The Glu298Asp polymorphism in the endothelial nitric oxide synthase gene is strongly associated with coronary spasm

BACKGROUND: Coronary spasm seems to be associated with coronary nitric oxide deficiency. OBJECTIVES: We investigated whether the Glu298Asp polymorphism in the endothelial nitric oxide synthase (eNOS) gene is a definite risk factor for coronary spasm and whether diffuse spasm involving normal-looking coronary artery correlates significantly with the Glu298Asp polymorphism, in contrast with focal spasm superimposed on an atherosclerotic plaque. METHODS: A polymerase chain reaction followed by restriction fragment length polymorphism analysis was performed in 118 control participants and in 102 patients with variant angina and a similar degree of atherosclerotic burden. Patients with coronary spasm were divided into diffuse spasm and focal spasm subgroups according to morphological criteria. RESULTS: There was a significantly higher incidence of the Glu298Asp polymorphism in the coronary spasm group than in the control group (21.5% compared with 8.5%, P=0.006). Multiple logistic regression analysis using risk factors and the Glu298Asp polymorphism showed that the most important predictive factor for coronary spasm was the Glu298Asp polymorphism (odds ratio 2.83, 95% confidence interval 1.25-6.41, P=0.009). The diffuse spasm subgroup had a significantly higher frequency of the Glu298Asp polymorphism than the control group (25.9% compared with 8.5%, P=0.002). However, the focal spasm subgroup did not differ from the control group in the frequency of Glu298Asp polymorphism. CONCLUSION: The Glu298Asp polymorphism in the eNOS gene is a definite risk factor for coronary spasm, especially for diffuse coronary spasm. This result supports the notion that diffuse coronary spasm is significantly associated with endothelial dysfunction, in contrast to focal spasm.     

Coronary spasm is associated with chronic low-grade inflammation.

BACKGROUND: Coronary spasm plays an important role in the pathogenesis of ischemic heart disease and it may be associated with low-grade inflammation. METHODS AND RESULTS: Intracoronary injection of acetylcholine was done in 199 patients (99 men, 100 women, mean age, 64.5+/-11.0 years) with chest pain and normal coronary angiograms. According to the results of the provocation test, the study subjects were divided into 2 groups: the spasm group of 112 patients and the non-spasm group of 87 patients. Clinical data including high-sensitivity C-reactive protein (hs-CRP) and other coronary risk factors were compared between the 2 groups. Serum levels of hs-CRP were significantly higher in the spasm group than in the non-spasm group (median: 1.2 mg/L vs 0.5 mg/L, p<0.005). Multivariate analysis showed that hs-CRP and smoking history were independently associated with coronary spasm with an odds ratio of 2.28 (p=0.027) and 2.25 (p=0.037), respectively, with a hs-CRP value of > or = 2 mg/L as cutoff point. CONCLUSIONS: Minor elevations of the serum hs-CRP level are significantly associated with coronary spasm, suggesting that chronic low-grade inflammation may be involved in the pathogenesis of coronary spasm.     

Ergonovine-Induced Changes of Coronary Artery Diameter in Patients with Nonsignificant Coronary Artery Stenosis

BACKGROUND AND PURPOSE: Serum cholesterol is positively associated with the risk of developing coronary heart disease. The aim of this study was to determine the relation between response of coronary arteries to ergonovine provocation and lipid profile in patients with nonsignificant coronary artery disease. PATIENTS AND METHODS: 105 patients (46 male, 59 female, mean age 52 +/- 8 years) with chest pain syndrome and nonsignificant coronary artery stenosis (< 50% diameter stenosis) were analyzed. Ergonovine test was performed at the end of diagnostic catheterization. Coronary spasm was defined as total or near total obstruction of the coronary artery. By quantitative coronary arteriography, changes of minimal luminal diameter (MLD) during ergonovine provocation were evaluated. Total cholesterol, LDL and HDL cholesterol, and triglycerides were measured. RESULTS: There was a significant negative correlation between resting MLD and LDL cholesterol (r = -0.215; p = 0.034), and a significant positive correlation between MLD decrease provoked by ergonovine and total cholesterol (r = 0.275; p = 0.006), as well as LDL cholesterol (r = 0.284; p = 0.004), but not for HDL cholesterol and triglycerides (p = NS [not significant]). CONCLUSION: In patients with nonsignificant coronary artery stenosis evaluated by ergonovine provocation, there was not only a significant negative correlation between MLD and LDL cholesterol, but also a positive correlation between coronary vasoconstriction induced by ergonovine provocation and both total and LDL cholesterol.     

Long lasting spasticity in controlled vasospastic angina

OBJECTIVE: To evaluate changes in coronary artery spasticity in patients with vasospastic angina who had been stable for years under continuous drug treatment. METHODS: Follow up coronary angiography was performed under intracoronary ergonovine provocation in 27 well controlled patients with vasospastic angina and no organic stenosis; the tests were done > 24 months after the initial coronary angiography, in which occlusive spasm had been induced by the same regimen of ergonovine provocation. RESULTS: The mean (SD) follow up period was 47.2 (21.6) months. All patients had been free from angina attack for more than 24 months under treatment with antianginal drugs. During this follow up period, organic stenosis developed in only one case. Occlusive spasm was observed during follow up coronary angiography in 23 patients. Spasm with 90% narrowing was observed in three other patients, and diffuse significant narrowing was seen in the final patient. No significant difference was found in spasticity (p = 0.75) between the initial and the follow up tests. CONCLUSIONS: Repeated ergonovine provocation during coronary angiography after a controlled period of several years showed that coronary spasm remains inducible in most patients. Discontinuance of drug treatment during the remission from anginal attacks achieved by medication may put the patient at high risk.     

Coronary artery spasm and the polymorphisms of the endothelial nitric oxide synthase gene.

BACKGROUND: Coronary artery spasm plays an important role in the pathogenesis of vasospastic angina, and contributes to the development of several acute coronary syndromes. Endothelial nitric oxide synthase (ecNOS) catalyzes the synthesis of nitric oxide, which regulates vascular tone, and may be related to coronary vasospasm. The present study investigated whether coronary spasm is related to particular polymorphisms of the ecNOS gene. METHODS AND RESULTS: Spasm provocation by serial infusions of acetylcholine was performed on 165 patients who were clinically suspected of having angina. In both study patients and healthy controls (n=400), genomic polymorphisms of the ecNOS gene were determined by using polymerase chain reaction. Quantitative luminal diameter measurements of the 3 major coronary arteries were initially obtained before and after acetylcholine injection, and then after isosorbide dinitrate injection, by using a computer-assisted analysis system. Logistic multiple regression analysis identified the a/a or a/b genotype in intron 4 of ecNOS (NOS4a: p=0.0431, odds ratio (OR) 2.43) and diabetes mellitus (p=0.0060, OR 4.88) as significant predictors of coronary spasm. In the patients with NOS4a, both the induced and spontaneous contractions were augmented. CONCLUSION: The present study results indicated that NOS4a could be a good marker for coronary artery spasm.     

Genetic risk and gene-environment interaction in coronary artery spasm in Japanese men and women.

AIMS: The aim of the study was to identify genes that confer susceptibility to coronary artery spasm and clarify the interaction between genetic and environmental factors in this condition. METHODS AND RESULTS: The study population comprised 2188 Japanese individuals, including 593 subjects with coronary artery spasm (453 men, 140 women) and 1595 controls (762 men, 833 women). The genotypes for 35 polymorphisms of 29 candidate genes were determined with an allele-specific DNA primer-probe assay. Multivariable logistic regression analysis adjusted for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolaemia, and hyperuricaemia revealed a significant association with coronary artery spasm of one polymorphism (242C-->T in the NADH/NADPH oxidase p22 phox gene) in men and two polymorphisms (-1171/5A-->6A in the stromelysin-1 gene and -634C-->G in the interleukin-6 gene) in women. A stepwise forward selection procedure revealed that smoking was the most important risk factor for coronary artery spasm and that the effects of these polymorphisms on this condition were statistically independent of smoking. CONCLUSION: The NADH/NADPH oxidase p22 phox gene is a susceptibility locus for coronary artery spasm in men, and the stromelysin-1 and interleukin-6 genes are susceptibility loci in women.     

NADH/NADPH oxidase p22 phox gene polymorphism is associated with improved coronary endothelial vasodilator function.

AIMS: The NADH/NADPH oxidase system plays a central role in vascular superoxide anion production, which appears to cause coronary endothelial dysfunction. Recently, it has been suggested that the C242T polymorphism of the NADH/NADPH oxidase p22 phox gene can reduce susceptibility to coronary artery disease. We therefore tested whether this polymorphism is associated with an altered endothelium-dependent vasodilator capacity of human coronary arteries in vivo. METHODS AND RESULTS: The vasodilator function of epicardial arteries in 93 patients was assessed by endothelium-mediated, flow-dependent dilation and nitroglycerin, which is endothelium-independent. NADH/NADPH oxidase p22 phox polymorphism was determined by restriction fragment length polymorphism. Carriers of the CC genotype of the C242T p22 phox polymorphism (n = 44) revealed a significantly blunted endothelium-dependent dilator response (11 +/- 9.2% luminal area change vs 17 +/- 10%;P = 0.007), which was, by multivariate analysis, independent of other risk factors or atherosclerosis itself. There was only a trend towards decreased endothelium-independent dilation in patients bearing the p22 phox CC genotype (P = 0.07). CONCLUSIONS: The C242T polymorphism of the p22 phox gene is an important independent determinant of coronary endothelial vasodilator function. These results provide the first clinical evidence for the functional significance of a polymorphism of a gene related to superoxide anion production in the vascular wall.     

Need for documentation of guidelines for coronary artery spasm: an investigation by questionnaire in Japan.

BACKGROUND: Because there are no guidelines concerning coronary spasm in Japan, the present study examined the current status of the spasm provocation test. METHODS AND RESULTS: Questionnaires concerning the number of cases of coronary angiography, percutaneous coronary intervention, and invasive/non-invasive spasm provocation tests over 3 years (2001-2003) and the status of spasm provocation tests were sent to members of the Japanese Circulation Society in 120 cardiology hospitals in the Chugoku and Shikoku areas. Completed surveys were returned from 45 hospitals, giving a collection rate of 38%. As a spasm provocation agent, acetylcholine tests were performed in 29 hospitals, and ergonovine tests in 18 hospitals. Non-invasive spasm provocation tests were performed in only 9 hospitals (20%). In total, 5,267 patients underwent acetylcholine spasm provocation test (2,387 patients) or ergonovine spasm provocation test (2,880 patients) and vasospastic angina was diagnosed in 1,663 (2.4%) patients. Invasive spasm provocation tests were performed in 7.8% of patients with diagnostic catheterization and the spasm-positive rate was 31.6%. The difference among hospitals concerning the number of invasive spasm provocation tests was remarkable, and the angiographic spasm-positive standard and acetylcholine/ergonovine dose varied among the hospitals. CONCLUSIONS: Guidelines on coronary spasm in Japan are essential to overcome the current differences between institutions.     

The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study

OBJECTIVES: We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD). BACKGROUND: Endothelial dysfunction foretells cardiovascular events and can be genetically determined. METHODS: We genotyped for the promoter (T(-786)C) and exon 7 (Glu298Asp, G(894)T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5'- and 3'-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T(-786)C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD. RESULTS: The overall genotype distribution of T(-786)C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T(-786)C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T(-786)C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041). CONCLUSIONS: The C allele at the T(-786)C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.     

Association Between Inflammatory Markers,Hemostatic Markers,and Traditional Risk Factors on Coronary Artery Spasm in Patients with Normal Coronary Angiography

Background

Coronary artery spasm is an important pathophysiological mechanism in some forms of myocardial ischemic disease. The relationship between inflammatory markers, mean platelet volume (MPV), and coronary artery spasm is unclear.

Methods and Results

During coronary angiography, methylergometrin was injected intravenously to 345 patients with chest pain but without significant coronary disease on angiogram to provoke coronary artery spasm. Based on provocation test results, patients were divided into 2 groups: spasm group (60 patients) and nonspasm group (285 patients). Inflammatory markers (C‐reactive protein, CRP; white blood cells; polymorphonuclear neutrophils, PMN; monocytes, MO; lymphocytes, LY), hemostasis markers (MPV; platelet count; fibrinogen [FIB]; D‐dimers), and traditional risk factors (body mass index; hyperlipidemia; triglycerides [TGs]; total, low‐density, and high‐density lipoprotein cholesterol [TC, LDL‐C, and HDL‐C]) were measured and compared between groups. More male patients experienced spasm (23.56% vs. 11.11%, P = 0.002). CRP, PMN, and MO were significantly higher in the spasm group (P < 0.05). There was no significant difference in serum levels of LDL‐C, HDL‐C, TG, TC, LY, MPV, and FIB between groups. Smoking and hyperlipidemia were more common among patients with spasm; males more frequently were smokers (58.04% vs. 46.78%, P = 0.041). By multivariate analysis, smoking, PMN, and MO were significantly associated with coronary artery spasm with odds ratios of 3.52 (95% CI 1.79–6.90, P = 0.0001), 1.21 (95% CI 1.07–1.46, P = 0.04), and 5.35 (95% CI 1.37–21.07, P = 0.01), respectively.

Conclusions

Inflammation may partake in the pathogenesis of coronary artery spasm. Smoking, PMN count, and MO count appear to be clinical risk factors for coronary artery spasm. Conversely, coronary artery spasm does not seem to be associated with abnormalities in thrombogenesis. (J Interven Cardiol 2014;27:29–35)

     

Comparison of frequency of coronary spasm in Korean patients with versus without myocardial bridging

The longstanding compression-relaxation effects of myocardial bridging may produce endothelial dysfunction by direct stress on the endothelium. We tested the hypothesis that myocardial bridging induces endothelial dysfunction and subsequently increases the risk of coronary spasm and investigated the symptomatic response to medication in patients with documented myocardial bridging and coronary spasm. In 81 patients with myocardial bridging (44 men; mean age 57.2 years) and 195 control patients without bridging and atherosclerotic lesions confirmed by angiography (97 men; mean age 58.4 years), spasm provocation testing was done by incremental acetylcholine infusion into the left coronary artery. Spasm was documented in 62 of 81 patients with bridging and in 31 of 195 controls (p <0.001). A focal spasm was limited to the bridging segments compared with controls (p <0.001). In conclusion, the results of this study showed that myocardial bridging increased the risk of coronary spasm by endothelial dysfunction in the bridging segment.     

Increased plasma level of endothelin-1 and coronary spasm induction in patients with vasospastic angina pectoris.

To elucidate the pathogenic contribution of a potent vasoconstrictor, endothelin-1, to coronary artery spasm, we provoked spasm with intracoronary administration of acetylcholine or ergonovine and performed sensitive immunoassays of plasma levels of endothelin-1 and atrial natriuretic factor (ANF) in the peripheral vein and coronary sinus of patients with a tentative diagnosis of vasospastic angina (VSA, n = 19). The validity of coronary sinus blood sampling was verified by simultaneous measurement of the ANF level. The plasma endothelin-1 levels in venous and coronary sinus blood of the spasm-provoked patients (n = 12) were 1.71-fold and 2.16-fold higher, respectively, than those of nonprovoked cases (n = 5, p less than 0.01). During left coronary spasm, the endothelin-1 level in coronary sinus transiently decreased from 2.27 +/- 0.14 to 1.76 +/- 0.14 pg/ml (p less than 0.01) and returned to the control level (1.98 +/- 0.20 pg/ml) after the spasm resolved, whereas the change was equivocal during right coronary spasm. In contrast, the patients in whom spasm was not provoked showed no changes and maintained low endothelin-1 levels both before and after the maximal provocation (0.90 +/- 0.13 versus 0.90 +/- 0.13 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity

OBJECTIVES: We investigated whether the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene modulates vasomotor tone and endothelial function. BACKGROUND: The deletion allele of the ACE I/D polymorphism has been associated with increased incidence of cardiovascular pathology. The risk is synergistically increased in patients who also possess the C allele at position 1,166 of the angiotensin type I (AT1) receptor gene. METHODS: In 177 patients with coronary atherosclerosis or its risk factors, we investigated endothelial function with intracoronary acetylcholine (ACH), endothelium-independent smooth muscle function with sodium nitroprusside (SNP) and basal nitric oxide activity with L-NG monomethyl arginine. RESULTS: Compared with ACE II genotype, patients with the ACE DD genotype had lower coronary microvascular and epicardial responses with SNP (coronary blood flow increase 196 +/- 26% vs. 121 +/- 11%, p = 0.003, and diameter increase 21.9 +/- 2% vs. 17 +/- 1%, p = 0.03, ACE II vs. DD, respectively). L-NG monomethyl arginine induced greater constriction in patients with the ACE DD compared with ACE II genotype (coronary blood flow -10 +/- 4% vs. 11 +/- 5%, p = 0.003, ACE DD vs. II and diameter constriction -6.3 +/- 1.2% vs. -1.9 +/- 1.2%, p = 0.01, respectively, in patients with atherosclerosis). No difference in ACH-mediated vasomotion was detected between the three ACE genotypes. The AT1 receptor polymorphism did not influence responses to either SNP or ACH. CONCLUSIONS: Patients possessing the D allele of the ACE gene have increased vascular smooth muscle tone. The enhanced tone appears to be counterbalanced by an increase in basal nitric oxide activity in patients with atherosclerosis.     

Role of Kozak sequence polymorphism of platelet glycoprotein Ibalpha as a risk factor for coronary artery disease and catheter interventions

OBJECTIVES: We sought to determine the role of the -5T/C polymorphism of the platelet glycoprotein (GP) Ibalpha as a potential risk factor for coronary artery disease (CAD) and adverse events complicating a coronary catheter intervention. BACKGROUND: The platelet GP Ib-IX-V receptor complex plays a crucial role in arterial thrombus formation. The -5T/C polymorphism of GP Ibalpha is associated with increased receptor density. METHODS: We genotyped 1,000 patients with angiographically confirmed CAD, as well as 1,000 age- and gender-matched control subjects, for this polymorphism by polymerase chain reaction/restriction fragment length polymorphism. Among the patients with CAD, 269 underwent percutaneous transluminal coronary angioplasty (PTCA), 103 underwent directional coronary atherectomy and 278 underwent stenting. This intervention group was followed for a 30-day composite end point of target vessel revascularization, myocardial infarction or death. RESULTS: Carriers of the -5C allele were significantly over-represented in the group of patients developing acute coronary syndromes (relative risk [RR] 1.43, 95% confidence interval [CI] 1.05 to 1.95, p = 0.02). The -5C allele furthermore predicted an increased risk for developing complications after PTCA (RR 3.75, 95% CI 1.15 to 12.27, p = 0.029). CONCLUSIONS: The -5C allele of the GP Ibalpha Kozak polymorphism may represent a risk factor in clinical conditions in which thrombosis plays an important role, such as in acute coronary syndromes and in complications after PTCA.     

A985G polymorphism of the endothelin-2 gene and atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND: It was recently suggested that the angiotensin-converting enzyme insertion/insertion genotype, which is considered to be protective against cardiovascular disease, was a significant risk factor for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to investigate the association between the endothelin-2 (EDN2) A985G polymorphism and AF in patients with HCM. METHODS AND RESULTS: The EDN2 A985G polymorphism (rs 5800) was genotyped in 110 patients with HCM who had no clinically documented AF before medical treatment. The distribution of the EDN2 genotypes (G/G, G/A, and A/A) was 77.3%, 19.1%, and 3.6%, respectively. The EDN2 A allele frequency was 0.21 in 26 patients who subsequently developed AF during long-term follow-up and 0.11 in 84 patients who remained in sinus rhythm. The distribution of genotypes of the dominant EDN2 A allele between the two groups was significantly different by chi-square analysis (42.3% vs 16.7%, p=0.014). In a multivariate model, the A985 allele of the EDN2 gene was associated with increased adjusted risk for the occurrence of AF (p=0.018). CONCLUSION: The EDN2 A985 allele, which is considered to be protective in cardiovascular disease, may be a risk factor for AF in patients with HCM.     

Variations in plasma endothelin concentrations during coronary spasm

A provocation test using methylergometrine was carried out inpatients with a normal coronary angiogram. Patients exhibitingspasm (Group I, n = 6) were compared with non-spasm patients(Group II, n = 6). The endothelin concentration was determinedin all cases at 0800, 1100, 1400, 1600, 1900, 2100, 2300 and0100 h. The provocation test was carried out at 1700 h and anadditional determination was made during spasm if the test waspositive. The two groups had similar clinical characteristics and didnot differ in terms of risk factors. Apart from the value recordedduring spasm, the endothelin plasma level was significantlyhigher in Group I. A time x measurement interaction was notedin both groups, with a higher endothelin level in the morning.The endothelin level increased signficantly during spasm inGroup I patients. The plasma concentration of endothelin appeared to be higherin the basal state and during spasm in patients exhibiting spasticangina.     

Myocardial bridging in adult patients with hypertrophic cardiomyopathy

OBJECTIVES: This investigation examined the risk of sudden cardiac death and other mortality in adult patients with hypertrophic cardiomyopathy (HCM) who have myocardial bridging diagnosed at coronary angiography. BACKGROUND: Several reports have associated myocardial bridging with an adverse prognosis in pediatric HCM patients, but the prognosis of myocardial bridging in adult patients with HCM is unknown. METHODS: The coronary angiograms of 425 patients with HCM (mean age 60 +/- 15 years [range 18 to 89 years]) at the Mayo Clinic were examined for the presence of myocardial bridging. Clinical follow-up was conducted to assess mortality. Survival of patients with bridging was compared with HCM patients who also underwent angiography but who did not have evidence of bridging. RESULTS: A total of 64 patients (15%) had myocardial bridging. The mean follow-up for the entire study was 6.8 +/- 5.4 years. There was no difference in survival free of all-cause mortality (5-year estimate, bridging vs. no bridging, 91% vs. 85%; p = 0.42), all cardiac death (93% vs. 89%; p = 0.60), and sudden cardiac death (95% vs. 97%; p = 0.72). Univariate and multivariate proportional hazards models also did not identify the presence of bridging or specific characteristics of the degree or extent of bridging with a poor outcome. CONCLUSIONS: This study observed no increased risk of death, including sudden cardiac death, among adult patients with HCM who had myocardial bridging diagnosed at coronary angiography.     

Myocardial bridging increases the risk of coronary spasm

BACKGROUND: Myocardial bridging (MB) has been associated with cardiac events. Whether coronary spasm is one factor contributing to those events is unknown. HYPOTHESIS: This study investigated whether the likelihood of coronary spasm is increased in patients with MB. METHODS: A spasm-provocation test was performed by infusing acetylcholine into the left coronary artery in 114 Japanese patients with chest pain. The test result was defined as positive when the diameter of the coronary artery was reduced by > or = 50% and ST-segment changes were documented. Myocardial bridging was defined as a > 15% reduction in coronary arterial diameter during systole after intracoronary injection of nitroglycerin. RESULTS: Myocardial bridging was identified in 41 patients (36%) and was located in the mid-segment of the left anterior descending coronary artery (LAD) in all patients. Patients with MB experienced coronary spasm more frequently than patients without MB (MB+: 73%; MB-: 40%, p = 0.0006). Furthermore, among patients with a positive spasm-provocation test, coronary spasm occurred more frequently in the mid-segment of the LAD in patients with MB than in those without MB (MB+: 73%; MB-: 45%, p = 0.0259). Multivariate regression analysis demonstrated that MB was a predictor of coronary spasm (odds ratio: 3.478, p = 0.0088). CONCLUSIONS: These results suggest that MB increases the risk of coronary spasm and that coronary spasm may be the proximate etiology of cardiac events associated with MB.     

Transient myocardial perfusion abnormalities during cold provocation test in patients with arterial hyperreactivity.

The effect of peripheral cold provocation on myocardial perfusion was evaluated utilizing thallium-201 perfusion imaging in 13 selected patients with arterial hyperreactivity (Raynaud's phenomenon: n = 8; migraine: n = 6) and angiographically documented coronary artery spasm. Eleven out of 13 subjects with coronary arterial spasm--but none of a group of patients with obstructive coronary artery disease--had transient myocardial perfusion defects during cold provocation. The localization of transient perfusion abnormalities during myocardial scintigraphy correlated with the myocardial areas distal to the spontaneous or ergonovine-induced coronary arterial spasm detected by angiography. Transient reduction of tracer uptake during cold provocation and normalization of myocardial perfusion by redistribution imaging was paralleled by areas of hypokinesia observed during the test by contrast ventriculography (n = 8). The described findings in the coronary system during peripheral cold pressor test occurred independently of the presence of Raynaud's phenomenon, and without achieving the ischemic threshold.     

Association between urokinase gene 3'-UTR T/C polymorphism and Chinese patients with rheumatoid arthritis in Taiwan

OBJECTIVES: The purpose of this study was to investigate whether the urokinase gene 3'-UTR C/T polymorphism is a marker of susceptibility to or severity of rheumatoid arthritis (RA) in Chinese patients. METHODS: A total of 145 RA patients and 134 healthy control subjects were enrolled in this study. We identified the C/T polymorphism of the urokinase gene, which is mapped on the 3'-untranslated region (3'-UTR) on chromosome 10 by polymerase chain reaction (PCR). RESULTS: There were significant differences in the distribution of the urokinase gene 3'-UTR C/T polymorphism frequency between RA patients and subjects in the control group. However, we did not detect an, association between the urokinase gene 3'-UTR C/T polymorphism and rheumatoid factor (RF), extraarticular involvement or bone erosion in RA patients. CONCLUSION: The urokinase gene 3'-UTR "T" allele was associated with RA in Chinese patients in Taiwan.