MSCs: what’s in a name?

Whether they are "stem" or "stromal", from adult tissues or from umbilical cord blood, MSCs are being used for a lot of clinical trials. Read more

Mopping up immune troublemakers after transplant

Memory CD8+ T cells play an important role in kidney transplant rejection, and they resist drugs that would otherwise improve Read more

Tracking a frameshift through the ribosome

Ribosomal frameshifting, visualized through X-ray Read more

Emory Clinical Cardiovascular Research Institute

Racial disparities in a CV biomarker

Because circulating progenitor cells repair blood vessels, they are a measure of regenerative capacity in the cardiovascular system. Cardiologist Arshed Quyyumi, MD and his colleagues at Emory Clinical Cardiovascular Research Institute have intensively studied this cell type as a marker of vulnerability or resilience.

A recent paper from Quyyumi’s team in Circulation Research examines circulating progenitor cells (CPCs) through the lens of racial disparity. The authors find that African-Americans tend to have lower levels of this regenerative biomarker:

In a large well-characterized biracial cohort, we demonstrate that black participants had significantly lower CPC counts compared with whites, even after adjustment for differences in demographic factors and CVD risk factors. These results were validated in an independent cohort. Thus, on average, after adjustment for sex and other CVD risk factors, blacks have CPC levels that are ≈15% to 30% lower compared with whites, even in subjects free of risk factors. CPC levels decline with age, reaching on average half the levels at age 80 compared with age 20. We found that blacks have CPC counts equivalent to those in whites who are 14 years older. CPC levels are higher after AMI as a result of mobilization because of injury. We show for first time that blacks have 30% to 35% lower CPC mobilization in the setting of AMI.

This is a tricky area to study. How many socioeconomic and environmental factors go into the racial disparities of cardiovascular disease risk? Diet. Exercise. Geography, education, access to healthcare. Air pollution. Psychological stress and inflammation associated with discrimination. It is possible to view CPCs as summing up many of these influences, analogous to the way hemoglobin A1C measurements integrate someone’s blood sugar levels over time as a marker of diabetes. Read more

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Elevated (but still low) troponin as a long term cardio biomarker

This weekend (March 10) at the American College of Cardiology meeting, data will emerge on whether expensive and much-discussed PCSK9 inhibitors can lower the risk of heart disease as much as they reduce LDL cholesterol.

To help doctors decide who should take cholesterol-lowering drugs that cost thousands of dollars a year, the focus of discussion could fall on risk models, such as the Framingham score and its successors, or other biomarkers besides various forms of cholesterol. What a coincidence! We have experts on those topics at Emory Clinical Cardiovascular Research Institute: ECCRI co-director Arshed Quyyumi, MD and Laurence Sperling, MD, Director of Preventive Cardiology at the Emory Clinic.

Cardiologists led by Quyyumi have a recent paper in Journal of the American Heart Association looking at troponin as a long-term cardiovascular disease biomarker. Troponin is familiar to cardiologists because it is a sign of acute damage to the heart muscle. If someone with chest pain goes to the emergency department of a hospital, a test for troponin in the blood can say whether a heart attack occurred.

However, as clinical tests for troponin have become more sensitive in the last decade, interpretation has moved past just a “yes/no” question. The levels of troponin now detectable are much smaller than those used to confirm a heart attack. Elevated troponin can be detected in all sorts of situations where the heart is under stress, including after strenuous exercise in healthy individuals. The “optimal cutoff” the Emory authors use in some of their statistical analyses is 5.2 picograms per milliliter. This graph, derived from a 2011 Circulation paper, illustrates just how low that is. Read more

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When circulating ambulances disappear

Someone driving around a city on a regular basis will see ambulances. At times they’re going somewhere fast; sometimes they’re just driving. What if, on a given day, fewer ambulances are visible?

One possible conclusion might be: the ambulances are away responding to a group of people who need help. This effect resembles what Arshed Quyyumi and colleagues from Emory Clinical Cardiovascular Research Institute observed in a recent paper, published in the Journal of the American Heart Association.

Arshed Quyyumi, MD

Quyyumi’s team looked at progenitor cells, which circulate in the blood and are attracted to sites of injury.  In a group of 356 patients with stable coronary artery disease, the researchers saw that some (31 percent) had “ExMI” – exercise-mediated myocardial ischemia. That means impairments in blood flow were visible via cardiac imaging under the stress of exercise. This is a relatively mild impairment; participants did not report chest pain. This paper emerges from the MIPS (Mental Stress Ischemia Prognosis) study, 2011-2014.

The ambulance-progenitor cell analogy isn’t perfect; exercise, generally a good thing, increases progenitor cell levels in the blood, says co-first author and cardiology fellow Muhammad Hammadah. The study supports the idea that patients with coronary artery disease may benefit from cardiac rehab programs, which drive the progenitor cells into the ischemic tissue, so they can contribute into vascular repair and regeneration. Read more

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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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Food deserts and cardiovascular risk

Heval Mohamed Kelli, MD got some attention at the American College of Cardiology meeting over the weekend with his work on food deserts — low-income areas distant from access to healthy food.

As Medscape summarized the results: “Atlantans living in disadvantaged areas where the nearest supermarket was a mile or more away were more likely to have hypertension or hyperlipidemia, smoke, be obese, and have higher levels of systemic inflammatory markers and stiffer arteries.”

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Kelli at Clarkston Health Clinic, which Emory doctors helped establish in 2015. Clarkston is considered a “food desert”.

For more on Kelli’s journey from Syrian refugee to Clarkston, GA teenager to Emory cardiology researcher, check out this feature in Emory Magazine.

His research was conducted through the Emory Clinical Cardiovascular Research Institute, using information on 712 community participants from the META-Health study and 709 Emory/Georgia Tech employees from the Predictive Health study.

Three possibilities for further investigation:

*Income, education, race and geography are intertwined. “Whether lack of access to healthy foods, low income, or low education is driving these processes needs to be further studied,” Kelli and colleagues concluded.

*For detailed maps of food deserts, not just in Atlanta and/or determined using different criteria, the U.S. Department of Agriculture makes it possible.

*This Atlantic article makes the point that “when it comes to nutrition access, the focus should be on poverty, not grocery-store location.” You can lead people to the supermarket (or build one close to where they live), but you can’t make them eat a Mediterranean diet. Studies from Los Angeles showed that obesity increased more in some neighborhoods, even despite a ban on new fast food restaurants.

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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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