Integrated Discrimination Index Research Articles

Low caveolin-1 levels and symptomatic intracranial haemorrhage risk in large-vessel occlusive stroke patients after endovascular thrombectomy.

Caveolin-1 (Cav-1) is reported to mediate blood-brain barrier integrity after ischaemic stroke. Our purpose was to assess the role of circulating Cav-1 levels in predicting symptomatic intracranial haemorrhage (sICH) amongst ischaemic stroke patients after endovascular thrombectomy (EVT). Patients with large-vessel occlusive stroke after EVT from two stroke centres were prospectively included. Serum Cav-1 level was tested after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. Of 325 patients (mean age 68.6 years; 207 men) included, 47 (14.5%) were diagnosed with sICH. Compared with patients without sICH, those with sICH had a lower concentration of Cav-1. After adjusting for potential confounders, multivariate regression analysis demonstrated that the increased Cav-1 level was associated with a lower sICH risk (odds ratio 0.055; 95% confidence interval 0.005-0.669; p = 0.038). Similar results were obtained when Cav-1 levels were analysed as a categorical variable. Using a logistic regression model with restricted cubic splines, a linear and negative association of Cav-1 concentration was found with sICH risk (p = 0.001 for linearity). Furthermore, the performance of the conventional risk factors model in predicting sICH was substantially improved after addition of the Cav-1 levels (integrated discrimination index 2.7%, p = 0.002; net reclassification improvement 39.7%, p = 0.007). Our data demonstrate that decreased Cav-1 levels are related to sICH after EVT. Incorporation of Cav-1 into clinical decision-making may help to identify patients at a high risk of sICH and warrants further consideration.

CatLet score and clinical CatLet score as predictors of long-term outcomes in patients with acute myocardial infarction presenting later than 12 hours from symptom onset

Background Our recently developed C oronary A rtery T ree description and L esion E valua T ion (CatLet) angiographic scoring system is unique in its description of the variability in the coronary anatomy, the degree of stenosis of a diseased coronary artery, and its subtended myocardial territory, and can be utilized to predict clinical outcomes for patients with acute myocardial infarction (AMI) presenting ≤12 h after symptom onset. The current study aimed to assess whether the Clinical CatLet score (CCS), as compared with CatLet score (CS), better predicted clinical outcomes for AMI patients presenting >12 h after symptom onset. Methods CS was calculated in 1018 consecutive AMI patients enrolled in a retrospective registry. CCS was calculated by multiplying CS by the ACEF I score (age, creatinine, and left ventricular ejection fraction). Primary endpoint was major adverse cardiac events (MACEs) at 4-year-follow-up, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Results Over a 4-year follow-up period, both scores were independent predictors of clinical outcomes after adjustment for a broad spectrum of risk factors. Areas-under-the-curve (AUCs) for CS and CCS were 0.72(0.68–0.75) and 0.75(0.71–0.78) for MACEs; 0.68(0.63–0.73) and 0.78(0.74–0.83) for all-cause death; 0.73(0.68–0.79) and 0.83(0.79–0.88) for cardiac death; and 0.69(0.64–0.73) and 0.75(0.7–0.79) for myocardial infarction; and 0.66(0.61–0.7) and 0.63(0.58–0.68) for revascularization, respectively. CCS performed better than CS in terms of the above-mentioned outcome predictions, as confirmed by the net reclassification and integrated discrimination indices. Conclusions CCS was better than CS to be able to risk-stratify long-term outcomes in AMI patients presenting >12 h after symptom onset. These findings have indicated that both anatomic and clinical variables should be considered in decision-making on management of patients with AMI presenting later.

Serum lipopolysaccharide associated with new-onset atrial fibrillation in patients with non-small-cell lung cancer a retrospective observational study

Lipopolysaccharide (LPS) is related to atrial fibrillation (AF). But so far, the relationship between LPS and new-onset AF (NOAF) in patients with lung cancer is unrevealed. This study was to investigate the association between LPS and NOAF in patients after lung cancer surgery. This was a single-center retrospective clinical observational study. Patients diagnosed with non-small-cell lung cancer (NSCLC) were enrolled. All patients receiving lung cancer surgery and at least 24 h electrocardiogram (ECG) examination was recorded during the hospitalization. The incidence of NOAF in this study was 34/406 (8.4%). The univariate analysis showed that NOAF was associated with age, intraoperative blood transfusion (IBT), chronic obstructive pulmonary disorder (COPD), and LPS. After adjusting risk factors, it was found that age, IBT and LPS (OR, 1.031; 95% CI: 1.001–1.042; P = 0.002) were still risk factors for NOAF. The area under curve (AUC) value was 0.709 for the LPS. When the LPS was added to the conventional model, the Net reclassification index (NRI) and integrated discrimination index (IDI) were improved significantly. Elevated LPS is associated with an increased risk of NOAF in patients after lung cancer surgery. LPS contributed to the discrimination of the NOAF risk model and improved it markedly.

White matter hyperintensity, parent artery steno-occlusion, and neurological deterioration in anterior circulation single subcortical infarction patients.

The evidence for the association between white matter hyperintensity (WMH) severity and neurological deterioration (ND) in patients with single subcortical infarction (SSI) remains unclear and whether the association between them is modified by anterior circulation parent artery steno-occlusion (PAS) is unknown. Herein, we aimed to prospectively investigate the internal relevance. In this prospective study, the severity of WMH and PAS were assessed in 288 consecutive patients with anterior circulation SSI arriving at our hospital, a tertiary teaching hospital affiliated with Fudan University, 24h after onset from January 2017 to December 2018. The multivariable logistic regression model was used to estimate the association between WMH severity and the risk of ND within 7 days after stroke onset as well as the interactive effect between WMH severity and PAS on ND among patients with SSI. PAS modified the association between WMH severity and ND among patients with SSI (pinteraction=.029). After multivariate adjustment, the odds ratios of moderate-severe WMH associated with ND were 1.61 (95% CI, 0.50-5.19; ptrend=.428) for patients with PAS, and 0.37 (95% CI, 0.14-0.97; ptrend=.043) for those without PAS. Adding WMH severity to conventional risk factors improved risk prediction for ND in patients without PAS (net reclassification improvement: 48.2%, p=.005; integrated discrimination index: 2.5%, p=.004) but not in those with PAS. There was a modified effect of PAS on the association between WMH severity and ND within 7 days after stroke onset among patients with anterior circulation SSI, which deserves more research attention. WMH was negatively associated with ND in anterior circulation SSI patients without PAS.

Serum YKL-40 as a Predictive Biomarker of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage Recurrence.

Neuroinflammation is a major cause of secondary brain injury in intracerebral hemorrhage (ICH). To date, the prognostic value of YKL-40 (chitinase-3-like-1 protein), a biomarker of neuroinflammation, in cerebral amyloid angiopathy-related intracerebral hemorrhage (CAA-ICH) remains undiscovered. To evaluate the relationships between serum YKL-40 and CAA-ICH recurrence. Clinical and imaging information of 68 first-onset probable CAA-ICH cases and 95 controls were collected at baseline. Serum YKL-40 was measured by Luminex assay. Cox proportional hazards model was used to analyze the associations between YKL-40 level and CAA-ICH recurrence. Serum YKL-40 level was significantly higher in CAA-ICH cases than healthy controls (median [interquartile range, IQR], 46.1 [19.8, 93.4] versus 24.4 [13.9, 59.0] ng/mL, p = 0.004). Higher level of YKL-40 predicted increased risk of CAA-ICH recurrence adjusted for age, ICH volume and enlarged perivascular space score (ePVS) (above versus below 115.5 ng/ml, adjusted hazard ratios 4.721, 95% confidence intervals 1.829-12.189, p = 0.001) within a median follow-up period of 2.4 years. Adding YKL-40 to a model of only MRI imaging markers including ICH volume and ePVS score improved the discriminatory power (concordance index from 0.707 to 0.772, p = 0.001) and the reclassification power (net reclassification improvement 28.4%; integrated discrimination index 11.0%). Serum YKL-40 level might be a candidate prognostic biomarker for CAA-ICH recurrence.

Value of the monocyte-to-high-density lipoprotein cholesterol ratio in refining the detection of prevalent heart failure: Insights from the NHANES 1999-2018.

The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is a novel marker that can help estimate the degree of atherosclerosis by considering inflammation and lipid abnormalities. This study aimed to assess the association between the MHR and prevalent heart failure (HF) and to explore the value of the MHR in detecting prevalent HF in the general US population. Our study included 25,374 participants from the National Health and Nutrition Examination Survey (1999-2018). Among the participants, 749 (2.95%) reported a history of HF, and the HF group had a significantly higher MHR than the non-HF group. Adjusted analyses revealed that each standard deviation increase in the MHR was associated with a 27.8% increase in the risk of HF. The association between the MHR and prevalent HF was linear across the entire MHR range. Adding the MHR to conventional cardiovascular risk factors significantly improved the area under the curve (0.875; p < 0.001), continuous net reclassification index (0.187; p < 0.001), and integrated discrimination index (0.004; p < 0.001). Our study suggests a potential association between the MHR and HF risk, and the findings enhance HF risk stratification and provide novel insights into the interplay between the coronary atherosclerotic burden and HF in clinical settings.

Association of cardiac biomarkers with long-term cardiovascular events in a community cohort

Introduction: We hypothesized that combining biomarkers of atherosclerotic cardiovascular disease (ASCVD) would improve prediction of ASCVD events in a primary prevention cohort. Materials and methods The study assessed major adverse cardiac events (MACE) (myocardial infarction, coronary artery bypass graft, percutaneous intervention, stroke, and death. Cox proportional hazards models assessed apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), ceramide score, cystatin C, galectin-3 (Gal3), LDL-C, Non-HDL-C, total cholesterol (TC), N-terminal B-type natriuretic peptide (NT proBNP), high-sensitivity cardiac troponin (HscTnI) and soluble interleukin 1 receptor-like 1. In adjusted models, Ceramide score was defined by from N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)] and N-lignoceroyl-sphingosine [Cer(24:0)]. Multi-biomarker models were compared with C-statistics and Integrated Discrimination Index (IDI). Results A total of 1131 patients were included. Adjusted NT proBNP per 1 SD resulted in a 31% increased risk of MACE/death (HR = 1.31) and a 31% increased risk for stroke/MI (HR = 1.31). Adjusted Ceramide per 1 SD showed a 13% increased risk of MACE/death (HR = 1.13) and a 29% increased risk for stroke/MI (HR = 1.29). These markers added to clinical factors for both MACE/death (p = 0.003) and stroke/MI (p = 0.034). HscTnI was not a predictor of outcomes when added to the models. Discussion Ceramide score and NT proBNP improve the prediction of MACE and stroke/MI in a community primary prevention cohort.

Classification of the Urgency of the Procedure and Outcome of Acute Type A Aortic Dissection

Surgery for type A aortic dissection (TAAD) is associated with high risk of early mortality. The prognostic impact of a new classification of the urgency of the procedure was evaluated in this multicenter cohort study.Data on consecutive patients who underwent surgery for acute TAAD were retrospectively collected in the multicenter, retrospective European Registry of TAAD (ERTAAD).The rates of in-hospital mortality of 3902 consecutive patients increased along with the ERTAAD procedure urgency grades: urgent procedure, 10.0%; emergency procedure grade 1, 13.3%; emergency procedure grade 2, 22.1%; salvage procedure grade 1, 45.6%; and salvage procedure grade 2, 57.1% (p<0.0001). Preoperative arterial lactate correlated with the urgency grades. Inclusion of the ERTAAD procedure urgency classification significantly improved the area under the receiver operating characteristics curves of the regression model as well as the integrated discrimination indices and the net reclassification indices. The risk of postoperative stroke/global brain ischemia, mesenteric ischemia, lower limb ischemia, dialysis, and acute heart failure increased along with the urgency grades.In conclusion, the urgency of surgical repair of acute TAAD seems to have a significant impact on the risk of in-hospital mortality may be useful to improve the stratification of the operative risk of these critically ill patients. This study showed that salvage surgery for TAAD is justified because half of patients may survive to discharge.

Incremental values of AOPP, IL-6, and GDF15 for identifying arteriosclerosis in patients with obstructive sleep apnea

BackgroundThe objective of this study was to determine the independent and incremental values of advanced oxidative protein product (AOPP), interleukin 6 (IL-6), and growth differentiation factor 15 (GDF15) in identifying arteriosclerosis in patients with obstructive sleep apnea (OSA).MethodsA total of 104 individuals diagnosed with OSA by polysomnography were recruited in our study. Arteriosclerosis was defined by measuring the ultrafast pulse wave velocity of the carotid artery. Peripheral venous blood samples were collected to analyze the levels of AOPP, IL-6, and GDF15 utilizing commercially available enzyme-linked immunosorbent assays.ResultsCompared to OSA patients without arteriosclerosis, those with arteriosclerosis exhibited significantly higher levels of AOPP, IL-6, and GDF15. GDF15 remained significantly associated with arteriosclerosis even after accounting for clinical factors such as age, gender, body mass index, systolic blood pressure, fasting blood glucose, smoking, and the apnea–hypoxia index (AHI). GDF15 demonstrated the largest area under the curve (AUC) for identifying arteriosclerosis in OSA patients (AUC, 0.85 [0.77–0.94]). The logistic regression model, combining clinical factors and AHI, was enhanced by the inclusion of AOPP and IL-6 (Chi-square = 25.06), and even further improved when GDF15 was added (Chi-square = 50.74). The integrated discrimination index increased by 0.06 to 0.16 when GDF15 was added to the models including clinical factors, AOPP, and IL-6.ConclusionsThis study verified the independent and incremental value of GDF15 in identifying arteriosclerosis in OSA patients, surpassing clinical risk factors and other serum biomarkers such as AOPP and IL-6.

Nomogram for hospital-acquired venous thromboembolism among patients with cardiovascular diseases

BackgroundIdentifying venous thromboembolism (VTE) is challenging for patients with cardiovascular diseases due to similar clinical presentation. Most hospital-acquired VTE events are preventable, whereas the implementation of VTE prophylaxis in clinical practice is far from sufficient. There is a lack of hospital-acquired VTE prediction models tailored specifically designed for patients with cardiovascular diseases. We aimed to develop a nomogram predicting hospital-acquired VTE specifically for patients with cardiovascular diseases.Material and methodsConsecutive patients with cardiovascular diseases admitted to internal medicine of Fuwai hospital between September 2020 and August 2021 were included. Univariable and multivariable logistic regression were applied to identify risk factors of hospital-acquired VTE. A nomogram was constructed according to multivariable logistic regression, and internally validated by bootstrapping.ResultsA total of 27,235 patients were included. During a median hospitalization of four days, 154 (0.57%) patients developed hospital-acquired VTE. Multivariable logistic regression identified that female sex, age, infection, pulmonary hypertension, obstructive sleep apnea, acute coronary syndrome, cardiomyopathy, heart failure, immobility, central venous catheter, intra-aortic balloon pump and anticoagulation were independently associated with hospital-acquired VTE. The nomogram was constructed with high accuracy in both the training set and validation (concordance index 0.865 in the training set, and 0.864 in validation), which was further confirmed in calibration. Compared to Padua model, the Fuwai model demonstrated significantly better discrimination ability (area under curve 0.865 vs. 0.786, net reclassification index 0.052, 95% confidence interval 0.012–0.091, P = 0.009; integrated discrimination index 0.020, 95% confidence interval 0.001–0.039, P = 0.051).ConclusionThe incidence of hospital-acquired VTE in patients with cardiovascular diseases is relatively low. The nomogram exhibits high accuracy in predicting hospital-acquired VTE in patients with cardiovascular diseases.

Sex-specific association between monocyte to high-density lipoprotein cholesterol and extensive abdominal aortic calcification in humans.

Recent studies have identified monocyte-to-high-density lipoprotein cholesterol ratio (MHR) as a simple marker of atherosclerosis. Abdominal aortic calcification (AAC) is a direct result of vascular atherosclerosis. Our study aims to investigate the association between MHR and the prevalent extensive AAC and assess the value of MHR for identifying prevalent extensive AAC. 2857 subjects (28.07%) from the cross-sectional National Health and Nutrition Examination Survey 2013-2014 were included in our study. AAC was detected through dual-energy x-ray absorptiometry and quantified by Kauppila score. Extensive AAC was identified in 153 (10.44% of 1465) females and 146 (10.49% of 1392) males. With the full adjustment, each SD increase of MHR resulted in an 87.3% additional risk for extensive AAC in females. When dividing into quartiles, the top quartile had a 3.472 times risk of prevalent extensive AAC than the bottom quartile. However, no significant association was observed in males. Furthermore, smooth curve fitting implicated that the significant association was linear in the whole range of MHR among females. Additionally, ROC demonstrated an improvement in the identification of extensive AAC only among females when introducing MHR into established risk factors of atherosclerosis (0.808 vs. 0.864, p < 0.001). Finally, category-free net reclassification index and integrated discrimination index also supported the improvement by MHR in females. Our study revealed a linear association between MHR and prevalent extensive AAC in females. Moreover, our results implicated the potential value of MHR to refine the identification of prevalent extensive AAC in females.

P452 Serum Amyloid A for Predicting Surgery and Disease Exacerbation in Patients with Newly Diagnosed Crohn’s Disease

Abstract Background Crohn's disease (CD) is characterized by relapsing-remitting course with highly heterogenous prognosis, ranging from quiescent disease to complicated course with stricturing, penetrating or need of abdominal surgery. Identifying biomarkers that determine their disease course can enable implementing more aggressive preventive strategies. Serum amyloid A (SAA) has been demonstrated to involve in the pathogenesis of Crohn’s disease (CD); however, its prognostic value is still uncertain. This study was determined to explore the prognostic value of SAA for CD-related surgery and disease exacerbation in newly diagnosed CD. Methods We conducted a retrospective cohort study and recruited newly-diagnosed CD patients at the First Affiliated Hospital of Sun Yat-sen University. Level of SAA was detected at diagnosis. The primary outcome was CD-related surgery. The secondary outcome was disease exacerbation, defining as newly developed structuring or penetrating lesions. Association between variables and outcome was evaluated through Kaplan–Meier method and Cox proportional hazard regression analysis. For continuous variables, the optimal cutoff values were determined by using the survminer R package in the analysis of primary outcome. The prognostic model was developed by cox proportional-hazards model. Concordance-index (c-index) was used to assess the predictive ability of the prognostic model. Results During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease exacerbation events were documented. After adjustment, a 14% higher risk for surgery (adjusted hazard ratio, aHR [95% confidence interval]: 1.14 [1.05–1.23]; p=0.001) and a 12% higher risk for disease exacerbation (1.12 [1.05–1.19]; p&amp;lt;0.001) were observed with a 100-unit increase in SAA level. Patients with SAA levels ≥89.2 mg/L had aHRs of 2.08 [1.31–3.28] and 1.72 [1.22–2.41] for CD-related surgery and disease exacerbation, respectively. The association between SAA and outcomes was assessed as linear by the restricted cubic spline. Adding SAA into the model including known risk factors, including age at diagnosis ≥40 years, disease behavior, disease location, and initial biological treatment, led to significant improvement in its predictive ability for surgery (net reclassification index and integrated discrimination index, p&amp;lt;0.001) and disease exacerbation (net reclassification index and integrated discrimination index, p&amp;lt;0.001). Sensitivity analyses showed robust results. Conclusion Our study shows that higher serum SAA level at diagnosis was associated with poorer prognosis, including risk of surgery and disease exacerbation. And prognostic models based on SAA and known risk factors could better predict prognosis.

High-Serum Brain-Derived Neurotrophic Factor Levels Are Associated With Decreased Risk of Poststroke Cognitive Impairment.

BDNF (brain-derived neurotrophic factor) is widely implicated in the pathophysiological process of stroke, but the effect of BDNF on poststroke cognitive impairment (PSCI) remains unclear. We aimed to investigate the association between baseline serum BDNF and the risk of PSCI at 3 months in a multicenter study based on a preplanned ancillary study of the CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke). We examined serum BDNF levels at baseline and used the Mini-Mental State Examination and Montreal Cognitive Assessment to evaluate cognitive function at 3-month follow-up after ischemic stroke. PSCI was defined as Mini-Mental State Examination score <27 or Montreal Cognitive Assessment score <25. Logistic regression analyses were performed to evaluate the association between serum BDNF and the risk of 3-month PSCI. In this ancillary study, a total of 660 patients with ischemic stroke with hypertension were included, and 593 patients (mean age, 59.90±10.44 years; 410 males and 183 females) were finally included in this analysis. According to mini-mental state examination score, after adjustment for age, sex, education, baseline National Institutes of Health Stroke Scale score, APOE ɛ4 carriers, and other potential confounders, the odds ratio of PSCI for the highest tertile of BDNF was 0.60 ([95% CI, 0.39-0.94]; P=0.024) compared with the lowest tertile. Multiple-adjusted spline regression model showed a linear association of serum BDNF levels with PSCI at 3 months (P value for linearity=0.010). Adding serum BDNF to conventional prognostic factors slightly improved the risk reclassification of PSCI (net reclassification improvement: 27.46%, P=0.001; integrated discrimination index: 1.02%, P=0.015). Similar significant findings were observed when PSCI was defined by the Montreal Cognitive Assessment score. Elevated serum BDNF levels were associated with a decreased risk of PSCI at 3 months, suggesting that serum BDNF might be a potential predictive biomarker for PSCI among patients with ischemic stroke with hypertension.

Prognostic value of right ventricular trabecular complexity in patients with arrhythmogenic cardiomyopathy.

The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.

Predictive improvement of adding coronary calcium score and a genetic risk score to a traditional risk model for cardiovascular event prediction.

Coronary artery calcium score (CACS) and polygenic risk score have been used as novel markers to predict cardiovascular (CV) events of asymptomatic individuals compared with traditional scores. No previous studies have directly compared the additive capacity of these two markers relative to conventional scores. The aim of the study was to evaluate the change in CV risk prediction ability when CACS, genetic risk score (GRS), or both are added to Systematic Coronary Risk Evaluation 2 (SCORE2). In a prospective, observational population-based study, 1002 asymptomatic subjects (mean age 53.1 ± 6.8 years, 73.8% male), free of clinical coronary disease and diabetes, were selected from GENEMACOR-study controls. SCORE2, CACS, and GRS were estimated to evaluate CV events' predictive and discriminative ability through Harrell's C-statistics. Net reclassification improvement (NRI) and integrated discrimination index were used to reclassify the population. Multivariable Cox proportional hazard ratio (HR) analysis assessed the variables independently associated with CV events. C-statistic demonstrated that the discriminative value for CV event occurrence was 0.608 for SCORE2, increasing to 0.749 (P = 0.001) when CACS was added, and improved to 0.802 (P = 0.0008) with GRS, showing a better discriminative capacity for CV events. Continuous NRI reclassified >70% of the population. Cox proportional analysis showed that the highest categories of SCORE2, CACS, and GRS remained in the equation with an HR of 2.9 (P = 0.003), 5.0 (P < 0.0001), and 3.2 (P = 0.003), respectively, when compared with the lowest categories. In our population, CACS added to SCORE2 had better ability than GRS in CV event risk prediction, discrimination, and reclassification. However, adding the three scores can become clinically relevant, especially in intermediate-risk persons.

Leg strength and incidence of heart failure in patients with acute coronary syndrome.

The risk of developing heart failure (HF) after acute coronary syndrome (ACS) remains high. It is unclear whether skeletal muscle strength, in addition to existing risk factors, is a predictor for developing HF after ACS. We aimed to clarify the relationship between quadriceps isometric strength (QIS), a skeletal muscle strength indicator, and the risk of developing HF in patients with ACS. We included 1053 patients with ACS without a prior HF or complications of HF during hospitalization. The median (interquartile range) age was 67 (57-74) years. The patients were classified into two groups-high and low QIS-using the sex-specific median QIS. The endpoint was HF admissions. During a mean follow-up period of 4.4 ± 3.7 years, 75 (7.1%) HF admissions were observed. After multivariate adjustment, a high QIS was associated with a lower risk of HF [hazard ratio: 0.52, 95% confidence interval (CI): 0.32-0.87]. Hazard ratio (95% CI) per 5% body weight increment increase of QIS for HF incidents was 0.87 (0.80-0.95). Even when competing risks of death were taken into account, the results did not change. The inclusion of QIS was associated with increases in net reclassification improvement (0.26; 95% CI: 0.002-0.52) and an integrated discrimination index (0.01; 95% CI: 0.004-0.02) for HF. The present study showed that a higher level of QIS was strongly associated with a lower risk of developing HF after ACS. These findings suggest that skeletal muscle strength could be one of the factors contributing to the risk of developing HF after ACS.

Prognostic value of CT-derived fractional flow reserve and fat attenuation index in patients with suspected coronary artery disease: a sex-disaggregated analyses

BackgroundThere are sex differences in many risk factors associated with coronary artery disease (CAD). CT-derived fractional flow reserve (CT-FFR) and fat attenuation index (FAI) have been shown to independently predict cardiovascular events. We aimed to examine the impact of sex on the prognostic value of CT-FFR and FAI in suspected CAD patients, and to examine the incremental prognostic value of FAI over CT-FFR in both sex.MethodsA total of 1334 consecutive suspected CAD subjects who underwent coronary computed tomographic angiography (CCTA) were retrospectively collected. We divided the patients into males and females and calculated CT-FFR and FAI data from CCTA images. Kaplan-Meier analysis was used to assess the risk of major adverse cardiovascular events (MACE) stratified by CT-FFR and FAI in both sex. Cox regression models were used to assess the incremental prognostic value of FAI by adding the variable to a model that included CT-FFR and clinical variables.ResultsDuring a median follow-up of 2.08 years, 212 patients had MACE. CT-FFR ≤ 0.80 was significantly associated with MACE in both sex. FAI value of left anterior descending artery (FAI[LAD]) and FAI value of left circumflex (FAI[LCX]) ≥ 70.1 were significantly associated with MACE in females. FAI[LCX] added incremental prognostic value over clinical and CT-FFR variables in females, with hazard ratio (HR) 3.230 (1.982–5.265, P = 0.000), Harrel’s C 0.669 (P < 0.001), net reclassification improvement (NRI) 0.161 (0.073–0.260, P < 0.001), and integrated discrimination index (IDI) 0.036 (0.008–0.090, P = 0.010). FAI[LAD] did not enhance risk prediction in females (Harrel’s C 0.643, P = 0.054; NRI 0.041, P = 0.189; IDI 0.005, P = 0.259). The decision curve analysis demonstrated that the model including FAI[LCX] resulted in the highest net benefit.ConclusionsIn suspected CAD patients, the prognostic value of CT-FFR is not significantly biased by sex. The prognostic value of FAI[LAD] and FAI[LCX] were significantly associated with MACE in females, but not males. FAI[LCX], not FAI[LAD], added incremental prognostic value over CT-FFR and might enhance CT-FFR risk stratification in females.

Heart rhythm complexity analysis in patients with inferior ST-elevation myocardial infarction

Heart rhythm complexity (HRC), a subtype of heart rate variability (HRV), is an important tool to investigate cardiovascular disease. In this study, we aimed to analyze serial changes in HRV and HRC metrics in patients with inferior ST-elevation myocardial infarction (STEMI) within 1 year postinfarct and explore the association between HRC and postinfarct left ventricular (LV) systolic impairment. We prospectively enrolled 33 inferior STEMI patients and 74 control subjects and analyzed traditional linear HRV and HRC metrics in both groups, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We also analyzed follow-up postinfarct echocardiography for 1 year. The STEMI group had significantly lower standard deviation of RR interval (SDNN), and DFAα2 within 7 days postinfarct (acute stage) comparing to control subjects. LF power was consistently higher in STEMI group during follow up. The MSE scale 5 was higher at acute stage comparing to control subjects and had a trend of decrease during 1-year postinfarct. The MSE area under scale 1–5 showed persistently lower than control subjects and progressively decreased during 1-year postinfarct. To predict long-term postinfarct LV systolic impairment, the slope between MSE scale 1 to 5 (slope 1–5) had the best predictive value. MSE slope 1–5 also increased the predictive ability of the linear HRV metrics in both the net reclassification index and integrated discrimination index models. In conclusion, HRC and LV contractility decreased 1 year postinfarct in inferior STEMI patients, and MSE slope 1–5 was a good predictor of postinfarct LV systolic impairment.

Development and validation of a novel death risk stratification scale in patients with hemorrhagic fever with renal syndrome: a 14-year ambispective cohort study

ObjectivesTo develop and validate a simple and effective death risk stratification scale for hemorrhagic fever with renal syndrome (HFRS). MethodsIn this ambispective cohort study, we investigated the epidemiological and clinical data of 2245 patients with HFRS (1873 enrolled retrospectively and constituting the training cohort, 372 prospectively recruited as the validation cohort) from September 2008 to December 2021, and identified independent risk factors for 30-day death of HFRS. Using logistic regression analysis, a nomogram prediction model was established and was further simplified into a novel scoring scale. Calibration plot, receiver operating characteristic curve, net reclassification index, integrated discrimination index, and decision curve analysis were used to assess the calibration, discrimination, precision, and clinical utility in both training and validation cohorts. ResultsOf 2245 patients with HFRS, 132 (5.9%) died during hospitalization. The nomogram prediction model and scoring scale were developed using six predictors: comorbid hypertension, hypotensive shock, hypoxemia, neutrophils, aspartate aminotransferase, and activated partial thromboplastin time. Both the scale and nomogram were well calibrated (near-diagonal calibration curves) and demonstrated significant predictive values (areas under receiver operating characteristic curves >0.9, sensitivity and specificity >90% in the training cohort and >84% in the validation cohort). The simplified scoring scale demonstrated equivalent discriminative ability to the nomogram, with net reclassification index and integrated discrimination index of 0.022 and 0.007 in the training cohort, 0.126 and 0.022 in the validation cohort. Decision curve analysis graphically represented significant clinical utility and comparable net benefits of the nomogram and scoring scale across a range of threshold probabilities. DiscussionThis evidence-based, factor-weighted, accurate score could help clinicians swiftly stratify HFRS mortality risk and facilitate the implementation of patient triage and tiered medical services during epidemic peaks.

Genetic risk score and epicardial adipose tissue: the new tools with impact on cardiovascular risk assessment

Abstract Background Cardiovascular disease (CVD) remains the leading cause of death worldwide. One of its main contributors is coronary artery disease (CAD), a complex multifactorial disease influenced by hereditary and environmental factors. A better cardiovascular risk assessment is a real challenge in our daily clinical practice. Evidence points to high Epicardial Adipose Tissue (EAT) volume as an essential player in the pathophysiology of CAD. On the other hand, genetic predisposition to CAD remains crucial to improve cardiovascular risk assessment and treatment. It is unknown whether the association between these two risk markers improved the ability to predict CV events. Objective Evaluate whether a high EAT volume added to a Genetic Risk Score (GRS) improves the predictive ability to discriminate CV events in an asymptomatic population without known CVD. Methods A prospective cohort was performed with 1024 participants (mean age 51.6±8.2 years, 75.6% male) selected from controls of the GENEMACOR Study. The GRS was created from 33 genetic variants associated with CAD by GWAS, choosing those with a hazard ratio (HR) higher than 1. EAT volume was measured with a quantitative semi-automated procedure using a postprocessing workstation-TeraRecon Aquarius Workstation (version 4.4.7, TeraRecon, Inc., San Mateo, CA, USA). We evaluated the discriminative ability of the GRS model without (model 1) and with EAT volume (model 2) using the Harrel C statistics. Categorical free Net Reclassification Improvement (cfNRI) and Integrated Discrimination Index (IDI) reclassified patients. Results Cox regression analysis showed that GRS and EAT remained in the equation with an HR of 1.140 (p=0.002) and HR of 1.221 (p=0.002), respectively. C-statistic demonstrated that the predictive value for MACE was 0.588 (95%CI 0.445-0.731) for GRS and increased to 0.689 (95%CI 0.577-0.801) when EAT volume was added to GRS, showing a better discrimination capacity for MACE. The difference between the two C indexes was significant (p=0.003). CfNRI reclassified 58.9% of the population (p=0.001), and IDI improved the discrimination when EAT was included in the GRS model (IDI=0.012; p=0.015). Conclusion Our results displayed that the GRS associated with a high EAT volume increased the discriminative ability to predict MACE occurrence. Improving the identification of high-risk patients at a subclinical stage could avoid atherosclerosis progression and events occurrence through more rigorous and earlier preventive and even therapeutic measures.