Table 5. Association of LINE-1 methylation and other risk factors with non-cardiovascular and total mortality—Crude estimates and multivariable models.
| Non cardiovascular mortality | Total Mortality | |||||||
|---|---|---|---|---|---|---|---|---|
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| crude | multivariablea | crude | multivariablea | |||||
| HR | (95%CI) | HR | (95%CI) | HR | (95%CI) | HR | (95%CI) | |
| LINE-1 methylation | ||||||||
| 86.3-77.5 (%5mC)b | 1.0 | 1.0 | 1.0 | 1.0 | ||||
| 77.4-68.1 (%5mC) | 1.6 | (0.8 to 2.9) | 1.5 | (0.8 to 3.0) | 2.1 | (1.3 to 3.4) | 2.0 | (1.2 to 3.3) |
| Age (continuous, 10 yrs) | 2.5 | (1.4 to 4.6) | 3.2 | (2.1 to 5.0) | ||||
| BMI (continuous, 5 kg/m2) | 1.3 | (0.8 to 1.9) | 1.1 | (0.8 to 1.5) | ||||
| Smoking (ever) | 1.5 | (0.7 to 3.5) | 1.6 | (0.9 to 2.8) | ||||
| Pack-years (continuous, 35 pack-yrs) | 1.3 | (0.9 to 1.7) | 1.2 | (1.0 to 1.5) | ||||
| Alcohol drinking (two drinks or more/day) | 0.9 | (0.3 to 2.4) | 1.0 | (0.5 to 1.9) | ||||
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| Diagnosis of hypertension | 0.5 | (0.2 to 1.0) | 0.9 | (0.5 to 1.7) | ||||
| Systolic blood pressure (continuous, 20 mmHg) | 1.0 | (0.6 to 1.7) | 0.8 | (0.6 to 1.1) | ||||
| Diastolic blood pressure (continuous, 20 mmHg) | 1.7 | (1.0 to 2.8) | 1.7 | (1.2 to 2.3) | ||||
| Diabetes | 1.7 | (0.7 to 3.8) | 1.8 | (1.0 to 3.1) | ||||
| Statin use | 0.9 | (0.4 to 2.0) | 1.0 | (0.6 to 1.7) | ||||
| Serum total cholesterol (continuous, 150 mg/dl) | 0.8 | (0.5 to 1.2) | 0.9 | (0.7 to 1.1) | ||||
| Serum HDL (continuous, 15 mg/dl) | 1.0 | (0.6 to 1.5) | 0.9 | (0.6 to 1.2) | ||||
| Total homocysteine (continuous, 4 nmol/ml) | 1.1 | (0.8 to 1.4) | 1.1 | (0.9 to 1.3) | ||||
| Glomerular filtration rate (continuous, 25 ml/min/1.73m2) | 0.5 | (0.3 to 0.9) | 0.6 | (0.4 to 0.9) | ||||
| Percent neutrophils (continuous, 10%) | 1.2 | (0.8 to 1.7) | 1.2 | (0.9 to 1.5) | ||||
| Percent lymphocytes (continuous, 10%) | 0.8 | (0.5 to 1.3) | 0.9 | (0.7 to 1.2) | ||||
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| LINE-1 methylation (continous, -2.5 %mC)c | 1.44 | (0.99 to 2.11) | 1.56 | (0.99 to 2.46) | 1.49 | (1.14 to 1.93) | 1.51 | (1.10 to 2.08) |
The multivariable models included all the listed variables as independent variables. For continuous independent variables other than LINE-1, the table reports Hazard Ratios (HRs) and 95 CIs for an increase equal to the number of units indicated. The number of units was selected as a round number that approximates the interquartile range of each of the variables. The exact interquartile ranges were the following: age, 9 years; BMI, 4.8 kg/m2; pack-years, 35; HDL, 15 mg/dl; total cholesterol 138 mg/dl; total homocysteine, 3.5 nmol/ml; glomerular filtration rate, 22.9 ml/min/1.73m2; percent neutrophils, 11%, percent lymphocytes, 10%.
Reference category.
Results from a second set of models fitting LINE-1 methylation as a continuous independent variable. HRs and 95% CI estimates per each 2.5 %5mC decrease in LINE-1 methylation (LINE-1 interquartile range was 2.55 %5mC).