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

Fatigue is common in multiple sclerosis and may be influenced by cardiovascular comorbidities.

To test whether cardiovascular comorbidity burden relates to fatigue at baseline and over time, and to assess dose response.

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.

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.

Cardiovascular comorbidity burden is associated with greater fatigue, with a dose response over time.