# Risk-Based Primary Prevention of Heart Failure

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2022 · $135,000

## Abstract

ABSTRACT
Despite declines in total cardiovascular mortality rates in the United States, heart failure (HF) mortality rates,
as well as hospitalizations and readmissions, are increasing with the greatest increases in mortality rates
observed among non-Hispanic Black adults under the age of 65 years. Identification of individuals at risk of HF
and specific HF subtypes (HFrEF and HFpEF) within diverse samples is critical to inform much-needed
strategies to reduce the burden of HF. Although guideline-directed medical therapies are increasingly available
for HF with reduced ejection fraction (HFrEF), prognosis remains dismal with 50% survival at 5 years. Further,
few effective disease-modifying therapies currently exist for patients with HF with preserved ejection fraction
(HFpEF), which is the most common HF subtype. The significant and growing burden of heart failure highlights
the need for preventive interventions prior to the development of clinical symptoms. As a result, risk
prediction to target prevention of HF, particularly for HFpEF, is a critical next step to improve
outcomes. Whereas risk-based prevention (matching the intensity of prevention with the absolute risk of the
individual) is widely accepted in the primary prevention of atherosclerotic cardiovascular disease, no such
prevention paradigm currently exists for HF, in part, due to the lack of a well-established and generalizable risk
model. To address multi-society practice guideline recommendations, our group recently developed and
validated the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) using classic statistical modeling
techniques in a population-based cohort sample. The current proposal builds upon our prior work and expands
it to leverage novel machine learning methods to efficiently integrate large, multidimensional data across
multiple domains and from two integrated health systems (Northwestern Medicine and Kaiser Permanente).
This will allow us to create a geographically, racially/ethnically, and socioeconomically diverse real-world
cohort of approximately 800,000 individuals to inform effective and equitable risk-based prevention
strategies focused on HF. We will analyze individual-level data from the two health systems (e.g., clinical risk
factor levels, comorbidities, medication use, social determinants of health) alongside innovative statistical
techniques (e.g., machine learning) to develop optimal risk prediction models. The aims of the current proposal
are: (1) develop and validate sex-specific risk prediction models for incident HF and HF subtype (HFrEF and
HFpEF) and (2) define the comparative effectiveness of preventive HF therapies (e.g., angiotensin converting
enzyme inhibitors, sodium glucose co-transporter 2 inhibitors) stratified by predicted HF risk. This project will
lay the groundwork for future dissemination and implementation of clinical decision support tools to personalize
HF prevention strategies. Completion of these aims will directly a...

## Key facts

- **NIH application ID:** 10516468
- **Project number:** 1R21HL165376-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Sadiya Sana Khan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $135,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10516468

## Citation

> US National Institutes of Health, RePORTER application 10516468, Risk-Based Primary Prevention of Heart Failure (1R21HL165376-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10516468. Licensed CC0.

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