Tse-Min Lu

Plasma asymmetric dimethylarginine predicts death and major adverse cardiovascular events in individuals referred for coronary angiography

BACKGROUND Elevated plasma level of asymmetric dimethylarginine (ADMA) was reported to be associated with endothelial dysfunction and atherosclerotic risk factors. We assessed the prognostic value of plasma ADMA levels in 997 consecutive individuals referred for coronary angiography from July 2006 to June 2009. METHODS ADMA was measured by high performance liquid chromatography. All subjects were followed for a median period of 2.4years for the occurrence of all-cause mortality, major adverse cardiovascular events (MACE, defined as cardiovascular death, non-fatal myocardial infarction and stroke), and MACE plus clinically-driven target vessel revascularization (TVR). RESULTS Plasma ADMA levels were significantly higher in patients with significant coronary artery disease (CAD) (≥50% stenosis, n=655) than those with insignificant CAD (20-50% stenosis, n=272) and normal coronary artery (<20% stenosis, n=70) (0.47±0.10μmol/l vs 0.44±0.10μmol/l vs 0.42±0.08μmol/l, p <0.001). By multivariate analysis, plasma ADMA level was identified as a significant independent risk factor of significant CAD (OR: 1.29, 95% CI: 1.10-1.50; p=0.002). Moreover, multivariate Cox regression analysis showed that, comparing with the ADMA tertile I, the highest ADMA tertile was a significant independent predictor for all adverse long-term clinical outcomes. Notably, plasma ADMA level remained associated with the long-term outcomes in non-diabetic individuals, but not in those with diabetes (interaction p=0.04 for MACE plus TVR). CONCLUSIONS Our findings suggest that elevated plasma ADMA level might be a risk factor of significant CAD, and might predict worse long-term clinical outcomes in subjects referred for cardiac catheterization, especially in non-diabetic individuals.

Pulsatility of Ascending Aorta and Restenosis After Coronary Angioplasty in Patients >60 Years of Age With Stable Angina Pectoris

A recent study has demonstrated that the pulsatility of the ascending aorta is a strong predictive factor for restenosis after coronary angioplasty. However, whether the pulsatility of the ascending aorta is still a significant predictor for restenosis in elderly patients with a stiffer aorta is unknown. We investigated the relation between arterial pulsatility in the ascending aorta and restenosis after coronary angioplasty in patients aged > 60 years. Eighty-seven consecutive patients (80 men, aged 72.5 +/- 5.1 years) with stable angina were included. Before angioplasty, the arterial systolic, diastolic, and mean pressure waveforms of the ascending aorta were measured. We used fractional pulse pressure (PPf, the ratio of pulse pressure to mean pressure) and pulsatility index (PI, the ratio of pulse pressure to diastolic pressure) to estimate the pulsatility of the ascending aorta. Angiographic restenosis occurred in 39 patients. Pulse pressure, PPf, and PI were significantly higher in patients with restenosis after coronary angioplasty (restenosis vs without restenosis: pulse pressure, 77.6 +/- 12.2 vs 66.1 +/- 15.4 mm Hg [p < 0.001]; PPf, 0.80 +/- 0.09 vs 0.69 +/- 0.11 [p < 0.001]; PI, 1.19 +/- 0.20 vs 0.98 +/- 0.21 [p < 0.001]). After multivariate stepwise adjustment of risk factors of restenosis and using receiver-operating characteristic analysis, the odds ratio (OR) of restenosis was: pulse pressure > 66 mm Hg, OR 5.88 (95% confidence interval [CI] 2.17 to 15.93); PPf > 0.72, OR 13.71 (95% CI 4.81 to 39.05); PI > 1.06, OR 13.56 (95% CI 4.67 to 39.38). Moreover, among patients aged > 70 years (n = 60), the predictive values of PPf and PI were even higher than those in patients aged < or = 70 years (n = 27). Thus, in elderly patients with stable angina, the pulsatility of the ascending aorta is a powerful predictor of restenosis after coronary angioplasty.

Asymmetric dimethylarginine predicts clinical outcomes in ischemic chronic heart failure.

BACKGROUND Elevated plasma level of asymmetric dimethylarginine (ADMA) has been reported to be associated with endothelial dysfunction and atherosclerotic risk factors, and may predict adverse cardiovascular events in patients with coronary artery disease. In this study, we aimed to assess the association between plasma ADMA and long-term outcome in patients with angiography-documented ischemic chronic heart failure (HF). METHODS AND RESULTS We evaluated 285 patients with ischemic chronic HF and measured their plasma ADMA levels by high performance liquid chromatography. The mean age was 70 ± 12 years and the mean left ventricular ejection fraction was 36 ± 8%. Plasma ADMA levels were positively correlated with NYHA functional class (p < 0.001) and log N-terminal pro-B type natriuretic peptide (NT-proBNP) level (p < 0.001). During the median follow-up period of 2.2 years, we observed 58 major adverse cardiovascular events (MACE) (20.4%) and 95 MACE plus cardiac decompensation (33.3%). Multivariate Cox regression analysis adjusted for age, ejection fraction, renal function and log NT-proBNP level revealed that ADMA might be a significant independent risk factor and the relative risk of MACE and MACE plus cardiac decompensation would increase by 23% and 25% respectively when plasma ADMA level increased by 1 SD of value (p = 0.05 and 0.007). CONCLUSIONS In patients with ischemic chronic HF, elevated plasma ADMA levels might be associated with higher NYHA functional classes and elevated NT-proBNP level, and appear to be an independent predictor of long-term adverse clinical outcomes.

Comparison of the predictive value of EuroSCORE, SYNTAX score, and clinical SYNTAX score for outcomes of patients undergoing percutaneous coronary intervention for unprotected left main coronary artery disease†

Objectives: We aimed to assess the prognostic values of the EuroSCORE, SYNTAX score, and the novel Clinical SYNTAX score (CSS) for 30‐day and 1‐year outcomes in patients undergoing left main (LM) percutaneous coronary intervention (PCI). Background: PCI has become an alternative treatment for LM coronary artery disease, and risk scoring system might be beneficial for pre‐PCI risk stratification. Methods and Results: We enrolled 198 consecutive patients with unprotected LM disease undergoing PCI (mean age 71.5 ± 10.7 years). The CSS was calculated by multiplying the SYNTAX Score to (age/left ventricular ejection fraction +1 for each 10 mL the estimated glomerular filtration rate <60 mL/min per 1.73 m2). The endpoints were 30‐day, and 1‐year all‐cause death and major adverse cardiovascular events (MACE), which were defined as all‐cause death, nonfatal MI, and clinical‐driven target vessel revascularization. Comparing with the SYNTAX score, the predictive accuracy of CSS for 30‐day and 1‐year all‐cause death and MACE were significantly higher (c‐statistics, CSS versus SYNTAX score: P < 0.01 for 30‐day and 1‐year all‐cause death; P < 0.05 for 30‐day and 1‐year MACE, respectively). Furthermore, in the multivariate Cox regression analysis, both EuroSCORE and CSS were identified as the independent predictors of 30‐day and 1‐year all‐cause death and MACE, but the SYNTAX score was not. Conclusions: In the general practice among a high‐risk population undergoing LM PCI, EuroSCORE and CSS might be independent predictors for 30‐day and 1‐year all‐cause death and MACE. Furthermore, the CSS had a superior discriminatory ability in predicting the 30‐day and 1‐year clinical outcomes comparing with the SYNTAX score.

Extracorporeal membrane oxygenation use, expenditure, and outcomes in taiwan from 2000 to 2010.

Background No study to date has systematically examined use, expenditure, and outcomes associated with extracorporeal membrane oxygenation (ECMO) use in Taiwan. The aim of this study was to examine ECMO use, expenditure, and outcomes during an 11-year period in Taiwan. Methods Claims data were collected from the Taiwan National Health Insurance Research Database for patients who received ≥1 ECMO treatment between January 2000 and December 2010. Measurements included demographics, indications for ECMO use, length of hospital stay, outcome, and expenditure. Results A total of 3969 patients received ECMO during the study period (median age: 54.6 years). The number of patients receiving ECMO increased from 52 in 2000 to 1045 in 2010. The major indication for ECMO was cardiovascular disease (68.7%), followed by respiratory disease (17.9%). Median length of hospital stay was 13 days in 2000 and 17 days in 2010. Median expenditure (New Taiwan dollars) was

The association of dimethylarginine dimethylaminohydrolase 1 gene polymorphism with type 2 diabetes: a cohort study

604 317 in 2000 and

Application of the Sequential Organ Failure Assessment score for predicting mortality in patients with acute myocardial infarction

673 888 in 2010. Some variables significantly differed by age, sex, hospital setting, calendar year, and indication for ECMO, and were associated with in-hospital and after-discharge mortality. Conclusions ECMO use has increased dramatically in Taiwan over the last decade. The high mortality rate of ECMO users suggested that ECMO may be being used in Taiwan for situations in which it provides no added benefit. This situation may be a reflection of the current reimbursement criteria for National Health Insurance in Taiwan. Refinement of the indications for use of ECMO is suggested.

Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control

BackgroundElevated plasma levels of asymmetric dimethylarginine (ADMA) has been reported to be associated with insulin resistance and micro/macrovascular diabetic complications, and may predict cardiovascular events in type 2 diabetic patients. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme eliminating ADMA in humans, but the effect of genetic variations in DDAH1 on type 2 diabetes and its long-term outcome are unknown.MethodsFrom July 2006 to June 2009, we assessed the association between polymorphisms in DDAH1 and type 2 diabetes in 814 consecutive unrelated subjects, including 309 type 2 diabetic patients and 505 non-diabetic individuals. Six single nucleotide polymorphisms (SNPs) in DDAH1, rs233112, rs1498373, rs1498374, rs587843, rs1403956, and rs1241321 were analyzed. Plasma ADMA levels were determined by high performance liquid chromatography. Insulin sensitivity was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR).ResultsAmong the 6 SNPs, only rs1241321 was significantly associated with a decreased risk of type 2 diabetes (AA vs GG+AG, OR = 0.64, 95% CI 0.47-0.86, p = 0.004). The association remained unchanged after adjustment for plasma ADMA level. The fasting plasma glucose and log HOMA-IR tended to be lower in subjects carrying the homozygous AA genotype of rs1241321 compared with the GG+AG genotypes. Over a median follow-up period of 28.2 months, there were 44 all-cause mortality and 50 major adverse cardiovascular events (MACE, including cardiovascular death, non-fatal myocardial infarction and stroke). Compared with the GG and AG genotypes, the AA genotype of rs1241321 was associated with reduced risk of MACE (HR = 0.31, 95% CI: 0.11-0.90, p = 0.03) and all-cause mortality (HR = 0.18, 95% CI: 0.04-0.80, p = 0.02) only in subgroup with type 2 diabetes. One common haplotype (GGCAGC) was found to be significantly associated with a decreased risk of type 2 diabetes (OR = 0.67, 95% CI = 0.46-0.98, p = 0.04).ConclusionsOur results provide the first evidence that SNP rs1241321 in DDAH1 is associated with type 2 diabetes and its long-term outcome.

Determinants of low-density lipoprotein cholesterol goal attainment: Insights from the CEPHEUS Pan-Asian Survey

BACKGROUND Thrombolysis in Myocardial Infarction (TIMI) score and Global Registry of Acute Coronary Events (GRACE) score have been validated as predictors of death in patients with acute myocardial infarction (AMI). This study was undertaken to determine whether the Sequential Organ Failure Assessment (SOFA) score had good accuracy for predicting mortality in AMI patients, and to compare the discriminatory performance of the 3 risk scores (RSs). METHODS This was a retrospective study. We calculated the TIMI RS, GRACE RS, and SOFA score for 726 consecutive AMI patients. The study endpoint was all-cause mortality. All patients were followed up for at least 3 years or until the occurrence of death. The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive ability of each score at different time points. RESULTS For in-hospital death, the AUC were 0.67 for TIMI RS, 0.73 for GRACE RS, and 0.79 for SOFA score (P<0.001, respectively). However, the SOFA score and GRACE RS were significantly better for predicting the 1-year (P<0.001, respectively) and 3-year (P<0.001, respectively) mortality than the TIMI RS was. Multivariate Cox regression analysis revealed that the SOFA score was an independent predictor of long-term mortality in AMI patients [hazard ratio (HR), 1.313; 95% CI, 1.191-1.447]. CONCLUSIONS The SOFA score provides potentially valuable prognostic information on clinical outcome when applied to patients with AMI. Compared with TIMI RS, both SOFA score and GRACE RS provide better discrimination for long-term mortality in patients presenting with AMI.

Identification and Management of Noncompliance in Atrial Fibrillation Patients Receiving Dabigatran: The Role of a Drug Monitor

Background and aimsElevated plasma asymmetric dimethylarginine (ADMA) levels have been observed in patients with insulin resistance and diabetes, and have been reported to predict adverse cardiovascular events in type 2 diabetic patients. However, the relationship between ADMA and glycemic control in patients with type 2 diabetes remained controversial.Methods and resultsWe evaluated 270 patients with type 2 diabetes and measured their plasma ADMA and hemoglobin A1c (HbA1c) levels by high performance liquid chromatography. The mean age was 67 ± 12 years. The mean plasma ADMA and HbA1c level were 0.46 ± 0.09 μmol/l and 7.8 ± 1.6%, respectively. There was no significant correlation between plasma ADMA level and HbA1c level (r = −0.09, p = 0.13). During the median follow-up period of 5.7 years (inter-quartile range: 5.0 − 7.3 years), major adverse cardiovascular event (MACE, including cardiovascular death, myocardial infarction and stroke) was observed in 55 patients (20.4%). Multivariate Cox regression analysis revealed that the ADMA tertile was an independent risk factor for MACE (ADMA tertile III versus ADMA tertile I: p = 0.026, HR: 2.31, 95% CI: 1.10 − 4.81). The prognosis predictive power of ADMA disappeared in patients with well glycemic control (HbA1c ≤6.5%), and the ADMA-HbA1c interaction p value was 0.01.ConclusionsIn patients with type 2 diabetes, ADMA might be an independent risk factor for long-term adverse cardiovascular events. However, ADMA was not correlated with serum HbA1c level, and in diabetic patients with HbA1c ≤6.5%, elevated ADMA level was no longer associated with increased risk of long-term prognosis. Our findings suggested that the prognosis predictive value of ADMA in type 2 diabetes might be modified by the glycemic control.