Gi Soo Park

Effects of statin on plaque stability and thrombogenicity in hypercholesterolemic patients with coronary artery disease

OBJECTIVE Plaque stability and thrombogenicity contribute to development and clinical expression of atherosclerosis. Experimental studies have shown that lipoproteins or mevalonate regulate matrix metalloproteinase (MMP)-9, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1) expression, providing nonlipid mechanism. METHODS We administered simvastatin 20 mg daily during 14 weeks to 32 hypercholesterolemic patients with coronary artery disease. RESULTS Compared with pretreatment values, simvastatin significantly lowered lipoprotein levels (all P<0.01). Compared with pretreatment values, simvastatin significantly lowered plasma levels of MMP-9, TF, and PAI-1 (P=0.009, P=0.032, and P=0.007, respectively). There were significant inverse correlations between pretreatment MMP-9, TF activity or PAI-1 antigen and the degree of change in those levels after simvastatin (r=-0.793, P<0.001; r=-0.482, P=0.005 and r=-0.590, P<0.001, respectively). Of interest, there were significant correlation between pretreatment or percent changes in MMP-9 levels and pretreatment or percent changes in PAI-1 antigen (r=0.293, P=0.019 and r=0.375, P=0.034, respectively). However, no significant correlations between lipoprotein levels and levels of plaque stability or thrombogenicity markers were determined. CONCLUSIONS Reduction of plaque stability and thrombogenicity markers with statin may contribute to the cardiovascular event reduction and explain the early clinical benefit in clinical trials, independent of lipoprotein changes.

Comparative study of efficacy and safety of low-dose diltiazem or betaxolol in combination with digoxin to control ventricular rate in chronic atrial fibrillation: randomized crossover study

BACKGROUND The combination therapy of low-dose diltiazem or bexatolol with digoxin can be a useful adjunct for achieving heart rate control with minimal side effects. But there has not been a study including patients with impaired left ventricular function and evaluating whether the beneficial effects of medication will be maintained during a follow-up period. OBJECTIVES The purpose of this study was three-fold: (1) to compare the efficacy of digoxin with low-dose diltiazem and digoxin with low-dose betaxolol on randomized crossover study; (2) to evaluate whether the beneficial effects of medication will be maintained after 7 months; (3) to evaluate the safety of the combination therapy in patients with impaired left ventricular function. METHODS We did a prospective randomized crossover study in 35 patients with chronic atrial fibrillation (AF) including 15 patients with left ventricular dysfunction. After enrollment, each patient was evaluated for heart rate, blood pressure, rate-pressure products, maximal exercise tolerance at rest and during symptom-limited treadmill test before medication, at 4 weeks after medication of digoxin (0.125-0.5 mg daily) with diltiazem (90 mg twice daily), and at 4 weeks after digoxin with betaxolol (20 mg once daily). We performed 24-h ambulatory electrocardiogram (ECG) in 15 patients at the end of each phase of treatment. We repeated symptom-limited treadmill test like above method in 15 patients at 7 months of medication. RESULTS (1) Ventricular rates were significantly reduced in digoxin with low-dose betaxolol therapy at rest and during exercise (67 +/- 3, 135 +/- 5 (mean +/- S.E.M.) beats/min, respectively) in comparison to digoxin with low-dose diltiazem therapy (80 +/- 7, 154 +/- 5) (P < 0.05). (2) Rate-pressure products were significantly less in digoxin with low-dose betaxolol at rest and during exercise (85 +/- 4, 213 +/- 12 x 10(2) mmHg/min) than in digoxin with low-dose diltiazem therapy (105 +/- 6, 269 +/- 12) (P < 0.05). (3) Exercise capacity was significantly improved in digoxin with low-dose betaxolol (9.3 +/- 0.5 METS) or digoxin with low-dose diltiazem (9.7 +/- 0.5) in comparison to control state (8.3 +/- 0.5) (P < 0.05). (4) At 7 months evaluation, there was no significant difference between at 4 weeks and at 7 months. (5) Results on 24-h ambulatory ECG showed the same findings as on treadmill test. (6) Although side effects occurred more frequently in digoxin with low-dose betaxolol therapy, they were minimal and no patient had to withdraw medication. Worsening of left ventricular dysfunction was not observed. CONCLUSION Our study suggested that (1) combination therapy of low-dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin in controlling ventricular rate and reducing rate-pressure products; (2) the effects controlling ventricular rate, reducing rate-pressure products and improving exercise capacity have been well maintained even after 7 months of medication with each combination therapy.

Effects of hormone replacement therapy on plaque stability, inflammation, and fibrinolysis in hypertensive or overweight postmenopausal women ☆

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Non-lipid effects of statin on hypercholesterolemic patients established to have coronary artery disease who remained hypercholesterolemic while eating a step-II diet.

BackgroundResults of clinical trials of statin therapy demonstrate that an improvement in incidence of cardiovascular end points and coronary stenosis can be achieved. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that affect endothelial function, such as inflammatory responses, formation of thrombi, and stabilization of plaque. ObjectiveTo investigate levels of serologic markers, which may be useful surrogates for activity of vascular disease after administration of statin. MethodsWe administered 20–40 mg simvastatin daily for 14 weeks to 13 patients established to have coronary artery disease who remained hypercholesterolemic during step‐II diet therapy. ResultsAdministration of simvastatin significantly lowered lipoprotein levels and the low : high‐density lipoprotein cholesterol level ratio and apolipoprotein B : A‐I level ratio compared with pretreatment values (P  < 0.01). Administration of simvastatin significantly lowered plasma levels of matrix metalloproteinase‐9 (MMP‐9) and monocyte chemoattractant protein‐I [33 ± 46 and 13 ± 19%, respectively (P  = 0.027 and 0.020, respectively)]. Furthermore, administration of simvastatin tended to lower plasma levels of plasminogen activator inhibitor type‐1 and tumor necrosis factor‐α [by 20 ± 44 and 13 ± 29%, respectively (P  = 0.066 and 0.110, respectively)]. There were significant inverse correlations between pretreatment levels of MMP‐9 and the degree of change in those levels after administration of simvastatin (r  = –0.714, P  = 0.005). However, there was no significant correlation between levels of lipoprotein and levels of MMP‐9, monocyte chemoattractant protein‐I, and plasminogen activator inhibitor type‐1 during administration of simvastatin. ConclusionsOur current data support the hypothesis that nonlipid mechanisms elicited by administration of simvastatin contribute to the decrease in incidence of cardiovascular events and explain the early clinical benefit observed in clinical trials, independent of changes in levels of lipoprotein.

Comparison of clinical and laboratory findings between patients with diffuse three-vessel coronary artery spasm and other types of coronary artery spasm.

Our purpose was to compare patients with diffuse three-vessel coronary artery spasm and other types of coronary artery spasm without significant organic stenosis, and to elucidate clinical characteristics and risk factors. Patients were divided into two groups: group I consisted of 26 patients showing other types of coronary artery spasm; group II consisted of 5 patients with diffuse three-vessel coronary artery spasm. The mean age of patients in groups I and II was 52 and 50 years, respectively. The incidence of variant angina was higher in men than in women. The incidence of smoking was high in each group, but not significantly different. Exercise tests showed no significant differences between groups. All mean values of laboratory data, including lipoprotein (a) and low-density lipoprotein cholesterol in the two groups, were within normal ranges. There was no significant difference between groups. The incidence of spontaneous spam was much higher in patients with diffuse three-vessel coronary artery spasm (P < 0.01). Electrocardiographic (ECG) findings before the spasm were almost normal. All 5 patients with diffuse three-vessel coronary artery spasm demonstrated no important ST segment changes with episodes of angina during a coronary angiography on 12-lead ECG, compared to patients with other types of coronary artery spasm (P < 0.01). First, we conclude, diffuse three-vessel coronary artery spasm mostly occurs spontaneously. Second, we emphasize that diffuse three-vessel coronary artery spasm must be considered when 12-lead ECG shows no important ST segment changes with episodes of angina. Third, it is not easy to distinguish diffuse three-vessel coronary artery spasm from other types of coronary artery spasm on the basis of history, laboratory data, or electrocardiographic findings, including exercise tests.

Variant Aangina Diagnosed by Beta-Blocker Provocation Test and a Case of Subendocardial inFarction Induced by This Test

The provocation test of variant angina are known as ergonovine test, hyperventilation, acetylcholine, exercise and cold pressor test, but beta-blocker provocation test has not been reported as a case. So, this paper reports on the diagnosis of variant angina by beta-blocker provocation test and the case of subendocardial infarction induced by this test. This study reports with literature and investigation about the following case: A 45-year-old man with a history of recurrent episode of typical angina on the early morning for the past 20 days. He was administrated beta-blocker given by oral route, and on the next morning there was chest pain as same degree as before, Holter EKG displayed ST segment elevation and ventricular tachycardia. It was confirmed focal spasm on coronary angiography, ST segment elevation on EKG, and newly developed hypokinesia on left ventriculogram and followed-up echocardiography. When the chest pain is absent, EKG was normal. And we confirmed that the elevation of cardiac enzyme was absent as a result of serial follow up study.