Heart Failure
Influence of Age-Related Versus Non–Age-Related Renal Dysfunction on Survival in Patients With Left Ventricular Dysfunction

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Normal aging results in a predictable decrease in glomerular filtration rate (GFR), and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age-related decreases in estimated GFR (eGFR) carry the same prognostic importance as disease-attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction limited data set (n = 6,337). The primary analysis focused on determining if the eGFR-mortality relation differed by the extent to which the eGFR was consistent with normal aging. Mean eGFR was 65.7 ml/min/1.73 m2 (SD = 19.0). Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73 m2/year (95% confidence interval [CI] 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p for interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted hazard ratio 1.0 per 10 ml/min/1.73 m2, 95% CI 0.97 to 1.1, p = 0.53), whereas a disease-attributable decrease in eGFR above the median carried significant risk (adjusted hazard ratio 2.8, 95% CI 1.6 to 4.7, p <0.001). In conclusion, in the setting of left ventricular dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis.

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Methods

The Studies Of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials were National Heart, Lung and Blood Institute–sponsored, randomized, double-blind, placebo-controlled trials of the effect of enalapril in patients with asymptomatic and symptomatic left ventricular dysfunctions and comprise the overall SOLVD population. Methods and results have been previously published.17, 18 Briefly, 4,228 patients were enrolled in the prevention trial and 2,569 patients in the treatment

Results

Baseline characteristics of patients in this analysis are presented in Table 1. The age of the population ranged from 27 to 80 years with a mean of 59 ± 10 years. The mean eGFR was 65.7 ml/min/1.73 m2 (SD = 19.0), which is 51.0% (41.3% to 59.2%) below a truly normal GFR of 130 ml/min/1.73 m2 (Figure 1). In the overall population, 35.1% (27.2% to 43.6%) of this deviation from true normal was consistent with expected age-related loss, and 62.9% (54.4% to 70.3%) was consistent with a

Discussion

The principal finding of this analysis was that the association between a low eGFR and survival appears to be significantly modified by whether the low eGFR was consistent with the normal aging process. Notably, in patients with a lower eGFR that was consistent with that which could be found with normal aging, eGFR demonstrated a weak association with mortality. However, patients with a low eGFR that could not be explained by normal age-related losses (i.e., disease-attributable loss in GFR)

Acknowledgment

This report was prepared using SOLVD research materials obtained from the National Heart, Lung and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center and does not necessarily reflect the opinions or views of the SOLVD study investigators or the NHLBI.

References (25)

  • M. Dupont et al.

    Determinants of dynamic changes in serum creatinine in acute decompensated heart failure: the importance of blood pressure reduction during treatment

    Eur J Heart Fail

    (2013)
  • C.G. Musso et al.

    Aging and physiological changes of the kidneys including changes in glomerular filtration rate

    Nephron Physiol

    (2011)
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