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Cardiovascular Medicine

Big data, Cardiovascular Medicine, Chronic Disease, Research, Science, Stanford News, Videos

Big data approach identifies new stent drug that could help prevent heart attacks

Big data approach identifies new stent drug that could help prevent heart attacks

Ziad Ali, MD, PhD, was a cardiovascular fellow at Stanford with a rather unique skill when a 6-year study published today online in The Journal of Clinical Investigation first began.

The multi-talented physician-scientist – who is now associate director of translational medicine at Columbia University Medical Center – had figured out a way to put tiny little stents into mice with clogged arteries as a PhD student.

The skill would become key as he and colleagues set out to find a better pharmaceutical for the drug-eluting stents that are used in combination with angioplasty to treat coronary artery disease. In order to prevent stent disease, the often serious medical problem caused by stents themselves, chemotherapy drugs were added to bare metal stents. But these drug-eluting stents have their own problems: The drugs work like “hitting a pin with a sledgehemmer,” as Ali describes it, often damaging the lining of the arteries which can lead to heart attacks. As a result, patients are required to take blood thinners for up to a year after the procedure to prevent clots.

“A lot of our patient population is on the elderly side with bad hips or diabetes,” Ali told me. “Once you get a drug-coated stent, you can’t have surgery for a year. And if you stop the blood thinners for any reason, you’re at risk of a stent clotting off. And that actually causes a heart attack. Stent thrombosis has a high mortality rate.”

By using a “big data” computational approach, learning about the genetic pathways involved in coronary artery disease, then testing the new theories on mice models in the lab, researchers were able to pinpoint a potential new treatment for patients: Crizotinib, a pharmaceutical approved by the FDA for treatment in certain cases of lung cancer.

“This could have major clinical impact,” Euan Ashley, MD, PhD, senior author of the study, who discusses the work alongside Ali in the video above, said.

Previously: Euan Ashley discusses harnessing big data to drive innovation for a healthier world, New computing center at Stanford supports big data, Trial results promising for new anti-clotting drug and A call to use the “tsunami of biomedical data” to preserve life and enhance health
Photo in featured entry box by Mark Tuschman

Bioengineering, Cardiovascular Medicine, Clinical Trials, Research, Science, Stanford News

Using “nanobullets” for good – not evil

Using "nanobullets" for good - not evil

14858598815_b572bddbf9_zMy husband, a big science fiction fan, perked up the other day when I told him I was writing a medical science story about nanotechnology. Apparently, nanotechnology – the study and application of extremely small things – has long been big in the world of science fiction. There, authors have used it to create lots of cool-sounding phantasmagorical stuff like the “nanoprobes” used by the Borg in the movie Star Trek: The Next Generation to assimilate individuals into their collective.

I’m not sure how the fictional nanoprobe was supposedly built, but in my real-life story on the modern day use of nanotechnology to design better methods for heart disease treatment, I do describe the creation of “nanobullets” by Stanford researchers. And it’s pretty cool.

Jayakumar Rajadas, PhD and his colleagues detailed their work in a scientific paper published this month in the journal Biomaterials. Their idea was to create a new and improved delivery system for the delicate peptide apelin into the heart as a treatment for hypertrophic heart disease, which I discuss in the piece:

In a treatment model similar to giving insulin to diabetes patients, physicians have attempted to treat these heart conditions with doses of apelin. The therapeutic agent is delivered intravenously through to the cardiovascular tissue, but due to its short half-life — the drug is quickly eliminated from the blood plasma — the success of this treatment has been limited.

Rajadas considered the possibility for improving the delivery system of the peptide using nanotechnoloy because it has been used for the past 10 years to stabilize therapeutic agents in the body and target them to specific tissues, he said. In this case, the idea was to protect the quickly degrading apelin peptides with large, stable molecules to help transport them to their target organ - the heart:

The research team developed a novel technique to increase the stability of the fragile apelin peptides by protecting them with a lipid cover that Rajadas calls the ‘Trojan Horse’ method of delivery. The liposome ‘nanocarriers’ encapsulates the apelin and sneaks it through the blood to the heart tissue.

The resulting apelin “nanobullets,” as the researchers refer to them, were then delivered through the blood system to the cardiovascular tissue of mice with induced hypertrophic heart conditions. The theory was that the apelin would not be released until it was near the heart tissue.

Researchers then tried it out, shooting the nanobullets into the hearts of mice with hypertrophic heart disease. They delivered two shots over a 14-day period. Results showed that symptoms dramatically improved in the mice that received the shots with the apelin nanobullets when compared to mice shot with saline treatments or even treatments of apelin not protected with the liposome covering.

“Apelin in this form could eventually be used as treatment for humans delivered as a shot rather than intravenously as in the past,” Rajadas told me. “The idea is that regular monthly or bimonthly shots could lesson symptoms.”

Previously: Stanford team develops nanotech-based microchip to diagnose Type 1 diabetes
Photo by NMK Photography

Cardiovascular Medicine, Medicine X, Patient Care, Surgery

Operation Heart: Engaging patients in caring for patients

Operation Heart: Engaging patients in caring for patients

Stanford’s Medicine X is a catalyst for new ideas about the future of medicine and health care. This new series, called The Engaged Patient, provides a forum for some of the patients who have participated in or are affiliated with the program. Our inaugural post comes from Sarah E. Kucharski.

mended heartRivulets of deep brown iodine trickled across the patient’s body as nurses swabbed with sponges and unfurled blue surgical drapes. I contemplated his bare feet. I wondered if they were cold. I wondered if he wore no socks so that the nurses might palpitate for his dorsalis pedis and posterior tibial pulses. And I thought about how many times the patient on the operating table had been me.

When given the opportunity to observe surgery, I had accepted eagerly. One hardly could have called it an exercise in learning self-care techniques — no matter how empowered I am as a patient, even I draw a line at doing by own arterial bypass. Rather I wanted to see how the other half lived. For once I entered the operating room wearing scrubs and surgical mask instead of an open-backed gown and an IV line pushing Versed through my veins.

My conscious presence meant I represented not just myself but my fellow patients who clamored for meaningful engagement. There is much talk about being able to view health care and the medical establishment from another perspective, but few truly have an opportunity to do so. It has been pointed out that doctors attend school to learn how to be doctors, yet patients do not attend school to learn how to be patients. More importantly there is no school to teach doctors how to be patients and, save for those patients whose condition manifests early enough to motivate medical school, no method of teaching patients how to be doctors. Collaborations to re-imagine health care for our joint benefit will be ineffective unless we expand medical education to regularly include the patient, which will facilitate empathy and improved health literacy through shared experiences.

As surgery preparations continued, the operating room nurses appeared apprehensive they were going to share an experience with me. I had signed on with a go big or go home philosophy — the aortic root and mitral valve replacement would be my first surgery. Each nurse’s eyes widened for two tell-tale seconds when I told them my novice status, and their voices caught as they tried to mitigate surprise, “Ooh.” Their apprehension meant I had something to prove. There would be no circumstance under which I would faint.

And with the loud whine of the sternum saw, we were underway.

Continue Reading »

Behavioral Science, Cardiovascular Medicine, Medicine and Society, Research, Stanford News

The lonely are more likely to die. But why?

The lonely are more likely to die. But why?

11317715623_e27537b3f3_zLoneliness isn’t healthy — most everyone knows that. But why exactly does isolation lead to disease, or even death? Stanford researcher Sylvia Kreibig, PhD, set out to answer that question by digging through data from the Heart and Soul Study, an inquiry that followed more than 1,000 coronary heart disease patients for about 10 years, starting in 2000.

Turns out that socially isolated patients are 61 percent more likely to die in any given year than other patients, Kreibig and her team found. Yet you don’t need many friends to stave off the ill effects of solitude. Those with at least one to three regular contacts fared no better than the most-social butterfly. Even tossing in factors that affect mortality such as age and weight didn’t affect general conclusion: friendless folks die sooner. But why?

Kreibig’s team, which included Stanford psychologist James Gross, PhD, delved deeper to figure it out.

It isn’t depression. Depression is independently related to mortality, but it couldn’t explain the link between solitude and risk of death. Instead, Kreibig and colleagues found a strong link between several behavior factors such as smoking, omega-3 concentration (a representative of diet quality), and medication adherence and isolation.

“If you are more integrated, you have people around that look after you and care for you, making sure you’re eating healthy foods, not smoking and taking medications as directed,” Kreibig told me. “You yourself as a patient actually have a lot of control over factors that affect your health… Just by integrating some salmon into your diet, you have a better chance of survival.”

The team classified 1,019 patients into four categories of social integration (low, medium, medium-high and high), based on whether or not they had a partner, strength of linkages with family and friends and membership in religious congregations and community groups. Patients in the low category were more likely to smoke, eat unhealthy foods and skip their medications, the study found.

She cautioned that the study, which appears in this month’s issue of Psychosomatic Medicine, demonstrated correlation, not causation. In addition, the patients were primary male and, as they suffered from heart disease, could be affected differently than healthy, or younger, patients.

Next, Kreibig said she plans to examine the emotions related to social isolation and their effect on health.

Previously: The importance of human connection as part of the patient experience, How social media and online communities can improve clinical care for elderly patients and How loneliness can impact the immune system
Photo by Alex Krasavtsev 

Cardiovascular Medicine, Mental Health, Research

The link between mental-health conditions and cardiovascular disease

The link between mental-health conditions and cardiovascular disease

14496537236_932d9a9acd_zA growing body of research has shown the connection between our emotional well-being and physical health. Among the latest findings: Schizophrenia, bipolar disorders and major depressive and anxiety disorders can greatly increase a person’s risk of heart disease and stroke.

In a study presented at this year’s Canadian Cardiovascular Congress in Vancouver, Canada, researchers examined connections between mental-health conditions, use of psychiatric medication, and heart health using data from the Canadian Community Health Survey. Medical News Today reports:

They found that patients who had a mental illness at any point in their life were twice as likely to have had a stroke or experienced heart disease than the general population, while patients who had not experienced heart disease or stroke had a higher long-term risk of cardiovascular disease.

Furthermore, patients who used psychiatric medications for their mental illness were twice as likely to have heart disease and three times as likely to have had a stroke than those who did not use such medications.

“This population is at high risk,” says [Katie Goldie, PhD, lead author of the study and a postdoctoral fellow at the Centre for Addiction and Mental Health in Toronto], “and it’s even greater for people with multiple mental health issues.”

Goldie and colleague said that there are three main factors that contribute to mental-health patients’ increase cardiovascular risk. They are: lifestyle behaviors, such as tobacco and alcohol use, poor diet and physical inactivity; psychiatric medications, which can induce weight gain and inhibit the body from breaking down fats; and inadequate access to health care.

The findings are significant in light of statistics (.pdf) from the National Alliance of Mental Health showing that 1 in 4 adults in the United States experience a mental health disorder in annually and that serious mental illness costs the nation $193.2 billion in lost earnings per year.

Previously: Examining how mental stress on the heart affects men and women differently, Study shows link between traffic noise, heart attack and Study offers insights into how depression may harm the heart
Photo by Holly Lay

Cardiovascular Medicine, Chronic Disease, In the News, Research, Science, Stanford News

How best to treat dialysis patients with heart disease

How best to treat dialysis patients with heart disease

523392_4923732760_zKidney failure patients on dialysis often have other chronic diseases – heart disease topping the list. They’re prescribed an average of 12 pills a day by physicians, according to Stanford nephrologist Tara Chang, MD, and they spend three-to-four hours at a treatment center three times a week connected to an artificial kidney machine.

For Chang, this makes it all the more important that any medication she prescribes for a patient on dialysis is both essential and effective.

The problem is, particularly in the case of treating kidney patients with heart disease, evidence-based treatment guidelines just aren’t available. Kidney doctors are left making best guesses based on guidelines written for the general population.

“Our patients might be different from patients not on dialysis,” said Chang. “Dialysis patients have a lot of heart disease, yet rarely does a cardiology study enroll patients on dialysis, so we just don’t know.”

This was part of the motivation behind Chang’s most recent study examining the use of anti-platelet drugs such as clopidogrel, one of the most commonly prescribed drugs for kidney patients. The researchers looked at the use of anti-platelet medications such as clopidogrel as treatment following stenting procedures to unclog arteries in the heart in 8,458 dialysis patients between 2007 and 2010. The data suggests that longer-duration of drug use may be of benefit to patients on dialysis who get drug-eluding stents but not those who get bare metal stents. Chang told me:

We found that for those who got drug-eluting stents who took the drug for 12 months compared to those who had stopped the drug at some earlier time point, there was a non-statistically significant trend towards lower risks of death and heart attacks. So for this group, following the same guidelines as for the general population may be appropriate. However, we found no indication of benefit with longer duration of anti-platelet drug use for patients on dialysis who got bare metal stents.

About half of the 400,000 patients in the U.S. on dialysis also have coronary artery disease, as referenced in the study. The number of those getting stents inserted to unclog arteries also has increased 50 percent in the past decade, the study states. The results of the study, while not definitive as to exactly how long doctors should prescribe the drug, does stress the need for more clinical research on patients with kidney failure to provide guidance on treatment strategies for heart disease.

“Because our study was not a randomized trial,” said Chang, “we tried to be very measured in how we interpreted the results. What it does point to is the fact that we can’t assume that what works in non-dialysis patients works in dialysis patients. Hopefully our study will help convince researchers to include our dialysis patients in their studies.”

The paper was published this week in the Journal of the American Heart Association.

Previously: Keeping kidney failure patients out of the hospitalStudy shows higher rates of untreated kidney disease among older adults and Study shows daily dialysis may boost patients’ heart function, physical health.
Photo by newslighter

Cardiovascular Medicine, Men's Health, Mental Health, Research, Women's Health

Examining how mental stress on the heart affects men and women differently

Examining how mental stress on the heart affects men and women differently

stress_womanPast research has shown that stress, anger and depression can increase a person’s risk for stroke and heart attacks. Now new findings published in the Journal of the American College of Cardiology show that cardiovascular and psychological reactions to mental stress vary based on gender.

In the study (subscription required), participants with heart disease completed three mentally stressful tasks. Researchers monitored changes in their heart using echocardiography, measured blood pressure and heart rate, and took blood samples during the test and rest periods. According to a journal release:

Researchers from the Duke Heart Center found that while men had more changes in blood pressure and heart rate in response to the mental stress, more women experienced myocardial ischemia, decreased blood flow to the heart. Women also experienced increased platelet aggregation, which is the start of the formation of blood clots, more than men. The women compared with men also expressed a greater increase in negative emotions and a greater decrease in positive emotions during the mental stress tests.

“The relationship between mental stress and cardiovascular disease is well known,” said the study lead author Zainab Samad, M.D., M.H.S., assistant professor of medicine at Duke University Medical Center, Durham, North Carolina. “This study revealed that mental stress affects the cardiovascular health of men and women differently. We need to recognize this difference when evaluating and treating patients for cardiovascular disease.”

Previously: Study shows link between traffic noise, heart attack, Ask Stanford Med: Cardiologist Jennifer Tremmel responds to questions on women’s heart health and Study offers insights into how depression may harm the heart
Photo by anna gutermuth

Cardiovascular Medicine, Events, Patient Care, Stanford News

A ssathi (partner) to thwart heart disease in South Asians

A ssathi (partner) to thwart heart disease in South Asians

heart-66892_1280S.S., a 44-year-old male South Asian engineer, visited Rajesh Dash, MD, PhD, at his Stanford clinic not long ago.

“He had come to see me almost as a third option,” Dash told a crowd of 25-or-so listeners at a presentation on South Asians and heart disease sponsored by the Stanford Health Library last week. Dash didn’t mention why S.S. originally visited a doctor. But he said S.S. exercised three times a week and ate relatively healthy food. He smoked socially. His blood pressure was only slightly elevated. He didn’t appear to be at high risk for heart disease.

One doctor had left S.S. with little more information than he had before the visit after the results of a standard diagnostic questionnaire were inconclusive. Another doctor recommended an angiogram. S.S. balked – why, he asked.

So he came to see Dash, who directs SSATHI, or the Stanford South Asian Translational Heart Initiative, a clinical program that specializes in coronary disease and insulin resistance in South Asians, which is defined to include people from India, Pakistan, Bangladesh, Nepal, Bhutan, Maldives and Sri Lanka.

Dash asked S.S. a question no one else had: What about your family? “Well,” S.S. responded, “my older brother, who is 46, had a heart attack recently. My mother has four stents in her arteries. Three of my mother’s brothers died of heart attacks before they were 60.”

Now, no medical degree was needed to see that S.S. was clearly at high risk for heart disease. Dash prescribed a coronary CT scan that revealed that one of S.S.’s heart vessels was 99 percent blocked. In other words, S.S. was a walking time bomb. Doctors treated his condition aggressively with a combination of drugs, surgery, recommended lifestyle changes and follow-up care.

S.S. had three questions for Dash: Why did this happen to me? How can I prevent it from happening again? And, how can I prevent it from happening to my children?

Dash doesn’t have the answers to all the questions — yet. But his SSATHI team (Ssathi also means companion or partner in Hindi) is working to figure them out – and to keep S.S. healthy for decades to come. The team surrounds patients with experts — cardiologists, nutritionists, surgeons and others. And they provide social-media tools and encourage around-the-clock commitments from patients. The program is no cake walk.

Dash also shared some startling statistics: More than half of all South Asians who suffer heart attacks get them before age 50. In California, South Asians have four times more heart attacks than other ethnic groups. South Asians also have a high rate of diabetes and heart disease is now the top cause of death in India, Dash said.

Ssathi hopes to treat South Asians of all ages, but they’re particularly looking for new patients from ages 20 to 55 because heart disease in South Asians begins at young ages. The SSATHI program is focusing South Asians in California, but Dash said they also plan to introduce programs in India.

Previously: Global community must do a better job of managing risk of Nipah virus, expert says, A closer look Asian American health and Gap exists in women’s knowledge of heart disease
Image by geralt

Cardiovascular Medicine, Genetics, Research, Science, Stanford News, Stem Cells

Stem cell study explains how mutation common in Asians affects heart health

Stem cell study explains how mutation common in Asians affects heart health

10011881004_d5ab6d7cd9_zMany Asians carry a mutation that causes their faces to flush when they drink alcohol. The affected gene is called ALDH2, and it also plays a role in cardiovascular health. Carriers are more susceptible to coronary artery disease and tend to recover more poorly than non-carriers from the damage caused by a heart attack. Now Stanford cardiologist Joseph Wu, MD, PhD, and postdoctoral scholar Antje Ebert, PhD, have learned why.

The researchers used a type of stem cell called an induced pluripotent stem cell, or iPS cell, to conduct the study. The stem cells are made from easily obtained tissue like skin, and they can be coaxed in the laboratory to become other types of tissue, like heart muscle cells. It’s one of the first times iPS cells have been used to examine ethnic-specific differences among populations. The research was published yesterday in Science Translational Medicine.

From our release:

The study showed that the ALDH2 mutation affects heart health by controlling the survival decisions cells make during times of stress. It is the first time ALDH2, which is involved in many common metabolic processes in cells of all types, has been shown to play a role in cell survival. In particular, ALDH2 activity, or the lack of it, influences whether a cell enters a state of programmed cell death called apoptosis in response to stressful growing conditions. [...]

The use of heart muscle cells derived from iPS cells has opened important doors for scientists because tissue samples can be easily obtained and maintained in the laboratory for study. Until recently, researchers had to confine their studies to genetically engineered mice or to human heart cells obtained through a heart biopsy, an invasive procedure that yields cells which are difficult to keep alive long term in the laboratory.

You’ve likely read about Wu’s previous work with heart muscle cells derived from iPS cells. Now he’s shown iPS cells are also a good way to compare the effect of genetic differences among populations, and he has big plans. More details about his plans from our release:

Wu is working to start a biobank at the Stanford Cardiovascular Institute of iPS cells from about 1,000 people of many different ethnic backgrounds and health histories. “This is one of my main priorities,” he said. “For example, in California, we boast one of the most diverse populations on Earth. We’d like to include male and female patients of major representative ethnicities, age ranges and cardiovascular histories. This will allow us to conduct ‘clinical trials in a dish’ on these cells, a very powerful new approach, to learn which therapies work best for each group. This would help physicians to understand for the first time disease process at a population level through observing these cells as surrogates.”

Previously: Induced pluripotent stem cell mysteries explored by Stanford researchers, A new era for stem cells in cardiac medicine? A simple, effective way to generate patient-specific heart muscle cells and “Clinical trial in a dish” may make common medicines safer, say Stanford scientists

Photo by Nicholas Raymond

Cardiovascular Medicine, Research, Science, Stanford News

Scientists preferentially cite successful studies, new research shows

Scientists preferentially cite successful studies, new research shows

Say you’re a medical researcher. You slave over a project for months, even years, and you’re thrilled when a stellar journal agrees to publish it. That’s it, right? Well, no. Now, you need others to spot your work – and cite it in their studies. You can court citations just as you court Twitter followers: by producing high-quality content worthy of a bigger audience.

That said, sometimes bias creeps in. For example, studies by superstar scientists are cited more often than those by their junior colleagues — no surprise there. But now, Stanford medical resident Alex Perino, MD; cardiologist Mintu Turakhia, MD, MAS; and colleagues have shown that studies documenting higher success rates of a certain procedure are more likely to be cited than studies of the same procedure with lower success rates.

“This is an indication that we as clinicians and investigators need to be mindful of how we present the data,” Turakhia told me.

In a study released yesterday in Circulation: Cardiovascular Quality and Outcomes, Perino, Turakhia and other colleagues examined research papers on catheter ablation for atrial fibrillation, a treatment with widely varying success rates. For example, among the examined studies, the success of a single treatment varied between 10 and 92 percent. The variation is perfectly understandable, Turakhia said. Atrial fibrillation, an irregular heart rhythm, can be caused by a variety of underlying conditions and can vary in severity, he explained. The procedure itself, which uses energy to destroy tissue in key areas of the left atrium, can also vary, Turakhia said.

That’s why ablation for atrial fibrillation was an apt treatment to examine. The team included 174 studies with 36,289 patients published since 1990. They found that for every 10 point increase in reported success rate, there was an 18 percent increase in the mean citation count. The citation bias remained significant even when accounting for time since publication, the journal’s impact rating, sample size and study design.

The bias is important when considering the efficacy of new and evolving treatments, Turakhia said: “We just wanted to make sure the totality of evidence is being presented fairly and completely to readers of the medical literature, which may be clinicians, scientists, insurance companies and policy makers. However, in this case, we found that ablation could be perceived to be more effective than the totality of evidence would suggest.”

Turakhia said he hopes this study prompts other researchers to examine bias in other treatments and specialties.

Previously: Re-analyses of clinical trial results rare, but necessary, say Stanford researchers, John Ioannidis discusses the popularity of his paper examining the reliability of scientific research, A discussion on the reliability of scientific research, U.S. effect leads to publication of biased research, says Stanford’s John Ioannidis

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