The results of the present investigation are consistent with previous trials2,7
demonstrating that a higher BMI, although it increases the risk for the development of HF8
, improves survival once a patient is diagnosed with this condition. Previous investigations have used various low-end thresholds to define normal weight including ≥18.5 kg/m2 9
and ≥22.0 kg/m2 10
. Our findings are consistent with previous investigations by demonstrating prognosis was poor in normal weight individuals using both of these low-end thresholds to define this BMI class. Recognizing the limitations of BMI in accurately reflecting true body composition in all instances, using a threshold of ≥22.0 kg/m2
to define the beginning of the normal weight classification may indicate the protective effect of a higher BMI in HF is not entirely explained by malnourishment and cardiac cachexia.11
Our findings indicate that, despite differences in age, gender distribution, BMI, and pharmacologic management, both ischemic and non-ischemic HF patients classified as obese have the most favorable survival trends.
Several physiologic mechanisms for the protective effect of a higher BMI in HF have been proposed, including the ability of adipose tissue to counteract higher levels of circulating inflammatory markers such as tumor necrosis factor.2
Previous research has also demonstrated inflammatory cytokines are significantly lower in patients with non-ischemic HF compared to those with an ischemic etiology.12
Perhaps the lower adipose tissue levels in overweight patients with ischemic HF are not sufficient to provide a favorable prognostic effect. Conversely, although higher than that in apparently healthy individuals, the generally lower levels of inflammatory cytokines in patients with non-ischemic HF may be better counteracted with the adipose tissue levels associated with a BMI between 25.0 and 29.0 kg/m2
. B-type natriuretic peptide has also been found to decrease as BMI increases in patients with HF.13
As with inflammatory cytokines, this important neurohormone has also been found to be lower in patients with non-ischemic HF compared to those with an ischemic etiology.14
These findings may lend further support to the hypothesis that BMI levels in the obese range are needed for improved outcomes in patients with ischemic HF while overweight BMI levels may be sufficient for the non-ischemic population. The present data do not allow for assessment of this hypothesis, but suggest further research in this area.
A limitation of our study in common with prior reports is that we cannot exclude a potential contribution of non-intentional weight loss, which may comprise a substantial portion of sustained weight loss in general patient populations. Also like other studies, there were relatively few patients with morbid obesity (BMI ≥ 40) and thus there is uncertainty whether the trends in prognosis with BMI extend to such patients. It is possible that exercise-induced weight loss, which has been shown to favorably impact inflammatory cytokines15
and neurohormonal levels16,17
in other populations, may allow for achievement of optimal body composition without an increased risk for adverse events in patients with HF. Ultimately, randomized intervention studies will be required to fully understand the relationship of BMI with HF outcomes and its mechanisms.
slope has been shown to be related to cardiovascular function.18,19
The fact that this CPX variable is less dependent upon subject effort, and thus potentially a better reflection of cardiovascular health in many patients, may be a primary reason significant differences between normal weight and overweight/obese subjects were apparent in both HF-etiology based subgroups. However, even with a mean VE/VCO2
slope similar to those classified as obese, an unfavorable prognosis persisted in patients with ischemic HF who were overweight. This finding may have important clinical implications when using this CPX variable to assess prognosis in this HF subgroup (i.e. a lower VE/VCO2
slope does not necessarily equate to improved prognosis in overweight patients with ischemic HF).
A large body of evidence supports the prognostic application of CPX in patients with HF.20-24
While peak VO2
is well established from a clinical assessment perspective, there is now strong evidence supporting the VE/VCO2
slope as the CPX variable with the highest prognostic value.25
The results of the present study support findings from previous investigations in this area in the following ways: 1) the VE/VCO2
slope provides superior prognostic value in both patients with ischemic and non-ischemic HF; and 2) while peak VO2
was a significant univariate predictor of mortality in both etiology-based subgroups, it was only retained in the multivariate analysis conducted in patients with ischemic HF. Novel findings from this component of the present study include the fact that BMI was retained in the multivariate prognostic analysis for both patients with ischemic and non-ischemic HF, although its additive value was stronger in the former subgroup. Moreover, the dichotomous BMI threshold used in the Cox multivariate regression analysis differed in the ischemic (obese vs. overweight/normal weight) and non-ischemic (obese/overweight vs. normal weight) subgroups.
Previous investigations examining the prognostic value of BMI in HF have done so in non-select HF cohorts.2
The present investigation confirms the prognostic value of BMI and introduces the possibility on an etiology-based influence. The present cohort was clinically referred for CPX, introducing the possibility of selection bias. In addition, assessing the prognostic value of more accurate assessments of lean and fat mass in a prospective fashion may be fruitful as BMI has inherent limitations in this respect. For the time being, our findings should exclusively be used to support the clinical consideration of BMI for patients with HF undergoing CPX.