N-Terminal Pro-Brain Natriuretic Peptide and Heart Failure Risk Among Individuals With and Without Obesity

Ndumele CE, Matsushita K,  Sang Y, et al.
Circulation. 2016;133:631-638

Background

The addition of NT-proBNP, the N-terminal fragment of the prohormone for BNP, to traditional risk factors significantly improves the risk prediction of HF [10], since it is:

• a diagnostic marker for HF severity [1]
• associated with subclinical LV dysfunction in asymptomatic subjects [2]
• independently associated to incident HF in the general population [3]

On the other hand: 

• proBNP is inversely associated with BMI, e.g. lower among obese individuals irrespective of the existence or absence of HF [4], although obesity is associated with HF [5]
• there is a poor correlation between natriuretic peptide levels and LV filling pressures among obese subjects compared with those who are not obese [6]
• obese patients undergoing cardiac catheterization have lower NT-proBNP levels, despite higher average LV end-diastolic pressures [7]

The inverse relationship between BMI and NT-proBNP has led to concerns about the use of NT-proBNP for the diagnosis of HF in obese individuals [8], however there are no data on the prognostic value of NT-proBNP for HF risk prediction of obese individuals.
This study assessed the utility of NT-proBNP for HF risk prediction across different BMI categories in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based cohort of 15.792 middle-aged individuals, who had no history of HF at baseline, and were followed-up for a median of 20.6 years. 12.230  ARIC participants free of prior HF at baseline and with BMI ≥ 18.5 kg/m² were followed up.

Main results

• NT-proBNP was inversely correlated with BMI: Pearson correlation coefficient: −0.10; P<0.001
• Higher BMI category at baseline was associated with higher rates of HF, with incidence rates per
1000 person-years:

• normal weight: 5.6
• overweight: 7.5
• obesity: 11.6
• severe obesity: 16.8

• At each NT-proBNP level, higher BMI was associated with greater absolute HF risk. For NT-proBNP of 100 to <200 pg/mL, the average 10-year HF risk was:

• normal-weight: <5%
• severe obesity: >10%

• NT-proBNP increase from 25 to 150 pg/mL was associated with an incidence rate difference for HF (per 1000 person-years) of

• severe obesity: 11.0
• normal weight:  5.1

• NT-proBNP improved HF risk prediction overall, even among those with severe obesity: BMI ≥35 kg/m²: improvement in C statistic 0.032; 95% CI: 0.011–0.053
• Assessment of the NT-proBNP levels leading to pre-specified 10-year HF risk of 10% in each BMI category at mean levels of all covariates:

• severe obesity: median NT-proBNP levels of 119 pg/mL (95% CI: 83–177 pg/mL)
• obesity: median NT-proBNP levels of 289 pg/mL (95% CI: 195–500 pg/mL)
• overweight: median NT-proBNP levels of 473 pg/mL (95% CI: 318–778 pg/mL)
• normal-weight: median NT-proBNP levels of 489 pg/mL (95% CI: 367–703 pg/mL)

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Conclusion

In a large community-based cohort with a long follow-up, NT-proBNP provided significant prognostic information regarding the risk of developing HF even among individuals with obesity, despite its inverse relationship with BMI. Due to the higher baseline HF risk among obese individuals, slight elevations in NT-proBNP may flag an increased absolute HF risk.

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References

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