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

Abstract

Background: 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, etiological 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)), etiology (Trial of Org 10172 in Acute Stroke Treatment (TOAST)), premorbid disability (modified Rankin Scale (mRS)), and non-CCI risk factors (hypertension, hyperlipidemia, atrial fibrillation, smoking, deprivation, anxiety/depression).

Results: Among 2454 stroke patients (M/SD age: 74.1/13.9 years; 48.9% male; M/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 ⩾ 2 vs 0) predicted (all ps < 0.001) mortality at 1 year (aHR = 1.57, 95% CI = 1.38-1.78), 5 years (aHR = 1.73, 95% CI = 1.53-1.96), and 10 years (aHR = 1.79, 95% CI = 1.58-2.03). Although multimorbidity was independently associated with premorbid disability (mRS > 2: aOR = 2.76, 2.13-3.60) and non-CCI risk factors (hypertension: 1.56, 1.25-1.95; hyperlipidemia: 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 (p_int < 0.001), age < 75 years (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.

Conclusion: 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 favorable risk/benefit ratio.

Data access statement: Data requests will be considered by the Oxford Vascular Study (OXVASC) Study Director (P.M.R.-peter.rothwell@ndcn.ox.ac.uk).

Keywords: Chronic disease; epidemiology; long-term outcomes; multimorbidity; post-stroke mortality; prognosis.

Figure 1.

Kaplan–Meier curves for all-cause mortality up to 10 years post-stroke across multimorbidity groups (unweighted Charlson Index), in the overall cohort and stratified by adjusted THRIVE score. Log-rank tests shown in respective Kaplan–Meier plots. Original THRIVE scoring includes the following NIHSS categories (NIHSS ⩽ 10: 0 points, 11–20: 2 points, ⩾ 21: 4 points) based on NIHSS at presentation. This figure used adjusted THRIVE categories with altered NIHSS scoring (NIHSS ⩽ 4: 0 points, 5–9: 2 points, ⩾ 10: 4 points) as the present study included sub-acute phase NIHSS as opposed to NIHSS on presentation. Only three CCI (unweighted) categories are presented for the panels using THRIVE scores, with gray representing all patients with ⩾ 2 CCI comorbidities. Curves stratified by original THRIVE scores are found in the Supplemental Appendix.

Figure 2.

Kaplan–Meier curves for all-cause mortality up to 10 years post-stroke across multimorbidity groups, stratified by age, premorbid disability level, or stroke severity. Log-rank tests shown in respective Kaplan–Meier plots. Unweighted CCI groups were used.