ATLANTA — Visit-to-visit variability in office blood pressure in patients with treated hypertension proved to be a far more powerful predictor of stroke and coronary events than did mean blood pressure in a provocative new analysis of the ASCOT trial.
Indeed, the average blood pressure maintained during 5.5 years of follow-up in the massive study had no effect at all on cardiovascular outcomes and only minimal impact on stroke risk in these patients, Dr. Peter Sever reported at the annual meeting of the American College of Cardiology.
“One of the take-home messages is if you're on treatment, you're better off with a higher pressure and less variability than with a lower pressure and more variability. And that's worrying,” observed Dr. Sever, codirector of the International Centre for Circulatory Health at Imperial College London.
ASCOT (the Anglo-Scandinavian Cardiac Outcomes Trial) randomized nearly 20,000 hypertensive subjects with three additional cardiovascular risk factors to antihypertensive therapy with a calcium channel blocker–based regimen using amlodipine, with the ACE inhibitor perindopril added as needed, or to a beta-blocker–based therapy featuring atenolol with or without the diuretic bendroflumethiazide. The study included more than 1 million blood pressure measurements.
The calcium channel blocker–based regimen produced significantly better outcomes, including a previously reported 24% reduction in the risk of cardiovascular mortality relative to the beta-blocker–based regimen, and a 23% decrease in the risk of fatal or nonfatal stroke.
The new analysis focused on the relationship between blood pressure variability over time and risk of the study end points. When the researchers compared patients in the highest and lowest 10% for between-visit variability in systolic or diastolic blood pressure, they found that those in the top decile had a fourfold greater risk of stroke and a threefold greater risk of cardiovascular events.
Moreover, Dr. Sever and his coworkers showed that the calcium channel blocker–treated group had significantly less blood pressure variability over time than did those treated with atenolol. This finding provides a plausible mechanistic explanation for the previously reported superior clinical outcomes with the calcium channel blocker.
Patients on the amlodipine-based regimen had a mean visit-to-visit variability in systolic blood pressure of 10.9 mm Hg, compared with 13.4 mm Hg in those on the atenolol-based regimen. Only 9.1% of patients on the amlodipine-based regimen had a systolic blood pressure reading of 180 mm Hg or more at any time during follow-up, compared with 19.2% of those on atenolol-based therapy.
Blood pressure was measured three times at each office visit. In addition, more than 1,900 ASCOT participants underwent annual 24-hour ambulatory blood pressure monitoring. Although greater within-visit and 24-hour blood pressure variability were statistically associated with increased rates of stroke and coronary events, those were much less robust predictors than was visit-to-visit blood pressure variability, Dr. Sever said.
Several recent large meta-analyses indicate that although calcium channel blockers and diuretics reduce blood pressure variability, beta-blockers, angiotensin receptor blockers, and ACE inhibitors actually increase it, he continued.
Within the ASCOT population, older age, diabetes, known vascular disease, and smoking were associated with greater between-visit blood pressure variability.
“We believe variability is a surrogate for vascular stiffness, and probably for the aging-related impairment in the baroreceptor reflex, a hypothesis we'll look at more closely in the near future,” Dr. Sever said.
Discussant Dr. Carlo Di Mario of Royal Brompton Hospital, London, proposed “a more mundane theory” to explain the better outcomes in the amlodipine-treated group: Isn't it likely that a calcium channel blocker–based antihypertensive regimen would be better tolerated than a more fatiguing beta-blocker–based therapy, with resultant better treatment compliance?
Dr. Sever replied that ASCOT included pill counts as a compliance measure, which showed similar results for the two study arms.
In an interview, Dr. Sever suggested that the regular occurrence of more than about a 10- to 15-mm Hg difference in systolic blood pressure from office visit to visit can be viewed as a practical indicator of excessive variability. It's something that physicians have traditionally shrugged off as random variation and clinically unimportant, but the new ASCOT findings indicate otherwise.
“If those patients aren't on a calcium channel blocker, you should be thinking about switching them to a calcium channel blocker,” he advised.
Disclosures: The ASCOT study was funded by Pfizer and Servier. Dr. Sever disclosed having served on the speakers bureau for Pfizer.
“We believe variability is a surrogate for vascular stiffness,” Dr. Peter Sever said.
Source Courtesy Dr. Peter Seversenate.gov
My Take
BP Variability Emerging as Predictor of Stroke Risk
The post hoc analysis by Dr. Sever and his colleagues of the ASCOT trial demonstrates that blood pressure variability is a stronger predictor of stroke and coronary events compared with mean BP. This is an important observation.