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BackgroundObesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors.MethodsThe sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels.ResultsAmong 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth.ConclusionsThere was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.

Cardiovascular diseases (CVD) including heart attacks, strokes, heart failure, and uncontrolled hypertension are leading causes of death among women of all ages. Despite efforts to increase awareness about CVD among women, over the past decade there has been stagnation in the reduction of CVD in women, and CVD among younger women and women of color has in fact increased. We recommend taking action using policy levers to address CVD in women including: (1) Promoting periodic screening for risk factors including blood pressure, lipids/cholesterol, diabetes for all women starting at 18-21 years, with calculated atherosclerotic CVD (ASCVD) risk score use among women 40 years or older. (2) Considering coronary artery calcium (CAC) screening for those with intermediate risk per current guidelines. (3) Enhancing Obstetrics and Gynecology and primary care physician education on reproductive age CVD risk markers, and that follow-up is needed, including extended postpartum follow-up. (4) Offering Health Coaching/motivational Interviewing to support behavior change. (5) Funding demonstration projects using different care models. (6) Creating a Stop High Blood Pressure consult line (for providers and patients) and providing other support resources with actions consumers can take, modeled after the California tobacco quit line. And (7) Requiring inclusion of adverse pregnancy outcomes in all Electronic Health Records, with reminder systems to follow-up on hypertension post-partum.

Rationale: Knowledge gaps exist regarding health implications of sleep-disordered breathing (SDB) identified in pregnancy and/or after delivery. Objectives: To determine whether SDB in pregnancy and/or after delivery is associated with hypertension (HTN) and metabolic syndrome (MS). Methods: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study) (N = 4,508) followed participants initially recruited during their first pregnancy. Participants returned for a visit 2-7 years after pregnancy. This study examined a subgroup who underwent SDB assessments during their first pregnancy (n = 1,964) and a repeat SDB assessment after delivery (n = 1,222). Two SDB definitions were considered: 1) apnea-hypopnea index (AHI) ⩾ 5 and 2) oxygen desaturation index (ODI) ⩾ 5. Associations between SDB and incident HTN and MS were evaluated with adjusted risk ratios (aRRs). Measurements and Main Results: The aRR for MS given an AHI ⩾ 5 during pregnancy was 1.44 (95% confidence interval [CI], 1.08-1.93), but no association with HTN was found. ODI ⩾ 5 in pregnancy was associated with both an increased risk for HTN (aRR, 2.02; 95% CI, 1.30-3.14) and MS (aRR, 1.53; 95% CI, 1.19-1.97). Participants with an AHI ⩾ 5 in pregnancy that persisted after delivery were at higher risk for both HTN (aRR, 3.77; 95% CI, 1.84-7.73) and MS (aRR, 2.46; 95% CI, 1.59-3.76). Similar associations were observed for persistent ODI ⩾ 5 after delivery. Conclusions: An AHI ⩾ 5 in pregnancy was associated with an increased risk of MS. An ODI ⩾ 5 in pregnancy was significantly associated with both HTN and MS. Participants with persistent elevations in AHI and ODI during pregnancy and at 2-7 years after delivery were at the highest risk for HTN and MS. Clinical trial registered with www.clinicaltrials.gov (NCT02231398).

Background: Younger women with chronic disease (

Acquired cardiovascular conditions are a leading cause of maternal morbidity and mortality. A growing number of pregnant women have acquired and heritable cardiovascular conditions and cardiovascular risk factors. As the average age of childbearing women increases, the prevalence of acute coronary syndromes, cardiomyopathy, and other cardiovascular complications in pregnancy are also expected to increase. This document, the third of a 5-part series, aims to provide practical guidance on the management of such conditions encompassing pre-conception through acute management and considerations for delivery.

Background Cardiovascular risk in young adulthood is an important determinant of lifetime cardiovascular disease risk. Women with adverse pregnancy outcomes (APOs) have increased cardiovascular risk, but the relationship of other factors is unknown. Methods and Results Among 4471 primiparous women, we related first-trimester atherogenic markers to risk of APO (hypertensive disorders of pregnancy, preterm birth, small for gestational age), gestational diabetes mellitus (GDM) and hypertension (130/80 mm Hg or antihypertensive use) 2 to 7 years after delivery. Women with an APO/GDM (n=1102) had more atherogenic characteristics (obesity [34.2 versus 19.5%], higher blood pressure [systolic blood pressure 112.2 versus 108.4, diastolic blood pressure 69.2 versus 66.6 mm Hg], glucose [5.0 versus 4.8 mmol/L], insulin [77.6 versus 60.1 pmol/L], triglycerides [1.4 versus 1.3 mmol/L], and high-sensitivity C-reactive protein [5.6 versus 4.0 nmol/L], and lower high-density lipoprotein cholesterol [1.8 versus 1.9 mmol/L]; P

Background Patients with stable ischemic heart disease represent a heterogeneous population at variable risk for major adverse cardiac events (MACE). Because MACE typically occurs outside the hospital, we studied whether biometric and psychometric remote patient monitoring are associated with MACE risk biomarkers. Methods and Results In 198 patients with stable ischemic heart disease (mean age 65±11 years, 60% women), we evaluated baseline measures, including biometric (FitBit 2) and psychometric (acquired via smartphone-administered patient-reported outcomes) remote monitoring, in the PRE-MACE (Prediction, Risk, and Evaluation of Major Adverse Cardiac Events) study. In multivariable adjusted regression analyses, we examined the association of these measures with biomarkers of MACE risk, including NT-proBNP (N-terminal pro-b-type natriuretic peptide), u-hs-cTnI (ultra-high sensitivity cardiac-specific troponin I), and hs-CRP (high-sensitivity C-reactive) protein. Both biometric and psychometric measures were associated with NT-proBNP. Specifically, step count, heart rate, physical activity, global health score, and physical function score were all inversely related, whereas physical limitation score was directly related (P≤0.05 for all). However, only biometric measures (step count and heart rate) were associated with u-hs-cTnI (inversely related, P

Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal stress years after pregnancy. The 10-item Perceived Stress Scale (PSS) (0-40 range) was completed in the first and third trimesters, and 2-7 years after delivery among a subsample (n = 4161) of nulliparous women enrolled at eight US medical centers between 2010 and 2013 in a prospective, observational cohort study. Demographics, medical history, and presence of APOs (gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preeclampsia (PE), and medically indicated or spontaneous preterm birth (miPTB, sPTB)) were obtained. The associations of prenatal PSS and the presence of APOs with PSS scores years after delivery were estimated using multivariable linear regression. Mean PSS scores were 12.5 (95% CI 12.3, 12.7) and 11.3 (95% CI 11.1, 11.5) in the first and third trimesters respectively and 14.9 (95% CI 14.7, 15.1) 2-7 years later, an average increase of 2.4 points (95% CI 2.2, 2.6) from the start of pregnancy. Regressing PSS scores after delivery on first-trimester PSS and PSS increase through pregnancy showed positive associations, with coefficients (95% CI) of 2.8 (2.7, 3.0) and 1.5 (1.3, 1.7) per 5-point change, respectively. Adding APO indicator variables separately showed higher PSS scores for women with HDP (0.7 [0.1, 1.3]), PE (1.3 [0.6, 2.1]), and miPTB (1.3 [0.2, 2.4]), but not those with GDM or sPTB. In this geographically and demographically diverse sample, prenatal stress and some APOs were positively associated with stress levels 2-7 years after pregnancy.ClinicalTrials.gov Registration number NCT02231398.

Constructing statistical models using personal sensor data could allow for tracking health status over time, thereby enabling the possibility of early intervention. The goal of this study was to use machine learning algorithms to classify patient-reported outcomes (PROs) using activity tracker data in a cohort of patients with stable ischemic heart disease (SIHD). A population of 182 patients with SIHD were monitored over a period of 12 weeks. Each subject received a Fitbit Charge 2 device to record daily activity data, and each subject completed eight Patient-Reported Outcomes Measurement Information Systems short form at the end of each week as a self-assessment of their health status. Two models were built to classify PRO scores using activity tracker data. The first model treated each week independently, whereas the second used a hidden Markov model (HMM) to take advantage of correlations between successive weeks. Retrospective analysis compared the classification accuracy of the two models and the importance of each feature. In the independent model, a random forest classifier achieved a mean area under curve (AUC) of 0.76 for classifying the physical function PRO. The HMM model achieved significantly better AUCs for all PROs (p < 0.05) other than Fatigue and Sleep Disturbance, with a highest mean AUC of 0.79 for the physical function-short form 10a. Our study demonstrates the ability of activity tracker data to classify health status over time. These results suggest that patient outcomes can be monitored in real time using activity trackers.

ImportanceCertain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear.ObjectiveTo determine the demographic and clinical characteristics associated with increased severity of Covid-19 infection.DesignRetrospective observational study. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation.SettingA large, multihospital healthcare system in Southern California.ParticipantsAll patients with confirmed Covid-19 infection (N = 442).ResultsOf all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P

BackgroundWomen with symptoms and signs of ischemia, preserved left ventricular ejection fraction (LVEF), and no obstructive coronary artery disease (CAD), often have coronary microvascular dysfunction (CMD), and are at risk of future heart failure with preserved ejection fraction (HFpEF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used to evaluate HF and myocardial ischemia. Relationships between NT-proBNP and CMD are not well defined in this population.MethodsWe evaluated resting NT-proBNP levels in 208 women with symptoms and signs of ischemic heart disease, preserved LVEF and no obstructive CAD undergoing clinically indicated invasive coronary flow reserve (CFR) as a measure of CMD-related ischemia and resting left ventricular end-diastolic pressure (LVEDP). Chi-square testing was used for categorical variables and ANOVA or Kruskal-Wallis tests were used for continuous variables.ResultsOverall, 79% had an elevated resting LVEDP, and mean NT-proBNP was 115 ± 158 pg/mL. NT-proBNP levels correlated directly with age (r = 0.28, p =

Background: Spontaneous preterm delivery (sPTD) is associated with a twofold increased risk of future maternal cardiovascular disease. We hypothesized that women with sPTD would demonstrate greater vascular dysfunction postpartum compared to women with term delivery. Materials and Methods: In a case-controlled, matched pilot study, we enrolled 20 women with sPTD (gestation ≤34 weeks), and 20 term control women (gestation ≥39 weeks) were matched for age (±5 years), parity, ethnicity, and route of delivery. Vascular function, serum lipids, C-reactive protein, and interleukin-6 were completed within 24-72 hours postpartum. Statistical analysis included paired t-tests based on match and mixed effects linear regression models and adjusted for potential confounders. Results: The mean age for sPTD and term controls was 33 ± 6 years and 32 ± 6 years, respectively. Women with sPTD had significantly lower augmentation index-75 (24.1% ± 16.1% vs. 39.9% ± 15.2%, p = 0.001) and central pulse pressure (29.1 ± 5.4 mmHg vs. 34.6 ± 4.7 mmHg, p = 0.004), but no difference in pulse wave velocity (5.1 ± 1.6 m/s vs. 5.6 ± 1.5 m/s, p = 0.12) compared to controls. Women with sPTD had significantly lower high-density lipoprotein cholesterol (59.4 ± 12.5 mg/dL vs. 67.6 ± 13.1 mg/dL, p = 0.035) compared to controls. Analysis of chorioamnionitis and magnesium sulfate did not alter the results. Conclusions: Women with sPTD have signs of lower smooth muscle tone in the early postpartum period compared to women with term delivery. Further research is required to understand mechanistic pathways in sPTD and future maternal cardiovascular disease risk.

Background Identifying pregnancy-associated risk factors before the development of major cardiovascular disease events could provide opportunities for prevention. The objective of this study was to determine the association between outcomes in first pregnancies and subsequent cardiovascular health. Methods and Results The Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be Heart Health Study is a prospective observational cohort that followed 4484 women 2 to 7 years (mean 3.2 years) after their first pregnancy. Adverse pregnancy outcomes (defined as hypertensive disorders of pregnancy, small-for-gestational-age birth, preterm birth, and stillbirth) were identified prospectively in 1017 of the women (22.7%) during this pregnancy. The primary outcome was incident hypertension (HTN). Women without adverse pregnancy outcomes served as controls. Risk ratios (RR) and 95% CIs were adjusted for age, smoking, body mass index, insurance type, and race/ethnicity at enrollment during pregnancy. The overall incidence of HTN was 5.4% (95% CI 4.7% to 6.1%). Women with adverse pregnancy outcomes had higher adjusted risk of HTN at follow-up compared with controls (RR 2.4, 95% CI 1.8-3.1). The association held for individual adverse pregnancy outcomes: any hypertensive disorders of pregnancy (RR 2.7, 95% CI 2.0-3.6), preeclampsia (RR 2.8, 95% CI 2.0-4.0), and preterm birth (RR 2.7, 95% CI 1.9-3.8). Women who had an indicated preterm birth and hypertensive disorders of pregnancy had the highest risk of HTN (RR 4.3, 95% CI 2.7-6.7). Conclusions Several pregnancy complications in the first pregnancy are associated with development of HTN 2 to 7 years later. Preventive care for women should include a detailed pregnancy history to aid in counseling about HTN risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT02231398.

ObjectiveTo determine whether early vascular aging may be present in flight attendants with remote in-cabin secondhand smoke (SHS) exposure.MethodsTwenty-six flight attendants with a history of in-cabin SHS exposure prior to the airline smoking bans were recruited. Pulse wave analysis, peripheral arterial tonometry, and brachial artery reactivity testing evaluated their arterial compliance and endothelial function.ResultsFlight attendants with remote in-cabin SHS exposure have normal blood pressure, pulse wave velocity, and reactive hyperemia index, but abnormal pulse pressure, augmentation index, flow-mediated dilation, and hyperemic mean flow ratio.ConclusionThese preliminary findings suggest that flight attendants with remote in-cabin SHS exposure have preclinical signs of accelerated vascular aging and raise new questions about the relationship between remote SHS exposure and vascular health.

BackgroundAlthough leisure-time physical activity (PA) contributes to overall health, including pregnancy health, patterns across pregnancy have not been related to birth outcomes. We hypothesized that women with sustained low leisure-time PA would have excess risk of adverse pregnancy outcomes, and that changing patterns across pregnancy (high to low and low to high) may also be related to risk of adverse pregnancy outcomes.MethodsNulliparous women (n = 10,038) were enrolled at 8 centers early in pregnancy (mean gestational age in weeks [SD] = 12.05 [1.51]. Frequency, duration, and intensity (metabolic equivalents) of up to three leisure activities reported in the first, second and third trimesters were analyzed. Growth mixture modeling was used to identify leisure-time PA patterns across pregnancy. Adverse pregnancy outcomes (preterm birth, [PTB, overall and spontaneous], hypertensive disorders of pregnancy [HDP], gestational diabetes [GDM] and small-for-gestational-age births [SGA]) were assessed via chart abstraction.ResultsFive patterns of leisure-time PA across pregnancy were identified: High (35%), low (18%), late decreasing (24%), early decreasing (10%), and early increasing (13%). Women with sustained low leisure-time PA were younger and more likely to be black or Hispanic, obese, or to have smoked prior to pregnancy. Women with low vs. high leisure-time PA patterns had higher rates of PTB (10.4 vs. 7.5), HDP (13.9 vs. 11.4), and GDM (5.7 vs. 3.1, all p

AimsPathologic evidence supports unique sex-specific mechanisms as precursors for acute cardiovascular (CV) events. Current evidence on long-term CV risk among women when compared with men based on measures of coronary artery calcium (CAC) remains incomplete.Methods and resultsA total of 63 215 asymptomatic women and men were enrolled in the multicentre, CAC Consortium with median follow-up of 12.6 years. Pooled cohort equation (PCE) risk scores and risk factor data were collected with the Agatston score and other CAC measures (number of lesions and vessels, lesion size, volume, and plaque density). Cox proportional hazard models were employed to estimate CV mortality (n = 919). Sex interactions were calculated. Women and men had average PCE risk scores of 5.8% and 9.1% (P

BackgroundIt has recently been shown that magnetic resonance (MR) "native T1" mapping is capable of characterizing abnormal microcirculation in patients with obstructive coronary artery disease (CAD). In studies involving women with signs and symptoms of ischemia and no obstructive CAD (INOCA), however, the potential role of native T1 as an imaging marker and its association with indices of diastolic function or vasodilator-induced myocardial ischemia have not been explored. We investigated whether native T1 in INOCA is associated with reduced myocardial perfusion reserve index (MPRI) or with diastolic dysfunction.MethodsTwenty-two female patients with INOCA and twelve female reference controls with matching age and body-mass index were studied. The patients had evidence of vasodilator-induced ischemia without obstructive CAD or any prior infarction. All 34 subjects underwent stress/rest MR including native T1 mapping (MOLLI 5(3)3) at 1.5-Tesla.ResultsCompared with controls, patients had similar morphology/function. As expected, MPRI was significantly reduced in patients compared to controls (1.78 ± 0.39 vs. 2.49 ± 0.41, p

Telemedicine has been used to remotely diagnose and treat patients, yet previously applied telemonitoring approaches have been fraught with adherence issues. The primary goal of this study was to evaluate the adherence rates using a consumer-grade continuous-time heart rate and activity tracker in a mid-risk cardiovascular patient population. As a secondary analysis, we show the ability to utilize the information provided by this device to identify information about a patient's state by correlating tracker information with patient-reported outcome survey scores. We showed that using continuous-time activity trackers with heart rate monitors can be effective in a telemonitoring application, as patients had a high level of adherence (90.0% median usage) and low attrition (0.09% decrease per day) over a 90-day period. Furthermore, data collected correlated significantly with clinically relevant patient surveys (r2=0.15 for PROMIS global health scores, p

BackgroundThe utility of exercise-induced ST-segment depression for diagnosing ischemic heart disease (IHD) in women is unclear.HypothesisBased on evidence that IHD pathophysiology in women involves coronary vascular dysfunction, we hypothesized that coronary vascular dysfunction contributes to exercise electrocardiography (Ex-ECG) ST-depression in the absence of obstructive coronary artery disease, so-called false positive results. We tested our hypothesis in a pilot study evaluating the relationship between peripheral vascular endothelial function and Ex-ECG.MethodsTwenty-nine asymptomatic women without cardiac risk factors underwent maximal Bruce protocol exercise treadmill testing and peripheral endothelial function assessment using peripheral arterial tonometry (Itamar EndoPAT 2000) to measure reactive hyperemia index (RHI). The relationship between RHI and Ex-ECG ST-segment depression was evaluated using logistic regression and differences in subgroups using 2-tailed t tests.ResultsMean age was 54 ± 7 years, body mass index 25 ± 4 kg/m2 , and RHI 2.51 ± 0.66. Three women (10%) had RHI 0.05). RHI did not predict ST-segment depression.ConclusionsOur pilot study demonstrates high prevalence of exercise-induced ST-segment depression in asymptomatic, middle-aged, overweight women. Peripheral vascular endothelial dysfunction did not predict Ex-ECG ST-segment depression. Further work is needed to investigate the utility of vascular endothelial testing and Ex-ECG for IHD diagnostic and management purposes in women.

BackgroundWomen with chest pain, ischemia, and no obstructive coronary artery disease often have coronary vascular dysfunction (CVaD). Peripheral vascular reactivity to mental stress may contribute mechanistic understanding of stress-induced ischemia in women with CVaD.Methods62 women (41 CVaD and 21 controls) underwent mental stress testing (MST) with anger recall, mental arithmetic, and forehead cold pressor (COP) challenge. Emotional arousal was measured (Likert scale). Reactive hyperemia index (RHI) was calculated before and after MST by peripheral arterial tonometry (PAT). Stress PAT ratio (SPR) of pulse amplitude during stress to rest was obtained to measure vasoconstriction. Wilcoxson rank sum test was used for analysis.ResultsMean age of CVaD and control groups was 58±9 and 55±10years (p=0.73). Baseline RHI correlated with coronary endothelial function (r=0.36, p=0.03) and inversely with RHI change post-MST (r=-0.51, p

BackgroundIschemia, in the absence of obstructive coronary artery disease, is prevalent in women, and associated with increased risk for major cardiovascular events. Coronary microvascular dysfunction is prevalent in these patients, and associated with impaired diastolic function. Despite our general understanding, however, optimal treatment of this cohort remains elusive.MethodsTo address this knowledge gap, we performed an open-label treatment trial to assess whether phosphodiesterase type 5 inhibition improves coronary microvascular perfusion and diastolic function in women with signs and symptoms of ischemia but no evidence of obstructive coronary artery disease. Left ventricular morphology and function, along with myocardial perfusion reserve index, were assessed by contrast-enhanced cardiac magnetic resonance imaging.ResultsA total of five women enrolled of which four completed the trial, while one was withdrawn by the investigators after developing dyspnea 1 week after treatment. Her symptoms resolved after cessation of the study medication. In contrast to our hypothesis, phosphodiesterase type 5 inhibition reduced the rate of circumferential strain in diastole in all four women who completed the trial (that is, diastolic dysfunction). This impairment could not be explained by changes in heart rate, contractility, blood pressure, or preload, and was not associated with a change in myocardial perfusion reserve index. Frequency of angina also tended to increase with treatment, with the greatest increase occurring in the patient with the greatest impairment in diastolic strain.ConclusionsTaken together, these data question the efficacy of phosphodiesterase type 5 inhibition to treat women with ischemic heart disease, and highlight the need for further investigation.

BackgroundPatients with obstructive (≥50% stenosis) left main (LM) coronary artery disease (CAD) are at high risk for adverse events; prior studies have also documented worse outcomes among women than men with severe multivessel/LM CAD. However, the prognostic significance of nonobstructive (1%-49% stenosis) LM CAD, including sex-specific differences, has not been previously examined.Methods and resultsIn the long-term CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) registry, patients underwent elective coronary computed tomographic angiography for suspected CAD and were followed for 5 years. After excluding those with obstructive LM CAD, 5166 patients were categorized as having normal LM or nonobstructive LM (18% of cohort). Cumulative 5-year incidence of death, myocardial infarction, or revascularization was higher among patients with nonobstructive LM than normal LM in both women and men: women (34.3% versus 15.4%; P

ObjectivesThe aim of this work is the development of coronary atherosclerosis T1-weighted characterization with integrated anatomical reference (CATCH) technique and the validation by comparison with high-risk plaque features (HRPF) observed on intracoronary optical coherence tomography (OCT) and invasive coronary angiography.BackgroundT1-weighted cardiac magnetic resonance with or without contrast media has been used for characterizing coronary atherosclerosis showing promising prognostic value. Several limitations include: 1) coverage is limited to proximal coronary segments; 2) spatial resolution is low and often anisotropic; and 3) a separate magnetic resonance angiography acquisition is needed to localize lesions.MethodsCATCH acquired dark-blood T1-weighted images and bright-blood anatomical reference images in an interleaved fashion. Retrospective motion correction with 100% respiratory gating efficiency was achieved. Reference control subjects (n = 13) completed both pre- and post-contrast scans. Stable angina patients (n = 30) completed pre-contrast scans, among whom 26 eligible patients also completed post-contrast scans. After cardiac magnetic resonance, eligible patients (n = 22) underwent invasive coronary angiography and OCT for the interrogation of coronary atherosclerosis. OCT images were assessed and scored for HRPF (lipid-richness, macrophages, cholesterol crystals, and microvessels) by 2 experienced analysts blinded to magnetic resonance results.ResultsPer-subject analysis showed none of the 13 reference control subjects had coronary hyperintensive plaques (CHIP) in either pre-contrast or post-contrast CATCH. Five patients had CHIP on pre-contrast CATCH and 5 patients had CHIP on post-contrast CATCH. Patients with CHIP had greater lipid abnormality than those without. Per-segment analysis showed elevated pre- and post-contrast plaque to myocardium signal ratio in the lesions with HRPF versus those without. Positive correlation was observed between plaque to myocardium signal ratio and OCT HRPF scoring. CHIP on pre-contrast CATCH were associated with significantly higher stenosis level than non-CHIP on invasive coronary angiography.ConclusionsCATCH provided accelerated whole heart coronary plaque characterization with simultaneously acquired anatomical reference. CHIP detected by CATCH showed positive association with high-risk plaque features on invasive imaging studies.

AimsThe mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.Materials and resultsRandomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR

PurposeAccurate quantification of myocardial perfusion is dependent on reliable electrocardiogram (ECG) triggering. Measuring myocardial blood flow (MBF) in patients with arrhythmias or poor ECGs is currently infeasible with MR. The purpose of this study was to demonstrate the feasibility of a non-ECG-triggered method with clinically useful three-slice ventricular coverage for measurement of MBF in healthy volunteers.MethodsA saturation recovery magnetization-prepared gradient recalled echo acquisition was continuously repeated during first-pass imaging. A slice-interleaved radial trajectory was employed to enable image-based retrospective triggering. The arterial input function was generated using a beat-by-beat T1 estimation method. The proposed technique was validated against a conventional ECG-triggered dual-bolus technique in 10 healthy volunteers. The technique was further demonstrated under adenosine stress in 12 healthy volunteers.ResultsThe proposed method produced MBF with no significant difference compared with the ECG-triggered technique. The proposed method yielded mean myocardial perfusion reserve comparable to published literature.ConclusionWe have developed a non-ECG-triggered quantitative perfusion imaging method. In this preliminary study, our results demonstrate that our method yields comparable MBF compared with the conventional ECG-triggered method and that it is feasible for stress imaging.

AimsThe mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.Materials and resultsRandomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR

Nonobstructive coronary artery disease (CAD) in women is associated with adverse cardiovascular (CV) outcomes; however, information regarding genetic variants that predispose women to nonobstructive CAD is lacking. Women from the Women's Ischemia Syndrome Evaluation (WISE) Study and the St. James Women Take Heart (WTH) Study were genotyped with the Cardio-MetaboChip. WISE enrolled women with symptoms and signs of ischemia referred for coronary angiography; WTH enrolled asymptomatic, community-based women without heart disease. Analyses were conducted with a case (WISE)--control (WTH) design and multivariate logistic regression models to investigate genetic variation associated with likelihood of nonobstructive CAD. One genetic marker, single nucleotide polymorphism (SNP) rs2301753 on chromosome 6 in RNF39, achieved chip-wide significance for nonobstructive CAD (P < 9.5 × 10(-7)). After adjusting for baseline characteristics, we found no variants achieved chip-wide significance. However, SNP rs2301753 on chromosome 6 in RNF39 was associated with reduced likelihood of nonobstructive CAD [odds ratio (OR) 0.42 and 95% confidence interval (CI) of 0.29 to 0.68], at a nominal level of P = 5.6 × 10(-6), while SNP rs12818945 in the ATP2B1 locus on chromosome 12 was associated with increased odds for nonobstructive CAD (OR 2.38 and 95% CI of 1.63 to 3.45) and nominal P = 5.8 × 10(-6). The functions of RNF39 and ATP2B1 raise the possibility that genes involved in cardio-dysfunction may contribute to nonobstructive CAD in Caucasian women and may provide insights into novel approaches for therapy and prevention. If replicated, incorporation of these genetic variants into diagnostic evaluation may identify women at high risk for nonobstructive CAD.

PurposeTo develop and test the feasibility of a new method for non-ECG-gated first-pass perfusion (FPP) cardiac MR capable of imaging multiple short-axis slices at the same systolic cardiac phase.MethodsA magnetization-driven pulse sequence was developed for non-ECG-gated FPP imaging without saturation-recovery preparation using continuous slice-interleaved radial sampling. The image reconstruction method, dubbed TRACE, used self-gating based on reconstruction of a real-time image-based navigator combined with reference-constrained compressed sensing. Data from ischemic animal studies (n = 5) was used in a simulation framework to evaluate temporal fidelity. Healthy subjects (n = 5) were studied using both the proposed approach and the conventional method to compare the myocardial contrast-to-noise ratio (CNR). Patients (n = 2) underwent adenosine stress studies using the proposed method.ResultsTemporal fidelity of the developed method was shown to be sufficient at high heart-rates. The healthy volunteers studies demonstrated normal perfusion and no dark-rim artifacts. Compared with the conventional scheme, myocardial CNR for the proposed method was slightly higher (8.6 ± 0.6 versus 8.0 ± 0.7). Patient studies showed stress-induced perfusion defects consistent with invasive angiography.ConclusionThe presented methods and results demonstrate feasibility of the proposed approach for high-resolution non-ECG-gated FPP imaging of 3 myocardial slices at the same systolic phase, and indicate its potential for achieving desirable image quality (high CNR and no dark-rim artifacts).

PurposeMR myocardial perfusion imaging is dependent on reliable electrocardiogram (ECG) triggering for accurate measurement of myocardial blood flow (MBF). A non-ECG-triggered method for quantitative first-pass imaging may improve clinical feasibility in patients with poor ECG signal. The purpose of this study is to evaluate the feasibility of a non-ECG-triggered method for myocardial perfusion imaging in a single slice.MethodsThe proposed non-ECG-triggered technique uses a saturation-recovery magnetization preparation and golden-angle radial acquisition for integrated arterial input function (AIF) measurement. Image based self-gating with a temporal resolution of 42.6 ms is used to generate a first-pass image series with consistent cardiac phase. The AIF is measured using beat-by-beat T1 estimation of the ventricular blood pool. The proposed technique was performed on 14 healthy volunteers and compared against a conventional ECG-triggered dual-bolus acquisition.ResultsThe proposed method produced MBF with no significant difference compared with ECG-triggered technique (mean of 0.63 ± 0.22 mL/min/g to 0.73 ± 0.21 mL/min/g).ConclusionWe have developed a non-ECG-triggered perfusion imaging method with T1 based measurement of the AIF in a single slice. In this preliminary study, our results demonstrate that MBF measured using the proposed method is comparable to the conventional ECG-triggered method.

BackgroundAlthough fear of falling is prevalent among older adults recovering from hip fracture, current instruments are inadequate due to focus on specific situations and measurement of self-efficacy rather than fear.MethodsThe authors revised and tested a form of the Fear of Falling Questionnaire with three groups of older adults: 405 recovering from hip fracture, 89 healthy community dwelling, and 42 with severe fear of falling. Test-retest reliability was evaluated in a subsample of 16 hip fracture patients. Internal consistency was compared across all groups. Construct validity was established through factor analysis, convergent validity with a measure of fall-related self-efficacy, and discriminant validity with measures of depression and affect.ResultsA revised two-factor, six-item scale appears to have adequate psychometric properties. Scores were lower in the healthy comparison group relative to the hip fracture and fear of falling groups. Cronbach's α ranged from 0.72-0.83, with test-retest reliability of 0.82. Correlations with a measure of fall-related self-efficacy were moderate for the hip fracture group (0.42) and high with the healthy comparison (0.68) and fear of falling (0.70) groups. Correlations with depression and negative and positive affect were low to moderate.ConclusionsThe Fear of Falling Questionnaire - Revised shows promise as a self-report measure of fear of falling, and is one of the first to be tested in older adults recovering from hip fracture. Advantages are that it is global rather than situation-specific and measures fear rather than self-efficacy. Future research on this scale is recommended in other older adult samples for whom fear of falling is relevant.

BackgroundPancreatic cancer has poor prognosis and existing interventions provide a modest benefit. Statin has anti-cancer properties that might enhance survival in pancreatic cancer patients. We sought to determine whether statin treatment after cancer diagnosis is associated with longer survival in those with pancreatic ductal adenocarcinoma (PDAC).MethodsWe analyzed data on 7813 elderly patients with PDAC using the linked Surveillance, Epidemiology, and End Results (SEER) - Medicare claims files. Information on the type, intensity and duration of statin use after cancer diagnosis was extracted from Medicare Part D. We treated statin as a time-dependent variable in a Cox regression model to determine the association with overall survival adjusting for follow-up, age, sex, race, neighborhood income, stage, grade, tumor size, pancreatectomy, chemotherapy, radiation, obesity, dyslipidemia, diabetes, chronic pancreatitis and chronic obstructive pulmonary disease (COPD).ResultsOverall, statin use after cancer diagnosis was not significantly associated with survival when all PDAC patients were considered (HR = 0.94, 95%CI 0.89, 1.01). However, statin use after cancer diagnosis was associated with a 21% reduced hazard of death (Hazard ratio = 0.79, 95% confidence interval (CI) 0.67, 0.93) in those with grade I or II PDAC and to a similar extent in those who had undergone a pancreatectomy, in those with chronic pancreatitis and in those who had not been treated with statin prior to cancer diagnosis.ConclusionsWe found that statin treatment after cancer diagnosis is associated with enhanced survival in patients with low-grade, resectable PDAC.

BackgroundBlack women are less likely to be evaluated and treated for anginal symptoms, despite a higher premature cardiac mortality rate compared to white women. Our objective was to compare angina symptoms in black versus white women regarding (1) angina symptoms characterization; (2) relationship with obstructive coronary artery disease (CAD); and (3) relationship with subsequent mortality.MethodsA cohort of 466 women (69 black and 397 white) undergoing coronary angiography for suspected ischemia and without prior history of CAD completed symptom checklists. Four symptom clusters (CHEST, UPPER, STOMACH, and TYPICAL TRIGGERS) were derived by factor analysis. All angiograms were analyzed by core lab. Mortality data over 10 years were obtained from National Death Index.Results(1) Black women had lower mean CHEST cluster scores (0.60±0.30 vs. 0.73±30, p=0.002), but higher STOMACH scores (0.41±0.25 vs. 0.30±0.25, p=0.011) than white women. (2) Prevalence and severity of CAD did not differ in black and white women and was not predicted by symptom cluster scores. (3) All-cause mortality rates were 24.9% in blacks versus 14.5% in whites, p=0.007; and cardiovascular mortality 22.5% vs.8.8%, p=0.001. Symptom clusters were not predictive of adverse events in white women. However, black women with a low TYPICAL score had significantly higher mortality compared to those with a high TYPICAL score (43% vs. 10%, p=0.006).ConclusionsAmong women undergoing coronary angiography, black women report fewer chest-related and more stomach-related symptoms, regardless of presence or severity of CAD, and these racial symptom presentation differences are linked with the more adverse prognosis observed in the black women. Atypical symptom presentation may be a barrier to appropriate and timely diagnosis and treatment and contribute to poorer outcomes for black women.