Table 2.
Association between individual metabolites and systolic blood pressure (SBP, mmHg)
| Metabolites | Pathway | Loading in lipid pattern* | Model 1 | Model 2 | |||
|---|---|---|---|---|---|---|---|
| Coefficient (95% CI) | q-value | Coefficient (95% CI) | q-value | ||||
| tricosanoyl sphingomyelin (d18:1/23:0)† | Sphingomyelins | ─ | 7.56 (4.52, 10.61) | 0.002 | 6.53 (3.43, 9.62) | 0.015 | |
| lignoceroyl sphingomyelin (d18:1/24:0)† | Sphingomyelins | ─ | 6.37 (3.59, 9.14) | 0.005 | 5.61 (2.83, 8.39) | 0.024 | |
| palmitoylcarnitine (C16)† | Fatty Acid Metabolism (Acyl Carnitine, Long Chain Saturated) | 0.50 | 7.26 (3.97, 10.56) | 0.007 | 6.95 (3.71, 10.2) | 0.015 | |
| 1-myristoyl-2-arachidonoyl-GPC (14:0/20:4)† | Phosphatidylcholine (PC) | ─ | 4.34 (2.32, 6.37) | 0.007 | 3.53 (1.45, 5.61) | 0.059 | |
| sphingomyelin (d18:2/24:2)† | Sphingomyelins | ─ | 4.53 (2.41, 6.64) | 0.007 | 4.46 (2.38, 6.54) | 0.015 | |
| 1-palmitoyl-2-linoleoyl-GPI (16:0/18:2)† | Phosphatidylinositol (PI) | ─ | 5.83 (3.02, 8.64) | 0.010 | 5.38 (2.59, 8.16) | 0.037 | |
| 1-palmitoyl-2-arachidonoyl-GPC (16:0/20:4n6)† | Phosphatidylcholine (PC) | ─ | 7.91 (4.01, 11.82) | 0.010 | 6.7 (2.77, 10.63) | 0.059 | |
| 1-palmitoyl-2-arachidonoyl-GPI (16:0/20:4)† | Phosphatidylinositol (PI) | ─ | 4.96 (2.51, 7.41) | 0.010 | 4.44 (2.01, 6.87) | 0.046 | |
| sphingomyelin (d18:1/21:0, d17:1/22:0, d16:1/23:0)† | Sphingomyelins | ─ | 6.38 (3.28, 9.49) | 0.010 | 5.03 (1.82, 8.25) | 0.088 | |
| behenoyl sphingomyelin (d18:1/22:0)† | Sphingomyelins | ─ | 7.35 (3.57, 11.14) | 0.014 | 5.91 (2.05, 9.77) | 0.092 | |
| sphingomyelin (d18:1/14:0, d16:1/16:0)† | Sphingomyelins | ─ | 7.21 (3.4, 11.01) | 0.019 | 5.65 (1.75, 9.55) | 0.118 | |
| cerotoylcarnitine (C26)† | Fatty Acid Metabolism (Acyl Carnitine, Long Chain Saturated) | 0.42 | 4.29 (2.02, 6.56) | 0.019 | 3.91 (1.66, 6.16) | 0.059 | |
| pantothenate (Vitamin B5) | Pantothenate and CoA Metabolism | ─ | 7.77 (3.63, 11.91) | 0.019 | 6.86 (2.74, 10.97) | 0.064 | |
| N2,N2-dimethylguanosine | Purine Metabolism, Guanine containing | ─ | 8.74 (3.99, 13.49) | 0.020 | 8.09 (3.4, 12.78) | 0.059 | |
| cholesterol† | Sterol | ─ | 8.48 (3.89, 13.07) | 0.020 | 7.67 (3.12, 12.22) | 0.062 | |
| sphingomyelin (d18:2/14:0, d18:1/14:1)† | Sphingomyelins | ─ | 5.75 (2.58, 8.91) | 0.022 | 4.57 (1.36, 7.79) | 0.121 | |
| adrenate (22:4n6) | Long Chain Polyunsaturated Fatty Acid (n3 and n6) | 0.71 | 3.15 (1.36, 4.93) | 0.028 | 2.9 (1.14, 4.67) | 0.066 | |
| 1-palmitoleoylglycerol (16:1)† | Monoacylglycerol | 0.57 | 2.26 (0.98, 3.53) | 0.028 | 1.75 (0.45, 3.05) | 0.143 | |
| 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1) | Phosphatidylcholine (PC) | ─ | 3.57 (1.54, 5.59) | 0.028 | 3.01 (0.98, 5.04) | 0.107 | |
| myristoylcarnitine (C14)† | Fatty Acid Metabolism (Acyl Carnitine, Long Chain Saturated) | 0.53 | 2.96 (1.27, 4.64) | 0.029 | 3.01 (1.35, 4.66) | 0.046 | |
| branched-chain, straight-chain, or cyclopropyl 10:1 fatty acid (1) | Partially Characterized Molecules | ─ | 2.66 (1.13, 4.19) | 0.030 | 2.58 (1.07, 4.08) | 0.059 | |
| sphingomyelin (d18:2/16:0, d18:1/16:1)† | Sphingomyelins | ─ | 8.35 (3.52, 13.17) | 0.031 | 6.84 (1.99, 11.69) | 0.122 | |
| picolinoylglycine | Fatty Acid Metabolism (Acyl Glycine) | ─ | 3.34 (1.41, 5.28) | 0.031 | 2.75 (0.81, 4.69) | 0.122 | |
| N6-carbamoylthreonyladenosine | Purine Metabolism, Adenine containing | ─ | 6.16 (2.54, 9.78) | 0.032 | 5.57 (1.99, 9.16) | 0.088 | |
| dihomolinolenate (20:3n3 or 3n6)† | Long Chain Polyunsaturated Fatty Acid (n3 and n6) | 0.73 | 4.25 (1.75, 6.74) | 0.032 | 3.65 (1.16, 6.14) | 0.113 | |
| 1-stearoyl-2-arachidonoyl-GPC (18:0/20:4) | Phosphatidylcholine (PC) | ─ | 6.08 (2.52, 9.64) | 0.032 | 5.01 (1.44, 8.58) | 0.122 | |
| acetylcarnitine (C2) | Fatty Acid Metabolism (Acyl Carnitine, Short Chain) | 0.50 | 6.57 (2.63, 10.5) | 0.038 | 7 (3.13, 10.86) | 0.046 | |
| retinol (Vitamin A) | Vitamin A Metabolism | ─ | 5.16 (2.04, 8.28) | 0.040 | 4.48 (1.39, 7.58) | 0.118 | |
| argininate | Urea cycle; Arginine and Proline Metabolism | ─ | 3.93 (1.56, 6.3) | 0.040 | 3.19 (0.81, 5.57) | 0.148 | |
| 2,3-dihydroxy-5-methylthio-4-pentenoate (DMTPA) | Methionine, Cysteine, SAM and Taurine Metabolism | ─ | 7.88 (3.11, 12.66) | 0.040 | 6.51 (1.73, 11.29) | 0.135 | |
| laurylcarnitine (C12)† | Fatty Acid Metabolism (Acyl Carnitine, Medium Chain) | 0.49 | 2.25 (0.88, 3.62) | 0.042 | 2.36 (1.02, 3.71) | 0.059 | |
| Metabolites with 25–50% below detection limits (BDL): Reference=BDL | |||||||
| linoleoyl-linoleoyl-glycerol (18:2/18:2) [1] | Diacylglycerol | Below median | ─ | 2.29 (−1.6, 6.17) | 0.022 | 3.5 (−0.37, 7.37) | 0.046 |
| Above median | −4.56 (−8.39, −0.73) | −3.45 (−7.26, 0.36) | |||||
| oleoyl-linoleoyl-glycerol (18:1/18:2) [2] | Diacylglycerol | Below median | ─ | −3.07 (−6.99, 0.85) | 0.042 | −2.49 (−6.36, 1.38) | 0.088 |
| Above median | −7.31 (−11.39, −3.24) | −6.8 (−10.82, −2.78) | |||||
| Metabolites with >50% BDL: Reference=BDL | |||||||
| phenylalanylalanine | Dipeptide | Above limit of detection | ─ | −4.86 (−7.86, −1.85) | 0.047 | −4.94 (−7.89, −1.98) | 0.064 |
CI, confidence interval. Coefficient indicates SBP associated with a fold increase of the abundance or per category change of a metabolite in linear regression (n=434). The statistical significance of metabolites with 25–50% BDL was assessed using a Wald test. Model 1 was adjusted for age, sex, provinces, batch, urbanization index (≤64.2, 64.2–81.5, >81.5), per-capita household income (≤10, 10–21.6, >21.6), education, total energy intake, animal-source food, sodium, physical activity (≤57.4, 57.4–152, >152), smoking, alcohol, and estimated glomerular filtration rate (eGFR). Model 2 was additionally adjusted for BMI.
*
Pattern was derived from principal component analysis followed by a varimax rotation. Loadings>0.4 are listed.
†
Metabolites also associated with diastolic blood pressure.