Data Mining Identifies Digit Symbol Substitution Test Score and Serum Cystatin C as Dominant Predictors of Mortality in Older Men and Women

Background: Characterization of long-term health trajectory in older individuals is important for proactive health management. However, the relative prognostic value of information contained in clinical profiles of nonfrail older adults is often unclear. Methods: We screened 825 phenotypic and genetic measures evaluated during the Health, Aging, and Body Composition Study (Health ABC) baseline visit (3,067 men and women aged 70-79). Variables that best predicted mortality over 13 years of follow-up were identified using 10-fold cross-validation. Results: Mortality was most strongly associated with low Digit Symbol Substitution Test (DSST) score (DSST <25; 21.9% of cohort; hazard ratio [HR] = 1.87 +/- 0.06) and elevated serum cystatin C (>= 1.30 mg/mL; 12.1% of cohort; HR = 2.25 +/- 0.07). These variables predicted mortality better than 823 other measures, including baseline age and a 45-variable health deficit index. Given elevated cystatin C (>= 1.30 mg/mL), mortality risk was further increased by high serum creatinine, high abdominal visceral fat density, and smoking history (2.52 <= HR <= 3.73). Given a low DSST score (<25) combined with low-to-moderate cystatin C (< 1.30 mg/mL), mortality risk was highest among those with elevated plasma resistin and smoking history (1.90 <= HR <= 2.02). Conclusions: DSST score and serum cystatin C warrant priority consideration for the evaluation of mortality risk in older individuals. Both variables, taken individually, predict mortality better than chronological age or a health deficit index in well-functioning older adults (ages 70-79). DSST score and serum cystatin C can thus provide evidence-based tools for geriatric assessment.