Obesity Paradox and the Effect of NT-proBNP on All-Cause and Cause-Specific Mortality

In heart failure patients, obesity is associated with better outcomes as compared to normal weight, a phenomenon called the obesity paradox.

To examine if obesity modifies the relationship between NT-proBNP and all-cause and cause-specific mortality in adults without coronary artery disease or heart failure history.

We used the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and linked it with mortality through December 31, 2019. Participants > 18 years were categorized into normal weight (BMI ≤ 25 kg/m²), overweight (BMI > 25-29.9 kg/m²) and obese (BMI > 29.9 kg/m²). NT-proBNP levels were categorized as low (< 126 pg/mL) or high (≥ 126 pg/mL). Using Cox proportional hazard models, we examined effect modification by obesity using interaction, without and with adjusting for potential confounders.

Of the 12 621 participants, 2794 (22%) died during 202 859 person-years follow-up. In adjusted models, normal-weight participants with high NT-proBNP had 2 times higher all-cause mortality risk than those with low NT-proBNP (HR = 2.05; 95%CI = 1.74, 2.41; p < 0.001); however, this mortality risk was 27% lower in obese participants (HR interaction = 0.73; 95%CI = 0.59, 0.92; p = 0.008). Similarly, in normal-weight participants, the difference in other-cause mortality risk between high and low NT-proBNP participants was significant in adjusted models (HR = 2.27; 95%CI = 1.81, 2.85; p < 0.001) and obese participants had 48% lower other-cause mortality risk between those with high and low NT-proBNP (interaction HR = 0.52; 95%CI = 0.36, 0.77; p = 0.001). Conversely, obesity did not modify the relationship between NT-proBNP and cardiovascular or cancer mortality.

In patients free of heart failure or coronary artery disease, obesity may be protective against mortality associated with high NT-proBNP.