Predicting the risk of 1-year mortality among patients hospitalized for acute heart failure in China.

BACKGROUND: We aimed to develop and validate a model to predict 1-year mortality risk among patients hospitalized for acute heart failure (AHF), build a risk score and interpret its application in clinical decision making. METHODS: By using data from China Patient-Centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, which prospectively enrolled patients hospitalized for AHF in 52 hospitals across 20 provinces, we used multivariate Cox proportional hazard model to develop and validate a model to predict 1-year mortality. RESULTS: There were 4,875 patients included in the study, 857 (17.58%) of them died within 1-year following discharge of index hospitalization. A total of 13 predictors were selected to establish the prediction model, including age, medical history of chronic obstructive pulmonary disease and hypertension, systolic blood pressure, Kansas City Cardiomyopathy Questionnaire-12 score, angiotensin converting enzyme inhibitor or angiotensin receptor blocker at discharge, discharge symptom, N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T, serum creatine, albumin, blood urea nitrogen, and highly sensitive C-reactive protein. The model showed a high performance on discrimination (C-index was 0.759 [95% confidence interval: 0.739, 0.778] in development cohort and 0.761 [95% confidence interval: 0.731, 0.791] in validation cohort), accuracy, calibration, and outperformed than several existed risk scores. A point-based risk score was built to stratify low- (0-12), intermediate- (13-16), and high-risk group (≥17) among patients. CONCLUSIONS: A prediction model using readily available predictors was developed and internal validated to predict 1-year mortality risk among patients hospitalized for AHF. It may serve as a useful tool for individual risk stratification and informing decision making to improve clinical care.

[Effects of PM_(2. 5) exposure on synaptic plasticity and Wnt/ß-catenin pathway in rat hippocampus].

OBJECTIVE: To investigate the effects of PM_(2. 5) exposure on the development of synaptic plasticity and Wnt/ß-catenin pathway in hippocampus of offspring rats. METHODS: Healthy 7-week-old SPF SD rats(n=36) mated with a male to female ratio of 2∶1. Pregnant rats were randomly divided into three groups, including control group, low PM_(2. 5) group, and high PM_(2. 5) group, with eight rats in each group. The low and high PM_(2. 5) concentrations in dynamic exposure cabinet were approximately two times and four times higher than the annual average PM_(2. 5) concentration in Tangshan city respectively. The exposure started from pregnant day 0, until postnatal day 21(PND21) of offspring rats. After weaning, the offspring rats continued to be exposed to PM_(2. 5) until PND42. PND21 and PND42 pups were subjected to Morris water maze and new object recognition experiments. Western blot was used to detect post synaptic density-95(PSD-95), synaptophysin(SYN), growth associated protein(GAP-43), glycogen synthase kinase 3ß(GSK-3ß), ß-catenin protein levels and phosphorylation levels of GSK-3ß and ß-catenin in the hippocampus of offspring rats. RESULTS: Compared with the control group, the learning and memory abilities of the pups of each PM_(2. 5) group were significantly decreased with a dose dependent manner. Compared with the control group, the protein level of SYN, GAP-43 and PSD-95 in hippocampus of PND0 rats of each PM_(2. 5)groups were decreased(P<0. 05), and the protein level of SYN of each PM_(2. 5)group and PSD-95 of high PM_(2. 5) group in PND21 and PND42 were decreased(P<0. 05), and the level of GAP-43 of low PM_(2. 5) group in PND42 were decreased(P<0. 05). Compared with the low PM_(2. 5) group, the level of PSD-95 of high PM_(2. 5) group in PND0 and PND21, the level of PSD-95 of high PM_(2. 5) group in PND0 and PND42 were decreased(P<0. 05). Compared with the control group, the level of p-GSK-3ß in hippocampus of each PM_(2. 5)group in PND0, PND21 and PND42 was decreased(P<0. 05), and with the increase of PM_(2. 5) exposure dose, the trend is more obvious. The protein level of p-ß-catenin in hippocampus of high PM_(2. 5) group in PND0 and PND42 was significantly increased(P<0. 05). The level of p-ß-catenin in high-dose PND21 pups compared with the control group was significantly reduced(P<0. 05). CONCLUSION: Exposure to PM_(2. 5) in early life can damage the synaptic plasticity and decrease the protein levels of ß-catenin and p-GSK-3ß in the Wnt/ß-catenin pathway of hippocampus in offspring rats.

The associations of "weekend warrior" and regularly active physical activity with abdominal and general adiposity in US adults.

OBJECTIVE: This study examined the association between physical activity patterns and abdominal and general adiposity. METHODS: Data were extracted among 20- to 59-year-old participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Abdominal and general adiposity was assessed by dual-energy x-ray absorptiometry (DXA) and anthropometric measures. DXA-measured indicators were further normalized into z scores. Physical activity levels were collected by questionnaire and classified as inactive, "weekend warrior" (WW), and regularly active (RA). Survey linear regression models were used to assess associations between physical activity patterns and adiposity indicators. RESULTS: Among 9629 participants, 772 (8.2%) reported the WW pattern and 3277 (36.9%) reported the RA pattern. Compared with inactive, both WW and RA had lower DXA-measured abdominal adiposity (WW: ß: -0.24, 95% CI: -0.38 to -0.10; RA: -0.18, 95% CI: -0.29 to -0.07), waist circumference (WW: ß: -1.94, 95% CI: -3.16 to -0.73; RA: -1.31, 95% CI: -2.32 to -0.29), whole-body fat mass (WW: ß: -0.16, 95% CI: -0.25 to -0.08; RA: -0.11, 95% CI: -0.18 to -0.04), and BMI (WW: ß: -0.78, 95% CI: -1.27 to -0.28; RA: -0.47, 95% CI: -0.89 to -0.04). CONCLUSIONS: The WW pattern was associated with similarly lower abdominal and general adiposity to the RA pattern versus the inactive pattern.

Associations of cumulative depressive symptoms within 1-year of discharge with subsequent mortality among patients hospitalized for acute heart failure: Findings from The China PEACE Prospective Heart Failure Study.

BACKGROUND: To examine the associations between cumulative depressive symptoms and subsequent mortality among patients hospitalized for acute hear failure (AHF). METHODS: By using data from a prospective cohort study of patients with HF, depressive symptoms were measured by using Patient Health Questionnaire-2 (PHQ-2) at admission, 1-and 12-month after discharge. Cumulative depressive symptoms were interpreted by cumulative PHQ-2 score and cumulative times of depressive symptoms. Outcomes included subsequent 3-year all-cause and cardiovascular mortality. RESULTS: We included 2347 patients with the median follow-up of 4.4 (interquartile range [IQR]: 4.0-5.0) years. Tertile 3 of cumulative PHQ-2 score had the highest risk of all-cause (hazard ratio [HR]: 1.47, 95 % confidence interval [CI]: 1.21-1.78) and cardiovascular mortality (HR: 1.51, 95 % CI: 1.21-1.89) compared with Tertile 1; patients with≥2 times of depressive symptoms had the highest risk of all-cause (HR: 1.62, 95 % CI: 1.31-2.00) and cardiovascular mortality (HR: 1.60, 95 % CI: 1.25-2.05) compared with patients without any depressive symptom. Cumulative PHQ-2 score provided the highest level of incremental prognostic ability in predicting the risk of all-cause (C-statistics: 0.64, 95 % CI: 0.62-0.66) and cardiovascular mortality (C-statistics: 0.65, 95 % CI: 0.62-0.67) on the basis of Get With The Guidelines-Heart Failure score. CONCLUSION: Cumulative depressive symptoms were associated with the increased risk of subsequent mortality and provided incremental prognostic ability for the outcomes among patients with HF. Repeated depressive symptom measurements could be helpful to monitor long-term depressive symptoms, identify targeted patients and perform psychological interventions and social support to improve clinical outcomes among patients with AHF.

Effects of Cumulative Cognitive Function Within 1 Year of Discharge on Subsequent Mortality Among Patients Hospitalized for Acute Heart Failure: A Nationwide Prospective Cohort Study.

BACKGROUND: To examine the association between cumulative cognitive function and subsequent mortality among patients hospitalized for acute heart failure (AHF). METHODS: Based on a prospective cohort of patients hospitalized for AHF, cognitive function was measured using Mini-Cog test at admission, 1- and 12-month following discharge. Cumulative cognitive function was interpreted by cumulative Mini-Cog score and cumulative times of cognitive impairment. Outcomes included subsequent all-cause and cardiovascular mortality. RESULTS: 1 454 patients hospitalized for AHF with median follow-up of 4.76 (interquartile range [IQR]: 4.18-5.07) years were included. Tertile 1 of cumulative Mini-Cog score had the highest risk of all-cause (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.14-2.03) and cardiovascular mortality (HR: 1.40, 95% CI: 1.02-1.93) compared with Tertile 3; patients with ≥2 times of cognitive impairment had the highest risk of all-cause (HR: 1.34, 95% CI: 1.03-1.73) and cardiovascular mortality (HR: 1.25, 95% CI: 0.93-1.67) compared with patients without any cognitive impairment. Cumulative Mini-Cog score provided the highest incremental prognostic ability in predicting all-cause (C-statistics: 0.64, 95% CI: 0.61-0.66) and cardiovascular mortality (C-statistics: 0.63, 95% CI: 0.60-0.67) risk on the basis of Get With The Guidelines-Heart Failure score. CONCLUSIONS: Poor cumulative cognitive function was associated with increased risk of subsequent mortality and provided incremental prognostic ability for the outcomes among patients with AHF. Longitudinal assessment and monitoring of cognitive function among patients with AHF would be of great importance in identifying patients at greater risk of self-care absence for optimizing personal disease management in clinical practice.

Association of cumulative health status with subsequent mortality in patients with acute heart failure.

OBJECTIVE: We aim to examine the association between long-term cumulative health status and subsequent mortality among patients with acute heart failure (HF). METHODS: Based on a national prospective cohort study of patients hospitalized for HF, we measured health status by Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 at 4 time points, i.e. admission, 1-,6- and 12-month after discharge. Cumulative health status was interpreted by cumulative KCCQ-12 score and cumulative times of good health status. Outcomes included subsequent all-cause and cardiovascular mortality. Multivariable Cox proportional hazard models were performed to examine the association between cumulative health status and subsequent mortality. RESULTS: Totally, 2328 patients (36.7% women and median age 66 [IQR: 56-75] years) were included, the median follow-up was 4.34 (IQR: 3.93-4.96) years. Compared with Quartile 4, the lowest Quartile 1 had the highest HR for all-cause mortality (2.96; 95% CI: 2.26-3.87), followed by Quartile 2 (1.79; 95% CI: 1.37-2.34) and Quartile 3 (1.62; 95% CI: 1.23-2.12). Patients with 0-time of good health status had the highest risk of all-cause mortality (HR: 2.41, 95% CI: 1.69-3.46) compared with patients with 4-times of good health status. Similar associations persisted for cardiovascular mortality. CONCLUSIONS: A greater burden of cumulative health status indicated worse survival among patients hospitalized for HF. Repeated KCCQ measurements could be helpful to monitor long-term health status and identify patients vulnerable to death. Clinical Trial Registration: www.clinicaltrials.gov (NCT02878811).

New York Heart Association Class and Kansas City Cardiomyopathy Questionnaire in Acute Heart Failure.

Importance: Sparse data exist regarding how clinician-assigned New York Heart Association (NYHA) class compares with heart failure (HF)-specific Kansas City Cardiomyopathy Questionnaire (KCCQ) in acute HF. Objective: To compare concordance between NYHA class and KCCQ overall summary score (KCCQ-OS) in acute HF and investigate associations of changes in NYHA class and KCCQ-OS with long-term outcomes. Design, Setting, and Participants: In this cohort study, patients with HF were enrolled from 52 hospitals in China between August 2016 and May 2018. Among patients with NYHA class and KCCQ-OS at admission and 1 month, levels of each scale were categorized into 4 groups from worst to best. Mild and moderate to severe discordance were defined as NYHA class and KCCQ-OS differing by 1 level or 2 or more levels, respectively. Multivariable models evaluated associations between improvements in the 2 measures and outcomes. Analysis was conducted from January to March 2023. Exposure: Changes in NYHA class and KCCQ-OS from admission to 1 month. Main Outcomes and Measures: All-cause mortality, cardiovascular death, or first HF rehospitalization. Results: A total of 2683 patients (1709 [63.7%] male; median [IQR] age, 66 [56-75] years) were included. NYHA class II, III, and IV were presented in 374 patients (13.9%), 1179 patients (44.0%), and 1130 patients (42.1%), respectively, and the median (IQR) KCCQ-OS was 44.4 (28.3-61.9). Concordance, mild discordance, and moderate to severe discordance between admission NYHA class and KCCQ-OS occurred in 954 patients (35.6%), 1203 patients (44.8%), and 526 patients (19.6%), respectively. For KCCQ-OS, kernel density overlaps were 73.6% between NYHA II and III, 63.8% between NYHA II and IV, and 88.3% between NYHA III and IV. Most patients experienced improvements in NYHA and KCCQ-OS from admission to 1 month. After adjustment, there was no significant association between improvements in NYHA class and 4-year all-cause mortality, whereas 5 or more point improvements in KCCQ-OS were independently associated with a lower risk of 4-year mortality (hazard ratio, 0.84; 95% CI, 0.74-0.96; P = .01). NYHA class and KCCQ-OS improvements were both associated with decreased risk of 1-year composite cardiovascular death or HF rehospitalization. Conclusions and Relevance: In this cohort study of acute HF, discordance between NYHA class and KCCQ was common, and KCCQ was more relevant to subsequent mortality than NYHA class.

Long-Term Cumulative High-Sensitivity C-Reactive Protein and Mortality Among Patients With Acute Heart Failure.

Background Elevated hsCRP (high-sensitivity C-reactive protein) level is associated with worse prognosis among patients hospitalized for heart failure. However, the prognostic value of the long-term cumulative hsCRP remains unknown. Methods and Results We consecutively enrolled patients hospitalized for heart failure and collected their hsCRP data at admission and 1 and 12 months after discharge. Long-term cumulative hsCRP was evaluated using 2 approaches, cumulative hsCRP level quartiles and cumulative times of high hsCRP levels. Patients were classified into 4 groups by cumulative hsCRP level quartiles and cumulative times of high hsCRP levels (0- to 3-times: number of times that hsCRP levels were higher than cutoff values at admission or 1 or 12 months), respectively. Multivariable Cox models were used to assess the association of mortality with cumulative hsCRP. A total of 1281 patients were included; the median age was 64 (interquartile range, 54-73) years, and 35.4% were women. Over a 4.8-year (interquartile range, 4.2-5.1) follow-up, 374 (29.2%) patients died. Elevated long-term cumulative hsCRP level was related to higher mortality. Specifically, taking the quartile 1 as the reference, the hazard ratios (HRs) were 1.29 (95% CI, 0.92-1.81) for quartile 2, 1.62 (95% CI, 1.16-2.25) for quartile 3, and 2.38 (95% CI, 1.75-3.23) for quartile 4. Similarly, compared with the patients with 0-times (hsCRP level lower than the cutoff values in all 3 time points) of high hsCRP level, the HRs were 1.36 for 1-time (hsCRP level higher than the cutoff value in one of the 3 time points) (95% CI, 0.92-2.01), 1.95 for 2-times (hsCRP levels higher than the cutoff values in 2 of the 3 time points) (95% CI, 1.34-2.82), and 2.80 for 3-times (hsCRP levels higher than the cutoff values in the 3 time points) (95% CI, 1.97-4.00). Conclusions Increasing long-term cumulative hsCRP level was associated with worse outcomes in patients hospitalized for acute heart failure. Repeated hsCRP measurements could assist physicians in identifying patients with a high risk of death. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02878811.

Long-Term Trajectories of High-Sensitivity C-Reactive Protein Level Among Patients with Acute Heart Failure.

Background: Inflammation contributes to the progression of heart failure (HF). However, long-term inflammatory trajectories and their associations with outcomes in patients with acute HF remain unclear. Methods: Data was obtained from the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, and high-sensitivity C-reactive protein (hsCRP) was used to reflect the inflammatory level. Only patients who survived over 12-month and had hsCRP data at admission, 1-, and 12-month after discharge were included. The latent class trajectory modeling was used to characterize hsCRP trajectories. Multivariable Cox regression models were used to explore the association between hsCRP trajectories and following mortality. Results: Totally, 1281 patients with a median 4.77 (interquartile range [IQR]: 4.24-5.07) years follow-up were included. The median age was 64 years (IQR: 54-73 years); 453 (35.4%) were female. Four distinct inflammatory trajectories were characterized: persistently low (n = 419, 32.7%), very high-marked decrease (n = 99, 7.7%), persistently high (n = 649, 50.7%), and persistently very high (n = 114, 8.9%). Compared with the persistently low trajectory, the all-cause mortality was increased in a graded pattern in the persistently high (hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.23-2.07) and persistently very high (HR: 2.56, 95% CI: 1.83-3.70) trajectories; nevertheless, the mortality was not significantly increased in very high-marked decrease trajectory (HR: 0.94, 95% CI: 0.57-1.54). Conclusion: Four distinct inflammatory trajectories were identified among patients with acute HF who survived over 12-month. Patients with persistently high and very high trajectories had significantly higher mortality than those with the persistently low trajectory.

Age-Related Trends in the Predictive Value of Carotid Intima-Media Thickness for Cardiovascular Death: A Prospective Population-Based Cohort Study.

Background The age-related trends in the predictive ability of carotid intima-media thickness (CIMT) for cardiovascular risk remain unclear. We aimed to identify the age-related trends in the predictive value of CIMT for cardiovascular death. Methods and Results In a prospective cohort of adults aged 35 to 75 years without history of cardiovascular disease who were enrolled between 2014 and 2020, we measured CIMT at baseline and collected the vital status and cause of death. We divided the study population into 4 age groups (35-44, 45-54, 55-64, and 65-75 years). Competing risk models were fitted to estimate the associations between CIMT and cardiovascular death. The added values of CIMT in prediction were assessed by the differences of the Harrell's concordance index and the net reclassification improvement index. We included 369 478 adults and followed them for a median of 4.7 years. A total of 4723 (1.28%) cardiovascular deaths occurred. After adjusting for the traditional risk factors, the hazard ratios for CIMTmean per SD decreased with age, from 1.27 (95% CI, 1.17-1.37) in the 35 to 44 years age group to 1.14 (95% CI, 1.10-1.19) in the 65 to 75 years age group (P for interaction <0.01). Meanwhile, the net reclassification improvement indexes for CIMTmean were attenuated with age, from 22.60% (95% CI, 15.56%-29.64%) in the 35 to 44 years age group to 7.00% (95% CI, -6.82% to 20.83%) in the 65 to 75 years age group. Similar results were found for maximum CIMT in all age groups. Conclusions CIMT may improve cardiovascular risk prediction in the young and middle-aged populations, rather than those aged ≥55 years.

Long-term cumulative high-sensitivity cardiac troponin T and mortality among patients with acute heart failure.

AIMS: This study aimed to evaluate the cumulative high-sensitivity cardiac troponin T (hs-cTNT) from admission to 12 months after discharge and its association with mortality after 12 months among patients with acute heart failure (HF). METHODS: We used data from the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study), which enrolled patients hospitalized primarily for HF from 52 hospitals between 2016 and 2018. We included patients who survived within 12 months and had hs-cTNT data at admission (within 48 h of admission) and 1 and 12 months after discharge. To evaluate the long-term cumulative hs-cTNT, we calculated cumulative hs-cTNT levels and cumulative times of high hs-cTNT level. Patients were divided into groups according to the quartiles of cumulative hs-cTNT levels (Quartiles 1-4) and cumulative times of high hs-cTNT levels (0-3 times). Multivariable Cox models were constructed to examine the association of cumulative hs-cTNT with mortality during the follow-up period. RESULTS: We included 1137 patients with a median age of 64 [interquartile range (IQR), 54-73] years; 406 (35.7%) were female. The median cumulative hs-cTNT level was 150 (IQR, 91-241) ng/L*month. Based on the cumulative times of high hs-cTNT levels, 404 (35.5%) patients were with zero time, 203 (17.9%) with one time, 174 (15.3%) with two times, and 356 (31.3%) with three times. During a median follow-up of 4.76 (IQR, 4.25-5.07) years, 303 (26.6%) all-cause deaths occurred. The increasing cumulative hs-cTNT level and cumulative times of high hs-cTNT level were independently associated with excess all-cause mortality. Compared with Quartile 1 group, Quartile 4 had the highest hazard ratio (HR) of all-cause mortality [4.14; 95% confidence interval (CI): 2.51-6.85], followed by Quartile 3 (HR: 3.35; 95% CI: 2.05-5.48) and Quartile 2 (HR: 2.47; 95% CI: 1.49-4.08) groups. Similarly, taking the patients with zero time of high hs-cTNT level as the reference, the HRs were 1.60 (95% CI: 1.05-2.45), 2.61 (95% CI: 1.76-3.87), and 2.86 (95% CI: 1.98-4.14) in patients who had one, two, and three times of high hs-cTNT level, respectively. CONCLUSIONS: Elevated cumulative hs-cTNT from admission to 12 months after discharge was independently associated with mortality after 12 months among patients with acute HF. Repeated measurements of hs-cTNT after discharge may help monitor the cardiac damage and identify patients with high risk of death.

Associations of long-term fine particulate matter exposure with all-cause and cause-specific mortality: results from the ChinaHEART project.

Background: The chronic effects of fine particulate matter (PM2.5) at high concentrations remains uncertain. We aimed to examine the relationship of long-term PM2.5 exposure with all-cause and the top three causes of death (cardiovascular disease [CVD], cancer, and respiratory disease), and to analyze their concentration-response functions over a wide range of concentrations. Methods: We enrolled community residents aged 35-75 years from 2014 to 2017 from all 31 provinces of the Chinese Mainland, and followed them up until 2021. We used a long-term estimation dataset for both PM2.5 and O3 concentrations with a high spatiotemporal resolution to assess the individual exposure, and used Cox proportional hazards models to estimate the associations between PM2.5 and mortalities. Findings: We included 1,910,923 participants, whose mean age was 55.6 ± 9.8 years and 59.4% were female. A 10 µg/m3 increment in PM2.5 exposure was associated with increased risk for all-cause death (hazard ratio 1.02 [95% confidence interval 1.012-1.028]), CVD death (1.024 [1.011-1.037]), cancer death (1.037 [1.023-1.052]), and respiratory disease death (1.083 [1.049-1.117]), respectively. Long-term PM2.5 exposure nonlinearly related with all-cause, CVD, and cancer mortalities, while linearly related with respiratory disease mortality. Interpretation: The overall effects of long-term PM2.5 exposure on mortality in the high concentration settings are weaker than previous reports from settings of PM2.5 concentrations < 35 µg/m³. The distinct concentration-response relationships of CVD, cancer, and respiratory disease mortalities could facilitate targeted public health efforts to prevent death caused by air pollution. Funding: The Chinese Academy of Medical Sciences Innovation Fund for Medical Science, the National High Level Hospital Clinical Research Funding, the Ministry of Finance of China and National Health Commission of China, the 111 Project from the Ministry of Education of China.