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. 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. 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. 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.gov NCT00832702.
Background: Coronary flow reserve (CFR) of <2.5 predicts major adverse outcomes in predominantly male populations, while prior work demonstrates that CFR <2.32 is the best discriminating threshold for cardiovascular (CV) adverse outcomes in women with evidence of ischemia but no obstructive coronary artery disease (CAD). We evaluated whether the prognostic utility of coronary vascular function testing is improved by using gender specific thresholds during longer-term follow-up in the National Heart, Lung and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE). Methods: Women (n=200) with signs and symptoms of ischemia and predominately non-obstructive CAD underwent coronary vascular function testing using intra-coronary adenosine, acetylcholine, and nitroglycerin (TNG). CV events defined as CV death, non-fatal MI, heart failure hospitalization or stroke were evaluated over a median follow-up of 6 years. Standard thresholds included CFR<2.5 to adenosine, coronary blood flow response (CBF)...
Women with signs and symptoms of ischemia and no obstructive coronary artery disease (CAD)have previously been shown to have an increased risk of heart failure (HF) hospitalization. However, risk p...
Introduction: Urine albumin-creatinine ratio (UACR) is a measure of renal microvascular endothelial dysfunction and predicts adverse cardiovascular events. Coronary microvascular dysfunction (CMD) is prevalent in symptomatic women with ischemia but no obstructive coronary artery disease (CAD), and predicts adverse cardiovascular events. We evaluated renal microvascular dysfunction and CMD measured by invasive coronary reactivity testing (CRT). Methods: We measured UACR in 74 women with symptoms/signs of ischemia and no obstructive CAD who underwent (CRT). Coronary flow reserve response to intracoronary adenosine (nonendothelial-dependent function) and left anterior descending coronary artery diameter change in response to intracoronary acetylcholine and forearm cold pressor testing (endothelial-dependent function) were obtained. Univariate linear regression was used to evaluate log UACR and CMD parameters. Results: The group mean age was 53 ± 11 years, BMI 30 ± 9 kg/m2, Caucasian (64%), hypertensive (42%)...
Women with signs and symptoms of ischemia, no obstructive coronary artery disease (CAD) and preserved left ventricular ejection fraction (EF) often have diastolic dysfunction and experience elevated rates of major adverse cardiac events (MACE), including heart failure (HF) hospitalization with preserved ejection fraction (HFpEF). We evaluated the predictive value of inflammatory biomarkers for long-term HF hospitalization and all-cause mortality in these women.We performed a cross-sectional analysis to investigate the relationships between inflammatory biomarkers [serum interleukin-6 (IL-6), C-reactive protein (hs-CRP) and serum amyloid A (SAA)] and median of 6 years follow-up for all-cause mortality and HF hospitalization among women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF. Multivariable Cox regression analysis tested associations between biomarker levels and adverse outcomes.Among 390 women, mean age 56 ± 11 years, median follow up of 6 years, we observed that there is continuous association between IL-6 level and HF hospitalization (adjusted hazard ratio [AHR] 2.5 [1.2-5.0], p = 0.02). In addition, we found significant association between IL-6, SAA levels and all-cause mortality AHR (1.8 [1.1-3.0], p = 0.01) (1.5 [1.0-2.1], p = 0.04), respectively.In women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF, elevated IL-6 predicted HF hospitalization and all-cause mortality, while SAA level was only associated with all-cause mortality. These results suggest that inflammation plays a role in the pathogenesis of development of HFpEF, as well all-cause mortality.
Background: Cardiovascular magnetic resonance imaging (CMRI) derived myocardial perfusion reserve index (MPRI) has recently been shown to detect coronary microvascular dysfunction (CMD) in women with signs and symptoms of ischemia and no obstructive coronary artery disease (CAD).The aim of this study was to determine the inter-scan reproducibility of MPRI in this patient group in order to assess its diagnostic robustness in serial scans and assess its utility as a marker of potential therapies for CMD.Methods: Rest/stress perfusion CMR was performed at 1.5T using a standardized protocol in 17 women with signs and symptoms of ischemia and no obstructive CAD on two separate days (within 90 days of each other).The same pharmacological stress agent (adenosine/ regadenoson) was used for both scans.MPRI was calculated from time-intensity curves of the whole myocardium and blood pool at stress and rest.One experienced observer, blinded to clinical data, performed all measurements.Intra-class correlation coefficients (ICC), coefficient of variation (CoV), and Bland-Altman plots were determined.Results: Mean age was 53±10 years old and BMI 28±7 kg/m2; 47% had hypertension, 4% diabetes, 9% hyperlipidemia and 10% family history of CAD.Mean MPRI for the 17 women was higher for scan 2 compared to scan 1 (1.98±0.3 vs. 1.65±0.78,respectively, p<0.001); and this relationship persisted even when corrected for resting rate pressure product (RPP) (2.42±0.81 vs. 1.97±0.92,respectively, 0.002).The mean bias for MPRI between sequential scans was 0.34 (95% CI: 0.18 to 0.49, limits of agreement: -0.31, 0.98 and when corrected for resting RPP it was 0.45 (95% CI: 0.21 to 0.68, limits of agreement: -0.52, 1.41).ICC and CoV also indicated modest inter-scan reproducibility (ICC 0.57; CoV 20.3%), but both measures were comparable to values seen in prior studies in CAD populations and healthy volunteers. Conclusion:Inter-scan reproducibility of CMRI-derived MPRI in women with suspected CMD is modest, with relatively wide limits of agreement.This variability is similar to that seen in other populations, suggesting that some caution must be exercised when using absolute MPRI cut-offs in isolation for the diagnosis of CMD or repeated measures of MPRI to track response to therapy.Additional work is ongoing to improve reproducibility from both biological and technological standpoints.
