Does Adiponectin Inform Cardiovascular Risk in Older Adults? :  The ARIC Study

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Abstract

Background

Adiponectin, an atheroprotective adipokine, is associated with adverse outcomes in older age. It is unclear whether this is due to overlapping pathophysiological pathways with N-terminal pro–B-type natriuretic peptide (NT-proBNP).

Objectives

The authors investigated adiponectin's associations with cardiovascular disease (CVD) risk in older adults.

Methods

Among Atherosclerosis Risk in Communities prospective cohort study participants without baseline CVD at visit 5 (n = 4,729, mean age 75), adiponectin and adiponectin/NT-proBNP category associations with incident CVD events (heart failure [HF], atherosclerotic cardiovascular disease, and death during median follow-up of 5.5 years) and echocardiographic parameters were assessed. Metabolomic signatures of adiponectin/NT-proBNP categories were explored.

Results

Higher adiponectin was associated with older age, female sex, and less obesity, diabetes, and hypertension but increased risk for incident HF (HR: 1.91 [95% CI: 1.49-2.44], per natural-log unit increase) and CVD death (HR: 1.67 [95% CI: 1.19-2.32]). Interaction of NT-proBNP with adiponectin was significant for HF ( P-interaction = 0.03). There was no significant association between adiponectin and heart failure with preserved ejection fraction after adjusting for NT-proBNP. Elevations of both biomarkers (A+ [upper tertile]/N+ [≥125 pg/mL]) had higher risk (vs A+/N−; HF: HR 5.41 [95% CI: 2.72-10.78]; CVD death: HR 3.50 [95% CI: 1.48-8.24]). Compared with A+/N−, A−/N+ had increased risk for HF (HR 2.84 [95% CI: 1.41-5.72]) while A−/N− had no increased event risk. A+/N+'s metabolomic signature (88% similar to NT-proBNP's) showed acylcarnitine species consistent with incomplete beta-oxidation; top-associated metabolites were significantly associated with HF and CVD death.

Conclusions

Elevated adiponectin and NT-proBNP in older adults are associated with increased risk for HF and CVD death beyond traditional risk factors.

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Most cited references 36

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Heart Disease and Stroke Statistics—2021 Update: A Report From the American Heart Association

Salim S. Virani, Alvaro Alonso, Hugo Aparicio … (2021)

The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year’s worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

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Epidemiology of heart failure with preserved ejection fraction

Shannon Dunlay, Véronique L Roger, Margaret M. Redfield (2017)

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome associated with poor quality of life, substantial health-care resource utilization, and premature mortality. Dunlay and colleagues summarize the epidemiological data on HFpEF, with a focus on the prevalence and incidence of HFpEF in the community as well as associated conditions and risk factors, morbidity and mortality after diagnosis, and quality of life.

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Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.

C Weyer, T. Funahashi, S. Tanaka … (2001)

Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.

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Author and article information

Contributors

Layla A. Abushamat: @LaylaAbushamat

Journal

Journal ID (nlm-ta): JACC Adv

Journal ID (iso-abbrev): JACC Adv

Title: JACC: Advances

Publisher: Elsevier

ISSN (Electronic): 2772-963X

Publication date PMC-release: 20 February 2025

Publication date Collection: March 2025

Publication date (Electronic): 20 February 2025

Volume: 4

Issue: 3

Electronic Location Identifier: 101625

Affiliations

[a ]Section of Cardiovascular Research, Population Science, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

[b ]Section of Cardiology, and Population Science, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

[c ]Section of Epidemiology and Population Science, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

[d ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

[e ]Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

[f ]Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA

[g ]Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center, Houston, Texas, USA

[h ]Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA

[i ]Winters Center for Heart Failure Research, Baylor College of Medicine, Houston, Texas, USA

[j ]Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

Author notes

[∗ ] Address for correspondence: Dr Layla A. Abushamat, Baylor College of Medicine, 1 Baylor Plaza, BCM 285, Houston, Texas 77030, USA. Layla.abushamat@ 123456bcm.edu @LaylaAbushamat

[∗]

These authors are co–first authors.

Article

Publisher Item ID: S2772-963X(25)00042-0 Publisher ID: 101625

DOI: 10.1016/j.jacadv.2025.101625

PMC ID: 11891717

PubMed ID: 39983616

SO-VID: 4f5dc2d5-a851-4c39-9f80-6995f4754fb1

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

History

Date received : 15 March 2024

Date revision received : 7 January 2025

Date accepted : 17 January 2025

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Does Adiponectin Inform Cardiovascular Risk in Older Adults? : The ARIC Study

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Abstract

Background

Objectives

Methods

Results

Conclusions

Central Illustration

Related collections

Cardiovascular Innovations and Applications

Most cited references 36

Heart Disease and Stroke Statistics—2021 Update: A Report From the American Heart Association

Epidemiology of heart failure with preserved ejection fraction

Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.

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