Hypertension and metabolic abnormalities later in life after preeclampsia

Abstract

Aim: The present study examined Japanese women who had preeclampsia 10 or more years earlier, and documented the frequency of hypertension as well as their current clinical and chemical characteristics.

Methods: We recruited 119 women for whom 10 or more years had passed since an indexed pregnancy (58 with a history of severe preeclampsia and 61 with normal pregnancies). A physical examination assessed blood pressure, weight, abdominal circumference (AC) and other compositional indices. Fasting blood samples were examined for glucose, total cholesterol (TCHOL), high and low density lipoprotein cholesterol (HDLC, LDLC), and triglycerides (TG). A questionnaire was used to collect demographic data. Data were analyzed using the Student’s t-test.

Results: The frequency of hypertension later in life was significantly higher in the preeclampsia group compared to the control (53.4% versus 11.5%, P=0.013). Body mass index (BMI), AC, and levels of TCHOL, TG and LDLC were significantly higher in the group of patients with preeclampsia who did not have hypertension later in life (P<0.05), and there were no significant differences in the levels of glucose and HDLC. Despite the lack of evidence for hypertension, metabolic abnormalities were observed later in life in those who experienced preeclampsia during pregnancy.

Conclusions: Since hypertension after preeclampsia was associated with metabolic abnormalities, those who experienced preeclampsia should schedule regular check-ups to monitor for clinical manifestations of hypertension.

Introduction

Preeclampsia is a disease characterized by endothelial dysfunction, systemic inflammation, and insulin resistance in pregnant women.^1,2,3,4) While preeclampsia is traditionally considered a disease that resolves completely after delivery of the fetus and the placenta, more recent evidence indicates that women with a history of preeclampsia appear to be at a significantly increased risk for developing cardiovascular disease (CVD) later in life.^5,6,7) For example, primigravid women with preeclampsia who were evaluated 17 years after the pregnancy presented a positive association with elevated insulin resistance and blood pressure levels.⁸⁾

Insulin resistance, which may be a cause or consequence of preeclampsia, contributes to an increased risk of CVD, and yields a higher likelihood for developing diseases such as diabetes mellitus (DM), high systemic arterial pressure and ischemic coronary disease.^8,9) Although several risk factors, such as positive family history of CVD, low levels of physical activity, obesity and high body mass index (BMI) have been traditionally recognized, it remains unclear whether preeclampsia and the traditional risk factors for CVD interact to compound the risks for CVD, especially in Japan.

In this study, we examined the frequency of hypertension among Japanese women who had preeclampsia during their pregnancies 10 or more years prior to this study. We evaluated current clinical and chemical characteristics as a way to assess their status later in life.

Materials and methods

Study population

We selected patients with severe preeclampsia who delivered at Hachioji Medical Center of Tokyo Medical University between 1993 and 2001. Normotensive controls comprised normotensive pregnant women who delivered the same year as the women in the preeclamptic group. Control subjects were matched as a group for age, parity, pre-pregnancy BMI, smoking habits and family history of DM, CVD and preeclampsia identified from medical records. Patients who had CVD prior to pregnancy were excluded.

Diagnosis of severe preeclampsia

Severe preeclampsia was defined as a blood pressure ≥160/110 mmHg and proteinuria ≥2+(2 or more episodes, 2 times). Blood pressure levels for all subjects had returned to normal levels within 12 weeks after delivery.

Study subjects

Invitation letters were sent to the patients of the study population. Those who visited the hospital were informed of the study objectives. Written informed consent was obtained from all patients who agreed to participate in the study.

Data collection

Demographic data were obtained by using a questionnaire on age, parity, smoking habits, daily physical activities including exercise routines and any family history of DM, CVD, and preeclampsia. A physical examination was performed to measure blood pressure, height, weight, abdominal circumference (AC) and hip circumference (HC). Blood pressure was measured with the cuff over the bandage around the left arm with patients in a sitting position following a >30-minute resting period, and calculated as the average of two measurements. AC was recorded at the minimal waist, and HC was measured at the largest horizontal expansion of the buttocks using a flexible tape measure. BMI, AC/HC ratio and AC/height ratio were calculated.

All patients underwent a laboratory examination after 12 hours of fasting, which assessed blood glucose, triglycerides (TG), total cholesterol (TCHOL), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDLC). Blood glucose, TCHOL, HDLC, LDLC, and TG were measured by an automated colorimetric enzymatic method using an Olympus AU5400 (Olympus Company, Japan). The study protocol was approved by the Research Ethics Committee of the Hachioji Medical Center of Tokyo Medical University.

Statistical analyses

GraphPad Prism 6 (GraphPad Software Inc. CA, USA) was used for all statistical analyses. Clinical and chemical variables are presented as mean±standard deviation (SD) and categorical variables as number and percent. Student’s t-test and Chi-square test were used to compare clinical data between the preeclampsia and control groups, and to compare chemical data between the control group and the preeclampsia group that did not have hypertension later on in life.

Statistical differences for which P<0.05 were considered statistically significant.

Results

We examined a total of 119 patients (58 with preeclampsia and 61 controls) who delivered at Hachioji Medical Center of Tokyo Medical University between 1998 and 2001. Patient clinical characteristics are shown in Table 1. Mean patient ages at the time of study enrollment did not differ significantly between the control (39.54±10.26 years) and preeclampsia groups (38.26±12.63 years). Mean time elapsed since delivery was 12.3±3.17 years in the preeclampsia group and 12.7±3.33 years in the control group.

Table 1. Clinical charactors of subjects

	Preeclampsia group	Control group	P value
Numbers of group	58	61	n.s.
Age	38.26±12.63	39.54±10.26	n.s.
Parity	0.896±1.344	0.874±1.286	n.s.
Age at delivery	27.37±3.44	28.13±4.26	n.s.
Elapse time from delivery	12.3 ±3.17	12.7 ±3.33	n.s.
Smoking habit	6 (10.3%)	6 ( 9.8%)	n.s.
Exercise routines	21 (36.2%)	27 (44.3%)	n.s.
Frequency of the later hypertension	31 (53.4%)	7 (11.5%)	0.013
Family history of
DM	7 (12.1%)	6 (19.4%)	n.s.
CVD	5 ( 8.6%)	3 ( 9.7%)	n.s.
preeclampsia	2 ( 3.4%)	3 ( 4.9%)	n.s.
Pre-pregnant BMI (kg/m2)	24.66±5.88	23.78±4.62	n.s.
BMI (kg/m2)	28.93±3.78	25.43±3.06	0.024
AC (cm)	92.85±7.86	78.65±8.65	0.017
AC/HC ratio	0.846±0.069	0.894±0.078	n.s
AC/height ratio	0.513±0.048	0.473±0.054	n.s
Systolic BP (mmHg)	127.6±18.8	122.2±14.2	n.s.
Diastolic BP (mmHg)	88.7±12.86	70.55±14.25	0.023
Disease in the later life
DM	0 (0%)	0 (0%)	n.s.
CVD	3 (5.2%)	2 (3.3%)	n.s.
stroke	0 (0%)	1 (1.6%)	n.s.

DM; diabetes mellitus, CVD; cardiovascular disease

BMI; body mass index, AC; abdominal circumference HC; hip circumference,

BP; blood pressure, n.s.; not significant

The women in the preeclampsia group had significantly higher mean BMI, AC and diastolic blood pressure compared to women in the control group. Parity and smoking habits did not differ significantly between the two groups. Twenty-one women in the preeclampsia group (36.2%) and 27 women in the control group (44.3%) exercised habitually. Frequency of hypertension later in life was significantly higher in the preeclamptic group (53.4%) relative to the control (11.5%) (P=0.013). The two groups did not differ significantly in terms of their family histories of DM, CVD, or preeclampsia.

Table 2 shows chemical data for patients within the preeclampsia group, and compares those who developed hypertension later in life to those who did not, as well as to the control patients. Levels of TCHOL, TG and LDLC were significantly higher in the preeclampsia groups than those in the control group, but within the preeclampsia group, no significant difference was apparent between those with hypertension later in life and those without. Within the preeclampsia group, frequency of abnormal values in patients without hypertension later in life was significantly higher for BMI, AC, blood glucose, TCHO, LDLC and TG (Table 3).

Table 2. Chemical data of preeclampsia without the later hypertension group and the control group

	Preeclampsia with the later hypertension group	Preeclampsia without the later hypertension group	Control group	P value
Number of the group	15	16	31
Fasting glycemia (mg/dl)	93.65±11.15	91.27± 9.87	92.65±10.25	n.s.
TCHOL(mg/dl)	208.64±31.14*	205.54±27.18*	198.78±25.15	P<0.05
HDL (mg/dl)	52.14±13.27*	54.67±13.17*	51.68±12.13	n.s.
LDL (mg/dl)	129.25±29.15	138.68±32.15	101.81±33.27	P<0.05
Triglyceride (mg/dl)	119.13±34.23*	115.69±47.18*	108.78±32.13	P<0.05

BUN; blood urea nitrogen, Cr; creatinine, UA; uric acid, (TCHOL; total cholesterol, HDL; high-density lipoprotein-cholesterol, LDL; low-density lipoprotein-cholesterol, n.s.; not significant, *; significantly different versus Control group

Table 3. Frequency of abnormal value

	Preeclampsia without the later hypertension group (n=27)	The control group (n=61)
BMI	18 (66.7%)	16 (26.2%)	0.026
AC	15 (55.6%)	13 (21.3%)	0.023
AC/HC ratio	8 (29.6%)	17 (27.9%)	n.s.
Fasting glycemia	1 ( 3.7%)	0 (   0%)	n.s.
TG	8 (29.6%)	4 ( 6.5%)	0.015
TCHOL	5 (18.5%)	7 (11.5%)	n.s.
HDLC	5 (18.5%)	8 (13.1%)	n.s.
LDLC	6 (22.2%)	9 (14.8%)	n.s.
Metabolic syndrome by NCEP III	2 ( 7.4%)	2 ( 3.3%)	0.043

Normal values: fasting glycemia <110 mg/dl, TG (triglycerides) <150 mg/dl, TCHOL (total cholesterol) <200 mg/dl, HDL (high density lipoprotein cholesterol); <40 mg/dl is low and >60 mg/dl is high, LDL (low density lipoprotein cholesterol) <160 mg/dl AC/HC ratio; 0.85, AC (abdominal circumference) >88 cm.

Discussion

In our study of 58 women with a history of severe preeclampsia 10 or more years prior to the study, occurrence rate of hypertension later in life reached 53.4%. This is significantly higher than the 20.2% prevalence of hypertension recorded in the general population of Japanese women aged 40–49 years.¹⁰⁾ This shows that Japanese women were also at a higher risk for hypertension later in life after a pregnancy complicated with preeclampsia as the same as the women in the foreign countries ever reported.^5,6,7)

Irgens et al. demonstrated that mortality by CVD is 1.2 times greater among patients with preeclampsia and 8.2 times greater in cases of acute preeclampsia, compared to those without it.⁵⁾ In a study of women who had preeclampsia 15–19 years prior to their study, Smith et al. found that these women exhibited twice the likelihood for hospital admission and death due to ischemic heart disease relative to pregnant women without preeclampsia.⁶⁾ In a retrospective study¹¹⁾ of 1.03 million women in Canada, still others identified a risk of CVD that was twice as great among pregnant women with some type of placental syndrome (hypertensive gestational disease, placental abruption or preeclampsia) than among pregnant women without placental syndromes. Other authors have also reported that history of preeclampsia was correlated with more frequent CVD.^8,12,13,14) Moreover, preeclampsia is considered to correlate not only with CVD but also with other diseases including stroke,¹⁵⁾ peripheral arterial disease¹²⁾ and metabolic syndrome.^16,17) In the context of complications following preeclampsia, metabolic syndrome is receiving significant attention from many researchers as a critical link between preeclampsia and later complications.^{3,4,8,13,16,17,18,19,20,21,22)}

In this study, very few subjects fulfilled the criteria for metabolic syndrome by NCEP III,²³⁾ but the BMI and AC were significantly higher among women in the preeclampsia group, even though AC/HC ratios and AC/height ratios did not differ significantly from that of the control group, which may indicate the presence of abdominal fat. The chemical examination data also suggest that several metabolic abnormalities were present even in the group of women with preeclampsia without hypertension later in life. Both abdominal fat distribution and abnormal metabolic readings are risk factors for CVD, hypertension and insulin resistance.^24,25) While 39.7% of preeclampsia patients had hypertension at the time of this study, more patients had metabolic abnormalities according to the clinical and chemical findings. Thus, within the preeclampsia group, even if some patients did not have chronic hypertension at the time of the study, it is possible that they could develop it later on. Metabolic abnormalities greatly influence preeclampsia and complications after preeclampsia, so medical check-ups after preeclampsia are needed, regardless of whether clinical findings of hypertension are observed or not.

Currently, medical check-up protocols and schedules remain controversial in Japan. The “Boshi kenkou techou (Mother and baby health handbook)” is used in Japan to record blood pressure and proteinuria measurements (among other things) throughout the pregnancy, and could be very instrumental towards health management in hypertensive women. A similar system may be effective for health management after preeclampsia.

The present study results are limited by the small sample size, and do not provide a prognosis or management strategies for later in life for those who experience preeclampsia. Larger prospective studies are required to establish preventive strategies for chronic hypertension and other complications after preeclampsia.

Conflict of interest

None.

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