Acetylcholine Provocation Test Research Articles

Late gadolinium enhancement on cardiac magnetic resonance imaging is associated with coronary endothelial dysfunction in patients with dilated cardiomyopathy.

Myocardial fibrosis and coronary endothelial dysfunction are important determinants of outcome in patients with heart failure. However, the relationship of these factors in patients with dilated cardiomyopathy (DCM) is not fully understood. This study aimed to investigate the relationship between endothelium-dependent coronary vasomotor abnormality and late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) in patients with DCM. We examined 38 consecutive patients with DCM. All patients underwent CMR and the acetylcholine (ACh) provocation test using cardiac catheterization. During the ACh provocation test, we sampled blood simultaneously from the coronary sinus and aortic root to compare lactate concentrations, and quantified coronary blood flow volume using an intracoronary Doppler-tipped guidewire. LGE was detected in 17 (44.7%) patients. The lactate extraction ratio (LER) in the ACh provocation test was significantly decreased in the LGE-positive group (before vs after ACh, 18.6±13.6 vs -13.3±24.8%; p<0.001) and in the LGE-negative group (before vs after ACh, 14.2±19.5 vs 3.3±16.2%; p=0.02). The rate of patients with an LER<0% (indicating myocardial lactate production due to myocardial ischemia) was significantly higher in the LGE-positive group than in the LGE-negative group [12 (70.6%) vs 7 (33.3%); p=0.02]. Multivariable logistic regression analysis showed that a post-ACh LER<0% was a significant predictor of LGE positivity (odds ratio 7.75; 95% confidence interval 1.37-43.68; p=0.02). In conclusion, ACh-provoked coronary vasomotor abnormality is associated with myocardial fibrosis in patients with DCM. These results suggest that coronary endothelial dysfunction is involved in myocardial fibrosis and worsening heart failure concomitant with DCM.

Five-year major clinical outcomes according to severity of coronary artery spasm as assessed by intracoronary acetylcholine provocation test

Long-term clinical outcome data according to severity of coronary artery spasm (CAS) as assessed by an intracoronary acetylcholine provocation test are limited in series of Asian patients. To investigate 5-year clinical outcomes in patients with CAS according to CAS severity. In total, 5873 consecutive patients with insignificant coronary artery disease (<70% fixed stenosis) who underwent an acetylcholine provocation test were enrolled and divided into four groups according to CAS severity during the acetylcholine provocation test: negative, borderline positive, moderately positive and severely positive. CAS severity was assessed by quantitative coronary angiography. We investigated 5-year clinical outcomes according to CAS severity. Over a follow-up period of up to 5 years, before adjustment, the severely-positive CAS group showed a significantly higher incidence of major adverse cardiac events (MACE; composite of death, myocardial infarction and de novo revascularization) (hazard ratio [HR]: 1.834, 95% confidence interval [CI]: 1.047-3.211; P=0.033), total death (HR: 3.124, 95% CI: 1.047-9.322; P=0.041), myocardial infarction (HR: 3.190, 95% CI: 1.069-9.519; P=0.037) and recurrent angina (HR: 1.762, 95% CI: 1.363-2.278; P<0.001) compared with the negative group. However, after adjustment for baseline confounders, only the incidence of recurrent angina (HR: 1.323, 95% CI: 1.014-1.726; P=0.039) was significantly higher in the severely-positive CAS group compared with the negative group. The severity of CAS in the positive group was not associated with an increased incidence of MACE after adjustment for covariates compared with the negative group, but the severely-positive CAS group was associated with a higher incidence of recurrent angina compared with the negative group.

TCT-378 Prognosis of Patients with Significant Coronary Artery Spasm without Fixed Stenosis and Treated with/without Calcium Channel Blockers

Our previous study showed that the long-term outcomes of coronary artery spasm (CAS) were good and did not differ depending on the vasomotion subtype in the acetylcholine (Ach) provocation test. we determined whether recurrent chest pain is really attributable to significant CAS in patients (pts)

Echocardiographic Epicardial Adipose Tissue Thickness Is Associated with Symptomatic Coronary Vasospasm during Provocative Testing

Epicardial adipose tissue (EAT) is the ectopic visceral fat surrounding the heart, which plays an important role in atherosclerosis of the coronary arteries via endothelial damage. Several studies have also suggested that vasospasm with angina (VSA) causes endothelial dysfunction in the coronary arteries. The aim of this study was to evaluate the thickness of EAT in the anterior interventricular groove (EAT-AIG) using echocardiography in patients who had no obstructive coronary artery disease and were suspected of having VSA. Sixty-five patients who underwent intracoronary acetylcholine provocation testing for clinical indicationswere prospectively enrolled. VSA was diagnosed by coronary artery stenosis increase of >90% and the presentation of chest pain with ischemic changes on electrocardiography. Subjects were divided into two groups, with and without significant coronary spasm (VSA group, 30 patients; non-VSA group, 35 patients), consistent with acetylcholine provocation testing. EAT-AIG thickness was significantly greater in the VSA group than in the non-VSA group (8.2±2.7 vs 6.1±2.5mm, P=.002). By receiver operating characteristic analysis, EAT-AIG thickness had a high C statistic (area under the curve=0.81, P<.001) after adjustment for conventional risk factors (smoking, diabetes mellitus, and dyslipidemia). EAT-AIG thickness had incremental diagnostic value over other conventional risk factors (area under the curve=0.81 vs 0.64, P for comparison=.020). EAT-AIG thickness, which is noninvasively and easily measured using transthoracic echocardiography, can be one of multiple clinical variables associated with VSA.

Impact of endothelial dysfunction by FMD on long-term outcomes of coronary artery spasm induced by acetylcholine provocation test-EAS 2017

Aim: Endothelial dysfunction (ED) plays a major role in coronary artery spasm (CAS). However, there is no study that investigated the impact of ED on prognosis in patients with CAS induced by the acetylcholine provocation test (ACH-test).

P5313Impact of serum lipoprotein (a) on coronary artery spasm as assessed by intracoronary acetylcholine provocation test

P5313Impact of serum lipoprotein (a) on coronary artery spasm as assessed by intracoronary acetylcholine provocation test

Relation between severity of myocardial bridge and vasospasm

BackgroundMyocardial bridge (MB) has been reported to induce cardiac complications including coronary vasospasm. Although MB has some anatomical and morphological variations, the association of these variations with vasospasm is unclear. The aim of this study was to investigate the relation between morphological severity of MB and vasospasm induced by acetylcholine (ACh) provocation test. MethodsA total of 392 patients without coronary stent in the left anterior descending artery (LAD) undergoing intracoronary ACh provocation test were included. Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation. MB was identified on coronary angiography as a milking effect. Total bridged length and maximum percent systolic compression of MB in the LAD were analyzed quantitatively. ResultsMBs in the LAD were identified in 140 patients (36%), mostly in the mid segment. Patients with MB in the LAD had greater number of provoked vasospasm in the LAD and positive ACh provocation test compared to those without. The bridged length positively correlated with percent systolic compression of MB (r=0.37, p<0.001). In the receiver operating characteristic curve analysis, both bridged length and percent systolic compression of MB significantly predicted the provoked LAD spasm (AUC 0.74, p<0.001, and AUC 0.68, p<0.001). Multivariate regression analysis demonstrated these factors as independent predictors for provoked LAD spasm. ConclusionMB, especially morphologically severe MB, may induce greater coronary vasospasm.

CYP2C19 variants and epoxyeicosatrienoic acids in patients with microvascular angina

BackgroundCategorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the impact of CYP2C19 polymorphisms and EETs on the patients with microvascular angina (MVA) caused by coronary microvascular dysfunction. Methods and resultsWe examined CYP2C19 genotypes in patients with MVA (n=81). MVA was defined as absence of coronary artery stenosis and epicardial spasms, and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite.In MVA, the patients with CYP2C19 PM were 34.6% and high sense C-reactive protein (hs-CRP) levels in CYP2C19 PM were significantly higher than that of non-PM group (0.165±0.116 vs. 0.097±0.113mg/dL, P=0.026). Moreover, DHET levels in CYP2C19 PM were significantly lower than that of non-PM (10.4±4.58 vs. 15.6±11.1ng/mL, P=0.003 (11,12-DHET); 12.1±3.79 vs. 17.3±6.49ng/mL, P=0.019 (14,15-DHET)). ConclusionsThe decline of EET owing to CYP2C19 variants may affects coronary microvascular dysfunction via chronic inflammation.

Three-year follow-up of patients with acetylcholine-induced coronary artery spasm combined with insignificant coronary stenosis

BackgroundCoronary artery spasm (CAS) and significant coronary stenosis are known to be major causes of myocardial ischemia. However, their association and the impact of insignificant coronary stenosis (ICS) on long-term clinical outcomes of CAS patients are largely unknown. MethodsA total of 2797 patients without significant coronary artery disease (CAD) who underwent the acetylcholine (ACH) provocation test between November 2004 and October 2010 were enrolled. Significant CAS was defined as having ≥70% of temporary narrowing by ACH test and ICS as having <70% of fixed stenosis on angiography. Patients were divided into two groups: ICS group (n=764) and non-ICS group (n=845). To adjust potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. Primary endpoint was the composite of total death, myocardial infraction (MI), de novo percutaneous coronary intervention (PCI), and cerebrovascular accidents (CVA). Secondary endpoint was the incidence of recurrent angina requiring repeat coronary angiography (CAG) at 3years. ResultsAfter PSM analysis, two well-balanced groups (548 pairs, total=1096) were generated. The baseline clinical characteristics were similar between the two groups. During the ACH test, compared with the non-ICS group, the ICS group had smaller spastic narrowing diameter (0.69±0.35 vs. 0.73±0.37, P=0.039) and incidence of ST-segment depression (4.0% vs. 0.9%, P=0.001). The incidence of primary and secondary endpoints was similar between the two groups up to 3years. ConclusionsAlthough, the ICS group was expected to have more adverse long-term clinical outcomes, it was not associated with the increased incidence of major adverse clinical outcomes compared with the non-ICS group up to 3years. Longer term follow-up studies are needed.

Ultra-long acting calcium channel blockers may decrease accuracy of the acetylcholine provocation test

BackgroundWhen drug-induced coronary spasm provocation tests are performed, a washout period of >48h for calcium channel blockers (CCBs) is uniformly recommended. However, each CCB has a distinct half-life, and little is known about the influence of prior oral administration of CCBs on acetylcholine provocation test to evaluate coronary vasomotor reaction. Methods and resultsWe examined 245 consecutive patients with suspected vasospastic angina who had undergone acetylcholine provocation test. Of those patients, 29 patients had been on amlodipine, an ultra-long term acting CCB (group A), 34 on other CCBs (group O), and 182 patients on no CCB (group N). After CCBs had been withheld > 48h, we performed acetylcholine provocation, which resulted in 152 positive, 36 intermediate, and 57 negative reactions. We evaluated coronary artery tone calculated as follows: (luminal diameter after nitrate−baseline luminal diameter)÷(luminal diameter after nitrate)×100 (%). In group A patients, coronary artery tone was lower (A:9.1±6.9% vs. O:11.7±8.3% vs. N:12.1±8.5%, p=0.0011) and the positive rate of acetylcholine provocation test was lower than group O and group N (A:41% vs. O:68% vs. N:64%, p=0.047). Multivariate logistic analysis showed that taking amlodipine until 2days before acetylcholine provocation test was a significant inverse predictor for acetylcholine-provoked coronary spasm (odds ratio 0.327; 95% confidence interval 0.125–0.858, p=0.023). ConclusionsResidual vasodilatory effects of ultra-long acting CCB may decrease coronary artery tone and the vasoconstrictive reaction to acetylcholine suggesting that a 2-day pre-test drug holiday may not be long enough.

CRT-100.04 Impact of Ambient Air Pollution on Coronary Artery Spasm

Ambient air pollution is well-known to be a serious risk factor for cardiovascular diseases, stroke, and death. However, the association between air pollutants (AP) exposure and coronary artery spasm (CAS) by acetylcholine (Ach) provocation test is not well elucidated yet. A total of 5,822

Inferior J waves in patients with vasospastic angina might be a risk factor for ventricular fibrillation

BackgroundThere is little information about the relationship between J waves and the occurrence of ventricular fibrillation (VF) in patients with vasospastic angina (VSA). The present study aimed to assess the incidence of J waves and the occurrence of VF in patients with VSA. MethodsThe subjects consisted of 62 patients with VSA diagnosed by acetylcholine provocation tests in our institution from 2002 to 2014. We investigated the VF events, prevalence of J waves, and relationship between the VF events and J waves. ResultsJ waves were observed in 16 patients (26%) and VF events were documented in 11 (18%). The incidence of VF in the patients with J waves was significantly higher than that in those without J waves (38% vs 11%, p=0.026). J waves were observed in the inferior leads in 14 patients, lateral leads in 5, and anterior leads in 3. A univariate analysis indicated that the incidence of VF in the inferior leads of J wave positive patients (46%=6/14) was significantly (p=0.01) higher than that in the inferior leads of J wave negative patients (10%=5/48). The J waves in the anterior and/or lateral leads were not related to the incidence of VF. Notched type and slurred type J waves were not associated with VF. A multivariate analysis revealed that J waves in VSA patients were associated with VF [odds ratio (OR) 6.41, 95% confidence interval (CI) 1.37–29.93, p=0.02] and organic stenosis (OR 6.98, 95% CI 1.39–35.08, p=0.02). Further, J waves in the inferior leads were strongly correlated with VF (OR 11.85, 95% CI 2.05–68.42, p=0.006). ConclusionsThe results suggest that the existence of J waves, especially in the inferior leads, might be a risk factor for VF in VSA patients.

Malondialdehyde-Modified Low Density Lipoprotein as Oxidative-Stress Marker in Vasospastic Angina Patients.

Serum MDA-LDL was evaluated in candidate VSA patients.The subjects were 84 patients admitted to our hospital because of chest pain at rest. We stratified the patients into 3 groups; definite VSA, suspected VSA, and unlikely VSA according to a Japanese Circulation Society (JCS) guideline. The patients classified as definite VSA or suspected VSA were considered as "clinical VSA".Forty cases were classified as definite VSA, 35 as suspected VSA, and 9 as unlikely VSA. Thus, clinical VSA was the diagnosis in 75 cases. The patient characteristics showed that the average age of the patients was 60.2 years old (men, 61%). The serum MDA-LDL level of the clinical VSA group (126.3 ± 38.0 U/L) was significantly higher than the unlikely VSA group (98.7 ± 31.1 U/L). Serum MDA-LDL was positively correlated with total cholesterol (T-Chol), lowdensity lipoprotein cholesterol (LDL-C), triglycerides, and fasting blood glucose. Multivariate analysis showed that serum MDA-LDL was the most predictive marker for making a diagnosis of clinical VSA (Odds ratio 1.064, 95% confidence interval 1.014-1.145, P = 0.008). In a population with positive or borderline ECG change, the positive rate in the acetylcholine provocation test was significantly higher in the MDA-LDL higher group compared to the MDA-LDL lower group (81% versus 37%, P = 0.032).: Serum MDA-LDL might be a useful biomarker of VSA and have additional value for the diagnosis of clinical VSA.

Paroxysmal atrial fibrillation during intracoronary acetylcholine provocation test.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. However, paroxysmal atrial fibrillation (AF) often occurs during intracoronary ACh provocation test, leading to disabling symptoms. The aim of this study was to investigate the incidence and predictors of paroxysmal AF during the test. A total of 377 patients without persistent AF who underwent intracoronary ACh provocation test were included. Paroxysmal AF during ACh provocation test was defined as documented AF on electrocardiogram during the procedure. There were 31 patients (8%) with paroxysmal AF during the test. Of these, 11 (35%) required antiarrhythmic drugs, but none received electrical cardioversion. All of them recovered sinus rhythm within 48h. At procedure, paroxysmal AF occurred mostly during provocation for the right coronary artery (RCA) rather than for the left coronary artery (LCA) (90 vs. 10%). Multivariate logistic regression analysis demonstrated that a history of paroxysmal AF (OR 4.38 CI 1.42-13.51, p=0.01) and body mass index (OR 0.88 CI 0.78-0.99, p=0.03) were independent predictors for occurrence of paroxysmal AF during intracoronary ACh provocation test. In conclusions, paroxysmal AF mostly occurs during ACh provocation test for the RCA, especially in patients with a history of paroxysmal AF and lower body mass index. It may be better to initially administer intracoronary ACh in the LCA when the provocation test is performed.

Manifestation of J wave induced by acetylcholine applied for a coronary spasm provocation test in a patient with aborted sudden cardiac death

A 51-year-old man with a resuscitation episode was referred to our hospital. Coronary angiography revealed a focal spasm overlapped with organic stenosis where a bare metal stent was implanted. Acetylcholine (ACh) provocation test did not induce chest pain. It revealed no discernible ST-T changes but unmasked a J wave at the end of the QRS complex, which was associated with short-coupled repetitive premature ventricular beats. A J wave reportedly appears immediately before the onset of ventricular fibrillation caused by vasospastic angina. However, a J wave observed newly after a coronary spasm provocation test using ACh without ST-T changes is informative when considering the mechanisms of the J wave.

Feasibility of omitting provocation test with 50μg of acetylcholine in left coronary artery.

According to the Japanese Circulation Society guideline of vasospastic angina, incremental doses of acetylcholine (ACh) are prescribed for coronary spasm provocation: 20 and 50μg for the right coronary artery (RCA), and 20, 50 and 100μg for the left coronary artery (LCA). However, provocation by low doses of ACh in patients with low vasoreactivity may be less needed, and the requirement of 50μg of ACh for the LCA in these patients has not been evaluated. In the present study, patients who underwent ACh provocation test for both the RCA and LCA were included. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing (i.e., angiographic coronary artery spasm) accompanied by chest pain and/or ischemic electrocardiographic changes. Coronary artery constriction was visually evaluated and defined as coronary artery diameter reduction <25 or 25-90% in patients without angiographic coronary artery spasm by 20µg of ACh in the LCA. There were 33 out of 249 patients (13%) with LCA spasm by 20µg of ACh. In subjects without LCA spasm by 20µg of ACh, patients with coronary constriction <25% (n=101) by 20µg of ACh in the LCA rarely showed coronary artery spasm induced by 50μg of ACh in the LCA, in comparison to those with coronary constriction 25-90% (n=115) (2.6 vs. 32.7%, p<0.001). None of the patients with coronary constriction <25% by 20µg of ACh in the LCA had cardiac complications associated with administration of ACh. In conclusion, omission of 50µg of ACh in the LCA may be possible when there is little coronary artery constriction by 20µg of ACh in the LCA during provocation test, leading to less contrast and shortens overall procedure time.

Abstract 13476: Usefulness of Dual Induction Tests for Coronary Artery Spasm and Lethal Ventricular Arrhythmias in Patients Surviving Out-of-Hospital Cardiac Arrest

Background: It remains to be established how to treat patients with out-of-hospital cardiac arrest (OHCA) without significant organic heart disease, especially regarding the use of implantable cardioverter-defibrillator (ICD). Among the possible causes of OHCA, coronary artery spasm (CAS) and lethal ventricular arrhythmias (VAs) are important causes of the disorder. Methods and Results: In 47 consecutive OHCA survivors without organic heart disease who had fully recovered (M/F 44/3, 43±13 yrs.), we performed dual induction tests for CAS and VAs. We first performed acetylcholine provocation test with subsequent calcium channel blocker-based antianginal medications and then performed ventricular fibrillation (VF) induction test with programmed stimulation at an interval of 1~2 weeks. ICD was implanted in all patients. According to the results of the dual induction tests, we divided them into 4 groups; CAS-alone (n=7), VAs-alone (n=13), both-positive (n=24), and both-negative (n=3) ( Figure A ). Among the 4 groups, no significant difference was noted in the factors that could influence the development of VF, such as QTc, late potential, familial history of sudden cardia death, or serum levels of electrolytes. During a median follow-up of 38 months, VF recurred in all groups except the both-negative group, of which 13 cases had appropriate ICD shocks to terminate fatal VAs. When we analyzed the 16 patients with Brugada-like ECG pattern (34%) separately, no VF episode was noted in the CAS-alone or both-negative group throughout the study period. Kaplan-Meier analysis showed that the CAS-alone group was at lower risk for OHCA recurrence as compared with the Brugada syndrome group (log-rank test, P=0.036) ( Figure B ). Conclusions: These results indicate that among OHCA survivors, those with CAS-alone and without Brugada syndrome in the dual induction tests may be at low risk for recurrent sudden death and ICD firing.

Impact of Diltiazem Alone versus Diltiazem with Nitrate on Five-Year Clinical Outcomes in Patients with Significant Coronary Artery Spasm.

PurposeCalcium channel blockers diltiazem and nitrate have been used as selective coronary vasodilators for patients with significant coronary artery spasm (CAS). However, no study has compared the efficacy of diltiazem alone versus diltiazem with nitrate for long-term clinical outcomes in patients with CAS.Materials and MethodsA total of 2741 consecutive patients without significant coronary artery disease with positive CAS by acetylcholine (Ach) provocation test between November 2004 and May 2014 were enrolled. Significant CAS was defined as a narrowing of >70% by incremental intracoronary injection of 20, 50, and 100 µg of Ach into the left coronary artery. Patients were assigned to either the diltiazem group (n=842) or the dual group (diltiazem with nitrate, n=1899) at physician discretion. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM analysis, two well-balanced groups (811 pairs, n=1622, C-statistic=0.708) were generated.ResultsAt 5 years, there were similar incidences in primary endpoints, including mortality, myocardial infarction, revascularization, and recurrent angina requiring repeat coronary angiography between the two groups. Diltiazem alone was not an independent predictor for major adverse cardiovascular events or recurrent angina requiring repeat coronary angiography.ConclusionDespite the expected improvement of endothelial function and the relief of CAS, the combination of diltiazem and nitrate treatment was not superior to diltiazem alone in reducing mortality and cardiovascular events up to 5 years in patients with significant CAS.

Predictive value of coronary artery dilation response to nitrate for a positive intracoronary acetylcholine provocation test

Baseline coronary artery diameter and coronary artery dilation response to nitrate are associated with coronary vasoreactivity. The present study investigated the predictive value of coronary artery tone for a positive intracoronary acetylcholine (ACh) provocation test. A total of 197 patients who underwent an ACh provocation test in the right coronary artery were included. A positive ACh provocation test was defined as transient total or subtotal occlusion of a coronary artery with signs/symptoms of myocardial ischemia. The segment, from the ostium to the bifurcation, of the right coronary artery was analyzed quantitatively. Coronary artery dilation response to isosorbide dinitrate (ISDN) was defined as the mean lumen diameter after an intracoronary injection of ISDN divided by the diameter before administration of ACh (i.e. baseline coronary artery diameter). After the administration of ACh, 49 patients (24.9%) had a positive ACh provocation test. Smaller baseline right coronary artery diameter (2.35±0.45 vs. 2.73±0.48 mm, P<0.001) and greater right coronary artery dilation response to ISDN (1.34±0.12 vs. 1.15±0.11, P<0.001) were observed in patients with a positive ACh provocation test. The receiver operating characteristic curve for baseline coronary artery diameter poorly predicted the occurrence of a positive ACh provocation test (area under the curve 0.71). The predictive values of dilation response of the right coronary artery to ISDN for the occurrence of a positive ACh provocation test (area under the curve 0.87) was significantly better compared with that of baseline right coronary artery diameter (P<0.001). Coronary artery dilation response to nitrate is a more accurate predictor of a positive intracoronary ACh provocation test compared with baseline coronary artery diameter.

TCT-489 Impact of Left Ventricular Hypertrophy on Coronary Artery Spasm as assessed by Acetylcholine Provocation Test

In our previous study, hypertensive patients with uncontrolled blood pressure had a significantly lower incidence of coronary artery spasm (CAS) than those with controlled blood pressure. However, it is unknown whether hypertensive patients with target-organ damage have a lower incidence of CAS than