cardiovascular-agents and trimethyloxamine

Topics: Adult; Atherosclerosis; Cardiovascular Agents; Carnitine; Diet; Female; HEK293 Cells; Humans; Male; Methylamines; Methylhydrazines; Organic Cation Transport Proteins; Seafood; Solute Carrier Family 22 Member 5

Trimethylamine-N-oxide (TMAO) is a novel cardiovascular risk marker. We explored the association of commonly used cardiovascular medications with TMAO levels in patients and validated the identified associations in mice.. Detailed history of drug treatment was recorded in 300 patients with cardiovascular disease without diabetes in an observational, cross-sectional study. Animal study was performed in CD1 mice.. Median plasma TMAO (interquartile range) level was 2.144 (1.570-3.104) μmol l. Loop diuretics increased plasma TMAO concentration by decreasing its urinary excretion rate. Loop diuretic use should be considered a potential confounder in TMAO studies.

Topics: Aged; Animals; Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Cross-Sectional Studies; Female; Heart; Humans; Kidney; Liver; Male; Methylamines; Mice; Middle Aged; Sodium Potassium Chloride Symporter Inhibitors

Trimethylamine-N-oxide (TMAO), a metabolite derived from gut microbes and dietary phosphatidylcholine, is linked to both coronary artery disease pathogenesis and increased cardiovascular risks. The ability of plasma TMAO to predict 5-year mortality risk in patients with stable coronary artery disease has not been reported. This study examined the clinical prognostic value of TMAO in patients with stable coronary artery disease who met eligibility criteria for a patient cohort similar to that of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial.. We examined the relationship between fasting plasma TMAO and all-cause mortality over 5-year follow-up in sequential patients with stable coronary artery disease (n=2235) who underwent elective coronary angiography. We identified the COURAGE-like patient cohort as patients who had evidence of significant coronary artery stenosis and who were managed with optimal medical treatment. Higher plasma TMAO levels were associated with a 4-fold increased mortality risk. Following adjustments for traditional risk factors, high-sensitivity C-reactive protein, and estimated glomerular filtration rate, elevated TMAO levels remained predictive of 5-year all-cause mortality risk (quartile 4 versus 1, adjusted hazard ratio 1.95, 95% CI 1.33-2.86; P=0.003). TMAO remained predictive of incident mortality risk following cardiorenal and inflammatory biomarker adjustments to the model (adjusted hazard ratio 1.71, 95% CI 1.11-2.61; P=0.0138) and provided significant incremental prognostic value for all-cause mortality (net reclassification index 42.37%, P<0.001; improvement in area under receiver operator characteristic curve 70.6-73.76%, P<0.001).. Elevated plasma TMAO levels portended higher long-term mortality risk among patients with stable coronary artery disease managed with optimal medical treatment.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Stenosis; Epidemiologic Methods; Female; Gastrointestinal Microbiome; Humans; Male; Methylamines; Middle Aged; Myocardial Revascularization; Prognosis