Relative B-Type Natriuretic Peptide Deficiency May Exist in Diastolic Dysfunction in Subclinical Population

Abstract

Background: Heart failure patients are deficient in B-type natriuretic peptide (BNP) but the significance of subclinical BNP deficiency is unclear. Methods and Results: A total of 1,398 subjects without cardiovascular disease, with left ventricular ejection fraction (LVEF) ≥50% and BNP level <100 pg/mL, were selected from a 2005-2008 health checkup in Arita-cho, Japan, and divided into 2 groups: with and without LV diastolic dysfunction (DD+ or DD-). We performed propensity score matching on non-cardiac factors affecting BNP levels and analyzed 470 subjects in each group (372/940 men; median age, 66 years). The DD(+) group showed higher lateral E/e', an index of estimated left ventricular filling pressure, and greater prevalence of concentric hypertrophy (CH) despite similar BNP levels, suggesting a relative deficiency of BNP in DD(+) compared with DD(-). Multivariable logistic regression analysis revealed an increase in BNP correlated with decreased odds of CH (adjusted odds ratio [aOR] 0.663, 95% confidence interval (CI) 0.484-0.909, P=0.011), whereas an increase in lateral E/e' was associated with increased odds of CH (aOR, 2.881; 95% CI, 1.390-5.973; P=0.004). Furthermore, CH in combination with diastolic dysfunction independently predicted major adverse cardiovascular events (hazard ratio 3.272, 95% CI 1.215-8.809; P=0.019). Conclusions: Relative BNP deficiency was associated with CH, which had a poor prognosis in patients with diastolic dysfunction.

Keywords: B-type natriuretic peptide; Diastolic dysfunction; Left ventricular hypertrophy.

Figure 1.

Study flowchart. The study population included 1,632 participants in the Arita-cho health check program from 2005 to 2008 (the Arita-cho cohort study); we enrolled 1,398 participants without heart disease and divided them into “no LV diastolic dysfunction” and “LV diastolic dysfunction” groups. We then used propensity score matching for age, sex, body mass index, systolic blood pressure, eGFR, and medical history (hypertension, dyslipidemia, and diabetes mellitus). Ultimately, we analyzed 470 participants in each group for a total of 940 participants. BNP, B-type natriuretic peptide; eGFR, estimated glomerular filtration rate; LV, left ventricle; LVEF, left ventricular ejection fraction.

Figure 2.

Correlation between lateral E/e' and plasma BNP levels in subjects with and without LV diastolic dysfunction. (A) Correlation in subjects without LV diastolic dysfunction (N=470), showed a significant positive correlation between lateral E/e' and plasma BNP levels (r=0.187, P<0.001). (B) Same correlation in subjects with LV diastolic dysfunction (N=470) was not statistically significant (r=0.062, P=0.183). Data points are color-coded based on LV geometries: normal geometry is shown in blue, concentric remodeling in red, concentric hypertrophy in green, and eccentric hypertrophy in orange. The effect of concentric hypertrophy on the correlation between lateral E/e' and plasma BNP levels is highlighted, with a significantly different pattern observed in subjects with LV diastolic dysfunction (P=0.008) compared with other geometries, in contrast to those without (P=0.141). BNP, B-type natriuretic peptide; LV, left ventricle; r, Pearson's correlation coefficient.

Figure 3.

Kaplan-Meier analysis of LV diastolic dysfunction and concentric hypertrophy. (A) Kaplan-Meier analysis for MACE (composite endpoint of cardiovascular death, occurrence of acute myocardial infarction and stroke, hospitalization due to heart failure, and ischemic cardiovascular events) showed that the presence of LV diastolic dysfunction did not stratify the risk of MACE (log-rank P=0.425). (B) In the population without LV diastolic dysfunction (N=470), the presence of LV concentric hypertrophy did not stratify the risk of MACE (log-rank P=0.897). (C) In patients with LV diastolic dysfunction (N=470), LV concentric hypertrophy was associated with higher rates of MACE (log-rank P=0.039). LV, left ventricle; MACE, major adverse cardiovascular events.