Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population

Fuseya, Takahiro; Furuhashi, Masato; Yuda, Satoshi; Muranaka, Atsuko; Kawamukai, Mina; Mita, Tomohiro; Ishimura, Shutaro; Watanabe, Yuki; Hoshina, Kyoko; Tanaka, Marenao; Ohno, Kohei; Akasaka, Hiroshi; Ohnishi, Hirofumi; Yoshida, Hiroyuki; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Miura, Tetsuji

doi:10.1186/s12933-014-0126-7

Cited by 66 publications

(62 citation statements)

References 42 publications

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“…The previous publications are not directly comparable to our investigation because of their smaller sample sizes11 (N<200), referral bias,25, 26, 27 and focus on obese individuals,25, 26, 27 whereas our study sample comprised relatively healthy individuals. In this context, it is noteworthy that experimental studies have also yielded variable results.…”

Section: Discussionmentioning

confidence: 75%

“…Accordingly, investigators have related circulating concentrations of adipokines to imaging indices of cardiac remodeling. These prior studies have typically been conducted in small samples, or samples with an overrepresentation of obese individuals or elderly people, and usually focused on a single adipokine 10, 11, 13, 21, 22, 23, 24, 25, 26…”

Section: Discussionmentioning

confidence: 99%

“…We observed an inverse association between circulating FABP4 levels and LVMI. Prior studies analyzing associations between FABP4 levels and LVMI have been inconsistent with reports of both no associations11 and of positive associations 25, 26, 27…”

Section: Discussionmentioning

confidence: 99%

“…In this context, it is noteworthy that the adipose tissue is an endocrine tissue which secretes hormones (referred to as adipokines) that mediate several of the cardiometabolic consequences of obesity. Several adipokines have receptors on cardiac myocytes,7, 8, 9 exhibit prohypertrophic and antihypertrophic effects on the myocardium,10, 11, 12, 13 and have been associated with risk of overt HF 14. Prior investigations relating adipokines to cardiac structure and function have focused on single adipokines10, 11, 15, 16, 17, 18, 19, 20, 21 and related them to traditional measures of cardiac remodeling (such as LV mass [LVM]).…”

mentioning

confidence: 99%

“…Several adipokines have receptors on cardiac myocytes,7, 8, 9 exhibit prohypertrophic and antihypertrophic effects on the myocardium,10, 11, 12, 13 and have been associated with risk of overt HF 14. Prior investigations relating adipokines to cardiac structure and function have focused on single adipokines10, 11, 15, 16, 17, 18, 19, 20, 21 and related them to traditional measures of cardiac remodeling (such as LV mass [LVM]). These studies often focused on obese individuals with comorbidities16, 22, 23, 24, 25, 26, 27, 28 or the elderly20, 21, 29 and were limited by modest sample sizes.…”

mentioning

confidence: 99%

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Association of Circulating Adipokines With Echocardiographic Measures of Cardiac Structure and Function in a Community‐Based Cohort

Jeinsen

Short

Xanthakis

et al. 2018

JAHA

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BackgroundAdipokines mediate cardiometabolic risk associated with obesity but their role in the pathogenesis of obesity‐associated heart failure remains uncertain. We investigated the associations between circulating adipokine concentrations and echocardiographic measures in a community‐based sample.Methods and ResultsWe evaluated 3514 Framingham Heart Study participants (mean age 40 years, 53.8% women) who underwent routine echocardiography and had select circulating adipokines measured, ie, leptin, soluble leptin receptor, fatty acid–binding protein 4, retinol‐binding protein 4, fetuin‐A, and adiponectin. We used multivariable linear regression, adjusting for known correlates (including weight), to relate adipokine concentrations (independent variables) to the following echocardiographic measures (dependent variables): left ventricular mass index, left atrial diameter in end systole, fractional shortening, and E/e′. In multivariable‐adjusted analysis, left ventricular mass index was inversely related to circulating leptin and fatty acid–binding protein 4 concentrations but positively related to retinol‐binding protein 4 and leptin receptor levels (P≤0.002 for all). Left atrial end‐systolic dimension was inversely related to leptin but positively related to retinol‐binding protein 4 concentrations (P≤0.0001). E/e′ was inversely related to leptin receptor levels (P=0.0002). We observed effect modification by body weight for select associations (leptin receptor and fatty acid–binding protein 4 with left ventricular mass index, and leptin with left atrial diameter in end systole; P<0.05 for interactions). Fractional shortening was not associated with any of the adipokines. No echocardiographic trait was associated with fetuin‐A or adiponectin concentrations.ConclusionsIn our cross‐sectional study of a large, young to middle‐aged, relatively healthy community‐based sample, key indices of subclinical cardiac remodeling were associated with higher or lower circulating concentrations of prohypertrophic and antihypertrophic adipokines in a context‐specific manner. These observations may offer insights into the pathogenesis of the cardiomyopathy of obesity.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Association of Circulating Adipokines With Echocardiographic Measures of Cardiac Structure and Function in a Community‐Based Cohort

Jeinsen

Short

Xanthakis

et al. 2018

JAHA

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Pathophysiological role of fatty acid‐binding protein 4 in Asian patients with heart failure and preserved ejection fraction

et al. 2020

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Aims Systemic metabolic impairment is the key pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). Fatty acid-binding protein 4 (FABP4) is highly expressed in adipocytes and secreted in response to lipolytic signals. We hypothesized that circulating FABP4 levels would be elevated in patients with HFpEF, would correlate with cardiac structural and functional abnormalities, and could predict clinical outcomes. Methods and results Serum FABP4 measurements and echocardiography were performed in patients with HFpEF (n = 92) and those with coronary artery disease free of HF (n = 20). Patients were prospectively followed-up for a composite endpoint of all-cause mortality or HF hospitalization. Compared with patients with coronary artery disease, those with HFpEF had higher FABP4 levels [12.5 (9.1-21.0) vs. 43.5 (24.6-77.4) ng/mL, P < 0.0001]. FABP4 levels were associated with cardiac remodelling (left ventricular mass index: r = 0.29, P = 0.002; left atrial volume index: r = 0.40, P < 0.0001), left ventricular systolic and diastolic dysfunction (global longitudinal strain: r = À0.24, P = 0.01; E/e′ ratio: r = 0.29, P = 0.002; and N-terminal pro-B-type natriuretic peptide: r = 0.62, P < 0.0001), and right ventricular dysfunction (tricuspid annular plane systolic excursion: r = À0.43, P < 0.0001). During a median follow-up of 9.1 months, there were 28 primary endpoints in the HFpEF cohort. Event-free survival was significantly decreased in patients with FABP4 levels ≥43.5 ng/mL than in those with FABP4 levels <43.5 ng/mL (P = 0.003). Conclusions Serum FABP4 levels were increased in HFpEF and were associated with cardiac remodelling and dysfunction, and poor outcomes. Thus, FABP4 could be a potential biomarker in the complex pathophysiology of HFpEF.

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Prospective association of serum adipocyte fatty acid‐binding protein with heart failure hospitalization in diabetes

et al. 2021

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Aims Adipocyte fatty acid-binding protein (AFABP) is associated with cardiovascular diseases in type 2 diabetes. Whether circulating AFABP levels are associated with the risk of heart failure (HF) in type 2 diabetes remains undefined. We investigated the prospective association of circulating AFABP levels with incident HF hospitalization in type 2 diabetes, and its relationship to the use of sodium glucose co-transporter 2 inhibitors (SGLT2i) which reduce HF risk. Methods and results Baseline serum AFABP level was measured in 3322 Chinese participants without known history of cardiovascular diseases or hospitalization for HF, recruited from the Hong Kong West Diabetes Registry. Its association with incident HF hospitalization was evaluated using multivariable Cox regression analysis. Use of SGLT2i was included as a time-dependent covariate. Among these 3322 participants (52.9% men; mean age 60.0 ± 12.6), 176 (5.3%) developed HF hospitalization over a median follow-up of 8 years. Seven hundred and thirty-one (22%) were started on SGLT2i during the study period (empagliflozin 55.1%, dapagliflozin 44.2%, canagliflozin 0.4%, and ertugliflozin 0.3%). Serum AFABP levels were significantly higher in participants who developed HF hospitalization than those who did not (men: 14.8 vs. 8.3 ng/mL; women: 21.5 vs. 14.6 ng/mL; all: 18.6 vs. 10.9 ng/mL, P < 0.001). In multivariable Cox regression analysis, baseline serum AFABP level was significantly associated with incident HF hospitalization [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.06-1.80, P = 0.019] independent of the use of SGLT2i, in a model also consisting of age; sex; body mass index; smoking status; duration of diabetes; hypertension, dyslipidaemia; atrial fibrillation; presence of chronic kidney disease and albuminuria; glycated haemoglobin and high-sensitivity C-reactive protein levels; and use of metformin, insulin, aspirin, furosemide, and beta-blockers at baseline. High cumulative defined daily dose (cDDD) of SGLT2i was protective of incident HF hospitalization (HR 0.10, 95% CI 0.01-0.68, P = 0.019). The addition of circulating AFABP level to a clinical model of conventional HF risk factors provided significant improvement in the category-free net reclassification index (11.5%, 95% CI 1.6-22.1, P = 0.02) and integrated discrimination improvement (0.3%, 95% CI 0.1-1.7, P = 0.04). A dose-dependent reduction in cumulative incidence of HF hospitalization in response to SGLT2i, based on cDDD, was more clearly observed in participants with a higher baseline AFABP level above the sex-specific median (P for trend <0.01). Conclusions Circulating AFABP level is independently associated with incident HF hospitalization in type 2 diabetes and is potentially helpful in risk stratification for the prevention of HF hospitalization.

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Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population

Cited by 66 publications

References 42 publications

Association of Circulating Adipokines With Echocardiographic Measures of Cardiac Structure and Function in a Community‐Based Cohort

Association of Circulating Adipokines With Echocardiographic Measures of Cardiac Structure and Function in a Community‐Based Cohort

Pathophysiological role of fatty acid‐binding protein 4 in Asian patients with heart failure and preserved ejection fraction

Prospective association of serum adipocyte fatty acid‐binding protein with heart failure hospitalization in diabetes

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