From the, Departments of, Department of, Medicine, Stavanger University Hospital, Stavanger, Norway.
Department of, Heart Disease, Haukeland University Hospital, Bergen, Norway.
J Intern Med. 2020 Oct;288(4):446-456. doi: 10.1111/joim.13067. Epub 2020 Apr 27.
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.
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.
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 = 0.035). Plasma TML and TMAO were strongly correlated (r = 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.
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.
肉碱前体三甲胺-N-氧化物（TMAO）与动脉粥样硬化的进展有关，可能通过与三甲胺-N-氧化物（TMAO）的关系。核黄素是 TMAO 合成的辅助因子。我们研究了循环 TML 和 TMAO 与急性心肌梗死（AMI）的前瞻性关系，以及核黄素状态的潜在影响修饰。
通过 Cox 建模，在 4098 名疑似稳定型心绞痛患者中检查了风险关联（71.8%为男性）。根据中位数血浆核黄素进行亚组分析。
在中位数为 4.9 年的随访期间，336 名（8.2%）患者发生 AMI。与第 4 四分位 TML 相比，第 1 四分位 TML 的年龄和性别调整危险比（HR）（95%CI）为 2.19（1.56-3.09）。仅对传统心血管危险因素和肾功能指数进行多变量调整，略微减弱了风险估计值[HR（95%CI）1.79（1.23-2.59）]，在核黄素水平高于中位数的患者中，风险估计值尤其强烈（P = 0.035）。血浆 TML 和 TMAO 之间呈强相关性（r = 0.41；P < 0.001）；然而，在调整分析中，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。
在疑似稳定型心绞痛患者中，血浆 TML 而不是 TMAO 独立预测 AMI 风险。我们的结果激发了对确定 TML 水平的代谢过程及其与心血管疾病潜在关联的进一步研究。我们没有进行多次比较调整，因此应谨慎解释亚组分析的结果。
