Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial
Abstract
:1. Introduction
2. Results
2.1. Baseline Glycolysis Intermediate Metabolites, Other Related Metabolites, and Risk of AF
2.2. Baseline Glycolysis Intermediate Metabolites, Other Related Metabolites, and Risk of HF
2.3. Baseline Glycolysis Intermediate Metabolites, Other Related Metabolites, and Risk of AF and HF by Diabetes Status
3. Discussion
4. Materials and Methods
4.1. Study Design and Participants
4.2. Sample Collection and Metabolomic Analysis
4.3. Outcome Assessment
4.4. Covariates Assessment
4.5. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Atrial Fibrillation | Heart Failure | |||||
---|---|---|---|---|---|---|
Variables | Controls (n = 545) | Cases (n = 512) | p-Value | Controls (n = 408) | Cases (n = 334) | p-Value |
Age (years) | 68.39 (6.21) | 68.28 (6.07) | 0.772 | 70.12 (5.92) | 70.34 (5.90) | 0.615 |
Women (%) | 271 (49.7) | 255 (49.8) | 1 | 224 (54.9) | 196 (58.7) | 0.337 |
BMI (kg/m2) | 29.71 (3.7) | 30.67 (3.8) | <0.001 | 29.24 (3.6) | 31.07 (3.8) | <0.001 |
LTFA (METs-min/d) | 231.2 (223.0) | 228.1 (216.6) | 0.823 | 212.9 (218.6) | 216.1 (203.1) | 0.837 |
Systolic blood pressure (mmHg) | 146 (19) | 149 (22) | 0.239 | 145 (20) | 151 (20) | 0.009 |
Diastolic blood pressure (mmHg) | 82 (10) | 82 (12) | 0.765 | 80 (10) | 81 (11) | 0.812 |
Fasting glucose (mg/dL) | 120.5 (39.0) | 121.8 (44.3) | 0.631 | 121 (40) | 130 (52) | 0.011 |
LDL cholesterol (mg/dL) | 130.5 (31.5) | 128.1 (34.4) | 0.255 | 128.6 (34.4) | 127.2 (34.8) | 0.591 |
Hypertension (%) | 447 (82.0) | 452 (88.3) | 0.006 | 335 (82.1) | 293 (87.7) | 0.045 |
Dyslipidemia (%) | 382 (70.1) | 332 (64.8) | 0.079 | 281 (68.9) | 214 (64.1) | 0.193 |
T2D (%) | 278 (51.0) | 245 (47.9) | 0.335 | 212 (52.0) | 197 (59.0) | 0.066 |
Family history of premature CHD (%) | 110 (20.2) | 98 (19.1) | 0.727 | 0.46 (1.54) | 0.52 (1.69) | 0.645 |
Oral hypoglycemic agents (%) | 117 (32.5) | 156 (30.5) | 0.525 | 134 (32.8) | 134 (40.1) | 0.048 |
Lipid-lowering agents (%) | 225 (41.3) | 207 (40.4) | 0.826 | 166 (40.7) | 133 (39.8) | 0.870 |
Antihypertensive agents (%) | 110 (20.2) | 143 (27.9) | 0.004 | 96 (23.5) | 85 (25.4) | 0.603 |
Other medication use (%) | 137 (25.1) | 152 (29.7) | 0.112 | 109 (26.7) | 136 (40.7) | <0.001 |
Smoking (%) | 0.893 | |||||
Current smoker | 76 (13.9) | 73 (14.3) | 46 (11.3) | 48 (14.4) | 0.442 | |
Former smoker | 154 (28.3) | 138 (27.0) | 109 (26.7) | 84 (25.1) | ||
Never smoker | 315 (57.8) | 301 (58.8) | 253 (62.0) | 202 (60.5) | ||
Intervention group (%) | 0.224 | 0.059 | ||||
Control | 188 (34.5) | 189 (36.9) | 148 (36.3) | 122 (36.5) | ||
MedDiet plus EVOO | 201 (36.9) | 163 (31.8) | 156 (38.2) | 104 (31.1) | ||
MedDiet plus nuts | 156 (28.6) | 160 (31.2) | 104 (25.5) | 108 (32.3) |
Metabolite | Q1 | Q2 | Q3 | Q4 | P-Trend | Per 1-SD |
---|---|---|---|---|---|---|
Phosphoglycerate 1 | 122/188 | 141/182 | 132/179 | 117/185 | 512/734 | |
Crude model | 1 (Ref) | 1.21 (0.86, 1.71) | 1.06 (0.74, 1.52) | 0.89 (0.62, 1.3) | 0.4212 | 0.98 (0.86, 1.11) |
Multivariate model | 1 (Ref) | 1.21 (0.85, 1.73) | 1.05 (0.72, 1.52) | 0.87 (0.59, 1.28) | 0.3796 | 0.96 (0.84, 1.1) |
Hexose monophosphate 1 | 135/177 | 120/177 | 122/191 | 131/182 | 508/727 | |
Crude model | 1 (Ref) | 0.88 (0.62, 1.24) | 0.8 (0.57, 1.14) | 0.92 (0.65, 1.3) | 0.6319 | 0.95 (0.84, 1.07) |
Multivariate model | 1 (Ref) | 0.87 (0.61, 1.24) | 0.79 (0.55, 1.15) | 0.94 (0.65, 1.36) | 0.7371 | 0.94 (0.82, 1.07) |
Fructose/glucose/galactose 1 | 144/188 | 122/184 | 117/180 | 129/182 | 512/734 | |
Crude model | 1 (Ref) | 0.84 (0.61, 1.17) | 0.79 (0.57, 1.11) | 0.9 (0.65, 1.25) | 0.4974 | 1.00 (0.89, 1.13) |
Model 2 | 1 (Ref) | 0.83 (0.59, 1.18) | 0.75 (0.51, 1.09) | 0.94 (0.63, 1.42) | 0.6463 | 1.03 (0.89, 1.19) |
Lactate 1 | 113/184 | 135/181 | 120/188 | 144/181 | 512/734 | |
Crude model | 1 (Ref) | 1.2 (0.85, 1.69) | 1.13 (0.8, 1.60) | 1.4 (0.98, 2.01) | 0.0848 | 1.09 (0.97, 1.24) |
Multivariate model | 1 (Ref) | 1.21 (0.85, 1.74) | 1.1 (0.77, 1.59) | 1.28 (0.88, 1.86) | 0.2571 | 1.05 (0.92, 1.20) |
Sucrose 1 | 125/185 | 118/182 | 132/190 | 137/177 | 512/734 | |
Crude model | 1 (Ref) | 0.93 (0.67, 1.29) | 1.04 (0.75, 1.46) | 1.09 (0.78, 1.53) | 0.5279 | 1.04 (0.92, 1.18) |
Multivariate model | 1 (Ref) | 0.86 (0.61, 1.21) | 1 (0.7, 1.42) | 1.02 (0.71, 1.46) | 0.7782 | 1.01 (0.89, 1.15) |
α-glycerophosphate 1 | 125/179 | 114/184 | 146/186 | 127/184 | 512/733 | |
Crude model | 1 (Ref) | 0.91 (0.64, 1.28) | 1.25 (0.88, 1.77) | 1.11 (0.77, 1.59) | 0.3700 | 1.08 (0.95, 1.24) |
Multivariate model | 1 (Ref) | 0.94 (0.66, 1.35) | 1.27 (0.88, 1.83) | 1.14 (0.78, 1.68) | 0.3189 | 1.10 (0.96, 1.27) |
PEP 1 | 99/162 | 111/160 | 98/155 | 125/154 | 433/631 | |
Crude model | 1 (Ref) | 1.3 (0.88, 1.91) | 1.13 (0.75, 1.68) | 1.41 (0.94, 2.13) | 0.1560 | 1.13 (0.98, 1.3) |
Multivariate model | 1 (Ref) | 1.36 (0.89, 2.06) | 1.15 (0.75, 1.75) | 1.42 (0.91, 2.22) | 0.1892 | 1.12 (0.96, 1.31) |
Ratio PEP:lactate 1 | 98/158 | 94/157 | 122/162 | 119/154 | 433/631 | |
Crude model | 1 (Ref) | 0.93 (0.63, 1.37) | 1.25 (0.85, 1.83) | 1.21 (0.81, 1.82) | 0.2311 | 1.08 (0.94, 1.24) |
Multivariate model | 1 (Ref) | 0.82 (0.54, 1.24) | 1.27 (0.84, 1.92) | 1.21 (0.78, 1.88) | 0.2125 | 1.09 (0.94, 1.27) |
Metabolite | Q1 | Q2 | Q3 | Q4 | P-Trend | Per 1-SD |
---|---|---|---|---|---|---|
Phosphoglycerate 1 | 72/122 | 82/130 | 84/119 | 95/136 | 333/507 | |
Crude model | 1 (Ref) | 1.08 (0.72, 1.63) | 1.30 (0.83, 2.03) | 1.25 (0.81, 1.93) | 0.2808 | 1.17 (1.00, 1.38) |
Multivariate model | 1 (Ref) | 1.30 (0.81, 2.1) | 1.43 (0.86, 2.38) | 1.54 (0.94, 2.54) | 0.0975 | 1.28 (1.06, 1.53) |
Hexose monophosphate 1 | 88/133 | 73/126 | 72/123 | 96/122 | 329/504 | |
Crude model | 1 (Ref) | 0.87 (0.57, 1.35) | 0.89 (0.58, 1.36) | 1.24 (0.8, 1.9) | 0.3519 | 1.08 (0.92, 1.27) |
Multivariate model | 1 (Ref) | 0.93 (0.57, 1.53) | 0.86 (0.54, 1.39) | 1.16 (0.71, 1.88) | 0.6258 | 1.05 (0.87, 1.25) |
Fructose/glucose/galactose 1 | 73/133 | 77/119 | 90/134 | 94/122 | 334/508 | |
Crude model | 1 (Ref) | 1.21 (0.8, 1.82) | 1.26 (0.83, 1.9) | 1.42 (0.96, 2.11) | 0.0827 | 1.17 (1.01, 1.35) |
Multivariate model | 1 (Ref) | 1.09 (0.68, 1.74) | 0.88 (0.52, 1.49) | 0.93 (0.53, 1.63) | 0.7498 | 1.04 (0.85, 1.27) |
Lactate 1 | 79/136 | 88/126 | 70/123 | 97/123 | 334/508 | |
Crude model | 1 (Ref) | 1.12 (0.75, 1.67) | 0.94 (0.59, 1.48) | 1.39 (0.89, 2.18) | 0.2012 | 1.08 (0.92, 1.27) |
Multivariate model | 1 (Ref) | 1.00 (0.64, 1.56) | 0.91 (0.55, 1.51) | 1.13 (0.68, 1.86) | 0.6855 | 1.00 (0.83, 1.20) |
Sucrose 1 | 68/125 | 78/136 | 68/124 | 120/123 | 334/508 | |
Crude model | 1 (Ref) | 1.09 (0.72, 1.66) | 1.16 (0.73, 1.83) | 1.92 (1.26, 2.94) | 0.0014 | 1.26 (1.08, 1.47) |
Multivariate model | 1 (Ref) | 1.01 (0.64, 1.61) | 0.94 (0.56, 1.57) | 1.57 (0.98, 2.52) | 0.0461 | 1.18 (0.99, 1.40) |
α-glycerophosphate 1 | 82/129 | 85/130 | 85/125 | 82/123 | 334/507 | |
Crude model | 1 (Ref) | 1.15 (0.75, 1.77) | 1.15 (0.74, 1.78) | 1.19 (0.75, 1.88) | 0.4946 | 1.02 (0.87, 1.2) |
Multivariate model | 1 (Ref) | 0.98 (0.6, 1.62) | 0.99 (0.6, 1.62) | 1.23 (0.73, 2.08) | 0.4054 | 1.04 (0.87, 1.25) |
PEP 1 | 63/108 | 74/115 | 50/116 | 94/122 | 281/461 | |
Crude model | 1 (Ref) | 0.93 (0.57, 1.51) | 0.77 (0.47, 1.27) | 1.12 (0.68, 1.82) | 0.7114 | 1.07 (0.90, 1.28) |
Multivariate model | 1 (Ref) | 0.62 (0.35, 1.10) | 0.8 (0.46, 1.41) | 0.89 (0.51, 1.56) | 0.9817 | 1.03 (0.84, 1.25) |
Ratio PEP:lactate 1 | 65/111 | 68/111 | 77/113 | 71/126 | 281/461 | |
Crude model | 1 (Ref) | 1.05 (0.65, 1.68) | 1.11 (0.7, 1.77) | 0.91 (0.56, 1.5) | 0.7976 | 1.02 (0.85, 1.21) |
Multivariate model | 1 (Ref) | 0.91 (0.52, 1.61) | 0.98 (0.58, 1.68) | 0.89 (0.51, 1.57) | 0.7650 | 1.03 (0.85, 1.26) |
Atrial Fibrillation | Heart failure | |||
---|---|---|---|---|
Metabolite | Without Diabetes | With Diabetes | Without Diabetes | With Diabetes |
Phosphoglycerate | 0.89 (0.73, 1.07) | 1.03 (0.87, 1.23) | 0.95 (0.72, 1.25) | 1.57 (1.24, 1.98) |
Hexose monophosphate | 0.90 (0.75, 1.09) | 0.97 (0.81, 1.16) | 0.83 (0.63, 1.1) | 1.19 (0.95, 1.48) |
Fructose/glucose/galactose | 1.12 (0.88, 1.43) | 0.99 (0.82, 1.19) | 1.04 (0.73, 1.47) | 1.01 (0.79, 1.28 |
Lactate | 1.01 (0.85, 1.21) | 1.10 (0.92, 1.31) | 1.01 (0.77, 1.32) | 1.01 (0.8, 1.27) |
Sucrose | 1.05 (0.88, 1.25) | 0.97 (0.81, 1.17) | 1.11 (0.87, 1.41) | 1.18 (0.94, 1.48) |
α-glycerophosphate | 1.18 (0.97, 1.43) | 1.04 (0.86, 1.26) | 1.15 (0.87, 1.52) | 0.95 (0.76, 1.18) |
PEP | 1.13 (0.93, 1.37) | 1.11 (0.89, 1.38) | 1.00 (0.76, 1.31) | 1.10 (0.86, 1.4) |
Ratio PEP:lactate | 1.12 (0.92, 1.37) | 1.05 (0.85, 1.29) | 1.01 (0.76, 1.34) | 1.09 (0.85, 1.39) |
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Becerra-Tomás, N.; Ruiz-Canela, M.; Hernández-Alonso, P.; Bulló, M.; Li, J.; Guasch-Ferré, M.; Toledo, E.; Clish, C.B.; Estruch, R.; Ros, E.; et al. Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial. Metabolites 2021, 11, 306. https://doi.org/10.3390/metabo11050306
Becerra-Tomás N, Ruiz-Canela M, Hernández-Alonso P, Bulló M, Li J, Guasch-Ferré M, Toledo E, Clish CB, Estruch R, Ros E, et al. Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial. Metabolites. 2021; 11(5):306. https://doi.org/10.3390/metabo11050306
Chicago/Turabian StyleBecerra-Tomás, Nerea, Miguel Ruiz-Canela, Pablo Hernández-Alonso, Mònica Bulló, Jun Li, Marta Guasch-Ferré, Estefanía Toledo, Clary B. Clish, Ramon Estruch, Emilio Ros, and et al. 2021. "Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial" Metabolites 11, no. 5: 306. https://doi.org/10.3390/metabo11050306
APA StyleBecerra-Tomás, N., Ruiz-Canela, M., Hernández-Alonso, P., Bulló, M., Li, J., Guasch-Ferré, M., Toledo, E., Clish, C. B., Estruch, R., Ros, E., Fitó, M., Lee, C. -H., Pierce, K., Arós, F., Serra-Majem, L., Liang, L., Razquin, C., Gómez-Gracia, E., Martínez-González, M. A., ... Salas-Salvadó, J. (2021). Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial. Metabolites, 11(5), 306. https://doi.org/10.3390/metabo11050306