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Plasma acylcarnitines and risk of cardiovascular disease: effect of Mediterranean diet interventions
Marta Guasch-Ferré1, Yan Zheng2, Miguel Ruiz-Canela3
1Departments 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;
Insights
Elevated acylcarnitines are linked to higher cardiovascular disease (CVD) risk in primary prevention. Mediterranean diet interventions may reduce this risk, offering a protective dietary strategy.
Area of Science:
- Metabolomics and cardiovascular disease research.
- Nutritional epidemiology and primary prevention.
Background:
- Previous studies linked elevated acylcarnitines to cardiovascular disease (CVD) risk in patients with existing coronary disease.
- This association has not been previously evaluated in the context of primary CVD prevention.
Purpose of the Study:
- To evaluate the association between 28 plasma acylcarnitine species and the risk of incident CVD.
- To investigate the potential modifying effect of Mediterranean diet (MedDiet) interventions on this association.
Main Methods:
- A case-cohort study within the PREDIMED trial (n=751 subcohort, n=229 CVD cases).
- Plasma acylcarnitines were measured using liquid chromatography-tandem mass spectrometry at baseline and 1-year follow-up.
- Acylcarnitines were analyzed individually and as short-, medium-, and long-chain scores.
Main Results:
- Higher baseline short- and medium-chain acylcarnitines were associated with increased CVD risk (HRs 1.80 and 1.55, respectively).
- Increased short-chain acylcarnitines after 1 year correlated with higher risks of total CVD and stroke.
- Individuals with higher acylcarnitine concentrations in the control group showed greater CVD risk compared to those on MedDiet with lower concentrations.
Conclusions:
- Elevated acylcarnitine concentrations are independently associated with increased risks of total CVD and stroke in high-risk individuals.
- Mediterranean diet interventions may mitigate the adverse effects of high acylcarnitine levels on CVD risk.
- Findings support acylcarnitines as potential biomarkers for CVD risk in primary prevention settings.
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.
Objectives:
We evaluated the association between 28 plasma acylcarnitine species and risk of incident CVD and the potential modifying effect of Mediterranean diet (MedDiet) interventions.
Design:
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.
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