News | December 12, 2013

Racial Difference in Blood Clotting Warrants Closer Look at Heart Attack Medications

clinical trial study antiplatelet thomas jefferson cath function monitors
December 12, 2013 — Thomas Jefferson University researchers discovered that the formation of blood clots follows a different molecular route in African Americans versus European Americans, providing a new understanding of the effects of race on heart disease. The finding could one day help doctors provide more individualized treatment of heart disease and other blood-clot-related illnesses, according to research publishing online Nov. 10 in Nature Medicine.
 
The finding may also provide an additional explanation for the disparity between outcomes in black and white patients with heart disease, which is the most common killer of white and black Americans. Compared to white patients, black patients have a two-fold increased incidence of heart disease and have a lower long-term survival. The reasons for this racial disparity are complex and include racial bias, a higher prevalence of traditional risk factors in blacks and differences in socioeconomic status, management and environment. However, even when these factors are considered, the survival rate of black heart attack patients is two-fifths the survival rate of white heart attack patients. This suggests there are yet-to-be identified factors accounting for the racial disparity in heart disease.
 
“We may need to consider our patient’s race when using certain heart disease therapies,” said lead author of the research Paul Bray, M.D., director, Cardeza Foundation for Hematologic Research, Thomas Jefferson University, and lead author of the research.
 
Antiplatelet medications, such as aspirin, are commonly prescribed to prevent heart attack or stroke. These medications function by blocking the clot-forming activity of platelets. The plaques in atherosclerotic vessels can occasionally rupture, causing the formation of a platelet plug that clogs blood vessels and can lead to heart attack or stroke. However, there is considerable variability in how patients respond to these medications, which confounds physicians who must deduce the appropriate drug and proper dose for each patient. Now, researchers from Thomas Jefferson University have identified some of the genetic differences behind these variations, which could help doctors treat racial groups with a more personalized and effective approach.
 
“Differences in platelet biology could be part of the explanation of the disparity,” said Bray.
 
To investigate whether the variation among different individuals had a racial component, Bray and collaborators from Baylor Medical College, Harvard Medical School and the New York and Puget Sound Blood Centers analyzed platelets from blood samples of 154 young healthy subjects that included 70 blacks and 84 whites. Self-reported race was confirmed with genetic tests that verified geographic (African or European) ancestry. Unexpectedly, the researchers found that platelets from black donors clotted faster and to a greater extent in response to the naturally occurring clotting agent, thrombin that specifically triggered one of the platelet-activating receptors, called PAR4. No racial differences were seen with other clotting agents.
 
Thrombin is the most potent platelet activator in the body, and it is targeted for suppression by numerous blood-thinning medications. However, newer drugs that target thrombin inhibit specific members of the PAR family of receptors. For example, the drug vorapaxar, currently in development for patients with a history of heart disease, specifically inhibits the PAR1 receptor. If PAR1 is blocked by vorapaxar, then PAR4 is the only means by which thrombin can activate platelets, and the Jefferson scientists showed that in this setting thrombin more potently activated platelets from blacks. It remains to be determined how or if these findings relate to drugs that are currently prescribed or to those currently in development.
Further molecular studies identified a novel gene called PCTP that mediated platelet activation through PAR4. PCTP was expressed at higher levels in platelets from blacks and appears to be a major contributor to the racial difference in blood clotting. Furthermore, a microRNA was identified that silenced the expression of PCTP; this microRNA was expressed at higher levels in platelets from whites than blacks and may contribute to the lower levels of thrombin activation through the PAR4 receptor in whites.
 
In fact, the researchers found many silencing microRNAs were more actively expressed in whites than in blacks, at least in platelets, suggesting that other aspects of platelet biology may be regulated differently depending on race. Uncovering the genes that these microRNAs suppress could help researchers hone in on individual differences in platelet function, and eventually how these differences contribute to disease and response to anti-clotting treatments.
 
“In this age where there is such a focus on delivering personalized medicine, we should embrace these differences to try to give our patients better care,” said Bray.
 
This work was supported by National Institutes of Health grant HL102482 and the Cardeza Foundation for Hematologic Research, as well as support from NIH grants DK48872 and DK56626. The authors report no conflicts of interest.
 
For more information: www.jefferson.edu, www.nature.com

Related Content

A key slide from Elnabawi's presentation, showing cardiac CT plaque evaluations, showing the impact of psoriasis medication on coronary plaques at baseline and one year of treatment. It shows a reversal of vulnerable plaque development. #SCAI, #SCAI2018

A key slide from Elnabawi's presentation, showing cardiac CT plaque evaluations, showing the impact of psoriasis medication on coronary plaques at baseline and one year of treatment. It shows a reversal of vulnerable plaque development.  

Feature | Cardiovascular Clinical Studies | May 14, 2018
May 14, 2018 – New clinical evidance shows common therapy options for psoriasis (PSO), a chronic inflammatory skin di
Intravenous Drug Use is Causing Rise in Heart Valve Infections, Healthcare Costs. #SCAI, #SCAI2018
News | Cardiovascular Clinical Studies | May 14, 2018
May 14, 2018 — The opioid drug epidemic is impacting cardiology, with a new study finding the number of patients hosp
Patient Enrollment Completed in U.S. IDE Study of THERMOCOOL SMARTTOUCH SF Catheter
News | Cardiovascular Clinical Studies | March 15, 2018
March 15, 2018 –  Johnson & Johnson Medical Devices Companies announced today that Biosense Webster, Inc., who wo
Lexington Begins HeartSentry Clinical Trial
News | Cardiovascular Clinical Studies | February 20, 2018
February 20, 2018 – Lexington Biosciences, Inc., a development-stage medical device company, announced the commenceme
Endologix Completes Patient Enrollment in the ELEVATE IDE Clinical Study
News | Cardiovascular Clinical Studies | February 06, 2018
February 6, 2018 – Endologix, a developer and marketer of treatments for aortic disorders, announced the completion o
12-Month Results from Veryan Medical's MIMICS-2 IDE Study Presented at LINC
News | Cardiovascular Clinical Studies | February 01, 2018
February 1, 2018 – Thomas Zeller (Bad Krozingen, Germany) presented the 12-month results from Veryan Medical’s MIMICS
LimFlow Completes U.S. Feasibility Study Enrollment, Receives FDA Device Status
News | Cardiovascular Clinical Studies | February 01, 2018
February 1, 2018 –  LimFlow SA, developer of minimally-inv
ESC 2017 late breaking trial hot line study presentations.
News | Cardiovascular Clinical Studies | September 12, 2017
September 12, 2017 – The European Society of Cardiology (ESC) Congress 2017 includes several Hot Line Late-breaking C
U.K., NHS studies, weekend effect, hospital admission, atrial fibrillation, heart failure
News | Cardiovascular Clinical Studies | June 28, 2016
New research shows patients admitted to National Health Service (NHS) hospitals in the United Kingdom for atrial...
stroke risk
News | Cardiovascular Clinical Studies | August 28, 2015
Most people assume strokes only happen to octogenarians, but recent evidence suggests that survivors of childhood can
Overlay Init