Table 3.
The associations between CV risk factors and the ECG-based cardiac ages and the role of DNAm AgeAccel as a mediator of these relationships
| ECG-based cardiac age | Model | Effect type | Body Mass Index | Diabetes | High cholesterol | Hypertension | Cardiovascular disease | Any CV risk factor | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| β (95% CI) | p value | β (95% CI) | p value | β (95% CI) | p value | β (95% CI) | p value | β (95% CI) | p value | β (95% CI) | p value | |||
| Bayesian A-ECG age | M1 | Total |
0.32 (0.21, 0.44) |
< 2e−16 |
1.30 (0.09, 2.62) |
0.034 |
2.31 (0.89, 3.57 |
< 2e−16 |
2.67 (1.70, 3.74) |
< 2e−16 |
1.81 (− 0.58, 4.27) |
0.150 |
2.70 (1.61, 3.74) |
< 2e−16 |
|
M2 (AgeAccelHannum) |
ACME |
0.00 (0.00, 0.01) |
0.940 |
− 0.01 (− 0.11, 0.09) |
0.950 |
0.01 (− 0.09, 0.11) |
0.910 |
− 0.01 (− 0.08, 0.09) |
0.940 |
0.01 (− 0.11, 0.23) |
0.820 |
− 0.02 (− 0.17, 0.11) |
0.740 | |
| ADE |
0.32 (0.21, 0.44) |
< 2e−16 |
1.31 (0.08, 2.64) |
0.036 |
2.30 (0.88, 3.55) |
< 2e−16 |
2.68 (1.70, 3.75) |
< 2e−16 |
1.80 (− 0.60, 4.23) |
0.150 |
2.72 (1.61, 3.74) |
< 2e−16 | ||
|
M3 (AgeAccelHorvath) |
ACME |
0.02 (− 0.01, 0.04) |
0.19 |
0.02 (− 0.17, 0.22) |
0.818 |
0.03 (− 0.23, 0.35) |
0.850 |
0.12 (− 0.02, 0.38) |
0.160 |
0.07 (− 0.10, 0.54) |
0.540 |
0.15 (− 0.07, 0.45) |
0.170 | |
| ADE |
0.30 (0.19, 0.43) |
< 2e−16 |
1.28 (0.07, 2.62) |
0.036 |
2.28 (0.91, 3.57) |
< 2e−16 |
2.55 (1.60, 3.61) |
< 2e−16 |
1.74 (− 0.70, 4.15) |
0.160 |
2.55 (1.41, 3.59) |
< 2e−16 | ||
|
M4 (AgeAccelPheno) |
ACME |
0.02 (− 0.01, 0.06) |
0.160 |
0.23 (0.01, 0.52) |
0.028 |
0.34 (0.03, 0.74) |
0.026 |
0.08 (− 0.07, 0.28) |
0.290 |
0.26 (− 0.05, 0.88) |
0.150 |
0.17 (0.01, 0.41) |
0.048 | |
| ADE |
0.30 (0.21, 0.44) |
< 2e−16 |
1.08 (− 0.16, 2.45) |
0.098 |
1.97 (0.53, 3.21) |
0.002 |
2.59 (1.62, 3.64) |
< 2e−16 |
1.55 (− 0.81, 4.01) |
0.150 |
2.53 (1.40, 3.61) |
< 2e−16 | ||
|
M5 (AgeAccelGrim) |
ACME |
0.02 (− 0.01, 0.05) |
0.064 |
0.24 (0.01, 0.60) |
0.030 |
0.34 (− 0.02, 0.74) |
0.068 |
0.19 (0.00, 0.42) |
0.048 |
0.33 (− 0.06, 0.91) |
0.100 |
0.26 (− 0.04, 0.57) |
0.092 | |
| ADE |
0.30 (0.18, 0.43) |
< 2e−16 |
1.06 (− 0.19, 2.43) |
0.118 |
1.97 (− 0.02, 0.74) |
0.068 |
2.48 (1.50, 3.74) |
0.04 |
1.48 (− 0.91, 3.92) |
0.250 |
2.44 (1.28, 3.50) |
< 2e−16 | ||
|
DNN ECG-based age |
M1 | Total |
0.59 (0.37, 0.82) |
< 2e−16 |
1.72 (− 0.93, 4.35) |
0.200 |
2.71 (− 0.05, 5.49) |
0.054 |
2.72 (0.43, 5.01) |
0.020 |
4.16 (0.18, 8.69) |
0.040 |
3.20 (0.84, 5.74) |
0.008 |
|
M2 (AgeAccelHannum) |
ACME |
0.00 (− 0.02, 0.02) |
0.920 |
0.02 (− 0.16, 0.31) |
0.850 |
0.01 (− 0.23, 0.28) |
0.910 |
0.05 (− 0.11, 0.33) |
0.560 |
− 0.10 (− 0.58, 0.43) |
0.752 |
0.09 (− 0.11, 0.44) |
0.500 | |
| ADE |
0.59 (0.37, 0.82) |
< 2e−16 |
1.70 (− 0.92, 4.36) |
0.200 |
2.70 (− 0.05, 5.49) |
0.058 |
2.67 (0.33, 4.99) |
0.024 |
4.26 (0.16, 8.68) |
0.042 |
3.11 (0.76, 5.71) |
0.010 | ||
|
M3 (AgeAccelHorvath) |
ACME |
0.02 (− 0.02, 0.08) |
0.280 |
0.04 (− 0.28, 0.36) |
0.840 |
0.05 (− 0.48, 0.67) |
0.860 |
0.23 (− 0.04, 0.72) |
0.152 |
0.21 (0.30, 1.14) |
0.524 |
0.31 (− 0.16, 0.80) |
0.206 | |
| ADE |
0.57 (0.35, 0.80) |
< 2e−16 |
1.68 (− 0.96, 4.34) |
0.210 |
2.66 (− 0.03, 5.29) |
0.054 |
2.49 (0.09 4.83) |
0.034 |
3.95 (0.06, 8.47) |
0.046 |
2.89 (0.49, 5.54) |
0.020 | ||
|
M4 (AgeAccelPheno) |
ACME |
0.03 (− 0.05, 0.11) |
0.530 |
0.24 (− 0.15, 0.74) |
0.270 |
0.36 (− 0.24, 1.14) |
0.276 |
0.13 (− 0.12, 0.53) |
0.370 |
0.51 (− 0.12, 1.61) |
0.176 |
0.27 (− 0.08, 0.82) |
0.140 | |
| ADE |
0.56 (0.34, 0.80) |
< 2e−16 |
1.48 (− 0.93, 4.35) |
0.250 |
2.35 (− 0.23, 5.05) |
0.084 |
2.59 (0.25, 4.95) |
0.030 |
2.65 (− 0.24, 8.01) |
0.064 |
2.93 (0.50, 5.52) |
0.016 | ||
|
M5 (AgeAccelGrim) |
ACME |
0.04 (− 0.01, 0.11) |
0.100 |
0.48 (0.02, 1.22) |
0.028 |
0.76 (0.04, 1.71) |
0.036 |
0.46 (0.01, 1.07) |
0.046 |
0.69 (− 0.10, 1.97) |
0.100 |
0.68 (− 0.04, 1.47) |
0.064 | |
| ADE |
0.55 (0.33, 0.79) |
< 2e−16 |
1.24 (− 1.36, 4.03) |
0.342 |
1.95 (0.04, 1.71) |
0.160 |
2.26 (− 0.05, 4.70) |
0.060 |
3.47 (− 0.40, 7.85) |
0.070 |
2.52 (− 0.08, 5.18) |
0.056 | ||
All reported analyses consisted of generalized linear models with Gaussian distributions and identity links. Significant p-values are in bold
M1 aimed to evaluate the total effects, and was adjusted for chronological age, sex, SEP (as a binary variable: manual and non-manual), smoking status (as current smoker, ex-smoker and never-smoked), alcohol comsunption (as the average number of alcohol units drank per day), physical activity status (as active or inactive) and white cell counts (i.e., naïve and exhausted CD8 + T-lymphocytes, CD4 + T-lymphocytes, B-cells, natural killer cells, granulocytes, and monocytes). Compared to M1, M2 was in addition adjusted for AgeAccelHannum, M3 for AgeAccelHorvath, M4 for AgeAccelPheno and M5 for AgeAccelGrim
ACME = average causal mediation effect; ADE = average direct effect; M = model. Other abbreviations as in Table 2