Plasma acylcarnitines and risk of cardiovascular disease: effect of Mediterranean diet interventions.
BACKGROUND
Previous studies have suggested that metabolite profiles of elevated acylcarnitines were associated with increased risk of cardiovascular disease (CVD) in populations with established coronary disease. However, to our knowledge, this association has not been evaluated in the context of primary cardiovascular prevention.


OBJECTIVE
We evaluated the association between 28 plasma acylcarnitine species and risk of incident CVD and the potential modifying effect of Mediterranean diet (MedDiet) interventions.


METHODS
We measured plasma acylcarnitines with the use of high-throughput liquid chromatography-tandem mass spectrometry at baseline and after 1 y of follow-up, both individually and classified into short-, medium-, or long-chain scores, in a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED) study, which is a randomized Mediterranean dietary intervention for primary cardiovascular prevention. A randomly selected subcohort (n = 751) and all available incident CVD cases (n = 229) after 4.8 y of follow-up were included in the current study.


RESULTS
After adjustment for age, sex, body mass index, and other CVD risk factors, participants in the highest quartile of baseline short- and medium-chain acylcarnitines had a higher risk of CVD than did participants in the lowest quartile [HRs: 1.80 (95% CI: 1.11, 2.91; P-trend 0.01) and 1.55 (95% CI: 1.01, 2.48; P-trend = 0.04), respectively]. Increased short-chain acylcarnitines after 1 y were associated with higher risks of total CVD and stroke. Participants with higher baseline concentrations of short-, medium-, and long-chain acylcarnitines who were randomly assigned to the control group had a higher risk of CVD than did subjects with lower concentrations of acylcarnitines who were assigned to the MedDiet group.


CONCLUSIONS
Our data support the conclusion that metabolite profiles characterized by elevated concentrations of acylcarnitines are independently associated with risks of total CVD and stroke alone in participants at high risk of CVD. MedDiet interventions may mitigate the adverse associations shown between higher concentrations of acylcarnitines and CVD. This trial was registered at www.controlled-trials.com as ISRCTN35739639.
Departments of Nutrition and Human Nutrition Department, Pere Virgili Research Institute, University Hospital of Sant Joan de Reus, Rovira i Virgili University, Reus, Spain; The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain;
Marta
http://orcid.org/0000-0002-5141-1796
M
Guasch-Ferré
Departments of Nutrition and.
Yan
Y
Zheng
The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain; Department of Preventive Medicine and Public Health, University of Navarra-Medical Research Institute of Navarra, Pamplona, Spain;
Miguel
M
Ruiz-Canela
Departments of Nutrition and.
Adela
A
Hruby
The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain; Department of Preventive Medicine and Public Health, University of Navarra-Medical Research Institute of Navarra, Pamplona, Spain;
Miguel A
MA
Martínez-González
Broad Institute of MIT and Harvard University, Cambridge, MA;
Clary B
CB
Clish
The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain; Department of Preventive Medicine, University of Valencia, Valencia, Spain;
Dolores
D
Corella
The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain; Department of Internal Medicine and.
Ramon
R
Estruch
The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain; Lipid Clinic, Department of Endocrinology and Nutrition, Biomedical Research Institute Agustí Pi Sunyer, Clinic Hospital, University of Barcelona, Barcelona, Spain;
Emilio
E
Ros
The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain; Cardiovascular and Nutrition Research Group, Hospital del Mar Research Institute, Barcelona, Spain;
Montserrat
M
Fitó
Broad Institute of MIT and Harvard University, Cambridge, MA;
Courtney
C
Dennis
Department of Infirmary, Faculty of Health Science, University of Malaga, Malaga, Spain;
Isabel M
IM
Morales-Gil
Department of Cardiology, University Hospital of Alava, Vitoria, Spain;
Fernando
F
Arós
Institute of Health Sciences of University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain;
Miquel
M
Fiol
The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain; Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain;
José
J
Lapetra
The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain; Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain; and.
Lluís
L
Serra-Majem
Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Frank B
FB
Hu
Human Nutrition Department, Pere Virgili Research Institute, University Hospital of Sant Joan de Reus, Rovira i Virgili University, Reus, Spain; The Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Health Institute Carlos III, Madrid, Spain; jordi.salas@urv.cat.
Jordi
http://orcid.org/0000-0003-2700-7459
J
Salas-Salvadó
D000368:Aged; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000517:prevention & control*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D015331:Cohort Studies; D038441:Diet, Mediterranean; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control
C116917:acylcarnitine; D002331:Carnitine
Mediterranean diet; PREDIMED; acylcarnitines; cardiovascular disease; metabolomics