Investigation and management of young-onset hypertension: British and Irish hypertension society position statement.

National and international hypertension guidelines recommend that adults with young-onset hypertension (aged <40 years at diagnosis) are reviewed by a hypertension specialist to exclude secondary causes of hypertension and optimise therapeutic regimens. A recent survey among UK secondary care hypertension specialist physicians highlighted variations in the investigation of such patients. In this position statement, the British and Irish Hypertension Society seek to provide clinicians with a practical approach to the investigation and management of adults with young-onset hypertension. We aim to ensure that individuals receive consistent and high-quality care across the UK and Ireland, to highlight gaps in the current evidence, and to identify important future research questions.

Retinopathy among women with hypertensive disorders of pregnancy attending hospitals in Mbarara city, south-western Uganda: a cross-sectional study.

OBJECTIVE: Retinopathy is one of the complications occurring among women with hypertensive disorders of pregnancy. We sought to determine the prevalence and factors associated with retinopathy among women with hypertensive disorders of pregnancy in southwestern Uganda. DESIGN: This was a hospital-based cross-sectional study from November 2019 to March 2020. SETTING: Three selected hospitals in Mbarara city, south-western Uganda. PARTICIPANTS: The study included all pregnant women with hypertensive disorders of pregnancy. PRIMARY AND SECONDARY OUTCOME MEASURES: The participants were screened for retinopathy using a fundus camera. Data on participant's sociodemographics, obstetrics and medical factors were collected. The prevalence of retinopathy was determined and multivariable logistic regression was used to determine the independent factors associated with retinopathy. RESULTS: A total of 216 women with hypertensive disorders of pregnancy were enrolled in this study. The prevalence of retinopathy was 60.2% (130/216). The most common retinal lesions were grade 1 retinopathy (narrowing of arterioles) accounting for 86.9% (113/130), grade 3 (retinal haemorrhages) was present in 10% (13/130) of women and grade 4 (papilloedema) in 3% (4/130). In an adjusted analysis, severe hypertension was significantly associated with retinopathy (aOR=2.8; 95% CI: 1.36 to 5.68). Grandmultigravida women were also associated with retinopathy (aOR=2.4; 95% CI: 0.99 to 5.72) with a tendency towards significancy, p=0.051. CONCLUSIONS: In our study, retinopathy was common among women with hypertensive disorders of pregnancy. Women presenting with severe hypertension were likely to have retinopathy. There is a need to integrate screening for retinopathy in the care cascade of women with hypertensive disorders of pregnancy.

Placental syndromes and maternal cardiovascular health.

The placental syndromes gestational hypertension, preeclampsia and intrauterine growth restriction are associated with an increased cardiovascular risk to the mother later in life. In this review, we argue that a woman's pre-conception cardiovascular health drives both the development of placental syndromes and long-term cardiovascular risk but acknowledge that placental syndromes can also contribute to future cardiovascular risk independent of pre-conception health. We describe how preclinical studies in models of preeclampsia inform our understanding of the links with later cardiovascular disease, and how current pre-pregnancy studies may explain relative contributions of both pre-conception factors and the occurrence of placental syndromes to long-term cardiovascular disease.

Circulating testosterone levels and health outcomes in chronic obstructive pulmonary disease: results from ECLIPSE and ERICA.

The relationship of circulating testosterone levels with health outcomes in people with chronic obstructive pulmonary disease (COPD) is unknown. AIM: To determine whether serum testosterone levels predict hospitalised acute exacerbations of COPD (H-AECOPD), cardiovascular disease outcome, and mortality in people with COPD. METHODS: Separate analyses were carried out on two observational, multicentre COPD cohorts, Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) and Evaluation of the Role of Inflammation in Chronic Airways Disease (ERICA), both of which had serum testosterone measured using a validated liquid chromatography assay at the same laboratory. Data from 1296 male participants in ECLIPSE and 386 male, 239 female participants in ERICA were analysed. All analyses were sex-specific. Multivariate logistic regression was used to determine associations with H-AECOPD during follow-up (3 years ECLIPSE, 4.5 years ERICA), a composite endpoint of cardiovascular hospitalisation and cardiovascular death, and all-cause mortality. RESULTS: Mean (SD) testosterone levels were consistent across cohorts; 459 (197) and 455 (200) ng/dL for males in ECLIPSE and ERICA, respectively, and in ERICA females: 28 (56) ng/dL. Testosterone was not associated with H-AECOPD (ECLIPSE: OR: 0.76, p=0.329, ERICA males: OR (95% CI): 1.06 (0.73 to 1.56), p=0.779, ERICA females: OR: 0.77 (0.52 to 1.12), p=0.178) or cardiovascular hospitalisation and death. Testosterone was associated with all-cause mortality in Global Initiative for Obstructive Lung Disease (GOLD) stage 2 male patients only, in ECLIPSE (OR: 0.25, p=0.007) and ERICA (OR: (95% CI): 0.56 (0.32 to 0.95), p=0.030). CONCLUSIONS: Testosterone levels do not relate to H-AECOPD or cardiovascular outcome in COPD, but are associated with all-cause mortality in GOLD stage 2 COPD male patients, although the clinical significance of this finding is uncertain.

Impact of perinatal factors on biomarkers of cardiovascular disease risk in preadolescent children.

BACKGROUND: This review aims to summarize associations of the perinatal environment with arterial biophysical properties in childhood, to elucidate possible perinatal origins of adult cardiovascular disease (CVD). METHODS: A systematic search of PubMed database was performed (December 2020). Studies exploring associations of perinatal factors with arterial biophysical properties in children 12 years old or less were included. Properties studied included: pulse wave velocity; arterial stiffness or distensibility; augmentation index; intima-media thickness of aorta (aIMT) or carotids; endothelial function (laser flow Doppler, flow-mediated dilatation). Two reviewers independently performed study selection and data extraction. RESULTS: Fifty-two of 1084 identified records were included. Eleven studies explored associations with prematurity, 14 explored maternal factors during pregnancy, and 27 explored effects of low birth weight, small-for-gestational age and foetal growth restriction (LBW/SGA/FGR). aIMT was consistently higher in offspring affected by LBW/SGA/FGR in all six studies examining this variable. The cause of inconclusive or conflicting associations found with other arterial biophysical properties and perinatal factors may be multifactorial: in particular, measurements and analyses of related properties differed in technique, equipment, anatomical location, and covariates used. CONCLUSION: aIMT was consistently higher in LBW/SGA/FGR offspring, which may relate to increased long-term CVD risk. Larger and longer term cohort studies may help to elucidate clinical significance, particularly in relation to established CVD risk factors. Experimental studies may help to understand whether lifestyle or medical interventions can reverse perinatal changes aIMT. The field could be advanced by validation and standardization of techniques assessing arterial structure and function in children.

Persistent hypertension at 3 months postpartum among women with hypertensive disorders of pregnancy at a tertiary hospital in Southwestern Uganda.

BACKGROUND: Hypertension is a key contributor to the global epidemic of cardiovascular disease and is responsible for more deaths worldwide than any other cardiovascular risk factor. Hypertensive disorders of pregnancy, of which preeclampsia and eclampsia are the most common forms, have been shown to be a female-specific risk factor for chronic hypertension. OBJECTIVE: This study aimed to determine the proportion and risk factors for persistent hypertension at 3 months after delivery among women with hypertensive disorders of pregnancy in Southwestern Uganda. STUDY DESIGN: This was a prospective cohort study of pregnant women with hypertensive disorders of pregnancy admitted for delivery at Mbarara Regional Referral Hospital in Southwestern Uganda from January 2019 to December 2019; however, women with chronic hypertension were excluded from the study. The participants were followed up for 3 months after delivery. Participants with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg or receiving antihypertension therapy at 3 months after delivery were considered to have persistent hypertension. Multivariable logistic regression was used to determine independent risk factors associated with persistent hypertension. RESULTS: A total of 111 participants with hypertensive disorders of pregnancy diagnosed at hospital admission were enrolled with a follow-up rate of 49% (54/111) at 3 months after delivery. Of these women, 21 of 54 (39%) had persistent hypertension 3 months after delivery. In the adjusted analyses, an elevated serum creatinine level (>106.08 µmol/L [≤1.2 mg/dL]) at admission for delivery was the only independent risk factor for persistent hypertension at 3 months after delivery (adjusted relative risk, 1.93; 95% confidence interval, 1.08-3.46; P=.03), controlling for age, gravidity, and eclampsia. CONCLUSION: Approximately 4 of 10 women presenting with hypertensive disorders of pregnancy at our institution remained hypertensive 3 months after delivery. Innovative strategies are needed to identify these women and provide long-term care to optimize blood pressure control and reduce future cardiovascular disease after hypertensive disorders of pregnancy.

Aortic Pulse Wave Velocity as Adjunct Risk Marker for Assessing Cardiovascular Disease Risk: Prospective Study.

BACKGROUND: Aortic pulse wave velocity is a noninvasive measure of aortic stiffness and arterial aging. Its current value in cardiovascular risk estimation practice is unknown. We aimed to establish whether aortic pulse wave velocity identified individuals with higher risk of incident major adverse cardiovascular events and improved performance of the American Heart Association/American College of Cardiology atherosclerotic cardiovascular disease risk score. METHODS: This prospective analysis included 3837 Whitehall II cohort participants screened in 2008 to 2009, and followed for 11.7 years (mean=10.3, SD=1.81), without history of stroke, myocardial infarction, or coronary heart disease. RESULTS: Mean age of the sample was 65.0 years (SD=5.6), 2831 participants (73.8%) were male and mean atherosclerotic cardiovascular disease risk score was 13.8%. At the end of follow-up, 411 individuals (10.7%) had suffered a major cardiovascular event. Those in the highest aortic pulse wave velocity quartile were at high risk (hazard ratio, 2.99 [95% CI, 2.25-3.97]) and reached the threshold for statin medication (7.5% risk) after 5 years whereas others reached it after 10 years (difference P<0.001). The addition of aortic pulse wave velocity to the risk score improved the C statistic (0.68 versus 0.67, P=0.03) and net reclassification index (4.6%, P=0.04 and 11.3%, P=0.02). CONCLUSIONS: Our results show that aortic stiffness predicted major adverse cardiovascular events in a cohort of elderly individuals, improving the performance of a widely used cardiovascular disease risk estimator. Aortic pulse wave velocity measurement is scalable, radiation-free, and easy to perform. Further studies on its applicability in cardiovascular disease risk assessment in primary care settings are needed.

Twenty-Four-Hour Central (Aortic) Systolic Blood Pressure: Reference Values and Dipping Patterns in Untreated Individuals.

Central (aortic) systolic blood pressure (cSBP) is the pressure seen by the heart, the brain, and the kidneys. If properly measured, cSBP is closer associated with hypertension-mediated organ damage and prognosis, as compared with brachial SBP (bSBP). We investigated 24-hour profiles of bSBP and cSBP, measured simultaneously using Mobilograph devices, in 2423 untreated adults (1275 women; age, 18-94 years), free from overt cardiovascular disease, aiming to develop reference values and to analyze daytime-nighttime variability. Central SBP was assessed, using brachial waveforms, calibrated with mean arterial pressure (MAP)/diastolic BP (cSBPMAP/DBPcal), or bSBP/diastolic blood pressure (cSBPSBP/DBPcal), and a validated transfer function, resulting in 144 509 valid brachial and 130 804 valid central measurements. Averaged 24-hour, daytime, and nighttime brachial BP across all individuals was 124/79, 126/81, and 116/72 mm Hg, respectively. Averaged 24-hour, daytime, and nighttime values for cSBPMAP/DBPcal were 128, 128, and 125 mm Hg and 115, 117, and 107 mm Hg for cSBPSBP/DBPcal, respectively. We pragmatically propose as upper normal limit for 24-hour cSBPMAP/DBPcal 135 mm Hg and for 24-hour cSBPSBP/DBPcal 120 mm Hg. bSBP dipping (nighttime-daytime/daytime SBP) was -10.6 % in young participants and decreased with increasing age. Central SBPSBP/DBPcal dipping was less pronounced (-8.7% in young participants). In contrast, cSBPMAP/DBPcal dipping was completely absent in the youngest age group and less pronounced in all other participants. These data may serve for comparison in various diseases and have potential implications for refining hypertension diagnosis and management. The different dipping behavior of bSBP versus cSBP requires further investigation.

Quantitative 18F-fluorodeoxyglucose positron emission tomography/computed tomography to assess pulmonary inflammation in COPD.

RATIONALE: COPD and smoking are characterised by pulmonary inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker. OBJECTIVES: To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in "usual" (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients. METHODS: Data from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKi and systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKi values at baseline and at 4-month follow-up. RESULTS: COPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001 versus 0.0028±0.001 mL·cm-3·min-1, respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi (ß=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory volume in 1 s % predicted, systemic neutrophils and C-reactive protein levels. Mean percentage difference in nKi between the baseline and follow-up was 3.2%, and the within subject coefficient of variability was 7.7%. CONCLUSIONS: FDG PET/CT has potential as a noninvasive tool to enable whole lung and regional quantification of FDG uptake to assess smoking- and COPD-related pulmonary inflammation.

Diurnal pattern of salivary cortisol and progression of aortic stiffness: Longitudinal study.

BACKGROUND: The positive direct relation between stress and the development of cardiovascular disease has increasingly been recognized. However, the link between hypothalamic-pituitary-adrenal (HPA) dysregulation and subclinical cardiovascular disease has not been studied longitudinally. We investigated the relation of diurnal salivary cortisol, as a biological marker of stress levels, with progression of aortic stiffness over five years. METHODS: A total of 3281 people (mean age 65.5) in the Whitehall II prospective study provided six saliva samples on a single weekday. We assessed the diurnal salivary cortisol using the daytime slope and bedtime level. Aortic stiffness was measured by carotid-femoral pulse wave velocity (PWV) at baseline (2007-2009) and five years later (2012-2013). Linear mixed models were used to estimate the association of diurnal salivary cortisol with baseline PWV and five-year longitudinal changes. RESULTS: Diurnal salivary cortisol were not associated with PWV at baseline. Among women but not men, a 1-SD shallower salivary cortisol slope at baseline was associated with a five-year increase in PWV (ß = 0.199; 95% CI = 0.040, 0.358 m/s) and higher bedtime cortisol level (ß = 0.208, 95% CI = 0.062, 0.354 m/s). CONCLUSIONS: Dysregulation of the HPA axis measured using salivary cortisol (shallower slope, higher bedtime level) predicted the rate of progression of aortic stiffness among women.

Investigating the Lowest Threshold of Vascular Benefits from LDL Cholesterol Lowering with a PCSK9 mAb Inhibitor (Alirocumab) in Patients with Stable Cardiovascular Disease (INTENSITY-HIGH): protocol and study rationale for a randomised, open label, parallel group, mechanistic study.

INTRODUCTION: Elevated low-density lipoprotein cholesterol (LDL-C) is a strong independent risk predictor of cardiovascular (CV) events, while interventions to reduce it remain the only evidence-based approach to reduce CV morbidity and mortality. Secondary prevention statin trials in combination with ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors showed that there is no 'J shaped curve' in LDL-C levels with regard to CV outcomes. The lowest threshold beyond which reduction of LDL-C confers no further CV benefits has not been identified.The INTENSITY-HIGH study seeks to explore physiological mechanisms mediating CV benefits of LDL-C lowering by PCSK9 inhibition in patients with established cardiovascular disease (CVD). The study examines the changes in measures of endothelial function and vascular inflammation imaging following intervention with PCSK9 and against standard of care. METHODS AND ANALYSIS: This is a single-centre, randomised, open label, parallel group, mechanistic physiological study. It will include approximately 60 subjects with established CVD, with LDL-C of <4.1 mmol/L on high-intensity statins. All eligible participants will undergo 18-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) scanning of the aorta and carotid arteries, as well as baseline endothelial function assessment. Subsequently, they will be randomised on a 1:1 basis to either alirocumab 150 mg or ezetimibe 10 mg/day. Repeat FDG-PET/CT scan and vascular assessments will be undertaken after 8 weeks of treatment. Any changes in these parameters will be correlated with changes in lipid levels and systemic inflammation biomarkers. ETHICS AND DISSEMINATION: The study received a favourable opinion from the Wales Research Ethics Committee 4, was registered on clinicaltrials.gov and conformed to International Conference for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice. The results of this study will be reported through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT03355027.

Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial.

[Figure: see text].

Dyslipidemia, Insulin Resistance, Ectopic Lipid Accumulation, and Vascular Function in Resistance to Thyroid Hormone ß.

PURPOSE: In resistance to thyroid hormone due to mutations in thyroid hormone receptor ß, peripheral tissues are variably refractory to the action of circulating thyroid hormones. We evaluated parameters contributing to atherosclerotic risk in this disorder. METHODS: We measured low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), nonesterified fatty acids (NEFA), intrahepatic lipid (IHL) and intramyocellular lipid (IMCL), Homeostasis-model assessment of insulin resistance (HOMA-IR), augmentation index (AIx) and pulse wave velocity (PWV), flow-mediated dilatation, and carotid intima-media thickness (cIMT) in an unselected, genetically confirmed cohort of adult RTHß patients (n = 27-77) and compared these with measurements in healthy subjects (up to n = 100) and thyrotoxic patients (n = 40). RESULTS: Resistance to thyroid hormone beta (RTHß) patients exhibited higher LDL-C (P = 0.008) and TG (P = 0.002) and lower HDL-C concentrations (P = 0.015 × 10-2) than control subjects, with LDL-C being higher than in thyrotoxic patients with comparable hyperthyroxinemia. Proprotein convertase subtilisin/kexin 9 (P = 0.002) and apolipoprotein B (P = 0.0009) levels were reduced in thyrotoxic patients but not lower in RTHß patients or control subjects. Intrahepatic lipid (P = 0.02 × 10-4), IMCL (P = 0.002), HOMA-IR (P = 0.01 × 10-2), and NEFA (P = 0.04 × 10-6) were significantly higher in RTHß patients than control subjects. Flow-mediated dilatation was increased (P = 0.04) but cIMT (P = 0.71), PWV P = 0.81), and AIx (P = 0.95) were unaltered in RTHß patients. CONCLUSIONS: We have documented mixed dyslipidemia with hepatic and IMCL accumulation in RTHß, suggesting that surveillance for these metabolic abnormalities is warranted. How they combine with enhanced endothelial function and unaltered vessel wall thickness and compliance to determine overall cardiometabolic risk in this disorder remains to be defined.

Validation of a Non-invasive Inverse Problem-Solving Method for Stroke Volume.

Stroke volume (SV) is a major biomarker of cardiac function, reflecting ventricular-vascular coupling. Despite this, hemodynamic monitoring and management seldomly includes assessments of SV and remains predominantly guided by brachial cuff blood pressure (BP). Recently, we proposed a mathematical inverse-problem solving method for acquiring non-invasive estimates of mean aortic flow and SV using age, weight, height and measurements of brachial BP and carotid-femoral pulse wave velocity (cfPWV). This approach relies on the adjustment of a validated one-dimensional model of the systemic circulation and applies an optimization process for deriving a quasi-personalized profile of an individual's arterial hemodynamics. Following the promising results of our initial validation, our first aim was to validate our method against measurements of SV derived from magnetic resonance imaging (MRI) in healthy individuals covering a wide range of ages (n = 144; age range 18-85 years). Our second aim was to investigate whether the performance of the inverse problem-solving method for estimating SV is superior to traditional statistical approaches using multilinear regression models. We showed that the inverse method yielded higher agreement between estimated and reference data (r = 0.83, P < 0.001) in comparison to the agreement achieved using a traditional regression model (r = 0.74, P < 0.001) across a wide range of age decades. Our findings further verify the utility of the inverse method in the clinical setting and highlight the importance of physics-based mathematical modeling in improving predictive tools for hemodynamic monitoring.

Cardiovascular risk prediction using physical performance measures in COPD: results from a multicentre observational study.

OBJECTIVES: Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD. Traditional CV risk scores have been tested in different populations but not uniquely in COPD. The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown. We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors. DESIGN: Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV COPD were used. Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up. SETTING: Five UK centres interested in COPD. PARTICIPANTS: Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks. INTERVENTIONS: Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima-media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test. PRIMARY AND SECONDARY OUTCOME MEASURES: New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality. RESULTS: Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD. The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction. CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all). However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728). CONCLUSION: Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD. TRIAL REGISTRATION NUMBER: ID 11101.

Role of Vascular Adaptation in Determining Systolic Blood Pressure in Young Adults.

Background Two individuals can have a similar pulse pressure (PP) but different levels of systolic blood pressure (SBP), although the underlying mechanisms have not been described. We hypothesized that, for a given level of PP, differences in SBP relate to peripheral vascular resistance (PVR); and we tested this hypothesis in a large cohort of healthy young adults. Methods and Results Demographic, biochemical, and hemodynamic data from 3103 subjects were available for the current analyses. In both men and women, for a given level of PP, higher SBP was associated with significantly higher body weight, body mass index, heart rate, and PVR (P<0.05 versus those with lower BP for all comparisons). Moreover, stratifying individuals by quartiles of PP and PVR revealed a stepwise increase in SBP from the lowest to highest quartile for each variable, with the highest SBP occurring in those in the highest quartile of both PP and PVR (P<0.001 for overall trend for both sexes). PVR was also increased with increasing tertile of minimum forearm vascular resistance, in both men (P=0.002) and women (P=0.03). Conclusions Increased PVR, mediated in part through altered resistance vessel structure, strongly associates with the elevation of SBP for a given level of PP in young adults. An impaired ability to adapt PVR appropriately to a given level of PP may be an important mechanism underlying elevated SBP in young adults.

Maternal Cardiovascular Dysfunction is Associated with Hypoxic Cerebral and Umbilical Doppler Changes.

We investigate the relationship between maternal cardiovascular (CV) function and fetal Doppler changes in healthy pregnancies and those with pre-eclampsia (PE), small for gestational age (SGA) or fetal growth restriction (FGR). This was a three-centre prospective study, where CV assessment was performed using inert gas rebreathing, continuous Doppler or impedance cardiography. Maternal cardiac output (CO) and peripheral vascular resistance (PVR) were analysed in relation to the uterine artery, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI, expressed as z-scores by gestational week) using polynomial regression analyses, and in relation to the presence of absent/reversed end diastolic (ARED) flow in the UA. We included 81 healthy controls, 47 women with PE, 65 with SGA/FGR and 40 with PE + SGA/FGR. Maternal CO was inversely related to fetal UA PI and positively related to MCA PI; the opposite was observed for PVR, which was also positively associated with increased uterine artery impedance. CO was lower (z-score 97, p = 0.02) and PVR higher (z-score 2.88, p = 0.02) with UA ARED flow. We report that maternal CV dysfunction is associated with fetal vascular changes, namely raised impedance in the fetal-placental circulation and low impedance in the fetal cerebral vessels. These findings are most evident with critical UA Doppler changes and represent a potential mechanism for therapeutic intervention.

Correction to: ChemoPROphyLaxIs with hydroxychloroquine For covId-19 infeCtious disease (PROLIFIC) to prevent covid-19 infection in frontline healthcare workers: A structured summary of a study protocol for a randomised controlled trial.

An amendment to this paper has been published and can be accessed via the original article.

Psychological Wellbeing and Aortic Stiffness: Longitudinal Study.

This study investigated 2 distinct aspects of positive wellbeing: affective wellbeing and eudaimonia with progression of aortic stiffness, an index of subclinical cardiovascular disease. A total of 4754 participants (mean age 65.3 years, 3466 men, and 1288 women) from the Whitehall II cohort study provided data on affective and eudaimonic wellbeing using subscales from the control, autonomy, self-realization and pleasure-19 questionnaire. Aortic stiffness was measured by aortic pulse wave velocity (PWV) at baseline (2008-2009) and 5 years later (2012-2013). Linear mixed models were used to measure the effect of affective and eudaimonic wellbeing on baseline PWV and 5-year PWV longitudinal change. A 1-SD higher eudaimonic wellbeing was associated with lower baseline PWV in men (ß=-0.100 m/s [95% CI=-0.169 to -0.032]), independent of social, behavioral, and biological factors. This association persisted over 5 years. No such association was found in women (ß=-0.029 m/s [95% CI=-0.126 to 0.069]). We did not find any association of positive wellbeing with change in PWV over time in either men or women. In older men, higher levels of eudaimonic wellbeing were associated with lower long-term levels of arterial stiffness. These findings support the notion that the pattern of association between positive wellbeing and cardiovascular health outcomes involves eudaimonic rather than affective wellbeing and is sex-specific.