The Plasma Level of B-Type Natriuretic Peptide is a Useful Predictor of Cardiac Events for Out-Clinic Patients with Asymptomatic Heart Failure

Tojo T; Yamaoka-Tojo M

Research Article

Austin J Cardiovasc Dis Atherosclerosis. 2021; 8(1): 1041.

The Plasma Level of B-Type Natriuretic Peptide is a Useful Predictor of Cardiac Events for Out-Clinic Patients with Asymptomatic Heart Failure

Tojo T¹ and Yamaoka-Tojo M²*

¹Department of General Medicine, Sagamihara Kyodo Hospital, Sagamihara, Japan

²Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara, Japan

*Corresponding author: Yamaoka-Tojo M, Department of Rehabilitation, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0373, Japan

Received: February 19, 2021; Accepted: March 04, 2021; Published: March 11, 2021

Abstract

Purpose: The circulating level of B-type Natriuretic Peptide (BNP) is recognized as a biomarker of ventricular dysfunction. In the field of primary prevention, BNP is a useful predictor of cardiac death, heart failure, cerebral infarction, and atrial fibrillation. On the other hand, the predictive value of BNP has not been fully elucidated in patients with coronary artery disease and/or those who are prone to atherosclerosis.

Methods: We analyzed 679 patients (average age, 65.3 years; 29.2% women) with asymptomatic heart failure (ACC/AHA stage A to B) undergoing total risk management for cardiovascular disease prevention in the Kitasato Registry for Cardiovascular Disease Prevention. The mean follow-up period was 8.4 years (range, 73–3686 days) for all study patients.

Results: Among all patients, 54.0% had coronary artery disease, 54.2% had hypertension, 55.7% had dyslipidemia, 31.2% had diabetes mellitus, and 15.5% had atrial fibrillation. The baseline level of plasma BNP was 47.5 (63.8) [mean (SD)] pg/mL. The plasma BNP level correlated with age and the serum creatinine level. The presence of coronary artery disease or atrial fibrillation significantly affected the plasma level of BNP (P <0.05, P <0.01; respectively). Plasma BNP levels were significantly higher in the event group than in the event-free group [80.4 (123.3) vs. 43.4 (50.8) pg/mL, P <0.0001]. Of all patients, 59 experienced cardiac events and 10 died during the study period. In the multivariate analysis, plasma BNP level, age, and diabetes mellitus were identified as predictive factors. The Cox proportional hazards model showed that the plasma BNP level was an independent predictor of cardiac death. The event-free rate was significantly higher in patients with BNP of 40 pg/mL or less than in those with BNP of 40pg/mL or more.

Conclusions: In the present long-term follow-up study, we found that the plasma level of BNP of patients who are in a stable condition was a useful prognostic marker. Circulating levels of plasma BNP could be an independent predictor of cardiac events in patients with asymptomatic heart failure.

Keywords: B-type Natriuretic Peptide; Atrial fibrillation; Atherosclerosis

Background

The circulating level of B-type Natriuretic Peptide (BNP) is recognized as a biomarker of increasing atrial and ventricular pressure and volume overloads [1,2]. Increasing plasma BNP levels are related to myocardial hypoxia [3,4]. In the field of primary prevention, BNP is a useful predictor of cardiac death, heart failure, cerebral infarction, atrial fibrillation, cardiac surgery [5], and ischemic heart disease [6-10].

Accumulating evidence revealed that BNP is an important indicator in risk stratification for patients with acute myocardial ischemia [11], with reduced event-free survival rate [12-14]. Circulating BNP concentration is associated with adverse long-term clinical outcomes among patients with Non-ST-Segment Elevation Acute Myocardial Infarction (NSTEMI) without Creatinine Kinase (CK) elevation (NSTEMI-CK) who considered low risk [15]. Although the usefulness of plasma BNP measurement for ischemic heart disease in the acute phase has been clarified, the predictivity of BNP as a prognosis biomarker in the chronic phase is controversial. In chronic patients with Coronary Artery Disease (CAD), the predictive value of BNP has not been fully elucidated [16]. The aim of the study is to examine whether or not the circulating levels of BNP could be a predictive biomarker in patients with CAD and/or those who are prone to atherosclerosis.

Methods

Subjects

The study included 679 Japanese patients of atherosclerosisprone or coronary artery disease with asymptomatic heart failure (ACC/AHA stage A or B) undergoing total risk management for cardiovascular disease prevention in the Kitasato Registry for Cardiovascular Disease Prevention, Kitasato University East Hospital. The study project was approved by the Scientific and Ethical Committee of the Kitasato University School of Medicine, Japan. Patients were monitored for major adverse cardiac events and recurrences of CAD over a median 8.4 years.

Blood sample collection and measurement of clinical biomarkers

Blood samples were collected by venipuncture after an overnight fast from all patients. Biochemical markers, such as triglyceride, Low Density Lipoprotein (LDL) cholesterol, High Density Lipoprotein (HDL) cholesterol, plasma glucose, glycated haemoglobin (HbA1c), uric acid, Gamma-Glutamyl Transpeptidase (γ-GTP), C - Reactive Protein (CRP), and BNP were measured in annual health checkup in the Kitasato East Hospital.

Statistical analysis

Continuous data were summarized as either mean ± SD or median and quartiles, and categorical data were expressed as percentages. Data were compared by unpaired t-test or Mann- Whitney U-test where appropriate. Differences in proportions of variables were determined by chi-squared analysis. To evaluate the correlations between BNP and selected variables, we calculated Spearman correlation coefficients between circulating levels of BNP and other clinical biomarkers. Survival curves were estimated using Kaplan-Meier analysis. The cumulative incidence of all-cause death and Major Adverse Cardiac Events (MACE) for each biomarker was compared using log-rank test. A two-sided P value less than 0.05 was considered statistically significant.

Results

Study population and patient characteristics

A total of 679 patients in CAD or its prone, who have taken appropriate cardiovascular disease management with annual health checkup in Kitasato University East Hospital, were included (female 27.9%). Comprehensive data on demographics, medical history, medication use, smoking status and anthropometric parameters including body mass index and blood pressure were recorded at enrollment.

Their median age was 66 years old, and average follow-up period was 7.9 years (median 8.4 years). All patients received evidence-based medical therapies and guideline-based instruction for cardiovascular disease management.

Among all patients, 54.0% had coronary artery disease, 54.2% had hypertension, 55.7% had dyslipidemia, 31.2% had diabetes mellitus, and 15.5% had atrial fibrillation. The baseline level of plasma BNP was 47.5 ± 63.8 pg/mL. The plasma BNP level correlated with age and the serum creatinine level. The presence of coronary artery disease or atrial fibrillation significantly affected the plasma level of BNP (P <0.05, P <0.01; respectively). Plasma BNP levels were significantly higher in the event group than in the event-free group (80.4 ± 123.3 vs. 43.4 ± 50.8 pg/mL, P <0.0001).

Baseline characteristics for patients with and without CAD are presented in (Table 1). The presence of hypertension, diabetes, dyslipidemia, smoking, and obesity, were high in CAD patients. Risk scores as total numbers of coronary risk factors, like as hypertension, diabetes, dyslipidemia, smoking and obesity, were high in CAD patients.

Table 1: Baseline characteristics of the patients.




  
    
    Non-CAD (n=305)
    CAD (n=374)
  
  
    Age (years), mean ± SD
    63.6 ± 11.2
    65.9 ± 9.9*
  
  
    Female (%)
    116 (38.0)
    80 (21.4)*
  
  
    BMI (kg/m2)
    24.1 ± 3.2
    24.3 ± 3.7
  
  
    Medical History
    
    
  
  
    Hypertension (%)
    192 (63.0)
    162 (43.3)*
  
  
    Diabetes (%)
    67 (22.0)
    135 (36.1)*
  
  
    Dyslipidemia (%)
    135 (44.3)
    232 (62.0)*
  
  
    Risk Scores¶, mean ± SD
    1.4 ± 1.0
    2.6 ± 1.0*
  
  
    BNP (pg/mL), mean ± SD
    38.2 ± 40.9
    47.3 ± 56.9*
  
  
    HbA1c (%), mean ± SD
    5.3 ± 1.3
    5.7 ± 1.4*
  
  
    Cr (mg/dL), mean ± SD
    0.8 ± 0.2
    0.9 ± 0.5*
  
  
    Mean ± SD

      *Statistically    significant.

      ¶Risk    scores are total numbers of coronary risk factors (hypertension, diabetes,    dyslipidemia, smoking, and obesity).

      CAD: Coronary Artery Disease; BMI: Body Mass    Index; BNP: Brain Natriuretic Peptide; Cr: Serum Creatinine.



Table 1: Baseline characteristics of the patients.

As expected, serum levels of HbA1c, creatinine BNP were significantly increased in CAD patients compared with non-CAD patients. Serum levels of HbA1c, creatinine BNP were significantly increased in CAD patients compared with non-CAD patients.

Total events and death

During the follow-up period 10 (1.5%) died and 59 (8.7%) patients experienced a cardiac event. during the follow-up period (Figure 1).

Figure 1: Proportion of total events and death during the study period in patients who registered in the Kitasato Registry for Cardiovascular Prevention. In total, 679 patients (female 27.9%) were included and their median age was 66 years old. Average follow-up period was 7.9 years (median 8.4 years).

    
    
    Figure 1: Proportion of total events and death during the study period in
patients who registered in the Kitasato Registry for Cardiovascular Prevention.
In total, 679 patients (female 27.9%) were included and their median age was
66 years old. Average follow-up period was 7.9 years (median 8.4 years).

Plasma BNP levels in patients with or without CAD

The presence of CAD significantly affected the plasma level of BNP (Figure 2). Of course, history of hospitalization for heart failure or chronic kidney disease (CKD) also strongly correlated with circulating level of BNP. Plasma BNP levels had no correlated with CRP or white blood cell counts, which are general indicators of systemic inflammation (Figure 2).

Figure 2: Plasma BNP levels in patients with or without CAD.

    
    
    Figure 2: Plasma BNP levels in patients with or without CAD.

Circulating plasma levels of BNP was significantly increased in CAD patients rather than non-CAD patients. Values are means (red line) P <0.05. BNP: Brain Natriuretic Peptide; CAD: Coronary Artery Disease.

MACE in patients with adequate disease management

Interestingly, the history of CAD was not affected cardiac events in the future between stable high-risk patients with atherosclerosisprone and stable CAD (Figure 3).

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Citation: Tojo T and Yamaoka-Tojo M. The Plasma Level of B-Type Natriuretic Peptide is a Useful Predictor of Cardiac Events for Out-Clinic Patients with Asymptomatic Heart Failure. Austin J Cardiovasc Dis Atherosclerosis. 2021; 8(1): 1041.

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