Abstract
Hypertensive disorders of pregnancy (HDP) are associated with cardiovascular disease (CVD) later in life. The authors investigated the association of HDP with blood pressure (BP) and arterial stiffness 1‐year postpartum. Seventy‐four participants, 33 with an HDP and 41 with uncomplicated pregnancies, were examined using applanation tonometry to measure BP, carotid‐femoral pulse wave velocity (cfPWV), and augmentation index (AIx). On average, women with HDP had a 9 mm higher systolic BP (P<.01), 0.8 m/s faster cfPWV (P=.09), and 5.4% greater AIx (P=.09) at the 1‐year examination. After adjustment for covariates, there was no significant difference in cfPWV between groups, while a 7.3% greater AIx (P<.05) remained. These findings suggest that reduced endothelial function may be detected 1 year after HDP. Large prospective studies are needed to further understand the contribution of arterial stiffness and endothelial dysfunction in the evolution of CVD after these complicated pregnancies.
Epidemiologic studies have demonstrated a link between hypertensive disorders of pregnancy (HDP; preeclampsia [PE] and gestational hypertension [GHTN]) and future risk of hypertension and cardiovascular disease (CVD) in women.1, 2, 3 Specifically, estimates suggest that women with a history of PE are four times as likely to develop hypertension and have twice the risk of early CVD and CVD mortality compared with women who had healthy pregnancies.1, 4 The American Heart Association (AHA) and others recommend that this pregnancy history be considered a risk factor for CVD.5, 6
Increasing arterial stiffness has been found, in diverse populations, to be an independent predictor of hypertension and CVD.7, 8, 9, 10, 11, 12 Carotid‐femoral pulse wave velocity (cfPWV) is currently considered the gold‐standard measure of arterial stiffness.9 Both cfPWV and wave reflection, as quantified by the augmentation index (AIx), appear to reflect global endothelial function.11 If arterial stiffness contributes to future CVD risk among women who had pregnancy complications, it could be used to further identify those at greatest risk.8 A number of small studies have revealed increased arterial stiffness during a preeclamptic pregnancy, thought to be related to endothelial dysfunction characteristic of PE.12 However, it is unclear whether this increase in stiffness persists following delivery13 and whether it reflects residual effects of the pregnancy on endothelial function.
In the present study we examine the relationship between HDP, BP, and arterial stiffness, measured 12 to 18 months after delivery. In addition, we investigate the association of pregnancy complications and stiffness measures with systemic biomarkers of inflammation thought to be associated with CVD risk.14
Materials and Methods
Patients
The source population for this study was a cohort recruited in 2011–2012 from the postpartum service of a large community‐based academic healthcare system. This prospective cohort included women who had a complicated pregnancy and women who were part of an uncomplicated pregnancy comparison group recruited using a stratified approach to ensure equal percentages of women who were obese prior to pregnancy (body mass index [BMI] ≥30 kg/m2) and African American. Women were excluded if they had prepregnancy diabetes or were younger than 18 years of age at delivery.
Women were invited to attend a study visit 3 months and again 12 to 18 months after delivery if they had consented to future contact. The 3‐month visit included a standardized interview and measures of BP and weight. The 1‐year visit was attended between 12 and 18 months postpartum, and included a standardized interview, anthropometry, and noninvasive measures of arterial stiffness using the SphygmoCor CVMS system (AtCor Medical, Sydney, New South Wales, Australia). All patients were instructed to arrive after an overnight fast, to refrain from taking any antihypertensive or decongestive medications, and to avoid any products containing nicotine or caffeine. Blood and urine samples were collected and stored. The study was approved by the Christiana Care Health System's institutional review board and all patients provided written informed consent.
In the analysis presented here we included all patients who attended both the 3‐month and 1‐year visits. The exposed group was comprised of women who had a clinical diagnosis of HDP, defined as new‐onset BP ≥140/90 mm Hg after 20 weeks' gestation as identified by their admitting clinician during their hospital stay for labor and delivery and confirmed by review of inpatient medical records. Women with a diagnosis of chronic hypertension or known hypertension prior to pregnancy were excluded. The unexposed control group included women recruited from the uncomplicated pregnancy comparison group.
Measures
Height and waist were measured to the nearest centimeter, and weight was measured with the patients' shoes and heavy clothing removed using a mechanical weigh beam scale (Detecto, Webb City, MO). Peripheral BP was measured using a hospital‐grade, automated oscillometric device (Welch Allyn, Skaneateles Falls, NY) with the patient rested in a seated position using a standard protocol.
Applanation tonometry was used to record a radial arterial waveform by placing a high‐fidelity strain‐gauge transducer over the radial artery (Millar Instruments, Gulf Freeway, Houston, TX ). All studies were conducted by a single operator. Applanation tonometry has previously been shown to record a pressure wave that does not differ from waveforms obtained from intra‐arterial measurements.15 The radial waveform was calibrated from the brachial sphygmomanometric measurement of systolic and diastolic pressures as reported elsewhere.16 A central aortic pressure wave was synthesized from the measured radial artery pressure waveform with the SphygmoCor CVMS system, which uses a transfer function and is approved by the US Food and Drug Administration. The use of a transfer function to approximate the central pressure wave from the radial wave has been validated using both intra‐arterially17, 18, 19 and noninvasively20 obtained radial pressure waves. Central pressures and augmentation index (AIx) were obtained from the synthesized wave. AIx is an index of wave reflection and is influenced by arterial stiffness. AIx was defined as the ratio of reflected wave amplitude and pulse pressure, or AI=(P s−P i)/(P s−P d), where P s is peak systolic pressure, P d is end‐diastolic pressure, and Pi is an inflection point marking the beginning upstroke of the reflected pressure wave. AIx75 is calculated by the device, normalizing the measure to a heart rate of 75 beats per minute. Mean arterial pressure (MAP) was estimated from the pulse wave analysis. With the patient supine, cfPWV was measured using 3‐lead electrocardiography and applanation tonometry (SphygmoCor CVMS system).
Biomarkers high‐sensitivity C‐reactive protein (hs‐CRP), tumor necrosis factor α (TNF‐α), and interleukin 6 (IL‐6) were measured12 using commercially available enzyme‐linked immunosorbant assays (R&D Systems, Minneapolis, MN). All assays were performed according to the manufacturer's instructions at the University of Delaware Neuroendocrine Core Laboratory (Newark, DE).
Statistical Analysis
Data were nearly complete for all measures except cfPWV, where there were eight missing measures (four from the HDP group and four from the unexposed control group), and AIx, where there were four missing measures from the unexposed control group. The characteristics of the patients with missing data suggest that their exclusion did not bias the results. Analyses of AIx were also conducted in the group of patients with complete data for cfPWV to ensure that there were no substantive differences in the results.
Descriptive statistics were used to examine characteristics of the patients at baseline, at 3 months, and at the 1‐year follow‐up visit, reporting means and standard deviations or median and interquartile range where measures were not normally distributed. Significance testing, comparing the HDP group with the unexposed control group, was conducted using Student t test and chi‐square test for continuous and categorical measures, respectively, setting an α of 0.05 to define significance. Rank‐sum test was used for non‐normally distributed measures. Univariate and multiple linear regressions models were also used to isolate the independent associations.
We found a strong relation of cfPWV to both BMI and waist circumference. This was likely related to measurement error introduced during the determination of the linear distances used for the velocity measure, as has been reported previously.21 To account for this, and improve the precision of our measures, we used the method developed for the Chronic Renal Insufficiency Cohort (CRIC) study21 and used both the unadjusted PWV (cfPWV) and adjusted PWV (adjPWV) in the analyses.
All analyses were conducted using R version 2.15.3 (R Foundation for Statistical Computing, Vienna, Austria).
Results
We analyzed data for a total of 74 study patients: 33 with a diagnosis of HDP and 41 from the unexposed control group. Overall, 24.3% of the women were African American and 73.0% were privately insured. More than half the patients were obese prior to pregnancy: 54.5% in the HDP and 48.8% in the control group. The average age of women with HDP was 30.4 years, which was not significantly different than the control group average of 32.0 years. There were no significant differences between the groups in prepregnancy BMI, tobacco use, or the percentage of women who were African American or nulliparous. Women in the control group were less likely to be privately insured and more likely to report a positive family history of CVD (P<.05 for each). Those in the HDP group were more likely to have delivered preterm and the mean birth weight of their offspring was 248 grams less (P<.05 for each).
At both the 3‐month and 1‐year visits, women weighed more on average than their self‐reported prepregnancy weight, but there was no difference in the differences between the groups. There were also no significant differences between the groups in mean BMI, waist circumference, or percentage with a waist circumference of 35 inches (89 cm) or more at the 1‐year visit.
As shown in Table 1, HDP was significantly associated with all measures of central, peripheral, and mean BP measures (P<.01) at both the 3‐month and 1‐year visits. These differences were substantial, with an 8.6‐mm difference in peripheral SBP, a 5.5‐mm difference in peripheral DBP, and a 7.5‐mm difference in MAP, between groups. In addition, incident hypertension at 1 year was more common among women in the HDP group than in the control group (P<.01).
Table 1.
Three‐Month and 1‐Year Measures
| Timing | Measure | Controls (n=41) | Hypertensive Disorder of Pregnancy (n=33) | P Value |
|---|---|---|---|---|
| Mean (SD) or No. (%) | ||||
| 3‐month visit | Peripheral SBP, mm Hg | 108.9 (8.8) | 117.3 (10.6) | <.01 |
| Peripheral DBP, mm Hg | 71.1 (5.5) | 77.7 (8.5) | <.01 | |
| 1‐y visit | Central SBP, mm Hg | 101.3 (10.6) | 110.1 (11.6) | <.01 |
| Central DBP, mm Hg | 73.8 (7.6) | 79.5 (9.0) | <.01 | |
| Peripheral SBP, mm Hg | 111.1 (9.7) | 119.7 (11.5) | <.01 | |
| Peripheral DBP, mm Hg | 72.9 (7.4) | 78.4 (9.0) | <.01 | |
| Central pulse pressure, mm Hg | 27.5 (5.4) | 30.6 (5.5) | <.05 | |
| Mean arterial pressure, mm Hg | 86.4 (8.9) | 93.9 (10.0) | <.01 | |
| HTN or BP ≥140/90 mm Hg, No. (%) | 1 (2.4) | 7 (21.2) | <.01 | |
| Antihypertensive medication, No. (%) | 0 (0) | 2 (6.2) | NS | |
Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; HTN, diagnosis of chronic hypertension reported; NS, not significant; SD, standard deviation; SBP, systolic blood pressure.
Table 2 shows the measures of arterial stiffness using the SphygmoCor CVMS system and inflammatory biomarkers collected at the 1‐year visit. There were no significant differences in unadjusted cfPWV between groups, although the 0.8‐m/s difference in the mean velocity among women who had HDP was nearly significant (P=.1) and potentially clinically meaningful. After the adjustment for waist circumference, the difference between groups fell to 0.5 m/s, also of marginal significance (P<.1). The average unadjusted AIx was 5.4% higher in the HDP group (P<.1), and the 16.4% difference in the heart rate–adjusted AIx (AIx 75) was statistically significant (P<.05). Central augmented pressure was also significantly higher (P<.05) in the HDP group.
Table 2.
Comparison of Pulse Wave Velocity, AIx, and Inflammatory Biomarkers
| Measure | Controls (n=41) | Hypertensive Disorder of Pregnancy (n=33) | P Value |
|---|---|---|---|
| Mean (SD) | |||
| Vascular measures | |||
| cfPWV, unadjusted, m/s (n=66) | 6.3 (1.2) | 7.1 (2.0) | NS |
| cfPWV, adjusted for waist size, m/s (n=66) | 5.7 (1.0) | 6.2 (1.5) | <.01 |
| AIx, unadjusted | 16.6 (13.0) | 22.0 (13.4) | <.01 |
| AIx, adjusted for HR 75 | 12.0 (12.5) | 18.4 (13.1) | <.05 |
| Central augmented pressure | 4.9 (4.2) | 7.1 (4.6) | <.05 |
| Central augmented pressure, HR 75 | 3.3 (3.8) | 5.8 (4.1) | .01 |
| Mean arterial pressure, mm Hg | 86.4 (8.9) | 93.9 (10.0) | <.01 |
| Heart rate | 65.5 (9.6) | 67.8 (12.3) | NS |
| Inflammatory biomarkers | |||
| hs‐CRP, ng/mL | 8.66 (12.1) | 12.0 (15.3) | NS |
| IL‐6, pg/mL | 8.14 (2.47) | 8.28 (2.36) | NS |
| TNF‐α, pg/mL | 3.93 (5.29) | 8.46 (12.83) | <.05 |
Abbreviations: AIx, augmentation index; cfPWV, carotid‐femoral pulse wave velocity; HR, heart rate; hs‐CRP, high‐sensitivity C‐reactive protein; IL‐6, interleukin 6; NS, not significant; TNF‐α, tumor necrosis factor α.
Measures of the inflammatory biomarkers are shown in Table 2. On average, TNF‐α was significantly higher among women with HDP (P<.05), while differences in hs‐CRP or IL‐6 were not significant. All were positively related to unadjusted cfPWV, with Spearman correlation coefficients of 0.13, 0.16, and 0.20, respectively. However, there were no significant relationships between inflammatory biomarkers and adjPWV or AIx.
Adjustment of adjPWV for MAP using linear regression (results not shown) eliminated any difference between the group, as did further adjustment for age, BMI, race, family history of CVD, ever tobacco use, and insurance type. The two factors that were significantly related to adjPWV were MAP (P<.001) and age (P<.05).
There was a significant association of AIx with HDP after adjusting for heart rate and height. The results of the full multiple linear regression model of AIx, adjusted also for age, BMI, race, insurance, family history of CVD, and a history of ever using tobacco, are shown in Table 3. The association with HDP remained significant (P<.05), and age at the time of the measure contributed significantly (P<.001).
Table 3.
Multiple Linear Regression Predicting Augmentation Index (n=72)
| Estimate (Standard Error) | Standardized Beta | |
|---|---|---|
| Hypertensive disorder of pregnancy | 7.281 (2.995)a | 0.274 |
| Heart rate, beats per min | −0.293 (0.134)a | −0.242 |
| Height, in | −0.983 (0.541) | −0.192 |
| Age, y | 0.871 (0.247)b | 0.388 |
| Body mass index, kg/m2 | −0.026 (0.183) | −0.017 |
| African American race | 3.835 (3.861) | 0.123 |
| Privately insured for delivery | −5.817 (3.715) | −0.194 |
| Family history of cardiovascular disease | 3.831 (3.255) | 0.140 |
| Smoking | 2.621 (3.190) | 0.094 |
| Intercept | 73.255 (35.559)a | |
| Adjusted R 2 | 0.25 |
a P<.05. b P<.001.
Because prior studies suggest that there may be differences in the associations among women who had a clinical presentation consistent with PE rather than GHTN, we conducted a subgroup analysis. The 16 women with PE had a lower mean gestational age at delivery (P<.01), and their offspring had a lower mean birth weight (P<.01), than the 17 women with GHTN. When we examined the HDP subgroups with PE and GHTN in relation to adjPWV and AIx75, we found small differences between the groups. There was a higher mean AIx75 in the GHTN group (mean difference of 6%) and higher mean adjPWV measures in the PE group (mean difference of 0.2 m/s), but neither difference was statistically significant.
Discussion
We found differences in BP and AIx but not PWV among women 1 year after a pregnancy complicated by HDP when compared with similarly obese women with unaffected pregnancies. Through the use of an unexposed control group of women with a similar degree of adiposity, but who did not develop HDP, we were better able to account for the confounding effects of prepregnancy obesity, postpartum weight retention, and other CVD risk factors, than earlier studies. Although the sample size was modest, by accounting for both BP and measurement error related to abdominal adiposity, we provide a more precise comparison of PWV between groups than previous studies. The significant difference in AIx between groups suggests this might be a more sensitive indicator of early changes in the cardiovascular system of women only 1 year postpartum.
Our main finding is the significantly higher AIx, after adjustment for confounders, but no significant difference in cfPWV when women with HDP were compared with equally obese women in the control group. Although PWV is the gold standard, noninvasive measure of arterial stiffness as measured by PWV, AIx depicts reflected wave characteristics of individuals representing a composite of arterial stiffness, vascular resistance, heart rate, and left ventricular ejection. One potential mechanism for the increased wave reflection in HDP may be altered amplitude and site of wave reflections as a result of increased resistance, suggested by differences in MAP. Previous work has demonstrated that declines in endothelial function are associated with increased PWV and wave reflection,22 thus impaired endothelial function in HDP may explain the increase in AIx.
The higher peripheral and central BP measures among women with HDP, and their elevated rate of incident hypertension, are consistent with prior studies.23, 24 As expected, the inflammatory markers were positively correlated with cfPWV11, 25 but the magnitudes were small and not statistically significant. None of these markers were associated with AIx. Together these findings do not provide evidence to support inflammation outside of pregnancy in a mechanistic role.
A 2011 systematic review and meta‐analysis of 23 studies examined the association between PE and arterial stiffness both during and after pregnancy.13 A synthesis of the evidence suggested that measures of arterial stiffness and wave reflection are increased during pregnancy among women with both PE and GHTN. However, data were conflicting as to whether these changes persisted after delivery. Heterogeneity in findings across the studies may have been related to disease severity. For example, small case‐control studies that found women with early‐onset, but not late‐onset, PE had differences in PWV and AIx postpartum when compared with women with healthy pregnancies.26, 27 Other differences could be related to the lack of precision of the stiffness measures related to central adiposity, as we found here, and was found in a study of the CRIC cohort.21 A failure to account for measurement error might lead to an erroneous association of HDP and PWV.
Study Limitations
The main limitation of this study is the small sample size, which may have masked a significant independent association of diagnosis with arterial stiffness measures with a small effect size. Some heterogeneity among women may have resulted from timing of menstrual cycle, since there is evidence of hormonal effects on measures of stiffness.26 In addition, we included women with both PE and GHTN and had small numbers of women with more severe disease, potentially decreasing the effect size. Finally, as in prior investigations, the absence of prepregnancy data limits our ability to draw conclusions about a causal role of HDP on BP trajectory and arterial stiffness. Early pregnancy data might not adequately reflect prepregnancy characteristics because of changes in BP typically observed very early in the first trimester of pregnancy, limiting its potential utility as a proxy for prepregnancy values.28, 29
Conclusions
The higher average BP among women 1 year after delivery of a pregnancy complicated by HDP was independent of obesity and of sufficient magnitude to play an important role in their future risk of CVD. Higher AIx suggests that complicated pregnancy may play a role as a causal factor. Large prospective studies, ideally starting prior to starting prior to conception, are needed to further understand the contribution of arterial stiffness and endothelial dysfunction to the evolution of hypertension and CVD in women after affected pregnancies.
Acknowledgments
Grants and other support: National Institute of General Medical Sciences—NIGMS (8 P20 GM103446‐13) from the National Institutes of Health to Deborah Ehrenthal.
Disclosure
The authors have nothing to disclose.
J Clin Hypertens (Greenwich). 2014;16:695–699. DOI: 10.1111/jch.12398 © 2014 Wiley Periodicals, Inc.
References
- 1. McDonald SD, Malinowski A, Zhou Q, et al. Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta‐analyses. Am Heart J. 2008;156:918–930. [DOI] [PubMed] [Google Scholar]
- 2. Sattar N, Greer IA. Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? BMJ. 2002;325:157–160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Lykke JA, Langhoff‐Roos J, Sibai BM, et al. Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother. Hypertension. 2009;53:944–951. [DOI] [PubMed] [Google Scholar]
- 4. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre‐eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta‐analysis. BMJ. 2007;335:974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness‐based guidelines for the prevention of cardiovascular disease in women–2011 update: a guideline from the American Heart Association. Circulation. 2011;123:1243–1262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Roberts JM, Catov JM. Pregnancy is a screening test for later life cardiovascular disease: now what? Research recommendations. Womens Health Issues. 2012;22:e123–e128. [DOI] [PubMed] [Google Scholar]
- 7. Kaess BM, Rong J, Larson MG, et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA. 2012;308:875–881. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Wang X, Keith JC Jr, Struthers AD, Feuerstein GZ. Assessment of arterial stiffness, a translational medicine biomarker system for evaluation of vascular risk. Cardiovasc Ther. 2008;26:214–223. [DOI] [PubMed] [Google Scholar]
- 9. Cavalcante JL, Lima JA, Redheuil A, Al‐Mallah MH. Aortic stiffness: current understanding and future directions. J Am Coll Cardiol. 2011;57:1511–1522. [DOI] [PubMed] [Google Scholar]
- 10. Nichols WW, Edwards DG. Arterial elastance and wave reflection augmentation of systolic blood pressure: deleterious effects and implications for therapy. J Cardiovasc Pharmacol Ther. 2001;6:5–21. [DOI] [PubMed] [Google Scholar]
- 11. McEniery CM, Spratt M, Munnery M, et al. An analysis of prospective risk factors for aortic stiffness in men: 20‐year follow‐up from the Caerphilly prospective study. Hypertension. 2010;56:36–43. [DOI] [PubMed] [Google Scholar]
- 12. Germain AM, Romanik MC, Guerra I, et al. Endothelial dysfunction: a link among preeclampsia, recurrent pregnancy loss, and future cardiovascular events? Hypertension. 2007;49:90–95. [DOI] [PubMed] [Google Scholar]
- 13. 'Hausvater A, Giannone T, Sandoval YH, et al. The association between preeclampsia and arterial stiffness. J Hypertens. 2011;30:17–33. [DOI] [PubMed] [Google Scholar]
- 14. Folsom AR. Classical and novel biomarkers for cardiovascular risk prediction in the United States. J. Epidemiol. 2013;23:158–162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Kelly R, Hayward C, Avolio A, O'Rourke M. Noninvasive determination of age‐related changes in the human arterial pulse. Circulation. 1989;80:1652–1659. [DOI] [PubMed] [Google Scholar]
- 16. Nichols WW, O'Rourke MF. McDonald's Blood Flow in Arteries. New York, NY: Oxford University Press; 2005. [Google Scholar]
- 17. Pauca AL, O'Rourke MF, Kon ND. Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform. Hypertension. 2001;38:932–937. [DOI] [PubMed] [Google Scholar]
- 18. Kelly RP, Millasseau SC, Ritter JM, Chowienczyk PJ. Vasoactive drugs influence aortic augmentation index independently of pulse‐wave velocity in healthy men. Hypertension. 2001;37:1429–1433. [DOI] [PubMed] [Google Scholar]
- 19. Chan RH, Gordon NF, Chong A, Alter DA. Influence of socioeconomic status on lifestyle behavior modifications among survivors of acute myocardial infarction. Am J Cardiol. 2008;102:1583–1588. [DOI] [PubMed] [Google Scholar]
- 20. Gallagher D, Adji A, O'Rourke MF. Validation of the transfer function technique for generating central from peripheral upper limb pressure waveform. Am J Hypertens. 2004;17:1059–1067. [DOI] [PubMed] [Google Scholar]
- 21. Townsend RR, Wimmer NJ, Chirinos JA, et al. Aortic PWV in chronic kidney disease: a CRIC ancillary study. Am J Hypertens. 2010;23:282–289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. McEniery CM, Wallace S, Mackenzie IS, et al. Endothelial function is associated with pulse pressure, pulse wave velocity, and augmentation index in healthy humans. Hypertension. 2006;48:602–608. [DOI] [PubMed] [Google Scholar]
- 23. Hermes W, Franx A, van Pampus MG, et al. Cardiovascular risk factors in women who had hypertensive disorders late in pregnancy: a cohort study. Am J Obstet Gynecol. 2013;208:474.e471–474.e478. [DOI] [PubMed] [Google Scholar]
- 24. Smith GN, Walker MC, Liu A, et al. A history of preeclampsia identifies women who have underlying cardiovascular risk factors. Am J Obstet Gynecol. 2009;200:58.e51–58.e58. [DOI] [PubMed] [Google Scholar]
- 25. Schumacher W, Cockcroft J, Timpson NJ, et al. Association between C‐reactive protein genotype, circulating levels, and aortic pulse wave velocity. Hypertension. 2009;53:150–157. [DOI] [PubMed] [Google Scholar]
- 26. Robb AO, Mills NL, Din JN, et al. Influence of the menstrual cycle, pregnancy, and preeclampsia on arterial stiffness. Hypertension. 2009;53:952–958. [DOI] [PubMed] [Google Scholar]
- 27. Franz MB, Burgmann M, Neubauer A, et al. Augmentation index and pulse wave velocity in normotensive and pre‐eclamptic pregnancies. Acta Obstet Gynecol Scand. 2013;92:960–966. [DOI] [PubMed] [Google Scholar]
- 28. Clapp JF 3rd, Capeless E. Cardiovascular function before, during, and after the first and subsequent pregnancies. Am J Cardiol. 1997;80:1469–1473. [DOI] [PubMed] [Google Scholar]
- 29. Mahendru AA, Everett TR, Wilkinson IB, et al. A longitudinal study of maternal cardiovascular function from preconception to the postpartum period. J Hypertens. 2014;32:849–856. [DOI] [PubMed] [Google Scholar]