Hypertensive disorders of pregnancy complicate around 5-10% of all pregnancies [1]. It is one of the major causes of maternal & perinatal morbidity and mortality. [2,3] These diverse conditions include chronic hypertension, gestational hypertension, pre-eclampsia, pre-eclampsia superimposed on chronic hypertension. Hypertensive illnesses accounts for over 10% of all maternal deaths. [4] It has been observed that roughly 10% of first pregnancies experience hypertensive disorders. [1]

Diastolic blood pressure in a typical pregnancy starts to decline in the first trimester and keeps going down until it reaches between weeks 22 and

24. Then, by term, it rises steadily to the prepregnant levels. The decreased vascular tone, which causes peripheral vasodilatation, is the cause of this fall. The vasospastic phenomenon found in PIH is caused by altered lipid synthesis, which lowers the PGI 2: TXA2 ratio, in the kidney, uterus, placenta and brain. [5] In all cells and organs, lipid peroxidation takes place at low levels. In optimal health, free radical oxidation and antioxidant neutralization are in equilibrium. Oxidative stress happens when there are lots of reactive oxygen species (ROS) and it's assumed that this is the factor that causes PIH. [6] Changes in lipid profiles are caused by the mother's body experiencing several hormonal and metabolic changes during pregnancy. Studies have shown that in healthy pregnant women, the levels of blood total cholesterol (TC), serum triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) rise with increasing gestational age. Reduced PGI2:TXA2 ratio as a consequence of modified lipid synthesis is thought to be the etiology of PIH. [5] Bizarre lipid metabolism is associated with PIH. [7]

 Early detection of pregnancies at risk could facilitate the creation of novel approaches to prenatal surveillance, allowing for the earlier detection of illness and the appropriate intervention to improve maternal and neonatal outcomes. Pregnancy-related lipid physiology and pathology have not been thoroughly investigated in larger population-based cohorts. Therefore, the goal of the current study is to assess the association between pregnancy-induced hypertension and dyslipidemia.

The present longitudinal and prospective study was conducted in the Obstetrics and Gynaecology department OPD at Dr. D.Y. Patil Medical College, Hospital & Research Institute, Kolhapur, after institutional ethical committee approval from December, 2022 to May, 2024. A total of 98 patients satisfying the inclusion and exclusion criteria were involved in the study.

Inclusion criteria: Primigravida and multigravida with a singleton pregnancy with 14–20 weeks as determined by LMP or scan.

Exclusion criteria Multiple pregnancy, chronic diseases (chronic hypertension, diabetes mellitus, severe anemia, grade III and Grade IV heart disease, renal disease), previous h/o dyslipidemia or on treatment, patients with bad obstetric history, smoking, Molar pregnancy, H/o hypertensive disorder in a previous pregnancy.

METHODOLOGY

Study was conducted at the Obstetrics and Gynaecology department OPD of D.Y Patil Hospital, after the approval of the Ethical committee and after taking the required written, informed and valid consent. Study period is from December, 2022 to May, 2024.

After taking detailed history and clinical examination, venous blood samples were collected from all the patients for the measurement of the lipid profile during 14 to 20 weeks of gestation for analysis.

Samples from all subjects were collected after a minimum of 8 hrs of overnight fasting. After the clot retracts, the sample was centrifuged at 4000 rpm for 5 min for the serum to get separated and stored at 4°C pending assay. Lipid profile estimation was done by enzymatic spectrophotometry.

Patients were followed up 4 weekly till 28 weeks,2 weekly till 36 weeks and every week till delivery for the development of PIH. BP and urine protein was recorded at each visit.

A total of 98 patients satisfying the inclusion and exclusion criteria were involved in the study. Their fasting lipid profile was sent to the lab during their antenatal visit in the second trimester and results were tabulated and analysed. Patients were followed up 4 weekly till 28 weeks,2 weekly till 36 weeks and every week till delivery for the development of PIH. BP and urine protein was recorded at each visit.

The patients who developed PIH or pre-eclampsia were grouped as hypertensive cohort. And the rest of the patients who remained normotensive till delivery were grouped as normotensive cohort.

The factors that were analysed were age, parity, gestational age, mode of delivery, total cholesterol, HDL, VLDL, LDL and BMI.

AGE DISTRIBUTION

Patients who were willing to participate in the study and fulfilled the inclusion criteria were enrolled for the study. Out of 98 patients selected for the study,32 were found to have hypertension and 66 were normotensive. The age groups of the patients were tabulated and compared. There was no significant statistical correlation between them.

There were 12 patients (37.5%) in the hypertensive group between the age of 21 and 25. Thirteen patients (40.6%) in the age group of 26-30 and seven patients (21.8%) above the age of 30. In the normotensive group there were 16 (24.2 %) patients between the age of 21 and 25. Thirtythree patients (50 %) were aged between 26 and 30. There were 17 patients (25.7 %) above the age of thirty.

OBSTETRIC SCORE OF PATIENTS IN THE STUDY

There were 23 primigravidas in the hypertensive group (71.8%) and 44 in the normotensive group (66.6%). There were 9 multigravidas in the hypertensive group (28.2 %) and 22 in the normotensive group (33.4 %)

TABLE 1: DISTRIBUTION OF PARITY

Gestational age

The gestational age at which blood sample was collected for measurement of lipid profile was tabulated for each patient. The mean gestational age in the second trimester for hypertensive group was 16.6 weeks and for the normotensive group was 17.1 weeks.

As all the patients were in their second trimester there is no statistical significance between outcome and gestational age.

TABLE 2: GESTATIONAL AGE

MODE OF DELIVERY

In the hypertensive group 13 patients underwent LSCS,10 had spontaneous vaginal delivery,8 had induced vaginal delivery and one patient had a prolonged vaginal delivery. In the normotensive group 20 patients underwent LSCS,17 had spontaneous vaginal delivery,23 had induced vaginal delivery and six patients had a prolonged vaginal delivery.

TOTAL CHOLESTEROL

The lipid profile was analysed for every patient and a value above 200 mg/dL was considered as deranged.

The mean total cholesterol for the hypertensive group was 216 with a standard deviation of 24.3. There were 24 patients out of 32 (75 %) who had elevated levels of total cholesterol in this group. The mean total cholesterol for the normotensive group was 187 with a standard deviation of 26.15. There were 18 patients out of 66 (27 %) who had elevated levels of total cholesterol in this group (27.2 %).

Odd’s ratio - 8

CI - 3.044 to 21.025

Chi square - 4.21 P value -0.00012

Since p value less than 0.05 we can understand that there is significantly higher number of patients with elevated total cholesterol in the hypertensive group compared to the normotensive group.

GRAPH 2: TOTAL CHOLESTEROL

HDL

The mean HDL for the hypertensive group was 38.5with a standard deviation of 7.5. There were 23 patients out of 32 (71.8 %) who had elevated levels of HDL in this group.

The mean HDL for the normotensive group was 45.4with a standard deviation of 8.8. There were 20 patients out of 32 (62.5 %) who had elevated levels of HDL in this group.

An inverse relationship between HDL and hypertension in the second trimester is seen. As the levels of HDL decreases there are more chances of finding hypertension in those patients.

Odd’s ratio - 7.66 CI - 3.049 to 19.275

Chi square - 4.3, P value - 0.00007

Since p value less that 0.05 we can understand that there is significantly higher number of patients with decreased HDL levels in the hypertensive group compared to the normotensive group.

LDL

The mean LDL for the hypertensive group was 137 with a standard deviation of 12.54. There were 24 patients out of 32 (75 %) who had elevated levels of LDL in this group.

The mean LDL for the normotensive group was 116 with a standard deviation of 9.07. There were 17 patients out of 66 (25.7 %) who had elevated levels of LDL in this group.

A directly proportional relationship between LDL and hypertension in the second trimester is seen. We can come to the inference that as the levels of LDL increases there are more chances of finding hypertension in those patients.

Odd’s ratio - 8.6

CI - 3.272 to 22.854

Chi square - 4.35 P value - 0.00007

TRIGLYCERIDES

The mean T.G level for the hypertensive group was 203.84 with a standard deviation of 24. There were 19 patients out of 32 (59.3 %) who had elevated levels of triglycerides in this group.

The mean T.G level for the normotensive group was 158.7 with a standard deviation of 26.9. There were 23 patients out of 66 (34.8 %) who had elevated levels of triglycerides in this group.

A directly proportional relationship between triglyceride levels and hypertension in the second trimester is seen. We can come to the inference that as the levels of triglycerides increases there are more chances of finding hypertension in those patients.

Odd’s ratio - 3.36

CI - 1.427 to 7.948

Chi square - 2.7 P value - 0.002

VLDL

The mean VLDL level for the hypertensive group was 36.5 with a standard deviation of 4.6. There were 22 patients out of 32 (68.75 %) who had elevated levels of triglycerides in this group.

The mean VLDL level for the normotensive group was 32.4 with a standard deviation of 5.4. There were 15 patients out of 66 (22.7%) who had elevated levels of triglycerides in this group.

A directly proportional relationship between VLDL levels and hypertension in the second trimester is seen. We can come to the inference that as the levels of VLDL increases there are more chances of finding hypertension in those patients.

Odd’s ratio - 7.48 CI - 2.91 to 19.2

Chi square - 4.18 P value - 0.00001

BMI

The heights and weights of patients were measured during their second trimester antenatal visit and BMI was calculated. The average BMI of the hypertensive group was found to be 26.2 and that of the normotensive group was 23.4. A significant increase in BMI is evident in the hypertensive group.

TABLE 3: BODY MASS INDEX

RELATIONSHIP BETWEEN TOTAL CHOLESTEROL AND BMI

                         TABLE 4: TOTAL CHOLESTEROL AND BMI

Using the two tailed T test, the p value between BMI and total cholesterol of the hypertensive group tends to be very small and hence there is statistical significance between total cholesterol levels and the patients BMI.

Pregnancy-related hypertension disorders rank second in terms of medical prevalence. In conjunction with infection, it plays a major role in maternal mortality and morbidity [8].

Pre-eclampsia is a common condition in pregnancy and is strongly associated with morbidity and mortality in mothers prenatally and perinatally also [9].

The mother experiences several physiological changes during pregnancy.

This includes modifications to renal and cardiovascular function to meet the evolving needs of both the mother and the developing fetus. Normal pregnancy changes include the following:

An increase in maternal cardiac output and volume of blood by 40- 50% [10,11,12].

Decrease in total peripheral resistance and arterial blood pressure.

An increase of renal plasma flow and GFR by 30-40% [13].

Increase in renin levels, activity of renin and angiotensin-II levels [14]

A decrease in vascular responsiveness to angiotensin-II

But in women with PIH, these alterations don't happen. Renal plasma flow and GFR are decreased, peripheral resistance is elevated and vascular reactivity to angiotensin-II is enhanced. It is commonly established that essential hypertension and alterations in the serum lipid profile are linked. Hormonal imbalance is assumed to be the main cause of pregnancy-induced hypertension (PIH), which alters blood lipid profiles.  Changes in lipid synthesis in the kidney, uterus, placenta and brain lower the PGI 2: TXA2 ratio, which in turn causes the vasospastic phenomena associated with PIH. Low amounts of lipid peroxidation occur in all cells and tissues. Antioxidant neutralization and free radical oxidation are in balance in optimal health.

Reactive oxygen species (ROS) are the cause of oxidative stress, which is thought to be the cause of peripheral ischemic heart disease. Changes in lipid profiles are caused by the mother's body going through several hormonal and metabolic changes during pregnancy. Studies have shown that in healthy pregnant women, the levels of blood total cholesterol (TC), serum triglycerides (TG) and low-density lipoprotein (LDL) rise with increasing gestational age.

The vitals, height, weight, BMI, detailed history of the current and previous pregnancies was noted for all patient who were enrolled in the study. The lipid profile during the second trimester were sent for all patients and they were divided into two groups based on their blood pressure as hypertensive and normotensive. The hypertensive group had 32 patients and the normotensive group has 66 patients.

There were 32 patients in the hypertensive group and 66 in the normotensive group in our study. Comparing to the studies published by Kumari et al, Nidhi et al, Singh et al our sample size in each group is comparable. In the study by Surbhi et al more number of participants in the study belonged to the hypertensive group.

The average age in our study was found to be 28.08 ± 3.48 years. This was comparable to the other studies. The age of the patient and development of hypertension did not have any statistical relationship. The mean age for the hypertensive group was 27.8 and for the normotensive group was 28.3 years.

In this study we have seen an increased number of primigravidas developing hypertension during the second trimester of pregnancy.  In our study 71.8 % of the patients in the hypertensive group were primigravidas.

Mode of delivery:

All the patients enrolled in the study were followed upto delivery and the mode of delivery was tabulated. Of the 32 patients in the hypertensive group 13 underwent LSCS and the remaining 19 had vaginal deliveries of which 8 were induced 10 were spontaneous and 1 was a prolonged vaginal delivery.Of the 66 patients in the normotensive group, 20 underwent LSCS and the remaining 46 had vaginal deliveries of which 23 were induced,17 were spontaneous and 6 were prolonged vaginal deliveries.

Lipid profile

Total cholesterol:

There were 18 patients out of 66 (75 %) who had elevated levels of total cholesterol in this group (27.2 %). These values were comparable to peer studies and was statistically significant, indicating that there is high association between elevated total cholesterol levels and development of hypertension in pregnancy.

Studies by Leela K. Pett al. [15] and Archana S. et al. [16] also produced findings that were comparable. The possibility that hypercholesterolemia facilitated the production of free radicals explains the correlation between total cholesterol levels and pre-eclampsia.

HDL

A similar trend was seen in the other peer studies also. Higher levels of HDL are desirable in the body and during derangement of this balance, underlying factors come to play and may result in hypertension in pregnancy.

Studies by Leela KP et al. and Soundararajan P et al. also produced findings that were comparable.

The connection between HDL and the pathophysiology of hypertension in pregnancy may be explained by the fact that HDL cholesterol helps to move the excess and potentially dangerous cholesterol from peripheral tissue to the liver through a process known as reverse cholesterol transport. The pathophysiology of pre-eclampsia involves extra harmful cholesterol, which is caused by low HDL in hypertension during pregnancy possibly due to hypo-estrogenaemia and insulin resistance.

LDL

Similar values were also seen in the recently published studies also. The Odd’s ratio for LDL in our study was more than one and the p value being very less we can come to a conclusion that increase in LDL levels during pregnancy is highly correlatable to the chance of developing hypertension during pregnancy.

It makes biological sense that preeclampsia and LDL levels are related. It has been observed that oxidized LDL inhibits epithelial-dependent vasodilatation and increases sensitivity to presser agents. It was discovered that plasma lipid peroxidase and free radicals were activated and that the lipid fractions rose in pre- eclamptic patients. The antioxidant mechanisms in the membranes of platelets and erythrocytes were also deactivated [17]. Studies by Leela KP et al. and Soundararajan P et al. also produced findings that were comparable

Triglycerides:

Higher TG, which is present along with hypertension in pregnancy, is likely to accumulate in vulnerable vessels, such as the uterine spiral arteries and it both directly and indirectly causes endothelial dysfunction by producing small and dense LDL and hypertriglyceridemia, which may be linked to a hypercoagulable state.

BMI

A positive correlation has been demonstrated by Ray et al. between a greater body mass index and a higher risk of hypertension during pregnancy. Additionally, in our study, the patients who went on to develop preeclampsia had a greater BMI than the normotensive group.

Numerous studies have found a strong correlation between preeclampsia and higher body mass index, impaired (or aberrant) glucose tolerance and chronic hypertension—the three main characteristics of metabolic syndrome.

 According to a 1999 study by Barden et al., pregnant women with pre- eclampsia had higher BMIs than pregnant women with normotensive pregnancies, regardless of the obstetric score.

In our view, the contradictory findings could be attributed to variations in the research methodology, limited sample sizes, insufficient control for confounding variables and variations in the study populations.

The sample time is another issue that needs to be addressed. It will take more parallel research to investigate the underlying mechanisms of this disparity.

In light of this, we could potentially draw the conclusion that lipid profile can be used as an early, affordable and non-invasive method of determining the possibility and severity of hypertensive disorders of pregnancy.

In the context of clinical practice, lipid profiles can be an effective screening tool for early identification of pregnant women at risk of hypertension before the symptoms and consequences of pre-eclampsia and eclampsia materialize, thereby improving the prognosis for the mother and fetus.

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