Table 3. Mediation (by Incident Atrial Fibrillation) Analysis of Left Atrial Measures and Dementia: Atherosclerosis Risk in Communities Study, 2011-2019.
| Exposurea | Quintile, No. (% range) | Adjusted for age, sex, race and center, education, body mass index, smoking status, diabetes, systolic blood pressure, antihypertensive medications, coronary heart disease, heart failure | |||||
|---|---|---|---|---|---|---|---|
| Quintile incidence rate (per 100 person-years)b | Hazard ratio (95% CI)c | % Mediated (95% CI)d | |||||
| Lowest | Highest | Lowest | Highest | Additional incident dementia cases (per 100 person-years)b,e | |||
| LA reservoir strain | 819 (≤26.72) | 819 (≥39.43) | |||||
| Natural direct effect | 6.64 | 4.43 | 2.21 | 2.06 (1.55 to 2.80) | 99.98 (94.72 to 104.32) | ||
| Natural indirect effect | 4.430 | 4.433 | −0.003 | 1.00 (0.97 to 1.03) | 0.02 (−4.32 to 5.28) | ||
| Total effect | 6.64 | 4.43 | 2.21 | 2.06 (1.57 to 2.78) | 100 | ||
| LA conduit strain | 819 (≤9.90) | 819 (≥19.53) | |||||
| Natural direct effect | 5.65 | 4.30 | 1.35 | 1.80 (1.35 to 2.49) | 99.62 (97.90 to 101.28) | ||
| Natural indirect effect | 4.303 | 4.299 | 0.004 | 1.00 (0.99 to 1.01) | 0.38 (−1.28 to 2.10) | ||
| Total effect | 5.65 | 4.30 | 1.35 | 1.80 (1.36 to 2.49) | 100 | ||
| LA contractile strain | 819 (≤13.47) | 818 (≥22.38) | |||||
| Natural direct effect | 5.52 | 4.31 | 1.21 | 1.68 (1.24 to 2.27) | 98.40 (89.98 to 104.33) | ||
| Natural indirect effect | 4.32 | 4.31 | 0.01 | 1.01 (0.98 to 1.04) | 1.60 (−4.33 to 10.05) | ||
| Total effect | 5.53 | 4.31 | 1.22 | 1.70 (1.27 to 2.27) | 100 | ||
| LA emptying fraction | 819 (≤50.92) | 819 (≥66.18) | |||||
| Natural direct effect | 6.01 | 4.26 | 1.75 | 1.92 (1.45 to 2.56) | 99.68 (95.21 to 103.79) | ||
| Natural indirect effect | 4.263 | 4.264 | −0.001 | 1.00 (0.98 to 1.03) | 0.32 (−3.79 to 4.79) | ||
| Total effect | 6.01 | 4.26 | 1.75 | 1.93 (1.45 to 2.57) | 100 | ||
| LA active emptying fraction | 819 (≤35.15) | 819 (≥51.89) | |||||
| Natural direct effect | 5.45 | 4.28 | 1.17 | 1.63 (1.27 to 2.19) | 98.75 (92.07 to 104.73) | ||
| Natural indirect effect | 4.29 | 4.28 | 0.01 | 1.01 (0.98 to 1.03) | 1.25 (−4.73 to 7.95) | ||
| Total effect | 5.46 | 4.28 | 1.18 | 1.64 (1.28 to 2.19) | 100 | ||
Abbreviation: LA, left atrial.
a
Lowest vs highest (reference) quintiles were compared.
b
Estimates are from the additive hazards model with time-independent effects.
c
Natural direct effect estimates the effect of the LA measure on dementia that does not act through the mediator, incident atrial fibrillation. Natural indirect effect estimates the effect of the LA measure on dementia that acts through the mediator, incident atrial fibrillation.
d
Percent mediated estimates the percent of the total LA measure effect, on the log(HR) scale, that acts through the mediator, incident atrial fibrillation.
e
Additional incident dementia cases (per 100 person-years) comparing lowest vs highest quintile.