Table 5.
Mediation of the HDP-CVD relationship by chronic hypertension, hypercholesterolemia, type 2 diabetes, and BMI changes
| Hypertensive Disorder in First Pregnancy Status | ||||
|---|---|---|---|---|
| Normotensive Pregnancy n=52,668 (90.9%) | Gestational Hypertension n=1,675 (2.9%) | Preeclampsia n=3,631 (6.3%) | Hypertensive Disorders of Pregnancy n=5,306 (9.2%) | |
|
|
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| Cases/Person-Years | 752/1,676,801 | 37/50,326 | 95/112,328 | 132/162,654 |
|
| ||||
| Without Mediators (Total Effect) | 1.00 (ref) | 1.52 (1.09, 2.12) | 1.73 (1.24, 2.42) | 1.67 (1.38, 2.01) |
| With Mediators (Direct Effect)* | 1.00 (ref) | 1.07 (0.77, 1.49) | 1.26 (0.90, 1.77) | 1.20 (1.00, 1.45) |
| Proportion mediated (95% CI) † | Ref | 83.8% (3.6, 99.9) | 57.3% (24.2, 84.9) | 63.8% (38.6, 83.2) |
| Individually mediated by: | ||||
| Chronic hypertension | Ref | 80.7% (6.1, 99.6) | 48.0% (21.9, 75.3) | 56.2% (35.2, 75.1) |
| Hypercholesterolemia | Ref | 19.2% (8.0, 39.2) | 15.3% (8.0, 27.4) | 16.2% (10.9, 23.4) |
| Type 2 diabetes mellitus | Ref | 13.1% (5.3, 29.0) | 9.1% (4.4, 18.0) | 10.1% (6.3, 15.7) |
| Changes in BMI | Ref | 30.4% (12.1, 58.1) | 23.0% (11.8, 40.2) | 24.8% (16.3, 35.8) |
BMI: body mass index; CVD: cardiovascular disease; HDP: hypertensive disorders of pregnancy. This mediation analysis was restricted to 57,974 parous women, after excluding women who had hypercholesterolemia (n=1,654) or type 2 diabetes mellitus (n=11) before first pregnancy, were missing date of hypercholesterolemia diagnosis (n=239), or missing body mass index (BMI; n=501). Hazard ratios and corresponding 95% confidence intervals are provided for the total and direct effects. Models are adjusted for age at first birth (years), age at NHSII enrollment (years), race/ethnicity (Black, Hispanic/Latina, Asian, White [ref], other/multi-race), parental education (<9, 9–11, 12, 13–15, ≥16 years [ref]), and the following pre-pregnancy variables updated over follow-up: physical activity (never, 1–3 (ref), 4–6, 7–9, 10–12 mo/yr), smoking (never (ref), past, current), BMI (<18.5, 18.5–24.9 (ref), 25–29.9, ≥30 kg/m2), alcohol consumption (none (ref), ≤1 drink/week, 2–6 drink/week, ≥1 drinks/day), Alternative Healthy Eating Index (AHEI) score (quintiles with the fifth quintile (ref) representing the healthiest diet category), oral contraceptive use (never (ref), <2, 2–<4, ≥4 years), hypercholesterolemia (no [ref], yes), and parental history of coronary artery disease (CAD) and/or stroke before age 60 (CAD only for CAD model, stroke only for stroke model, CAD or stroke for CVD models; no [ref], yes)
Direct effect obtained from a model including chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus, and body mass index
Proportion of the association jointly mediated by the development of chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus, and changes in body mass index after first pregnancy; p <0.0001 for all proportion mediated statistics. Additional inclusion of breastfeeding in these models did not increase the proportion mediated (data not shown).
Note: individual proportion mediated statistics may not sum to the joint proportion mediated statistic and may exceed 100% due to shared pathways, as an individual may develop multiple CVD risk factors between the HDP and CVD event and the presence of one risk factor may affect another.