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Novel Therapies to Improve Cardiac and Skeletal Muscle O2 Supply-Demand Mismatch in Older Adults with Peripheral Arterial Disease

Award Number: R21AG054940
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary / Abstract Aging is the strongest predictor for the development of cardiovascular disease. Peripheral arterial disease (PAD) is a common and debilitating form of cardiovascular disease characterized by atherosclerotic lesions in the large and medium sized arteries of the legs. Data from 2015 suggest that > 200 million people worldwide have PAD; PAD is prevalent in 7% of people age 55-59 and in 20% of people age 80-84. More than $4.4 billion is spent on PAD each year in the United States. PAD is associated with pain during walking (i.e., “intermittent claudication”), decreased functional independence, and an extremely high risk of coronary heart disease and cardiac death. Stated another way, patients with stage I or stage II PAD (also called “claudication”) visit their doctor because they have leg pain, but coronary disease is what will most likely kill them. Therefore, effective strategies that improve walking ability and coronary vascular health in PAD patients are needed. In this R21 application we propose mechanistic-driven intervention studies to improve a disease that is highly prevalent in the geriatric population. We will use a T1 translational approach. Specifically, we are applying basic and clinical findings toward new strategies to improve walking ability and coronary vascular function in human subjects with diagnosed PAD. In Aim 1, we will evaluate the effect of acute cardioselective ß1 blockade (with esmolol) on coronary blood flow, calf muscle oxygenation, and systemic BP during exercise in PAD. In Aim 2, we will evaluate the effect of four to six days of dietary nitrate supplementation (beetroot juice) on coronary blood flow, calf muscle oxygenation, and systemic BP during exercise in PAD. There is a strong scientific premise to conduct the proposed studies. Despite the prevalence of PAD and the associated poor coronary outcomes, only our recently published study (Ross et al 2017) has measured coronary blood flow during exercise in PAD patients. Moreover, the single study that evaluated the effects of dietary nitrate supplementation on walking performance and peripheral vascular responses in PAD was underpowered and did not use a true placebo. In this T1 translational project, we will fill these gaps in knowledge by conducting rigorously designed, mechanism-driven intervention studies in older adults (55-85 yr) with symptomatic PAD. If these exploratory studies identify ß1-blockade and/or dietary nitrate as safe and efficacious for PAD, our team of investigators will be well positioned to conduct a multi-center study (which would be needed to ultimately change the standard of care in these patients).


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$9 )
2023	2019	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Aging Research	000	2	10/21/2022	NON-COMPETING CONTINUATION	-$9
														Subtotal = -$9

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Aging Research	000	2	3/22/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $195,063 )
2019	2019	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Aging Research	000	2	5/10/2019	NON-COMPETING CONTINUATION	$195,063
														Subtotal = $195,063

Issue Date FY: 2018 ( Subtotal = $233,448 )
2018	2018	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Aging Research	000	1	9/21/2018	NEW	$233,448
														Subtotal = $233,448

Grand Total All Awards = $428,502

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Novel Therapies to Improve Cardiac and Skeletal Muscle O2 Supply-Demand Mismatch in Older Adults with Peripheral Arterial Disease

Award Number: R21AG054940

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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