This statement summarizes evidence that adverse pregnancy outcomes (APOs) such as hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age delivery, ...placental abruption, and pregnancy loss increase a woman's risk of developing cardiovascular disease (CVD) risk factors and of developing subsequent CVD (including fatal and nonfatal coronary heart disease, stroke, peripheral vascular disease, and heart failure). This statement highlights the importance of recognizing APOs when CVD risk is evaluated in women, although their value in reclassifying risk may not be established. A history of APOs is a prompt for more vigorous primordial prevention of CVD risk factors and primary prevention of CVD. Adopting a heart-healthy diet and increasing physical activity among women with APOs, starting in the postpartum setting and continuing across the life span, are important lifestyle interventions to decrease CVD risk. Lactation and breastfeeding may lower a woman's later cardiometabolic risk. Black and Asian women experience a higher proportion APOs, with more severe clinical presentation and worse outcomes, than White women. More studies on APOs and CVD in non-White women are needed to better understand and address these health disparities. Future studies of aspirin, statins, and metformin may better inform our recommendations for pharmacotherapy in primary CVD prevention among women who have had an APO. Several opportunities exist for health care systems to improve transitions of care for women with APOs and to implement strategies to reduce their long-term CVD risk. One proposed strategy includes incorporation of the concept of a fourth trimester into clinical recommendations and health care policy.
Debate over the cardiometabolic risk associated with metabolically healthy obesity (MHO) continues. Many studies have investigated this relationship by examining MHO at baseline with longitudinal ...follow-up, with inconsistent results.
The authors hypothesized that MHO at baseline is transient and that transition to metabolic syndrome (MetS) and duration of MetS explains heterogeneity in incident cardiovascular disease (CVD) and all-cause mortality.
Among 6,809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) the authors used Cox proportional hazards and logistic regression models to investigate the joint association of obesity (≥30 kg/m2) and MetS (International Diabetes Federation consensus definition) with CVD and mortality across a median of 12.2 years. We tested for interaction and conducted sensitivity analyses for a number of conditions.
Compared with metabolically healthy normal weight, baseline MHO was not significantly associated with incident CVD; however, almost one-half of those participants developed MetS during follow-up (unstable MHO). Those who had unstable MHO had increased odds of CVD (odds ratio OR: 1.60; 95% confidence interval CI: 1.14 to 2.25), compared with those with stable MHO or healthy normal weight. Dose response for duration of MetS was significantly and linearly associated with CVD (1 visit with MetS OR: 1.62; 95% CI: 1.27 to 2.07; 2 visits, OR: 1.92; 95% CI: 1.48 to 2.49; 3+ visits, OR: 2.33; 95% CI: 1.89 to 2.87; p value for trend <0.001) and MetS mediated approximately 62% (44% to 100%) of the relationship between obesity at any point during follow-up and CVD.
Metabolically healthy obesity is not a stable or reliable indicator of future risk for CVD. Weight loss and lifestyle management for CVD risk factors should be recommended to all individuals with obesity.
Display omitted
Depression is associated with heart failure independent of traditional cardiovascular disease risk factors. Enhanced platelet activation has been suggested as a potential mechanism and has been ...associated with negative inotropic effects that can affect left ventricular ejection fraction (LVEF). We examined 131 consecutive acute coronary syndrome (ACS) patients to assess whether depression increased the risk for developing LV dysfunction, and to determine the effects of platelet serotonin signaling in this relationship. Major depression was assessed using the Structured Clinical Interview and depressive symptoms were measured using the Beck Depression Inventory (BDI), with BDI ≥ 10 defined as abnormal. LV dysfunction was defined as LVEF ≤ 45%. Platelet serotonin response was measured by serotonin augmented platelet aggregation and platelet serotonin receptor density. Mean age of ACS participants was 59 years, 78.6% male and 74.0% Caucasian. 34.4% of patients had a reduced LVEF ≤ 45% on presentation. Almost half (47.0%) of patients had BDI ≥ 10 and 18.0% had major depressive disorder. Platelet serotonin response was found to be augmented in depressed patients with low LVEF compared to depressed patients with normal LVEF (
p
<
0.020
). However, the presence of LV dysfunction was found to be similar in both depressed (32.3%) and non-depressed (36.2%) patients (
p
=
0.714
). This suggests alternative factors contribute to poor cardiovascular outcomes in depressed patients that are independent of LV function in post ACS patients.
The pro-inflammatory cytokine interleukin (IL)-6 has been associated with outcomes in small pulmonary arterial hypertension (PAH) cohorts composed largely of patients with severe idiopathic PAH ...(IPAH). It is unclear whether IL-6 is a marker of critical illness or a mechanistic biomarker of pulmonary vascular remodelling. We hypothesised that IL-6 is produced by pulmonary vascular cells and sought to explore IL-6 associations with phenotypes and outcomes across diverse subtypes in a large PAH cohort.IL-6 protein and gene expression levels were measured in cultured pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) from PAH patients and healthy controls. Serum IL-6 was measured in 2017 well-characterised PAH subjects representing each PAH subgroup. Relationships between IL-6 levels, clinical variables, and mortality were analysed using regression models.Significantly higher IL-6 protein and gene expression levels were produced by PASMCs than by PAECs in PAH (p<0.001), while there was no difference in IL-6 between cell types in controls. Serum IL-6 was highest in PAH related to portal hypertension and connective tissue diseases (CTD-PAH). In multivariable modelling, serum IL-6 was associated with survival in the overall cohort (hazard ratio 1.22, 95% CI 1.08-1.38; p<0.01) and in IPAH, but not in CTD-PAH. IL-6 remained associated with survival in low-risk subgroups of subjects with mild disease.IL-6 is released from PASMCs, and circulating IL-6 is associated with specific clinical phenotypes and outcomes in various PAH subgroups, including subjects with less severe disease. IL-6 is a mechanistic biomarker, and thus a potential therapeutic target, in certain PAH subgroups.
This study prospectively evaluated endomyocardial biopsies in patients with heart failure with preserved ejection fraction (HFpEF) to identify histopathologic phenotypes and their association with ...clinical characteristics.
Myocardial tissue analysis from a prospectively defined HFpEF cohort reflecting contemporary comorbidities is lacking.
Patients with HFpEF (EF ≥50%) referred to the Johns Hopkins HFpEF Clinic between August 2014 and September 2018 were enrolled for right heart catheterization and endomyocardial biopsy. Clinical features, echocardiography, hemodynamics, and tissue histology were determined and compared with controls (unused donor hearts) and HF with reduced EF (HFrEF).
Of the 108 patients enrolled, median age was 66 years (25th to 75th percentile: 57 to 74 years), 61% were women, 57% were African American, 62% had a previous HF hospitalization, median systolic blood pressure was 141 mm Hg (25th to 75th percentile: 125 to 162 mm Hg), body mass index (BMI) was 37 kg/m2 (25th to 75th percentile: 32 to 45 kg/m2), and 97% were on a loop diuretic. Myocardial fibrosis and myocyte hypertrophy were often present (93% and 88%, respectively); however, mild in 71% with fibrosis and in 52% with hypertrophy. Monocyte infiltration (CD68+ cells/mm2) was greater in patients with HFpEF versus controls (60.4 cells/mm2 25th to 75th percentile: 36.8 to 97.8 vs. 32.1 cells/mm2 25th to 75th percentile: 22.3 to 59.2; p = 0.02) and correlated with age and renal disease. Cardiac amyloidosis (CA) was diagnosed in 15 (14%) patients (HFpEF-CA: 7 patients with wild-type transthyretin amyloidosis ATTR, 4 patients with hereditary ATTR, 3 patients with light-chain amyloidosis, and 1 patient with AA (secondary) amyloidosis), of which 7 cases were unsuspected. Patients with HFpEF-CA were older, with lower BMI, higher left ventricular mass index, and higher N-terminal pro−B-type natriuretic peptide and troponin I levels.
In this large, prospective myocardial tissue analysis of HFpEF, myocardial fibrosis and hypertrophy were common, CD68+ inflammation was increased, and CA prevalence was 14%. Tissue analysis in HFpEF might improve precision therapies by identifying relevant myocardial mechanisms.
Display omitted
Introduction: Colonoscopies can have suboptimal outcomes due to poor quality bowel preparation leading to missed identification of polyps, exposure to unnecessary anesthesia, and decreased patient ...and clinician satisfaction. In multivariate analysis, factors associated with cancellation included age (OR = 1.026, 95% CI 1.005-1.047), history of constipation (OR = 1.949, 95% CI 1.181 – 3.218), and a higher score on the color-based self-assessment stool scale (OR = 2.741, 95% CI 2.129 - 3.529). Patients Who Did Not Have Their Colonoscopies Cancelled Compared to Those Who Had Their Colonoscopies Cancelled During Pre-Operative Evaluation or During the Procedure Variable Non-Cancellation Cancellation P-Value Age (years), mean (SD) 52.821 (11.859) 56.065 (11.844) 0.011 Race 0.006 White 53.9% 46.7% Black 27.3% 43.5% Asian 10.5% 4.3% Other 7.5% 5.4% Unknown 0.7% 0.0% Completion of Bowel Preparation 0.007 No 13.0% 22.8% Yes 87.0% 77.2% Preparation Solution 0.18 PEG 71.8% 78.3% Miralax and Dulcolax 17.1% 8.7% Suprep 8.3% 10.9% Sutab 1.3% 0.0% Clenpiq 0.7% 1.1% Unknown 0.7% 1.1% History of Constipation 0.001 No 77.1% 60.9% Yes 22.8% 37.0% Unknown 0.1% 2.2% Language Barrier 0.78 No 93.9% 93.5% Yes 5.8% 6.5% Unknown 0.3% 0.0% Primary Care referral or Gastroenterologist referral 0.96 Primary Care 50.7% 51.1% Gastroenterologist 42.5% 42.4% Unknown 6.7% 6.5% Color of stool, mean (SD) 1.179 (0.537) 1.890 (1.027) < 0.001 Colonoscopy Cancelled in Pre-Operative Evaluation < 0.001 No 100.0% 70.7% Yes 0.0% 29.3% Boston Bowel Prep Score, mean (SD) 7.299 (1.355) 4.000 (2.523) < 0.001 Colonoscopy Aborted During Procedure < 0.001 No 100.0% 0.0% Yes 0.0% 70.7% N/A; cancelled in pre-op 0.0% 29.3% Author Notes *Presenter
Levels of circulating of sex hormones are associated with glucose metabolism and adiposity, but little is known about their association with ectopic fat. We aimed to characterize the association ...between circulating sex hormones and liver fat.
We conducted a cross-sectional analysis by using data from the Multiethnic Study of Atherosclerosis to assess the association of the circulating levels of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) with fatty liver. Fatty liver was defined as a reduction of ≤40 Hounsfield units, measured by computed tomography, in 2835 postmenopausal women and 2899 men (45-84 years old; white, black, Hispanic, or Chinese) at 6 centers in the United States.
Women in the highest tertile of bioavailable testosterone were significantly more likely to have fatty liver than women in the lowest tertile (odds ratio, 1.77; 95% confidence interval, 1.07-2.92). We found an even greater difference for level of estradiol (odds ratio, 2.49; 95% confidence interval, 1.41-4.39) after adjusting for age, race/ethnicity, waist-to-hip ratio, hypertension, total and high-density lipoprotein cholesterol, smoking, insulin sensitivity, and hormone replacement therapy use. Men in the highest tertile of estradiol level were significantly more likely to have fatty liver than men in the lowest tertile (odds ratio, 2.10; 95% confidence level, 1.29-3.40). Men in the highest tertile of SHBG were less likely to have fatty liver than those in the lowest tertile (odds ratio, 0.46; 95% confidence interval, 0.27-0.77). Other associations between hormone levels and fatty liver were not statistically significant.
On the basis of a cross-sectional study, postmenopausal women with high levels of bioavailable testosterone are at greater risk for fatty liver. In men, higher levels of SHBG are associated with reduced risk for fatty liver. Higher levels of estradiol are associated with fatty liver in both sexes. This pattern is consistent with the sex-specific associations of sex hormones with other cardiometabolic risk factors.
Abstract
Context
Sex differences exist in heart failure (HF) phenotypes, but there is limited research on the role of sex hormones in HF and its subtypes.
Objective
To examine the associations of ...total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) with incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF).
Design
Atherosclerosis Risk in Communities (ARIC) study (prospective cohort study). Median follow-up is 19.2 years.
Setting
General community.
Participants
4107 men and 4839 postmenopausal women, with mean age of 63.2 (standard deviation SD 5.7) and 62.8 (5.5) years, respectively.
Exposure
Plasma sex hormone levels were measured at visit 4 (1996-1998).
Main Outcome Measures
Incident HF events were identified through hospital discharge codes and death certificates.
Results
The Hazard Ratios for HF associated with 1 SD decrease in log-transformed total testosterone, DHEA-S, and SHBG were 1.10 (95% confidence interval 1.03, 1.17), 1.07 (1.00, 1.15), and 1.04 (0.96, 1.11) in men, and 1.05 (0.99, 1.13), 1.17 (1.09, 1.24), and 0.93 (0.85, 1.01) in women, respectively. The associations between sex hormones with subtypes of HF had similar patterns but were attenuated and became statistically insignificant.
Conclusion
In this prospective cohort, lower levels of endogenous testosterone and DHEA-S in men and DHEA-S in postmenopausal women were associated with the development of HF. Similar directions of association in both sexes and both HF subtypes suggest that sex hormones play a role in the development of HF through common pathways regardless of sex.
Brachial artery reactivity (BAR) is usually determined as the maximum brachial artery diameter (BAD) following release of an occluding pressure cuff compared to a BAD before cuff inflation. BAD early ...after cuff deflation can also serve as baseline for estimating total brachial artery reactivity (TBAR). We investigate whether TBAR is associated with first time coronary heart disease events.
Participants of the Multi-Ethnic Study of Atherosclerosis (n = 5499) consisting of whites, African-Americans, Chinese and Hispanics were followed longitudinally for a mean of 12.5 years. Brachial artery ultrasound was performed following five minutes of cuff occlusion at the forearm. TBAR was estimated from BAD following cuff release as the difference between maximum and minimum brachial artery diameters divided by the minimum diameter multiplied by 100%. TBAR was added to multivariable Cox proportional hazards models with Framingham risk factors as predictors and time to first coronary heart disease event as outcome.
Average TBAR was 9.7% (9.7 SD). Mean age was 61.7 years, 50.9% women. Increased TBAR was associated with lower risk of CHD events with a hazard rate of 0.78 per SD increase (95% C.I. 0.67, 0.91; p = 0.001). A TBAR below the median of 7.87% (Inter Quartile Range: 4.16%, 13.0%) was associated with a 31% lower risk of coronary heart disease event (Hazard Ratio: 0.69; 95% C.I.: 0.55, 0.87).
TBAR is an independent predictor of first time coronary heart disease events and is exclusively measured after release of a blood pressure occlusion cuff.
Background
Extracorporeal membrane oxygenation (ECMO) is associated with neurologic morbidity and mortality. We investigated whether cerebral regional oxygen saturation (rSO
2
) is associated with ...neurologic outcomes and survival in children on ECMO.
Methods
This was a retrospective observational study of children aged 1 day to 20 years who underwent ECMO with routine cerebral rSO
2
monitoring in the pediatric intensive care unit at a single academic center between February 2008 and September 2014. We collected all serial rSO
2
values recorded in the electronic medical record during the ECMO course. Favorable outcome was defined as survival with Pediatric Cerebral Performance Category (PCPC) ≤ 2 at hospital discharge or no decline from baseline PCPC.
Results
We reviewed data from 153 patients who underwent 156 ECMO runs. The median age was 12.5 days (interquartile range IQR, 2 days—15 months). Ninety-nine (64%) patients survived to hospital discharge, and 82/99 (83%) survivors had favorable neurologic outcome by discharge PCPC. Neuroimaging studies were obtained in 135 (87%) patients, 59 (44%) of which showed abnormal findings. Ninety-two (59%) patients had any rSO
2
≤ 50%, 60 (38%) had any rSO
2
decline > 20% from baseline, and 26 (17%) had any rSO
2
decline > 20% from the reading 1 h prior. Any rSO
2
≤ 50% and any rSO
2
decline > 20% from baseline were each associated with unfavorable outcome at hospital discharge (multivariable-adjusted odds ratio OR, 2.82 95% CI 1.10–7.25 and 4.52 95% CI 1.76–11.58, respectively). rSO
2
decline > 20% from the reading 1 h prior was not significantly associated with the outcomes.
Conclusion
Among children in one institution who underwent routine clinical rSO
2
monitoring during ECMO, rSO
2
decline was associated with unfavorable short-term neurologic outcome and death after adjusting for potential confounders. The effectiveness of initiating early preventative measures in these high-risk patients needs further study.
PDF
