UC Irvine study explores protein-rich diet’s effect on cardiac patients.

Lorraine Evangelista, UC Irvine

A passion for patient care led Lorraine Evangelista into nursing, but through research she is finding a way to make a greater impact, especially for those who suffer from heart disease.

Evangelista has gained national recognition for her involvement in studies to help people with heart conditions, and her latest effort may produce her most significant research achievement yet.

The associate professor of nursing science at UC Irvine is leading a multi-university study to see whether a protein-rich diet can increase the long-term health prospects for overweight patients with congestive heart failure.

The Pro-Heart study aims to determine if heart failure patients can benefit from a diet in which 30 percent of calories are from protein. The average American gets about 15 percent of calories from protein.

Supported by UCI’s Institute for Clinical & Translational Science, Pro-Heart is, however, more than a weight management plan. Evangelista believes it represents a dietary approach that can help delay the onset and progression of a muscle-wasting condition called cachexia that can affect many individuals with congestive heart failure.

In cachexia, which also occurs with cancer, multiple sclerosis and other diseases, the body metabolizes muscle mass as a protein source, causing muscle atrophy, fatigue and weakness.

Evangelista created the Pro-Heart protocols, which do not include supplements and which stress gradual and reasonable changes to eating and exercise habits, while on the nursing faculty at UCLA. The study recruits subjects there and at UCI, which she joined in 2011.

“I’m excited about how Pro-Heart is going,” Evangelista says. “We’ve already seen that the diet has resulted in improvements in cardiac structure and function, even showing signs of reversal of the disease process.”

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Groundbreaking 10-year UCSF research examines causes of death among HIV patients.

What is the connection, if any, between sudden cardiac death and people with HIV/AIDS? And can that knowledge help prolong their lives?

In a comprehensive, retrospective 10-year UC San Francisco study, researchers found patients with HIV/AIDS suffered sudden cardiac death at a rate four times higher than the general population.

“As part of my ongoing research in 2010, we were looking at every instance of sudden death in San Francisco,” said first author Zian H. Tseng, M.D., an electrophysiologist and an associate professor of medicine in the UCSF Division of Cardiology. “I noticed that many of these cases involved individuals with HIV infection, who were dying suddenly. I wondered if there was some sort of connection there.”

He posed this question to Priscilla Hsue, M.D., a UCSF associate professor of medicine and the director of the HIV Cardiology Clinic at San Francisco General Hospital and Trauma Center (SFGH), who is one of a few cardiologists in the country who specializes in HIV. To her knowledge, no one had ever explored the link between HIV and sudden death, and that is when they began collaborating on this research.

In a paper scheduled to be published May 15 in the Journal of the American College of Cardiology, Tseng, Hsue and other researchers conducted a retrospective study of 2,860 HIV patients from April 2000 to August 2009 at SFGH’s Ward 86, the first HIV/AIDS-specialized clinic, to comprehensively characterize all deaths. They studied medical records, death certificates, paramedic reports, and interviews with family members, doctors, and other clinicians.

Sudden cardiac death and HIV/AIDS

During that period, eight percent died during an average of 3.7 years of follow up. Cardiac-related deaths accounted for 15 percent of overall mortality. Of that group, 86 percent died of sudden cardiac death.

“To put that in context, we’re able to compare the rate of sudden death in this population with the overall San Francisco population,” Tseng said. “So adjusted for age, race, demographics, and other variables, the rate of sudden death in the HIV population is more than four times higher than the general population.”

“The fact that the vast majority of cardiac deaths were sudden is surprising and implies that we as clinicians need to be aware of this potential health issue among patients with HIV,” Hsue added. “Our findings also highlight many things that we still don’t know about HIV and sudden death. Did these individuals die of unrecognized coronary artery disease? What can we be doing as clinicians to identify patients at risk and to intervene beforehand?”

Categorizing sudden cardiac death

By 2003, sudden cardiac death made up the largest number of non-AIDS deaths among HIV-positive patients in San Francisco.  These deaths were largely among individuals with evidence of well-controlled HIV disease.

Researchers used well-published criteria for retrospectively identifying death as either HIV-related or sudden death-related. If there was any doubt, they classified sudden death as an HIV death.

“In other words, for someone with a CD4 (T-cell) count less than 50 who died suddenly, we classified that as an HIV death, rather than a sudden death because of the profound immunodeficiency,” Tseng said.

More than 17,000 people with AIDS in the United Stated died in 2009, and more than 619,000 people have died since the epidemic began. Still, the number of people living with HIV continues to rise. More than 1.2 million people in the United States are HIV-positive, according to the U.S. Centers for Disease Control and Prevention.

“Now that HIV-infected individuals are living longer with the benefit of antiretroviral therapy, non-AIDS conditions are becoming increasingly important and at the top of this list is cardiovascular disease,” Hsue said.

Researchers believe HIV changes the electrophysiology of the heart in a way so pronounced that it causes conduction abnormalities. And many HIV medications can throw off the heart’s electrical cycle, which increases the risk of sudden death. These and other variables could be contributing factors.

“Acknowledging the limitations of a retrospective analysis, what’s interesting about this study is that it opens up many related questions we can ask in future studies, such as which high-risk patients might benefit from defibrillator implantation?” Tseng said.

Tseng is in the middle of a prospective citywide study on sudden cardiac death, including studying HIV patients and monitoring their progress.

Tseng is the first author of the paper; Hsue is the senior author; co-authors include Eric Secemsky, M.D., of the UCSF Department of Medicine; David Dowdy, M.D., Ph.D., Sc.M., of the Johns Hopkins Bloomberg School of Public Health’s Department of Epidemiology; Eric Vittinghoff, Ph.D., M.P.H., of the UCSF Department of Epidemiology and Biostatistics; Brian Moyers, M.D., of the UCSF Division of Cardiology; Joseph Wong, M.D., of the UCSF Department of Medicine and San Francisco VA Medical Center; and Diane Havlir, M.D., of the San Francisco General Hospital HIV/AIDS Division.

This study was supported by funds from the U.S. National Institutes of Health (NIH). Tseng has received minor honorarium from Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For further information, please visit www.ucsf.edu.

Extensive UCSF study finds flaws in previous study’s analytic methods.

UC San Francisco's Judith Prochaska speaks with one of her patients.

A popular smoking cessation medication has been under a cloud of suspicion ever since the Canadian Medical Association Journal (CMAJ) published a study in July reporting “risk of serious adverse cardiovascular events associated with varenicline.” Varenicline, also known as Chantix, blocks the pleasant effects of nicotine on the smoker’s brain and lessens nicotine withdrawal symptoms.

UC San Francisco researchers, however, question the way the previous study was conducted, and their new analysis, scheduled to be published May 4 in BMJ, reaches a very different conclusion.

“We found no clinically or statistically significant increase in serious adverse cardiovascular events associated with using varenicline,” said lead author Judith J. Prochaska, Ph.D., M.P.H., an associate professor in UCSF’s Department of Psychiatry and researcher with the Center for Tobacco Control Research and Education. “The findings from 22 trials with more than 9,200 participants indicate a difference in risk of only 0.27 percent between those on varenicline versus placebo, or about a quarter of one percent.”

Prochaska identified the need for the re-analysis after reading the CMAJ publication and finding the conclusion inconsistent with the small differences within trials. Prochaska had received an “investigator-initiated research award” from Pfizer, the maker of Chantix, that spring for a separate study of varenicline in hospitalized smokers, many with heart disease. Prochaska says she was compelled to more closely examine the data to quantify the level of risk before using the medication on UCSF patients.

Differences in meta-analytic methods

Prochaska and Joan F. Hilton, Sc.D., M.P.H., a professor in UCSF’s Department of Epidemiology & Biostatistics, conducted the new study, which, like the prior one, used meta-analytic statistical techniques to combine results from different trials of varenicline with tobacco users. The UCSF and prior analysis, however, differed in several fundamental ways.

The previous study, led by Sonal Singh, M.D., M.P.H., assistant professor of medicine at Johns Hopkins University, looked at a sample size of 8,216 patients in 14 trials and ­­­reported a 72 percent (relative) increase in risk of heart attack or other serious heart problems.

The UCSF analysis included 22 double-blind, randomized controlled trials with 9,232 participants. More than half of the studies included participants with active or past history of cardiovascular disease. Eight trials had no events. The UCSF study found a 0.27 percent (absolute) risk difference, which it determined was neither clinically nor statistically significant.

“We identified eight separate trials with nearly 1,600 tobacco users randomized to varenicline or placebo that did not have a single serious cardiovascular event,” Prochaska said. “This information is meaningful and the Singh analysis excluded these trials.”

UCSF researchers say varenicline lasts in the body about seven days after a person stops using the medication. The new analysis examined events occurring during the drug treatment window or within 30 days after a patient stopped using the drug, rather than the entire trial period, which in many cases was a year in Singh’s study.

“The longer you follow heavy, long-term tobacco users – and in these studies, the average participant smoked a pack a day for 25 years – the more likely you will see serious cardiovascular events related to their compromised health,” Prochaska said. “In addition, 13 of the 14 studies in the Singh analysis experienced greater attrition in the placebo group than in the test group, which could inflate the treatment effect.”

Absolute difference vs. relative difference

Singh’s study found that 1.06 percent of those who took varenicline had serious heart-related complications, compared to 0.82 percent of the placebo group. Although the simple absolute difference was only 0.24 percent – similar to the UCSF study finding based on meta-analytic methods – Singh’s paper reported the weighted, relative difference, which was 72 percent.

“What made the headlines is this claim of a huge increase, but it’s a relative measure; it’s a unit-less measure,” Prochaska said. “And so if you increase something small by a little bit, you can claim that it’s a 72 percent increase, but that obscures the fact that it’s still a very small risk.”

“For someone not accustomed to these measures, it might not be obvious that the 72 percent increase was relative to a very small base – interpretations the Singh study didn’t stress,” Hilton said.

The new meta-analysis provides a more comprehensive examination of varenicline by presenting and comparing the four most relevant summary measures for this type of analysis.

“Among these, we found that the methods used by Singh and colleagues produced the most extreme estimates of treatment effect,” said Hilton. “We identified the specific conditions under which this statistic is inflated. We recommended the summary based on the (absolute) risk difference because it is methodologically appropriate in our setting and gives a clear quantitative sense of the excess risk.”

Smoking and cardiovascular risk

Cardiovascular disease is the leading cause of death among smokers. Tobacco use also increases a person’s risk of stroke, cancer and lung disease.

“One of the most important things you can do for your heart is to quit smoking,” Prochaska said. “Clinical practice guidelines recommend the use of FDA medications to quit smoking. All medications carry some risk; however, we hope the FDA and other experts compare the Singh analysis to ours to determine what action, if any, should be taken with regard to varenicline and cardiovascular risk. Tobacco is a deadly addiction, and patients need effective treatments.”

Funding for this meta-analysis was provided by grants to Prochaska from the UC-administered Tobacco-Related Disease Research Program and the National Institute on Drug Abuse.

Hilton is funded by federal grants and has no current funding from any pharmaceutical company.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

UC Irvine findings could boost on-the-job productivity.

Stephen Voida (left) and Gloria Mark, UC Irvine

Being cut off from work email significantly reduces stress and allows employees to focus far better, according to a new study by UC Irvine and U.S. Army researchers.

Heart rate monitors were attached to computer users in a suburban office setting, while software sensors detected how often they switched windows. People who read email changed screens twice as often and were in a steady “high alert” state, with more constant heart rates. Those removed from email for five days experienced more natural, variable heart rates.

“We found that when you remove email from workers’ lives, they multitask less and experience less stress,” said UCI informatics professor Gloria Mark. She co-authored the study, “A Pace Not Dictated by Electrons,” with UCI assistant project scientist Stephen Voida and Army senior research scientist Armand Cardello. The UCI team will present the work Monday, May 7, at the Association for Computing Machinery’s Computer-Human Interaction Conference in Austin, Texas.

The study was funded by the Army and the National Science Foundation. Participants were computer-dependent civilian employees at the Army’s Natick Soldier Systems Center outside Boston. Those with no email reported feeling better able to do their jobs and stay on task, with fewer stressful and time-wasting interruptions.

Measurements bore that out, Mark said. People with email switched windows an average of 37 times per hour. Those without changed screens half as often – about 18 times in an hour.

She said the findings could be useful for boosting productivity and suggested that controlling email login times, batching messages or other strategies might be helpful. “Email vacations on the job may be a good idea,” she noted. “We need to experiment with that.”

Mark said it was hard to recruit volunteers for the study, but “participants loved being without email, especially if their manager said it was OK. In general, they were much happier to interact in person.”

Getting up and walking to someone’s desk offered physical relief too, she said. Other research has shown that people with steady “high alert” heart rates have more cortisol, a hormone linked to stress. Stress on the job, in turn, has been linked to a variety of health problems.

Study subjects worked in a variety of positions and were evenly split between women and men. The only downside to the experience was that the individuals without email reported feeling somewhat isolated. But they were able to garner critical information from colleagues who did have email.

The Army is examining use of smartphones and such applications as email for soldiers on battlefields, said David Accetta, spokesman for the Natick facility’s research and development section. “This data may very well prove helpful,” he said.

About the University of California, Irvine: Founded in 1965, UCI is a top-ranked university dedicated to research, scholarship and community service. Led by Chancellor Michael Drake since 2005, UCI is among the most dynamic campuses in the University of California system, with nearly 28,000 undergraduate and graduate students, 1,100 faculty and 9,000 staff. Orange County’s second-largest employer, UCI contributes an annual economic impact of $4 billion. For more UCI news, visit www.today.uci.edu.

UC Irvine findings point to importance of cardiac testing in lung disease prognosis, treatment.

Nathan Wong, UC Irvine

A simple test for heart disease risk can go a long way toward determining the long-term prognosis for people with chronic obstructive pulmonary disease, according to UC Irvine researchers.

Dr. Hwa Mu Lee and Nathan Wong of the UC Irvine Heart Disease Prevention Program found that individuals with moderate to severe COPD who had a low Framingham Heart Study 10-year risk assessment rate lived longer and healthier than COPD patients who scored high on the heart test.

Study results point to the importance of cardiovascular health for those with COPD and strongly suggest that heart disease risk evaluations be part of the diagnostic and treatment procedures for lung diseases such as emphysema and bronchitis that affect 64 million people worldwide and are the third-leading cause of death in the U.S.

“There is a close connection between COPD and cardiovascular events like heart attacks, but too often physicians who see COPD patients do not assess the impact of heart disease risk factors as part of a treatment plan,” said Lee, associate research director of the UC Irvine program and an assistant clinical professor of medicine specializing in pulmonary and critical care.

“We’re learning that addressing cardiac risk factors may significantly improve outcomes in persons with COPD,” added Wong, program director and a professor of cardiology and epidemiology. “The connection between these two diseases is underappreciated.”

Lee and Wong examined the severity of COPD in 6,266 U.S. adults over 40 in relation to their 10-year cardiovascular disease risk, which can be estimated by the Framingham Heart Study’s risk calculator.

They noted that there are current National Institutes of Health-funded studies on whether statins — cholesterol-lowering drugs often prescribed for heart patients — can help lessen COPD-related lung inflammation.

Janet Lee, Katherine Lee and Yanting Luo of UC Irvine, as well as Dr. Don Sin of St. Paul’s Hospital in Vancouver, also contributed to the study, which appears online in the journal Chest.

About the University of California, Irvine: Founded in 1965, UC Irvine is a top-ranked university dedicated to research, scholarship and community service. Led by Chancellor Michael Drake since 2005, UC Irvine is among the most dynamic campuses in the University of California system, with nearly 28,000 undergraduate and graduate students, 1,100 faculty and 9,000 staff. Orange County’s second-largest employer, UC Irvine contributes an annual economic impact of $4 billion. For more news, visit www.today.uci.edu.

Gold Seal of Approval denotes commitment to highest quality of patient care.

Terry Belmont, UC Irvine

UC Irvine Medical Center‘s heart failure program and Stroke & Cerebrovascular Center have again earned the Gold Seal of Approval from The Joint Commission, health care’s predominant standards-setting and accrediting body.

Joint Commission certification recognizes an organization’s diligence in meeting rigorous performance standards accepted nationwide as benchmarks of superior patient care.

“The Joint Commission’s renewal of our heart failure and stroke programs certification reflects the commitment our doctors and staff make each day to provide the Orange County community with the best care possible,” said Terry A. Belmont, CEO of UC Irvine Medical Center.

To achieve the Gold Seal of Approval, an organization must undergo a voluntary on-site survey by a Joint Commission team at least every two years and satisfy performance requirements in such key areas as patients’ rights, patient treatment and infection control.

In April, Joint Commission staff reviewed UC Irvine’s heart failure program and Stroke & Cerebrovascular Center and interviewed personnel to gauge their adherence to the best clinical practices, quantify their use of data to improve performance and learn how they maintain a consistently high level of care.

The UC Irvine heart failure program’s certification for disease-specific care in 2008 was the first awarded by The Joint Commission to a Southern California hospital or medical center. The Stroke & Cerebrovascular Center has held advanced certification from The Joint Commission since 2004 and was among the nation’s first academic medical facilities to be designated a primary stroke center.

Led by Dr. Vivek Jain, the Stroke & Cerebrovascular Center offers state-of-the-art diagnosis and treatment — including specialty care by stroke neurologists, neurointerventionalists and neurosurgeons — for stroke patients and others with diseases affecting the blood vessels that supply the brain. For more information, visit www.healthcare.uci.edu/stroke/index.asp.

The heart failure program, directed by Dr. Dawn Lombardo, provides comprehensive inpatient and outpatient care — utilizing the most current medicines, devices, surgical therapies and technology — and fosters new approaches to heart failure through a large, active research effort. For more information, visit www.healthcare.uci.edu/cs_heart_failure.asp.

About UC Irvine Medical Center: Orange County’s only university hospital, UC Irvine Medical Center offers acute- and general-care services at its new, 482,000-square-foot UC Irvine Douglas Hospital and is home to the county’s only Level I trauma center, American College of Surgeons-verified regional burn center and National Cancer Institute-designated comprehensive cancer center. U.S. News & World Report has included UC Irvine for 11 consecutive years on its list of America’s Best Hospitals, giving special recognition to its urology, gynecology, kidney disorders and cancer programs.

UCSF study sheds light on tricky task of diagnosing thickening of arteries.

Priscilla Hsue, UC San Francisco

By Kate Rauch

With the remarkable success of antiretroviral drugs, people with HIV are living longer. However, recent attention is turning to the link between HIV and chronic conditions, including cardiovascular illness.

As it turns out, people with HIV are at greater risk for heart disease than others. But the reasons for this vulnerability aren’t well understood.

A recent study by UC San Francisco cardiologist Priscilla Hsue, M.D., who in 2004 started the world’s first cardiology clinic for HIV patients at San Francisco General Hospital, sheds light on one conundrum facing doctors in the field — the tricky task of diagnosing atherosclerosis, or thickening of the arteries, a precursor of heart attacks.

Often referred to as a silent killer, atherosclerosis progresses without obvious symptoms. Hsue, an associate professor at UCSF’s School of Medicine, looked at two methods used to diagnose the condition — carotid ultrasound, which measures the inside thickness of the carotid artery, and a CT scan, which tests for calcium in the coronary artery. Calcium deposits in the coronary artery or thickening in the carotid artery can indicate advancing atherosclerosis.

Hsue confirmed that HIV indeed is a risk for atherosclerosis. She also discovered that looking at the carotid artery rather than calcium was more effective at gauging the condition in people with the virus.

For reasons that remain unclear, a significant number of HIV parents in the study showed thicker carotid arteries, without any unusual calcium, compared to the control group without the virus.

Hsue is already applying the results in new research. In a current five-year investigation of atherosclerosis in HIV patients, she is tracking 400 participants, regularly measuring their carotid artery thickness, along with HIV disease characteristics and traditional cardiovascular risk factors such as smoking.

The goal is better prevention and treatment, Hsue said, adding that an urgent need exists to be able to better diagnose and treat individuals with HIV who are at increased risk for cardiovascular disease.

Hsue is also conducting a unique investigation of pulmonary hypertension in HIV patients, a rare and deadly form of elevated pressures on the right side of the heart..

About one in 2,000 people with HIV develop pulmonary hypertension, compared to one in one million in the general population. “It’s a quick-moving, devastating disease,” Hsue said. “We don’t know what puts people at risk. Are there things we can do with respect to HIV infection or on the cardiovascular side to prevent this or delay disease progression?”

Some study participants have advanced pulmonary hypertension, some early signs, and some are symptom-free. Over five-years, Hsue is regularly monitoring their pulmonary artery pressures, HIV disease characteristics, symptoms and exercise tolerance.

Much of this work, including the regular blood tests, heart ultrasound, right heart catheterization, lung tissue sampling and caring for patients after procedures, is being provided through Clinical Research Services (CRS) offered by UCSF’s Clinical and Translational Science Institute (CTSI).

“The infrastructure and resources provided by CTSI are crucial,” Hsue said. “They help streamline clinical research, allowing researchers like me to see more patients, and perform more complicated procedures for research purposes.”

CTSI is a member of the National Institutes of Health-funded Clinical and Translational Science Awards network. Under the banner of Accelerating Research to Improve Health, it provides a wide range of services for researchers, and promotes online collaboration and networking through tools such as UCSF Profiles.

CTSI also recently launched the UCSF Participant Recruitment Service, which offers a suite of services to support investigators in efforts to recruit study participants, potentially making it easier for researchers such as Hsue to engage in research.

New building is first LEED Gold certified acute care medical facility in San Diego region.

UC San Diego Sulpizio Cardiovascular Center

The UC San Diego Sulpizio Cardiovascular Center is the first hospital-based project in the region to receive LEED Gold certification from the United States Green Building Council. Representatives from the USGBC – San Diego Chapter recently presented a plaque to the building project and design team.

“I am extremely proud of this team and the UC San Diego Sulpizio Cardiovascular Center,” said Randy Leopold, LEED accredited professional, director of Health Care Architectural Services, UC San Diego Facilities Design & Construction. “The design decision we made from the beginning laid the foundation for our being able to pursue LEED certification. This Gold level certification recognition is the jewel in our crown.”

LEED — Leadership in Energy and Environmental Design — promotes a “whole-building” approach to sustainability by recognizing performance in several key areas. Though the Sulpizio Cardiovascular Center project began in 2005, prior to LEED guideline establishment, leadership at UC San Diego, along with the design and construction teams, believed in creating a building that was environmentally thoughtful.

The facility design takes full advantage of the movement of the sun with shading devices and massing elements to minimize heat gain and reduce energy consumption. The design also embraces the idea of blurring the lines between interior and exterior regions, to provide the facility with a “natural” feel that picks up on the stunning geography of the nearby coastal canyons.

“It is no small task to achieve LEED certification after the design of the project was mostly complete,” said Doug Kot, executive director of the USGBC – San Diego Chapter. “This team had established the right goals and accountability and was intuitively on their way toward building sustainability when we started working with them.”

Kot went on to explain that the indoor environmental quality of UC San Diego Sulpizio Cardiovascular Center makes this building a superior facility for patients and staff. “This building promotes good health by combining energy conservation techniques with the very best care available and that is what we are here to celebrate in this LEED project,” said Kot.

UCSF researchers find higher risk of heart attack when abnormalities are detected.

Can a simple diagnostic test used to measure a heart’s electrical activity help predict heart attacks? And can that knowledge help doctors reroute their patients away from coronary heart disease?

These are the questions researchers at UC San Francisco asked in a comprehensive eight-year study focused on senior citizens in the United States. Researchers found a higher risk of heart attack when abnormalities showed up on electrocardiogram (EKG) results of healthy elderly people.

“We did not include them if they reported a previous heart attack,” said lead author Reto Auer, M.D., a research fellow at UCSF’s Department of Epidemiology and Biostatistics. “So we looked at people who lived independently — not in assisted living facilities — with no history of heart attacks or coronary heart disease.”

The findings, scheduled to be published tomorrow in the Journal of the American Medical Association (JAMA), help answer the question of whether or not EKGs can be used to detect heart disease earlier in patients who don’t have chest pain or other symptoms.

“This research is taking the information from an EKG and adding it to other traditional risk factors to better predict who is going to have a heart attack,” said second author Douglas Bauer, M.D., director of the UCSF Division of General Internal Medicine Research Program.

Focus on healthy senior citizens

Researchers studied 2,192 healthy adults aged 70 and older for eight years in Memphis, Tenn., and Pittsburgh. Those with EKG abnormalities had more heart attacks. The results were consistent even when researchers took into account known risk factors for heart attacks, such as smoking, high cholesterol, high blood pressure and diabetes.

At baseline, 276 (13 percent) participants had minor and 506 (23 percent) major EKG abnormalities. During follow-up, 351 participants (16 percent) had coronary heart disease (CHD) events (96 heart-related deaths, 101 heart attacks, 154 hospitalizations for chest pain or a procedure to restore blood flow to the heart). Both baseline minor and major EKG abnormalities were associated with an increased risk of heart disease after adjusting for traditional risk factors.

Each abnormality was categorized in terms of the level of experienced risk. High risk markers included left bundle branch block, a cardiac condition in which the left ventricle contracts later than the right ventricle, as well as major ST-T wave changes in an EKG, among others. Low risk markers included subtle ST-T wave changes and T-wave abnormalities.

“There was a trend towards increased coronary heart disease (CHD) risk from no abnormality to minor, and from minor up to major abnormality,” Auer said. “But both minor and major EKG changes were significantly associated with an increased risk of CHD.”

Gender and racial variations?

Researchers were also interested in whether or not gender or self-reported racial differences played a role in determining a healthy person’s likelihood of a future heart attack among the 2,192 participants who identified themselves as either Caucasian or African American. Researchers found no correlation between elevated risk factors and gender or race.

“It was a good surprise,” Auer said. “It shows that it’s really the EKG changes that predict risk.”

Researchers say it is premature to advocate for the widespread use of their findings in a clinical setting, but that their initial evidence suggests there may be a role for EKG in adding to traditional risk factors, to better predict who is at risk for a heart attack.

“Anytime someone goes into the emergency room, especially elderly people, they typically get an EKG,” Auer said. “So in the patient’s electronic record system, you could include these EKG abnormalities as part of the patient’s overall risk — but we’re not there yet.”

For now, though, researchers recommend patients become familiar with well-established risk factors that health care providers use to counsel individuals for their risk of future heart attacks and other heart problems.

Controversy surrounding EKGs

Organizations such as the American Academy of Family Physicians recommends against ordering annual EKGs or any other cardiac screening for low-risk patients without symptoms. They say “there is little evidence that detection of coronary artery stenosis in asymptomatic patients at low risk for coronary heart disease improves health outcomes.”

The American Heart Association (AHA), however, recommends that EKG is reasonable for assessing the risk of coronary heart disease events of adults with hypertension or diabetes even though the U.S. Preventive Services Task Force (USPSTF) found that there is insufficient evidence to recommend for or against routine screening in adults at increased risk of heart disease. For adults at low risk, the AHA recommends that it may be considered while the USPSTF recommends against screening. However, prediction of heart attack by major cardiovascular risk factors is not as reliable in elderly adults as in younger individuals.

“Our view is that novel screening interventions should be tested on clinical outcomes,” Auer said. “Just because you know you might be at increased risk does not mean that you will be better off if your treatment is modified as a consequence of the test.”

This finding, still, could help an estimated 785,000 Americans who will have a first heart attack this year, and 470,000 who will have a recurrent attack. Heart disease remains the number one killer in the United States, accounting for one out of every three deaths, according to the American Heart Association.

Auer is the lead author of the paper; Bauer is the second author; co-authors are  Pedro Marques-Vidal, M.D., Ph.D., and Jacques Cornuz, M.D., M.P.H., of the University of Lausanne, Switzerland; Javed Butler, M.D., M.P.H., of Emory University School of Medicine; Lauren J. Min, Ph.D.; Suzanne Satterfield, M.D., of the University of Tennessee Health Science Center; Anne B. Newman, M.D., M.P.H., of the University of Pittsburgh’s Department of Epidemiology; Eric Vittinghoff, Ph.D., of the UCSF Department of Epidemiology and Biostatistics; and Nicolas Rodondi, M.D., M.A.S. of the University of Lausanne, Switzerland.

The Health ABC cohort study was supported by funds from the U.S. National Institute on Aging (NIA) and the National Institutes of Health (NIH). Additional funding came from the Swiss National Science Foundation and the Swiss Heart Foundation.

Unique procedure combines minimally invasive method with traditional surgical techniques.

UCLA Dr. Jamil Aboulhosn checks patient Patti Crawford after a hybrid surgery saved her life.

Patricia Crawford had literally been tinged blue all her life because her heart couldn’t pump enough oxygenated blood through her body. And that was the least of her worries.

A huge aneurysm the size of a softball in her pulmonary artery was a ticking time bomb. Her heart and liver were failing, too — all adding to the reasons it was too risky for the 49-year-old to receive the heart-lung transplant she desperately needed to survive. She had been told that she was out of options.

But a team of UCLA adult congenital cardiologists and cardiac surgeons would not give up hope. They performed a unique, high-risk hybrid procedure that combined minimally invasive method with traditional surgical techniques. They stopped the massive balloon-like aneurysm, replaced a failed heart valve, repaired another valve and also closed a hole in Crawford’s heart.

Now, just a few weeks since the successful Feb. 7 procedure, Crawford is much more active and energetic, and only taking medications for her heart. Most importantly, she no longer needs a heart-lung transplant.

She can’t believe it and has to pinch herself as a reminder that it’s real, Crawford said. She had been told since childhood that she would not survive for more than a few years. Her sister Kathy Crawford said it’s the first time since her sister’s birth that she has a positive prognosis.

Such hybrid surgeries are the start of a major medical trend, said Dr. Jamil Aboulhosn, director of the Ahmanson-UCLA Adult Congenital Heart Disease Center.

“We’re able to do more for high-risk patients like Patti than ever before. We’re performing more creative procedures that blend traditional surgery and minimally invasive techniques to help patients who previously had few or no options,” said Aboulhosn, who is also an assistant clinical professor of cardiology at the David Geffen School of Medicine at UCLA.

There were major challenges to Crawford’s procedure. Aboulhosn says the 12 centimeter aneurysm threatening her life was one of the largest he’d seen. The presence of severe lung pressure elevation, or pulmonary hypertension, increased the likelihood that the aneurysm could burst at any moment.

Patients like Crawford with pulmonary hypertension are deemed too high risk to undergo open-heart surgery on a heart-lung machine, which takes over work of the heart and lungs in providing circulation and oxygen to the body during the operation.

Aboulhosn and Dr. Hillel Laks, a UCLA professor of cardiothoracic surgery, devised a plan to perform the operation using a novel hybrid intervention to shorten the time needed on the heart-lung machine and thereby give Crawford a better chance of surviving the operation. Hybrid interventions are performed by a surgeon and an interventional cardiologist. The team combines the strengths of traditional heart surgery with less invasive catheter-based interventions to reduce procedure duration, making them less invasive and improving safety.

“By incorporating newer interventions with traditional surgery, we can customize heart operations and that can lead to the best patient outcome,” said Laks, who is also a distinguished UCLA Chancellor’s Professor.

Laks and the operating room team started with traditional surgical methods, placing her on the heart-lung machine and opening the aneurysm by her heart.

Aboulhosn then employed the hybrid intervention by using a new balloon-mounted “melody valve” to replace her failing pulmonary valve and to close the hole in her heart. These two procedures, which normally would take more than an hour to complete surgically, only took 10 minutes thanks to the less-invasive valve-replacement technique.

Laks then used traditional techniques, removed the portion of the artery that had the aneurysm and placed a synthetic tube in its place. He also surgically repaired the tricuspid heart valve.

The use of the hybrid technique with the melody valve shortened the need for the heart-lung machine by more than an hour and the procedure had no complications. Crawford’s circulating oxygen saturation improved from 72 percent immediately before the surgery to 97 percent immediately afterwards, meaning her tissues were finally receiving adequate oxygen, giving her more energy. Her complexion and skin are also now pink and healthy.

“I’m able to do more every day without having to rest, like making a bed, walking down the driveway, packing a suitcase and preparing food,” Crawford said. “Before the operation I would not have dreamed of making my own bed and I would have needed to rest for hours afterwards. It’s been many years since I’ve been able to do anywhere near this level of activity.”

First study of relationship between cumulative traumatic stress exposure, inflammation.

Aoife O'Donovan

Greater lifetime exposure to the stress of traumatic events was linked to higher levels of inflammation in a study of almost 1,000 patients with cardiovascular disease led by researchers at the San Francisco VA Medical Center and the University of California, San Francisco.

In the first study to examine the relationship between cumulative traumatic stress exposure and inflammation, the scientists found that the more traumatic stress a patient was exposed to over the course of a lifetime, the greater the chances the patient would have elevated levels of inflammatory markers in his or her bloodstream.

“This may be significant for people with cardiovascular disease, because we know that heart disease patients with higher levels of inflammation tend to have worse outcomes,” said lead author Aoife O’Donovan, Ph.D., a Society in Science: Branco Weiss Fellow in psychiatry at SFVAMC and UCSF.

The study was published electronically in February in Brain, Behavior, and Immunity.

The authors looked at exposures to 18 different types of traumatic events, all of which involved either experiencing or witnessing a direct a threat to life or physical integrity, in 979 patients age 45 to 90 with stable heart disease. They then measured a number of clinical markers of inflammation that circulate in the bloodstream, and found a direct correlation between degree of lifetime stress exposure and levels of inflammation.

Five years later, they measured the surviving patients’ inflammation markers again, and found that the patients who had originally reported the highest levels of trauma at the beginning of the study still had the highest levels of inflammation.

“Even though we lost some study participants because they died, we still observed the same relationship in those who remained,” O’Donovan said. “This suggests that it wasn’t just the people who were the most sick at the outset who were driving this effect.”

Senior investigator Beth Cohen, M.D., a physician at SFVAMC, emphasized that the effect remained even after the researchers adjusted for psychiatric diagnoses such as post-traumatic stress disorder (PTSD), anxiety and depression.

“Not everyone who is exposed to trauma develops PTSD,” said Cohen, who is also an assistant professor of medicine at UCSF. “This study emphasizes that traumatic stress can have a long-term negative impact on your health even if you don’t go on to develop PTSD. It also tells us that, as clinicians, we need to think about not just which diagnostic box someone might fit into, but what their lifetime trauma exposure has been.”

Although the study did not probe the potential causes for the link between lifetime stress and inflammation, O’Donovan offered one possible explanation.

“We know that in the aftermath of traumatic stress, people become more sensitive to threats,” she said. “This is actually pro-survival, because if you’re in a dangerous environment, that alertness can help you avoid future harm.”

However, she explained, people with heightened threat sensitivity may also show increased inflammatory responses. “What we think is happening is that people with a history of multiple traumatic stress exposures have increased inflammatory response more often and for longer periods, and so inflammation becomes chronically high,” she said.

Cohen noted that “this is a study of older people, and the cumulative effects that decades of traumatic experiences have on their bodies. If we could intervene with young people,” she said, “using techniques that we know help fight stress, such as exercise, yoga and other integrative health techniques, it would be interesting to know if we might be able to prevent some of this.”

The study subjects were all participants in the Heart and Soul Study, an ongoing investigation into the link between psychological factors and the risk of heart events and mortality in patients with stable heart disease. The Heart and Soul study is directed by Mary Whooley, M.D., a physician at SFVAMC and a professor of medicine at UCSF.

Co-authors of the study are Thomas Neylan, M.D., of SFVAMC and UCSF, and Thomas Metzler, M.A., of SFVAMC.

The study was supported by funds from the National Institutes of Health, the U.S. Department of Defense, the Irene Perstein Foundation, the Department of Veterans Affairs and a Society in Science: Branco Weiss Fellowship. Some of the funds were administered by the Northern California Institute for Research and Education.

NCIRE – The Veterans Health Research Institute – is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.

SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

UC Davis student to study condition that mimics heart attack brought on by stressful situations.

Annahita Sarcon, UC Davis

Annahita Sarcon, a fourth-year medical student at the UC Davis School of Medicine, was awarded a $2,500 grant from the American Medical Association (AMA) Foundation’s Seed Grant Research Program to support investigations on broken-heart syndrome, a temporary condition that mimics a heart attack brought on by stressful situations.

Broken-heart syndrome, also known as takotsubo cardiomyopathy, is thought to affect 2.5 percent of patients seeking treatment for a heart attack worldwide. While blood flow in coronary arteries is not blocked, the flow is reduced, and a part of the heart temporarily enlarges and may not pump well.

First described in Japan in 1991, the condition gets its name from characteristic change in the shape of the heart that occurs during the stress, which resembles an octopus pot, or tako-tsubo. The condition is treatable, with normal heart function typically being restored in a week.

“The exact cause and molecular mechanisms of heart-muscle damage from broken-heart syndrome are unclear,” said Sarcon, who is currently conducting stem cell research in Spain as a Fulbright scholar. “While adrenaline and other stress hormones may be involved, the goal of my research is to identify specific biological markers and risk factors associated with this condition, which primarily affects post-menopausal women. Because current blood tests cannot distinguish between heart attack and broken-heart syndrome, finding specific markers could lead to a new diagnostic test that could help practitioners better utilize health-care resources, such as cardiac catheterization.”

Cardiac catheterization is the gold standard for treating patients with acute blockages in coronary arteries. According to the Agency for Healthcare Research and Quality, cardiac catheterization is the fourth most commonly performed hospital procedure in the U.S. But the lifesaving treatment is expensive and invasive, and research suggests that a third of individuals with symptoms will have no artery blockage. A diagnostic biomarker for broken-heart syndrome could help rule out heart attack and inform clinical decisions regarding the need for cardiac catheterization.

With the AMA Foundation research funds, Sarcon also will expand the international registry for patients with takotsubo cardiomyopathy under the mentorship of Christian Templin, cardiologist and founder of the international registry for takotsubo cardiomyopathy. She will conduct her studies at the University Hospital Zurich in Switzerland, one of Europe’s largest and most renowned medical centers, and anticipates using the opportunity to initiate future collaborations between the UC Davis School of Medicine and her colleagues in Switzerland.

Established in 2000, the Seed Grant Research Program provides small grants to medical students, physician residents and fellows to conduct basic science or clinical research projects. It was created to encourage more physicians to consider research careers. The program not only supports the scientific discoveries of researchers but also gives young investigators a positive grant experience early in their careers.

Sarcon is one of only 43 individuals nationwide who received a seed grant this year.

“The AMA Foundation Seed Grant Research Program provides important financial support, motivation and professional development to outstanding investigators who are in the beginning stages of their research careers,” said AMA Foundation President Owen Garrick. “Many recipients of this program go on to publish their work, present at conferences and secure larger grants to continue their research advancements.”

The AMA Foundation advances public health and medical scholarship through philanthropic support of physician-directed initiatives.

The UC Davis School of Medicine is among the nation’s leading medical schools, recognized for its research and primary care programs. The school offers fully accredited master’s degree programs in public health and in informatics, and its combined M.D.-Ph.D. program is training the next generation of physician-scientists to conduct high-impact research and translate discoveries into better clinical care. Along with being a recognized leader in medical research, the school is committed to serving underserved communities and advancing rural health. For more information, visit UC Davis School of Medicine at medschool.ucdavis.edu.