|Year : 2022 | Volume
| Issue : 2 | Page : 121-124
Association of D-dimer and lipid biomarkers with preeclampsia and their role in prediction from a rural tertiary care setting
K Jhansi, JM Harsoda
Department of Physiology, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara, Gujarat, India
|Date of Submission||24-Mar-2022|
|Date of Acceptance||12-May-2022|
|Date of Web Publication||23-Aug-2022|
PhD Scholar, Department of Physiology, Smt. BK Shah Medical Institute and Research Centre, Sumandeep Vidyapeeth Deemed to be University, Vadodara, Gujarat
Source of Support: None, Conflict of Interest: None
Background: Preeclampsia affects 5%–7% of all pregnancies globally and is the leading cause of maternal and fetal death and morbidity. The mechanisms responsible for the pathogenesis of preeclampsia are unclear. Preeclampsia is characterized as hypertension with or without proteinuria after the 20th week of pregnancy and is associated with endothelial dysfunction, systemic vasoconstriction, inflammation, oxidative stress, and intrauterine growth restriction, and multiorgan dysfunction. Materials and Methods: A total of 120 women were divided into two groups: 60 women without PE (control group) and 60 women with PE in a prospective observational case–control study conducted in a rural tertiary care setting in India. This study was done from January 2019 to December 2019, after approval from the local ethical committee. Women with singleton pregnancy either primiparous or multiparous, aged between18 and 40 years were included in both case and control groups. Results: The participants in this study ranged in age from 18 to 38 years old, with an average age of 26.38 ± 4.38 years. The average age of the women in the case group was 26.42 + 3.92 years, while the average age of the women in the control group was 27.38 ± 4.52 years. Most of the patients were between the ages of 31 and 40 (51.67%) years. The mean gestational age in the case group was 26.60 ± 2.19 weeks, while it was 26.73 ± 2.39 weeks in the control group. Conclusion: Early screening of pregnant women for high D-dimer levels and lipid profile can play a significant role in reducing the morbidity and mortality of both mother and fetus.
Keywords: Biomarker, D-dimer, lipid, preeclampsia, pregnancy
|How to cite this article:|
Jhansi K, Harsoda J M. Association of D-dimer and lipid biomarkers with preeclampsia and their role in prediction from a rural tertiary care setting. J Sci Soc 2022;49:121-4
|How to cite this URL:|
Jhansi K, Harsoda J M. Association of D-dimer and lipid biomarkers with preeclampsia and their role in prediction from a rural tertiary care setting. J Sci Soc [serial online] 2022 [cited 2022 Dec 2];49:121-4. Available from: https://www.jscisociety.com/text.asp?2022/49/2/121/354277
| Introduction|| |
Preeclampsia affects 5%–7% of all pregnancies globally and is the leading cause of maternal and fetal death and morbidity. The mechanisms responsible for the pathogenesis of preeclampsia are unclear. Preeclampsia is characterized as hypertension with or without proteinuria after the 20th week of pregnancy and is associated with endothelial dysfunction, systemic vasoconstriction, inflammation, oxidative stress, intrauterine growth restriction, and multiorgan dysfunction., Preeclampsia is a pregnancy-specific syndrome with multisystem involvement which leads to fetal, neonatal, and maternal morbidity and mortality. This syndrome is characterized by the onset of clinical signs and symptoms and delivery before (early-onset preeclampsia), or after (late-onset preeclampsia), the 34 weeks of gestation., The more exacerbated hypercoagulable condition, which includes platelet activation, thrombin overproduction, and changes in fibrinolytic factors, is a major feature identified in PE. Platelet activation can result in thrombosis in the target organ's terminal vascular branches. Endothelial dysfunction, platelet activation, and pro-inflammatory cytokines are hypothesized to be linked to increased thrombin production. Anti-type-1 angiotensin II receptor autoantibodies also promote the production of plasminogen activator inhibitor-1. Fibrin deposition was detected throughout PE, implying that the balance between coagulation and fibrinolysis had been disrupted. D-dimer is the final breakdown product of a factor XIII-cross-linked fibrin clot. Increased levels of lipid oxidation products and lower levels of antioxidants involved in preeclampsia pathogenesis. In comparison to normotensive pregnant women, women with greater levels of oxidized low-density lipoprotein (LDL) and triglycerides (TG) and lower levels of circulating Vitamin C had a higher risk of preeclampsia. The essential event in the onset and progression of atherosclerosis and hypertension is the oxidative conversion of LDL-cholesterol (LDL-c) to oxidized LDL form. Dyslipidemia in the first trimester of pregnancy is linked to an increased risk of preeclampsia. The mother is anabolic in the early stages of pregnancy, and the lipid serves as a source of energy for both the growing fetus and the mother in the third trimester. There are numerous facts that suggest aberrant lipid profiles may be linked to the risk of preeclampsia. Lipid profiles such as TG, LDL-c, total cholesterol (TC), and very LDL levels are greater in preeclamptic women compared to normal pregnancies, whereas high-density lipoprotein (HDL) levels are lower., The risk of lipid profile abnormalities rises as the mother's gestational age rises. A meta-analysis research that included a good number of case–control studies found a strong link between hypertriglyceridemia and the likelihood of preeclampsia. There are no studies from the Indian tertiary care setting assessing the role of D-dimer and Lipid parameters as the biomarkers to predict preeclampsia.
Hence, this study is undertaken to evaluate and validate the role of D-dimer and Lipid biomarkers to predict the pathogenesis of preeclampsia from a rural Indian setting.
| Materials and Methods|| |
A total of 120 women were divided into two groups: 60 women without PE (control group) and 60 women with PE in a prospective observational case–control study conducted in a rural tertiary care setting in India. This study was done from January 2019 to December 2019, after approval from the local ethical committee. Women with singleton pregnancy either primiparous or multiparous, aged between18 and 35 years were included in both case and control groups. The control group consisted of all women who were not hypertensive and had a normal pregnancy according to clinical and ultrasound results. The PE group included all women who met the American College of Obstetricians and Gynecologists diagnostic criteria for PE, which included blood pressure of <140/90 mmHg and proteinuria of <300 mg or, in the absence of proteinuria, any of the following conditions: thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or cerebral or visual symptoms. Both groups were excluded based on the following criteria: past gestational diabetes mellitus, cardiovascular illness, autoimmune diseases, renal or hepatic diseases, and women taking lipid-interfering medication. Prior to participating in the trial, all women were told of the study's goals and gave their signed consent.
From the medical records, clinical data such as age, BMI, gravidity, parity, gestational age, blood pressure on admission, and pregnancy outcomes were obtained. Each subject's whole blood (4 mL and 2 mL) was collected in ethylenediaminetetraacetic acid tubes (4 mL) and sodium citrate tubes (2 mL) from an antecubital vein. To obtain plasma, these samples were centrifuged at 2500 rpm for 15 min. D-dimer levels were determined using an immunoturbidimetry test, and plasma lipid profile (T-Chol, TAG, HDL-c, Apo-A, and Apo-B) was determined using commercially available kits in a Hitachi 902 autoanalyzer (Boehringer Mannheim) (Roche Diagnostics, Mannheim Alemania and Wako Chemicals, USA). The Friedewald formula, as modified by DeLong, was used to calculate LDL-c.
IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp. was used to enter and analyze the data. The results are presented as means with standard deviations. For quantitative factors including age, gestational age, parity, and BMI, descriptive statistics were used to compute mean and standard deviation. For qualitative variables like high levels of D-dimer (yes/no), frequencies and percentages were determined. The link between preeclampsia and high D-dimer levels was determined using the Chi-square test. The significance level was set at P = 0.05.
| Results|| |
The participants in this study ranged in age from 18 to 35 years old, with an average age of 26.38 ± 4.38 years. The average age of the women in the case group was 27.38 + 5.92 years, while the average age of the women in the control group was 26.42 ± 3.52 years. Most of the patients were between the ages of 31 and 40 (52.47%) years. The mean gestational age in the case group was 26.42 ± 2.36 weeks, while it was 25.78 ± 2.34 weeks in the control group. The average parity was 1.96 ± 0.52. In preeclamptic mean, systolic BP was 152 ± 0.46 mm Hg, in controls mean, systolic BP was 112 ± 0.48 mm Hg. In preeclamptic mean diastolic BP was 104 ± 0.72 mm Hg, in controls mean diastolic BP was 72 ± 0.84 mm Hg. Mean systolic and diastolic BP were statistically significantly higher in preeclamptic as compared to controls (P < 0.05). Mean cholesterol levels were within the normal range in preeclamptic and controls (196.73 mg/dl ± 9.22 vs. 173.48 mg/dl ± 7.82) and were not statistically significant in preeclamptic as compared to controls (P > 0.05). Mean HDL-C, levels were (37.85 mg/dl ± 7.42 vs. 54 mg/dl ± 5.38) statistically significantly lower in preeclamptic as compared to normal controls (P < 0.05). Mean LDL-C levels were (133.82 mg/dl ± 35.38 vs. 98.37 mg/dl ± 18.78) statistically significantly higher in preeclamptic as compared to normal controls (P < 0.05). Mean TG levels were (256 mg/dl ± 0.48 118.56 mg/dl ± 4.6) statistically significantly higher in preeclamptic as compared to normal controls (P < 0.05) [Table 1]. High D-dimer levels were found in 38 (63.33%) of the women in the case group (preeclampsia) and in 8 (13.33%) of the women in the control group (normotensive) [Table 2].
|Table 1: Stratification of lipid levels among preeclamptic women and controls|
Click here to view
|Table 2: Stratification of high D-dimer levels with respect to age, gestational age, parity, and body mass index|
Click here to view
| Discussion|| |
Preeclampsia is a complex condition characterized by hypertension and proteinuria after 20 weeks of pregnancy. The accumulation of fibrin in the walls of tiny blood vessels is a symptom of preeclampsia. Because its plasma content has a strong predictive value for the assessment of venous thromboembolism, D-dimer was used as a marker for fibrin degradation/synthesis and thus developed as a valuable indicator in the diagnosis of thrombotic disorders. In comparison to a normal pregnancy, Manolov et al. discovered that increased D-dimer levels are linked to the onset of preeclampsia in the third trimester.
Endothelial cell destruction is a hallmark of PE, and lipid alterations may play a role. Antioxidant nutrients are used in excess in PE to counteract cellular alterations caused by free radicals such as lipid peroxides. Abnormal lipid metabolism is not just a symptom of PE; it also plays a role in the disease's etiology. Endothelial hyperstimulation, which leads to malfunction and damage, is likely to be exacerbated by lipid-mediated oxidative stress. When reactive oxygen species interact with polyunsaturated fatty acids, they produce lipid peroxides with a substantially longer half-life than in a normal pregnancy, causing oxidative stress, which is hypothesized to be the cause of pregnancy-induced hypertension.
It was discovered that the mean standard deviation (SD) serum triglyceride level in the preeclampsia group was 256 ± 0.48. The mean SD of serum triglyceride levels in the control group was 118.56 ± 4.6; the difference was statistically significant. Preeclampsia women had significantly higher triglyceride levels than normotensive women, according to Njoku et al. In their investigation, Enaruna et al. determined that there is a link between elevated maternal levels and the incidence of PE. In comparison to the control group (173.48 ± 7.82), there was a non-significant increase in total cholesterol (196.73 ± 9.22). The findings are comparable to those of Mustafa et al., who discovered that preeclampsia patients had higher total cholesterol levels, but that the rise was not significant. In the current investigation, a substantial drop in HDL-C was detected in the study group mean SD (37.85 ± 7.42) compared to the control group (54 ± 5.38), which is consistent with the findings of Jayanta D et al. When compared to normotensive pregnant women, preeclampsia patients had higher LDL-C levels, although the difference was statistically insignificant. The findings are analogous to those of Lakshmiprabha et al., who found similar results in their research.
Patients with plasma D-dimer >0.5 g/ml had significantly higher mean systolic and diastolic blood pressures than those with plasma D-dimer 0.5 g/ml (P = 0.026). The majority of preeclamptic women (68.4%) with plasma D-dimer >0.5 g/ml had systolic blood pressure <160 mm Hg, compared to 44.2% of those with plasma D-dimer <0.5 g/ml (P = 0.034). Nearly 84% of preeclamptic women with plasma D-dimer >0.5 g/ml had severe proteinuria, compared to 48.6% of preeclamptic women with plasma D-dimer <0.5 g/ml (P = 0.027). The study finds that the plasma D-dimer level can be simply employed in preeclamptic patients to screen for hypercoagulable states, which has both preventative and therapeutic implications. The link between preeclampsia and high D-dimer levels (>0.5 g/ml) was investigated in this study, where high D-dimer levels were found in 38 (63.33%) of the women in the case group (preeclampsia), but only in 08 (13.33%) of the women in the control group (normotensive). The P = 0.025 is significant, indicating that there is a link between preeclampsia and high D-dimer levels (>0.5 g/ml). The current investigation found that preeclamptic women's D-dimer levels were considerably higher than normal controls, which is consistent with the findings of Tacoosian et al. Kucukgoz Gulec et al. found that D-dimer levels were significantly higher in the study group than in the control group and that they were also significantly higher in patients with severe preeclampsia than in those with mild preeclampsia.
| Conclusion|| |
Pregnant women with a tendency to develop gestational hypertensive complications tend to have higher concentrations of lipid profile and D-dimer. A significant rise in lipid and D-dimer levels are observed in the pregnant mothers of preeclampsia, which was a major observation and breakthrough from this study. Early screening of pregnant women for high D-dimer levels and lipid profile can play a significant role in reducing the morbidity and mortality of both mother and fetus.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Marín R, Chiarello DI, Abad C, Rojas D, Toledo F, Sobrevia L. Oxidative stress and mitochondrial dysfunction in early-onset and late-onset preeclampsia. Biochim Biophys Acta Mol Basis Dis 2020;1866:165961.
Haire G, Egan K, Parmar K, McKinnon T, Monteith C, O'Connor H, et al.
Alterations in fibrin formation and fibrinolysis in early onset-preeclampsia: Association with disease severity. Eur J Obstet Gynecol Reprod Biol 2019;241:19-23.
Henderson JT, Thompson JH, Burda BU, Cantor A. Preeclampsia screening: Evidence report and systematic review for the US preventive services task force. JAMA 2017;317:1668-83.
Correa PJ, Palmeiro Y, Soto MJ, Ugarte C, Illanes SE. Etiopathogenesis, prediction, and prevention of preeclampsia. Hypertens Pregnancy 2016;35:280-94.
Duan Z, Li C, Leung WT, Wu J, Wang M, Ying C, et al.
Alterations of several serum parameters are associated with preeclampsia and may be potential markers for the assessment of PE severity. Dis Markers 2020;2020:7815214.
Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: Pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol 2019;15:275-89.
Kim SJ, Ahn HJ, Park JY, Kim BJ, Hwang KR, Lee TS, et al.
The clinical significance of D-dimer concentrations in patients with gestational hypertensive disorders according to the severity. Obstet Gynecol Sci 2017;60:542-8.
Enquobahrie DA, Williams MA, Butler CL, Frederick IO, Miller RS, Luthy DA. Maternal plasma lipid concentrations in early pregnancy and risk of preeclampsia. Am J Hypertens 2004;17:574-81.
Timalsina S, Gyawali P, Bhattarai A. Comparison of lipid profile parameters and oxidized low-density lipoprotein between normal and preeclamptic pregnancies in a tertiary care hospital in Nepal. Int J Womens Health 2016;8:627-31.
Thathagari V, Veerendra Kumar CM. Evaluation of serum lipids in preeclampsia: A comparative study. Int J Reprod Contracept Obstet Gynecol 2018;7:1372-5.
Gohil JT, Patel PK, Gupta P. Estimation of lipid profile in subjects of preeclampsia. J Obstet Gynaecol India 2011;61:399-403.
Gallos ID, Sivakumar K, Kilby MD, Coomarasamy A, Thangaratinam S, Vatish M. Pre-eclampsia is associated with, and preceded by, hypertriglyceridaemia: A meta-analysis. BJOG 2013;120:1321-32.
Manolov V, Marinov B, Masseva A, Vasilev V. Plasma D-dimer levels in preeclampsia. Akush Ginekol (Sofiia) 2014;53 Suppl 2:15-8.
Ahmed AA, El Omda FA, Mousa MS. Maternal lipid profile as a risk factor for preeclampsia. Egypt J Hosp Med 2018;71:3434-8.
Njoku TK. Evaluation of Serum Lipid Profile in Women with Pre-Eclampsia in Federal Medical Center, Owerri: A Case Control Study; Unpublished 2017. p. 1-34.
Enaruna NO, Idemudia JO, Aikoriogie PI. Serum lipid profile and uric acid levels in preeclampsia in University of Benin Teaching Hospital. Niger Med J 2014;55:423-7.
] [Full text]
Cekmen MB, Erbagci AB, Balat A, Duman C, Maral H, Ergen K, et al.
Plasma lipid and lipoprotein concentrations in pregnancy induced hypertension. Clin Biochem 2003;36:575-8.
De J, Mukhopadhyay A, Saha PK. Study of serum lipid profile in pregnancy induced hypertension. Indian J Clin Biochem 2006;21:165-8.
Lakshmiparbha S, Biswajit M, Pradipta KM, Diwakar A, Dhanyasi AK, Viyatprajna A, et al
. A study of serum lipid profile and oxidative stress marker in healthy pregnancy and in preeclampsia. Int J Curr Res 2011;3:160-2.
Tacoosian Z, Javadi HE, Farzam S, Javadi A. Evaluation of correlation between pre-eclampsia with D-Dimer. J Qazvin Univ Med Sci 2007;11:62-6.
Kucukgoz Gulec U, Tuncay Ozgunen F, Baris Guzel A, Buyukkurt S, Seydaoglu G, Ferhat Urunsak I, et al.
An analysis of C-reactive protein, procalcitonin, and D-dimer in pre-eclamptic patients. Am J Reprod Immunol 2012;68:331-7.
[Table 1], [Table 2]