scholarly journals Association of placental pathology and postpartum cardiovascular risk screening following preeclampsia: an observational cohort study

2021 ◽  
Author(s):  
Samantha Benton ◽  
Erika Mery ◽  
David Grynspan ◽  
Laura Gaudet ◽  
Graeme Smith ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cardiovascular Risk ◽  
High Risk ◽  
Risk Score ◽  
Observational Cohort Study ◽  
Cvd Risk ◽  
Risk Screening ◽  
Cardiovascular Screening ◽  
Increased Risk ◽  
Observational Cohort

Objective: To determine the association between placental lesions and lifetime cardiovascular disease (CVD) risk screening at 6 months postpartum following preeclampsia (PE). Design: Observational cohort study. Setting: Tertiary care centres in Ottawa and Kingston, Ontario, Canada. Population: Women diagnosed with PE who received cardiovascular screening at 6 months postpartum. Methods: Placentas from women diagnosed with PE were evaluated for histopathological lesions according to a standardised synoptic data collection form with blinding to clinical outcomes apart from gestational age at delivery. At 6 months postpartum, each participant was screened for cardiovascular risk factors and a lifetime cardiovascular risk score was calculated. A risk score >35% was deemed high risk for lifetime CVD. Main Outcome Measures: The association between placental lesions and lifetime CVD risk was assessed using odds ratios (OR, 95% confidence intervals). Results: Of the 85 participants, 53 (62.4%) screened high-risk for lifetime CVD. High-risk women had more severe lesions of maternal vascular malperfusion (MVM). MVM lesions with a severity score >2 resulted in a 3-fold increased risk of screening high risk for lifetime CVD (OR 3.10 [1.20-7.92]). MVM lesion score >2 was moderately predictive of high-risk screening (AUC 0.63 [0.51,0.75]; sensitivity: 71.8% [54.6,84.4]; specificity: 54.7% [41.5,67.3]). When clinical data was added, the model’s predictive performance improved (AUC 0.73 [0.62,0.84] sensitivity 78.4% [65.4,87.5]; specificity 51.6% [34.8,68.0]). Conclusions: PE women with MVM are more likely to screen high-risk for lifetime CVD compared to women without these lesions. Placenta pathology may provide a unique modality to identify women for postpartum cardiovascular screening.

scholarly journals Risk of QTc Interval Prolongation Associated With Circulating Anti‐Ro/SSA Antibodies Among US Veterans: An Observational Cohort Study

2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Pietro Enea Lazzerini ◽  
Gabriele Cevenini ◽  
Yongxia Sarah Qu ◽  
Frank Fabris ◽  
Nabil El‐Sherif ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Small Sample ◽  
Observational Cohort Study ◽  
Current Evidence ◽  
Qtc Interval ◽  
Qtc Prolongation ◽  
Increased Risk ◽  
Observational Cohort ◽  
Us Veterans

Background Anti‐Sjögren's syndrome‐related antigen A‐antibodies (anti‐Ro/SSA‐antibodies) are responsible for a novel form of acquired long‐QT syndrome, owing to autoimmune‐mediated inhibition of cardiac human ether‐a‐go‐go‐related gene‐potassium channels. However, current evidence derives only from basic mechanistic studies and relatively small sample‐size clinical investigations. Hence, the aim of our study is to estimate the risk of QTc prolongation associated with the presence of anti‐Ro/SSA‐antibodies in a large population of unselected subjects. Methods and Results This is a retrospective observational cohort study using the Veterans Affairs Informatics and Computing Infrastructure. Participants were veterans who were tested for anti‐Ro/SSA status and had an ECG. Descriptive statistics and univariate and multivariate logistic regression analyses were performed to identify risk factors for heart rate‐corrected QT interval (QTc) prolongation. The study population consisted of 7339 subjects (61.4±12.2 years), 612 of whom were anti‐Ro/SSA‐positive (8.3%). Subjects who were anti‐Ro/SSA‐positive showed an increased prevalence of QTc prolongation, in the presence of other concomitant risk factors (crude odds ratios [OR], 1.67 [1.26–2.21] for QTc >470/480 ms; 2.32 [1.54–3.49] for QTc >490 ms; 2.77 [1.66–4.60] for QTc >500 ms), independent of a connective tissue disease history. Adjustments for age, sex, electrolytes, cardiovascular risk factors/diseases, and medications gradually attenuated QTc prolongation estimates, particularly when QT‐prolonging drugs were added to the model. Nevertheless, stepwise‐fully adjusted OR for the higher cutoffs remained significantly increased in anti‐Ro/SSA‐positive subjects, particularly for QTc >500 ms (2.27 [1.34–3.87]). Conclusions Anti‐Ro/SSA‐antibody positivity was independently associated with an increased risk of marked QTc prolongation in a large cohort of US veterans. Our data suggest that within the general population individuals who are anti‐Ro/SSA‐positive may represent a subgroup of patients particularly predisposed to ventricular arrhythmias/sudden cardiac death.

scholarly journals Genetic and pharmacological relationship between P-glycoprotein and increased cardiovascular risk associated with clarithromycin prescription: An epidemiological and genomic population-based cohort study in Scotland, UK

PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003372
Author(s):  
Ify R. Mordi ◽  
Benjamin K. Chan ◽  
N. David Yanez ◽  
Colin N. A. Palmer ◽  
Chim C. Lang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Observational Cohort Study ◽  
Chronic Obstructive ◽  
Antibiotic Prescribing ◽  
Nucleotide Polymorphisms ◽  
Major Pathway ◽  
P Glycoprotein ◽  
Increased Risk ◽  
History Of ◽  
Observational Cohort

Background There are conflicting reports regarding the association of the macrolide antibiotic clarithromycin with cardiovascular (CV) events. A possible explanation may be that this risk is partly mediated through drug–drug interactions and only evident in at-risk populations. To the best of our knowledge, no studies have examined whether this association might be mediated via P-glycoprotein (P-gp), a major pathway for clarithromycin metabolism. The aim of this study was to examine CV risk following prescription of clarithromycin versus amoxicillin and in particular, the association with P-gp, a major pathway for clarithromycin metabolism. Methods and findings We conducted an observational cohort study of patients prescribed clarithromycin or amoxicillin in the community in Tayside, Scotland (population approximately 400,000) between 1 January 2004 and 31 December 2014 and a genomic observational cohort study evaluating genotyped patients from the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) study, a longitudinal cohort study of 18,306 individuals with and without type 2 diabetes recruited between 1 December 1988 and 31 December 2015. Two single-nucleotide polymorphisms associated with P-gp activity were evaluated (rs1045642 and rs1128503 –AA genotype associated with lowest P-gp activity). The primary outcome for both analyses was CV hospitalization following prescription of clarithromycin versus amoxicillin at 0–14 days, 15–30 days, and 30 days to 1 year. In the observational cohort study, we calculated hazard ratios (HRs) adjusted for likelihood of receiving clarithromycin using inverse proportion of treatment weighting as a covariate, whereas in the pharmacogenomic study, HRs were adjusted for age, sex, history of myocardial infarction, and history of chronic obstructive pulmonary disease. The observational cohort study included 48,026 individuals with 205,227 discrete antibiotic prescribing episodes (34,074 clarithromycin, mean age 73 years, 42% male; 171,153 amoxicillin, mean age 74 years, 45% male). Clarithromycin use was significantly associated with increased risk of CV hospitalization compared with amoxicillin at both 0–14 days (HR 1.31; 95% CI 1.17–1.46, p < 0.001) and 30 days to 1 year (HR 1.13; 95% CI 1.06–1.19, p < 0.001), with the association at 0–14 days modified by use of P-gp inhibitors or substrates (interaction p-value: 0.029). In the pharmacogenomic study (13,544 individuals with 44,618 discrete prescribing episodes [37,497 amoxicillin, mean age 63 years, 56% male; 7,121 clarithromycin, mean age 66 years, 47% male]), when prescribed clarithromycin, individuals with genetically determined lower P-gp activity had a significantly increased risk of CV hospitalization at 30 days to 1 year compared with heterozygotes or those homozygous for the non-P-gp–lowering allele (rs1045642 AA: HR 1.39, 95% CI 1.20–1.60, p < 0.001, GG/GA: HR 0.99, 95% CI 0.89–1.10, p = 0.85, interaction p-value < 0.001 and rs1128503 AA 1.41, 95% CI 1.18–1.70, p < 0.001, GG/GA: HR 1.04, 95% CI 0.95–1.14, p = 0.43, interaction p-value < 0.001). The main limitation of our study is its observational nature, meaning that we are unable to definitively determine causality. Conclusions In this study, we observed that the increased risk of CV events with clarithromycin compared with amoxicillin was associated with an interaction with P-glycoprotein.

Risk results from screening for a high cardiovascular disease risk by means of traditional risk factor measurement or coronary artery calcium scoring in the ROBINSCA trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Van Der Aalst ◽  
S.J.A.M Denissen ◽  
M Vonder ◽  
J.-W.C Gratema ◽  
H.J Adriaansen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery ◽  
High Risk ◽  
Risk Score ◽  
Coronary Artery Calcium ◽  
Preventive Treatment ◽  
Low Risk ◽  
Funding Source ◽  
Cvd Risk ◽  
Increased Risk

Abstract Aims Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease (CHD)-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or Coronary Artery Calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. Methods and results Individuals at expected elevated CVD risk were randomized (1:1:1) into the control arm (n=14,519; usual care); screening arm A (n=14,478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n=14,450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. 12,185 participants (84.2%) in arm A and 12,950 (89.6%) in arm B were screened. 48.7% were women, and median age was 62 (InterQuartile Range 10) years. SCORE screening identified 45.1% at low risk (SCORE&lt;10%), 26.5% at intermediate risk (SCORE 10–20%), and 28.4% at high risk (SCORE≥20%). According to CAC screening, 76.0% were at low risk (Agatston&lt;100), 15.1% at high risk (Agatston 100–399), and 8.9% at very high risk (Agatston≥400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). Conclusion We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. ROBINSCA flowchart Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Advanced Research Grant

scholarly journals Fetal sex modifies the effect of maternal macronutrient intake on the incidence of small-for-gestational-age births: a prospective observational cohort study

2018 ◽  
Vol 108 (4) ◽  
pp. 814-820 ◽  
Author(s):  
A Mukhopadhyay ◽  
T Thomas ◽  
R J Bosch ◽  
P Dwarkanath ◽  
A Thomas ◽  
...  
Keyword(s):  
Cohort Study ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Observational Cohort Study ◽  
Prospective Observational Cohort Study ◽  
Macronutrient Intake ◽  
Fetal Sex ◽  
Increased Risk ◽  
Observational Cohort

Abstract Background Maternal macronutrient intake is likely to play a pivotal role in fetoplacental growth. Male fetuses grow faster and their growth is more responsive to maternal size. Objective We assessed the role of fetal sex in modifying the effect of maternal macronutrient intake on the risk of small-for-gestational-age (SGA) birth. Design This was a prospective, observational cohort study of 2035 births from an urban South Asian Indian population. Maternal intakes of total energy and macronutrients were recorded by validated food-frequency questionnaires. The interaction of trimester 1 macronutrient intake with fetal sex was tested on the outcome of SGA births. Results The prevalence of SGA was 28%. Trimester 1 macronutrient composition was high in carbohydrate and low in fat (means ± SDs—carbohydrate: 64.6% ± 5.1%; protein: 11.5% ± 1.1%; and fat: 23.9% ± 4.4% of energy). Higher carbohydrate and lower fat consumption were each associated with an increased risk of SGA [adjusted OR (AOR) per 5% of energy (95% CI): carbohydrate: 1.15 (1.01, 1.32); fat: 0.83 (0.71, 0.97)] specifically among male births (males: n = 1047; females: n = 988). Dietary intake of &gt;70% of energy from carbohydrate was also associated with increased risk (AOR: 1.67; 95% CI: 1.00, 2.78), whereas &gt;25% of energy from fat intake was associated with decreased risk (AOR: 0.61; 95% CI: 0.41, 0.90) of SGA in male births. Conclusions Higher carbohydrate and lower fat intakes early in pregnancy were associated with increased risk of male SGA births. Therefore, we speculate that fetal sex acts as a modifier of the role of maternal periconceptional nutrition in optimal fetoplacental growth.

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