Circulating serum amyloid A levels but not SAA1 variants predict long-term outcomes of angiographically confirmed coronary artery disease.

Objectives: Circulating serum amyloid A (SAA) levels are strongly associated with atherosclerotic cardiovascular disease risk and severity. The association between SAA1 genetic variants, SAA levels, inflammatory marker levels, and coronary artery disease (CAD) prognosis has not been fully understood. Materials and Methods: In total, 2199 Taiwan Biobank (TWB) participants were enrolled for a genome-wide association study (GWAS), and the long-term outcomes in 481 patients with CAD were analyzed. The primary endpoint was all-cause mortality, and the secondary endpoint was the combination of all-cause death, myocardial infarction, stroke, and hospitalization for heart failure. Results: Through GWAS, SAA1 rs11024600 and rs7112278 were independently associated with SAA levels (P = 3.84 × 10-145 and P = 1.05 × 10-29, respectively). SAA levels were positively associated with leukocyte counts and multiple inflammatory marker levels in CAD patients and with body mass index, hemoglobin, high-density lipoprotein cholesterol, and alanine aminotransferase levels in TWB participants. By stepwise linear regression analysis, SAA1 gene variants contributed to 27.53% and 8.07% of the variation of the SAA levels in TWB and CAD populations, respectively, revealing a stronger influence of these two variants in TWB participants compared to CAD patients. Kaplan-Meier survival analysis revealed that SAA levels, but not SAA1 gene variants, were associated with long-term outcomes in patients with CAD. Cox regression analysis also indicated that high circulating SAA levels were an independent predictor of both the primary and secondary endpoints. Conclusion: SAA1 genotypes contributed significantly to SAA levels in the general population and in patients with CAD. Circulating SAA levels but not SAA1 genetic variants could predict long-term outcomes in patients with angiographically confirmed CAD.

Dual Fresnel mirror system for 360 degree viewable three-dimensional displays.

360-degree viewable three-dimensional (3D) display systems have gained considerable attention for the unique manner in which they display objects. Most of the optical display devices in these systems employ two parabolic mirrors facing each other separated by a distance equal to the focal length of the mirrors. However, the current configuration is limited to unity magnification and provides a small image relative to the volume of the system. This paper presents a novel 3D display system based on two Fresnel mirrors with different focal lengths facing each other. The distance between the mirrors can be adjusted to alter the magnification of the resulting 3D image. Wave-optics analysis of an optical dual-lens system equivalent to the proposed dual-mirror system was used to simulate the image distance, the transverse and longitudinal magnification, and the minimum length of the proposed system. This paper also addresses issues pertaining to the design and manufacture of Fresnel mirrors. An experiment system using Fresnel mirrors with focal lengths of 60mm and 90mm clearly demonstrated the efficacy of the proposed scheme in terms of 3D image magnification.

Combined corrected QT interval and growth differentiation factor-15 level has synergistic predictive value for long-term outcome of angiographically confirmed coronary artery disease.

BACKGROUND: The corrected QT interval (QTc) predicts prognosis for the general population and patients with coronary artery disease (CAD). Growth differentiation factor-15 (GDF-15) is a biomarker of myocardial fibrosis and left ventricular (LV) remodelling. The interaction between these two parameters is unknown. SUBJECTS AND METHODS: This study included 487 patients with angiographically confirmed CAD. QTc was calculated using the Bazett formula. Multiple biochemistries and GDF-15 levels were measured. The primary endpoint was total mortality, and the secondary endpoints comprised the combination of total mortality, myocardial infarction and hospitalisation for heart failure and stroke. RESULTS: The mean follow-up period was 1029 ± 343 days (5-1692 days), during which 21 patients died and 47 had secondary endpoints. ROC curve analysis for the optimal cut-off value of primary endpoint is 1.12 ng/mL for GDF-15 (AUC = 0.787, P = 9.0 × 10-6 ) and 438.5 msec for QTc (AUC = 0.698, P = .002). Utilising linear regression, QTc has a positive correlation with Log-GDF-15 (r = .216, P = 1.0 × 10-6 ). Utilising Kaplan-Meier analysis, both QTc interval and GDF-15 level are significant predictors for primary end point (P = .000194, P = 2.0 × 10-6 , respectively) and secondary endpoint (P = .00028, P = 6.15 × 10-8 , respectively). When combined these two parameters together, a significant synergistic predictive power was noted for primary and secondary endpoint (P = 2.31 × 10-7 , P = 1.26 × 10-8 , respectively). This combined strategy also showed significant correlation with the severity of CAD (P < .001). CONCLUSION: In Chinese patient with angiographically confirmed CAD, a combined strategy utilising an ECG parameter (QTc) and a circulating biomarker (GDF-15) has good correlation with the severity of CAD, and improves the predictive power for total mortality.

Osteoprotegerin and osteopontin levels, but not gene polymorphisms, predict mortality in cardiovascular diseases.

Aim: This study aims to investigate whether osteoprotegerin (OPG) or osteopontin (OPN) single nucleotide polymorphisms (SNPs) will predict survival. Materials & methods: This study enrolled 617 participants undergoing health examination, 536 coronary artery disease (CAD) patients and 86 peripheral artery disease (PAD) patients. Genotypes of OPG SNP rs2073618 and OPN SNP rs11730582 were determined. OPG and OPN levels were measured. Results: In both CAD and PAD populations, high OPG and OPN levels were strong predictors of all-cause death. The OPG rs2073618 CC genotype and the OPN rs11730582 TT genotype did not predict mortality. Conclusion: High OPG and high OPN levels, but not OPG rs2073618 CC genotype or OPN rs11730582 TT genotype, were strong predictors of mortality in both CAD and PAD patients.

Circulating Chemerin Levels, but not the RARRES2 Polymorphisms, Predict the Long-Term Outcome of Angiographically Confirmed Coronary Artery Disease.

Chemerin, a novel adipokine, has been associated with metabolic, inflammatory, and atherosclerotic diseases. We aimed to determine the genetic basis of chemerin levels by conducting a genome-wide association study (GWAS) and to investigate the role of RARRES2 polymorphisms and circulating chemerin levels in the long-term outcome of coronary artery disease (CAD). A total of 2197 participants from the Taiwan Biobank (TWB) were recruited for the GWAS analysis, and 481 patients with angiographically confirmed CAD were enrolled for long-term outcome analysis. One locus of genome-wide significance with a single independent association signal was identified in the GWAS for chemerin levels with the peak association at the RARRES2 gene promoter region polymorphism rs3735167 (p = 2.35 × 10-21). In the CAD population, borderline significance was noted between RARRES2 polymorphisms and chemerin levels, whereas high chemerin levels were associated with obesity, female sex, diabetes mellitus, hypertension, current smoking, high platelet and leukocyte counts, anemia, impaired renal function, high C-reactive protein (CRP) levels, and multi-vessel disease. Kaplan⁻Meier survival curves indicated that the patients with high chemerin and CRP levels, but not those with RARRES2 polymorphisms, had a lower survival rate and higher combined cerebral and cardiovascular event rates. Combined chemerin and CRP levels further revealed a stepwise increase in poor clinical outcomes from low- to high-risk subgroups. In conclusion, rs3735167 is the lead RARRES2 polymorphism for chemerin levels in Taiwanese. Chemerin levels, but not the rs3735167 genotypes, predicted the long-term outcome of CAD, especially when combined with CRP levels.

Doses of renin-angiotensin system inhibitors but not beta-blockers predict outcome after ST-elevation myocardial infarction.

Objectives: In patients with ST-elevation myocardial infarction (STEMI), it is not clear whether low-dose renin-angiotensin system inhibitors and beta-blockers can result in the same benefits achievable with higher target doses. This observational study aims to investigate whether higher doses of angiotensin converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB) and beta-blockers can improve outcomes in patients with STEMI. Methods: We recorded daily doses of ACEI, ARB, and beta-blockers in 331 patients with STEMI. Echocardiographic studies were performed at baseline and were repeated 6 months later. Clinical events, including all-cause death and heart failure, were followed for 2 years. Results: Patients receiving high-dose ACEI/ARB had less increase in left ventricular end-diastolic volume index (LVEDVI) at 6 months. In multivariable linear regression model, ACEI/ARB dose or beta-blocker dose was not an independent predictor of increase in LVEDVI at 6 months. Kaplan-Meier survival curves showed that doses of ACEI/ARB (p = 0.003) and beta-blockers (p = 0.027) were significant predictors of death and heart failure. In multivariable Cox regression analysis, independent predictors of all-cause death and heart failure were diabetes mellitus (p = 0.001), left ventricular ejection fraction (p = 0.026), and ACEI/ARB dose (p = 0.025). Beta-blockers dose was not a predictor of clinical events in multivariable analysis (p = 0.413). Conclusion: High-dose ACEI/ARB, but not beta-blocker, was associated with lower rate of all-cause death and heart failure in patients with STEMI.

In-Hospital Implementation of Evidence-Based Medications is Associated with Improved Survival in Diabetic Patients with Acute Coronary Syndrome - Data from TSOC ACS-DM Registry.

BACKGROUND: Patients with acute coronary syndrome (ACS) and diabetes mellitus (DM) receive less aggressive treatment and have worse outcomes in Taiwan. We sought to explore whether the current practices of prescribing guideline-directed medical therapy (GDMT) for ACS and clinical outcomes have improved over time. METHODS: A total of 1534 consecutive diabetic patients with ACS were enrolled between 2013 and 2015 from 27 hospitals in the nationwide registry initiated by the Taiwan Society of Cardiology (the TSOC ACS-DM Registry). Baseline and clinical demographics, treatment, and clinical outcomes were compared to those of 1000 ACS patients with DM recruited in the Taiwan ACS-full spectrum (ACS-FS) Registry, which was performed between 2008 and 2010. RESULTS: Compared to the DM patients in the Taiwan ACS-FS Registry, even though reperfusion therapy was carried out in significantly fewer patients, the primary percutaneous coronary intervention (PCI) rate for ST-segment elevation myocardial infarction (STEMI) and the prescription rates of GDMT for ACS including P2Y12 inhibitors, renin-angiotensin blockers, beta-blockers, and statins were significantly higher in those in the TSOC ACS-DM Registry. Moreover, significant reductions in 1-year mortality, recurrent nonfatal MI and stroke were observed compared to those of the DM patients in the Taiwan ACS-FS Registry. Multivariate analysis identified reperfusion therapy in combination with GDMT as a strong predictor of better 1-year outcomes [hazard ratio (95% confidence interval) = 0.54 (0.33-0.89)]. CONCLUSIONS: Marked improvements in performing primary PCI for STEMI and prescribing GDMT for ACS were observed over time in Taiwan. This was associated with improved 1-year event-free survival in the diabetic patients with ACS.

Growth Differentiation Factor 15 May Predict Mortality of Peripheral and Coronary Artery Diseases and Correlate with Their Risk Factors.

Plasma GDF15 concentrations were measured in 612 Taiwanese individuals without overt systemic disease. Clinical parameters, GDF15 genetic variants, and 22 biomarker levels were analyzed. We further enrolled 86 patients with PAD and 481 patients with CAD, who received endovascular intervention and coronary angiography, respectively, to examine the role of GDF15 level in predicting all-cause mortality. Significant associations were found between GDF15 genotypes/haplotypes and GDF15 levels. The circulating GDF15 level was positively associated with age, smoking, hypertension, and diabetes mellitus as well as circulating levels of lipocalin 2 and various biomarkers of inflammation and oxidative stress. Kaplan-Meier survival analysis showed that baseline GDF15 levels of above 3096 pg/mL and 1123 pg/mL were strong predictors of death for patients with PAD and CAD, respectively (P = 0.011 and P < 0.001). GDF15 more accurately reclassified 17.3% and 29.2% of patients with PAD and CAD, respectively (P = 0.0046 and P = 0.0197), compared to C-reactive protein. Both genetic and nongenetic factors, including cardiometabolic and inflammatory markers and adipokines, were significantly associated with GDF15 level. A high level of GDF15 was significantly associated with an increase of all-cause mortality in patients with high-risk PAD and in patients with angiographically documented CAD.

IL1RL1 single nucleotide polymorphism predicts sST2 level and mortality in coronary and peripheral artery disease.

BACKGROUND AND AIMS: There are many IL1RL1 single nucleotide polymorphisms (SNP) significantly associated with circulating sST2 concentration. Little is known about the effects of IL1RL1 SNP on the outcome of cardiovascular disease. The aim of this study is to investigate whether IL1RL1 SNP can predict mortality. METHODS: We enrolled 601 individuals receiving health examination, 532 patients with coronary artery disease (CAD), and 86 patients with peripheral artery disease (PAD). Genotyping for SNP rs950880 and rs13001325 was performed and sST2 level was measured. The primary endpoint was all-cause death. The secondary endpoints were cardiovascular death, myocardial infarction, hospitalization for heart failure, stroke, and amputation. RESULTS: Individuals having rs950880 AA genotype all had rs13001325 TT genotype and tended to have lower sST2 levels in all 3 populations. Kaplan-Meier survival curves showed that patients with high sST2 level and rs950880 AA genotype had the lowest survival rate in presence of CAD (p < 0.001) and PAD (p = 0.007). In multivariable Cox regression analysis, the independent predictors of all-cause death were rs950880 AA homozygote (p = 0.018), age (p = 0.002), log sST2 level (p = 0.014), and log GDF-15 level (p = 0.017) in CAD patients. The independent predictor of all-cause death was rs950880-AA homozygote (p = 0.019) in PAD patients. There was no significant difference in secondary endpoints between rs950880 AA homozygote and C allele carriers. CONCLUSIONS: Individuals having rs950880 AA genotype also have rs13001325 TT genotype and tend to have lower sST2 levels. The rs950880 AA homozygote is an independent predictor of all-cause mortality in CAD and PAD patients.

Association between NF-κB Pathway Gene Variants and sICAM1 Levels in Taiwanese.

Intercellular adhesion molecule-1 (ICAM1) is crucial to the development and progression of atherosclerosis. Recent genome-wide association studies (GWAS) have revealed that single nucleotide polymorphisms (SNPs) in two of the nuclear factor-κB (NF-κB) pathway genes, NFKBIK and RELA, are associated with soluble ICAM1 (sICAM1) levels. However, neither of these two gene variants is found in the Asian populations. This study aimed to elucidate whether other candidate gene variants involved in the NF-κB pathway may be associated with sICAM1 levels in Taiwanese. After excluding carriers of the ICAM1 rs5491-T allele, three SNPs in the ICAM1 gene and eight SNPs in six of the NF-κB pathway genes (NFKB1, PDCD11, TNFAIP3, NKAPL, IKBKE, and PRKCB) were analyzed for their association with sICAM1 levels in 480 individuals. Our data showed that two SNPs, rs5498 of ICAM1 and rs1635 of NKAPL, were significantly associated with sICAM1 levels (P = 0.002 and 0.004, respectively) in the Taiwanese population. Using a multivariate analysis, rs5498 and rs1635 as well as the previously reported ABO genotypes and rs12051272 of the CDH13 gene were independently associated with sICAM1 levels (P = 0.001, 0.001, 0.006 and 0.031, respectively). An analysis with combined risk alleles of four candidate SNPs in the ICAM1, NKAPL, ABO, and CDH13 genes showed an increase in sICAM1 levels with added numbers of risk alleles and weighted genetic risk score. Our findings thus expanded the repertoire of gene variants responsible for the regulation of sICAM1 levels in the Asian populations.

Activin A Predicts Left Ventricular Remodeling and Mortality in Patients with ST-Elevation Myocardial Infarction.

BACKGROUND: Activin A levels increase in a variety of heart diseases including ST-elevation myocardial infarction (STEMI). The aim of this study is to investigate whether the level of activin A can be beneficial in predicting left ventricular remodeling, heart failure, and death in patients with ST-elevation myocardial infarction (STEMI). METHODS: We enrolled 278 patients with STEMI who had their activin A levels measured on day 2 of hospitalization. Echocardiographic studies were performed at baseline and were repeated 6 months later. Thereafter, the clinical events of these patients were followed for a maximum of 3 years, including all-cause death and readmission for heart failure. RESULTS: During hospitalization, higher activin A level was associated with higher triglyceride level, lower left ventricular ejection fraction (LVEF), and lower left ventricular end diastolic ventricular volume index (LVEDVI) in multivariable linear regression model. During follow-up, patients with activin A levels > 129 pg/ml had significantly lower LVEF, and higher LVEDVI at 6 months. Kaplan-Meier survival curves showed that activin A level > 129 pg/ml was a predictor of all-cause death (p = 0.022), but not a predictor of heart failure (p = 0.767). CONCLUSIONS: Activin A level > 129 pg/ml predicts worse left ventricular remodeling and all-cause death in STEMI.

Interactive effects of C-reactive protein levels on the association between APOE variants and triglyceride levels in a Taiwanese population.

BACKGROUND: Apolipoprotein E (APOE) plays a major role in lipid metabolism and inflammation. However, the association between APOE gene polymorphisms and serum triglyceride levels remains controversial. We tested the effects of APOE variants on triglyceride levels and their interactions with the inflammatory marker C-reactive protein (CRP) in a Taiwanese population. METHODS: Two APOE single nucleotide polymorphisms (SNPs) rs429358 and rs7412 were genotyped by TaqMan Assay using real time PCR in 595 healthy subjects attending the clinic for routine visits. RESULTS: After adjustment for clinical covariates, subjects carrying the rs429358-TT genotype and non-ε4 alleles were found to have higher CRP levels, whereas those with rs7412-CC genotype and non-ε2 alleles had significantly higher total and low-density lipoprotein cholesterol levels (all P < 0.01). Using subgroup and interaction analyses, we observed significantly lower triglyceride levels in subjects carrying the rs429358-TT genotype and non-ε4 alleles in the low CRP group (P = 2.71 × 10(-4) and P = 4.32 × 10(-4), respectively), but not in those in the high CRP group (interaction P = 0.013 and 0.045, respectively). In addition, multivariate stepwise linear regression analysis showed that subjects carrying the rs429358-TT genotype and non-ε4 alleles with low CRP levels had significantly lower triglyceride levels (P < 0.001 and P < 0.001, respectively). In addition, when combined with the risk alleles of GCKR, APOA5 and LPL gene variants, we observed that triglyceride levels increased significantly with the number of risk alleles (P = 2.9 × 10(-12)). CONCLUSIONS: The combination of SNPs and ε alleles at the APOE locus is involved in managing lipid and CRP levels in the Taiwanese population. APOE polymorphisms interact with CRP to regulate triglyceride levels, thus triglyceride concentration is influenced by both the genetic background of the APOE locus and the inflammatory status of a subject.

Effects of obesity on the association between common variations in the TBX5 gene and matrix metalloproteinase 9 levels in Taiwanese.

OBJECTIVES: The TBX5 gene, a member of the T-box family, is associated with congenital heart disease, electrocardiographic parameters, and development of atrial fibrillation in the general population. This study aimed to elucidate the role of TBX5 gene polymorphisms in metabolic and inflammatory profiles possibly linked to TBX5-related pathologies. MATERIALS AND METHODS: A sample population of 597 individuals having routine health examinations was enrolled. Five tagging TBX5 single nucleotide polymorphisms (SNPs) were analyzed using polymerase chain reaction and restriction enzyme digestion or TaqMan SNP genotyping assays. Associations between genotypes/haplotypes and matrix metalloproteinase 9 (MMP9) levels were investigated using generalized linear model analysis. Interactions between each genotype/haplotype, MMP9 level, and obesity status were tested using two-way analysis of variance with Golden Helix SVS Win32 7.3.1 software. RESULTS: After adjusting for clinical covariates, TBX5 genotypes were found to be associated with MMP9 levels (p = 0.002 and p = 0.001 for rs4113925 and rs3825214, respectively) in a dominant inheritance model. Haplotype analysis using three tag SNPs (rs11067101, rs1247973, and rs3825214) revealed a significant association between TBX5 haplotype GCG and MMP9 levels (uncorrected p = 0.0093 and the corrected false discovery rate p = 0.0435). Multivariate analysis identified that SNP rs3825214, in addition to the MMP9 and E-selectin genotypes, was independently associated with MMP9 levels (p < 0.001). Using a dominant inheritance model, subgroup and interaction analysis showed associations between the rs4113925, rs3825214, and MMP9 levels only in nonobese individuals (p = 1.04 × 10-4 and p = 7.11 × 10-5, respectively; interaction p = 0.009 and 0.018, respectively). Subgroup analysis showed a borderline significant association between haplotype GCG and MMP9 levels (uncorrected p = 0.020 and corrected false discovery rate p = 0.073), but with no evidence of interaction. CONCLUSION: TBX5 genotypes/haplotypes are independently associated with MMP9 in Taiwanese individuals and occur predominantly in nonobese people. These associations may broaden our understanding of the mechanism underlying T-box family gene activity and related cardiovascular pathologies.

QT interval Independently Predicts Mortality and Heart Failure in Patients with ST-Elevation Myocardial Infarction.

OBJECTIVES: Heart-rate corrected QT (QTc) interval predicts cardiovascular mortality or all-cause mortality in the general population. Little is known about the best cut-off value of QTc interval for predicting clinical events in patients with ST-elevation myocardial infarction (STEMI). METHODS: We enrolled 264 patients with STEMI who received measurement of QTc intervals at ER (QTc-ER), on day 2 (QTc-D2), and on day 3 (QTc-D3) of hospitalization. Clinical events, including all-cause death and readmission for heart failure, were followed for 2 years. RESULTS: Prolonged QTc-ER, but not QTc-D2 or QTc-D3, well predicted clinical events with the best cut-off value of 445 ms. Patient with QTc-ER > 445 ms had lower left ventricular ejection fraction at baseline and at 6 months. Kaplan-Meier survival curves showed that the combination of QTc-ER > 445 ms and N-terminal pro-brain natriuretic peptide (NT-pro BNP) > 936 pg/mL was a strong predictor of clinical events (p<0.001). In multivariable Cox regression analysis, the independent predictors of death and heart failure were QTc-ER (p<0.001), log NT-proBNP (p<0.001), diabetes mellitus (p<0.001), history of stroke (p=0.001), and left ventricular end diastolic volume index (p<0.001). CONCLUSION: QTc-ER > 445 ms independently predicts clinical events in STEMI, providing incremental prognostic value to established clinical predictors and NT-proBNP.

Associations between TRPV4 genotypes and body mass index in Taiwanese subjects.

Body weight regulation is influenced neuronally via the hypothalamus, which strongly expresses TRPV4. TRPV4 deficiency in mice confers resistance against diet-induced obesity. We investigated the association between TRPV4 gene variants and body mass index (BMI) in Taiwanese subjects. A sample population of 617 Taiwanese subjects was enrolled, and ten TRPV4 gene polymorphisms were selected and genotyped. After adjusting for clinical covariates, significant associations were observed between three studied polymorphisms and BMI using a dominant model (P = 4.83 × 10(-4), P = 1.17 × 10(-4), and P = 3.37 × 10(-4) for rs3742037, rs10735104, and rs3742035, respectively). Obesity as defined according to both the Asian and National Institutes of Health (NIH) criteria was significantly associated with rs10735104 (P = 0.003 and P = 0.037, respectively) in a dominant model. Genotypes at the TRPV4 locus independently affect BMI and obesity status in Taiwanese subjects. This association may broaden our understanding of the role of neuronal influence on body weight regulation. The regulation of TRPV4 channels in skeletal muscle and adipose tissue could also be a new therapeutic target for preventing the development of obesity.

Diagnostic role of inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes in tuberculous pleural effusion.

BACKGROUND AND OBJECTIVE: Early diagnosis of tuberculous pleural effusion (TPE) remains difficult. While some inflammatory markers in pleural effusion (PE) are helpful in diagnosis, the roles of anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes have not been investigated. METHODS: Lymphocyte-predominant exudative PE samples were assayed for inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes. Logistic regression analysis was used to predict the probability of TPE and identify independently associated factors. Receiver operating characteristic (ROC) curve analysis was applied to determine the optimal cut-off value for the predicted probability. RESULTS: Of 95 patients enrolled, 35 had TPE, 46 had malignant PE and 14 had PE due to other aetiologies. Interferon-γ (IFN-γ), adenosine deaminase (ADA), decoy receptor (DcR) 3, monocyte chemo-attractant protein (MCP)-1, IFN-induced protein (IP)-10, granzyme A and perforin were higher in TPE than in PE of other aetiologies. By logistic regression analysis, IFN-γ ≥ 75 pg/mL, ADA ≥ 40 IU/mL, DcR3 ≥ 9.3 ng/mL and soluble tumour necrosis factor receptor 1 (TNF-sR1) ≥ 3.2 ng/mL were independent factors associated with TPE. The predicted probability based on the four predictors had an area under the ROC curve of 0.920, with 82.9% sensitivity and 86.7% specificity under the cut-off value of 0.303. In the TPE group, patients with positive PE/pleural culture for Mycobacterium tuberculosis had higher pleural IFN-γ, MCP-1, IP-10 and perforin than those with positive sputum but negative PE culture. CONCLUSIONS: While pleural interferon-γ and ADA are conventional markers for diagnosing TPE, simultaneous measurements of DcR3 and TNF-sR1 can improve the diagnostic efficacy.

Growth-differentiation factor-15 and major cardiac events.

BACKGROUND: Growth-differentiation factor (GDF)-15 is a strong predictor of cardiovascular events in patients with ST-elevation myocardial infarction (STEMI). However, the effects of GDF-15 on left ventricular (LV) remodeling have not been clearly elucidated. The aim of this study is to investigate whether GDF-15 will be of benefit in predicting LV remodeling, heart failure and death in patients with STEMI. METHODS: The authors enrolled 216 patients with STEMI who received measurement of GDF-15 level on day 2 of hospitalization. Echocardiographic studies were performed at baseline and were repeated 6 months later. Clinical events, including all-cause death and readmission for heart failure, were followed up for a maximum of 3 years. RESULTS: Patients with GDF-15 levels above the median had lower LV ejection fraction at baseline (43.9% versus 48.0%, P = 0.041) and at 6 months (51.5% versus 56.9%, P = 0.025). In univariable regression model, log-transformed GDF-15 level was not a predictor of increase in LV end-diastolic volume index at 6 months (P = 0.767). Kaplan-Meier survival curves showed that the combination of high GDF-15 and high N-terminal pro-B-type natriuretic peptide was a strong predictor of death and heart failure (P < 0.001). In multivariable Cox regression model, the independent predictors of death and heart failure were age, GDF-15 level and diabetes mellitus. CONCLUSIONS: High GDF-15 level is a strong predictor of death and heart failure in patients with STEMI. Although patients with higher GDF-15 levels tend to have lower LV ejection fraction, they have similar degree of the increase in LV end-diastolic volume index at 6 months.

Genetic variants associated with circulating MMP1 levels near matrix metalloproteinase genes on chromosome 11q21-22 in Taiwanese: interaction with obesity.

BACKGROUND: MMP1 is implicated in the pathogenesis of atherothrombotic cardiovascular disease. We aimed to elucidate genetic determinants of inflammatory marker levels, including circulating MMP1, in Taiwanese, and their association with obesity. METHODS: Five genetic polymorphisms around matrix metalloproteinase genes on chromosome 11q21-22 region were genotyped in 519 subjects. RESULTS: After adjusting for clinical covariates, two polymorphisms were significantly associated with MMP1 levels, rs1799750 and rs495366, using an additive inheritance model (P = 1.5x10-4 and P = 2.57x10-5, respectively). Using dominant model, minor alleles of rs1799750 and rs495366 were associated with higher MMP1 levels (P = 1.3x10-4 and P = 1.95x10-5, respectively). In haplotype analysis, two haplotypes inferred from five SNPs (A2GATA and A1GATG) were associated with MMP1 levels (P = 5x10-4 and P = 8.47x10-5, respectively). Subgroup and interaction analysis revealed an association of rs1799750 and rs495366 with MMP1 levels only in non-obese subjects (P = 6.66x10-6 and P = 4.38x10-5, respectively, and interaction P = 0.008 for rs1799750). Haplotype interaction analysis also showed significant interaction for haplotype A1GATG (interaction P = 0.003). CONCLUSIONS: Genotypes/haplotypes around MMP1 locus are associated with MMP1 levels in Taiwanese. Further, since genotypes/haplotypes near MMP1 locus interact with obesity to set MMP1 levels, genetic determinants for MMP1 level may be different between obese and non-obese individuals.

Correlates of impaired global right ventricular function in patients with a reperfused acute myocardial infarction and without right ventricular infarction.

BACKGROUND: The frequency and clinical correlates of global right ventricular (RV) dysfunction in patients treated with primary percutaneous coronary intervention for a first acute ST-elevation myocardial infarction (STEMI) without a coexisting RV infarction is not well known. MATERIALS AND METHODS: One hundred seven consecutive patients underwent conventional echocardiography and pulsed-wave tissue Doppler imaging (TDI) within 72 hours after a successful primary percutaneous coronary intervention to assess their RV function. Global RV function was quantified with the RV myocardial performance index (MPI) by pulsed-wave TDI. An abnormal TDI-derived RV MPI was defined as greater than the upper reference limit of 0.55. RESULTS: Global RV dysfunction was present in 18 (17%) of the 107 patients enrolled. The patients with global RV dysfunction had significantly higher glucose levels on admission (216 ± 102 vs 163 ± 86 mg/dL; P = 0.027), higher peak creatine kinase (4027 ± 2171 vs 2660 ± 1980 IU/L; P = 0.014), and more frequently had anterior infarcts (89% vs 58%; P = 0.016) than those without RV dysfunction. Patients with global RV dysfunction also had a significantly lower left ventricular (LV) ejection fraction (45.1 ± 10.8% vs 51.1 ± 9.7%; P = 0.021), a higher global wall motion score index (1.9 ± 0.3 vs 1.7 ± 0.4; P = 0.007), and greater LV MPI (0.65 ± 0.19 vs 0.47 ± 0.11; P = 0.001) than patients without. With the use of multivariate regression analysis, TDI-derived LV MPI (odds ratio [OR], 3.40; 95% confidence interval [CI], 1.20-9.67; P = 0.022), the ratio of transmitral peak early (E) to late diastolic filling (A) velocities (E/A ratio) (OR, 0.41; 95% CI, 0.18-0.92; P = 0.031), and admission plasma glucose level (OR, 1.01; 95% CI, 1.0-1.02; P = 0.039) were independently associated with the presence of global RV dysfunction. CONCLUSIONS: In patients with a first acute STEMI without an associated RV infarction, depressed global LV function reflected by increased TDI-derived LV MPI, a lower mitral E/A ratio, and a higher glucose level on admission are independent correlates of early global RV dysfunction. Routine assessment of global RV function should be implemented in patients with STEMI with these characteristics.

Association of SELE genotypes/haplotypes with sE-selectin levels in Taiwanese individuals: interactive effect of MMP9 level.

BACKGROUND: E-selectin is implicated in various inflammatory processes and related disorders. We aimed to investigate the role of SELE-gene genotypes/haplotypes on plasma levels of MMP9 and sE-selectin in Taiwanese individuals. METHODS: Five hundred twenty individuals were enrolled. Seven tagging SELE single nucleotide polymorphisms were analyzed. RESULTS: SELE genotypes were found associated with MMP9 and sE-selectin levels. Multivariate analysis identified that the most significant genetic polymorphism (rs5368 genotype) was independently associated with MMP9 levels (P < 0.001). One haplotype (GGAGAGT) was marginally associated with MMP9 levels (P = 0.0490). One SELE SNP, (rs3917406, P = 0.031) was associated with sE-selectin levels after adjusting for MMP9 and sICAM1 levels. Subgroup and interaction analysis revealed association of SELE SNP rs10800469 with sE-selectin levels only in the highest quartile of MMP9 level (P = 0.002, interaction P = 0.023). Haplotype analysis showed one haplotype (AAAAAGC) borderline associated with sE-selectin level (P = 0.0511). CONCLUSION: SELE genotypes/haplotypes are independently associated with MMP9 and E-selectin levels in Taiwanese individuals. The associations of SELE genotypes/haplotypes with sE-selectin levels are affected by MMP9 levels.