The Relationship Between Blood N-terminal Pro-B-type Natriuretic Peptide Level And Frailty In Elderly Hospitalized Patients And Its Clinical Application

[Background]With the aging of the population,cardiovascular disease has become the leading cause of death in China.Frailty is also quite common in the elderly population,especially in the elderly hospitalized patients.Frailty and cardiovascular disease often coexist and promote each other.N-terminal type B natriuretic peptide(NT-proBNP)is a widely used biomarker in cardiovascular diseases,especially in heart failure,and has predictive value for prognosis.There are few studies on the relationship between NT-proBNP and frailty,and its impact on prognosis of elderly hospitalized patients without heart failure[Objective]To investigate the association of NT-proBNP levels and frailty in elderly inpatients without heart failure and its impact on the prognosis,and analyze the different prognostic value between males and females.[Methods]Patients aged 65 years or older admitted to Beijing Hospital from September 2018 to February 2019 were enrolled in this study.Patients with clinical diagnosis of heart failure or left ventricular ejection fraction(LVEF)<50%were excluded.All participants were divided into robust,pre-frail and frail groups based on Fried phenotype.Clinical data,laboratory test and echocardiographic parameters were collected including NT-proBNP levels.The information about the ability of daily living activities and cognitive functions was also collected.We analyzed the association of NT-proBNP levels and frailty and evaluated the diagnostic value of NT-proBNP and NT-proBNP combined with other biomarkers for frailty.Patients were divided into two groups based on serum NT-proBNP levels:low NT-proBNP group and high NT-proBNP group.Patients were followed up at 3 months,6 months,and 12 months after enrollment,and the composite endpoint events were recorded.The composite endpoint events included all-cause mortality,hospital readmission or emergency department visits[Results]A total of 604 patients were included in the analysis,with an average age of 74.9 ± 6.5 years,including 130 cases(21.5%)in the frail group,327 cases(54.1%)in the pre-frail group and 147 cases(24.3%)in the robust group.NT-proBNP was elevated with the severity of frailty(P<0.001).The level of NT-proBNP in the frail group was significantly higher than that in the pre-frail group[235.7(104.1,650.3)vs.123.2(67.7,281.7)ng/L,P<0.001],and NT-proBNP in pre-frail group was significantly higher than that in the robust group[123.2(67.7,281.7)to 88.2(49.9,203.1)ng/L,P<0.001].The size of the left atrium increased(P<0.05),while left ventricular ejection fraction(LVEF)decreased with the severity of frailty(P<0.05).Logistic regression analysis showed that NT-proBNP was independently related to frailty(Log NT-proBNP OR=2.581,95%CI=1.52 to 4.381,P<0.001).NT-proBNP has diagnostic value for frailty,with AUC of 0.688(95%CI:0.647～0.727,P<0.001).NT-proBNP combined with prealbumin,hypersensitive C-reactive protein(hsCRP),and 25-hydroxy vitamin D3[25(OH)D3)]had the greatest diagnostic value for frailty with AUC of 0.717(95%CI:0.677～0.756),significantly better than the 3-biomarker-combination without NT-proBNP[AUC 0.0426(95%CI:0.0114～0.0737),P=0.0074].No gender difference was found with different biomarker combinations(P>0.05).According to the diagnostic cutoff(170.6 ng/L)of NT-proBNP for frailty in the previous study,the patients were divided into two groups:low NT-proBNP group(<170.6 ng/L)and high NT-proBNP group(≥170.6 ng/L).The median follow-up time was 344 days(265,359).During the follow-up,178(29.5%)had composite end point events,19 died(3.2%),and 12 lost to follow up(2.0%).Three hundred and fifty-six patients(58.9%)were in the low NT-proBNP group and 248 patients(41.1%)were in the high NT-proBNP group.Patients in the high NT-proBNP group were older(77.6±6.3 vs 73.1±6.0 years old,P<0.001),more likely to be women(54.4%vs 46.1%,P=0.043),with lower body mass index(24.4±3.5 to 25.5±3.4 kg/m2,P<0.001);more atrial fibrillation(28.6%vs 9.8%,P<0.001),more myocardial infarction(12.9%vs 4.8%,P<0.001)and stroke/TIA(25%vs 17.7%,P=0.029);Blood hemoglobin(125.9 ± 15.7 vs 131.2±14.4 g/L,P<0.001),albumin(39.1±3.1vs 39.7±3.1 g/L,P=0.020),triglyceride(1.3±0.7 vs.1.4± 0.9 mmol/l,P=0.026),creatinine clearance rate(65.4±21.5 vs.81.7±22.9ml/min,P<0.001)were lower;and cognitive function and daily activity ability were lower;the grip strength was weaker,the walking speed was slower,and the peak expiratory flow rate was lower(P<0.05).During One-year follow-up,the incidence of composite end point events(35.1%vs 25.6%,P=0.013),cardiovascular events(16.9%vs.10.7%,P=0.028)and all-cause mortality(4.8%vs 2.0%,P=0.048)were higher in high NT-proBNP group.Kaplan-Meier survival analysis showed the same trend.In addition,the readmission rates and emergency visits in the high NT-proBNP group were significantly higher than those in the low NT-proBNP group(all P<0.05).Multivariate Cox regression analysis showed that NT-proBNP was an independent risk factor for composite endpoint events(log NT-proBNP HR=1.314,95%CI:1.002～1.721,P=0.048)and cardiovascular events(log NT-proBNP HR=1.777,95%CI:1.185～2.664,P=0.005).Frailty is an independents factor for all-cause mortality(HR=4.412,95%CI:1.273～15.288,P=0.019).Kaplan-Meier survival analysis was used to analyze the effects of NT-proBNP and frailty on the prognosis of patients across different genders.The results found that among male patients,the event-free survival rate of the high NT-proBNP group was significantly lower than the low NT-proBNP group(log-rank P=0.0234);among female patients,the 1-year event-free survival rate of frail patients was significantly lower than that of non-frail patients(log-rank P=0.0030).[Conclusion]NT-proBNP is elevated in elderly frail inpatients without heart failure.After adjusting atrial fibrillation and creatinine clearance rates,it is still an independent factor of frailty.NT-proBNP has diagnostic value for frailty.NT-proBNP combined with pre-albumin,hsCRP,25(OH)D3 has highest diagnostic value for inpatients with frailty,and there was no significant gender difference.NT-proBNP is an independent predictor of composite end point events and cardiovascular events,and frailty is an independent predictor of all-cause death.There is a gender difference in the impact of the two on prognosis.