Chih-Lu Han

Serum uric acid as an independent predictor of mortality in high-risk patients with obstructive coronary artery disease: A prospective observational cohort study from the ET-CHD registry, 1997–2003

BACKGROUND Serum uric acid (SUA) has been observed to be highly associated with the development of cardiovascular disease for more than 50 years. Several studies have reported elevated SUA as an independent predictor of mortality in patients with coronary artery disease (CAD) after adjustment for classic risk factors but some studies did not find similar results. METHODS Between January 1997 and December 2003, a prospective cohort study was performed in 1054 patients with angiographically defined CAD, and their classic risk factors and SUA levels were determined at enrollment. The study cohort was followed for an average of 3.2 years, with a median of 3.1 years. The main outcome measure was death from cardiac disease and any cause. RESULTS Of all study patients, 789 (74.9%) were men and 265 (25.1%) were women. The mean age of the male and female patients was 64.8 and 66.9 years, respectively. The mean SUA level of all patients was 410.4 μmol/L. There were grading effects of SUA quartiles on cardiac and all-cause mortality in univariate and multivariate Cox regression analyses. After adjustment, the multivariate analyses revealed that patients in the highest SUA quartile (>487 μmol/L) had 2.08 (95% CI=1.19-3.62, p=0.01) fold increased risk of cardiac death, and 1.68 (95% CI=1.10-2.57, p=0.017) fold increase risk of overall mortality compared with the lowest quartile (<315 μmol/L). CONCLUSIONS SUA may be a significant predictor of cardiac and overall mortality, independent of classic risk factors in high-risk patients with obstructive CAD.

Relation of body mass index to mortality among patients with percutaneous coronary intervention longer than 5 years follow-up: A meta-analysis

percutaneous coronary intervention longer than 5 years follow-up: A meta-analysis Yi-Hwei Li ⁎, Gen-Min Lin ⁎, Chin-Lon Lin , Ji-Hung Wang , Chih-Lu Han d a Department of Public Health, Tzu-Chi University, Hualien, Taiwan b Department of Medicine, Hualien Armed Forces General Hospital, Hualien, Taiwan c Division of Cardiology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan d Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Relation of serum uric acid and body mass index to mortality in high-risk patients with established coronary artery disease: a report from the ET-CHD registry, 1997-2006.

BACKGROUND Hyperuricemia is associated with a higher risk of death in patients with coronary artery disease (CAD). In contrast, overweight or obesity was associated with survival benefits in this population. However, the relation of body mass index (BMI) and serum uric acid (SUA) to mortality has not been clarified in this population. METHODS We studied a cohort of 1202 patients with angiographic CAD from the ET-CHD registry during 1997-2003 in Taiwan. To evaluate the relation of BMI and SUA on mortality, the subjects were categorized into 4 groups by BMI >/= 25 kg/m(2) (overweight or obesity) or BMI<25 kg/m(2) (normal- or under-weight), and SUA levels higher or lower than the median of 6.6 mg/dl. At a median follow-up of 5.4 years, cardiac and all-cause deaths were the primary end points. RESULTS Multivariate analyses demonstrated that high SUA group had a significantly higher cardiac mortality [hazard ratio (HR): 1.79, 95% confidence interval (CI): 1.14-2.82, p=0.023] and overall mortality (HR: 1.68, 95% CI: 1.19-2.36, p=0.003) than low SUA group only in overweight or obese patients. Additionally, high BMI was associated with a significantly lower cardiac mortality (HR: 0.58, 95% CI: 0.38-0.99, p=0.023) and overall mortality (HR: 0.62, 95% CI: 0.41-0.82, p=0.003) than low BMI in patients with low SUA levels. Furthermore, normal-low weight and underweight patients (BMI<21 kg/m(2)) were found to have a higher risk of mortality regardless of SUA levels. CONCLUSIONS Among patients with established CAD, SUA may be a potent predictor to mortality in overweight or obese patients. Moreover, the obesity-mortality paradox phenomenon was mainly driven by higher mortality risk in underweight patients and lower mortality risk in overweight and obese patients with low SUA.

Gender differences in the impact of diabetes on mortality in patients with established coronary artery disease: A report from the Eastern Taiwan integrated health care delivery system of Coronary Heart Disease (ET-CHD) registry, 1997–2006

OBJECTIVES The effect of type 2 diabetes mellitus (DM) on mortality was more pronounced in women than men with coronary artery disease (CAD) in the pre-stent era before 1996. However this relationship is controversial in the post-stent era. METHODS We studied a cohort of 1073 patients with angiographically defined CAD from the Eastern Taiwan integrated health care delivery system of Coronary Heart Disease (ET-CHD) registry during 1997-2003 in Tzu-Chi General Hospital, Hualien, Taiwan. To evaluate gender-specific DM effect on mortality, the subjects were divided into 4 groups: diabetic women (n=147), non-diabetic women (n=127), diabetic men (n=239), and non-diabetic men (n=560). At a mean follow-up of 5.4 years, cardiac and all-cause mortality were the primary end points. RESULTS Annual total mortality rates were 10.2%, 5.1%, 7.2%, and 4.8%; annual cardiac mortality rates were 8.2%, 3.0%, 4.3%, and 2.6% for diabetic women, non-diabetic women, diabetic men, and non-diabetic men, respectively. Multivariate Cox regression models, adjusted for possible confounders showed that gender-specific hazard ratios (HRs) of DM for total mortality were 2.02 (95% CI: 1.32-3.09), and 1.72 (95% CI: 1.32-2.25) for women and men, respectively. The HRs for total mortality associated with diabetes were not different between women and men (p=0.53). Similarly, adjusted gender-specific HRs of DM for cardiac mortality were 2.46 (95% CI: 1.45-4.19) for women, and 1.83 (95% CI: 1.28-2.62) for men, which were also not significantly different (p=0.36). CONCLUSIONS Among patients with CAD, the impact of DM on mortality was consistently higher in women than in men, but the differences across sexes were not statistically significant after 1996 in Taiwan.

The influence of inflammation outweighing the metabolic syndrome on cardiovascular risk and mortality

☆ The authors declare no conflict of interests and no financial support from any institute. ⁎ Corresponding author. Department of Internal Medicine, Hualien Armed Forces General Hospital. No.163, Jiali Rd., Xincheng Township, Hualien County 97144, Hualien, Taiwan. Tel.: +886 3 826 0601. E-mail address: farmer507@yahoo.com.tw (G.-M. Lin). In a systemic review andmeta-analysis, the metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality [1]. Most participants came from general populations and were free of cardiovascular disease. However, we have observed that the influence of metabolic syndrome on cardiovascular risk was blunted in the cohorts of the placebo arm in the JUPITER trial [2]. In the subgroup analysis, the cardiovascular hazard ratio for menwithmetabolic syndrome to thosewithout it was estimated at 0.92, for women: 1.02, for the elderlyN70 years old: 0.80 and for the total placebo cohorts: 0.92 [3,4]. Since the populations enrolled in JUPITER are unique for their baseline characteristics without diabetes, with normal lipid profiles and high C-reactive protein levels (N2 mg/L), those with metabolic syndrome should mainly include central obesity and systemic hypertension in addition to one or more of the other metabolic abnormalities such as an increase of triglyceride, reduction of the HDL-cholesterol and impaired fasting glucose. Obviously obesity, which demonstrates the phenomenon of reverse epidemiology regardless of age and gender, is the only variable in the components of metabolic syndrome (except the cardiovascular incidence rate of fasting glucose was not shown in JUPITER) that could reduce the cardiovascular risk [3,4]. Previously, Aizawa et al. suggested that the five metabolic components do cluster and obesity and insulin resistance were likely to be linked with metabolic syndrome more than hypertension or high triglyceride [5]. As we know, those with obesity and insulin resistance have an increase of inflammatory status and cardiovascular risk compared to general populations. It is surprising that to replace the risk factor of obesity or insulin resistance by inflammation would not alter the cardiovascular incidence for those who have not fulfilled the criteria of themetabolic syndrome. This reflects that inflammation may play a central role in the genesis of metabolic syndrome related cardiovascular risk [6]. Accordingly, the influence of inflammation outweighing metabolic syndrome on cardiovascular risk and mortality is clinically proven. Further, we reason that the finding of Aizawa et al. why obesity and insulin resistance prefer to be clustered in the metabolic syndrome than in other components, is possibly due to these two factors just representing a status of inflammation. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [7].

Relation of body mass index to mortality among patients with percutaneous coronary intervention in the drug-eluting stent era: A systematic review and meta-analysis

with percutaneous coronary intervention in the drug-eluting stent era: A systematic review and meta-analysis Gen-Min Lin ⁎, Yi-Hwei Li ⁎, Chin-Lon Lin , Ji-Hung Wang , Chih-Lu Han d a Department of Public Health, Tzu-Chi University, Hualien, Taiwan b Department of Medicine, Hualien Armed Forces General Hospital, Hualien, Taiwan c Division of Cardiology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan d Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

The obesity paradox of mortality in patients with coronary artery disease undergoing percutaneous coronary intervention

We readwith interest the work by Younge et al. which reported that in their study population overweight, but not obesity, was associated with a lower risk for 7-year mortality in patients undergoing percutaneous coronary intervention (PCI). Health status measured by the SF-36 Health Survey did not seem to play a role in explaining the obesity paradox [1]. The obesity paradox, also called reverse epidemiology, is observed among patients with established cardiovascular disease (CVD) such as heart failure, hypertension and stroke, dyslipidemia or end-stage renal disease [2]. In patients with severe coronary artery disease, the obesity paradox of mortality is present in patients with acute myocardial infarction and those undergoing coronary bypass grafting surgery [3,4]. There were some possible mechanisms to explain this phenomenon, which include malnutrition–inflammation complex syndrome, endotoxin–lipoprotein hypothesis, survival bias, reverse causation, and discrepancies among competitive factors [2]. In recent reports, metabolically-obese normal-weight individuals whowere 24% of normal-weight adults in theUnited States, and 13% in a Korean cohort, conferred a high risk of mortality. Besides, sarcopenic obesity defined by high body fat and reduced lean body mass is associated with a reduction in cardio-respiratory fitness and physical function, probably leading to disability and premature death [5]. In fact, risk factors for CVD may have a more hazardous effect on patients with a lower body mass index (BMI). For example, cigarette smoking and diabetesmay precipitate a higher mortality risk in thinner populations [6]. In addition, the association of increased blood pressure with CVD risk tends to be weaker in those with relatively high BMI [7]. Furthermore, in the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial, C-reactive protein, a systemic inflammation biomarker, was found to have a higher impact on CVD occurrence in the participants with a lower BMI. This finding was not gender-sensitive [2]. We therefore believe that the inert factors such as systolic blood pressure, inflammation status and diabetes, and external stress such as cigarette smoking, modulate the impact of BMI not only on the development of CVD among the healthy population but also onmortality for patients with established CVD, including severe coronary artery disease. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

Reverse epidemiology in patients with heart failure: The role of circulatory power and cardiac reserve

a Department of Medicine, Hualien-Armed Forces General Hospital, Hualien, Taiwan b Department of Public Health, Tzu-Chi University, Hualien, Taiwan c Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan d Department of Internal Medicine, Mennorite Christian Hospital, Hualien, Taiwan e Department of Medicine, Tri-Service General Hospital-SongShan Branch, National Defense Medical Center, Taipei, Taiwan f Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Warfarin may reduce risk of ischemic stroke by preventing atrial fibrillation for patients with heart failure and sinus rhythm

As compared with the general population, patients with reduced ejection fractionwho are in sinus rhythmare observedwith ahigher risk for ischemic stroke. This relationship is caused by left ventricular stasis, a systemic hypercoagulable state, and endocardial dysfunction in a situation of impaired left ventricular systolic function [1,2]. Therefore, the issue whether antithrombotic agents especially aspirin or warfarin could successfully prevent stroke for patients with heart failure and sinus rhythmhas been tested in a series of clinical trials. The former two trials (theWarfarin/Aspirin Study in Heart Failure (WASH) trial in 2004 and the Heart Failure Long-Term Antithrombotic Study (HELAS) trial in 2006) had too small sample size to detect a significant difference in ischemic stroke rate between patients receiving warfarin and those receiving aspirin [3,4]. Until recently, the following two largest trials, the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial in 2009and theWarfarinversusAspirin inReducedCardiacEjection Fraction (WARCEF) in 2012 demonstrated that warfarin could reduce risk of ischemic stroke among heart failure patients in sinus rhythm [5,6]. In these two trials, warfarinwas observed with a protective trend to reduce risk of stroke by preventing the development of atrial fibrillation (AF) in addition to the anticoagulation effect. In the WATCH trial, the incidence of paroxysmal AF was marginally higher in the aspirin group than in the warfarin group if patients who discontinued drug therapy during the study periodwere taken into account (13.2% for aspirin vs 9.6% for warfarin, respectively; P=0.08) [7]. Similarly, in theWARCEF trial, the incidence of AF/atrial flutter/supraventricular tachycardia was significantly higher in the aspirin group than that in the warfarin group at the end of the study (4.8% for aspirin vs. 3.1% for warfarin, respectively; P=0.032). Atrialfibrillation is oneof themost encountered cardiac arrhythmia in patients with systolic heart failure and warfarin can reduce risk of ischemic stroke mainly by its anticoagulation effect. However, as we know, warfarin has never been found to show an anti-arrhythmic effect clinically and pharmacologically. On the basis of current knowledge, warfarin may prevent AF via the anti-inflammation effect [8]. As compared to aspirin, warfarin may lower plasma interleukin-6 which is a potent inflammatory marker to predict the occurrence of AF [9]. Since the AFwas not the primary end point in each trial, this association should be further adjusted by some baseline variables such as themeasurement of left atriumdimension by echocardiography and the presence of severe cardiac valve disease that has higher risk to AF. In conclusion, the following study should be conducted and focus on the incidence of AF for patients with systolic heart failure and sinus rhythm. Meanwhile, a long-term electrocardiographic record has to be performed to distinguish the effect of different antithrombotic agents on AF.

Pexelizumab may be hazardous to those with ST-segment elevation myocardial infarction undergoing primary percutaneous interventions without using glycoprotein IIb–IIIa inhibitors

Angioplasty Complications (CADILLAC) trial. J Am Coll Cardiol 2004;44:547–53. [16] Aronson D, Suleiman M, Agmon Y, et al. Changes in haemoglobin levels during hospital course and long-term outcome after acute myocardial infarction. Eur Heart J 2007;28:1289–96. [17] Most AS, Ruocco Jr NA, Gewirtz H. Effect of a reduction in blood viscosity on maximal myocardial oxygen delivery distal to a moderate coronary stenosis. Circulation 1986;74:1085–92. [18] Levy PS, Quigley RL, Gould SA. Acute dilutional anemia and critical left anterior descending coronary artery stenosis impairs end organ oxygen delivery. J Trauma 1996;41:416–23. [19] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.