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Intensive BP therapy reduces white matter hyperintensity in elderly
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NEW ORLEANS — In the INFINITY trial, intensive therapy to target 24-hour ambulatory systolic BP of 130 mm Hg resulted significantly reduced accrual of subcortical white matter intensity over 3 years compared with standard BP management in elderly patients with hypertension.
However, the reduction in brain lesions did not translate to a significant improvement in mobility and cognitive function, according to data presented at the American College of Cardiology Scientific Session. The INFINITY researchers said it is likely that 3 years was not long enough for that benefit to be seen.
William B. White, MD, and colleagues evaluated the effect of intensive BP lowering (target 130 mm Hg) compared with standard BP management (target 145 mm Hg) on prevention of functional decline due to less accrual of microvascular disease of the brain.
“Subcortical microvascular disease of the brain, represented by white matter hyperintensity on magnetic resonance images, is associated with functional decline in older people with hypertension,” White, a professor of medicine and chief of the division of hypertension and clinical pharmacology in the Calhoun Cardiology Center at the University of Connecticut School of Medicine, said during a presentation. “The use of ambulatory blood pressure to guide longitudinal therapy is actually novel in clinical research and practice, despite its superiority to predict target organ involvement with patients with hypertension.”
INFINITY was a randomized, blinded-endpoint trial that enrolled 199 older adults aged 75 years and older with systolic hypertension, MRI-evidence of white matter hyperintensity and baseline cognitive and mobility function. The mean age was 81 years, 54% were women and 87% were white. At baseline, mean clinic systolic BP was 151 mm Hg, 24-hour systolic BP was 149 mm Hg and white matter hyperintensity/total brain volume on MRI was 1.4%.
At 3 years, patients in the standard BP control group maintained an average systolic BP of 146 mm Hg and the intensive group maintained a target level of 131 mm Hg, both close to the trial’s BP targets.
Patients assigned intensive control had about a 40% relative reduction in the accumulation of white matter lesions — a co-primary endpoint of the trial — compared with the standard BP group. From baseline to 3 years, the mean change in white matter hyperintensity lesion accrual was 0.29 in the intensive group vs. 0.48 in the standard group (P = .03). In a sensitivity analysis for those whose BP stayed in the assigned group, the mean change from baseline to 3 years was 0.23 in the intensive group vs. 0.58 in the standard group (P < .01).
However, the other co-primary endpoint — change in mobility parameters — did not change over follow-up. The researchers reported no significant differences at 3 years in mobility parameters such as gait time, four-stair descent and ascent time, sit-to-stand time, supine-to-sit-time and unipedal balance between the two groups.
There were also no changes in observed in cognitive function.
Significantly fewer major CV events, including MI, stroke, hospitalization for HF and arrhythmias, occurred in the intensive BP group, White said. Occurrence of falls or syncope did not differ between the groups. – by Earl Holland Jr
Reference:
White WB, et al. Late-Breaking Clinical Trials IV. Presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.
Disclosure: White reports he received research grants from NIH.
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Martha Gulati, MD, MS, FACC, FAHA
I hope nobody ends up calling it a negative trial in terms of meeting their endpoint because the researchers were looking at lessening functional decline in this elderly population and I’m not sure 3 years is enough time to say that this is a negative or a neutral result.
What was interesting to me was that our concerns about lowering BP intensively were not an issue in this elderly population over the age of 75.
So, although they didn’t yet meet the difference in functional changes, CV outcomes are equally important, and I really appreciate that because a lot of people still question if we have enough data on our elderly population.
It’s a small study, we may need to study more people, and we may need to study them longer to know about the neurologic effects.
More than 85% of these patients were white, so we still need more ethnic representation so that we know how to treat our other populations, and if there would be a difference from the white population.
This impressive study tells me it’s safe to be more intensive about lowering BP in an older population, which often a source of hesitation in clinical practice.
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Raymond R. Townsend, MD
These findings show that ambulatory BP monitoring can be used to manage hypertension; hitherto it’s been mostly diagnostic use only, in adults. The study also shows that management can have a potentially measurable outcome.
How the findings will affect the clinical realm will depend on the actual cognitive function.
This was measured along with the MRI results, but acknowledged as pending in the abstract. The findings in the abstract are encouraging but will be much more impactful if accompanied by an actual true benefit.
The SPRINT MIND study found that more aggressive BP management reduced the emergence of mild cognitive impairment but did not significantly affect emergence of probable dementia as a standalone outcome.
Further research should be done people of a younger age, and perhaps people with a higher dementia risk — those with established mild cognitive impairment.
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