Prehypertension Is Linked to Higher Risk for Stroke



Prehypertension is associated with a 55% increased risk for stroke, according to research reported in the October 4 issue of Neurology.

The risk is substantially increased for patients who have higher blood pressure levels within the prehypertension range and is especially relevant among nonelderly persons. In addition, the risk for stroke remained evident after investigators adjusted for established cardiovascular risk factors such as age, gender, obesity, diabetes, and cholesterol level.

“We found that persons with a baseline presence of prehypertension had a robust and significant risk of future stroke that was consistent across diverse race-ethnicities,” stated principal investigator Bruce Ovbiagele, MD, Professor at the Stroke Center and Department of Neuroscience, University of California, San Diego, in La Jolla, and colleagues. “Importantly, we observed that incident stroke risk appeared more strongly driven by higher systolic blood pressure or diastolic blood pressure values within the prehypertensive range.”

Prehypertension—as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC)—is a slightly elevated level of blood pressure, though still considered within the normal range. The designation comprises persons with a systolic blood pressure measure between 120 and 139 mm Hg or diastolic blood pressure measure between 80 and 89 mm Hg.

Prehypertension and the Risk of Incident Stroke
The findings are based on a meta-analysis of 12 prospective cohort studies, which included 518,520 participants from the general population. Studies were included if they reported multivariate-adjusted relative risks (RR) and corresponding 95% confidence intervals of stroke with respect to baseline prehypertension. The final primary analysis included 13 articles from 12 prospective cohort studies.

The researchers observed a prevalence of prehypertension ranging from 25% to 46%. Sample study sizes ranged from 1,702 participants to 158,666 participants, and the duration of follow-up ranged from 2.7 to 32 years.

Overall, prehypertension was associated with an RR of stroke of 1.55. Seven studies from the meta-analysis further distinguished participants with a low prehypertension level—systolic blood pressure from 120 to 129 mm Hg or diastolic blood pressure of 80 to 84 mm Hg—and high prehypertension level—systolic blood pressure of 130 to 139 mm Hg or diastolic blood pressure of 85 to 89 mm Hg.

“Among those with lower-range prehypertension, stroke risk was not significantly increased (RR 1.22),” reported the researchers. “However, for persons with higher values within the prehypertensive range, stroke risk was substantially increased (RR 1.79).”

Age, Blood Pressure, and Stroke Risk
A subgroup analysis showed that prehypertension significantly predicted higher stroke risk across sex, race-ethnicity, stroke end point, stroke subtypes, and follow-up duration. “However, significant heterogeneity existed between estimates among participants with different average age at entry (less than 65 years vs greater than or equal to 65 years), sample size of studies (less than 10,000 vs greater than or equal to 10,000), and study quality (good vs fair),” stated the investigators. “There was no heterogeneity within good-quality studies.”

According to Dr. Ovbiagele’s group, elderly persons who had prehypertension did not have an increased risk of incident stroke. “This finding may not be that surprising, given the immense impact of elderly status itself on stroke risk, as well as observational data indicating that the contribution of frank hypertension to the risk of stroke is rather diminished in elderly cohorts,” the researchers commented.

“An immediate potential implication of our findings is that young and middle-aged persons with higher systolic or diastolic blood pressure values within the prehypertensive range may benefit from relatively safe, nonpharmacologic blood pressure–lowering methods, such as reduction in salt intake and weight to reduce their risk of stroke,” stated Dr. Ovbiagele and colleagues. “Nonetheless, randomized controlled trials evaluating the effect/efficacy of blood pressure reduction on reducing subsequent risk for stroke are warranted.”

The investigators pointed out several limitations to their findings, including the fact that baseline blood pressure in most of the studies was obtained from a single-day measurement, “which may lead to a misclassification of blood pressure levels and a dilution bias.” Also, they noted that meta-analyses can be biased when the literature does not identify all relevant studies or when selection criteria are applied subjectively. Furthermore, substantial heterogeneity was observed among the studies.

“Despite these limitations, the results of this systematic review probably represent the most precise and accurate estimate of the strength of the relation between prehypertension and incident stroke currently available,” the researchers commented.

Are New Treatment Recommendations Needed?
In an accompanying editorial, Amytis Towfighi, MD, and Gordon Kelley, MD, noted that the Seventh Report of the JNC currently recommends lifestyle modification, including diet and exercise, for all persons with prehypertension and hypertension. In addition, medication initiation is recommended when lifestyle modification fails to meet the blood pressure goal of less than 140/90 mm Hg.

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