The team found that three of these variants were associated with impaired sensitivity to the common blood thinner clopidogrel, and a fourth that affects a blood platelet receptor involved in platelet aggregation and clot formation. Analyzing these gene variants will help researchers identify patients at risk for early stent thrombosis and take measures to prevent it.
The data also provide a clinical and genomic score that indicates the best predictive accuracy for stent thrombosis risk. The findings are published in the Oct. 26 issue of the Journal of the American Medical Association.
Through a partnership with the Institut de Cardiologie at Pitié-Salpêtrière University Hospital in Paris, France, the research team evaluated the DNA of 123 patients who had undergone stent implantation and developed early ST while treated with dual antiplatelet therapy, which is a combination of aspirin and clopidogrel. The patient information was shared as part of ONline ASSIstance for Stent Thrombosis (ONASSIST), a nationwide web registry of patients in France.
Looking at 23 genetic variants previously associated with clopidogrel metabolism, platelet receptor function, and the control of blood clotting, they found four that were predictive risk factors of early ST. They also found that a low dose of clopidogrel in combination with a proton pump inhibitor, which is a drug to treat acid reflux, also increased the risk of early ST.
"Our research indicates that early stent thrombosis is strongly related to ineffectiveness of clopidogrel in certain patients," said Jean-Sebastien Hulot, MD PhD, Associate Professor of Medicine in the Division of Cardiology and Director Pharmacogenomics and Personalized Therapeutics at the Cardiovascular Research Center at Mount Sinai School of Medicine. "Now that we have a clearer understanding of the mechanism behind the development of stent thrombosis, we can take preventive measures to protect our patients from this deadly complication."
The research team compared the genetic code of people registered in the ONASSIST program with 246 coronary patients without early ST. They evaluated alleles, which are types of genetic variation that arise from mutations, of 23 genes. They found that CYP2C19*2 allele, which is commonly associated with loss of enzyme function, was highly prevalent in people presenting with early ST, as was the allele ABCB1 3435T, and both were infrequent in the control group. Two other alleles, CYP2C19*17 and ITGB3, were prevalent in the healthy control group but not in the early ST group indicating a protective effect. The scientists developed a genetic score where the more of these mutations that the patient had, the higher their risk for developing early ST. This risk was independent of clinical risk factors, including the use of proton pump inhibitors, acuteness of PCI, complexity of cardiac lesions, left ventricular heart function, and a high dose of clopidogrel. Only two of these risk factors– clopidogrel dose and proton pump inhibitor use – are modifiable in reducing risk for early ST. Eventually, the best prediction was achieved using the combination of both clinical and genetic factors. The authors conclude that this "clinico-genomic" approach could be useful prior to stent implantation to identify the patients with high-ST risk.
"We found that, independent of other clinical risk factors, these genetic factors play a critical role in the development of early ST," said Dr. Hulot. "Altogether, our data will help clinicians understand the factors contributing to early ST, and allow them to reduce the outcome risk to these patients. Understanding the genetic factors provides researchers with new drug targets for future study to reduce the genetic risk as well."
Mount Sinai's Cardiovascular Research Center plans to continue the partnership with the Institut de Cardiologie at Pitié-Salpêtrière University Hospital in Paris to develop an international cardiogenomic laboratory to better understand genetic risk factors associated with heart disease and treatments for heart disease to improve and better target clinical care for patients.
PCI is a minimally invasive technique used to treat patients with diseased coronary arteries caused by a buildup of plaque and cholesterol. During the procedure, a catheter is threaded through the body, typically from an artery in the groin to a blocked or occluded vessel in the heart. The occlusion is removed and a stent is often inserted to maintain flow within the blood vessel. Up to four percent of patients undergoing PCI experience early ST, which is deadly in 40 percent of those patients.
Mount Sinai Press Office | EurekAlert!
Researchers find trigger that turns strep infections into flesh-eating disease
19.02.2019 | Houston Methodist
Loss of identity in immune cells explained
18.02.2019 | Technische Universität München
Up to now, OLEDs have been used exclusively as a novel lighting technology for use in luminaires and lamps. However, flexible organic technology can offer much more: as an active lighting surface, it can be combined with a wide variety of materials, not just to modify but to revolutionize the functionality and design of countless existing products. To exemplify this, the Fraunhofer FEP together with the company EMDE development of light GmbH will be presenting hybrid flexible OLEDs integrated into textile designs within the EU-funded project PI-SCALE for the first time at LOPEC (March 19-21, 2019 in Munich, Germany) as examples of some of the many possible applications.
The Fraunhofer FEP, a provider of research and development services in the field of organic electronics, has long been involved in the development of...
For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.
The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...
Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens
Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...
Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light
When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...
The so-called Abelian sandpile model has been studied by scientists for more than 30 years to better understand a physical phenomenon called self-organized...
11.02.2019 | Event News
30.01.2019 | Event News
16.01.2019 | Event News
21.02.2019 | Life Sciences
21.02.2019 | Earth Sciences
21.02.2019 | Life Sciences