Association of multimorbidity with mortality after stroke stratified by age, severity, aetiology, and prior disability.

INTRODUCTION: Multimorbidity is common in patients with stroke, and is associated with increased medium to long-term mortality, but its value for clinical decision-making and case-mix adjustment will depend on other factors, such as age, stroke severity, aetiological subtype, prior disability, and vascular risk factors. AIMS: In the absence of previous studies, we related multimorbidity to long-term post-stroke mortality with stratification by these factors. METHODS: In patients ascertained in a population-based stroke incidence study (Oxford Vascular Study; 2002-2017), we related pre-stroke multimorbidity (weighted/unweighted Charlson Comorbidity Index-CCI) to all-cause/vascular/non-vascular mortality (1/5/10-years) using regression models adjusted/stratified by age, sex, predicted early outcome (THRIVE Score), stroke severity (NIH Stroke Scale-NIHSS), aetiology (TOAST), pre-morbid disability (modified Rankin Scale-mRS), and non-CCI risk factors (hypertension, hyperlipidaemia, atrial fibrillation, smoking, deprivation, anxiety/depression). RESULTS: Among 2454 stroke patients (mean/SD age 74.1/13.9; 48.9% male; mean/SD NIHSS 5.7/7.0), 1375/56.0% had ≥1 CCI comorbidity and 685/27.9% had ≥2. After age/sex adjustment, multimorbidity (unweighted CCI≥2vs0) predicted (all p<0.001) mortality at 1-year (aHR=1.57, 95%CI=1.38-1.78), 5-years (1.73, 1.53-1.96), and 10-years (1.79, 1.58-2.03). Although multimorbidity was independently associated with pre-morbid disability (mRS>2: aOR=2.76, 2.13-3.60) and non-CCI risk factors (hypertension-1.56, 1.25-1.95; hyperlipidaemia-2.58, 2.03-3.28; atrial fibrillation-2.31; 1.78-2.98; smoking-1.37, 1.01-1.86), it predicted death after adjustment for all measured confounders (10-year-aHR=1.56, 1.37-1.78, p<0.001), driven mainly by non-vascular death (aHR=1.89, 1.55-2.29). Predictive value for 10-year all-cause death was greatest in patients with lower expected early mortality: lower THRIVE Score (pint<0.001), age<75 (aHR=2.27, 1.71-3.00), NIHSS<5 (1.84, 1.53-2.21), and lacunar stroke (3.56, 2.14-5.91). Results were similar using the weighted CCI. CONCLUSIONS: Pre-stroke multimorbidity is highly prevalent and is an independent predictor of death after stroke, supporting its inclusion in case-mix adjustment models and in informing decision-making by patients, families, and carers. Prediction in younger patients and after minor stroke, particularly for non-vascular death, suggests potential clinical utility in targeting interventions that require survival for 5-10 years to achieve a favourable risk/benefit ratio. DATA ACCESS STATEMENT: Data requests will be considered by the OXVASC Study Director (PMR-peter.rothwell@ndcn.ox.ac.uk).