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Background Primary prevention risk scores are commonly used to predict cardiovascular (CVD) outcomes. The applicability of these scores in patients with evidence of myocardial ischemia but no obstructive coronary artery disease is unclear. Methods and Results Among 935 women with signs and symptoms of ischemia enrolled in WISE (Women's Ischemia Syndrome Evaluation), 567 had no obstructive coronary artery disease on angiography. Of these, 433 had had available risk data for 6 commonly used scores: Framingham Risk Score, Reynolds Risk Score, Adult Treatment Panel III, Atherosclerotic Cardiovascular Disease, Systematic Coronary Risk Evaluation, Cardiovascular Risk Score 2. Score‐specific CVD rates were assessed. For each score, we evaluated predicted versus observed event rates at 10‐year follow‐up using c statistic. Recalibration was done for 3 of the 6 scores. The 433 women had a mean age of 56.9±9.4 years, 82.5% were white, 52.7% had hypertension, 43.6% had dyslipidemia, and 16.9% had diabetes mellitus. The observed 10‐year score‐specific CVD rates varied between 5.54% (Systematic Coronary Risk Evaluation) to 28.87% (Framingham Risk Score), whereas predicted event rates varied from 1.86% (Systematic Coronary Risk Evaluation) to 6.99% (Cardiovascular Risk Score 2). The majority of scores showed moderate discrimination (c statistic 0.53 for Atherosclerotic Cardiovascular Disease and Systematic Coronary Risk Evaluation; 0.78 for Framingham Risk Score) and underestimated risk (statistical discordance −58% for Adult Treatment Panel III; −84% for Atherosclerotic Cardiovascular Disease). Recalibrated Reynolds Risk Score, Atherosclerotic Cardiovascular Disease, and Framingham Risk Score had improved performance, but significant underestimation remained. Conclusions Commonly used CVD risk scores fail to accurately predict CVD rates in women with ischemia and no obstructive coronary artery disease. These results emphasize the need for new risk assessment scores to reliably assess this population.

Background Multiple biomarkers have been independently and additively associated with major adverse cardiovascular events in patients with coronary artery disease. We investigated the prognostic value of suPAR (soluble urokinase‐type plasminogen activator receptor) and hsTnI (high‐sensitivity troponin I) levels in symptomatic patients with no obstructive coronary artery disease. We hypothesized that high levels of these biomarkers will be associated with the risk of future adverse outcomes. Methods and Results Plasma levels of suPAR and hsTnI were measured in 556 symptomatic patients with no obstructive coronary artery disease. A biomarker risk score was calculated by counting the number of biomarkers above the median in this cohort (suPAR>2523 pg/mL and hsTnI>2.7 pg/mL). Survival analyses were performed with models adjusted for traditional risk factors. All‐cause death and major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, and heart failure) served as clinical outcomes over a median follow‐up of 6.2 years. Mean age was 57±10 years, 49% of the cohort patients were female, and 68% had a positive stress test. High suPAR and hsTnI levels were independent predictors of all‐cause death (hazard ratio=3.2 [95% CI, 1.8–5.7] and 1.3 [95% CI, 1.0–1.7], respectively; both P

Purpose: We investigated whether impaired flow-mediated dilation (FMD) and plasma biomarkers reflecting endothelial dysfunction are associated with coronary microvascular dysfunction (CMD) in women with angina and no obstructive coronary artery disease (CAD). Methods: Patients (n = 194) were randomly selected women with angina pectoris and no obstructive CAD (<50% stenosis). A reference population of asymptomatic women without CAD (n = 25) was included. We measured FMD in the brachial artery by high-resolution ultrasound. Coronary flow velocity reserve (CFVR) was assessed by transthoracic Doppler flow echocardiography (TTDE) of the left anterior descending artery during rest and high-dose dipyridamole infusion. CMD was defined as CFVR <2. Results: FMD and CFVR were measured in 128 patients and 21 controls. Mean (SD) age was 64.5 (8.9) years, mean CFVR was 2.3 (2.0-2.7), and mean FMD was 8.4% (4.8%) in angina patients. Angina patients had a higher risk factor burden compared with the reference population. Measures of peripheral endothelial dysfunction and endothelial plasma biomarkers did not differ according to angina or CFVR. CFVR and FMD did not correlate (Spearman ρ = -0.07, p = 0.45). Conclusions: FMD and biomarkers of endothelial dysfunction did not identify individuals with CMD assessed as impaired CFVR by TTDE in women with angina and no obstructive CAD. [ABSTRACT FROM AUTHOR]

Objectives This study investigated whether digital reactive hyperemia index (RHI) measured by digital pulse amplitude tonometry is a sensitive indicator of coronary microvascular dysfunction (CMD). Background CMD is an early marker of cardiovascular disease. However, CMD is a complex diagnosis and consists of multiple abnormalities of the coronary circulation. Impaired RHI is a noninvasive measure of peripheral vascular dysfunction that can identify individuals with acetylcholine induced coronary vascular dysfunction. It is largely unknown whether there is also an association between RHI and the endothelial-independent aspect of CMD assessed as a coronary flow velocity reserve (CFVR). Methods We included 339 women with chest pain suggestive of angina pectoris and a diagnostic invasive coronary angiogram without significant coronary artery stenosis (<50%). CFVR was measured by transthoracic pulsed wave Doppler echocardiography during dipyridamole infusion (0.84 mg/kg). RHI was assessed by digital pulse amplitude tonometry. Participants were categorized in 3 RHI and 3 CFVR groups. We examined the association between CFVR and RHI and the distribution of cardiovascular risk factors between the CFVR and RHI groups. Results CFVR and RHI were successfully measured in 322 participants. Median CFVR was 2.3 (interquartile range: 2.0 to 2.8) and median RHI was 2.1 (interquartile range: 1.6 to 2.6). No correlation was found between CFVR and RHI (Spearman’s rho = –0.067, p = 0.23), and mean RHI did not differ between CFVR categories (p = 0.39). Participants with low CFVR were significantly older and had a significantly greater burden of hypertension, whereas participants with an impaired RHI had a higher body mass index and were more likely to have diabetes and be current smokers. Conclusions RHI does not identify individuals with CMD assessed as impaired CFVR by dipyridamole stress echocardiography in women with no obstructive coronary artery disease. The two methods are likely to identify different aspects of vascular pathology, as indicated by the different association with cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

The aim of the project was to compare patients treated with percutaneous transluminal coronary angioplasty (PTCA), who also had undergone PTCA in the past, with a group of people who had had no angiographic stenosis in the lumen of the coronary arteries in the past, and who also required PTCA during index hospitalization. The secondary aim was to compare the obtained data with the characteristics of a group of people who had undergone angiography twice and for whom no significant stenosis had been found in their coronary arteries. The study used registry data concerning 3085 people who had undergone at least two invasive procedures. Acute coronary syndrome (ACS) was significantly more often observed (Non-ST-segment elevation myocardial infarction (NSTEMI) OR 2.76 [1.91–3.99] and ST-segment elevation myocardial infarction (STEMI) OR 2.35 [1.85–2.99]) in patients with no significant coronary stenosis in the past (who required coronary angioplasty at the time of the study), compared to patients who had already had PTCA. They also demonstrated more frequent occurrence of 'multivessel disease'. This was probably most likely caused by inadequate control of cardiovascular risk factors, as determined by higher total cholesterol levels ([mg/dL] 193.7 ± 44.4 vs. 178.2 ± 43.7) and LDL (123.4 ± 36.2 vs. 117.7 ± 36.2). On the other hand, patients in whom no significant stenosis was found in two consecutive angiographies were more likely to be burdened with chronic obstructive pulmonary disease, atrial fibrillation and chronic kidney disease. [ABSTRACT FROM AUTHOR]

Background Multiple biomarkers have been independently and additively associated with major adverse cardiovascular events in patients with coronary artery disease. We investigated the prognostic value of suPAR (soluble urokinase-type plasminogen activator receptor) and hsTnI (high-sensitivity troponin I) levels in symptomatic patients with no obstructive coronary artery disease. We hypothesized that high levels of these biomarkers will be associated with the risk of future adverse outcomes. Methods and Results Plasma levels of suPAR and hsTnI were measured in 556 symptomatic patients with no obstructive coronary artery disease. A biomarker risk score was calculated by counting the number of biomarkers above the median in this cohort (suPAR>2523 pg/mL and hsTnI>2.7 pg/mL). Survival analyses were performed with models adjusted for traditional risk factors. All-cause death and major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, and heart failure) served as clinical outcomes over a median follow-up of 6.2 years. Mean age was 57±10 years, 49% of the cohort patients were female, and 68% had a positive stress test. High suPAR and hsTnI levels were independent predictors of all-cause death (hazard ratio=3.2 [95% CI, 1.8-5.7] and 1.3 [95% CI, 1.0-1.7], respectively; both P <0.04) and major adverse cardiovascular events (hazard ratio=2.7 [95% CI, 1.4-5.4] and 1.5 [95% CI, 1.2-2.0], respectively; both P <0.002). Compared with a biomarker risk score of 0, biomarker risk scores of 1 and 2 were associated with 19- and 14-fold increased risk of death and development of major adverse cardiovascular events, respectively. Conclusions Among symptomatic patients with no obstructive coronary artery disease, higher levels of suPAR and hsTnI were independently and additively associated with an increased risk of adverse events. Whether modification of these biomarkers will improve risk in these patients needs further investigation.

Background Primary prevention risk scores are commonly used to predict cardiovascular (CVD) outcomes. The applicability of these scores in patients with evidence of myocardial ischemia but no obstructive coronary artery disease is unclear. Methods and Results Among 935 women with signs and symptoms of ischemia enrolled in WISE (Women's Ischemia Syndrome Evaluation), 567 had no obstructive coronary artery disease on angiography. Of these, 433 had had available risk data for 6 commonly used scores: Framingham Risk Score, Reynolds Risk Score, Adult Treatment Panel III, Atherosclerotic Cardiovascular Disease, Systematic Coronary Risk Evaluation, Cardiovascular Risk Score 2. Score-specific CVD rates were assessed. For each score, we evaluated predicted versus observed event rates at 10-year follow-up using c statistic. Recalibration was done for 3 of the 6 scores. The 433 women had a mean age of 56.9±9.4 years, 82.5% were white, 52.7% had hypertension, 43.6% had dyslipidemia, and 16.9% had diabetes mellitus. The observed 10-year score-specific CVD rates varied between 5.54% (Systematic Coronary Risk Evaluation) to 28.87% (Framingham Risk Score), whereas predicted event rates varied from 1.86% (Systematic Coronary Risk Evaluation) to 6.99% (Cardiovascular Risk Score 2). The majority of scores showed moderate discrimination (c statistic 0.53 for Atherosclerotic Cardiovascular Disease and Systematic Coronary Risk Evaluation; 0.78 for Framingham Risk Score) and underestimated risk (statistical discordance -58% for Adult Treatment Panel III; -84% for Atherosclerotic Cardiovascular Disease). Recalibrated Reynolds Risk Score, Atherosclerotic Cardiovascular Disease, and Framingham Risk Score had improved performance, but significant underestimation remained. Conclusions Commonly used CVD risk scores fail to accurately predict CVD rates in women with ischemia and no obstructive coronary artery disease. These results emphasize the need for new risk assessment scores to reliably assess this population.

A large proportion of women with chest pain have no obstructive coronary artery disease. Recent studies have demonstrated that these women continue to have symptoms and are at increased risk of cardiovascular morbidity and mortality. Coronary microvascular dysfunction (CMD) leads to an impairment of blood flow regulation to the myocardium and possible transient ischaemia. CMD is a disease entity with several pathophysiologic aspects and diagnostic modalities continue to be developed. However, due to the complexity of the disease, it remains elusive whether CMD is the explanation for the symptoms and the poor prognosis in women with angina and no obstructive coronary artery disease., Competing Interests: Disclosure: The authors have no conflicts of interest to declare.