Association of pre-pregnancy subclinical insulin resistance with cardiac dysfunction in healthy nulliparous women

Abstract

Objectives:

To investigate the association between pre-pregnancy subclinical insulin resistance and cardiovascular dysfunction in healthy nulliparous women, and with hypertension in subsequent pregnancy.

Study Design:

Secondary analysis of a single center prospective observational study conducted November 2011 – June 2014. Healthy nulliparous women underwent detailed cardiovascular and metabolic assessment. Insulin resistance was determined by homeostasis model assessment (HOMA-IR). Associations of HOMA-IR with metabolic and cardiovascular measurements were assessed with Spearman correlations. Charts were reviewed in women who conceived singleton pregnancies.

Main outcome measures:

Metabolic measurements included serum glucose, insulin, creatinine, CRP, and lipids. HOMA-IR was calculated using fasting serum insulin and glucose. Indices of cardiovascular stiffness were determined from pulse wave velocity and response to volume challenge. Pregnancy outcomes included delivery mode and gestational age, birthweight, and hypertension.

Results:

HOMA-IR was positively associated with BMI (r = 0.462, p < 0.001), body fat percentile (r = 0.463, p <0.001), CRP (r = 0.364, p = 0.003), and negatively associated with serum HDL (r = −0.38, p = 0.002) and creatinine (r = −0.242, p = 0.049). HOMA-IR was positively associated with blood pressure (r = 0.347, p = 0.004), resting heart rate (r = 0.433, p = <0.001), response to volume challenge (r = 0.325, p < 0.01). Increased HOMA-IR was associated with a faster cardiac ejection time in response to volume challenge (r = −0.415, p < 0.001), which is a marker of decreased cardiac compliance to volume increase, or cardiac stiffness.

Conclusion:

HOMA-IR is associated with pre-pregnancy cardiac stiffness. Cholesterol was not associated with cardiovascular dysfunction. A non-significant trend was observed between HOMA-IR and hypertension in subsequent pregnancy.

1. Introduction

Preeclampsia, characterized by new-onset hypertension after 20 weeks’ gestation with associated proteinuria and/or evidence of end organ injury, affects approximately 7-10% of pregnancies with significant associated maternal and neonatal morbidity and mortality [1]. Complications of hypertension in pregnancy account for 14% of maternal mortality globally, and 7% in the United States [2, 3]. Long-term, hypertensive disorders of pregnancy are associated with increasing lifetime risks of a spectrum of cardiovascular disease, dependent primarily on the gestational age at onset of preeclampsia. Specifically, while women with prior term preeclampsia carry a 1.5-fold increased risk of death from cardiovascular disease, those with prior preterm or recurrent diagnoses have a substantially higher risk of cardiovascular mortality [4–8]. The impact of preeclampsia on cardiovascular disease is not limited to cardiovascular mortality, but also includes hemorrhagic stroke, heart failure, ischemic heart disease, thromboembolic events, and angina [4, 9–11]. In women with a history of preeclampsia, asymptomatic heart failure detectable by cardiovascular measures shortly after delivery and persistent in the first year postpartum [12, 13]. A large retrospective study conducted in postpartum Taiwanese women identified an increased risk of heart failure in women with a history of preeclampsia as soon as 13 years postpartum [14].

The cardiovascular events associated with a history of preeclampsia implicate a subclinical cardiovascular dysfunction that persists following pregnancy. In normal pregnancy, progressive plasma volume expansion requires cardiovascular adaptations to manage increased cardiac output, such as decreased systemic vascular resistance and increased cardiovascular compliance. These adaptations have been shown to persist at least a year postpartum, with a cumulative effect in subsequent pregnancies, such that normal pregnancy may lower lifetime cardiovascular risk [15, 16]. However, women with preeclampsia have demonstrated impaired adaptation to the volume expansion of pregnancy that ranges from asymptomatic to frank diastolic dysfunction that persists postpartum [17, 18]. Our previous work in women with a history of preeclampsia uniquely demonstrate evidence of arterial stiffness in the non-pregnant state in the absence of clinical hypertension [19].

Emerging evidence suggests that pre-gestational subclinical cardiovascular dysfunction, and subsequent impaired adaptation to the physiologic changes of pregnancy, may contribute to development of preeclampsia [20]. Our previous work has demonstrated a relationship between pre-pregnancy measures of arterial stiffness, subclinical elements of metabolic syndrome, and the subsequent development of hypertension in pregnancy [21, 22].

Metabolic syndrome consists of a constellation of clinical characteristics associated with hypertension and cardiovascular disease outside of pregnancy, and is also suspected to be an independent risk factor for hypertensive disorders of pregnancy [23–26]. In normal pregnancy, insulin resistance progressively increases with advancing gestation, in some women manifesting as overt gestational diabetes mellitus. Both pre-gestational and gestational diabetes are associated with an increased risk of hypertension in pregnancy [27].

While the euglycemic insulin clamp historically has been the gold standard for measuring insulin resistance, the homeostasis model assessment (HOMA-IR) is a less invasive mathematical approach to determining insulin resistance, and is a useful epidemiologic tool outside of pregnancy. [28]. HOMA-IR as a calculated measure of insulin resistance has also been studied during pregnancy in association with hypertension. Several studies have identified increased HOMA-IR in women who ultimately develop preeclampsia compared to normotensive women, both prior to clinical diagnosis at mid-gestation, as well as at postpartum time points [29–34]. However, efforts to confirm this relationship between antepartum insulin resistance and preeclampsia have yielded inconsistent results, with other works failing to identify a significant difference in antepartum HOMA-IR between hypertensive and normotensive women [35–38]. The pre-gestational relationship between insulin resistance as measured by HOMA-IR and cardiovascular dysfunction has not been described with consideration for subsequent pregnancy outcomes.

We hypothesize that subclinical insulin resistance as measured by HOMA-IR in healthy nulliparous women may be associated with cardiovascular dysfunction pre-pregnancy, including both cardiac and arterial measures, as well as hypertension during subsequent pregnancy.

2. Methods

2.1. Study design

This was a secondary analysis of a larger prospective observational study conducted at a single tertiary care center. The research protocols were approved by the University of Vermont Human Investigational Committees. Healthy women planning pregnancy were recruited by open enrollment between November 2011 and June 2014. Consent was obtained from 156 women who met inclusion criteria, of whom 124 were evaluated in the pre-pregnant state. Women were excluded if they had a BMI > 40, were on systemic hormonal contraception, currently smoking, or had preexisting type 2 diabetes. The current analysis focused on the 79 nulliparous participants, all of whom underwent cardiovascular assessment prior to pregnancy. Of this nulliparous cohort, 67 women subsequently achieved singleton pregnancies, for whom pre-pregnancy cardiovascular and metabolic assessments were performed.

Chart review was performed to obtain subsequent pregnancy outcomes (Figure 1). Hypertensive disorders of pregnancy were defined according to the American College of Obstetrics and Gynecology (ACOG). Preeclampsia was defined as the presence of new-onset hypertension (blood pressure 140/90 on two occasions at least 4 hours apart after 20 weeks of gestation) either with presence of 300 mg protein in a 24-hour urinary collection, or with serum evidence of transaminitis, thrombocytopenia, or renal insufficiency in the absence of proteinuria. Gestational hypertension was defined as blood pressure elevation after 20 weeks of gestation in the absence of proteinuria or the aforementioned systemic findings [39]. Birth weight percentile was determined based on previously reported cross-sectional Vermont hybrid growth curve [40].

Figure 1.

Study flow chart.

Detailed cardiovascular assessment was performed pre-pregnancy in the follicular phase. Women were placed on three days of sodium, potassium, and calorie standardized dietary control prior to participation. Women abstained from alcohol and caffeine for at least 24 hours, and from decongestants and nonsteroidal anti-inflammatory medications for 48 hours prior to the study. Assessments were obtained following overnight fasting. Compliance with this dietary and medication restriction was confirmed by a registered dietician and the study team on the day of evaluation.

2.2. Cardiovascular measures

Pre-pregnancy cardiovascular assessment consisted of multiple measures. At the time of study assessment, demographic information including age, pregnancy history, and medical history, were confirmed. Height and weight were measured. Blood was obtained for metabolic assessment by antecubital puncture. Continuous non-invasive tonometric digital artery blood pressure standardized to the brachial artery and cardiac output monitoring were performed using Finometer PRO (Finapres Medical Systems, Amsterdam, Netherlands). Assessment of vascular compliance was performed using a volume challenge with the goal of mimicking the volume expansion of pregnancy. Response to volume challenge was measured by the change in cardiac output and pulse as area under the curve following IV infusion of 500 mL Lactated Ringers saline over 10 minutes via antecubital venous catheter. Subjects underwent 15 minutes of post-infusion monitoring and concomitant continuous non-invasive blood pressure monitoring on the contralateral arm.

Arterial stiffness was assessed using multiple parameters including pulse wave velocity and beta stiffness. Doppler ultrasound using a 10 MHz transducer was used to measure pulse wave velocity, estimated as the time from aortic root peak flow to brachial and popliteal peak systolic flow, respectively. Distance from the heart to brachial artery and popliteal artery was estimated post hoc as [height*(1/3)] and [height*(2/3)], respectively, β stiffness index is used to evaluate arterial wall stiffness independent of blood pressure. This was determined using CINE clips of vascular ultrasounds for baseline brachial and popliteal artery diameter and diameter change through the cardiac cycle with associated changes in supine blood pressure. β stiffness index is calculated using the systolic over diastolic blood pressure divided by change in vessel diameter difference over minimum vessel diameter, with increasing values indicating stiffer arteries. Values are averages of three measurements.

2.3. Metabolic measures

Metabolic profiles were obtained following an overnight fast and serum collection. Laboratory values collected included serum fasting glucose and insulin, which were used to calculate HOMA-IR, as well as creatinine, C reactive protein (CRP), and lipid profiles (total cholesterol, triglycerides, HDL and LDL). HOMA-IR was calculated based on the fasting glucose multiplied by fasting insulin, divided by 22.5, as previously described [28]. Body mass index (BMI) was calculated as the weight in kilograms, divided by the square of the height in meters. Dual-energy X-ray absorptiometry (DEXA) scans were performed in order to calculate total, gynecoid, and android body fat composition, as previously described [41].

2.4. Statistical analysis

Spearman’s rank correlation coefficients were calculated to evaluate the association between HOMA-IR and pre-pregnancy metabolic markers. Welch-Satterthwaite T-test was used to evaluate the relationship between HOMA-IR and subsequent hypertensive disorders of pregnancy. All statistical analysis were performed using SAS statistical software Version 9.3 (SAS Institute, Cary, NC). Statistical significance determined based on α = 0.05.

Results

Table 1 depicts participant demographic characteristics and pre-pregnancy cardiovascular measurements. In the nulliparous study population, participants were a mean age of 30.6 ± 4.3 years and predominantly Caucasian. Women were of normal mean BMI (24.4 ± 5.4 kg/m²)with normal mean body fat percentage and android:gynoid fat ratios. Women demonstrated normal blood pressure and pulse. Mean HOMA-IR was consistent with normal range at 1.00 ± 0.50.

Table 1.

Pre-pregnancy demographic characteristics of nulliparous participants. Values are mean ± SD or n (%) unless otherwise specified.

Pre-pregnancy demographic and cardiovascular characteristics	n = 79
Age (years)	30 ± 4
BMI (kg/m2)	24.4 ± 5.4
Caucasian race	66 (83%)
Body fat (%)	24.2 ± 12.0
Android:Gynoid fat ratio	0.34 ± 0.12
Systolic blood pressure (mmHg)	109 ± 11
Diastolic blood pressure (mmHg)	67 ± 8
Mean arterial pressure (mmHg)	81 ± 8
Resting heart rate (bpm)	63 ± 9
Brachial PWV (m/s)	2.78 ± 0.28
Popliteal PWV (m/s)	2.53 ± 0.21
β stiffness index	18.47 ± 18.22
Cardiac output response to volume challenge (L/min)	6.48 ± 11.50
HOMA-IR*	1.00 ± 0.50

^*Represents n = 67.

There was a significant positive association between HOMA-IR and pre-pregnancy BMI (r = 0.462, p < 0.001) and serum CRP (r = 0.364, p = 0.003) (Table 2). Unexpectedly, there was no association between HOMA-IR and total cholesterol or triglycerides. We observed a significant negative relationship between HOMA-IR and HDL (r = −0.38, p = 0.002) as well as between HOMA-IR and pre-pregnancy creatinine (r = −0.242, p = 0.049) (Table 2).

Table 2.

Association of serum metabolic markers with insulin resistance as measured by HOMA-IR in non-pregnant nulliparous women (n = 67). Units of serum markers is mg/dL unless otherwise noted.

Serum metabolic markers	Spearman correlation coefficients
	R value	p-value
BMI (kg/m2)	0.46	< 0.001*
CRP (ng/L)	0.36	0.003*
Creatinine	−0.24	0.049*
Total cholesterol	−0.15	0.212
Triglycerides	0.30	0.13
HDL	−0.38	0.002*
LDL	−0.10	0.426

^*p <0.05.

HOMA-IR was significantly and positively associated with pre-pregnancy systolic blood pressure (r = 0.347, p = 0.004) and resting heart rate (r = 0.433, p = <0.001). A positive association of HOMA-IR with cardiac output response to volume challenge (r = 0.325, p < 0.01) and concurrent negative association cardiac ejection time (r = −0.415, p < 0.001) indicates a relationship between insulin resistance and decreased cardiovascular compliance to volume expansion. Measures of peripheral arterial stiffness including β stiffness, brachial, and popliteal pulse wave velocity, were not significantly associated with HOMA-IR (Table 3).

Table 3.

Association of clinical cardiovascular measures with insulin resistance as measured by HOMA-IR in non-pregnant nulliparous women (n = 79).

Pre-pregnancy clinical cardiovascular measures	Spearman correlation coefficients
	R value	p value
Systolic blood pressure (mmHg)	0.34	0.004*
Diastolic blood pressure (mmHg)	0.24	0.055
Resting heart rate (bpm)	0.43	<0.001*
Cardiac output response to volume challenge (L/min)	0.33	<0.01*
Cardiac ejection time (seconds)	−0.42	<0.001*
β stiffness index	0.09	0.469
Brachial PWV (m/s)	−0.09	0.478
Popliteal PWV (m/s)	−0.09	0.477

^*p <0.05.

We next examined the relationship between the metabolic markers significantly associated with HOMA-IR prior to pregnancy and measures of cardiac stiffness. CRP was not significantly associated with cardiac output response to volume challenge (r = 0.147, p = 0.210) (Figure 2). Not only were cholesterol and triglycerides not significantly associated with insulin resistance, there was no significant association of these serum metabolic markers with cardiac ejection time (cholesterol r-value = −0.075, p = 0.546; triglycerides r-value −0.064, p = 0.607) (data not shown).

Figure 2.

Spearman rank correlation coefficients were used to evaluate the relationship between CRP, a metabolic marker associated with insulin resistance, and measures of cardiac stiffness. (A) Correlation of serum CRP and cardiac output response to volume challenge (AUC), and (B) cardiac ejection time, a measure of cardiac stiffness.

Of our nulliparous cohort, 67 women achieved singleton pregnancies, whose demographics are described in Table 4. Within this subgroup, none of the subjects were taking low dose aspiring for preeclampsia prophylaxis. Four women had a documented diagnosis of infertility, but all achieved pregnancy; three conceived spontaneously and the fourth by in vitro fertilization. Chart review was conducted to obtain pregnancy outcomes for each subject. None of the women who conceived were diagnosed with gestational diabetes. Additionally, all subjects demonstrated a pre-pregnancy fasting serum glucose less than 100 mg/dL, consistent with intact glucose tolerance as defined by American Diabetes Association [42]. Timing of delivery ranged from 26 to 42 weeks of gestation, and mean delivery occurred at 39.4 ± 2.2 weeks gestation. The majority delivered vaginally (73.9%), resulting in a neonate of normal birthweight (81.3%). 24.6% of women developed a hypertensive disorder during pregnancy, 11.6% of whom developed preeclampsia. Of those that developed preeclampsia, 75% developed the diagnosis at term compared to 25% preterm, defined as prior to 37 weeks of gestation (Table 4).

Table 4.

Pregnancy outcomes in nulliparous women achieving singleton pregnancies with livebirth. Birthweight percentile was calculated using the previously described cross-sectional Vermont Hybrid growth curve [35]. Values are mean ± SD or n (%) unless otherwise specified.

Pregnancy outcomes	n = 69
Gestational age at delivery (weeks)	39.4 ± 2.2
Vaginal delivery	51 (73.9)
Birthweight (g)	3397 ± 570
Birthweight percentile
<10 percentile	5 (7.8)
11-90 percentile	52 (81.3)
>91 percentile	7 (10.9)
Hypertensive disorders of pregnancy	17 (24.6)
Gestational hypertension	9 (13.0)
Preeclampsia	8 (11.6)
Preterm diagnosis	2 (25)
Term diagnosis	6 (75)

There was a nonsignificant trend towards increased HOMA-IR in pregnant women who developed hypertension compared to normotensive women (1.24 ± 0.79 versus 0.92 ± 0.34, p= 0.14) (Table 5). Consistent with pre-pregnancy findings, women who developed hypertension in pregnancy demonstrated significantly lower serum creatinine compared to those without hypertension (0.61 ± 0.09 mg/dL versus 0.68 ± 0.09 mg/dL, p = 0.034). Conversely, CRP was significantly elevated (p = 0.02) in women with hypertensive pregnancies compared to those with normal pregnancies (5.05 ± 2.81 ng/L versus 2.41 ± 3.01 ng/L, p = 0.02) (Table 5).

Table 5.

Association of serum metabolic markers with pregnancy outcomes in nulliparous women who achieved subsequent pregnancy. Values are mg/dL unless otherwise noted.

	Normal Pregnancy Outcome (n = 51)	Hypertension in Pregnancy (n = 16)	p-value
BMI (kg/m2)	23.36 ± 5.19	26.98 ± 5.07	0.02*
HOMA-IR	0.92 ± 0.34	1.24 ± 0.79	0.14
CRP (ng/L)	2.41 ± 3.01	5.05 ± 2.81	0.02*
Creatinine	0.68 ± 0.09	0.61 ± 0.09	0.034*
Total cholesterol	153.6 ± 24.86	160.2 ± 17.53	0.33
Triglycerides	75.33 ± 30.36	81.19 ± 42.32	0.54
HDL	53.71 ± 9.99	49.06 ± 12.35	0.13
LDL	84.71 ± 20.89	94.88 ± 18.05	0.085

^*p <0.05.

Discussion

Attempts to correlate subclinical insulin resistance with antepartum cardiovascular dysfunction, and to assess the predictive value of HOMA-IR for preeclampsia development, have yielded conflicting results. Multiple metabolic risk factors for cardiovascular disease in the non-pregnant state, including insulin resistance and hyperlipidemia, are also risk factors for the development of preeclampsia in pregnancy. This overlap suggests a biologic plausibility for subclinical insulin resistance and cardiovascular dysfunction prior to pregnancy contributing to the development of preeclampsia in pregnancy. The subsequent long-term impact of preeclampsia on long-term health is considerable. For example, Spaan et al. characterized uniquely elevated HOMA-IR and microvascular changes in middle-aged women with a history of preeclampsia 23 years following the index pregnancy, compared to women with normal pregnancy outcomes [31]. This suggests that metabolic changes, in addition to cardiovascular dysfunction, associated with preeclampsia, persist long after delivery and have a significant impact on long-term health. In the United States, cardiovascular disease is the leading cause of mortality among women of all ages, therefore there are clearly lasting implications for women’s health and opportunities for risk reduction [43].

In healthy nulliparous women, subclinical insulin resistance is associated with measures of metabolic and cardiovascular dysfunction. Specifically, HOMA-IR was positively associated with both systolic blood pressure and resting heart rate in the non-pregnant state. The comprehensive nature of our cardiovascular measures obtained prior to pregnancy allowed for the interpretation of cardiac and arterial function and response to volume changes. The association of HOMA-IR with cardiac output in response to volume challenge, as well as shorter cardiac ejection times, suggests impaired cardiac compliance to volume expansion and therefore increased cardiac stiffness. However, measures of peripheral arterial stiffness such as β stiffness and pulse wave velocity were not significantly associated with HOMA-IR. From this data we can conclude that pre-pregnancy insulin resistance may be more strongly associated with cardiac stiffness as opposed to peripheral arterial stiffness.

Our inclusion of metabolic markers in the nulliparous cohort prior to pregnancy additionally allowed for the assessment of contributing risk factors for cardiovascular disease such as renal impairment and hyperlipidemia. HOMA-IR has been associated with hyperlipidemia and hypertriglyceridemia mid-gestation, as well as in older non-pregnant populations with impaired insulin tolerance and cardiovascular disease [44–47]. Unexpectedly, cholesterol and triglyceride levels were not associated with HOMA-IR or cardiac stiffness in our population. This may be due to a small sample size, but may also reflect selection bias. Our nulliparous cohort was young, normal weight and predominantly Caucasian, and women with comorbid conditions such as diabetes and obesity were excluded. In addition, the relationship between HOMA-IR and abnormal cholesterol profiles demonstrated in pregnancy has been assessed mid-gestation, and may be affected by the physiologic insulin resistance and hypertriglyceridemia of pregnancy. In contrast, our data suggests that pre-pregnancy glucose metabolism, more so than lipids, may contribute to cardiac stiffness. This is consistent with literature in an older, non-pregnant population, reporting a strong relationship between insulin resistance and cardiac remodeling [48, 49].

Consistent with the known relationship between metabolic syndrome and hyperfiltration, we identified a significant negative association between HOMA-IR and creatinine prior to pregnancy and in normotensive women compared to those that developed hypertension during pregnancy [50]. We identified increased serum CRP in women that went on to develop hypertension in pregnancy. This is consistent with a body of literature demonstrating a strong correlation of systemic inflammation as measured by circulating CRP with myocardial damage and dysfunction in non-pregnant adults with a spectrum of cardiovascular disease [51–55]. Women who demonstrate subclinical systemic inflammation prior to pregnancy with elevated CRP may therefore be predisposed to myocyte damage and ultimately impaired adaptation of the myocardium to the physiologic volume expansion of pregnancy.

We failed to identify a significant association between pre-pregnancy HOMA-IR and development of hypertension in subsequent pregnancy. However, there was a non-significant trend towards increased pre-pregnancy HOMA-IR in women who developed hypertension compared to normotensive women. While our study was underpowered to individually evaluate gestational hypertension, preterm and term preeclampsia, we identified a trend towards increased pre-pregnancy insulin resistance in women with preeclampsia specifically. This was a small, homogenous and healthy population evaluated at a single center, which may limit its generalizability. Notably, we observed a higher than anticipated incidence of hypertension, and preeclampsia specifically, as defined by 2013 ACOG guidelines compared to national population health data [39]. Pre-pregnancy BMI was significantly greater in women who developed hypertension compared to those with normal pregnancy outcomes; otherwise these groups were predominantly Caucasian, and comparable in age and prevalence of fertility procedures. Study exclusion criteria included known risk factors for hypertension such as diabetes and obesity; however, we are not able to assess the contribution of family history, new partner, or ongoing diet in pregnancy. Subjects with pregnancy outcome data may be more likely to deliver at our tertiary care center with a hypertensive disorder of pregnancy. Finally, epigenetic and geographic variation may have contributed to this finding, as a contemporary national study by Ananth et al. identify Vermont among the ten states with the highest adjusted prevalence of hypertensive disorders of pregnancy [56].

The present study is unique in that pre-pregnancy cardiovascular assessments were performed on healthy nulliparous women without the influence of cardiovascular adaptation to prior pregnancies. Comprehensive cardiovascular measures allowed for distinction between arterial stiffness and cardiac stiffness [15, 16]. Most participants went on to have pregnancies, which allowed for the evaluation of the relationship between both cardiovascular and metabolic measures and pregnancy outcomes.

In conclusion, subclinical insulin resistance determined by HOMA-IR is associated with measures of both metabolic and cardiovascular dysfunction in otherwise healthy nulliparous women. HOMA-IR has previously been associated with diagnoses of hypertension in midgestation and postpartum. Its role as a potential predictor or risk-stratifying factor for hypertension in pregnancy remains unclear. To our knowledge, this is the first evaluation of pre-pregnancy HOMA-IR in relation to cardiovascular function, and subsequent hypertension in pregnancy, as well as the first study of its kind in healthy women to suggest pre-pregnancy insulin resistance may be more strongly associated with cardiac stiffness as opposed to arterial stiffness in a manner that impacts risk of hypertension in pregnancy. The broader implications of this work suggests a role for cardiovascular and metabolic assessment and optimization prior to conception to positively influence both pregnancy and long-term health. Further study is required to better understand the predictive value as well as long-standing impact of these pre-pregnancy sub-clinical findings on women’s reproductive and overall health.

Highlights:

Non-pregnant women with prior preeclampsia demonstrate subclinical arterial stiffness

Impaired adaptation to volume changes of pregnancy underlies preeclampsia

Hypertension in pregnancy is related to pre-pregnancy cardiovascular dysfunction

Subclinical insulin resistance is related to pre-pregnancy cardiovascular dysfunction

Abbreviations:

HOMA-IR

homeostatic model assessment for insulin resistance

BMI

body mass index

CRP

C reactive protein

HDL

high-density lipoprotein

LDL

low-density lipoprotein

DEXA

Dual-energy X-ray absorptiometry