Liang-Miin Tsai

Incidence and cumulative recurrence rates of venous thromboembolism in the Taiwanese population

Summary.  Background: Little information is available on the epidemiology of venous thromboembolism (VTE) in Asian populations. Objectives: To investigate VTE incidence, VTE cumulative recurrence rates and risk factors for VTE recurrence among the adult Taiwanese population. Methods: This population‐based cohort study used the Taiwanese National Health Insurance claims databases to identify 5347 adult patients (2463 men, 46.1%) with VTE diagnosed in 2001 and 2002. We calculated the crude incidence of VTE and its recurrence. We also conducted a nested case–control study (n = 3576) among this population to estimate the association between VTE recurrence and exposure to potential VTE risk factors by conditional logistic regression. Results: The crude incidence of VTE was 15.9 per 100 000 person‐years, and its recurrence rate was 5.1% per person‐year. During 11 566 person‐years of follow‐up, the cumulative rates of VTE recurrence at 6, 12, 24, 36 and 47 months were 6.7%, 9.4%, 12.4%, 13.9%, and 14.4%, respectively. By conditional logistic regression, histories of VTE [adjusted odds ratio (OR) 1.71, 95% confidence interval (CI) 1.32–2.16] or malignant neoplasm (adjusted OR 1.64, 95% CI 1.26–1.99), major extremity trauma (adjusted OR 2.76, 95% CI 1.82–4.52), serious neurologic diseases (adjusted OR 1.43, 95% CI 1.12–1.84) or undergoing major surgery (adjusted OR 4.57, 95% CI 1.72–12.50) were associated with higher risks of VTE recurrence. Conclusions: The incidence of VTE is lower in the Taiwanese population than in Caucasians. Most VTE recurrences occur within 12 months, but they continue to occur beyond 1 year. The VTE recurrences are associated with malignancy, history of VTE, and major surgery after a previous VTE.

Elevation of Soluble Adhesion Molecules Is Associated With the Severity of Myocardial Damage in Acute Myocardial Infarction

In 20 patients with acute myocardial infarction, blood samples were taken to study the serial changes in the soluble intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1) and E-selectin. Results indicated that soluble ICAM-1 increased significantly and persisted throughout the study period; however, soluble E-selectin was significantly elevated only transiently and decreased rapidly thereafter, and the VCAM-1 did not increase during entire study period. There was a significant correlation between the levels of ICAM-1, E-selectin 6 hours after admission, and peak creatine kinase level; the levels of ICAM-1 and E-selectin were also positively correlated with total leukocyte count at admission.

G-33A Mutation in the Promoter Region of Thrombomodulin Gene and Its Association With Coronary Artery Disease and Plasma Soluble Thrombomodulin Levels

Thrombomodulin is an endothelial glycoprotein that decreases thrombin activity and activates protein C. A recent study has shown that G-33A promoter mutation of the thrombomodulin gene occurs particularly in Asians. In this study, we analyzed the distribution of G-33A mutation in the promoter region of the thrombomodulin gene in the Chinese population and determined whether the mutation might be a risk for coronary artery disease (CAD). In addition, the influence of this mutation on plasma soluble thrombomodulin levels in patients with CAD was also examined. We studied 320 consecutive patients (mean age 63 years; 73% men) with CAD and 200 age- and sex-matched control subjects. Screening for thrombomodulin G-33A promoter mutation was conducted using polymerase chain reaction, single-strand conformation polymorphism, and direct deoxyribonucleic acid sequencing. The frequency of the G-33A mutation (GA+AA genotypes) was significantly higher in the CAD group (23.8% vs 15.5%, odds ratio [OR] 1.70, p = 0.031). Multiple logistic regression analysis showed that the mutation was an independent risk factor (OR 1.81, p = 0.016) for CAD, as was hypertension (OR 1.44, p = 0.040), diabetes mellitus (OR 2.50, p <0.001), and smoking (OR 2.15, p <0.001). In CAD patients with GG genotype, the soluble thrombomodulin level increased with the extent of CAD (36 +/- 15 vs 47 +/- 18 vs 55 +/- 36 ng/ml in 1-, 2-, or 3-vessel CAD, p <0.001). However, in CAD patients with G-33A mutation, there was no difference between the levels of soluble thrombomodulin (39 +/- 17 vs 37 +/- 15 vs 42 +/- 18 ng/ml, p = NS) in 1-, 2-, or 3-vessel CAD. Our observations suggest that there is a significant association of the G-33A mutation in thrombomodulin gene with CAD, and this mutation may influence the soluble thrombomodulin levels in patients with CAD.

Association of Left Ventricular Longitudinal Strain with Mortality among Stable Hemodialysis Patients with Preserved Left Ventricular Ejection Fraction

BACKGROUND AND OBJECTIVES Little is known about the optimal echocardiographic parameters for risk stratification in stable dialysis patients with preserved left ventricular ejection fraction (LVEF) (ejection fraction ≥ 50%). Left ventricular (LV) global peak systolic longitudinal strain (GLS) is the ratio of the maximal change in myocardial longitudinal length in systole to the original length and reliably and accurately assesses LV function. During systole, LV myocardium in the longitudinal direction shortens and GLS is represented by a negative value. The more negative value of GLS, the better the LV function is. This study hypothesized that subtle abnormalities of GLS are associated with an adverse prognosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This prospective study collected clinical and echocardiographic data (including GLS) from 88 stable hemodialysis patients (mean age 67.0 ± 11.2 years; 35% men) with preserved LVEF. These patients were enrolled from December 2008 to January 2009 and were followed-up for 25.6 ± 9.9 months. The primary outcome was all-cause mortality. Multivariate Cox regression analysis was used to investigate risk factors for mortality. RESULTS The mortality group (n=24) had lower albumin levels, less negative GLS, and higher prevalence of coronary artery disease and diabetes mellitus than the survival group. Using a GLS cutoff value of -15%, the less negative GLS group (GLS ≥-15%) had a higher mortality rate. Cox regression analyses revealed that lower albumin level (hazard ratio, 0.16; 95% confidence interval, 0.05 to 0.53; P=0.003) and less negative GLS (hazard ratio, 3.57; 95% confidence interval, 1.41 to 9.04; P=0.01) were independent predictors of all-cause mortality. Furthermore, less negative GLS was associated with a higher cardiovascular death rate. CONCLUSIONS Less negative GLS is predictive of poor prognosis among stable hemodialysis patients with preserved LVEF.

Natural history of left atrial spontaneous echo contrast in nonrheumatic atrial fibrillation

A prospective study was designed to investigate potential changes of left atrial (LA) spontaneous echo contrast with time and the effects of antithrombotic therapy on its presence in 77 patients with chronic nonrheumatic atrial fibrillation (AF), using serial transesophageal echocardiography (TEE). During a mean follow-up period of 20 +/- 15 months (range 6 to 77), a total of 197 TEE studies were performed in these patients. Baseline TEE revealed that LA spontaneous echo contrast was absent in 43 patients (group 1) and present in 34 (group 2). LA thrombus was found in 8 of group 2 but in none of the group 1 patients. During the follow-up period, only 2 of the group 1 patients were receiving antithrombotic agents; the patients in group 2 without LA thrombus were treated with either warfarin or aspirin, whereas those with LA thrombus were treated with warfarin. On the latest TEE study, LA spontaneous echo contrast was observed in 19 of the group 1 patients (44%) and was persistently found in all of the group 2 patients. During the study period, no patient was found to develop new LA thrombus formation and only 4 episodes of transient ischemic attack were recorded in 4 patients (embolic event rate = 3.1% per year). Of these, 2 were observed in group 1 and the remaining 2 were from group 2 and under aspirin therapy (event rate = 2.2% and 4.7% per year, respectively). In the subgroup of patients with LA thrombus receiving warfarin therapy, follow-up TEE revealed complete resolution of the thrombi in 6 and partial resolution in the remaining 2 in spite of the persistence of LA spontaneous echo contrast; none of these patients developed clinical thromboembolic events during the study period. Thus, future occurrence of LA spontaneous echo contrast could be observed by serial TEE at a substantial rate in patients with nonrheumatic AF who have no LA spontaneous echo contrast; follow-up TEE should be recommended for these patients to detect early the potential occurrence of LA spontaneous echo contrast if preventive antithrombotic therapy is not considered. Although warfarin therapy is associated with resolution of LA thrombus, neither warfarin nor aspirin is effective for suppressing the presence of LA spontaneous echo contrast in nonrheumatic AF.

Prevalence and clinical significance of left atrial thrombus in nonrheumatic atrial fibrillation

The prevalence and clinical significance of left atrial thrombus were prospectively investigated in a consecutive series of 219 patients with chronic nonrheumatic atrial fibrillation using transesophageal echocardiography. Fifteen left atrial thrombi were detected in 15 of the 219 patients (6.8%); 12 of these thrombi (80%) were confined to the left atrial appendage. Left atrial spontaneous echo contrast was visualized in 85 patients (39%). All the thrombi were found in the left atria with spontaneous echo contrast. Patients with left atrial thrombus had significantly lower left ventricular ejection fraction than those without (49 +/- 14% vs. 59 +/- 14%; P < 0.05). Multivariate analysis among clinical and transthoracic echocardiographic variables showed that left ventricular ejection fraction < 50% was the only independent predictor for the presence of left atrial thrombus. A history of thromboembolism was significantly more frequent in patients with left atrial thrombus than in those without (73% vs. 32%; P < 0.005). The presence of left atrial thrombus was more specific than spontaneous echo contrast for predicting history of thromboembolism (97% vs. 80%), but its sensitivity was significantly lower (14% vs. 73%). We conclude that: (1) Transesophageal echo-detected left atrial thrombus is not uncommon in patients with chronic nonrheumatic atrial fibrillation and is exclusively observed in those with left atrial spontaneous echo contrast. (2) Impaired left ventricular systolic function may predispose the left atrial thrombus formation. (3) Left atrial thrombus is a highly specific but insensitive predictor for thromboembolic events.

Platelet-activating factor-acetylhydrolase A379V (exon 11) gene polymorphism is an independent and functional risk factor for premature myocardial infarction

Summary.  Background: Oxidation of low density lipoproteins is an initial step of atherogenesis that generates pro‐inflammatory phospholipids, including platelet‐activating factor (PAF). PAF is degraded by PAF‐acetylhydrolase (PAF‐AH), which has been postulated to be a risk factor for myocardial infarction (MI). The role of PAF‐AH for the onset of premature MI is unclear. Methods: Polymorphisms located in putatively functional regions were investigated in a cohort of patients having premature MI onset prior to 46 years of age (n = 200) and a sex‐age‐matched control group (n = 200). The activity of PAF‐AH and coronary angiograms were evaluated for the severity of coronary atherosclerosis. Results: The V allele of A379V (exon 11) polymorphism on PAF‐AH gene was more frequent in patients with premature MI (P = 0.001). This V allele polymorphism was also associated with a lower activity of plasma PAF‐AH and a more complex coronary atherosclerosis (p Trends <0.05). Multiple logistic regression analysis showed that this polymorphism was an independent risk factor (Odds Ratio [OR] 1.66, 95% CI 1.14.1 to 5.80, P = 0.008) as well as smoking (OR 3.72, 95% CI 1.77 to 9.28, P = 0.001), diabetes mellitus (OR 2.25, 95% CI 1.40 to 5.32, P = 0.007) and hypertension (OR 1.88, 95% CI 1.25 to 5.36, P = 0.003) for the onset of premature MI. Conclusion: We conclude that a functional and significant association between the A379V polymorphism on exon 11 of PAF‐AH gene and premature MI exists in this Taiwanese population. This polymorphism is significantly associated with the PAF‐AH activity and the severity of coronary atherosclerosis.

Diagnostic Value of Segmental Longitudinal Strain by Automated Function Imaging in Coronary Artery Disease without Left Ventricular Dysfunction

BACKGROUND The aim of this study was to investigate the role of segmental longitudinal strain for the diagnosis of coronary artery disease (CAD) assessed by automated function imaging. METHODS One hundred fifty-two subjects (mean age, 63 ± 12 years; 77 men) referred for assessment of cardiac function under suspicion of CAD were recruited for this study. Patients with left ventricular dysfunction or with acute coronary syndromes were excluded. RESULTS Peak systolic global longitudinal strain (GLS) was significantly decreased in patients with CAD. Peak segmental longitudinal strain difference (LSD) and its ratio to peak systolic GLS were significant higher in patients with CAD. The areas under receiver operating characteristic curves for the diagnosis of CAD were 0.813 for peak systolic GLS, 0.851 for the number of abnormal segments, 0.805 for peak segmental LSD, and 0.862 for the ratio of peak segmental LSD to peak systolic GLS. Using 1.0 as a cutoff point for the ratio of peak segmental LSD to peak systolic GLS, sensitivity was 77.3% and specificity 79.2%. CONCLUSIONS This study suggests that it may be possible to assess CAD with strain by automated function imaging, but further larger scale studies are needed to confirm this.

Prognostic significance of elevated hemostatic markers in patients with acute myocardial infarction.

OBJECTIVES The purpose of this study was to determine whether the elevated levels of hemostatic markers in the early phase of myocardial infarction may serve as risk factors for subsequent cardiac mortality. BACKGROUND Increased plasma hemostatic markers were noted in acute myocardial infarction, indicating that the blood coagulation system is highly activated in those patients. However, there are few clinical data concerning the association between the elevated hemostatic markers and survival in patients with myocardial infarction. METHODS Blood samples were obtained from 64 patients (mean age 67 +/- 11 years; 49 male) with acute myocardial infarction within 12 h after the onset of symptoms and before the initiation of any antithrombotic treatment. We measured plasma concentrations of fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) using the enzyme-linked immunosorbent assay method, and examined the associations between the level of these markers and survival with Cox proportional hazards models. RESULTS The follow-up time was 27 +/- 17 months, and 19 patients died of cardiac causes during the follow-up. Univariate survival analysis identified Killip class IV (hazard ratio 4.86; 95% confidence interval [CI] 1.55-15.19), left ventricular ejection fraction (hazard ratio 0.94; 95% CI 0.90-0.99), FPA (hazard ratio 1.54; 95% CI 1.13-2.10), F1+2 (hazard ratio 2.03; 95% CI 1.17-3.53) and TAT (hazard ratio 1.88; 95% CI 1.27-2.79) as significant factors associated with cardiac mortality. In multivariate analyses, only FPA level (hazard ratio 1.84; 95% CI 1.03-3.30) and left ventricular ejection fraction (hazard ratio 0.93; 95% CI 0.88-0.98) were independent predictors of cardiac mortality. CONCLUSIONS Elevated FPA in the early phase of myocardial infarction identifies patients with increased risk for subsequent cardiac death. This association appears to be independent of residual left ventricular function after infarction.

Acute myocardial infarction in young and very old Chinese adults: clinical characteristics and therapeutic implications

To characterize acute myocardial infarction (AMI) in young adults and octogenarians, 475 AMI patients, in age subsets, were examined. The clinical features, risk factors and in-hospital mortality were compared among 17 young patients (< 40 years), 426 patients of common age (40-79 years), and 32 very elderly patients (> or = 80 years). The octogenarian patients were mainly female (male/female ratio, 0.9 vs. 4.7 in other subgroups, P < 0.005), and had more frequent atypical presentation and postinfarctional congestive heart failure; whereas infarct size, location and development of Q-wave, major arrhythmias and cardiac wall rupture were not different among these age subsets. The most common risk factors in the young group were dyslipidemia (67%) and cigarette smoking (65%), and in the octogenarian group were dyslipidemia (52%) and hypertension (50%). Among age subsets, however, the prevalence of risk factors was not significantly different except for a relatively lower smoking rate in the octogenarians. Compared with 40- to 79-year-old patients who had predominantly multi-vessel diseases, the young patients had milder coronary atherosclerosis and were more likely to have normal coronaries (27% vs. 5%, P < 0.01). Significantly more octogenarians than young patients succumbed to AMI in the hospital (44% vs. 18%, P < 0.005), usually because of a cardiogenic complication (93%). Also, the octogenarians were less likely than the younger patients to have received thrombolytic therapy, mostly because of delayed diagnosis and arrival at the hospital, or because of old age itself.(ABSTRACT TRUNCATED AT 250 WORDS)