e2440d6936bc4a595cc864cdb6cd4681 pmc_10044995.pdf 499840b57e89f6fbeb588b4cd5b834a363b1010b pmc_10044995.pdf 6030e3e51675218e9c129631933490c171cc449d1721c1036b784d68ddbed68c pmc_10044995.pdf Title: 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 Subject: 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. Keywords: FABP3; FABP4; chronic heart failure; diabetic patients; all-cause death; cardiovascular death; rehospitalization Author: Ricardo Rodríguez-Calvo, Minerva Granado-Casas, Alejandra Pérez-Montes de Oca, María Teresa Julian, Mar Domingo, Pau Codina, Evelyn Santiago-Vacas, Germán Cediel, Josep Julve, Joana Rossell, Lluís Masana, Didac Mauricio, Josep Lupón, Antoni Bayes-Genis and Núria Alonso Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Mar 4 10:36:08 2023 CET ModDate: Sat Mar 4 10:48:16 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1007273 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- RMHMUC+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 PYTBSR+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 MQGBZY+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 FFDGWE+CMSY10 Type 1 Builtin yes yes no 23 0 IBTYZX+VnURWPalladioL Type 1 Custom yes yes no 27 0 DGBDNV+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 78 0 AEBBVM+EURM10 Type 1 Builtin yes yes no 82 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 97 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 101 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 105 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 109 0 BCDIEE+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes no 116 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 132 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 136 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 140 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 144 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-19 02:36:43 CEST RepresentationInformation: pmc_10044995.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-07-18 02:26:24 CEST Size: 1007273 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 393 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Clinical and Biochemical Data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Serum FABPs Determination Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: T2D Diagnosis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Info: Title: 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 Author: Ricardo Rodríguez-Calvo, Minerva Granado-Casas, Alejandra Pérez-Montes de Oca, María Teresa Julian, Mar Domingo, Pau Codina, Evelyn Santiago-Vacas, Germán Cediel, Josep Julve, Joana Rossell, Lluís Masana, Didac Mauricio, Josep Lupón, Antoni Bayes-Genis and Núria Alonso Subject: 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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