The Mediterranean diet, plasma metabolome, and cardiovascular disease risk
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The Mediterranean diet, plasma metabolome, and cardiovascular disease risk. / Li, Jun; Guasch-Ferré, Marta; Chung, Wonil; Ruiz-Canela, Miguel; Toledo, Estefaniá; Corella, Dolores; Bhupathiraju, Shilpa N.; Tobias, Deirdre K.; Tabung, Fred K.; Hu, Jie; Zhao, Tong; Turman, Constance; Feng, Yen Chen Anne; Clish, Clary B.; Mucci, Lorelei; Eliassen, A. Heather; Costenbader, Karen H.; Karlson, Elizabeth W.; Wolpin, Brian M.; Ascherio, Alberto; Rimm, Eric B.; Manson, Jo Ann E.; Qi, Lu; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Hu, Frank B.; Liang, Liming.
In: European Heart Journal, Vol. 41, No. 28, 2020, p. 2645-2656.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Mediterranean diet, plasma metabolome, and cardiovascular disease risk
AU - Li, Jun
AU - Guasch-Ferré, Marta
AU - Chung, Wonil
AU - Ruiz-Canela, Miguel
AU - Toledo, Estefaniá
AU - Corella, Dolores
AU - Bhupathiraju, Shilpa N.
AU - Tobias, Deirdre K.
AU - Tabung, Fred K.
AU - Hu, Jie
AU - Zhao, Tong
AU - Turman, Constance
AU - Feng, Yen Chen Anne
AU - Clish, Clary B.
AU - Mucci, Lorelei
AU - Eliassen, A. Heather
AU - Costenbader, Karen H.
AU - Karlson, Elizabeth W.
AU - Wolpin, Brian M.
AU - Ascherio, Alberto
AU - Rimm, Eric B.
AU - Manson, Jo Ann E.
AU - Qi, Lu
AU - Martínez-González, Miguel Ángel
AU - Salas-Salvadó, Jordi
AU - Hu, Frank B.
AU - Liang, Liming
N1 - Publisher Copyright: © 2020 Published on behalf of the European Society of Cardiology. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Aims: To investigate whether metabolic signature composed of multiple plasma metabolites can be used to characterize adherence and metabolic response to the Mediterranean diet and whether such a metabolic signature is associated with cardiovascular disease (CVD) risk. Methods and results: Our primary study cohort included 1859 participants from the Spanish PREDIMED trial, and validation cohorts included 6868 participants from the US Nurses' Health Studies I and II, and Health Professionals Follow-up Study (NHS/HPFS). Adherence to the Mediterranean diet was assessed using a validated Mediterranean Diet Adherence Screener (MEDAS), and plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry. We observed substantial metabolomic variation with respect to Mediterranean diet adherence, with nearly one-third of the assayed metabolites significantly associated with MEDAS (false discovery rate < 0.05). Using elastic net regularized regressions, we identified a metabolic signature, comprised of 67 metabolites, robustly correlated with Mediterranean diet adherence in both PREDIMED and NHS/HPFS (r = 0.28-0.37 between the signature and MEDAS; P = 3 × 10-35 to 4 × 10-118). In multivariable Cox regressions, the metabolic signature showed a significant inverse association with CVD incidence after adjusting for known risk factors (PREDIMED: Hazard ratio [HR] per standard deviation increment in the signature = 0.71, P < 0.001; NHS/HPFS: HR = 0.85, P = 0.001), and the association persisted after further adjustment for MEDAS scores (PREDIMED: HR = 0.73, P = 0.004; NHS/HPFS: HR = 0.85, P = 0.004). Further genome-wide association analysis revealed that the metabolic signature was significantly associated with genetic loci involved in fatty acids and amino acids metabolism. Mendelian randomization analyses showed that the genetically inferred metabolic signature was significantly associated with risk of coronary heart disease (CHD) and stroke (odds ratios per SD increment in the genetically inferred metabolic signature = 0.92 for CHD and 0.91 for stroke; P < 0.001). Conclusions: We identified a metabolic signature that robustly reflects adherence and metabolic response to a Mediterranean diet, and predicts future CVD risk independent of traditional risk factors, in Spanish and US cohorts.
AB - Aims: To investigate whether metabolic signature composed of multiple plasma metabolites can be used to characterize adherence and metabolic response to the Mediterranean diet and whether such a metabolic signature is associated with cardiovascular disease (CVD) risk. Methods and results: Our primary study cohort included 1859 participants from the Spanish PREDIMED trial, and validation cohorts included 6868 participants from the US Nurses' Health Studies I and II, and Health Professionals Follow-up Study (NHS/HPFS). Adherence to the Mediterranean diet was assessed using a validated Mediterranean Diet Adherence Screener (MEDAS), and plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry. We observed substantial metabolomic variation with respect to Mediterranean diet adherence, with nearly one-third of the assayed metabolites significantly associated with MEDAS (false discovery rate < 0.05). Using elastic net regularized regressions, we identified a metabolic signature, comprised of 67 metabolites, robustly correlated with Mediterranean diet adherence in both PREDIMED and NHS/HPFS (r = 0.28-0.37 between the signature and MEDAS; P = 3 × 10-35 to 4 × 10-118). In multivariable Cox regressions, the metabolic signature showed a significant inverse association with CVD incidence after adjusting for known risk factors (PREDIMED: Hazard ratio [HR] per standard deviation increment in the signature = 0.71, P < 0.001; NHS/HPFS: HR = 0.85, P = 0.001), and the association persisted after further adjustment for MEDAS scores (PREDIMED: HR = 0.73, P = 0.004; NHS/HPFS: HR = 0.85, P = 0.004). Further genome-wide association analysis revealed that the metabolic signature was significantly associated with genetic loci involved in fatty acids and amino acids metabolism. Mendelian randomization analyses showed that the genetically inferred metabolic signature was significantly associated with risk of coronary heart disease (CHD) and stroke (odds ratios per SD increment in the genetically inferred metabolic signature = 0.92 for CHD and 0.91 for stroke; P < 0.001). Conclusions: We identified a metabolic signature that robustly reflects adherence and metabolic response to a Mediterranean diet, and predicts future CVD risk independent of traditional risk factors, in Spanish and US cohorts.
KW - Cardiovascular disease
KW - Dietary metabolic response
KW - Mediterranean diet
KW - Mendelian randomization analysis
KW - Metabolomics
KW - Risk prediction
U2 - 10.1093/eurheartj/ehaa209
DO - 10.1093/eurheartj/ehaa209
M3 - Journal article
C2 - 32406924
AN - SCOPUS:85088610256
VL - 41
SP - 2645
EP - 2656
JO - European Heart Journal
JF - European Heart Journal
SN - 0195-668X
IS - 28
ER -
ID: 357885851