Even Prehypertension Increases Stroke Risk: Meta-Analysis

March 14, 2014

Borderline-high blood pressure, known as prehypertension, was associated with an increased risk for stroke in a new meta-analysis that included more than 700,000 participants.

Although the increased risk was largely driven by high-range prehypertension, the risk was also increased in people with low-range prehypertension.

The study, published online in Neurology on March 12, was conducted by a Chinese group. The authors conclude that: "In this study, we had sufficient power to demonstrate that the risk of stroke is increased even in individuals with relatively mild BP elevations. Our findings reaffirm the importance of the definition of 'prehypertension' rather than being 'normal' for individuals with BP of 120–139/80–89 mm Hg."

Senior author, Dingli Xu, MD, Southern Medical University in Guangzhou, China, said the findings had important clinical and public health implications. "Considering the high proportion of the population who have higher than normal blood pressure (30-50% of the population), successful treatment of this condition could prevent many strokes and make a major difference in public health," he stated.

"Important" Study

Commenting for Medscape Medical News, Ralph L. Sacco, MD, University of Miami Miller School of Medicine, Florida, said, "This is an important study that adds to the accumulating evidence that borderline elevated blood pressure levels, also called prehypertension, significantly increases the risk of stroke."

This meta-analysis provides further evidence to physicians and patients that we need to take blood pressure seriously even at borderline levels. Dr. Ralph L. Sacco

He stated: "This meta-analysis provides further evidence to physicians and patients that we need to take blood pressure seriously even at borderline levels. The first step is lifestyle modification with increasing physical activity, losing weight and eating healthy including reducing salt consumption. If these do not work or are unsuccessful, then medications may be warranted, particularly among those with elevated risk of stroke such as family history, diabetes, or other vascular conditions."

Dr. Sacco noted that the study is timely because there has been some controversy regarding the recently released JNC8 recommendations that loosened the level of blood pressure defined as abnormal for those older than age 60 years and moved the level to a systolic pressure of 150 mm Hg.

"But in this study the effects of borderline elevations of blood pressure were significantly increased for those under 55 as much as those over 55," Dr. Sacco pointed out. He added that the American Heart Association has defined ideal blood pressure as 120/80 mm Hg, and the study also confirms this as the optimal level.

In the Neurology paper, the authors explain that previous studies on the risk for stroke with prehypertension have shown mixed results. Therefore, a comprehensive meta-analysis of prospective cohort studies that examined the association between prehypertension and stroke, as well as the heterogeneity of risk within this category, may help to clarify this issue.


19 Prospective Studies

For the meta-analysis, the researchers analyzed data from 762,393 participants from 19 prospective cohort studies looking at the association of blood pressure and stroke. All the studies included multivariate-adjusted relative risks. The prevalence of prehypertension, defined as blood pressure of 120 to139/80 to 89 mm Hg, ranged from 25.2% to 54.2%, and the duration of follow-up ranged from 4 years to 36 years.

Results showed that after adjustment for multiple cardiovascular risk factors, prehypertension increased the risk for stroke by 66% compared with optimal blood pressure.

While the risk was greater for patients in the high range of prehypertension (130 to 139/85 to 89 mm Hg), patients with low-range prehypertension (120 to 129/80 to 84 mm Hg) still had a significantly increased risk for stroke.

Table. Risk for Stroke With Prehypertension vs Optimal Blood Pressure

Blood Pressure Relative Risk (95% Confidence Interval)
Any prehypertension (120 - 139/80 - 89 mm Hg) 1.66 (1.51 - 1.81)
High prehypertension (130 - 139/85 - 89 mm Hg) 1.95 (1.73 - 2.21)
Low prehypertension (120 - 129/80 - 84 mm Hg) 1.44 (1.27 - 1.63)


The authors note that the term "prehypertension" defined by the JNC7 guidelines has been controversial, and they point out that other international hypertension guidelines have not adopted this term.

For example, the 2013 report from the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension and the Society of Cardiology classified the 120 to 129/80 to 84 mm Hg group as "normal blood pressure" and 130 to 139/85 to 89 mm Hg group as "high normal." The authors say their results validate the term "prehypertension" and that blood pressures in this range should not be considered normal.

They also point out that the results are supported by another meta-analysis recently published by their group, showing that even low-range prehypertension increased the risk for cardiovascular events.

They further note that they used a wider search than some other meta-analyses on these issues, which, they say, is important to avoid missing potentially relevant studies.

The researchers also echo Dr. Sacco's view on management of this patient group. They write: "Health care professionals should recommend lifestyle changes to subjects with prehypertension. High-risk subpopulations with prehypertension, especially individuals with high-range prehypertension combined with other cardiovascular risk factors, should be considered for future controlled trials of pharmacologic treatment to prevent stroke."

No targeted funding for the study was reported. Dr. Xu reports receiving research support from the Natural Science Foundation of Guangdong Province, Guangdong Provincial Science and Technology projects, Guangzhou City Science and Technology projects, and the National Natural Science Foundation of China. Full disclosures are available at Neurology.org.

Neurology. Published online March 12, 2014. Abstract


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