How Low to Go for Blood Pressure? Lower Target Could Affect Millions of Americans

Systolic Blood Pressure Intervention Trial recommendations may have broad impact

Newswise, November 10, 2015 - A new study finds that at least 16.8 million Americans could potentially benefit from lowering their systolic blood pressure (SBP) to 120 mmHg, much lower than current guidelines of 140 or 150 mmHg.

The collaborative investigation between the University of Utah, University of Alabama at Birmingham, and Columbia University, will be published Nov. 9 online in the Journal of the American College of Cardiology (JACC).

The scientists calculated the potential impact of preliminary results from the Systolic Blood Pressure Intervention Trial (SPRINT) that will be presented in full at the American Heart Association meeting and published online in the New England Journal of Medicine, also on Nov. 9.

The initial analysis of SPRINT, reported in September, 2015, showed that using antihypertensive medications to reach a lower SBP target of 120 mmHg could greatly reduce risk for heart failure, heart attack, and death, compared to a target of 140 mmHg (SBP is the top number in a blood pressure reading).

 It’s estimated that one in three U.S. adults have high blood pressure, or hypertension, a significant health concern.

“SPRINT could have broad implications,” says lead author Adam Bress, Pharm.D., M.S., assistant professor of pharmacotherapy at the University of Utah College of Pharmacy. “Millions of Americans whose blood pressure is under control according to current guidelines may be considered uncontrolled if new guidelines adopt the intensive target of less than 120 mmHg studied in SPRINT.”

While new medical guidelines for treating hypertension could be months to years away, this research finds that more than 16.8 million Americans, 7.6 percent of the population, could be recommended for intensive blood pressure management if guidelines incorporate a new, lower, SBP target based on SPRINT results. The number represents Americans who meet the same criteria as SPRINT participants: they are age 50 or older, have an SBP between 130-180 mmHg, are at high risk for cardiovascular disease, and do not have diabetes or a history of stroke, among other inclusion and exclusion criteria.

The current study also reports that new guidelines may affect some segments of the population more than others. Compared to Caucasians, African Americans and Hispanics were less likely to meet SPRINT eligibility criteria (9 percent vs. 4.8 percent, 4.3 percent).

The differences are largely due to the fact that these minority populations have a higher prevalence of diabetes and other health conditions that could preclude them from being SPRINT eligible. Men were also more likely to be eligible for SPRINT than women (8.8 percent vs. 6.5 percent), in part because unlike men, women tend not to show increased risk for cardiovascular disease until they are over 65.

However in practice, it’s common for physicians to prescribe treatments to patients who may have not been eligible for a clinical trial that demonstrated the efficacy and safety of a particular treatment.

For example, some physicians may deviate from SPRINT eligibility by aggressively treating the blood pressure of any adult over 50, even if they do not have a high risk of cardiovascular disease. “Physicians are going to need to decide how far outside the SPRINT inclusion criteria to go,” says co-author Rachel Hess, M.D., M.S., also a professor of internal medicine and population health sciences at the University of Utah School of Medicine. “It’s going to be a tough decision.”

The numbers of Americans meeting each sequential SPRINT eligibility requirement are:
• 219 million adults
• 95.1 million age 50 or older
• 37.3 million with elevated blood pressure (≥130 mmHg)
• 26.4 million at high risk for cardiovascular disease
• 16.8 million with no diabetes, history of stroke, or other SPRINT exclusion criteria

Potential impacts of SPRINT results on the U.S. population were based on analyzing data from the 16,260 participants in the National Health and Nutrition Examination Survey (NHANES) between 2007 – 2012 who met certain SPRINT inclusion and exclusion criteria. NHANES includes a representative cross-section of the American population, allowing for projection of these findings to the overall population.

Most, but not all, SPRINT inclusion and exclusion criteria were accounted for in NHANES. For example information on subclinical cardiovascular disease and a history of medical non-adherence are not represented in the national survey.

New blood pressure guidelines will have to weight potential adverse effects that could overshadow its benefits, and whether increasing blood pressure medications over the course of multiple years is cost-effective.

But the numbers obtained in this study offer a glimpse into the potentially wide ranging impact of changing blood pressure guidelines.

“Given that millions of U.S. adults meet SPRINT eligibility criteria, the implementation of SPRINT recommendations could have a profound impact on how blood pressure is treated in this country,” says senior author Paul Muntner, Ph.D., a professor of epidemiology at the University of Alabama.

“Even more important, is its potential for greatly reducing the incidence of cardiovascular disease.”

In addition to Bress, Hess, and Muntner, the co-authors are Rikki Tanner and Lisandro Colantonio from the University of Alabama, and Daichi Shimbo from Columbia University.

“Generalizability of results from the Systolic Blood Pressure Intervention Trial (SPRINT) to the US adult population” will be published online in the Journal of the American College of Cardiologists on Nov. 9, 2015

First, Do No Harm: Hospital Patients Given Anti-Heartburn Drugs Have Higher Risk of Dying, Study Finds

U-M/VA computer model suggests that common use of acid-reducing medicine to prevent stomach bleeding increases mortality from infections

Newswise, November 10, 2015 — Right now, in any American hospital, about half of the patients have a prescription for an acid-reducing drug to reduce heartburn or prevent bleeding in their stomach and gut.

But that well-intentioned drug may actually boost their risk of dying during their hospital stay, a new study finds – by opening them up to infections that pose more risk than bleeding would.

In fact, according to a computer simulation based on real-world risk and benefit data, around 90 percent of hospital inpatients who were first prescribed these drugs in the hospital have a higher risk of dying when they’re taking them, compared with their risk if they hadn’t gotten the prescription.

And for around 80 percent of patients who were already on these common drugs, called proton-pump inhibitors or PPIs, when they arrived at the hospital, staying on them also may lead to a small increase in the risk of dying.

The extra risk of death comes from the fact that reducing acid in the stomach can increase the risk of infections – especially pneumonia and Clostridium difficile, both of which pose a serious risk to hospitalized patients who develop them.

The study, which uses a computer model to achieve a result that otherwise would require an impractically large clinical trial, is published in the Journal of General Internal Medicine by a team from the University of Michigan Medical School and VA Ann Arbor Healthcare System.

“Many patients who come into the hospital are on these medications, and we sometimes start them in the hospital to try to prevent gastrointestinal, or GI, bleeds,” says lead author Matthew Pappas, M.D., MPH.

“But other researchers have shown that these drugs seem to increase the risk of pneumonia and C. diff, two serious and potentially life-threatening infections that hospitalized patients are also at risk for,” he continues. 

“Our new model allows us to compare that increased risk with the risk of upper GI bleeding. In general, it shows us that we’re exposing many inpatients to higher risk of death than they would otherwise have – and though it’s not a big effect, it is a consistent effect.”

As a result of the new findings, he says, very few hospital patients should start taking or continue on PPIs as a preventive measure against gastrointestinal bleeding.

Pappas, a hospitalist physician at U-M with an engineering background and a VA Health Services Fellow, worked with Sandeep Vijan, M.D., MPH, who treats patients at the VAAHS and is a member of the VA Center for Clinical Management Research and U-M’s Institute for Healthcare Policy and Innovation.

 Pappas is a clinical lecturer, and Vijan a professor, in the U-M Medical School’s Division of General Medicine. The project’s only funding was Pappas’s fellowship support.

Cutting PPI use to cut infection risk

Pappas notes that nationally, some efforts have already shown ways to reduce the rate of new PPI prescriptions to hospitalized patients – about 20 percent of whom receive such orders right now.

But truly reducing PPI use in hospitals to the most appropriate patients – those with existing GI bleeding – will take more effort, Pappas predicts.

That’s because PPIs are built into many heuristics, or rules of thumb, that guide much hospital care. For instance, when a patient receives high-dose steroids in the hospital, the physician may automatically also prescribe a PPI to prevent the GI bleeding that steroids can cause.

“In fact, in running our simulation, we thought we would find some populations such as those on steroids or other medications often prescribed together with PPIs, who would not experience the increased mortality risk,” Pappas says. 

“But that turned out not to be the case.” GI bleeds are risky, it’s true. But hospital-acquired pneumonia and C. diff are much more common.

Although research is still needed on why PPI use increases a patient’s vulnerability to hospital-acquired pneumonia and C. diff infection, the effect of the acid-reducing drugs on gut bacteria likely has a direct impact. In the case of pneumonia, suppressing acid production may increase the amount of bacteria in the stomach and throat, which can then get into the lungs and cause pneumonia.

Model can be used for other risk-benefit balancing

Pappas notes that the model he developed with Vijan and recent U-M Ford School of Public Policy graduate Sanjay Jolly could be applied to many other situations where a common preventive or treatment measure in medicine also carries with it an increased risk of an unwanted effect.

Using such models, based on data from observational studies, could answer important questions in medicine without needing to carry out massive prospective clinical trials. 

To answer the question of whether the predicted increase in mortality risk caused by PPIs in inpatients is real, he says, would take a clinical trial of more than 64,000 patients randomly assigned to receive PPIs or not. Since PPIs are available as generic medications, the likelihood of such a study being funded and performed is nearly zero.

“Any time there are complex risk/benefit tradeoffs, without the possibility of a high-quality trial, this kind of simulation can help us come up with answers to inform clinical care,” he says.

For instance, he’s now studying the issue of “bridging” medication in patients who have been prescribed blood-thinning medications to prevent a stroke. Such patients often receive a prescription for an injected drug that will reduce stroke risk during the week or two before their regular oral drugs take effect. 

But that injection carries its own risk.

“Humans aren’t very good at recognizing very rare events, and reacting appropriately to things that are unlikely to happen,” says Pappas. 

“Physicians have an instinct to want to prevent very bad, though rare events – but everything we do carries risks. We need to be mindful of the things we are doing to prevent rare outcomes, and keep the risks in perspective. Computers can help.”

Reference: Journal of General Internal Medicine, DOI:10.1007/s11606-015-3536-7

Study Shows Benefits of Intensive Blood Pressure Management

Systolic Blood Pressure Intervention Trial could impact medical guidelines for treating hypertension, but questions remain

Newswise, November 10, 2015 — Patients whose blood pressure target was lowered by medications to reach a systolic goal of 120 mmHg had their risk for heart attack and heart failure reduced by 38 percent, and their risk for death lowered by 27 percent.

Aggressive treatment appeared to be as effective for adults age 75 and older as for adults age 50-74, according to results from the Systolic Blood Pressure Intervention Trial (SPRINT) presented at the American Heart Association meeting and published online in the <i>New England Journal of Medicine (NEJM) on Nov. 9, 2015.

Intensive blood pressure management was also associated with an increased risk for each of a group of adverse events categorized as life threatening or requiring prolonged hospitalization or disability, including hypotension, fainting, and kidney abnormalities. 

Among these, there was greatest increased risk, 64 percent, for acute kidney injury or acute renal failure, although there was no evidence for permanent kidney damage. Future studies will investigate effects of treatment on kidney disease in more detail.

“The positive results of this trial has taken everyone by surprise, and the strong benefits of treatment seem to outweigh the risks,” says Alfred Cheung, M.D., chief of nephrology & hypertension at University of Utah Health Care, and co-author on the study. He led a network of 17 out of the 102 participating clinical sites in the U.S. and Puerto Rico. 

“Before deciding to treat blood pressure aggressively, it may be smarter to wait until additional questions are answered.”

He notes that results are still pending on how intensive treatment might impact dementia, cognition, and kidney disease. 

Additionally, nothing is known about long-term effects of sustained treatment, nor cost effectiveness. On average, SPRINT trial participants were followed for just over three years.

In Sept, 2015, the National Institutes of Health announced that the SPRINT trial was stopped one year early due to the marked benefits of lowering systolic blood pressure to 120 mmHg, well below the current guidelines of 140, or 150 for those over age 60. 

Now, the details of the study are published in NEJM. The results may have implications for the 79 million Americans and 1 billion adults worldwide with hypertension, or high blood pressure, the leading cause of heart disease and stroke.

Adults age 75 and older could potentially benefit the most from interventions based on positive SPRINT results because this age group carries the burden of hypertension: over 75 percent have the condition. 

At the same time, they would be predicted to be most at risk for any potential side effects that are still under investigation, says Mark Supiano, M.D., chief of geriatrics at University of Utah Health Care and director of the VA Salt Lake City Geriatric Research, Education, and Clinical Center.

“If there were a single drug with this kind of beneficial outcome, it would be a billion-dollar drug,” says Supiano. “But we can’t just treat the heart, we need to treat the whole person. We will need to exercise caution when implementing this information.”

SPRINT randomly assigned over 9,300 participants one of two blood pressure targets: less than 120 mmHg or less than 140. Participants were age 50 or older, at increased risk for cardiovascular disease, had an systolic blood pressure of at least 130 mmHg, and did not have diabetes, history of stroke, or kidney disease. 

Blood pressure was adjusted with antihypertensive medication over the course of the first year, and participants were monitored for an average of three additional years.

The results from SPRINT differ from previous trials demonstrating that a blood pressure target of 120 mmHg did not significantly reduce risk for death. 

Cheung says the difference in outcomes may stem from SPRINT’s large sample size and its unique eligibility requirements, which included an older population and individuals with high risk for cardiovascular disease, and excluded patients with diabetes.

“We saw great health improvements in just three years, but it could be that outcomes will improve even more over the course of 10 years, or 30,” says Cheung.

It remains to be determined whether SPRINT results will influence official medical guidelines for treating hypertension.

The research was supported by the National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Department of Veterans Affairs

“Principle Results of the Systolic Blood Pressure Intervention Trial (SPRINT)” will be published online in NEJM on Nov. 9

Fractures Can Lead to Premature Death in Older People

New study looks at falls, fractures and osteoporosis in people age 45 and older

Newswise, November 9, 2015—A new study, presented this week at the American College of Rheumatology Annual Meeting in San Francisco, shows certain fractures due to osteoporosis can cause premature death in people 45 and older. This is the largest study, to date, that shows a connection between these fractures and premature death.

Osteoporosis is a common condition where bones become weak, affecting both men and women, mainly as they grow older. Osteoporosis results from a loss of bone mass, measured as bone density, and from a change in bone structure.

Osteoporosis is more common in older women, mainly non-Hispanic white and Asian women. In the U.S., about 4.5 million women and 0.8 million men over the age of 50 have osteoporosis.

Risk factors for developing osteoporosis include a sedentary lifestyle, use of glucocorticoids, smoking and having inflammatory arthritis, among others.

Osteoporosis can increase fracture risk, and falls and fractures due to osteoporosis are a growing concern as the population ages. In fact, one-third of all fall-related deaths are attributed to low bone density.

Despite this, according to researchers in the 45 & Up study – a study of 125,174 women and 113,499 men in New South Wales, Australia — osteoporosis isn’t always well-managed and treated, and they suspect that is because of a lack of awareness about just how dangerous osteoporotic fractures can be.

“Health professionals have been aware for some time that having a hip fracture when you are older increases your risk of dying in one to two years after the fracture, but we have not been so aware that other fractures could increase this risk as well, explains Lyn March, MD, PhD; University of Sydney Liggins Professor of Rheumatology and Musculoskeletal Epidemiology at Kolling Institute of Bone and Joint Research and Sydney's Royal North Shore Hospital.

“We embarked on this study to highlight the impact of such fractures.”
Dr. March’s team obtained initial health information from participants in the study (who were, on average, 63 years old at the time of recruitment between 2006 and 2008 and followed up on average every 5.7 years until their death or December 31, 2013) via questionnaire and linked that information to medical codes signifying fractures that were obtained from emergency department visits as well hospital admissions.

Finally, they obtained information on participants through birth, marriage and death registries.

Taking into consideration age, gender, co-existing diseases and conditions and previous fractures, the researchers looked at fractures and deaths among the participants.

During the course of the study, 14,827 fractures were reported; 9,145 of these were seen in women, and 5,682 were seen in men. 

The researchers also noted 15, 621 deaths during the study; 5,604 were in women, and 10,017 were in men.

When looking at death in the group, Dr. March’s team noted 15.7 men died for every 1,000 person years in the study, which was calculated by multiplying the number of people in the study by the number of years in the study.

Conversely, 7.9 women died for every 1,000 person years. However, these rates went up two-fold when fractures were involved: 33 men and 19 women with fractures died for every 1,000 person years of the study.

The researchers not only noted the increase of death among participants with fractures, they were also able to narrow down the types of fractures that seemed to cause more death.

“We were surprised to find that almost all fractures (apart from fingers and toes) in the elderly were associated with increased risk of dying when compared to other men and women of the same age who had not had a fracture,” says Dr. March

“Common fractures like spinal fractures that cause older people to stoop over, arm, collarbone and wrist fractures from a simple fall, or pelvic fractures from a trip on the stairs or a slip on the ice all increase the risk of the sufferer dying in the next few years.”

Given these outcomes, Dr. March’s team believes there need to be more studies on the risk of osteoporotic fractures and premature deaths.

“This is the largest study of its kind and the first to find the increased risk of dying from such a wide range of fractures including hip, vertebral (spinal) and non-hip non-vertebral (shoulders, wrists, collarbone) fractures while being able to adjust for other potential risks of dying.

“Our study highlights the need for research into the reasons for this increased risk of dying after fractures and also highlights the need to treat osteoporosis as a serious condition to prevent the fractures from occurring,” concludes Dr. March.

About the American College of Rheumatology
Headquartered in Atlanta, Ga., the American College of Rheumatology is an international medical society representing over 9,400 rheumatologists and rheumatology health professionals with a mission to Advance Rheumatology! 

In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases. For more information, visit www.rheumatology.org.

Poor Air Quality Increases Heart Patients’ Risk of Suffering Most Serious Type of Heart Attack, New Study Finds

Newswise, November 9, 2015— People with heart disease face an increased risk of a serious heart attack during poor air quality days, according to a major new study presented today (Sunday, Nov. 8) at the American Heart Association Scientific Session in Orlando.

The study of more than 16,000 patients by researchers at the Intermountain Medical Center Heart Institute in Salt Lake City examined patients who had suffered three types of heart attacks – STEMI, non-STEMI, and unstable angina – to identify which type of heart attack was more likely on days when the air was especially polluted.

For the study, researchers compared air quality measurements to the number of patients treated for heart attacks at Intermountain Healthcare hospitals in the urban areas in and around Salt Lake City between Sept. 1993 and May 2014.

The Intermountain Medical Center Heart Institute research team identified a strong association between bad air quality days – those with a threshold above 25 micrograms of fine particulate matter per cubic meter of air – with a greater risk of STEMIs, the most dangerous type of heart attack.

Findings of the study were reported at the 2015 American Heart Association Scientific Session in Orlando on Sunday, November 8, 2015.

“Our research indicated that during poor air quality days, namely those with high levels of PM2.5, patients with heart disease are at a higher risk of suffering from a STEMI heart attack,” said Kent Meredith, MD, cardiologist and researcher at the Intermountain Medical Center Heart Institute.

A ST-segment elevation myocardial infarction, or STEMI, is a serious form of a heart attack in which a coronary artery is completely blocked and a large part of the heart muscle is unable to receive blood. 

If left untreated for too long, the lack of oxygen to the heart will damage the heart muscles and cause irreparable damage or death.

“By making this association, physicians can better counsel their heart patients to avoid exposure to poor air quality, and thus decrease their chances of suffering a heart attack on days that they are potentially at highest risk,” said Dr. Meredith.

“The study suggests that during many yellow air quality days, and all red quality air days, people with known coronary artery disease may be safer if they limit their exposure to particulate matter in the air by exercising indoors, limiting their time outdoors, avoiding stressful activities, and remaining compliant with medications,” said Dr. Meredith.

“These activities can reduce inflammation in the arteries, and therefore make patients less sensitive to the fine particulate matter present on poor air quality days.”

Other members of the study include C. Arden Pope; Joseph B. Muhlestein, MD; Jeffrey L. Anderson, MD; John B Cannon, Nicholas M. Hales; Viet Le; and Benjamin Horne.

Intermountain Medical Center is the flagship facility for the Intermountain Healthcare system, which is based in Salt Lake City.

Sleep Interruptions Worse for Mood Than Overall Reduced Amount of Sleep, Study Finds

Newswise, November 2, 2015 — A study led by Johns Hopkins Medicine researchers suggests that awakening several times throughout the night is more detrimental to people’s positive moods than getting the same shortened amount of sleep without interruption.

As they report in the November 1 issue of the journal Sleep, researchers studied 62 healthy men and women randomly subjected to three sleep experimental conditions in an inpatient clinical research suite: three consecutive nights of either forced awakenings, delayed bedtimes or uninterrupted sleep.

Participants subjected to eight forced awakenings and those with delayed bedtimes showed similar low positive mood and high negative mood after the first night, as measured by a standard mood assessment questionnaire administered before bedtimes. Participants were asked to rate how strongly they felt a variety of positive and negative emotions, such as cheerfulness or anger.

But the researchers say significant differences emerged after the second night: The forced awakening group had a reduction of 31 percent in positive mood, while the delayed bedtime group had a decline of 12 percent compared to the first day.

Researchers add they did not find significant differences in negative mood between the two groups on any of the three days, which suggests that sleep fragmentation is especially detrimental to positive mood.

“When your sleep is disrupted throughout the night, you don’t have the opportunity to progress through the sleep stages to get the amount of slow-wave sleep that is key to the feeling of restoration,” says study lead author Patrick Finan, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

Although the study was conducted on healthy subjects with generally normal sleep experiences, Finan says the results are likely to apply to those who suffer from insomnia.

Frequent awakenings throughout the night are common among new parents and on-call health care workers, he says. It is also one of the most common symptoms among people with insomnia, who make up an estimated 10 percent of the U.S. adult population.

“Many individuals with insomnia achieve sleep in fits and starts throughout the night, and they don’t have the experience of restorative sleep,” Finan says.

Depressed mood is a common symptom of insomnia, Finan says, but the biological reasons for this are poorly understood. To investigate the link, he and his team used a test called polysomnography to monitor certain brain and body functions while subjects were sleeping to assess sleep stages.

Compared with the delayed bedtime group, the forced awakening group had shorter periods of deep, slow-wave sleep. The lack of sufficient slow-wave sleep had a statistically significant association with the subjects’ reduction in positive mood, the researchers say.

They also found that interrupted sleep affected different domains of positive mood; it reduced not only energy levels, but also feelings of sympathy and friendliness.

Finan says the study also suggests that the effects of interrupted sleep on positive mood can be cumulative, since the group differences emerged after the second night and continued the day after the third night of the study.

“You can imagine the hard time people with chronic sleep disorders have after repeatedly not reaching deep sleep,” Finan says. However, he says, further studies are needed to learn more about sleep stages in people with insomnia and the role played by a night of recovering sleep.

Other authors of the study are Phillip J. Quartana of the Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research; and Michael T. Smith of the Johns Hopkins University School of Medicine, who was the principal investigator of the study.

This research was supported by grants from the National Institute on Drug Abuse (grant number K23 DA035915), the National Institute of Nursing Research (grant number P30 NR014131), and the National Institute of Neurological Disorders and Stroke (grant numbers R21 NS051771 and K23 NS47168).

Physical Activity and Falls in Older Men – Do Mobility Limitations Make a Difference?

Newswise, November 2, 2015 — Moderately vigorous physical activity (MVPA) is good for all older men, and according to new research conducted at University College London (UK), it also reduces the risk of falls in some over-70s. 

One third of men aged 70-90 years have trouble getting about outdoors.

For them, 30 minutes of MVPA daily— enough to cause slight breathlessness and sweating— almost halves the risk of falling. MVPA strengthens their leg muscles and improves fitness and includes activities like walking for errands or gardening.

However, among the two thirds who have no mobility limitations, only the most active 10 percent— who do 30 minutes of MVPA or walk more than 9000 steps daily — actually increased their risk of falls by half. 

It’s likely they are going beyond their strength and balance capability, so would benefit from balance-challenging exercise programs to prevent falls. 

Overall, the benefits of exercise outweigh the risks for older men and they should all do some exercise rather than none.

View the study’s abstract or contact the author.