# Chronic Renal Insufficiency and Silent Progression of Aortic Stenosis (CRISP-AS)

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $763,809

## Abstract

PROJECT SUMMARY
Aortic stenosis (AS), is common and progression to symptomatic, severe AS is universally fatal without treatment
with aortic valve replacement (AVR), though only 1/3 of individuals receive AVR, due in part to concerns about
high perioperative risk and rapid valvular calcification/degeneration. Despite more than half a century of
research on this topic, comparatively little is known about risk factors for hemodynamic progression of
AS and there are no medical therapies of proven benefit for slowing or preventing AS progression. In
this setting, chronic kidney disease (CKD) represents an attractive model to study AS progression due to rapid
and premature valvular calcification, yielding mechanistic insights that could be applied to non-CKD population.
This proposal leverages the unique and granular phenotyping of participants in the Chronic Renal Insufficiency
Cohort (CRIC) and Atherosclerosis Risk in Communities (ARIC) Studies. CRIC is a large, multicenter,
prospective, well-phenotyped observational study, begun in 2003 and funded by NIDDK, enrolling adults (aged
21-74) with varying severity of CKD, with a goal to examine progression of cardiovascular disease amongst CKD
patients. A total of 3,552 CRIC participants had comprehensive transthoracic echocardiograms (TTEs) at years
1, 4, and 7 post-enrollment and upon initiation of dialysis, making it the only prospective population-based
cohort enrolling a large number of adults with CKD with serial TTEs, and thus uniquely allows us to test
several important biologic hypotheses in Aims 1-3 (to be additionally tested in individuals without CKD
who received TTEs in visits 5 [2011-2013] and 7 [2018-2019] of the Atherosclerosis Risk in Communities
[ARIC] Study in Aim 4). Preliminary data from CRIC indicate that progression of aortic peak velocity was greater
than the general population but lower than prior estimates in the dialysis population. As this measure is only one
of several AS severity measures and is influenced by transvalvular flow, we propose to review existing CRIC
TTE images (7,317 TTEs) to calculate all AS severity parameters, and then analyze existing and newly
measured data to address several questions. In Aim 1, we will evaluate if AS progression in CKD varies
according to two measures of kidney function (estimated glomerular filtration and albuminuria) and quantify the
inter-individual variability in AS progression rate. In Aim 2, we will identify clinical and biomarker risk factors that
associate with progression of AS, and whether these associations vary by kidney function. In Aim 3, we will
determine the relationship between rapid AS progression in CKD and adverse cardiovascular outcomes, and
whether this varies by kidney function. In Aim 4, in the ARIC cohort, we will examine if similar clinical and
biomarker risk factors identify an analogous risk of AS progression in a cohort without CKD. Doing so, we will
leverage the unique physiology of CKD to improve understand...

## Key facts

- **NIH application ID:** 10844441
- **Project number:** 5R01HL169517-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Jordan Blair Strom
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $763,809
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844441

## Citation

> US National Institutes of Health, RePORTER application 10844441, Chronic Renal Insufficiency and Silent Progression of Aortic Stenosis (CRISP-AS) (5R01HL169517-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10844441. Licensed CC0.

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