Circulating trimethyllysine and risk of acute myocardial infarction in patients with suspected stable coronary heart disease
Circulating trimethyllysine and risk of acute myocardial infarction in patients with suspected stable coronary heart disease
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DOI：
10.1111/joim.13119
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发表时间：
2020-10-01
影响因子：
11.1
通讯作者：
Halalau, A.
中科院分区：
文献类型：
--
作者：
Imam, Z.;Odish, F.;Halalau, A.
背景：肉毒碱前体三甲基赖氨酸（TML）与动脉粥样硬化的进展有关，可能与氧化三甲胺（TMAO）有关。核黄素是TMAO合成中的辅因子。我们研究了循环TML和TMAO与急性心肌梗死（AMI）的前瞻性关系以及核黄素状态对潜在效应的影响。方法采用考克斯模型对4098例可疑稳定型心绞痛患者（71.8%为男性）进行危险因素分析。根据血浆核黄素中位数进行亚组分析。结果在平均4.9年的随访中，336例（8.2%）患者发生了AMI。比较第4个与第1个TML四分位数，年龄和性别校正的风险比（HR）（95% CI）为2.19（1.56-3.09）。传统心血管风险因素和肾功能指数的多变量校正仅略微降低了风险估计值[HR（95% CI）1.79（1.23-2.59）]，这在核黄素水平高于中位数的患者中尤其明显（P-int = 0.035）。血浆TML和TMAO强相关（r（s）= 0.41;P < 0.001）;然而，在校正分析中，血浆TMAO与AMI风险无关[HR（95%CI）0.81（0.58-1.14）]。未观察到TML和TMAO之间的相互作用。结论在疑似稳定型心绞痛患者中，血浆TML而非TMAO可独立预测AMI的风险。我们的研究结果激发了对决定TML水平的代谢过程及其与心血管疾病的潜在关联的进一步研究。我们没有调整多重比较，亚组分析应谨慎解释。
Background The carnitine precursor trimethyllysine (TML) is associated with progression of atherosclerosis, possibly through a relationship with trimethylamine-N-oxide (TMAO). Riboflavin is a cofactor in TMAO synthesis. We examined prospective relationships of circulating TML and TMAO with acute myocardial infarction (AMI) and potential effect modifications by riboflavin status. Methods By Cox modelling, risk associations were examined amongst 4098 patients (71.8% men) with suspected stable angina pectoris. Subgroup analyses were performed according to median plasma riboflavin. Results During a median follow-up of 4.9 years, 336 (8.2%) patients experienced an AMI. The age- and sex-adjusted hazard ratio (HR) (95% CI) comparing the 4th vs. 1st TML quartile was 2.19 (1.56-3.09). Multivariable adjustment for traditional cardiovascular risk factors and indices of renal function only slightly attenuated the risk estimates [HR (95% CI) 1.79 (1.23-2.59)], which were particularly strong amongst patients with riboflavin levels above the median (P-int = 0.035). Plasma TML and TMAO were strongly correlated (r(s) = 0.41;P < 0.001); however, plasma TMAO was not associated with AMI risk in adjusted analyses [HR (95% CI) 0.81 (0.58-1.14)]. No interaction between TML and TMAO was observed. Conclusion Amongst patients with suspected stable angina pectoris, plasma TML, but not TMAO, independently predicted risk of AMI. Our results motivate further research on metabolic processes determining TML levels and their potential associations with cardiovascular disease. We did not adjust for multiple comparisons, and the subgroup analyses should be interpreted with caution.