Plasma Atherogenicity in Relapsing–Remitting Multiple Sclerosis: A Cross-Sectional Analysis of Perceived Fatigue and Objective Performance

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Background/Objectives: Fatigue in relapsing–remitting multiple sclerosis (RRMS) may involve metabolic and neurological mechanisms. We examined between-group differences in the atherogenic index of plasma (AIP) and its associations with perceived fatigue and objective performance. Methods: This single-center cross-sectional study included 115 patients with RRMS and 100 controls frequency-matched by age and sex. AIP was calculated as log10[triglycerides/high-density lipoprotein cholesterol], using mmol/L concentrations. Perceived fatigue was assessed with the Fatigue Severity Scale (FSS); objective tests assessed walking speed, manual dexterity, walking endurance, and information-processing speed. Models adjusted for age and sex in between-group analyses and additionally for Expanded Disability Status Scale (EDSS) in RRMS analyses. Heteroscedasticity-consistent covariance estimator type 3 (HC3) standard errors were used for objective-performance models, and six secondary tests were controlled using the Benjamini–Hochberg procedure. Results: The adjusted RRMS–control AIP difference was 0.073 units (95% confidence interval [CI], 0.008–0.137; p = 0.028; q = 0.055). In the prespecified primary model, the AIP coefficient for FSS mean item score was 0.093 points per 0.1-unit increase (95% CI, −0.002 to 0.188; p = 0.056). In secondary analyses, higher AIP was associated with shorter Six-Minute Walk Test distance (−7.70 m per 0.1 unit; 95% CI, −12.52 to −2.87; p = 0.002; q = 0.006) and fewer correct Symbol Digit Modalities Test responses (−1.43; 95% CI, −2.21 to −0.65; p < 0.001; q = 0.002). Estimates for walking speed and manual dexterity were inconclusive. Conclusions: Higher AIP was associated with poorer walking endurance and information-processing speed in RRMS, whereas its relationship with perceived fatigue remained inconclusive.