沙库巴曲缬沙坦钠对老年射血分数保留型心力衰竭伴高血压患者血浆同型半胱氨酸和尿酸的影响及预后研究

Effect and prognosis of sacubitril-valsartan sodium on plasma homocysteine and uric acid in elderly patients with heart failure with preserved ejection fraction and hypertension

目的探讨沙库巴曲缬沙坦钠(诺欣妥)对老年射血分数保留型心力衰竭(HFpEF)伴高血压患者患者血浆同型半胱氨酸和尿酸的影响及其是否能更好改善患者的预后。方法入选了2021年6月至2023年1月在青岛大学附属医院住院的HFpEF伴高血压患者138例,其中70例接受诺欣妥治疗,68例接受缬沙坦治疗。诺欣妥组患者应用沙库巴曲缬沙坦钠50~100 mg,2次/d,缬沙坦组患者应用缬沙坦胶囊80~160 mg,1次/d。如血压控制不佳,可联合应用其他降压药物,两组患者在2~4周内血压均控制在理想降压目标值内(即<130/80 mmHg,但不能低于120/70 mmHg)。随访3个月,比较两组患者的有效率、超声心动图指标[左心房内径(LAD)、左心室舒张末期内径(LVDd)、室间隔厚度(IVST)、左心室后壁厚度(LVPWT)、舒张早期二尖瓣血流最大速度/舒张早期二尖瓣环峰值速度(E/e′)、舒张早期二尖瓣环峰值速度(e′)、左心室射血分数(LVEF),同时计算左心房容积(LAV)、左心房容积指数(LAVI)、左心室质量(LVM)、左心室质量指数(LVMI)、相对室壁厚度(RWT)]、血流动力学指标[收缩压、舒张压、肺动脉收缩压(PASP)]、生化指标[同型半胱氨酸(Hcy)、尿酸(UA)、N末端B型利钠肽原(NT-proBNP)],同时评估两组间主要不良药物反应及再入院率。结果老年HFpEF伴高血压患者血浆同型半胱氨酸与尿酸水平呈中度正相关,女性血浆同型半胱氨酸与尿酸水平的相关性强于男性(P<0.01);两组治疗后血压水平、NT-proBNP、E/e′、LAV、LAVI、LVMI、RWT均较治疗前下降,e′值较治疗前升高(P<0.05)。治疗后诺欣妥组Hcy、UA、PASP水平较治疗前下降(P<0.01);缬沙坦组Hcy、UA、PASP水平较治疗前无明显下降趋势(P>0.05)。随访结束时,同缬沙坦组相比,诺欣妥组血压水平、NT-proBNP、Hcy、UA、E/e′、PASP、LAVI、LVM、LVMI值下降更加明显,e′值升高更明显(P<0.05);诺欣妥组、缬沙坦组治疗后总有效率分别为61.4%和35.3%(χ^(2)=9.433,P<0.01),因心衰再入院率诺欣妥组、缬沙坦组分别为14.3%和30.9%(χ^(2)=5.455,P<0.05)。结论沙库巴曲缬沙坦钠可以降低NT-proBNP、Hcy、UA、PASP水平,改善老年HFpEF伴高血压患者心脏舒张功能,降低因心衰再入院率,具有良好的安全性;老年HFpEF伴高血压患者心血管危险因素调查时有按性别分层的必要性。

Objective To investigate the effects of Sacubitril-valsartan sodium(Entresto)on plasma levels of homocysteine and uric acid in elderly patients with heart failure with preserved ejection fraction(HFpEF)and hypertension,and whether it can better improve the prognosis of elderly patients with HFpEF and hypertension.Methods This study enrolled 138 patients with HFpEF and hypertension hospitalized in the Affiliated Hospital of Qingdao University from June 2021 to January 2023.Among them,70 patients received treatment with Sacubitril-valsartan sodium and 68 patients received treatment with Valsartan.Patients in the Entresto group used Sacubitril-valsartan sodium at a dose of 50-100 mg,twice a day,while patients in the Valsartan group used Valsartan capsules at a dose of 80-160 mg,once a day.If blood pressure was poorly controlled,other antihypertensive drugs could be used in combination.The blood pressure in both groups was controlled at the ideal target value within 2-4 weeks(i.e.,<130/80 mmHg,but not lower than 120/70 mmHg).All groups were followed up for 3 months,the study compared the effective rate,echocardiographic parameters[Left atrial diameter(LAD),left ventricular end-diastolic diameter(LVDd),interventricular septal thickness(IVST),left ventricular posterior wall thickness(LVPWT),peak early diastolic mitral valve velocity/early diastolic peak mitral annular velocity(E/e′),early diastolic mitral annular peak velocity(e′),left ventricular ejection fraction(LVEF),and simultaneously calculate left atrial volume(LAV),left atrial volume index(LAVI),left Ventricular mass(LVM),left ventricular mass index(LVMI),relative wall thickness(RWT)],hemodynamic parameters[systolic,diastolic,pulmonary artery systolic pressure(PASP)],and biochemical parameters[homocysteine(Hcy),uric acid(UA),N-terminal pro-brain natriuretic peptide(NT-proBNP)]between the two groups.Additionally,the study accessed the main adverse drug reactions and the hospital readmission rates between the two groups.Results There was a moderate positive correlation between plasma homocysteine and uric acid levels in elderly patients with HFpEF and hypertension,and the correlation between plasma homocysteine and uric acid levels was stronger in females than in males(P<0.01).Following treatment,the blood pressure levels,N-terminal pro-brain natriuretic peptide(NT-proBNP),peak value of early mitral diastolic flow/early diastolic mitral annulus velocity(E/e′),left atrial volume(LAV),left atrial volume index(LAVI),left ventricular mass index(LVMI),and relative wall thickness(RWT)in both groups decreased compared with before treatment,while the e'value increased(P<0.05);the levels of Hcy,UA,and PASP in the Entresto group decreased compared with before treatment(P<0.01),while there was no obvious decreasing trend in the levels of Hcy,UA,and PASP was observed compared with before treatment in the Valsartan group(P>0.05).After followed up for 3 months,compared with the Valsartan group,the Entresto group had a more significant decrease in blood pressure levels,NT-proBNP,Hcy,UA,E/e′,PASP,LAVI,LVM,LVMI,and a more significant increase in e'value(P<0.05).The total effective rates of the Entresto group and the Valsartan group were 61.4%and 35.3%respectively(χ^(2)=9.433,P<0.01),and the readmission rates caused by heart failure were 14.3%in the Entresto group and 30.9%in the Valsartan group respectively(χ^(2)=5.455,P<0.05).Conclusions Sacubitril-valsartan sodium can reduce the levels of NT-proBNP,Hcy,UA,and PASP,improve the cardiac diastolic function of elderly patients with HFpEF and hypertension,and reduce the rate of readmission rate caused by heart failure,which has a good safety profile.It is necessary to stratify by gender when investigating cardiovascular risk factors in elderly patients with HFpEF and hypertension.