Functional and structural vascular biomarkers in women 1 year after a hypertensive disorder of pregnancy

OBJECTIVES: Women with a previous hypertensive disorder of pregnancy (HDP: gestational hypertension and preeclampsia) have increased long-term cardiovascular disease risk. Recent meta-analyses show adverse levels of non-invasive functional and structural cardiovascular risk markers such as pulse wave velocity (PWV), heart-rate adjusted augmentation index (AIx75), carotid intima-media thickness (CIMT), and reactive hyperemia index (RHI) after HDPs, and suggest using these for cardiovascular risk stratification. However, it is not known if a previous HDP predict levels of these markers beyond classical cardiovascular risk factors. Study design and main outcome measures. We assessed PWV, AIx75, CIMT, RHI, classical cardiovascular risk factors, and pregnancy characteristics in 221 women 1 year postpartum (controls: 95, previous HDP: 126). Uni- and multi- variate regression analysis were conducted to assess associations between previous HDP and PWV, AIx75, CIMT or RHI. We adjusted for classical cardiovascular risk factors and pregnancy characteristics. A p-level < 0.05 was considered statistically significant. RESULTS: PWV was associated with previous HDP on univariate analysis. This effect was confounded by blood pressure and not significant after adjustment. We found no significant associations between AIx75, RHI, CIMT, and a previous HDP, neither before nor after adjustments. CONCLUSIONS: Associations between a previous HDP and PWV, AIx75, CIMT, or RHI 1 year postpartum can largely be explained by adverse levels of classical cardiovascular risk markers in women with a previous HDP. Women with previous HDP should receive primary prevention of cardiovascular disease, but PWV, AIx75, CIMT or RHI are unlikely to aid in cardiovascular risk stratification 1 year postpartum

COVID-19 outbreak at a reception centre for asylum seekers in Espoo, Finland

Publisher Copyright: © 2021Background shared accommodation may increase the risk of SARS-CoV-2 transmission. In April 2020, an increasing number of asylum seekers at a reception centre in Espoo, Finland presented with COVID-19 despite earlier implementation of preventive measures. We decided to screen the entire population of the centre for SARS-CoV-2. Methods we offered nasopharyngeal swab collection and SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) analysis to the centre's clients. Symptoms were recorded at the time of diagnostic sample collection using electronic forms and followed up for two weeks through phone interviews and a review of medical records. Findings 260 clients were screened. Of them, 96 (37%) were found positive for SARS-CoV-2 and isolated. The high attack rate prompted the local public health authority to set the other clients in quarantine for 14 days to prevent further spread. Of the positive cases, 61 (64%) reported having had symptoms at the time of the screening or one week prior. Of the 35 initially asymptomatic individuals, 12 developed symptoms during follow-up, while 23 (or 18% of all screened SARS-CoV-2 positive clients) remained asymptomatic. No widespread transmission of COVID-19 was detected after the quarantine was lifted. Interpretation in this large COVID-19 outbreak, voluntary mass screening provided valuable information about its extent and helped guide the public health response. Comprehensive quarantine and isolation measures were likely instrumental in containing the outbreak. Funding Finnish Institution for Health and Welfare, Finnish Immigration Agency, City of EspooPeer reviewe

Circulating HLA-G and its association with cardiovascular markers in pregnancy

Human Leukocyte Antigen-G (HLA-G) prevents the activity of immune cells and is decreased in women with preeclampsia. We aimed to investigate the associations between circulating soluble HLA-G (sHLA-G) and 92 cardiovascular disease-related biomarkers from a previously published multiplex study in women with preeclampsia and controls. We found 15 markers significantly associated with circulating sHLA-G in univariate analyses. After multivariable adjusted regression, only proto-oncogene tyrosine-protein kinase Src (SRC) and vascular endothelial growth factor D were significantly associated with sHLA-G. Low SRC, previously observed in the circulation of preeclamptic women, may be regulated by low sHLA-G, and reflect decreased trophoblast differentiation and syncytical formation

Kidney injury caused by preeclamptic pregnancy recovers postpartum in a transgenic rat model

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum

Risk prediction of maternal cardiovascular disease one year after hypertensive pregnancy complications or gestational diabetes mellitus

BACKGROUND: Previous preeclampsia, gestational hypertension and gestational diabetes mellitus show a firm epidemiological association to maternal cardiovascular disease risk. Cardiovascular disease risk assessment is recommended in women after these pregnancy complications, but not offered in most countries. We therefore wanted to evaluate the applicability of currently recommended cardiovascular disease risk scores for women one-year postpartum of such pregnancy complications. DESIGN AND METHODS: We tested applicability of three scoring systems, the Atherosclerotic Cardiovascular Disease (ASCVD) score, the Joint British Societies for the Prevention of Cardiovascular Disease (JBS3) score and Framingham 30 year Risk Score-Cardiovascular Disease (FRS-CVD) in 235 women one-year postpartum (controls: 94, gestational hypertension: 35, preeclampsia: 81, gestational diabetes mellitus: 25). Statistical analysis was performed with Mann-Whitney U test for continuous and Fisher's mid-corrected p and Pearson's r for dichotomous variables. A value of p < 0.050 was considered significant. RESULTS: Most women (87.7%) were below 40 years of age, rendering 10-year risk estimations recommended by American and European societies inapplicable. FRS-CVD could be assessed in all women. Significantly fewer could be assessed by the ASCVD (81.5%) and JBS3 (91.6%). All scoring systems showed small, but significant increases in risk scores for one or more of the pregnancy complication groups, but none at the risk magnitude for cardiovascular disease shown in epidemiological studies. CONCLUSION: We demonstrate that ASCVD, JBS3 and FRS-CVD are inadequate in assessing cardiovascular disease risk one-year postpartum. We suggest that pregnancy complications need to be considered separately when evaluating maternal cardiovascular disease risk and need for postpartum follow-up

Multiplex analysis of circulating maternal cardiovascular biomarkers comparing preeclampsia subtypes

Preeclampsia, a hypertensive pregnancy disorder, links to increased long-term maternal cardiovascular disease (CVD). The risk is further increased with early-onset preeclampsia (EPE) and delivery of a growth-restricted child. We hypothesized that circulating biomarkers associated with CVD risk differed between preeclampsia subtypes and controls. We compared EPE; n=37, delivery <week 34, late-onset preeclampsia (LPE); n=29, delivery ≥week 34, and normotensive controls (n=49) using Olink Proseek multiplex CVD I assay (targeting 92 biomarkers). We stratified analysis to uteroplacental spiral artery acute atherosis presence in preeclampsia patients, sharing morphological similarities with atherosclerosis. We found 47 CVD-related biomarkers differing between the groups, 42 markers between normotensive controls and EPE, 28 markers between normotensive controls and LPE, and 9 markers between EPE and LPE. Among these 9 markers, ST2 (ST2 protein), MMP (matrix metalloproteinase) 1, MMP3, and fractalkine (CX3CL1) were uniquely dysregulated in EPE. Principal component (PC) analysis of the differing markers identified 4 clusters (named PC1-PC4) that largely separated the preeclampsia and control groups as well as pregnancies with low and high circulating PlGF (placental growth factor). The combination of the single markers PlGF, ST2, MMP1, MMP3, and CX3CL1 had a high discriminatory property to differentiate between EPE and LPE. Preeclampsia with acute atherosis or with fetal growth restriction could be differentiated by Olink biomarkers as compared with preeclampsia without these features. We identified specific CVD-related biomarkers in pregnancy depending on preeclampsia subtypes and uteroplacental acute atherosis. Assessment of these pregnancy measured biomarkers' relation to long-term cardiovascular dysfunction and hard end points is warranted

Classical cardiovascular risk markers in pregnancy and associations to uteroplacental acute atherosis

Uteroplacental acute atherosis (AA) is a pregnancy-specific arterial lesion resembling early stages of atherosclerosis. AA is frequent in preeclamptic pregnancies, which associate with increased long-term maternal risk of atherosclerotic cardiovascular disease. We hypothesized that AA in pregnant women associates with classical risk factors for cardiovascular disease, including hypertension, hyperlipidemia, glucose intolerance, elevated C-reactive protein, age, and body mass index. We included 237 women delivered by cesarean section (healthy pregnancies, n=94; preeclampsia, n=87; pregestational and gestational diabetes mellitus, n=39; diabetes mellitus with preeclampsia, n=17). They provided blood before delivery for biomarker analyses. AA was diagnosed by immunohistochemistry in uteroplacental (decidual) tissue collected after placental removal. Statistical analyses were performed with Mann-Whitney test. Levels of traditional cardiovascular markers were not associated with decidual AA within the groups of women with normotensive pregnancies, preeclampsia, diabetes mellitus, or diabetes mellitus superimposed with preeclampsia. However, the oldest patient age quartile (36-43 years old) with AA had significantly higher levels of LDL (low-density lipoprotein) and apolipoprotein B (both P<0.01) than women of the same age without AA. AA was associated with elevated median prepregnancy/early pregnancy systolic blood pressure (P=0.01) in the total cohort, but as preeclampsia was strongly associated with this finding (P<0.01), this was likely caused by a large proportion of preeclamptic pregnancies in the AA group (62.7%). Our findings emonstrate that dyslipidemia associated with cardiovascular risk is a feature of uteroplacental AA in older women, not of AA in pregnancy in general