Table 4. Association of LINE-1 methylation and other risk factors with mortality from ischemic heart disease or stroke – Crude estimates and multivariable models.
| Ischemic Heart Disease | Stroke | Ischemic Heart Disease or Stroke | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
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| crude | multivariablea | crude | multivariablea | crude | multivariablea | |||||||
| HR | (95%CI) | HR | (95%CI) | 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 | 1.0 | 1.0 | ||||||
| 77.4-68.1 (%5mC) | 3.4 | (1.5 to 7.9) | 3.3 | (1.3 to 8.4) | 2.0 | (0.5 to 7.9) | 2.8 | (0.6 to 14.3) | 3.0 | (1.5 to 6.1) | 2.9 | (1.3 to 6.2) |
| Age (continuous, 10 yrs) | 2.6 | (1.3 to 5.2) | 47.0 | (5.5 to 403) | 4.1 | (2.1 to 7.8) | ||||||
| BMI (continuous, 5 kg/m2) | 1.2 | (0.7 to 1.9) | 0.4 | (0.1 to 1.5) | 1.0 | (0.6 to 1.5) | ||||||
| Smoking (ever) | 1.7 | (0.6 to 4.5) | 2.8 | (0.3 to 24.6) | 1.7 | (0.7 to 3.9) | ||||||
| Pack-years (continuous, 35 pack-yrs) | 1.1 | (0.8 to 1.7) | 0.9 | (0.2 to 3.0) | 1.1 | (0.8 to 1.6) | ||||||
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| Alcohol drinking (two drinks or more/day) | 0.6 | (0.2 to 2.3) | 5.8 | (0.6 to 54.1) | 1.1 | (0.4 to 3.0) | ||||||
| Diagnosis of hypertension | 2.7 | (0.8 to 9.5) | 1.0 | (0.1 to 11.4) | 2.4 | (0.8 to 7.1) | ||||||
| Systolic blood pressure (continuous, 20 mmHg) | 0.8 | (0.5 to 1.4) | 0.2 | (0.1 to 0.8) | 0.7 | (0.4 to 1.1) | ||||||
| Diastolic blood pressure (continuous, 20 mmHg) | 1.3 | (0.8 to 2.2) | 6.0 | (1.7 to 21.9) | 1.7 | (1.1 to 2.7) | ||||||
| Diabetes | 1.0 | (0.4 to 2.6) | 21.4 | (2.5 to 184) | 1.9 | (0.8 to 4.2) | ||||||
| Statin use | 0.9 | (0.4 to 2.1) | 2.0 | (0.4 to 11.3) | 1.1 | (0.5 to 2.2) | ||||||
| Serum total cholesterol (continuous, 150 mg/dl) | 1.0 | (0.7 to 1.4) | 0.6 | (0.2 to 1.8) | 0.9 | (0.7 to 1.3) | ||||||
| Serum HDL (continuous, 15 mg/dl) | 0.9 | (0.5 to 1.5) | 0.2 | (0.1 to 1.2) | 0.7 | (0.5 to 1.2) | ||||||
| Total homocysteine (continuous, 4 nmol/ml) | 1.0 | (0.7 to 1.6) | 1.0 | (0.3 to 2.9) | 1.0 | (0.7 to 1.5) | ||||||
| Glomerular filtration rate (continuous, 25 ml/min/1.73m2) | 0.6 | (0.3 to 1.2) | 1.1 | (0.2 to 5.6) | 0.7 | (0.4 to 1.3) | ||||||
| Percent neutrophils (continuous, 10%) | 1.1 | (0.7 to 1.6) | 1.7 | (0.7 to 3.8) | 1.2 | (0.8 to 1.7) | ||||||
| Percent lymphocytes (continuous, 10%) | 1.1 | (0.8 to 1.6) | 0.6 | (0.2 to 1.4) | 0.9 | (0.7 to 1.3) | ||||||
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| LINE-1 methylation (continous, -2.5 %mC)c | 1.60 | (1.07 to 2.38) | 1.73 | (1.06 to 2.83) | 1.28 | (0.59 to 2.82) | 1.00 | (0.32 to 3.08) | 1.53 | (1.07 to 2.18) | 1.50 | (0.96 to 2.34) |
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).