Arch Gynecol Obstet (2009) 280:921–924 DOI 10.1007/s00404-009-1029-9

O R I G I N A L A R T I CL E

A new metabolic scoring system for analyzing the risk of hypertensive disorders of pregnancy Banu Dane · Cem Dane · Murat Kiray · Macit Koldas · Ahmet Cetin

Received: 21 November 2008 / Accepted: 2 March 2009 / Published online: 20 March 2009 © Springer-Verlag 2009

Abstract Objective The aim of this study was to investigate the relationship between some components of metabolic syndrome (MS) and pregnancy induced hypertension (PIH). Study design Forty-one patients with PIH (gestational hypertension or preeclampsia) after 32 weeks of gestation were compared with 97 normotensive pregnant women. Metabolic scores (0–4) were created using standard deviations in normotensive cases: mean level + 1SD for BMI (>31 kg/m2), mean level + 1SD for triglyceride (>287 mg/dl), mean level + 1SD for fasting serum glucose (>90 mg/dl)) and mean level ¡ 1SD for HDL (<48 mg/dl). Results The mean values for BMI (31.6 § 5.7 vs. 27.7 § 3.6; P < 0.0001), fasting triglyceride (341 § 129 vs. 220.7 § 67; P < 0.0001) and glucose (87.5 § 17.1 vs. 79.6 § 10.4; P = 0.0009) were higher in hypertensive group. The proportions of the women with a positive result for each of the components were signiWcantly higher in the group of PIH. The percentage of the cases having 2 (35.2 vs. 8.2%; P = 0.0002) and 3 or more (27 vs. 4.1%; P = 0.0003) components of MS was higher in the hypertensive group and the percentage of the cases with none of these factors was high in the normotensive group (10.8 vs. 56.7%; P < 0.0001). B. Dane · C. Dane · M. Kiray · A. Cetin Department of Gynecology and Obstetrics, Haseki Training and Research Hospital, Istanbul, Turkey M. Koldas Department of Biochemistry, Haseki Training and Research Hospital, Istanbul, Turkey B. Dane (&) Emlakbank Bloklari B:1 D:12, Vatan Caddesi Fatih, 34019 Istanbul, Turkey e-mail: [email protected]

Conclusion The presence of multiple components of MS may be a risk factor in the development of PIH. New scoring systems according to the gestational age might be useful in analyzing the risk of PIH. Keywords Metabolic syndrome · Pregnancy induced hypertension · Preeclampsia · Metabolic scoring

Introduction The metabolic syndrome (MS) is a major risk factor for cardiovascular and metabolic diseases [1, 2]. Normal physiologic adaptations of pregnancy, including increased insulin resistance and hyperlipidemia are also considered to be risk factors for cardiovascular disease [3]. Many of the individual risk factors that compose MS also have been noted to be risk factors in the development of preeclampsia (PE) and eclampsia [4, 5]. The National Cholesterol Education Program–Adult Treatment Panel III Guidelines (NCEP-ATP III) deWne metabolic syndrome as the presence of 3 or more of the following 5 risk factors: abdominal obesity, high level of triglycerides, low level of high-density lipoprotein (HDL) cholesterol, high blood pressure, and high fasting glucose [6]. Women with high glucose and insulin levels were found to be more likely to develop PE [7]. Increased prepregnancy BMI is reported as an important risk factor [8, 9], and a previous report reviewing the literature showed also the correlation of hypertriglyceridemia with the development of PE [10]. Almost all of the previous studies examined the individual components of MS during pregnancy, but in a recent study from Mazar et al. [11], the relationship of MS and PE

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was evaluated by creating metabolic scores using body mass index, presence of chronic hypertension, and diabetes. They concluded that metabolic score appeared to be associated independently with developing PE, particularly severe disease. Pregnancy induced hypertension (PIH), which includes both gestational hypertension (GHT) and PE, is a morbid pregnancy complication. In the absence of severe disease manifestations, discrimination between PE and gestational hypertension may be diYcult [12] and in the presence of severe GHT the risk of adverse perinatal outcomes is reported to be higher than in mild PE [13]. The aim of our study was to investigate the relationship between the clinical and laboratory components of MS and PIH and to create a metabolic scoring system for the cases at third trimester.

Materials and methods We studied 169 pregnant women. We compared forty-one cases after 32 weeks of gestation which were found to have PIH in 97 healthy women with uncomplicated pregnancy. Twenty-one of the cases were lost from follow-up. They were admitted to our clinic for antenatal care during the same period. Patients with lipid-altering diseases (hepatobiliary lesions, nephritic syndrome, and hypothyroidism) and pre-existing history of hypertension were excluded from the study. Verbal informed consent to participate in the study was obtained from the patients. The study was approved by the Local Ethical and Research Committees. Collection of the data Information on age, parity, gestational age, and family history of hypertension and diabetes were recorded at Wrst visit. The main outcome measures included plasma lipids, glucose, and body mass index levels. Body mass index was calculated based on measured maternal weight and height. Fasting levels of plasma glucose, triglyceride, and HDL were determined at time of the antenatal visit or in the following morning. Maternal blood pressure was recorded at each antenatal visit until delivery. DeWnitions Blood pressure recording of >140/90 mmHg on >2 occasions for at least 4-h intervals after week 20 of pregnancy was termed as GHT. Proteinuria was considered on the basis of >300 mg protein per 24 h that were assessed by 24h urine collection. Women with GHT (non-proteinuric PIH) and women with PE (proteinuric PIH) were then placed into the PIH group.

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As the components of MS are increasing with maternal and gestational age, cutoV values for metabolic scores were created using standard deviations in normotensive group (n = 97): mean level + 1SD for BMI (>31 kg/m2),mean level + 1SD for triglyceride (>287 mg/dl), mean level + 1SD for fasting serum glucose (>90 mg/dl) and mean level-1SD for HDL (<48 mg/dl). Each variable was dichotomized as yes/no, and could present one point. We categorized women as having zero, one, two, three or four features of MS. This score was collapsed to 0, 1, 2 and 3 or more for analyses, given that only four women were observed to have a value of 4. Statistical analysis Data entry and analysis were performed with use of the MedCalc for Windows, version 8.1.00 (MedCalc Software, Mariakerke, Belgium). Continuous variables are presented as mean and standard deviation, while categorical variables are presented as percentages. DiVerences between groups were compared using independent t test (2-tailed).

Results The mean BMI, fasting serum TG and glucose levels were signiWcantly high in cases with PIH (Table 1). Ten of the cases with PIH (24.4%) were also found to have proteinuria. The mean values of the components did not show any signiWcant diVerence between the groups with or without proteinuria. The cases with PE were found have signiWcantly higher mean systolic and diastolic blood pressure (Table 2). The proportions of the women with positive results for each of the components were signiWcantly higher in the group of PIH (Table 3).The percentage of the cases with 2 and 3 or more components of MS was signiWcantly higher in the hypertensive group and the percentage of the cases

Table 1 Mean values (§SD) and signiWcance of the diVerence between some clinical laboratory Wndings of cases and controls Normotensive (n = 97)

Hypertensive (n = 41)

Maternal age (years)

30.4 § 3.9

31.8 § 4.9

0.077

Gestational age (weeks)

35.1 § 2

35.8 § 2.2

0.07

27.7 § 3.6

31.6 § 5.7

<0.0001*

220.7 § 67

341 § 129

<0.0001*

2

BMI (kg/m ) Triglyceride (mg/dl)

P value

HDL (mg/dl)

61.4 § 13.3

57.2 § 14.7

0.1

Glucose (mg/dl)

79.6 § 10.4

87.5 § 17.1

0.0009*

BMI Body mass index * P < 0.05 is signiWcant

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Table 2 Mean values and signiWcance of the diVerence between the hypertensive cases with or without proteinuria GHT (n = 31) BMI (kg/m2)

31.7 § 5.4

Triglyceride (mg/l)

328 § 129

PE (n = 10) 31.4 § 6.9 379.3 § 130.4

P value 0.88 0.28

HDL (mg/dl)

57.9 § 15

52.1 § 9.2

0.25

Glucose (mg/dl)

85.6 § 17.8

93.6 § 13.6

0.2

Diastolic blood pressure (mmHg)

93.2 § 4.7

100 § 6.6

0.0009*

Systolic blood pressure (mmHg)

144.5 § 12

160 § 23,5

0.0087*

BMI Body mass index * P < 0.05 is signiWcant

Table 3 Comparison of the components of MS between normotensive and hypertensive cases Component

Normotensive (N = 97)

Hypertensive (N = 41)

P value

BMI >31 kg/m2

16.5% (16)

53.6% (22)

<0.0001*

TG >287 mg/l

18.5% (18)

65.8% (27)

<0.0001*

HDL <48 mg/dl

13.4% (13)

36.5% (15)

0.0043*

Glucose >90 mg/dl

11.3% (11)

36.5% (15)

0.0013*

0

56.7% (55)

10.8% (4)

<0.0001*

1

31% (30)

27% (11)

0.79

2

8.2% (8)

35.2% (13)

0.0002*

3 or more

4.1% (4)

27% (13)

0.0003*

Metabolic score

TG triglyceride, BMI body mass index * P < 0.05 is signiWcant

with none of these factors was higher in the normotensive group (Table 3).

Discussion The risk factors of metabolic syndrome have been investigated in various combinations [14]. There is a lack of consensus on which components are fundamentally necessary and most clinically relevant for diagnosis [15]. Current deWnitions of the metabolic syndrome cannot be used during pregnancy as the normal physiology of pregnancy includes several components of MS. In this study, we found a relationship between the presence and combination of the components of MS and PIH by using a new scoring system. Previous studies have reported that diVerences in triglyceride levels between preeclamptics and controls have tended to be larger than diVerences in other lipids [16, 17]. The Wndings of the study from Bodnar et al. [18] suggested that approximately one-third of the total eVect of body mass

index on PE risk is mediated through inXammation and triglyceride levels. Although the authors do not advocate measuring TG in clinical practice, a recent study presented hypertriglyceridemia as a major feature of the metabolic syndrome positively correlated with the development of PE [10]. In our study we also found a higher mean triglyceride level in cases with PIH and the proportion of the cases above the cutoV was also higher in this group. The mean HDL level did not show any signiWcant diVerence between hypertensive and normotensive cases. Also in the study from Isezuo et al. [5], the HDL levels were found not to be associated with eclampsia. But the percentage of the cases below the cutoV was signiWcantly higher in the group of PIH. The mean value of fasting glucose was signiWcantly higher in the group of PIH in our study population. In the deWnition of MS according to WHO and NCEP-ATP III, a cut oV level of 105 mg/dl for fasting glucose was proposed for pregnant women [19]. But in the recent study of Hyperglycemia and Adverse Outcome (HAPO) Study Cooperative Research Group, the authors calculated adjusted odds ratios for adverse pregnancy outcomes associated with an increase in the plasma glucose levels of 1 SD (fasting plasma level >89 mg/dl), and they found a signiWcant association for PE with the glucose levels below those diagnostic of diabetes [20]. We also used a new cutoV for fasting plasma glucose (>90 mg/dl) which was calculated from the data of the group (mean + 1SD) of normotensive pregnant women at the same gestational and maternal age. The proportion of the women with a glucose level above this cutoV was also signiWcantly higher in the group of the cases with PIH. The inclusion of patients with diVerent types of PIH in a single group could lead to bias. Although there are diVerences, PE and GHT were reported to be sharing many risk factors [21]. The prevalence of MS was also found to have almost the same prevalence (35% in GHT and 30% in PE) in cases of GHT and PE in a previous study [19]. The mean levels of the components were also comparable between the groups of PE and non-proteinuric hypertensive patients in our study. Therefore, we decided to include the cases with diVerent types of PIH in the same group. Although the usual onset of PIH is in late pregnancy, a time when the insulin resistance characteristic of pregnancy is maximal, the cases in high risk could be detected before the onset [12, 22, 23]. Parretti et al. [24] reported that the determination of insulin resistance might be useful in predicting the development of PE even in early pregnancy, before the disease become clinically evident. In our study, we included only the hypertensive cases after 32 weeks of gestation; new studies about the presence of the components of MS at early gestation or prepegnancy might be valuable in predicting PIH [25].

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The persistent relative elevation of blood pressure in the non-pregnant state in cases of PE was detected in previous studies [26, 27]. Despite the fact that none of our cases was receiving antihypertensive before 20 weeks of gestation, the information about their pregestational blood pressure was collected from the patients and this may be a bias of this study. Another limitation is the small number of the cases. In this study, we demonstrated the association between the presence of some clinical and laboratory components of MS and PIH by using a new metabolic scoring system including new cut oV values. We suggest that this new system might be useful in assessing the individual risk of PIH at third trimester. ConXict of interest statement

None.

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