Search Results (360)

Background: Empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, improves outcomes in heart failure (HF) patients, yet inter-individual variability in response remains unclear. Genetic variants in Brain-Derived Neurotrophic Factor BDNF (rs6265) and ATPase Sarcoplasmic/Endoplasmic Reticulum Ca²⁺ Transporting 2 ATP2A2 (rs1860561) may influence the treatment efficacy. Objective: To assess the association of BDNF and ATP2A2 polymorphisms with the response to low-dose empagliflozin (10 mg) in Pakistani patients with heart failure and a reduced ejection fraction (HFrEF). Methods: In this prospective study, 120 HF patients with an ejection fraction of 25–45% who had been on stable standard heart failure therapy for at least 3 months were initiated on 10 mg of empagliflozin. The brain natriuretic peptide (BNP) and LVEF left ventricular ejection fraction (LVEF) were assessed at 6 and 12 months. Genotyping for rs6265 and rs1860561 was performed via Sanger sequencing. A response was defined as a ≥5% EF increase or ≥20% BNP reduction. Associations were analyzed using chi-square and logistic regression. Results: Among 99 genotyped patients, BDNF T allele carriers (CT/TT) had a significantly lower EF (p = 0.028) and BNP (p < 0.001) response. The CC genotype was associated with improved outcomes (BNP OR: 7.70; EF OR: 5.97). For ATP2A2, the GG genotype showed a strong association with EF improvement (OR: 5.97; p = 0.001), with no BNP association. Variant allele frequencies were higher among Punjabis and Kashmiris than Pathans. Conclusions: BDNF rs6265 and ATP2A2 rs1860561 polymorphisms appear to influence the individual response to empagliflozin in HFrEF patients. These findings underscore the potential of pharmacogenetic profiling to guide personalized therapy and optimize treatment outcomes in heart failure. Full article

Regular physical activity has a beneficial impact on the cardiovascular system. However, the intense and prolonged exertion typical of professional athletes and amateur marathon runners can lead to adaptive changes in the heart. These changes encompass both structural and functional modifications, which may have positive or negative effects on cardiac function and contribute to the development of so-called “athlete’s heart.” Prolonged exercise induces adaptations at the molecular and cellular levels, including altered gene expression and remodeling of myocardial proteins. It may also cause transient elevations in biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin. Some athletes experience cardiac arrhythmias, including atrial fibrillation. Morphological changes, such as myocardial hypertrophy or chamber dilation, can be assessed using echocardiography. Studies have reported potentially benign valvular abnormalities, as well as cases of myocardial fibrosis and arrhythmias. Early diagnosis of cardiac conditions in marathon runners is essential for effective prevention and health monitoring. This article reviews the current data on cardiac changes in endurance athletes, based on the literature from the past decade. Full article

Background: Chronic heart failure (CHF) continues to present significant prognostic challenges despite advances in diagnosis and therapy. While the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is widely recognized as a key marker of cardiac stress, and serum albumin reflects systemic inflammation and nutritional status, their integration into a single parameter—the NT-proBNP-to-albumin ratio (NTAR)—may improve risk stratification. This study aimed to evaluate the NTAR as a novel biomarker for predicting in-hospital mortality in patients with CHF. Methods: We performed an exploratory, retrospective, observational, single-center study involving 542 patients (306 males) admitted for CHF between January 2022 and August 2024. NTAR was calculated as log₁₀(NT-proBNP/albumin). Statistical analyses included ROC curves, univariate and multivariable Cox regression, and Kaplan–Meier survival analysis. Sex-specific performance of NTAR was compared against NT-proBNP and serum albumin alone. Results: Females had significantly lower serum albumin levels than males, while NT-proBNP levels were similar across sexes. NTAR increased with NYHA functional class and was highest in patients with heart failure with reduced ejection fraction (HFrEF). NTAR showed very good discriminatory performance for predicting in-hospital mortality (AUC = 0.840, 95% CI: 0.794–0.879, p < 0.001), marginally but statistically outperforming NT-proBNP in the male subgroup. In univariate Cox regression analyses, higher serum albumin was significantly associated with reduced in-hospital mortality risk in males (HR = 0.352; 95% CI: 0.154–0.803; p = 0.010) and females (HR = 0.169; 95% CI: 0.072–0.399; p < 0.001). Elevated NT-proBNP levels were associated with increased mortality risk in males (HR = 8.627; 95% CI: 1.956–38.042; p < 0.001) and females (HR = 6.060; 95% CI: 1.498–24.521; p = 0.002) with similar findings in NTAR (HR_males = 10.318, 95% CI: 2.452–43.417, p < 0.001 and HR_females = 7.542, 95% CI: 1.874–30.358, p < 0.001). Multivariable analysis identified NTAR as the strongest independent predictor for in-hospital mortality among males. Conclusions: These findings suggest that NTAR effectively integrates cardiac and systemic dysfunction to improve mortality risk stratification in CHF, particularly in male patients. Its ease of calculation from routinely available biomarkers supports its clinical applicability. Full article

Heart failure (HF), particularly of an ischemic etiology, is steadily increasing worldwide. Non-anemic iron deficiency (ID) is highly prevalent among HF patients, and it has been related to worse outcomes. Growth differentiation factor 15 (GDF15) has been related to atherosclerotic cardiovascular (CV) disease, HF and iron pathophysiology. Nevertheless, the specific potential role of GDF15 in HF patients with ID has not been fully explored. In this cross-sectional study we determined serum GDF15 levels in 60 HF patients with ID from the IRON-PATH II study. The discriminative capacity of GDF15 in logistic regression models for classifying these patients according to ischemic etiology was defined as the primary endpoint. Additionally, relationships between GDF15 levels and impaired right ventricle function, impaired functional capacity and HF were included as secondary endpoints. GDF15 was inversely related to tricuspid annular plane systolic excursion (TAPSE) and the six-minute walking test (6MWT), and positively related to hallmarks of HF [i.e., N-terminal prohormone of brain natriuretic peptide (NT-proBNP)] and other molecules influenced by HF progression [i.e., creatinine and ferritin]. Moreover, GDF15 was inversely related to hemoglobin, suggesting a potential link to iron homeostasis. Furthermore, GDF15 showed good classification capacity and improved the accuracy of a logistic regression model for ischemic HF classification in patients with ID. Overall, the findings of this study propose serum GDF15 levels as a potential tool for the classification of HF patients with ID according to the ischemic etiology. Full article

Brain natriuretic peptide (BNP) is an important biomarker for the diagnosis and prediction of chronic heart failure (CHF). Aiming at the problems of the low sensitivity and poor portability of traditional BNP detection methods, this study proposes a Surface-enhanced Raman-scattering (SERS) fiber-optic sensor based on a multimode fiber (MMF)–no core fiber (NCF) structure. The sensor achieves BNP detection by significantly amplifying the Raman signal of the toluidine blue (TB) marker through the synergistic effect of NCF’s unique optical transmission modes and localized surface plasmon resonance (LSPR). To optimize the sensor performance, we first investigated the effect of the NCF length on the Raman signal, using Rhodamine 6G (R6G), and determined the optimal structural parameters. Combined with the microfluidic chip integration technology, the antibody–BNP–antibody sandwich structure was adopted, and TB was used as the Raman label to realize the quantitative detection of BNP. Experimental results demonstrate that the detection limit of the sensor is lower than the clinical diagnostic threshold and exhibits stability. The sensor sensitivity can be adjusted by regulating the laser power. With its stability and high portability, this sensor provides a new solution for the early diagnosis of heart failure and demonstrates broad application prospects in biomarker detection. Full article

Background: Cardiovascular disease is the leading cause of death in chronic kidney disease populations. The risk of major adverse cardiovascular events (MACE) is greater than that of progression to end-stage kidney disease. An exponential increase in mortality risk is associated with declining kidney function. This study aimed to review the current landscape of traditional and novel blood biomarkers in predicting MACE in ESKD patients. Methods: The systematic review was registered on PROSPERO (CRD42024497403). Standard and extensive Cochrane search methods were used. The latest search date was July 2023. Participants were aged ≥18 years with end-stage kidney disease. Descriptive analysis was performed and data was presented in tabular form. The hazard ratio or odds ratio was presented for potential biomarkers discovered. Results: Overall, 14 studies (4965 participants) were included for analysis; 12 focused on participants requiring haemodialysis and 2 on haemodialysis and peritoneal dialysis. The biomarkers analysed were Troponin I (n = 3), Troponin T (n = 3), B-type natriuretic peptide (n = 2), N-Terminal Pro-Brain-Natriuretic Peptide (n = 7), soluble receptors for advanced glycation end products (n = 2), Galectin 3 (n = 4), and the serum-soluble suppression of tumorigenicity-2 (n = 2). Reported study outcomes included all-cause mortality (n = 11), MACE (n = 5), cardiac specific mortality (n = 6), sudden cardiac death (n = 2), and first cardiovascular event (n = 3). Conclusions: This review outlines the potential role of traditional and novel biomarkers in predicting MACE in end-stage kidney disease. Further larger-scale research is required to establish the validity of the study outcomes to develop new methods of cardiovascular risk prediction in this high-risk population. Full article

White muscle disease (WMD) is a degenerative condition of the skeletal and/or cardiac muscle associated with selenium (Se) and/or vitamin E deficiency, which can present in acute, subacute, or chronic forms, and is most commonly observed in young, rapidly growing animals, though it may also occur in older individuals. This study aims to determine the serum concentrations of galectin-3 (Gal-3), cardiac troponin I (cTnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP), as well as the activity of creatine kinase-myocardial band (CK-MB), in lambs diagnosed with WMD, and to investigate the diagnostic potential of these biomarkers in the evaluation of myocardial injury and skeletal and/or cardiac muscle necrosis associated with WMD. A total of 50 lambs, 20 healthy and 30 with WMD, were included in the study. The diagnosis of WMD was made based on clinical signs, laboratory results, necropsy findings, and blood vitamin E and Se concentrations. The lambs in the WMD group were categorized into two subgroups: confirmed, severe aWMD (acute animals, n = 10) lambs and presumed sWMD (subacute animals, n = 20), based on the clinical progression and severity of the disease. Serum levels of NT-proBNP, Gal-3, and cTnI were assessed using the ELISA technique. Levels of cTnI and CK-MB indicative of myocardial injury were found to be considerably elevated in the aWMD group (p < 0.001) in comparison to both the sWMD and control groups. CK-MB showed a strong positive correlation with cTnI (r = 0.819, p < 0.001). The serum concentrations of Gal-3 and NT-proBNP in healthy lambs were 2.55 ± 0.52 ng/mL and 3.28 ± 0.71 ng/mL, respectively. Serum Gal-3 concentrations were measured as 2.99 ± 0.44 ng/mL in the aWMD group and 3.07 ± 0.42 ng/mL in the sWMD group, while NT-proBNP concentrations were 2.15 ± 0.32 ng/mL and 2.64 ± 0.55 ng/mL in the aWMD and sWMD groups, respectively. No statistically significant differences were found in serum Gal-3 or NT-proBNP levels among the three groups (p > 0.05). In conclusion, this study is the first investigation assessing serum concentrations of Gal-3 and NT-proBNP in lambs afflicted with WMD. The results suggest that Gal-3 and NT-proBNP are ineffective biomarkers for assessing myocardial injury and skeletal and/or cardiac muscle necrosis associated with WMD in lambs. However, cTnI and CK-MB appear to be significant indicators of cardiac involvement in both acute and subacute scenarios. Further research is required to elucidate the molecular function of Gal-3 in muscle and cardiac disease in lambs afflicted with WMD. Full article

Background: Atrial fibrillation (AF) is common complication of heart failure with preserved ejection fraction (HFpEF) that sufficiently intervenes in the prognosis. The aim of the study is a) to investigate the possible discriminative value of adropin for newly onset AF in patients with HFpEF without a previous history of AF and who are being treated in accordance with conventional guideline and b) to compare it with predictive potencies of conventionally used predictors. Methods: A total of 953 patients with HFpEF who had sinus rhythm on ECG were enrolled in the study. The course of the observation was 3 years. Echocardiography and assessment of conventional hematological, biochemical parameters and biomarker assay including N-terminal brain natriuretic pro-peptide (NT-proBNP), high-sensitivity cardiac troponin T, tumor necrosis factor-alpha, high-sensitivity C-reactive protein (hs-CRP), galectin-3, interleukin-6, soluble suppressor tumorigenisity-2 (sST2) and adropin, were performed at baseline. Results: Incident atrial fibrillation was found in 172 patients with HFpEF, whereas 781 had sinus rhythm. In unadjusted rough Cox regression model, age ≥ 75 years, type 2 diabetes mellitus, chronic kidney disease (CKD) stages 1–3, left atrial volume index (LAVI) ≥ 40 mL/m², NT-proBNP ≥ 1440 pmol/mL, hs-CRP ≥ 5.40 mg/L, adropin ≤ 2.95 ng/mL, sST2 ≥ 15.5 ng/mL were identified as the predictors for new onset AF in HFpEF patients. After adjusting for age ≥ 75 years, a presence of type 2 diabetes mellitus and CKD stages 1–3, the levels of NT-proBNP ≥ 1440 pmol/mL and adropin ≤ 2.95 ng/mL were independent predictors of new onset AF in patients HFpEF. We also found that discriminative value of adropin was superior to NT-proBNP, while adding adropin to NT-proBNP did not improve predictive information of adropin alone. Conclusions: adropin ≤ 2.95 ng/mL presented more predictive information than NT-proBNP ≥ 1440 pmol/mL alone for new cases of AF in symptomatic patients with HFpEF, whereas the combination of both biomarkers did not improve the predictive ability of adropin alone. Full article

Thirst is usually characterized as an unpleasant sensation provoking drinking of water. The purpose of the present review is to draw attention to the importance of thirst in overall regulation of body fluid homeostasis in health and pathology. Intensity of thirst is determined by signals generated in multiple groups of osmosensitive neurons engaged in dipsogenic and antidipsogenic activities, which are located in the brain cortex, the insula, the amygdala, the median preoptic area, the hypothalamic nuclei and the organum vasculosum laminae terminalis. Water ingestion is also influenced by signals generated in the cardiovascular system, the gastrointestinal system, the pancreas, the liver and the kidney and by changes of body temperature. Regulation of thirst engages the autonomic nervous system and several neuroactive factors synthetized in the brain and the peripheral organs. Among them are components of the renin–angiotensin system, vasopressin, atrial natriuretic peptide, cholecystokinin, ghrelin, gaseous transmitters, cytokines and prostaglandins. Experimental studies provide evidence that elevation of fluid osmolality, which is the most frequent cause of thirst, influences function of the voltage-gated sodium channel and calcium-dependent kinase II subunit alpha. Regulation of thirst may be inappropriate in old age and under some pathological conditions including infections, heart failure, diabetes insipidus, diabetes mellitus, and psychogenic disorders. The molecular background of the abnormal regulation of thirst in the clinical disorders is not yet sufficiently recognized and requires further examination. Full article

Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due to multi-morbidity, polypharmacy, and age-related physiological changes. Given advancements in medicine and more prolonged cumulative exposure to risk factors in the elderly population, it is likely that the prevalence of chronic kidney disease (CKD) and heart failure (HF) will continue to rise going forward. Hence, understanding the mechanisms involved in the development of CRS is paramount. There are five different CRS types—they are categorised depending on the primary organ involved the acuity of disease. The pathophysiological process behind CRS is complex, involving the interplay of many processes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction and vascular stiffness. The numerous diagnostic and management challenges associated with CRS are significantly further exacerbated in an elderly population. Biomarkers used to aid the diagnosis of CRS, such as serum creatinine and brain natriuretic peptide (BNP), can be challenging to interpret in the elderly population due to age-related renal senescence and multiple comorbidities. Polypharmacy can contribute to the development of CRS and therefore, before initiating treatment, coordinating a patient-centred, multi-speciality, holistic review to assess potential risks versus benefits of prescribed treatments is crucial. The overall prognosis of CRS in the elderly remains poor. Treatments are primarily directed at addressing the sequelae of the underlying aetiology, which often involves the removal of fluid through diuretics or ultrafiltration. Careful considerations when managing elderly patients with CRS is essential due to the high prevalence of frailty and functional decline. As such, in these patients, early discussions around advance care planning should be prioritised. Full article

Hibiscus syriacus L. (HS), native to Eastern and Southern Asia, has been traditionally used in Asian herbal medicine for its anticancer, antimicrobial, and anti-inflammatory properties. Despite these recognized bioactivities, its potential cardioprotective effects, particularly in the setting of heart failure (HF), remain largely unexplored. This study aimed to investigate the effects of HS extracts and its bioactive constituents on angiotensin II (Ang II)-induced cardiac injury using an in vitro model with H9c2 rat cardiomyocytes. Cells exposed to Ang II were pretreated with HS extracts, and assays were performed to assess cell viability, reactive oxygen species (ROS) generation, protein synthesis, and secretion of inflammatory mediators, including tumor necrosis factor-alpha, interleukin 1β (IL-1β), and interleukin 6 (IL-6), as well as chemokine (CCL20) and HF-related biomarkers, such as brain natriuretic peptide (BNP) and endothelin-1. The results demonstrated that HS extracts significantly and dose-dependently attenuated Ang II-induced ROS accumulation and suppressed the secretion of pro-inflammatory cytokines, chemokines, BNP, and endothelin-1. Additionally, HS and its purified components inhibited Ang II-induced protein synthesis, indicating anti-hypertrophic effects. Collectively, these findings highlight the antioxidative, anti-inflammatory, and antihypertrophic properties of HS in the context of Ang II-induced cardiac injury, suggesting that HS may represent a promising adjunctive therapeutic candidate for HF management. Further in vivo studies and mechanistic investigations are warranted to validate its clinical potential. Full article

The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients. Full article

Background/Objectives: Sotatercept has demonstrated efficacy in pulmonary arterial hypertension (PAH), but its use has not been studied in patients with Group 3 pulmonary hypertension (PH). Additionally, patients with connective tissue disease-associated PAH (CTD-PAH) were underrepresented in the STELLAR trial. Given the limited treatment options for pulmonary hypertension in patients with interstitial lung disease (PH-ILD), this study aimed to evaluate the use of sotatercept in CTD-PAH patients with concomitant ILD. Methods: Eligible patients (n = 7) had a confirmed diagnosis of CTD-PAH with concomitant ILD. The patients were already receiving background PAH therapy. Baseline hemodynamic and clinical measurements were reassessed after 24 weeks of sotatercept therapy. The variables assessed included six-minute walk distance (6MWD), pulmonary vascular resistance (PVR), echocardiographic right ventricular systolic pressure (eRVSP), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, and supplemental oxygen requirements. Results: The study included seven patients with a mean age of 57 years (range: 39–73 years). After 24 weeks, the mean 6MWT distance increased from 211 m to 348 m (p < 0.01). Mean PVR decreased from 7.77 WU at baseline to 4.53 WU (p < 0.01). Mean eRVSP decreased from 79.43 mmHg to 54.14 mmHg (p < 0.01). NT-proBNP decreased from 3056.86 pg/mL to 1404.29 pg/mL (p < 0.01). The WHO functional class and supplemental oxygen requirements improved in all patients. Conclusions: Sotatercept was tolerated in patients with CTD-PAH and ILD, with no evidence of adverse respiratory effects. When added to foundational PAH therapy, sotatercept resulted in significant improvements across multiple parameters. These findings suggest that sotatercept may be a promising therapeutic option as an adjunctive treatment in this patient population. Full article

Objectives: Kawasaki Disease (KD) is an acute vasculitis associated with systemic inflammation. This study aimed to investigate the level and clinical significance of soluble ST2 (sST2) in children with KD. Methods: A retrospective analysis was conducted on 287 pediatric KD patients treated at the Pediatric Cardiology Department of Shengjing Hospital, China Medical University, from November 2021 to December 2022. Patients were stratified into subgroups based on the presence of myocardial damage (MD), coronary artery lesions (CAL), multi-organ involvement (MOD; ≥3 organs) and/or intravenous immunoglobulin-resistant KD (IVIG-R KD). In each group, we analyzed the correlation between sST2 levels and various laboratory parameters, including white blood cell count (WBC), hemoglobin (HB), platelet count (PLT), C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), N-terminal pro-brain natriuretic peptide (NT-pro BNP), D-dimer, and albumin (ALB). Results: Patients in the CAL group were significantly younger and predominantly male (p < 0.05). In the MD, CAL, MOD, and IVIG-R KD groups, levels of sST2, CRP, NT-pro BNP, and D-dimer were significantly higher than in their respective comparison groups (p < 0.05). sST2 showed weak positive correlations with WBC, CRP, IL-6, NT-pro BNP, and D-dimer, and weak negative correlations with HB and ALB (p < 0.05). sST2, HB, and IL-6 were identified as independent risk factors for MOD (p < 0.05). sST2 and HB were independent risk factors for IVIG-R KD (p < 0.05). Among acute-phase patients, four cases had sST2 levels > 200 ng/mL—all were classified as IVIG-R KD and MOD; three of these also developed coronary artery aneurysms (CAA). Conclusions: Elevated sST2 levels in the acute phase of KD may serve as a clinical indicator of IVIG-R KD, CAA, MOD, and MD. Full article

The aim of this study was to evaluate and synthesize the existing evidence on N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) as biomarkers for preeclampsia as compared with a healthy pregnant group, but also comparing them in early-onset preeclampsia (EOP) versus late-onset preeclampsia (LOP). Five electronic databases, PubMed, EMBASE, Web of Science, Scopus, and LILACS, were searched for studies on pregnant women comparing NT-proBNP and BNP levels in preeclampsia vs. healthy pregnancies and EOP vs. LOP. From the 752 identified records, 31 studies were included in the review, referring to 3915 participants. When comparing PE to healthy pregnancies and EOP to LOP, there was a considerable increase in NT-proBNP levels in the PE group, respectively, in EOP: 206.19 pg/mL (95% CI 139.68–272.69) (p ≤ 0.001) in the PE group, and 182.42 pg/mL (95% CI 99.65–265.19) (p ≤ 0.001) in the EOP group. Regarding BNP, the levels were higher in the PE group (30.13 (95% CI 17.22–43.04), p ≤ 0.001), respectively in the EOP group (33.35 pg/mL (95% CI 20.26–46.43), p ≤ 0.001). NT-proBNP and BNP levels are consistently elevated in preeclampsia compared to healthy pregnancies and in EOP compared to LOP. Full article