Table 3.
Risk of all-cause and cause-specific mortality associated with annualized changes in plasma TMAO levels (per IQR) among 5614 adults in MESA with two serial TMAO measures
| All-cause mortality | Adjudicated CVD mortalitya | Underlying cause of death from death certificateb | ||||
|---|---|---|---|---|---|---|
| Kidney failure | Cancer | Dementia | Other | |||
| ICD code | N/A | N/A | N17-N19 | C00-C97 | G30, F00, F01, F03 | N/A |
| No. of deaths | 1166 | 281 | 27 | 331 | 112 | 415 |
| Unadjusted | 1.08 (1.03–1.13) | 0.99 (0.87–1.12) | 1.32 (1.19–1.46) | 1.07 (0.97–1.17) | 0.94 (0.77–1.15) | 1.11 (1.03–1.20) |
| Multivariable | ||||||
| Model 1 | 1.10 (1.05–1.14) | 1.04 (0.93–1.15) | 1.43 (1.22–1.68) | 1.05 (0.95–1.17) | 1.00 (0.82–1.21) | 1.13 (1.06–1.20) |
| Model 2 | 1.10 (1.05–1.15) | 1.04 (0.94–1.16) | 1.47 (1.22–1.77) | 1.05 (0.95–1.17) | 0.98 (0.81–1.19) | 1.14 (1.07–1.21) |
| Model 3 (primary) | 1.10 (1.05–1.14) | 1.03 (0.93–1.15) | 1.54 (1.26–1.89) | 1.04 (0.93–1.16) | 1.00 (0.84–1.20) | 1.13 (1.07–1.21) |
| Model 3 + eGFRc | 1.06 (1.01–1.12) | 1.00 (0.89–1.13) | 1.23 (0.98–1.55) | 1.02 (0.91–1.15) | 1.02 (0.86–1.21) | 1.09 (1.02–1.17) |
Model 1 adjusted for age, sex, race/ethnicity, study site, and exam 1 TMAO.
Model 2 further adjusted for education (<high school, high school, some college, bachelor’s degree, graduate school), household income (<$20,000, $20,000 − < $50,000, $50,000 − < $100,000, ≥ $100 000), alternate healthy eating index, total energy intake, and exam 4 smoking status (never, former, and current), alcohol intake(drinks/week), physical activity (MET-MIN per week), and antibiotics use in the past 2 weeks.
Model 3 further adjusted for exam 4 BMI, waist circumference, systolic blood pressure, diastolic blood pressure, LDL-C, HDL-C, triglycerides, CRP, diabetes, interim nonfatal cardiovascular events (MI, resuscitated cardiac arrest, angina, or stroke prior to exam 4), anti-hypertensive medication, lipid-lowering mediation, and comorbidities (for all-cause mortality only) including emphysema, liver disease, and cancer (except for non-melanoma skin cancer).
CVD deaths included those due to atherosclerotic coronary heart disease (CHD) (with sub-classifications of definite fatal MI, definite fatal CHD, and possible fatal CHD), stroke, other atherosclerotic disease, and other cardiovascular disease.
For kidney failure, ICD codes included N17-N19; for cancer, C00-C97; and for dementia, G30, F00, F01, and F03.Other causes of death: deaths due to any causes except for CVD, kidney failure, cancer, and dementia.
eGFR was included as a continuous linear term (mL/min/1.73m2).
IQR, inter-quintile range, comparing the midpoints of the first and fifth quintiles (2.1 µmol/L annualized increase).