Gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) is emerging as a new potentially important cause of increased cardiovascular risk. The purpose of this meta-analysis was to systematically estimate and quantify the association between TMAO plasma levels, mortality, and major adverse cardio and cerebrovascular events (MACCE). MEDLINE, ISI Web of Science, and SCOPUS databases were searched for ad hoc studies published up to April 2017. Associations between TMAO plasma levels, all-cause mortality (primary outcome) and MACCE (secondary outcome) were systematically addressed. A total of 17 clinical studies were included in the analytic synthesis, enrolling 26 167 subjects. The mean follow-up in our study population was 4.3 ± 1.5 years. High TMAO plasma levels were associated with increased incidence of all-cause mortality [14 studies for 16 cohorts enrolling 15 662 subjects, hazard ratio (HR): 1.91; 95% confidence interval (CI): 1.40–2.61, P < 0.0001, I² = 94%] and MACCE (5 studies for 6 cohorts enrolling 13 944 subjects, HR: 1.67, 95% CI: 1.33–2.11, P < 0.00001, I² = 46%,). Dose-response meta-analysis revealed that the relative risk (RR) for all-cause mortality increased by 7.6% per each 10 μmol/L increment of TMAO [summary RR: 1.07, 95% CI (1.04–1.11), P < 0.0001; based on seven studies]. Association of TMAO and mortality persisted in all examined subgroups and across all subject populations. This is the first systematic review and meta-analysis demonstrating the positive dose-dependent association between TMAO plasma levels and increased cardiovascular risk and mortality.

Background: Regression of left ventricular ( LV ) hypertrophy ( LVH ) has been a goal in clinical trials. This study tests the external validity of results of clinical trials on LVH regression using a large registry from a tertiary care center, to identify phenotypes less likely to achieve regression of LVH . Methods and Results: Patients from the Campania Salute Network, free of prevalent cardiovascular disease, but with echocardiographic LVH (defined as LV mass index [LVMi] >47 g/m ^2.7 in women and >50 g/m ^2.7 in men) were included. During a median follow‐up of 67 months, clear‐cut regression of LVH was documented in 14% of patients (13±8% reduction of initial LVMi ) or 23% when also considering those with a reduction of LVMi ≥5 g/m ^2.7 . Patients with persistent LVH were older with longer duration of hypertension, suboptimal blood pressure (BP) control, larger body mass index, LV mass, and carotid intima‐media thickness and included more women and subjects with diabetes mellitus, isolated systolic hypertension, and metabolic syndrome (all P <0.05). Number and class of antihypertensive drugs during follow‐up did not differ between groups. In multiple logistic regression analysis, older age, female sex, obesity, higher baseline LVMi and carotid intima‐media thickness, and suboptimal BP control were significant covariates of persistent LVH (all P ≤0.01), independent of diabetes, duration of hypertension, isolated systolic hypertension, follow‐up time and number and class of antihypertensive drugs. Conclusions: Early initiation of antihypertensive treatment, aggressive BP control, and attention to metabolic aspects are critical to avoid irreversible LVH .