Hsueh-Wei Yen

Effect of Withdrawal of Statin on C-Reactive Protein

Background: C-reactive protein is considered a risk factor for coronary artery disease. In addition to its lipid-lowering properties, statin decreases the level of C-reactive protein. Abrupt cessation of statin therapy during treatment could increase the incidence of cardiac events in patients with atherosclerotic heart disease. The changes of C-reactive protein after withdrawal of statin therapy are still unknown. Methods: Twenty patients with hyperlipidemia received statin (atorvastatin, 10 mg/day) therapy for 3 months. The levels of lipid profiles and C-reactive protein were assessed before receiving the statin therapy, immediately after 3 months of therapy, and on the 3 consecutive days after withdrawal of statin treatment. Results: After 3 months of statin therapy, the total cholesterol, low-density lipoprotein cholesterol (LDL-chol), and C-reactive protein were significantly reduced (264.94 ± 16.23 vs. 183.44 ± 16.34 mg/dl, 183.17 ± 34.56 vs. 122.00 ± 17.66 mg/dl, and 2,309.00 ± 437.85 vs. 1,257.95 ± 207.99 ng/ml, respectively). The level of C-reactive protein increased on the second day after withdrawal of statin therapy (2,590.14 ± 1,045.05 vs. 1,257.95 ± 207.99 ng/ml); however, the total cholesterol and LDL-chol did not increase during the 3-day period after withdrawal of statin therapy. Conclusions: The increase in the level of C-reactive protein after withdrawal of statin therapy may be a contributing factor to the increased incidence of cardiac events in patients who have abruptly stopped statin therapy.

JNK/ATF2 pathway is involved in iodinated contrast media-induced apoptosis.

Background/Aims: Notably, activating transcriptional factor 2 (ATF2), a histone-modification gene, is involved in oxidative stress-induced apoptosis. The aim of this study was to clarify the role of ATF2 in contrast media-induced nephropathy. Methods: Human embryonic kidney 293T cells were treated with four different contrast media:ionic high-osmolar diatrizoate; ionic low-osmolar iothalamate; non-ionic low-osmolar iohexol, and non-ionic iso-osmolar iodixanol. The mRNA expression of ATF2 was determined by real-time PCR. Short interfering RNA was used to knock down ATF2 mRNA expression. Phosphorylation of ATF2 was measured by Western blotting. Wistar rats were administered either diatrizoate or a normal saline injection. Apoptosis in kidney tubular cells was determined by the presence of positive TUNEL stain. Results: Diatrizoate, iodixanol and iothalamate, but not iohexol, induced the expression of ATF2 mRNA and phosphorylation of ATF2 in 293T cells in a time-dependent manner. More apoptotic cells were in diatrizoate-treated kidney cells than in the saline injection group (p < 0.00001). Cell death was significantly increased by knockdown ATF2 expression in the presence of diatrizoate, indicating a protective role of ATF2 in contrast media-induced apoptosis. Conclusions: Differential activation of ATF2 by different contrast media provides a new insight into the mechanism and prevention of contrast-induced nephropathy.

Left Ventricular Tei Index: Comparison between Flow and Tissue Doppler Analyses

Background: It is still unknown whether a correlation exists between left ventricular Tei index obtained by tissue Doppler imaging and that determined by flow Doppler waveforms. This study was conducted to evaluate their relationship and to assess the positional effect on them. Methods: Twenty‐six healthy subjects and 25 patients with essential hypertension were included. On the tissue Doppler images, the time interval from the end to the onset of the mitral annular velocity pattern during diastole and the duration of the S‐wave were used to calculate tissue Doppler Tei index. Results: The tissue Doppler Tei index correlated with the flow Doppler Tei index at sitting position (r = 0.406, P = 0.003), but not at left lateral decubitus position. The limits of agreement for the Tei index measured by both methods were −0.26 to 0.62 at left lateral decubitus position and −0.09 to 0.55 at sitting position. Preload reduction associated with sitting position with dangling feet raised the Tei index both in the healthy controls [0.54 (0.14) vs 0.42 (0.12), P < 0.001] and in the hypertensives [0.53 (0.15) vs 0.46 (0.12), P = 0.005]. There was a similar positional effect on the tissue Doppler Tei index in the control subjects [0.75 (0.12) vs 0.53 (0.10), P < 0.001]. Conclusions: Tissue Doppler Tei index does not seem to be a suitable substitute for flow Doppler Tei index. Flow Doppler Tei index is preload dependent and the loading status should be taken into consideration at the application of Tei index to the evaluation of myocardial performance.

Impact of short-duration administration of N-acetylcysteine, probucol and ascorbic acid on contrast-induced cytotoxicity.

BACKGROUND The best pharmaceutical prevention of contrast-medium-induced nephropathy for emergency procedures remains unknown. The aim of this study was to examine the impact of short-duration antioxidant pretreatment on contrast-medium-induced cytotoxicity. METHODS Human embryonic kidney cells were treated with three different contrast media: ionic ioxitalamate, non-ionic low-osmolar iopromide, and iso-osmolar iodixanol. The doses and durations of pretreatment with antioxidants were 2 mM/L N-acetylcysteine for 15 minutes, 40 µM/L probucol for 30 minutes, and 30 µM/L ascorbic acid for 30 minutes. A supplementary dose of 2 mM/L N-acetylcysteine was administered 12 hours after contrast medium treatment. Cell viability was determined by tetrazolium MTT assay. RESULTS All three contrast media caused significant reduction of cell viability at 24 hours (p<0.001). In the groups receiving iopromide or iodixanol, N-acetylcysteine pretreatment significantly improved cell viability compared with no N-acetylcysteine pretreatment (p<0.001). In the group receiving ioxitalamate, N-acetylcysteine pretreatment followed by a supplementary dose of N-acetylcysteine at 12 hours rather than N-acetylcysteine pretreatment alone significantly improved cell viability compared with no N-acetylcysteine pretreatment (p=0.038). Probucol or ascorbic acid pretreatment was unable to reduce cell death caused by the three contrast media. CONCLUSIONS Short-duration pretreatment with N-acetylcysteine significantly reduced contrast-medium-induced cytotoxicity. These findings provide new insight into the prevention of contrast-medium-induced nephropathy in clinical emergency scenarios.

Chewing areca nut increases the risk of coronary artery disease in taiwanese men: a case-control study

BackgroundAreca nut chewing has been reported to be associated with obesity, metabolic syndrome, hypertension, and cardiovascular mortality in previous studies. The aim of this study was to examine whether chewing areca nut increases the risk of coronary artery disease (CAD) in Taiwanese men.MethodsThis study is a hospital-based case-control study. The case patients were male patients diagnosed in Taiwan between 1996 and 2009 as having a positive Treadmill exercise test or a positive finding on the Thallium-201 single-photon emission computed tomography myocardial perfusion imaging. The case patients were further evaluated by coronary angiography to confirm their CAD. Obstructive CAD was defined as a ≥ 50% decrease in the luminal diameter of one major coronary artery. The patients who did not fulfill the above criteria of obstructive CAD were excluded.The potential controls were males who visited the same hospital for health check-ups and had a normal electrocardiogram but no history of ischemic heart disease or CAD during the time period that the case patients were diagnosed. The eligible controls were randomly selected and frequency-matched with the case patients based on age. Multiple logistic regression analyses were used to estimate the odds ratio of areca nut chewing and the risk of obstructive CAD.ResultsA total of 293 obstructive CAD patients and 720 healthy controls, all men, were analyzed. Subjects who chewed areca nut had a 3.5-fold increased risk (95% CI = 2.0-6.2) of having obstructive CAD than those without, after adjusting for other significant covariates. The dose-response relationship of chewing areca nut and the risk of obstructive CAD was also noted. After adjusting for other covariates, the 2-way additive interactions for obstructive CAD risk were also significant between areca nut use and cigarette smoking, hypertension and dyslipidemia.ConclusionsLong-term areca nut chewing was an independent risk factor of obstructive CAD in Taiwanese men. Interactive effects between chewing areca nut and cigarette smoking, hypertension, and dyslipidemia were also observed for CAD risk. Further exploration of their underlying mechanisms is necessary.

Cardiovascular events in patients with atherothrombotic disease: a population-based longitudinal study in Taiwan.

Background Atherothrombotic diseases including cerebrovascular disease (CVD), coronary artery disease (CAD), and peripheral arterial disease (PAD), contribute to the major causes of death in the world. Although several studies showed the association between polyvascular disease and poor cardiovascular (CV) outcomes in Asian population, there was no large-scale study to validate this relationship in this population. Methods and Results This retrospective cohort study included patients with a diagnosis of CVD, CAD, or PAD from the database contained in the Taiwan National Health Insurance Bureau during 2001–2004. A total of 19954 patients were enrolled in this study. The atherothrombotic disease score was defined according to the number of atherothrombotic disease. The study endpoints included acute coronary syndrome (ACS), all strokes, vascular procedures, in hospital mortality, and so on. The event rate of ischemic stroke (18.2%) was higher than that of acute myocardial infarction (5.7%) in our patients (P = 0.0006). In the multivariate Cox regression analyses, the adjusted hazard ratios (HRs) of each increment of atherothrombotic disease score in predicting ACS, all strokes, vascular procedures, and in hospital mortality were 1.41, 1.66, 1.30, and 1.14, respectively (P≦0.0169). Conclusions This large population-based longitudinal study in patients with atherothrombotic disease demonstrated the risk of subsequent ischemic stroke was higher than that of subsequent AMI. In addition, the subsequent adverse CV events including ACS, all stroke, vascular procedures, and in hospital mortality were progressively increased as the increase of atherothrombotic disease score.

Ionic contrast media induced more apoptosis in diabetic kidney than nonionic contrast media

BACKGROUND Contrast-induced nephropathy is a major cause of hospital-acquired acute renal failure, and its risk is significantly increased in patients with diabetes mellitus. This study aimed to examine both the role of apoptosis in low-osmolar contrast media-induced kidney injury in normal and diabetic rats and the difference in the induced kidney injury between ionic and nonionic contrast media. METHODS Normal and streptozotocin-induced diabetic Wistar rats were administered with ionic low-osmolar ioxaglate, nonionic low-osmolar iopromide or normal saline injection. Apoptosis in kidney tubular cells was determined by the presence of positive terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end-labeling (TUNEL) stain. RESULTS At 24 hours after administration, both ioxaglate and iopromide injections induced more apoptosis in diabetic (49.7% vs. 25.3% for ioxaglate; 37.7% vs. 25.3% for iopromide; both p<0.001) and normal (36.2% vs. 27.4%, p=0.002, for ioxaglate; 33.6% vs. 27.4%, p=0.029, for iopromide) kidney tubular cells than normal saline injections. Additionally, ioxaglate induced more apoptotic tubular cells in diabetic kidneys than in normal kidneys (p<0.001). Moreover, ioxaglate significantly induced more apoptotic cells than iopromide in diabetic kidneys, but not in normal kidneys (p<0.001, for diabetic rats; p=0.345, for normal rats). CONCLUSION Ionic low-osmolar contrast media induced more apoptosis in tubular cells in diabetic kidneys than in normal kidneys. Notably, ionic contrast media induced more apoptosis than nonionic contrast media in diabetic kidneys.

Changes of coronary risk factors after eradication of Helicobacter pylori infection.

Several epidemiological studies have shown a positive correlation between chronic gastric infection with Helicobacter pylori (HP) and coronary artery disease. A number of reports also claimed that there are strong relationships between HP infection and coronary risk factors. However, clinical studies concerning the changes of coronary risk factors after eradication of HP infection are few and contradictory. We conducted a prospective study aiming to compare sugar, lipid and fibrinolytic profiles before HP eradication with those after HP eradication. HP infection was confirmed by endoscope-based examinations and eradicated by a standard OAC (omeperazole-amoxicillin-clarithromycin) regimen. We measured and compared pre- and post-eradication blood sugar, lipid profiles (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride) and fibrinolytic profiles (tissue-plasminogen activator, plasminogen activator inhibitor-1, fibrinogen, and D-dimer levels). Forty-eight patients (male:female, 25:23; mean age, 50.8 +/- 11.3 years) with gastric HP infection were enrolled in this study. Although HP infection was confirmed to have been successfully eradicated, no significant changes of blood fasting sugar, lipids or fibrinolytic profiles were found in patients after treatment. Coronary risk factors including fasting sugar, lipid and fibrinolytic profiles were not changed after successful HP eradication treatment. The relationship between HP infection and coronary artery disease needs to be clarified.

Effects of Different Contrast Media on Glutathione Peroxidase and Superoxide Dismutase Activities in the Heart and Kidneys of Normal and Streptozotocin-induced Diabetic Rats

BACKGROUND/PURPOSE Hemodynamic changes and contrast nephropathy are well known complications of contrast media injection. However, the mechanisms of toxicity leading to these complications remain unclear. We hypothesized that contrast media toxicity would manifest as a change in antioxidant enzyme activity, thus leading to tissue damage. METHODS This study investigated the effects of injection of ionic high-osmolar diatrizoate, ionic low-osmolar ioxaglate, and nonionic low-osmolar iopromide on the activities of two antioxidant enzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), in the heart and kidney tissue of normal male Wistar rats (n = 51) and streptozotocin (STZ)-induced diabetic rats (n = 54). Activities of GPX and SOD were assayed spectrophotometrically. RESULTS Renal GPX activities were significantly decreased in both normal (458.3 +/- 64.6 to 385.5 +/- 63.4 mU/mg, p = 0.005) and diabetic rats (669.0 +/- 98.1 vs. 564.0 +/- 153.3 mU/mg, p = 0.035) at 1 hour after diatrizoate injection. Renal SOD activities were not affected after contrast injection. Ioxaglate and iopromide injection did not cause any change in renal antioxidant enzyme activity. In contrast to kidney tissue, there was no significant change in GPX and SOD activities in heart tissue at 1 hour after injection of different contrast media. CONCLUSION Intravenous injection of ionic high-osmolar diatrizoate reduced renal GPX activity during the first hour in both normal and STZ-induced diabetic rats. Heart tissue was not prone to antioxidant enzyme activity changes after intravenous contrast media injection. GPX activity reduction can be an important mechanism of nephrotoxicity after contrast media injection.

The effect of fluvastatin on fibrinolytic factors in patients with hypercholesterolemia.

Several studies have shown cardiovascular benefit in treating hypercholesterolemia with HMG-CoA reductase inhibitor. However, in addition to the lowering of cholesterol, the beneficial effects of this inhibitor reflect other pharmacological activities. Whether these beneficial effects are partly mediated by changes in fibrinolytic factors remains to be proven, since clinical studies on the effects of HMG-CoA reductase inhibitors on fibrinolytic factors have not yielded consistent results. The purpose of this study was to evaluate the effects of fluvastatin on fibrinolytic factors in hypercholesterolemic patients. After 6 weeks on a low-fat, low-cholesterol diet, 23 outpatients known to have primary hypercholesterolemia with low density lipoprotein cholesterol (LDL-C) > or = 130 mg/dl with at least 2 risk factors or fasting LDL-C > or = 160 mg/dl were selected for the study. Venous blood samples were collected at baseline and at 8 weeks after fluvastatin therapy (40 mg/day) to measure of tissue plasminogen activator (t-PA), plasminogen activators inhibitor-1 (PAI-1), fibrinogen, D-dimer and lipid profile. After 8 weeks of therapy, fluvastatin reduced serum cholesterol by 11% (261.9 mg/dl vs 233.2 mg/dl, P < 0.01) and LDL-C by 22% (191.9 mg/dl vs 149.3 mg/dl, P < 0.01). D-dimer was significantly decreased (0.38 ng/L vs 0.28 ng/L, P = 0.02) and tPA, PAI-1 and fibrinogen tended to decrease after therapy. Fluvastatin therapy improved fibrinolytic profile; the result of this study may in part explain the benefit of HMG-CoA reductase inhibitor on cardiovascular system other than lipid lowering.