Cardiovascular comorbidities are associated with cross-sectional and longitudinal measures of multiple sclerosis fatigue

Background: Fatigue is common in multiple sclerosis and may be influenced by cardiovascular comorbidities. Objective: To test whether cardiovascular comorbidity burden relates to fatigue at baseline and over time, and to assess dose response. Methods: We analyzed prospectively collected data from MS PATHS across 10 centers. Fatigue was measured with Neuro-QoL Fatigue T -scores. Cardiovascular comorbidity was defined as a composite (any vs none) and as a count of hypertension, diabetes, and dyslipidemia. Cross-sectional associations and longitudinal trajectories were modeled using multivariable regression. Extended models also included depression, anxiety, and sleep disturbance. Results: Among 5507 participants, 49% had no cardiovascular comorbidity, 32% had one, 16% had two, and 3% had three. In minimally adjusted cross‑sectional models, any comorbidity was associated with higher fatigue (beta = 0.85; 95% CI, 0.18 to 1.53), with attenuation after adjustment for depression, anxiety, and sleep (beta = 0.20; 95% CI, −0.09 to 0.49). A graded dose response was evident across 0–3 conditions. In longitudinal analyses, effect sizes were larger and remained positive after adjustment (Any vs None: beta = 1.06 in minimal models; beta = 0.39 after adjustment), consistent with a greater comorbidity burden associated with higher fatigue over time. Conclusions: Cardiovascular comorbidity burden is associated with greater fatigue, with a dose response over time.