Urinary Fatty Acid Binding Protein 3 Has Prognostic Value in Peripheral Artery Disease
BackgroundDespite its significant association with limb loss and death, peripheral artery disease (PAD) remains underdiagnosed and undertreated. The current accepted gold-standard for PAD screening, the ankle brachial index (ABI), is limited by operator dependence, erroneous interpretation, and unre...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.875244/full |
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| author | Ben Li Abdelrahman Zamzam Muzammil H. Syed Niousha Jahanpour Shubha Jain Rawand Abdin Mohammad Qadura Mohammad Qadura Mohammad Qadura |
| author_facet | Ben Li Abdelrahman Zamzam Muzammil H. Syed Niousha Jahanpour Shubha Jain Rawand Abdin Mohammad Qadura Mohammad Qadura Mohammad Qadura |
| author_sort | Ben Li |
| collection | DOAJ |
| description | BackgroundDespite its significant association with limb loss and death, peripheral artery disease (PAD) remains underdiagnosed and undertreated. The current accepted gold-standard for PAD screening, the ankle brachial index (ABI), is limited by operator dependence, erroneous interpretation, and unreliability in patients with diabetes. Fatty acid binding protein 3 (FABP3) is an intracellular protein that becomes released into circulation and excreted into urine following skeletal muscle injury. We examined the prognostic ability of urinary FABP3 (uFABP3) in predicting adverse PAD-related events.MethodsIn this prospective case-control study, urine samples were collected from patients with PAD (n = 142) and without PAD (n = 72). The cohort was followed for 2 years. uFABP3 was normalized to urinary creatinine (uCr) (uFABP3/uCr). The primary outcome was major adverse limb event (MALE; composite of vascular intervention [open or endovascular] or major limb amputation). The secondary outcome was worsening PAD status (drop in ABI≥0.15). Cox regression analyses with multivariable adjustment for baseline demographic and clinical variables were performed to assess the prognostic value of uFABP3/uCr with regards to predicting MALE and worsening PAD status.ResultsPatients with PAD had significantly higher median [IQR] uFABP3/uCr levels (3.46 [2.45–6.90] vs. 2.61 [1.98–4.62], p = 0.001). MALE and worsening PAD status were observed in 21 (10%) and 28 (14%) patients, respectively. uFABP3/uCr predicted MALE and worsening PAD status with adjusted hazard ratios (HR) of 1.28 (1.16–1.41, p = 0.001) and 1.16 (1.02–1.27, p = 0.021), respectively. Patients with high uFABP3/uCr had a lower 2-year freedom from MALE (86 vs. 96%, p = 0.047) and worsening PAD status (78 vs. 99%, p = 0.001). There was good discriminatory ability for uFABP3/uCr in predicting the primary outcome of MALE, with an area under the receiver operating characteristics curve (AUROC) of 0.78.ConclusionsMeasuring uFABP3/uCr levels in patients with PAD can help identify those at high risk of adverse PAD-related events. This study highlights the prognostic value of uFABP3 in risk-stratifying individuals for further diagnostic vascular evaluation or aggressive medical management. |
| first_indexed | 2024-04-12T13:34:15Z |
| format | Article |
| id | doaj.art-e86054c1508842d79764b0fdddb006c4 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-12T13:34:15Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-e86054c1508842d79764b0fdddb006c42022-12-22T03:31:05ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01910.3389/fcvm.2022.875244875244Urinary Fatty Acid Binding Protein 3 Has Prognostic Value in Peripheral Artery DiseaseBen Li0Abdelrahman Zamzam1Muzammil H. Syed2Niousha Jahanpour3Shubha Jain4Rawand Abdin5Mohammad Qadura6Mohammad Qadura7Mohammad Qadura8Division of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, CanadaDivision of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, CanadaDivision of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, CanadaDivision of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, CanadaDivision of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, CanadaDepartment of Medicine, McMaster University, Hamilton, ON, CanadaDivision of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, CanadaDepartment of Surgery, University of Toronto, Toronto, ON, CanadaKeenan Research Center for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, CanadaBackgroundDespite its significant association with limb loss and death, peripheral artery disease (PAD) remains underdiagnosed and undertreated. The current accepted gold-standard for PAD screening, the ankle brachial index (ABI), is limited by operator dependence, erroneous interpretation, and unreliability in patients with diabetes. Fatty acid binding protein 3 (FABP3) is an intracellular protein that becomes released into circulation and excreted into urine following skeletal muscle injury. We examined the prognostic ability of urinary FABP3 (uFABP3) in predicting adverse PAD-related events.MethodsIn this prospective case-control study, urine samples were collected from patients with PAD (n = 142) and without PAD (n = 72). The cohort was followed for 2 years. uFABP3 was normalized to urinary creatinine (uCr) (uFABP3/uCr). The primary outcome was major adverse limb event (MALE; composite of vascular intervention [open or endovascular] or major limb amputation). The secondary outcome was worsening PAD status (drop in ABI≥0.15). Cox regression analyses with multivariable adjustment for baseline demographic and clinical variables were performed to assess the prognostic value of uFABP3/uCr with regards to predicting MALE and worsening PAD status.ResultsPatients with PAD had significantly higher median [IQR] uFABP3/uCr levels (3.46 [2.45–6.90] vs. 2.61 [1.98–4.62], p = 0.001). MALE and worsening PAD status were observed in 21 (10%) and 28 (14%) patients, respectively. uFABP3/uCr predicted MALE and worsening PAD status with adjusted hazard ratios (HR) of 1.28 (1.16–1.41, p = 0.001) and 1.16 (1.02–1.27, p = 0.021), respectively. Patients with high uFABP3/uCr had a lower 2-year freedom from MALE (86 vs. 96%, p = 0.047) and worsening PAD status (78 vs. 99%, p = 0.001). There was good discriminatory ability for uFABP3/uCr in predicting the primary outcome of MALE, with an area under the receiver operating characteristics curve (AUROC) of 0.78.ConclusionsMeasuring uFABP3/uCr levels in patients with PAD can help identify those at high risk of adverse PAD-related events. This study highlights the prognostic value of uFABP3 in risk-stratifying individuals for further diagnostic vascular evaluation or aggressive medical management.https://www.frontiersin.org/articles/10.3389/fcvm.2022.875244/fullfatty acid binding protein 3urineprognosisperipheral artery diseasebiomarker |
| spellingShingle | Ben Li Abdelrahman Zamzam Muzammil H. Syed Niousha Jahanpour Shubha Jain Rawand Abdin Mohammad Qadura Mohammad Qadura Mohammad Qadura Urinary Fatty Acid Binding Protein 3 Has Prognostic Value in Peripheral Artery Disease Frontiers in Cardiovascular Medicine fatty acid binding protein 3 urine prognosis peripheral artery disease biomarker |
| title | Urinary Fatty Acid Binding Protein 3 Has Prognostic Value in Peripheral Artery Disease |
| title_full | Urinary Fatty Acid Binding Protein 3 Has Prognostic Value in Peripheral Artery Disease |
| title_fullStr | Urinary Fatty Acid Binding Protein 3 Has Prognostic Value in Peripheral Artery Disease |
| title_full_unstemmed | Urinary Fatty Acid Binding Protein 3 Has Prognostic Value in Peripheral Artery Disease |
| title_short | Urinary Fatty Acid Binding Protein 3 Has Prognostic Value in Peripheral Artery Disease |
| title_sort | urinary fatty acid binding protein 3 has prognostic value in peripheral artery disease |
| topic | fatty acid binding protein 3 urine prognosis peripheral artery disease biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.875244/full |
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