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Introduction: Preeclampsia (PE) represents a hypertensive pregnancy disorder that is associated with increased cardiovascular disease (CVD) risk. This increased risk has been attributed to accelerated atherosclerosis, with inflammation being a major contributor. Neutrophils play an important role in the onset and progression of atherosclerosis and have been associated with vascular damage in the placenta as well as the chronic inflammatory state in women with PE. We therefore investigated whether circulating neutrophil numbers or reactivity were associated with the presence and severity of subclinical atherosclerosis in women with a history of PE. Methods: Women aged 45–60 years with a 10 to 20 years earlier history of early onset preeclampsia (delivery <34 weeks of gestation) (n = 90), but without symptomatic CVD burden were screened for the presence of subclinical coronary artery disease (CAD) using both contrast-enhanced and non-contrast coronary CT angiography. Subclinical CAD was defined as a coronary artery calcium (CAC) score ≥100 Agatston Units and/or ≥50% coronary luminal stenosis. We assessed whether the numbers and activity of circulating neutrophils were associated with the presence of subclinical CAD and as secondary outcome measurements, with the presence of any calcium (CAC score > 0 AU) or stenosis, categorized as absent (0%), minimal to mild (>0 and <50%), and moderate to severe (≥50%) narrowing of the coronary artery. Blood was drawn just before CT and neutrophil numbers were assessed by flow cytometry. In addition, the presence of the chemokine receptors CXCR2 and CXCR4, which are known to be instrumental in neutrophil recruitment, and neutrophil activity upon stimulation with the bacterial peptide N-Formylmethionyl-leucyl-phenylalanine (fMLF) was assessed by flow cytometry. Results: Of the participating women, with an average age of 49 years, 13% (12 out of 90) presented with subclinical signs of CAD (CAC score ≥100 AU and/or ≥50% luminal stenosis), and 37% (33 out of 90) had a positive CAC score (>0). Total white blood cell count and neutrophil counts were not associated with the presence of subclinical CAD or with a positive CAC score. When assessing the presence of the chemokine receptors CXCR4 and CXCR2, we observed a slight decrease of neutrophil CXCR2 expression in women with CAC (median MFI 22.0 [interquartile range (IQR) 20.2–23.8]) compared to women without CAC (23.8 [IQR 21.6–25.6], p = 0.02). We observed no differences regarding neutrophil CXCR4 expression. In addition, expression of the early activity marker CD35 was slightly lower on neutrophils of women with subclinical CAD (median MFI 1.6 [IQR 1.5–1.9] compared to 1.9 [IQR 1.7–2.1] in women without CAD, p = 0.02). However, for all findings, statistical significance disappeared after adjustment for multiple testing. Conclusion: Our findings indicate that neutrophil counts and (re)activity are not directly associated with silent CAD disease burden and as such are not suitable as biomarkers to predict the presence of subclinical CAD in a high-risk population of women with a history of preeclampsia.
Introduction: Preeclampsia (PE) represents a hypertensive pregnancy disorder that is associated with increased cardiovascular disease (CVD) risk. This increased risk has been attributed to accelerated atherosclerosis, with inflammation being a major contributor. Neutrophils play an important role in the onset and progression of atherosclerosis and have been associated with vascular damage in the placenta as well as the chronic inflammatory state in women with PE. We therefore investigated whether circulating neutrophil numbers or reactivity were associated with the presence and severity of subclinical atherosclerosis in women with a history of PE. Methods: Women aged 45–60 years with a 10 to 20 years earlier history of early onset preeclampsia (delivery <34 weeks of gestation) (n = 90), but without symptomatic CVD burden were screened for the presence of subclinical coronary artery disease (CAD) using both contrast-enhanced and non-contrast coronary CT angiography. Subclinical CAD was defined as a coronary artery calcium (CAC) score ≥100 Agatston Units and/or ≥50% coronary luminal stenosis. We assessed whether the numbers and activity of circulating neutrophils were associated with the presence of subclinical CAD and as secondary outcome measurements, with the presence of any calcium (CAC score > 0 AU) or stenosis, categorized as absent (0%), minimal to mild (>0 and <50%), and moderate to severe (≥50%) narrowing of the coronary artery. Blood was drawn just before CT and neutrophil numbers were assessed by flow cytometry. In addition, the presence of the chemokine receptors CXCR2 and CXCR4, which are known to be instrumental in neutrophil recruitment, and neutrophil activity upon stimulation with the bacterial peptide N-Formylmethionyl-leucyl-phenylalanine (fMLF) was assessed by flow cytometry. Results: Of the participating women, with an average age of 49 years, 13% (12 out of 90) presented with subclinical signs of CAD (CAC score ≥100 AU and/or ≥50% luminal stenosis), and 37% (33 out of 90) had a positive CAC score (>0). Total white blood cell count and neutrophil counts were not associated with the presence of subclinical CAD or with a positive CAC score. When assessing the presence of the chemokine receptors CXCR4 and CXCR2, we observed a slight decrease of neutrophil CXCR2 expression in women with CAC (median MFI 22.0 [interquartile range (IQR) 20.2–23.8]) compared to women without CAC (23.8 [IQR 21.6–25.6], p = 0.02). We observed no differences regarding neutrophil CXCR4 expression. In addition, expression of the early activity marker CD35 was slightly lower on neutrophils of women with subclinical CAD (median MFI 1.6 [IQR 1.5–1.9] compared to 1.9 [IQR 1.7–2.1] in women without CAD, p = 0.02). However, for all findings, statistical significance disappeared after adjustment for multiple testing. Conclusion: Our findings indicate that neutrophil counts and (re)activity are not directly associated with silent CAD disease burden and as such are not suitable as biomarkers to predict the presence of subclinical CAD in a high-risk population of women with a history of preeclampsia.
Введение. Согласно последним данным, одним из наиболее частых осложнений беременности у пациентов с почечным трансплантатом являются инфекции мочевых путей – 40%, преэклампсия встречается в 32–47% случаев, по-прежнему имеет место острое отторжение трансплантата во время беременности – у 2,8% пациентов и в послеродовом периоде – у 4,1%, у 8% пациентов необратимая дисфункция трансплантата требует ретрансплантации в течение 2 лет после родов.Цель. Поиск дополнительных предикторов развития осложнений у беременных с почечным трансплантатом.Материалы и методы. В исследование включено 57 беременных женщин: 40 беременных с почечным трансплантатом (23 беременные ретроспективного и 17 – проспективного этапа), группа «случай – контроль» – 17 практически здоровых беременных женщин.Результаты и обсуждение. Разработанный комплексный метод ведения беременности и родов у женщин с почечным трансплантатом, включающий проведение медицинской профилактики, своевременную диагностику и лечение ранней стадии инфекции мочевых путей, способствовал предупреждению развития дисфункции трансплантата на фоне воспалительных изменений паренхимы и позволил снизить сывороточные и мочевые лейкоцитарные показатели воспаления: количество лейкоцитов в анализе мочи по Нечипоренко с 1,240 (0,279–3,193) 106/л у пациентов ретроспективной группы до 0,341 (0,248–0,465) 106/л у пациентов проспективной группы, U=76,5, p=0,023; удельный вес палочкоядерных лейкоцитов в сыворотке крови с 8,1 (7,4–12,1)% у пациентов ретроспективной группы до 6,2 (4,8–8,2)% у пациентов проспективной группы, U=61,5, p=0,003. Перечисленные изменения способствовали сохранению высокой фильтрационной и азотовыделительной способности трансплантата и сопровождались соответствием концентрации маркера почечного канальцевого повреждения диапазону нормальных значений: концентрация NGAL в проспективной группе пациентов с почечным трансплантатом в динамике беременности соответствовала концентрации маркера в группе практически здоровых пациентов: 20,44 (17,73–46,68) нг/мл и 15,35 (13,37–18,45) нг/мл соответственно, U=18,0, p>0,005, что позволило предупредить манифестацию осложнений и увеличить срок родоразрешения. Концентрация NGAL у беременных с почечным трансплантатом в подгруппе пациентов с преэклампсией составила 63,38 (46,68–70,82) нг/мл и была значимовыше, чем у беременных с почечным трансплантатом без преэклампсии – 18,12 (12,8–22,26) нг/мл, U=4,0, p=0,023.Заключение. NGAL может быть использован в качестве предиктора развития осложнений, в частности преэклампсии, у беременных с почечным трансплантатом, что подтверждается данными клинических исследований. Introduction. According to the latest data, one of the most frequent pregnancy complications in patients with a kidney transplant is urinary tract infections – 40%, preeclampsia – from 32% to 47%, acute graft rejection still occurs during pregnancy – in 2.8% of patients and in the postpartum period – in 4.1%, in 8% of patients, irreversible graft dysfunction requires retransplantation within 2 years after delivery.Purpose: search for additional predictors of complications in female kidney transplant recipients. Materials and methods. The study included 57 pregnant women: 40 pregnant women with kidney transplant (23 pregnant women of the retrospective and 17 – prospective stages, the case-control group – 17 practically healthy pregnant women.Results and discussion. The developed comprehensive method of managing pregnancy and childbirth in women with a kidney transplant, including medical prevention, timely diagnosis and treatment of early stage urinary tract infection, helped prevent the development of graft dysfunction against the background of inflammatory changes in the parenchyma and allowed reducing serum and urinary leukocyte indicators of inflammation: the number of white blood cells in the Urine test from 1.240 (0.279–3.193) 106/L in patients of the retrospective group to 0.341 (0.248–0.465) 106/L in patients of the prospective group, U=76.5, p=0.023; the specific weight of rod-shaped white blood cells in serum from 8.1 (7.4–12.1)% in patients of the retrospective group to 6.2 (4.8–8.2)% in patients of the prospective group, U=61.5, p=0.003. These changes helped to preserve high filtration and nitrogen-releasing the ability of the transplant, and was accompanied by a concentration of compliance marker of renal tubular damage to a range of normal values of: the concentration of NGAL in a prospective group of patients with renal transplant in the dynamics of pregnancy corresponded to the concentration of marker in the group of healthy patients: of 20.44 (17.73–46.68) ng/ml and 15.35 (13.37–18.45) ng/ml, respectively, U=18.0, p>0.005, which enabled to prevent the manifestation of complications and increase the gestational age of delivery. The concentration of NGAL in pregnant women with a kidney transplant in the subgroup of patients with preeclampsia was 6338 (46.68–70.82) ng/ml and was significantly higher than in pregnant women with a kidney transplant without preeclampsia – 18.12 (12.8–22.26) ng/ml, U=4.0, p=0.023. Conclusion. NGAL can be used as a predictor of complications, in particular preeclampsia, in pregnant women with a kidney transplant, which is confirmed by data from clinical studies.
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