Centre for Nutrition, Department of Clinical Science, University of Bergen, Bergen, Norway.
Mohn Nutrition Research Laboratory, University of Bergen, Bergen, Norway.
J Intern Med. 2023 Apr;293(4):508-519. doi: 10.1111/joim.13610. Epub 2023 Feb 2.
Elevated plasma methylmalonic acid (MMA) is reported in patients with established coronary heart disease (CHD) and is considered a marker of vitamin B12 deficiency. Moreover, MMA-dependent reactions have been linked to alterations in mitochondrial energy metabolism and oxidative stress, key features in the pathophysiology of cardiovascular diseases (CVDs).
We examined whether plasma MMA prospectively predicted the long-term risk of acute myocardial infarction (AMI) and mortality.
Using Cox modeling, we estimated hazard ratios (HRs) for endpoints according to per 1-SD increment of log-transformed plasma MMA in two independent populations: the Western Norway Coronary Angiography Cohort (WECAC) (patients evaluated for CHD; n = 4137) and the Norwegian Vitamin Trial (NORVIT) (patients hospitalized with AMI; n = 3525). In WECAC and NORVIT, 12.8% and 18.0% experienced an AMI, whereas 21.8% and 19.9% died, of whom 45.5% and 60.3% from CVD-related causes during follow-up (range 3-11 years), respectively. In WECAC, age- and gender-adjusted HRs (95% confidence interval) were 1.18 (1.09-1.28), 1.25 (1.18-1.33), and 1.28 (1.17-1.40) for future AMI, total mortality, and CVD mortality, respectively. Corresponding risk estimates were 1.19 (1.10-1.28), 1.22 (1.14-1.31), and 1.30 (1.19-1.42) in NORVIT. These estimates were only slightly attenuated after multivariable adjustments. Across both cohorts, the MMA-risk association was stronger in older adults, women, and non-smokers.
Elevated MMA was associated with an increased risk of AMI and mortality in patients with suspected or verified CHD.
已有研究报道，患有明确冠心病（CHD）的患者其血浆中甲基丙二酸（MMA）水平升高，且该指标被认为是维生素 B12 缺乏的标志物。此外，MMA 依赖性反应与线粒体能量代谢和氧化应激的改变有关，这些改变是心血管疾病（CVD）病理生理学的关键特征。
我们旨在研究血浆 MMA 是否可前瞻性预测急性心肌梗死（AMI）和死亡的长期风险。
我们采用 Cox 模型，根据两个独立人群中 log 转换后血浆 MMA 每 1-SD 递增，估计终点的风险比（HR）：西部挪威冠状动脉造影队列（WECAC）（评估 CHD 的患者；n=4137）和挪威维生素试验（NORVIT）（因 AMI 住院的患者；n=3525）。在 WECAC 和 NORVIT 中，12.8%和 18.0%的患者发生 AMI，21.8%和 19.9%的患者死亡，其中分别有 45.5%和 60.3%的患者死于 CVD 相关原因（随访时间为 3-11 年）。在 WECAC 中，经年龄和性别调整后的 HR（95%置信区间）分别为 1.18（1.09-1.28）、1.25（1.18-1.33）和 1.28（1.17-1.40），用于预测未来 AMI、总死亡率和 CVD 死亡率。在 NORVIT 中，相应的风险估计值分别为 1.19（1.10-1.28）、1.22（1.14-1.31）和 1.30（1.19-1.42）。这些估计值在多变量调整后略有减弱。在两个队列中，MMA 风险相关性在年龄较大、女性和非吸烟者中更强。
在疑似或确诊 CHD 的患者中，MMA 升高与 AMI 和死亡率风险增加相关。
