Associations of Multimorbidity With Stroke Severity, Subtype, Premorbid Disability, and Early Mortality: Oxford Vascular Study

BACKGROUND AND OBJECTIVES: Patients with multimorbidity are underrepresented in clinical trials. Inclusion in stroke trials is often limited by exclusion based on premorbid disability, concerns about worse poststroke outcomes in acute treatment trials, and a possibly increased proportion of hemorrhagic vs ischemic stroke in prevention trials. Multimorbidity is associated with an increased mortality after stroke, but it is unclear whether this is driven by an increased stroke severity or is confounded by particular stroke subtypes or premorbid disability. We aimed to determine the independent association of multimorbidity with stroke severity taking account of these main potential confounders. METHODS: In a population-based incidence study (Oxford Vascular Study; 2002–2017), prestroke multimorbidity (Charlson Comorbidity Index [CCI]; unweighted/weighted) in all first-in-study strokes was related to postacute severity (≈24 hours; NIH Stroke Scale [NIHSS]), stroke subtype (hemorrhagic vs ischemic; Trial of Org 10172 in Acute Stroke Treatment [TOAST]), and premorbid disability (modified Rankin scale [mRS] score ≥2) using age-adjusted/sex-adjusted logistic and linear regression models and to 90-day mortality using Cox proportional hazard models. RESULTS: Among 2,492 patients (mean/SD age = 74.5/13.9 years; 1,216/48.8% male; 2,160/86.7% ischemic strokes; mean/SD NIHSS = 5.7/7.1), 1,402 (56.2%) had at least 1 CCI comorbidity, and 700 (28.1%) had multimorbidity. Although multimorbidity was strongly related to premorbid mRS ≥2 (adjusted odds ratio [aOR] per CCI comorbidity 1.42, 1.31–1.54, p < 0.001), and comorbidity burden was crudely associated with an increased severity of ischemic stroke (OR per comorbidity 1.12, 1.01–1.23 for NIHSS 5–9, p = 0.027; 1.15, 1.06–1.26 for NIHSS ≥10; p = 0.001), no association with severity remained after stratification by TOAST subtype (aOR 1.02, 0.90–1.14, p = 0.78 for NIHSS 5–9 vs 0–4; 0.99, 0.91–1.07, p = 0.75 for NIHSS ≥10 vs 0–4), or within any individual subtype. The proportion of intracerebral hemorrhage vs ischemic stroke was lower in patients with multimorbidity (aOR per comorbidity 0.80, 0.70–0.92, p < 0.001), and multimorbidity was only weakly associated with 90-day mortality after adjustment for age, sex, severity, and premorbid disability (adjusted hazard ratio per comorbidity 1.09, 1.04–1.14, p < 0.001). Results were unchanged using the weighted CCI. DISCUSSION: Multimorbidity is common in patients with stroke and is strongly related to premorbid disability but is not independently associated with an increased ischemic stroke severity. Greater inclusion of patients with multimorbidity is unlikely therefore to undermine the effectiveness of interventions in clinical trials but would increase external validity.