Erythrocyte Fatty Acid Compositional Patterns and Cardiovascular-Kidney-Metabolic Stage Burden

Erythrocyte fatty acids (RBC-FAs) are objective biomarkers of longer-term fatty acid status, but their relationship with cardiovascular-kidney-metabolic (CKM) syndrome stage burden remains unclear. We aimed to derive biologically interpretable RBC-FA patterns and examine their associations with CKM stage burden.

In this population-based cross-sectional study of US adults, isometric log-ratio principal component analysis was performed among 5118 eligible nonpregnant participants with complete 21-part RBC-FA profiles to derive RBC-FA pattern scores. Associations were then evaluated in 2427 participants with positive fasting subsample weights and classifiable CKM stage. Survey-weighted logistic regression was used for the primary outcome, defined as CKM stage ≥2, and survey-weighted linear regression was used for CKM stage modeled continuously from 0 to 4. Subgroup analyses were performed by age and sex.

Three retained principal components (PCs) explained 66.2% of total RBC-FA variance. PC1 represented an omega-3-enriched pattern, PC2 a saturated fatty acid/monounsaturated fatty acid-enriched and polyunsaturated fatty acid-depleted contrast, and PC3 a stearoyl-CoA desaturase-16/delta-6 desaturase-related desaturation proxy pattern. In fully adjusted models, PC1 was associated with lower odds of CKM stage ≥2 (OR: 0.66; 95% CI: 0.49-0.90), whereas PC3 was associated with higher odds (OR: 3.09; 95% CI: 1.61-5.92). PC2 showed no robust association. Secondary analyses using continuous CKM stage showed consistent directions, and no robust effect modification by age or sex was observed.

Distinct RBC-FA patterns were differentially associated with CKM stage burden, suggesting that RBC-FA profiles may provide objective biomarker information on integrated CKM burden.