Elevated plasma fatty acid-binding protein 3 is related to prolonged corrected QT interval and reduced ejection fraction in patients with stable angina

Lu, Yung‐Chuan; Lee, Thung-Lip; Hsuan, Chin-Feng; Hung, Wei‐Chin; Wu, Cheng‐Ching; Wang, Chao-Ping; Wei, Ching‐Ting; Yu, Teng‐Hung; Chung, Fu‐Mei; Lee, Yau-Jiunn; Tsai, I‐Ting

doi:10.7150/ijms.54508

Cited by 7 publications

(8 citation statements)

References 52 publications

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“…More specifically, the pericardial fat secretome has been associated with reduced I Kr and increased I CaL currents in metabolic syndrome, resulting in APD prolongation ( 18 ). Serum levels of the adipokine fatty-acid binding protein has also been suggested as a biochemical proxy for prolonged QTc interval and reduced ejection fraction in patients with stable angina ( 19 ). Similarly, plasma adiponectin may modulate ventricular repolarisation and thereby QTc interval ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank

Patel

Li²,

Xu³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundSmall-scale studies have linked obesity (Ob) and metabolic ill-health with proarrhythmic repolarisation abnormalities. Whether these are observed at a population scale, modulated by individuals’ genetics, and confer higher risks of ventricular arrhythmias (VA) are not known.Methods and ResultsFirstly, using the UK Biobank, the association between adiposity and QTc interval was assessed in participants with a resting 12-lead ECG (n = 23,683), and a polygenic risk score (PRS) was developed to investigate any modulatory effect of genetics. Participants were also categorised into four phenotypes according to the presence (+) or absence (–) of Ob, and if they were metabolically unhealthy (MU+) or not (MU-). QTc was positively associated with body mass index (BMI), body fat (BF), waist:hip ratio (WHR), and hip and waist girths. Individuals’ genetics had no significant modulatory effect on QTc-prolonging effects of increasing adiposity. QTc interval was comparably longer in those with metabolic perturbation without obesity (Ob-MU+) and obesity alone (Ob+MU-) compared with individuals with neither (Ob-MU-), and their co-existence (Ob+MU+) had an additive effect on QTc interval. Secondly, for 502,536 participants in the UK Biobank, odds ratios (ORs) for VA were computed for the four clinical phenotypes above using their past medical records. Referenced to Ob-MU-, ORs for VA in Ob-MU+ men and women were 5.96 (95% CI: 4.70–7.55) and 5.10 (95% CI: 3.34–7.80), respectively. ORs for Ob+MU+ were 6.99 (95% CI: 5.72–8.54) and 3.56 (95% CI: 2.66–4.77) in men and women, respectively.ConclusionAdiposity and metabolic perturbation increase QTc to a similar degree, and their co-existence exerts an additive effect. These effects are not modulated by individuals’ genetics. Metabolic ill-health is associated with a higher OR for VA than obesity.

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Section: Discussionmentioning

confidence: 99%

Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank

Patel

Li²,

Xu³

et al. 2022

Front. Cardiovasc. Med.

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“…Most (but not all) studies investigating the relationship between FABP3 and atrial remodeling have shown evidence for a contribution of FABP3 to the atrial remodeling and AF based on FABP3 plasma levels or tissue messenger RNA (mRNA) (14)(15)(16)(17). From a mechanistic perspective, the protein concentration of FABP3 in the RA may be better suited to reflect the correlation between FABP3 regulation and RA function.…”

Section: Discussionmentioning

confidence: 99%

“…Fatty acid-binding protein 3 (FABP3) is an intracellular FA carrier, which has been evaluated as a biomarker of atrial maladaptive remodeling in patients with metabolic disease (12,13). Correlation of the plasma levels and genetic expression of FABP3 with atriomyopathy suggest a relation between FABP3 expression in the atrial tissue and atrial function; however, this has not yet been explored (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Impaired Relaxation and Reduced Lusitropic Reserve in Atrial Myocardium in the Obese Patients

Wen

Primeßnig

Dushe

et al. 2021

Front. Cardiovasc. Med.

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Background: Obesity can influence the structure and function of the atrium, but most studies focused on the relationship of body mass index (BMI) and overt left atrium (LA) dysfunction as assessed by clinical imaging. We combined the assessment of right atrium (RA) function in vivo and in vitro in obese and non-obese patients scheduled for elective cardiac surgery.Methods: Atrial structure and function were quantified pre-operatively by echocardiography. RA tissue removed for the establishment of extracorporeal support was collected and RA trabeculae function was quantified in vitro at baseline and with adrenergic stimulation (isoproterenol). Fatty acid-binding protein 3 (FABP3) was quantified in RA tissue. Results were stratified according to the BMI of the patients.Results: About 76 patients were included pre-operatively for the echocardiographic analysis. RA trabeculae function at baseline was finally quantified from 46 patients and RA function in 28 patients was also assessed with isoproterenol. There was no significant correlation between BMI and the parameters of atrial function measured by the clinical echocardiography. However, in vitro measurements revealed a significant correlation between BMI and a prolonged relaxation of the atrial myocardium at baseline, which persisted after controlling for the atrial fibrillation and diabetes by the partial correlation analysis. Acceleration of relaxation with isoproterenol was significantly lower in the obese group (BMI ≥ 30 kg/m2). As a result, relaxation with adrenergic stimulation in the obese group remained significantly higher compared to the overweight group (25 kg/m2 ≤ BMI < 30 kg/m2, p = 0.027) and normal group (18.5 kg/m2 ≤ BMI < 25 kg/m2, p = 0.036). There were no differences on impacts of the isoproterenol on (systolic) developed force between groups. The expression of FABP3 in the obese group was significantly higher compared to the normal group (p = 0.049) and the correlation analysis showed the significant correlations between the level of FABP3 in the RA trabeculae function.Conclusion: A higher BMI is associated with the early subclinical changes of RA myocardial function with the slowed relaxation and reduced adrenergic lusitropy.

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“…An increasing body of evidence supports the notion that both FABP3 and FABP4 serum concentrations can predict both all-cause [ 36 , 37 , 38 , 39 , 40 , 41 , 42 ] and CV mortality [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]; however, the potential role of these FABPs as predictive biomarkers for the mortality risk among subjects with T2D and chronic HF (CHF) has not been explored yet. Thus, the aim of this study was to assess the prognostic value of these two FABPs (i.e., FABP3 and FABP4) for both all-cause and CV mortality in outpatient CHF subjects with T2D.…”

Section: Introductionmentioning

confidence: 93%

Fatty Acid Binding Proteins 3 and 4 Predict Both All-Cause and Cardiovascular Mortality in Subjects with Chronic Heart Failure and Type 2 Diabetes Mellitus

et al. 2023

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Subjects with type 2 diabetes mellitus (T2D) are at increased risk for heart failure (HF). The cardiac-specific (FABP3) and adipose-tissue-specific (FABP4) types of the fatty acid binding proteins have been associated with both all-cause and cardiovascular (CV) mortality. The aim of this study was to explore the prognosis value of FABP3 and FABP4 in ambulatory subjects with chronic HF (CHF), with and without T2D. A prospective study involving 240 ambulatory CHF subjects was performed. Patients were followed-up for a mean of 5.78 ± 3.30 years and cause of death (if any) was recorded. Primary endpoints were defined as all-cause and CV death, and a composite endpoint that included CV death or hospitalization for HF was included as a secondary endpoint. Baseline serum samples were obtained and the serum FABP3 and FABP4 concentrations were assessed by sandwich enzyme-linked immunosorbent assay. Survival analysis was performed with multivariable Cox regressions, using Fine and Gray competing risks models when needed, to explore the prognostic value of FABP3 and FABP4 concentrations, adjusting for potential confounders. Type 2 diabetes mellitus was highly prevalent, accounting for 47.5% for total subjects with CHF. Subjects with T2D showed higher mortality rates (T2D: 69.30%; non-T2D: 50.79%, p = 0.004) and higher serum FABP3 (1829.3 (1104.9–3440.5) pg/mL vs. 1396.05 (820.3–2362.16) pg/mL, p = 0.007) and FABP4 (45.5 (27.6–79.8) ng/mL vs. 34.1 (24.09–55.3) ng/mL, p = 0.006) concentrations compared with non-T2D CHF subjects. In the whole study cohort, FABP3 was independently associated with all-cause death, and both FABP3 and FABP4 concentrations were associated with CV mortality. The predictive values of these two molecules for all-cause (FABP3: HR 1.25, 95% CI 1.09–1.44; p = 0.002. FABP4: HR 2.21, 95% CI 1.12–4.36; p = 0.023) and CV mortality (FABP3: HR 1.28, 95% CI 1.09–1.50; p = 0.002. FABP4: HR 4.19, 95% CI 2.21–7.95; p < 0.001) were only statistically significant in the subgroup of subjects with T2D. Notably, FABP4 (HR 2.07, 95% CI 1.11–3.87; p = 0.022), but not FABP3, also predicted the occurrence of the composite endpoint (death or hospitalization for HF) only in subjects with T2D. All these associations were not found in CHF subjects without T2D. Our findings support the usefulness of serum FABP3 and FABP4 concentrations as independent predictors for the occurrence of all-cause and CV mortality in ambulatory subjects with CHF with T2D.

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Elevated plasma fatty acid-binding protein 3 is related to prolonged corrected QT interval and reduced ejection fraction in patients with stable angina

Cited by 7 publications

References 52 publications

Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank

Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank

Impaired Relaxation and Reduced Lusitropic Reserve in Atrial Myocardium in the Obese Patients

Fatty Acid Binding Proteins 3 and 4 Predict Both All-Cause and Cardiovascular Mortality in Subjects with Chronic Heart Failure and Type 2 Diabetes Mellitus

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