Dataset Information

The Mediterranean diet, plasma metabolome, and cardiovascular disease risk.

ABSTRACT:

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.

SUBMITTER: Li J

PROVIDER: S-EPMC7377580 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

The Mediterranean diet, plasma metabolome, and cardiovascular disease risk.

Li Jun J Guasch-Ferré Marta M Chung Wonil W Ruiz-Canela Miguel M Toledo Estefanía E Corella Dolores D Bhupathiraju Shilpa N SN Tobias Deirdre K DK Tabung Fred K FK Hu Jie J Zhao Tong T Turman Constance C Feng Yen-Chen Anne YA Clish Clary B CB Mucci Lorelei L Eliassen A Heather AH Costenbader Karen H KH Karlson Elizabeth W EW Wolpin Brian M BM Ascherio Alberto A Rimm Eric B EB Manson JoAnn E JE Qi Lu L Martínez-González Miguel Ángel MÁ Salas-Salvadó Jordi J Hu Frank B FB Liang Liming L

European heart journal 20200701 28

<h4>Aims</h4>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.<h4>Methods and results</h4>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 Profes ...[more]

PMID: 32406924

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Project description:BackgroundThe relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions.Methods and resultsWe designed a case-cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography-tandem mass spectrometry to measure, at baseline and at 1 year of follow-up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N-oxide, betaine, choline, phosphocholine, and α-glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1-SD increase in choline and α-glycerophosphocholine metabolites were 1.24 (1.05-1.46) and 1.24 (1.03-1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21-fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36-3.59; P<0.001 for trend) and a 2.27-fold higher risk of stroke (95% confidence interval, 1.24-4.16; P<0.001 for trend). Participants in the higher quartiles of the score who were randomly assigned to the control group had a higher risk of CVD compared with participants in the lower quartile and assigned to the Mediterranean diet groups (P=0.05 for interaction). No significant associations were observed for 1-year changes in individual plasma metabolites and CVD.ConclusionsA metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk.Clinical trial registrationURL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.

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Dataset Information

The Mediterranean diet, plasma metabolome, and cardiovascular disease risk.

Aims

Methods and results

Conclusions

Publications

The Mediterranean diet, plasma metabolome, and cardiovascular disease risk.

Similar Datasets

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