The prognostic significance of heart-type fatty acid binding protein in patients with stable coronary heart disease.
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ABSTRACT:
SUBMITTER: Ho SK
PROVIDER: S-EPMC6158177 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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The prognostic significance of heart-type fatty acid binding protein in patients with stable coronary heart disease.
Ho Sing-Kong SK Wu Yen-Wen YW Tseng Wei-Kung WK Leu Hsin-Bang HB Yin Wei-Hsian WH Lin Tsung-Hsien TH Chang Kuan-Cheng KC Wang Ji-Hung JH Yeh Hung-I HI Wu Chau-Chung CC Chen Jaw-Wen JW
Scientific reports 20180926 1
To investigate the prognostic value of heart-type fatty acid binding protein (H-FABP) in patients with stable coronary heart disease (SCHD). A total of 1,071 patients with SCHD were prospectively enrolled in this Taiwan multicenter registry study, followed for 24 months. The cut-off value of H-FABP, 4.143 pg/mL, was determined using receiver operating characteristic curves. The primary cardiovascular (CV) outcome was composite CV events, defined as cardiovascular or cerebrovascular death, myocar ...[more]
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Project description:BACKGROUND:Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM. METHODS:A total of 4594 patients with angiography-proven coronary artery disease (CAD) were enrolled and divided into subgroup according to glucose metabolism status (normal glucose regulation [NGR], pre-DM, and DM). Baseline levels of H-FABP were measured using latex immunoturbidimetric method. The cardiovascular events (CVE) were defined as cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression and Kaplan-Meier analysis were used to evaluate the relations of H-FABP and glucose metabolism status to CVEs. RESULTS:During the follow-up period with up to 7.1 years, 380 CVEs occurred. Patients with CVE had higher levels of H-FABP compared to those without CVE (p?<?0.001). Interestingly, H-FABP levels were also elevated in DM and pre-DM groups compared with NGR group (p?<?0.001), when combined glucose metabolism status with H-FABP stratification, patients in the highest tertile of H-FABP appeared to have higher risk of CVEs with pre-DM (adjusted hazard ratio [HR]: 1.855, 95% confidential intervals [CIs] 1.076-3.214; p?=?0.033) and DM (adjusted HR: 2.560, 95% CIs 1.409-4.650; p?=?0.002). The Kaplan-Meier curve indicated that DM patients with the highest H-FABP levels were associated with the greatest risk of CVEs (p?<?0.05). CONCLUSIONS:Our data firstly showed that elevated H-FABP levels were associated with worse outcomes in CAD patients with pre-DM and DM, which provided the novel information that H-FABP might be a prognostic marker for clinical outcomes among patients with CAD and IGM.
| S-EPMC7011523 | biostudies-literature
Project description:BackgroundThis study investigated the impact on all-cause mortality of airflow limitation indicative of chronic obstructive pulmonary disease or restrictive spirometry pattern (RSP) in a stable systolic heart failure population.HypothesisDecreased lung function indicates poor survival in heart failure.MethodsInclusion criteria: NYHA class II-IV and left ventricular ejection fraction (LVEF) < 45%. Prognosis was assessed with multivariate Cox proportional hazards models. Two criteria of obstructive airflow limitation were applied: FEV1 /FVC < 0.7 (GOLD), and FEV1 /FVC < lower limit of normality (LLN). RSP was defined as FEV1 /FVC > 0.7 and FVC<80% or FEV1 /FVC > LLN and FVC <LLN.ResultsThere where 573 patients in the cohort (85% of eligible patients in study period). Median follow-up was 4.7 years and 176 patients died (31%). Age, NYHA class, smoking, body mass index and LVEF were independent prognostic factors (p<0.01). Obstructive airflow limitation increased mortality using both criteria (HRGOLD 2.07 [95% CI 1.45-2.95] p<0.01 and HRLLN 2.00 [1.40-2.84] p<0.01) and was an independent marker when using LLN criteria (HR 1.74 [1.17-2.59] p=0.006). RSP was independently associated with mortality when defined as FVC < LLN (HR 1.54 [1.01-2.35] p=0.04) but not as FVC < 80%. Multivariate hazard ratios for a 10% decrease in predicted value of FEV1 or FVC were 1.42 (p<0.001) and 1.33 (p<0.001) in patients exhibiting airflow obstruction, and 1.36 (p=0.031) and 1.38 (p=0.041) in RSP.ConclusionsPresence of obstructive airflow limitation indicative of COPD or RSP were associated with increased all-cause mortality, however only independently when using the LLN definition.
| S-EPMC6490355 | biostudies-literature
Project description:Recent advances in the characterization of fatty acid-binding proteins (FABPs) by NMR have enabled various research groups to investigate the function of these proteins in aqueous solution. The binding of fatty acid molecules to FABPs, which proceeds through a portal region on the protein surface, is of particular interest. In the present study we have determined the three-dimensional solution structure of human heart-type FABP by multi-dimensional heteronuclear NMR spectroscopy. Subsequently, in combination with data collected on a F57S mutant we have been able to show that different fatty acids induce distinct conformational states of the protein backbone in this portal region, depending on the chain length of the fatty acid ligand. This indicates that during the binding process the protein accommodates the ligand molecule by a "selected-fit" mechanism. In fact, this behaviour appears to be especially pronounced in the heart-type FABP, possibly due to a more rigid backbone structure compared with other FABPs, as suggested by recent NMR relaxation studies. Thus differences in the dynamic behaviours of these proteins may be the key to understanding the variations in ligand affinity and specificity within the FABP family.
| S-EPMC1221651 | biostudies-literature
Project description:RationaleLipid metabolism contributes to the formation of obesity-related glomerulopathy (ORG). Heart-type fatty acid binding protein (H-FABP or FABP3) is involved in lipid metabolism and was predicted to relate to renal lesions in obesity.MethodsA total of 28 patients with ORG were investigated, and renal tissue from 7 kidney donors served as controls. Db/db mice with albuminuria were treated with Simvastatin for 12 weeks.ResultsImmunohistochemistry demonstrated the H-FABP staining in glomerular and tubular areas of patients with ORG, and the percentage of H-FABP in the glomerular area was significantly higher than in controls (15.8±1.62 versus 4.51±0.56%, P<0.001). Moreover, H-FABP expression correlated with proteinuria, high-density lipoprotein (HDL) cholesterol, waist circumference and the homeostatic model assessment - insulin resistance (HOMA-IR) among patients with ORG. Enhanced expression of H-FABP was also detected in the db/db mice, and expression increased from 8 to 20 weeks of age and was weakly related to increased albuminuria (r = 0.433; P = 0.020). Furthermore, H-FABP was co-localized with synaptopodin and demonstrated a podocyte pattern distribution. After Simvastation treatment, the urine albumin levels decreased with lipid levels and H-FABP expression in the glomeruli. The expression of H-FABP was related to Simvastatin treatment, albuminuria and triglycerides, while it was only linked with triglycerides and albuminuria (r = 0.643, P = 0.036).ConclusionsThis study confirmed an association of H-FABP with the pathogenesis of clinical and experimental ORG, and suggests that such a process might be related to podocytes and lipid dysmetabolism.
| S-EPMC3445507 | biostudies-literature
Project description:AimsFew biomarkers to evaluate pathophysiological changes in extra-cardiac tissues have been identified in patients with heart failure (HF). Fatty acid-binding protein 1 (FABP), also known as liver FABP, is predominantly expressed in the liver. Circulating FABP1 has been proposed to be a sensitive biomarker for liver injury. However, little is known about the potential role of FABP1 as a biomarker for HF.Methods and resultsMeasurements of serum FABP1 and echocardiography were performed in subjects with compensated HF (n = 162) and control subjects without HF (n = 20). Patients were prospectively followed-up for a composite outcome of all-cause mortality or HF hospitalization. Compared with control subjects, levels of FABP1 were elevated in HF patients [7.9 (6.4-11.7) vs. 17.6 (10.4-28.9) ng/mL, P < 0.0001]. There were significant correlations between FABP1 levels and estimated right ventricular systolic pressure and right atrial pressure. During a median follow-up of 12.0 months, there were 55 primary composite endpoints in the HF cohort. The highest FABP1 tertile was associated with a three-fold increased risk of the composite outcome compared with the lowest tertile [95% confidence interval (1.46-6.68), P = 0.003], but other conventional hepatobiliary markers did not predict the outcome. After adjusting for age, sex, atrial fibrillation, and N-terminal pro-B-type natriuretic peptide levels, serum FABP1 remained independently associated with the outcome. Adding FABP1 to the model based on clinical factors and N-terminal pro-B-type natriuretic peptide significantly improved the prognostic value (global χ2 20.8 vs. 15.5, P = 0.01).ConclusionSerum FABP1 levels are elevated in compensated HF patients, and the magnitude of elevation is independently associated with pulmonary hypertension, right atrial hypertension, and worse clinical outcomes. FABP1 may serve as a new potential biomarker for the assessment of hitherto unrecognized derangement of cardio-hepatic interaction in HF.
| S-EPMC8006713 | biostudies-literature
Project description:BackgroundTo evaluate diagnostic and long-term prognostic values of hFABP compared to NT-proBNP and troponin I (TnI) in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF).Methods401 patients with acute dyspnea or peripheral edema, 122 suffering from AHF, were prospectively enrolled and followed up to 5 years. hFABP combined with NT-proBNP versus NT-proBNP alone was tested for AHF diagnosis. Prognostic value of hFABP versus TnI was evaluated in models predicting all-cause mortality (ACM) and AHF related rehospitalization (AHF-RH) at 1 and 5 years, including 11 conventional risk factors plus NT-proBNP.ResultsAdditional hFABP measurements improved diagnostic specificity and positive predictive value (PPV) of sole NT-proBNP testing at the cutoff <300 ng/l to "rule out" AHF. Highest hFABP levels (4th quartile) were associated with increased ACM (hazard ratios (HR): 2.1-2.5; p = 0.04) and AHF-RH risk at 5 years (HR 2.8-8.3, p = 0.001). ACM was better characterized in prognostic models including TnI, whereas AHF-RH was better characterized in prognostic models including hFABP. Cox analyses revealed a 2 % increase of ACM risk and 3-7 % increase of AHF-RH risk at 5 years by each unit increase of hFABP of 10 ng/ml.ConclusionsCombining hFABP plus NT-proBNP (<300 ng/l) only improves diagnostic specificity and PPV to rule out AHF. hFABP may improve prognosis for long-term AHF-RH, whereas TnI may improve prognosis for ACM.Trial registrationClinicalTrials.gov identifier: NCT00143793 .
| S-EPMC4488120 | biostudies-literature
Project description:BackgroundHeart-type fatty acid binding protein (hFABP) functions as a myocardial fatty acid transporter and is released into the circulation early after myocardial injury. We hypothesized that hFABP is superior to conventional cardiac biomarkers for predicting early perioperative myocardial injury after coronary artery bypass graft (CABG) surgery.MethodsA prospective cohort study of 1298 patients undergoing primary CABG with cardiopulmonary bypass (CPB) was performed at 2 institutions. Four plasma myocardial injury biomarkers (hFABP; cardiac troponin I [cTnI]; creatine kinase, MB [CK-MB] fraction; and myoglobin) were measured at 7 perioperative time points. The association among perioperative cardiac biomarkers and ventricular dysfunction, hospital length of stay (HLOS), and up to 5-year postoperative mortality (median 3.3 years) was assessed using Cox proportional hazard models. We defined in-hospital ventricular dysfunction as a new requirement for 2 or more inotropes, or new placement of an intraaortic balloon pump, or ventricular assist device either during the intraoperative period after the patient separated from CPB or postoperatively in the intensive care unit.ResultsThe positive and negative predictive values of mortality for hFABP are 13% (95% confidence interval [CI], 9%-19%) and 95% (95% CI, 94%-96%), respectively, which is higher than for cTnI and CK-MB. After adjusting for clinical predictors, both postoperative day (POD) 1 and peak hFABP levels were independent predictors of ventricular dysfunction (P < 0.0001), HLOS (P < 0.05), and 5-year mortality (P < 0.0001) after CABG surgery. Furthermore, POD1 and peak hFABP levels were significantly superior to other evaluated biomarkers for predicting mortality. In a repeated-measures analysis, hFABP outperformed all other models of fit for HLOS. Patients with POD2 hFABP levels higher than post-CPB hFABP levels had an increased mortality compared with those patients whose POD2 hFABP levels decreased from their post-CPB level (hazard ratio, 10.9; 95% CI, 5.0-23.7; P = 7.2 × 10(-10)). Mortality in the 120 patients (10%) with a later hFABP peak was 18.3%, compared with 4.7% in those who did not peak later. Alternatively, for cTnI or CK-MB, no difference in mortality was detected.ConclusionCompared with traditional markers of myocardial injury after CABG surgery, hFABP peaks earlier and is a superior independent predictor of postoperative mortality and ventricular dysfunction.
| S-EPMC3006085 | biostudies-literature
Project description:The present study aimed to determine the clinical significance of heart-type fatty acid-binding protein (H-FABP) in patients with sepsis-induced cardiac dysfunction. A total of 30 healthy subjects served as the control group and 80 patients with sepsis were recruited for the present single-center prospective observational study for the final analysis. Among these patients, 50 developed cardiac dysfunction, while no cardiac dysfunction was detected in the remaining 30 patients. Echocardiography was performed on days 1, 3, 7 and 10 of hospitalization. Routine blood biochemistry, serum H-FABP, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin I were also analyzed. Alterations in cardiac biomarkers and echocardiography results were compared between patients with sepsis who did and who did not develop any cardiac dysfunction to determine the time of the occurrence of sepsis-induced cardiac dysfunction. Furthermore, the significance of H-FABP in the prediction of the 28-day mortality rate was evaluated using binary logistic regression analysis for sepsis and receiver operating characteristic (ROC) curve analysis. In addition, the specificity and sensitivity of H-FABP in the prediction of sepsis-induced cardiac dysfunction were verified using ROC curve analysis. For patients with cardiac dysfunction, the levels of cardiac output (CO), stroke volume (SV), mitral early diastolic peak velocity to mitral atrial systolic peak velocity ratio (E/A) and left ventricle ejection fraction (LVEF) were relatively decreased, while the levels of H-FABP and NT-proBNP were markedly increased compared with patients with sepsis and without cardiac dysfunction. CO and SV initially increased and subsequently decreased. EF was elevated, and E/A initially decreased and subsequently increased. Furthermore, H-FABP and NT-proBNP decreased in sepsis patients with cardiac dysfunction. The results of the ROC curve and binary logistic regression analyses suggest that H-FABP was associated with the 28-day prognosis for patients with sepsis. An H-FABP level of >35.7 ng/ml was able to predict the 28-day mortality for patients with sepsis, with an area under the curve (AUC) of 0.680. Furthermore, >30.3 ng/ml was the threshold for the prediction of sepsis-induced cardiac dysfunction, and the sensitivity and specificity were 76.27 and 61.76%, respectively, with an AUC of 0.673. In summary, patients with sepsis had an increased risk of cardiac insufficiency on days 7-10 of hospitalization. In addition, H-FABP may serve as an indicator to predict the prognosis of patients with sepsis in the short term, which has a certain significance in the diagnosis of sepsis-induced cardiac dysfunction.
| S-EPMC7485322 | biostudies-literature
Project 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.
| S-EPMC9250966 | biostudies-literature
Project description:IMPORTANCE:The role of ?-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE:To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5?-3), docosapentaenoic acid (DPA; 22:5?-3), and docosahexaenoic acid (DHA; 22:6?-3) and plant-derived ?-linolenic acid (ALA; 18:3?-3) for incident CHD. DATA SOURCES:A global consortium of 19 studies identified by November 2014. STUDY SELECTION:Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ?-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS:Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ?-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES:Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS:The 19 studies comprised 16 countries, 45?637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ?-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ?-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE:On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ?-3 fatty acids are associated with a modestly lower incidence of fatal CHD.
| S-EPMC5183535 | biostudies-literature