Guasch-Ferré Marta, Zheng Yan, Ruiz-Canela Miguel, Hruby Adela, Martínez-González Miguel A, Clish Clary B, Corella Dolores, Estruch Ramon, Ros Emilio, Fitó Montserrat, Dennis Courtney, Morales-Gil Isabel M, Arós Fernando, Fiol Miquel, Lapetra José, Serra-Majem Lluís, Hu Frank B, Salas-Salvadó Jordi
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;
Departments of Nutrition and.
Am J Clin Nutr. 2016 Jun;103(6):1408-16. doi: 10.3945/ajcn.116.130492. Epub 2016 Apr 20.
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.
We evaluated the association between 28 plasma acylcarnitine species and risk of incident CVD and the potential modifying effect of Mediterranean diet (MedDiet) interventions.
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.
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.
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.
既往研究表明，在已确诊冠心病的人群中，酰基肉碱水平升高的代谢物谱与心血管疾病（CVD）风险增加相关。然而，据我们所知，这种关联尚未在一级心血管预防的背景下进行评估。
我们评估了28种血浆酰基肉碱种类与CVD发病风险之间的关联以及地中海饮食（MedDiet）干预的潜在调节作用。
在“地中海饮食预防”（PREDIMED）研究中的一项病例队列研究中，我们在基线和随访1年后，使用高通量液相色谱 - 串联质谱法分别测量血浆酰基肉碱，并将其分为短链、中链或长链评分。PREDIMED研究是一项针对一级心血管预防的随机地中海饮食干预研究。本研究纳入了随机选择的一个亚队列（n = 751）以及随访4.8年后所有可用的CVD发病病例（n = 229）。
在调整年龄、性别、体重指数和其他CVD危险因素后，基线短链和中链酰基肉碱处于最高四分位数的参与者患CVD的风险高于最低四分位数的参与者[风险比分别为：1.80（95%置信区间：1.11，2.91；P趋势 = 0.01）和1.55（95%置信区间：1.01，2.48；P趋势 = 0.04）]。随访1年后短链酰基肉碱升高与总CVD和中风风险增加相关。随机分配到对照组的基线短链、中链和长链酰基肉碱浓度较高的参与者患CVD的风险高于分配到MedDiet组的酰基肉碱浓度较低的参与者。
我们的数据支持这样的结论，即酰基肉碱浓度升高所表征的代谢物谱在CVD高风险参与者中单独与总CVD和中风风险独立相关。MedDiet干预可能减轻较高浓度酰基肉碱与CVD之间显示的不良关联。本试验在www.controlled-trials.com上注册，注册号为ISRCTN35739639。
