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September 3, 2026Circulation Journal0 citationsOpen Access

Association Between Changes in Serum N-Terminal Pro B-Type Natriuretic Peptide Levels and All-Cause and Cause-Specific Mortality ― The Hisayama Study ―

AKAsahi KatoHeart Failure / CardiomyopathyEOEmi OishiGeneral / Preventive / LipidsAMAkihiro MaezonoElectrophysiology

Key Result

An increase in serum NT-proBNP concentrations of 25% or more over 5 years was associated with a 73% higher risk of all-cause mortality (HR 1.73) compared to no change in a Japanese community cohort.

Key Points

  • Investigate the association between dynamic changes in serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and risks of all-cause and cause-specific mortality in a general Asian population.
  • Evaluated longitudinal changes in circulating serum NT-proBNP concentrations within the population-based Hisayama Study cohort.
  • Assessed prospective risk associations for all-cause and cause-specific death over long-term follow-up.
  • Tracked temporal shifts in NT-proBNP to determine prognostic value for general and specific mortality risks.
  • Identified longitudinal increases in cardiac strain biomarkers as indicators of elevated long-term mortality risk.

Study Design

Type

Cohort (n=2,703)

Multicenter

No

Structured PICO

Does an increase in serum NT-proBNP concentrations over 5 years predict higher all-cause and cause-specific mortality in a general Asian population?

P
Population
2,703 community-dwelling Japanese residents aged ≥40 years with serial NT-proBNP measurements, followed for a median of 10.3 years.
E
Exposure
Increasing serum NT-proBNP concentrations (change ≥+25%) over a 5-year period (2002-2003 to 2007-2008).
C
Comparator
No change in serum NT-proBNP concentrations (-25% < change < +25%) over the same 5-year period.
O
Outcome
All-cause and cause-specific mortality (cardiovascular, non-cardiovascular, cancer, or other causes) over a median 10.3 years follow-up.hard clinical

Longitudinal increases in serum NT-proBNP over 5 years are significantly associated with higher risks of all-cause and cardiovascular mortality in the general Japanese population.

Main Result

Hazard Ratio: 1.73 (95% CI 1.37–2.17)

Absolute Event Rate: 26.7% vs 16.1%

p-value: p=<0.001

Limitations

  • Could not account for influencing factors such as lifestyle modifications, medication use, or hospitalizations for heart failure during the 5-year evaluation period.
  • Lacked data on morphological and functional cardiac information, such as echocardiography.
  • Limited number of cause-specific deaths and relatively short follow-up period precluded detailed examination of cause-specific mortality.
  • Potential reverse causality, as higher serum NT-proBNP concentrations may reflect subclinical disease, frailty, or systemic illness.
  • Selection bias due to the exclusion of approximately 18% of the study population who lacked health checkup data from 2007–2008.
  • Limited generalizability because the study was conducted in a single region of Japan.
  • residual confounding
  • reverse causation

Abstract

Background: Few epidemiological studies have investigated the association between changes in serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and mortality in the general Asian population.

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Cite This Study

Kato et al. (2026) conducted a cohort in General population (n=2,703). Increasing serum NT-proBNP (change ≥ +25%) vs. No change in serum NT-proBNP (-25% < change < +25%) was evaluated on All-cause mortality (HR 1.73, 95% CI 1.37-2.17, p=<0.001). An increase in serum NT-proBNP concentrations of 25% or more over 5 years was associated with a 73% higher risk of all-cause mortality (HR 1.73) compared to no change in a Japanese community cohort.

synapsesocial.com/papers/6a993511636c6408cfa7ce35https://doi.org/10.1253/circj.cj-25-1168
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