Ahmad Shafqat, Moorthy M Vinayaga, Lee I-Min, Ridker Paul M, Manson JoAnn E, Buring Julie, Demler Olga V, Mora Samia
Center for Lipid Metabolomics, Brigham and Women's Hospital, Harvard Medical School, Boston.
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
medRxiv. 2023 Oct 3:2023.10.02.23296458. doi: 10.1101/2023.10.02.23296458.
Higher consumption of Mediterranean diet (MED) intake has been associated with reduced risk of all-cause mortality but limited data are available examining long-term outcomes in women or the underlying molecular mechanisms of this inverse association in human populations. We aimed to investigate the association of MED intake with long-term risk of all-cause mortality in women and to better characterize the relative contribution of traditional and novel cardiometabolic factors to the MED-related risk reduction in morality.
In a prospective cohort study of 25,315 initially healthy women from the Women's Health Study, we assessed dietary MED intake using a validated semiquantitative food frequency questionnaire according to the usual 9-category measure of MED adherence. Baseline levels of more than thirty cardiometabolic biomarkers were measured using standard assays and targeted nuclear magnetic resonance spectroscopy, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small metabolites, and clinical factors. Mortality and cause of death was ascertained prospectively through medical and death records.
During a mean follow-up of 25 years, 3,879 deaths were ascertained. Compared to the reference group of low MED intake (0-3, approximately the bottom tertile), and adjusting for age, treatment, and energy intake, risk reductions were observed for the middle and upper MED groups with respective HRs of 0.84 (95% CI 0.78-0.90) and 0.77 (95% CI 0.70-0.84), p for trend <0.0001. Further adjusting for smoking, physical activity, alcohol intake and menopausal factors attenuated the risk reductions which remained significant with respective HRs of 0.92 (95% CI 0.85-0.99) and 0.89 (95% CI 0.82-0.98), p for trend 0.0011. Risk reductions were generally similar for CVD and non-CVD mortality. Small molecule metabolites (e.g., alanine and homocysteine) and inflammation made the largest contributions to lower mortality risk (accounting for 14.8% and 13.0% of the benefit of the MED-mortality association, respectively), followed by triglyceride-rich lipoproteins (10.2%), adiposity (10.2%) and insulin resistance (7.4%), with lesser contributions (<3%) from other pathways including branched-chain amino acids, high-density lipoproteins, low-density lipoproteins, glycemic measures, and hypertension.
In the large-scale prospective Women's Health Study of 25,315 initially healthy US women followed for 25 years, higher MED intake was associated with approximately one fifth relative risk reduction in mortality. The inverse association was only partially explained by known novel and traditional cardiometabolic factors.
较高的地中海饮食（MED）摄入量与全因死亡率风险降低有关，但关于女性长期结局或人群中这种反向关联的潜在分子机制的可用数据有限。我们旨在研究MED摄入量与女性全因死亡率长期风险的关联，并更好地描述传统和新型心脏代谢因素对MED相关死亡风险降低的相对贡献。
在一项对来自女性健康研究的25315名最初健康的女性进行的前瞻性队列研究中，我们根据MED依从性的常用9分类测量方法，使用经过验证的半定量食物频率问卷评估饮食中的MED摄入量。使用标准检测方法和靶向核磁共振光谱法测量了三十多种心脏代谢生物标志物的基线水平，包括脂质、脂蛋白、载脂蛋白、炎症、葡萄糖代谢和胰岛素抵抗、支链氨基酸、小分子代谢物和临床因素。通过医疗和死亡记录前瞻性地确定死亡率和死亡原因。
在平均25年的随访期间，确定了3879例死亡。与低MED摄入量的参考组（0-3，大约是最低三分位数）相比，并调整年龄、治疗和能量摄入量后，中等和高MED组的风险降低，相应的风险比分别为0.84（95%置信区间0.78-0.90）和0.77（95%置信区间0.70-0.84），趋势p<0.0001。进一步调整吸烟、体育活动、酒精摄入量和绝经因素后，风险降低幅度有所减弱，但仍具有统计学意义，相应的风险比分别为0.92（95%置信区间0.85-0.99）和0.89（95%置信区间0.82-0.98），趋势p为0.0011。心血管疾病（CVD）和非CVD死亡率的风险降低通常相似。小分子代谢物（如丙氨酸和同型半胱氨酸）和炎症对降低死亡风险的贡献最大（分别占MED与死亡率关联益处的14.8%和13.0%），其次是富含甘油三酯的脂蛋白（10.2%）、肥胖（10.2%）和胰岛素抵抗（7.4%），其他途径（包括支链氨基酸、高密度脂蛋白、低密度脂蛋白、血糖指标和高血压）的贡献较小（<3%）。
在对25315名最初健康的美国女性进行的为期25年的大规模前瞻性女性健康研究中，较高的MED摄入量与死亡率相对风险降低约五分之一有关。这种反向关联仅部分由已知的新型和传统心脏代谢因素解释。
