small and often unconvincing. This study was conducted on 27,000 patients across 52 countries. Although there are still confounding factors in its case control design, there is statistical significance. The use of acute MI as the outcome measure might limit the transference of the findings to all cardiovascular disease, particularly as heterogeneity has been found with respect to cardiovascular disease outcomes in different groups, but this is not a major criticism.

Results:

Waist-to-hip ratio shows a graded and highly significant association with MI risk worldwide that is superior to both BMI and waist circumference. The authors suggest reliance on BMI has underestimated the impact of obesity on cardiovascular health.

Conclusion:

The argument for moving to waist measurements of obesity is established, although we still need to establish reference ranges and agree the best measure to adopt.

What I am going to do:

Incorporate the consideration of body fat distribution in addition to BMI when evaluating cardiovascular risk.

Does 'metabolic syndrome' aid cardiovascular risk prediction?

The paper:

Clinical value of the metabolic syndrome for long-term prediction of total and cardiovascular mortality: prospective, population based cohort study. BMJ 2006; 332:878-882

Method:

The design of this prospective population-based cohort study is beyond reproach. The authors tested two definitions of metabolic syndrome and, where waist circumference data was not available, a BMI proxy was adopted. The metabolic syndrome was then compared with established cardiovascular risk factors to determine whether any further predictive value was present.

Results:

Based on one of the definitions, after 15 years there seems to be a small predictive benefit. The strength of this relationship is tenuous and the use of Framingham cardiovascular risk scoring would have been more desirable. The conventional risk factors employed by the authors did not include HDL which would reduce the predictive accuracy of Framingham scoring.

Conclusion:

The findings suggest metabolic syndrome has little (if any) value in predicting heart disease but is more useful as a predictor of diabetes.

What I am going to do:

Consider metabolic syndrome as a pointer to a pre-diabetic state with central obesity prompting a check for raised blood pressure, dyslipidaemia and impaired glucose handling.

How does a very high dose of statin affect atheroma?

The paper:

Effect of very high-intensity statin therapy on regression of coronary atherosclerosis. The ASTEROID trial. JAMA 2006;295:1556-65

Method:

This was essentially an observational study as there was no comparator. Patients were started on a high dose of rosuvastatin and intravascular ultrasound was used to measure changes in coronary atheroma. The manufacturer of the study drug funded the trial.Results: In patients with evaluable lesions there was a reported net regression in atheroma. Only 'evaluable lesions' were analysed, not intention to treat.

Conclusion:

The study design was weighted towards demonstrating a reduction in atheroma. Recent studies with other statin agents have not demonstrated regression. The dose of the study drug was high and is not routinely recommended for primary care while the outcomes measured were surrogate markers for coronary heart disease rather than clinical outcomes.

What I am going to do:

Atherosclerosis can progress and regress so the findings of regression are not entirely new and this study did not measure clinical outcomes. Despite the publicity created around this trial by the manufacturer, simvastatin still firmly remains the treatment of choice.

How useful are JBS 2 recommendations for treating cardiovascular disease?

The paper:

JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. British Cardiac Society; British Hypertension Society; Diabetes UK; HEART UK; PCCS; Stroke Association. Heart 2005; Suppl 5:v1-52

Method:

No formal methodology was employed. Draft recommendations were produced and circulated to key members of the authoring organisations. It is produced by a number of professional societies that represent different special interest groups and health care professions. Many of the authoring organisations receive funding from the pharmaceutical industry.

Results:

A very late (three years overdue), very long (52 pages) and very detailed guideline that attempts to address all atherosclerotic cardiovascular disease and the full spectrum of multifactorial risk factor assessment. There are some useful algorithms for managing impaired glucose tolerance and some soon-to-be-updated algorithms from the British Hypertension Society. Where the ABCD algorithm is presented it is reassuring to see that ACE inhibitors precede the angiotensin receptor antagonists.There appear to be several errors in the blood pressure and lipid targets specified and they often contradict each other. Similarly the evidence base for how recommendations have been developed is not clear and patients' involvement is lacking.

Conclusion:

Applying a guideline validation tool, this did not score very well mainly because of the lack of disclosure of conflicts of interest and the rather opaque production methodology. Many of the far-reaching recommendations and conclusions are without evidence.

What I am going to do:

With regard to hypertension, I will await the updated joint NICE/ BHS guidance. The algorithms on managing impaired fasting glycaemia and impaired glucose tolerance are worthwhile using in clinical practice. The lipid targets are not supported by evidence and would increase the proportion of patients taking proprietary statins so I will continue to use 5mmol/l for total cholesterol and 3mmol/l for LDL cholesterol.

Can we trust trials on hypertension?

The paper:

Recent trials in hypertension: compelling science or commercial speech? JAMA 2006; 295; 1704-6

Method:

This was an editorial in the Journal of the American Medical Association.

Results:

The best editorial review of hypertension written in the last five years and certainly the one paper you must read of all those I have reviewed here. The authors describe how the marketing of trials can lead to treatment recommendations that do not really address patients' clinical needs and can form the basis of equally dubious treatment recommendations in clinical guidelines ­ as illustrated by several of the other papers reviewed here. The role of industry-initiated trials is discussed (the ones you read about via the newspapers, sponsored meetings or are handed by drug reps) and how often the logical treatment comparisons have not been tested. The logic supporting recent trials such as LIFE, ASCOT and so on is demolished. The ALLHAT study is reviewed and, in particular, the role of diuretics as unsurpassed first-line treatment is highlighted. The authors point out that most 'new' drugs haven't been tested against established drugs like diuretics but against ?-blockers, which have long been suspected as inferior to other antihypertensives in relation to CHD prevention.

Conclusion: Not all that glitters is gold. Trials sponsored by the manufacturer of the study drug can have a strong marketing role.

What I am going to do:

The bottom line clinical message is that getting the blood pressure down is the aim. The evidence base supports diuretics as a good place to start and, in many cases, several drugs will eventually be needed.

Rubin Minhas is a GP in Gillingham, Kent ­ he is chair of the cardiovascular working group of the South Asian Health Foundation and a standing member of NICE's independent technology appraisal committee

Competing interests None declared

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