TABLE 2.
Pooled Associations Between Lignans Intake and CHD Risk in NHS (1984–2014), NHSII (1991–2017), HPFS (1986–2016)a
| Q1 | Q2 | Q3 | Q4 | Q5 | P for Trendb | |
|---|---|---|---|---|---|---|
| Total lignans | ||||||
| Median (IQR), μg/dc | 167.1 (146.1–182.9) | 215.3 (204.1–227.1) | 254.5 (242.6–267.6) | 302.7 (286.3–320.5) | 405.2 (362.0–491.8) | |
| Total CHD | ||||||
| Case/person-year | 2,344/1,099,137 | 2,128/1,101,960 | 2,002/1,104,119 | 1,977/1,105,423 | 1,793/1,106,586 | |
| Age-adjusted | 1 | 0.85 (0.80–0.90) | 0.79 (0.74–0.84) | 0.75 (0.71–0.80) | 0.65 (0.61–0.69) | <0.001 |
| Multivariable-adjustedd | 1 | 0.94 (0.89–1.00) | 0.93 (0.87–0.99) | 0.93 (0.87–1.00) | 0.85 (0.79–0.92) | <0.001 |
| Nonfatal MI | ||||||
| Case/person-year | 1,398/1,099,145 | 1,316/1,101,965 | 1,231/1,104,121 | 1,252/1,105,427 | 1,086/1,106,594 | |
| Age-adjusted | 1 | 0.89 (0.82–0.96) | 0.81 (0.75–0.88) | 0.80 (0.75–0.87) | 0.67 (0.62–0.72) | <0.001 |
| Multivariable-adjustedd | 1 | 0.96 (0.89–1.04) | 0.94 (0.86–1.02) | 0.98 (0.90–1.07) | 0.88 (0.80–0.97) | 0.07 |
| Fatal CHD | ||||||
| Case/person-year | 946/1,100,426 | 812/1,103,217 | 771/1,105,286 | 725/1,106,584 | 707/1,107,604 | |
| Age-adjusted | 1 | 0.80 (0.72–0.87) | 0.75 (0.68–0.82) | 0.68 (0.61–0.75) | 0.63 (0.57–0.69) | <0.001 |
| Multivariable-adjustedd | 1 | 0.91 (0.83–1.00) | 0.92 (0.83–1.02) | 0.87 (0.78–0.97) | 0.82 (0.73–0.92) | 0.002 |
| Matairesinol | ||||||
| Median (IQR), μg/dc | 4.5 (3.9–5.2) | 6.5 (5.7–7.2) | 8.5 (7.3–9.6) | 11.5 (9.9–13.0) | 18.9 (15.9–24.2) | |
| Total CHD | ||||||
| Case/person-year | 2,387/1,096,970 | 2,114/1,101,975 | 1,999/1,104,802 | 1,903/1,106,655 | 1,841/1,106,820 | |
| Age-adjusted | 1 | 0.86 (0.81–0.91) | 0.78 (0.74–0.83) | 0.70 (0.66–0.74) | 0.61 (0.57–0.64) | <0.001 |
| Multivariable-adjustedd | 1 | 0.93 (0.87–0.99) | 0.89 (0.84–0.94) | 0.83 (0.78–0.89) | 0.76 (0.71–0.82) | <0.001 |
| Nonfatal MI | ||||||
| Case/person-year | 1,419/1,096,978 | 1,259/1,101,981 | 1,273/1,104,807 | 1,214/1,106,660 | 1,118/1,106,826 | |
| Age-adjusted | 1 | 0.86 (0.80–0.93) | 0.85 (0.79–0.91) | 0.77 (0.71–0.83) | 0.66 (0.61–0.72) | <0.001 |
| Multivariable-adjustedd | 1 | 0.89 (0.82–0.96) | 0.90 (0.83–0.97) | 0.85 (0.78–0.92) | 0.77 (0.71–0.84) | <0.001 |
| Fatal CHD | ||||||
| Case/person-year | 968/1,098,295 | 855/1,103,132 | 726/1,105,989 | 689/1,107,811 | 723/1,107,888 | |
| Age-adjusted | 1 | 0.86 (0.78–0.94) | 0.69 (0.63–0.76) | 0.60 (0.54–0.66) | 0.53 (0.48–0.59) | <0.001 |
| Multivariable-adjustedd | 1 | 0.99 (0.90–1.09) | 0.86 (0.78–0.95) | 0.80 (0.72–0.89) | 0.76 (0.68–0.84) | <0.001 |
| Secoisolariciresinol | ||||||
| Median (IQR), μg/dc | 49.9 (42.0–55.7) | 67.9 (63.8–71.7) | 81.1 (77.2–84.9) | 95.6 (90.9–100.5) | 122.9 (111.6–149.8) | |
| Total CHD | ||||||
| Case/person-year | 2,197/1,099,679 | 2,186/1,102,049 | 2,010/1,103,139 | 2,006/1,105,836 | 1,845/1,106,520 | |
| Age-adjusted | 1 | 0.90 (0.85–0.96) | 0.81 (0.76–0.86) | 0.78 (0.74–0.83) | 0.70 (0.66–0.74) | <0.001 |
| Multivariable-adjustedd | 1 | 0.99 (0.93–1.05) | 0.92 (0.86–0.98) | 0.93 (0.87–1.00) | 0.87 (0.81–0.93) | 0.001 |
| Nonfatal MI | ||||||
| Case/person-year | 1,299/1,099,683 | 1,334/1,102,056 | 1,230/1,103,147 | 1,266/1,105,841 | 1,154/1,106,526 | |
| Age-adjusted | 1 | 0.95 (0.88–1.03) | 0.85 (0.79–0.92) | 0.85 (0.79–0.92) | 0.75 (0.69–0.81) | <0.001 |
| Multivariable-adjustedd | 1 | 1.01 (0.94–1.10) | 0.94 (0.87–1.02) | 0.98 (0.90–1.07) | 0.92 (0.84–1.00) | 0.19 |
| Fatal CHD | ||||||
| Case/person-year | 898/1,100,909 | 852/1,103,281 | 780/1,104,294 | 740/1,107,030 | 691/1,107,602 | |
| Age-adjusted | 1 | 0.82 (0.75–0.91) | 0.74 (0.67–0.82) | 0.69 (0.62–0.76) | 0.62 (0.56–0.69) | <0.001 |
| Multivariable-adjustedd | 1 | 0.95 (0.86–1.04) | 0.89 (0.80–0.98) | 0.87 (0.78–0.96) | 0.80 (0.72–0.90) | <0.001 |
| Pinoresinol | ||||||
| Median (IQR), μg/dc | 34.3 (29.3–38.6) | 47.3 (43.9–51.0) | 58.8 (54.9–62.8) | 73.3 (68.5–78.4) | 102.6 (91.6–122.4) | |
| Total CHD | ||||||
| Case/person-year | 2,454/1,097,715 | 2,064/1,102,943 | 1,945/1,104,651 | 1,973/1,105,866 | 1,808/1,106,048 | |
| Age-adjusted | 1 | 0.83 (0.78–0.88) | 0.77 (0.72–0.82) | 0.76 (0.71–0.80) | 0.67 (0.63–0.71) | <0.001 |
| Multivariable-adjustedd | 1 | 0.92 (0.87–0.98) | 0.91 (0.86–0.97) | 0.95 (0.89–1.02) | 0.89 (0.83–0.95) | 0.002 |
| Nonfatal MI | ||||||
| Case/person-year | 1,474/1,097,720 | 1,280/1,102,949 | 1,205/1,104,654 | 1,236/1,105,871 | 1,088/1,106,056 | |
| Age-adjusted | 1 | 0.85 (0.79–0.91) | 0.79 (0.73–0.85) | 0.79 (0.73–0.85) | 0.67 (0.62–0.73) | <0.001 |
| Multivariable-adjustedd | 1 | 0.92 (0.85–0.99) | 0.90 (0.83–0.98) | 0.95 (0.88–1.03) | 0.89 (0.81–0.97) | 0.03 |
| Fatal CHD | ||||||
| Case/person-year | 980/1,099,077 | 784/1,104,155 | 740/1,105,785 | 737/1,107,047 | 720/1,107,053 | |
| Age-adjusted | 1 | 0.80 (0.72–0.87) | 0.74 (0.68–0.82) | 0.71 (0.65–0.79) | 0.66 (0.60–0.73) | 0.0001 |
| Multivariable-adjustedd | 1 | 0.93 (0.85–1.03) | 0.93 (0.84–1.03) | 0.96 (0.86–1.06) | 0.89 (0.80–0.99) | 0.05 |
| Lariciresinol | ||||||
| Median (IQR), μg/dc | 63.7 (55.3–70.0) | 84.1 (79.6–88.9) | 101.9 (97.2–106.9) | 123.9 (117.5–131.2) | 166.7 (150.9–194.0) | |
| Total CHD | ||||||
| Case/person-year | 2,390/1,099,878 | 2,041/1,102,948 | 1,991/1,104,893 | 1,935/1,104,805 | 1,887/1,104,696 | |
| Age-adjusted | 1 | 0.82 (0.78–0.87) | 0.80 (0.75–0.85) | 0.76 (0.71–0.81) | 0.70 (0.66–0.74) | <0.001 |
| Multivariable-adjustedd | 1 | 0.92 (0.86–0.97) | 0.94 (0.88–1.00) | 0.92 (0.86–0.99) | 0.89 (0.83–0.95) | 0.003 |
| Nonfatal MI | ||||||
| Case/person-year | 1,444/1,099,886 | 1,248/1,102,954 | 1,266/1,104,898 | 1,225/1,104,811 | 1,100/1,104,701 | |
| Age-adjusted | 1 | 0.84 (0.77–0.90) | 0.83 (0.77–0.90) | 0.79 (0.73–0.85) | 0.68 (0.63–0.74) | <0.001 |
| Multivariable-adjustedd | 1 | 0.91 (0.84–0.99) | 0.96 (0.89–1.04) | 0.95 (0.88–1.04) | 0.88 (0.80–0.97) | 0.04 |
| Fatal CHD | ||||||
| Case/person-year | 946/1,101,229 | 793/1,104,119 | 725/1,106,115 | 710/1,105,937 | 787/1,105,716 | |
| Age-adjusted | 1 | 0.80 (0.73–0.88) | 0.74 (0.67–0.82) | 0.71 (0.64–0.78) | 0.73 (0.66–0.80) | <0.001 |
| Multivariable-adjustedd | 1 | 0.92 (0.83–1.01) | 0.90 (0.81–0.99) | 0.87 (0.79–0.97) | 0.89 (0.80–1.00) | 0.04 |
Values are hazard ratio (95% confidence interval) unless otherwise indicated.
a
Hazard ratios were meta-analyzed using fixed effect models.
b
Median value in each quintile category was used to calculate P value for trend.
c
Data were combined from 3 cohorts to calculate the median (IQR).
d
Models were age- (months) and calendar-time stratified and adjusted for ethnicity (White, Black, Asian, others), smoking status (never smoked, past smoker, currently smoke 1–14 cigarettes per day, 15–24 cigarettes per day, or $25 cigarettes per day), time-varying body mass index (<21.0, 21.0–22.9, 23.0–24.9, 25.0–26.9, 27.0–29.9, 30.0–32.9, 33.0–34.9, or $35.0 kg/m2), alcohol intake (0, 0.1–4.9, 5.0– 9.9, 10.0–14.9, 15.0–29.9, and $30.0 g/d), multivitamin use (yes, no), physical activity (quintiles), healthy plant-based diet index (quintiles), and family history of myocardial infarction. For women, postmenopausal hormone use (premenopausal, never, former, current, or missing), and oral contraceptive use were further adjusted.
CHD = coronary heart disease; IQR = interquartile range; other abbreviations as in Table 1.