Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Arshed Quyyumi

Elevated troponin after exercise refines cardiac risk prediction

High levels of troponin, a sign of acute stress to the heart, in the blood reveal whether someone recently experienced a heart attack. Advances in testing have made it possible to detect much lower levels of troponin — but still elevated above zero. For example, elevated troponin can be detected after strenuous exercise, even in healthy young athletes.

With that exercise-induced response in mind, Emory Clinical Cardiovascular Research Institute investigators have been studying whether high-sensitivity troponin measurements might be used to replace cardiac stress tests. These procedures are expensive and sometimes involve nuclear imaging, which exposes patients to radiation.

A new paper in American Journal of Cardiology shows how elevated high-sensitivity troponin levels in response to exercise on a treadmill can predict future outcomes in patients with coronary artery disease — better than stress tests with imaging.

Read more

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Take heart, Goldilocks — and get more sleep

Sleeping too little or too much increases the risk of cardiovascular events and death in those with coronary artery disease, according to a new paper from Emory Clinical Cardiovascular Research Institute.

Others have observed a similar U-shaped risk curve in the general population, with respect to sleep duration. The new study, published in American Journal of Cardiology, extends the finding to people who were being evaluated for coronary artery disease.

Arshed Quyyumi, MD and colleagues analyzed data from a registry of 2846 patients undergoing cardiac catheterization at Emory. The “sweet spot” appeared to be those who report sleeping between 6.5 and 7.5 hours per night.

39 percent of patients with coronary artery disease reported that they slept fewer than 6.5 hours per night, and 35 percent slept longer than 7.5 hours. For the next few years, both groups had higher risks of all-cause mortality: elevated risk of 45 percent and 41 percent, respectively. Patients were followed for an average of 2.8 years.

The extreme ends of sleep duration both had even higher risk: people who reported less than 4.5 hours per day had almost double mortality risk (96 percent), and those more than 8.5 hours had 84 percent higher mortality risk.

Patients with short sleep durations also had higher cardiovascular mortality (48 percent), but adjusting for cardiovascular risk factors attenuated the association between long sleep duration and CV risk.

A detailed assessment of someone’s sleep can require PSG (polysomnography). In this study,  researchers were able to get information by simply asking about sleep duration.

The participants in the Emory study were simply asked: “How many hours of sleep do you usually get each night (or when you usually sleep)?” This question may not always be answered accurately, since time in bed isn’t necessarily time asleep. Still, the broad strokes show that the sleep-CV health relationship is robust.

“What is most stunning to me are that these data were collected from cardiac patients about to undergo an invasive procedure, who still reported an aspect of their sleep that was meaningful and predictive of future survival,” says Donald Bliwise, PhD, a specialist in sleep and aging research who is a co-author on the Emory study. “Often, epidemiologic studies collect data far away from a clinic setting, where anxiety is less and estimations may be sharper. We have here in this clinical study beautiful evidence that estimates made ‘from the gurney’ may be just as meaningful as those collected in the field.”

Quyyumi says if patients with heart disease are sleeping poorly, it’s important to recognize that they are at higher risk and counsel them regarding getting more sleep, as well as factors that can disrupt sleep, such as caffeine, alcohol and looking at screens late in the day.

More specific treatments may depend what is interfering with high-quality sleep in a given patient. Several conditions can lead to difficulty sleeping, such as sleep apnea, restless leg syndrome, as well as depression, all of which have been linked with heart disease. Physiologically, several mechanisms are probably exerting their effects, such as weakening circadian rhythms and sleep fragmentation with aging, and obesity/metabolic syndrome driving inflammation. Read more

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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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Before the cardiologist goes nuclear w/ stress #AHA17

Exercise stress testing to diagnose heart disease has a long history. This year, cardiologists can celebrate the 50-year anniversary of a study connecting abnormal stress test results and obstructive coronary artery disease (CAD).

The basic stress test procedure can involve walking on a tilting treadmill as the heart is monitored via electrocardiogram. A variant called the nuclear stress test involves introducing a radioactive tracer into the body to visualize alterations in blood flow within the heart.

Some stress tests are considered inappropriate, leading to additional medical costs. Arshed Quyyumi and colleagues from Emory Clinical Cardiovascular Research Institute presented research on Sunday at the American Heart Association Scientific Sessions meeting on the use of a blood test along with an exercise stress test. First author Bryan Kindya is a 2017-18 internal medicine resident.

The blood test detects troponin, a sign of recent damage to the cardiac muscle. Very high levels indicate that someone is having a heart attack. As testing for troponin has become more sensitive in recent years, the implications of lower but still detectable troponin levels need to be backed up by follow-up outcomes. That’s what the Emory data can provide.

Quyyumi’s team found that more than 25 percent of CAD patients will have troponin levels below a certain cut-off (2.45 picograms per milliliter), predicting that they have a low risk of having heart problems during a stress test or adverse events (hospitalization/heart attack/death) over the next three years.

The researchers conclude that measuring troponin in CAD patients before embarking on stress testing “may provide major cost-savings.” Disclosure: the research was done in cooperation with Abbott Labs, the maker of the high-sensitivity troponin test.

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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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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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