Risk differences comparing the expected probability of adverse outcomes (hospital admission, ICU admission, or death) from COVID-19 at 30 days due to the total effect from diabetes, effect through the mediator (average causal mediation effect (ACME)), and direct effect due to diabetes (average direct effect (ADE)) for candidate cardiovascular disease-related mediators in veterans (28 February 2020–31 July 2020)
| Candidate mediators | |||||||||||||
| Cardiovascular disease | Heart failure | Chronic kidney disease | ACE inhibitor or ARB use | Statin use | Upper quartile of BNP or NT-pro BNP at COVID-19 diagnosis | Elevated troponin at COVID-19 diagnosis | |||||||
| Risk difference (%) | Risk difference (%) | 95% CI | Risk difference (%) | 95% CI | Risk difference (%) | 95% CI | Risk difference (%) | 95% CI | Risk difference (%) | 95% CI | Risk difference (%) | 95% CI | |
| Hospital admission | |||||||||||||
| Total effect | 1.9 | 1.9 | 1.3 to 2.5 | 2.0 | 1.4 to 2.6 | 1.8 | 1.2 to 2.4 | 1.8 | 1.2 to 2.4 | 1.6 | −0.7 to 4.2 | 1.1 | −0.8 to 3.1 |
| Average causal mediation effect | 0.3 | 0.3 | 0.2 to 0.4 | 0.4 | 0.3 to 0.5 | −0.1 | −0.2 to 0.1 | −0.2 | −0.4 to −0.1 | 0.4 | 0.1 to 0.7 | 0.2 | 0.1 to 0.6 |
| Average direct effect | 1.6 | 1.6 | 0.9 to 2.2 | 1.6 | 1.0 to 2.2 | 1.9 | 1.3 to 2.5 | 2.0 | 1.4 to 2.6 | 1.2 | −1.1 to 3.9 | 0.9 | −1.0 to 2.8 |
| Proportion mediated* | 14.7 | 16.0 | 10.5 to 30.0 | 19.8 | 13.9 to 33.5 | * | * | * | * | ||||
| ICU admission | |||||||||||||
| Total effect | 3.1 | 3.1 | 2.4 to 3.8 | 3.2 | 2.5 to 4.0 | 3.1 | 2.4 to 3.8 | 3.1 | 2.4 to 3.8 | 3.7 | 0.7 to 6.3 | 3.5 | 1.4 to 5.9 |
| Average causal mediation effect | 0.4 | 0.5 | 0.4 to 0.6 | 0.3 | 0.2 to 0.4 | 0.0 | −0.1 to 0.2 | 0.0 | −0.1 to 0.2 | 0.3 | 0.0 to 0.7 | 0.1 | 0.0 to 0.4 |
| Average direct effect | 2.7 | 2.6 | 1.8 to 3.3 | 2.9 | 2.2 to 3.7 | 3.1 | 2.4 to 3.8 | 3.0 | 2.3 to 3.7 | 3.4 | 0.4 to 5.9 | 3.4 | 1.2 to 5.7 |
| Proportion mediated* | 13.2 | 15.2 | 11.7 to 23.3 | 9.2 | 6.2 to 14.0 | * | * | * | 3.8 | 1.2 to 31.0 | |||
| Death | |||||||||||||
| Total effect | 5.8 | 5.7 | 4.7 to 6.8 | 5.7 | 4.7 to 6.8 | 5.8 | 4.7 to 6.8 | 5.8 | 4.8 to 6.8 | 3.6 | 0.6 to 6.0 | 7.7 | 4.9 to 11.1 |
| Average causal mediation effect | 1.1 | 1.0 | 0.9 to 1.3 | 0.6 | 0.4 to 0.8 | 0.2 | 0.0 to 0.4 | 0.4 | 0.2 to 0.7 | 0.2 | 0.0 to 1.0 | 0.2 | 0.0 to 0.5 |
| Average direct effect | 4.7 | 4.7 | 3.6 to 5.7 | 5.2 | 4.1 to 6.3 | 5.6 | 4.5 to 6.7 | 5.4 | 4.3 to 6.5 | 3.4 | 0.4 to 6.0 | 7.6 | 4.7 to 10.9 |
| Proportion mediated* | 18.2 | 18.3 | 15.0 to 25.2 | 10.2 | 7.5 to 14.6 | 6.7 | 2.8 to 12.1 | 2.3 | 0.6 to 7.7 | ||||
Models run using 1000 simulations with bootstrapped CIs.
Models additionally adjusted for sex, age group, race/ethnicity, BMI category, smoking status, station, and urban/rural status.
n=28 933 with data available on CVD, HF, CKD, ACE inhibitor or ARB use, and statin use; n=3803 with data available on BNP; n=5503 with data available on troponin.
*Proportion mediated is not reported when ACME or ADE is not significant or when the CI for the proportion mediated includes numbers >100% or <0%, which occurs when the ADE and ACME have possibly opposite effects (ie, one negative and one positive).
ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; BMI, body mass index; BNP, brain natriuretic peptide; CKD, chronic kidney disease; CVD, cardiovascular disease; HF, heart failure; ICU, intensive care unit; NT-pro BNP, N-terminal pro BNP.