高岩
中国医学科学院阜外医院 阜外牛津国际研究中心
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.
ESC heart failure 2023
AIMS:Mortality risk assessment in patients with heart failure (HF) with preserved ejection fraction (HFpEF) presents a major challenge. We sought to construct a polygenic risk score (PRS) to accurately predict the mortality risk of HFpEF.METHODS AND RESULTS:We first carried out a microarray analysis of 50 HFpEF patients who died and 50 matched controls who survived during 1-year follow-up for candidate gene selection. The HF-PRS was developed using the independent common (MAF > 0.05) genetic variants that showed significant associations with 1-year all-cause death (P < 0.05) in 1442 HFpEF patients. Internal cross-validation and subgroup analyses were performed to evaluate the discrimination ability of the HF-PRS. In 209 genes identified by microarray analysis, 69 independent variants (r < 0.1) were selected to develop the HF-PRS model. This model yielded the best discrimination capability for 1-year all-cause mortality with an area under the curve (AUC) of 0.852 (95% CI 0.827-0.877), which outperformed the clinical risk score consisting of 10 significant traditional risk factors for 1-year all-cause mortality (AUC 0.696, 95% CI 0.658-0.734, P = 4 × 10-11), with net reclassification improvement (NRI) of 0.741 (95% CI 0.605-0.877; P < 0.001) and integrated discrimination improvement (IDI) of 0.181 (95% CI 0.145-0.218; P < 0.001). Individuals in the medium and the highest tertile of the HF-PRS had nearly a five-fold (HR = 5.3, 95% CI 2.4-11.9; P = 5.6 × 10-5) and 30-fold (HR = 29.8, 95% CI 14.0-63.5; P = 1.4 × 10-18) increased risk of mortality compared to those in the lowest tertile, respectively. The discrimination ability of the HF-PRS was excellent in cross validation and throughout the subgroups regardless of comorbidities, gender, and patients with or without a history of heart failure.CONCLUSION:The HF-PRS comprising 69 genetic variants provided an improvement of prognostic power over the contemporary risk scores and NT-proBNP in HFpEF patients.
European journal of preventive cardiology 2023
BACKGROUND:Inappropriate antimicrobial use is common among patients undergoing surgery. It remains unclear whether a multi-faceted computerized antimicrobial stewardship programme is effective and safe in reducing inappropriate antimicrobial use in surgical settings.METHODS:A multi-faceted computerized antimicrobial stewardship intervention system was developed, and an open-label, cluster-randomized, controlled trial was conducted among 18 surgical teams that enrolled 2470 patients for open chest cardiovascular surgery. The surgical teams were divided at random into intervention and control groups at a ratio of 1:1. The primary endpoints were days of therapy (DOT)/1000 patient-days, defined daily dose (DDD)/1000 patient-days and length of therapy (LOT)/1000 patient-days.RESULTS:Mean DOT, DDD and LOT per 1000 patient-days were significantly lower in the intervention group compared with the control group (472.2 vs 539.8, 459.5 vs 553.8, and 438.4 vs 488.7; P<0.05), with reductions of 14.2% [95% confidence interval (CI) 11.8-16.7%], 18.7% (95% CI 15.9-21.4%) and 11.9% (95% CI 9.6-14.1%), respectively. The daily risk of inappropriate antimicrobial use after discharge from the intensive care unit decreased by 23.9% [95% CI 15.5-31.5% (incidence risk ratio 0.76, 95% CI 0.69-0.85)] in the intervention group. There was no significant difference in rates of infection or surgical-related complications between the groups. Median antimicrobial costs were significantly lower in the intervention group {873.4 [interquartile range (IQR) 684.5-1255.4] RMB vs 1178.7 (IQR 869.1-1814.5) RMB; P<0.001} (1 RMB approximately equivalent to 0.16 US$ in 2022).CONCLUSIONS:The multi-faceted computerized antimicrobial stewardship interventions reduced inappropriate antimicrobial use safely.CLINICAL TRIAL REGISTRATION:Clinicaltrials.gov: NCT04328090.
International journal of antimicrobial agents 2023
Background:Prior studies have found an unexplained inverse or U-shaped relationship between body mass index (BMI) and mortality in heart failure (HF) patients. However, little is known about the independent effects of each body component, i.e., lean body mass (LBM) and fat mass (FM), on mortality.Methods:We used data from the China Patient-centered Evaluative Assessment of Cardiac Events-Prospective Heart Failure Study. LBM and FM were calculated using equations developed from the National Health and Nutrition Examination Survey. LBM and FM index, calculated by dividing LBM or FM in kilograms by the square of height in meters, were used for analysis. We used restricted cubic spline and Cox model to examine the association of LBM and FM index with 1-year all-cause mortality.Results:Among 4,305 patients, median (interquartile range) age was 67 (57-76) years, 37.7% were women. During the 1-year follow-up, 691 (16.1%) patients died. After adjustments, LBM index was inversely associated with mortality in a linear way (P-overall association < 0.01; P-non-linearity = 0.52), but no association between FM index and mortality was observed (P-overall association = 0.19). Compared with patients in the 1st quartile of the LBM index, those in the 2nd, 3rd, and 4th quartiles had lower risk of death, with hazard ratio of 0.80 (95% CI 0.66-0.97), 0.65 (95% CI 0.52-0.83), and 0.61 (95% CI 0.45-0.82), respectively. In contrast, this association was not observed between FM index quartiles and mortality.Conclusion:Higher LBM, not FM, was associated with lower 1-year mortality among HF patients.
Frontiers in cardiovascular medicine 2022
AIMS:This study explored the association between socio-economic status (SES) and mortality among patients hospitalized for heart failure (HF) in China.METHODS AND RESULTS:We used data from the China Patient-centred 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. SES was measured using the income, employment status, educational attainment, and partner status. Individual socio-economic risk factor (SERF) scores were assigned based on the number of coexisting SERFs, including low income, unemployed status, low education, and unpartnered status. We assessed the effects of SES on 1 year all-cause mortality using Cox models. We used the Harrell c statistic to investigate whether SES added incremental prognostic information for mortality prediction. A total of 4725 patients were included in the analysis. The median (interquartile range) age was 67 (57-76) years; 37.6% were women. In risk-adjusted analyses, patients with low/middle income [low income: hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.21-2.14; middle income: HR 1.32, 95% CI 1.00-1.74], unemployment status (HR 1.43, 95% CI 1.10-1.86), low education (HR 1.25, 95% CI 1.03-1.53), and unpartnered status (HR 1.22, 95% CI 1.03-1.46) had a higher risk of death than patients with high income, who were employed, who had a high education level, and who had a partner, respectively. Compared with the patients without SERFs, those with 1, 2, 3, and 4 SERFs had 1.52-, 2.01-, 2.45-, and 3.20-fold increased risk of death, respectively. The addition of SES to fully adjusted model improved the mortality prediction, with increments in c statistic of 0.01 (P < 0.01).CONCLUSIONS:In a national Chinese cohort of patients hospitalized for HF, low income, unemployment status, low education, and unpartnered status were all associated with a higher risk of death 1 year following discharge. In addition, incorporating SES into a clinical-based model could better identify patients at risk for death. Tailored clinical interventions are needed to mitigate the excess risk experienced by those socio-economic deprived HF patients.
ESC heart failure 2022
BACKGROUND:Sex differences in clinical characteristics and in-hospital outcomes among patients with non-ST-segment-elevation myocardial infarction have been described in Western countries, but whether these differences exist in China is unknown.METHODS:We used a 2-stage random sampling design to create a nationally representative sample of patients admitted to 151 Chinese hospitals for non-ST-segment-elevation myocardial infarction in 2006, 2011, and 2015 and examined sex differences in clinical profiles, treatments, and in-hospital outcomes over this time. Multivariable logistic regression models adjusting for age or other potentially confounding clinical covariates were used to estimate these sex-specific differences.RESULTS:Among 4611 patients, the proportion of women (39.8%) was unchanged between 2006 and 2015. Women were older with higher rates of hypertension, diabetes, and dyslipidemia. Among patients without contraindications, women were less likely to receive treatments than men, with significant differences for aspirin in 2015 (90.3% versus 93.9%) and for invasive strategy in 2011 (28.7% versus 45.7%) and 2015 (34.0% versus 48.4%). After adjusting for age, such differences in aspirin and invasive strategy in 2015 were not significant, but the difference in invasive strategy in 2011 persisted. The sex gaps in the use of invasive strategy did not narrow. From 2006 to 2015, a significant decrease in in-hospital mortality was observed in men (from 16.9% to 8.7%), but not in women (from 11.8% to 12.0%), with significant interaction between sex and study year (P=0.023). After adjustment, in-hospital mortality in women was significantly lower than men in 2006, but not in 2011 or 2015.CONCLUSIONS:Sex differences in cardiovascular risk factors and invasive strategy after non-ST-segment-elevation myocardial infarction were observed between 2011 and 2015 in China. Although sex gaps in in-hospital mortality were largely explained by age differences, efforts to narrow sex-related disparities in quality of care should remain a focus.REGISTRATION:URL: http://www.CLINICALTRIALS:gov; Unique identifier: NCT01624883.
Circulation. Cardiovascular quality and outcomes 2022
OBJECTIVE:Long-term weight loss (LTWL) has been shown to be associated with lower metabolic risk in young adults with overweight/obesity. However, the dose-response association is uncertain.METHODS:In a large-scale nationwide screening project in China, the participants aged 35 to 64 years who recalled overweight/obesity at age 25 years and experienced LTWL or maintained stable weight were included. The dose-response association between LTWL from age 25 to screening (35 to 64 years) and the odds of metabolic syndrome at screening were assessed using multivariable adjusted regression models with restricted cubic splines.RESULTS:A total of 40,150 participants (66.4% women) were included. The increment of LTWL was associated with continuously decreased odds of metabolic syndrome. The odds of metabolic syndrome were 0.64 (0.60 to 0.67), 0.42 (0.40 to 0.45), 0.27 (0.25 to 0.29), and 0.15 (0.13 to 0.17) for those with LTWL of 5% to 9.9%, 10% to 14.9%, 15% to 19.9%, and 20% or greater compared with <5% LTWL, respectively. Moreover, the incremental pattern was observed across all population subgroups.CONCLUSIONS:An incremental association between LTWL from young adulthood and odds of later-life metabolic syndrome was observed. Our findings highlight the effective ways to achieve LTWL to improve lifetime metabolic health for young adults with overweight/obesity.
Obesity (Silver Spring, Md.) 2022
BACKGROUND:Clinical decision support systems (CDSS) are low-cost, scalable tools with the potential to improve guideline-based antihypertensive treatment in primary care, but their effectiveness needs to be tested, especially in low- and middle-income countries such as China.METHODS:The Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) trial is a pragmatic, four-stage, cluster-randomized trial conducted in 94 primary care sites in China. For each city-based stage, sites are randomly assigned to either implementation of the CDSS for hypertension management (which guides doctors' treatment recommendations based on measured blood pressure and patient characteristics), or usual care. Patients are enrolled during the first 3 months after site randomization and followed for 9 months. The primary outcome is the proportion of hypertension management visits at which guideline-based treatment is provided. In a nested trial conducted within the CDSS, with the patient as the unit of randomization, the LIGHT-ACD trial, patients are randomized to receive different initial mono- or dual-antihypertensive therapy. The primary outcome of the LIGHT-ACD trial is the changes in blood pressure.DISCUSSION:The LIGHT trial will provide evidence on the effectiveness of a CDSS for improving guideline adherence for hypertension management in primary care in China. The nested trial, the LIGHT-ACD trial, will provide data on the effect of different initial antihypertensive regimens for blood pressure management in this setting.TRIAL REGISTRATION:ClinicalTrials.gov, identifier: LIGHT (NCT03636334) and LIGHT-ACD (NCT03587103). Registered on 3 July 2018.
Trials 2022
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.
Atherosclerosis 2022
BACKGROUND:Epidemiologic studies have explored the association between a single cardiovascular risk factor (CVRF) and resting heart rate (RHR), but the research on the relation of multiple risk factors with RHR remains scarce. This study aimed to explore the associations between CVRFs clustering and the risk of elevated RHR.METHODS:In this cross-sectional study, adults aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August 2020. We focused on seven risk factors: hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, alcohol use, and low physical activity. Multivariate logistic regression was used to calculate odds ratios (OR) for elevated RHR (> 80 beats/min).RESULTS:Among 1,045,405 participants, the mean age was 55.67 ± 9.86 years, and 60.4% of participants were women. The OR (95% CI) for elevated RHR for the groups with 1, 2, 3, 4 and ≥ 5 risk factor were 1.11 (1.08-1.13), 1.36 (1.33-1.39), 1.68 (1.64-1.72), 2.01 (1.96-2.07) and 2.58 (2.50-2.67), respectively (P trend < 0.001). The association between the CVRFs clustering number and elevated RHR was much more pronounced in young males than in other age-sex subgroups. Clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk factors.CONCLUSIONS:There was a significant positive association between the CVRFs clustering number and the risk of elevated RHR, particularly in young males. Compared clusters comprising more behavioral risk factors, clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR. RHR may serve as an indicator of the cumulative effect of multiple risk factors.
Journal of geriatric cardiology : JGC 2022
