Prevalence of Coronary Endothelial and Microvascular Dysfunction in Women with Symptoms of Ischemia and No Obstructive Coronary Artery Disease Is Confirmed by a New Cohort: The NHLBI-Sponsored Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction (WISE-CVD)

Objective In a separate, contemporary cohort, we sought to confirm findings of the original Women's Ischemia Syndrome Evaluation (WISE). Background The original WISE observed a high prevalence of both invasively determined coronary endothelial and coronary microvascular dysfunction (CMD) that predicted adverse events in follow-up. Methods We comparatively studied the WISE-Coronary Vascular Dysfunction (CVD) cohort (2009-2011), with signs and symptoms of ischemia but without significant CAD, to the original WISE (1997-2001) cohort. CMD was defined as coronary flow reserve (CFR) ≤2.5, or endothelial dysfunction as epicardial coronary artery constriction to acetylcholine (ACH), or <20% epicardial coronary dilation to nitroglycerin (NTG). Results In WISE (n=181) and WISE-CVD (n=235) women, mean age in both was 54 years, and 83% were white (WISE) vs 74% (WISE-CVD, p=0.04). Use of hormone replacement therapy was less frequent in WISE-CVD vs WISE (46% vs 57%, p=0.026) as was presence of hypertension (40% vs 52%, p=0.013), hyperlipidemia (20% vs 46%, p<0.0001), and smoking (46% vs 56%, p=0.036). Similar rates were observed in WISE-CVD and WISE cohorts for CMD (mean CFR 2.7±0.6 vs 2.6±0.8, p=0.35), mean change in diameter with intracoronary ACH (0.2±10.0 vs 1.6±12.8 mm, p=0.34), and mean change in diameter with intracoronary NTG (9.7±13.0 vs 9.8±13.5 mm, p=0.94), respectively. Conclusions This study confirms prevalence of CMD in the contemporary WISE-CVD cohort similar to that of the original WISE cohort, despite a lower risk factor burden in WISE-CVD. Because these coronary functional abnormalities predict major adverse cardiac events, clinical trials of therapies targeting these abnormalities are indicated.

[1]  T. Meinertz,et al.  Endothelial Dysfunction, Oxidative Stress, and Risk of Cardiovascular Events in Patients With Coronary Artery Disease , 2001, Circulation.

[2]  Steven E. Nissen,et al.  High Prevalence of Coronary Atherosclerosis in Asymptomatic Teenagers and Young Adults: Evidence From Intravascular Ultrasound , 2001, Circulation.

[3]  Carl J Pepine,et al.  Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. , 2010, Journal of the American College of Cardiology.

[4]  Thomas de Quincey [C] , 2000, The Works of Thomas De Quincey, Vol. 1: Writings, 1799–1820.

[5]  Carl J Pepine,et al.  Adverse outcomes among women presenting with signs and symptoms of ischemia and no obstructive coronary artery disease: findings from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) angiographic core laboratory. , 2013, American heart journal.

[6]  O. Rimoldi,et al.  Effects of Sex on Coronary Microvascular Dysfunction and Cardiac Outcomes , 2014, Circulation.

[7]  K. Smith,et al.  An intravascular ultrasound analysis in women experiencing chest pain in the absence of obstructive coronary artery disease: a substudy from the National Heart, Lung and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). , 2010, Journal of interventional cardiology.

[8]  R Jay Widmer,et al.  Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease. , 2015, JACC. Cardiovascular interventions.

[9]  P. Alam,et al.  R , 1823, The Herodotus Encyclopedia.

[10]  D. Kereiakes,et al.  Endothelial dysfunction. , 2003, Circulation.

[11]  F Van de Werf,et al.  Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators. , 1999, The New England journal of medicine.

[12]  C. Noel Bairey Merz,et al.  Women and ischemic heart disease: evolving knowledge. , 2009, Journal of the American College of Cardiology.

[13]  P. Alam ‘E’ , 2021, Composites Engineering: An A–Z Guide.

[14]  Pepine,et al.  Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. , 2001, American heart journal.

[15]  C. Pepine,et al.  Gender differences in the treatment for acute myocardial infarction: bias or biology? , 2007, Circulation.

[16]  Miss A.O. Penney (b) , 1974, The New Yale Book of Quotations.

[17]  P. Alam ‘A’ , 2021, Composites Engineering: An A–Z Guide.

[18]  K. Smith,et al.  In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: A double-blind randomized study from the National Heart, Lung and Blood Institute Women's Ischemia , 2011, American heart journal.

[19]  Galen Cook-Wiens,et al.  A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve , 2015, European heart journal.

[20]  Piotr J Slomka,et al.  Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. , 2011, JACC. Cardiovascular imaging.

[21]  N Reichek,et al.  The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report. , 1999, Journal of the American College of Cardiology.

[22]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[23]  P. Alam ‘L’ , 2021, Composites Engineering: An A–Z Guide.

[24]  Carl J Pepine,et al.  Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. , 2009, Archives of internal medicine.

[25]  Christopher J. Rush,et al.  Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. , 2018, Journal of the American College of Cardiology.

[26]  R. Califf,et al.  Sex differences in mortality following acute coronary syndromes. , 2009, JAMA.

[27]  P. Alam ‘T’ , 2021, Composites Engineering: An A–Z Guide.

[28]  R. Sarpong,et al.  Bio-inspired synthesis of xishacorenes A, B, and C, and a new congener from fuscol† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c9sc02572c , 2019, Chemical science.

[29]  K. Smith,et al.  Abnormal Coronary Vasomotion as a Prognostic Indicator of Cardiovascular Events in Women: Results From the National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE) , 2004, Circulation.

[30]  Erik Jørgensen,et al.  Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. , 2012, European heart journal.

[31]  P. Alam ‘S’ , 2021, Composites Engineering: An A–Z Guide.

[32]  J. Hochman,et al.  Sex and Race Are Associated With the Absence of Epicardial Coronary Artery Obstructive Disease at Angiography in Patients With Acute Coronary Syndromes , 2010, Clinical cardiology.

[33]  S. Reis,et al.  Coronary microvascular reactivity is only partially predicted by atherosclerosis risk factors or coronary artery disease in women evaluated for suspected ischemia: results from the NHLBI Women's Ischemia Syndrome Evaluation (WISE) , 2007, Clinical cardiology.

[34]  A M Zeiher,et al.  Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. , 2000, Circulation.

[35]  Gebräuchliche Fertigarzneimittel,et al.  V , 1893, Therapielexikon Neurologie.

[36]  F. Crea,et al.  Effects of ivabradine and ranolazine in patients with microvascular angina pectoris. , 2013, The American journal of cardiology.

[37]  I. Chetter,et al.  Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials. , 2011, Atherosclerosis.

[38]  Danna Zhou,et al.  d. , 1840, Microbial pathogenesis.

[39]  S. Higano,et al.  Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. , 2000, Circulation.