title: Mercury exposure and risk of cardiovascular disease: a nested case-control study in the PREDIMED (PREvention with MEDiterranean Diet) study.
abstract: Substantial evidence suggests that consuming 1-2 servings of fish per week, particularly oily fish (e.g., salmon, herring, sardines) is beneficial for cardiovascular health due to its high n-3 polyunsaturated fatty acid content. However, there is some concern that the mercury content in fish may increase cardiovascular disease risk, but this relationship remains unclear.
  
  
  
  The PREDIMED trial included 7477 participants who were at high risk for cardiovascular disease at baseline. In this study, we evaluated associations between mercury exposure, fish consumption and cardiovascular disease. We randomly selected 147 of the 288 cases diagnosed with cardiovascular disease during follow-up and matched them on age and sex to 267 controls. Instrumental neutron activation analysis was used to assess toenail mercury concentration. In-person interviews, medical record reviews and validated questionnaires were used to assess fish consumption and other covariates. Information was collected at baseline and updated yearly during follow-up. We used conditional logistic regression to evaluate associations in the total nested case-control study, and unconditional logistic regression for population subsets.
  
  
  
  Mean (±SD) toenail mercury concentrations (μg per gram) did not significantly differ between cases (0.63 (±0.53)) and controls (0.67 (±0.49)). Mercury concentration was not associated with cardiovascular disease in any analysis, and neither was fish consumption or n-3 fatty acids. The fully-adjusted relative risks for the highest versus lowest quartile of mercury concentration were 0.71 (95% Confidence Interval [CI], 0.34, 1.14; ptrend= 0.37) for the nested case-control study, 0.74 (95% CI, 0.32, 1.76; ptrend= 0.43) within the Mediterranean diet intervention group, and 0.50 (95% CI, 0.13, 1.96; ptrend= 0.41) within the control arm of the trial. Associations remained null when mercury was jointly assessed with fish consumption at baseline and during follow-up. Results were similar in different sensitivity analyses.
  
  
  
  We found no evidence that mercury exposure from regular fish consumption increases cardiovascular disease risk in a population of Spanish adults with high cardiovascular disease risk and high fish consumption. This implies that the mercury content in fish does not detract from the already established cardiovascular benefits of fish consumption.
  
  
  
  ISRCTN35739639 .
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, USA.|Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Downer
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martínez-González
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, USA.|CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gea
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, USA.
authors.forename: Meir
authors.initials: M
authors.lastname: Stampfer
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Preventive Medicine, University of Malaga, Malaga, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Warnberg
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Ruiz-Canela
authors.affiliation: Human Nutrition Unit, Faculty of Medicine and Health Sciences, IISPV, Rovira i Virgili University, Reus, Spain.|CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Salas-Salvadó
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Preventive Medicine, University of Valencia, Valencia, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Lipid Clinic, Endocrinology and Nutrition Service, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Cardiovascular Risk and Nutrition (Regicor Study Group), Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Montse
authors.initials: M
authors.lastname: Fitó
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Internal Medicine, August Pi i Sunyer Institute of Biomedical Research (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Estruch
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Cardiology, University Hospital Araba, Vitoria, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Arós
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Institute of Health Sciences, University of Balearic Islands and Son Espases Hospital, Palma de Mallorca, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Fiol
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Lapetra
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Serra-Majem
authors.affiliation: Human Nutrition Unit, Faculty of Medicine and Health Sciences, IISPV, Rovira i Virgili University, Reus, Spain.|CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Bullo
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Department of Preventive Medicine, University of Valencia, Valencia, Spain.
authors.forename: Jose V
authors.initials: JV
authors.lastname: Sorli
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.|Cardiovascular Risk and Nutrition (Regicor Study Group), Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Muñoz
authors.affiliation: Department of Preventive Medicine, University of Malaga, Malaga, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: García-Rodriguez
authors.affiliation: Department of Preventive Medicine, University of Malaga, Malaga, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Gutierrez-Bedmar
authors.affiliation: CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain. egomezgracia@uma.es.|Department of Preventive Medicine, University of Malaga, Malaga, Spain. egomezgracia@uma.es.|Campus Teatinos, Facultad de Medicina, 29071, Malaga, Spain. egomezgracia@uma.es.
authors.forename: Enrique
authors.initials: E
authors.lastname: Gómez-Gracia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001822:Body Burden; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D016022:Case-Control Studies; D038441:Diet, Mediterranean / Q000009:adverse effects; D005260:Female; D005506:Food Contamination / Q000032:analysis*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008767:Methylmercury Compounds / Q000009:adverse effects / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D009262:Nails / Q000737:chemistry*; D016017:Odds Ratio; D011446:Prospective Studies; D065840:Protective Factors; D064167:Recommended Dietary Allowances; D018570:Risk Assessment; D012307:Risk Factors; D017747:Seafood / Q000009:adverse effects; D013030:Spain; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000009:adverse effects / Q000032:analysis*
chemical_list: D008767:Methylmercury Compounds; D014874:Water Pollutants, Chemical
keywords: Cardiovascular disease; Fish; Mediterranean diet; Mercury; PREDIMED; Toenail biomarker