Table 4. Incidence and hazard ratios (HR) for cardiovascular diseases (CVD) and total mortality depending on the MCM6-rs3754686 proxy for milk intake after 4.8 years of median follow-up in the PREDIMED trial.
| CVD incidence (men + women): n = 7,185 | Model 3 | Model 4 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cases | Non-cases | person-y | Incidence rate* | Model 1 | Model 2 | |||||||
| HR | 95% CI | P-value | HR | 95% CI | P-value | P-value | P-value | |||||
| MCM6 genotypes** | ||||||||||||
| TT | 74 | 1908 | 8612 | 8.6 | 1.00 | (reference) | 1.00 | (reference) | ||||
| CT | 136 | 3410 | 15361 | 8.9 | 1.04 | (0.79–1.39) | 0.768 | 1.02 | (0.77–1.36) | 0.890 | 0.941 | 0.945 |
| CC | 57 | 1600 | 7016 | 8.1 | 0.94 | (0.66–1.33) | 0.733 | 0.95 | (0.69–1.35) | 0.764 | 0.981 | 0.815 |
| TT (ref.)*** | 1.00 | (reference) | 1.00 | (reference) | ||||||||
| (CC + TC) vs TT | 1.01 | (0.77–1.33) | 0.932 | 1.00 | (0.76–1.31) | 0.989 | 0.928 | 0.969 | ||||
| Per variant allele (T)**** | 1.03 | (0.87–1.22) | 0.767 | 1.02 | (0.86–1.22) | 0.785 | 0.792 | 0.829 | ||||
| P§-interaction sex*MCM6 polymorphism: 0.005 | ||||||||||||
| Total mortality (men + women): n = 7,185 | ||||||||||||
| Model 1 | Model 2 | Model 3 | Model 4 | |||||||||
| MCM6 genotypes** | ||||||||||||
| TT | 104 | 1878 | 8622 | 12.1 | 1.00 | (reference) | 1.00 | (reference) | ||||
| CT | 139 | 3407 | 15375 | 9.0 | 0.73 | (0.58–0.97) | 0.029 | 0.75 | (0.58–0.97) | 0.028 | 0.028 | 0.030 |
| CC | 79 | 1579 | 7027 | 11.2 | 0.89 | (0.86–1.19) | 0.424 | 0.89 | (0.66–1.21) | 0.464 | 0.455 | 0.549 |
| TT (ref.)*** | 1.00 | (reference) | 1.00 | (reference) | ||||||||
| (CC + CT) vs TT | 0.80 | (0.63–1.01) | 0.057 | 0.79 | (0.62–1.01) | 0.058 | 0.057 | 0.068 | ||||
| Per variant allele (T)**** | 1.08 | (0.92–1.26) | 0.338 | 1.07 | (0.92–1.26) | 0.378 | 0.371 | 0.446 | ||||
| P§§-interaction sex*MCM6 polymorphism: 0.032 | ||||||||||||
*Crude incidence rates were expressed per 1000 person-years of follow-up.
**Codominant model. ***Recessive model.****Additive model.
We used multivariable Cox regression models with length of follow-up as the primary time variable. Separate models were fitted for CVD and total mortality to estimate the corresponding HRs depending on the model.
Model 1: Adjusted for sex, age, field center and dietary intervention group.
Model 2: Model 1 adjusted for variables in model 1 plus BMI, diabetes, drinking, smoking, physical activity, medication (hypertension, dyslipidemia and glucose) and total energy intake at baseline.
Model 3: Model 2 adjusted for variables in model 2 plus total milk intake. Model 4: Model 3 additionally adjusted for total fat and carbohydrates at baseline.
§P-value for interaction sex*MCM6 polymorphism in determining CVD incidence, obtained in Model 2. Further adjustments did not change the statistical significance.
§§P-value for interaction sex*MCM6 polymorphism in determining mortality, obtained in Model 2. Further adjustments did not change the statistical significance.