Table 2.
Cross-sectional associations between selected comorbidities and medication use at baseline and oxysterol concentrations by metabolic pathway.
| Exposure | Categories | n (%)c | Geometric mean (95% CI), nM | % diff | Geometric mean (95% CI), nM | % diff | Geometric mean (95% CI), nM | % diff | Geometric mean (95% CI), nM | % diff | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Cholesterol precursors | 2282 (100%) | Lanosterol (n = 2282) | 24-DHLan (n = 1027) | Desmosterol (n = 2281) | 7-DC (n = 2221) | ||||||
| CVD | No | 1136 (49.8) | 543.5 (528.1,559.3) | . Ref | 40.6 (38.7,42.6) | Ref | 1866.9 (1811.8,1923.6) | Ref | 442.6 (414.5,472.6) | Ref | |
| Yes | 1146 (50.2) | 524.7 (509.9,539.9) | − 3.45 | 38.8 (36.9,40.8) | − 4.57 | 1561.0 (1515.2,1608.2) | − 16.38 | 558.2 (522.1,596.9) | 26.13 | ||
| p-value, extreme categories | 0.099 | 0.201 | < .0001 | < .0001 | |||||||
| Diabetes | No | 2070 (90.7) | 540.1 (529.1,551.3) | Ref | 95.5 (94.2,96.9) | Ref | 1738.1 (1700.9,1776.2) | Ref | 491.5 (468.5,515.6) | Ref | |
| Yes | 207 (9.1) | 475.7 (445.2,508.3) | − 11.93 | 84.2 (80.5,88.1) | − 11.84 | 1427.2 (1331.1,1530.2) | − 17.89 | 528.5 (452.4,617.3) | 7.52 | ||
| p-value, extreme categories | 0.0004 | < .0001 | < .0001 | 0.384 | |||||||
| Statin use | No | 1378 (60.4) | 555.8 (542.0,570.0) | Ref | 40.0 (38.4,41.8) | Ref | 1786.6 (1739.8,1834.8) | Ref | 516.9 (487.3,548.2) | Ref | |
| Yes | 300 (13.1) | 450.7 (427.2,475.6) | − 18.91 | 34.6 (31.3,38.3) | − 13.53 | 1468.5 (1387.6,1554.2) | − 17.80 | 470.8 (414.8,534.4) | − 8.91 | ||
| Unknown | 601 (26.3) | 530.6 (510.9,551.1) | − 4.53 | 41.4 (38.9,44.2) | 3.52 | 1658.4 (1593.2,1726.3) | − 7.18 | 462.7 (423.3,505.6) | − 10.49 | ||
| p-value, extreme categories | < .0001 | 0.010 | < .0001 | 0.191 | |||||||
| Aspirin use | No | 1416 (62.1) | 542.1 (528.7,555.8) | . Ref | 39.4 (37.7,41.1) | Ref | 1758.3 (1712.6,1805.3) | Ref | 505.0 (476.4,535.2) | Ref | |
| Yes | 265 (11.6) | 499.1 (471.1,528.9) | − 7.93 | 37.7 (34.0,41.9) | − 4.22 | 1551.2 (1459.4,1648.7) | − 11.78 | 527.7 (461.0,604.1) | 4.51 | ||
| Unknown | 601 (26.3) | 530.8 (510.9,551.5) | − 2.08 | 41.4 (38.8,44.2) | 5.27 | 1658.5 (1593.0,1726.6) | − 5.68 | 463.0 (423.7,506.0) | − 8.30 | ||
| p-value, extreme categories | 0.010 | 0.454 | 0.0002 | 0.557 | |||||||
| Cholesterol metabolites: “enzymatic pathway”b | 27-HC (n = 2282) | 25-HC (n = 2282) | 24S-HC (n = 2279) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| CVD | No | 1136 (49.8) | 211.2 (208.1,214.3) | Ref | 19.9 (19.2,20.6) | Ref | 95.5 (93.6,97.4) | Ref | |||
| Yes | 1146 (50.2) | 207.5 (204.5,210.6) | − 1.72 | 19.9 (19.2,20.6) | 0.14 | 93.3 (91.5,95.2) | − 2.27 | ||||
| p-value, extreme categories | 0.113 | 0.959 | 0.118 | ||||||||
| Diabetes | No | 2070 (90.7) | 210.9 (208.7,213.2) | Ref | 19.8 (19.3,20.3) | Ref | 95.5 (94.2,96.9) | Ref | |||
| Yes | 207 (9.1) | 194.0 (187.5,200.8) | − 8.00 | 20.7 (19.0,22.5) | 4.54 | 84.2 (80.5,88.1) | − 11.84 | ||||
| p-value, extreme categories | < .0001 | 0.325 | < .0001 | ||||||||
| Statin use | No | 1378 (60.4) | 207.9 (205.2,210.6) | Ref | 19.6 (19.0,20.3) | Ref | 93.8 (92.1,95.4) | Ref | |||
| Yes | 300 (13.1) | 209.0 (203.2,214.9) | 0.54 | 20.5 (19.2,22.0) | 4.77 | 97.3 (93.8,101.0) | 3.80 | ||||
| Unknown | 601 (26.3) | 213.0 (208.8,217.2) | 2.44 | 20.2 (19.2,21.2) | 2.85 | 94.4 (92.0,97.0) | 0.69 | ||||
| p-value, extreme categories | 0.734 | 0.228 | 0.077 | ||||||||
| Aspirin use | No | 1416 (62.1) | 209.5 (206.8,212.2) | Ref | 19.9 (19.3,20.5) | Ref | 95.1 (93.4,96.7) | Ref | |||
| Yes | 265 (11.6) | 200.6 (194.7,206.7) | − 4.24 | 19.2 (17.8,20.7) | − 3.43 | 90.9 (87.4,94.7) | − 4.34 | ||||
| Unknown | 601 (26.3) | 212.9 (208.8,217.1) | 1.63 | 20.2 (19.2,21.2) | 1.40 | 94.4 (91.9,96.9) | − 0.71 | ||||
| p-value, extreme categories | 0.009 | 0.394 | 0.046 | ||||||||
| Cholesterol metabolites: “non-enzymatic pathway”b | 2282 (100%) | 5a6a-EC (n = 2281) | 5b6b-EC (n = 2278) | THC (n = 2282) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| CVD | No | 1136 (49.8) | 28.3 (27.3,29.3) | Ref | 111.6 (107.8,115.5) | Ref | 4.8 (4.5,5.2) | Ref | |||
| Yes | 1146 (50.2) | 27.6 (26.7,28.6) | − 2.44 | 109.4 (105.7,113.2) | 1.72 | 4.4 (4.1,4.8) | − 7.77 | ||||
| p-value, extreme categories | 0.336 | 0.430 | 0.162 | ||||||||
| Diabetes | No | 2070 (90.7) | 28.1 (27.4,28.8) | Ref | 111.0 (108.3,113.7) | Ref | 4.7 (4.4,5.0) | Ref | |||
| Yes | 207 (9.1) | 26.5 (24.5,28.8) | − 5.52 | 105.3 (97.3,114.0) | − 5.10 | 4.2 (3.5,5.0) | − 11.34 | ||||
| p-value, extreme categories | 0.186 | 0.217 | 0.212 | ||||||||
| Statin use | No | 1378 (60.4) | 27.9 (27.1,28.8) | Ref | 109.5 (106.2,112.8) | Ref | 4.6 (4.3,4.9) | Ref | |||
| Yes | 300 (13.1) | 27.7 (26.0,29.6) | − 0.64 | 111.0 (104.1,118.5) | 1.46 | 4.3 (3.7,5.0) | − 5.98 | ||||
| Unknown | 601 (26.3) | 28.2 (26.9,29.5) | 0.89 | 112.5 (107.5,117.7) | 2.77 | 4.9 (4.4,5.5) | 7.16 | ||||
| p-value, extreme categories | 0.861 | 0.692 | 0.456 | ||||||||
| Aspirin use | No | 1416 (62.1) | 28.1 (27.3,29.0) | Ref | 110.8 (107.6,114.2) | Ref | 4.7 (4.4,5.0) | Ref | |||
| Yes | 265 (11.6) | 26.5 (24.8,28.5) | − 5.68 | 104.2 (97.3,111.7) | − 5.97 | 3.8 (3.3,4.5) | − 18.17 | ||||
| Unknown | 601 (26.3) | 28.2 (26.9,29.5) | 0.03 | 112.4 (107.4,117.7) | 1.45 | 4.9 (4.4,5.5) | 5.08 | ||||
| p-value, extreme categories | 0.132 | 0.110 | 0.022 | ||||||||
| Cholesterol metabolites: “non-enzymatic pathway”b | 2282 (100%) | 7a-HC (n = 2271) | 7b-HC (n = 2272) | 7-KC (n = 2282) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| CVD | No | 1136 (49.8) | 289.5 (279.7,299.6) | Ref | 187.2 (177.1,197.9) | Ref | 203.5 (193.5,214.1) | Ref | |||
| Yes | 1146 (50.2) | 288.1 (278.4,298.1) | − 0.49 | 187.9 (177.8,198.5) | 0.36 | 208.7 (198.5,219.4) | 2.53 | ||||
| p-value, extreme categories | 0.847 | 0.930 | 0.504 | ||||||||
| Diabetes | No | 2070 (90.7) | 286.8 (279.8,293.9) | Ref | 187.7 (180.3,195.3) | Ref | 205.3 (198.0,212.9) | Ref | |||
| Yes | 207 (9.1) | 308.8 (285.3,334.2) | 7.67 | 185.1 (162.8,210.3) | − 1.37 | 213.1 (189.7,239.4) | 3.80 | ||||
| p-value, extreme categories | 0.081 | 0.840 | 0.549 | ||||||||
| Statin use | No | 1378 (60.4) | 284.0 (275.5,292.7) | Ref | 182.7 (173.9,191.8) | Ref | 202.0 (193.2,211.2) | Ref | |||
| Yes | 300 (13.1) | 297.7 (279.1,317.5) | 4.82 | 188.5 (169.8,209.2) | 3.18 | 218.0 (198.2,239.7) | 7.91 | ||||
| Unknown | 601 (26.3) | 295.2 (282.0,309.0) | 3.95 | 198.4 (184.3,213.6) | 8.59 | 209.5 (195.9,224.1) | 3.73 | ||||
| p-value, extreme categories | 0.196 | 0.594 | 0.155 | ||||||||
| Aspirin use | No | 1416 (62.1) | 287.6 (279.2,296.4) | Ref | 184.9 (176.2,194.0) | Ref | 207.8 (198.9,217.1) | Ref | |||
| Yes | 265 (11.6) | 280.5 (261.8,300.5) | − 2.49 | 177.9 (159.2,198.9) | − 3.76 | 190.2 (171.8,210.6) | − 8.45 | ||||
| Unknown | 601 (26.3) | 295.1 (281.9,308.9) | 2.61 | 198.3 (184.2,213.5) | 7.27 | 209.4 (195.8,223.9) | 0.77 | ||||
| p-value, extreme categories | 0.512 | 0.537 | 0.118 | ||||||||
Geometric means (95% CI) calculated using generalized linear models adjusted for age at diagnosis (continuous; except exposure category age), BMI (continuous; except exposure category BMI), and study region (Hamburg, Rhine-Neckar-Karlsruhe; except exposure category study region). Table 2 includes exposures significantly associated with at least one oxysterol and with > 10% difference between exposure categories.
Significance level after Bonferroni correction p < 0.0001.
amissing oxysterol values due to levels below LOD or levels exceeding calibration range; missing exposure categories values: diabetes, n = 5; statin use, n = 3.
bplease note that these are not fixed subgroups but only created for a better overview,
nM = nanomolar; LOD = level of detection; p-diff = percentage difference between extreme categories; CVD = cardiovascular disease; 24-DHLan = 24,25-dihydrolanosterol; 7-DC = 7-dehydrocholesterol; 27-HC = 27-hydroxycholesterol; 25-HC = 25-hydroxycholesterol; 24S-HC = 24S-hydroxycholesterol; 5a6a-EC = 5α,6α-epoxycholesterol; 5b6b-EC = 5β,6β-epoxycholesterol; THC = 5α,6β-dihydroxycholestanol; 7a-HC = 7α-hydroxycholesterol; 7b-HC = 7β-hydroxycholesterol; 7-KC = 7-ketocholesterol.