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. 2022 Apr;61(3):1353-1362.
doi: 10.1007/s00394-021-02713-x. Epub 2021 Nov 19.

Ten-year changes in plasma L-carnitine levels and risk of coronary heart disease

Yoriko Heianza  1 , Wenjie Ma  2 , Joseph A DiDonato  3 , Qi Sun  4   5 , Eric B Rimm  4   6   5 , Frank B Hu  4   6   5 , Kathryn M Rexrode  5   7   8 , JoAnn E Manson  6   5   7 , Lu Qi  9   10   11
Affiliations

Ten-year changes in plasma L-carnitine levels and risk of coronary heart disease

Yoriko Heianza et al. Eur J Nutr. 2022 Apr.

Abstract

Purpose: L-Carnitine is abundant in animal source foods, particularly red meat, and circulating L-carnitine may be related to the incidence of coronary heart disease (CHD). We investigated whether long-term changes in plasma L-carnitine over 10 years were associated with the CHD incidence and also examined joint associations of carnitine-rich red meat consumption and L-carnitine changes on the subsequent risk of CHD.

Methods: This prospective nested case-control study included 772 healthy women at baseline (386 incident CHD cases and 386 healthy controls). Plasma L-carnitine levels were measured both at the first (1989-90) and second blood collections (2000-02). Incident cases of CHD were prospectively followed from the date of the second blood collection through 2016.

Results: Overall, a greater increase in L-carnitine from the first to the second time point was related to a higher risk of CHD, regardless of the initial L-carnitine levels (relative risk: 1.36 (95% CI 0.999, 1.84) per 1-SD increase). The 10-year changes in L-carnitine were positively associated with red meat consumption over time, and women with higher red meat intake (≥ 36 g/day) and with greater increases in L-carnitine had a 1.86 (95% CI 1.13, 3.09) times increased risk of CHD, as compared to those with lower red meat intake and lesser increases in L-carnitine.

Conclusion: Long-term increases in L-carnitine levels were associated with the subsequent incidence of CHD, especially among women with higher intake of red meat. Our results suggest the importance of atherogenic L-carnitine changes and dietary intakes over time in the prevention of CHD.

Keywords: Coronary heart disease; Diet; Gut microbiota-related metabolite; L-Carnitine; Risk; Trimethylamine N-oxide.

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Conflict of interest statement

Conflict of interest The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Linear association of 10-year changes in L-carnitine levels with the risk of coronary heart disease (CHD). Solid line: relative risk (RR) estimate; dotted lines: 95% CIs. Reference value = 0. P for linear trend = 0.0486 by the spline regression analysis. The spline regression analysis was performed to calculate RR (95% CIs) using after adjusting for the initial L-carnitine levels + “matched factors” (age, smoking habit, fasting status, and date of blood collection) + “demographic and diet/lifestyle factors assessed at the first time point” (family history of myocardial infarction, peri/postmenopausal status and hormone use, the Alternative Healthy Eating Index [AHEI] without alcohol or red meat, physical activity, alcohol intake) + “changes in diet and physical activity” (changes in AHEI without alcohol or red meat, changes in alcohol intake, and changes in physical activity) + “obesity and metabolic status” (body mass index at the first time point, changes in weight, hypertension (none [no at both time points], new incidence [no at the first time point and yes at the second time point], or prevalent [yes at the first or second time point except for new incidence]), dyslipidemia (none/new incidence/prevalent) and diabetes (none/new incidence or prevalent)
Fig. 2
Fig. 2
Risk of coronary heart disease (CHD) according to 10-year changes in L-carnitine levels and red meat intake (A) or fish intake (B). RR., relative risk. [−] or [+] in the figure indicates a lower or higher median category of L-carnitine changes; the [+] group includes women with greater increases in L-carnitine. Low red meat intake: 0 to < 36 g/day (median 23 g/day); high red meat intake: 36 g/day or more (median 56 g/day). Low fish intake: 0 to < 20 g/day (median 13 g/day); high fish intake: 20 g/day or more (median 32 g/day). Data are [n = incident cases/n = controls] or relative risks (95% CIs) for CHD using the conditional logistic regression model. The RRs in model 1 adjusting for L-carnitine levels at the first time point + “matched factors” (age, smoking, fasting status, and date of blood collection), + “demographic and diet/lifestyle factors assessed at the first time point” (family history of myocardial infarction, peri/postmenopausal status and hormone use, the Alternative Healthy Eating Index [AHEI] without alcohol or the respective dietary intake (red meat or fish), physical activity, alcohol intake, and total energy intake) + “changes in diet/lifestyle factors between the first and second time points” (changes in AHEI without alcohol or the respective dietary intake [red meat or fish], changes in physical activity, changes in alcohol intake, and changes in total energy intake). The RRs in model 2 adjusting for model 1 + “obesity and metabolic status at the first time point and changes between the first and second time points” (body mass index at the first time point, changes in weight, hypertension (none [no at both time points], new incidence [no at the first time point and yes at the second time point], or prevalent [yes at the first or second time point except for new incidence]), dyslipidemia (none/new incidence/prevalent) and diabetes (none/new incidence or prevalent)
Fig. 3
Fig. 3
Risk for coronary heart disease (CHD) by a combination of trimethylamine N-oxide (TMAO) changes and L-carnitine changes. Participants were categorized into four groups based on two groups of TMAO changes or two groups of L-carnitine changes (based on median values among controls); [−] or [+] in the figure indicates a lower or higher median group of TMAO changes or L-carnitine changes; the [+] group includes women with greater increases in each metabolite. Median [25th, 75th] values of a lower or higher median category of TMAO changes among controls were −2.0 [−5.7, −0.6] μM or 1.9 [0.9, 4.5] μM, respectively. Median [25th, 75th] values of a lower or higher median group of L-carnitine changes among controls were −9.8 [−25.5, −4.7] μM or 2.9 [0.9, 6.8] μM, respectively. N indicates [n = incident cases/n = controls]. Relative risks (RRs) and 95% CIs using the conditional logistic regression model. The RRs in model 1 after adjusting for the initial L-carnitine levels and the initial TMAO levels + “matched factors” (age, smoking habit, fasting status, and date of blood collection) + “demographic and diet/lifestyle factors assessed at the first time point” (family history of myocardial infarction, peri/postmenopausal status and hormone use, the Alternative Healthy Eating Index [AHEI] without alcohol, physical activity, and alcohol intake) + “changes in diet and physical activity” (changes in AHEI without alcohol, changes in alcohol intake, and changes in physical activity). The RRs in model 2 after adjusting for model 1 + “obesity and metabolic status” (body mass index at the first time point, changes in weight, hypertension (none [no at both time points], new incidence [no at the first time point and yes at the second time point], or prevalent [yes at the first or second time point except for new incidence]), dyslipidemia (none/new incidence/prevalent) and diabetes (none/new incidence or prevalent)
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