Blood pressure and stroke risk gets more complicated

For patients who have suffered an ischemic stroke, traditional treatment prescribes keeping subsequent blood pressure levels as low as possible to reduce the risk of another stroke. A new international study, however, suggests this conventional approach may not be helpful, and could actually increase recurrent stroke risk – at least in the first few months after the first event. 

The findings, from a team of scientists led by Bruce Ovbiagele, MD, professor of neurosciences at the University of California, San Diego School of Medicine, are published in the November 16 issue of JAMA, the Journal of the American Medical Association. 

The 5-year study examined the cases of 20,330 patients (age 50 years and older) at 695 centers in 35 countries who had suffered a recent non-cardioembolic ischemic stroke, which is caused by drifting blood clots formed outside of the heart. Patients were categorized by their average Systolic blood pressure (SBP) level: very low-normal (less than 120 mmHg), 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). 

The occurrence rate for the primary or first stroke was highest in patients with a very high SBP (14.1 percent), followed by patients with high SBP (8.7 percent). Next came patients with very low-normal SBP at 8 percent, low-normal SBP at 7.2 percent and then high-normal SBP at 6.8 percent. The occurrence rate for a second stroke or other vascular event followed the same pattern. 

SBP is the maximum pressure applied to arterial walls as blood is pumped through the body. Diastolic blood pressure (DBP) is the minimum. Typically, normal blood pressure is defined as less than 120 mm Hg for SBP and less than 80 mm Hg for DBP. 

"For most patients at high vascular risk, including diabetics, the general approach has been that much lower is much better," said Ovbiagele. "For stroke patients, whose condition is most strongly related to elevated blood pressure, it has been believed that much, much lower is much, much better, and that the relationship of SBP with stroke was likely a linear one." 

The new findings indicate the association between blood pressure and stroke risk is more complicated than previously suspected. While the researchers said it was not surprising to find that higher-than-normal SBP levels boosted recurrent stroke risk, it was somewhat unexpected to discover the same effect among patients with very low SBP levels. 

The apparent narrowing of what constitutes a "healthy" SBP for stroke patients may not be the only relevant factor. Ovbiagele said timing also appears to be important because the effects were most pronounced in the first six months after the primary stroke. 

"It's conceivable that the brain may still require a certain threshold of blood perfusion early-on after the index vascular brain injury and so is susceptible to more strokes if SBP dips below that threshold. This is just a theory, but there are a couple of other clinical studies that suggest early BP reduction after an acute stroke may be associated with some harm." 

Ovbiagele said the message to patients and clinicians is that "it increasingly appears there is no one-size-fits-all approach with regard to treating blood pressure to prevent stroke. This study and other recent data now suggest that there are several factors to take into consideration when lowering blood pressure to prevent stroke, including the age of the patient, level of blood pressure, any history of prior stroke, type of prior stroke and timing of prior stroke." 

Source: University of California - San Diego [November 15, 2011]

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Your stroke risk profile may also help predict your risk of memory problems

A new study shows a person's stroke risk profile, which includes high blood pressure, smoking, and diabetes, may also be helpful in predicting whether a person will develop memory and thinking problems later in the life. The research is published in the Nov. 8, 2011, issue of Neurology®, the medical journal of the American Academy of Neurology. 

Researchers in the REGARDS study followed 23,752 people with an average age of 64 who were free of stroke and cognitive problems at the start of the study. Participants underwent a Framingham Stroke Risk Profile, which is used to determine a person's risk of stroke by measuring their age, blood pressure, education level, history of heart disease, smoking and diabetes status, and whether they have left ventricular hypertrophy (a thickening of the heart muscle) and an abnormal heart rhythm. 

After an average of four years of follow-up, 1,907 people had developed memory and thinking problems. 

The study found the higher a person's score on the Stroke Risk Profile, the greater the chance of developing cognitive problems four years later. Fifteen percent of people who scored among the highest 25 percent on the Stroke Risk Profile test (greater than 11.99 points) had cognitive problems compared to three percent of those who scored among the bottom 25 percent with a score below 3.4 points. 

"Overall, it appears that the total Stroke Risk Profile score, while initially created to predict stroke, is also useful in determining the risk of cognitive problems," said study author Frederick Unverzagt, PhD, of Indiana University School of Medicine in Indianapolis. 

The study found older age and the presence of thickening in the heart muscle, which is a result of long-term high blood pressure, were the only Stroke Risk Profile factors independently associated with future cognitive problems. This association remained even after controlling for age, sex, race, where a person lived and education. In addition, the study also found high systolic blood pressure was related to cognitive problems in people without a thickening of the heart muscle. 

"Our findings suggest that elevated blood pressure and thickening of the heart muscle may provide a simple way for doctors to identify people at risk for memory and thinking problems," said Unverzagt. "Increased focus on preventing and treating high blood pressure may be needed to preserve cognitive health." 

Source: American Academy of Neurology [November 07, 2011]

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Scientists identify gene critical for cell responses to oxygen deprivation

Scientists at the Gladstone Institutes have identified a protein that kick–starts the response to low levels of oxygen, suggesting new lines of research relevant to a variety of potentially fatal disorders associated with diminished oxygen supply, including cancer, heart disease, stroke and other neurological conditions that affect millions of people worldwide. 

Blood vessels (shown in red) in a mouse retina that is missing the p75NTR protein. Black areas indicate a lack of blood vessels in the absence of p75NTR. Dr. Akassoglou's lab found that p75NTR was critical for kick-starting increased blood vessel production during hypoxia [Credit: Natacha Le Moan/Gladstone Institutes]

In a paper being published today in Molecular Cell, the laboratory of Gladstone Associate Investigator Katerina Akassoglou, PhD, maps out the chain of events that take place during hypoxia. Hypoxia is a condition that can occur in people with diseases such as heart disease and stroke. It deprives tissues and organs of an adequate oxygen supply. 

"This discovery provides a novel understanding of the steps by which cells normally respond to hypoxia, a fundamental biological process that is implicated in many medical conditions," said Dr. Akassoglou, whose research at Gladstone—a leading and independent biomedical-research organization—investigates the mechanisms of inflammation and tissue repair in the brain. 

The paper details how Dr. Akassoglou's lab discovered the previously unknown biological function of a protein called p75NTR. When activated by hypoxia, p75NTR sets off the cascading series of events that results in increased blood-vessel production to replenish oxygen levels during disease. 

Previous research had indicated that hypoxia triggers the activation of a protein called HIF1–alpha—an activation that ultimately leads to more blood vessels and an ensuing improvement in oxygen flow. There has been much interest among researchers in modifying levels of the HIF1–alpha protein to spur blood-vessel production in individuals with hypoxic conditions. But Dr. Akassoglou decided to take a different approach in her research. 

By monitoring the responses of mice under hypoxic conditions, Dr. Akassoglou found that hypoxia first activated the p75NTR protein, which then activated HIF1-alpha and set everything in motion. 

"What was most striking to us was what happened when we removed the gene that makes p75NTR," said Natacha Le Moan, PhD, a Gladstone postdoctoral fellow and the first author of the paper. "By effectively silencing p75NTR, the mice's response to hypoxia was impaired and blood-vessel production decreased." 

"Now that we've shown that p75NTR spurs the activation of HIF1-alpha and the production of blood vessels during hypoxia, we can move forward with exploring potential therapies," said Dr. Akassoglou, who is also an associate professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. In addition, Dr. Akassoglou is also an associate adjunct professor of pharmacology at the University of California, San Diego. 

"Dr. Akassoglou's trailblazing discovery could enable the development of pharmaceutical therapies for conditions that are caused or exacerbated by reduced oxygen levels," added Lennart Mucke, MD, who directs neurological research at Gladstone. "This is important news for those who suffer from hypoxia-related illnesses such as heart disease, stroke and certain types of cancer." 

Source: Gladstone Institutes [November 03, 2011]

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