Risk Factor For Coronary Spasm Research Articles

Changes in the risk factors for coronary spasm

Changes in the risk factors for coronary spasm

Novel Roles for Kv7 Channels in Shaping Histamine-Induced Contractions and Bradykinin-Dependent Relaxations in Pig Coronary Arteries.

Voltage-gated Kv7 channels are inhibited by agonists of Gq-protein-coupled receptors, such as histamine. Recent works have provided evidence that inhibition of vascular Kv7 channels may trigger vessel contractions. In this study, we investigated how Kv7 activity modulates the histamine-induced contractions in “healthy” and metabolic syndrome (MetS) pig right coronary arteries (CAs). We performed isometric tension and immunohistochemical studies with domestic, lean Ossabaw, and MetS Ossabaw pig CAs. We found that neither the Kv7.2/Kv7.4/Kv7.5 activator ML213 nor the general Kv7 inhibitor XE991 altered the tension of CA rings under preload, indicating that vascular Kv7 channels are likely inactive in the preloaded rings. Conversely, ML213 potently dilated histamine-pre-contracted CAs, suggesting that Kv7 channels are activated during histamine applications and yet partially inhibited by histamine. Immunohistochemistry analysis revealed strong Kv7.4 immunostaining in the medial and intimal layers of the CA wall, whereas Kv7.5 immunostaining intensity was strong in the intimal but weak in the medial layers. The medial Kv7 immunostaining was significantly weaker in MetS Ossabaw CAs as compared to lean Ossabaw or domestic CAs. Consistently, histamine-pre-contracted MetS Ossabaw CAs exhibited attenuated ML213-dependent dilations. In domestic pig CAs, where medial Kv7 immunostaining intensity was stronger, histamine-induced contractions spontaneously decayed to ~31% of the peak amplitude within 4 minutes. Oppositely, in Ossabaw CAs, where Kv7 immunostaining intensity was weaker, the histamine-induced contractions were more sustained. XE991 pretreatment significantly slowed the decay rate of histamine-induced contractions in domestic CAs, supporting the hypothesis that increased Kv7 activity correlates with a faster rate of histamine-induced contraction decay. Alternatively, XE991 significantly decreased the amplitude of bradykinin-dependent dilations in pre-contracted CAs. We propose that in CAs, a decreased expression or a loss of function of Kv7 channels may lead to sustained histamine-induced contractions and reduced endothelium-dependent relaxation, both risk factors for coronary spasm.

Differences and interactions between risk factors for coronary spasm and atherosclerosis--smoking, aging, inflammation, and blood pressure.

Objective Coronary spasm as well as atherosclerosis plays an important role in the pathogenesis of coronary heart disease. However, the relationship between coronary spasm and atherosclerosis is not well known. The purpose of the present study was to examine the differences and interactions between risk factors for coronary spasm and atherosclerosis and thereby explore the pathogenesis of coronary spasm. Methods The study subjects consisted of 938 patients with chest discomfort (522 men and 416 women, mean age 65.2±11.0) who underwent intracoronary-acetylcholine provocation tests for coronary spasm. Coronary risk factors, including age, gender, body mass index, blood pressure, high-sensitivity C-reactive protein (hsCRP), white blood cells, glucose, lipid profiles, and other laboratory chemistries were examined. Results Four hundred and ninety-six patients (315 men and 181 women, mean age: 65.1±11.4) were diagnosed with coronary spastic angina (CSA), while the remaining 442 patients (207 men and 235 women, mean age: 65.3±10.7) were diagnosed with non-CSA. A multiple logistic regression analysis revealed men, smoking, hsCRP, and low diastolic blood pressure (DBP) to be predictors (p=0.001, p=0.009, p=0.034, and p=0.041, respectively) for CSA, while age, diabetes mellitus, low high-density lipoprotein-cholesterol, systolic blood pressure (SBP), uric acid and male gender were found to be predictors (p<0.001, p<0.001, p<0.001, p=0.002, p=0.006 and p=0.029, respectively) for atherosclerosis. Conclusion Predictors for coronary spasm were smoking, hsCRP and low DBP, whereas those for atherosclerosis were age, diabetes mellitus, high SBP, and uric acid in that order. These findings suggest that the pathogenesis of coronary spasm differs from that of atherosclerosis.

Recurrent acute coronary syndrome due to coronary artery spasm in different coronary arteries

Coronary artery spasm (CAS) plays an important role in the pathogenesis of a wide variety of ischemic heart diseases. Several case reports have shown that CAS due to hypocalcemia can mimic myocardial infarction. However, in all these cases there were coexisting electrolyte abnormalities or other medical conditions that are risk factors for coronary spasm. We describe recurrent acute coronary syndrome in an otherwise healthy young woman without cardiac risk factors caused by coronary spasms, alternatively occurring in all three major coronary arteries.<Learning objective: Isolated hypocalcemia may cause acute coronary artery spasm, leading to recurrent acute coronary syndrome. This unusual cause of recurrent acute coronary syndrome occurred in a young, otherwise healthy female with no risk factors for coronary artery diseases. Medical treatment would resolve the spasm in the large majority of the patients. However, in patients having medically resistant vasospasm, mechanical revascularization may be an option.>

Lack of Association of NOS3 and ACE Gene Polymorphisms with Coronary Artery Disease in Southern Tunisia

-arginine and molecular oxygen in vascular endothelial cells (Kincl et al.2009). Angiotensin-converting enzyme (ACE), present on the surface of vascularendothelial cells, generates the potent vasoconstrictor angiotensin II from angio-tensin I and inactivates the vasodilator bradykinin (Erdo¨s 1990). Angiotensin IImodulates NO synthesis in cardiovascular tissue, and NO modulates the action ofangiotensin II (Dubey et al. 1995; Nakagami et al. 1999). Many polymorphismslocated in the ACE and NOS3 genes have been reported to play a major role in thepathogenesis of coronary artery disease (CAD) and related outcomes (Cambienet al. 1992; Yoshimura et al. 2000; Bor-Kucukatay et al. 2010; Hamelin et al. 2011).The -T786C polymorphism in the NOS3 gene causes a reduction of promoteractivity and has been reported as a risk factor for coronary spasm in a Japanesepopulation (Nakayama et al. 1999). The Glu298Asp polymorphism has been

A Delta-Sarcoglycan Gene Polymorphism as a Risk Factor for Hypertrophic Cardiomyopathy

The C allele of c.-94C>G polymorphism of the delta-sarcoglycan gene was associated as a risk factor for coronary spasm in Japanese patients with hypertrophic cardiomyopathy (HCM). We evaluated whether the c.-94C>G polymorphism can be a risk factor for HCM in Mexican patients. The polymorphism was genotyped and the risk was estimated in 35 HCM patients and 145 healthy unrelated individuals. Data of this polymorphism reported in Mexican Amerindian populations were included. The C allele frequency in HCM patients was higher with an odds ratio (OR) of 2.37, and the risk for the CC genotype increased to 5.0. The analysis with Mexican Amerindian populations showed that the C allele frequency was significantly higher in HCM patients with an OR of 2.96 and for CC genotype the risk increased to 7.60. The C allele of the c.-94C>G polymorphism is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients.

Coronary artery spasm—Clinical features, diagnosis, pathogenesis, and treatment

Coronary (artery) spasm plays an important role in the pathogenesis of ischemic heart disease, including stable angina, unstable angina, myocardial infarction, and sudden death. The prevalence of coronary spasm differs among populations, is higher in Japan and Korea than in the Western countries probably due to genetic as well as environmental factors. Coronary spasm occurs most often from midnight to early morning and is usually not induced by exercise in the daytime. The attacks of coronary spasm are associated with either ST segment elevation or depression, or negative U wave on ECG. Patients with multi-vessel coronary spasm may suffer from lethal arrhythmia, including advanced AV block, ventricular tachycardia or fibrillation, or even sudden death, and they are often resistant to conventional medical therapy including Ca-channel blockers (CCBs). Endothelial nitric oxide (NO) activity is reduced and markers of oxidative stress are elevated in patients with coronary spasm. Thrombogenesis is enhanced and plasma levels of hsCRP and P-selection are elevated in patients with coronary spasm. Thus, patients with coronary spasm have endothelial dysfunction and are suffering from a low-grade chronic inflammation. Polymorphisms of endothelial NO synthase, smoking, and low-grade inflammation are the most important risk factors for coronary spasm. Coronary spasm is a hyper-contraction of coronary smooth muscle triggered by an increase of intracellular Ca2+ in the presence of an increased Ca2+ sensitivity. It has been shown that RhoA/ROCK pathway is involved in Ca2+ sensitivity and that the reduced endothelial NO activity results in increased Ca2+ sensitivity through enhanced RhoA/ROCK pathway. Accordingly, it is possible that in addition to CCBs, RhoA/ROCK pathway blockers may prove to be useful for the treatment of coronary spasm.

Impact of Delta-Sarcoglycan Gene Polymorphism on the Occurrence of Coronary Spastic Angina in Japanese Patients With Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy (HCM) frequently complain of angina-like symptoms in the absence of organic coronary stenoses. Coronary spasm might cause myocardial ischemia in HCM patients. Delta-sarcoglycan plays a crucial role in the pathogenesis of HCM and coronary spasm in a mouse model. This is a retrospective, single-center study with a small sample size. Seventy patients with HCM underwent coronary angiography and received acetylcholine provocation test. Coronary risk factors and 5'-untranslated region (UTR) G to C polymorphism on delta-sarcoglycan gene (n=64) were evaluated in the HCM patients. In 31 (44.3%) of 70 HCM patients, coronary spasm was induced by the provocation. None of the coronary risk factors was significantly different between the coronary spasm group and the non-coronary spasm group. The 5'-UTR gene polymorphism was associated with the occurrence of coronary spasm with an additive effect on the coexistence (p=0.025). Multiple logistic regression analysis showed that the C allele of 5'-UTR polymorphism was a significant risk factor for coronary spasm in patients with HCM (odds ratio, 3.1; 95% confidence interval, 1.0 to 9.5; p=0.045) that was independent of traditional coronary risk factors. The 5'-UTR polymorphism on delta-sarcoglycan gene was associated with coronary spasm in Japanese patients with HCM.

C-Reactive Protein Cutoff Point as a Risk Factor for Coronary Spasm

C-Reactive Protein Cutoff Point as a Risk Factor for Coronary Spasm

Comparison of the risk factors for coronary artery spasm with those for organic stenosis in a Japanese population: role of cigarette smoking

We compared the risk factors for coronary spasm with those for coronary atherosclerosis in 183 patients with coronary spasm, 132 patients with coronary organic stenosis, and 224 control subjects with chest pain syndrome. Our findings confirmed that, when compared with controls, age, gender, total cholesterol, LDL-cholesterol, hypertension, diabetes mellitus, and cigarette smoking are all significant risk factors for coronary organic stenosis. On the other hand, only cigarette smoking proved to be a significant risk factor for coronary spasm. Also, when compared between coronary spasm group and coronary organic stenosis group, the incidence of cigarette smoking in males was significantly higher in the coronary spasm group than in the coronary organic stenosis group. We conclude that cigarette smoking is a crucial risk factor for coronary spasm. On the other hand, serum lipid levels and the incidence of hypertension and diabetes mellitus were within the normal ranges in the coronary spasm patients and were thus poorly associated with coronary spasm. These results showed that the risk factors for coronary spasm differ significantly from those for atherosclerosis-based coronary stenosis in the Japanese. Among the risk factors for coronary atherosclerosis (organic stenosis) smoking alone was a significant preventable risk factor for coronary artery spasm.

49-Year-Old Woman With Chest Pain

49-Year-Old Woman With Chest Pain

T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm.

Coronary spasm plays an important role in the pathogenesis of ischemic heart diseases in general. However, the precise mechanism(s) responsible for coronary spasm remains to be elucidated, and we examined the molecular genetics of coronary spasm. We searched for the possible mutations in the endothelial nitric oxide synthase (eNOS) gene in patients with coronary spasm. In this study, we demonstrate the existence of 3 linked mutations in the 5'-flanking region of the eNOS gene (T-786-->C, A-922-->G, and T-1468-->A). The incidence of the mutations was significantly greater in patients with coronary spasm than in the control group (P<0.0001). Multiple logistic regression analysis with forward stepwise selection using the environmental risk factors and the eNOS gene variant revealed that the most predictive independent risk factor for coronary spasm was the mutant allele (P<0.0001). As assessed by luciferase reporter gene assays, the T-786-->C mutation resulted in a significant reduction in eNOS gene promoter activity (P<0.05), whereas neither the A-922-->G nor the T-1468-->A mutation had any affect. Taken together, these findings strongly suggest that the T-786-->C mutation in the eNOS gene reduces the endothelial NO synthesis and predisposes the patients with the mutation to coronary spasm.

Coronary Spasm: Clinical Features and Pathogenesis.

Coronary artery spasm (coronary spasm) is an abnormal contraction of an epicardial coronary artery resulting in myocardial ischemia and its incidence is relatively high in Japanese as compared with Caucasians. Coronary spasm occurs most often from midnight to early morning when the patient is at rest and it is usually not induced by exercise in the daytime. Coronary spasm can be induced by acetylcholine, an endothelium-dependent vasodilator which causes vasodilatation in the normal coronary artery. Spasm artery is hyperresponsive to the vasodilator effect of nitroglycerin, an nitric oxide (NO) donor and is deficient in NO activity. The major risk factor for coronary spasm is cigarette smoking. Coronary spasm can be a cause of not only variant angina but also ischemic heart disease in general, including unstable angina, acute myocardial infarction and sudden ischemic death.

Eosinophil — Mediated immunological mechanism and inflammation in vasospastic angina — Novel coronary risk factor for coronary spasm —

Eosinophil — Mediated immunological mechanism and inflammation in vasospastic angina — Novel coronary risk factor for coronary spasm —

Cigarette smoking is a major risk factor for coronary spasm.

Although there have been many studies on the risk factors for coronary artery disease, the etiology of coronary artery spasm has not yet been determined. After diagnosis by coronary arteriography, various risk factors were compared between two groups of subjects using logistic regression analysis. The vasospasm group included 175 patients with angiographically determined coronary artery spasm but no coronary artery narrowing exceeding 25% of the luminal diameter. The control group comprised 176 subjects with completely normal coronary arteries and a negative response to ergonovine maleate. The adjusted odds ratio and 95% confidence interval for smoking as a risk factor for vasospasm was 2.41 and 1.53-3.82, respectively (p < 0.05). The adjusted odds ratios for total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, diabetes mellitus, and body mass index, calculated by multivariate logistic regression analysis, were not statistically nonsignificant. Smoking appears to be a major risk factor for vasospastic angina without significant coronary narrowing. The other risk factors for coronary artery disease may not contribute to coronary vasospasm.

Smoking is a risk factor for coronary spasm in young women.

Risk factors for pure coronary spasm are not known. Clinical observations have pointed to cigarette smoking, a known risk factor for obstructive coronary artery disease. We conducted a case-neighborhood control study of premenopausal women, a population segment with the lowest prevalence of obstructive coronary artery disease. The cases were 21 premenopausal women (age range, 36-41 years) with angiographically proven coronary spasm. All coronary arteriograms were analyzed by two independent experienced cardiologists on two occasions. There were no differences between analyses; all cases had normal baseline coronary angiogram except for two, who had less than 20% coronary luminal stenosis in segments other than the site of the focal vasospasm. All cases had normal hemodynamics at rest, normal left ventricular function, and were in sinus rhythm. Ascertainment of the cases was done by angiographic demonstration of focal coronary spasm spontaneously or by ergonovine provocation. Six cases developed spontaneous coronary spasm before catheter engagement, and in 15, coronary spasm was induced by ergonovine provocation. Each case was asked to name as many as possible female neighborhood acquaintances of similar age and racial background who were willing to answer the same standardized questionnaire. The same standardized questionnaire was completed for each case and each control (n = 63). The standardized questionnaire was designed to obtain information on health characteristics, habits, socioeconomic status, and education. Only cigarette smoking was significantly more prevalent among coronary spasm cases. Cigarette smokers were 13 cases (62%) and 11 controls (17.5%) (p less than 0.001). The odds ratio was 7.7, with a 95% confidence interval of 2.6-23.1. These findings suggest that there is a very strong association between cigarette smoking and pure coronary spasm in young women.