High blood pressure, also called hypertension, is a risk factor for stroke. That is one of the reasons that many of us take a daily medication to reduce blood pressure. Hypertension can be viewed as a disease of modernity. Hypertension is widespread in industrialized countries and is increasingly common as our population ages and becomes more overweight.

Treating hypertension over the long term can reduce strokes and heart attacks. But what should we do about blood pressure in the acute phase of stroke? The majority of strokes are ischemic, caused by a blockage of an artery. The acute phase of ischemic stroke is accompanied by high blood pressure. This link is so common, in fact, that consulting neurologists might discount the likelihood of stroke if a patient’s blood pressure is normal in the ER. Those with the highest blood pressures (and also the lowest) are at the greatest risk for a bad outcome, leading many to advocate for blood pressure treatments for stroke.

This strategy has a poor track record. A randomized controlled trial of the anti-hypertensive candesartan showed no improvement of functional outcomes when given after acute stroke. Why did this and other studies show no benefit? One reason has to do with the penumbra in stroke. The penumbra is vulnerable brain region that has diminished blood flow surrounding a core irretrievable area with absent flow. Higher blood pressure delivers more blood and oxygen to the penumbra.

These observations raise the evolutionary question: is hypertension after stroke an evolved trait that salvages damaged tissue after injury or stroke? There several possibilities here. First, hypertension could be simply pathological – part of the disease process that caused the ischemic stroke in the first place. If so, its treatment might improve outcomes. Second, post-stroke hypertension could be a conditionally adaptive trait. This idea predicts that reducing blood pressure will worsen outcomes. A third possibility is that the regulation of blood pressure in stroke might be adaptive, but not for stroke. Hypertension that increases blood flow to ischemic tissues might promote survival in different, more common, conditions. We will examine a recent New England Journal of Medicine study with those alternative hypotheses in mind.

This study by Li and colleagues involved 2404 patients randomized to receive blood pressure reduction initiated in the ambulance for patients suspected stroke, shown by this graphic from the NEJM website:

The top line result was no overall effect of blood pressure reduction on functional outcomes. Of the 1205 patients with blood pressure reduction and the 1199 who received usual care, no improvement in functional outcome was seen in the intervention group; odds ratio of 1, with a 95% confidence interval of 087 to 1.15.

Next, the authors of the study considered separately those patients who had a stroke resulting from bleeding, a hemorrhagic stroke, and those who had an ischemic stroke, as confirmed in the hospital by brain imaging. When the study examined hemorrhagic strokes, blood pressure reduction improved outcomes. On the other hand, when patients with confirmed acute ischemic stroke were examined separately, reducing blood pressure worsened functional outcomes.

This study highlights what Hong et al. call “the blood pressure paradox in acute ischemic stroke.” They wrote: “In patients with acute ischemic stroke, especially those with large vessel occlusion or a proximal stenosis, higher BP may help sustain collateral perfusion, which may minimize final infarction. However, high BP may also increase the risk of complications, such as brain edema and hemorrhagic transformation.”  Indeed, patients with brain bleeding in the Li et al. study did better with blood pressure lowering medication.

From this study alone, it would be hard to conclude that higher blood pressures in stroke are adaptive overall , since lowering blood pressure seemed to help those with hemorrhage. However, the proportion of hemorrhagic stroke in this study (46%) was unusually high, even for China. In North America, patients with hemorrhage strokes make up about 1 in 5 strokes overall, while ischemic strokes are 4 in 5. Putting generalizability concerns aside, if we extrapolated this study to other locations, we would expect to see more harm from blood pressure lowering, since ischemic strokes are more common than hemorrhagic ones. (A major concern about generalizability is that the medication used in this study, Urapidil, is unavailable outside of China.)

The trial by Li and colleagues is consistent with other recent findings, including another randomized controlled trial out of China showing worse outcomes with aggressive efforts to lower blood pressure after mechanical clot removal in patients with ischemic strokes. Together, these results are consistent with high blood pressure in ischemic stroke being conditionally adaptive. Many neurologists agree that hypertension resulting from blood pressure auto-regulation can improve blood flow to the ischemic stroke penumbra. However, that does not mean that it evolved to protect the brain from stroke. Strokes, after all, occur late in life, and are rare in humans living traditional lifestyles thought to be more representative of our evolutionary ancestors. Human populations living a traditional lifestyle have a very low incidence of hypertension, along with low cholesterol and little evidence of cardiovascular disease, suggesting that high levels of hypertension, heart disease and stroke are atypical for most of human evolution and should be viewed as an evolutionary mismatch. Still, small areas of brain ischemia are relatively common throughout the lifespan, because of small vessel disease, micro-emboli, or brain injury. Hypertension that accompanies large vessel ischemic strokes may be the most visible outcome of autoregulation that is adaptive in a variety of common brain conditions.

Li et al’s results suggest that hypertension might be beneficial in acute ischemic stroke but maladaptive in hemorrhagic stroke. Their results highlight that many traits are a complex bundle of benefits and costs. What to do medically is often unclear. Still, it is a smart principle to stop trying to fix things that don’t need fixing. The lesson for emergency physicians like myself is that we should not try to immediately lower blood pressure for our patients with ischemic stroke.

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Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine