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High — and Low — Blood Pressure May Raise Risk of Recurrent Stroke

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A post-hoc analysis of data from the Prevention Regimen for Effectively Avoiding Second Strokes (PROFESS) trial of over 20,000 patients shows that systolic blood pressure levels below 120 mm Hg, or of 140 mm Hg and above, are associated with increased risk for recurrent stroke.

ORLANDO, FL — Among patients with recent noncardioembolic stroke, very low as well as very high blood pressure may increase the risk of future vascular events.

A post-hoc analysis of data from the Prevention Regimen for Effectively Avoiding Second Strokes (PROFESS) trial of over 20,000 patients shows that systolic blood pressure (SBP) levels below 120 mm Hg, or of 140 mm Hg and above, are associated with increased risk for recurrent stroke (HRs 1.23 to 2.08).

“Our results indicate that there may be thresholds of benefit or harm with regard to short-term to longer-term SBP levels after a recent noncardioembolic ischemic stroke, and imply that clinicians regularly caring for stroke patients in the outpatient setting may need to be vigilant about how low a given patient's BP is within the normal range to promote favorable outcomes,” concluded the researchers, led by Bruce Ovbiagele, MD, professor of neurosciences at the University of -California, San Diego.

Still, “the data are hypothesis-generating, and the notion that aggressively and consistently lowering BP levels within the normal range in the short term to longer term after an index ischemic stroke is not beneficial remains unproven,” Dr. Ovbiagele said.

The study was published online in the Nov. 16 issue of the Journal of American Medical Association, a cardiovascular disease theme issue that was released early to coincide with the American Heart Association (AHA) Scientific Sessions 2011.

Current AHA guidelines suggest maintaining a normal BP, defined as SBP less than 120 mm Hg and diastolic BP less than 80 mm Hg, in patients with a prior stroke, Dr. Ovbiagele and colleagues note. However, limited data specifically address the role of BP lowering for vascular risk reduction after stroke.

Hypertension —- blood pressure readings of 140/90 mm Hg or higher, or systolic readings of 90 mm Hg and above — is one of several factors that raise the risk of a first stroke or myocardial infarction. The Framingham Risk Score, widely used to calculate a patient's risk of cardiovascular disease over 10 years, takes into account systolic blood pressure as well as age, diabetes, smoking, HDL and total cholesterol levels, and body-mass index.

Seventy-seven percent of Americans treated for a first stroke have blood pressure readings over 140/90 mm Hg, as do 69 percent of Americans who have a first MI, according to the American Heart Association.

DR. BRUCE OVBIAGELE: “Our results indicate that there may be thresholds of benefit or harm with regard to short-term to longer-term SBP levels after a recent noncardioembolic ischemic stroke, and imply that clinicians regularly caring for stroke patients in the outpatient setting may need to be vigilant about how low a given patients BP is within the normal range to promote favorable outcomes.”

A trial published last year in the New England Journal of Medicine, ACCORD-BP, showed that lowering SBP levels below 120 mm Hg in high-risk patients with diabetes not only failed to produce vascular benefit, but was associated with a higher incidence of adverse events. Data from the INVEST trial — reported in 2010 in JAMA — also suggested no benefit, and potential harm, to tight control of SBP to below 130 mg Hg in patients with diabetes and coronary artery disease.

To further explore the association between BP and second strokes, the researchers utilized data from the PROFESS trial.

The trial compared aspirin and extended-release dipyridamole with clopidogrel and also telmisartan with placebo for the prevention of recurrent stroke. None of the treatments significantly improved outcomes over an average 2.5 years of follow-up.

PROFESS DATA

POST-HOC ANALYSIS

So for the post-hoc analysis, the researchers grouped all the patients together and divided them based on their average SBP level: very low-normal (less than 120 mm Hg), low-normal (120 to less than 130 mm Hg), high-normal (130 to less than 140 mm Hg), high (140 to less than 150 mm Hg), and very high (150 mm Hg or greater). (See “PROFESS Data” for more detail.)

The primary outcome was first recurrence of stroke of any type and the secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes.

The new analysis suggests timing of blood-pressure-lowering may be important, Dr. Ovbiagele said. “We found the J-shaped association of SBP with recurrent vascular risk after stroke to be most pronounced in the first 90 to 180 days after the qualifying event,” he explained.

EXPERTS COMMENT

Larry B. Goldstein, MD, professor of medicine (neurology) and director of the Duke Stroke Center at Duke University Medical Center in Durham, NC, said that's a very important point.

“If you lower blood pressure too much right around the time of the stroke — in this study, in the first 180 days — you may end up with another vascular event,” said Dr. Goldstein, who was not involved with the trial.

Dr. Goldstein also said that neurologists should aim to improve stroke patients' overall vascular risk profile, not just their blood pressure.

“Lifestyle is of paramount importance,” he said. “Make sure patients follow appropriate diet and exercise plans and don't smoke and aren't exposed to secondhand smoke. And ensure they are prescribed an anti-thrombotic regimen if indicated,” Dr. Goldstein said.

As the authors point out, this is a post-hoc analysis, he added. Despite controlling for established prognosticators, the possibility that some unmeasured confounding factor may explain some of the findings cannot be excluded, he said.

Stroke neurologists continually grapple with the issue of how much to lower BP after an acute stroke best prevent recurrence without causing adverse problems, said Philip B. Gorelick, MD, John S. Garvin Professor and head of the department of neurology and rehabilitation and director of the Center for Stroke Research at the University of Illinois College of Medicine in Chicago.

DR. PHILIP B. GORELICK: “This hypothesis-generating study tells us that at either extreme of blood pressure — that is, less than 120 mm Hg or greater than 140 mm Hg — patients are at increased risk of recurrent stroke.”

Elevated BP is the most important modifiable risk factor for stroke, and reduction of BP generally lowers the risk of stroke, said Dr. Gorelick, who was a member of the steering committee for the PROFESS trial.

“This hypothesis-generating study tells us that at either extreme of blood pressure — that is, less than 120 mm Hg or greater than 140 mm Hg — patients are at increased risk of recurrent stroke,” he said.

“For now, it's probably best to follow JNC-VII [Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure] guidelines and aim for a blood pressure goal of less than 140 mm Hg in uncomplicated hypertensives,” he said.

Dr. Ovbiagele agreed. While awaiting dedicated clinical trials comparing intensive with usual BP reduction in the stable follow-up period after a stroke, clinicians should treat recent ischemic stroke patients to a SBP goal of less than 140 mm Hg and a diastolic blood pressure goal of less than 90 mm Hg, he said.

Several ongoing trials may help to guideline neurologists in the future. The Prevention of Decline in Cognition After Stroke Trial (PODCAST) is examining the impact of SBP on cognition after a recent ischemic or hemorrhagic stroke, and the Secondary Prevention of Small Subcortical Strokes (SPS3) is evaluating higher BP cutoffs in a subset of patients with small-vessel disease strokes.

Boehringer-Ingelheim funded the PROFESS trial.

REFERENCES:

• Ovbiagele B, Diener HC, Bath PM, et al, for the PROFESS Investigators. Level of systolic blood pressure within the normal range and risk of recurrent stroke. JAMA 2011; 16;306(19):2137-2144.
    • Cushman WC, Evans GW, Ismaail-Biegi F, et al, for the ACCORD Study Group. Effects of intensive blood pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-1585.
    • Cooper-DeHoff RM,Gong Y, Pipinr CJ, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA 2010;304:61-68.