Ma Xiong-Bin, Lv Yan-Lin, Qian Lin, Yang Jing-Fen, Song Qian, Liu Yong-Ming
The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China.
The First Clinical Medical College of Guangdong Medical University, Zhanjiang, Guangdong, China.
Front Cardiovasc Med. 2025 Apr 15;12:1453106. doi: 10.3389/fcvm.2025.1453106. eCollection 2025.
To assess the causal relationship between coffee consumption and cardiac structure and function in elderly European populations using multiple genetic methodologies.
Leveraging genome-wide association study (GWAS) data from elderly European populations, we conducted linkage disequilibrium score regression (LDSC), two-step Mendelian randomization (MR), and colocalization analyses to investigate genetic associations, causal relationships, and mediating effects among these factors. Robustness of findings was verified through comprehensive sensitivity analyses.
LDSC regression analysis revealed positive genetic correlations between coffee consumption and cardiac parameters, excluding left ventricular (LV) ejection fraction and right ventricular (RV) ejection fraction. MR results demonstrated favorable associations between increased coffee consumption and cardiac parameters. After applying the Bonferroni adjustment to IVW analysis, as coffee consumption increased by each 1-cup/day, LV end-diastolic volume increased ( = 0.128; 95% CI: 0.043-0.212; = 0.002), an increase in LV end-systolic volume ( = 0.143; 95% CI: 0.053-0.232; = 0.001), an increase in RV end-diastolic volume ( = 0.200; 95% CI: 0.095-0.305; < 0.001), and an increase in RV stroke volume ( = 0.209; 95% CI: 0.104-0.313; < 0.001). Mediation analyses indicated that each 1-cup/day increase in coffee consumption significantly correlated with reduced diastolic blood pressure (DBP) and elevated body mass index (BMI). Notably, higher DBP exhibited inverse associations with ventricular systolic/diastolic functional parameters, whereas increased BMI demonstrated positive associations with these parameters, collectively mitigating age-related ventricular volume loss. No U-shaped associations were detected in linear MR frameworks. Colocalization analyses confirmed shared causal genetic variants between coffee intake and cardiac remodeling phenotypes.
Genetically predicted coffee consumption may counteract age-associated ventricular volume loss in elderly Europeans through dual mediation pathways involving DBP reduction and BMI elevation. These structural adaptations suggest potential cardioprotective mechanisms against senile cardiac atrophy. Future studies should prioritize the integration of coffee consumption into cardiovascular risk assessment frameworks and develop personalized recommendations based on individual health profiles.
运用多种遗传方法评估欧洲老年人群中咖啡摄入量与心脏结构和功能之间的因果关系。
利用来自欧洲老年人群的全基因组关联研究（GWAS）数据，我们进行了连锁不平衡评分回归（LDSC）、两步孟德尔随机化（MR）和共定位分析，以研究这些因素之间的遗传关联、因果关系和中介效应。通过全面的敏感性分析验证了研究结果的稳健性。
LDSC回归分析显示，除左心室（LV）射血分数和右心室（RV）射血分数外，咖啡摄入量与心脏参数之间存在正遗传相关性。MR结果表明，咖啡摄入量增加与心脏参数之间存在有益关联。在对IVW分析应用Bonferroni校正后，咖啡摄入量每增加1杯/天，左心室舒张末期容积增加（β = 0.128；95%CI：0.043 - 0.212；P = 0.002），左心室收缩末期容积增加（β = 0.143；95%CI：0.053 - 0.232；P = 0.001），右心室舒张末期容积增加（β = 0.200；95%CI：0.095 - 0.305；P < 0.001），右心室每搏输出量增加（β = 0.209；95%CI：0.104 - 0.313；P < 0.001）。中介分析表明，咖啡摄入量每增加1杯/天，与舒张压（DBP）降低和体重指数（BMI）升高显著相关。值得注意的是，较高的DBP与心室收缩/舒张功能参数呈负相关，而BMI升高与这些参数呈正相关，共同减轻了与年龄相关的心室容积损失。在线性MR框架中未检测到U型关联。共定位分析证实了咖啡摄入量与心脏重塑表型之间存在共同的因果遗传变异。
遗传预测的咖啡摄入量可能通过涉及降低DBP和升高BMI的双重中介途径抵消欧洲老年人与年龄相关的心室容积损失。这些结构适应性提示了针对老年心脏萎缩的潜在心脏保护机制。未来的研究应优先将咖啡摄入量纳入心血管风险评估框架，并根据个体健康状况制定个性化建议。
