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 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.

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.

Calcium Supplements and Risk of CVD: A Meta-Analysis of Randomized Trials.

Background:Vitamin D supplements may only be beneficial for the prevention of osteoporotic fractures when administered with calcium and in individuals with low blood levels of 25(OH)D, but possible hazards of calcium supplements on CVD cannot be excluded.Objectives:We conducted a meta-analysis of all placebo-controlled randomized trials assessing the effects of calcium supplements alone or with vitamin D on CHD, stroke, and all-cause mortality.Methods:A meta-analysis of 11 trials included 7 comparisons of calcium alone compared with control (n = 8634) and 6 comparisons of calcium plus vitamin D compared with control (n = 46,804). Aggregated study-level data were obtained from individual trials and combined using a fixed-effects meta-analysis. The main outcomes included MI, CHD death, any CHD, stroke, and all-cause mortality.Results:Among trials of calcium alone (mean daily dose 1 g), calcium was not significantly associated with any excess risk of MI (RR, 1.15; 95% CI: 0.88, 1.51; n = 219 events), CHD death (RR, 1.24; 95% CI: 0.89, 1.73; n = 142), any CHD (RR, 1.01; 95% CI: 0.75, 1.37; n = 177), or stroke (RR, 1.15; 95% CI, 0.90, 1.46, n = 275). Among 6 trials of combined treatment, supplementation with calcium plus vitamin D was not significantly associated with any excess risk of MI (RR, 1.09; 95% CI: 0.95, 1.25; n = 854), CHD death (RR, 1.04; 95% CI: 0.85, 1.27; n = 391), any CHD (RR, 1.05; 95% CI: 0.93, 1.19; n = 1061), or stroke (RR, 1.02; 95% CI: 0.89, 1.17; n = 885). Likewise, calcium alone, or with vitamin D had no significant associations with all-cause mortality.Conclusions:This meta-analysis demonstrated that calcium supplements were not associated with any significant hazard for CHD, stroke, or all-cause mortality and excluded excess risks above 0.3%-0.5% per year for CHD or stroke. Further trials of calcium and vitamin D are required in individuals with low blood levels of 25(OH)D for the prevention of fracture and other disease outcomes.

Individual Trajectories of Health Status During the First Year of Discharge From Hospitalization for Heart Failure and Their Associations With Death in the Following Years.

Background Improving health status is one of the major goals in the management of heart failure (HF). However, little is known about the long-term individual trajectories of health status in patients with acute HF after discharge. Methods and Results We enrolled 2328 patients hospitalized for HF from 51 hospitals prospectively and measured their health status via the Kansas City Cardiomyopathy Questionnaire-12 at admission and 1, 6, and 12 months after discharge, respectively. The median age of the patients included was 66 years, and 63.3% were men. Six patterns of Kansas City Cardiomyopathy Questionnaire-12 trajectories were identified by a latent class trajectory model: persistently good (34.0%), rapidly improving (35.5%), slowly improving (10.4%), moderately regressing (7.4%), severely regressing (7.5%), and persistently poor (5.3%). Advanced age, decompensated chronic HF, HF with mildly reduced ejection fraction, HF with preserved ejection fraction, depression symptoms, cognitive impairment, and each additional HF rehospitalization within 1 year of discharge were associated with unfavorable health status (moderately regressing, severely regressing, and persistently poor) (P<0.05). Compared with the pattern of persistently good, slowly improving (hazard ratio [HR], 1.50 [95% CI, 1.06-2.12]), moderately regressing (HR, 1.92 [1.43-2.58]), severely regressing (HR, 2.26 [1.54-3.31]), and persistently poor (HR, 2.34 [1.55-3.53]) were associated with increased risks of all-cause death. Conclusions One-fifth of 1-year survivors after hospitalization for HF experienced unfavorable health status trajectories and had a substantially increased risk of death during the following years. Our findings help inform the understanding of disease progression from a patient perception perspective and its relationship with long-term survival. 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.

Multi-Biomarker Points and Outcomes in Patients Hospitalized for Heart Failure: Insights From the China PEACE Prospective Heart Failure Study.

Objective:To quantitatively characterize the pattern of systemic impairment reflected by conventional biomarkers and assess how it relates to clinical outcomes and quality of life among patients hospitalized for heart failure (HF).Methods:Patients hospitalized for HF from 52 hospitals in China were enrolled between 2016 and 2018. They were divided into developing and validating cohorts; the developing cohort was used for calculating the weights of biomarkers and constructing the multi-biomarker panel, while the validating one was used for evaluating the relationship between multi-biomarker points and outcomes. In total, five conventional biomarkers reflecting various pathophysiological processes were included in the panel: N-terminal pro-B type natriuretic peptide, high-sensitivity troponin T, hemoglobin, albumin, and creatinine. The weights of the biomarkers were defined based on their relationship with cardiovascular death, and each patient had a multi-biomarker point ranging from 0 to 12. The primary clinical outcome was cardiovascular death, and the other clinical outcomes included rehospitalization for HF, all-cause death, and all-cause rehospitalization in 1-year. The quality of life was measured using Kansas City Cardiovascular Questionnaire. Multi-variable Cox proportional hazard models were used to assess the risks of clinical outcomes, and generalized linear models were used to evaluate the quality of life.Results:In total, 4,693 patients hospitalized for HF were included in this analysis; the median (interquartile range, IQR) age was 67 (57-75) years old and 1,763 (37.6%) were female. The median multi-biomarker point was 5 (IQR, 2-6). There were 18.0% of patients in the low point group (<2), 29.4% in the mid-low point group (2-4), 27.8% in the mid-high point group (5-6), and 24.7% in the high point group (>6). Compared with those in the low point group, the patients in the high point group had a significantly excess risk of cardiovascular death (adjusted hazard ratio: 5.69, 95% CI, 3.33-9.70). Furthermore, patients with higher points were also more prone to worse quality of life.Conclusion:Systemic impairment reflected by abnormal conventional biomarker values was common amongst patients hospitalized for HF and had substantially cumulative adverse influence on clinical outcomes and quality of life.

Impact of Non-cardiac Comorbidities on Long-Term Clinical Outcomes and Health Status After Acute Heart Failure in China.

Background:Individual non-cardiac comorbidities are prevalent in HF; however, few studies reported how the aggregate burden of non-cardiac comorbidities affects long-term outcomes, and it is unknown whether this burden is associated with changes in health status.Aims:To assess the association of the overall burden of non-cardiac comorbidities with clinical outcomes and quality of life (QoL) in patients hospitalized for heart failure (HF).Methods:We prospectively enrolled patients hospitalized for HF from 52 hospitals in China. Eight key non-cardiac comorbidities [diabetes, chronic renal disease, chronic obstructive pulmonary disease (COPD), anemia, stroke, cancer, peripheral arterial disease (PAD), and liver cirrhosis] were included, and patients were categorized into four groups: none, one, two, and three or more comorbidities. We fitted Cox proportional hazards models to assess the burden of comorbidities on 1-year death and rehospitalization.Results:Of the 4,866 patients, 25.3% had no non-cardiac comorbidity, 32.2% had one, 22.9% had two, and 19.6% had three or more in China. Compared with those without non-cardiac comorbidities, patients with three or more comorbidities had higher risks of 1-year all-cause death [heart rate, HR 1.89; 95% confidence interval (CI) 1.48-2.39] and all-rehospitalization (HR 1.35; 95%CI 1.15-1.58) after adjustment. Although all patients with HF experienced a longitudinal improvement in QoL in the 180 days after discharge, those with three or more non-cardiac comorbidities had an unadjusted 11.4 (95%CI -13.4 to -9.4) lower Kansas City Cardiomyopathy Questionnaire (KCCQ) scores than patients without comorbidities. This difference decreased to -6.4 (95%CI -8.6 to -4.2) after adjustment for covariates.Conclusion:Among patients hospitalized with HF in this study, a higher burden of non-cardiac comorbidities was significantly associated with worse health-related QoL (HRQoL), increased risks of death, and rehospitalization post-discharge. The findings highlight the need to address the management of comorbidities effectively in standardized HF care.

Development and validation of a risk prediction model for in-hospital major cardiovascular events in patients hospitalised for acute myocardial infarction.

OBJECTIVES:Patients admitted to hospital with acute myocardial infarction (AMI) have considerable variability in in-hospital risks, resulting in higher demands on healthcare resources. Simple risk-assessment tools are important for the identification of patients with higher risk to inform clinical decisions. However, few risk assessment tools have been built that are suitable for populations with AMI in China. We aim to develop and validate a risk prediction model, and further build a risk scoring system.DESIGN:Data from a nationally representative retrospective study was used to develop the model. Patients from a prospective study and another nationally representative retrospective study were both used for external validation.SETTING:161 nationally representative hospitals, and 53 and 157 other hospitals were involved in the above three studies, respectively.PARTICIPANTS:8010 patients hospitalised for AMI were included as development sample, and 4485 and 11 223 other patients were included as validation samples in their corresponding studies.PRIMARY AND SECONDARY OUTCOME MEASURES:The in-hospital major adverse cardiovascular events (MACE) was defined as death from any cause, recurrent AMI, or ischaemic stroke.RESULTS:The proportion of in-hospital MACE was 11.7%, 8.8% and 11.4% among the development sample and two external-validation samples, respectively. Nine predictors (ie, age, sex, left ventricular ejection fraction, Killip class, systolic blood pressure, creatinine, white blood cell count, heart rate and blood glucose) were independently associated with in-hospital MACE. The model performed well on both discrimination and calibration capability, with areas under the Receiver Operating Characteristic Curve (ROC) curve of 0.85, 0.74 and 0.80, and calibration slopes of 0.98, 0.84 and 0.97 in the development sample and two external validation samples, respectively. A point-based risk scoring system was built with good discrimination and reclassification ability.CONCLUSIONS:A prediction model using readily available clinical parameters was developed and externally validated to estimate risks of in-hospital MACE among patients with AMI, thereby better informing decision-making in improving clinical care.

Use of Run-in Periods in Randomized Trials.

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 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.

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.

Calcium Supplements and Risk of CVD: A Meta-Analysis of Randomized Trials.

Background:Vitamin D supplements may only be beneficial for the prevention of osteoporotic fractures when administered with calcium and in individuals with low blood levels of 25(OH)D, but possible hazards of calcium supplements on CVD cannot be excluded.Objectives:We conducted a meta-analysis of all placebo-controlled randomized trials assessing the effects of calcium supplements alone or with vitamin D on CHD, stroke, and all-cause mortality.Methods:A meta-analysis of 11 trials included 7 comparisons of calcium alone compared with control (n = 8634) and 6 comparisons of calcium plus vitamin D compared with control (n = 46,804). Aggregated study-level data were obtained from individual trials and combined using a fixed-effects meta-analysis. The main outcomes included MI, CHD death, any CHD, stroke, and all-cause mortality.Results:Among trials of calcium alone (mean daily dose 1 g), calcium was not significantly associated with any excess risk of MI (RR, 1.15; 95% CI: 0.88, 1.51; n = 219 events), CHD death (RR, 1.24; 95% CI: 0.89, 1.73; n = 142), any CHD (RR, 1.01; 95% CI: 0.75, 1.37; n = 177), or stroke (RR, 1.15; 95% CI, 0.90, 1.46, n = 275). Among 6 trials of combined treatment, supplementation with calcium plus vitamin D was not significantly associated with any excess risk of MI (RR, 1.09; 95% CI: 0.95, 1.25; n = 854), CHD death (RR, 1.04; 95% CI: 0.85, 1.27; n = 391), any CHD (RR, 1.05; 95% CI: 0.93, 1.19; n = 1061), or stroke (RR, 1.02; 95% CI: 0.89, 1.17; n = 885). Likewise, calcium alone, or with vitamin D had no significant associations with all-cause mortality.Conclusions:This meta-analysis demonstrated that calcium supplements were not associated with any significant hazard for CHD, stroke, or all-cause mortality and excluded excess risks above 0.3%-0.5% per year for CHD or stroke. Further trials of calcium and vitamin D are required in individuals with low blood levels of 25(OH)D for the prevention of fracture and other disease outcomes.

Individual Trajectories of Health Status During the First Year of Discharge From Hospitalization for Heart Failure and Their Associations With Death in the Following Years.

Background Improving health status is one of the major goals in the management of heart failure (HF). However, little is known about the long-term individual trajectories of health status in patients with acute HF after discharge. Methods and Results We enrolled 2328 patients hospitalized for HF from 51 hospitals prospectively and measured their health status via the Kansas City Cardiomyopathy Questionnaire-12 at admission and 1, 6, and 12 months after discharge, respectively. The median age of the patients included was 66 years, and 63.3% were men. Six patterns of Kansas City Cardiomyopathy Questionnaire-12 trajectories were identified by a latent class trajectory model: persistently good (34.0%), rapidly improving (35.5%), slowly improving (10.4%), moderately regressing (7.4%), severely regressing (7.5%), and persistently poor (5.3%). Advanced age, decompensated chronic HF, HF with mildly reduced ejection fraction, HF with preserved ejection fraction, depression symptoms, cognitive impairment, and each additional HF rehospitalization within 1 year of discharge were associated with unfavorable health status (moderately regressing, severely regressing, and persistently poor) (P<0.05). Compared with the pattern of persistently good, slowly improving (hazard ratio [HR], 1.50 [95% CI, 1.06-2.12]), moderately regressing (HR, 1.92 [1.43-2.58]), severely regressing (HR, 2.26 [1.54-3.31]), and persistently poor (HR, 2.34 [1.55-3.53]) were associated with increased risks of all-cause death. Conclusions One-fifth of 1-year survivors after hospitalization for HF experienced unfavorable health status trajectories and had a substantially increased risk of death during the following years. Our findings help inform the understanding of disease progression from a patient perception perspective and its relationship with long-term survival. 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.

Multi-Biomarker Points and Outcomes in Patients Hospitalized for Heart Failure: Insights From the China PEACE Prospective Heart Failure Study.

Objective:To quantitatively characterize the pattern of systemic impairment reflected by conventional biomarkers and assess how it relates to clinical outcomes and quality of life among patients hospitalized for heart failure (HF).Methods:Patients hospitalized for HF from 52 hospitals in China were enrolled between 2016 and 2018. They were divided into developing and validating cohorts; the developing cohort was used for calculating the weights of biomarkers and constructing the multi-biomarker panel, while the validating one was used for evaluating the relationship between multi-biomarker points and outcomes. In total, five conventional biomarkers reflecting various pathophysiological processes were included in the panel: N-terminal pro-B type natriuretic peptide, high-sensitivity troponin T, hemoglobin, albumin, and creatinine. The weights of the biomarkers were defined based on their relationship with cardiovascular death, and each patient had a multi-biomarker point ranging from 0 to 12. The primary clinical outcome was cardiovascular death, and the other clinical outcomes included rehospitalization for HF, all-cause death, and all-cause rehospitalization in 1-year. The quality of life was measured using Kansas City Cardiovascular Questionnaire. Multi-variable Cox proportional hazard models were used to assess the risks of clinical outcomes, and generalized linear models were used to evaluate the quality of life.Results:In total, 4,693 patients hospitalized for HF were included in this analysis; the median (interquartile range, IQR) age was 67 (57-75) years old and 1,763 (37.6%) were female. The median multi-biomarker point was 5 (IQR, 2-6). There were 18.0% of patients in the low point group (<2), 29.4% in the mid-low point group (2-4), 27.8% in the mid-high point group (5-6), and 24.7% in the high point group (>6). Compared with those in the low point group, the patients in the high point group had a significantly excess risk of cardiovascular death (adjusted hazard ratio: 5.69, 95% CI, 3.33-9.70). Furthermore, patients with higher points were also more prone to worse quality of life.Conclusion:Systemic impairment reflected by abnormal conventional biomarker values was common amongst patients hospitalized for HF and had substantially cumulative adverse influence on clinical outcomes and quality of life.

Impact of Non-cardiac Comorbidities on Long-Term Clinical Outcomes and Health Status After Acute Heart Failure in China.

Background:Individual non-cardiac comorbidities are prevalent in HF; however, few studies reported how the aggregate burden of non-cardiac comorbidities affects long-term outcomes, and it is unknown whether this burden is associated with changes in health status.Aims:To assess the association of the overall burden of non-cardiac comorbidities with clinical outcomes and quality of life (QoL) in patients hospitalized for heart failure (HF).Methods:We prospectively enrolled patients hospitalized for HF from 52 hospitals in China. Eight key non-cardiac comorbidities [diabetes, chronic renal disease, chronic obstructive pulmonary disease (COPD), anemia, stroke, cancer, peripheral arterial disease (PAD), and liver cirrhosis] were included, and patients were categorized into four groups: none, one, two, and three or more comorbidities. We fitted Cox proportional hazards models to assess the burden of comorbidities on 1-year death and rehospitalization.Results:Of the 4,866 patients, 25.3% had no non-cardiac comorbidity, 32.2% had one, 22.9% had two, and 19.6% had three or more in China. Compared with those without non-cardiac comorbidities, patients with three or more comorbidities had higher risks of 1-year all-cause death [heart rate, HR 1.89; 95% confidence interval (CI) 1.48-2.39] and all-rehospitalization (HR 1.35; 95%CI 1.15-1.58) after adjustment. Although all patients with HF experienced a longitudinal improvement in QoL in the 180 days after discharge, those with three or more non-cardiac comorbidities had an unadjusted 11.4 (95%CI -13.4 to -9.4) lower Kansas City Cardiomyopathy Questionnaire (KCCQ) scores than patients without comorbidities. This difference decreased to -6.4 (95%CI -8.6 to -4.2) after adjustment for covariates.Conclusion:Among patients hospitalized with HF in this study, a higher burden of non-cardiac comorbidities was significantly associated with worse health-related QoL (HRQoL), increased risks of death, and rehospitalization post-discharge. The findings highlight the need to address the management of comorbidities effectively in standardized HF care.

Development and validation of a risk prediction model for in-hospital major cardiovascular events in patients hospitalised for acute myocardial infarction.

OBJECTIVES:Patients admitted to hospital with acute myocardial infarction (AMI) have considerable variability in in-hospital risks, resulting in higher demands on healthcare resources. Simple risk-assessment tools are important for the identification of patients with higher risk to inform clinical decisions. However, few risk assessment tools have been built that are suitable for populations with AMI in China. We aim to develop and validate a risk prediction model, and further build a risk scoring system.DESIGN:Data from a nationally representative retrospective study was used to develop the model. Patients from a prospective study and another nationally representative retrospective study were both used for external validation.SETTING:161 nationally representative hospitals, and 53 and 157 other hospitals were involved in the above three studies, respectively.PARTICIPANTS:8010 patients hospitalised for AMI were included as development sample, and 4485 and 11 223 other patients were included as validation samples in their corresponding studies.PRIMARY AND SECONDARY OUTCOME MEASURES:The in-hospital major adverse cardiovascular events (MACE) was defined as death from any cause, recurrent AMI, or ischaemic stroke.RESULTS:The proportion of in-hospital MACE was 11.7%, 8.8% and 11.4% among the development sample and two external-validation samples, respectively. Nine predictors (ie, age, sex, left ventricular ejection fraction, Killip class, systolic blood pressure, creatinine, white blood cell count, heart rate and blood glucose) were independently associated with in-hospital MACE. The model performed well on both discrimination and calibration capability, with areas under the Receiver Operating Characteristic Curve (ROC) curve of 0.85, 0.74 and 0.80, and calibration slopes of 0.98, 0.84 and 0.97 in the development sample and two external validation samples, respectively. A point-based risk scoring system was built with good discrimination and reclassification ability.CONCLUSIONS:A prediction model using readily available clinical parameters was developed and externally validated to estimate risks of in-hospital MACE among patients with AMI, thereby better informing decision-making in improving clinical care.

Use of Run-in Periods in Randomized Trials.