Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, 31008 Pamplona, Spain.
IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
Int J Environ Res Public Health. 2022 Oct 21;19(20):13653. doi: 10.3390/ijerph192013653.
Causal reductions in cardiovascular disease (CVD) with the Mediterranean diet (MedDiet) are supported by randomized trials, but the ability of nonrandomized studies to provide causal inferences in nutritional epidemiology is questioned. The "Seguimiento Universidad de Navarra" (SUN) project, conducted during 1999-2019 with 18,419 participants, was used to try to refute non-causal explanations for the inverse association found between adherence to the MedDiet and reduced CVD risk. A framework of different analytical strategies is proposed: alternative definitions of the exposure, exploration of residual confounding, resampling methods, depiction of absolute risks across the follow-up period, trial emulation, and negative controls. Additionally, we calculated the rate advancement period (RAP). We found that one standard deviation increase in the most frequently used MedDiet score was associated with a 29% relative reduction in CVD risk (95% Confidence Interval [CI] 14-41%), which is almost identical to that found in 2 randomized trials. The RAP of CVD would be postponed by an average of 7.9 years (95% CI: 1.6 to 14.2 years) by switching from low (MDS = 0 to2) to high (MDS = 7 to 9) adherence to the MedDiet in the fully adjusted model. Sensitivity analyses, graphical representations of absolute risks, trial emulation, and negative controls also supported causality. In conclusion, a framework of analytical approaches supported the causal effect of the MedDiet on CVD prevention using observational data. Similar methodology could be applied for causal inferences regarding other hypotheses.
采用地中海饮食（MedDiet）可降低心血管疾病（CVD）的发病率，这一结论得到了随机试验的支持，但非随机研究在营养流行病学中提供因果推断的能力仍受到质疑。“纳瓦拉大学随访研究（SUN）”项目于 1999 年至 2019 年期间对 18419 名参与者进行了调查，我们利用该项目来反驳非因果解释，即发现坚持地中海饮食与降低 CVD 风险之间呈反比关系的原因。为此，我们提出了一套不同的分析策略框架：暴露因素的替代定义、剩余混杂因素的探索、重采样方法、随访期间绝对风险的描述、试验模拟以及阴性对照。此外，我们还计算了速率提前期（RAP）。我们发现，最常用的地中海饮食评分每增加一个标准差，CVD 风险相对降低 29%（95%置信区间 [CI] 14-41%），这与两项随机试验的结果几乎一致。在充分调整的模型中，从低（MDS = 0 至 2）到高（MDS = 7 至 9）坚持地中海饮食，CVD 的 RAP 将平均推迟 7.9 年（95%CI：1.6 至 14.2 年）。全因调整模型、敏感性分析、绝对风险的图形表示、试验模拟和阴性对照均支持因果关系。总之，采用观察性数据的分析方法框架支持了地中海饮食对 CVD 预防的因果效应。类似的方法也可应用于其他假说的因果推断。
