Multimorbidity, Mortality, and Long-Term Physical Functioning in 3 Prospective Cohorts of Community-Dwelling Adults

Abstract

Multimorbidity is prevalent, but its optimal quantification and associations with mortality rate and physical functioning in young through older adults are uncertain. We used data collected using the Short Form-36 in the Nurses' Health Study (enrollment started in 1976), Nurses' Health Study II (begun in 1989), and Health Professionals Follow-up Study (begun in 1986) to identify associations of a multimorbidity-weighted index (MWI) and common alternative indices with mortality and future physical functioning. We used Cox proportional hazard ratios to determine incident 10-year mortality and general linear models to obtain coefficients for the associations of MWI with 4- and 8-year physical functioning. At baseline, mean values for the 219,950 participants were 55.0 (standard deviation, 3.7) years for age; 3.8 (range, 0-51) for MWI; 2.7 (range, 0-23) for disease count, and 0.43 (range, 0-13) for Charlson Comorbidity Index (CCI). During follow-up, 23,709 deaths (10.8%) occurred. CCI, MWI, and disease count were 0 for 77%, 12%, and 19% of participants, respectively. When comparing persons in the highest quartiles with those in the lowest, the hazard ratios for mortality were 6.04 (95% confidence interval (CI): 6.00, 6.09; P for trend < 0.0001) for the MWI, 4.86 (95% CI: 4.81, 4.91; P for trend < 0.0001) for disease count, and 3.29 (95% CI: 3.26, 3.32; P for trend < 0.0001) for the CCI. For future physical functioning, MWI had the best model fit and explained the greatest variance. Multimorbidity has important associations with future physical functioning and mortality that are easily captured with a readily measured index.

Keywords: Charlson Comorbidity Index; Short Form-36; comorbidity; mortality; multimorbidity; multiple chronic conditions; physical functioning; simple disease count.

Figure 1.

Distribution of multimorbidity indices at baseline in pooled cohorts from the Nurses’ Health Study (2000), Health Professionals Follow-Up Study (2000), and Nurses’ Health Study II (2001). Units of multimorbidity are as follows: Charlson Comorbidity Index units, determined by summing conditions weighted by risk of 1-year mortality; simple disease count units, which are the summation of unweighted conditions; and multimorbidity-weighted index units, determined by summing conditions weighted by their impact on the Short Form-36 physical functioning scale.

Figure 2.

Restricted cubic splines for 10-year incident mortality in the Nurses’ Health Study (2000–2010; A), Health Professionals Follow-Up Study (2000–2010; B), and Nurses’ Health Study II (2001–2010; C). Gray area, 95% confidence interval.

Figure 3.

Forest plot displaying adjusted Cox proportional hazards ratios (HR) for mortality by participant characteristics and the overall estimate for each point increase in the multimorbidity-weighted index, Nurses’ Health Study (2000–2010), Health Professionals Follow-Up Study (2000–2010), and Nurses’ Health Study II (2001–2010). The overall model estimate was adjusted for all covariates, including age, body mass index (BMI; calculated as weight (kg)/height (m)²), tobacco use, race, and geographic region; models within each stratum were adjusted for all other covariates. Boxes represent the hazard ratios by strata of participant characteristics, whereby the size of the box is proportional to the weight assigned to the characteristic (i.e., larger boxes represent larger sample sizes). The dotted vertical line represents the combined overall estimate. The horizontal lines represent the 95% confidence intervals (CI) around the estimates. The width of the diamond represents the 95% confidence interval around the overall estimate.