In the U.S., one in every three deaths is attributable to cardiovascular disease (CVD). Healthy diet and lifestyle are crucial for CVD prevention. The traditional Mediterranean dietary pattern has received increasing attention because of its potential beneficial effects on CVD risk. Recently, the landmark PREDIMED randomized trial (n=7,447 participants free of diagnosed CVD at baseline) demonstrated that a Mediterranean dietary pattern, supplemented with either virgin olive oil or tree nuts, significantly reduced the risk of major clinical CVD events by ~30%, compared to a control diet, after a median follow-up of 4.8 years. The goal of this project is to examine the effects of the randomized PREDIMED dietary interventions on plasma levels of metabolites, and to determine whether these resulting metabolic profiles mediate the interventions'benefits on CVD risk. A nested case-cohort design will be used, incorporating all 288 incident cases of CVD and 745 (10%) randomly selected trial participants at baseline. Stored fasting blood specimens collected at baseline and at year 1 of the trial will be measured for a well-validated panel of ~300 metabolites, using the state-of-the-art LC-MS technology developed by the Broad Institute of MIT and Harvard. We will focus on classes of metabolites that have been implicated in cardio-metabolic risk. Our project includes three specific aims: 1) To examine the effects of the randomized dietary interventions on changes in plasma levels of metabolites from baseline to year 1 in 745 randomly selected trial participants;2) To examine whether 1-year changes in plasma levels of metabolites mediate the effect of the randomized dietary interventions on subsequent clinical CVD outcomes from years 2 to 5, using the efficient case-cohort design;and 3) To examine whether baseline metabolite levels modify the effects of the randomized dietary interventions on CVD risk, using a case-cohort design. As a secondary aim, we will examine whether 1-year changes in metabolites mediate the benefits of dietary interventions on subsequent occurrence of the metabolic syndrome, among 745 randomly selected trial participants. The PREDIMED is the first randomized primary prevention trial to evaluate the effects of Mediterranean-style dietary interventions on hard CVD endpoints. The current proposal outlines an extremely efficient and innovative study that applies the state-of-the-art metabolomics technology to a rigorously conducted dietary intervention trial. This study provides an ideal opportunity to discover novel pathways through which diet influences CVD risk, with access to archived plasma samples at baseline and follow-up, well-documented CVD endpoints, and long-term, randomized interventions with excellent compliance. The 2010 Dietary Guidelines for Americans has recognized the Mediterranean dietary pattern, along with the Dietary Approaches to Stop Hypertension (DASH) diet, as a healthy diet for CVD prevention. Results from this study will provide further evidence to support public health recommendations for dietary prevention of CVD.

Public Health Relevance

Cardiovascular disease (CVD) is a leading cause of death in the U.S. and world-wide. Diet and lifestyle are crucial for CVD prevention. The PREDIMED trial (n=7,447 participants free of diagnosed CVD at baseline) recently demonstrated that a Mediterranean dietary pattern significantly reduced the risk of major clinical CVD events by approximately 30%, compared to a control diet. The goal of this project is to examine the effects of the randomized PREDIMED dietary interventions on plasma levels of metabolites and to determine whether these resulting metabolic profiles mediate the benefits of the Mediterranean diet on CVD risk, using a cost- effective case-cohort design. The study has the potential to discover novel pathways through which diet influences CVD risk, and will provide further evidence to support public health recommendations for dietary prevention of CVD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL118264-02
Application #
8853010
Study Section
Cardiovascular and Sleep Epidemiology Study Section (CASE)
Program Officer
Wright, Jacqueline
Project Start
2013-07-15
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Harvard University
Department
Nutrition
Type
Schools of Public Health
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Satija, Ambika; Hu, Frank B (2018) Plant-based diets and cardiovascular health. Trends Cardiovasc Med 28:437-441
Pan, An; Lin, Xu; Hemler, Elena et al. (2018) Diet and Cardiovascular Disease: Advances and Challenges in Population-Based Studies. Cell Metab 27:489-496
Razquin, Cristina; Liang, Liming; Toledo, Estefanía et al. (2018) Plasma lipidome patterns associated with cardiovascular risk in the PREDIMED trial: A case-cohort study. Int J Cardiol 253:126-132
Yu, Edward; Malik, Vasanti S; Hu, Frank B (2018) Cardiovascular Disease Prevention by Diet Modification: JACC Health Promotion Series. J Am Coll Cardiol 72:914-926
Guasch-Ferré, Marta; Hu, Frank B; Ruiz-Canela, Miguel et al. (2017) Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study. J Am Heart Assoc 6:
Toledo, Estefanía; Wang, Dong D; Ruiz-Canela, Miguel et al. (2017) Plasma lipidomic profiles and cardiovascular events in a randomized intervention trial with the Mediterranean diet. Am J Clin Nutr 106:973-983
(2017) Erratum for Yu et al. Increases in plasma tryptophan are inversely associated with incident cardiovascular disease in the Prevención con Dieta Mediterránea (PREDIMED) Study. J Nutr 2017;147:314-22. J Nutr 147:1234
Ruiz-Canela, Miguel; Hruby, Adela; Clish, Clary B et al. (2017) Comprehensive Metabolomic Profiling and Incident Cardiovascular Disease: A Systematic Review. J Am Heart Assoc 6:
Yu, Edward; Ruiz-Canela, Miguel; Hu, Frank B et al. (2017) Plasma Arginine/Asymmetric Dimethylarginine Ratio and Incidence of Cardiovascular Events: A Case-Cohort Study. J Clin Endocrinol Metab 102:1879-1888
Yu, Edward; Ruiz-Canela, Miguel; Guasch-Ferré, Marta et al. (2017) Increases in Plasma Tryptophan Are Inversely Associated with Incident Cardiovascular Disease in the Prevención con Dieta Mediterránea (PREDIMED) Study. J Nutr 147:314-322

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