TABLE 3.
Subgroup analysis of high concentration TMAO for hypertension prevalence according to study characteristics1
| Overall effect | Heterogeneity | |||||
|---|---|---|---|---|---|---|
| Subgroups | Studies, n (references) | Effects model | RR (95% CI) | P value | I 2, % | P value |
| All | 8 (24–31) | Random | 1.12 (1.06, 1.17) | <0.0001 | 64 | 0.007 |
| Study location | ||||||
| United States | 4 (24, 25, 27, 29) | Random | 1.09 (1.03, 1.15) | 0.004 | 73 | 0.01 |
| Europe | 2 (28, 30) | Fixed | 1.18 (1.10, 1.27) | <0.00001 | 0 | 0.45 |
| Asia | 2 (26, 31) | Fixed | 1.24 (1.08, 1.42) | 0.002 | 0 | 0.51 |
| Participants, n | ||||||
| <900 | 4 (26, 27, 29, 31) | Fixed | 1.07 (1.02, 1.12) | 0.008 | 48 | 0.12 |
| ≥900 | 4 (24, 25, 28, 30) | Random | 1.14 (1.08, 1.21) | <0.00001 | 55 | 0.08 |
| Study quality | ||||||
| High | 6 (24, 25, 27–30) | Random | 1.10 (1.05, 1.17) | 0.0003 | 70 | 0.005 |
| Low/moderate | 2 (26, 31) | Fixed | 1.24 (1.08, 1.42) | 0.002 | 0 | 0.15 |
| Target population | ||||||
| Patients with cardiovascular impairments | 6 (25–27, 29–31) | Fixed | 1.08 (1.04, 1.12) | <0.0001 | 24 | 0.26 |
| Patients with renal impairments | 1 (28) | Fixed | 1.20 (1.11, 1.29) | <0.00001 | — | — |
| Patients with T2DM | 1 (24) | Fixed | 1.17 (1.11, 1.24) | <0.00001 | — | — |
| Hypertension definition | ||||||
| High BP and/or antihypertensive agents | 2 (28, 31) | Fixed | 1.20 (1.12, 1.28) | <0.00001 | 0 | 0.96 |
| Hypertension history | 6 (24–27, 29, 30) | Random | 1.09 (1.04, 1.15) | 0.001 | 60 | 0.03 |
| Mean/median age, y | ||||||
| <65 | 4 (24–26, 28) | Random | 1.15 (1.09, 1.22) | <0.00001 | 61 | 0.05 |
| ≥65 | 4 (27, 29–31) | Fixed | 1.06 (1.01, 1.12) | 0.02 | 24 | 0.27 |
| Male, % | ||||||
| <60 | 3 (24, 27, 28) | Random | 1.14 (1.05, 1.23) | 0.003 | 77 | 0.01 |
| ≥60 | 5 (25, 26, 29–31) | Fixed | 1.09 (1.05, 1.13) | <0.0001 | 29 | 0.23 |
| Mean circulating TMAO, μmol/) | ||||||
| <4 | 4 (25, 27, 28, 31) | Random | 1.16 (1.07, 1.25) | 0.0009 | 59 | 0.06 |
| ≥4 | 4 (24, 27, 29, 30) | Random | 1.08 (1.00, 1.17) | 0.04 | 73 | 0.01 |
| Mean/median eGFR, mL/(min · 1.73 m2) | ||||||
| <90 | 6 (24, 26, 27, 29–31) | Random | 1.11 (1.03, 1.19) | 0.004 | 64 | 0.02 |
| ≥90 | 2 (25, 28) | Random | 1.14 (1.02, 1.26) | 0.02 | 82 | 0.02 |
| Current smoker, % | ||||||
| <70 | 5 (24, 26, 28, 30, 31) | Fixed | 1.18 (1.13, 1.25) | <0.00001 | 0 | 0.85 |
| ≥70 | 2 (25, 29) | Fixed | 1.07 (1.03, 1.12) | 0.0003 | 35 | 0.21 |
| N/A | 1 (27) | Fixed | 1.04 (0.96, 1.12) | 0.37 | — | — |
| Hypertension, % | ||||||
| <60 | 3 (26, 28, 30) | Fixed | 1.19 (1.11, 1.28) | <0.00001 | 0 | 0.57 |
| ≥60 | 5 (24, 25, 27, 29, 31) | Random | 1.10 (1.04, 1.16) | 0.0008 | 69 | 0.001 |
| Diabetes, % | ||||||
| <30 | 2 (28, 31) | Fixed | 1.20 (1.12, 1.28) | <0.00001 | 0 | 0.96 |
| 30–70 | 5 (25–27, 29, 30) | Fixed | 1.07 (1.04, 1.11) | 0.0001 | 0 | 0.41 |
| >70 | 1 (24) | Fixed | 1.17 (1.11, 1.24) | <0.00001 | — | — |
| ACEI/ARB use, % | ||||||
| ≤55 | 2 (25, 26) | Fixed | 1.10 (1.05, 1.15) | 0.0001 | 32 | 0.23 |
| >55 | 4 (24, 27, 29, 31) | Random | 1.10 (1.02, 1.19) | 0.01 | 76 | 0.006 |
| N/A | 2 (29, 30) | Fixed | 1.18 (1.10, 1.27) | <0.00001 | 0 | 0.45 |
| β-blocker use, % | ||||||
| <50 | 2 (26, 31) | Fixed | 1.24 (1.08, 1.42) | 0.002 | 0 | 0.51 |
| ≥50 | 4 (24, 25, 27, 29) | Random | 1.09 (1.03, 1.15) | 0.004 | 73 | 0.01 |
| N/A | 2 (28, 30) | Fixed | 1.18 (1.10, 1.27) | <0.00001 | 0 | 0.45 |
| Statins use, % | ||||||
| <70 | 3 (24, 27, 31) | Random | 1.13 (1.03, 1.24) | 0.01 | 72 | 0.03 |
| ≥70 | 3 (25, 26, 29) | Fixed | 1.08 (1.04, 1.12) | <0.0001 | 39 | 0.19 |
| N/A | 2 (28, 30) | Fixed | 1.18 (1.10, 1.27) | <0.00001 | 0 | 0.45 |
1
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BP, blood pressure; eGFR, estimated glomerular filtration rate; N/A, not applicable; TMAO, trimethylamine N-oxide; T2DM, type 2 diabetes mellitus.