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Blood Pressure Patterns and Subsequent Coronary Artery Calcification in Women Who Delivered Preterm Births

Originally publishedhttps://doi.org/10.1161/HYPERTENSIONAHA.117.10693Hypertension. 2018;72:159–166

Abstract

Women who delivered preterm infants have excess cardiovascular disease, but vascular pathways linking these conditions are not understood. We considered that higher blood pressure over 25 years among women with preterm delivery may be associated with coronary artery calcification (CAC). The CARDIA study (Coronary Artery Risk Development in Young Adults) enrolled 1049 black and white women with births between 1985 and 2010 (n=272 ever preterm [<37 weeks]; n=777 all term births [≥37 weeks]). Latent mixture modeling identified blood pressure trajectories across 20 years, and these were related to CAC at years 20 and 25. Three systolic blood pressure (SBP) patterns were identified: low stable (n=563; 53%), moderate (n=416; 40%), and moderate increasing (n=70; 7%). Women with moderate-increasing SBP were more likely to have delivered preterm compared with those in the low-stable group (40% versus 21%; P<0.0001), and they were more likely to have CAC (38.5% versus 12.2%). The SBP and CAC association varied by preterm birth (P interaction=0.04). Women with preterm delivery and a moderate-increasing SBP had a 2.17-fold higher hazards of CAC (95% confidence interval, 1.14–4.12) compared with women with term births and a lower SBP pattern, adjusted for cardiovascular disease risk factors and other pregnancy features. There was no excess CAC in women with moderate-increasing SBP and term births (adjusted hazard ratio, 1.02; 95% confidence interval, 0.49–2.14). Associations were stronger in women with hypertensive disorders of pregnancy but also detected in those with normotensive preterm deliveries. Women who deliver preterm infants are more likely to follow a high-risk blood pressure pattern throughout the childbearing years that is associated with CAC at midlife.

Introduction

Maternal history of preterm delivery (PTD) identifies excess cardiovascular morbidity and mortality for women,14 but mechanisms linking preterm birth to the emergence of cardiovascular disease (CVD) are not well understood. Compared with women with term births, those with PTD have modestly higher blood pressure (BP) before, during, and after pregnancy,59 but the long-term associations of these differences with future CVD risk are unknown.

Nonpregnant longitudinal BP measurements in men and women over 25 years reveal that increasing BP patterns are associated with coronary artery calcification (CAC) in middle age.10 Similarly, the accumulation of exposure to modest elevation in BP across adulthood (eg, systolic >115 or 120 mm Hg) is linked to excess cardiovascular risk.11,12 Indeed, the newest guidelines classify stage 1 hypertension as BP ≥130/80 mm Hg, although treatment is not recommended at this lower threshold unless 10-year predicted CVD risk is ≥10%.13 Women have lower BP than men across adulthood.14 They are, therefore, overrepresented in low-risk BP trajectories. Herein, we focus on women across the childbearing years and consider that adverse pregnancy outcomes, such as preterm birth history could help identify women with BP patterns representing an excess risk for CVD.

CARDIA (Coronary Artery Risk Development in Young Adults) is one of the few longitudinal cohorts in which BP was measured before and after pregnancy, and we have reported that women with PTD had a modestly higher BP compared with women with term births before pregnancy (2 mm Hg) and after 20 years of follow-up (4 mm Hg). Indeed, differences in BP increased more dramatically over time compared with women with term births, even among those with normotensive preterm births.6 How the vascular burden of modest BP increments might accumulate across the life course among women who deliver preterm pregnancies is unknown. To examine this, we first characterized BP patterns across 20 years from young adulthood to midlife in women with at least 1 birth and hypothesized that women with preterm when compared with term births would be more likely to follow a high-risk BP pattern. We then considered whether these BP patterns were related to CAC at midlife and whether these associations were similar in women with preterm when compared with full-term births.

Methods

Study materials, data, and samples from CARDIA are available at https://www.cardia.dopm.uab.edu/ and through the National Heart, Lung, and Blood Institute BioLINCC (Biologic Specimen and Data Repositories Information Coordinating Center) program at https://biolincc.nhlbi.nih.gov/home/.

CARDIA is a US multi-center, longitudinal, observational study designed to describe the development of risk factors for coronary heart disease in young black and white men and women.15,16 Participants were recruited from 4 US areas: Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. From 1985 to 1986, 5115 subjects (2787 women; 52% black) aged 18 to 30 years were enrolled and provided written informed consent. Retention rates were 92%, 86%, 81%, 79%, 74%, 72%, and 72% of the surviving cohort at years 2, 5, 7, 10, 15, 20, and 25 after baseline.

Of the 2787 women enrolled in CARDIA, we excluded women with hysterectomy at baseline (n=25), those who did not deliver live births between baseline and year 25 of follow-up (n=1377), and those with <4 visits with BP measurements (n=69; Figure S1 in the online-only Data Supplement). Women with twin births or births with no reported gestational age were also excluded (n=81). Of those remaining (n=1232), we further limited our analysis to women with coronary calcium assessed at year 20 or 25. Eligible women with CAC measurements (n=1049) compared with those with no CAC measures (n=183) were about a year older at baseline, were less likely to be of black race, and had higher levels of education and modestly lower triglycerides measured at baseline (Table S1).

Pregnancies and Preterm Birth Status

All births that occurred after enrollment (baseline) in CARDIA are included in this analysis. These were assessed at exams that occurred every 2 to 5 years, and for each postbaseline birth, women reported the gestational age at delivery (weeks) and birth weight. Preterm births were those delivered <37 completed weeks. A validation study compared maternal report of gestational age to medical record abstractions (n=211). Maternal report of ever delivering preterm (<37 weeks) was good (sensitivity was 84% [16/19]; specificity was 89% [170/192]).6 Women were categorized into 2 exposure groups: those who ever experienced a PTD and those with all term births.

Women also reported if each birth was complicated by gestational diabetes mellitus or hypertensive disorders of pregnancy. Self-report of gestational diabetes mellitus history was excellent (100% sensitivity and 92% specificity).17 Self-reported hypertensive disorders of pregnancy were overreported (positive predictive value was 42%), but the negative predictive value of self-report of no preeclampsia or gestational hypertension was 90%.18 Thus, although our study cannot definitively identify women with hypertensive disorders of pregnancy, we can be assured that the group reporting normotensive births were likely to have been normotensive during pregnancy. Parity status (number of births) before baseline was assessed at enrollment.

Coronary Artery Calcium

Calcified coronary artery plaque was measured at year 20 or 25 using computed tomography of the chest.19 In brief, at year 20, an electron-beam computed tomography scanner (at Chicago and Oakland centers) and a multidetector computed tomography scanner (at Birmingham and Minneapolis centers) were used to obtain contiguous 2.5- to 3-mm-thick transverse images from the root of the aorta to the apex of the heart. At year 25, all centers used the multidetector computed tomography scanner. The accuracy, comparability, and reproducibility of CAC measurement is excellent.19,20 Scans were obtained, and image analysts blinded to participant characteristics calculated a total coronary artery calcium score using a modified Agatston method21 with select over-reading by a physician expert in cardiovascular imaging. The presence of CAC was defined as a total calcification score >0 Agatston units measured at year 20 or 25 given the low prevalence of advanced calcification among women. Results were replicated when CAC was defined as ≥10 Agatston units.

Blood Pressure

BP was measured at baseline and each follow-up examination by standardized research methods.15,16 Three resting seated measurements were obtained with a random-zero sphygmomanometer through year 15 and with the Omron (Omron Corp, Schaumburg, IL) HEM907XL oscillometer at years 20 and 25; the mean of the second and third readings was used for this report. Omron results were calibrated to be consistent with the random-zero results.18 Systolic BP (SBP) and diastolic BP (DBP) were analyzed separately for trajectory analyses. Mid-BP (MBP; average of SBP and DBP) was also evaluated given the evidence that it may better predict CVD events than other composite measures such as pulse pressure or mean arterial pressure.22,23 Antihypertension medication or statin use was reported at each visit.

Other Variables

Fasting blood samples were sent to the Northwest Lipid Research Laboratories (Seattle, WA) for lipid determination within 6 weeks of collection.24 LDL (low-density lipoprotein) cholesterol was calculated using the Friedewald equation when triglycerides were <400 mg/dL.25 Height and weight were measured during each examination and used to calculate body mass index (kg/m2). Waist circumference was measured as the abdominal girth midway between the iliac crest and the bottom of the ribcage. Demographic characteristics (age, sex, and race) were obtained at baseline; educational achievement was self-reported on standardized questionnaires as was smoking status (nonsmoker, ex-smoker, and current smoker).

Statistical Analysis

BP trajectories were modeled for women with ≥1 births and at least 4 BP measurements from baseline through follow-up. Latent class models identified subgroups of women with a similar underlying trajectory in BP using SAS Proc Traj (details provided in online-only Data Supplement).26

To maximize the sample size and avoid bias that may be introduced by requiring attendance at the year 25 visit, we first constructed BP trajectories through year 20 and related these to CAC detected at year 20 or year 25. This approach also allowed early presence of CAC to be considered which was relevant to our hypothesis, as 73% of women had CAC measured at both time points. We used a variation of the Cox proportional hazards model that accounts for interval-measured data to estimate the relative hazards of CAC presence according to BP latent class.27 Multivariable models adjusted for demographic characteristics (race, education, and age), lifestyle features (time-varying body mass index and smoking), medication use (antihypertensives and statins), and other pregnancy features (gestational diabetes mellitus and hypertensive disorders of pregnancy). Models were also adjusted for the posterior probability of being included in a trajectory to account for the variability in-class assignment. Additional adjustment for parity, lipids, or baseline BP did not change any estimates by >10%, and thus, these were not included. We tested for a differential association between BP trajectories and CAC according to preterm birth history using a multiplicative interaction term (P<0.10) and also tested for relative excess risk due to interaction on the additive scale as this may be more biologically plausible and of greater public health relevance (relative excess risk due to interaction >1).28 Given the evidence of effect modification on both scales, exposure groups that combined BP patterns and preterm birth history were evaluated. Women with term births and a low-stable or moderate BP pattern were the referent as the prevalence of CAC was similar in these groups (12.2% and 16.1%, respectively). We then modeled trajectories through year 25 to account for steeper increases in BP that may occur after year 20 and related these patterns to CAC presence at year 25 using logistic regression. Covariate adjustment was as above. Sensitivity analyses were conducted defining CAC as Agatston units ≥10. We also stratified results by race, by hypertensive status (ever/never; defined as BP ≥140/90 mm Hg or taking antihypertensive medication), and by self-reported hypertensive disorders of pregnancy (ever/never) to ensure that associations were similar in subgroups.

Results

Across 25 years of follow-up, 272 women experienced preterm birth and 777 reported all term births. Women with PTD history compared with those with all term births were more likely to be of black race, less likely to have attended college, and had modestly higher SBP at baseline which was before the births included in this analysis (Table 1). By year 25, women with preterm deliveries had higher SBP, DBP, and MBP; were more likely to report having experienced hypertension in pregnancy; and to be using antihypertensive medications.

Table 1. Characteristics of Women at Baseline and During Follow-Up According to Preterm Birth Status*

Maternal CharacteristicsBaselineYear 25
TermPretermP ValueTermPretermP Value
(N=777)(N=272)(N=777)(N=272)
Black, %40.566.9<0.0001
Nulliparous (no prior births), %71.465.80.082
Parity0.4±0.80.5±0.90.0421.7±0.82.0±1.10.0001
Education, %<0.00010.004
 High school or equivalent29.444.916.627.2
 College education58.850.754.256.3
 Graduate or professional degree11.84.429.216.5
Age, y24.3±3.723.6±3.60.00749.4±3.748.8±3.60.017
Current smoking, %22.328.40.06512.119.90.009
Body mass index, kg/m223.5±4.824.0±5.00.09529.4±7.431.4±7.70.0003
Waist circumference, cm72.2±9.872.6±10.30.59988.9±15.991.7±15.60.018
Systolic blood pressure, mm Hg105.2±9.2106.5±8.70.038115.2±15.0120.5±17.9<0.0001
Diastolic blood pressure, mm Hg65.9±8.965.7±9.00.72672.6±11.576.0±11.9<0.0001
Mid-blood pressure, mm Hg85.6±8.086.1±7.60.32093.9±13.498.3±14.4<0.0001
Total cholesterol, mg/dL177.1±31.5177.3±34.20.924193.3±34.1193.9±39.60.834
LDL cholesterol, mg/dL108.4±29.3107.7±31.10.745109.8±29.8112.8±34.60.220
HDL cholesterol, mg/dL55.6±12.457.5±13.30.03763.6±18.661.9±18.80.200
Triglycerides, mg/dL, median (IQR)58 (33)56 (31)0.03484 (57)80.5 (53)0.350
Fasting glucose, mg/dL79.6±8.379.9±8.60.56794.8±22.595.8±25.20.556
During follow-up
 GDM (ever), %11.511.80.890
 Hypertension during pregnancy (ever), %12.219.10.005
 Antihypertensive medication use, %20.328.60.007
 Statin use, %11.311.20.994

GDM indicates gestational diabetes mellitus; HDL, high-density lipoprotein; IQR, interquartile range; and LDL, low-density lipoprotein.

*Mean±SD unless otherwise noted.

Three trajectories in SBP, DBP, and MBP were identified (Figure 1): 53% of women maintained low SBP across follow-up (low stable, n=563), 40% maintained moderate SBP (moderate, n=416), and 7% started with moderate SBP that increased rapidly after ≈10 years of follow-up (moderate increasing, n=70). Trends were similar for DBP and MBP but most pronounced for SBP.

Figure 1.

Figure 1. Blood pressure trajectories. Systolic blood pressure trajectory (A) across 20 years in women with at least 1 birth in CARDIA study (Coronary Artery Risk Development in Young Adults): low stable (n=563), moderate (n=416), and moderate increasing (n=70). Diastolic blood pressure trajectory (B): low stable (n=425), moderate (n=513), and moderate increasing (n=111). Midblood pressure trajectory: low stable (n=418), moderate (n=500), and moderate increasing (n=131).

Women in the moderate-increasing SBP group were more likely to be of black race and to have a higher body mass index and waist circumference at baseline and after 25 years of follow-up. They also were more likely to experience preterm birth and pregnancies complicated by hypertension compared with the low-stable SBP group (Table 2). After accounting for race, age, education, smoking, body mass index, and total cholesterol, women with PTD tended to be more likely to be in the moderate-increasing SBP group (odds ratio, 1.46; 95% confidence interval [CI], 0.85–2.49). As expected, women in the moderate-increasing SBP group were also more likely to have CAC at year 20 or 25; 38.6% of women in the moderate-increasing SBP trajectory had CAC compared with 13.5% of women in the low SBP trajectory (P<0.0001).

Table 2. Characteristics of CARDIA Women According to Systolic Blood Pressure Trajectory Groups at Year 20

Maternal CharacteristicsLowModerateElevatedP Value
(N=563)(N=416)(N=70)
Baseline
 Age at enrollment, y24.3±3.723.7±3.725.1±3.30.004
 Black, %31.663.280<0.0001
 Parous, %25.632.750<0.0001
Education, %<0.0001
 High school or equivalent28.137.750.0
 College59.355.344.3
 Graduate or professional12.67.05.7
Blood pressure and other cardiovascular risk factors
 Never smoking, %
  Baseline62.56553.60.0002
  Year 2566.765.358.80.0075
 Body mass index, kg/m2
  Baseline22.4±3.624.7±5.526.8±6.5<0.0001
  Year 2528.0±6.532.0±7.833.4±8.8<0.0001
 Waist circumference, cm
  Baseline70.0±7.574.2±10.879.4±15.0<0.0001
  Year 2585.2±13.694.4±16.597.9±17.4<0.0001
 Systolic blood pressure, mm Hg
  Baseline101.0±7.1109.6±7.6117.7±9.5<0.0001
  Year 25109.3±12.6123.0±15.3137.6±21.4<0.0001
 Diastolic blood pressure, mm Hg
  Baseline63.4±7.968.2±8.772.3±11.2<0.0001
  Year 2568.7±9.878.1±10.585.4±13.5<0.0001
 Mid-blood pressure, mm Hg
  Baseline82.2±6.588.9±6.995.0±9.2<0.0001
  Year 2589.0±10.7100.5±12.3111.5±16.5<0.0001
 Total cholesterol, mg/dL
  Baseline175.6±31.1178.7±31.9180.4±41.90.200
  Year 25195.4±34.6190.8±35.6193.4±42.60.147
During follow-up
 Preterm birth (<37 wk), %21.030.340.0<0.0001
 GDM ever, %11.211.812.90.900
 Hypertension during any pregnancy, %6.020.042.9<0.0001
 Antihypertensive medication use, %4.536.680.9<0.0001
 Statin use, %6.116.223.9<0.0001
 CAC presence at year 25, %13.519.238.6<0.0001

P value derived from ANOVA or χ2; results are mean±SD unless noted. CAC indicates coronary artery calcification; CARDIA, Coronary Artery Risk Development in Young Adults; and GDM, gestational diabetes mellitus.

Among women with moderate-increasing SBP, those with preterm deliveries were more likely to have CAC than women with term births (P for multiplicative interaction=0.04; relative excess risk due to interaction=1.30 for additive interaction; Figure 2). Women in the moderate-increasing SBP trajectory and a history of preterm birth had 2.17-fold higher hazards of CAC (95% CI, 1.14–4.12; P=0.018; Table 3) by year 25 compared with women with term births and low-stable or moderate SBP after accounting for covariates. In contrast, excess risk of CAC in women with a moderate-increasing SBP pattern and all term births was not detected (adjusted hazard ratio [HR], 1.02; 95% CI, 0.49–2.14; P=0.952). When restricted to those in the higher BP trajectory, women with PTD tended to have higher risk of CAC than women with full-term births, although this estimate was not statistically significant (HR, 2.12; 95% CI, 0.88–5.09; P=0.094; Table S2). Risk of CAC also tended to be higher when related to MBP trajectories and preterm birth history (adjusted HR for moderate-increasing MBP and preterm birth, 1.85; 95% CI, 0.97–3.51; P=0.061) but was not higher for DBP trajectories.

Table 3. Blood Pressure Trajectories Through Year 20 and Preterm Birth History, Related to Hazards of Coronary Artery Calcification at Year 20 or 25 (n=1049)

GroupCAC, N, %HR95% CIP Value
Term birth, low-stable or moderate SBP trajectory117 (15.9)Ref
Preterm birth, low-stable or moderate SBP trajectory39 (16.0)0.750.47–1.180.215
Term birth, moderate-increasing SBP trajectory14 (33.3)1.020.49–2.140.952
Preterm birth, moderate-increasing SBP trajectory13 (46.4)2.171.14–4.120.018
Term birth, low-stable or moderate DBP trajectory111 (15.9)Ref
Preterm birth, low-stable or moderate DBP trajectory43 (18.0)0.880.57–1.350.556
Term birth, moderate-increasing DBP trajectory20 (25.0)0.900.50–1.640.733
Preterm birth, moderate-increasing DBP trajectory9 (29.0)1.210.52–2.780.658
Term birth, low-stable or moderate MBP trajectory103 (14.8)Ref
Preterm birth, low-stable or moderate MBP trajectory37 (16.5)0.840.53–1.330.448
Term birth, moderate-increasing MBP trajectory28 (33.7)1.360.80–2.330.259
Preterm birth, moderate-increasing MBP trajectory15 (31.3)1.850.97–3.510.061

Adjusted for age at baseline, race, education, years smoking, statins, hypertensive medication use, posterior probability of SBP group assignment and time-varying BMI, gestational hypertension, and GDM. BMI indicates body mass index; CAC, coronary artery calcification; CI, confidence interval; DBP, diastolic blood pressure; GDM, gestational diabetes mellitus; HR, hazard ratio; MBP, midblood pressure; and SBP, systolic blood pressure.

Figure 2.

Figure 2. Proportion of women with coronary artery calcification (CAC) at year 25 according to systolic, diastolic, and midblood pressure (mid-BP) trajectories (low-stable trajectory, moderate trajectory, moderate increasing trajectory) and stratified by term and preterm birth status.

Results were amplified when the risk of CAC at year 25 was estimated according to BP trajectories through year 25 (Table S3). Those in the moderate-increasing SBP trajectory had significantly increased the risk of CAC, and this was strongest in women with history of preterm birth (adjusted odds ratio, 4.40; 95% CI, 1.80–10.75; P≤0001). The associations were more modest in participants with only term births. The associations of SBP trajectories and PTD persisted when the presence of CAC was defined as ≥10 Agatston units but were diminished for DBP and MBP (Table S4). Results were of similar magnitude but less precise in white and black women (Table S5). Results were also similarly significant, after removing women who were hypertensive at baseline (n=20).

We, then, stratified according to hypertension (ever versus never) rather than BP trajectories. Women with hypertension and a history of preterm birth had higher risk of CAC compared with those with no hypertension (HR, 2.76; 95% CI, 1.29–5.90), adjusted for covariates. Women with hypertension and term births also had excess CAC, but this risk was more modest compared with estimates in women with preterm deliveries (HR, 1.62; 95% CI, 0.96–2.71; Pinteraction=0.08).

We further considered that preterm deliveries complicated by hypertensive disorders of pregnancy may be influencing our results. Those who reported a history of hypertensive disorders of pregnancy and an increasing SBP trajectory had excess CAC risk regardless of PTD (HR, 3.40; 95% CI, 1.18–9.74 for term births; HR, 3.59; 95% CI, 1.31–9.79 for preterm births; Table S6). Women with normotensive preterm births and increasing SBP also had excess CAC risk (HR, 2.45; 95% CI, 0.97–6.23). In contrast, those with an increasing SBP trajectory but all normotensive term births had no excess CAC.

Discussion

Our results indicate that women with preterm deliveries combined with an increasing BP trajectory had a particularly strong risk of CAC that was independent of other traditional CVD risk factors and pregnancy complications. In contrast, CAC risk tended to be smaller among women with term births and an increasing BP trajectory. Of note, women with preterm deliveries were also more likely to follow an increasing BP pattern compared with women with term births. Our results highlight the importance of race in these associations. Black women were much more likely to have preterm deliveries, to follow an increasing BP pattern, and to have CAC. The average age of women at the end of follow-up was <50, and thus, most women were at overall low risk for CVD. Preterm birth may identify women with high risk of increasing BP and progression to atherosclerosis early in the life course.

Early detection of hypertension or modest elevations in BP is crucial, as treatment is widely available, inexpensive, and cardioprotective. Yet, up to 38% of hypertension goes undetected before age 40.29 Importantly, hypertension contributes to more CVD events in women relative to men.30 There is also evidence that the accumulation of modest BP elevation over young adulthood is linked to atherosclerosis, left ventricular mass, and vascular mortality.11,12 Our data suggest that at an average age of 24 at baseline, women with modestly higher BP go on to follow an elevated trajectory and thus modest BP elevations in young adulthood may warrant closer clinical attention. Our results indicate that preterm birth history may identify a subgroup of women susceptible to increasing BP and higher risk for development of atherosclerosis. It is unknown if preventing the preterm birth may also prevent maternal progression to CAC, but our results amplify the importance of preterm birth for maternal long-term health. Recent evidence indicates that presence of any CAC, including those with low scores as we include here, is linked to coronary heart disease events and death.31,32 Indeed, some have called for the inclusion of CAC screening to stratify women and men for treatment.33 Our results raise important questions about how pregnancy history may help inform CVD screening and treatment guidelines for women.

There are few studies of the vascular pathways linking PTD to CVD. Our results are aligned with evidence from the Nurses’ Health Study that women with preterm deliveries have excess CVD risk, not explained by obesity, lifestyle, or sociodemographic risk factors.34 Our findings raise the possibility that there may be novel endothelial factors leading to increasing BP and CAC in women with preterm deliveries. Alternatively, it is possible that the modest elevations in BP detected even before preterm births may be related to occult inflammation or oxidative stress35 that instigate vascular remodeling, culminating in arterial plaque formation by age 50. Recent work has identified maternal genes related to BP control, carotid intima-medial thickness, and metabolic risk that are also related to PTD.36 In addition, familial aggregation of PTD may have developmental origins, such that women who themselves were born small or preterm may have excess risk of PTD, as well as hypertension, and CVD.37,38 We did not collect information about a mother’s own birth history, but future work should explore these associations.

Our results must be considered in the context of study limitations. CARDIA is a large, biracial cohort, and yet the number of women with CAC is still small. Longer follow-up is needed to accrue more events and to understand if PTD history discerns risk across the aging continuum. It is possible that reproductive features can best identify risk among premenopausal women.7 CAC was not measured at baseline, and thus, we were unable to determine if women in the highest BP trajectory group or those with preterm birth may have had prior CAC. We also relied on self-report of pregnancy complications. Although our validation study demonstrated good recall of preterm birth, studies with medical record data are needed to determine if subtypes of preterm birth such as spontaneous preterm birth or clinically indicated early delivery may be driving the risk estimates we detected. Although this may hamper the etiologic interpretation of our findings, our results suggest that reliably recalled pregnancy features such as PTD can mark excess CVD risk in women. Maternal recall of hypertensive disorders of pregnancy in our study, similar to others, was poor. The high negative predictive value of maternal recall of this complication, however, does reassure us that our findings in women having reported normotensive preterm deliveries are robust. In addition, future studies are needed to understand the timing of BP changes relative to each birth. Self-reported preterm deliveries before the baseline visit were missing for many women, and, therefore, we were unable to consider these in our analysis. Most women in CARDIA were nulliparous at baseline (70%), and thus, this may only modestly affect our estimates. Strengths of our study include the large number of black women as rates of preterm birth and CVD are high in this group. We also could evaluate a long continuum from before pregnancy through 25 years of follow-up with robust measurements of BP and pregnancy history. In contrast to pregnancy cohorts that study a single birth, we described the entire pregnancy history after enrollment in CARDIA. As a result, the overall preterm birth rate in this childbearing cohort was high.

Perspectives

Our results provide evidence that women with preterm deliveries are more likely to follow an increasing BP trajectory from before to many years after pregnancy compared with women who deliver all births at term. This high-risk BP pattern combined with a history of preterm birth is associated with excess risk of coronary atherosclerosis that does not seem to be explained by traditional CVD risk factors. Preterm birth history coupled with higher BP may identify women in whom further risk stratification may be warranted.

Footnotes

The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA.117.10693/-/DC1.

Correspondence to Janet M. Catov, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, 204 Craft Ave, Suite 2315, Pittsburgh, PA 15213. E-mail

References

  • 1. Mosca L, Benjamin EJ, Berra K, et al.; American Heart Association. Effectiveness-based guidelines for the prevention of cardiovascular disease in women–2011 update: a guideline from the American Heart Association.J Am Coll Cardiol. 2011; 57:1404–1423. doi: 10.1016/j.jacc.2011.02.005.CrossrefMedlineGoogle Scholar
  • 2. Catov JM, Wu CS, Olsen J, Sutton-Tyrrell K, Li J, Nohr EA. Early or recurrent preterm birth and maternal cardiovascular disease risk.Ann Epidemiol. 2010; 20:604–609. doi: 10.1016/j.annepidem.2010.05.007.CrossrefMedlineGoogle Scholar
  • 3. Heida KY, Velthuis BK, Oudijk MA, Reitsma JB, Bots ML, Franx A, van Dunné FM; Dutch Guideline Development Group on Cardiovascular Risk Management after Reproductive Disorders. Cardiovascular disease risk in women with a history of spontaneous preterm delivery: a systematic review and meta-analysis.Eur J Prev Cardiol. 2016; 23:253–263. doi: 10.1177/2047487314566758.CrossrefMedlineGoogle Scholar
  • 4. Robbins CL, Hutchings Y, Dietz PM, Kuklina EV, Callaghan WM. History of preterm birth and subsequent cardiovascular disease: a systematic review.Am J Obstet Gynecol. 2014; 210:285–297. doi: 10.1016/j.ajog.2013.09.020.CrossrefMedlineGoogle Scholar
  • 5. Catov JM, Dodge R, Barinas-Mitchell E, Sutton-Tyrrell K, Yamal JM, Piller LB, Ness RB. Prior preterm birth and maternal subclinical cardiovascular disease 4 to 12 years after pregnancy.J Womens Health (Larchmt). 2013; 22:835–843. doi: 10.1089/jwh.2013.4248.CrossrefMedlineGoogle Scholar
  • 6. Catov JM, Lewis CE, Lee M, Wellons MF, Gunderson EP. Preterm birth and future maternal blood pressure, inflammation, and intimal-medial thickness: the CARDIA study.Hypertension. 2013; 61:641–646. doi: 10.1161/HYPERTENSIONAHA.111.00143.LinkGoogle Scholar
  • 7. Xu J, Barinas-Mitchell E, Kuller LH, Youk AO, Catov JM. Maternal hypertension after a low-birth-weight delivery differs by race/ethnicity: evidence from the National Health and Nutrition Examination Survey (NHANES) 1999-2006.PLoS One. 2014; 9:e104149. doi: 10.1371/journal.pone.0104149.CrossrefMedlineGoogle Scholar
  • 8. Macdonald-Wallis C, Tilling K, Fraser A, Nelson SM, Lawlor DA. Associations of blood pressure change in pregnancy with fetal growth and gestational age at delivery: findings from a prospective cohort.Hypertension. 2014; 64:36–44. doi: 10.1161/HYPERTENSIONAHA.113.02766.LinkGoogle Scholar
  • 9. Zhang J, Villar J, Sun W, Merialdi M, Abdel-Aleem H, Mathai M, Ali M, Yu KF, Zavaleta N, Purwar M, Nguyen TN, Campodonico L, Landoulsi S, Lindheimer M, Carroli G. Blood pressure dynamics during pregnancy and spontaneous preterm birth.Am J Obstet Gynecol. 2007; 197:162.e1–162.e6. doi: 10.1016/j.ajog.2007.03.053.CrossrefGoogle Scholar
  • 10. Allen NB, Siddique J, Wilkins JT, Shay C, Lewis CE, Goff DC, Jacobs DR, Liu K, Lloyd-Jones D. Blood pressure trajectories in early adulthood and subclinical atherosclerosis in middle age.JAMA. 2014; 311:490–497. doi: 10.1001/jama.2013.285122.CrossrefMedlineGoogle Scholar
  • 11. Pletcher MJ, Bibbins-Domingo K, Lewis CE, Wei GS, Sidney S, Carr JJ, Vittinghoff E, McCulloch CE, Hulley SB. Prehypertension during young adulthood and coronary calcium later in life.Ann Intern Med. 2008; 149:91–99.CrossrefMedlineGoogle Scholar
  • 12. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.Lancet. 2002; 360:1903–1913. doi: https://doi.org/10.1016/S0140-6736(02)11911-8.CrossrefMedlineGoogle Scholar
  • 13. Cifu AS, Davis AM. Prevention, detection, evaluation, and management of high blood pressure in adults.JAMA. 2017; 318:2132–2134. doi: 10.1001/jama.2017.18706.CrossrefMedlineGoogle Scholar
  • 14. Wills AK, Lawlor DA, Matthews FE, Sayer AA, Bakra E, Ben-Shlomo Y, Benzeval M, Brunner E, Cooper R, Kivimaki M, Kuh D, Muniz-Terrera G, Hardy R. Life course trajectories of systolic blood pressure using longitudinal data from eight UK cohorts.PLoS Med. 2011; 8:e1000440. doi: 10.1371/journal.pmed.1000440.CrossrefMedlineGoogle Scholar
  • 15. Cutter GR, Burke GL, Dyer AR, Friedman GD, Hilner JE, Hughes GH, Hulley SB, Jacobs DR, Liu K, Manolio TA. Cardiovascular risk factors in young adults. The CARDIA baseline monograph.Control Clin Trials. 1991; 12(suppl 1):1S–77S.CrossrefMedlineGoogle Scholar
  • 16. Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR, Liu K, Savage PJ. CARDIA: study design, recruitment, and some characteristics of the examined subjects.J Clin Epidemiol. 1988; 41:1105–1116.CrossrefMedlineGoogle Scholar
  • 17. Gunderson EP, Lewis CE, Tsai AL, Chiang V, Carnethon M, Quesenberry CP, Sidney S. A 20-year prospective study of childbearing and incidence of diabetes in young women, controlling for glycemia before conception: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.Diabetes. 2007; 56:2990–2996. doi: 10.2337/db07-1024.CrossrefMedlineGoogle Scholar
  • 18. Gunderson EP, Chiang V, Lewis CE, Catov J, Quesenberry CP, Sidney S, Wei GS, Ness R. Long-term blood pressure changes measured from before to after pregnancy relative to nonparous women.Obstet Gynecol. 2008; 112:1294–1302. doi: 10.1097/AOG.0b013e31818da09b.CrossrefMedlineGoogle Scholar
  • 19. Carr JJ, Nelson JC, Wong ND, McNitt-Gray M, Arad Y, Jacobs DR, Sidney S, Bild DE, Williams OD, Detrano RC. Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study.Radiology. 2005; 234:35–43. doi: 10.1148/radiol.2341040439.CrossrefMedlineGoogle Scholar
  • 20. Detrano RC, Anderson M, Nelson J, Wong ND, Carr JJ, McNitt-Gray M, Bild DE. Coronary calcium measurements: effect of CT scanner type and calcium measure on rescan reproducibility–MESA study.Radiology. 2005; 236:477–484. doi: 10.1148/radiol.2362040513.CrossrefMedlineGoogle Scholar
  • 21. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography.J Am Coll Cardiol. 1990; 15:827–832.CrossrefMedlineGoogle Scholar
  • 22. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Prospective studies collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.Lancet. 2003; 361:1060.CrossrefGoogle Scholar
  • 23. Mosley WJ, Greenland P, Garside DB, Lloyd-Jones DM. Predictive utility of pulse pressure and other blood pressure measures for cardiovascular outcomes.Hypertension. 2007; 49:1256–1264. doi: 10.1161/HYPERTENSIONAHA.106.083592.LinkGoogle Scholar
  • 24. Bild DE, Jacobs DR, Liu K, Williams OD, Hilner JE, Perkins LL, Marcovina SM, Hulley SB. Seven-year trends in plasma low-density-lipoprotein-cholesterol in young adults: the CARDIA Study.Ann Epidemiol. 1996; 6:235–245.CrossrefMedlineGoogle Scholar
  • 25. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.Clin Chem. 1972; 18:499–502.CrossrefMedlineGoogle Scholar
  • 26. Nagin DS. Group-based trajectory modeling: an overview.Ann Nutr Metab. 2014; 65:205–210. doi: 10.1159/000360229.CrossrefMedlineGoogle Scholar
  • 27. Prentice RL, Gloeckler LA. Regression analysis of grouped survival data with application to breast cancer data.Biometrics. 1978; 34:57–67.CrossrefMedlineGoogle Scholar
  • 28. VanderWeele T, Knol M. A tutorial on interaction.Epidemiol Methods. 2014; 3:33–72.CrossrefGoogle Scholar
  • 29. Johnson HM, Thorpe CT, Bartels CM, Schumacher JR, Palta M, Pandhi N, Sheehy AM, Smith MA. Undiagnosed hypertension among young adults with regular primary care use.J Hypertens. 2014; 32:65–74. doi: 10.1097/HJH.0000000000000008.CrossrefMedlineGoogle Scholar
  • 30. Cheng S, Claggett B, Correia AW, Shah AM, Gupta DK, Skali H, Ni H, Rosamond WD, Heiss G, Folsom AR, Coresh J, Solomon SD. Temporal trends in the population attributable risk for cardiovascular disease: the Atherosclerosis Risk in Communities Study.Circulation. 2014; 130:820–828. doi: 10.1161/CIRCULATIONAHA.113.008506.LinkGoogle Scholar
  • 31. Carr JJ, Jacobs DR, Terry JG, Shay CM, Sidney S, Liu K, Schreiner PJ, Lewis CE, Shikany JM, Reis JP, Goff DCAssociation of coronary artery calcium in adults aged 32 to 46 years with incident coronary heart disease and death.JAMA Cardiol. 2017; 2:391–399. doi: 10.1001/jamacardio.2016.5493.CrossrefMedlineGoogle Scholar
  • 32. Poornima IG, Mackey RH, Allison MA, Manson JE, Carr JJ, LaMonte MJ, Chang Y, Kuller LH. Coronary artery calcification (CAC) and post-trial cardiovascular events and mortality within the Women’s Health Initiative (WHI) Estrogen-Alone Trial.J Am Heart Assoc. 2017; 6:e006887.LinkGoogle Scholar
  • 33. Nakanishi R, Li D, Blaha MJ, Whelton SP, Darabian S, Flores FR, Dailing C, Blumenthal RS, Nasir K, Berman DS, Budoff MJ. All-cause mortality by age and gender based on coronary artery calcium scores.Eur Heart J Cardiovasc Imaging. 2016; 17:1305–1314. doi: 10.1093/ehjci/jev328.CrossrefMedlineGoogle Scholar
  • 34. Tanz LJ, Stuart JJ, Williams PL, Rimm EB, Missmer SA, Rexrode KM, Mukamal KJ, Rich-Edwards JW. Preterm delivery and maternal cardiovascular disease in young and middle-aged adult women.Circulation. 2017; 135:578–589. doi: 10.1161/CIRCULATIONAHA.116.025954.LinkGoogle Scholar
  • 35. Ferguson KK, Meeker JD, McElrath TF, Mukherjee B, Cantonwine DE. Repeated measures of inflammation and oxidative stress biomarkers in preeclamptic and normotensive pregnancies.Am J Obstet Gynecol. 2017; 216:527.e1–527.e9. doi: 10.1016/j.ajog.2016.12.174.CrossrefGoogle Scholar
  • 36. Zhang G, Feenstra B, Bacelis J, et al.. Genetic associations with gestational duration and spontaneous preterm birth.N Engl J Med. 2017; 377:1156–1167. doi: 10.1056/NEJMoa1612665.CrossrefMedlineGoogle Scholar
  • 37. Boivin A, Luo ZC, Audibert F, Mâsse B, Lefebvre F, Tessier R, Nuyt AM. Pregnancy complications among women born preterm.CMAJ. 2012; 184:1777–1784. doi: 10.1503/cmaj.120143.CrossrefMedlineGoogle Scholar
  • 38. Boivin A, Luo ZC, Audibert F, Mâsse B, Lefebvre F, Tessier R, Nuyt AM. Risk for preterm and very preterm delivery in women who were born preterm.Obstet Gynecol. 2015; 125:1177–1184. doi: 10.1097/AOG.0000000000000813.CrossrefMedlineGoogle Scholar

Novelty and Significance

What Is New?

  • Women with preterm deliveries are more likely to follow an increasing blood pressure pattern across 25 years.

  • Preterm birth together with an increasing blood pressure pattern is associated with excess risk of coronary artery calcification, a strong predictor of cardiovascular disease.

  • These patterns persisted when limited to women with normotensive preterm births.

What Is Relevant?

  • Preterm birth is reliably reported by women and could identify a group who may benefit from blood pressure surveillance.

  • Blood pressure elevations in women with a prior preterm birth may mark excess risk for coronary artery calcification.

Summary

Preterm birth may identify women who are susceptible to hypertension and subclinical atherosclerosis.