# Cardiac Calcification and Cholesterol Efflux in Older Adults

> **NIH NIH K23** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $190,171

## Abstract

Calcification of the coronary arteries and aortic valve is prevalent in older adults and associated with
myocardial infarction, congestive heart failure and stroke. Centenarians and their offspring have a lower
burden of cardiovascular disease than their peers with usual longevity. Since cholesterol and lipid deposition
are a potent trigger for calcification, it is possible that improved release of cholesterol from cardiac tissues to
serum may be a protective mechanism in exceptionally long-lived individuals. Cholesterol efflux is the
movement of cholesterol and phospholipid out of cell membranes to lipid-poor apolipoprotein acceptors, the
first step in reverse cholesterol transport. The proposed study builds on the applicant’s previous and ongoing
work into the determinants of coronary and aortic valve calcification by leveraging the LonGenity study to relate
longevity with reduced calcification, improved cholesterol efflux capacity, and identify genetic
variants underlying these phenotypes. Specifically, this cross-sectional study is designed to add a
measurement of coronary artery and aortic valve calcification by computed tomography (CT) and cholesterol
efflux to LonGenity, a longitudinal cohort study of up to 1400 genetically homogenous older Ashkenazi Jewish
adults, of whom half are the offspring of exceptionally long-lived parents resilient to pathologic cardiovascular
aging and half are the offspring of usual-lived parents. The LonGenity cohort is ideal for this study because the
cohort is older, characterized phenotypically and genotypically, and its homogeneous population makes
detecting genetic variants more efficient. This study aims to assess the prevalence and severity of coronary
and aortic valve calcification in the offspring of exceptionally long-lived parents as compared to age and sex-
matched peers of usual-lived parents (Aim 1); the association of cholesterol efflux with cardiac calcification and
the exceptional-longevity offspring group (Aim 2); and candidate genes associated with increased cholesterol
efflux and decreased cardiac calcification (Aim 3). This study responds to the NHLBI’s strategic research
priority on pathobiology of calcification of the coronary arteries and heart valves and NIA’s focus on identifying
determinants of resiliency to disease. LonGenity has advantages for addressing whether calcification is
reduced in individuals resilient to pathologic aging who have little calcification late in life, if cholesterol efflux is
a potential protective mechanism against aortic valve calcification (in which such efflux-related proteins have
been identified), and if major candidate genes are involved in these processes. These findings could lead to
identification of key pathways that could be targeted with small molecules to protect against calcification,
offering new approaches to prevention of disorders that currently lack medical treatment. Importantly, through
a mentored research experience by a multi-disciplina...

## Key facts

- **NIH application ID:** 9892260
- **Project number:** 1K23HL146982-01A1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Anna E Bortnick
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,171
- **Award type:** 1
- **Project period:** 2020-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892260

## Citation

> US National Institutes of Health, RePORTER application 9892260, Cardiac Calcification and Cholesterol Efflux in Older Adults (1K23HL146982-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9892260. Licensed CC0.

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