# Modeling Aortic Valve Calcification and Risk of Aortic Valve Events In Asymptomatic Individuals from the Multi-Ethnic Study of Atherosclerosis

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $127,245

## Abstract

Calcific aortic valve disease (CAVD) is slowly progressive and begins in midlife. Calcification of
the aortic valve leaflets is the core underlying process leading to severe aortic stenosis with both
inflammation and Lp(a) serving as key underlying pathophysiologic contributors. Severe aortic
stenosis is the most common heart valve disorder in the US. It predominantly affects older individuals
and with an increasing life expectancy in the United States, the proportion of individuals ≥75 years old
is expected to be 12% by the year 2050. Accordingly, the number of individuals requiring aortic valve
replacement (AVR) is expected to nearly double between 2025 and 2015 to 1.4 million individuals.
 The only approved treatment available is AVR, although a recent subgroup analysis from the
SEAS trial demonstrated a reduced rate of AVR for patients with a LDL >155 mg/dL and mild aortic
stenosis who were treated with simvastatin and ezetimibe. There is no accepted risk stratification
method for the long-term prediction of which patients are most likely to require AVR. Therefore, it is
imperative to develop novel strategies to identify patients with early AVC who have the highest
lifetime risk for developing severe aortic stenosis, as these patients are most likely to benefit from
new treatment therapies/strategies.
 The 2011 NIH Working Group on Calcific Aortic Valve Disease highlighted crucial areas for
future research including 1) developing imaging modalities to identify early AVC prior to detection by
echocardiography, 2) determining whether the measurement of early AVC may identify patients most
likely to benefit from earlier pharmacologic interventions, and 3) determining whether there are
interactions between risk factors for aortic stenosis. Non-contrast cardiac computed tomography (CT)
is the ideal imaging modality for measuring early CAVD, because it provides a precise, absolute, and
direct measurement of aortic leaflet damage from the very earliest stage. However, the long-term
relationship between AVC and clinical aortic stenosis events is unknown, as prior studies
investigating CT visualized AVC have had small sample sizes, used a cross-sectional design, or
focused on determining the optimal timing for AVR.
 By leveraging the AVC measurements from coronary artery calcium scans performed at MESA
Visit 1 we will create an adjudicated severe aortic stenosis outcome, making MESA the only NHLBI
cohort with the ability to comprehensively describe the long-term relationship between AVC and
clinical aortic stenosis events. Accordingly, these results will have a direct impact on 1) long-term
personalized risk stratification, 2) identification of high-risk patients most likely to benefit from new or
earlier therapies/strategies, and 3) reducing future aortic valve morbidity and mortality.

## Key facts

- **NIH application ID:** 10226914
- **Project number:** 5R21HL150458-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Seamus Paul Whelton
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $127,245
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226914

## Citation

> US National Institutes of Health, RePORTER application 10226914, Modeling Aortic Valve Calcification and Risk of Aortic Valve Events In Asymptomatic Individuals from the Multi-Ethnic Study of Atherosclerosis (5R21HL150458-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10226914. Licensed CC0.

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