Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
Department of Neurology, School of Medicine, Boston University, Chobanian & Avedisian, Boston, MA, USA.
BMC Med. 2023 Nov 16;21(1):443. doi: 10.1186/s12916-023-03149-2.
Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.
Cumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, physical activity, BMI, and familial relationship. Cox models were used to test the association of alcohol-related metabolite scores with fatal and nonfatal incident CVD (myocardial infarction, coronary heart disease, stroke, and heart failure).
We identified 60 metabolites associated with cumulative average alcohol consumption (p < 0.05/211 ≈ 0.00024). For example, 1 g/day increase of alcohol consumption was associated with higher levels of cholesteryl esters (e.g., CE 16:1, beta = 0.023 ± 0.002, p = 6.3e - 45) and phosphatidylcholine (e.g., PC 32:1, beta = 0.021 ± 0.002, p = 3.1e - 38). Survival analysis identified that 10 alcohol-associated metabolites were also associated with a differential CVD risk after adjusting for age, sex, and batch. Further, we built two alcohol consumption weighted metabolite scores using these 10 metabolites and showed that, with adjustment age, sex, batch, and common CVD risk factors, the two scores had comparable but opposite associations with incident CVD, hazard ratio 1.11 (95% CI = [1.02, 1.21], p = 0.02) vs 0.88 (95% CI = [0.78, 0.98], p = 0.02).
We identified 60 long-term alcohol consumption-associated metabolites. The association analysis with incident CVD suggests a complex metabolic basis between alcohol consumption and CVD.
长期饮酒的代谢特征尚不清楚。为了更好地了解将饮酒与心血管疾病（CVD）联系起来的分子基础，我们研究了与长期饮酒相关的循环代谢物，并检查了这些代谢物是否与 CVD 的发生有关。
在 2428 名弗雷明汉心脏研究后代参与者（平均年龄 56 岁，52%为女性）中，根据 19 年的啤酒、葡萄酒和白酒平均总摄入量，得出累积平均酒精摄入量（g/天）。我们使用线性混合模型来研究饮酒与 211 个经对数转换的血浆代谢物之间的关联，调整因素包括年龄、性别、批次、吸烟、饮食、体力活动、BMI 和家族关系。Cox 模型用于检验与酒精相关的代谢物评分与致命和非致命性 CVD 事件（心肌梗死、冠心病、中风和心力衰竭）之间的相关性。
我们确定了 60 种与累积平均酒精摄入量相关的代谢物（p<0.05/211 ≈ 0.00024）。例如，饮酒量增加 1g/天与胆固醇酯（例如 CE 16:1，β=0.023±0.002，p=6.3e-45）和磷脂酰胆碱（例如 PC 32:1，β=0.021±0.002，p=3.1e-38）水平升高有关。生存分析表明，在调整年龄、性别和批次后，10 种与酒精相关的代谢物也与 CVD 风险的差异相关。此外，我们使用这 10 种代谢物构建了两种酒精摄入加权代谢物评分，并表明在调整年龄、性别、批次和常见 CVD 危险因素后，这两个评分与 CVD 事件发生的相关性相当，但方向相反，风险比为 1.11（95%CI[1.02,1.21]，p=0.02）与 0.88（95%CI[0.78,0.98]，p=0.02）。
我们确定了 60 种与长期饮酒相关的代谢物。与 CVD 事件的相关性分析表明，饮酒与 CVD 之间存在复杂的代谢基础。
