U-shaped link of health checkup data and need for care using a time-dependent cox regression model with a restricted cubic spline

Abstract

We explored risk indicators likely to result in older adults needing certified long-term care in Japan and ascertained whether this relationship forms a U-shaped link. We analyzed a community-based cohort of residents in Kitanagoya City, Aichi Prefecture, Japan. Participants were 3718 individuals aged 65 years and above who underwent health examinations between April 1, 2011 and March 31, 2012. For continuous clinical variables, we applied a time-dependent Cox regression model. Two types of models were applied-a linear and nonlinear model with restricted cubic splines-to assess the U-shaped association. Statistical significance (set at 0.05) for the nonlinearity was tested by comparing the spline and linear models. Among the participants, 701 were certified as needing Level 1 care or higher during a follow-up. Among the continuous clinical variables, the nonlinear model for body mass index, systolic blood pressure, high-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase revealed significant U-shaped associations as compared with the linear model in which the outcome was a certification of the need for nursing care. These results provide an important insight into the usefulness of nonlinear models for predicting the risk of such certification.

Figure 1

Flowchart of subjects.

Figure 2

Hazard ratios of certified need for care estimated by a time-dependent Cox model with a restricted cubic spline model (three knots). The black straight line indicates the hazard ratio (HR) estimated for the spline model. The gray area represents the 95% confidence intervals of HR for the spline model. The vertical gray straight line indicates the reference value for the clinical parameter. The reference value was calculated as a median value of the clinical parameter. The dot-dash line indicates the HR estimated for the linear model. HRs are estimated when age is fixed at median age at baseline and gender is fixed at female. The p-values shown in the figures were calculated by the likelihood ratio test of the spline model against the null model. All p-values for nonlinearity were less than 0.05. BMI body mass index, SBP systolic blood pressure, HDL-cho high-density lipoprotein cholesterol, AST aspartate aminotransferase, ALT alanine aminotransferase, γ-GTP γ-glutamyl transpeptidase.

Figure 3

Hazard ratios of all-cause death estimated by a time-dependent Cox model with a restricted cubic spline model (three knots). The black straight line indicates the hazard ratio (HR) estimated for the spline model. The gray area represents the 95% confidence intervals of HR for the spline model. The vertical gray straight line indicates the reference value for the clinical parameter. The reference value was calculated as a median value of the clinical parameter. The dot-dash line indicates the HR estimated for the linear model. HRs are estimated when age is fixed at median age at baseline and gender is fixed at female. The p-values shown in the figures were calculated by the likelihood ratio test of the spline model against the null model. All p-values for nonlinearity were less than 0.05. BMI body mass index, SBP systolic blood pressure, DBP diastolic blood pressure, HDL-cho high-density lipoprotein cholesterol, AST aspartate aminotransferase, ALT alanine aminotransferase, γ-GTP γ-glutamyl transpeptidase.