Analysis of Predictive Information From Biomarkers Added to Clinical Models of Preeclampsia: Consideration of PAPP-A2, Activin A, and sFlt-1:PlGF Ratio.

BACKGROUND: Preeclampsia remains a major cause of maternal and fetal adverse outcomes in pregnancy; however, accurate and universally acceptable predictive tools remain elusive. We investigated whether a panel of biomarkers could improve risk prediction for preeclampsia when measured at various pregnancy time points. METHODS: In this prospective cohort study, 192 women with first-trimester high-risk singleton pregnancies were consecutively recruited from tertiary obstetrics clinics in Montréal, Canada. Clinical information (height, pre-pregnancy weight, personal and family medical history, medication use) was collected at baseline. Blood pressure was measured and blood samples collected at each trimester to quantify soluble Fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), pregnancy-associated plasma protein A2 (PAPP-A2), PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. A random-effects hierarchic logistic regression model was used to relate change in biomarker levels to incidence of preeclampsia. RESULTS: When added to a clinical model composed of maternal age, pre-pregnancy body mass index, race, and mean arterial pressure, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% [95% confidence interval (CI) 78.57%-100%] vs 66.67% [57.14%-100%]), while maintaining a comparable high negative predictive value (97.69% [95% CI 95.34%-100%] vs 96.00% [92.19%-99.21%]). CONCLUSIONS: Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and therefore could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies.

Diabetes, antidiabetic medications and risk of dementia: A systematic umbrella review and meta-analysis.

AIMS: The objective of this umbrella review and meta-analysis was to evaluate the effect of diabetes on risk of dementia, as well as the mitigating effect of antidiabetic treatments. MATERIALS AND METHODS: We conducted a systematic umbrella review on diabetes and its treatment, and a meta-analysis focusing on treatment. We searched MEDLINE/PubMed, Embase, PsycINFO, CINAHL and the Cochrane Library for systematic reviews and meta-analyses assessing the risk of cognitive decline/dementia in individuals with diabetes until 2 July 2023. We conducted random-effects meta-analyses to obtain risk ratios and 95% confidence intervals estimating the association of metformin, thiazolidinediones, pioglitazone, dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors, meglitinides, insulin, sulphonylureas, glucagon-like peptide-1 receptor agonists (GLP1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) with risk of dementia from cohort/case-control studies. The subgroups analysed included country and world region. Risk of bias was assessed with the AMSTAR tool and Newcastle-Ottawa Scale. RESULTS: We included 100 reviews and 27 cohort/case-control studies (N = 3 046 661). Metformin, thiazolidinediones, pioglitazone, GLP1RAs and SGLT2is were associated with significant reduction in risk of dementia. When studies examining metformin were divided by country, the only significant effect was for the United States. Moreover, the effect of metformin was significant in Western but not Eastern populations. No significant effect was observed for dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors, or insulin, while meglitinides and sulphonylureas were associated with increased risk. CONCLUSIONS: Metformin, thiazolidinediones, pioglitazone, GLP1RAs and SGLT2is were associated with reduced risk of dementia. More longitudinal studies aimed at determining their relative benefit in different populations should be conducted.

Alterations in Vessel Hemodynamics Across Uncomplicated Pregnancy.

Pregnancy is marked by the onset of rapid hemodynamic alterations in order to accommodate the needs of the developing fetus. Arterial stiffness is an independent predictor of cardiovascular events and mortality, and its measurement in clinical practice has been recommended. It follows a U-shaped curve in uncomplicated pregnancy, decreasing to a nadir in mid-pregnancy and rising at term. Systemic vasodilation occurs due to elevated nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, estrogen, progesterone, and relaxin. Vascular resistance decreases to a nadir in mid-pregnancy, while endothelial function is enhanced starting in the first trimester. Plasma volume increases by about 50%, and total red blood cell mass increases by up to 40%. Cardiac output increases by up to 45%, at first due primarily to elevated stroke volume, then mainly due to increased heart rate. Along with echocardiography, cardiac magnetic resonance imaging is safe for use in pregnancy. It may assess cardiac function more accurately than echocardiography, and may be indicated in specific clinical cases. Moreover, blood pressure decreases to a nadir in mid-pregnancy and rises to near preconception values postpartum. An appreciation of the vascular changes occurring in healthy pregnancy can aid in the prediction and diagnosis of pregnancy complications, such as preeclampsia and other hypertensive disorders of pregnancy, and inform treatment. In particular, noninvasive arterial stiffness/hemodynamics assessment provides unique clinical information beyond blood pressure and traditional maternal characteristics, and can signal a need for further testing, or be used in combination with other tests to predict or diagnose complications of pregnancy.

Arterial stiffness measurements in pregnancy as a predictive tool for hypertensive disorders of pregnancy and preeclampsia: Protocol for a systematic review and meta-analysis.

Hypertensive disorders of pregnancy (HDPs) are a leading cause of maternal morbidity and mortality worldwide. Unfortunately, accurate early clinical screening methods for the development of these disorders are lacking. Arterial stiffness (AS) is an important hemodynamic indicator of vascular health that has shown promising results for the prediction of HDP onset. Past systematic reviews in the field have reported an increase in AS indices in women who develop HDPs and have highlighted the potential of AS measurements as a predictive tool early in pregnancy. The most recent systematic review, including papers up to 2015, assessed the differences in AS parameters between women with and without pregnancy complications. Since then, there has been a substantial influx of published research on the topic and a growing interest in the incorporation of AS measurements into clinical practice. Thus, we propose a systematic review and meta-analysis that is more inclusive to all HDP subsets and various hemodynamic indices of vascular health to provide a comprehensive overview of the current state of evidence. Specifically, we aim to evaluate these measures in women who develop HDPs compared to normotensive pregnancies to determine which measures are most associated with and/or can predict the development of HDPs. Major databases (Medline, Embase, The Cochrane Library, Web of Science, PubMed, and CINAHL), grey literature (Google Scholar) and clinical trials (clinicaltrials.gov) will be searched to identify studies that report AS and hemodynamic measurements in pregnant women with and without HDPs. No restrictions will be made on study type or year. Articles will be independently evaluated by three authors to determine eligibility based on inclusion and exclusion criteria. Methodological quality of included studies will be assessed. Pooled analyses will be conducted using a random-effects model. Publication bias and between-study heterogeneity will also be assessed. Sources of heterogeneity will be explored by sensitivity, subgroup, and/or meta-regression analyses. Results from this study will be shared through scientific conferences and publications in scientific journals. The analysis of potential AS and hemodynamic markers for HDP onset will help inform the development of screening guidelines and clinically relevant cut-off values of AS and hemodynamic markers for HDP risk, guiding future research. There are no applicable ethical considerations to the writing of this protocol.

Association of HIV Infection and Antiretroviral Therapy With Arterial Stiffness: A Systematic Review and Meta-Analysis.

[Figure: see text].

Methodological considerations for the measurement of arterial stiffness using applanation tonometry.

INTRODUCTION: Accurate comparisons of carotid--femoral pulse wave velocity (cfPWV) within and across studies require standardized procedures. Guidelines suggest reporting the average of at least two cfPWV measurements; if the difference exceeds 0.5 m/s, a third measurement should be taken, and the median reported. Another method involves repeating measurements until two values are within 0.5 m/s. However, in many studies, duplicate measurements are averaged irrespective of the difference between readings. We evaluated the impact of these methods on the reported cfPWV value. METHODS: Measurements of cfPWV (SphygmoCor) from five studies included individuals spanning a wide age range, with or without comorbid conditions, and pregnant women. In participants with at least three high-quality measurements, differences between the median value (MED) and the average of the first two cfPWV measurements (AVG1) and the average of two cfPWV measurements within 0.5 m/s (AVG2) were evaluated using paired t-tests and Bland--Altman plots. RESULTS: Participants' mean age was 50 ±â€Š14 years and BMI was 28.0 ±â€Š5.5 kg/m2 (N = 306, 79% women). The overall mean difference was -0.10 m/s (95% CI 0.17 to -0.04) between MED and AVG1, and 0.11 m/s (95% CI 0.05--0.17) between MED and AVG2. The absolute difference exceeded 0.5 m/s in 34% (MED-AVG1) and 22% (MED-AVG2) of participants, and 1 m/s in 8% of participants (both MED-AVG1 and MED-AVG2). Scatter around the bias line increased with higher mean cfPWV values. CONCLUSION: Although the overall mean difference in cfPWV between protocols was not clinically relevant, large variation led to absolute differences exceeding 0.5 m/s in a large proportion of participants.