Risk of Cardiovascular Disease Among Postmenopausal Women with Prior Pregnancy Loss: The Women’s Health Initiative

Donna R. Parker; Bing Lu; Megan Sands-Lincoln; Candyce H. Kroenke; Cathy C. Lee; Mary O’Sullivan; Hannah L. Park; Nisha Parikh; Robert S. Schenken; Charles B. Eaton

doi:10.1370/afm.1668

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Figure 1
Women’s Health Initiative (WHI) participants included in the current study

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Table 1

Baseline Characteristics of Observational Study Women from the Women’s Health Initiative

Characteristic	Women With History of Miscarriage (n=23,538)	Women With History of Stillbirth (n=1,670)	Women With History of Miscarriage and Stillbirth (n=1,673)	Women With No History of Stillbirth or Miscarriage (n=50,820)
Sociodemographic, %^a
Age, y
<60	30.5	27.3	28.2	33.9
60–70	45.8	46.2	46.1	43.8
70+	23.8	26.5	25.7	22.4
Race/ethnicity
African American	9.0	14.8	15.4	7.2
Hispanic/Latino	3.9	7.9	9.2	3.6
White	82.6	71.3	70.8	84.4
Other	4.4	5.9	4.5	4.9
Smoking status
Current	7.0	7.3	8.0	5.8
Former	43.8	40.4	42.6	42.3
Never	49.2	52.3	49.5	51.9
Marital status, married	64.9	61.0	59.1	65.8
Educational level
≤High school	21.1	27.6	26.8	21.7
≥College	69.2	60.5	62.4	68.6
Other	9.7	11.9	10.9	9.7
Income
<$20,000	16.4	22.1	24,7	14.3
$20,000–$74,999	63.3	62.4	60.3	63.7
≥$75,000	20.4	15.6	15.1	22.1
Physiologic, mean (SD)^a
Body mass index, kg/m²	27.4 (5.9)	28.2 (6.0)	28.6 (6.6)	27.0 (5.7)
Waist-to-hip ratio	0.81 (0.08)	0.81 (0.08)	0.82 (0.09)	0.80 (0.08)
Systolic blood pressure, mm Hg	127.0 (17.9)	129.3 (18.6)	129.5 (17.9)	126.4 (17.8)
Diastolic blood pressure, mm Hg	74.9 (9.3)	75.6 (9.6)	75.9 (9.5)	74.9 (9.3)
White blood cell count, No./μL	6,200 (12,300)	6,000 (2,800)	6,200 (9,900)	6,100 (12,100)
Behavioral^a
Dietary total fat Intake, mean g (SD)	54.3 (34.3)	55.1 (42.8)	57.9 (44.3)	53.1 (32.7)
Physical activity, mean MET h/wk (SD)	13.8 (14.5)	12.6 (13.8)	12.9 (4.6)	14.1 (14.5)
Alcohol consumption, %
None	9.9	15.6	15.3	11.5
<1/wk	31.8	30.2	31.1	32.1
1–7/wk	26.6	22.5	21.8	26.2
>7/wk	12.6	8.9	9.8	12.8
Past drinker	19.2	22.9	21.9	17.4
Medical history, %^a
Familial congestive heart disease	41.6	38.4	39.0	40.7
Early hypertension^b	3.0	4.4	5.1	2.7
Hypertension^c	24.3	28.9	28.9	22.7
Diabetes	3.0	4.9	5.9	2.5
Hyperlipidemia	7.3	8.8	8.8	7.6
Reproductive history
Gravidity, %
1	2.5	3.7	0.4	11.2
2–4	74.3	59.3	66.1	76.1
≥5	23.2	37.1	33.5	12.7
Parity, %
1	8.9	11.5	11.3	11.2
2–4	68.7	67.6	63.1	75.1
≥5	17.6	16.9	21.5	11.2
Drug use at baseline, %^a
Aspirin	21.1	19.9	18.8	20.5
Antihypertensive medications	28.8	32.9	34.1	26.7
Lipid-lowering medications	7.8	9.3	9.4	8.0
Diabetic medication	3.2	5.1	6.0	2.6
Antidepressants	7.4	6.5	7.2	7.2
β-Blockers	6.9	7.5	7.5	6.7
Diuretics	13.8	14.6	16.4	12.3
ACE inhibitors/ARBs	10.3	13.7	12.7	9.9
Calcium channel blockers	8.4	10.5	10.9	7.7
Psychosocial history of depression,^d %	10.6	9.8	11.9	9.4

ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; MET = metabolic equivalent task.
↵a Values may vary slightly because of missing data.
↵b Reported before age 40 years.
↵c Reported age ≥40 years.
↵d Burnam screening algorithm, a short version of the Center for Epidemiologic Studies Depression Scale (CES-D).

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Table 2

Unadjusted, Age-Adjusted, and Multivariable-Adjusted Odds Ratios of the Association Between Pregnancy Loss and Risk of Total Coronary Heart Disease

Pregnancy Loss	Events No.	Unadjusted OR (95% CI)	Age Adjusted OR (95% CI)	Multivariable Adjusted^a OR (95% CI)
Miscarriage
0	1,868	1.00	1.00	1.00
1	746	1.26 (1.15–1.37)	1.23 (1.13–1.35)	1.19 (1.08–1.32)
≥2	408	1.37 (1.23–1.53)	1.31 (1.17–1.46)	1.18 (1.04–1.34)
Stillbirth
0	2,809	1.00	1.00	1.00
≥1	179	1.43 (1.22–1.43)	1.36 (1.16–1.59)	1.27 (1.07–1.51)

OR = odds ratio; ACE = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker.
↵a Adjusted for: age, race, education, income, smoking status, marital status, gravidity, family history of myocardial infarction, hypertension, history of diabetes, history of lipid disorder, body mass index, waist-to-hip ratio, aspirin use, diuretic use, ACE inhibitor/ARB use, calcium channel blocker use, alcohol use, depression, physical activity, and white blood cell count.

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Table 3

Unadjusted, Age-Adjusted, and Multivariable-Adjusted Odds Ratios of the Association Between Pregnancy Loss and Risk of Ischemic Stroke

Pregnancy Loss	Events No.	Unadjusted OR (95% CI)	Age Adjusted OR (95% CI)	Multivariable Adjusted^a OR (95% CI)
Miscarriage
0	964	1.00	1.00	1.00
1	347	1.12 (0.99–1.27)	1.09 (0.97–1.24)	1.05 (0.91–1.19)
≥2	188	1.21 (1.04–1.42)	1.14 (0.97–1.33)	0.93 (0.77–1.13)
Stillbirth
0	1,406	1.00	1.00	1.00
≥1	97	1.38 (1.10–1.71)	1.29 (1.03–1.60)	1.13 (0.89–1.43)

OR=odds ratio; ACE=angiotensin-converting enzyme; ARB=angiotensin receptor blocker.
↵a Adjusted for age, race, education, income, smoking status, marital status, gravidity, family history of myocardial infarction, hypertension, history of diabetes, history of lipid disorder, body mass index, waist-to-hip ratio, aspirin use, diuretic use, ACE inhibitor/ARB use, calcium channel blocker use, alcohol use, depression, physical activity, and white blood cell count.

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In Brief

Risk of Cardiovascular Disease Among Postmenopausal Women with Prior Pregnancy Loss: The Women's Health Initiative

Donna R. Parker , and colleagues

Background Growing evidence suggests that metabolic, hormonal and hemostatic changes associated with pregnancy loss may contribute to the development of coronary heart disease. This study, in a diverse, geographically dispersed cohort of women, examines the association of miscarriages and stillbirths with cardiovascular conditions.

What This Study Found Women with a history of pregnancy loss appear to be at increased risk of future coronary heart disease but not ischemic stroke. The association between pregnancy loss and heart disease appears to be independent of hypertension, body mass index, waist-to-hip ratio, and white blood cell count. The risk appears greater among women with a history of stillbirths than among women with a history of miscarriage.

Implications

Women with a history of miscarriage or a single stillbirth may be considered candidates for closer surveillance and/or early intervention by their primary care physicians so that risk factors can be carefully monitored and controlled.