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Impact of age and sex on plasma natriuretic peptide levels in healthy adults

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Abstract

Assays for natriuretic peptides have received considerable attention as potential screening tests for congestive heart failure and left ventricular dysfunction. However, information regarding the impact of age, sex, and other physiologic characteristics on natriuretic peptide levels is limited. We examined a healthy reference sample of 911 subjects (mean age 55 years, 62% women) from the Framingham Heart Study who were free of hypertension, valvular disease, diabetes, atrial fibrillation, obesity, coronary heart disease, congestive heart failure, and renal failure, and who had normal left ventricular systolic function. Plasma brain natriuretic peptide and N-terminal atrial natriuretic peptide levels were measured, and multivariable regression used to assess correlates of natriuretic peptide levels. The strongest predictors of higher natriuretic peptide levels were older age and female sex. Other multivariable predictors included lower diastolic blood pressure (higher pulse pressure), lower body mass index, and higher left atrial size. Reference limits were then formulated based on the empirical distribution of natriuretic peptide levels by gender both across all ages and partitioned by age. Age-pooled reference limits compared with age-specific limits classified a higher proportion of healthy elderly subjects (17% vs 2.5%), but a lower proportion of healthy young subjects (1% vs 2.5%) as “abnormal.” We conclude that interpretation of natriuretic peptide levels should take into consideration gender and possibly age. The reference limits derived from this large, healthy community-based sample will aid in the identification of elevated natriuretic peptide levels in clinical practice.

Section snippets

Study sample:

The selection criteria and design of the Framingham Heart Study have been described previously.7 The offspring cohort began in 1971 with the recruitment of 5,124 men and women who were offspring or spouses of the offspring of the original Framingham cohort. The 3,532 participants who attended the sixth offspring examination cycle (1995 to 1998) were eligible for the present investigation. All attendees underwent routine physical examination (with a medical history), laboratory assessment of

Results

Characteristics of the subjects in the reference sample are displayed in Table 1. Mean age was 55 years, and 62% were women. Compared with men, women had higher mean levels of BNP and NT-ANP (both p ≤0.0001).

Impact of gender on natriuretic peptide levels:

Women had markedly higher natriuretic peptide levels than men, a finding that has been reported by several other investigators.11, 12, 13 The physiologic basis for these sex-related differences is unclear, although the stimulatory effect of female sex hormones on natriuretic peptide gene expression14 and extracardiac sources of natriuretic peptides within the female reproductive tract have been proposed.15 It is notable that a sexual dimorphism in plasma renin levels also exists, with higher

Acknowledgements

We would like to thank Marc A. Pfeffer, MD, PhD, and Hisako Tsuji, MD, for their valuable input. In addition, Shionogi & Co., Ltd. provided important assistance and performed the natriuretic peptide assays.

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    This work was supported in part by Contracts N01-HC-25195, R01 HL64753, R01-NS-17950, and 1R01HL67288-01 and Dr. Vasan was supported by Contract K24 HL 04334-01A1 from the National Institutes of Health/National Heart, Lung, and Blood Institute, Bethesda, Maryland.

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