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. Author manuscript; available in PMC: 2022 Jun 19.
Published in final edited form as: Metabolism. 2021 Oct 20;125:154915. doi: 10.1016/j.metabol.2021.154915

Table 2.

Associations of baseline individual TCA cycle-related metabolites levels with the risk of incident atrial fibrillation in a nested case-control study of the PREDIMED study1.

Quartiles of plasma metabolite levels
Metabolite Q1 Q2 Q3 Q4 P trend2 OR per 1 SD increment P value2
Succinate
Cases 101 130 116 165
Crude model 1 (Ref.) 1.33 (0.94–1.87) 1.27 (0.87–1.84) 1.84 (1.27–2.66) 0.006 1.19 (1.04–1.35) 0.016
MV1 1 (Ref.) 1.41 (0.99–2.01) 1.35 (0.92–1.99) 1.83 (1.25–2.68) 0.006 1.17 (1.02–1.33) 0.033
MV2 1 (Ref.) 1.41 (0.99–2.02) 1.35 (0.92–1.99) 1.84 (1.25–2.71) 0.006 1.17 (1.02–1.33) 0.033
Malate
Cases 98 114 111 189
Crude model 1 (Ref.) 1.23 (0.87–1.73) 1.24 (0.87–1.76) 2.18 (1.54–3.10) 0.006 1.28(1.13–1.45) 0.006
MV1 1 (Ref.) 1.23 (0.87–1.76) 1.28 (0.88–1.84) 2.14 (1.49–3.08) 0.003 1.28 (0.13–1.45) 0.003
MV2 1 (Ref.) 1.21 (0.85–1.73) 1.28 (0.89–1.85) 2.16 (1.49–3.12) 0.003 1.29 (1.13–1.47) 0.003
Citrate
Cases 103 127 131 151
Crude model 1 (Ref.) 1.24 (0.86–1.80) 1.40 (0.95–2.07) 1.78 (1.22–2.61) 0.010 1.16 (1.02–1.32) 0.026
MV1 1 (Ref.) 1.24 (0.86–1.79) 1.39 (0.94–2.05) 1.79 (1.23–2.62) 0.004 1.20 (1.04–1.37) 0.018
MV2 1 (Ref.) 1.24 (0.86–1.80) 1.40 (0.94–2.07) 1.78 (1.22–2.61) 0.004 1.19 (1.04–1.37) 0.022
Aconitate
Cases 112 111 145 144
Crude model 1 (Ref.) 0.95 (0.67–1.34) 1.33 (0.95–1.88) 1.41 (0.98–2.00) 0.027 1.18 (1.03–1.35) 0.019
MV1 1 (Ref.) 0.97 (0.68–1.38) 1.33 (0.94–1.90) 1.35 (0.94–1.96) 0.064 1.16 (1.01–1.33) 0.038
MV2 1 (Ref.) 0.96 (0.67–1.37) 1.34 (0.94–1.91) 1.34 (0.93–1.94) 0.072 1.16 (1.01–1.33) 0.045
Isocitrate
Cases 113 122 124 153
Crude model 1 (Ref.) 1.07 (0.75–1.52) 1.09 (0.77–1.52) 1.43 (1.01–2.02) 0.031 1.14 (1.01–1.29) 0.029
MV1 1 (Ref.) 1.06 (0.74–1.51) 1.07 (0.75–1.52) 1.32 (0.92–1.90) 0.116 1.11 (0.98–1.26) 0.101
MV2 1 (Ref.) 1.05 (0.73–1.50) 1.06 (0.75–1.51) 1.30 (0.90–1.88) 0.134 1.10 (0.97–1.26) 0.126
D/L-2-Hydroxyglutarate
Cases 100 110 142 160
Crude model 1 (Ref.) 1.15 (0.81–1.63) 1.40 (0.99–1.97) 1.59 (1.13–2.25) 0.010 1.21 (1.07–1.37) 0.006
MV1 1 (Ref.) 1.19 (0.83–1.71) 1.46 (1.02–2.09) 1.82 (1.26–2.62) 0.003 1.24 (1.09–1.41) 0.003
MV2 1 (Ref.) 1.20 (0.83–1.73) 1.46 (1.02–2.09) 1.83 (1.26–2.67) 0.003 1.24 (1.09–1.41) 0.003
1

Values are OR (95% CI). A natural logarithmic transformation was applied to the raw values of individual metabolites. Conditional logistic regression analysis was used. MV1 adjusted for smoking, family history of premature coronary heart disease, physical activity, alcohol intake, BMI (kg/m2), intervention groups, dyslipidemia, hypertension and type 2 diabetes; MV2 additionally adjusted for medication use (lipid-modifying, antihypertensive, and antidiabetic medication). Abbreviations: Ref, reference; TCA, tricarboxylic acid.

2

Adjusted with the Benjamini-Hochberg False Discovery Rate method. Case and control subjects were matched on age, sex and recruitment center.