Table 4 Associations between blood pressure or hypertension and DNA methylation age
From: Accelerated epigenetic age in hypertension: a systematic review and meta-analysis
Author, Year | Quality1 | Population | Male (%), age (SD), sample size, country | Platform | Clock | Measure of Epigenetic Age | Definition of HTN/BP | Tissue | Associations between epigenetic age and hypertension and/or blood pressure. |
|---|---|---|---|---|---|---|---|---|---|
Ammous et al. 2021 [22] | 7/9 | GENOA-AA | 29, 57.1 (10.6), 1100, USA | 850k | Horvath (Pan tissue), Hannum, PhenoAge, GrimAge | IEAA EEAA AA | BP: measured 3 times after 5 minute rest with the second and third averaged. HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 and/or antihypertensive medication usage. | PBC | Horvath: 1 year increase in IEAA associated with 0.37 mmHg ↑ SBP (95%Cl: 0.109, 0.627; P = 0.005), 0.16 mmHg ↑ DBP (95%Cl: 0.009, 0.303; P = 0.037), 0.23 mmHg ↑ MAP (95%Cl: 0.056, 0.393; P = 0.009) and 0.22 mmHg ↑ PP (95%Cl: 0.026, 0.414; P = 0.027). Hannum: 1 year increase in EEAA associated with 0.27 mmHg ↑ SBP (95%Cl: 0.055, 0.485; P = 0.0014) and 0.24 mmHg ↑ in PP (95%Cl: 0.082, 0.403; P = 0.003). PhenoAge: 1 year increase in AA associated with 0.22 mmHg ↑ SBP (95% Cl: 0.050, 0.395; P = 0.012), 0.12 mmHg ↑ MAP (95%Cl: 0.004, 0.229; P = 0.042) and 0.16 mmHg increase in PP (0.033, 0.293; P = 0.014). GrimAge: 1 year increase in AA associated with 0.36 mmHg ↑ SBP (95%Cl: 0.093, 0.627; P = 0.008) and 0.35 mmHg ↑ PP (95%Cl: 0.145, 0.544; P = 0.001). |
Arpon et al. 2019 [202] | 6/9 | MENA OBEKIT + NormoP | MENA: 36.1, 47.3 (15.4), 366, Consortia OBEKIT + NormoP: 29.5, 44.8 (10.2), 268, Consortia | 450 K | Horvath (Pan tissue), GrimAge | AA | BP: measured using standardised protocols. | PBC | MENA: Horvath: No association GrimAge: No association OBEKIT + NormoP: GrimAge: No association |
Chen et al. 2023 [203] | 7/9 | HRS-VBS | HRS-VBS: 40.4, 77.0 (5.5), 1047, USA | 850k | Horvath (Pan tissue), Horvath (Skin and blood), Hannum, Weidner (99 CpG), Weidner (102 CpG), VidalBralo, epiTOC, Bocklandt, Garagnami, PhenoAge, Zhang, GrimAge, DunedinPoAm38, | AA | BP: measured 3 times with 45 s intervals between with SBP variability calculated as coefficients of variation. | WB | HRS-VBS: Horvath: SBP variability was associated with increased AA after adjustment with multiple covariates (β = 0.084; 95% CI: 0.020, 0.147). Zhang: SBP variability was associated with increased AA after adjustment for multiple covariates (β = 0.079; 95% CI: 0.020, 0.138). PhenoAge: SBP variability was associated with increased AA after adjustment for age and sex (β = 0.100; 95% CI: 0.038, 0.161). |
Chilunga et al. 2021 [24] | 8/9 | RODAM | Ghanian Migrants: 30, 52.4 (9.8), 347, Europe Ghanian Non-Migrants: 55, 49.9 (9.8), 365, Ghana | 450k | Horvath (Pan tissue), Hannum PhenoAge GrimAge | IEAA EEAA AA | BP: measured 3 times after sitting at rest for 5 minutes. | WB | Ghanian Migrants: Horvath: No association. Hannum: No association. PhenoAge: No association. GrimAge: No association. Ghanian Non-Migrants: Horvath: No association. Hannum: No association. PhenoAge: No association. GrimAge: No association. |
Dugue et al. 2018 [204] | 8/9 | MCCS | 61, 59.0 (7.6), 2818, Australia | 450k | Horvath (Pan tissue) Hannum | AA IEAA | BP: indication of measurement. HTN: self-reported antihypertensive medication usage. | BC | Horvath: No association. Hannum: No association. |
Föhr et al. 2024 [74] | 6/9 | Discovery: FTC ERMA Replication: YFS EH-Epi | Discovery: 42.9, 52.6 (14.6), 268, Finland Replication YFS: 58.4, 43.3 (4.6), 1564, Finland EH-Epi: 44.3, 61.6 (3.7), 293, Finland | 450k 850k | GrimAge DunedinPACE | AA | BP: measured repeatedly using standardised methods. | WB | Discovery GrimAge: No Association. DunedinPACE: Positive association with DBP in 2 models (P = 0.017 and P = 0.046). Positive association with DBP using within-twin-pair analysis (P = 0.005). Replication YFS GrimAge: Positive association with SBP and DBP across all models (P < 0.05). DunedinPACE: Positive association with SBP and DBP across all models (P < 0.001). EH-Epi GrimAge: No Association. DunedinPACE: Positive association with DBP after full adjustment (P < 0.05). |
Gao et al. 2018 [68] | 7/9 | NAS | First visit: 100, 71.6 (6.5), 546, USA Second visit: 100, 75.4 (6.5), 546, USA | 450k | Horvath (Pan tissue) Hannum PhenoAge | AA ΔAA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive usage. | WB | Horvath: ↑ AA in HTN vs NTs in the first (HTN: β = 0.18 vs NT: β = 0.09; P = 0.016) and second (HTN: β = -0.01 vs β = -0.18; P = 0.016) visits. ↑ ΔAA HTN vs NTs in the first (HTN: β = 0.03 vs β = -0.14; P = 0.007) and second (HTN: β = 0.01 vs β = -0.12; P = 0.007) visits. No direct association between HTN, SBP or DBP and AA at either visit. Hannum: HTN was associated with AA at the first visit (β = 2.15, P = 0.003) after adjustment for all covariates. PhenoAge: HTN was associated with AA at the first visit (β = 1.687, P = 0.002) after adjustment for all covariates. HTN was associated with AA at the second visit (β = 1.732, P = 0.003) after adjustment for age, leukocyte distribution and batch effects. |
Hernández Cordero et al. 2022 [205] | 5/9 | St Paul’s Hospital HIV Bronchoscopy cohort, START | Broncho: 78, 56 (52–63)2, 18, Canada START: 90.3, 40 (34–49)2, 378, International | 850k | GrimAge | AA | BP: indication of measurement HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage | Broncho: airway epithelial brushings START: WB | Broncho: No association with HTN or BP performed. START: GrimAge: ↑ AA was associated with HTN (P = 0.010). |
Horvath et al. 2016 [23] | 8/9 | BHS, WHI | WHI: 0, 50–792, 1462, USA BHS: N/A3, 28–51.32, 969, USA | 450k | Horvath (Pan tissue), Hannum | AA IEAA EEAA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage and/or HTN diagnosis | WHI: WBC BHS: WB | WHI: Horvath: No association. Hannum: No association. BHS: Horvath: ↑ IEAA in HTN vs Controls in the total cohort (P = 0.0035) and in African Americans (P = 0.00049) Hannum: HTN was associated with EEAA (β = 1.25, P = 1.7E-05). ↑ EEAA in HTN vs Controls in the total cohort (P = 8E-05) and when stratified by race (Caucasian: P = 0.00039; African American: P = 0.0025). |
Horvath et al. 2022 [206] | 6/9 | NNAB, MHBB, NNTC | N/A3, 27.9–91.22, 133 (75 infected with HIV), USA | 450k | Horvath (Pan tissue), Horvath (Skin and blood) | AA | HTN: self-reported and/or medical record review. | Adipose, WB, Bone, marrow, Heart, Kidney, Liver, Lung, Lymph Node, Muscle, Spleen, Pituitary gland | NNAB, MHBB, NNTC combined: Horvath (Pan tissue): ↑ AA in HTN vs NT in all tissues combined (P = 4.5E-05), in kidney (P = 0.0048), liver (P = 0.028) and lymph nodes (P = 0.033). Horvath (Skin and Blood): ↑ AA in HTN vs NT in all tissues combined (P = 0.00036) and kidney (P = 0.0095). |
Irvin et al 2018 [25] | 7/9 | GOLDN | 42, 46.6–50.72, 993, USA | 450k | Horvath (Pan tissue) Hannum | IEAA EEAA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. | CD4 + T Cells | Horvath: No association. Hannum: ↑ prevalence of HTN was associated with above the median EEAA (P = 0.0001). |
Jiang et al. 2022 [75] | 8/9 | CATHGEN | 58.4, 60.1 (12.4), 562, USA | 850k | Horvath (Pan tissue) PhenoAge, GrimAge | AA | BP: taken from medical records. HTN: medical history. | WB | Horvath: Positive association between AA and DBP (P = 0.007). PhenoAge: No association. GrimAge: Negative association between AA and SBP (P = 0.002). |
Kresovich et al. 2023 [82] | 6/9 | Sister Study | 0, 56 (9.0), 4419, USA and Puerto Rico | 450 K | PhenoAge GrimAge DunedinPACE | AA | BP: measured in a sitting position 3 times 2 min apart. HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. | WB | PhenoAge: Positive association with HTN (OR: 1.16, 95%CI: 1.05-1.28). GrimAge: Positive association with HTN (OR :1.28, 95%CI: 1.14, 1.45). DunedinPACE: Positive association with HTN (OR: 1.16, 95%CI: 1.03, 1.30). Normotensive women at baseline with higher AA were more likely to be diagnosed with incident HTN for PhenoAge (HR: 1.09, 95%CI: 0.97, 1.23), GrimAge (HR: 1.16, 95%CI: 0.99, 1.36) and DunedinPACE (HR: 1.16, 95%CI: 1.01, 1.33). |
Levine et al. 2018 [18] | 8/9 | WHI | 0, 50–792, 4771, USA | 450k | PhenoAge | AA | BP: measured seated after 5 min rest. Average taken. HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. | WBC | PhenoAge: Positive association between AA and SBP (Bicor= 0.08, P = 1E-06). |
Li et al. 2019 [207] | 7/9 | InterGEN | 0, 31.7 (5.7), 232, USA | 850k | Horvath (Pan tissue) | AA | HTN: self-reported. | Saliva | Horvath: 1.49-year ↑ AA in HTN vs NT individuals (β: 1.49; 95% Cl: 0.11, 2.86). |
Lin et al. 2023 [208] | 5/9 | TWB | 50.2, 50.3 (11.3), 2474, Taiwan | 850 K | Horvath (Pan tissue) Hannum PhenoAge GrimAge DunedinPACE | AA | HTN: SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg and/or antihypertensive medication usage | WB | No association (P < 4E-04). |
Lind et al. 2018 [69] | 6/9 | Gen Pop | N/A3, 70.2 (0.2), 967, Sweden | 450k | Horvath (Pan tissue) Hannum | DiffAge | BP: measured 3 times after 30 minutes rest. | WB | Horvath: Positive association between DiffAge and SBP (β = 0.02; 95%Cl: 0, 0.03; P = 0.012). |
Lo et al. 2022 [209] | 6/9 | TWB | 50.2, 49.8 (11.1), 2474, Taiwan | 850k | Horvath (Pan tissue), Hannum, PhenoAge, GrimAge | IEAA, AA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or self-reported history of HTN. Ideal BP: SBP ≤ 120 mmHg and/or DBP ≤ 80 mmHg. | WB | Horvath: More participants with ideal BP in the lowest tertile of IEAA (P < 0.001). Hannum: More participants with idea BP in lowest tertile of AA (P < 0001). PhenoAge: More participants with ideal BP in the lowest tertile of AA (P < 0.01). GrimAge: More participants with ideal BP in the lowest tertile of AA (P < 0.001). |
Lu et al. 2019 [19] | 7/9 | FHS WHI JHS InCHIANTI | FHS: 47, 66.9 (8.6), 625, USA WHI BA23: 0, 65.1 (7.1), 2107, USA WHI EMPC: 0, 63.3 (7.0), 1972, USA JHS: 37, 56.2 (12.3), 1747 USA InCHIANTI: 46, 67.0 (16.6), Italy | 450k | GrimAge | AA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. | FHS: BC WHI: WB InCHIANTI: BC JHS: PBC | GrimAge: ↑ AA was associated with HTN (OR = 1.04, P = 5.1E-13). ↑ AA was associated with SBP (bicor = 0.07; P = 9E-07). |
Marinello et al. 2024 [210] | 4/9 | SPHERE | 24.4, 51.7 (18.1), 190, Italy | MSP | Zbieć-Piekarska | AA | BP: indication of measurements HTN: use of antihypertensive medications | BC | Zbieć-Piekarska: Positive association between SBP and AA (β = 0.045, P = 0.019). |
Marioni et al. 2015 [20] | 8/9 | LBC1921 LBC1936 FHS NAS | LBC1921: 40, 79.1 (0.6), 446, Scotland LBC1936: 51, 69.5 (0.8), 920, Scotland FHS: 46, 66.3 (8.9), 2635, USA NAS: 100, 72.9 (6.9), 657, USA | 450k | Horvath (Pan tissue), Hannum | ΔAge | LBC: HBP: self-reported yes/no FHS and NAS: HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. | LBC1921: WB LBC1936: WB FHS: PBC NAS: BC | LBC1921: Horvath: No association. Hannum: No association. LBC1936: Horvath: No association. Hannum: No association. FHS: Horvath: Negative association between Horvath ΔAge and HBP (β = -0.22, P = 8.6E-07). Hannum: No association. NAS: Horvath: No association. Hannum: No association. |
McCartney et al. 2018 [80] | 8/9 | Generation Scotland | 37.6, 48.51 (13.99), 5101, Scotland | 850k | Horvath (Pan tissue), Hannum | IEAA EEAA | HBP: self-reported BP yes/no | PBC | Horvath: No association. Hannum: Positive association between EEAA and HBP (β = 0.177; 95%Cl: 0.064, 0.29; P = 0.002). |
Perez et al. 2022 [211] | 6/9 | InterGEN | 0, 31.2 (27.3–35.6)2, 227, USA | 850k | Horvath (Pan tissue) | AA | HTN: self-reported. | WB | Horvath: Positive association between AA and HTN (β = 0.08; 95%Cl: 1.01, 1.17). |
Philibert et al. 2024 [212] | 5/9 | ProSAAF | 41, 49.6 (9.3), 278, USA | 850 K | GrimAge DunedinPACE | AA | HTN: self-reported | WB | GrimAge: Positive correlation with HTN (P < 0.05) DundinPACE: Positive correlation with HTN (P < 0.05). |
Pottinger et al. 2021 [85] | 7/9 | WHI | 0, 64.2 (7.1), 2170, USA | 450k | Horvath (Pan tissue) Hannum | IEAA EEAA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage | WB | Horvath: No association. Hannum: No association. |
Qin et al. 2021 [213] | 7/9 | SJLIFE | 47, 31.6 (6.0, 66.4)2, 2139, USA | 850k | PhenoAge | AA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage | WB | PhenoAge: HTN was associated with EAA in time to event analysis (third vs first tertile, relative rate [RR] = 1.83; 95%CI: 1.17, 2.83; Ptrend = 0.005) |
Quach et al. 2017 [70] | 7/9 | WHI InCHIANTI | WHI: 0, 64 (7.1), 4173, USA InCHIANTI: 44, 71 (16), 402, Italy | 450k | Horvath (Pan tissue) Hannum | IEAA EEAA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage. BP: measured seated after 5 min rest. Average taken. | WB | Horvath: ↑ IEAA correlated with SBP (bicor=0.04, P = 5E-03) and DBP (bicor=0.05, P = 3E-03). Hannum: ↑ EEAA correlated with SBP (bicor=0.07, P = 4E-06) and DBP (bicor=0.04, P = 0.01). |
Roberts et al. 2021 [72] | 8/9 | ARIC CHS FHS | ARIC: 36.1, 56.5 (5.8), 2159, USA CHS: 38.4, 74.1 (5.2), 719, USA FHS: 44.4, 65.8 (8.8), 2362, USA | 450k | Horvath, Hannum, PAI-1, PhenoAge, GrimAge | AA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage BP: measured seated after 5 min rest. Average taken. | WB | Horvath: Positive association between AA and anti-HTN medication usage (OR = 1.07; 95%Cl: 1.02, 1.12; P = 0.0011). Hannum: Positive association between AA and SBP (β = 0.76; 95%Cl: 0.28, 1.24; P = 0.002) and anti-HTN medication usage (OR = 1.11; 95%Cl: 1.04, 1.18; P = 0.0011). PhenoAge: Positive association between AA and SBP (β = 0.71; 95%Cl: 0.34, 1.09; P = 0.0002) and anti-HTN medication usage (OR = 1.11; 95%Cl: 1.02, 1.22; P = 0.0157). PAI-1: Positive association between AA and SBP (β = 1.67; 95%Cl: 1.15, 2.19; P < 0.0001) and anti-HTN medication usage (β = 1.44; 95%Cl: 1.16, 1.77; P = 0.0008). GrimAge: Positive association between AA and SBP (β = 1.07; 95%Cl: 0.36, 1.77; P = 0.0031). Negative association with DBP (OR = -0.50; 95%Cl: -0.92, -0.08; P = 0.0206). |
Robinson et al. 2020 [77] | 8/9 | Airwave | 60.5, 41.24 (9.1), 2238, UK | 850 K | Horvath Hannum PhenoAge | AA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage | WB | Horvath: No association. Hannum: No association. PhenoAge: Positive association between AA and HTN (β = 1.15; 95%Cl: 0.46, 1.84; P = 0.0012). |
Roetker et al. 2018 [78] | 7/9 | ARIC | 35, 57 (6), 2543, USA | 450k | Horvath (Pan tissue), Hannum | AA | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or antihypertensive medication usage | WBC | Horvath: No association. Hannum: Positive association between AA and anti-HTN use (β = 0.47; P = 0.04). |
Smith et al. 2019 [73] | 8/9 | GENOA | 28.9, 58.0 (10.1), 1390, USA | 850k | Horvath (Pan tissue) Hannum | IEAA EEAA | BP: BP was measured twice seated after 5 minutes, average taken. HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 and/or antihypertensive medication usage | PBC | Horvath: No association. Hannum: Positive association between EEAA and SBP when adjusting for antihypertensive medication (β = 0.188; P = 0.015). |
Tamman et al. 2019 [67] | 6/9 | NHRVS | 100, 63.1 (14.0), 1135, USA | 850k | Horvath (Pan tissue) | ΔAge | HTN: self-reported. | Saliva | Horvath: ↑ HTN prevalence as associated with ↑ odds of ΔAge (OR: 1.48, 95%Cl: 1.02-2.15). |
Tang et al. 2023 [66] | 5/9 | SATSA | 58.8, 66.6 (7.6) 672, Sweden | 450 K | Horvath (Pan tissue) Hannum PhenoAge GrimAge | PCAge | HTN: SBP ≥ 140 mmHg and/or DBP ≥ 90 and/or antihypertensive medication usage | WBC | GrimAge: Negative association between anti-HTN usage and PCGrimAge (β = -0.39; 95% CI: -0.67, -0.12). |
Wan et al. 2024 [65] | 6/9 | HRS | 42.1, 67.3 (9.5), 3708, USA | 850 K | GrimAge | DiffAge | HTN: self reported (yes/no). | WB | GrimAge: ↑ GrimAge in participants with HTN and cognition (β = 0.963; 95% CI: 0.711, 1.214). |
Wang et al. 2023 [169] | 7/9 | FHS | 53.8, 58.1 (24, 94) 3823, USA | 450 K | PhenoAge GrimAge | AA | HTN: SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg and/or antihypertensive medication usage | WB | PhenoAge: Positive association between AA and HTN (OR: 1.09, 95%Cl: 1.05-1.12). GrimAge: Positive association between AA and HTN (OR: 1.05, 95%Cl: 1.03-1.08). |
Xia et al. 2024 [76] | 6/9 | SCS | 52.6, 61.5 (8.4), 95, China | 850 K | Horvath (Pan tissue) | AA | BP: indication of measurement HTN: ≥140 mmHg and/or ≥90 mmHg and/or antihypertensive medication usage. | WB | Horvath: ↑ DBP in individuals with AA compared to non-AA individuals (P < 0.007). No association with SBP or HTN. |
Xiao et al. 2022 [71] | 7/9 | Gen pop | 42.9, 78.5 (16.1), 280, China | 850k | Horvath (Pan tissue), Hannum | ΔAge, Aging rate | BP: measured 2-3 times seated at rest for 5 minutes. HTN: ≥140 mmHg and/or ≥90 mmHg and/or antihypertensive medication usage. | WBC | Horvath: 10 mmHg increment of SBP was associated with ↑ 0.608 years of ΔAge (95%Cl: 0.23, 0.98; P = 0.002) and ↑ 0.007 increase in aging rate (95%Cl: 0.002, 0.012; 0.004). 10 mmHg increment of PP was associated with ↑ 1.12 years of ΔAge (95%Cl: 0.63, 1.61; P < 0.001) and ↑ 0.013 in aging rate (95%Cl: 0.007, 0.020; P < 0.001). Positive association between HTN and ΔAge (β = 3.10; 95%Cl: 1.07, 5.13; P = 0.003) and aging rate (β = 0.04; 95%Cl: 0.015, 0.065; P = 0.002). Hannum: 10 mmHg increment of SBP was associated with ↑ 0.613 year of ΔAge (95%Cl: 0.28, 1.08; P = 0.001) and ↑ 0.009 in aging rate (95%Cl: 0.003, 0.014; P = 0.003). 10 mmHg increment of PP was associated with ↑1.22 years of ΔAge (95%Cl: 0.70, 1.75; P < 001) and ↑ 0.016 in aging rate (95%Cl: 0.008, 0.023; P < 001). |
