Duration of Clopidogrel-Based Dual Antiplatelet Therapy and Clinical Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention　- A Real-World Observation in Taiwan From 2012 to 2015.

BACKGROUND: Little information is available in Asia about the real-world practice of dual antiplatelet therapy (DAPT) duration for acute coronary syndrome (ACS) and its influence on clinical outcomes.Methods and Results:The Taiwan ACS STENT Registry was a prospective, multicenter study to observe ACS patients using clopidogrel-based DAPT after percutaneous coronary intervention (PCI). The primary outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Overall, 2,221 ACS patients (62 years, 83% men) were included. DAPT duration was ≤9 months in 935 (42.1%). The incidence of primary outcome was higher in patients receiving DAPT ≤9 months compared with those receiving DAPT >9 months at 1 year (3.5% vs. 1.6%, P=0.0026). The incidence of stent thrombosis (overall 0.5%) was similar between groups. Multivariable analysis showed that DAPT >9 months was associated with a significantly lower risk of primary outcome (odds ratio 0.725, 95% confidence interval 0.545-0.965). CONCLUSIONS: Our data showed that short duration of DAPT (≤9 months) was common (42.1%) in Taiwan for ACS patients undergoing PCI. DAPT ≤9 months increased the risk of the primary outcome.

Changing Practice Pattern of Acute Coronary Syndromes in Taiwan from 2008 to 2015.

BACKGROUND: Patients with acute coronary syndrome (ACS), including ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation (NSTE)-ACS have a significant risk of morbidity and mortality. This study evaluated the practice patterns of ACS care in Taiwan from 2005 to 2018. METHODS: Data from two nationwide ACS registries (2008-2010 and 2012-2015) were used. ACS patients who received percutaneous coronary interventions (PCIs) during admission were compared between the two registries. RESULTS: In STEMI, the door-to-balloon time for primary PCI decreased by 25 min from a median of 96 to 71 min (p < 0.0001) from the first to second registry. More complex PCI procedures and drug-eluting stents were used for ACS. However, the onset-to-door time was still long for both STEMI and NSTE-ACS. The D2B time for NSTE-ACS was long, especially in the elderly and female patients. Although the prescription rate of secondary preventive medications for ACS increased, it was still relatively low compared with Western data, especially in NSTE-ACS. CONCLUSIONS: The registry data showed that ACS care quality has improved in Taiwan. However, areas including onset-to-door time and use of secondary preventive medications still need further improvements.

Prostaglandin E2 Receptor 2 Modulates Macrophage Activity for Cardiac Repair.

Background Prostaglandin E2 has long been known to be an immune modulator. It is released after tissue injury and plays a role in modulating macrophage activities, which are essential for tissue regeneration. However, the involvement of prostaglandin E2 receptor 2 ( EP 2)-dependent regulation of macrophages in postischemic heart is unclear. This study aims to evaluate the role of EP 2 in damaged heart. Methods and Results The effect of EP 2 in postischemic heart was evaluated using EP 2-deficient transgenic mice. We demonstrated that cardiac function was worse after myocardial injury on loss of EP 2. Furthermore, EP 2 deficiency also altered proinflammatory response and resulted in a defect in macrophage recruitment to the injured myocardium. Transcriptome analysis revealed that the expression of erythroid differentiation regulator 1 ( Erdr1) was significantly induced in EP 2-deficient macrophages. Knocking down Erdr1 expression restored migration ability of EP 2-deficient cells both in vitro and in vivo. By using a genetic fate-mapping approach, we showed that abolishment of EP 2 expression effectively attenuated cell replenishment. Conclusions The EP 2-dependent signaling pathway plays a critical role in regulating macrophage recruitment to the injured myocardium, thereby exerting a function in modulating the inflammatory microenvironment for cardiac repair.

Hemodynamic, biological, and right ventricular functional changes following intraatrial shunt repair in patients with flow-induced pulmonary hypertension.

OBJECTIVES: Atrial septal defects may result in pulmonary hypertension and right heart remodeling. We analyzed improvements in patients with flow-induced pulmonary hypertension and the activation of endothelial progenitor cells after flow reduction. DESIGN: This prospective cohort study included 37 patients who were admitted for an occluder implantation. Blood samples were collected before and after the procedure. We determined the number of endothelial progenitor cells in outgrowth colonies and serum Hsp27 concentrations. Daily performance and cardiothoracic ratio were reevaluated later. RESULTS: Closure of the defect significantly reduced the pulmonary pressure and B-type natriuretic peptide levels. The cardiothoracic ratio and daily performance status also improved. The number of endothelial progenitor cell outgrowth colony-forming units significantly increased and was positively correlated with daily performance. In patients with enhanced colony formation, Hsp27 levels were significantly increased. CONCLUSIONS: The implantation of an occluder successfully improved hemodynamic, right ventricular, and daily performance. Qualitative enhancement of colony formation for endothelial progenitor cells was also noted and positively correlated with daily performance. Closure of defects may serve as a valid, reliable model to obtain a deeper understanding of the modulation of endothelial progenitor cell activity and its relationship with pulmonary hypertension prognosis.

The 2017 Focused Update of the Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS) for the Management of Hypertension.

Hypertension (HT) is the most important risk factor for cardiovascular diseases. Over the past 25 years, the number of individuals with hypertension and the estimated associated deaths has increased substantially. There have been great debates in the past few years on the blood pressure (BP) targets. The 2013 European Society of Hypertension and European Society of Cardiology HT guidelines suggested a unified systolic BP target of 140 mmHg for both high-risk and low-risk patients. The 2014 Joint National Committee report further raised the systolic BP targets to 150 mmHg for those aged ≥ 60 years, including patients with stroke or coronary heart disease, and raised the systolic BP target to 140 mmHg for diabetes. Instead, the 2015 Hypertension Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society suggested more aggressive BP targets of < 130/80 mmHg for patients with diabetes, coronary heart disease, chronic kidney disease with proteinuria, and atrial fibrillation patients on antithrombotic therapy. Based on the main findings from the Systolic Blood Pressure Intervention Trial (SPRINT) and several recent meta-analyses, the HT committee members of the Taiwan Society of Cardiology and the Taiwan Hypertension Society convened and finalized the revised BP targets for management of HT. We suggested a new systolic BP target to < 120 mmHg for patients with coronary heart disease, chronic kidney disease with an eGFR of 20-60 ml/min/1.73 m2, and elderly patients aged ≥ 75 years, using unattended automated office BP measurement. When traditional office BP measurement is applied, we suggested BP target of < 140/90 mmHg for elderly patients with an age ≥ 75 years. Other BP targets with traditional office BP measurement remain unchanged. With these more aggressive BP targets, it is foreseeable that the cardiovascular events will decrease substantially in Taiwan.

2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the management of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia. Both the incidence and prevalence of AF are increasing, and the burden of AF is becoming huge. Many innovative advances have emerged in the past decade for the diagnosis and management of AF, including a new scoring system for the prediction of stroke and bleeding events, the introduction of non-vitamin K antagonist oral anticoagulants and their special benefits in Asians, new rhythm- and rate-control concepts, optimal endpoints of rate control, upstream therapy, life-style modification to prevent AF recurrence, and new ablation techniques. The Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology aimed to update the information and have appointed a jointed writing committee for new AF guidelines. The writing committee members comprehensively reviewed and summarized the literature, and completed the 2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the Management of Atrial Fibrillation. This guideline presents the details of the updated recommendations, along with their background and rationale, focusing on data unique for Asians. The guidelines are not mandatory, and members of the writing committee fully realize that treatment of AF should be individualized. The physician's decision remains most important in AF management.

Functional Improvement and Regression of Medial Hypertrophy in the Remodeled Pulmonary Artery after Correction of Systemic Left-to-Right Shunt.

The presence of systemic left-to-right shunt and increased pulmonary blood flow can result in right heart failure and pulmonary arteriopathy. Correction of left-to-right shunt has been shown to improve cardiac function and physical performance. However, the cardiopulmonary remodeling processes following cessation of left-to-right shunt have yet to be reported. In this experimental study, excessive pulmonary flow was restored through ligation of the aortocaval fistula in rats with flow-induced pulmonary hypertension. The cardiopulmonary morphometric functions were assessed, and phenotypic switching of pulmonary vascular smooth muscle cells (VSMC) was determined. Ligation of aortocaval fistula significantly attenuated pulmonary blood flow and right ventricular mass, and potentiated the isometric contraction of pulmonary artery. Inflammatory cytokines IL-1ß and IL-6 were reduced in the lung after ligation. Reduction of pulmonary blood flow restored the expressions of smooth muscle myosin heavy chain and α-smooth muscle actin in pulmonary artery, indicating the switching of VSMCs to the contractile phenotype. Our study demonstrated that normalization of pulmonary blood flow in flow-induced pulmonary hypertension reverses the remodeling in the right ventricle and pulmonary artery. The remodeling process of flow-induced pulmonary hypertension is functionally and morphometrically reversible by inducing transdifferentiation of pulmonary VSMC to contractile phenotypes and modulation of tissue inflammatory cytokines.

Cilostazol improves high glucose-induced impaired angiogenesis in human endothelial progenitor cells and vascular endothelial cells as well as enhances vasculoangiogenesis in hyperglycemic mice mediated by the adenosine monophosphate-activated protein kinase pathway.

OBJECTIVE: Cilostazol is an antiplatelet agent with vasodilatory effects that works by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP). This study investigated the effects of cilostazol in preventing high glucose (HG)-induced impaired angiogenesis and examined the potential mechanisms involving activation of AMP-activated protein kinase (AMPK). METHODS: Assays for colony formation, adhesion, proliferation, migration, and vascular tube formation were used to determine the effect of cilostazol in HG-treated endothelial progenitor cells (EPCs) or human umbilical vein endothelial cells (HUVECs). Animal-based assays were performed in hyperglycemic ICR mice undergoing hind limb ischemia. An immnunoblotting assay was used to identify the expression and activation of signaling molecules in vitro and in vivo. RESULTS: Cilostazol treatment significantly restored endothelial function in EPCs and HUVECs through activation of AMPK/acetyl-coenzyme A carboxylase (ACC)-dependent pathways and cAMP/protein kinase A (PKA)-dependent pathways. Recovery of blood flow in the ischemic hind limb and the population of circulating CD34(+) cells were significantly improved in cilostazol-treated mice, and these effects were abolished by local AMPK knockdown. Cilostazol increased the phosphorylation of AMPK/ACC and Akt/endothelial nitric oxide synthase signaling molecules in parallel with or downstream of the cAMP/PKA-dependent signaling pathway in vitro and in vivo. CONCLUSIONS: Cilostazol prevents HG-induced endothelial dysfunction in EPCs and HUVECs and enhances angiogenesis in hyperglycemic mice by interactions with a broad signaling network, including activation of AMPK/ACC and probably cAMP/PKA pathways.

Defined MicroRNAs Induce Aspects of Maturation in Mouse and Human Embryonic-Stem-Cell-Derived Cardiomyocytes.

Pluripotent-cell-derived cardiomyocytes have great potential for use in research and medicine, but limitations in their maturity currently constrain their usefulness. Here, we report a method for improving features of maturation in murine and human embryonic-stem-cell-derived cardiomyocytes (m/hESC-CMs). We found that coculturing m/hESC-CMs with endothelial cells improves their maturity and upregulates several microRNAs. Delivering four of these microRNAs, miR-125b-5p, miR-199a-5p, miR-221, and miR-222 (miR-combo), to m/hESC-CMs resulted in improved sarcomere alignment and calcium handling, a more negative resting membrane potential, and increased expression of cardiomyocyte maturation markers. Although this could not fully phenocopy all adult cardiomyocyte characteristics, these effects persisted for two months following delivery of miR-combo. A luciferase assay demonstrated that all four miRNAs target ErbB4, and siRNA knockdown of ErbB4 partially recapitulated the effects of miR-combo. In summary, a combination of miRNAs induced via endothelial coculture improved ESC-CM maturity, in part through suppression of ErbB4 signaling.

The role of echocardiographic study in patients with chronic kidney disease.

Despite the recent enormous advances in medicine, high mortality and morbidity rates among the chronic kidney disease (CKD) patients remain an important but unresolved issue. Cardiovascular disease is a major cause of mortality and morbidity in patients with CKD. Abnormal left ventricular geometry and functions are common in this patient group and have been proven to be correlated with a high cardiovascular mortality/morbidity and all-cause mortality. For this reason, echocardiographic study plays an important role in evaluating cardiac structure and functions as well as in stratifying prognostic risk. We here summarize the reported findings on the usefulness of echocardiographic methodologies and identify their roles in diagnostic and prognostic clinical approaches.

Fetuin-A as a predicator of sarcopenic left ventricular dysfunction.

Sarcopenia is an aging condition involving low muscle mass and function. Fetuin-A (FetA) appears to be a factor for body composition remodeling. We hypothesized that age increases FetA levels and deteriorates the myocardial function by affecting diastolic function, especially in people with sarcopenia. We enrolled 541 asymptomatic elderly (≥ 65 years) patients. Compared with non-sarcopenic population, FetA levels were significantly elevated in the ninety-two (17%) patients (79 ± 6 years; male: 34.7%) diagnosed with sarcopenia (621.1 ± 140.7 vs. 697.3 ± 179.6 µg/ml, < 0.001). Sarcopenic left ventricular dysfunction (S-LVD) was defined by the coexistence of sarcopenia and systolic impairment (LVEF < 50%) and 23 (4.3%) of them met the criteria. Patients with S-LVD showed relatively reduced systolic heart function, higher end-diastolic pressure and a higher FetA level (all p < 0.001) than did those with sarcopenia but without LV dysfunction (S-NLVD). Conversely, in the group without sarcopenia, FetA levels were similar regardless of systolic function. Multivariable logistic regression showed that older age, impaired diastolic function, and higher FetA levels were significantly associated with S-LVD. In conclusion, we found that FetA was significantly higher in elderly patients with sarcopenia, which was associated with impaired diastolic and systolic functions.

The time window for therapy with peptide nanofibers combined with autologous bone marrow cells in pigs after acute myocardial infarction.

BACKGROUND: We previously showed that injection of peptide nanofibers (NF) combined with autologous bone marrow mononuclear cells (MNC) immediately after coronary artery ligation improves cardiac performance in pigs. To evaluate the clinical feasibility, this study was performed to determine the therapeutic time window for NF/MNC therapy in acute myocardial infarction (MI). METHODS AND RESULTS: A total of 45 adult minipigs were randomly grouped into 7 groups: sham or MI plus treatment with NS (normal saline), or NF or MNC alone at 1 day (1D) post-MI, or NF/MNC at 1, 4, or 7 days post-MI (N≥6). Cardiac function was assessed by echocardiography and ventricular catheterization. Compared with the NS control, pigs treated with NF/MNC at 1 day post-MI (NF/MC-1D) had the greatest improvement in left ventricle ejection fraction (LVEF; 55.1±1.6%; P<0.01 vs. NS) 2 months after MI. In contrast, pigs treated with either NF/MNC-4D or NF/MNC-7D showed 48.9±0.8% (P<0.05 vs. NS) and 43.5±2.3% (n.s. vs. NS) improvements, respectively. The +dP/dt and -dP/dt, infarct size and interstitial collagen content were also improved in the NF/MNC-1D and -4D groups but not in the -7D group. Mechanistically, MNC quality and the states of systemic inflammation and damaged heart tissue influence the therapeutic efficiency of NF/MNC therapy, as revealed by another independent study using 16 pigs. CONCLUSIONS: Injection of NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance and prevents ventricular remodeling, confirming the importance of early intervention when using this therapy for acute MI.

Injection of Peptide nanogels preserves postinfarct diastolic function and prolongs efficacy of cell therapy in pigs.

Accumulating evidence suggests that the benefits of cell therapy for cardiac repair are modest and transient due to progressive harmful cardiac remodeling as well as loss of transplanted cells. We previously demonstrated that injection of peptide nanofibers (NFs) reduces ventricular remodeling and facilitates cell retention at 1 month after acute myocardial infarction (MI) in pigs. However, it remains unclear whether these benefits still persist as the material is being degraded. In this study, 2 mL of placebo or NFs, with or without 1×10(8) mononuclear cells (MNCs), was injected into the pig myocardium after MI (n≥5 in each group), and cardiac function was assessed by echocardiography, including myocardial deformation analyses and catheterization at 3 months post-MI. Our results reveal that MNC-only injection slightly improved cardiac systolic function at 1 month post-MI, but this benefit was lost at later time points (ejection fraction: 42.0±2.3 in MI+normal saline [NS] and 43.5±1.1 in MI+MNCs). In contrast, NF-only injection resulted in improved cardiac diastolic function and reduced pathological remodeling at 3 months post-MI. Furthermore, combined injection of MNCs/NFs provided a greater and longer term cardiac performance (52.1±1.2 in MI+MNCs/NFs, p<0.001 versus MI+NS and MI+MNCs) and 11.3-fold transplanted cell retention. We also found that about 30% NFs remained at 3 months after injection; however, endogenous myofibroblasts were recruited to the NF-injected microenvironment to replace the degraded NFs and preserved cardiac dimensions and mechanics. In conclusion, we demonstrated that injection of NFs contributes to preservation of ventricular mechanical integrity and sustains MNC efficacy at 3 months postinjection.

Association of circadian genes with diurnal blood pressure changes and non-dipper essential hypertension: a genetic association with young-onset hypertension.

Recent studies have suggested that circadian genes have important roles in maintaining the circadian rhythm of the cardiovascular system. However, the associations between diurnal BP changes and circadian genes remain undetermined. We conducted a genetic association study of young-onset hypertension, in which 24-h ambulatory blood pressure (BP) monitoring was performed. A total of 23 tag single-nucleotide polymorphisms (SNPs) on 11 genes involved in circadian rhythms were genotyped for correlations with diurnal BP variation phenotypes. A permutation test was used to correct for multiple testing. Five tag SNPs within five loci, including rs3888170 in NPAS2, rs6431590 in PER2, rs1410225 in RORßß, rs3816358 in BMAL1 and rs10519096 in RORα, were significantly associated with the non-dipper phenotype in 372 young hypertensive patients. A genetic risk score was generated by counting the risk alleles and effects for each individual. Genotyping was performed in an additional independent set of 619 young-onset hypertensive subjects. Altogether, non-dippers had a higher weighted genetic risk score than dippers (1.67±0.56 vs. 1.54±0.55, P<0.001), and the additive genetic risk score also indicated a graded association with decreased diurnal BP changes (P=0.006), as well as a non-dipper phenotype (P=0.031). After multivariable logistic analysis, only the circadian genetic risk score (odds ratio (OR), 1550; 95% confidence interval (CI), 1.225-1.961, P<0.001) and the use of ß-blockers (OR, 1.519; 95% CI, 1.164-1.982, P=0.003) were independently associated with the presence of non-dippers among subjects with young-onset hypertension. Genetic variants in circadian genes were associated with the diurnal phenotype of hypertension, suggesting a genetic association with diurnal BP changes in essential hypertension.

2015 guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the management of hypertension.

It has been almost 5 years since the publication of the 2010 hypertension guidelines of the Taiwan Society of Cardiology (TSOC). There is new evidence regarding the management of hypertension, including randomized controlled trials, non-randomized trials, post-hoc analyses, subgroup analyses, retrospective studies, cohort studies, and registries. More recently, the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) published joint hypertension guidelines in 2013. The panel members who were appointed to the Eighth Joint National Committee (JNC) also published the 2014 JNC report. Blood pressure (BP) targets have been changed; in particular, such targets have been loosened in high risk patients. The Executive Board members of TSOC and the Taiwan Hypertension Society (THS) aimed to review updated information about the management of hypertension to publish an updated hypertension guideline in Taiwan. We recognized that hypertension is the most important risk factor for global disease burden. Management of hypertension is especially important in Asia where the prevalence rate grows faster than other parts of the world. In most countries in East Asia, stroke surpassed coronary heart disease (CHD) in causing premature death. A diagnostic algorithm was proposed, emphasizing the importance of home BP monitoring and ambulatory BP monitoring for better detection of night time hypertension, early morning hypertension, white-coat hypertension, and masked hypertension. We disagreed with the ESH/ESH joint hypertension guidelines suggestion to loosen BP targets to <140/90 mmHg for all patients. We strongly disagree with the suggestion by the 2014 JNC report to raise the BP target to <150/90 mmHg for patients between 60-80 years of age. For patients with diabetes, CHD, chronic kidney disease who have proteinuria, and those who are receiving antithrombotic therapy for stroke prevention, we propose BP targets of <130/80 mmHg in our guidelines. BP targets are <140/90 mmHg for all other patient groups, except for patients ≥80 years of age in whom a BP target of <150/90 mmHg would be optimal. For the management of hypertension, we proposed a treatment algorithm, starting with life style modification (LSM) including S-ABCDE (Sodium restriction, Alcohol limitation, Body weight reduction, Cigarette smoke cessation, Diet adaptation, and Exercise adoption). We emphasized a low-salt strategy instead of a no-salt strategy, and that excessively aggressive sodium restriction to <2.0 gram/day may be harmful. When drug therapy is considered, a strategy called "PROCEED" was suggested (Previous experience, Risk factors, Organ damage, Contraindications or unfavorable conditions, Expert's or doctor's judgment, Expenses or cost, and Delivery and compliance issue). To predict drug effects in lowering BP, we proposed the "Rule of 10" and "Rule of 5". With a standard dose of any one of the 5 major classes of anti-hypertensive agents, one can anticipate approximately a 10-mmHg decrease in systolic BP (SBP) (Rule of 10) and a 5-mmHg decrease in diastolic BP (DBP) (Rule of 5). When doses of the same drug are doubled, there is only a 2-mmHg incremental decrease in SBP and a 1-mmHg incremental decrease in DBP. Preferably, when 2 drugs with different mechanisms are to be taken together, the decrease in BP is the sum of the decrease of the individual agents (approximately 20 mmHg in SBP and 10 mmHg in DBP). Early combination therapy, especially single-pill combination (SPC), is recommended. When patient's initial treatment cannot get BP to targeted goals, we have proposed an adjustment algorithm, "AT GOALs" (Adherence, Timing of administration, Greater doses, Other classes of drugs, Alternative combination or SPC, and LSM + Laboratory tests). Treatment of hypertension in special conditions, including treatment of resistant hypertension, hypertension in women, and perioperative management of hypertension, were also mentioned. The TSOC/THS hypertension guidelines provide the most updated information available in the management of hypertension. The guidelines are not mandatory, and members of the task force fully realize that treatment of hypertension should be individualized to address each patient's circumstances. Ultimately, the decision of the physician decision remains of the utmost importance in hypertension management.

Trends in the incidence and management of acute myocardial infarction from 1999 to 2008: get with the guidelines performance measures in Taiwan.

BACKGROUND: The American Heart Association Get With the Guidelines (GWTG) program has improved care quality of acute myocardial infarction (AMI) with important implications for other countries in the world. This study evaluated the incidence and care of AMI in Taiwan and assessed the compliance of GWTG in Taiwan. METHODS AND RESULTS: We used the Taiwan National Health Insurance Research Database (1999-2008) to identify hospitalized patients ≥18 years of age presenting with AMI. The temporal trends of annual incidence and care quality of AMI were evaluated. The age-adjusted incidence of AMI (/100 000 person-years) increased from 28.0 in 1999 to 44.4 in 2008 (P<0.001). The use of guideline-based medications for AMI was evaluated. The use of dual antiplatelet therapy (DAPT) increased from 65% in 2004 to 83.9% in 2008 (P<0.001). Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) was used in 72.6% in 2004 and 71.7% in 2008 (P=NS) and ß-blocker was used in 60% in 2004 and 59.7% in 2008 (P=NS). Statin use increased from 32.1% to 50.1% from 2004 to 2008 (P<0.001). The in-hospital mortality decreased from 15.9% in 1999 to 12.3% in 2008 (P<0.0001). Multivariable analysis showed that DAPT, ACE inhibitor/ARB, ß-blocker, and statin use during hospitalization were all associated with reduced in-hospital mortality in our AMI patients. CONCLUSIONS: AMI incidence was increasing, but the guideline-based medications for AMI were underutilized in Taiwan. Quality improvement programs, such as GWTG, should be promoted to improve AMI care and outcomes in Taiwan.

A novel SNP associated with nighttime pulse pressure in young-onset hypertension patients could be a genetic prognostic factor for cardiovascular events in a general cohort in Taiwan.

BACKGROUND: Pulse pressure (PP) is a risk factor for cardiovascular disease. It has been reported that ambulatory blood pressure (BP) and nighttime BP parameters are heritable traits. However, the genetic association of pulse pressure and its clinical impact remain undetermined. METHOD AND RESULTS: We conducted a genome-wide association study of PP using ambulatory BP monitoring in young-onset hypertensive patients and found a significant association between nighttime PP and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted gene FLJ16124. Young-onset hypertension patients carrying TT genotypes at rs897876 had higher nighttime PP than those with CT and CC genotypes (TT, 41.6 ± 7.3 mm Hg; CT, 39.1 ± 6.0 mm Hg; CC, 38.9 ± 6.3 mm Hg; p<0.05,). The T risk allele resulted in a cumulative increase in nighttime PP (ß = 1.036 mm Hg, se. = 0.298, p<0.001 per T allele). An independent community-based cohort containing 3325 Taiwanese individuals (mean age, 50.2 years) was studied to investigate the genetic impact of rs897876 polymorphisms in determining future cardiovascular events. After an average 7.79 ± 0.28 years of follow-up, the TT genotype of rs897876 was independently associated with an increased risk (in a recessive model) of coronary artery disease (HR, 2.20; 95% CI, 1.20-4.03; p = 0.01) and total cardiovascular events (HR, 1.99; 95% CI, 1.29-3.06; p = 0.002), suggesting that the TT genotype of rs897876C, which is associated with nighttime pulse pressure in young-onset hypertension patients, could be a genetic prognostic factor of cardiovascular events in the general cohort. CONCLUSION: The TT genotype of rs897876C at 2p14 identified in young-onset hypertensive had higher nighttime PP and could be a genetic prognostic factor of cardiovascular events in the general cohort in Taiwan.

Independent value of cardiac troponin T and left ventricular global longitudinal strain in predicting all-cause mortality among stable hemodialysis patients with preserved left ventricular ejection fraction.

Using a speckle-tracking echocardiography (STE), we recently demonstrated that a left ventricular (LV) global longitudinal strain (GLS) ≥ -15% and the serum cardiac troponin T (cTnT) concentration are associated with mortality in stable hemodialysis patients with preserved LV ejection fraction (LVEF). In this study, we explored the relationship between cTnT and echocardiographic parameters and evaluated whether the prognostic value provided by cTnT is independent of a GLS ≥ -15% and vice versa. Eighty-eight stable hemodialysis patients with preserved LVEF were followed for 31 months. STE studies and measurements of cTnT were performed at baseline. CTnT concentration had a modest correlation with GLS (rs = 0.44; P < 0.001) but had a weak or nonsignificant correlation with other echocardiographic parameters. Adjusting for clinical parameters, hazard ratios for each increase of 0.01 ng/mL in cTnT, and a GLS ≥ -15% on mortality were 1.13 (P = 0.009) and 3.09 (P = 0.03) without significant interaction between cTnT and GLS ≥ -15%. In addition, an increased cTnT concentration, a GLS ≥ -15%, or their combination showed significant additional predictive value for mortality when included in models consisting of clinical parameters. Therefore, both cTnT and a GLS ≥ -15% are independent predictors of mortality and are useful for risk stratification.

Elevated serum interleukin-18 level is associated with all-cause mortality in stable hemodialysis patients independently of cardiac dysfunction.

BACKGROUND: High circulating interleukin (IL)-18 level predicts a higher hospitalization rate among dialysis patients, possibly through cardiovascular mechanisms; however, whether higher IL-18 level is associated with mortality in dialysis patients is less clear. In addition, its impacts on left ventricular (LV) function are also unknown. We conducted a cohort study to examine the impacts of IL-18 level on LV function and prognosis among clinically stable hemodialysis patients. METHODS: Clinically stable patients undergoing maintenance hemodialysis (≥ 3 months) were prospectively enrolled from December 2008 to January 2009, and were followed up for 31 months. The enrolled patients (41% male, 66.4 ± 10.9 years of age) received 2-dimensional echocardiography and myocardial deformation (strain) analysis, including LV peak systolic longitudinal strain (GLS) and circumferential strain (CS). Laboratory measurements were also performed. Cox regression analysis was used to investigate prognostic factors. RESULTS: Seventy-five patients were stratified into 2 groups by the median value of IL-18 (654.2 pg/ml). Between these 2 groups, there was no significant difference in baseline characteristics including LV ejection fraction. The high IL-18 group had a worse LV systolic function as demonstrated by reduced GLS and CS. Seventeen patients (22.7%) died during the follow-up period. Multivariate Cox regression analysis showed that low serum albumin, the presence of hypertension, high serum IL-18, and less negative GLS (>-15%) were independently associated with all-cause mortality. No significant interaction between IL-18 and less negative GLS was noted in the final Cox model. CONCLUSION: Hemodialysis patients with high IL-18 levels tend to have worse LV systolic function and higher mortality rate. However, elevated serum IL-18 level is predictive of poor prognosis among stable hemodialysis patients, independently of LV dysfunction. This suggests an additional value of IL-18 to echocardiographic study in predicting all-cause mortality, and IL-18 may be helpful in early risk stratification of hemodialysis patients.