Table 3 Mediation analyses identified potential eicosanoid and eicosanoid-related metabolite mediators of association of BMI, diabetes, and HTN with HFpEF

From: Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction

   

Mediation

Covariate → EIC

EIC → HFpEF

Direct effect

Total effect

m/z

RT

Putative ID

Effect

p-value

ß

SE

p-value

ß

SE

p-value

ß

SE

p-value

ß

SE

p-value

Body mass index

              

377.2305

4.8408

8(9)-EpETE

0.21

<E−16

−0.35

0.04

1.41 E−16

−0.37

0.10

3.27 E−04

0.50

0.11

3.68 E−06

0.63

0.10

1.22 E−09

313.2388

3.4472

12,13 diHOME

0.18

<E−16

−0.31

0.04

4.94 E−13

−0.37

0.10

2.59 E−04

0.52

0.11

9.90 E−07

0.63

0.10

1.22 E−09

353.2336

2.3865

11ß-PGE1

0.10

0.005

0.22

0.04

2.83 E−07

0.29

0.10

0.004

0.57

0.10

7.10 E−08

0.63

0.10

1.22 E−09

Diabetes

                

377.2305

4.8408

8(9)-EpETE

0.25

<E−16

−0.57

0.12

2.03 E−06

−0.48

0.10

1.49 E−06

0.79

0.27

0.003

1.02

0.26

9.09 E−05

313.2388

3.4472

12,13 diHOME

0.24

<E−16

−0.58

0.12

1.35 E−06

−0.46

0.10

3.68 E−06

0.80

0.27

0.003

1.02

0.26

9.09 E−05

293.2122

3.9713

9(S) HOTrE

0.16

0.005

−0.54

012

6.15 E−06

−0.32

0.10

0.0014

0.87

0.27

0.001

1.02

0.26

9.09 E−05

293.2123

4.1502

13(S) HOTrE(y)

0.15

0.002

−0.50

0.12

2.80 E−05

−0.32

0.09

7.12 E−04

0.88

0.27

9.39 E−04

1.02

0.26

9.09 E−05

353.2336

2.2385

11ß-PGE1

0.14

0.002

0.41

0.12

6.83 E−04

0.37

0.10

3.15 E−04

0.90

0.27

7.12 E−04

1.02

0.26

9.09 E−05

Hypertension

              

313.2388

3.4471

12,13 diHOME

0.20

<E−16

−0.50

0.09

7.42 E−09

−0.42

0.10

2.33 E−05

0.80

0.19

2.17 E−05

0.98

0.18

8.98 E−08

377.2305

4.8408

8(9)-EpETE

0.16

<E−16

−0.36

0.09

5.22 E−05

−0.48

0.10

2.02 E−06

0.86

0.19

4.94 E−06

0.98

0.18

8.98 E−08

293.2123

4.1502

13(S) HOTrE(y)

0.12

0.004

−0.45

0.09

2.78 E−07

−0.29

0.10

0.003

0.86

0.18

3.73 E−06

0.98

0.18

8.98 E−08

293.2122

3.9713

9(S) HOTrE

0.12

0.012

−0.43

0.09

1.14 E−06

−0.30

0.10

0.004

0.87

0.19

3.25 E−06

0.98

0.18

8.98 E−08

353.2336

2.3865

11ß-PGE1

0.10

0.003

0.30

0.09

6.15 E−04

0.36

0.10

5.42 E−04

0.90

0.19

1.42 E−06

0.98

0.18

8.98 E−08

  1. Metabolites displayed were found to mediate >10% of the association between body mass index, diabetes, or hypertension with HFpEF.
  2. Mediation effect represents the proportion of the effect of covariate on HFpEF that is mediated by the specific eicosanoid.
  3. Direct effect represents the residual effect of the covariate on HFpEF independent of mediated effects from the specific eicosanoid. Total effect represents the total effect of the covariate on HFpEF. p < 0.05 considered significant mediation effect based on mediation analyses. Standardized ß-coefficients are shown.
  4. CI confidence interval, DiHDPA dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid, diHOME dihydroxy-9Z-octadecenoic acid, EIC eicosanoid, EpETE epoxy-5Z,11Z,14Z,17Z-eicosatetraenoic acid, EpOME epoxy-9Z-octadecenoic acid, HFpEF heart failure with preserved ejection fraction, m/z mass to charge ratio, PGF2α prostaglandin F2α, RT retention time, SE standard err.
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