Novel prognostic impact and cell specific role of endocan in patients with coronary artery disease.

BACKGROUND: Both the clinical and mechanistic impacts of endocan were not well elucidated especially in coronary artery disease (CAD). OBJECTIVE: This study aimed to investigate the prognostic and potential pathological role of endocan for cardiovascular (CV) events in stable CAD patients. METHODS: A total of 1,071 stable CAD patients with previous percutaneous coronary intervention (PCI) were enrolled prospectively in a nationwide Biosignature study. Another cohort of 76 CAD patients with or without PCI were enrolled for validation. Baseline biomarkers including endocan level was measured and total CV events especially hard CV events (including CV mortality, non-fatal myocardial infection and stroke) during follow-up were identified. Circulating endothelial progenitor cells (EPCs) as an in vivo biological contributor to vascular repairment from CAD patients were used for the in vitro functional study. RESULTS: After 24 months, there were 42 patients (3.92%) with hard CV events and 207 (19.3%) with total CV events in the study group. The incidence of both events was increased with the tertiles of baseline endocan level (hard events: 1.7%,3.4%, and 6.7% in 1st,2nd, and 3rd tertile respectively, p = 0.002; total events: 13.8%vs.16.2%vs.28.0%, p < 0.0001). Multivariate regression analysis revealed the independent association of endocan level with total and hard CV events. These findings were validated in another cohort with a 5-year follow-up. Furthermore, in vitro inhibition of endocan improved cell migration and tube formation capacities, and reduced cell adhesiveness of EPCs from CAD patients. CONCLUSIONS: Endocan might be a novel prognostic indicator, mechanistic mediator, and potential therapeutic target for clinical CAD.

Sex and age differences of major cardiovascular events in patients after percutaneous coronary intervention.

BACKGROUND: Women usually have higher risk after receiving percutaneous coronary interventions (PCIs) than men with coronary artery disease (CAD). The aim of this study was to investigate the association of sex differences with future outcomes in CAD patients undergoing PCI, to assess the role of age, and to extend observed endpoints to stroke and congestive heart failure. METHODS: Six thousand six hundred forty-seven patients with CAD who received successful PCIs. The associations between clinic outcomes and sex were analyzed. The primary outcome was major cardiovascular events (MACE), including cardiac death, nonfatal myocardial infraction, and nonfatal stroke. The secondary outcome was MACE and hospitalization for heart failure (total CV events). RESULTS: During a mean of 52.7 months of follow-up, 4833 men and 1614 women received PCI. Univariate and multivariate analyses showed that women were independently associated with an increased risk of cardiac death (HR, 1.78; 95% CI, 1.32-2.41), hospitalization for heart failure (HR, 1.53; 95% CI, 1.23-1.89), MACE (HR, 1.34; 95% CI, 1.10-1.63), and total CV events (HR, 1.39; 95% CI, 1.20-1.62). In the subgroup analysis, women aged under 60 years had higher cardiovascular risks than men of the same age category. CONCLUSION: Women with CAD after successful PCI had poorer cardiovascular outcomes than men. Additionally, younger women (aged <60 years) were especially associated with a higher risk of developing future adverse cardiovascular outcomes.

Renal function during hospitalization and outcome in Chinese patients with acute decompensated heart failure: A retrospective study and literature review.

BACKGROUND: The heart and kidneys had demonstrated a bidirectional interaction that dysfunction of the heart or kidneys can induce dysfunction in the other organ. HYPOTHESIS: Renal function and its decline during hospitalization may have impact on cardiovascular outcomes in patients with acute decompensated heart failure (ADHF). METHODS: A total of 119 consecutive Chinese patients admitted for ADHF were prospectively enrolled. The course of renal function was presented with estimated glomerular filtration rate (eGFR), calculated by the four-variable equation proposed by the Modification of Diet in Renal Disease (MDRD) Study. Worsening renal function (WRF) was defined as eGFR decline between admission (eGFRadmission ) and predischarge (eGFRpredischarge ). Clinical outcomes were defined as 4P-major adverse cardiovascular events (4P-MACE), including the composition of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal HF hospitalization. RESULTS: During an average 2.6 ± 3.2 years follow-up, 66 patients (55%) experienced 4P-MACE. Patients with impaired eGFRpredischarge (<60 ml/min/1.73 m2 ) had more 4P-MACE than those with preserved eGFRpredischarge (64.7% vs. 43.1%, p = .019). The Kaplan-Meier survival curves showed significantly higher incidence of 4P-MACE in patients with impaired eGFRpredischarge than those with preserved eGFRpredischarge (p = .002). Cox regression analysis revealed that impaired eGFRpredischarge was significantly correlated with the development of 4P-MACE (hazard ratio, 2.003; 95% confidence interval, 1.072-3.744; p = .029). In contrast, outcomes would be similar with regard to eGFR on admission and eGFR decline during hospitalization. CONCLUSIONS: Impaired renal function before discharge, but not impaired renal function on admission or WRF, is a significant risk factor for poor outcomes in patients with ADHF.

Association between visit-to-visit blood pressure variability and adverse events in coronary artery disease patients after coronary intervention.

Blood pressure variability (BPV) is independently associated with higher cardiovascular risks. However, whether BPV is associated with poor outcomes for coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remained undetermined. We aimed to investigate the relationship between BPV and the outcomes of CAD patients undergoing PCI. Two thousand seven hundred and sixty-two CAD patients (1938 males, mean age 69.6 ± 12.9) who received PCI at Taipei Veterans General Hospital from 2006 to 2015 with multiple blood pressure measurements before and after the index PCI were enrolled. We calculated the standard deviation of systolic blood pressure, diastolic blood pressure, and pulse pressure as parameters of BPV. The primary endpoint was the composite of major adverse cardiovascular events [MACE comprising of cardiovascular death, nonfatal myocardial infarction (MI), and non-fatal stroke] and heart failure hospitalization (HHF). The key secondary endpoint was MACE. Both pre-PCI and post-PCI BPV were associated with CV events even after adjusting for co-morbidities and mean blood pressure. In Cox analysis, for every 1 mmHg increase in systolic BPV, the hazard ratio for the MACE + HHF, MACE, HHF, and cardiovascular death was 1.04 (95%CI: 1.03-1.05), 1.04 (95%CI: 1.02-1.05), 1.05 (95%CI: 1.04-1.06), and 1.06 (95%CI: 1.03-1.09), respectively. The association between BPV and cardiovascular risk is independent of blood pressure control status. The prognostic value of BPV was superior to mean blood pressure in both pre-PCI and post-PCI period. BPV is independently associated with cardiovascular events after PCI and has a better prognostic value than mean blood pressure suggesting the importance of maintaining stable blood pressure for CAD patients.

SLC12A3 Variation and Renal Function in Chinese Patients With Hypertension.

Objective: SLC12A3 (solute carrier family 12 member 3) gene variants are associated with diabetic nephropathy; however, their association with hypertensive nephropathy remains unknown. We aimed to investigate the association between SLC12A3 gene polymorphisms and renal function in patients with hypertension. Methods: Participants from three non-diabetic hypertensive cohorts, including young-onset hypertension (cohort 1, n = 882), treatment-naïve hypertension (cohort 2, n = 90), and follow-up cohort (cohort 3, n = 166), underwent genotyping for single nucleotide polymorphisms in SLC12A3. Renal events were defined as a >25 and >50% decline in estimated glomerular filtration rate (eGFR). Results: In cohort 1, SLC12A3 rs16963397 C/C or C/G (P = 0.005), rs13334864 C/C or C/T (P = 0.020), and rs7187932 A/A or A/G polymorphisms (P = 0.014) had higher eGFRs compared to their counterparts, with similar findings observed in cohort 2. In cohort 3, over a mean follow-up of 5.8 ± 1.7 years, participants with either SLC12A3 rs16963397 C/C or rs13334864 C/C polymorphisms had more >25 and >50% eGFR decline than their counterparts (log-rank test, P = 0.058 and P = 0.038, respectively). Cox regression analysis revealed that SLC12A3 rs16963397 C/C and rs13334864 C/C polymorphisms were significantly associated with an increased risk of >25% [hazard ratio (HR), 3.294; 95% confidence interval (CI), 1.158-9.368; P = 0.025] and >50% decline in eGFR (HR, 18.630; 95% CI, 1.529-227.005, P = 0.022) than their counterparts. Conclusion: SLC12A3 polymorphisms are associated with renal function in Chinese patients with hypertension.

Tolvaptan reduces angiotensin II-induced experimental abdominal aortic aneurysm and dissection.

Tolvaptan has been approved for the treatment of autosomal dominant polycystic kidney disease and heart failure. However, the role of tolvaptan in patients with abdominal aortic aneurysm (AAA) has not been examined. Human aortic smooth muscle cells (HASMCs) were used as the in vitro model. Via Ang II infusion, experimental AAAs were induced in Apo-E knockout mice. In vitro study showed that tolvaptan suppressed matrix metalloproteinase (MMP) expressions (MMP-2 and MMP-9) and apoptosis in Ang II-stimulated HASMCs. In the Apo-E knockout mice with Ang II-induced AAA, the animals exhibited AAA formation with elastic lamina degradation, dilatation of the suprarenal aorta, increased macrophage infiltration and higher expressions of MMPs. Treatment with a high dose of tolvaptan prevented experimental AAA formation while preserving the elastic lamina structure, reducing inflammatory macrophages, and inhibiting gelatinolytic activity, MMP expressions and apoptosis of SMCs in aorta tissue. Specifically, tolvaptan reduced the expression of receptor-interacting protein kinase 3 (RIP3) and decreased apoptosis of SMCs. Our data demonstrated that tolvaptan reduces experimental AAA formation and dissection by inhibiting destruction of the aortic structure integrity and reducing inflammatory macrophage infiltration, MMP-2 and MMP-9 expressions, and apoptosis of vascular SMCs, indicating tolvaptan may have therapeutic potential for AAA and dissection.

miR-548j-5p regulates angiogenesis in peripheral artery disease.

Peripheral artery disease (PAD) is a vascular disease involving diffuse atherosclerosis, and is associated with increased cardiovascular mortality and morbidity. Critical limb ischemia (CLI) is the most severe complication of PAD. In addition to medical and interventional treatment, therapeutic angiogenesis is a novel therapy for PAD. Circulating microRNAs (miRNAs) are considered key regulators of gene expression, but their role in ischemic-induced angiogenesis is poorly-characterized. There is currently a limited understanding of the specific miRNAs associated with PAD. To determine the regulation of miRNAs, we obtained miRNA profiles using RNA isolated from patients with PAD and a control group. The effects of specific miRNAs on angiogenesis were evaluated by assessing the in vitro angiogenic function of endothelial progenitor cells (EPCs), performing an in vivo angiogenesis assay, and employing a mouse hindlimb ischemic model. Our results demonstrated that circulating miR-548j-5p was significantly reduced in patients with PAD as compared with the controls. miR-548j-5p promoted EPC angiogenesis by enhancing migration and tube formation. The endothelial nitric oxide synthase (NOS) and stromal cell-derived factor (SDF)-1 signaling pathways appeared to be potential targets of miR-548j-5p. Furthermore, the results of a directed in vivo angiogenesis assay of EPCs and a hindlimb ischemia mouse model demonstrated that miR-548j-5p enhanced the capillary density and blood flow recovery in hindlimb ischemia. In conclusion, our data indicated that up-regulation of miR-548j-5p promotes angiogenesis in ischemic tissue and may represent a novel therapeutic approach for PAD.

Prediction of Masked Hypertension and Masked Uncontrolled Hypertension Using Machine Learning.

Objective: This study aimed to develop machine learning-based prediction models to predict masked hypertension and masked uncontrolled hypertension using the clinical characteristics of patients at a single outpatient visit. Methods: Data were derived from two cohorts in Taiwan. The first cohort included 970 hypertensive patients recruited from six medical centers between 2004 and 2005, which were split into a training set (n = 679), a validation set (n = 146), and a test set (n = 145) for model development and internal validation. The second cohort included 416 hypertensive patients recruited from a single medical center between 2012 and 2020, which was used for external validation. We used 33 clinical characteristics as candidate variables to develop models based on logistic regression (LR), random forest (RF), eXtreme Gradient Boosting (XGboost), and artificial neural network (ANN). Results: The four models featured high sensitivity and high negative predictive value (NPV) in internal validation (sensitivity = 0.914-1.000; NPV = 0.853-1.000) and external validation (sensitivity = 0.950-1.000; NPV = 0.875-1.000). The RF, XGboost, and ANN models showed much higher area under the receiver operating characteristic curve (AUC) (0.799-0.851 in internal validation, 0.672-0.837 in external validation) than the LR model. Among the models, the RF model, composed of 6 predictor variables, had the best overall performance in both internal and external validation (AUC = 0.851 and 0.837; sensitivity = 1.000 and 1.000; specificity = 0.609 and 0.580; NPV = 1.000 and 1.000; accuracy = 0.766 and 0.721, respectively). Conclusion: An effective machine learning-based predictive model that requires data from a single clinic visit may help to identify masked hypertension and masked uncontrolled hypertension.

Association between phosphate and long-term outcome in CAD patients underwent coronary intervention.

Phosphate has been linked to higher cardiovascular (CV) risk. However, whether phosphate is associated with poor outcomes for patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs) remained undetermined. 2,894 CAD patients (2,220 male, aged 71.6 ± 12.2), who received PCI at TVGH from 2006 to 2015, with phosphate measurement, were enrolled. The primary outcome was the composite of major adverse CV events [MACE, comprising of CV death, nonfatal MI, and nonfatal stroke] and heart failure hospitalization (HHF). The key secondary outcome was MACE. There was a J-curve association between phosphate and CV events after adjusted for comorbidities and renal function. Phosphate around 3.2 ± 0.1 mg/dL was associated with the lowest CV risk. In Cox analysis, each 1 mg/dL increases in phosphate was associated with a higher risk of MACE + HHF (HR: 1.12, 95% CI: 1.05-1.21): CV death (HR: 1.37, 95% CI: 1.22-1.55) and HHF (HR: 1.12, 95% CI: 1.02-1.23). Subgroup analyses showed more prominent association between phosphate and MACE + HHF in male, age > 65, bare-metal stents (BMSs), LVEF < 50%, eGFR < 60, LDL > 70 mg/dL, and emergent PCI. Phosphate has a significant association with the risk of CV events in CAD patients undergoing PCI that was independent of comorbidities and renal function.

Optimal blood pressure for patients with end-stage renal disease following coronary interventions.

Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end-stage renal disease (ESRD) (eGFR < 15 ml/min/1.73m2 ) still unclear. The authors aimed to investigate the ideal achieved BP in ESRD patients with CAD after coronary intervention. Five hundred and seventy-five ESRD patients who had undergone percutaneous coronary interventions (PCIs) were enrolled and their clinical outcomes were analyzed according to the category of systolic BP (SBP) and diastolic BP (DBP) achieved. The clinical outcomes included major cardiovascular events (MACE) and MACE plus hospitalization for congestive heart failure (total cardiovascular (CV) event).The mean systolic BP was 135.0 ± 24.7 mm Hg and the mean diastolic BP was 70.7 ± 13.1 mm Hg. Systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg had the lowest MACE (11.0%; 13.2%) and total CV event (23.3%; 21.1%). Patients with systolic BP < 120 mm Hg had a higher risk of MACE (HR: 2.01; 95% CI: 1.17-3.46, p = .008) than those with systolic BP 140-149 mm Hg. Patients with systolic BP ≥ 160 mm Hg (HR: 1.84; 95% CI, 3.27-1.04, p = .04) and diastolic blood BP ≥ 90 mm Hg (HR: 2.19; 95% CI: 1.15-4.16, p = .02) had a higher risk of total CV event rate when compared to those with systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg. A J-shaped association between systolic (140-149 mm Hg) and diastolic (80-89 mm Hg) BP and decreased cardiovascular events for CAD was found in patients with ESRD after undergoing PCI in non-Western population.

Significance of serum FGF-23 for risk assessment of contrast-associated acute kidney injury and clinical outcomes in patients undergoing coronary angiography.

BACKGROUND: Fibroblast growth factor (FGF)-23 levels rise as kidney function declines. Whether elevated FGF-23 levels are associated with an increased risk for contrast-associated acute kidney injury (CA-AKI) and major adverse cardiovascular events (MACE) in patients undergoing coronary angiography remain uncertain. METHODS: In total, 492 patients receiving coronary angiography were enrolled. Their serum FGF-23 levels were measured before administration of contrast media. The occurrence of CA-AKI was defined as a rise in serum creatinine of 0.5 mg/dL or a 25% increase from the baseline value within 48 h after the procedure. All patients were followed up for at least 1 year or until the occurrence of MACE including death, nonfatal myocardial infarction (MI), and ischemic stroke. RESULTS: Overall, CA-AKI occurred in 41 (8.3%) patients. During a median follow-up of 2.6 years, there were 24 deaths, 3 nonfatal MIs, and 7 ischemic strokes. Compared with those in the lowest FGF-23 tertile, individuals in the highest FGF-23 tertile had a significantly higher incidence of CA-AKI (P < 0.001) and lower incidence of MACE-free survival (P = 0.001). In multivariate regression analysis, higher FGF-23 level was found to be independently associated with a graded risk for CA-AKI (OR per doubling, 1.90; 95% CI 1.48-2.44) and MACE (HR per doubling, 1.25; 95% CI 1.02-1.52). CONCLUSIONS: Elevated FGF-23 levels were associated with an increased risk for CA-AKI and future MACE among patients undergoing coronary angiography. FGF-23 may play a role in early diagnosis of CA-AKI and predicting clinical outcomes after coronary angiography.

Economic Burden of Heart Failure in Asian Countries with Different Healthcare Systems.

BACKGROUND AND OBJECTIVES: Heart failure (HF) poses substantial economic burden, primarily driven by high hospitalization and mortality rates. This study aimed to understand the economic burden of HF in 4 Asian countries under varying healthcare systems. METHODS: This was a non-interventional, retrospective study conducted in South Korea, Taiwan, Thailand and Malaysia through medical chart review. Eligible patients included those who had either ≥1 hospitalization or ≥2 outpatient visits from January 1st to December 31st, 2014, and at least one year of follow-up. Resource use and direct healthcare costs (adjusted to 2015 USD) of HF were assessed. HF costs for subgroups stratified by age and sex were assessed. RESULTS: A total of 568 patients were recruited from South Korea (n=200), Taiwan (n=200), Thailand (n=100) and Malaysia (n=68). The proportion of patients hospitalized ranged from 20.0% to 93.5% (South Korea 20.0%, Thailand 49.0%, Malaysia 70.6%, and Taiwan 93.5%). The overall annual HF cost per patient was $2,357, $4,513, $3,513 and $1,443 in South Korea, Taiwan, Thailand, and Malaysia, respectively; hospitalized HF care costs were $10,714, $4,790, $7,181 and $1,776, respectively. The length of stay was more than 12.2 days except in Malaysia. No specific trend was observed in subgroup analysis. CONCLUSIONS: In Asia, HF poses significant economic burden and hospitalization has emerged as the major cost driver among healthcare costs. A streamlined treatment strategy reducing hospitalization rate can minimize the economic burden.

Prognostic indicators for the onset of ischaemic versus haemorrhagic stroke in stable coronary artery disease.

ABSTRACT: The incidence of stroke may be increased in patients with coronary artery disease (CAD). We aimed to investigate the specific risk factors for the development of ischaemic and haemorrhagic stroke in stable CAD patients.Patients with stable CAD were prospectively enrolled for future cardiovascular events in Taiwan. All the patients had received coronary interventions and were stable for least 1 month before enrolment. The incidence of ischaemic stroke was identified and confirmed by telephone and hospital records. Baseline characteristics, including demographic data, lipid profiles, medications, and biomarkers for potential inflammatory and atherosclerosis, were analysed.In total, 1428 patients (age, 63.07 ±â€Š11.4 years; 1207 males) were under standard medical treatment and regularly followed-up for at least 4 years. Multivariate logistic regression analysis showed that baseline serum myeloperoxidase (MPO) level (hazard ratio [HR]: 1.89, 95% CI: 1.16-3.10, P = .01) and statin use (HR: 0.37; 95% CI: 0.17-0.79, P = .01) were independently associated with the onset of ischaemic stroke. Age (HR: 1.07, 95% CI: 1.00-1.14, P = .04) and angiotensin receptor blocker (ARB) use (HR: 0.37, 95% CI: 0.17-0.79, P = .01) were independently associated with future onset of intracranial haemorrhage (ICH), implying the different mechanisms of ischaemic stroke and ICH.Age and ARB use were related to ICH onset. Baseline MPO level and statin use were independently associated with longer and shorter future ischaemic stroke onset in stable CAD patients, respectively. Further studies are indicated to confirm the potential mechanisms and advance individual risk stratification for the onset of different types of stroke in clinical CAD.

Sex difference in sympathetic nervous system activity and blood pressure in hypertensive patients.

Increased sympathetic nervous system (SNS) activity leads to increased risk of cardiovascular morbidity and mortality. This study investigated whether there were sex differences in SNS activity among Chinese patients with hypertension. Ethnic Chinese non-diabetic hypertensive patients aged 20-50 years were enrolled in Taiwan. A total of 970 hypertensive patients (41.0 ± 7.2 years) completed the study, 664 men and 306 women. They received comprehensive evaluations including office blood pressure (BP) measurement, 24-h ambulatory BP monitoring, and 24-h urine sampling assayed for catecholamine excretion. Compared to women, men were younger, had higher body mass index (BMI), office systolic BP (SBP), office diastolic BP (DBP), 24-h ambulatory BP, and 24-h urine catecholamine excretion. In men, 24-h urine total catecholamine levels were correlated with 24-h SBP (r = 0.103, p = .008) and 24-h DBP (r = 0.083, p = .033). In women, however, there was no correlation between 24-h urine total catecholamine levels and 24-h ambulatory BP. Multivariate linear regression indicated that being male (ß = 1.65, 95% confidence interval [CI] 0.01-3.29, p = .048) and 24-h urine total catecholamine (ß = 5.03, 95% CI 0.62-9.44, p = .025) were both independently associated with 24-h SBP; being male was independently associated with 24-h DBP (ß = 3.55, 95% CI 2.26-4.85, p < .001). In conclusion, Chinese men with hypertension had higher SNS activity than women, and SNS activity was independently associated with 24-h ambulatory BP in men rather than in women. These findings suggest that different hypertensive treatment strategies should be considered according to patient sex.

Effects of Postoperative Percutaneous Coronary Intervention, Pharmacologic Treatment, and Predisposing Factors on Clinical Outcomes in Patients With and Without Type 2 Diabetes Along With Critical Limb Ischemia.

PURPOSE: Critical limb ischemia (CLI) has been identified as being connected to rates of cardiovascular mortality and lower extremity amputation (LEA). This prospective study investigated the effects of percutaneous coronary intervention (PCI), pharmacologic treatment, and predisposing factors on clinical outcomes in patients with and without type 2 diabetes mellitus (DM) along with CLI after endovascular intervention. METHODS: 249 consecutive patients with CLI (Fontaine stages III-IV) received pharmacologic treatment after successful endovascular intervention. Their primary patency rates of infrapopliteal lesions and cardiovascular and amputation events during a 36-month follow-up period were assessed. FINDINGS: Patients with DM were more likely to be younger (P = 0.026); 50% (n = 63), 42.9% (n = 54), 52.4% (n = 66), and 77% (n = 97) of DM patients had arterial calcification, end-stage renal disease, diabetic neuropathy, and Fontaine stage IV (P < 0.001, P < 0.001, P < 0.001, and P = 0.019, respectively). The primary patency rates were 61%, 48.8%, and 42.3% at 12, 24, and 36 months, in the patients without DM (P = 0.034, P = 0.013, and P = 0.005). Patients with DM had higher risks of 36-month coronary artery disease, cerebrovascular accident, mortality, and LEA (P = 0.005, P = 0.042, P = 0.042, and P < 0.001). Patients with CLI receiving long-term cilostazol treatment had a better primary patency and amputation-free survival, and a lower risk of mortality at 36 months (P < 0.001, P < 0.001, and P = 0.001). Statin use was associated with 36-month amputation-free survival but not with primary patency (P = 0.032 and P = 0.088). Subgroup multivariate Cox analyses showed that primary patency was independently associated with long-term cilostazol treatment, PCI in the first postoperative year, and direct revascularization in the DM group, whereas in the control group, long-term cilostazol treatment was the main independent factor. The risk of amputation was independently associated with a high high-sensitivity chronic reactive protein level, diabetic neuropathy, sole use of an oral hypoglycemic agent, and lack of supervised exercise. IMPLICATIONS: Long-term cilostazol treatment, aggressive management of dyslipidemia, and meticulous assessment and prevention of postoperative unstable coronary artery disease should be considered in CLI patients with and without DM to maximize clinical outcomes. PCI in the first postoperative year may be a predisposing factor for patency failure in patients with CLI, especially those with DM. A large-scale prospective randomized trial should be conducted to confirm these findings (TVGH IRB No. 2013-08-020B).

Long-Term Cilostazol Treatment and Predictive Factors on Outcomes of Endovascular Intervention in Patients with Diabetes Mellitus and Critical Limb Ischemia.

INTRODUCTION: Despite improvements in endovascular interventions and multidisciplinary approaches, improving clinical outcomes and increasing limb salvage have become increasingly challenging. This prospective study investigated the associations of cilostazol treatment with clinical outcomes and predictive factors in patients with diabetes mellitus (DM) and critical limb ischemia (CLI) after endovascular revascularization of the affected angiosome. METHODS: In this study, 172 consecutive patients with CLI (Fontaine levels III-IV) received cilostazol treatment after successful endovascular intervention according to the angiosome concept, and their primary patency rates and cardiovascular and amputation events during a 24-month follow-up period were assessed. RESULT: The 24-month primary patency rate, mortality rate, and amputation rate were better in the patients under long-term cilostazol treatment (P < 0.001, P = 0.029, and P = 0.014). Weighted multivariate Cox analyses with a propensity scoring-based method showed that long-term cilostazol treatment [hazard ratio (HR) 0.2, 95% confidence interval (CI) 0.11-0.36, P < 0.001], direct revascularization (DR) (HR 0.46, 95% CI 0.28-0.74, P = 0.002), and supervised exercise (HR 0.4, 95% CI 0.24-0.66, P < 0.001) were independently associated with primary patency. Patients with lower-extremity amputation (LEA) had a higher risk of coronary artery disease (CAD) and mortality. Cellulitis and neuropathy were independently associated with LEA events (cellulitis: HR 2.89, 95% CI 1.66-5.05, P < 0.001; neuropathy: HR 2.2, 95% CI 1.31-3.7, P = 0.003). CONCLUSION: Our results showed that patients with DM who received cilostazol treatment for more than 3 months had significantly better outcomes and decreased amputation and mortality rates after DR, and cellulitis and neuropathy were highly associated with the risk of limb loss. A large-scale randomized trial should be conducted in the future to confirm these results. TRIAL REGISTRATION: Taipei Veterans General Hospital (TVGH) IRB no. 2013-08-020B. Registered 30 August 2013.

Association between Preoperative Nutritional Status and Clinical Outcomes of Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Malnutrition is associated with poor outcomes in patients with cancer, heart failure and chronic kidney disease. This study aimed to investigate the predictive value of the Controlling Nutritional Status (CONUT) score in coronary artery disease (CAD) patients. METHODS: We recruited a cohort of 3118 patients with CAD undergoing percutaneous coronary intervention (PCI) from 2005 to 2015. Nutritional status was evaluated using the CONUT score, with higher scores reflecting worse nutritional status. RESULTS: After adjustment for comorbidities and medication, an increased CONUT score was independently associated with a higher risk of acute myocardial infarction (AMI) (HR: 1.13; 95% CI: 1.03-1.24), cardiovascular (CV) death (HR: 1.18; 95% CI: 1.07-1.30), congestive heart failure (CHF) (HR: 1.11; 95% CI: 1.04-1.18), a major adverse cardiovascular event (MACE) (HR: 1.14; 95% CI: 1.07-1.22), and total CV events (HR: 1.11; 95% CI: 1.07-1.15). The subgroup analyses demonstrated that the association of the CONUT score existed independently of other established cardiovascular risk factors. In addition, CONUT significantly improved risk stratification for myocardial infarction (MI), cardiac death, CHF, MACEs and total CV events compared to conventional risk factors in CAD patients by the significant increase in the C-index (p < 0.05) and reclassification risk categories in cardiac death and MACEs. Conclusions The CONUT score improved the risk prediction of adverse events compared to traditional risk factors in CAD patients after percutaneous coronary intervention (PCI).

Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease.

BACKGROUND: This study examines the predictive value of a novel systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) in coronary artery disease (CAD) patients. METHODS: A total of 5602 CAD patients who had undergone a percutaneous coronary intervention (PCI) were enrolled. They were divided into two groups by baseline SII score (high SII vs low SII) to analyse the relationship between SII groups and the long-term outcome. The primary outcomes were major cardiovascular events (MACE) which includes nonfatal myocardial infarction (MI), nonfatal stroke and cardiac death. Secondary outcomes included a composite of MACE and hospitalization for congestive heart failure. RESULTS: An optimal SII cut-off point of 694.3 × 109 was identified for MACE in the CAD training cohort (n = 373) and then verified in the second larger CAD cohort (n = 5602). Univariate and multivariate analyses showed that a higher SII score (≥694.3) was independently associated with increased risk of developing cardiac death (HR: 2.02; 95% CI: 1.43-2.86), nonfatal MI (HR: 1.42; 95% CI: 1.09-1.85), nonfatal stroke (HR: 1.96; 95% CI: 1.28-2.99), MACE (HR: 1.65; 95% CI: 1.36-2.01) and total major events (HR: 1.53; 95% CI: 1.32-1.77). In addition, the SII significantly improved risk stratification of MI, cardiac death, heart failure, MACE and total major events than conventional risk factors in CAD patients by the significant increase in the C-index (P < .001) and reclassification risk categories by significant NRI (P < .05) and IDI (P < .05). CONCLUSIONS: SII had a better prediction of major cardiovascular events than traditional risk factors in CAD patients after coronary intervention.

Associated factors and impacts of sedentary behaviour in patients with heart failure: A longitudinal study.

BACKGROUND: Sedentary behaviours may be related to factors such as self-efficacy, mood and social support. However, there is a paucity of longitudinal follow-up studies examining factors related to sedentary behaviour from physical-psychosocial perspectives in patients with heart failure. AIMS: The purpose of this study was to explore the multidimensional associated factors and impacts of sedentary behaviour in heart failure patients. METHODS: A longitudinal design was used. A convenience sample of 128 heart failure patients recruited from two large medical centres in northern Taiwan was obtained. Patients were interviewed with structured questionnaires to assess physical activity, symptom distress, exercise self-efficacy, anxiety and depression, social support, sleep quality and quality of life before discharge and at 3 and 6 months after discharge. RESULTS: Heart failure patients reported low physical activity and tended to be sedentary. Sedentary behaviour was gradually reduced from hospitalization to 6 months after discharge. Sleep quality, quality of life, analgesic use, symptom distress and exercise self-efficacy were significant associated factors that explained 42.1-51% of the variance in sedentary behaviour. Patients with high sedentary behaviour had significantly greater depression and poorer sleep and quality of life than those with low sedentary behaviour at hospitalization and showed a significant improvement in depression at 3 and 6 months after discharge. CONCLUSION: Sedentary behaviour is common in heart failure patients and has impacts on depression and quality of life. An appropriate physical activity programme focusing on disease self-management and enhancing self-efficacy is needed for heart failure patients to improve their sedentary behaviour and quality of life.

Association of variability in uric acid and future clinical outcomes of patient with coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Hyperuricemia is independently associated with cardiovascular disease (CVD) and is considered to be one of the major risk factors for CVD. However, the impact of inter-visit uric acid (UA) variability on cardiovascular risk remains undetermined. METHODS: We enrolled 3202 patients with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from Taipei Veterans General Hospital from 2006 to 2015. All post-baseline visits UA measurements using standard deviation (SD) were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure. RESULTS: During an average 65.06 ± 32.1-month follow-up, there were 66 cardiovascular deaths, 175 nonfatal myocardial infarctions, 64 nonfatal strokes, 287 hospitalizations for heart failure, and 683 revascularization procedures. There was a linear association between high UA SD and future adverse events. Compared to the lowest quartile SD, subjects in the highest quartile SD had a higher risk of MACE (HR: 2.53, 95% CI: 1.78-3.59), myocardial infarction (HR: 2.43, 95% CI: 1.53-3.86), cardiovascular death (HR: 6.45, 95% CI: 2.52-16.55), heart failure-related hospitalization (HR: 3.43, 95% CI: 2.32-5.05), and total major CV events (HR: 2.72, 95% CI: 2.09-3.56). Furthermore, compared to the average achieved on-treatment UA value, increasing UA SD had a stronger association of higher risk of developing MACE (HR: 1.51, 95% CI: 1.36-1.68), myocardial infarction (HR: 1.37, 95% CI: 1.38-1.68), ischemic stroke (HR: 1.43, 95% CI: 1.13-1.82), CV death (HR: 1.77, 95% CI: 1.50-2.11), HF (HR: 1.43, 95% CI: 1.29-1.58), and total major CV events (HR: 1.46, 95% CI: 1.34-1.58). CONCLUSIONS: High UA variability is associated with a higher risk of developing future cardiovascular events, suggesting the importance of maintaining stable serum UA levels and avoiding large fluctuations in CAD patients after percutaneous coronary intervention (PCI).