Overweight, obese gain greater benefit from BP lowering
8 mars 2010
Paris, France - A new analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), looking at outcomes by body-mass index (BMI), has shown that blood-pressure-lowering therapy produced comparable risk reductions in vascular disease and stroke across the whole range of body weights .
But because overweight and obese people have a greater baseline cardiovascular risk than normal-weight individuals, they obtained the greatest benefit of all participants, say Dr Sébastien Czernichow (Faculté de Médecine SMBH, Paris, France) and colleagues in their paper published online March 8, 2010 in Hypertension.
"Obese patients have been shown to have higher levels of hypertension and higher use of antihypertensive drugs, yet their hypertension is less well-controlled," Czernichow, who is an obesity specialist, told heartwire.
Because of their higher cardiovascular risk, obese individuals are often excluded from trials of antihypertensive agents, he added. "So we did this analysis to try to clear up uncertainty about the efficacy of different BP-lowering drugs in the obese compared with normal-weight patients. We wanted to see if they reacted differently to BP-lowering drugs."
The results indicate that obese people should be treated "more aggressively" for hypertension than other people, he said. However, it remains unclear whether the effects of all BP-lowering drug classes are the same in the obese and nonobese, and this will require further research, he explained.
Consistent benefits seen across quartiles for vascular events, strokes
PROGRESS was first reported in 2001 and showed that in patients with a history of stroke, antihypertensive therapy with a combination of the ACE inhibitor perindopril and the diuretic indapamide prevented the recurrence of stroke, compared with placebo, even in those without raised blood pressure. The trial had no entry BP criteria : participants could be normotensive or hypertensive ; around half the patients did have raised BP.
Czernichow explained that he performed the BMI analysis of PROGRESS while at the George Institute, in Sydney, Australia, where he worked with the lead author of PROGRESS, Dr John Chalmers (University of Sydney, Australia), who is also senior author on the new paper.
They divided the 6105 PROGRESS participants into quartiles for BMI : <23.1 kg/m2, 23.1-25.3 kg/m2, 25.4-27.8 kg/m2, and >27.9 kg/m2.
A consistent treatment benefit was seen for protection against major vascular events across the quartiles, with similar results apparent for stroke and stroke subtypes.
Hazard ratios over five years for major vascular events and total stroke according to BMI category in PROGRESS
Absolute benefits greatest in highest BMI quartile ; target the obese
The absolute effects of treatment, however, were more than twice that in the highest compared with the lowest BMI quartile, say the researchers. Across increasing quartiles of BMI over five years, active therapy prevented one major vascular event among every 28, 23, 13, and 13 patients treated.
This is perhaps unsurprising, given that those with the highest BMI exhibited the highest prevalence of antihypertensive drug use, they observe, noting that the trial was done in 1995-1997, when there was a rather lower prevalence of obesity overall (12.2%) than there is today.
The results provide further impetus for the allocation of BP-lowering agents on the basis of overall vascular risk rather than BP alone "and identify the obese as another population that warrants special attention," they note.
No specific guidance for antihypertensive therapy in the obese
They add that current guidelines for the management of hypertension "do not provide specific recommendations for the pharmacological treatment of high BP in overweight or obese patients," which reflects "the limited data available about the effects of treatment in the hypertensive obese and the few prior analyses designed to address this question."
A recent statement of the working group on obesity of the European Society of Hypertension  has highlighted the need for more data to address this issue, they conclude.
1. Czernichow S, Ninomiya T, Huxley R, et al. Impact of blood pressure lowering on cardiovascular outcomes in normal weight, overweight and obese individuals : the PROGRESS trial. Hypertension 2010 ; in press.
2. Jordan J, Engeli S, Redon J, Sharma AM, et al. European Society of Hypertension Working Group on Obesity : Background, aims, and perspectives. J Hypertens 2007 ; 25:897-900.