Malnutrition outweighs the effect of the obesity paradox

Abstract

Background: High body mass index (BMI) is paradoxically associated with better outcome in patients with heart failure (HF). The effects of malnutrition on this phenomenon across the whole spectrum of HF have not yet been studied.

Methods: In this observational study, patients were classified by guideline diagnostic criteria to one of three heart failure subtypes: reduced (HFrEF), mildy reduced (HFmrEF), and preserved ejection fraction (HFpEF). Data were retrieved from the Viennese-community healthcare provider network between 2010 and 2020. The relationship between BMI, nutritional status reflected by the prognostic nutritional index (PNI), and survival was assessed. Patients were classified by the presence (PNI < 45) or absence (PNI ≥ 45) of malnutrition.

Results: Of the 11 995 patients enrolled, 6916 (58%) were classified as HFpEF, 2809 (23%) HFmrEF, and 2270 HFrEF (19%). Median age was 70 years (IQR 61-77), and 67% of patients were men. During a median follow-up time of 44 months (IQR 19-76), 3718 (31%) of patients died. After adjustment for potential confounders, BMI per IQR increase was independently associated with better survival (adj. hazard ratio [HR]: 0.91 [CI 0.86-0.97], P = 0.005), this association remained significant after additional adjustment for HF type (adj. HR: 0.92 [CI 0.86-0.98], P = 0.011). PNI was available in 10 005 patients and lowest in HFrEF patients. PNI was independently associated with improved survival (adj. HR: 0.96 [CI 0.95-0.97], P < 0.001); additional adjustment for HF type yielded similar results (adj. HR: 0.96 [CI 0.96-0.97], P < 0.001). Although obese patients experienced a 30% risk reduction, malnutrition at least doubled the risk for death with 1.8- to 2.5-fold higher hazards for patients with poor nutritional status compared with normal weight well-nourished patients.

Conclusions: The obesity paradox seems to be an inherent characteristic of HF regardless of phenotype and nutritional status. Yet malnutrition significantly changes trajectory of outcome with regard to BMI alone: obese patients with malnutrition have a considerably worse outcome compared with their well-nourished counterparts, outweighing protective effects of high BMI alone. In this context, routine recommendation towards weight loss in patients with obesity and HF should generally be made with caution and focus should be shifted on nutritional status.

Keywords: Heart failure; Malnutrition; Obesity paradox; PNI.

Figure 1

The obesity paradox across the spectrum of heart failure (HF). Distribution of body mass index (BMI) (left), the hazard ratios (HR) for all‐cause mortality with 95% confidence intervals (CI) according to the BMI strata (middle) and restricted spline curves examining the association of BMI and outcome (right) are shown for heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF).

Figure 2

Association of body mass index (BMI) and all‐cause mortality in various subgroups. The median value was used as the cut‐off for continuous data.

Figure 3

Distribution of the prognostic nutritional index (PNI) according to heart failure phenotype. The dashed vertical line indicates the cut‐off for malnutrition (PNI < 45).

Figure 4

(Left) Hazard ratios (HR) for all‐cause mortality with 95% confidence intervals are shown for body mass index (BMI) in relation to low and high prognostic nutritional index (PNI). (Right) Kaplan–Maier curves showing all‐cause mortality for prespecified BMI groups stratified by nutritional status. The P‐value of a log‐rank test for trend is shown for each plot.