March for Science ATL: photos

Emory scientists and supporters of science were out in substantial numbers Saturday at the March for Science Atlanta in Candler Park. March organizers, many of whom came from the Emory research community, say they want to continue their advocacy momentum and community-building after the event’s Read more

How race + TBI experience affect views of informed consent

The upcoming HBO movie of The Immortal Life of Henrietta Lacks reminds us that biomedical research has a complex legacy, when it comes to informed consent and people of color. A paper from Emory investigators touches on related issues important for conduct of clinical research Read more

Fecal transplant replants microbial garden

Emory physicians explain how FMT (fecal microbiota transplant) restores microbial balance when someone’s internal garden has been Read more

Arshed Quyyumi

Flow mediated dilation

On Friday, researchers from Emory Clinical Cardiovascular Research Institute demonstrated a test for how much blood vessels adjust to changes in blood flow. This test is known as “flow-mediated dilation” or FMD. A blood pressure measurement cuff is tightened on the arm for five minutes, restricting blood flow.

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ECCRI investigator Salman Sher, MD demonstrates flow-mediated dilation

When the cuff is released, blood flow increases, but how much the arm’s main artery expands depends on the endothelium – the lining of the artery — and its ability to respond to nitric oxide, which is induced by the increased flow. Researchers monitor the artery’s expansion by ultrasound.

ECCRI co-director Arshed Quyyumi and his colleagues at Emory have extensive experience using the FMD test. Impaired endothelial function is an early stage in the process of atherosclerosis.

The FMD test is relatively non-invasive, in that no catheter probe is necessary. However, practitioners need practice and careful study design to ensure accuracy, ECCRI investigator Salman Sher explained. Posture, time of day and whether the patient has eaten can all affect the results.

Lab Land asked Sher (seated in the photo) whether the effect was similar to the common experience of sleeping on an arm and having it turn numb, followed by “pins and needles” when the pressure is relieved. This feeling actually comes from nerve compression. Read more

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Emory clinical research highlights for #AHA16

Clinical research presentations at 2016 American Heart Association Scientific Sessions: telomeres + circulating progenitor cells, food deserts, and troponin as risk marker for atrial fibrillation.

 

Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes Nov. 13, 4:45 pm, Room 346-347

Aging, in general, depletes our bodies’ regenerative capacities. Arshed Quyyumi, MD and colleagues at Emory Clinical Cardiovascular Research Institute have shown how circulating progenitor cells or CPCs, which regenerate blood vessels and correlate with outcomes in cardiovascular disease, are a finite resource.

Working with Quyyumi, research fellow Muhammad Hammadah, MD is presenting data on how telomere length interacts with the levels of CPCs, in a study of mental stress ischemia in 566 patients with stable coronary artery disease. Telomeres tend to shorten with ageing and cellular stress, and their length has been a widely studied biomarker.

Hammadah concludes that low leukocyte telomere length is associated with decreased regenerative capacity, independently of age and cardiovascular risk factors. However, telomere length and CPC levels are independent and additive predictors of adverse cardiovascular outcomes (such as death, heart attack, stroke, or hospitalization for heart failure), he finds. Hammadah is a finalist for the Elizabeth Barrett-Connor Research Award for Young Investigators in Training. Read more

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Aging, CVD risk factors and progenitor cells

Cardiologists Ibhar Al Mheid, Arshed Quyyumi and colleagues from Emory’s Clinical Cardiovascular Research Institute recently published a paper that weaves together insights from past research on circulating progenitor cells. They tease apart the influences of age and cardiovascular disease (CVD) risk factors on these cells, whose regenerative capacity has made them the target of much investigation. From this research, one can infer that the circulatory system has a limited regenerative capacity, and stress upon the system earlier in life depletes it later.

Circulating progenitor cells are rare cells in the blood that can become white or red blood cells, as well as endothelial cells, which line blood vessels and repair them when damaged by cardiovascular disease. Quyyumi and his colleagues have sought to deliver progenitor cells, derived from the patient’s own bone marrow, to the heart – or less invasively, spur them out of the bone marrow with drugs. Read more

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When cardiac risk biomarkers will become really useful (and save money?)

The news is awash in studies of cholesterol-lowering statins and a much-anticipated (and expensive) class of drugs called PCSK9 inhibitors. Clinical trials show that now-generic (and cheap) statins reduce the risk of heart attack and stroke, although some patients report they can’t tolerate them. The data is still to come showing whether PCSK9 inhibitors have the same risk-lowering effect, as opposed to their effects on LDL cholesterol, which are robust.

When /if doctors have to start deciding who should take drugs that cost thousands of dollars a year and who shouldn’t, biomarkers may come in handy. How about a panel of markers like the one studied by Emory cardiologist Arshed Quyyumi, MD and colleagues?

At the recent American College of Cardiology meeting in Chicago, research fellow Salim Hayek, MD reported on a five-marker panel and how it could predict the risk of cardiovascular events (that is: death, heart attack, hospitalization for heart failure) in a group of patients who underwent cardiac catheterization at Emory hospitals.

The five biomarkers are: C-reactive protein (CRP, measures inflammation), suPAR (soluble urokinase-type plasminogen activator receptor or suPAR, predicts kidney disease), fibrin degradation products (FDP: blood coagulation), heat-shock protein-70 (HSP70, cellular stress) and troponin (hs-TnI, cardiac muscle damage). Data on three of these were published in 2013.

The Emory team keeps adding more biomarkers, and the ability of the accumulated information to add to what doctors can figure out easily — the Framingham score and its successors — becomes stronger.

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ACC 2016: Stem cell study sees improved heart failure outcomes

Patients with heart failure who received an experimental stem cell therapy experienced a reduced rate of death, hospitalization and unplanned clinic visits over the next year compared to a placebo group, according to results presented Monday at the American College of Cardiology meeting in Chicago.

The results of the ixCELL-DCM study were published online Monday by The Lancet. It was reportedly the largest cell therapy study done in patients with heart failure so far (58 treated vs 51 placebo).

Emory University School of Medicine investigators led by Arshed Quyyumi, MD, and their patients participated in the study, and Emory was one of the largest enrolling sites. Lead authors were Timothy Henry, MD of Cedars-Sinai Heart Institute in Los Angeles and Amit Patel, MD of the University of Utah.

“For the first time, a clinical trial has shown that administration of a cellular therapeutic results in an improvement in cardiac outcomes based on a prespecified analysis,” an editorial accompanying the paper in The Lancet says.

This study, which was sponsored by Vericel Corporation, was phase II, meaning that a larger phase III study will be needed before FDA approval. Read more

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ACC 2016: Elevated troponin linked to mental stress ischemia

Some people with heart disease experience a restriction of blood flow to the heart in response to psychological stress. Usually silent (not painful), the temporary restriction in blood flow, called ischemia, is an indicator of greater mortality risk.

Cardiologists at Emory University School of Medicine have discovered that people in this group tend to have higher levels of troponin — a protein whose increased presence in the blood that is a sign of recent damage or stress to the heart muscle– all the time, independently of whether they are experiencing stress or chest pain at that moment.

The results were presented Sunday by cardiology research fellow Muhammad Hammadah, MD at the American College of Cardiology meeting in Chicago, as part of the Young Investigator Awards competition. Hammadah works with Arshed Quyyumi, MD, and Viola Vaccarino, MD, PhD, and colleagues at the Emory Clinical Cardiovascular Research Institute.

“Elevated troponin levels in patients with coronary artery disease may be a sign that they are experiencing repeated ischemic events in everyday life, with either psychological or physical triggers,” Hammadah says.

Doctors test for troponin in the blood to tell whether someone has recently had a heart attack. But the levels seen in this study were lower than those used to diagnose a heart attack: less than a standard cutoff of 26 picograms per milliliter, in a range that only a high-sensitivity test for troponin could detect.

In a separate study, Emory investigators have shown that elevated troponin levels (especially: more than 10 pg/mL)  predict mortality risk over the next few years in patients undergoing cardiac catheterization, even in those without apparent coronary artery disease.

There is already a lot of information available for doctors about the significance of elevated troponin. It has even been detected at elevated levels after strenuous exercise in healthy individuals. One recent study suggested that low levels of troponin could be used to rule out heart attack for patients in the emergency department.

More information about the mental stress ischemia study: Read more

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Oxidative stress ain’t about free radicals, it’s about sulfur

This recent paper in Circulation, from Arshed Quyyumi and colleagues at the Emory Clinical Cardiovascular Research Institute, can be seen as a culmination of, even vindication for,  Dean Jones’ ideas about redox biology.

Let’s back up a bit. Fruit juices, herbal teas, yogurts, even cookies are advertised as containing antioxidants, which could potentially fight aging. This goes back to Denham Harman and the free radical theory of aging. [I attempted to explain this several years ago in Emory Medicine.]

We now know that free radicals, in the form of reactive oxygen species, can sometimes be good, even essential for life. So antioxidants that soak up free radicals to relieve you of oxidative stress: that doesn’t seem to work.

Dean Jones, who is director of Emory’s Clinical Biomarkers laboratory, has been an advocate for a different way of looking at oxidative stress. That is, instead of seeing cells as big bags of redox-sensitive chemicals, look at cellular compartments. Look at particular antioxidant proteins and sulfur-containing antioxidant molecules such as glutathione and cysteine.

That’s what the Circulation paper does. Mining the Emory Cardiovascular Biobank, Quyyumi’s team shows that patients with coronary artery disease have a risk of mortality that is connected to the ratio of glutathione to cystine (the oxidized form of the amino acid cysteine).

How this ratio might fit in with other biomarkers of cardiovascular risk (such as CRP, suPAR, PCSK9, more complicated combinations and gene expression profiles, even more links here) and be implemented clinically are still unfolding.

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Education is a life preserver, after heart attack

For the last decade, cardiology researchers have been collecting detailed information on the patients who come through Emory’s catheterization labs. The density of data (close to 7000 people) can make it possible to achieve some insights about mortality in American society.

Cardiology research fellow Salim Hayek, MD, presented some provocative findings yesterday in a poster competition at the American College of Physicians meeting in Boston. He has been working with Arshed Quyyumi, MD and colleagues at Emory’s Clinical Cardiovascular Research Institute.

Their analysis shows “college education as a discrete indicator of socioeconomic status was an independent predictor of survival.”

A key thing to remember when looking at this data is that most of the people in the cath lab at a given moment are not actually having a heart attack — just 13 percent are. (Abstract/poster available upon request). However, there’s enough suspicion or history of heart disease for doctors to take a look inside; most of them have hypertension and coronary artery disease, and many have had a heart attack in the past. The group is mostly men, average age 63. Read more

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ACC 2015: Newer heart risk calculator may better accounts for racial differences

A risk calculator for cardiovascular disease, developed as a companion for the 2013 American College of Cardiology/American Heart Association cholesterol guidelines, may account for racial differences in sub-clinical vascular function better than the Framingham Risk Score, Emory cardiology researchers say.

Their findings are scheduled for presentation Monday at the American College of Cardiology meeting in San Diego.

African Americans, especially men, tend to have a higher prevalence of cardiovascular disease, but this differences are not reflected in the Framingham Risk score. Arterial stiffness is a sign of heart disease risk that tends to appear more prominently among African Americans than whites. Cardiovascular research fellow Jia Shen, MD, MPH, and Emory colleagues analyzed data on arterial stiffness and structure from 1235 people – 777 whites and 458 African-Americans — enrolled in two large studies (Center for Health Discovery and Well Being and META-Health). Read more

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Lab Land looking back: Top ten themes for 2014

It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After diverting some of these topics into the 2015 crystal ball, I corralled them into themes.
1. Cardiac cell therapy
PreSERVE AMI clinical trial led by cardiologist Arshed Quyyumi. Emory investigators developing a variety of approaches to cardiac cell therapy.
2. Mobilizing the body’s own regenerative potential
Ahsan Husain’s work on how young hearts grow. Shan Ping Yu’s lab using parathyroid hormone bone drug to mobilize cells for stroke treatment.
3. Epigenetics
Many colors in the epigenetic palette (hydroxymethylation). Valproate – epigenetic solvent (anti-seizure –> anti-cancer). Methylation in atherosclerosis model (Hanjoong Jo). How to write conservatively about epigenetics and epigenomics.
4. Parkinson’s disease therapeutic strategies
Container Store (Gary Miller, better packaging for dopamine could avoid stress to neurons).
Anti-inflammatory (Malu Tansey, anti-TNF decoy can pass blood-brain barrier).
5. Personal genomics/exome sequencing
Rare disease diagnosis featured in the New Yorker. Threepart series on patient with GRIN2A mutation.
6. Neurosurgeons, like Emory’s Robert Gross and Costas Hadjpanayis, do amazing things
7. Fun vs no fun
Fun = writing about Omar from The Wire in the context of drug discovery.
No fun (but deeply moving) = talking with patients fighting glioblastoma.
8. The hypersomnia field is waking up
Our Web expert tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
Image guided cancer surgery (Shuming Nie/David Kooby). Cancer immunotherapy chimera (Jacques Galipeau). Fine tuning old school chemo drug cisplatin (Paul Doetsch)
10. Tie between fructose effects on adolescent brain (Constance Harrell/Gretchen Neigh) and flu immunology (embrace the unfamiliar! Ali Ellebedy/Rafi Ahmed)
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