Vasospastic Angina Group Research Articles

Decreased plasma extracellular superoxide dismutase level in patients with vasospastic angina

Objective Extracellular superoxide dismutase (EC-SOD) is the major extracellular scavenger of superoxides, and one of the main regulators of nitric oxide bioactivity in vessel walls. Here, we examined whether plasma EC-SOD level was associated with vasospastic angina (VSA), and if it was a risk factor for VSA. Methods and results We assigned 105 patients with normal or mildly stenotic coronary arteries into either a VSA ( n = 58) or chest pain syndrome (CPS) ( n = 47) groups. Plasma EC-SOD and other biochemical variables were measured, and major coronary risk factors were assessed. Results showed that apart from smoking status there were no significant differences in patient characteristics and biochemical variables between the two groups. In the VSA group, prevalence of smoking was significantly higher (53% versus 26%, p = 0.0055), and plasma EC-SOD level was significantly lower (68.9 ± 18.5 ng/ml versus 83.8 ± 25.9 ng/ml; p = 0.0009). Not only smoking (OR 2.742, 95% CI 1.032–7.287, p = 0.0431) but also plasma EC-SOD (OR 0.971, 95% CI 0.949–0.993, p = 0.0102) was an independent risk factor for VSA. Conclusions In patients with VSA, plasma EC-SOD level was substantially reduced. Furthermore, plasma EC-SOD level followed by cigarette smoking was the most predictive risk factor for coronary spasms.

Klotho gene polymorphism may be a genetic risk factor for atherosclerotic coronary artery disease but not for vasospastic angina in Japanese

Background The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes, including atherosclerosis. We tested the hypothesis that the G–395A polymorphism of the klotho gene is associated with increased risk for 2 types of ischemic heart disease in Japanese. Methods The study population consisted of 197 patients with coronary heart disease (CAD) who had > 75% luminal diameter narrowing, 77 patients with vasospastic angina (VSA) without significant fixed coronary artery disease, and 331 healthy control subjects. Results The frequency of the A allele carriers of the klotho gene was significantly higher in the CAD group than in the control group (29.9% vs. 19.0%). The unadjusted odds ratio for CAD in the A allele carriers compared with the control group was 1.82 ( p = 0.004) and a traditional risk-adjusted logistic regression model revealed that the A allele was an independent predictor of CAD (odds ratio, 1.76; p = 0.03). In contrast, the frequency of the A allele carriers was not significantly different in the VSA group (23.4%; adjusted odds ratio, 1.18. Conclusions The –395A polymorphism of the human klotho gene may be a genetic risk factor for IHD and not for VSA.

Significance of asymmetric dimethylarginine (ADMA) concentrations during coronary circulation in patients with vasospastic angina.

The basal activity of nitric oxide (NO) is reduced in spastic arteries of patients with vasospastic angina (VSA). Elevated concentrations of ADMA are associated with reduced NO production and impaired endothelium-dependent vasodilatation. The aim of this study was to elucidate the role of ADMA and its relationship to NO end-products (NOx; nitrate + nitrite) during coronary circulation in patients with VSA. The plasma ADMA and NOx concentrations during coronary circulation were evaluated in 16 VSA and 16 control patients. Blood samples were obtained from the coronary sinus (V) and the ostium of the left coronary artery (A), and the (V-A) differences of ADMA and NOx were determined. The coronary sinus plasma ADMA concentration in patients with VSA was higher than that in the control. The coronary sinus - arterial (V-A) difference of NOx was negative in the VSA group and approximately zero in the control group (VSA group =-1.4 micromol/L, control group =-0.1 micromol/L, p=0.0005). Furthermore, in the VSA patients, there was a negative correlation between the (V-A) difference of NOx and the basal coronary artery tone at the site of spasm (r=-0.60, p=0.015). A significant negative correlation between the (V-A) differences of NOx and ADMA was observed in patients with VSA (r=-0.52, p<0.05), but not in those of the control. Higher ADMA concentrations might cause the reduced formation of NO that underlies the pathophysiology of coronary vasospasm.

The Risk Factors of Vasospastic Angina

Background and Objectives:The causes of vasospastic angina are not well known. We attempted to elucidate the risk profiles of Korean patients with vasospastic angina. Subjects and Methods:The risk profiles were analyzed in 181 patients with vasospastic angina (VA), 1533 patients with obstructive coronary artery disease (CAD) who underwent coronary angiography at Samsung Seoul Hospital, and 455 normal control subjects, sex and age matched to the VA group and selected from the Health Promotion Center of Samsung Seoul Hospital. Results:The male to female ratio was significantly higher in the VA group (4.6:1) than the obstructive CAD group (2.7:1). The mean age of the VA group (52.2±10.7 years) was significantly younger than the mean age of the obstructive CAD group (59.0±10.6 years) (p<0.01). Additionally, the smoking rate was significantly higher in the VA group (49.2%) as compared with the obstructive CAD group (43.1%) (p<0.01). Other major risk factors such as hyperlipidemia, hypertension and diabetes mellitus were significantly more prevalent in the obstructive CAD group than the VA group. Among the obstructive CAD group, a subgroup of Q-wave myocardial infarction (MI) showed a significantly higher smoking rate (59.3%) as compared with VA group (49.2%) (p<0.01). Conclusion:The VA group showed a higher prevalence in males and younger subjects as compared with the obstructive CAD group, and smoking appeared to be the most important risk factor for VA. (Korean Circulation J 2002;32(3):224-232)

Endothelial dysfunction is an independent factor responsible for vasospastic angina

In order to evaluate peripheral endothelial function in patients with vasospastic angina (VSA), we measured flow-mediated dilation (FMD) of the brachial artery in patients with VSA and compared it with FMD in patients without VSA. Endothelial dysfunction is considered one of the mechanisms underlying VSA. However, its exact role remains to be clarified. The study included 30 patients with positive spasm-provocational test results without evidence of significant coronary stenosis (VSA group) and 30 patients with negative spasm-provocational test results without evidence of significant coronary stenosis (control group). In each patient, brachial artery diameter responses to hyperemic flow and glyceryl trinitrate spray were measured using high-resolution ultrasound. The carotid intima-media thickness was also measured as a marker of systemic atherosclerosis. FMD was lower in the VSA group (4.8+/-0.5%) compared with the control group (9.4+/-0.7%, P<0.0001). In the VSA group, FMD was not affected by coronary risk factors or the presence of atherosclerotic changes on coronary angiography. Glyceryl trinitrate-induced dilation did not differ between the two groups. The intima-media thickness was comparable between the VSA (0.85+/-0.04 mm) and control groups (0.81+/-0.05 mm). These findings indicated that peripheral endothelial function is impaired only in the VSA group, whereas the atherosclerotic changes were similar in the two groups. We conclude that endothelial dysfunction may be an independent factor responsible for the development of VSA.

Possible role of chronic infection with Chlamydia pneumoniae in Japanese patients with acute myocardial infarction.

Chlamydia pneumoniae, a common human respiratory pathogen, has been implicated in the pathogenesis of coronary heart diseases (CHD) in several seroepidemiological studies. The present case-control study investigated the relation between serologic evidence of C. pneumoniae infection and CHD in a Japanese population. Two groups of cases were enrolled: 26 patients with acute myocardial infarction (AMI) and 46 patients with effort angina pectoris (e-AP). Their data were compared with 58 age-matched healthy controls and also compared with 53 patients with vasospastic angina (VSA) as pathological control subjects. Anti-C. pneumoniae specific IgA and IgG antibody titers were measured by enzyme-linked immunosorbent assay (ELISA). The mean indices of IgG-type antibody in AMI and e-AP were not significantly different from those in either the normal controls or VSA group. On the other hand, the mean indices of IgA-type antibody in AMI were significantly higher than in the normal controls (1.39+/-0.83 in AMI vs 0.84+/-0.58 in controls, p<0.001) and VSA (1.39+/-0.83 in AMI vs 1.05+/-0.61 in VSA, p<0.05) group. However, the differences in the IgA titers in the e-AP group compared with the normal controls did not reach a significant level. The odds ratio associated with the seropositivity of IgA for AMI against the normal controls was 3.89 (95% confidence interval (CI): 1.16-13.10) and that against VSA was 6.90 (95% CI: 1.73-27.52) after adjustment for risk factors for CHD and/or age, sex and smoking status. In 6 patients the elevated IgA titers were sustained even at 3 months after the episode of AMI. These results suggest that seropositivity for IgA-type antibody against C. pneumoniae may be a significant risk factor for the development of AMI. The possible mechanisms include chronic inflammation in the coronary artery due to persistent C. pneumoniae infection.

Familial evidence of vasospastic angina and possible involvement of HLA-DR2 in susceptibility to coronary spasm.

An association between genetic factors and susceptibility to coronary spasm has not been proven. Because we encountered 7 patients with familial occurrence of vasospastic angina (VSA) in 3 families, the association of a genetic factor with coronary spasm was assumed. HLA typing as one of the genetic markers was performed in the 3 families, and the affected members in each family were found to share a HLA haplotype, carrying both HLA-DR52 and DQ6. This raised the possibility that one of the susceptibility genes for coronary spasm is located in the HLA region. To assess this possibility, HLA typing was performed and compared in 110 patients with VSA but without a family history of VSA (VSA group) and 55 patients with chest pain syndrome (CPS group) as control subjects. All patients underwent a provocation test for coronary spasm, and spasm was angiographically documented in the VSA group but not in the CPS group. Of all HLA antigens, the frequency of only HLA-DR2 was significantly higher in the VSA group than in the CPS group (39.1% vs 18.2%, p<0.01). The result implied that HLA-DR2 is in linkage disequilibrium with a susceptibility gene of VSA and thus is possibly involved in susceptibility to coronary spasm in some patients with VSA.

Basal Coronary Artery Tone and Insulin Resistance in Vasospastic Angina

Background：Insulin resistance syndrome has been proposed as a major promotor of atherosclerotic disease and earlier studies have implied the hyperinsulinemia itself may enhance coronary vasomotor tone. In patients with vasospastic angina, previous studies have been inconclusive whether to basal coronary artery tone is elevated at the spasm related and non-spasm related artery. This study was performed to investigate whether basal coronary artery tone is elevated and insulin resistance syndrome correlates to vasospastic angina. If insulin resistance syndrome correlates to vasospastic angina, we also investigated whether insulin resistance syndrome correlates to basal coronary artery tone. Methods：The study comprised 27 patients with vasospastic angina(M/F；19/8, mean age；52 ＋/-2 year and 21 control subjects with atypical chest pain(M/F；9/8, mean age；47＋/-3 year. We assessed basal coronary artery tone by obtaining the percent increase in coronary artery diameter induced by nitroglycerin and also examined glucose and insulin response to an oral glucose load of 75g. Results： 1 There were no significant differences in body surface area, abdominal hip ratio, body mass index, incidence of hypertension, lipid profile, von-Willebrand factor, fibrinogen, and microalbumin except smoking incidence [vasospastic angina；16(59% vs control；5(24%, p<0.05] between vasospastic angina group and control. 2 Basal coronary artery tone was greater at the nonspastic site of the spasm-related artery(28.1± 2.2% vs 13.1±0.9%, p<0.0001 and non-spasm related artery(23.7±1.6% vs 13.1±0.9, p<0.0001 in the patients with vasospastic angina than in control subjects. In the patients with vasospastic angina, high activity group had a greater basal coronary artery tone than low activity group at the nonspastic site of the spasm-related artery(31.7±2.6 vs 20.4±2.7%, p<0.001 and non-spasm related

A new noninvasive method of diagnosing vasospastic angina based on dilation response of the left main coronary artery to nitroglycerin as measured by echocardiography

Objectives.The purpose of the present study was to evaluate the feasibility of diagnosing vasospastic angina based on coronary artery tone as assessed by M-mode echocardiographic measurement of the dilation response of the left main coronary artery to nitroglycerin.Background.The definite diagnosis of vasospastic angina is done by a coronary spasm provocative test using ergonovine maleate or acetylcholine during cardiac catherization. Current noninvasive, nonpharmacologic diagnostic methods are not sensitive enough for the diagnosis of vasospastic angina.Methods.Thirty-eight patients who had an angiographically normal left main trunk were studied. These patients were classified into four groups based on the presence or absence of more than 50% stenosis in the coronary arteries except for the left main trunk and the results of the acetylcholine or ergonovine provocative test. At 7 a.m. and at noon on the same day, the left main trunk diameter was measured by M-mode echocardiography before and after sublingual administration of nitroglycerin (0.3 mg), and its percent dilation was calculated to assess coronary artery tone.Results.The percent dilation of the left main trunk diameter induced by sublingual nitroglycerin at 7 a.m. and at noon was 22.4 ± 4.7% (mean ± SD) and 18.1 ± 4.0% in 11 patients with vasospastic angina and without coronary stenosis, 14.9 ± 7.1% and 11.2 ± 6.9% in 9 patients with vasospastic angina and coronary stenosis, 6.1 ± 3.5% and 7.0 ± 5.1% in 8 patients without vasospastic angina but with coronary stenosis and 8.1 ± 5.6% and 7.8 ± 5.7% in 10 control subjects. The percent dilation at 7 a.m. was significantly greater in the vasospastic angina without coronary stenosis group than in the remaining three groups, and in the vasospastic angina groups, the percent dilation at 7 a.m. was significantly greater than that at noon. When percent dilation at 7 a.m. exceeding 15% was defined as positive for the diagnosis of vasospastic angina, the sensitivity was 80% and the specificity 94%.Conclusions.Basal tone of the left main trunk is elevated in the early morning in vasospastic angina. Dilation of the left main trunk diameter exceeding 15% induced by sublingual nitroglycerin in the early morning as measured by M-mode echocardiography is a highly sensitive and specific criterion for the diagnosis of vasospastic angina.

Study on lipid and glucose metabolism in patients with vasospastic angina.

The primary purpose of the present study was to evaluate the role of lipid and glucose metabolism in vasospastic angina. A group of 93 patients in whom the presence of ischemic heart disease was suggested, were classified into the control (C) group, consisting of 30 patients; the coronary artery disease (CAD) group, consisting of 47 patients; and the vasospastic angina (VSA) group, consisting of 16 patients. Among these three groups, age, total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), atherogenic index (AI), apolipoproteins and the prevalence of diabetes mellitus were compared. No age difference was seen among the three groups. The TC was the highest in the CAD group, followed by the VSA and C groups. A significant difference in TC was noted between the C and CAD groups and the C and VSA groups. TG levels were higher in the CAD group than in the C and VSA groups, without a significant difference among the three groups. The AI was significantly higher in the CAD group than in the C and VSA groups. No significant difference was noted in the prevalence of diabetes mellitus among the three groups. Apolipoprotein A-I (apo A-I) levels were higher in the VSA group than in the C and CAD groups, and the difference between the VSA and CAD groups was significant. Apolipoprotein A-II (apo A-II) levels were significantly higher in the VSA group than in the C and CAD groups.(ABSTRACT TRUNCATED AT 250 WORDS)