Research study on high blood pressure medication benefited from TL1 program

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A study that found that L-type calcium channel blockers (LCCBs) — a widely used drug for treating high blood pressure — may harm the heart as much as help it, benefited from the use of Penn State Clinical and Translational Science Institute's research population discovery tool, TriNetX. Martin Johnson, a graduate student and study co-author, is a graduate of the institute's year-long Translational Research Training Program (TL1)

A Penn State laboratory research team found that in rat and human cells LCCBs were implicated in activating a protein that actually increased the restructuring of blood vessels seen in chronic hypertension. By examining epidemiological data, the team found that LCCBs are associated with a greater risk for heart failure compared to other antihypertensive drugs. The findings suggest that care should be taken when prescribing these drugs to patients, particularly older adults and those with advanced hypertension.

"In the United States, nearly half of all adults — or just over a hundred million — have hypertension, and its prevalence is increasing; worldwide, the condition is expected to affect 1.56 billion people by 2025," Mohamed Trebak, Ph.D., professor of cellular and molecular physiology, said. "L-type calcium channel blockers are one of the most widely prescribed drugs to treat hypertension, yet we have found that these drugs may cause the same type of damage they are intended to prevent." 

The researchers found evidence that LCCBs induced growth and movement of blood vessel wall cells, which causes the walls to thicken and stiffen. This thickening leads to higher blood pressure. The researchers believe this is caused by the over-activation of a specific protein due to the extended use of LCCB.

"We wanted to see if these findings had clinical implications. Thus, we wanted to know if there were any associations of these drugs with long-term effects of blood vessel changes, like heart failure," Johnson said. "We used TriNetX to compare the incidence of heart failure in hypertensive patients treated exclusively with LCCBs to patients treated on non-LCCBs antihypertensive medications."

TrINetX allows Penn State researchers to search Penn State Health medical records for research population discovery and study feasibility. A recent update to the tool enables researchers to search nationally, search insurance claims data and search for COVID-19-related records. 

"TriNetX was extremely helpful in answering this question for us," Johnson said. 

Johnson learned about TriNetX when he was a scholar in the institute's Translational Research Training Program (TL1). This year-long program for graduate and M.D./Ph.D. students provides tailored educational opportunities to learn skills essential for conducting interdisciplinary clinical and translational research. The flexible curriculum includes courses in statistics, epidemiology, clinical research methods, bioinformatics, research ethics and scientific communication combined with training in team-based research.

"My Translational Research Training Program experience introduced me to TriNetX and many of the techniques to do clinical research," Johnson said. "I would not have been able to answer this epidemiological question without my participation in it."

Other Penn State College of Medicine authors on the paper include Xuexin Zhang, research associate; Ping Xin, laboratory manager; Scott Emrich, graduate student; Ryan Yoast, graduate student; Robert Nwokonko, graduate student; Donald Gill, Ph.D.,  professor and chair of the Department of Cellular and Molecular Physiology; Wei Li, Ph.D., assistant professor of pediatrics; Nadine Hempel, Ph.D., associate professor of pharmacology. Other authors include Aparna Gudlur and Patrick Hogan, La Jolla Institute for Immunology, and Raphael Courjaret and Khaled Machaca, Cornell University in Qatar and Qatar Foundation.

The National Heart Lung and Blood Institute, The National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Diseases, the U.S. Department of Defense, the Qatar National Research Fund and the Qatar Foundation, and the National Center for Advancing Translational Science (through use of TriNetX) supported this research.

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