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  • Ovid Technologies (Wolters Kluwer Health)  (7)
  • 1
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    Abstract P170: Cardiovascular Health Scores, Adverse Pregnancy Outcomes, And Angiogenic Biomarkers Associated With Cognition8-10 Years After Pregnancy
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 145, No. Suppl_1 ( 2022-03)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 145, No. Suppl_1 ( 2022-03)
    Abstract: Introduction: Women with adverse pregnancy outcomes (APO, preeclampsia, preterm birth, small for gestational age neonates), especially those with placental maternal vascular malperfusion (MVM), are at increased cardiovascular and cognitive risk, perhaps due to poor cardiovascular health (CVH) and other vascular pathology. Hypothesis: Including history of APO and MVM in CVH scores identifies women with lower cognitive function and circulating angiogenic biomarker profiles indicating ongoing vascular pathophysiology. Methods: CVH was evaluated in 39 women 8-10 years after pregnancy (mean age 39.8 ±6 years, 36% Black) using standard metrics (smoking, BMI, blood pressure, total cholesterol, fasting glucose, and physical activity; higher score is healthier). APO history was abstracted from the medical record and added to CVH (no APO [n=14], APO-MVM [n=13] , APO+MVM [n=13] to create a CVH-APO score. We evaluated cognitive function (memory, processing speed and executive function) as domain z scores using standard tests. Angiogenic biomarkers (VEGF-A, VEGF-C, VEGF-D, Tie-2, sFlt1, PlGF, and bFGF) were quantified using Angiogenesis Panel 1 (Meso Scale Diagnostics). Associations of CVH with cognition and biomarkers were evaluated using Pearson correlations. CVH groups (poor [CVH ≤7] vs. healthy [CVH 〉 8) were compared with and without APO history using t-test. Results: Women with APO+MVM had lower CVH scores compared to those with no APO, adjusted for age and race (-1.5, p=0.03). Poor CVH was associated with slower processing speed (r=0.350, p=0.031) and reduced executive function (r=0.353, p=0.03) but not memory. When APO history was added to CVH, associations became stronger (r=0.402, p=0.012 for processing speed; 0.422, p=0.008 for executive function). Poorer CVH scores also correlated with higher VEGF A (-0.501 p=0.001), VEGF C (-0.653, p 〈 0.001), PlGF (-0.326 p=0.045), and bFGF (-0.383, p=0.018). Using the combined CVH-APO score, women with poor CVH (n=18) compared to healthy CVH (n=20) had higher bFGF (18 vs 9.5 pg/mL p=0.013), VEGF-A (78 vs 44pg/mL p=0.002) and VEGF-C (1319 vs 828 p=0.023). Discussion: Poor CVH is associated with lower cognition and higher circulating angiogenic biomarker profiles in women, and APO history may further contribute to the cumulative vascular pathophysiological burden a decade after pregnancy.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.145.suppl_1.P170
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 2
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    Unique microRNA Signals in Plasma Exosomes from Pregnancies Complicated by Preeclampsia
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Hypertension Vol. 75, No. 3 ( 2020-03), p. 762-771
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 75, No. 3 ( 2020-03), p. 762-771
    Abstract: Although preeclampsia is a common and serious complication of pregnancy, insight into its pathobiology and diagnosis is lacking. Circulating plasma exosomes, which contain RNA and other molecules and have recently become accessible for diagnostics, may be informative in this regard. We tested the hypothesis that preeclampsia may affect the miRNA cargo within circulating maternal blood exosomes. We collected plasma from 60 pregnant women at term, including 20 women with pregnancy complicated by preeclampsia, and 20 women with fetal growth restriction and 20 with healthy pregnancy, serving as controls. We isolated exosomes from the maternal plasma by continuous density gradient ultracentrifugation. Our main outcome variable was exosomal miRNA cargo, analyzed by quantitative polymerase chain reaction-based TaqMan advanced miRNA assay in a card format and the expression of differentially expressed exosomal miRNA in whole plasma from the same participants. We found that 7 miRNA species were differentially expressed in exosomes from women with preeclampsia and those from controls. In contrast, there was no significant difference in exosomal miRNA expression between women with fetal growth restriction and controls. The results were not affected by fetal sex. Only one of the preeclampsia-related, differentially expressed exosomal miRNAs was significantly different in whole plasma miRNA analysis. We concluded that unlike whole plasma miRNA, exosomes extracted from the plasma of women with preeclampsia exhibit a unique miRNA profile, suggesting that plasma exosomal miRNA could provide insight into the pathophysiology of preeclampsia, and may play a role in disease diagnostics.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.119.14081
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2094210-2
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  • 3
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    Abstract P246: Association Between Life’s Essential 8 Cardiovascular Health Scores During Pregnancy and Vascular Integrity in the Placenta
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Circulation Vol. 147, No. Suppl_1 ( 2023-02-28)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 147, No. Suppl_1 ( 2023-02-28)
    Abstract: Background: Adverse pregnancy outcomes (APOs) identify pregnant people at increased risk of later cardiovascular disease. Poor antenatal cardiovascular health (CVH) quantified using components of the Life’s Simple 7 ideal CVH framework has been associated with higher APO incidence, indicating modifiable aspects of CVH during pregnancy may be related to pregnancy health. Placental pathology is also common in APOs, but it is unclear if antenatal CVH is directly related to placental health. Further, clinically-used dichotomous measures of placental pathology limit investigation of associations. Thus, the aim of this study was to examine the relationship between antenatal CVH and a novel, continuous marker of placental vascularization. Hypothesis: We hypothesized higher (healthier) antenatal CVH scores would be associated with higher (healthier) vascularization in the placenta. Methods: Participants enrolled in the Magee Obstetric Maternal & Infant Biobank and one of two prospective observational cohort studies examining activity patterns in pregnancy (MoM Health or Pregnancy 24/7). Antenatal CVH was quantified with a pregnancy-adapted Life’s Essential 8 framework assessed during each trimester and averaged across gestation. Components included sleep, diet, smoking, objective physical activity, pre-pregnancy BMI, blood pressure, 50g glucose challenge test results, and gestational weight gain. Component scores were averaged for a composite score (possible range, 0-100; higher indicated better CVH). Immunohistochemistry of placenta tissue was performed. Sections were stained with CD34 antibody to highlight vascular endothelial cells and counterstained with hematoxylin. Whole-slide images were digitized. Software computed the number of pixels positive for CD34 (numerator) and the total pixels (denominator); the ratio was the outcome of fetal vascular percentage (FV%), or the proportion of villous tissue occupied by fetal vessels. Linear regression associated CVH scores with FV%. Results: Placenta tissue was obtained from 64 participants (mean±SD age = 32±4.9 years). CVH score averaged across gestation was 72.6±10.7 points and decreased significantly from the first to third trimester (72.8±12.7 vs. 65.1±11.9, p 〈 0.01). FV% was 26.3±5.13 percentage points. Associations between CVH scores and FV% approached but did not reach significance (p 〈 0.2) in each trimester and across gestation. A 10-point increase in CVH averaged across gestation was non-significantly associated with a 0.82 percentage point increase in FV% (p=0.18). Post-hoc power analysis of this novel metric identified sufficient power to detect a 1.5 percentage point change in FV% per 10-point change in CVH score. Conclusion: Antenatal CVH was not significantly associated with placental vasculature, though a small sample size limits conclusions. Replication in a fully-powered sample is warranted.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.147.suppl_1.P246
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1466401-X
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  • 4
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    Transforming growth factor-beta differentially regulates oval cell and hepatocyte proliferation
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Hepatology Vol. 45, No. 1 ( 2007-01), p. 31-41
    Details
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 1 ( 2007-01), p. 31-41
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.1002/hep.v45:1
    DOI: 10.1002/(ISSN)1527-3350
    DOI: 10.1002/hep.21466
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1472120-X
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  • 5
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    Abstract MP65: Maternal Vascular Lesions in the Placenta May Identify Women Susceptible to Masked Hypertension a Decade After Pregnancy
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation Vol. 139, No. Suppl_1 ( 2019-03-05)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 139, No. Suppl_1 ( 2019-03-05)
    Abstract: Introduction: Women with placentally mediated pregnancy complications such as preeclampsia have excess hypertension and cardiovascular disease later in life, but the underlying pathophysiology linking these conditions is unknown. Hypothesis: We considered that histological examination of the placenta may reveal maternal vascular impairments that identify a group susceptible to blood pressure (BP) elevations a decade after delivery, including elevations that may only be detectable using out of office BP measurement. Method: Women with a singleton live birth at Magee-Womens Hospital (Pittsburgh, PA) during 2008-2009 were enrolled 8-10 years after delivery (n=248). Pregnancy features and placental pathology were abstracted from medical records. Women with placental vasculopathy (several related lesions arising from impaired remodeling of maternal myometrial and decidual arteries, n=24) or infarcts (n=32) were compared to women with neither lesion (n=192). Clinic BP was measured three times by trained research staff using a standard protocol and a validated home BP device. Women were trained to measure their BP twice daily for 7 days using the same device mentioned above. Subsequently, time and date stamped BP measures were downloaded (mean 12.2 measures ± 4.5). BP status (elevated, stage 1, stage 2) was identified using the 2018 ACC/AHA guidelines for clinic and home BP measures. Sustained normotensive, white coat, masked, and sustained hypertension status were classified. Results: Women were, on average, 37 years of age at measurement. In analysis controlled for age and race (p-value 〈 0.05) those with placental vasculopathy had higher mean diastolic BP in clinic and at home (80.5 ± 13.3 mmHg, 79.9 ± 10.4, respectively) than women without vascular lesions in the placenta (75.4 ± 9.8 mmHg and 74.3 ±8.6, respectively). In addition, women with placental vasculopathy had a higher prevalence of masked hypertension (higher elevated BP status measured at home vs. in clinic; 37.5% vs. 14.1%) that persisted after accounting for maternal age and race (adjusted OR 4.7, 95% confidence interval 1.6, 13.8). Vasculopathy associations were similar after excluding women with preeclampsia (n=42), the pregnancy complication most strongly associated with placental vascular pathology. There were modest, non-significant associations between placental infarcts and all measures of maternal blood pressure. Conclusions: Irrespective of prior preecclampsia, women with placental evidence of vasculopathy have excess hypertension and particularly masked hypertension in the decade after pregnancy. Our results emphasize the value of out of office blood pressure measurement, and indicate that placental vasculopathy may be pathophysiologically related to development of hypertension before age 50.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.139.suppl_1.MP65
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 6
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    Maternal Vascular Lesions in the Placenta Predict Vascular Impairments a Decade After Delivery
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Hypertension Vol. 79, No. 2 ( 2022-02), p. 424-434
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. 2 ( 2022-02), p. 424-434
    Abstract: Women with adverse pregnancy outcomes later experience excess hypertension and cardiovascular disease, but how the events are linked is unknown. Examination of the placenta may provide clues to vascular impairments after delivery. Maternal vascular malperfusion lesions (MVMs) were abstracted from clinical reports, validated and characterized using clinical guidelines and severity score. A total of 492 women (170 with MVMs and 322 without MVMs) participated in a study visit 8 to 10 years after delivery to assess blood pressure, cardiometabolic factors, and sublingual microvascular features using sidestream dark field imaging. Covariates included age, race, adverse pregnancy outcomes (preeclampsia, small for gestational age, and preterm birth), and health behaviors. Women with versus without MVM had a distinct sublingual microvascular profile comprised of (1) lower microvascular density (−410 μm/mm 2 , P =0.015), (2) higher red blood cell filling as a marker of perfusion (2%, P =0.004), and (3) smaller perfused boundary region (−0.07 µm, P =0.025) as a measure of glycocalyx integrity, adjusted for covariates including adverse pregnancy outcomes. Women with MVM also had higher adjusted diastolic blood pressure (+2.6 mm Hg, P =0.021), total and LDL (low-density lipoprotein)-cholesterol (+11.2 mg/dL, P =0.016; +8.7 mg/dL, P =0.031). MVM associations with subsequent cardiovascular measures did not vary by type of adverse pregnancy outcome, except among women with preterm births where blood pressure was higher only among those with MVM. Results were similar when evaluated as MVM severity. A decade after delivery, women with placental vascular lesions had an adverse cardiovascular profile comprised of microvascular rarefaction, higher blood pressure and more atherogenic lipids. Placental histopathology may reveal a woman’s early trajectory toward subsequent vascular disease.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.121.18394
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2094210-2
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  • 7
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    Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. 23 ( 2021-12-07), p. 1845-1855
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. 23 ( 2021-12-07), p. 1845-1855
    Abstract: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92] ; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.121.056290
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1466401-X
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