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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 3.

Associations of baseline individual TCA cycle-related metabolites levels with the risk of incident heart failure 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 81 70 92 91
Crude model 1 (Ref.) 0.86 (0.56–1.31) 1.14 (0.74–1.74) 1.20 (0.77–1.86) 0.251 1.14 (0.98–1.33) 0.093
MV1 1 (Ref.) 0.94 (0.60–1.47) 1.24 (0.79–1.95) 1.09 (0.68–1.74) 0.579 1.09 (0.93–1.28) 0.312
MV2 1 (Ref.) 0.95 (0.60–1.50) 1.25 (0.80–1.98) 1.11 (0.69–1.78) 0.534 1.10 (0.93–1.29) 0.285
Malate
Cases 63 78 84 109
Crude model 1 (Ref.) 1.35 (0.87–2.10) 1.54 (0.98–2.42) 2.18 (1.39–3.42) 0.002 1.32 (1.14–1.54) 0.002
MV1 1 (Ref.) 1.32 (0.82–2.13) 1.56 (0.96–2.52) 2.28 (1.41–3.70) 0.003 1.34 (1.14–1.57) 0.003
MV2 1 (Ref.) 1.35 (0.83–2.19) 1.62 (0.98–2.66) 2.30 (1.41–3.76) 0.003 1.33 (1.13–1.56) 0.003
Citrate
Cases 89 65 79 101
Crude model 1 (Ref.) 0.80 (0.53–1.20) 0.92 (0.61–1.38) 1.36 (0.88–2.10) 0.198 1.12 (0.96 −1.31) 0.140
MV1 1 (Ref.) 0.83 (0.54–1.27) 0.95 (0.62–1.47) 1.24 (0.77–1.98) 0.430 1.10 (0.93–1.30) 0.310
MV2 1 (Ref.) 0.83 (0.54–1.28) 0.96 (0.62–1.49) 1.26 (0.78–2.02) 0.390 1.10 (0.93–1.31) 0.285
Aconitate
Cases 56 78 91 109
Crude model 1 (Ref.) 1.36 (0.88–2.08) 1.76 (1.13–2.74) 2.35 (1.47–3.76) 0.002 1.38 (1.17–1.62) 0.002
MV1 1 (Ref.) 1.32 (0.83–2.10) 1.64 (1.02–2.63) 1.97 (1.19–3.26) 0.012 1.31 (1.10–1.57) 0.004
MV2 1 (Ref.) 1.38 (0.86–2.12) 1.64 (1.02–2.64) 2.03 (1.22–3.39) 0.010 1.31(1.10–1.56) 0.004
Isocitrate
Cases 58 75 75 126
Crude model 1 (Ref.) 1.45 (0.93–2.26) 1.51 (0.95–2.39) 2.69 (1.71–4.23) 0.002 1.43 (1.23–1.68) 0.002
MV1 1 (Ref.) 1.63 (1.01–2.63) 1.38 (0.83–2.27) 2.52 (1.54–4.11) 0.003 1.36 (1.16–1.60) 0.003
MV2 1 (Ref.) 1.66 (1.02–2.71) 1.45 (0.87–2.41) 2.66 (1.61–4.40) 0.003 1.38 (1.16–1.62) 0.003
D/L-2-Hydroxyglutarate
Cases 62 76 86 110
Crude model 1 (Ref.) 1.30 (0.84–2.02) 1.52 (0.98–2.35) 1.96 (1.26–3.04) 0.004 1.22 (1.05–1.43) 0.018
MV1 1 (Ref.) 1.15 (0.72–1.84) 1.54 (0.96–2.46) 1.84 (1.14–2.97) 0.012 1.24 (1.05–1.47) 0.016
MV2 1 (Ref.) 1.13 (0.70–1.81) 1.55 (0.96–2.49) 1.91 (1.17–3.10) 0.010 1.27 (1.06–1.51) 0.010
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.