Grant Underscores Importance of Treating Peripheral Arterial Disease as a Chronic Condition

Lawrence Sinoway, M.D., director, Penn State Hershey Heart and Vascular Institute, has been the lead investigator on “Acute and Chronic Afferent Engagement: Sympathetic and End Organ Responses,” a National Institutes of Health-funded project that started in 2010 and examines four separate aspects of peripheral arterial disease (PAD).

Exercise Blood Pressure in Peripheral Arterial DiseaseLess than 50 percent of PAD patients report the classic symptom of claudication, making the condition difficult to diagnose and treat. However, PAD is an alarming prognostic sign and correlates with significantly increased risk of cardiovascular mortality.¹ Sinoway describes another common therapeutic conundrum: “On the one hand, we as physicians see a disease caused by an arterial blockage and believe that by removing the blockage, patients will improve. While this may be true acutely, it is crucial to note that PAD, and indeed all forms of atherosclerosis, are chronic conditions that will return if patients don’t make lifestyle changes to reduce their future risk.”

In his primary study, Sinoway demonstrates that when PAD patients perform exercise with the affected leg, their arterial blood pressure becomes elevated as a result of the exercise pressor reflex, a cardiovascular change caused by muscular contractions. (Figure)

This blood pressure increase, which is directly related to the severity of the arterial blockage, can be controlled with high doses of ascorbic acid administered intravenously.

Researchers at Penn State Hershey are conducting additional studies that explore other components of PAD (including hypoxia and its role in altering blood vessel response, and neural and muscular response to arterial blockage) and add synergistic relevance to the primary study. “We realized that the exercise pressor reflex might be playing an underappreciated role, and have sought to understand the ramifications of this reflex engagement,” concludes Sinoway.

The goals for the next stage of this research, being conducted exclusively at Penn State Hershey Medical Center, examine the efficacy of three types of intervention: 1) IV ascorbic acid, 2) NSAIDs, and 3) placement of a stent in the blocked artery. Several larger issues will be addressed, including, but not limited to, is this elevated blood pressure positive or negative? If negative, does it explain the sharp increase in five-year cardiovascular mortality in PAD patients? Ultimately, it is hoped that these studies lead to earlier diagnosis and more effective treatment of PAD.

Lawrence Sinoway, M.D.Lawrence I. Sinoway, M.D.
Distinguished Professor, Medicine
Director, Penn State Hershey Heart and Vascular Institute
PHONE: 717-531-6853
FELLOWSHIP: Cardiovascular disease, Bronx Municipal Hospital Center-Jacobi Hospital, Bronx, New York
RESIDENCY: Internal medicine, Bronx Municipal Hospital Center- Jacobi Hospital, Bronx, New York
MEDICAL SCHOOL: Rutgers New Jersey Medical School, Newark, New Jersey


  1. Muller MD, Drew RC, Blaha CA, Mast JL, Cui J, Reed AB and Sinoway LI. Oxidative stress contributes to the augmented exercise pressor reflex in peripheral arterial disease patients. J Physiol 23 (2012);6237–6246.

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Filed under Patient Care, Research, Treatments

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