Associations between plasma natriuretic peptides and echocardiographic abnormalities in geriatric outpatients

Identification of patients with cardiac dysfunction can be difficult in the geriatric population. Recently, different subtypes of the natriuretic peptide family have been advocated as biomarker for the diagnosis of heart failure in the emergency department setting. In this study we looked at associations between natriuretic peptide plasma levels and echocardiographic abnormalities in geriatric outpatients. Two-dimensional transthoracic echocardiography was performed in 209 community-dwelling subjects, visiting the geriatric outpatient clinic of our university hospital. Subjects were 65 years or older and had no markedly impaired cognitive function. Mean atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) plasma levels were respectively 11.0 and 10.8pmol/l. BNP, but not ANP correlated with left ventricular dysfunction and left ventricular mass, whereas both peptides correlated with left atrial dimension and valvular lesions. A natriuretic peptide level in the highest tertile was associated with a higher risk of any echocardiographic abnormality, with odds ratios for BNP of 7.15 (range 2.15-23.71), and for ANP of 3.07 (range 1.15-8.16). In conclusion, elevated BNP and ANP plasma levels are closely related to cardiac abnormalities in elderly subjects. The association between cardiac abnormalities and natriuretic peptides is stronger for BNP than for ANP, hence for detection of cardiac abnormalities measurement of BNP plasma values are preferred over ANP plasma values.     

Atrial natriuretic peptides predict mortality in the elderly

Objectives. To ascertain whether atrial natriuretic peptides could be used as prospective and independent predictors of total mortality in an elderly population.
Design. Atrial natriuretic peptides, ANP(1–98) and ANP(99–126), were measured in 541 subjects from the 85-year-old population of Gothenburg, Sweden. Before the study cardiovascular disorders such as congestive heart failure, ischaemic heart disease, hypertension and atrial fibrillation were defined. Total mortality was recorded during the prospective 60-month follow-up period.
Setting. Individuals aged 85 years from the population of Gothenburg, Sweden, were visited once at home and made one visit to Vasa Hospital.
Main outcome measures. Sixty-month mortality in relation to circulating concentrations of atrial natriuretic peptides.
Results. Circulating concentrations of ANP(1–98) and ANP(99–126) were significantly correlated with 60-month mortality in the total study population (ANP(1–98), P <0.001; ANP(99–126), P <0.01). In subjects with cardiovascular disorders, 60-month mortality was significantly correlated with increased concentrations of ANP(1–98) ( P <0.01) and ANP(99–126) ( P <0.05). In subjects with no defined cardiovascular disorder, 60-month mortality was significantly correlated with increased ANP(1–98) concentrations ( P <0.01).
Conclusions. In the elderly population, atrial peptides predict mortality in subjects with defined cardiovascular disorders as well as in the total population and may predict future cardiovascular disorder.     

Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population

OBJECTIVE—To report the mortality of left ventricular systolic dysfunction (LVD), assessed objectively by echocardiography, and its association with natriuretic peptide hormones in a random sample of 1640 men and women aged 25-74 years from a geographical, urban population.
METHODS—Left ventricular function was measured by echocardiography in 1640 attendees studied in 1992-3. LVD was defined as a left ventricular ejection fraction (LVEF)  30%. Plasma concentrations of N-terminal atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP) were measured by standard radioimmunoassays. Mortality was documented at four years.
RESULTS—The four year all cause mortality rate in the whole cohort was 4.9% (80 deaths). It was 21% (nine deaths) in those with an LVEF  30% and 4% in those whose LVEF was > 30% (p < 0.001). The median (interquartile range) BNP concentration in those who died was 16.9 pg/ml (8.8-27) and 7.8 pg/ml (3.4-13) in survivors (p < 0.0001). Similarly, N-ANP had a median concentration of 2.35 ng/ml (1.32-3.36) in those with a fatal outcome and 1.27 ng/ml (0.9-2.0) in those alive at four years (p < 0.0001). Subjects with an LVEF  40% also had a significant mortality rate of 17% if they also had a BNP concentration  17.9 pg/ml compared with 6.8% if their BNP was below this concentration (p = 0.013). Multivariate analysis revealed the independent predictors of four year all cause mortality to be increasing age (p < 0.001), a BNP concentration  17.9 pg/ml (p = 0.006), the presence of ischaemic heart disease (p = 0.03), and male sex (p = 0.04).
CONCLUSIONS—LVD is associated with a considerable mortality rate in this population. BNP also independently predicts outcome. In addition to its role as a diagnostic aid in chronic heart failure and LVD, it provides prognostic information and clarifies the meaning of a given degree of LVD.


Keywords: epidemiology; left ventricular dysfunction; natriuretic peptides     

Predictors of left ventricular mass in old age: an echocardiographic, clinical and biochemical investigation of a random population sample

The potential predictors of left ventricular mass in old agewere studied in a random sample of people born in 1904, 1909,1914 (n=501; and 1920-35 (n=76). Data on the left ventriclewith mass calculation, quantitative data on value disordersand biochemical data were collected. Left ventricular mass (correctedfor height) was positively related to male gender, age, bodymass index and systolic blood pressure. It was also significantlyhigher in the presence of aortic valve calcification, a lowvelocity ratio (indicating aortic value obstruction), and aorticor mitral re gurgitation. In men, left ventricular mass washigher in the presence of coronary artery disease and inverselyrelated to serum high density lipoprotein cholesterol. In multivariateanalysis, independent predictors of left ventricular mass withoutsex interaction were age (standardized coefficient ß=0.23,P=0.000). male gender (ß=0.38, P=0.000), body massindex (ß=0.22, P=0.000), systolic blood pressure (ß=0.21,P=0.000), velocity ratio (ß=-0.11, P=0.010), detectableaortic regurgitation (ß=0.11, P=0.014) and moderate-to-severemitral regurgitation (ß=0.21, P=0.014) and moderate-to-severemitral regurgitation (ß=0.21, P=0.000). Thus, theincrease in left ventricular mass with age can largely be relatedto discrete predictors. The impact of valve disorders is substantial.     

Relationship between left atrial appendage function and plasma concentration of atrial natriuretic peptide.

BACKGROUND: It has been reported that the most intensely granuled cardiocytes secreting atrial natriuretic peptide (ANP) are located in the atrial appendages. AIMS: To evaluate the mechanisms of ANP release in congestive heart failure. METHODS AND RESULTS: The relationship between ANP and left atrial appendage (LAA) function was evaluated in 36 patients who underwent both transoesophageal echocardiography and cardiac catheterization. ANP level correlated positively with mean pulmonary capillary wedge pressure (mPCWP; r=0.75, P<0.0001), whereas it showed no significant correlation with the mean right atrial pressure. mPCWP correlated positively with the maximal LAA area (LAAa; r=0.79, P<0.0001) and negatively with the LAA ejection fraction during atrial contraction (LAA-EF; r=-0.61, P<0.0001) and peak late diastolic LAA emptying flow velocity (LAAF; r=-0.69, P<0.0001). ANP level correlated negatively with the LAA-EF (r=-0.56, P<0.001) and with LAAF (r=-0.61, P<0.0001). ANP level correlated more closely with the LAAa (r=0.79, P<0.0001) than with maximal LA volume (r=0.34, P<0.05). Multiple stepwise regression analysis selected LAAa as the only factor independently related to the plasma concentration of ANP (ANP=-22.4+28.6 LAAa, r=0.79, P<0.0001). CONCLUSIONS: We conclude that the factor most predictive for ANP in patients with left-sided cardiac dysfunction is distension of the LAA wall rather than elevation in the LA pressure or distension of the body of LA. This is consistent with the known distribution of ANP-secreting cardiocytes.     

应用多普勒组织成像技术评价原发性高血压左室舒张功能及其相关因素

目的:应用多普勒组织成像技术(DTI)探讨原发性高血压(EH)左室舒张功能的特点,同时检测血中心钠素(ANP)、脑钠素(BNP)的变化,分析两者与左室舒张功能的关系。方法:对照组20例,EH患者(EH组)61例,均行常规超声及DTI检查,EH患者根据左室质量指数(LVMI)分为左室心肌肥厚(LVH)亚组和无 LVH(NLVH )亚组。DTI测量二尖瓣侧环心肌舒张早期峰值运动速度(e)、晚期峰值运动速度(a)及其比值(e/a),测量二尖瓣瓣尖水平舒张早期的最大流速(E0)、舒张晚期的最大流速(A)及 E0 与A流速的比值E0/A。入选病例均测定血浆ANP、BNP浓度。结果:与对照组相比,EH患者E0/A、e/a减小,LVH亚组减小更明显;与对照组相比,EH血浆 ANP、BNP浓度升高, LVH升高更明显; E0/A、e/a比值与 ANP 呈负相关( r = - 0.56和 r = -0.60, 均P<0.01),与BNP呈负相关( r=-0.62和 r=-0.65,均 P<0.01)。结论:血浆 ANP、BNP与应用DTI技术评价的EH左室舒张功能均有较好相关性。     

Does the mechanism of action of biatrial pacing for atrial fibrillation involve changes in cardiac haemodynamics? Assessment by Doppler echocardiography and natriuretic peptide measurements.

AIMS: The antifibrillatory mechanism of biatrial (BI) pacing has not been fully elucidated. We investigated the role of a haemodynamic mechanism in eight patients implanted with a BI pacemaker (Chorus RM) by comparing changes in mitral Doppler flow and atrial and B-type natriuretic peptide levels (ANP, BNP) with BI pacing compared with sinus rhythm and right atrial (RA) pacing. METHODS AND RESULTS: Measurements were taken after 60 min in the supine position in each of two pairs of randomized pacing modes: (a) AAI40 beats x min(-1), (allows sinus rhythm mean rate 56 beats x min(-1), SR) vs AAI 40 beats x min(-1) with synchronized left atrial pacing (SRSync); (b) overdrive AAI RA pacing (89 beats x min(-1) (n = 6) or 70 beats x min(-1) (n = 2)) vs overdrive AAI BI pacing. Within each pair there was significant earlier activation of the left atrial Doppler signal in relation to the surface ECG P wave with BI pacing (SR 163 +/- 10 ms vs SRSync 144 +/- 21 ms (P = 0.02), and RA 232 +/- 14 ms vs BI 196 +/- 16 ms (P = 0.001)), and significant shortening of the P-R interval (SR 163 +/- 29 ms vs SRSync 148 +/- 20 (P = 0.007) and RA 261 +/- 27 ms vs BI 232 +/- 23 (P = 0.001)). The net observed effect was of no change in the atrioventricular timing sequence (delay of peak E or A to QRS/ mitral valve closure) and no change in other Doppler echo parameters. Levels of the cardiac peptides ANP and BNP were raised compared with healthy controls, but did not significantly change during the study. CONCLUSION: Acute BI pacing shortens the P-R interval and causes earlier left atrial contraction in relation to the surface electrocardiogram P wave. It does not alter the atrioventricular timing cycle, any other Doppler measurements or change cardiac peptide levels. This suggests that BI pacing does not cause haemodynamic changes that could account for any antifibrillatory properties.     

心房颤动患者脑钠素的变化及其与肾素血管紧张素醛固酮系统的关系

目的:探讨持续性心房颤动患者的血脑钠素(BNP)水平的改变及其与肾素血管紧张素醛固酮系统的关系.方法:对108例符合入选标准的住院患者分为持续性心房颤动组(55例)和对照组(53例),对2组患者的血BNP、肾素、血管紧张素Ⅱ、醛固酮水平进行检测,并行经胸超声心动图检查,测量左心房前后径.结果:2组血BNP分别为(79.65±16.23)/μg/L、(50.12±15.97)μg/L(均P＜0.01),多元线性逐步回归分析表明:左房内径、血管紧张素Ⅱ浓度是高血BNP水平的独立预测因素.结论:持续性心房颤动患者血BNP水平明显升高,与心房颤动患者的结构重构及肾素血管紧张素醛固酮系统密切相关.     

Comparison of B-type natriuretic peptide with left atrial enlargement by echocardiography for the diagnosis of new-onset congestive heart failure with a preserved left ventricular systolic function in the setting of longstanding hypertension

The present study attempted to determine the accuracy of B-type natriuretic peptide (BNP) compared with left atrial enlargement at echocardiography in the emergency diagnosis of new-onset heart failure with preserved systolic function (HFPSF) related to longstanding hypertension. The study comprised 57 patients in sinus rhythm hospitalized for acute dyspnea, 30 with hypertensive HFPSF and 27 with noncardiac cause. By stepwise logistic regression analysis, BNP provided independent and incremental diagnostic information over the score of Boston criteria. There was a trend toward superiority of this biomarker compared to the left atrial area index for the diagnosis of HFPSF. A BNP concentration > 142 pg/ml was 93% sensitive and 85% specific for the diagnosis of HFPSF in this clinical setting (area under the ROC curve of 0.91 [0.8–0.97], p < 0.001).     

起搏术后心房颤动的影响因素及心房颤动与心钠素的关系

目的观察心脏起搏术后发生心房颤动(简称房颤)的影响因素及房颤与血心钠素(ANP)的关系。方法选择安装心脏起搏器的患者103例进行随访,分析房颤与年龄、起搏方式、心律失常类型、左房内径(LAD)、左室射血分数(LVEF)和血ANP的关系。结果①65岁以下患者房颤发生率低于65岁以上组(P<0.05)。②VVI组房颤发生率高于DDD组(P<0.05)。③慢快综合征组房颤发生率较缓慢型病窦综合征和房室传导阻滞组高(P<0.05)。④VVI房颤组术后LAD增大、LVEF下降(P<0.05),VVI房颤组术后与DDD组比较有差异(P<0.05)。⑤VVI房颤组和VVI窦性心律组ANP浓度较DDD组高(P<0.05);各组不同心功能级别(NYHA)之间ANP浓度随着心功能级别的加重而升高。结论长期心脏起搏术后房颤的发生可能与年龄大、VVI起搏、病窦综合征(慢快型)、LAD增大、LVEF降低及ANP浓度升高相关。     

厄贝沙坦对老年高血压患者内皮素及心钠素的影响

目的:探讨厄贝沙坦对老年高血压患者血浆内皮素(ET)及心钠素(ANP)的影响。方法:随机开放选择,采用放射免疫法测定37例老年高血压患者服用厄贝沙坦前、后ET及ANP水平的变化。结果:与对照组比较,高血压组患者ET、ANP水平明显升高(P<0.01),厄贝沙坦治疗后ET、ANP水平显著降低(P<0.01)。结论:高血压患者血浆ET、及ANP水平明显升高,厄贝沙坦对老年高血压患者不但有较好的降压作用,还能够降低ET及ANP水平,可能有较好的血管内皮保护功能。     

慢性心力衰竭患者心钠素水平及与心功能关系的观察

目的探讨心钠素(ANP)在慢性心力衰竭发生与发展过程中的意义及与心功能的关系。方法选择35例慢性心力衰竭患者和32例正常对照,采用放射免疫法测定其血浆ANP水平,应用彩色多普勒超声心动图测定左心室收缩末期内径(LVSd)、左心室舒张末期内径(LNDd)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)及心动周期中二尖瓣舒张晚期心室充盈峰速度(A)与二尖瓣舒张早期心室充盈峰速度(E)的比值(A／E),观察ANP水平与心功能之间的关系。结果心力衰竭患者血浆ANP水平比健康对照组明显升高(P<0．001),且随着心功能程度的不断加重,ANP水平逐渐升高．依次为心功能Ⅱ级<心功能Ⅲ级<心功能Ⅳ级(P<0．05-0．001)。ANP水平与LVEF、LVFS呈负相关,r值分别为0．76(P<0．01)、-0．72(P<0．01);与LVSd、LVDd及A／E呈正相关,r值分别为0．65(P<0．01)、0．79(P<0．01)、0．72(P<0．01)。结论慢性心力衰竭进展中,ANP水平与心力衰竭的严重程度密切相关,能够反映不同的心功能状态,为慢性心力衰竭的诊断与治疗提供参考依据。     

Differential effects of atrial and brain natriuretic peptides on human pulmonary artery:An in vitro study

BACKGROUND The prevalence of cardiovascular diseases, especially heart failure, continues to rise worldwide. In heart failure, increasing levels of circulating atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP) are associated with a worsening of heart failure and a poor prognosis.AIM To test whether a high concentration of BNP would inhibit relaxation to ANP.METHODS Pulmonary arteries were dissected from disease-free areas of lung resection, as well as pulmonary artery rings of internal diameter 2.5–3.5 mm and 2 mm long,were prepared. Pulmonary artery rings were mounted in a multiwire myograph,and a basal tension of 1.61 gf was applied. After equilibration for 60 min, rings were pre-constricted with 11.21 μmol/L PGF_(2α)(EC_(80)), and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers.RESULTS Although both ANP and BNP were found to vasodilate the pulmonary vessels,ANP is more potent than BNP.pEC50 of ANP and BNP were 8.96 ± 0.21 and 7.54± 0.18, respectively, and the maximum efficacy(E_(max)) for ANP and BNP was-2.03 gf and-0.24 gf, respectively. After addition of BNP, the E_(max) of ANP reduced from -0.96 gf to-0.675 gf(P=0.28).CONCLUSION BNP could be acting as a partial agonist in small human pulmonary arteries, and inhibits relaxation to ANP. Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure. This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure.     

脑钠肽对老年人心房颤动复律和复发的评价作用

目的 通过测定老年人窦性心律（窦律）患者和心房颤动（房颤）患者复律前后的血清脑钠肽（BNP）浓度，探讨其对老年房颤患者的评价作用及在房颤复律前后中的应用价值。方法 选择心功能正常的老年患者102例，其中阵发性房颤28例，持续性房颤40例，窦律34例，采用放射免疫方法测定窦律患者血清BNP浓度，同时对房颤患者进行复律，测定复律前、复律后24h及30d的血清BNP浓度。结果 老年房颤患者的血清BNP浓度显著高于窦律患者，并在复律后显著降低，差异有统计学意义。窦律维持组的血清BNP浓度低于房颤复发组[（238．24±97．45）pg／ml vs（323．24±62．78）pg／ml，P〈0．05]。单因素分析显示年龄、左心房内径、房颤持续时间及BNP浓度与房颤的复发有关，多因素回归分析显示BNP浓度和年龄是复律后房颤复发的独立影响因子。结论 BNP的检测可能对老年人房颤的诊断和评估、预测复律的疗效及房颤的复发具有重要的临床价值。     

Plasma levels of atrial natriuretic peptide in patients with liver cirrhosis and its relation to ascites and renal function

Plasma immunoreactive a-human atrial natriuretic polypeptide (Ir-α-hANP) was measured by radioimmunoassay in 21 cirrhotics and 10 normal subjects. Average of Ir-α-hANP level in cirrhotics was significantly higher than in normal subjects (125.8 ± 79.6 versus 28.7 ± 12.2 pg/ml, P< 0.001). In cirrhotics without ascites, Ir-α-hANP levels were positively correlated with creatinine clearance (Ccr) and urinary sodium excretion, suggesting that α-hANP was closely related to renal circulation and sodium homeostasis. One the contrary, in cirrhotics with ascites Ir-α-hANP levels were negatively correlated with Ccr. Urinary sodium excretion in cirrhotics with ascites and Ccr more than 50 ml/min was positively correlated with Ir-α-hANP levels. However, cirrhotics with ascites and Ccr less than 50 ml/min excreted little sodium in spite of high Ir-α-hANP levels. On the basis of the Ir-α-hANP before and after treatment of ascites, cirrhotics with ascites were subdivided into 2 groups. In group I Ir-α-hANP decreased from high values and in group II it was further elevated from slightly high values by treatment. The difference in renal function and plasma volume may account for the difference in Ir-α-hANP changes in the 2 groups. This study was presented in part in the 22nd meeting of the Japanese Association for the Study of the Liver, June 6,1986, Tokyo, Japan and in 22nd meeting of the European Association for the Study of the Liver, September 5, 1987, Torino, Italy.     

Atrial natriuretic factor in essential hypertension: echocardiographic and humoral correlates.

Aim of this study was to assess the relationship between plasma concentration of atrial natriuretic factor (ANF) and its two-dimensional echocardiographic (left ventricular mass, left atrium diameter) and humoral (plasma renin and aldosterone) variables in essential hypertension (EH). We evaluated 32 patients with uncomplicated mild to moderate EH and 10 controls. They were studied in the supine position after 7 days of constant dietary sodium intake and were off therapy since at least 3 weeks. ANF values overlapped between EH patients and controls (27.8 +/- 11.5 vs. 19.5 +/- 7.4 pg/ml, p = NS). In EH, no significant correlation was found between ANF values and left ventricular mass (r = 0.29), left atrial diameter (r = 0.04), mean arterial blood pressure (r = 0.26), plasma renin activity (r = 0.00), and aldosterone (r = 0.26). In EH, ANF values overlapped between the 15 patients with hypertrophy and the 17 patients with normal ventricular mass: 30.3 +/- 17 vs. 25.6 +/- 10.6 pg/ms (p = NS). We conclude that there is a substantial overlap in plasma ANF values between mild to moderate uncomplicated EH and controls, and left ventricular hypertrophy is not a major independent stimulus to ANF release in EH.     

Relations between medical history, clinical findings and plasma N-terminal proatrial natriuretic peptide in patients in primary health care

BACKGROUND: recent studies indicate that measurement of natriuretic peptides may be a valuable tool to improve the quality of the diagnosis of heart failure in general practice. AIM: the aim of the present study was to examine the relationship between the plasma level of the natriuretic peptide N-terminal proANP and symptoms and signs of heart failure in patients from general practice in the Oslo area. Methods and RESULTS: we undertook a survey of 499 patients consecutively enrolled from the practice of 27 practitioners. One hundred and twenty-nine patients were classified as having possible or some degree of heart failure. The plasma concentration of N-terminal proANP increased with severity of heart failure as judged from clinical examination. In multivariate analysis age, history of heart disease, plasma creatinine, use of beta-blockers and digitalis, oedemas and atrial fibrillation were the main determinants of plasma N-terminal proANP. CONCLUSION: while there was an overall increase in N-terminal proANP values with increasing symptoms and degree of heart failure, no single finding was closely related to N-terminal proANP. Treatment effects and diagnostic errors may both influence the relationship between N-terminal proANP and clinical findings. The current study has demonstrated the feasibility of using N-terminal proANP by general practitioners for the potentially improved diagnosis of heart failure. Further research is required to determine the precise role of this assay in clinical practice.