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.

Simplified quantification of 13N-ammonia PET myocardial blood flow: A comparative study with the standard compartment model to facilitate clinical use.

BACKGROUND: Short imaging protocol to quantify myocardial blood flow (MBF) and myocardial flow reserve (MFR) may enhance the clinical application of 13N-ammonia cardiac PET. We assessed the flow quantitation of 13N-ammonia PET implementing simple retention model and two-compartment model. METHODS: Fourteen healthy volunteers (HVT) and twenty-three clinical patients received 13N-ammonia PET/CT. The simple retention model used the first 7-minute image to quantify MBF. Global and regional MBF and MFR of the two models were compared. RESULTS: Global and regional MBF and MFR of these two models were highly correlated with mildly inferior correlation in RCA territory (global R2: rest MBF = 0.79, stress MBF = 0.65, MFR = 0.77; regional R2: rest MBF ≥ 0.72, stress MBF ≥ 0.52, MFR ≥ 0.68). There were significant differences for MFR (4.04 ± 0.72, 3.66 ± 0.48, p = .02) and rest MBF (0.69 ± 0.12, 0.78 ± 0.12, p = .02) between the two models in the HVT group. CONCLUSIONS: 13N-ammonia global and regional MBF and MFR from the simple retention model demonstrate strong correlations with that from the two-compartment model. Significant differences of MFR and rest MBF are noted in the HVT group, with a proposed normal reference value for the 13N-ammonia short simple retention protocol.

SPECT myocardial blood flow quantitation toward clinical use: a comparative study with 13N-Ammonia PET myocardial blood flow quantitation.

OBJECTIVES: The aim of this study was to evaluate the accuracy of myocardial blood flow (MBF) quantitation of 99mTc-Sestamibi (MIBI) single photon emission computed tomography (SPECT) compared with 13N-Ammonia (NH3) position emission tomography (PET) on the same cohorts. BACKGROUND: Recent advances of SPECT technologies have been applied to develop MBF quantitation as a promising tool to diagnose coronary artery disease (CAD) for areas where PET MBF quantitation is not available. However, whether the SPECT approach can achieve the same level of accuracy as the PET approach for clinical use still needs further investigations. METHODS: Twelve healthy volunteers (HVT) and 16 clinical patients with CAD received both MIBI SPECT and NH3 PET flow scans. Dynamic SPECT images acquired with high temporary resolution were fully corrected for physical factors and processed to quantify K1 using the standard compartmental modeling. Human MIBI tracer extraction fraction (EF) was determined by comparing MIBI K1 and NH3 flow on the HVT group and then used to convert flow values from K1 for all subjects. MIBI and NH3 flow values were systematically compared to validate the SPECT approach. RESULTS: The human MIBI EF was determined as [1.0-0.816*exp(-0.267/MBF)]. Global and regional MBF and myocardial flow reserve (MFR) of MIBI SPECT and NH3 PET were highly correlated for all subjects (global R2: MBF = 0.92, MFR = 0.78; regional R2: MBF ≥ 0.88, MFR ≥ 0.71). No significant differences for rest flow, stress flow, and MFR between these two approaches were observed (All p ≥ 0.088). Bland-Altman plots overall revealed small bias between MIBI SPECT and NH3 PET (global: ΔMBF = -0.03Lml/min/g, ΔMFR = 0.07; regional: ΔMBF = -0.07 - 0.06 , ΔMFR = -0.02 - 0.22). CONCLUSIONS: Quantitation with SPECT technologies can be accurate to measure myocardial blood flow as PET quantitation while comprehensive imaging factors of SPECT to derive the variability between these two approaches were fully addressed and corrected.

Aliskiren directly improves endothelial progenitor cell function from Type II diabetic patients.

BACKGROUND: Endothelial progenitor cell (EPC) functions are impaired in the presence of diabetes mellitus. Aliskiren is a direct renin inhibitor, which is expected to modify proangiogenic cells. This study aimed to investigate whether and how aliskiren could improve the function of EPCs from patients with type II diabetes (T2DM). MATERIALS AND METHODS: Endothelial progenitor cells fibronectin adhesion assay, chamber assay and in vitro tube formation assay were used to estimate the degree of EPC adhesion, migration and tube formation abilities. EPC protein and mRNA expressions were evaluated by Western blot and quantitative RT-PCR, respectively. EPC vascular endothelial growth factor (VEGF) and (pro)renin receptor ((P)RR) expression was knocked down by VEGF and (P)RR siRNA. RESULTS: Aliskiren (0·1 or 10 µM) dose-dependently improved functions and increased both VEGF and stromal cell-derived factor-1α (SDF-1α) expression of EPCs from patients with T2DM or EPCs from healthy volunteers and treated with high glucose. Transfection with VEGF siRNA significantly reduced the aliskiren-induced SDF-1α expression. Furthermore, (P)RR siRNA transfection impaired the aliskiren-induced VEGF and SDF-1 expression. CONCLUSIONS: The results show that aliskiren improved EPC function from patients with T2DM in a dose-dependent manner probably via the (P)RR and VEGF/SDF-1α-related mechanisms.

Hypertension subtypes modify metabolic response to thiazide diuretics.

BACKGROUND: Blood pressure (BP) and metabolic response to thiazide diuretics might be varied in patients with different hypertension subtypes and ethnicities. This study aimed to investigate the response of BP and metabolic profiles to short-term thiazide treatment in an Asian cohort with different hypertension subtypes. DESIGN: Serial ethnic Chinese nondiabetic subjects with hypertension were evaluated. After diet instruction and lifestyle modification for 2 weeks, patients who still had elevated systolic BP (SBP≥140 mmHg) and/or diastolic BP (DBP≥90 mmHg) were given 50 mg of hydrochlorothiazide daily for 2 weeks. The responses of BP and metabolic profiles were evaluated before and after treatment according to the patient's baseline BP subtype - isolated systolic hypertension (ISH), systo-diastolic hypertension (SDH) and isolated diastolic hypertension (IDH). RESULTS: Hydrochlorothiazide treatment significantly reduced the BP in all 92 patients (62 males, aged 45·7 ± 9·6 years), irrespective of their baseline BP subtypes. In patients with SDH (n = 39) or IDH (n = 40), hydrochlorothiazide treatment significantly increased serum adiponectin (P = 0·001 and 0·007, respectively) and reduced asymmetric dimethylarginine levels (P < 0·001, in both groups). Serum cholesterol (P = 0·027) and fasting blood sugar levels (P = 0·044) were significantly improved only in the IDH patients. Furthermore, IDH was independently associated with changes in fasting blood sugar (ß = -11·178, P = 0·022) and cholesterol (ß = -22·654, P = 0·027). CONCLUSIONS: The characteristics of the Asian hypertensive patients with diastolic hypertension can present a favourable metabolic response to the short-term hydrochlorothiazide treatment. The potential positive effect on cardiovascular risk should be validated in long-term studies in this diastolic type of hypertension.

Aliskiren Inhibits Neointimal Matrix Metalloproteinases in Experimental Atherosclerosis.

BACKGROUND: The renin-angiotensin system (RAS) plays an important role in atherosclerosis. Acting via the angiotensin II receptor, type 1, oxidative stress increases and contributes to endothelial dysfunction and vascular inflammation. Renin exerts effects through a renin receptor causing an increase in the efficiency of angiotensinogen cleavage and facilitates angiotensin II (Ang II) generation and action on cell surfaces. Ang II enhances proliferation and migration of vascular smooth muscle cells, indicating a direct involvement of the RAS in smooth muscle cell proliferation during neointimal formation. Aliskiren, a direct renin inhibitor, is a new oral antihypertensive drug. However, the role of the direct renin inhibitor in neointimal formation and vascular matrix metalloproteinases remains unclear. METHODS: To investigate the effects of aliskiren on the expression of vascular matrix metalloproteinases, we evaluated the aortic neointimal formation of high-cholesterol-fed animals after vascular injury in vivo and the cellular function of the tumor necrosis factor-α stimulated human aortic smooth muscle cells in vitro. Thereafter, we evaluated vascular expression (by western blot), activity (by gelatin zymography) and molecular pathway. RESULTS: In this study we demonstrated that aliskiren reduced neointimal hyperplasia in hypercholesterolemic rabbits after vascular injury and the expression of matrix metalloproteinases in the neointima. Aliskiren also inhibited the expression and activities of matrix metalloproteinases on tumor necrosis factor-α (TNF-α)-stimulated human aortic smooth muscle cells via the mitogen-activated protein kinase pathway. CONCLUSIONS: The present study showed that aliskiren inhibited the expression of vascular matrix metalloproteinases. With these results, we have better clarified the potential role of renin inhibitors in human atherosclerosis.

Rivaroxaban, a factor Xa inhibitor, improves neovascularization in the ischemic hindlimb of streptozotocin-induced diabetic mice.

BACKGROUND: Factor Xa inhibitor is used for preventing venous thromboembolism (VTE) in adult patients receiving orthopedic operation. However, the role of factor Xa inhibitor, rivaroxaban, in angiogenesis is still unknown. METHODS AND RESULTS: Streptozotocin (STZ)-induced diabetic mice with model of hind-limb ischemia, were divided into non-diabetic control, diabetic control, and low- and high-dose rivaroxaban treatment groups, in order to evaluate the effect of rivaroxaban in angiogenesis. Doppler perfusion imaging showed that blood flow recovery was significantly increased, and more capillary density occurred in the rivaroxaban treatment group. In vitro studies, human endothelial progenitor cells (EPCs) treated with rivaroxaban had significant functional improvement in migration and senescence under hyperglycemic conditions. Rivaroxaban also increased endothelial nitric oxide synthase (eNOS) as well as vascular endothelial growth factor (VEGF) expressions in hyperglycemia-stimulated EPCs. CONCLUSIONS: Rivaroxaban promoted vessel formation in diabetic mice and improved endothelial progenitor cell function under hyperglycemic conditions. These effects may be associated with enhancement of expression of eNOS and VEGF.

Effects of pitavastatin versus atorvastatin on the peripheral endothelial progenitor cells and vascular endothelial growth factor in high-risk patients: a pilot prospective, double-blind, randomized study.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) reflect endothelial repair capacity and may be a significant marker for the clinical outcomes of cardiovascular disease. While some high-dose statin treatments may improve endothelial function, it is not known whether different statins may have similar effects on EPCs.This study aimed to investigate the potential class effects of different statin treatment including pitavastatin and atorvastatin on circulating EPCs in clinical setting. METHODS: A pilot prospective, double-blind, randomized study was conducted to evaluate the ordinary dose of pitavastatin (2 mg daily) or atorvastatin (10 mg daily) treatment for 12 weeks on circulating EPCs in patients with cardiovascular risk such as hypercholesterolemia and type 2 diabetes mellitus (T2DM). Additional in vitro study was conducted to clarify the direct effects of both statins on EPCs from the patients. RESULTS: A total of 26 patients (19 with T2DM) completed the study. While the lipid-lowering effects were similar in both treatments, the counts of circulating CD34+KDR+EPCs were significantly increased (from 0.021 ± 0.015 to 0.054 ± 0.044% of gated mononuclear cells, P < 0.05) only by pitavastatin treatment. Besides, plasma asymmetric dimethylarginine level was reduced (from 0.68 ± 0.10 to 0.53 ± 0.12 µmol/L, P < 0.05) by atorvastatin, and plasma vascular endothelial growth factor (VEGF) level was increased (from 74.33 ± 32.26 to 98.65 ± 46.64 pg/mL, P < 0.05) by pitavastatin. In the in vitro study, while both statins increased endothelial nitric oxide synthase (eNOS) expression, only pitavastatin increased the phosphorylation of eNOS in EPCs. Pitavastatin but not atorvastatin ameliorated the adhesion ability of early EPCs and the migration and tube formation capacities of late EPCs. CONCLUSIONS: While both statins similarly reduced plasma lipids, only pitavastatin increased plasma VEGF level and circulating EPCs in high-risk patients, which is probably related to the differential pleiotropic effects of different statins. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT01386853.

Quantitation of myocardial blood flow and myocardial flow reserve with 99mTc-sestamibi dynamic SPECT/CT to enhance detection of coronary artery disease.

PURPOSE: Conventional dual-head single photon emission computed tomography (SPECT)/CT systems capable of fast dynamic SPECT (DySPECT) imaging have a potential for flow quantitation. This study introduced a new method to quantify myocardial blood flow (MBF) and myocardial flow reserve (MFR) with DySPECT scan and evaluated the diagnostic performance of detecting coronary artery disease (CAD) compared with perfusion using invasive coronary angiography (CAG) as the reference standard. METHODS: This study included 21 patients with suspected or known CAD who had received DySPECT, ECG-gated SPECT (GSPECT), and CAG (13 with ≥ 50% stenosis in any vessel; non-CAD group: 8 with patent arteries or < 50% stenosis). DySPECT and GSPECT scans were performed on a widely used dual-head SPECT/CT scanner. The DySPECT imaging protocol utilized 12-min multiple back-and-forth gantry rotations during injections of (99m)Tc-sestamibi (MIBI) tracer at rest or dipyridamole-stress stages. DySPECT images were reconstructed with full physical corrections and converted to the physical unit of becquerels per milliliter. Stress MBF (SMBF), rest MBF (RMBF), and MFR were quantified by a one-tissue compartment flow model using time-activity curves derived from DySPECT images. Perfusion images were processed for GSPECT scan and interpreted to obtain summed stress score (SSS) and summed difference score (SDS). Receiver-operating characteristic (ROC) analyses were conducted to evaluate the diagnostic performance of flow and perfusion. RESULTS: Using the criteria of ≥ 50% stenosis as positive CAD, areas under the ROC curve (AUCs) of flow assessment were overall significantly greater than those of perfusion. For patient-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.91 ± 0.07, 0.86 ± 0.09, 0.64 ± 0.12, and 0.59 ± 0.13. For vessel-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.81 ± 0.05, 0.76 ± 0.06, 0.62 ± 0.07, and 0.56 ± 0.08, respectively. CONCLUSION: The preliminary data suggest that MBF quantitation with a conventional SPECT/CT system and the flow quantitation method is a clinically effective approach to enhance CAD detection.

Feasibility and operator variability of myocardial blood flow and reserve measurements with 99mTc-sestamibi quantitative dynamic SPECT/CT imaging.

PURPOSE: Myocardial blood flow (MBF) quantification with dynamic SPECT could lead to widespread utilization of MBF imaging in clinical practice with little cost increase over current standard SPECT myocardial perfusion imaging. This work evaluates the feasibility and operator-dependent variability of MBF and flow reserve measurements with (99m)Tc-sestamibi (MIBI) dynamic SPECT imaging using a standard dual-head SPECT camera. METHODS: Twenty-eight patients underwent dipyridamole-stress and rest imaging with dynamic SPECT/CT acquisition. Quantitative images were iteratively reconstructed with all physical corrections and then myocardial and arterial blood regions of interest (ROI) were defined semi-automatically. A compartmental model was fitted to these ROI-sampled time-activity-curves, and flow-dependent MIBI extraction correction was applied to derive regional MBF values. Myocardial flow reserve (MFR) was estimated as stress/rest MBF ratio. MBF and MFR in low and high risk populations were evaluated for ability to detect disease. Images were each processed twice (≥7 days apart) by one expert and one novice operator to evaluate intra- and inter-operator variability of MBF and MFR measurement in the three coronary artery vascular territories. RESULTS: Mean rest flow, stress flow, and MFR values were 0.83, 1.82 mL·minute(-1)·g(-1), and 2.45, respectively. For stress/rest MFR, the inter-operator reproducibility was r(2) = 0.86 with RPC = 1.1. Stress MBF and MFR were significantly reduced (P < .05) in high risk (n = 9) vs low risk populations (n = 19), indicating ability to detect disease. For expert and novice operators very good intra-operator correlations of r(2) = 0.98 and 0.95 (n = 168, P < .001) were observed for combined rest and stress regional flow values. Bland-Altman reproducibility coefficients (RPC) were 0.25 and 0.47 mL·minute(-1)·g(-1) for the expert and novice operators, respectively (P < .001). Inter-operator correlation was r(2) = 0.91 and Bland-Altman RPC = 0.58 mL·minute(-1)·g(-1) (n = 336). CONCLUSIONS: MBF and reserve measurements using (99m)Tc-sestamibi on a traditional, two-headed camera with fast rotation and with quantitative dynamic SPECT appears to be feasible, warranting further investigation.

Association of tamoxifen use and reduced cardiovascular events among asian females with breast cancer.

BACKGROUND: Tamoxifen is used for breast cancer treatment and has been reported to be beneficial for the cardiovascular system, but it is unclear whether tamoxifen exhibits a favorable cardiovascular effect in Asian patients. METHODS AND RESULTS: From January, 1998 to December, 2006, a breast cancer cohort study was conducted using the Taiwan National Health Insurance database. Patients were divided according to whether tamoxifen was used. Study endpoints were occurrence of acute myocardial infarction (AMI), ischemic or hemorrhagic stroke and total cardiovascular events. A total of 3,690 female subjects were enrolled (mean age 50.1±11.3), 2,056 of whom received tamoxifen and 1,634 did not. During a mean follow-up of 6.9 years, the tamoxifen group had a significantly lower incidence of AMI (0.15% vs. 0.67%, P=0.008), ischemic stroke (1.99% vs. 3.30%, P=0.008), hemorrhagic stroke (0.15% vs. 0.55%, P=0.029), and total cardiovascular events (2.24% vs. 4.16%, P<0.001) than the non-exposed group. After adjusting for comorbidities, tamoxifen was independently associated with a reduced risk of myocardial infarction (hazard ratio [HR] 0.22; 95% confidence interval [CI] 0.07-0.70, ischemic stroke (HR 0.52; 95% CI 0.35-0.78), hemorrhagic stroke (HR 0.25; 95% CI 0.07-0.92), and total cardiovascular events (HR 0.54; 95% CI 0.37-0.78). CONCLUSIONS: In Asian female breast cancer patients, tamoxifen use was associated with reduced risks of AMI, ischemic, hemorrhagic stroke and total cardiovascular events.

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.

Genetic variation in C-reactive protein in ethnic Chinese population in Taiwan.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is a sensitive inflammatory marker suggested for cardiovascular risk stratification. This study aimed to assess the potential genetic determinants for serum hs-CRP levels in a cohort with well-controlled nondiabetic hypertension. MATERIALS AND METHODS: Ethnic Chinese nondiabetic hypertensive patients were enrolled in Taiwan. They received comprehensive evaluation including history taking, physical check-up, blood pressure (BP) measurement, 24-h ambulatory BP monitoring and blood sampling. Serum hs-CRP levels were determined. CRP genotyping was performed in two stages. In the first stage, 4 single-nucleotide polymorphisms (SNPs) of CRP including rs1572970, rs2794520, rs3093077 and rs2808630 were investigated in the 400 participants. In the second stage, only SNPs significant in the first stage were selected for complete genotyping in the whole population. RESULTS: Total 915 consecutive patients (40·9 ± 7·3 years, 68·3% male) completed the study. Two of the 4 SNPs including rs1572970 and rs3093077 were correlated to hs-CRP levels in the whole population. Stepwise multiple linear regression indicated that age (P = 0·001), body mass index (P < 0·001), waist-hip ratio (P = 0·032), smoking habits (P = 0·001), night-time systolic BP (P = 0·040), total cholesterol (P = 0·005) and CRP rs3093077 polymorphism (P < 0·001) were independently associated with serum hs-CRP levels. Overall, genetic correlates explained 2·4%, BMI explained 11·9% and all other clinical correlates explained 4·8% of interindividual variability in serum hs-CRP level. CONCLUSION: C-reactive protein genotype contributed limitedly to serum hs-CRP levels in subjects with well-controlled hypertension, suggesting the impacts of clinical rather than genetic determinants to serum hs-CRP levels for cardiovascular risk stratification in this intermediate-risk Taiwanese cohort.

Baseline Serum Aldosterone-to-Renin Ratio is Associated with the Add-on Effect of Thiazide Diuretics in Non-Diabetic Essential Hypertensives.

BACKGROUND: The baseline status of renin-angiotensin-aldosterone system (RAAS) might modify the blood pressure (BP) lowering effects of thiazide diuretics. This study aimed to determine if baseline RAAS indicated by serum aldosterone-to-renin ratio (ARR) could be associated with the add-on effects of thiazide on BP lowering in patients with other concomitant antihypertensive medication. METHODS: Non-diabetic hypertensive patients, either untreated or unsatisfactorily treated, were enrolled if their office systolic BP was ≥ 140 or diastolic BP ≥ 90 mmHg. After 2 weeks of diet control and lifestyle modification, patients with persistently elevated BP were prospectively given hydrochlorothiazide 50 mg daily for 2 weeks. Serum aldosterone-to-renin ratio (ARR) was determined before thiazide treatment. Patients with a significant (≥ 10%) reduction of office mean artery pressure (MAP) by thiazide treatment were defined as responders. RESULTS: Among the 66 patients studied, 27 were defined as responders after a 2-week hydrochlorothiazide treatment. Baseline serum renin level was reduced and ARR increased (p = 0.009) in the responders as compared with the non-responders. A similar pattern was also apparent in patients with or without concomitant medications. Furthermore, baseline renin level was inversely and ARR positively correlated to the MAP reduction both in the whole patient group and in patients with concomitant medications. By stepwise multiple linear regression analysis, ARR was the only independent predictor for the response to thiazide treatment (ß = 0.051, p = 0.007). CONCLUSIONS: Baseline ARR could be associated with the add-on effects of hydrochlorothiazide on BP reduction in patients with other concomitant antihypertensive treatment. KEY WORDS: Add-on; Aldosterone-to-renin ratio; Blood pressure; Hydrochlorothiazide; Hypertension; Renin; Thiazide.

The Impacts of In-Hospital Invasive Strategy on Long-Term Outcome in Elderly Patients with Non-ST-Elevation Myocardial Infarction.

BACKGROUND: The benefit of utilizing an invasive strategy in elderly Chinese patients with non-ST-elevation myocardial infarction (NSTEMI) remains unclear. The aim of this study was to determine whether in-hospital revascularization is associated with long-term prognosis in elderly Chinese patients with NSTEMI, as compared with younger patients. METHODS: All patients were followed up for at least 3 years or until the occurrence of a major event. The primary endpoint was all-cause mortality, and the secondary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including death, nonfatal MI, and ischemic stroke. RESULTS: A total of 343 consecutive NSTEMI patients (148 over the age of 75 years and 195 aged < 75 years) were enrolled. Coronary angiography was performed less frequently in elderly patients (66% vs. 76%; p = 0.027). Multiple logistic regression analysis confirmed the benefit of in-hospital revascularization in the elderly and younger patients, with a statistically significant reduction in the odds of all-cause death and MACE at 1 year and 3 years, respectively. In a multivariable Cox regression analysis, in-hospital revascularization was an independent predictor of future MACE not only in elderly patients [hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.38-0.97] but also in younger patients as well (HR, 0.51; 95% CI, 0.31-0.84). CONCLUSIONS: In Chinese patients with NSTEMI, in-hospital revascularization was associated with significant benefits at 1 year and 3 years in both younger and elderly groups. These results are consistent with the published literature and suggest that advanced age alone should not be regarded as a contraindication to invasive management following presentation with NSTEMI. KEY WORDS: Elderly; Invasive strategy; Myocardial infarction.

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.

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.

Niacin improves ischemia-induced neovascularization in diabetic mice by enhancement of endothelial progenitor cell functions independent of changes in plasma lipids.

Niacin was shown to inhibit acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids. Here, we investigated whether niacin can increase blood flow recovery after tissue ischemia by enhancing endothelial progenitor cell (EPC) functions in diabetic mice. Starting at 4 weeks after the onset of diabetes, vehicle or niacin (40 mg/kg/day) was administered daily by gavage to streptozotocin (STZ)-induced diabetic mice and diabetic endothelial nitric oxide synthase (eNOS)-deficient mice. Unilateral hindlimb ischemia surgery was conducted after 2 weeks of vehicle or niacin treatment. Compared to the control group, the niacin group had significantly increased ischemic/non-ischemic limb blood perfusion ratio and higher capillary density. These effects were markedly reduced in STZ-induced diabetic eNOS-deficient mice. Flow cytometry analysis showed impaired EPC-like cell (Sca-1(+)/Flk-1(+)) mobilization after ischemia surgery in diabetic mice but augmented mobilization in the mice treated with niacin. Diabetes was induced by administering STZ to FVB mice that received eGFP mouse bone marrow cells to evaluate effects of niacin on bone marrow-derived EPC homing and differentiation to endothelial cells. Differentiation of bone marrow-derived EPCs to endothelial cells in the ischemic tissue around vessels in diabetic mice that received niacin treatment, was significantly increased than that in control group. By in vitro studies, incubation with niacin in high-glucose medium reduced H(2)O(2) production, cell apoptosis, and improved high glucose-suppressed EPC functions by nitric oxide-related mechanisms. Our findings demonstrate that niacin increases blood flow recovery after tissue ischemia in diabetic mice through enhancing EPC mobilization and functions via nitric oxide-related pathways.

Effect of invasive strategy on different genders of Chinese patients with non-ST-elevation myocardial infarction.

OBJECTIVES: The aim of this study was to determine the impact of in-hospital revascularization on different genders and to compare the gender difference in short- and long-term prognosis of Chinese patients with non-ST-elevation myocardial infarction (NSTEMI). BACKGROUND: The benefit of invasive strategy between the genders of Asian ethnic populations with NSTEMI remains unclear. METHODS: A total of 343 consecutive NSTEMI patients were enrolled, 104 (30%) of them were women. All patients were followed up for at least 3 years or until the occurrence of a major event. The primary end point was all-cause death. The secondary end point was the combined occurrence of death or myocardial (re-)infarction (MI). RESULTS: The adjusted in-hospital and long-term clinical outcomes were similar between men and women. However, in-hospital revascularization significantly reduced long-term mortality and composite endpoint in men (P < 0.001), but not in women. After risk stratification by GRACE score, there was favorable effect of invasive strategy in high-risk women. In a multivariate Cox regression analysis, GRACE score (hazard ratio; HR, 1.017; P < 0.001) and in-hospital revascularization (HR, 0.516; P = 0.008) were the independent predictors of death or MI in men. However, only GRACE score was the independent predictor of composite endpoint in women (HR, 1.012; P = 0.004). CONCLUSIONS: In Asian ethnic patients with NSTEMI, the in-hospital and long-term prognosis were similar between men and women. In-hospital revascularization has a benefit in men and high-risk women for reducing the all-cause death at 1 and 3 years. Our data provide evidence supporting the guideline recommendation for an invasive strategy in high-risk women.

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.