In-hospital initiation of angiotensin receptor-neprilysin inhibition in acute heart failure: the PREMIER trial.

BACKGROUND AND AIMS: The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients. METHODS: This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels. RESULTS: A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident. CONCLUSIONS: In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046).

Factors Contributing to Coronary Microvascular Dysfunction in Patients with Angina and Non-Obstructive Coronary Artery Disease.

BACKGROUND: Coronary microvascular dysfunction (CMD), characterised by a reduced coronary flow reserve (CFR) or an increased index of microcirculatory resistance (IMR), has received considerable attention as a cause of chest pain in recent years. However, the risks and causes of CMD remain unclear; therefore, effective treatment strategies have not yet been established. Heart failure or coronary artery disease (CAD) is a risk factor for CMD, with a higher prevalence among women. However, the other contributing factors remain unclear. In this study, we assessed the risk in patients with angina and non-obstructive coronary artery disease (ANOCA), excluding those with heart failure or organic stenosis of the coronary arteries. Furthermore, we analysed whether the risk of CMD differed according to component factors and sex. METHODS: This study included 84 patients with ANOCA (36 men and 48 women; mean age, 63 years) who underwent coronary angiography and functional testing (CFT). The CFT included a spasm provocation test (SPT), followed by a coronary microvascular function test (CMVF). In the SPT, patients were mainly provoked by acetylcholine (ACh), and coronary spasm was defined as >90% transient coronary artery constriction on coronary angiography, accompanied by chest pain or ischaemic changes on electrocardiography. In 15 patients (18%) with negative ACh provocation, ergonovine maleate (EM) was administered as an additional provocative drug. In the CMVF, a pressure wire was inserted into the left anterior descending coronary artery using intravenous adenosine triphosphate, and the CFR and IMR were measured using previously described methods. A CFR < 2.0 or IMR ≥ 25 was indicative of CMD. The correlations between various laboratory indices and CMD and its components were investigated, and logistic regression analysis was performed, focusing on factors where p < 0.05. RESULTS: Of the 84 patients, a CFR < 2.0 was found in 22 (26%) and an IMR ≥ 25 in 40 (48%) patients, with CMD identified in 46 (55%) patients. CMD was correlated with smoking (p = 0.020) and the use of EM (p = 0.020). The factors that correlated with a CFR < 2.0 included the echocardiograph index E/e' (p = 0.013), which showed a weak but positive correlation with the CFR (r = 0.268, p = 0.013). Conversely, the factors correlated with an IMR ≥ 25 included RAS inhibitor usage (p = 0.018) and smoking (p = 0.042). Assessment of the risk of CMD according to sex revealed that smoking (p = 0.036) was the only factor associated with CMD in men, whereas the left ventricular mass index (p = 0.010) and low glycated haemoglobin levels (p = 0.012) were associated with CMD in women. CONCLUSIONS: Our results indicated that smoking status and EM use were associated with CMD. The risk of CMD differed between the two CMD components and sex. Although these factors should be considered when treating CMD, smoking cessation remains important. In addition, CMD assessment should be performed carefully when EM is used after ACh provocation. Further validation of our findings using prospective studies and large registries is warranted.

Blood pressure reduction with empagliflozin in Japanese patients with type 2 diabetes and cardiovascular diseases: a post-hoc sub-analysis of the placebo-controlled randomized EMBLEM trial.

Detailed effect of sodium-glucose cotransporter 2 inhibitors on blood pressure (BP) in Japanese patients with type 2 diabetes (T2D) at a high risk of cardiovascular disease (CVD) is not fully understood. In this post-hoc sub-analysis of placebo-controlled randomized EMBLEM trial for Japanese patients with T2D and CVD, 105 participants (empagliflozin N = 52, placebo N = 53) were included, and office systolic/diastolic BPs and mean arterial pressure (MAP) over 24 weeks were estimated using mixed-effects models for repeated measures. Empagliflozin therapy, compared to placebo, reduced systolic/diastolic BPs (mean group difference in change from baseline to week 24; -5.9 [95% confidence interval (CI), -10.4 to -1.4] mmHg/-2.9 [95% CI, -6.2 to 0.4] mmHg) and MAP ( - 3.8 [95% CI, -7.0 to -0.7] mmHg). The systolic BP reduction was almost consistent across differing background clinical characteristics and usage status of anti-hypertensive medications.

Clinical Characteristics and Major Adverse Cardiovascular Events in Diabetic and Non-Diabetic Patients with Vasospastic Angina.

Purpose: The clinical background and prognostic impact of diabetes mellitus (DM) on vasospastic angina (VSA) are unclear; thus, in this retrospective study, we investigated whether they differ based on the presence or absence of DM in patients with VSA. Patients and Methods: We included 272 Japanese patients with VSA diagnosed by coronary angiography (CAG) and the spasm provocation test (SPT). The diagnosis of DM was determined by measuring fasting blood glucose and hemoglobin A1C and by the patient's current oral medications. On CAG, the presence of atherosclerotic lesions (20%-50%) was checked. On SPT, the coronary spasm was defined as transient coronary vasoconstriction >90% on CAG, accompanied by chest symptoms and/or ST-T changes. Focal spasm was defined as coronary spasm occurring within one segment of the American Heart Association classification on CAG. Blood and urine tests and vascular endothelial function were also evaluated when possible. A major adverse cardiovascular event (MACE), which is defined as cardiac mortality and rehospitalization due to cardiovascular illness, was the basis for determining the prognosis. Results: There were 49 patients (18%) in the DM group and 223 (82%) in the non-DM group. No significant differences in urinary albumin levels and peripheral vascular function were between groups. On CAG, atherosclerotic lesions were observed significantly more frequently in the DM group (63% vs 46%; P = 0.028). Results of SPT showed a trend toward fewer focal spasms in the DM group (24% vs 39%; P = 0.072). No significant differences in MACE were noted between groups in the primary analysis of DM, whereas sub-analyses of focal spasms showed lower MACE-free survival in the DM group (P = 0.042). Conclusion: The study results support the hypothesis that DM associated with VSA should be treated appropriately, especially in cases of focal spasm, which may require more attention in treatment.

Effects of ipragliflozin on left ventricular diastolic function in patients with type 2 diabetes: A sub-analysis of the PROTECT trial.

BACKGROUND: We hypothesized that the beneficial effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on diastolic function might depend on baseline left ventricular (LV) systolic function. METHODS: To investigate the effects of SGLT2 inhibitors on LV diastolic function in patients with type 2 diabetes mellitus (T2DM), we conducted a post-hoc sub-study of the PROTECT trial, stratifying the data according to LV ejection fraction (LVEF) at baseline. After excluding patients without echocardiographic data at baseline or 24 months into the PROTECT trial, 31 and 38 patients with T2DM from the full analysis dataset of the PROTECT trial who received ipragliflozin or no SGLT2 inhibitor (control), respectively, were included. The primary endpoint was a comparison of the changes in echocardiographic parameters and N-terminal pro-brain natriuretic peptide levels from baseline to 24 months between the two groups stratified according to baseline LVEF. RESULTS: Differences in diastolic functional parameters (e' and E/e') were noted between the two groups. Among the subgroups defined according to median LVEF values, those with higher LVEF (≥60 %) who received ipragliflozin appeared to have a higher e' and lower E/e' than did those who received the standard of care with no SGLT2 inhibitor, indicating longitudinal improvements between baseline and follow up (p = 0.001 and 0.016, respectively). CONCLUSIONS: Ipragliflozin generally improved LV diastolic function in patients with type 2 diabetes, the extent of this improvement might appear to vary with LV systolic function.

Do changes in intracoronary pressure aid coronary spasm diagnosis using the spasm provocation test?

BACKGROUND: Although the spasm provocation test (SPT) can diagnose coronary spasms, it would be helpful if it could also predict their occurrence. AIM: To investigate whether coronary spasms can be predicted using changes in intracoronary artery pressure measured using a pressure wire during the SPT. METHODS: Seventy patients underwent SPTs with pressure-wire measurement of intracoronary artery pressure. During each SPT, the pressure wire was advanced into the distal portion of the right coronary artery (RCA) and left anterior descending coronary artery, and the ratio of intracoronary pressure to aortic pressure (Pd/Pa) was monitored. Coronary spasm was defined as an arterial narrowing of > 90% in response to the administration of acetylcholine (ACh), with chest symptoms and/or ischemic electrocardiographic changes. ACh was administered to the RCA at low, moderate, or high doses of 20, 50, or 80 µg, respectively, and to the left coronary artery (LCA) at low, moderate, or high doses of 50, 100, or 200 µg, respectively. Coronary arteries with coronary spasms at low doses of ACh were defined as group L, and those with coronary spasms at moderate or high doses were defined as group MH. Those who did not occur coronary spasms at any ACh dose were designated as group N. RESULTS: Among the 132 coronary arteries assessed using a pressure wire, there were 49 in group N, 25 in group L, and 58 in group MH. Baseline Pd/Pa was the lowest in group L (P = 0.001). The decrease in the Pd/Pa between baseline to low doses of ACh was lower in group MH than in group N (P < 0.001). A receiver-operating characteristics analysis showed that the cutoff baseline Pd/Pa value for predicting group L was 0.95, with a sensitivity of 0.600 (15/25) and a specificity of 0.713 (76/107) and that the cutoff value of Pd/Pa from baseline to low doses of ACh for predicting group MH was -0.04, with a sensitivity of 0.741 (43/58) and a specificity of 0.694 (34/49). CONCLUSION: These findings suggest that indices of intracoronary pressure during SPT may be useful means for predicting the occurrence of coronary spasms.

Fatal myocardial infarction investigated using contrast-enhanced postmortem computed tomography: A case report.

Conventional autopsies are considered standard methods for clarifying cause of death. However, because of the increasing use of computed tomography, magnetic resonance imaging, and other diagnostic imaging techniques, autopsy imaging is now more frequently adopted to identify diseases with unknown causes and sudden deaths. A 84-year-old man was diagnosed with acute myocardial infarction using coronary angiography. After taking oral antiplatelet medication in the catheterization laboratory, the patient suddenly coughed violently, lost consciousness, and was diagnosed with cardiac arrest. Spontaneous circulation did not return after 50 min of cardiopulmonary resuscitation. To elucidate the cause of the cardiac arrest, we performed contrast-enhanced postmortem computed tomography (PMCT), which revealed cardiac tamponade due to cardiac rupture of the inferior myocardium. Our findings reaffirm the effectiveness of contrast-enhanced PMCT in the diagnosis of sudden death in the clinical setting.

Vasospastic Angina in a Young Woman: A Case Report.

Vasospastic angina (VSA) is a disease that causes myocardial ischemia due to transient vasoconstriction of the epicardial coronary arteries. This disease generally occurs in middle-aged and older adults, but there are also reports of it occurring in young people. We report a case of VSA in a woman in her 20's. Six months ago, a female patient in her 20s became aware of a strangling sensation in the chest that lasted for approximately 1-20 minutes at rest or during stress. She consulted her family doctor who prescribed nitroglycerin sublingual tablets, which were effective. She was a current smoker and had a history of bronchial asthma, with no family history of coronary artery disease. Resting electrocardiogram and echocardiography revealed no clear abnormalities. The patient was referred to our hospital for coronary angiography (CAG) and spasm provocation test (SPT), primarily to thoroughly examine her chest pain at rest. CAG revealed no significant stenosis. A subsequent SPT using acetylcholine demonstrated diffuse coronary spasm in the left anterior descending coronary artery (LAD). The coronary spasm resolved spontaneously, but the catheter was difficult to maneuver owing to the radial artery spasm at the puncture site; thus, nitroglycerin was administered, which alleviated the radial artery spasm. Another SPT was performed on the right coronary artery (RCA) and revealed no coronary spasm. Coronary microcirculatory function using a pressure wire in response to the peripheral infusion of adenosine triphosphate was assessed in the RCA and LAD, both of which were normal. The patient was discharged from the hospital on an oral calcium channel blocker (CCB). She continued to experience chest pain, but her chest symptoms improved with CCB medication and a change in her workplace. It must be kept in mind that coronary spasms can occur even in young women and should be one of the differentials of chest pain in such patients.

Which Coronary Artery Should Be Preferred for Starting the Coronary Spasm Provocation Test?

BACKGROUND: The spasm provocation test (SPT) is a critical test for diagnosing vasospastic angina (VSA). However, the choice of vessel to be preferred for initiating the SPT-the right coronary artery (RCA) or the left coronary artery (LCA)-is unclear. This study aimed to assess SPT results including SPT-related complications while initiating the SPT in the RCA and LCA. METHODS: We enrolled 225 patients who underwent coronary angiography and SPTs. The SPT was first performed in the RCA in 133 patients (RCA group) and the LCA in 92 patients (LCA group). We defined VSA as >90% narrowing of the coronary artery during the SPT, accompanied by chest pain and/or ST-T changes on the electrocardiogram. When coronary spasm occurs in two or more major coronary arteries, it is referred to as a multivessel spasm (MVS). SPT-related complications comprised atrial fibrillation, ventricular fibrillation, and unstable hemodynamics following catecholamine use. Analyses using propensity score matching (PSM) were performed in 120 patients. RESULTS: No significant differences in the frequencies of VSA and complications were observed between the two groups (RCA: 79% and 19%, respectively; LCA: 85% and 22%, respectively). In both groups, spasms were most frequently provoked in the left anterior descending coronary artery (both p < 0.001) whereas spasms in the left circumflex coronary artery (LCX) were higher in the LCA group than in the RCA group (p = 0.015). Furthermore, no significant difference in the frequency of MVS was observed between both groups (RCA: 50%, LCA: 62%; p = 0.122). After PSM, no significant difference in the frequencies of VSA and complications were observed between the two groups (RCA: 82% and 15%, respectively; LCA: 88% and 18%, respectively). The frequencies of LCX spasms (RCA: 8%, LCA: 23%; p = 0.022) and MVS (RCA: 40%, LCA: 62%; p = 0.020) were higher in the LCA group than in the RCA group. CONCLUSIONS: Although the diagnostic rate of VSA and frequency of SPT-related complications were similar in the two groups, the frequency of MVS was higher in the LCA group than in the RCA group because of the increase in the number of LCX spasms. A routine SPT may be started from the LCA.

Rationale and design of an investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized trial to evaluate the effects of finerenone on vascular stiffness and cardiorenal biomarkers in type 2 diabetes and chronic kidney disease (FIVE-STAR).

BACKGROUND: The overactivation of mineralocorticoid receptor (MR) plays a key pathological role in the progression of cardiovascular and renal diseases by promoting pro-inflammatory and pro-fibrotic signaling. Recently, it has been found that finerenone, a novel nonsteroidal selective MR antagonist, can robustly improve cardiorenal outcomes in patients with type 2 diabetes (T2D) and a wide spectrum of chronic kidney disease (CKD). However, the mechanisms underlying the cardiorenal benefits of finerenone are poorly understood. Further, whether the clinical benefits are mediated by an improvement in vascular stiffness is not confirmed. Therefore, the current study aims to evaluate the effects of finerenone on vascular stiffness as assessed using cardio ankle vascular index (CAVI) and relevant cardiorenal biomarkers in patients with T2D and CKD. METHODS: The Effects of Finerenone on Vascular Stiffness and Cardiorenal Biomarkers in Type 2 Diabetes and Chronic Kidney Disease (FIVE-STAR) is an ongoing, investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized clinical trial in Japan. Its target sample size is 100 subjects. Recruitment will be performed from September 2023 to July 2024. After obtaining informed consent, eligible participants with T2D and CKD (25 mL/min/1.73 m2 ≤ estimated glomerular filtration ratio [eGFR] < 90 mL/min/1.73 m2 and 30 mg/g Cr ≤ urinary albumin-to-creatinine ratio [UACR] < 3500 mg/g Cr) will be equally randomized to receive 24-week treatment with either finerenone (starting dose at 10 mg once daily in participants with a baseline eGFR < 60 mL/min/1.73 m2 or at 20 mg once daily in those with a baseline eGFR ≥ 60 mL/min/1.73 m2) or dose-matched placebo. The primary endpoint is the change from baseline in CAVI at 24 weeks. The secondary endpoints are changes from baseline in UACR at 12 and 24 weeks and relevant serum and urinary biomarkers at 24 weeks. As an exploratory endpoint, proteomic analysis using the Olink® Target 96 panels will be also performed. DISCUSSION: FIVE-STAR is the first trial evaluating the therapeutic impact of finerenone on vascular stiffness and relevant cardiorenal biomarkers in patients with T2D and CKD. This study will provide mechanistic insights on the clinical benefits of finerenone based on recent cardiovascular and renal outcome trials. Trial registration Unique Trial Number, NCT05887817 ( https://clinicaltrials.gov/ct2/show/NCT05887817 ) and jRCTs021230011 ( https://jrct.niph.go.jp/latest-detail/jRCTs021230011 ).

Frequency and Clinical Impact of Family History of Coronary Artery Disease in Patients with Vasospastic Angina.

BACKGROUND: Family history (FH) of coronary artery disease (CAD) [FH-CAD] is a well-known risk factor for atherosclerotic CAD. However, FH-CAD frequency in patients with vasospastic angina (VSA) remains unknown, and the clinical characteristics and prognosis of VSA patients with FH-CAD are unclear. Therefore, this study compared FH-CAD frequency between patients with atherosclerotic CAD and those with VSA and examined the clinical characteristics and prognosis of VSA patients with FH-CAD. METHODS: Coronary angiography and spasm provocation tests (SPT) were used to investigate chest pain of coronary artery origin in patients classified into atherosclerotic CAD (362 cases), VSA (221 cases; positive for SPT) and non-VSA (73 cases; negative for SPT) groups, with FH-CAD being defined. In the VSA group, flow-mediated vasodilation (FMD) and nitroglycerin-independent vasodilation (NID) via brachial artery echocardiography and clinical symptoms in the groups with and without FH-CAD were checked, with Kaplan-Meier curves revealing major adverse cardiovascular events (cardiac death and rehospitalisation for cardiovascular disease) between the two groups. RESULTS: The atherosclerotic CAD group had a significantly lower FH-CAD frequency (12%, p = 0.029) than the VSA (19%) and non-VSA groups (19%). FH-CAD was more common in females in the VSA and non-VSA groups than in the atherosclerotic CAD group (p < 0.001). Nonpharmacological treatment for CAD in FH-CAD was more common in the atherosclerotic CAD group (p = 0.017). In the VSA group, FH-CAD tended to be more common in females (p = 0.052). Although no differences in FMD of the brachial artery were observed between the groups, the FH-CAD (+) group had significantly higher NID than the FH-CAD (-) group (p = 0.023). Kaplan-Meier's analysis revealed a similar prognosis between the two groups, and other clinical characteristics did not differ. CONCLUSION: Patients with VSA have a higher FH-CAD frequency than those with atherosclerotic CAD, especially in females. Although FH-CAD may affect vascular function in patients with VSA, its effect on the severity and prognosis of VSA appears to be minimal. FH-CAD and its confirmation may assist in CAD diagnosis, especially in female patients.

Recognition of Pulseless Ventricular Tachycardia Through the Second Analysis of Automated External Defibrillators, Leading to Successful Shock Delivery in a Patient With Dilated Cardiomyopathy: A Case Report.

The use of a defibrillator with a monitor is recommended for the shock indication algorithm for in-hospital cardiac arrest; however, it is likely that many medical facilities are still equipped only with automated external defibrillators (AEDs). We experienced a case of dilated cardiomyopathy (DCM) complicated by pulseless ventricular tachycardia (pVT) in which an AED was used, but shock was deemed unnecessary after the first analysis. We believe that this case is suggestive of resuscitating cardiac arrest, for which defibrillation is indicated and reported here. A 65-year-old man who had DCM and diabetic nephropathy was admitted to our institution because of worsening heart failure. In the hospital, he suddenly had syncope and was diagnosed with cardiac arrest. Thereafter, cardiopulmonary resuscitation (CPR) was performed using an AED, and the monitor on the AED showed pVT. The first analysis of the AED announced unnecessary shock delivery. The pads of the AED were pressed firmly against the chest wall while continuous high-quality CPR was administered for two minutes. The second analysis of the AED revealed the necessity of providing shock for shockable rhythm. The patient experienced the return of spontaneous circulation after shock delivery. We were reminded that there are some clinical cases in which AED shock is not indicated for pVT and that even in such cases, it is important to continue high-quality CPR without panicking.

Acute Heart Failure Due to Multi-vessel Coronary Spasm.

A 46-year-old man presented to our hospital with chest pain followed by coughing and dyspnea. His myocardial enzyme levels were almost normal, and electrocardiography and echocardiography showed no obvious abnormalities. Chest radiography revealed congestion. He was diagnosed with heart failure with a preserved ejection fraction (HFpEF). Although subjective symptoms improved with intravenous diuretics, the patient was admitted to the hospital for a close examination. Coronary angiography showed no obvious stenosis, and a subsequent spasm provocation test demonstrated the presence of multi-vessel and diffuse spasms. Coronary spasm should be considered as a differential cause of heart failure, even in patients with HFpEF.

Japanese Herbal Medicine (Kampo) as a Possible Treatment for Ischemia With Non-obstructive Coronary Artery Disease.

Patients presenting with the syndrome of symptoms and signs suggesting ischemic heart disease but found to have no obstructed coronary arteries (INOCA) are increasingly recognized. Although there are non-invasive tests for the diagnosis of INOCA, such as transthoracic Doppler echocardiography, positron emission tomography, and cardiac magnetic resonance imaging to evaluate increased blood flow with adenosine and other agents, the diagnosis of INOCA by coronary angiography with the coronary spasm provocation test and coronary microvascular function evaluation using pressure wires has become the gold standard, but it is not well established in the treatment of INOCA. Despite the lack of objection to lifestyle modification and the use of coronary dilators, mainly calcium-channel blockers, for conditions involving epicardial coronary artery spasm, there is no entirely effective long-term treatment for microvascular spasm or coronary microvascular dysfunction. Although some combinations of drugs have been empirically administered in certain cases, it is difficult to conclude that they are sufficiently effective. Recently, it has been reported that some Japanese herbal medicines (Kampo) have been effective in the treatment of INOCA. In order to increase the knowledge on the treatment of INOCA, this review focuses on the effects of Japanese herbal medicine on INOCA and its presumed mechanisms and problems.

Vasospastic angina in women: Clinical backgrounds and prognoses of patients younger than and older than 60 years.

BACKGROUND: We frequently encounter cases of women with vasospastic angina (VSA). Additionally, some women with VSA are younger than 60 years old. However, it is unknown whether the characteristics of VSA in women aged < 60 years are different from those in women aged ≥ 60 years. AIM: To investigate and compare the clinical characteristics and prognosis of VSA in women aged < 60 years from those in women aged ≥ 60 years. METHODS: We enrolled 94 women with VSA who were diagnosed using the spasm provocation test. According to the age at diagnosis, the patients were divided into two groups: Group Y (age < 60 years, n = 17) and Group O (age ≥ 60 years, n = 77). Flow-mediated dilation (FMD) and nitroglycerin (NTG)-induced dilation (NID) of the brachial artery were performed and assessed using brachial ultrasonography. Moreover, conventional coronary risk factors, such as atherosclerotic lesions (stenosis > 20%) detected using coronary angiography and focal spasms (coronary spasm within one segment of one coronary artery), and major cardiovascular adverse events (MACE) were assessed in both groups. RESULTS: Smoking was more prevalent in Group Y than in Group O (P = 0.04). FMD was similar in both groups (Group O: 4.3% ± 3.2%, Group Y: 4.5% ± 3.3%; P = 0.75), whereas NID was higher in Group Y (20.5% ± 8.6%) than in Group O (13.6% ± 5.3%, P < 0.01). Atherosclerosis was not detected in Group Y but was detected in Group O (61%, P < 0.01). Focal spasms were less frequent in Group Y (12%) than in Group O (38%, P = 0.04). The incidence of major adverse cardiac events did not differ between the two groups (P = 0.40). CONCLUSION: Women aged < 60 years with VSA have less atherosclerotic lesions and focal spasms. These characteristics may be affected by smoking habits and vascular smooth muscle dysfunction.