Reviews of Progress ISSN:-2321-3485 ORIGINAL ARTICLE Vol - 1, Issue - 7, June 12 2013

SERUM LIPID PROFILES IN GESTATIONAL HYPERTENSION

N.MALLI KARJUNA RAO AND SHEEBA. M Deparment of Biochemistry, Vishnu Dental College, Bhimavaram ,India; Department of Biochemistry, G.S.L.Medical College, Rajahmundry, India. ABSTRACT: Gestational hypertension is multi factorial disorder of pregnancy affecting health of mother and fetus. To know relationship between serum lipids and gestational hypertension serum lipid levels of gestational hypertensive women were measured. Serum levels of triglycerides (TGL), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), very low density lipoprotein cholesterol (VLDLC) and high density lipoprotein cholesterol (HDLC) in 50 gestational hypertensive women and 30 normotensive pregnant women were measured by established methods. The serum lipid profiles of gestational hypertension women were compared with normotensive pregnant women. In gestational hypertension women serum TGL, TC, LDLC, VLDLC were elevated where as HDLC level was more in normotensive pregnant women. The elevated serum TGL.TC, LDLC,VLDLC and low HDLC levels may contribute to pathogenesis of gestational hypertension and lead to development of coronary artery disease. KEY WORDS: Gestational hypertension , Normotensive pregnancy, Lipoprotein cholesterol , Lipid profiles INTRODUCTION : Gestational hypertension occurs in about 6 percent of pregnancies (Yoder SR et al., 2009).Gestational hypertension is defined as systolic blood pressure 140 mmHg and/or diastolic blood pressure 90 mmHg in a previously normotensive pregnant woman who is 20 weeks of gestation and has no proteinuria and the blood pressure readings should be documented on at least two occasions at least six hours apart (Sibai
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SERUM LIPID PROFILES IN GESTATIONAL HYPERTENSION

BM, 2003; Report of the National High Blood Pressure Education Program, 2000).The rate of gestational hypertension ranges between 6% and 17% in healthy nulliparous women and between 2% and 4% in multiparous women (Knuist M et al., 1998) which is further increased in women with previous preeclampsia and in women with multifetal gestation (Baha M. Sibai, 2003). Some women with gestational hypertension will subsequently progress to preeclampsia (Barton JR et al., 2001). Gestational hypertension is multi factorial disorder of unknown etiology associated with increased risk of maternal coronary artery disease (Sattar N et al ., 1997., Ellen W Seeley,1999 ) and cesarean section, preterm delivery, and small for-gestationalage babies( Gofton EN et al.,2001). Hypertension, another multisystem disorder is characterized by multiple metabolic abnormalities including those concerning lipid profiles (Halperin O R et al.,1999). Like wise abnormal lipid profiles may play role in pathogenesis of gestational hypertension. Therefore the aim of the present study was to measure serum lipid profiles of gestational hypertension women and compare these with normotensive pregnant women lipid profiles to know any relationship exist between lipids and gestational hypertension. Meterials and Methods The present study was conducted in the department of Biochemistry (Central Laboratory) GSL Medical College and General Hospital. Selection of groups Two groups were included in the study Cases and Controls. Cases A total of 50 hypertensive pregnant women were taken up for the study with the ages 18-29 years. Only gestational hypertension patients were taken and the other types of hypertension in pregnancy like preeclampsia, chronic hypertension and preeclampsia superimposed on chronic hypertension were excluded in the present study. Controls A total of 30 age matched normotensive pregnant women were studied. Controls were defined as having a subjective perception of good health as determined by health questionnaire. Collection of Blood Samples 5 ml of venous blood was collected. The blood pressure was measured in all subjects as per the recommendations of NHBPEP(2000). Serum was separated and used for lipid testing. Serum lipids were analyzed using semi auto analyzer (Trans Asia). Serum triglyceride (TGL) was measured by ezymatic method using Accurex kit. Serum total cholesterol (TC) was estimated by enzymatic method (Allian C C et al.,1974) using kit. Serum HDL Cholesterol (HDLC) was determined by precipitation method using kit. Estimations of LDL Cholesterol (LDLC) and VLDL Cholesterol (VLDLC)was calculated from Frederickson-Friedewald's formula (Friedewald WT et al, 1972). Results A total of 80 subjects comprising of 50 hypertensive pregnant women and 30 controls were included in the present study. Measurement of blood pressure, serum total Cholesterol, serum HDL cholesterol, serum LDL cholesterol, serum VLDL cholesterol,
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SERUM LIPID PROFILES IN GESTATIONAL HYPERTENSION

and serum Triglycerides were estimated in both the groups. The results of the study were analyzed by using SPSS (software package for statistical studies). Care was taken in order to fulfill the essential characteristics of representative population in each group; cases (n=50) and controls (n=30) were investigated to avoid error due to chance. The results were expressed as Mean Standard Deviation (SD). Standard Deviation has been used to indicate whether the variation of difference of an individual from the mean is by chance. Statistical analysis was performed applying independent sample't' test to the data of independent samples for Equality of Means between the groups & Levene's Test for Equality of Variances within the group. The probability value (p) < 0.05 was considered statistically significant as this could be interpreted that the factor is less likely to occur due to chance, while a probability value(p)>0.05 was considered statistically not significant because such a difference could commonly occur due to chance and the factor under study may have no influence on the variables (Table1). Cases are in the age between 18-29 years (Mean age is 23.03). Controls are in the age between 18-27 years (Mean age is 21.53). The blood pressure is calculated separately as SBP and DBP. The mean SBP of cases is 146.410.4 mmHg and that of controls is 99.39.4 mmHg. The mean of SBP is significantly higher in cases than in controls (p<0.001). The mean DBP of cases is 88.47.1 mmHg and that of controls is 69.3.7.3 mmHg. The mean DBP of cases is higher than controls (p<0.001). (Table-1) The mean of serum total cholesterol in cases is 280.420.9 mg/dl and that of controls is 18432.7 mg/dl. The mean total cholesterol in cases is higher than that of controls (p<0.001). (Table-1, Fig.1).The mean serum TGL in cases is 222.438.62 mg/dl and that of controls is 167.1768.5 mg/dl. The mean of TGL in cases is significantly higher than in controls (p<0.001). (Table-1, Fig.1).The mean serum LDLC in cases is 204.920.8 mg/dl and that of controls is 110.424.5 mg/dl. The mean LDLC in cases is higher than in controls (p<0.001). (Table-1, Fig.1).The mean of serum VLDLC in cases is 44.327.5 mg/dl and that of controls is 33.113.7 mg/dl. The mean of VLDL is higher in cases than in controls. (p<0.001) (Table-1, Fig.1).The mean of serum HDL C in cases is 32.25.1 mg/dl and that of controls is 41.14.4 mg/dl. The mean is significantly lower in cases than in controls (p<0.001). (Table-1, Fig-2) Discussion The present study showed serum lipid elevations in gestational hypertensive patients and the results obtained from the present study showed significantly higher levels (p< 0.001) of plasma total cholesterol, TGL, LDLC, and VLDLC and significantly lower levels of HDLC levels in hypertensive pregnant women compared to the controls. Gratacos et al. (1996) showed a significantly higher levels of triglycerides, LDLC, HDLC, total lipid, apoA and apoB in hypertensive pregnancy. In our study, the results were similar to Gratacos et al's study, but were different for HDLC levels, which are decreased in our study. The total cholesterol level in gestational hypertensive cases was found to be higher (280.4mg/dl20.9) than controls (184mg/dl32.7) and the difference was statistically significant (p <0.001). These findings are in agreement with the studies reported by Cekmen MB et al. (2003) and Sattar et al. (1997). In the present study, the mean serum TGL levels of hypertensive cases (222.4mg/dl38.62) are higher than controls (167.17mg/dl68.5). This increase is statistically significant (p<0.001). It was found that serum TGL levels was more higher in hypertensive pregnancy cases than that of controls, which have also been reported in
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SERUM LIPID PROFILES IN GESTATIONAL HYPERTENSION

previous studies by Cekmen MB et al. (2003). The mean VLDLC in gestational hypertensive cases (44.32mg/dl7.5) rose significantly compared to the controls (33.1mg/dl13.7), which is due to hyper triglyceridemia leading to enhanced entry of VLDL that carries endogenous triglyceride into circulation. The increased VLDLC levels in the hypertensive pregnant women in the present study correlates with the findings of other researchers (Sattar et al., 1997). In the present study, the serum LDLC levels of gestational hypertensive cases (204.9mg/dl20.8) are significantly higher (p<0.001) and shows a 85% rise over the control group (110.4mg/dl24.5) which corroborated with the findings of other studies (Hubel et al., 1998 and Sattar et al., 1997). In addition, in the present study the mean serum HDLC levels in cases are low (32.2mg/dl5.1) while in controls were high (41.1mg/dl4.4). The HDLC levels decreased in the present study to about 21%. These findings are similar to the studies done by Kaaja R et al. (1995) and Ware JS et al. (1999). The low levels of HDLC in hypertensive pregnancy is not only because of hypo oestrogenaemia but also due to insulin resistance (Kaaja R et al., 1995). Therefore it is evident that dyslipidemia was found in gestational hypertensive patients. The elevated TC, TGL, VLDLC, & LDLC levels and reduced HDLC levels may be due to exaggerated insulin resistance and low estrogen levels which may contribute to the pathogenesis. Conclusion The present study suggests dyslipidemia in gestational hypertensive cases. The abnormal lipid metabolism particularly high triglycerides, high TC, high LDLC , and low HDLC levels may favor formation of atheromatous plaques that lead to cardiovascular disease. Therefore, it is recommended that blood lipid concentrations should be evaluated in pregnant women and gestational hypertensive women during antenatal care which may provide information to clinician about high risk pregnancies and helpful in prevention of complications .Further diets which can raise HDLC levels are recommended to gestational hypertensive women.. References Allain C C, Poon LS, Chan CSG. Enzymatic determination of total serum cholesterol. Clin Chem,1974;20:470-475. Barton JR, O'Brien JM, Bergauer NK, Jacques DL, Sibai BM. Mild gestational hypertension remote from term: progression and outcome. Am J Obstet Gynecol. 2001;184:979983. Cekmen MB, Erbagci AB, Balat A, Duman C, Maral H, Ergen K, Ozden M, Balat O, Kskay S. Plasma lipid and lipoprotein concentrations in pregnancy induced hypertension. Clin Biochem. 2003;36(7):575-8 Ellen W.Seeley. Hypertension in pregnancy: A potential window into long term cardiovascular risk in women. The J Clin Endocrinol & Met.1999;84(6) :1858-1861. Friedewald WT ., Levy RT., Frederickson DS. Estimation of VLDL and LDL Cholesterol. Clin Chem. 1972;(18): 499-502. Gofton EN, Capewell V, Natale R, Gratton RJ. Obstetrical intervention rates and maternal and neonatal outcomes of women with gestational hypertension. Am J Obstet Gynecol. 2001; 185:798-803. Gratacs E, Casals E, Sanllehy C, Cararach V, Alonso PL, Fortuny A. Variation in lipid
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SERUM LIPID PROFILES IN GESTATIONAL HYPERTENSION

levels during pregnancy in women with different types of hypertension. Acta Obstet Gynecol. 1996;75(10):896-901. Halperin O R, Sesso H D, Ma J, Buring J E, Stampfer M J, Gaziano M. Dyslipidemia and risk of incident hypertension in men. Hypertension.2006;47:45-50 Hubel C.A., Lyall F., Weissleld L., Gandley R.E. and Roberts J.M. Small low-density lipoproteins and vascular cell adhesion molecule-1 are increased in association with hyperlipidemia in pre-eclampsia.Metabolism.1998; 47(10):1281-1288. Kaaja R, Tikkanen MJ, Viinikka L, Ylikorkala O. Serum lipoproteins, insulin, and urinary prostanoid metabolites in normal and hypertensive pregnant women. Obstet Gynecol. 1995;85(3):353-6. Knuist M, Bonsel GJ, Zondervan HA, Treffers PE. Intensification of fetal and maternal surveillance in pregnant women with hypertensive disorders. Int J Gynecol Obstet. 1998;61:127. Luis B., Muriel C., Gaffney D., Silva S.A, Pereria L., Leite Changes in LDL size and HDL concentration in normal and preeclamptic pregnancy. Atherosclerosis. 2002;162:425-432. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183:S1-S22. Sattar N, Bendomir A , Berry C, Sheperd J, Greer I A, Packerd C J. Lipoprotein subfractions concentrations in preeclampsia: Pathogenic parallels atherosclerosis. Obstet Gynecol 1997;89:403-408 Sattar N., I.A. Greer., J.Louden, G.Lindsay, M.Mc Connell, J.Sheperd and C.J. Packard,. Lipoprotein subfraction changes in normal pregnancy:Threshold effect of plasma triglyceride on appearance of small ,dense low density lipoprotein. J.Clin.Endocrinol.Metab. 1997;82:2483-2491. Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol. 2003;102(1):181-192. Ware JS, Sanchez SE, Zhang C, Laraburre G. Plasma lipid concentrations in preeclamptic and normotensive peruvian women. Int J Gynecol Obstet. 1999;67:147-55. Yoder SR, Thornburg LL, Bisognano JD. Hypertension in pregnancy and women of childbearing age. Am J Med. 2009;122(10):890-895. Zicha, Jaroslav Kune and Marie-Aude Devynck. Abnormalities of membrane function and lipid metabolism in hypertension. Am J Hypertens. 1999;12:315-331.

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SERUM LIPID PROFILES IN GESTATIONAL HYPERTENSION

Table 1. The Mean , Standard deviation, Standard Error of the Mean, Level of significance, Systolic blood pressure (SBP),Diastolic blood pressure(DBP), Serum TGL, TC,LDLC,VLDLC,HDLC levels in gestational hypertensive women and normotensive pregnant women. l

N Mean Std.dev Std.Err t df iation n 0r,Mea n SBP Cases 50 146.40 10.451 1.477 20.202 78 Controls 30 99999. 9.444 1.724
33

Group

P valu e 0.00 0

Mean differenc e 47.067

DBP Cases 50 88.40 Controls 30 69.33 TC Case

7.103 7.397

1.004 1.350

11.445 78

0.00 11119.067 0 0.00 95.760 0 0.00 55.233 0 0.00 94.500 0 0.00 11.187 0 0.00 0000.8967 0

50 280.46 20.921 2.958 30 50 30 50 30 50 30 184.70 222.40 167.17 204.90 110.40 44.32

13

5.974

78

Controls TGL Cases Controls LDL Cases C Controls VLD Cases LC Controls

32.752 38.624 68.598 20.876 24.559 7.523 33333. 13.743 5.198 4.488

5.979 5.462 4.614 78 12.524 2.952 18.336 78 4.483 1.063 4.71 78 2.509 0.735 0.819 7.85 78

HDL Cases 50 32.20 C Controls 30 41.17

Figure 1. The Mean lipid profile values of gestational hypertensive women and normotensive pregnant women

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SERUM LIPID PROFILES IN GESTATIONAL HYPERTENSION

l Figure 2.The mean HDLC values of gestational hypertensive women and normotensive women.

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