Coordinated decrease in plasma citrate and related organic acids during longitudinal follow-up in patients with cardiovascular risk factors: an exploratory metabolomic pilot study

Abstract Objective Comprehensive metabolomic profiling can reveal changes in metabolic state that are not apparent from routine clinical measurements. We explored how the plasma metabolome of patients with cardiovascular risk factors changes over approximately 1 year, during which the clinical picture remained stable, and we examined whether any observed changes were biological or technical in origin. Results Eight patients (four men and four women; median age 62 years) were assessed at baseline and after a median of 334 days. No anthropometric or routine laboratory variable changed consistently across both statistical tests or after adjustment for multiple comparisons. Of 260 plasma metabolites, 37 differed between the two time points at an unadjusted P value below 0.05, of which 35 decreased; none remained significant after false discovery rate correction. Thirteen metabolites showed consistent nominal decreases across all analyses, including tricarboxylic acid cycle intermediates (citrate, malate), tartrate, lysophosphatidylcholines, and acylcarnitines. The change in citrate correlated with the changes in glycerol-3-phosphate, lactate, and tartrate. These changes were pathway-selective and unrelated to sample storage, sampling interval, or clinical variables. The findings are exploratory and identify candidate metabolites for confirmatory longitudinal studies.