OBJECTIVES To assess the prognostic value of a left ventricular energy-model in women with suspec... more OBJECTIVES To assess the prognostic value of a left ventricular energy-model in women with suspected myocardial ischemia. BACKGROUND The prognostic value of internal energy utilization (IEU) of the left ventricle in women with suspected myocardial ischemia is unknown. METHODS Women (n=227, mean age 59±12 years, range 31-86), with symptoms of myocardial ischemia, underwent myocardial perfusion imaging (MPI) assessment for regional perfusion defects along with measurement of ventricular volumes separately by gated Single Photon Emission Computed Tomography (SPECT) (n= 207) and magnetic resonance imaging (MRI) (n=203). During follow-up (40±17 months), time to first major adverse cardiovascular event (MACE, death, myocardial infarction or hospitalization for congestive heart failure) was analyzed using MRI and gated SPECT variables. RESULTS Adverse events occurred in 31 (14%). Multivariable Cox models were formed for each modality: IEU and wall thickness by MRI (Chi-squared 34, p<0.0...
Background There is growing evidence that women with ischemia and no obstructive coronary artery ... more Background There is growing evidence that women with ischemia and no obstructive coronary artery disease (INOCA) have an increased risk of major adverse cardiovascular events (MACE). Half of these women continue to experience persistent chest pain (PChP); however longer-term outcomes are unknown. Purpose To investigate the relationships between PChP at 1-year with obstructive and nonobstructive coronary artery disease (CAD) and longer-term all-cause mortality, MACE and angina hospitalization in women with suspected myocardial ischemia. Methods We studied 673 women with chest pain undergoing coronary angiography for suspected myocardial ischemia in the National Heart, Lung, and Blood Institute Women's Ischemia Syndrome Evaluation (WISE) study. PChP was defined as self-reported continuing chest pain at 1-year, obstructive CAD as >50 stenosis in any coronary artery and non-obstructive CAD was further divided as <20% stenosis and 20–50% stenosis in any coronary artery. The Kap...
Women with signs and symptoms of ischemia, no obstructive coronary artery disease (CAD) and prese... more 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, w...
Journal of Women's Health & Gender-Based Medicine, 2000
Physical activity and functional capacity have not been assessed by questionnaire for criterion v... more Physical activity and functional capacity have not been assessed by questionnaire for criterion validity in women. We wished to evaluate the ability of a physical activity and a functional capacity assessment questionnaire to predict functional capacity measured by treadmill exercise stress testing, as well as correlate with cardiac risk factors and angiographic coronary artery disease (CAD) in women. In a National Heart, Lung and Blood Institute (NHLBI)-sponsored cross-sectional population study involving four academic medical centers, 476 women with cardiac risk factors undergoing coronary angiography for evaluation for suspected myocardial ischemia were enrolled in the Women&#39;s Ischemia Syndrome Evaluation (WISE). The main outcome measures were functional capacity measured during symptom-limited exercise treadmill testing, cardiac risk factors, and CAD, using core laboratory-determined measures. Physical activity measured by the Postmenopausal Estrogen and Progesterone Intervention physical activity questionnaire (PEPI-Q) and functional capacity measured by the Duke Activity Status Index (DASI) questionnaire, correlated with functional capacity measured in metabolic equivalents (METS), as estimated during symptom-limited exercise treadmill testing (r = 0.27, p = 0.001 and r = 0.31, p = 0. 0002, respectively). The DASI was a significant independent predictor of functional capacity even after adjustment for cardiac risk factors, and the PEPI-Q was not. The DASI and PEPI-Q scores were inversely associated with higher numbers and levels of cardiac risk factors, as well as angiographic CAD. The DASI questionnaire is a reasonable correlate of functional capacity achieved during symptom-limited treadmill exercise testing in women with suspected myocardial ischemia. Lower functional capacity or physical activity measured by the DASI and PEPI-Q, respectively, is associated with more prevalent cardiac risk factors and angiographic CAD. These findings suggest that the DASI and, to a lesser extent, the PEPI-Q have criterion validity for use in health-related research in women.
Cardiovascular disease remains the leading cause of death in the USA and is associated with sever... more Cardiovascular disease remains the leading cause of death in the USA and is associated with several modifiable (hypertension, diabetes, high cholesterol, tobacco use, physical inactivity, obesity and unhealthy diet) and nonmodifiable (age, gender and family history) risk factors. The role of psychosocial risk factors in the development of cardiovascular disease has a growing body of literature, and differences in men and women have been identified. The Women's Ischemia Syndrome Evaluation provides insight into psychosocial risk factors in a cohort of women presenting with chest pain who had a comprehensive battery of psychosocial assessments and long-term follow-up. This review focuses on symptom presentation for chest pain and its relationship to cardiovascular disease morbidity and mortality, quality of life, healthcare costs and psychosocial predictor variables, including anxiety, depression, hostility and social networks. In the Women's Ischemia Syndrome Evaluation, pers...
Background— Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiova... more Background— Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. Methods and Results— As part of the Women’s Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less cha...
Background— Serum amyloid-α (SAA) is a sensitive marker of an acute inflammatory state. Like high... more Background— Serum amyloid-α (SAA) is a sensitive marker of an acute inflammatory state. Like high-sensitivity C-reactive protein (hs-CRP), SAA has been linked to atherosclerosis. However, prior studies have yielded inconsistent results, and the independent predictive value of SAA for coronary artery disease (CAD) severity and cardiovascular events remains unclear. Methods and Results— A total of 705 women referred for coronary angiography for suspected myocardial ischemia underwent plasma assays for SAA and hs-CRP, quantitative angiographic assessment, and follow-up evaluation. Cardiovascular events were death, myocardial infarction, congestive heart failure, stroke, and other vascular events. The women’s mean age was 58 years (range 21 to 86 years), and 18% were nonwhite. SAA and hs-CRP were associated with a broad range of CAD risk factors. After adjustment for these risk factors, SAA levels were independently but moderately associated with angiographic CAD ( P =0.004 to 0.04) and...
We sought to assess the impact of coronary angiography results on use of lipid-lowering agents am... more We sought to assess the impact of coronary angiography results on use of lipid-lowering agents among women enrolled in the Women&amp;amp;#39;s Ischemia Syndrome Evaluation [WISE] study. WISE is a multicenter study designed to evaluate new diagnostic modalities among women undergoing angiography for suspected coronary artery disease (CAD). History of atherosclerosis, risk factors for CAD, and low-density lipoprotein (LDL) cholesterol are determined at baseline. The percentage of women at LDL cholesterol goal, use of lipid-lowering agents, and eligibility for lipid-lowering therapy were determined based on National Cholesterol Education Program II guidelines at baseline and 6-week follow-up. Among the 212 women for whom angiographic data were available, 84 had known atherosclerosis, 80 had no history of atherosclerosis but &amp;amp;gt; or =2 risk factors (high risk), and 48 had no history of atherosclerosis and &amp;amp;lt;2 risk factors (low risk). At baseline, LDL cholesterol goals were met in 24% women with atherosclerosis, in 56% high-risk women, and in 88% low-risk women. Angiography revealed previously undiagnosed CAD in 70% of the high-risk and in 42% of the low-risk women. After angiography results were available, 6 women started lipid-lowering therapy and 2 stopped. Based on National Cholesterol Education Program II guidelines, 63 additional women would have been eligible for pharmacologic lipid-lowering therapy. Intensification of lipid-lowering therapy was not apparent 6 weeks after coronary angiography in women with newly diagnosed CAD or among women whose diagnosis was confirmed.
Background— Coronary angiography is one of the most frequently performed procedures in women; how... more Background— Coronary angiography is one of the most frequently performed procedures in women; however, nonobstructive (ie, <50% stenosis) coronary artery disease (CAD) is frequently reported. Few data exist regarding the type and intensity of resource consumption in women with chest pain after coronary angiography. Methods and Results— A total of 883 women referred for coronary angiography were prospectively enrolled in the National Institutes of Health–National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation (WISE). Cardiovascular prognosis and cost data were collected. Direct (hospitalizations, office visits, procedures, and drug utilization) and indirect (out-of-pocket, lost productivity, and travel) costs were estimated through 5 years of follow-up. Among 883 women, 62%, 17%, 11%, and 10% had nonobstructive and 1-vessel, 2-vessel, and 3-vessel CAD, respectively. Five-year cardiovascular death or myocardial infarction rates ranged from 4% to 38%...
Chronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiov... more Chronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiovascular events. Among women with symptoms and signs of ischemia enrolled in the Women's Ischemia Syndrome Evaluation (WISE), a relatively high mortality rate was observed in those with no obstructive coronary artery disease. Coronary microvascular dysfunction or reduced coronary flow reserve (CFR) was a strong and independent predictor of adverse outcomes. The objective of this analysis was to determine if renal function was associated with coronary microvascular dysfunction in women with signs and symptoms of ischemia. The WISE was a multicenter, prospective, cohort study of women undergoing coronary angiography for suspected ischemia. Among 198 women with additional measurements of CFR, we determined the estimated glomerular filtration rate (eGFR) with the CKD-EPI equation. We tested the association between eGFR and CFR with regression analysis. The median eGFR was 89 ml/min. The e...
Background: Menstrual cycling irregularity is being associated with greater frequency of diabetes... more Background: Menstrual cycling irregularity is being associated with greater frequency of diabetes and adverse cardiovascular (CV) events, suggesting a mechanistic link between ovarian dysfunction, CAD risk factors, and CAD. Confirmation of this link and potential explanatory mechanism(s) have not been established. Methods: We compared 686 postmenopausal women with and without a history of irregular cycles who were undergoing coronary angiography for suspected ischemia and enrolled in the WISE study. Coronary angiography was assessed by a core laboratory, and the women were prospectively followed for a median of 5.9 years. Chi square and rank sums analyses were used to compare the women on the presence and severity of CAD, CAD risk factors, and CV events. Multivariate Cox regression, adjusting for angiographic CAD and CAD risk factors was used to define time to death, MI, stroke, and angina hospitalization. Results: Overall mean age was 62, 18% were non-white, 130 (19%) reported a hi...
OBJECTIVES To assess the prognostic value of a left ventricular energy-model in women with suspec... more OBJECTIVES To assess the prognostic value of a left ventricular energy-model in women with suspected myocardial ischemia. BACKGROUND The prognostic value of internal energy utilization (IEU) of the left ventricle in women with suspected myocardial ischemia is unknown. METHODS Women (n=227, mean age 59±12 years, range 31-86), with symptoms of myocardial ischemia, underwent myocardial perfusion imaging (MPI) assessment for regional perfusion defects along with measurement of ventricular volumes separately by gated Single Photon Emission Computed Tomography (SPECT) (n= 207) and magnetic resonance imaging (MRI) (n=203). During follow-up (40±17 months), time to first major adverse cardiovascular event (MACE, death, myocardial infarction or hospitalization for congestive heart failure) was analyzed using MRI and gated SPECT variables. RESULTS Adverse events occurred in 31 (14%). Multivariable Cox models were formed for each modality: IEU and wall thickness by MRI (Chi-squared 34, p<0.0...
Background There is growing evidence that women with ischemia and no obstructive coronary artery ... more Background There is growing evidence that women with ischemia and no obstructive coronary artery disease (INOCA) have an increased risk of major adverse cardiovascular events (MACE). Half of these women continue to experience persistent chest pain (PChP); however longer-term outcomes are unknown. Purpose To investigate the relationships between PChP at 1-year with obstructive and nonobstructive coronary artery disease (CAD) and longer-term all-cause mortality, MACE and angina hospitalization in women with suspected myocardial ischemia. Methods We studied 673 women with chest pain undergoing coronary angiography for suspected myocardial ischemia in the National Heart, Lung, and Blood Institute Women's Ischemia Syndrome Evaluation (WISE) study. PChP was defined as self-reported continuing chest pain at 1-year, obstructive CAD as >50 stenosis in any coronary artery and non-obstructive CAD was further divided as <20% stenosis and 20–50% stenosis in any coronary artery. The Kap...
Women with signs and symptoms of ischemia, no obstructive coronary artery disease (CAD) and prese... more 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, w...
Journal of Women's Health & Gender-Based Medicine, 2000
Physical activity and functional capacity have not been assessed by questionnaire for criterion v... more Physical activity and functional capacity have not been assessed by questionnaire for criterion validity in women. We wished to evaluate the ability of a physical activity and a functional capacity assessment questionnaire to predict functional capacity measured by treadmill exercise stress testing, as well as correlate with cardiac risk factors and angiographic coronary artery disease (CAD) in women. In a National Heart, Lung and Blood Institute (NHLBI)-sponsored cross-sectional population study involving four academic medical centers, 476 women with cardiac risk factors undergoing coronary angiography for evaluation for suspected myocardial ischemia were enrolled in the Women&#39;s Ischemia Syndrome Evaluation (WISE). The main outcome measures were functional capacity measured during symptom-limited exercise treadmill testing, cardiac risk factors, and CAD, using core laboratory-determined measures. Physical activity measured by the Postmenopausal Estrogen and Progesterone Intervention physical activity questionnaire (PEPI-Q) and functional capacity measured by the Duke Activity Status Index (DASI) questionnaire, correlated with functional capacity measured in metabolic equivalents (METS), as estimated during symptom-limited exercise treadmill testing (r = 0.27, p = 0.001 and r = 0.31, p = 0. 0002, respectively). The DASI was a significant independent predictor of functional capacity even after adjustment for cardiac risk factors, and the PEPI-Q was not. The DASI and PEPI-Q scores were inversely associated with higher numbers and levels of cardiac risk factors, as well as angiographic CAD. The DASI questionnaire is a reasonable correlate of functional capacity achieved during symptom-limited treadmill exercise testing in women with suspected myocardial ischemia. Lower functional capacity or physical activity measured by the DASI and PEPI-Q, respectively, is associated with more prevalent cardiac risk factors and angiographic CAD. These findings suggest that the DASI and, to a lesser extent, the PEPI-Q have criterion validity for use in health-related research in women.
Cardiovascular disease remains the leading cause of death in the USA and is associated with sever... more Cardiovascular disease remains the leading cause of death in the USA and is associated with several modifiable (hypertension, diabetes, high cholesterol, tobacco use, physical inactivity, obesity and unhealthy diet) and nonmodifiable (age, gender and family history) risk factors. The role of psychosocial risk factors in the development of cardiovascular disease has a growing body of literature, and differences in men and women have been identified. The Women's Ischemia Syndrome Evaluation provides insight into psychosocial risk factors in a cohort of women presenting with chest pain who had a comprehensive battery of psychosocial assessments and long-term follow-up. This review focuses on symptom presentation for chest pain and its relationship to cardiovascular disease morbidity and mortality, quality of life, healthcare costs and psychosocial predictor variables, including anxiety, depression, hostility and social networks. In the Women's Ischemia Syndrome Evaluation, pers...
Background— Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiova... more Background— Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. Methods and Results— As part of the Women’s Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less cha...
Background— Serum amyloid-α (SAA) is a sensitive marker of an acute inflammatory state. Like high... more Background— Serum amyloid-α (SAA) is a sensitive marker of an acute inflammatory state. Like high-sensitivity C-reactive protein (hs-CRP), SAA has been linked to atherosclerosis. However, prior studies have yielded inconsistent results, and the independent predictive value of SAA for coronary artery disease (CAD) severity and cardiovascular events remains unclear. Methods and Results— A total of 705 women referred for coronary angiography for suspected myocardial ischemia underwent plasma assays for SAA and hs-CRP, quantitative angiographic assessment, and follow-up evaluation. Cardiovascular events were death, myocardial infarction, congestive heart failure, stroke, and other vascular events. The women’s mean age was 58 years (range 21 to 86 years), and 18% were nonwhite. SAA and hs-CRP were associated with a broad range of CAD risk factors. After adjustment for these risk factors, SAA levels were independently but moderately associated with angiographic CAD ( P =0.004 to 0.04) and...
We sought to assess the impact of coronary angiography results on use of lipid-lowering agents am... more We sought to assess the impact of coronary angiography results on use of lipid-lowering agents among women enrolled in the Women&amp;amp;#39;s Ischemia Syndrome Evaluation [WISE] study. WISE is a multicenter study designed to evaluate new diagnostic modalities among women undergoing angiography for suspected coronary artery disease (CAD). History of atherosclerosis, risk factors for CAD, and low-density lipoprotein (LDL) cholesterol are determined at baseline. The percentage of women at LDL cholesterol goal, use of lipid-lowering agents, and eligibility for lipid-lowering therapy were determined based on National Cholesterol Education Program II guidelines at baseline and 6-week follow-up. Among the 212 women for whom angiographic data were available, 84 had known atherosclerosis, 80 had no history of atherosclerosis but &amp;amp;gt; or =2 risk factors (high risk), and 48 had no history of atherosclerosis and &amp;amp;lt;2 risk factors (low risk). At baseline, LDL cholesterol goals were met in 24% women with atherosclerosis, in 56% high-risk women, and in 88% low-risk women. Angiography revealed previously undiagnosed CAD in 70% of the high-risk and in 42% of the low-risk women. After angiography results were available, 6 women started lipid-lowering therapy and 2 stopped. Based on National Cholesterol Education Program II guidelines, 63 additional women would have been eligible for pharmacologic lipid-lowering therapy. Intensification of lipid-lowering therapy was not apparent 6 weeks after coronary angiography in women with newly diagnosed CAD or among women whose diagnosis was confirmed.
Background— Coronary angiography is one of the most frequently performed procedures in women; how... more Background— Coronary angiography is one of the most frequently performed procedures in women; however, nonobstructive (ie, <50% stenosis) coronary artery disease (CAD) is frequently reported. Few data exist regarding the type and intensity of resource consumption in women with chest pain after coronary angiography. Methods and Results— A total of 883 women referred for coronary angiography were prospectively enrolled in the National Institutes of Health–National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation (WISE). Cardiovascular prognosis and cost data were collected. Direct (hospitalizations, office visits, procedures, and drug utilization) and indirect (out-of-pocket, lost productivity, and travel) costs were estimated through 5 years of follow-up. Among 883 women, 62%, 17%, 11%, and 10% had nonobstructive and 1-vessel, 2-vessel, and 3-vessel CAD, respectively. Five-year cardiovascular death or myocardial infarction rates ranged from 4% to 38%...
Chronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiov... more Chronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiovascular events. Among women with symptoms and signs of ischemia enrolled in the Women's Ischemia Syndrome Evaluation (WISE), a relatively high mortality rate was observed in those with no obstructive coronary artery disease. Coronary microvascular dysfunction or reduced coronary flow reserve (CFR) was a strong and independent predictor of adverse outcomes. The objective of this analysis was to determine if renal function was associated with coronary microvascular dysfunction in women with signs and symptoms of ischemia. The WISE was a multicenter, prospective, cohort study of women undergoing coronary angiography for suspected ischemia. Among 198 women with additional measurements of CFR, we determined the estimated glomerular filtration rate (eGFR) with the CKD-EPI equation. We tested the association between eGFR and CFR with regression analysis. The median eGFR was 89 ml/min. The e...
Background: Menstrual cycling irregularity is being associated with greater frequency of diabetes... more Background: Menstrual cycling irregularity is being associated with greater frequency of diabetes and adverse cardiovascular (CV) events, suggesting a mechanistic link between ovarian dysfunction, CAD risk factors, and CAD. Confirmation of this link and potential explanatory mechanism(s) have not been established. Methods: We compared 686 postmenopausal women with and without a history of irregular cycles who were undergoing coronary angiography for suspected ischemia and enrolled in the WISE study. Coronary angiography was assessed by a core laboratory, and the women were prospectively followed for a median of 5.9 years. Chi square and rank sums analyses were used to compare the women on the presence and severity of CAD, CAD risk factors, and CV events. Multivariate Cox regression, adjusting for angiographic CAD and CAD risk factors was used to define time to death, MI, stroke, and angina hospitalization. Results: Overall mean age was 62, 18% were non-white, 130 (19%) reported a hi...
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Papers by George Sopko