Vascular risk factors for depression and apathy | Part 1 34 Confounders Sociodemographic variables (sex and age), general health-related variables (functional limitations and cognitive impairments), and important stroke risk factors (diabetes mellitus, smoking, hypertension, and obesity) were included in the analyses as potential confounders. The number of functional limitations was scored with a 3-item questionnaire 24 as none, 1, or 2 or more. Cognitive impairments were measured with the MMSE 25. A history of diabetes mellitus was considered present if reported by the respondent, if the person used antidiabetic agents, or if a GP confirmed the diagnosis. The variable smoking included current smoking. Blood pressure was measured every 3 years, preferably from the arm but otherwise from the fingertip. Hypertension was categorized into stage 1 hypertension (a mean systolic blood pressure of 140-159 mm Hg or a mean diastolic blood pressure of 90-99 mm Hg) and stage 2 hypertension (a mean systolic blood pressure of ≥ 160 mm Hg or a mean diastolic blood pressure of ≥ 100 mm Hg) 26. Obesity was defined as a body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 or greater 27. Antidepressant use was established by asking about the use of medication and by visually checking all of the participants’ medications at each 3-yearly assessment. Statistical analyses All primary variables and covariates were checked for normality, collinearity, and proportionality of hazards. Missing data for covariates were restored by imputation of the most reported value, and the results for analyses with or without imputed data were checked for differences 28. Baseline characteristics for participants with or without depressive symptoms were compared using χ2 and t tests. Univariate Cox proportional hazards analyses of first strokes were conducted for primary and secondary variables. Models of stroke incidence, which included interaction terms of depression variables (depressive symptoms, CRDSs, and MDD) by cardiac disease status, were tested by multivariate Cox proportional hazard regression analyses. Subsequently, the sample was stratified for cardiac disease, and the relationship between depression variables and incident stroke was examined by multivariate Cox proportional hazard regression analysis. We used extended Cox proportional hazard models to examine the association between the severity of depressive symptoms or the chronicity of CRDSs or MDD and incident stroke, with these depression variables and possible confounders as time-dependent variables 29. Results Baseline characteristics The mean (SD) age of the 2965 elderly study participants (52.1% female) was 70.5 (8.7) years, and 39.6% had 1 or more functional limitations (Table 1). At baseline, 58 (2.0%) had MDD and 372 (12.5%) had SDD. Myocardial infarction was reported in 285 (9.6%), congestive heart failure in256 (8.7%), angina pectoris in283 (9.5%), and cardiac arrhythmia in 132 (4.4%). The CRDSs at baseline were associated with older age (P < .001), female sex (P < .001), more functional limitations (P < .001), poorer performance on the MMSE (P < .001), smoking (P = .04), diabetes mellitus (P = .03), and cardiac disease (P < .001).
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