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NT-proBNP for Risk Prediction in Heart Failure
Quick Takes
- BMI is an independent and inverse predictor of NT-proBNP levels despite adjusting for several other clinical covariates. NT-proBNP levels were higher in women across all BMI categories.
- NT-proBNP predicted all-cause and cardiac cause mortality in all BMI categories independent of LVEF.
- Compared to normal weight individuals, optimal cutoff for NT-proBNP levels for risk prediction was substantially higher in underweight patients and lower in overweight and obese patients.
Study Questions:
What is the impact of body mass index (BMI) on the association between N-terminal pro–B-type natriuretic peptide (NT-proBNP) and outcomes in patients with chronic heart failure (HF)?
Methods:
This was a retrospective analysis of the BIOS (Biomarkers In Heart Failure Outpatient Study) registry that enrolled patients with chronic stable HF. Patients were classified as: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), mildly obese (BMI 30-34.9), moderately obese (BMI 35-39.9), or severely obese (BMI ≥40). Based on left ventricular ejection fraction (LVEF), patients were characterized as HF with reduced EF (HFrEF: EF <40%), HF with midrange EF (EF 40-49%), or HF with preserved EF (HFpEF: ≥50%). Outcomes assessed included all-cause and cardiac cause mortality.
Results:
A total of 12,763 patients were included, comprising 33% normal weight, 40% overweight, 17% mildly obese, 5% moderately obese, 3% severely obese, and 2% underweight. Men were most often overweight (43%) and women were most often normal weight (36%). Across all BMI categories, HFrEF was the most common diagnosis but HFpEF was more common in obese. NT-proBNP levels decreased with increase in BMI and women had a higher NT-proBNP than men across all BMI categories. There was an inverse relationship between NT-proBNP levels and BMI despite adjustment for several other clinical confounders.
Over a median follow-up duration of 42 months, both all-cause and cardiac cause mortality were highest in underweight patients followed by normal weight, overweight, mildly obese, moderately obese, and severely obese. In multivariable Cox analyses, higher NT-proBNP levels were associated with higher risk for all-cause mortality independent of sex, LVEF, and other covariates in all BMI categories. Rising NT-proBNP levels were also associated with higher risk for cardiac mortality in all BMI categories except severely obese. Compared to normal weight patients, optimal NT-proBNP cutoff for risk prediction was 73% higher in underweight patients. However, it was 30%, 52%, 66%, and 60% lower in overweight, mild, moderate, and severely obese patients.
Conclusions:
In a large, international cohort of HF patients, BMI was an independent predictor of NT-proBNP levels despite adjustment for several other confounders. Rising NT-proBNP levels were an independent predictor of all-cause or cardiac cause mortality across all BMI categories. The optimal NT-proBNP cutoff level for risk prediction varied by BMI and was substantially higher in women across all BMI categories.
Perspective:
Inverse correlation between NT-proBNP levels and BMI has been extensively described. Proposed mechanisms include increased NT-proBNP clearance due to renal hyperfiltration or decreased production due to reduced wall stress from epicardial adiposity or increased androgen levels suppressing BNP gene expression. In this study, the predictive ability of NT-proBNP as a marker of adverse events in patients with HF across the full spectrum of LVEF was confirmed across all BMI categories. Important take-aways that are relevant to clinical practice include higher NT-proBNP levels noted in women compared to men across all BMI categories and the fact that the optimal NT-proBNP cutoff levels for risk prediction are very different for underweight, overweight, and obese patients compared to normal weight patients. This is particularly important as several HF trials still enroll patients based on a single BMI cutoff irrespective of their sex and BMI. With the rising prevalence of obesity, this needs to be reconsidered.
Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Adiposity, Biomarkers, Body Mass Index, Heart Failure, Natriuretic Peptide, Brain, Obesity, Outpatients, Overweight, Peptide Fragments, Risk Assessment, Secondary Prevention, Stroke Volume, Thinness, Ventricular Function, Left
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