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. 2021 Jul 16;1(1):oeab007.
doi: 10.1093/ehjopen/oeab007. eCollection 2021 Aug.

Trimethyllysine predicts all-cause and cardiovascular mortality in community-dwelling adults and patients with coronary heart disease

Espen Ø Bjørnestad  1 , Indu Dhar  2 , Gard F T Svingen  3 , Eva R Pedersen  3   4 , Mads M Svenningsson  3 , Grethe S Tell  5 , Per M Ueland  4 , Stein Ørn  1 , Gerhard Sulo  6 , Reijo Laaksonen  7 , Ottar Nygård  2   3
Affiliations

Trimethyllysine predicts all-cause and cardiovascular mortality in community-dwelling adults and patients with coronary heart disease

Espen Ø Bjørnestad et al. Eur Heart J Open. .

Abstract

Aims: Trimethyllysine (TML) is involved in carnitine synthesis, serves as a precursor of trimethylamine N-oxide (TMAO) and is associated with cardiovascular events in patients with established coronary heart disease (CHD). We prospectively examined circulating TML as a predictor of all-cause and cardiovascular mortality in community-dwelling adults and patients with CHD.

Methods and results: By Cox regression modelling, risk associations were examined in 6393 subjects in the community-based Hordaland Health Study (HUSK). A replication study was conducted among 4117 patients with suspected stable angina pectoris in the Western Norway Coronary Angiography Cohort (WECAC). During a mean follow-up of 10.5 years in the HUSK-cohort, 884 (13.8%) subjects died, of whom 287 from cardiovascular causes. After multivariable adjustments for traditional cardiovascular risk factors, the hazard ratio (HR) [95% confidence interval (95% CI)] for all-cause mortality comparing the 4th vs. 1st TML-quartile was 1.66 (1.31-2.10, P < 0.001). Particularly strong associations were observed for cardiovascular mortality [HR (95% CI) 2.04 (1.32-3.15, P = 0.001)]. Corresponding risk-estimates in the WECAC (mean follow-up of 9.8 years) were 1.35 [1.10-1.66, P = 0.004] for all-cause and 1.45 [1.06-1.98, P = 0.02] for cardiovascular mortality. Significant correlations between plasma TML and TMAO were observed in both cohorts (rs ≥ 0.42, P < 0.001); however, additional adjustments for TMAO did not materially influence the risk associations, and no effect modification by TMAO was found.

Conclusions: Elevated TML-levels were associated with increased risk of all-cause and cardiovascular mortality both in subjects with and without established CHD.

Keywords: Cardiovascular outcomes; Epidemiology; Mortality; Risk factor.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Kaplan–Meier curves showing event-free survival according to quartiles of plasma trimethyllysine in the Hordaland Health Study-cohort (A and C) and Western Norway Coronary Angiography Cohort (B and D).
Figure 2
Figure 2
Dose–response associations between plasma trimethyllysine and risk of total and cardiovascular mortality in the Hordaland Health Study-cohort (A and C) and Western Norway Coronary Angiography Cohort (B and D), adjusted for age and sex. The shaded areas covering the splines depicts 95% confidence intervals. Kernel density plots show the distribution of trimethyllysine.
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