Circulating trimethyllysine and risk of acute myocardial infarction in patients with suspected stable coronary heart disease.

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 (Pint  = 0.035). Plasma TML and TMAO were strongly correlated (rs  = 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.

Comparative utilization of fish selenium and inorganic selenite by rats of normal selenium status.

Rats of a normal selenium status were fed diets based on fish (rainbow trout) as the main protein source. A 4-week experiment with three dietary groups (low fish selenium, high fish selenium and selenite supplementation) was performed, and the selenium absorption, excretion and retention were recorded. Samples of blood serum, liver, kidneys, testes, hairs, spleen, lungs, heart, brain and skeletal muscle were collected for analysis of selenium. Glutathione peroxidase activity was measured in the blood serum. A selenium supplementation of approximately 1 mg/kg (high fish selenium and selenite group) yielded a selenium retention of only 7% of the intake, while in the group with a dietary selenium concentration of approximately 0.1 mg/kg (low fish selenium group) the selenium retention was 50%, resulting in almost the same absolute selenium retention in all three groups. The liver and kidneys showed the highest accumulations of selenium, reflecting the participation of these organs in the excretion of surplus selenium. The highest relative uptake of selenium was recorded in the testes, which increased equally in all dietary groups. The selenium concentration in the other tissues investigated, as well as the glutathione peroxidase activity in the blood serum responded little to the selenium supplementations. These results showed that the selenium levels normally found in fish were sufficient to satisfy the need for this element in rats of a good selenium status, and that inorganic selenite was absorbed and excreted at a high rate already after 1 week.