Risk of myocardial infarction in patients with multiple sclerosis: a systematic review and meta-analysis

Multiple sclerosis (MS) is associated with increased cardiovascular morbidity, yet the magnitude of myocardial infarction (MI) risk remains uncertain. With newer cohort studies and advances in meta-analytic methods, an updated evidence synthesis is warranted. We conducted a systematic review and meta-analysis to quantify MI risk in MS patients. We searched PubMed, Embase, and Scopus from inception through December 2025 for observational studies comparing MI risk between adults with MS and controls. Random-effects meta-analysis using restricted maximum likelihood estimation with Hartung-Knapp-Sidik-Jonkman adjustment was performed. Risk of bias was assessed using the Newcastle-Ottawa Scale, and certainty of evidence was evaluated using GRADE. Mendelian randomization evidence was synthesized separately. Twenty cohorts from 18 studies were included. Seven cohorts (97,996 MS patients; 824,497 controls) contributed to the primary meta-analysis after excluding one study due to overlapping populations. MS patients had significantly increased MI risk (RR 1.70, 95% CI: 1.57–1.85; p < 0.0001) with moderate heterogeneity (I²=40.3%). The 95% prediction interval (1.60–1.81) indicated consistently elevated risk across settings. Secondary analyses showed increased stroke risk (RR 1.66, 95% CI: 1.01–2.73). Subgroup analyses revealed no significant differences by geographic region (p = 0.066), adjustment status (p = 0.45), or effect measure type (p = 0.79). Leave-one-out sensitivity analysis confirmed robust findings (RR range: 1.69–1.76). Mendelian randomization evidence showed a weak genetic association (OR 1.03, 95% CI: 1.00-1.06). GRADE certainty was very low. MS patients have a 70% increased risk of MI compared to individuals without MS. This risk elevation, comparable to other autoimmune conditions with established cardiovascular screening guidelines, supports the need for enhanced cardiovascular surveillance in MS populations.