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Table 4 The association between CV risk factors and A-ECG disease scores and the role of DNAm AgeAccel as a mediator of these relationships

From: Accelerated DNA methylation age plays a role in the impact of cardiovascular risk factors on the human heart

A-ECG disease scores 

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

LVSD

M1

Total

− 0.06

(− 0.11, − 0.01)

0.010

− 0.25

(0.74, 0.17)

0.284

− 0.42

(− 0.92, 0.01)

0.058

− 0.28

(− 0.63, 0.06)

0.116

− 0.48

(− 1.29, 0.24)

0.184

− 0.26

(− 0.65, 0.08)

0.170

M2

(AgeAccelHannum)

ACME

0.00

(− 0.00, 0.00)

0.950

− 0.00

(− 0.04, 0.02)

0.860

− 0.00

(− 0.04, 0.03)

0.882

− 0.01

(− 0.05, 0.02)

0.690

0.01

(− 0.06, 0.08)

0.900

− 0.01

(− 0.06, 0.03)

0.670

ADE

− 0.06

(− 0.11, − 0.01)

0.010

− 0.25

(0.74, 0.18)

0.280

− 0.42

(− 0.92, 0.01)

0.058

− 0.27

(− 0.66, 0.07)

0.130

− 0.49

(− 1.29, 0.26)

0.180

− 0.25

(− 0.65, 0.11)

0.180

M3

(AgeAccelHorvath)

ACME

− 0.00

(− 0.01, 0.00)

0.282

− 0.01

(− 0.07, 0.03)

0.820

− 0.01

(− 0.07, 0.08)

0.902

− 0.03

(− 0.09, 0.01)

0.140

− 0.02

(− 0.13, 0.06)

0.680

− 0.04

(− 0.13, 0.01)

0.170

ADE

− 0.06

(− 0.11, − 0.01)

0.024

− 0.24

(− 0.74, 0.18)

0.290

− 0.41

(− 0.93, 0.01)

0.064

− 0.25

(− 0.63, 0.09)

0.160

− 0.46

(− 1.29, 0.30)

0.220

− 0.22

(− 0.62, 0.14)

0.250

M4

(AgeAccelPheno)

ACME

− 0.01

(− 0.02, − 0.00)

0.046

− 0.07

(− 0.18, − 0.01)

0.034

− 0.09

(− 0.20, − 0.01)

0.018

− 0.03

(− 0.09, 0.03)

0.300

− 0.08

(− 0.26, 0.02)

0.140

− 0.06

(− 0.14, − 0.01)

0.024

ADE

− 0.05

(− 0.10, 0.00)

0.056

− 0.18

(− 0.66, 0.24)

0.426

− 0.33

(− 0.84, 0.10)

0.140

− 0.25

(− 0.63, 0.07)

0.140

− 0.40

(− 1.21, 0.3(

0.300

− 0.20

(− 0.60, 0.15)

0.266

M5

(AgeAccelGrim)

ACME

− 0.01

(− 0.03, − 0.01)

0.016

− 0.11

(− 0.26, − 0.01)

0.014

− 0.18

(− 0.33, − 0.06)

0.002

− 0.12

(− 0.24, − 0.03)

0.006

− 0.12

(− 0.32, 0.02)

0.094

− 0.19

(− 0.33, − 0.07)

 < 2e−16

ADE

− 0.05

(− 0.09, − 0.01)

0.046

− 0.14

(− 0.61, 0.27)

0.520

− 0.24

(− 0.72, 0.17)

0.252

− 0.16

(− 0.53, 0.16)

0.334

− 0.36

(− 1.11, 0.35)

0.314

− 0.07

(− 0.48, 0.28)

0.710

LVER

M1

Total

− 0.28

(− 0.48, − 0.09)

0.004

− 1.34

(− 3.25, 0.44)

0.120

− 1.76

(− 3.85, − 0.16)

0.048

− 1.21

(− 2.52, 0.10)

0.082

− 2.75

(− 5.82, − 0.23)

0.036

− 1.61

(− 2.95, − 0.41)

0.004

M2

(AgeAccelHannum)

ACME

0.00

(− 0.01, 0.010

0.918

− 0.01

(− 0.17, 0.09)

0.820

− 0.00

(− 0.18, 0.11)

0.866

− 0.03

(− 0.21, 0.06)

0.598

0.05

(− 0.21, 0.31)

0.800

− 0.04

(− 0.25, 0.09)

0.544

ADE

− 0.28

(− 0.48, − 0.09)

0.002

− 1.33

(− 3.25, 0.42)

0.120

− 0.18

(− 3.85, 0.14)

0.074

− 1.18

(− 2.49, 0.17)

0.090

− 2.80

(− 5.86, − 0.20)

0.032

− 1.57

(− 2.82, − 0.35)

0.006

M3

(AgeAccelHorvath)

ACME

− 0.02

(− 0.05, 0.01)

0.174

− 0.02

(− 0.28, 0.13)

0.790

− 0.03

(− 0.28, 0.29)

0.884

− 0.13

(− 0.38, 0.03)

0.124

− 0.10

(− 0.47, 0.24)

0.650

− 0.18

(− 0.47, 0.03)

0.106

ADE

− 0.26

(− 0.47, − 0.09)

0.006

− 1.32

(− 3.16, 0.47)

0.130

− 1.73

(− 3.84, 0.18)

0.084

− 1.08

(− 2.45, 0.25)

0.118

− 2.65

(− 5.89, − 0.01)

0.049

− 1.43

(− 2.75, − 0.22)

0.008

M4

(AgeAccelPheno)

ACME

− 0.04

(− 0.09, − 0.00)

0.049

− 0.23

(− 0.58, − 0.01)

0.042

− 0.29

(− 0.73, 0.01)

0.054

− 0.11

(− 0.33, 0.10)

0.300

− 0.26

(− 0.88, 0.09)

0.172

− 0.22

(− 0.50, − 0.02)

0.030

ADE

− 0.24

(− 0.45, − 0.04)

0.018

− 1.11

(− 3.0, 0.71)

0.214

− 1.47

(− 3.67, 0.48)

0.152

− 1.10

(− 2.41, 0.25)

0.096

− 2.49

(− 5.70, 0.36)

0.080

− 1.39

(− 2.68, − 0.26)

0.012

M5

(AgeAccelGrim)

ACME

− 0.04

(− 0.09, − 0.01)

0.010

− 0.36

(− 0.87, − 0.02)

0.018

− 0.62

(− 1.20, − 0.15)

0.008

− 0.37

(− 0.77, − 0.07)

0.012

− 0.38

(− 1.12, 0.06)

0.110

− 0.56

(− 1.09, − 0.10)

0.004

ADE

− 0.24

(− 0.42, − 0.05)

0.008

− 0.98

(− 2.84, 0.68)

0.252

− 1.14

(− 3.15, 0.68)

0.244

− 0.84

(− 2.12, 0.51)

0.188

− 2.37

(− 5.22, 0.20)

0.068

− 1.05

(− 2.37, 0.13)

0.082

  1. All reported analyses consisted of generalized linear models with Gaussian distributions and identity links. Significant p-values are in bold
  2. 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 consumption (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. Abbreviations as in Table 3