Assessing cardiovascular disease risk in women with a history of hypertensive disorders of pregnancy: A guidance paper for studies using administrative data.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality, and their association with increased cardiovascular disease (CVD) risk represents a major public health concern. However, assessing CVD risk in women with a history of these conditions presents unique challenges, especially when studies are carried out using routinely collected data. OBJECTIVES: To summarise and describe key challenges related to the design and conduct of administrative studies assessing CVD risk in women with a history of HDP and provide concrete recommendations for addressing them in future research. METHODS: This is a methodological guidance paper. RESULTS: Several conceptual and methodological factors related to the data-generating mechanism and study conceptualisation, design/data management and analysis, as well as the interpretation and reporting of study findings should be considered and addressed when designing and carrying out administrative studies on this topic. Researchers should develop an a priori conceptual framework within which the research question is articulated, important study variables are identified and their interrelationships are carefully considered. CONCLUSIONS: To advance our understanding of CVD risk in women with a history of HDP, future studies should carefully consider and address the conceptual and methodological considerations outlined in this guidance paper. In highlighting these challenges, and providing specific recommendations for how to address them, our goal is to improve the quality of research carried out on this topic.

Is It Good to Have a Stiff Aorta with Aging? Causes and Consequences.

Aortic stiffness increases with advancing age, more than doubling during the human life span, and is a robust predictor of cardiovascular disease (CVD) clinical events independent of traditional risk factors. The aorta increases in diameter and length to accommodate growing body size and cardiac output in youth, but in middle and older age the aorta continues to remodel to a larger diameter, thinning the pool of permanent elastin fibers, increasing intramural wall stress and resulting in the transfer of load bearing onto stiffer collagen fibers. Whereas aortic stiffening in early middle age may be a compensatory mechanism to normalize intramural wall stress and therefore theoretically "good" early in the life span, the negative clinical consequences of accelerated aortic stiffening beyond middle age far outweigh any earlier physiological benefit. Indeed, aortic stiffness and the loss of the "windkessel effect" with advancing age result in elevated pulsatile pressure and flow in downstream microvasculature that is associated with subclinical damage to high-flow, low-resistance organs such as brain, kidney, retina, and heart. The mechanisms of aortic stiffness include alterations in extracellular matrix proteins (collagen deposition, elastin fragmentation), increased arterial tone (oxidative stress and inflammation-related reduced vasodilators and augmented vasoconstrictors; enhanced sympathetic activity), arterial calcification, vascular smooth muscle cell stiffness, and extracellular matrix glycosaminoglycans. Given the rapidly aging population of the United States, aortic stiffening will likely contribute to substantial CVD burden over the next 2-3 decades unless new therapeutic targets and interventions are identified to prevent the potential avalanche of clinical sequelae related to age-related aortic stiffness.

A Novel Recurrent COL5A1 Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia.

OBJECTIVE: While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the COL5A1 pathogenic variant c.1540G>A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The COL5A1 c.1540G>A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G>A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for COL5A1 variants. In this mFMD cohort, COL5A1 c.1540G>A and 6 additional relatively rare COL5A1 variants predicted to be deleterious in silico were identified and were associated with arterial dissections (P=0.005). CONCLUSIONS: COL5A1 c.1540G>A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare COL5A1 genetic variants predicted to be deleterious by in silico analysis were identified in ≈2.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for COL5A1 should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.

Sex-Specific Trends in Incidence and Mortality for Urban and Rural Ambulatory Patients with Heart Failure in Eastern Ontario from 1994 to 2013.

BACKGROUND: Differences in outcomes have previously been reported between urban and rural settings across a multitude of chronic diseases. Whether these discrepancies have changed over time, and how sex may influence these findings is unknown for patients with ambulatory heart failure (HF). We examined the temporal incidence and mortality trends by geography in these patients. METHODS AND RESULTS: We conducted a retrospective cohort study of 36,175 eastern Ontario residents who were diagnosed with HF in an outpatient setting from 1994 to 2013. The primary outcome was 1-year mortality. We examined temporal changes in mortality risk factors with the use of multivariable Cox proportional hazard models. The incidence of HF decreased in women and men across both rural and urban settings. Age-standardized mortality rates also decreased over time in both sexes but remained greater in rural men compared with rural women. CONCLUSIONS: The incidence of HF in the ambulatory setting was greater for men than women and greater in rural than urban areas, but mortality rates remained higher in rural men compared with rural women. Further research should focus on ways to reduce this gap in the outcomes of men and women with HF.

Sex differences in outcomes of heart failure in an ambulatory, population-based cohort from 2009 to 2013.

BACKGROUND: Heart failure remains a substantial cause of morbidity and mortality in women. We examined the sex differences in heart failure incidence, mortality and hospital admission in a population-based cohort. METHODS: All Ontario residents who were diagnosed with heart failure in an ambulatory setting between Apr. 1, 2009, and Mar. 31, 2014, were included in this study. Incident cases of heart failure were captured through physician billing using a validated algorithm. Outcomes were mortality and hospital admission for heart failure within 1 year of the diagnosis. Probability of death and hospital admission were calculated using the Kaplan-Meier method. The hazard of death was assessed using a multivariable Cox proportional hazard model. RESULTS: A total of 90 707 diagnoses of heart failure were made in an ambulatory setting during the study period (47% women). Women were more likely to be older and more frail, and had different comorbidities than men. The incidence of heart failure decreased during the study period in both sexes. The mortality rate decreased in both sexes, but remained higher in women than men. The female age-standardized mortality rate was 89 (95% confidence interval [CI] 80-100) per 1000 in 2009 and 85 (95% CI 75-95) in 2013, versus male age-standardized mortality rates of 88 (95% CI 80-97) in 2009 and 83 (95% CI 75-91) in 2013. Conversely, the rates of incident heart failure hospital admissions after heart failure diagnosis decreased in men and increased in women. INTERPRETATION: Despite decreases in overall heart failure incidence and mortality in ambulatory patients, mortality rates remain higher in women than in men, and rates of hospital admission for heart failure increased in women and declined in men. Further studies should focus on sex differences in health-seeking behaviour, medical therapy and response to therapy to provide guidance for personalized care.

Odontogenic sinusitis: a comprehensive review.

Odontogenic sinusitis (OS) is a highly prevalent, underappreciated and underdiagnosed disease that has been known for over 100 years. Apical periodontitis, periodontal disease and iatrogenic extrusion of foreign bodies into the sinus are the main causes of OS. Although the prevalence of sinus pathosis of dental origin is still controversial, otolaryngologists recognize that in the presence of recalcitrant sinusitis, a dental origin should be considered and properly treated. Currently, cone-beam computed tomography is the gold-standard imaging technique to assess the relationship between dental conditions, especially apical periodontitis and sinus diseases, and whenever this association is detected, patients should be seen by both a dentist and an otolaryngologist in order to achieve complete recovery. This article reviews the current concepts regarding the definitions, diagnosis and management of OS from a clinical point of view.

Normal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality.

BACKGROUND: The relationship between central obesity and survival in community-dwelling adults with normal body mass index (BMI) is not well-known. OBJECTIVE: To examine total and cardiovascular mortality risks associated with central obesity and normal BMI. DESIGN: Stratified multistage probability design. SETTING: NHANES III (Third National Health and Nutrition Examination Survey). PARTICIPANTS: 15,184 adults (52.3% women) aged 18 to 90 years. MEASUREMENTS: Multivariable Cox proportional hazards models were used to evaluate the relationship of obesity patterns defined by BMI and waist-to-hip ratio (WHR) and total and cardiovascular mortality risk after adjustment for confounding factors. RESULTS: Persons with normal-weight central obesity had the worst long-term survival. For example, a man with a normal BMI (22 kg/m2) and central obesity had greater total mortality risk than one with similar BMI but no central obesity (hazard ratio [HR], 1.87 [95% CI, 1.53 to 2.29]), and this man had twice the mortality risk of participants who were overweight or obese according to BMI only (HR, 2.24 [CI, 1.52 to 3.32] and 2.42 [CI, 1.30 to 4.53], respectively). Women with normal-weight central obesity also had a higher mortality risk than those with similar BMI but no central obesity (HR, 1.48 [CI, 1.35 to 1.62]) and those who were obese according to BMI only (HR, 1.32 [CI, 1.15 to 1.51]). Expected survival estimates were consistently lower for those with central obesity when age and BMI were controlled for. LIMITATIONS: Body fat distribution was assessed based on anthropometric indicators alone. Information on comorbidities was collected by self-report. CONCLUSION: Normal-weight central obesity defined by WHR is associated with higher mortality than BMI-defined obesity, particularly in the absence of central fat distribution. PRIMARY FUNDING SOURCE: National Institutes of Health, American Heart Association, European Regional Development Fund, and Czech Ministry of Health.

Arterial Health After Preeclampsia: Role of Chronic Hypertension in the Early Vascular Aging (EVA) Study.

BACKGROUND: Preeclampsia (PE) is associated with increased cardiovascular risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). We performed a comprehensive arterial hemodynamic assessment to evaluate the contribution of persistent HTN on arterial health after PE. METHODS: We recruited 40 women with PE history and 40 age-matched controls (6 months to 6 years postpartum). We evaluated arterial hemodynamics with validated techniques combining applanation tonometry and transthoracic echocardiography, comparing three groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls, using multivariable linear regression adjusted for age, body surface area, heart rate, diabetes, smoking history, creatinine, and gravidity. RESULTS: Eight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ±â€…3.9 years, median number of pregnancies was 2 (range 1-7), and time since last pregnancy 2.1 (range 0.5-5.7) years (not different between groups, P > 0.05). Compared to controls and to PE-noHTN, PE-HTN had higher aortic stiffness, wave reflections, pulsatile, and steady arterial load (P < 0.05 for each). Among PE-noHTN, aortic stiffness, wave reflections and steady arterial load were worse than controls (P < 0.05 for each), with smaller effect sizes. CONCLUSIONS: This is the most comprehensive assessment of arterial hemodynamics and first to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with cardiovascular events in the population, the combination of previous PE and chronic HTN may represent a higher risk subgroup who could benefit from targeted prevention strategies.

Female-Specific Considerations in Aortic Health and Disease.

The aorta plays a central role in the modulation of blood flow to supply end organs and to optimize the workload of the left ventricle. The constant interaction of the arterial wall with protective and deleterious circulating factors, and the cumulative exposure to ventriculoarterial pulsatile load, with its associated intimal-medial changes, are important players in the complex process of vascular aging. Vascular aging is also modulated by biomolecular processes such as oxidative stress, genomic instability, and cellular senescence. Concomitantly with well-established cardiometabolic and sex-specific risk factors and environmental stressors, arterial stiffness is associated with cardiovascular disease, which remains the leading cause of morbidity and mortality in women worldwide. Sexual dimorphisms in aortic health and disease are increasingly recognized and explain-at least in part-some of the observable sex differences in cardiovascular disease, which will be explored in this review. Specifically, we will discuss how biological sex affects arterial health and vascular aging and the implications this has for development of certain cardiovascular diseases uniquely or predominantly affecting women. We will then expand on sex differences in thoracic and abdominal aortic aneurysms, with special considerations for aortopathies in pregnancy.

L'aorte joue un rôle central dans la modulation du débit sanguin pour irriguer les organes cibles et optimiser la charge de travail du ventricule gauche. L'interaction constante entre la paroi artérielle et des facteurs protecteurs et délétères présents dans la circulation, ainsi que l'exposition cumulative à la charge pulsatile ventriculo-artérielle accompagnée des variations de l'épaisseur intima-média, sont des facteurs importants dans le processus complexe du vieillissement vasculaire. Le vieillissement vasculaire est également modulé par des processus biomoléculaires comme le stress oxydatif, l'instabilité génomique et la sénescence cellulaire. Conjointement avec les facteurs de risque cardiométaboliques et spécifiques au sexe bien établis et les sources de stress environnementales, la rigidité artérielle est associée aux maladies cardiovasculaires, qui demeurent la première cause de morbidité et de mortalité chez les femmes à l'échelle mondiale. Les dimorphismes sexuels en ce qui concerne la santé et les maladies de l'aorte sont de plus en plus reconnus et expliquent, du moins en partie, certaines des différences observables liées au sexe dans les maladies cardiovasculaires, ce qui a fait l'objet de cette analyse. Plus précisément, nous verrons le rôle que joue le sexe biologique dans la santé artérielle et le vieillissement vasculaire, et ce que cela implique dans l'évolution de certaines maladies cardiovasculaires qui touchent surtout ou uniquement les femmes. Nous élargirons ensuite l'étude des différences sexuelles aux anévrismes de l'aorte thoracique et abdominale, en accordant une attention particulière aux maladies de l'aorte pendant la grossesse.

Cardiovascular Disease Risk Factor Interventions in Women With Prior Gestational Hypertensive Disorders or Diabetes in North America: A Rapid Review.

Women with previous hypertensive disorders of pregnancy (HDP) or gestational diabetes mellitus (GDM) have a 2- to 3-fold increased risk of cardiovascular disease (CVD). The goal of this rapid review was to summarize evidence of the effectiveness of CVD risk factor interventions for postpartum women with a history of HDP or GDM. A comprehensive search strategy was used to search articles published in 5 databases-Ovid MEDLINE, PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and Embase). Observational and intervention studies that identified CVD prevention, screening, and/or risk factor management interventions among postpartum women with prior HDP or GDM in Canada and the US were included. The quality of observational and interventional studies, and their risk of bias, were assessed using appropriate critical appraisal checklists. Eight studies, including 4 observational cohorts, 3 randomized controlled trials, and 1 quasi-experimental study, merited inclusion for analysis. A total of 2449 participants were involved in the included studies. The most effective CVD risk factor intervention was comprised of postpartum transition and follow-up, CVD risk factor education, and advice on lifestyle changes. Most of the observational studies led to improvements in CVD risk factors, including improvements in CVD lifetime risk scores. However, none of the RCTs led to improvements in cardiometabolic risk factors. Few studies have investigated CVD risk factor interventions in the postpartum in women with previous HDP or GDM in North America. Further studies of higher quality are needed.

Les femmes ayant déjà souffert de troubles hypertensifs de la grossesse (THG) ou d'un diabète gestationnel (DG) présentent un risque de maladie cardiovasculaire (MCV) accru de 2 à 3 fois. Cette brève revue de littérature visait à colliger les évidences concernant l'efficacité des interventions se concentrant sur les facteurs de risque de MCV chez les femmes en post-partum ayant des antécédents de THG ou de DG. Une stratégie de recherche exhaustive a été employée pour rechercher des articles publiés dans 5 bases de données (Ovid MEDLINE, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO et Embase). Les études d'observation et d'intervention qui ont identifié des interventions de prévention, de dépistage et/ou de gestion des facteurs de risque des MCV chez les femmes en post-partum ayant déjà souffert de THG ou de DG au Canada et aux États-Unis ont été incluses. La qualité des études observationnelles et interventionnelles, ainsi que leur risque de biais, ont été évalués à l'aide de listes de contrôle d'évaluation critique appropriées. Huit études, dont quatre cohortes observationnelles, trois essais contrôlés randomisés (ECR) et une étude quasi expérimentale, ont été incluses pour l'analyse, impliquant au total 2 449 participantes. L'intervention la plus efficace sur les facteurs de risque de MCV incluait une transition et un suivi post-partum, une sensibilisation aux facteurs de risque de MCV et des conseils sur les changements de mode de vie. La plupart des études observationnelles ont conduit à des améliorations concernant les facteurs de risque de MCV. Cependant, aucun des ECR n'a conduit à des améliorations des facteurs de risque cardiométabolique. Peu d'études ont examiné les interventions sur les facteurs de risque de MCV pendant le post-partum chez les femmes ayant déjà souffert de THG ou de DG en Amérique du Nord. D'autres études de meilleure qualité sont nécessaires.

Sex differences in the perception of cardiovascular risk in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH), a common genetic condition, is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease (ASCVD). Recent data indicate an undertreatment of females with FH. OBJECTIVE: To characterize the role of sex in the perception of FH, its associated ASCVD risk and treatment. METHODS: A survey investigating for sex differences in the perception of FH was sent to 1073 patients with FH using a cross sectional study design. RESULTS: A total of 412 patients (51.9 % male) responded to the survey; mean age was 56.2 ± 14.4 years. There was a higher proportion of males with ASCVD than females (41.5 % vs. 16.5 %, respectively, p<0.001). Analyses of the survey responses showed that a majority of both males and females agreed that their risk of ASCVD is higher than healthy individuals of same age (70.8 % vs. 74.7 %, respectively, p = 0.434). Females were more concerned about having high LDL-C levels (67.5 % vs. 56.5 % in males, p = 0.024), especially those in secondary prevention programs. As for treatment of FH, approximately 75 % of both sex groups considered statins to be efficient in reducing the risk of myocardial infarction, but less than half of the females considered statins to be safe (44.8 % vs. 60.0 % in males, p = 0.003). No major sex differences were noted regarding the influence of the doctor in their understanding of FH as a disease. CONCLUSION: Overall, both males and females with FH were well informed about FH, although females were more concerned about having high LDL-C levels and they feared the safety of statins.

Pathophysiology of Myocardial Infarction With Nonobstructive Coronary Artery Disease: A Contemporary Systematic Review.

Background: Myocardial infarction with nonobstructive coronary artery disease (MINOCA) is defined as acute myocardial infarction (AMI) with angiographically nonobstructive coronary artery disease. MINOCA represents 6% of all AMI cases and is associated with increased mortality and morbidity. However, the wide array of pathophysiological factors and causes associated with MINOCA presents a diagnostic conundrum. Therefore, we conducted a contemporary systematic review of the pathophysiology of MINOCA. Methods: A comprehensive systematic review of MINOCA was carried out through the utilization of the PubMed database. All systematic reviews, meta-analyses, randomized controlled trials, and cohort studies available in English or French that reported on the pathophysiology of MINOCA published after January 1, 2013 were retained. Results: Of the 600 identified records, 80 records were retained. Central to the concept of MINOCA is the definition of AMI, characterized by the presence of myocardial damage reflected by elevated cardiac biomarkers in the setting of acute myocardial ischemia. As a result, a structured approach should be adopted to thoroughly assess and address clinically overlooked obstructive coronary artery disease, and cardiac and extracardiac mechanisms of myocyte injury. Once these options have been ruled out, a diagnosis of MINOCA can be established, and the appropriate multimodal assessment can be conducted to determine its specific underlying cause (plaque disruption, epicardial coronary vasospasm, coronary microvascular dysfunction, and coronary embolism and/or spontaneous coronary dissection or supply-demand mismatch). Conclusions: Integrating a suitable definition of AMI and understanding the pathophysiological mechanisms of MINOCA are crucial to ensure an effective multimodal diagnostic evaluation and the provision of adequate tailored therapies.

Contexte: L'infarctus du myocarde sans obstruction des artères coronaires (MINOCA) est défini comme un infarctus aigu du myocarde (IAM) en présence d'une coronaropathie non obstructive confirmée par angiographie. Le MINOCA représente 6 % de tous les cas d'IAM et est associé à une hausse des taux de mortalité et de morbidité. Cependant, le large éventail de facteurs physiopathologiques et de causes associés au MINOCA représente une énigme diagnostique. C'est pourquoi nous avons réalisé une analyse systématique des publications contemporaines sur la physiopathologie du MINOCA. Méthodologie: Une analyse exhaustive des publications sur le MINOCA a été menée au moyen de la base de données PubMed. L'ensemble des analyses systématiques, des méta-analyses, des essais contrôlés randomisés et des études de cohorte publiés en anglais ou en français après le 1er janvier 2013 qui faisaient état de la physiopathologie du MINOCA ont été retenus. Résultats: Parmi les 600 dossiers relevés, 80 ont été retenus. La définition de l'IAM était centrale au concept de MINOCA et était caractérisée par la présence d'une lésion myocardique attestée par des taux élevés de biomarqueurs cardiaques en contexte d'ischémie myocardique aiguë. Par conséquent, une approche structurée devrait être adoptée pour évaluer pleinement et traiter les coronaropathies obstructives qui passent inaperçues en clinique ainsi que les mécanismes cardiaques et extracardiaques des lésions aux myocytes. Une fois ces options exclues, un diagnostic de MINOCA peut être établi et l'évaluation multimodale appropriée peut être menée pour déterminer la cause sous-jacente précise (rupture de plaque, vasospasme d'une artère coronaire épicardique, dysfonction microvasculaire coronarienne et embolie coronarienne et/ou dissection spontanée d'une artère coronaire ou déséquilibre entre apports et besoins). Conclusions: Il est crucial d'intégrer une définition convenable de l'IAM et de comprendre les mécanismes physiopathologiques du MINOCA pour assurer une évaluation diagnostique multimodale efficace et une prestation de traitements adaptés et adéquats.

Canadian Cardiovascular Society/Canadian Women's Heart Health Alliance Clinical Practice Update on Myocardial Infarction With No Obstructive Coronary Artery Disease (MINOCA).

Myocardial infarction with no obstructive coronary artery disease (MINOCA) represents 6%-15% of all acute coronary syndromes, and women are disproportionately represented. MINOCA is an encompassing preliminary diagnosis, and emerging evidence supports a more expansive comprehensive diagnostic and therapeutic clinical approach. The current clinical practice update summarizes the latest evidence regarding the epidemiology, clinical presentation, and diagnostic evaluation of MINOCA. A cascaded approach to diagnostic workup is outlined for clinicians, for noninvasive and invasive diagnostic pathways, depending on clinical setting and local availability of diagnostic modalities. Evidence concerning the nonpharmacological and pharmacological treatment of MINOCA are presented and summarized according to underlying cause of MINOCA, with practical tips on the basis of expert opinion, outlining a real-life, evidence-based, comprehensive approach to management of this challenging condition.

The EVA Study: Early Vascular Aging in Women With History of Preeclampsia.

Background Early vascular aging (EVA) is associated with higher risk of adverse cardiovascular events and can be estimated noninvasively by assessing arterial hemodynamics. Women with a history of preeclampsia have increased risk of cardiovascular disease, but underlying mechanisms are incompletely understood. We hypothesized that women with a history of preeclampsia display persistent arterial abnormalities and EVA in the postpartum period. Methods and Results We performed a comprehensive, noninvasive arterial hemodynamic evaluation in women with a history of preeclampsia (n=40) and age-matched controls with previous normotensive pregnancies (n=40). We used validated methods integrating applanation tonometry with transthoracic echocardiography to obtain measures of aortic stiffness, steady and pulsatile arterial load, central blood pressure, and arterial wave reflections. Presence of EVA was defined as aortic stiffness higher than that predicted from reference values based on the participant's age and blood pressure. The association of preeclampsia with arterial hemodynamic variables was assessed with multivariable linear regression, and the association of severe preeclampsia with EVA was assessed with multivariable logistic regression, adjusted for confounders. We found that women with a history of preeclampsia had greater aortic stiffness, steady arterial load, central blood pressure, and arterial wave reflections when compared with controls. We observed a dose-response relationship, with the greatest abnormalities observed in subgroups with severe, preterm, or recurrent preeclampsia. Women with severe preeclampsia had 9.23 times greater odds of having EVA as compared with controls (95% CI, 1.67-51.06, P=0.011) and 7.87 greater odds of EVA as compared with women with nonsevere preeclampsia (95% CI, 1.29-47.77, P=0.025). Conclusions Our study comprehensively characterizes arterial hemodynamic abnormalities after preeclampsia and suggests that specific subgroups of women with a history of preeclampsia exhibit greater alterations in arterial hemodynamics related to arterial health. Our findings have important implications for understanding potential links between preeclampsia and cardiovascular events, and suggest women with severe, preterm, or recurrent preeclampsia as subgroups who may deserve intensification of efforts for prevention and early detection of cardiovascular disease.

The EVA (Early Vascular Aging) Study: Association of Central Obesity With Worse Arterial Health After Preeclampsia.

Background Women with preeclampsia have a higher risk of cardiovascular disease. This is partly explained by the worse arterial health after preeclampsia. Central obesity (CO) is a risk factor for both preeclampsia and cardiovascular disease. Whether CO contributes to further worsening of arterial health after preeclampsia remains unclear. Our objective was to evaluate the effect of CO and previous preeclampsia on arterial hemodynamics. Methods and Results We studied 40 women with previous preeclampsia (<6 years) and 40 age-matched controls with previous normotensive pregnancy in the same timeframe. We estimated arterial hemodynamics with validated techniques combining applanation tonometry and echocardiography. CO was defined as a waist-to-hip ratio ≥0.85. Differences in arterial hemodynamics across the 3 groups (preeclampsia with CO, preeclampsia without CO, and controls) were assessed with multivariable linear regression models adjusted for potential confounders. Twenty-six (65%) of the participants with preeclampsia had CO compared with 18 (45%) controls. Mean waist-to-hip ratio in patients with preeclampsia with CO, those with preeclampsia and no CO, and controls was 0.94±0.05, 0.80±0.04, and 0.83±0.07, respectively. In multivariable analyses, women with preeclampsia and CO had higher central blood pressure, arterial stiffness (carotid-femoral pulse wave velocity), steady arterial load (systemic vascular resistance), and wave reflections (reflected pressure wave amplitude, augmentation index) compared with controls (P<0.05 for each). Fewer hemodynamic domains were altered in the preeclampsia with no CO group, with higher central diastolic blood pressure, systemic vascular resistance, and wave reflections than controls (P<0.05). Conclusions Women with previous preeclampsia who also experience CO have the greatest alterations in arterial health and hemodynamics. Patients with preeclampsia with CO may represent a higher-risk subgroup who could be targeted for risk stratification and primary prevention of cardiovascular disease.

Sex Differences in Systemic and Coronary Arterial Hemodynamics in Heart Failure With Preserved Ejection Fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) predominantly affects females. Systemic and coronary arterial abnormalities are present in HFpEF and may contribute to HFpEF in females. We performed a cross-sectional study of 32 participants with HFpEF and 26 controls. Arterial hemodynamics were noninvasively assessed by combining arterial tonometry with echocardiography. Coronary microvascular function was assessed by rubidium-82 positron emission tomography as the myocardial flow reserve. Coronary vascular resistance (CVR) at rest and vasodilator stress were calculated using positron emission tomography. CVR reserve was calculated as stress - rest CVR. Multivariable linear regression assessed the associations of female sex with arterial hemodynamics in participants with and without HF, and the association of HF with arterial hemodynamics within each sex stratum. Demographics and left ventricular systolic and diastolic function were similar between males and females. Among those with HFpEF, females had a higher steady and pulsatile arterial load and more impaired (less negative) CVR reserve than males. Conversely, in controls, females had similar hemodynamics to males. We then divided the sample based on sex. Femaleswith HFpEF had a higher pulsatile arterial load and higher stress CVR than control females. Among males, arterial hemodynamics were similar, regardless of HFpEF status. The measures of early pulsatile arterial load were independently associated with higher E/e' and lower myocardial flow reserve in females only. In conclusion, despite similar left ventricular function between sexes, older females with HFpEF are characterized by additional systemic and coronary arterial hemodynamic abnormalities compared with males with HFpEF and similarly aged females without HFpEF.

Arterial Age and Early Vascular Aging, But Not Chronological Age, Are Associated With Faster Thoracic Aortic Aneurysm Growth.

Background Aneurysm size is an imperfect risk assessment tool for those with thoracic aortic aneurysm (TAA). Assessing arterial age may help TAA risk stratification, as it better reflects aortic health. We sought to evaluate arterial age as a predictor of faster TAA growth, independently of chronological age. Methods and Results We examined 137 patients with TAA. Arterial age was estimated according to validated equations, using patients' blood pressure and carotid-femoral pulse wave velocity. Aneurysm growth was determined prospectively from available imaging studies. Multivariable linear regression assessed the association of chronological age and arterial age with TAA growth, and multivariable logistic regression assessed associations of chronological and arterial age with the presence of accelerated aneurysm growth (defined as growth>median in the sample). Mean±SD chronological and arterial ages were 62.2±11.3 and 54.2±24.5 years, respectively. Mean baseline TAA size and follow-up time were 45.9±4.0 mm and 4.5±1.9 years, respectively. Median (interquartile range) TAA growth was 0.31 (0.14-0.52) mm/year. Older arterial age (ß±SE for 1 year: 0.004±0.001, P<0.0001) was independently associated with faster TAA growth, while chronological age was not (P=0.083). In logistic regression, each 5-year increase in arterial age was associated with a 23% increase in the odds of accelerated TAA growth (95% CI, 1.085-1.394; P=0.001). Conclusions Arterial age is independently associated with accelerated aneurysm expansion, while chronological age is not. Our results highlight that a noninvasive and inexpensive assessment of arterial age can potentially be useful for TAA risk stratification and disease monitoring as compared with the current clinical standard (chronological age).

Systematic review of validated case definitions to identify hypertensive disorders of pregnancy in administrative healthcare databases.

BACKGROUND: Administrative data are frequently used to study cardiovascular disease (CVD) risk in women with hypertensive disorders of pregnancy (HDP). Little is known about the validity of case-finding definitions (CFDs, eg, disease classification codes/algorithms) designed to identify HDP in administrative databases. METHODS: A systematic review of the literature. We searched MEDLINE, Embase, CINAHL, Web of Science and grey literature sources for eligible studies. Two independent reviewers screened articles for eligibility and extracted data. Quality of reporting was assessed using checklists; risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool, adapted for administrative studies. Findings were summarised descriptively. RESULTS: Twenty-six studies were included; most (62%) validated CFDs for a variety of maternal and/or neonatal outcomes. Six studies (24%) reported reference standard definitions for all HDP definitions validated; seven reported all 2×2 table values for ≥1 CFD or they were calculable. Most CFDs (n=83; 58%) identified HDP with high specificity (ie, ≥98%); however, sensitivity varied widely (3%-100%). CFDs validated for any maternal hypertensive disorder had the highest median sensitivity (91%, range: 15%-97%). Quality of reporting was generally poor, and all studies were at unclear or high risk of bias on ≥1 QUADAS-2 domain. CONCLUSIONS: Even validated CFDs are subject to bias. Researchers should choose the CFD(s) that best align with their research objective, while considering the relative importance of high sensitivity, specificity, negative predictive value and/or positive predictive value, and important characteristics of the validation studies from which they were derived (eg, study prevalence of HDP, spectrum of disease studied, methodological rigour, quality of reporting and risk of bias). Higher quality validation studies on this topic are urgently needed. PROSPERO REGISTRATION NUMBER: CRD42021239113.