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.

Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers.

OBJECTIVES: The purpose of this study was to determine whether a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) suppresses coronary spasm. BACKGROUND: Coronary spasm is associated with endothelial dysfunction. Statins have been shown to improve endothelial function. METHODS: This was a prospective, randomized, open-label, end point study. Sixty-four patients who had no significant organic coronary stenosis and in whom coronary spasm was induced by intracoronary injection of acetylcholine (ACh) were randomly assigned to fluvastatin 30 mg/day plus the conventional calcium-channel blocker (CCB) therapy (31 patients, statin group) or the conventional CCB therapy (33 patients, nonstatin group). After 6 months of treatment, the intracoronary injection of ACh was repeated and the coronary spasm was assessed. RESULTS: Coronary spasm was suppressed in 16 of the 31 patients (51.5%, p < 0.0001) of the statin group and in 7 of the 33 patients (21.2%, p = 0.0110) of the nonstatin group after 6 months of treatment. Thus, the number of patients with ACh-induced coronary spasm was significantly reduced in the statin group as compared with the nonstatin group (51.6% vs. 21.2%, p = 0.0231) after 6 months of treatment. CONCLUSIONS: The addition of fluvastatin 30 mg/day to the conventional CCB therapy for 6 months significantly reduced the number of patients with ACh-induced coronary spasm as compared with the conventional CCB therapy. Thus, a statin (fluvastatin) may possibly be a novel therapeutic drug for coronary 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.

Severe hypokalemia, rhabdomyolysis, muscle paralysis, and respiratory impairment in a hypertensive patient taking herbal medicines containing licorice.

A 93 year-old hypertensive woman was found to have severe hypokalemia (as low as 1.3 mEq/L) and developed paralysis of the all extremities associated with metabolic alkalosis, hypoxemia, hypercapnea, extremely high levels of creatine phosphokinase (up to 9280 U/L), myoglobin and myoglobinuria compatible with rhabdomyolysis. Plasma renin activity and aldosterone levels were below normal. She was found to have been taking licorice-containing herbal medicines for the last 7 years. With the discontinuation of the licorice-containing medicines and administration of spironolactone together with intravenous and oral potassium supplement, her serum potassium level was normalized and her clinical symptoms and hypertension improved within 2 weeks.

Low-grade inflammation, thrombogenicity, and atherogenic lipid profile in cigarette smokers.

BACKGROUND: Cigarette smoking is one of the major risk factors for atherosclerotic coronary disease, but the precise mechanism(s) by which cigarette smoking promotes atherosclerosis remains unknown. As there is now increasing evidence that atherosclerosis is an inflammatory condition, the present study investigated whether inflammation exists in smokers. METHODS AND RESULTS: The inflammatory markers and lipid profiles were compared among a current-smoker group (210 patients, mean age 61.8 +/- 11.0 years), past-smoker group (115 patients, 67.1 +/- 9.0 years) and never-smoked group (113 patients, 68.2 +/- 10.7 years), all of whom had no apparent signs of inflammation. The respective levels of blood leukocytes, platelets, C-reactive protein and fibrinogen were significantly higher in current-smokers than in the never-smoked group (6,600 +/- 1,723 /microl vs 5,638 +/- 1,313 /microl p<0.01; 22.7 +/- 6.8 x 10(4) /microl vs 18.7 +/- 7.4 x 10(4) /microl, p<0.01; 3.50+/-4.91 mg/L vs 1.92+/-3.02 mg/L, p<0.01; 334.2 +/- 90.9 mg/dl vs 314.7 +/- 80.2 mg/dl, p<0.05). The respective levels of plasma triglycerides, remnant-like particle cholesterol and apolipoprotein-B were significantly higher and that of high-density lipoprotein cholesterol significantly lower in the current-smokers than in the never-smoked group (152.4 +/- 96.2 mg/dl vs 120.5 +/- 58.1 mg/dl, p<0.01; 5.4+/-6.3 mg/dl vs 3.8 +/- 2.0 mg/dl, p<0.05; 101.6 +/- 23.7 mg/dl vs 95.0 +/- 21.2 mg/dl, p<0.05; 45.2 +/- 12.3 mg/dl vs 50.6 +/- 15.6 mg/dl, p<0.01). Past smokers had intermediate values between those of current-smokers and never-smoked. CONCLUSIONS: Low-grade inflammation, atherogenic dyslipidemia, and hypercoagulability are present in smokers compared with those who have never smoked among subjects without apparent inflammation who underwent coronary angiography on suspicion of coronary artery disease.