Urinary Liver-Type Fatty-Acid-Binding Protein Predicts Long-Term Adverse Outcomes in Medical Cardiac Intensive Care Units
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Definitions and Calculations
2.3. Biomarker Measurements
2.4. Statistical Analyses
3. Results
3.1. Baseline Characteristics and Outcomes
3.2. Prognostic Value of Urinary L-FABP
3.3. Discrimination and Reclassification of L-FABP for Adverse Outcomes
3.4. Combination of L-FABP and Creatinine-Defined AKI
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Acute coronary syndrome, n (%) | 529 (47) |
STEMI, n | 217 |
NSTEM, n | 264 |
Unstable angina, n | 48 |
Acute decompensated heart failure, n (%) | 424 (38) |
With reduced ejection fraction (LVEF < 40%), n | 217 |
With mid-range ejection fraction (40% ≤ LVEF < 50%), n | 67 |
With preserved ejection fraction (LVEF ≥ 50%), n | 140 |
Arrhythmia, n (%) | 51 (5) |
Supraventricular tachycardia, n | 6 |
Ventricular tachycardia, n | 14 |
Sick sinus syndrome, n | 13 |
Second- or third-degree atrioventricular block, n | 18 |
Primary pulmonary hypertension, n (%) | 32 (3) |
Acute aortic syndrome, n (%) | 24 (2) |
Infective endocarditis, n (%) | 14 (1) |
Takotsubo cardiomyopathy, n (%) | 11 (1) |
Others, n (%) | 34 (3) |
All Patients | Primary Endpoint (+) | Primary Endpoint (-) | p Value | |
---|---|---|---|---|
Number | 1119 | 242 | 877 | |
Age (year) | 68 ± 12 | 73 ± 9 | 67 ± 13 | <0.001 |
Male, n (%) | 732 (65) | 157 (65) | 575 (66) | 0.84 |
Hypertension, n (%) | 724 (65) | 158 (65) | 566 (65) | 0.83 |
Dyslipidemia, n (%) | 520 (47) | 97 (40) | 423 (48) | 0.02 |
Diabetes, n (%) | 420 (38) | 88 (36) | 332 (38) | 0.67 |
Current or ex-smoker, n (%) | 324 (29) | 70 (29) | 254 (29) | 0.99 |
Previous myocardial infarction, n (%) | 214 (19) | 61 (25) | 153 (17) | 0.007 |
Prior hospitalization for worsening heart failure, n (%) | 215 (19) | 53 (22) | 162 (19) | 0.23 |
Previous coronary revascularization, n (%) | 213 (19) | 59 (24) | 154 (18) | 0.02 |
Paroxysmal or persistent AF, n (%) | 248 (22) | 77 (32) | 171 (20) | <0.001 |
Acute decompensated heart failure, n (%) | 424 (38) | 143 (59) | 281 (32) | <0.001 |
SOFA score | 2 (1–4) | 4 (2–5) | 2 (1–4) | <0.001 |
Systolic blood pressure, mmHg | 141 ± 31 | 135 ± 32 | 143 ± 31 | <0.001 |
Heart rate, beats per minutes | 86 ± 25 | 90 ± 24 | 85 ± 26 | 0.001 |
Emergent CAG or PCI before admission, n (%) | 405 (36) | 69 (29) | 336 (38) | 0.005 |
Mechanical ventilation before admission, n (%) | 20 (1.8) | 6 (2.5) | 14 (1.6) | 0.36 |
IABP before admission, n (%) | 96 (8.6) | 20 (8.3) | 76 (8.7) | 0.84 |
White blood cell count, ×103/μL | 8.7 ± 3.6 | 8.4 ± 3.9 | 8.7 ± 3.4 | 0.19 |
Hemoglobin, g/dL | 12.7 ± 2.3 | 11.7 ± 2.3 | 13.0 ± 2.2 | <0.001 |
eGFR, mL/min/1.73 m2 | 66.6 ± 26.6 | 54.2 ± 25.2 | 70.0 ± 26.0 | <0.001 |
Glucose, mg/dL | 159 ± 70 | 170 ± 75 | 156 ± 68 | 0.006 |
hs-CRP, mg/L | 2.32 (0.75–10.3) | 4.50 (1.09–24.3) | 1.99 (0.69–8.18) | <0.001 |
BNP, pg/mL | 186 (53–631) | 581 (158–1210) | 133 (43–479) | <0.001 |
hs-TnT, pg/mL | 59 (17–445) | 56 (24–290) | 62 (15–51) | 0.43 |
Urinary L-FABP, ng/mL | 5.8 (2.4–16.9) | 9.2 (3.1–27.0) | 5.2 (2.2–14.5) | <0.001 |
LVEF, % | 47.3 ± 13.8 | 42.4 ± 14.4 | 48.7 ± 13.3 | <0.001 |
Treatment at enrollment, n (%) | ||||
Antiplatelet drugs | 387 (35) | 111 (46) | 276 (32) | <0.001 |
Statins | 355 (32) | 70 (29) | 285 (33) | 0.29 |
RAAS inhibitors | 469 (42) | 110 (46) | 359 (41) | 0.21 |
Beta-blockers | 301 (27) | 84 (35) | 217 (25) | 0.002 |
Diuretics | 305 (27) | 103 (43) | 202 (23) | <0.001 |
Anticoagulant drugs | 163 (15) | 52 (22) | 111 (13) | <0.001 |
Creatinine-defined AKI, n (%) | 207 (18.5) | 68 (28.1) | 139 (15.8) | <0.001 |
(A) Primary Endpoint | Model 1 | Model 2 | ||
Variables | HR (95% CI) | p Value | HR (95% CI) | p Value |
Age (per 10 years increment) | 1.54 (1.32–1.81) | <0.001 | 1.54 (1.32–1.80) | <0.001 |
Previous myocardial infarction | 0.81 (0.56–1.18) | 0.27 | 0.86 (0.59–1.25) | 0.43 |
Paroxysmal or persistent AF | 1.16 (0.87–1.55) | 0.32 | 1.16 (0.87–1.56) | 0.31 |
Previous coronary revascularization | 1.09 (0.75–1.59) | 0.66 | 1.06 (0.73–1.55) | 0.76 |
Acute decompensated heart failure | 1.03 (0.74–1.42) | 0.87 | 1.06 (0.77–1.47) | 0.72 |
Systolic blood pressure (per 10 mmHg increment) | 0.94 (0.90–0.98) | 0.004 | 0.93 (0.89–0.97) | 0.002 |
Heart rate (per 10 beats per minutes increment) | 1.03 (0.98–1.08) | 0.26 | 1.03 (0.98–1.09) | 0.26 |
Hemoglobin (per 1 g/dL increment) | 0.88 (0.83–0.94) | <0.001 | 0.88 (0.83–0.94) | <0.001 |
CKD | 1.14 (0.85–1.54) | 0.38 | 1.18 (0.88–1.58) | 0.28 |
hs-CRP (per 10-fold increment) | 1.08 (0.91–1.27) | 0.40 | 1.09 (0.93–1.29) | 0.29 |
BNP (per 10-fold increment) | 1.84 (1.37–2.49) | <0.001 | 1.80 (1.34–2.44) | <0.001 |
Urinary L-FABP (per 10-fold increment) | 1.47 (1.22–1.76) | <0.001 | ||
Urinary L-FABP (ng/mL) | ||||
< 9.0 (1st + 2nd + 3rd quintile) | Reference | |||
≥ 9.0 (4th + 5th quintile) | 1.63 (1.25–2.12) | <0.001 | ||
LVEF (per 10% increment) | 0.86 (0.78–0.96) | 0.005 | 0.87 (0.79–0.97) | 0.01 |
(B) All-cause Mortality | Model 1 | Model 2 | ||
Variables | HR (95% CI) | p Value | HR (95% CI) | p Value |
Age (per 10 years increment) | 1.66 (1.41–1.96) | <0.001 | 1.66 (1.40–1.96) | <0.001 |
Previous myocardial infarction | 0.85 (0.58–1.24) | 0.40 | 0.89 (0.61–1.31) | 0.56 |
Paroxysmal or persistent AF | 1.20 (0.89–1.61) | 0.24 | 1.20 (0.89–1.62) | 0.24 |
Previous coronary revascularization | 1.11 (0.75–1.63) | 0.60 | 1.08 (0.73–1.59) | 0.70 |
Acute decompensated heart failure | 1.00 (0.71–1.39) | 0.99 | 1.02 (0.73–1.43) | 0.90 |
Systolic blood pressure (per 10 mmHg increment) | 0.93 (0.89–0.97) | 0.002 | 0.92 (0.88–0.97) | <0.001 |
Heart rate (per 10 beats per minutes increment) | 1.03 (0.97–1.08) | 0.35 | 1.02 (0.97–1.08) | 0.37 |
Hemoglobin (per 1 g/dL increment) | 0.90 (0.85–0.96) | 0.002 | 0.91 (0.85–0.97) | 0.004 |
CKD | 1.02 (0.75–1.37) | 0.92 | 1.05 (0.78–1.42) | 0.74 |
hs-CRP (per 10-fold increment) | 1.13 (0.95–1.35) | 0.17 | 1.15 (0.97–1.37) | 0.10 |
BNP (per 10-fold increment) | 1.89 (1.39–2.57) | <0.001 | 1.86 (1.36–2.53) | <0.001 |
Urinary L-FABP (per 10-fold increment) | 1.43 (1.18–1.72) | <0.001 | ||
Urinary L-FABP (ng/mL) | ||||
< 9.0 (1st + 2nd + 3rd quintile) | Reference | |||
≥ 9.0 (4th + 5th quintile) | 1.50 (1.14–1.97) | 0.003 | ||
LVEF (per 10% increment) | 0.87 (0.78–0.97) | 0.009 | 0.88 (0.79–0.98) | 0.02 |
(A) Primary Endpoint | ||||||
C-index | p Value | NRI | p Value | IDI | p Value | |
Established risk factor model | 0.756 | Reference | Reference | Reference | ||
Established risk factor model + L-FABP | 0.763 | 0.76 | 0.252 | <0.001 | 0.013 | 0.002 |
(B) All-cause Mortality | ||||||
C-index | p Value | NRI | p Value | IDI | p Value | |
Established risk factor model | 0.760 | Reference | Reference | Reference | ||
Established risk factor model + L-FABP | 0.766 | 0.80 | 0.222 | 0.001 | 0.012 | 0.004 |
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Naruse, H.; Ishii, J.; Takahashi, H.; Kitagawa, F.; Nishimura, H.; Kawai, H.; Muramatsu, T.; Harada, M.; Yamada, A.; Fujiwara, W.; et al. Urinary Liver-Type Fatty-Acid-Binding Protein Predicts Long-Term Adverse Outcomes in Medical Cardiac Intensive Care Units. J. Clin. Med. 2020, 9, 482. https://doi.org/10.3390/jcm9020482
Naruse H, Ishii J, Takahashi H, Kitagawa F, Nishimura H, Kawai H, Muramatsu T, Harada M, Yamada A, Fujiwara W, et al. Urinary Liver-Type Fatty-Acid-Binding Protein Predicts Long-Term Adverse Outcomes in Medical Cardiac Intensive Care Units. Journal of Clinical Medicine. 2020; 9(2):482. https://doi.org/10.3390/jcm9020482
Chicago/Turabian StyleNaruse, Hiroyuki, Junnichi Ishii, Hiroshi Takahashi, Fumihiko Kitagawa, Hideto Nishimura, Hideki Kawai, Takashi Muramatsu, Masahide Harada, Akira Yamada, Wakaya Fujiwara, and et al. 2020. "Urinary Liver-Type Fatty-Acid-Binding Protein Predicts Long-Term Adverse Outcomes in Medical Cardiac Intensive Care Units" Journal of Clinical Medicine 9, no. 2: 482. https://doi.org/10.3390/jcm9020482