Socioeconomic disadvantage in pregnancy and postpartum risk of cardiovascular disease.

BACKGROUND: Pregnancy is an educable and actionable life stage to address social determinants of health (SDOH) and lifelong cardiovascular disease (CVD) prevention. However, the link between a risk score that combines multiple neighborhood-level social determinants in pregnancy and the risk of long-term CVD remains to be evaluated. OBJECTIVE: To examine whether neighborhood-level socioeconomic disadvantage measured by the Area Deprivation Index (ADI) in early pregnancy is associated with a higher 30-year predicted risk of CVD postpartum, as measured by the Framingham Risk Score. STUDY DESIGN: An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. Participant home addresses during early pregnancy were geocoded at the Census-block level. The exposure was neighborhood-level socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]) measured in the first trimester. Outcomes were the predicted 30-year risks of atherosclerotic cardiovascular disease (ASCVD, composite of fatal and nonfatal coronary heart disease and stroke) and total CVD (composite of ASCVD plus coronary insufficiency, angina pectoris, transient ischemic attack, intermittent claudication, and heart failure) using the Framingham Risk Score measured 2 to 7 years after delivery. These outcomes were assessed as continuous measures of absolute estimated risk in increments of 1%, and, secondarily, as categorical measures with high-risk defined as an estimated probability of CVD ≥10%. Multivariable linear regression and modified Poisson regression models adjusted for baseline age and individual-level social determinants, including health insurance, educational attainment, and household poverty. RESULTS: Among 4309 nulliparous individuals at baseline, the median age was 27 years (interquartile range [IQR]: 23-31) and the median ADI was 43 (IQR: 22-74). At 2 to 7 years postpartum (median: 3.1 years, IQR: 2.5, 3.7), the median 30-year risk of ASCVD was 2.3% (IQR: 1.5, 3.5) and of total CVD was 5.5% (IQR: 3.7, 7.9); 2.2% and 14.3% of individuals had predicted 30-year risk ≥10%, respectively. Individuals living in the highest ADI tertile had a higher predicted risk of 30-year ASCVD % (adjusted ß: 0.41; 95% confidence interval [CI]: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top 2 ADI tertiles had higher absolute risks of 30-year total CVD % (T2: adj. ß: 0.37; 95% CI: 0.03, 0.72; T3: adj. ß: 0.74; 95% CI: 0.36, 1.13). Similarly, individuals living in neighborhoods in the highest ADI tertile were more likely to have a high 30-year predicted risk of ASCVD (adjusted risk ratio [aRR]: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). CONCLUSION: Neighborhood-level socioeconomic disadvantage in early pregnancy was associated with a higher estimated long-term risk of CVD postpartum. Incorporating aggregated SDOH into existing clinical workflows and future research in pregnancy could reduce disparities in maternal cardiovascular health across the lifespan, and requires further study.

Coronary Microvascular Dysfunction: What Clinicians and Investigators Should Know.

PURPOSE OF REVIEW: Abnormal structure and function of the coronary microvasculature have been implicated in the pathophysiology of multiple cardiovascular disease processes. This article reviews recent research progress related to coronary microvascular dysfunction (CMD) and salient clinical takeaways. RECENT FINDINGS: CMD is prevalent in patients with signs and symptoms of ischemia and no obstructive epicardial coronary artery disease (INOCA), particularly in women. CMD is associated with adverse outcomes, including most frequently the development of heart failure with preserved ejection fraction. It is also associated with adverse outcomes in patient populations including hypertrophic cardiomyopathy, dilated cardiomyopathy, and acute coronary syndromes. In patients with INOCA, stratified medical therapy guided by invasive coronary function testing to define the subtype of CMD leads to improved symptoms. There are invasive and non-invasive methodologies to diagnose CMD that provide prognostic information and mechanistic information to direct treatment. Available treatments improve symptoms and myocardial blood flow; ongoing investigations aim to develop therapy to improve adverse outcomes related to CMD.

Clinical characteristics and prognosis of patients with microvascular angina: an international and prospective cohort study by the Coronary Vasomotor Disorders International Study (COVADIS) Group.

AIMS: To provide multi-national, multi-ethnic data on the clinical characteristics and prognosis of patients with microvascular angina (MVA). METHODS AND RESULTS: The Coronary Vasomotor Disorders International Study Group proposed the diagnostic criteria for MVA. We prospectively evaluated the clinical characteristics of patients according to these criteria and their prognosis. The primary endpoint was the composite of major cardiovascular events (MACE), verified by institutional investigators, which included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. During the period from 1 July 2015 to 31 December 2018, 686 patients with MVA were registered from 14 institutes in 7 countries from 4 continents. Among them, 64% were female and the main ethnic groups were Caucasians (61%) and Asians (29%). During follow-up of a median of 398 days (IQR 365-744), 78 MACE occurred (6.4% in men vs. 8.6% in women, P = 0.19). Multivariable Cox proportional hazard analysis disclosed that hypertension and previous history of coronary artery disease (CAD), including acute coronary syndrome and stable angina pectoris, were independent predictors of MACE. There was no sex or ethnic difference in prognosis, although women had lower Seattle Angina Questionnaire scores than men (P < 0.05). CONCLUSIONS: This first international study provides novel evidence that MVA is an important health problem regardless of sex or ethnicity that a diagnosis of MVA portends a substantial risk for MACE associated with hypertension and previous history of CAD, and that women have a lower quality of life than men despite the comparable prognosis.

Rationale and design of the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial.

BACKGROUND: Approximately half of all women with anginal symptoms and/or signs of ischemia and no obstructive coronary artery disease (INOCA) referred for coronary angiography have elevated risk for major adverse cardiac events (MACE), poor quality of life and resource consumption. Yet, guidelines focus on symptom management while clinical practice typically advocates only reassurance. Pilot studies of INOCA subjects suggest benefit with intensive medical therapy (IMT) that includes high-intensity statins and angiotensin converting enzyme inhibitors (ACE-I) or receptor blockers (ARB) to provide the rationale for a randomized pragmatic trial to limit MACE. METHODS: The Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD is a multicenter, prospective, randomized, blinded outcome evaluation (PROBE design) of a pragmatic strategy of IMT vs usual care (UC) in 4,422 symptomatic women with INOCA (NCT03417388) in approximately 70 United States sites. The hypothesis is that IMT will reduce the primary outcome of first occurrence of MACE by 20% vs. UC at ∼2.5 year followup. Secondary outcomes include quality of life, time to return to "duty"/work, healthcare utilization, angina, cardiovascular death and individual primary outcome components over 3 years follow-up. The study utilizes web-based data capture, e-consents, single IRB and centralized pharmacy distribution of strategy medications directly to patients' homes to reduce site and patient burden. A biorepository will collect blood samples to assess potential mechanisms. CONCLUSIONS: The results of this trial will provide important data necessary to inform guidelines regarding how best to manage this growing and challenging population of women with INOCA.

Design, methodology and baseline characteristics of the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD).

A significant number of women with signs and symptoms of ischemia with no obstructive coronary artery disease (INOCA) have coronary vascular dysfunction detected by invasive coronary reactivity testing (CRT). However, the noninvasive assessment of coronary vascular dysfunction has been limited. METHODS: The Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) was a prospective study of women with suspected INOCA aimed to investigate whether (1) cardiac magnetic resonance imaging (CMRI) abnormalities in left ventricular morphology and function and myocardial perfusion predict CRT measured coronary microvascular dysfunction, (2) these persistent CMRI abnormalities at 1-year follow-up predict persistent symptoms of ischemia, and (3) these CMRI abnormalities predict cardiovascular outcomes. By design, a sample size of 375 women undergoing clinically indicated invasive coronary angiography for suspected INOCA was projected to complete baseline CMRI, a priori subgroup of 200 clinically indicated CRTs, and a priori subgroup of 200 repeat 1-year follow-up CMRIs. RESULTS: A total of 437 women enrolled between 2008 and 2015, 374 completed baseline CMRI, 279 completed CRT, and 214 completed 1-year follow-up CMRI. Mean age was 55±â€¯11 years, 93% had 20%-50% coronary stenosis, and 7% had <20% stenosis by angiography. CONCLUSIONS: The WISE-CVD study investigates the utility of noninvasive CMRI to predict coronary vascular dysfunction in comparison to invasive CRT, and the prognostic value of CMRI abnormalities for persistent symptoms of ischemia and cardiovascular outcomes in women with INOCA. WISE-CVD will provide new understanding of a noninvasive imaging modality for future clinical trials.

Even "WISE-R?"-an Update on the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation.

PURPOSE OF REVIEW: For over 20 years, the Women's Ischemia Syndrome Evaluation (WISE), a program sponsored by the National Heart, Lung, and Blood Institute, has explored diverse and important aspects of ischemic heart disease in women. RECENT FINDINGS: Women with symptoms and signs of ischemia but no significant epicardial obstructive coronary artery disease (INOCA) were documented to be at elevated risk for recurrent angina hospitalization, major adverse cardiac events, death, and health resource consumption rivaling those with obstructive coronary disease. WISE investigators have advanced our understanding of cardiovascular outcomes, systemic manifestations, psychological variables, socioeconomic factors, genetic contributions, hormonal status, advanced imaging, coronary functional findings, biomarkers, patient-reported outcomes, and treatments pertaining to women with this disease entity. This review delves into the WISE findings subsequent to a prior review1, postulates directions for future research, and asks are we "Even 'WISE-R?'".

Sex Differences in Cardiovascular Aging and Heart Failure.

PURPOSE OF THE REVIEW: This review summarizes sex-related changes in the heart and vasculature that occur with aging, both in the presence and absence of cardiovascular disease (CVD). RECENT FINDINGS: In the presence of CVD risk factors and/or overt CVD, sex-specific changes in the number of cardiomyocytes, extent of the myocardial extracellular matrix, and myocellular hypertrophy promote unique patterns of LV remodeling in men and women. In addition, age- and sex-specific vascular stiffening is also well established, driven by changes in endothelial dysfunction, elastin-collagen content, microvascular dysfunction, and neurohormonal signaling. Together, these changes in LV chamber geometry and morphology, coupled with heightened vascular stiffness, appear to drive both age-related increases in systolic function and declines in diastolic function, particularly in postmenopausal women. Accordingly, estrogen has been implicated as a key mediator, given its direct vasodilating properties, association with nitric oxide excretion, and involvement in myocellular Ca2+ handling, mitochondrial energy production, and oxidative stress. The culmination of the abovementioned sex-specific cardiac and vascular changes across the lifespan provides important insight into heart failure development, particularly of the preserved ejection fraction variety, while offering promise for future preventive strategies and therapeutic approaches.

Association of Spontaneous Preterm Delivery and Future Maternal Cardiovascular Disease.

Cardiovascular disease (CVD) risk factors are well established. However, little is known about a woman's cardiovascular response to pregnancy, which appears to be an early marker of future maternal CVD risk. Spontaneous preterm delivery (sPTD) has been associated with a ≤3-fold increased risk of maternal CVD death later in life compared with having a term delivery. This review focuses on 3 key areas to critically assess the association of sPTD and future maternal CVD risk: (1) CVD risk factors, (2) inflammatory biomarkers of interest, and (3) specific forms of vascular dysfunction, such as endothelial function and arterial stiffness, and mechanisms by which each may be linked to sPTD. The association of sPTD with subsequent future maternal CVD risk suggests that a woman's abnormal response to pregnancy may serve as her first physiological stress test. These findings suggest that future research is needed to understand why women with sPTD may be at risk for CVD to implement effective interventions earlier in a woman's life.

Cardiovascular Disease in Women: Clinical Perspectives.

Cardiovascular disease continues to be the leading cause of death among women in the United States, accounting for ≈1 of every 3 female deaths. Sex-specific data focused on cardiovascular disease have been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focuses on novel and unique aspects of cardiovascular health in women and sex differences as they relate to clinical practice in the prevention, diagnosis, and treatment of cardiovascular disease. This review also provides current approaches to the evaluation and treatment of acute coronary syndromes that are more prevalent in women, including myocardial infarction associated with nonobstructive coronary arteries, spontaneous coronary artery dissection, and stress-induced cardiomyopathy (Takotsubo Syndrome). Other cardiovascular disease entities with higher prevalence or unique considerations in women, such as heart failure with preserved ejection fraction, peripheral arterial disease, and abdominal aortic aneurysms, are also briefly reviewed. Finally, recommendations for cardiac rehabilitation are addressed.

Mild renal dysfunction and long-term adverse outcomes in women with chest pain: results from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and adverse cardiovascular outcomes, but mechanisms are unclear. We hypothesized that mild CKD independently predicts adverse outcomes in women with symptoms and signs of ischemia. METHODS: We categorized 876 women from the Women's Ischemia Syndrome Evaluation cohort according to estimated glomerular filtration rate (eGFR) (eGFR ≥90 mL/min per 1.73 m(2) [normal], 60-89 mL/min per 1.73 m(2) [mild CKD], ≤59 mL/min per 1.73 m(2) [severe CKD]). Time to death from all-cause and cardiovascular causes and major adverse outcomes were assessed by multivariate regression adjusted for baseline covariates. RESULTS: Obstructive coronary artery disease (CAD) was present only in few patients (39%). Even after adjusting for CAD severity, renal function remained a strong independent predictor of all-cause and cardiac mortality (P < .001). Every 10-unit decrease in eGFR was associated with a 14% increased risk of all-cause mortality (adjusted hazard ratio [AHR] 1.14 [1.08-1.20], P < .0001), 16% increased risk of cardiovascular mortality (AHR 1.16 [1.09-1.23], P < .0001), and 9% increased risk of adverse cardiovascular events (AHR 1.09 [1.03-1.15], P = .002). CONCLUSIONS: Even mild CKD is a strong independent predictor of all-cause and cardiac mortality in women with symptoms/signs of ischemia, regardless of underlying obstructive CAD severity, underscoring the need to better understand the interactions between ischemic heart disease and CKD.

Female-specific factors for IHD: across the reproductive lifespan.

Ischemic heart disease (IHD) is the number one health threat to women in the USA. While significant advances in female-specific symptoms and pathophysiology have begun to improve mortality rates, a closer look at risk factors across a woman's lifespan needs to be explored. This review targets three time frames: premenopause, pregnancy, and postmenopause. During premenopause, menstrual cycle patterns and estrogen status provide information for IHD risk. Pregnancy conditions provide another window of time that potentially contributes to future cardiovascular risk. Lastly, there is a rise in IHD events and mortality after menopause. Research continues to decipher the impact of estrogen decline at this stage and the effect of menopause hormone therapy as they relate to the cardiovascular health of menopausal women.

Aldosterone inhibition and coronary endothelial function in women without obstructive coronary artery disease: an ancillary study of the national heart, lung, and blood institute-sponsored women's ischemia syndrome evaluation.

UNLABELLED: Endothelial dysfunction is highly prevalent and associated with adverse outcomes among patients without obstructive coronary artery disease (CAD). Angiotensin II inhibition may improve endothelial function, but with continued treatment, "aldosterone escape" may occur. Thus, it is unknown if adding aldosterone blockade further improves endothelial function. METHODS: In a double-blind, parallel-group, repeated-measures study, women with symptoms and signs of ischemia, no significant CAD, and coronary endothelial dysfunction receiving an angiotensin-converting enzyme inhibitor or receptor blocker were randomized to aldosterone blockade or placebo. The primary outcome at 16 weeks was percent change in coronary diameter to acetylcholine, and secondary outcome, coronary flow reserve to adenosine, both adjusted for baseline reactivity. RESULTS: Forty-one women completed the treatment period with repeat coronary reactivity testing. Their mean age was 54 ± 10 years; body mass index, 30 ± 7.4 kg/m2; 12% had diabetes; and 15% had metabolic syndrome. There were no significant differences between treatment groups. At baseline, the percent change in reference vessel coronary diameter to acetylcholine was -5.0% in the aldosterone blockade group and -3.4% in the placebo group and, at 16 weeks, -7.2% in the aldosterone blockade group versus -14.3% in the placebo group (P = .15). At 16 weeks, the change in coronary flow reserve to intracoronary adenosine was -0.13 in the aldosterone blockade group versus -0.25 in the placebo group (P = .66). CONCLUSION: Adding aldosterone receptor blockade to angiotensin II inhibition did not improve coronary endothelial or microvascular function among women with signs and symptoms of ischemia in the setting of nonobstructive CAD.

Towards elimination of the dark-rim artifact in first-pass myocardial perfusion MRI: removing Gibbs ringing effects using optimized radial imaging.

PURPOSE: Subendocardial dark-rim artifacts (DRAs) remain a major concern in first-pass perfusion (FPP) myocardial MRI and may lower the diagnostic accuracy for detection of ischemia. A major source of DRAs is the "Gibbs ringing" effect. We propose an optimized radial acquisition strategy aimed at eliminating ringing-induced DRAs in FPP. THEORY AND METHODS: By studying the underlying point spread function (PSF), we show that optimized radial sampling with a simple reconstruction method can eliminate the oscillations in the PSF that cause ringing artifacts. We conducted realistic MRI phantom experiments and in vivo studies (n = 12 healthy humans) to evaluate the artifact behavior of the proposed imaging scheme in comparison to a conventional Cartesian imaging protocol. RESULTS: Simulations and phantom experiments verified our theoretical expectations. The in vivo studies showed that optimized radial imaging is capable of significantly reducing DRAs in the early myocardial enhancement phase (during which the ringing effect is most prominent and may obscure perfusion defects) while providing similar resolution and image quality compared with conventional Cartesian imaging. CONCLUSION: The developed technical framework and results demonstrate that, in comparison to conventional Cartesian techniques, optimized radial imaging with the proposed optimizations significantly reduces the prevalence and spatial extent of DRAs in FPP imaging.

Single Nucleotide Polymorphisms in Coronary Microvascular Dysfunction.

Coronary microvascular dysfunction is an underdiagnosed pathologic process that is associated with adverse clinical outcomes. There are data to suggest that coronary microvascular dysfunction, in some cases, may be genetically determined. We present an updated review of single nucleotide polymorphisms in coronary microvascular dysfunction.

Comparison of risk profiles of participants in the Women's IschemiA TRial to Reduce events In non-ObstRuctive CAD (WARRIOR) trial, using Coronary Computed Tomography Angiography vs Invasive Coronary Angiography.

OBJECTIVE: To compare baseline characteristics of participants in the Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) trial by qualification by Coronary Computed Tomography Angiography (CCTA) or Invasive Coronary Angiography (ICA). METHODS: The WARRIOR trial (NCT03417388) is an ongoing multicenter, prospective, randomized, blinded outcome evaluation of intensive medical therapy vs. usual care in women with suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA) identified by either CCTA or ICA on the outcome of major adverse cardiovascular events (MACE). No obstructive coronary artery disease is defined as <50% luminal stenosis and normal coronary arteries is defined as no evidence of atherosclerosis including calcified and non-calcified plaque. Data presented was extracted on May 27, 2020. No clinical outcomes were assessed. RESULTS: An initial sample cohort of 797 women was included. The majority were younger than 65 years, White participants (73.3%), 159 had diabetes (19.9%), and 676 had angina (84.8%) with the remainder having symptoms of suspected ischemic heart disease. Over 50% of randomized participants had normal coronaries without luminal irregularities by ICA or CCTA. Participants randomized to ICA were more likely to have worse baseline clinical risk profiles with older age, higher burden of cardiac risk factors and poor quality of life with disabling angina. CONCLUSIONS: Among this initial sample of women with suspected INOCA randomized in the WARRIOR trial, there is a differential baseline cardiac risk of participants enrolled after CCTA or ICA. However, the majority had no evidence of atherosclerotic plaque or obstructive stenosis, after evaluation by ICA or CCTA. These results suggest that non-invasive evaluation with CCTA is likely to be associated with lower risk of MACE.

Endogenous androgens, coronary atheroma and remodeling in women with suspected ischemic heart disease: A report from the Women's Ischemia Syndrome Evaluation (WISE) study.

Background: Women have smaller coronary size than men independent of body surface area. Female to male heart transplantation demonstrates coronary lumen enlargement. Purpose: To investigate relationships between endogenous androgens and coronary luminal size in women with suspected ischemic heart disease (IHD). Methods: We analyzed 69 women with available androgen levels. Results: Group mean age was 54 ± 10 years with 64 % post-menopausal. Lumen cross-sectional area (CSA) and external elastic membrane (EEM) CSA positively correlated with free testosterone (FT) (r = 0.29, p = 0.049; r = 0.29, p = 0.01), respectively, and negatively correlated with SHBG (r = -0.26, p = 0.03; r = -0.29, p = 0.02), respectively. Atheroma CSA positively correlated with FT (r = 0.24. p = 0.05). These correlations became non-significant after adjusting for waist circumference. Conclusions: In women with suspected ischemic heart disease, endogenous androgens, coronary atheroma and luminal size are related, and may be moderated by waist circumference.

Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE.

Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n=4) from those without (n=7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. RNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and healthy control (HC) groups, with virus defense and interferon (IFN) signaling being the key pathways identified as enriched in SLE as expected. We next conducted a comparative analysis of genes differentially expressed in SLE-CMD and SLE-non-CMD relative to HC samples. Our analysis highlighted differences in IFN signaling, RNA sensing and ADP-ribosylation pathways between SLE-CMD and SLE-non-CMD. This is the first study to investigate possible gene signatures associating with CMD in SLE, and our data strongly suggests that distinct molecular mechanisms underly vascular changes in CMD and non-CMD involvement in SLE.

Elevated high-density lipoprotein cholesterol and adverse outcomes in women with symptoms of ischemic heart disease.

Background: Emerging data in the general population and those with coronary artery disease demonstrate higher risk of adverse outcomes with high (>70 mg/dL) HDL-C levels. There are limited data on the risk of adverse outcomes in women with suspected ischemic heart disease. Objective: To investigate relationships between high (>70 mg/dL), average (50-70 mg/dL), and low (<50 mg/dL) HDL-C levels with major adverse cardiac events (MACE) (death, myocardial infarction, stroke, and heart failure hospitalization), and all-cause mortality in women referred for coronary angiography for suspected myocardial ischemia. Methods: A total of 607 women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) original cohort (NCT00000554) with available HDL-C values were included in this analysis. Associations between HDL-C level and outcomes were evaluated using both multivariate Cox proportional hazard regression and spline regression analysis. Results: The mean age was 59 ± 12 years, 62 % had 3 or more cardiac risk factors, and 66 (10.9 %) had a high HDL-C. High and low HDL-C were both associated with higher MACE risk compared to average HDL-C after adjusting for demographic and clinical characteristics (HR 1.80, CI 1.03-3.14, p = 0.038; HR 1.63, CI 1.09-2.42, p = 0.016, respectively). Similarly, high, and low HDL-C were associated with higher risk of all-cause mortality (HR 3.64, CI 1.84-7.20, p < 0.001; HR 2.81, CI 1.67-4.71, p < 0.001, respectively). Conclusions: High and low HDL-C levels are both independently associated with higher MACE and all-cause mortality in women with suspected ischemia undergoing coronary angiography.

Pericardial fat volume is related to endothelial-mediated coronary blood flow in women with suspected coronary microvascular dysfunction. A report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study.

Background: Coronary microvascular dysfunction is prevalent in women with signs and symptoms of ischemia but no obstructive coronary artery disease (CAD) and is associated with an adverse prognosis. Elevated pericardial fat volume predicts adverse cardiac events, but mechanistic pathways of the association are not well understood. Methods: 118 women enrolled in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction study with suspected coronary microvascular dysfunction but no obstructive CAD underwent adenosine stress 1.5 T cardiovascular magnetic resonance imaging (CMR) imaging and invasive coronary reactivity testing. Semi-quantitative myocardial perfusion reserve index (MPR) index was derived from perfusion images. Pericardial fat volume was measured by manually contouring the cardiac margins and adjacent adipose tissue on a single trans-axial HASTE slice at the level of the left main coronary artery origin and indexed to body surface-area. Simple standard deviation analysis obtained for continuous variables and frequency (percent) for categorical variables. The relationships between pericardial fat volume and coronary reactivity testing parameters were examined by correlation and multivariable regression analyses. Results: Women with suspected coronary microvascular dysfunction had a mean age of 55 ± 10 years, body mass index (BMI) of 28 ± 7 kg/m2, 44 % had a history of smoking, 63 % hypertension, 8 % diabetes, and 20 % dyslipidemia. CMR imaging-derived pericardial fat volume and coronary blood flow response to intracoronary acetylcholine (Δ CBF) were negatively correlated (r = -0.32, p = 0.0013). After adjustment for age, number of risk factors, high-density lipoprotein (HDL), and cold pressor diameter response, pericardial fat volume remained a significant predictor of Δ coronary blood flow (p = 0.04). There was no association with other coronary reactivity testing measures or CMRI derived MPR index. Conclusions: Among women with suspected coronary microvascular dysfunction but no obstructive CAD, pericardial fat volume appears to be related in a hypothesized adverse direction to coronary microvascular endothelial function. These results support further work confirming and extending these results to investigate pericardial fat volume as mechanistic pathway and potential treatment target for coronary microvascular dysfunction-related adverse events.Trial registration: clinicaltrials.govNCT00832702.