Department of Public Health, Shiga University of Medical Science.
Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
J Atheroscler Thromb. 2024 Feb 1;31(2):135-147. doi: 10.5551/jat.64222. Epub 2023 Aug 23.
It remains inconclusive regarding alcohol intake and stroke risk because determining risk factors depends on the specific pathogenesis of stroke. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in cerebral small- and large-vessel diseases.
We studied 682 men (mean age, 70.0 years), without stroke, in a cross-sectional Mendelian randomization analysis. We assessed small-vessel diseases (SVDs), which comprised lacunar infarcts, white matter hyperintensities (WMHs), and cerebral microbleeds, and large intracranial artery stenosis (ICAS) on brain magnetic resonance imaging.
The median (25%tiles, 75%tiles) alcohol consumption by ALDH2-rs671 inactive A allele (n=313 [45.9%]) and non-A allele (n=369 [54.1%]) carriers was 3.5 (0.0, 16.0) and 32.0 (12.9, 50.0) g/day, respectively. Non-A allele carriers had higher prevalent hypertension and lower low-density lipoprotein cholesterol concentrations than A allele carriers. In age-adjusted ordinal logistic regression for graded burden, odds ratios (95% confidence intervals) for total SVDs, lacunar infarcts, WMHs, cerebral microbleeds, and ICAS in non-Aallele carriers were 1.46 (1.09-1.94), 1.41 (0.95-2.08), 1.39 (1.05-1.85), 1.69 (1.06-2.69), and 0.70 (0.50-0.98), respectively, compared with A allele carriers. These associations attenuated to statistical non-significance after considering covariates and amount of alcohol intake.
Our findings suggest a positive association of alcohol consumption with risk of cerebral SVDs and its inverse association with risk of large-vessel disease through intermediaries, such as hypertension or low-density lipoprotein cholesterol. These findings provide insight into potential causal mechanisms linking alcohol consumption with stroke risk.
由于确定风险因素取决于中风的具体发病机制，因此饮酒与中风风险之间的关系仍不明确。我们使用乙醛脱氢酶 2 基因（ALDH2）中的变体 rs671 作为工具，来研究饮酒对脑小血管和大血管疾病的因果作用。
我们在一项横断面孟德尔随机化分析中研究了 682 名（平均年龄 70.0 岁）无中风的男性。我们通过脑磁共振成像评估了小血管疾病（SVDs），包括腔隙性梗死、脑白质高信号（WMHs）和脑微出血，以及颅内大动脉狭窄（ICAS）。
ALDH2-rs671 无活性 A 等位基因（n=313 [45.9%]）和非-A 等位基因（n=369 [54.1%]）携带者的中位（25%分位数，75%分位数）饮酒量分别为 3.5（0.0，16.0）和 32.0（12.9，50.0）g/天。非-A 等位基因携带者比 A 等位基因携带者更容易患有高血压，且低密度脂蛋白胆固醇浓度更低。在按年龄调整的分级有序逻辑回归中，非-A 等位基因携带者的 SVD 总负荷、腔隙性梗死、WMHs、脑微出血和 ICAS 的比值比（95%置信区间）分别为 1.46（1.09-1.94）、1.41（0.95-2.08）、1.39（1.05-1.85）、1.69（1.06-2.69）和 0.70（0.50-0.98），与 A 等位基因携带者相比。考虑到协变量和饮酒量后，这些关联减弱至无统计学意义。
我们的研究结果表明，饮酒与脑 SVD 风险呈正相关，与大血管疾病风险呈负相关，其通过高血压或低密度脂蛋白胆固醇等中介物起作用。这些发现为饮酒与中风风险之间的潜在因果机制提供了新的认识。
