Predictive Value of Triglyceride-Glucose Index for In-hospital Mortality in Patients With Severe Fever With Thrombocytopenia Syndrome: A Multi-Center Observational Study

Background: Triglyceride-glucose (TyG) index has been proposed as a reliable indicator for insulin resistance and proved to be closely associated with the severity and mortality risk of infectious diseases. It remains indistinct whether TyG index performs an important role in predicting in-hospital mortality in patients with severe fever with thrombocytopenia syndrome (SFTS).Methods: The current study retrospectively recruited patients who were admitted for SFTS from January to December 2019 at five medical centers. TyG index was calculated in accordance with the description of previous study: Ln [fasting triglyceride (TG) (mg/dl) × fasting blood glucose (FBG) (mg/dl)/2]. The observational endpoint of the present study was defined as the in-hospital death.Results: In total, 79 patients (64.9 ± 10.5 years, 39.2% female) who met the enrollment criteria were enrolled in the current study. During the hospitalization period, 17 (21.5%) patients died in the hospital. TyG index remained a significant and independent predictor for in-hospital death despite being fully adjusted for confounders, either being taken as a nominal [hazard ratio (HR) 5.923, 95% CI 1.208–29.036, P = 0.028] or continuous (HR 7.309, 95% CI 1.854–28.818, P = 0.004) variate. TyG index exhibited a moderate-to-high strength in predicting in-hospital death, with an area under the receiver operating characteristic curve (AUC) of 0.821 (95% CI 0.712–0.929, P < 0.001). The addition of TyG index displayed significant enhancement on the predictive value for in-hospital death beyond a baseline model, manifested as increased AUC (baseline model: 0.788, 95% CI 0.676–0.901 vs. + TyG index 0.866, 95% CI 0.783–0.950, P for comparison = 0.041), increased Harrell's C-index (baseline model: 0.762, 95% CI 0.645–0.880 vs. + TyG index 0.813, 95% CI 0.724–0.903, P for comparison = 0.035), significant continuous net reclassification improvement (NRI) (0.310, 95% CI 0.092–0.714, P = 0.013), and significant integrated discrimination improvement (0.111, 95% CI 0.008–0.254, P = 0.040).Conclusion: Triglyceride-glucose index, a novel indicator simply calculated from fasting TG and FBG, is strongly and independently associated with the risk of in-hospital death in patients with SFTS.

Regulatory T Cell as Predictor of Intramyocardial Hemorrhage in STEMI Patients After Primary PCI

Background: Intramyocardial hemorrhage (IMH) is a result of ischemia-reperfusion injury in ST-segment elevation myocardial infarction(STEMI) after primary percutaneous coronary intervention (PPCI). Despite patients with IMH show poorer prognoses, studies investigating predictors of IMH occurrence are scarce. This study firstly investigated the effectiveness of regulatory T cell (Treg), peak value of Creatine Kinase MB (pCKMB), high-sensitivity C-reactive protein (hsCRP), and left ventricular end-systolic diameter (LVESD) as predictors for IMH in STEMI patients received PPCI.Methods: A prospective observational cohort study was performed in STEMI patients with cardiac magnetic resonance examination 6.3±2.3 days after PPCI. Logistic regression analysis was used to screen the risk factors for IMH. The predictive ability of risk factors for IMH were determined by Receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and C-index.Results: Of the 182 patients, 80 patients (44.0%) developed IMH. On multivariable analysis, all 4 biomarkers were independent predictors of IMH [odds radio (OR) and 95% confidence interval (CI): 0.350(0.202-0.606) for Treg, 1.004(1.001-1.006) for pCKMB, 1.060(1.022-1.100) for hsCRP, and 3.329(1.346-8.236) for LVESD]. After propensity score matching, the biomarkers individually and together significantly predicted IMH with areas under the curve of 0.750 for Treg, 0.721 for pCKMB, 0.656 for hsCRP, 0.633 for LVESD, and 0.821 for the integrated 4-marker panel. The addition of integrated 4-marker panel to a baseline risk model had an incremental effect on the predictive value for IMH [NRI: 0.197 (0.039 to 0.356); IDI: 0.200 (0.142 to 0.259); C-index: 0.806 (0.744 to 0.869), all p < 0.05].Conclusions: Treg individually or in combination with pCKMB, hsCRP, and LVESD can effectively predict the existence of IMH in STEMI patients received PPCI.Name of the registry: ClinicalTrials. govTrial registration number: NCT03939338Date of registration: 6 May 2019URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03939338?term=03939338&cntry=CN&draw=2&rank=1

Prognostic Implication of Serum Glycated Albumin for Patients With Non-ST-segment Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Background: It has been demonstrated that glycated albumin (GA) is significantly associated with diabetes complications and mortality. However, among patients diagnosed with non-ST-elevation acute coronary syndrome (NSTE-ACS) administered percutaneous coronary intervention (PCI), the predictive value of GA for poor prognosis is unclear.Methods: This study eventually included 2247 NSTE-ACS patients in Beijing Anzhen Hospital, Capital Medical University in January-December 2015 who received PCI. All patients were followed up until death or for 48 months post-discharge. The primary endpoint was major adverse cardio-cerebral events (MACCEs), including all-cause death, non-fatal myocardial infarction, ischemia-induced revascularization and non-fatal ischemic stroke.Results: In total, 547 (24.3%) MACCEs were recorded during the follow-up period. Upon adjusting for potential confounders, GA remained an important risk predictor of MACCEs (hazard ratio [HR]=1.051, 95% confidence interval [CI] 1.026-1.077; P<0.001). GA addition significantly enhanced the predictive ability of the traditional risk model (Harrell’s C-index, GA vs. Baseline model, 0.691 vs. 0.678, comparison P=0.001; continuous net reclassification improvement (continuous-NRI)=0.099, P=0.027; integrated discrimination improvement (IDI)=0.008, P=0.020).Conclusion: GA is highly correlated with poor prognosis in NSTE-ACS patients undergoing PCI, suggesting that it may be a major predictive factor of adverse events among these individuals.

Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson–Fabry disease

Enzyme replacement therapy (ERT) is a mainstay of treatment for Anderson–Fabry disease (AFD), a pathology with negative effects on the heart and kidneys. However, no reliable biomarkers are available to monitor its efficacy. Therefore, we tested a panel of four microRNAs linked with cardiac and renal damage in order to identify a novel biomarker associated with AFD and modulated by ERT. To this end, 60 patients with a definite diagnosis of AFD and on chronic ERT, and 29 age- and sex-matched healthy individuals, were enrolled by two Italian university hospitals. Only miR-184 met both conditions: its level discriminated untreated AFD patients from healthy individuals (c-statistic = 0.7522), and it was upregulated upon ERT (P < 0.001). On multivariable analysis, miR-184 was independently and inversely associated with a higher risk of cardiac damage (odds ratio = 0.86; 95% confidence interval [CI] = 0.76–0.98; P = 0.026). Adding miR-184 to a comprehensive clinical model improved the prediction of cardiac damage in terms of global model fit, calibration, discrimination, and classification accuracy (continuous net reclassification improvement = 0.917, P < 0.001; integrated discrimination improvement [IDI] = 0.105, P = 0.017; relative IDI = 0.221, 95% CI = 0.002–0.356). Thus, miR-184 is a circulating biomarker of AFD that changes after ERT. Assessment of its level in plasma could be clinically valuable in improving the prediction of cardiac damage in AFD patients.

Cardiovascular Family History Increases the Risk of Disease Recurrence After a First Myocardial Infarction

Background Family history of atherosclerotic cardiovascular disease (ASCVD) is easily accessible and captures genetic cardiovascular risk, but its prognostic value in secondary prevention is unknown. Methods and Results We followed 25 615 patients registered in SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) from their 1‐year revisit after a first‐time myocardial infarction during 2005 to 2013, until December 31, 2018. Data on relatives, diagnoses and socioeconomics were extracted from national registers. The association between family history and recurrent ASCVD was studied with Cox proportional‐hazard regression, adjusting for risk factors and socioeconomics. A family history of ASCVD was defined as hospitalization due to myocardial infarction, angina with coronary revascularization, stroke, or cardiovascular death in ≥1 parent or full sibling, with early‐onset defined as disease‐onset before 55 years in men and 65 in women. The additional discriminatory value of family history to Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention was assessed with Harrell’s C‐index difference and reclassification was studied with continuous net reclassification improvement. Family history of early‐onset ASCVD in ≥1 first‐degree relative was present in 2.3% and was associated with recurrent ASCVD (hazard ratio [HR] 1.31; 95% CI, 1.17–1.47), fully adjusted for risk factors (HR, 1.22; 95% CI, 1.05–1.42). Early‐onset family history improved the discriminatory ability of the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention, with Harrell’s C improving 0.003 points (95% CI, 0.001–0.005) from initial 0.587 (95% CI, 0.576–0.595) and improved reclassification (continuous net reclassification improvement 2.1%, P <0.001). Conclusions Family history of early‐onset ASCVD is associated with recurrent ASCVD after myocardial infarction, independently of traditional risk factors and improves secondary risk prediction. This may identify patients to target for intensified secondary prevention.

Incremental Value of Genotype Bins over the HAS-BLED Score for the Prediction of Bleeding Risk in Warfarin-Treated Patients with Atrial Fibrillation

Background. This study aimed to analyse the role of the HAS-BLED score with the addition of genotype bins for bleeding risk prediction in warfarin-treated patients with atrial fibrillation (AF). Methods and Results. Consecutive patients with AF on initial warfarin treatment were recruited. For each patient, CYP2C9 ∗ 3 and VKORC1-1639 A/G genotyping was performed to create 3 genotype functional bins. The predictive values of the HAS-BLED score with or without the addition of genotype bins were compared. According to the carrier status of the genotype bins, the numbers of normal, sensitive, and highly sensitive responders among 526 patients were 64 (12.17%), 422 (80.23%), and 40 (7.60%), respectively. A highly sensitive response was independently associated with clinically relevant bleeding (HR: 3.85, 95% CI: 1.88–7.91, P = 0.001 ) and major bleeding (HR:3.75, 95% CI: 1.17–11.97, P = 0.03 ). With the addition of genotype bins, the performance of the HAS-BLED score for bleeding risk prediction was significantly improved (c-statistic from 0.60 to 0.64 for clinically relevant bleeding and from 0.64 to 0.70 for major bleeding, P < 0.01 ). Using the integrated discriminatory, net reclassification improvement, and decision curve analysis, the HAS-BLED score plus genotype bins could perform better in predicting any clinically relevant bleeding than the HAS-BLED score alone. Conclusions. Genotypes have an incremental predictive value when combined with the HAS-BLED score for the prediction of clinically relevant bleeding in warfarin-treated patients with AF.

Performance of a Novel Risk Model for Deep Sternal Wound Infection after Coronary Artery Bypass Grafting

Clinical prediction models for deep sternal wound infections (DSWI) after coronary artery bypass graft (CABG) surgery exist, although they have a poor impact in external validation studies. We developed and validated a new predictive model for 30-day DSWI after CABG (REPINF) and compared it with the Society of Thoracic Surgeons model (STS). The REPINF model was created through a multicenter cohort of adults undergoing CABG surgery (REPLICCAR II Study) database, using least absolute shrinkage and selection operator (LASSO) logistic regression, internally and externally validated comparing discrimination, calibration in-the-large (CL), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), trained between the new model and the STS PredDeep, a validated model for DSWI after cardiac surgery. In the validation data, c-index = 0.83 (95% CI 0.72–0.95). Compared to the STS PredDeep, predictions improved by 6.5% (IDI). However, both STS and REPINF had limited calibration. Different populations require independent scoring systems to achieve the best predictive effect. As the STS, the REPINF external validation across multiple centers it’s important to guide healthcare professionals as a quality improvement tool in the prevention of DSWI after CABG surgery.

Albumin-corrected fructosamine predicts all-cause and non-CVD mortality among the very elderly aged ≥ 80 years without diabetes

Background Several guidelines have suggested alternative glycemic markers for hemoglobin A1c among older adults with limited life expectancy or multiple coexisting chronic illnesses. We evaluated associations between fructosamine, albumin-corrected fructosamine (AlbF) and fasting plasma glucose (FPG) and mortality in the diabetic and non-diabetic subpopulations, compared which marker better predicts mortality among participants aged 80 and above. Methods Included were 2,238 subjects from the Healthy Ageing and Biomarkers Cohort Study (2012-2018) and 207 participants had diabetes at baseline. Multivariable Cox proportional hazards regression models investigated the associations of fructosamine, AlbF, FPG and all-cause, cardiovascular disease (CVD), and non-CVD mortality in the diabetic and non-diabetic subpopulations. Restricted cubic splines (RCS) explored potential non-linear relations. C-statistic, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) evaluated the additive value of different glycemic markers to predict mortality. Results Overall, 1,191 deaths were documented during 6,793 person-years of follow-up. In the linear model, per unit increases of fructosamine, AlbF and FPG were associated with higher risk of mortality in non-diabetic participants, with hazard ratios of 1.02 (1.00, 1.05), 1.27 (1.14, 1.42) and 1.04 (0.98, 1.11) for all-cause mortality, and 1.04 (1.00, 1.07), 1.38 (1.19, 1.59) and 1.10 (1.01, 1.19) for non-CVD mortality, respectively. Comparisons indicated AlbF better predicts all-cause and non-CVD mortality in non-diabetic participants with significant improvement in IDI and NRI. Conclusions Higher concentrations of fructosamine, AlbF, and FPG were associated with higher risk of all-cause or non-CVD mortality among very elderly where AlbF may constitute an alternative prospective glycemic predictor of mortality.

Combining CHA2DS2-VASc score into RCRI for prediction perioperative cardiovascular outcomes in patients undergoing non-cardiac surgery: a retrospective pilot study

Background Treatment decisions in patients undergoing non-cardiac surgery are based on clinical assessment. The Revised Cardiac Risk Index (RCRI) is pragmatic and widely used but has only moderate discrimination. We aimed to test the efficacy of the CHA2DS2-VASc score and the combination of CHA2DS2-VASc and RCRI to predict perioperative risks for non-cardiac surgery. Methods This pre-specified analysis was performed in a retrospective cohort undergoing intra-abdominal surgery in our center from July 1st, 2007 to June 30th, 2008. The possible association between the baseline characteristics (as defined by CHA2DS2-VASc and RCRI) and the primary outcome of composite perioperative cardiac complications (myocardial infarction, cardiac ischemia, heart failure, arrhythmia, stroke, and/or death) and secondary outcomes of individual endpoints were explored using multivariate Logistic regression. The area under the receiver operating characteristic curve (C-statistic) was used for RCRI, CHA2DS2-VASc, and the combined models, and the net reclassification improvement (NRI) was calculated to assess the additional discriminative ability. Results Of the 1079 patients (age 57.5 ± 17.0 years), 460 (42.6%) were women. A total of 83 patients (7.7%) reached the primary endpoint. Secondary outcomes included 52 cardiac ischemic events, 40 myocardial infarction, 20 atrial fibrillation, 18 heart failure, four strokes, and 30 deaths. The endpoint events increased with the RCRI and CHA2DS2-VASc grade elevated (P < 0.05 for trend). The RCRI showed a moderate predictive ability with a C-statistics of 0.668 (95%CI 0.610–0.725) for the composite cardiac outcome. The C-statistics for the CHA2DS2-VASc was 0.765 (95% CI 0.709–0.820), indicating better performance than the RCRI (p = 0.011). Adding the CHA2DS2-VASc to the RCRI further increased the C-statistic to 0.774(95%CI 0.719–0.829), improved sensitivity, negative predictive value, and enhanced reclassification in reference to RCRI. Similar performance of the combined scores was demonstrated in the analysis of individual secondary endpoints. The best cut-off of a total of 4 scores was suggested for the combined CHA2DS2-VASc and RCRI in the prediction of the perioperative cardiac outcomes. Conclusions The CHA2DS2-VASc score significantly enhanced risk assessment for the composite perioperative cardiovascular outcome in comparison to traditional RCRI risk stratification. Incorporation of CHA2DS2-VASc scores into clinical-decision making to improve perioperative management in patients undergoing non-cardiac surgery warrants consideration.

Performance of different adiposity measures for predicting left ventricular remodeling in Chinese hypertensive youth

There is no consistent conclusion on which adiposity measure is best to predict cardiovascular risk factors in youth. The present study aims to assess the performance of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in predicting abnormal left ventricular structure in Chinese hypertensive youth. A total of 1180 youth aged 6–17 years with hypertension from the China Child and Adolescent Cardiovascular Health Study were included in this study. Logistic regression model, receiver operator characteristic (ROC) curve analysis and net reclassification improvement (NRI) method were used to assess performance of BMI, WC, and WHtR in predicting left ventricular hypertrophy (LVH) and left ventricular geometry (LVG). A 1-standard deviation increment in any of three indexes in predicting LVH and LVG were similar, e.g., with the odds ratios and 95% confidence intervals of 1.34 (1.16–1.55), 1.25 (1.08–1.45) and 1.40 (1.20–1.62), respectively. In addition, ROC analysis and NRI method confirmed the similar performance of three adiposity indexes in predicting LVH and LVG. In conclusion, BMI, WC and WHtR had similar performance in predicting abnormal left ventricular structure in Chinese hypertensive youth, but all three indexes had limited value in prediction. WHtR is a simple and convenient adiposity index for screening youth at high risk of target organ damage.