# Metabolic effects and mechanisms for heart failure in South Asians

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $1,241,180

## Abstract

PROJECT SUMMARY
The goal of this project is to fill gaps in our understanding of early heart failure stages and of heart failure with
preserved ejection fraction (HFpEF). Over half of all heart failure patients have HFpEF, and are more likely to
be older, diabetic, obese, hypertensive and have a prognosis that is equally poor as those with reduced
ejection fraction. No treatment has been shown to improve outcomes in patients with HFpEF, highlighting an
urgent need to understand the heterogeneous phenotypes and underlying biologic and physiologic
mechanisms for HFpEF. We have established a prospective cohort of South Asians called the Mediators of
Atherosclerosis in South Asians Living in America (MASALA) study that is closely tied to the Multi-Ethnic Study
of Atherosclerosis (MESA) for efficient cross-ethnic comparisons. We have found that South Asians have
significantly higher prevalence of diabetes and metabolic abnormalities, even with normal body mass index,
compared to the four MESA race/ethnic groups. Additionally, South Asians have very high levels of fat stored
in ectopic depots (in the liver, muscle and around the abdominal viscera). This unique cohort with its distinct
phenotype can be leveraged to understand the metabolic effects and mechanisms involved in heart failure. In
this proposed study, we will use the thorough baseline and repeated metabolic characterization of MASALA
study participants and will measure heart failure stages among 850 MASALA participants in a new Exam 3. We
will characterize heart failure stages by symptoms, dynamic echocardiography, NTproBNP, and HFpEF will be
confirmed by exercise stress echocardiography. We propose to 1) determine the epidemiology of heart failure
among middle to older aged South Asians and compare heart failure stages and HFpEF prevalence in South
Asians to the four MESA race/ethnic groups. We will determine whether differences in heart failure stages and
HFpEF prevalence between South Asians and MESA groups are mediated by differences in dysglycemia,
ectopic fat and other metabolic factors; 2) determine whether endothelial dysfunction, arterial stiffness, and
coronary microvascular dysfunction drive HFpEF in South Asians, and if they mediate the association between
dysglycemia, adiposity, and HFpEF; and 3) determine the blood-based proteomic signatures of heart failure
and HFpEF among South Asians. We will identify, verify, and validate the proteomics profile of heart failure
and HFpEF, and determine the immunologic signatures characterizing HFpEF. We expect that South Asians
will have a high prevalence of HFpEF, and that we will better define the phenotype and underlying
mechanisms for HFpEF relevant for metabolically unhealthy but normal weight populations.

## Key facts

- **NIH application ID:** 10049526
- **Project number:** 1R01HL149809-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** ALKA M. KANAYA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,241,180
- **Award type:** 1
- **Project period:** 2021-06-07 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049526

## Citation

> US National Institutes of Health, RePORTER application 10049526, Metabolic effects and mechanisms for heart failure in South Asians (1R01HL149809-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10049526. Licensed CC0.

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