Long-term Risk Of Cardiovascular Disease Research Articles

Hypertensive disorders of pregnancy and long-term risk of maternal stroke - a systematic review

Abstract Hypertensive disorders of pregnancy (HDP) are associated with a long-term risk for cardiovascular disease among parous patients later in life. However, relatively little is known about whether HDP are associated with an increased risk for ischaemic stroke (IS) or haemorrhagic stroke (HS) in later life. This systematic review aimed to synthesize the available literature on the association between HDP and the long-term risk for maternal stroke. PubMed, Web of Science, and CINAHL were searched from inception to December 19, 2022. Studies included were case-control or cohort studies, conducted with human participants, available in English, measuring the exposure of a history of HDP (preeclampsia (PE), gestational hypertension (GH), chronic hypertension (CH), or superimposed preeclampsia) and the outcome of maternal IS or HS. Three reviewers extracted the data and appraised the study quality following the Meta-analyses of Observational Studies in Epidemiology guidelines and using the Newcastle-Ottawa scale. The primary outcome was any undifferentiated stroke (AS) and secondary outcomes included IS and HS. The protocol for this systematic review was registered on PROSPERO (CRD42021254660). 24 studies were included (10,632,808 study participants). HDP were significantly associated with AS (aRR, 1.74; 95% CI, 1.45-2.10). PE was significantly associated with AS (aRR, 1.75; 95% CI, 1.56-1.97), IS (aRR, 1.74; 95% CI, 1.46-2.06), and HS (aRR, 2.77; 95% CI, 2.04-3.75). GH was significantly associated with AS (aRR, 1.23; 95% CI, 1.20-1.26), IS (aRR, 1.35; 95% CI, 1.19-1.53), and HS (aRR, 2.66; 95% CI, 1.02-6.98). CH was associated with IS (aRR, 1.49; 95% CI, 1.01-2.19). In conclusion, exposure to HDP, including PE and GH, seems to be associated with an increased risk for AS and IS among parous patients in later life. Preventive interventions may be warranted for patients who experience HDP to reduce their long-term risk for stroke. Key messages • Hypertensive disorders of pregnancy appear to be associated with an increased risk of maternal stroke in later life. • The strength of association between exposures and outcomes varies by hypertensive disorder of pregnancy subtype and stroke subtype.

Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis.

Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective. The objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers. This study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked primary-secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals. Systematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing (p < 0.01); the CPRD-HES data set indicated that 70% did not achieve target treatment levels, and demonstrated increased cardiovascular disease risk among these individuals, compared with controls (hazard ratio 9.14, 95% CI 8.55 to 9.76). The specialist familial hypercholesterolaemia register confirmed excessive cardiovascular morbidity (standardised morbidity ratio 7.17, 95% CI 6.79 to 7.56). Cost-effectiveness modelling found a net health gain from diagnosis of -0.27 to 2.51 quality-adjusted life-years at the willingness-to-pay threshold of £15,000 per quality-adjusted life-year gained. The cost-effective protocols cascaded from genetically confirmed index cases by contacting first- and second-degree relatives simultaneously and directly. Interviews found a service-led direct-contact approach was more reliable, but combining direct and indirect approaches, guided by index patients and family relationships, may be more acceptable. Systematic reviews were not used in the economic analysis, as relevant studies were lacking or of poor quality. As only a proportion of those with primary care-coded familial hypercholesterolaemia are likely to actually have familial hypercholesterolaemia, CPRD analyses are likely to underestimate the true effect. The cost-effectiveness analysis required assumptions related to the long-term cardiovascular disease risk, the effect of treatment on cholesterol and the generalisability of estimates from the data sets. Interview recruitment was limited to white English-speaking participants. Based on limited evidence, most cost-effective cascade-testing protocols, diagnosing most relatives, select index cases by genetic testing, with services directly contacting relatives, and contacting second-degree relatives even if first-degree relatives have not been tested. Combined approaches to contact relatives may be more suitable for some families. Establish a long-term familial hypercholesterolaemia cohort, measuring cholesterol levels, treatment and cardiovascular outcomes. Conduct a randomised study comparing different approaches to contact relatives. This study is registered as PROSPERO CRD42018117445 and CRD42019125775. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 16. See the NIHR Journals Library website for further project information.

Prevalence of Pediatric Masked Hypertension and Risk of Subclinical Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined MH and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4-25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00-12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m2.7 [95% CI, 2.51-5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50-3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14-0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long-term cardiovascular disease.

A deep learning-based electrocardiogram risk score for long term cardiovascular death and disease

The electrocardiogram (ECG) is the most frequently performed cardiovascular diagnostic test, but it is unclear how much information resting ECGs contain about long term cardiovascular risk. Here we report that a deep convolutional neural network can accurately predict the long-term risk of cardiovascular mortality and disease based on a resting ECG alone. Using a large dataset of resting 12-lead ECGs collected at Stanford University Medical Center, we developed SEER, the Stanford Estimator of Electrocardiogram Risk. SEER predicts 5-year cardiovascular mortality with an area under the receiver operator characteristic curve (AUC) of 0.83 in a held-out test set at Stanford, and with AUCs of 0.78 and 0.83 respectively when independently evaluated at Cedars-Sinai Medical Center and Columbia University Irving Medical Center. SEER predicts 5-year atherosclerotic disease (ASCVD) with an AUC of 0.67, similar to the Pooled Cohort Equations for ASCVD Risk, while being only modestly correlated. When used in conjunction with the Pooled Cohort Equations, SEER accurately reclassified 16% of patients from low to moderate risk, uncovering a group with an actual average 9.9% 10-year ASCVD risk who would not have otherwise been indicated for statin therapy. SEER can also predict several other cardiovascular conditions such as heart failure and atrial fibrillation. Using only lead I of the ECG it predicts 5-year cardiovascular mortality with an AUC of 0.80. SEER, used alongside the Pooled Cohort Equations and other risk tools, can substantially improve cardiovascular risk stratification and aid in medical decision making.

The long-term risk of cardiovascular disease among women with a history of hypertensive disorders of pregnancy: a systematic review of clinical practice guidelines

BackgroundThe lifelong risks of cardiovascular disease following preeclampsia and gestational hypertension are well-established. However, it is unclear whether this evidence has been translated into clinical practice guidelines. Thus, this review aimed to assess the quality and content of Australian clinical practice guidelines regarding the risk of cardiovascular disease following gestational hypertension and preeclampsia.MethodsWe conducted a systematic search of MEDLINE (Ovid), EMBASE (Ovid), and CINAHL databases, as well as hospital, obstetric society, and medical college websites. Publications were included if: they were a clinical practice guideline; were published in the previous ten years; and included recommendations for the management of future cardiovascular disease risk following hypertensive disorders of pregnancy. Quality assessment was performed using Appraisal of Guidelines for Research and Evaluation Instrument Version Two (AGREE-II) and AGREE Recommendations Excellence Instrument (AGREE-REX).ResultsEighteen guidelines were identified, and of these, less than half (n = 8) included recommendations for managing future cardiovascular risk following hypertensive disorders of pregnancy. Across these eight, four main counselling recommendations were found regarding (1) risk of future cardiovascular disease; (2) risk factor screening; (3) lifestyle interventions; and (4) prenatal counselling for future pregnancies. The quality and content of these recommendations varied significantly, and the majority of guidelines (87.5%) were assessed as low to moderate quality.ConclusionsThere are limited Australian clinical practice guidelines providing appropriate advice regarding future risk of cardiovascular disease following hypertensive disorders of pregnancy. The quality and content of these guidelines varied significantly. These findings highlight the need for improved translation from evidence-based research to enhance clinical care and guidance.

The association between cardiovascular disease and breast and gynecologic cancers among black female patients

IntroductionLittle is known about whether a breast or gynecologic cancer diagnosis increases long-term cardiovascular disease (CVD) risk among Black females. The purpose of this study was to determine whether a breast or gynecologic cancer diagnosis is associated with CVD risk and identify determinants of subsequent CVD risk among Black females with an incident breast or gynecologic cancer diagnosis. MethodsUsing the Southern Community Cohort Study data from 2002–2016, this study was designed to analyze CVD incidence among Black females without cancer or CVD at enrollment. Cox proportional hazards regression models with or without covariates were used to explore the relationship between a breast or gynecologic cancer diagnosis and CVD risk among women without cancer as well as without CVD at enrollment (N=11,486). In addition, Cox proportional hazards regression models, excluding those who developed CVD before breast and gynecologic cancer diagnosis and those with other types of cancers, were used to assess determinants of CVD risk among breast and gynecologic cancer survivors. ResultsOf 11,486 Black females, 531 developed a breast or gynecological cancer (4.6%) over a median follow-up of 140 months (interquartile range: 123-159 months). Compared to women without cancer, women with a breast or gynecological cancers had greater than 20% higher risk of incident CVD during the follow-up period. Without adjusting for covariates, positive association between CVD risk and breast cancer was observed (hazard ratio (HR) = 1.24; 95% confidence interval (CI) = 1.11 - 1.39; p < 0.001); as well as between CVD risk and a gynecological cancer (HR = 1.23; 95% CI = 1.03 - 1.46; p = 0.021). Yet, after adjusting for covariates, CVD risk was only significantly associated with breast cancer (p = 0.001) but not gynecologic cancer. In cancer case-only analyses, CVD risk was significantly increasing with age (p < 0.05). ConclusionsLike study populations of predominantly White females, our results suggest that, adjusting for covariates, Black females possess a higher risk of CVD following a breast cancer diagnosis compared to women who did not develop breast cancer. Our results suggest a need for active CVD surveillance in the cancer survivorship phase.

DNA methylation and 28-year cardiovascular disease risk in type 1 diabetes: the Epidemiology of Diabetes Complications (EDC) cohort study

BackgroundThe potential for DNA methylation (DNAm) as an early marker for cardiovascular disease (CVD) and how such an association might differ by glycemic exposure has not been examined in type 1 diabetes, a population at increased CVD risk. We thus performed a prospective epigenome-wide association study of blood leukocyte DNAm (EPIC array) and time to CVD incidence over 28 years in a childhood-onset (< 17 years) type 1 diabetes cohort, the Pittsburgh Epidemiology of Diabetes Complications (EDC) study (n = 368 with DNA and no CVD at baseline), both overall and separately by glycemic exposure, as measured by HbA1c at baseline (split at the median: < 8.9% and ≥ 8.9%). We also assessed whether DNAm-CVD associations were independent of established cardiometabolic risk factors, including body mass index, estimated glucose disposal rate, cholesterol, triglycerides, blood pressure, pulse rate, albumin excretion rate, and estimated glomerular filtration rate.ResultsCVD (first instance of CVD death, myocardial infarction, coronary revascularization, ischemic ECG, angina, or stroke) developed in 172 participants (46.7%) over 28 years. Overall, in Cox regression models for time to CVD, none of the 683,597 CpGs examined reached significance at a false discovery rate (FDR) ≤ 0.05. In participants with HbA1c < 8.9% (n = 180), again none reached FDR ≤ 0.05, but three were associated at the a priori nominal significance level FDR ≤ 0.10: cg07147033 in MIB2, cg12324048 (intergenic, chromosome 3), and cg15883830 (intergenic, chromosome 1). In participants with HbA1c ≥ 8.9% (n = 188), two CpGs in loci involved in calcium channel activity were significantly associated with CVD (FDR ≤ 0.05): cg21823999 in GPM6A and cg23621817 in CHRNA9; four additional CpGs were nominally associated (FDR ≤ 0.10). In participants with HbA1c ≥ 8.9%, DNAm-CVD associations were only modestly attenuated after cardiometabolic risk factor adjustment, while attenuation was greater in those with HbA1c < 8.9%. No pathways were enriched in those with HbA1c < 8.9%, while pathways for calcium channel activity and integral component of synaptic membrane were significantly enriched in those with HbA1c ≥ 8.9%.ConclusionsThese results provide novel evidence that DNAm at loci involved in calcium channel activity and development may contribute to long-term CVD risk beyond known risk factors in type 1 diabetes, particularly in individuals with greater glycemic exposure, warranting further study.

Long-term dietary iron intake and risk of non-fatal cardiovascular diseases in the China Health and Nutrition Survey.

We aimed to investigate the association of long-term dietary iron intake with the risk of non-fatal cardiovascular diseases (CVDs), myocardial infarction (MI), and stroke in Chinese populations with predominantly plant-based diets by sex. A total of 17 107 participants (8569 men and 8538 women) aged 18-80 years in the China Health and Nutrition Survey (CHNS) 1989-2015 were included. Dietary intake was assessed repeatedly by three consecutive 24-h dietary recalls. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 11.1 years, the adjusted HRs (95% CIs) for non-fatal CVDs risk across quintiles of total iron intake in men were 1.00, 0.65 (0.46-0.93), 0.54 (0.37-0.78), 0.66 (0.46-0.94), 0.69 (0.47-1.03), but no significant association in women. Similar associations were found for stroke risk, but not for MI risk. The dose-response curves for the association of total iron and non-heme iron intake with the risk of non-fatal CVDs and stroke followed a reverse J-shape only in men and similar reverse J-shaped association of heme iron intake with non-fatal CVDs and stroke risk in both men and women (P-non-linearity <0.05). Moderate dietary iron intake may protect against non-fatal CVDs and stroke, especially in Chinese men consuming plant-based diets. Both quantity and quality of dietary iron intake should be considered in the prevention of non-fatal CVDs due to differences in dietary patterns among diverse populations.

Dietary flavonoids intake contributes to delay biological aging process: analysis from NHANES dataset

BackgroundDiet may influence biological aging and the discrepancy (∆age) between a subject’s biological age (BA) and chronological age (CA). We aimed to investigate the correlation of dietary flavonoids with the ∆age of organs (heart, kidney, liver) and the whole body.MethodA total of 3193 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2007–2008 and 2017–2018. Dietary flavonoids intake was assessed using 24-h dietary recall method. Multiple linear regression analysis was performed to evaluate the association of dietary flavonoids intake with the ∆age of organs (heart, kidney, liver) and the whole body. BA was computed based on circulating biomarkers, and the resulting ∆age was tested as an outcome in linear regression analysis.ResultsThe ∆age of the whole body, heart, and liver was inversely associated with higher flavonoids intake (the whole body ∆age β = − 0.58, cardiovascular ∆age β = − 0.96, liver ∆age β = − 3.19) after adjustment for variables. However, higher flavonoids intake positively related to renal ∆age (β = 0.40) in participants with chronic kidney disease (CKD). Associations were influenced by population characteristics, such as age, health behavior, or chronic diseases. Anthocyanidins, isoflavones and flavones had the strongest inverse associations between the whole body ∆age and cardiovascular ∆age among all the flavonoids subclasses.ConclusionFlavonoids intake positively contributes to delaying the biological aging process, especially in the heart, and liver organ, which may be beneficial for reducing the long-term risk of cardiovascular or liver disease.

Association of COVID-19 with short- and long-term risk of cardiovascular disease and mortality: a prospective cohort in UK Biobank.

The evidence on the short- and long-term associations of COVID-19 with cardiovascular disease (CVD) outcomes and mortality is limited. This study aimed to evaluate these associations. COVID-19 patients (cases) diagnosed between 16 March 2020 and 30 November 2020 were identified from UK Biobank and followed prospectively for up to 18 months. Based on age and sex, cases were randomly matched with uninfected participants from two control cohorts - a contemporary cohort between 16 March 2020 and 30 November 2020, and a historical cohort between 16 March 2018 and 30 November 2018. Characteristics between groups were adjusted with propensity score-based marginal mean-weighting through stratification. The association of COVID-19 with CVD and mortality within 21 days of diagnosis (acute phase) and after this period (post-acute phase) was determined by Cox regression. In the acute phase, patients with COVID-19 (n = 7584) were associated with a significantly higher risk of CVD (hazard ratio [HR] 4.3 [95% confidence interval (CI) = 2.6 to 6.9]); 5.0 (95% CI = 3.0 to 8.1)] and all-cause mortality (HR 81.1 [95% CI = 58.5 to 112.4); 67.5 [95% CI = 49.9 to 91.1]) than the contemporary (n = 75 790) and historical controls (n = 75 774), respectively. In the post-acute phase, infected patients' (n = 7139) association with higher risk of CVD (HR 1.4 [95% CI = 1.2 to 1.8]; 1.3 [95% CI = 1.1 to 1.6]) and all-cause mortality (HR 5.0 [95% CI = 4.3 to 5.8); 4.5 (95% CI = 3.9 to 5.2]) persisted, compared with the contemporary (n = 71 296) and historical controls (n = 71 314), respectively. COVID-19 is associated with increased short- and long-term risks of CVD and mortality. Ongoing monitoring of signs and symptoms of developing cardiovascular complications post-diagnosis and up till at least a year post-recovery may benefit infected patients, especially those with severe disease.

Are Lipid-Lowering and Antihypertensive Medications Used as Complements to Heart-Healthy Diets? A Scoping Review.

In cardiovascular disease (CVD) prevention, whether antihypertensive and lipid-lowering medications are used as complements to heart-healthy diets has not been thoroughly assessed. This scoping review aimed to 1) analyze observational studies that assessed the relationship between diet and antihypertensive/lipid-lowering medication use and 2) evaluate whether medication was used as a complement to heart-healthy dietary intakes. We searched MEDLINE, Embase, Web of Science, and CINAHL through 14 January, 2023, for studies that assessed either 1) intraindividual changes in diet associated with lipid-lowering/antihypertensive medication initiation or use or 2) interindividual differences in diet between users and nonusers of these medications. A total of 17 studies were included. Of those, 3 prospectively assessed the intraindividual changes in diet associated with medication initiation or use, but none documented potential changes in diet prior to medication initiation. The 14 other studies compared dietary intakes of medication users and nonusers, most of which also relied on an incomplete assessment of the temporal dynamics between diet and medication use as they employed cross-sectional (n = 12) or repeated cross-sectional (n = 2) designs. Data from 8 studies, including 4 of the 5 studies from Europe, suggested that medication was used as a complement to heart-healthy diets, whereas data from the 9 other studies, including the 4 conducted in the United States, provided no such evidence, indicating potential between-country differences in this relationship. Finally, no studies investigated how the dynamics between diet and medication use influenced the long-term CVD risk. This scoping review suggests that the current literature on the relationship between lipid-lowering/antihypertensive medication use and diet provides an incomplete perspective on how medication may influence diet in CVD prevention. Prospective studies assessing intraindividual changes in diet associated with medication initiation and use and how these dynamics influence the CVD risk are thus needed. Adv Nutr 2023;x:xx.

O-095 Different phenotypes of PCOS: Implications to clinical practice

Abstract Polycystic ovary syndrome (PCOS) is a very common, heterogeneous syndrome which presents with a spectrum of clinical and biochemical features. It is associated with both reproductive and metabolic dysfunction and has a negative impact on long term health, including mental health. Although there appears to be a common genetic background to PCOS, regardless of presentation, environmental factors, including diet, play an important part in determining the phenotype. The most commonly used diagnostic criteria, the Rotterdam criteria, takes account of the heterogenous nature of the syndrome but the spectrum of presentation can be categorised as four clinical and biochemical subtypes which comprise (A) ovulatory dysfunction, hyperandrogenism, polycystic ovaries (PCO), (B) ovulatory dysfunction, hyperandrogenism but without PCO, (C) hyperandrogenism without ovulatory dysfunction but with PCO and (D) ovulatory dysfunction with PCO but without hyperandrogenism. These are not rigid categories since some women may go from one to another, for example weight gain may lead to anovulation in a woman who previously had hirsutism but regular cycles. Nevertheless, the diagnostic sub-category has a significance influence on clinical management. Women who have both hyperandrogenism and ovulatory dysfunction (A&amp;B) are at higher risk of metabolic dysfunction which is exacerbated by obesity (and carries a high long-term risk of diabetes and cardiovascular disease) and so merit thorough investigation which includes assessment of glucose tolerance and lipids. Those who have predominantly ovulatory problems may require fertility treatment or regulation of menses but some who simply have irregular menses may need no specific treatment. Symptoms of hyperandrogenism (hirsutism, acne, alopecia) can be particularly distressing and may be best managed in collaboration with a dermatologist. The negative impact of PCOS on mental health is a very common problem, the high prevalence of which has only recently been appreciated. Not surprisingly, it is particularly relevant in those women who have moderate to severe symptoms of hyperandrogenism. In summary, PCOS is a syndrome characterised by a variety of symptoms and endocrine abnormalities and it is important to tailor treatment individually, according to the need for symptom relief and with regard to concerns about long-term health.

#3236 CHANGE IN ALBUMINURIA IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS TREATED WITH AVACOPAN

Abstract Background and Aims Urinary albumin:creatinine ratio (UACR) is an important biomarker of active glomerulonephritis, a common complication of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. In most glomerular diseases, high UACR levels and low estimated glomerular filtration rates are associated with the long-term risk of end-stage kidney disease, cardiovascular disease, and death.[1] In the double-dummy, double-blind, controlled ADVOCATE Phase 3 trial, patients were randomized to receive avacopan, an oral C5a receptor (C5aR) antagonist that blocks C5a-mediated neutrophil activation and migration, or a prednisone taper. All patients received background immunosuppression with either cyclophosphamide followed by azathioprine, or rituximab. Primary endpoints were remission at week 26 and sustained remission at week 52. Prespecified secondary endpoints included the evaluation of kidney function.[2] The effect of avacopan on UACR in patients with ANCA-associated vasculitis is described. Method This post hoc analysis compared the time to achieve the maximum mean difference in percent change in UACR from baseline between the avacopan and prednisone taper groups using Kaplan-Meier survival analysis. Change in UACR from baseline was a prespecified secondary endpoint but was not adjusted for multiplicity. This analysis included patients from the ADVOCATE trial with kidney involvement (based on the Birmingham Vasculitis Activity Score) and a UACR of at least 10 mg/g at baseline. Results The baseline geometric mean UACR mg/g (range) in the avacopan group (n = 125) and the prednisone taper group (n = 128) was 433 (20 to 6461) and 312 (11 to 5367), respectively. A statistically significant UACR reduction (based on least-square means) in the avacopan group compared to the prednisone taper group occurred as early as week 2 (−25% vs. 6%, p = 0.0068, difference between groups: −29%, 95% confidence interval (CI) [−45%, −9%]). UACR continued to decrease at week 4 to the maximum difference between the two groups (−40% vs. 0%, p&amp;lt;0.0001, difference between groups: −40%, 95% CI [−53%, −22%]) (Figure 1). UACR was comparable between the two groups by week 13 (−55% vs. −49%, p = 0.3028, difference between groups: −12%, 95% CI [−32%, 13%]). During the 52-week treatment period, 84% (105/125) of patients in the avacopan group achieved a 40% UACR reduction from baseline within a median time of 29 days (95% CI [29, 88]), compared to 83% (106/128) of patients in the prednisone taper group within a median time of 92 days (95% CI [91, 180]) (logrank p = 0.0450) (Figure 2). At week 52, there was a greater overall mean improvement in estimated glomerular filtration rate (eGFR) of 7.6 mL/min/1.73 m2 in the avacopan group compared to 4.6 mL/min/1.73 m2 in the prednisone taper group (p = 0.0432). Conclusion In the ADVOCATE trial, UACR, an important early indicator of improving kidney function, improved three times faster in the avacopan group compared to the prednisone taper group. The rapid reduction in UACR seen in patients with ANCA-associated vasculitis receiving avacopan suggests more rapid control of glomerular inflammation which may have contributed to the observed subsequent greater improvement in eGFR.

Introduction to the Compendium on Early Cardiovascular Disease.

Introduction to the Compendium on Early Cardiovascular Disease.

Coronary Artery Calcification in women with a premenopausal RRSO compared to women with a postmenopausal RRSO

Introduction: BRCA1/2 pathogenic variant carriers are recommended to undergo premenopausal risk-reducing salpingo-oophorectomy (RRSO) to prevent ovarian cancer, leading to immediate surgical menopause. Although studies show that women with natural premature ovarian are at increased risk of developing cardiovascular disease (CVD), evidence about long-term CVD risk after early surgical menopause is scarce.

Risk of Cardiovascular Disease in Women With a History of Hyperemesis Gravidarum, With and Without Preeclampsia.

Background Hyperemesis gravidarum is associated with preeclampsia, but it is unclear whether hyperemesis gravidarum is a risk factor for cardiovascular disease. We assessed the long-term risk of cardiovascular disease in women who experienced hyperemesis gravidarum with or without preeclampsia. Methods and Results We analyzed a longitudinal cohort of 1 413 166 pregnant women in Quebec between 1989 and 2021. Women were followed from their first pregnancy up to 3 decades later. We computed hazard ratios (HRs) and 95% CIs for the association of hyperemesis gravidarum, preeclampsia, or both conditions with subsequent risk of cardiovascular hospitalization using Cox regression models adjusted for baseline characteristics. Among 1 413 166 women, 16 288 (1.2%) had hyperemesis gravidarum only, 69 645 (4.9%) preeclampsia only, and 1103 (0.08%) had both conditions. After 32 years of follow-up, cardiovascular disease incidence was 17.7 per 100 women with hyperemesis gravidarum only, 28.2 per 100 women with preeclampsia only, 30.9 per 100 women with both exposures, and 14.0 per 100 women with neither exposure. Compared with no exposure, women with both hyperemesis and preeclampsia had the greatest risk of cardiovascular hospitalization (HR, 3.54 [95% CI, 3.03-4.14]), followed by women with preeclampsia only (HR, 2.58 [95% CI, 2.51-2.64]) and hyperemesis only (HR, 1.46 [95% CI, 1.38-1.54]). Having both hyperemesis gravidarum and preeclampsia was strongly associated with valve disease (HR, 3.38 [95% CI, 1.69-6.75]), heart failure (HR, 3.43 [95% CI, 1.79-6.59]), and cardiomyopathy (HR, 4.17 [95% CI, 1.99-8.76]). Conclusions Hyperemesis gravidarum is associated with the development of cardiovascular disease, whether preeclampsia is present or not.

LEGACY OF ARTERIAL HYPERTENSION OF WOMEN WITH A PAST HISTORY OF PREECLAMPSIA

Objective: Preeclampsia increases the longterm risk of cardiovascular disease. Some of the women affected by this condition remain hypertensive after delivery. Hypertensive phenotypes can be detected with ambulatory BP monitoring (ABPM). This study aimed to determine the prevalence of hypertension using ABPM and office measurements. Design and method: We conducted a cross- sectional study which included women who delivered between January 2015 and June 2021 and were diagnosed and followed up for preeclampsia in three major obstetrical and gynaecologic units in Yaounde. We excluded from the study all women who had a history of chronic hypertension or a known Cardiopathy. Sociodemographic data and past history were recorded, a physical exam,ecg, an ultrasound and ABPM was performed to all participants. Results: 101 participants were included. The mean age was 30.56 years. 40.6% of women had hypertension (sustained hypertension, with sometime masked hypertension) with ABPM. Sustained hypertension was most common (26.7%), followed by masked hypertension (11.9%) and white-coat hypertension (2%). With office BP measurement, only 28.7% of women would have been diagnosed hypertensive. 29.8% of women had a disadvantageous dipping pattern. Among those that develop chronic hypertension, 18.8% had LVH at electrocardiography, 7.9% had both LVH and an abnormal left ventricular geometry on ultrasound while in normotensive women 1.9% had LVH at Ecg with 1% having both LVH and abnormal geometry at ultrasound. 20.8% of these women were obese during the follow up compared to 11.9% in the normotensive group. We had 26 patients (25,74%) with severe office hypertension and 32,3% were obeses. The fundus was normal in the majority of cases and we had no signs of neurological deficits or impaired cognition. Renal function was always normal or subnormal. Finally, we had two cases of heart failure. Conclusions: Many women affected by preeclampsia remain hypertensive after delivery. Masked hypertension and white-coat hypertension are risk factors for future cardiovascular disease and can only be diagnosed with ABPM. It is important to provide adequate follow-up for these women in order to intervene on the factors leading to this outcome.

Birth Weight in Consecutive Pregnancies and Maternal Cardiovascular Disease Mortality Among Spontaneous and Iatrogenic Term Births: A Population-Based Cohort Study.

Knowledge on the association between offspring birth weight and long-term risk of maternal cardiovascular disease (CVD) mortality is often based on firstborn infants without consideration of women's consecutive births. We studied long-term CVD mortality according to offspring birth weight patterns among women with spontaneous and iatrogenic term deliveries in Norway (1967-2020). We constructed birth weight quartiles (Qs) by combining standardized birth weight with gestational age in quartiles (Q1, Q2/Q3, and Q4) for the women's first 2 births. Mortality was estimated using Cox regression and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Changes in offspring birth weight quartiles were associated with long-term maternal CVD mortality. Compared with women who had 2 term infants in Q2/Q3, women with a first offspring in Q2/Q3 and a second in Q1 had higher mortality risk (HR=1.33, 95% CI: 1.18, 1.50), while risk was lower if the second offspring was in Q4 (HR=0.78, 95% CI: 0.67, 0.91). The risk increase associated with having a first infant in Q1 was eliminated if the second offspring was in Q4 (HR=0.99, 95% CI: 0.75, 1.31). These patterns were similar for women with iatrogenic and spontaneous deliveries. Inclusion of information from subsequent births revealed heterogeneity in maternal CVD mortality which was not captured when using only information based on the first offspring.

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

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). 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. 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. 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.

Exposure to multiple ion beams, broadly representative of galactic cosmic rays, causes perivascular cardiac fibrosis in mature male rats.

Long-duration space exploratory missions to the Earth's moon and the planet Mars are actively being planned. Such missions will require humans to live for prolonged periods beyond low earth orbit where astronauts will be continuously exposed to high energy galactic cosmic rays (GCRs). A major unknown is the potential impact of GCRs on the risks of developing degenerative cardiovascular disease, which is a concern to NASA. A ground-based rat model has been used to provide a detailed characterization of the risk of long-term cardiovascular disease from components of GCRs at radiation doses relevant to future human missions beyond low earth orbit. Six month old male WAG/RijCmcr rats were irradiated at a ground-based charged particle accelerator facility with high energy ion beams broadly representative of GCRs: protons, silicon and iron. Irradiation was given either as a single ion beam or as a combination of three ion beams. For the doses used, the single ion beam studies did not show any significant changes in the known cardiac risk factors and no evidence of cardiovascular disease could be demonstrated. In the three ion beam study, the total cholesterol levels in the circulation increased modestly over the 270 day follow up period, and inflammatory cytokines were also increased, transiently, 30 days after irradiation. Perivascular cardiac collagen content, systolic blood pressure and the number of macrophages found in the kidney and in the heart were each increased 270 days after irradiation with 1.5 Gy of the three ion beam grouping. These findings provide evidence for a cardiac vascular pathology and indicate a possible threshold dose for perivascular cardiac fibrosis and increased systemic systolic blood pressure for complex radiation fields during the 9 month follow up period. The development of perivascular cardiac fibrosis and increased systemic systolic blood pressure occurred at a physical dose of the three ion beam grouping (1.5 Gy) that was much lower than that required to show similar outcomes in earlier studies with the same rat strain exposed to photons. Further studies with longer follow up periods may help determine whether humans exposed to lower, mission-relevant doses of GCRs will develop radiation-induced heart disease.