Prognostic Value of a Multi-mRNA Signature for 1-Year All-Cause Death in Hospitalized Patients With Heart Failure With a Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction is a major global public health problem, while effective risk stratification tools are still lacking. We sought to construct a multi-mRNA signature to predict 1-year all-cause death. METHODS: We selected 30 patients with heart failure with preserved ejection fraction who died during 1-year follow-up and 30 who survived in the discovery set. One hundred seventy-one and 120 patients with heart failure with preserved ejection fraction were randomly selected as a test set and a validation set, respectively. We performed mRNA microarrays in all patients. RESULTS: We constructed a 5-mRNA signature for predicting 1-year all-cause death. The scores of the 5-mRNA signature were significantly associated with the 1-year risk of all-cause death in both the test set (hazard ratio, 2.72 [95% CI, 1.98-3.74]; P<0.001) and the validation set (hazard ratio, 3.95 [95% CI, 2.40-6.48]; P<0.001). Compared with a reference model, which included sex, ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) score, history of HF and NT-proBNP (N-terminal pro-B-type natriuretic peptide), the 5-mRNA signature had a better discrimination capability, with an increased area under the curve from 0.696 to 0.813 in the test set and from 0.712 to 0.848 in the validation set. A composite model integrating the 5-mRNA risk score and variables in the reference model demonstrated an excellent discrimination capability, with an area under the curve of 0.861 (95% CI, 0.784-0.939) in the test set and an area under the curve of 0.859 (95% CI, 0.755-0.963) in the validation set. The net reclassification improvement and integrated discrimination improvement indicated that the composite model significantly improved patient classification compared with the reference model in both sets (P<0.001). CONCLUSIONS: The 5-mRNA signature is a promising predictive tool for 1-year all-cause death and shows improved prognostic power over the established risk scores and NT-proBNP in patients with heart failure with preserved ejection fraction.

Cognitive impairment in young and middle-aged patients with acute heart failure.

AIMS: This study aimed to investigate the prevalence, risk factors and prognostic implications of cognitive impairment in young and middle-aged patients with acute heart failure (HF). METHODS: In a prospective cohort of patients with acute HF, we assessed cognitive function by the Mini-Cog, predictors of the cognitive impairment and its associations with 30 day and 1 year cardiovascular death or HF rehospitalization among young and middle-aged patients (<65 years old). RESULTS: Among 1958 young and middle-aged patients, the prevalence of cognitive impairment was 19.6%. Predictors of cognitive impairment included older age, females, lower education levels and prior strokes. Compared with patients having normal cognitive function, cognitive impairment was associated with a higher risk of 30 day cardiovascular death or HF rehospitalization [hazard ratio (HR), 1.52, 95% confidence interval (CI), 1.07-2.17, P = 0.02], but not for 1 year cardiovascular death or HF rehospitalization (HR, 1.06, 95% CI, 0.87-1.30, P = 0.55). CONCLUSIONS: Cognitive impairment is present in a notable proportion of young and middle-aged patients with acute HF and is associated with an increased risk of short-term adverse outcomes. Strategies for screening and intervention for cognitive impairment at a younger age are necessary, particularly for those at high risk.

Home Blood Pressure Monitoring and Its Association With Blood Pressure Control Among Hypertensive Patients With High Cardiovascular Risk in China.

Objective: Home blood pressure monitoring (HBPM) is viewed as a facilitating factor in the initial diagnosis and long-term management of treated hypertension. However, evidence remains scarce about the effectiveness of HBPM use in the real world. This study aimed to examine the associations of HBPM use with blood pressure (BP) control and medication adherence. Methods: This prospective cohort study included hypertensive patients with high cardiovascular risk who were aged ≥50 years. At baseline, information about types of BP monitor, frequency of HBPM, perception of anti-hypertensive treatment, and measured office BP were collected. During the 1-year follow-up (visits at 1, 2, 3, 6, and 12 months), information on medication adherence was collected at each visit. The 2 major outcomes were BP control at baseline and medication adherence during the 1-year follow-up. A log-binomial regression model was used to examine the association between frequency of HBPM and outcomes, stratified by the perceptions of anti-hypertensive treatment. Results: A total of 5,363 hypertensive patients were included in the analysis. The age was (64.6 ± 7.2) years, and 41.2% (2,208) were female. Of the total patients, 85.9% (4,606) had a home BP monitor and 47.8% (2,564) had an incorrect perception of anti-hypertensive treatment. Overall, 24.2% (1,299) of patients monitored their BP daily, 37.6% (2,015) weekly, 17.3% (926) monthly, and 20.9% (1,123) less than monthly. At baseline, the systolic BP and diastolic BP were (146.6 ± 10.8) mmHg and (81.9 ± 10.6) mmHg, respectively, and 28.5% (1,527) of patients had their BP controlled. Regardless of whether the patients had correct or incorrect perceptions of anti-hypertensive treatment, there is no significant association between HBPM frequency and BP control at baseline. During the 1-year follow-up, 23.9% (1,280) of patients had non-adherence to medications at least once. In patients with an incorrect perception of anti-hypertensive treatment, those monitoring BP most frequently (daily) had the highest non-adherence rate (29.9%, 175/585). Compared with those monitoring their BP less than monthly, patients who monitored their BP daily were more likely not to adhere to anti-hypertensive medications (adjusted relative risk = 1.38, 95% confidence interval: 1.11-1.72, P = 0.004). Conclusions: HBPM performance among hypertensive patients in China is, in general, sub-optimal. No association was observed between using HBPM alone and hypertension control, indicating that the effects of HBPM could be conditional. Patients' misconceptions about anti-hypertensive treatment may impair the role of BP monitoring in achieving medication adherence. Fully incorporating the correct perception of hypertension into the management of hypertensive patients is needed.

Left ventricular hypertrophy phenotype to predict incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIM: Left ventricular hypertrophy (LVH) has been shown to be associated with the occurrence of atrial fibrillation (AF). However, the predictive value of the LVH phenotype for incident AF remains uncertain. This study aimed to investigate the predictive value of LVH phenotype for incident AF. METHODS AND RESULTS: This study utilized the Multi-Ethnic Study of Atherosclerosis (MESA) data. LVH was defined by cardiac magnetic resonance measured LV mass index. Isolated LVH was determined as LVH without elevated cardiac biomarker and malignant LVH was determined as LVH with at least 1 elevated biomarker. Receiver-operating characteristic (ROC) analysis was performed to calculate areas under the curves (AUC) for predicting AF. A total of 4983 community-dwelling participants were included, with a mean age of 61.5 years. 279 (5.6 %) had isolated LVH, and 222 (4.5 %) had malignant LVH. During a median follow-up of 8.5 years, 272 incident AF was observed. Compared to participants without LVH and elevated cardiac biomarkers, those with isolated LVH (HR, 1.82; 95 % CI, 1.03-3.20) and malignant LVH (HR, 4.13; 95 % CI, 2.77-6.16) had a higher risk of incident AF. Malignant LVH carried a 1.5-fold increased risk of AF compared to isolated LVH (HR: 2.48, 95 % CI: 1.30-4.73). Including the LVH phenotype in the CHARGE-AF model improved model discrimination (AUC increase: 0.03, p < 0.001). CONCLUSIONS: The risks of AF incidence varied across LVH phenotypes. Malignant LVH carried the highest risk among LVH phenotypes. LVH phenotype provides incremental predictive value over the variables included in the CHARGE-AF model.

Influence of Socioeconomic Gender Inequality on Sex Disparities in Prevention and Outcome of Cardiovascular Disease: Data From a Nationwide Population Cohort in China.

Background Knowledge gaps remain in how gender-related socioeconomic inequality affects sex disparities in cardiovascular diseases (CVD) prevention and outcome. Methods and Results Based on a nationwide population cohort, we enrolled 3 737 036 residents aged 35 to 75 years (2014-2021). Age-standardized sex differences and the effect of gender-related socioeconomic inequality (Gender Inequality Index) on sex disparities were explored in 9 CVD prevention indicators. Compared with men, women had seemingly better primary prevention (aspirin usage: relative risk [RR], 1.24 [95% CI, 1.18-1.31] and statin usage: RR, 1.48 [95% CI, 1.39-1.57]); however, women's status became insignificant or even worse when adjusted for metabolic factors. In secondary prevention, the sex disparities in usage of aspirin (RR, 0.65 [95% CI, 0.63-0.68]) and statin (RR, 0.63 [95% CI, 0.61-0.66]) were explicitly larger than disparities in usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR, 0.88 [95% CI, 0.84-0.91]) or ß blockers (RR, 0.67 [95% CI, 0.63-0.71]). Nevertheless, women had better hypertension awareness (RR, 1.09 [95% CI, 1.09-1.10]), similar hypertension control (RR, 1.01 [95% CI, 1.00-1.02]), and lower CVD mortality (hazard ratio, 0.46 [95% CI, 0.45-0.47]). Heterogeneities of sex disparities existed across all subgroups. Significant correlations existed between regional Gender Inequality Index values and sex disparities in usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (Spearman correlation coefficient, r=-0.57, P=0.0013), hypertension control (r=-0.62, P=0.0007), and CVD mortality (r=0.45, P=0.014), which remained significant after adjusting for economic factors. Conclusions Notable sex disparities remain in CVD prevention and outcomes, with large subgroup heterogeneities. Gendered socioeconomic factors could reinforce such disparities. A sex-specific perspective factoring in socioeconomic disadvantages could facilitate more targeted prevention policy making.

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.

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.

Independent prognostic value of the congestion and renal index in patients with acute heart failure.

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS: In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

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.

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.

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.

Distinct Associations Between Postdischarge Cognitive Change Patterns and 1-year Outcomes in Patients Hospitalized for Heart Failure.

BACKGROUND: The patterns of patients' cognitive function after hospital discharge for heart failure (HF), their prognostic implication and the predictors for new-onset cognitive impairment remain unknown. METHODS AND RESULTS: We included 2307 patients (64 ± 14 years, 36.4% female sex) hospitalized for HF from a cohort who completed cognitive testing before discharge and after 1 month. Among 1658 patients with normal cognition before discharge, 229 (13.8%) and 1429 (86.2%) had new-onset cognitive impairment and normal cognition at 1 month, respectively. Of the 649 with cognitive impairment, 315 (48.5%) and 334 (51.5%) had transient and persistent cognitive impairment, respectively. Multivariable analyses showed that, compared with normal cognition, patients with new-onset cognitive impairment had an increased risk of cardiovascular death or HF rehospitalization (hazard ratio 1.35, 95% confidence interval 1.07-1.70); patients with persistent cognitive impairment showed an increased risk, but it was not statistically significant (hazard ratio 1.17, 95% confidence interval 0.95-1.44); patients with transient cognitive impairment had a similar risk (hazard ratio 0.91, 95% confidence interval 0.73-1.13). Older age, females, lower education level, prior atherosclerotic cardiovascular diseases, lower health status, and lower Mini-Cog score before discharge predicted new-onset cognitive impairment. CONCLUSIONS: Acute HF substantially affects short-term cognition. Patients who have developed new-onset cognitive impairment have an increased risk of adverse outcomes. Monitoring cognition is necessary, particularly in high-risk patients.

Prognostic value of Growth differentiation factors 15 in Acute heart failure patients with preserved ejection fraction.

AIMS: There is an increasing proportion of hospitalized heart failure (HF) patients classified as HF with preserved ejection fraction (HFpEF) around the world. Growth differentiation factor 15 (GDF-15) is a promising biomarker in HFpEF prognostication; however, the majority of the existing data has been derived from the research on undifferentiated HF, whereas the studies focusing on HFpEF are still limited. This study aimed to determine the prognostic power of GDF-15 in the hospitalized patients with HFpEF in a Chinese cohort. METHODS AND RESULTS: We analysed the levels of serum GDF-15 in 380 patients hospitalized for acute onset of HFpEF measured by heart ultrasound at admission in a prospective cohort. The associations of GDF-15 with 1 year risk of all-cause death and 1 year HF readmission were assessed by the Cox proportional hazards model. Area under the receiver operating characteristic curves was used to compare predictive accuracy. GDF-15 was strongly correlated with 1 year HF readmission and 1 year all-cause death, with event rates of 24.8%, 40.0%, and 50.0% for 1 year HF readmission (P < 0.001), respectively, and with 11.2%, 13.6%, and 24.6% for 1 year all-cause death (P = 0.004) in the corresponding tertile, respectively. In the multivariate linear regression model, GDF-15 had a significantly negative correlation with haemoglobin (P = 0.01) and a positive correlation with creatinine (P = 0.01), alanine transaminase (P = 0.001), and therapy of aldosterone antagonist (P = 0.018). The univariate Cox regression model of GDF-15 showed that c-statistic was 0.632 for 1 year HF readmission and 0.644 for 1 year all-cause death, which were superior to the N-terminal pro-brain natriuretic peptide (NT-proBNP) model with c-statistics of 0.595 and 0.610, respectively. In the multivariable Cox regression model, GDF-15 tertiles independently predicted 1 year HF readmission (hazard ratio 2.25, 95% confidence interval: 1.43-3.54, P < 0.001) after adjusting for baseline Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) risk score, history of HF, NT-proBNP, and high-sensitivity cardiac troponin T. Compared with the model including all the adjusted variables, the model with the addition of GDF-15 improved predictive power, with c-statistic increasing from 0.643 to 0.657 for 1 year HF readmission and from 0.638 to 0.660 for 1 year all-cause death. CONCLUSIONS: In hospitalized patients with HFpEF, GDF-15 measured within 48 h of admission is a strong independent biomarker for 1 year HF readmission and even better than NT-proBNP. GDF-15 combined with the traditional indicators provided incremental prognostic value in this population.

Change in Depressive Symptoms During the First Month of Discharge and 1-Year Clinical Outcomes in Patients Hospitalized for Heart Failure.

Background The patterns of depressive symptom change during the first month after discharge, as well as their prognostic implications, and predictors of persistent or new-onset depressive symptoms are not well characterized. Methods and Results We included patients hospitalized for heart failure undergoing Patient Health Questionnaire-2 before discharge and at 1 month after discharge in a multicenter prospective cohort. We characterized 4 patterns of change in depressive symptoms-persistent, new-onset, remitted depressive symptoms, and no depressive symptom-and examined the associations between the 4 patterns and 1-year clinical outcomes. We analyzed the factors associated with persistent or new-onset depressive symptoms. A total of 4130 patients were included. Among 1175 (28.5%) symptomatic patients and 2955 (71.5%) symptom-free patients before discharge, 817 (69.5%) had remission, and 366 (12.2%) had new-onset depressive symptoms, respectively. Compared with no depressive symptom, persistent depressive symptoms were associated with an increased risk of cardiovascular death (hazard ratio [HR], 2.10 [95% CI, 1.59-2.79]) and heart failure rehospitalization (HR, 1.56 [95% CI, 1.30-1.87]); new-onset depressive symptoms were associated with an increased risk of cardiovascular death (HR, 1.78 [95%CI, 1.32-2.40]) and heart failure rehospitalization (HR, 1.54 [95% CI, 1.29-1.83]). Remitted depressive symptoms were associated with a slightly increased risk of cardiovascular death but had no significant association with heart failure rehospitalization. Patients who were female or had poor socioeconomic status, stroke history, renal dysfunction, or poor health status had a higher risk of persistent or new-onset depressive symptoms. Conclusions Sex, socioeconomic status, clinical characteristics, and health status help identify patients with high risks of depressive symptoms at 1 month after discharge. Dynamic capture of depressive symptom change during this period informs long-term risk stratifications and targets patients who require psychological interventions and social support to improve clinical outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier (NCT02878811).

Prevalence and patient characteristics of familial hypercholesterolemia in a Chinese population aged 35-75 years: Results from China PEACE Million Persons Project.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a genetic disorder with a high burden of arteriosclerotic cardiovascular disease. The prevalence of heterozygous FH is currently 0.2%-0.5% in Europe, while no such data has yet been published about the general population in China. We aimed to investigate the prevalence and characteristics of FH in a Chinese population aged 35-75 years. METHODS: We used a nationwide general population from 31 provinces in mainland China (n = 1,059,936, age 35-75) based on the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) MPP (Million Persons Project). The diagnosis of FH was based on 2 (untreated LDL-C ≥4.7 mmol/L and first-degree relatives with premature ASCVD history) of the 3 diagnostic criteria from the Chinese expert consensus on diagnosis of FH (CEFH criteria). FH prevalence was estimated and clinical phenotypic characteristics were further analyzed. RESULTS: The overall FH prevalence was 0.13% (95% confidence interval [CI], 0.12-0.14) by the CEFH criteria, and age and sex standardized FH prevalence was slightly lower (0.11%; 95%CI, 0.10-0.12). FH prevalence in female was twice as high as in male (0.16% vs. 0.08%, p < 0.001). Across different age groups, the prevalence also varied and peaked among 55-to 64-year-olds. Regarding geographical areas, the prevalence ranged from 0.19% in Eastern, to 0.11% in Central, and 0.08% in Western China (p < 0.001). Participants living in rural areas had a lower prevalence than urban participants (0.10% vs. 0.18%, p < 0.001). The rate of coronary artery disease in FH patients was 5 folds higher than in the general population (10.5% vs. 2.1%, p < 0.001). The rate of FH patients receiving lipid-lowering medications was 18.1%. None of the treated patients achieved guideline recommended LDL-C targets. CONCLUSIONS: The prevalence of FH in the Chinese population aged 35-75 years was 0.13% (about 1 in 769) defined by 2 of the CEFH criteria, and the patients were seriously undertreated and under-controlled. The screened FH prevalence varied by age, sex, geographical distributions, and urban/rural areas.

Systolic Blood Pressure and 1-Year Clinical Outcomes in Patients Hospitalized for Heart Failure.

Background: High systolic blood pressure (SBP) is an important risk factor for the progression of heart failure (HF); however, the association between SBP and prognosis among patients with established HF was uncertain. This study aimed to investigate the association between SBP and long-term clinical outcomes in patients hospitalized for HF. Methods: This study prospectively enrolled adult patients hospitalized for HF in 52 hospitals from 20 provinces in China. SBPs were measured in a stable condition judged by clinicians during hospitalization before discharge according to the standard research protocol. The primary outcomes included 1-year all-cause death and HF readmission. The multivariable Cox proportional hazards regression models were fitted to examine the association between SBP and clinical outcomes. Restricted cubic splines were used to examine the non-linear associations. Results: The 4,564 patients had a mean age of 65.3 ± 13.5 years and 37.9% were female. The average SBP was 123.2 ± 19.0 mmHg. One-year all-cause death and HF readmission were 16.9 and 32.7%, respectively. After adjustment, patients with SBP < 110 mmHg had a higher risk of all-cause death compared with those with SBP of 130-139 mmHg (HR 1.71; 95% CI: 1.32-2.20). Patients with SBP < 110 mmHg (HR 1.36; 95% CI: 1.14-1.64) and SBP ≥ 150 mmHg (HR 1.26; 95% CI: 1.01-1.58) had a higher risk of HF readmission, and the association between SBP and HF readmission followed a J-curve relationship with the nadir SBP around 130 mmHg. These associations were consistent regardless of age, sex, left ventricular ejection fraction, hypertension, coronary heart disease, and medications for HF. Conclusion: In patients hospitalized for HF, lower SBP in a stable phase during hospitalization portends an increased risk of 1-year death, and a J-curve association has been observed between SBP and 1-year HF readmission. These associations were consistent among clinically important subgroups.

Prognostic Value of Multiple Circulating Biomarkers for 2-Year Death in Acute Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a major global public health burden and lacks effective risk stratification. We aimed to assess a multi-biomarker model in improving risk prediction in HFpEF. Methods: We analyzed 18 biomarkers from the main pathophysiological domains of HF in 380 patients hospitalized for HFpEF from a prospective cohort. The association between these biomarkers and 2-year risk of all-cause death was assessed by Cox proportional hazards model. Support vector machine (SVM), a supervised machine learning method, was used to develop a prediction model of 2-year all-cause and cardiovascular death using a combination of 18 biomarkers and clinical indicators. The improvement of this model was evaluated by c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: The median age of patients was 71-years, and 50.5% were female. Multiple biomarkers independently predicted the 2-year risk of death in Cox regression model, including N-terminal pro B-type brain-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), tumor necrosis factor-α (TNFα), endoglin, and 3 biomarkers of extracellular matrix turnover [tissue inhibitor of metalloproteinases (TIMP)-1, matrix metalloproteinase (MMP)-2, and MMP-9) (FDR < 0.05). The SVM model effectively predicted the 2-year risk of all-cause death in patients with acute HFpEF in training set (AUC 0.834, 95% CI: 0.771-0.895) and validation set (AUC 0.798, 95% CI: 0.719-0.877). The NRI and IDI indicated that the SVM model significantly improved patient classification compared to the reference model in both sets (p < 0.05). Conclusions: Multiple circulating biomarkers coupled with an appropriate machine-learning method could effectively predict the risk of long-term mortality in patients with acute HFpEF. It is a promising strategy for improving risk stratification in HFpEF.

Health Status Predicts Short- and Long-Term Risk of Composite Clinical Outcomes in Acute Heart Failure.

OBJECTIVES: This study aims to examine the association between the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score and the 30-day and 1-year rates of composite events of cardiovascular death and heart failure (HF) rehospitalization in patients with acute HF. BACKGROUND: Few studies reported the prognostic effects of KCCQ in acute HF. METHODS: This study prospectively enrolled adult patients hospitalized for HF from 52 hospitals in China and collected the KCCQ-12 score within 48 hour of index admission. The study used multivariable Cox regression to examine the association between KCCQ-12 score and 30-day and 1-year composite events and was further stratified by new-onset HF and acutely decompensated chronic heart failure (ADCHF). Subgroup analyses were performed to explore the potential heterogeneity. The study evaluated the incremental prognostic value of KCCQ-12 score over N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and established risk scores by C-statistics, net reclassification improvement, and integrated discrimination improvement. RESULTS: Among 4,898 patients, 29.4% had new-onset HF. After adjustment, each 10-point decrease in the KCCQ-12 score was associated with a 13% increase in 30-day risk and a 7% increase in 1-year risk. The associations were consistent regardless of new-onset HF or ADCHF, age, sex, left ventricular ejection fraction, New York Heart Association functional class, NT-proBNP level, comorbidities, and renal function. Adding KCCQ-12 score to NT-proBNP and established risk scores significantly improved prognostic capabilities measured by C-statistics, net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: In acute HF, a poor KCCQ-12 score predicted short- and long-term risks of cardiovascular death and HF rehospitalization. KCCQ-12 could serve as a convenient tool for rapid initial risk stratification and provide additional prognostic value over NT-proBNP and established risk scores.

Systolic blood pressure at admission and long-term clinical outcomes in patients hospitalized for heart failure.

AIMS: The study sought to investigate the association between admission systolic blood pressure (SBP) and 1-year clinical outcomes in patients hospitalized for heart failure (HF) and in subgroups. METHODS: This study was based on the China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, which prospectively enrolled patients hospitalized for HF in 52 hospitals from 20 provinces in China between August 2016 and May 2018. Patients were divided into four groups according to the quartiles of SBP at admission. The multivariable Cox proportional hazards regression models were fitted to examine the association between admission SBP and all-cause death and HF readmission within 1 year after the index hospitalization. Restricted cubic splines were used to explore the non-linear association between SBP and the clinical outcomes. RESULTS: Among 4896 patients, those with lower admission SBP were younger, more likely to be male, have left ventricular ejection fraction <40%, and receive ß-blockers, aldosterone antagonists, and diuretics. After adjustment for potential confounders, lower admission SBP was significantly associated with higher all-cause death and there is no threshold, while we only observed such an association with HF readmission when admission SBP was lower than 120 mmHg. Compared with the 4th SBP quartile, patients in the 1st SBP quartile had higher risk of all-cause death (hazard ratio, 1.85; 95% confidence interval 1.48-2.33; P < 0.001) and HF readmission (hazard ratio, 1.40; 95% confidence interval 1.19-1.65, P < 0.001). These associations were consistent in most subgroups, such as age, sex, and left ventricular ejection fraction. CONCLUSIONS: In patients hospitalized for HF, lower admission SBP portends an increased risk of 1 year all-cause death and HF readmission, and these associations were consistent among subgroups.