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PROGNOSTIC VALUE OF ELEVATED LEVELS OF INTESTINAL MICROFLORA-GENERATED METABOLITE TRIMETHYLAMINE N-OXIDE IN PATIENTS WITH HEART FAILURE: THE GUT HYPOTHESIS REVISITED
Background
Accumulation of intestinal microbial-dependent dietary phosphatidylcholine metabolite, trimethylamine N-oxide (TMAO), has been associated with coronary artery disease (CAD) pathogenesis. Potential pathophysiologic contributions of intestinal microflora in heart failure (HF) have not been described.
Methods
We examined the relationship between fasting plasma TMAO and all-cause mortality over 5-year follow-up in 720 stable subjects with history of HF.
Results
In our study cohort (mean age 66±10 years, 41% women, median BNP 294 [IQR 114-658]pg/ml), median TMAO level was 5.0 (IQR 3.0-8.5) ??, which was higher than in the non-HF cohort (3.5 [IQR 2.3-5.7]??, p<0.001). There was only modest correlation between TMAO and BNP (r=0.23, p<0.001). Higher (4th vs 1st quartile) plasma TMAO level was associated with a 3.4-fold increased mortality risk. Following adjustments for traditional risk factors and BNP, elevated TMAO levels remained predictive of 5-year mortality risk (Hazard ratio [HR] 2.2 [95%CI 1.42-3.43], p<0.001, Figure 1) including addition of eGFR to the model (HR 1.75 [95%CI 1.07-2.86], p<0.001).
Conclusion
High TMAO levels are observed in patients with HF, and dose-dependently portend higher long-term mortality risk independent of BNP and renal function.
