The high-density lipoprotein cholesterol (HDL-C)-concentration-dependent association between anti-inflammatory capacity and sepsis: A single-center cross-sectional study.

INTRODUCTION: Known to have pleiotropic functions, high-density lipoprotein (HDL) helps to regulate systemic inflammation during sepsis. As preserving HDL-C level is a promising therapeutic strategy for sepsis, the interaction between HDL and sepsis worth further investigation. This study aimed to determine the impact of sepsis on HDL's anti-inflammatory capacity and explore its correlations with disease severity and laboratory parameters. METHODS AND MATERIALS: We enrolled 80 septic subjects admitted to the intensive care unit and 50 controls admitted for scheduled coronary angiography in this cross-sectional study. We used apolipoprotein-B depleted (apoB-depleted) plasma to measure the anti-inflammatory capacity of HDL-C. ApoB-depleted plasma's anti-inflammatory capacity is defined as its ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical-vein endothelial cells. A subgroup analysis was conducted to investigate in septic subjects according to disease severity. RESULTS: ApoB-depleted plasma's anti-inflammatory capacity was reduced in septic subjects relative to controls (VCAM-1 mRNA fold change: 50.1% vs. 35.5%; p < 0.0001). The impairment was more pronounced in septic subjects with than in those without septic shock (55.8% vs. 45.3%, p = 0.0022). Both associations were rendered non-significant with the adjustment for the HDL-C level. In sepsis patients, VCAM-1 mRNA fold change correlated with the SOFA score (Spearman's r = 0.231, p = 0.039), lactate level (r = 0.297, p = 0.0074), HDL-C level (r = -0.370, p = 0.0007), and inflammatory markers (C-reactive protein level: r = 0.441, p <0.0001; white blood cell: r = 0.353, p = 0.0013). CONCLUSION: ApoB-depleted plasma's anti-inflammatory capacity is reduced in sepsis patients and this association depends of HDL-C concentration. In sepsis patients, this capacity correlates with disease severity and inflammatory markers. These findings explain the prognostic role of the HDL-C level in sepsis and indirectly support the rationale for targeting HDL-C as sepsis treatment.

Impacts of the SYNTAX score I, II and SYNTAX score II 2020 on left main revascularization.

Patients with left main coronary artery disease (LMCAD) with a high SYNTAX score (SS) were excluded from randomized studies that comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to compare PCI and CABG in the real-world practice and investigate the impact of SS I, SS II, and SS II 2020 on clinical outcomes. In total, 292 Patients with LMCAD (173 PCI, 119 CABG) treated between 2017 and 2021 were enrolled. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, stroke, or myocardial infarction (MI). The mean SS I was high in both groups (PCI vs. CABG: 31.64 ± 11.45 vs. 32.62 ± 11.75, p = 0.660). The primary outcome occurred in 28 patients (16.2%) in the PCI group and in 19 patients (16.0%) in the CABG group without significant difference [adjusted hazard ratio, 95% CI = 0.98 (0.51-1.90), p = 0.97] over the follow-up period (26.9 ± 17.7 months). No significant difference was observed in all-cause mortality (11.6% vs. 11.8%, p = 0.93) or stroke rates (3.5% vs. 5.0%, p = 0.51) between groups. However, PCI was associated with higher MI (4.6% vs. 0.8%, p < 0.05) and revascularization rates (26% vs. 5.9%, p < 0.001). Prognostic value of the SS I, SS II and SS II 2020 on the primary outcome was not relevant in the PCI group. Among patients with LMCAD, PCI and CABG did not significantly differ in the composite endpoint of all-cause death, stroke, and MI. These results support the potential expansion of PCI indications in LMCAD management for whom are ineligible for CABG with complex coronary artery disease.

Systemic vascular resistance predicts high-output cardiac failure in patients with high-flow arteriovenous fistula.

AIMS: Patients with high-flow arteriovenous (AV) access are at risk of developing high-output cardiac failure (HOCF) and subsequent hospitalization. However, diagnosing HOCF is challenging and often requires invasive procedures. The role of systemic vascular resistance (SVR) in diagnosing HOCF is underestimated, and its predictive value is limited. Our study aims to identify non-invasive risk factors for HOCF to facilitate early diagnosis and timely surgical interventions. METHODS AND RESULTS: We included 109 patients with high-flow AV access who underwent serial echocardiography. The retrospective cohort was divided into two groups based on their hospitalization due to HOCF. The two groups were matched for age and gender. After a mean follow-up of 25.1 months, 19 patients (17.4%) were hospitalized due to HOCF. The two groups had similar baseline characteristics. However, the HOCF group had a higher value of vascular access blood flow (Qa) (2168 ± 856 vs. 1828 ± 617 mL/min; P = 0.045). Echocardiographic analysis revealed that the HOCF group had more pronounced left ventricular diastolic dysfunction (E/e': 21.1 ± 7.3 vs. 16.2 ± 5.9; P = 0.002), more severe pulmonary hypertension (right ventricular systolic pressure: 41.4 ± 16.7 vs. 32.2 ± 12.8; P = 0.009), a higher Doppler-derived cardiac index (CI) (4.3 ± 0.8 vs. 3.7 ± 1.1; P = 0.031), and a lower Doppler-derived estimated SVR (eSVR) value (5.5 ± 0.3 vs. 6.9 ± 0.2; P = 0.002) than the non-HOCF group. Using multivariable Cox regression analysis, a low eSVR value (<6) emerged as an independent predictor of HOCF hospitalization with a hazard ratio of 9.084 (95% confidence interval, 2.33-35.39; P = 0.001). Receiver operating characteristic curve analysis indicated that CI/eSVR values more accurately predicted HOCF hospitalization [sensitivity: 94.7%, specificity: 51.0%, area under the curve (AUC): 0.75, P < 0.001] than the Qa/cardiac output ratio (AUC: 0.50, P = 0.955), Qa values ≥ 2000 mL/min (AUC: 0.60, P = 0.181), and Qa values indexed for height in metres (AUC: 0.65, P = 0.040). CONCLUSIONS: In patients with high-flow AV access, low eSVR values obtained through non-invasive Doppler echocardiography were associated with a high rate of HOCF hospitalizations. Therefore, routine eSVR screening in these patients might expedite the diagnosis of HOCF.

Vertical Sleeve Gastrectomy Offers Protection against Disturbed Flow-Induced Atherosclerosis in High-Fat Diet-Fed Mice.

Bariatric surgery reduces body weight, enhances metabolic and diabetic control, and improves outcomes on obesity-related comorbidities. However, the mechanisms mediating this protection against cardiovascular diseases remain unclear. We investigated the effect of sleeve gastrectomy (SG) on vascular protection in response to shear stress-induced atherosclerosis using an overweighted and carotid artery ligation mouse model. Eight-week-old male wild-type mice (C57BL/6J) were fed a high-fat diet (HFD) for two weeks to induce weight gain and dysmetabolism. SG was performed in HFD-fed mice. Two weeks after the SG procedure, partial carotid-artery ligation was performed to promote disturbed flow-induced atherosclerosis. Compared with the control mice, HFD-fed wild-type mice exhibited increased body weight, total cholesterol level, hemoglobin A1c, and enhanced insulin resistance; SG significantly reversed these adverse effects. As expected, HFD-fed mice exhibited greater neointimal hyperplasia and atherosclerotic plaques than the control group, and the SG procedure attenuated HFD-promoted ligation-induced neointimal hyperplasia and arterial elastin fragmentation. Besides, HFD promoted ligation-induced macrophage infiltration, matrix metalloproteinase-9 expression, upregulation of inflammatory cytokines, and increased vascular endothelial growth factor secretion. SG significantly reduced the above-mentioned effects. Moreover, HFD restriction partially reversed the intimal hyperplasia caused by carotid artery ligation; however, this protective effect was significantly lower than that observed in SG-operated mice. Our study demonstrated that HFD deteriorates shear stress-induced atherosclerosis and SG mitigates vascular remodeling, and this protective effect was not comparable in HFD restriction group. These findings provide a rationale for using bariatric surgery to counter atherosclerosis in morbid obesity.

Melatonin Improves Ischemia-Induced Circulation Recovery Impairment in Mice with Streptozotocin-Induced Diabetes by Improving the Endothelial Progenitor Cells Functioning.

Patients with diabetes mellitus tend to develop ischemia-related complications and have compromised endothelial progenitor cell (EPC) function. Melatonin protects against ischemic injury, possibly via EPC modulation. We investigated whether melatonin pretreatment could restore EPC function impairment and improve circulation recovery in a diabetic critical limb ischemia mouse model. Under 25 mM high-glucose medium in vitro, EPC proliferation, nitric oxide production, tube formation, and endothelial nitric oxide synthase (eNOS) phosphorylation were significantly suppressed. Hyperglycemia promoted EPC senescence and apoptosis as well as increased reactive oxygen species (ROS) production. Melatonin treatment reversed the harmful effects of hyperglycemia on EPC through adenosine monophosphate-activated protein kinase-related mechanisms to increase eNOS phosphorylation and heme oxygenase-1 expression. In an in-vivo study, after a 4-week surgical induction of hindlimb ischemia, mice with streptozotocin (STZ)-induced diabetes showed significant reductions in new vessel formation, tissue reperfusion, and EPC mobilization in ischemic hindlimbs compared to non-diabetic mice. Mice with STZ-induced diabetes that received melatonin treatment (10 mg/kg/day, intraperitoneal) had significantly improved blood perfusion ratios of ischemic to non-ischemic limb, EPC mobilization, and densities of capillaries. In addition, a murine bone marrow transplantation model to support these findings demonstrated that melatonin stimulated bone marrow-originated EPCs to differentiate into vascular endothelial cells in femoral ligation-induced ischemic muscles. In summary, this study suggests that melatonin treatment augments EPC function along with neovascularization in response to ischemia in diabetic mice. We illustrated the protective effects of melatonin on EPC H2O2 production, senescence, and migration through melatonin receptors and modulating eNOS, AMPK, and HO-1 activities at the cellular level. Thus, melatonin might be used to treat the impairment of EPC mobilization and circulation recuperation in response to ischemic injury caused by chronic hyperglycemia. Additional studies are needed to elucidate the applicability of the results in humans.

The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Ameliorates Endothelial Inflammation and Microvascular Thrombosis in a Sepsis Mouse Model.

The pathophysiology of sepsis involves inflammation and hypercoagulability, which lead to microvascular thrombosis and compromised organ perfusion. Dipeptidyl peptidase (DPP)-4 inhibitors, e.g., linagliptin, are commonly used anti-diabetic drugs known to exert anti-inflammatory effects. However, whether these drugs confer an anti-thrombotic effect that preserves organ perfusion in sepsis remains to be investigated. In the present study, human umbilical vein endothelial cells (HUVECs) were treated with linagliptin to examine its anti-inflammatory and anti-thrombotic effects under tumor necrosis factor (TNF)-α treatment. To validate findings from in vitro experiments and provide in vivo evidence for the identified mechanism, a mouse model of lipopolysaccharide (LPS)-induced systemic inflammatory response syndrome was used, and pulmonary microcirculatory thrombosis was measured. In TNF-α-treated HUVECs and LPS-injected mice, linagliptin suppressed expressions of interleukin-1ß (IL-1ß) and intercellular adhesion molecule 1 (ICAM-1) via a nuclear factor-κB (NF-κB)-dependent pathway. Linagliptin attenuated tissue factor expression via the Akt/endothelial nitric oxide synthase pathway. In LPS-injected mice, linagliptin pretreatment significantly reduced thrombosis in the pulmonary microcirculation. These anti-inflammatory and anti-thrombotic effects were independent of blood glucose level. Together the present results suggest that linagliptin exerts protective effects against endothelial inflammation and microvascular thrombosis in a mouse model of sepsis.

Elevated serum galectin-1 concentrations are associated with increased risks of mortality and acute kidney injury in critically ill patients.

BACKGROUND: Galectin-1 (Gal-1), a member of the ß-galactoside binding protein family, is associated with inflammation and chronic kidney disease. However, the effect of Gal-1 on mortality and acute kidney injury (AKI) in critically-ill patients remain unclear. METHODS: From May 2018 to March 2020, 350 patients admitted to the medical intensive care unit (ICU) of Taipei Veterans General Hospital, a tertiary medical center, were enrolled in this study. Forty-one patients receiving long-term renal replacement therapy were excluded. Serum Gal-1 levels were determined within 24 h of ICU admission. The patients were divided into tertiles according to their serum Gal-1 levels (low, serum Gal-1 < 39 ng/ml; median, 39-70 ng/ml; high, ≥71 ng/ml). All patients were followed for 90 days or until death. RESULTS: Mortality in the ICU and at 90 days was greater among patients with elevated serum Gal-1 levels. In analyses adjusted for the body mass index, malignancy, sepsis, Sequential Organ Failure Assessment (SOFA) score, and serum lactate level, the serum Gal-1 level remained an independent predictor of 90-day mortality [median vs. low: adjusted hazard ratio (aHR) 2.11, 95% confidence interval (CI) 1.24-3.60, p = 0.006; high vs. low: aHR 3.21, 95% CI 1.90-5.42, p < 0.001]. Higher serum Gal-1 levels were also associated with a higher incidence of AKI within 48 h after ICU admission, independent of the SOFA score and renal function (median vs. low: aHR 2.77, 95% CI 1.21-6.34, p = 0.016; high vs. low: aHR 2.88, 95% CI 1.20-6.88, p = 0.017). The results were consistent among different subgroups with high and low Gal-1 levels. CONCLUSION: Serum Gal-1 elevation at the time of ICU admission were associated with an increased risk of mortality at 90 days, and an increased incidence of AKI within 48 h after ICU admission.

Serum creatinine to cystatin C ratio is associated with major adverse cardiovascular events in patients with obstructive coronary artery disease.

BACKGROUND & AIMS: Sarcopenia is a clinical syndrome that features muscle atrophy and weakness, and has been associated with cardiovascular events and poor clinical outcomes. Recently, the sarcopenia index (SI) was developed as a simple screening tool based upon the serum creatinine to cystatin C (CysC) ratio. We investigated the association between SI and the prevalence of major adverse cardiovascular events (MACE) in patients with obstructive CAD. METHODS & RESULTS: Between January 2010 and December 2018, patients with angina pectoris and obstructive CAD requiring coronary artery intervention were enrolled. Serum levels of CysC and other biomarkers were assessed. Patients were divided into two groups according to the SI ([Cr/CysC] x 100). Demographic characteristics and clinical outcomes of the two groups were evaluated. A total of 427 patients (79.6% men, mean age 69.55 ± 12.04 years) were enrolled. Patients with SI < 120 (n = 214, 28%) were older, more likely to be of the female gender, and to have more hypertension and congestive heart failure (all p < 0.05). The prevalence of major adverse cardiovascular events (MACE) composed of myocardial infarction, stroke, and all-cause mortality was higher in patients with lower SI (p = 0.026). After adjusting for potential confounding factors, multivariate Cox regression (hazard ratio 2.08, p = 0.045) and Kaplan-Meier analyses (log-rank p = 0.0371) revealed that lower SI was significantly associated with a higher prevalence of MACE. CONCLUSIONS: Serum creatinine to cystatin C ratio (SI) may be a useful surrogate marker to predict the future prevalence of MACE in patients with obstructive CAD.

An oral absorbent, AST-120, restores vascular growth and blood flow in ischemic muscles in diabetic mice via modulation of macrophage transition.

Background Diabetes has a pronounced effect on the peripheral vasculature. The accumulation of advanced glycation end products (AGEs) is regarded as the crucial mechanism responsible for vascular damage in diabetes, but it is not easy to be avoided from food. In this study, we aimed to investigate the effects of an oral absorbent, AST-120, on the accumulation of AGEs and changes in blood flow recovery in diabetic mice. Methods The mice were divided into four groups, wild-type (WT) mice without treatment, WT mice treated with 5% AST-120 mixed into pulverized chow, streptozotocin-induced diabetes mellitus (DM) mice, and DM mice treated with 5% AST-120. Six weeks after hind-limb ischemia surgery, blood flow reperfusion, histology, plasma AGE, and cytokine were examined. Bone marrow cells were cultured and derived into macrophages to evaluate the effects of AGEs on macrophage polarization. Results Plasma AGEs were significantly increased in diabetic mice. AST-120 could bind to AGEs and reduced their plasma concentrations. Histological analysis revealed fewer collateral vessels with corresponding impairment of blood flow recovery in diabetic mice. In these mice, AGE-positive and AGE receptor-positive macrophages were numerous in ischemic limbs compared with non- diabetic mice. In diabetic mice, macrophages in ischemic tissues demonstrated greater M1 polarization than M2 polarization; this pattern was reversed in the AST-120 treatment group. The change in macrophage polarization was associated with the corresponding expression of pro-inflammatory cytokines in the ischemic tissues. In cell cultures, AGEs triggered the transformation of bone marrow-derived macrophages into the M1 phenotype. The alterations in the polarization of macrophages were reversed after treatment with AST-120. Conclusions Oral administration of AST-120 decreased the serum levels of AGEs in diabetic mice and improved neovascularization of ischemic limbs. This benefit may be due to, at least partially, the alterations in macrophage polarization and the associated changes in inflammatory cytokines.

Serum Activin A Levels and Renal Outcomes After Coronary Angiography.

Prevention for contrast-induced nephropathy (CIN) is limited by the lack of a single predictor. As activin A is upregulated in heart failure and chronic kidney disease, we aimed to clarify the association between activin A levels and renal outcomes after coronary angiography (CAG). This prospective observational study included 267 patients who received CAG between 2009 and 2015. CIN was defined as elevation of serum creatinine to >0.5 mg/dL or to >25% above baseline within 48 hours after CAG. During follow-up, laboratory parameters were measured every 3-6 months. Renal decline was defined as>2-fold increase in serum creatinine or initiation of dialysis. The patients were stratified into tertiles according to serum activin A levels at baseline. High activin A tertile was significantly associated more CIN and renal function decline compared to low activin A tertile (all p < 0.001). After adjusting potential confounding factors, high serum activin A tertiles was associated to CIN (Odds ratio 4.49, 95% CI 1.07-18.86, p = 0.040) and renal function decline (Hazard ratio 4.49, 95% CI 1.27-11.41, p = 0.017) after CAG.

Increased circulating galectin-1 levels are associated with the progression of kidney function decline in patients undergoing coronary angiography.

Galectin-1 modulates acute and chronic inflammation, and is associated with glucose homeostasis and chronic renal disease. Whether the serum galectin-1 level can predict short-term and long-term renal outcomes after contrast exposure in patients undergoing coronary angiography (CAG) remains uncertain. This study aimed to evaluate the relationship between the serum galectin-1 level and the incidence of contrast-induced nephropathy (CIN), and to investigate the predictive role of the circulating galectin-1 level for renal function decline in patients undergoing CAG. In total, 798 patients who had undergone CAG were enrolled. Baseline creatinine and serum galectin-1 levels were determined before CAG. CIN was defined as an increase in the serum creatinine level of 0.5 mg/dl or a 25% increase from baseline within 48 h after the procedure, and renal function decline was defined as > 30% reduction of the estimated glomerular filtration rate from baseline. All patients were followed for at least 1 year or until the occurrence of death after CAG. Overall, CIN occurred in 41 (5.1%) patients. During a median follow-up period of 1.4 ± 1.1 years, 80 (10.0%) cases showed subsequent renal function decline. After adjustment for demographic characteristics, kidney function, traditional risk factors, and medications, higher galectin-1 levels were found to be associated independently with a greater risk of renal function decline [tertile 2: hazard ratio (HR) 5.56, 95% confidence interval (CI) 1.79-17.22; tertile 3: HR 5.56, 95% CI 1.97-16.32], but not with CIN, regardless of the presence of diabetes. In conclusion, higher baseline serum galectin-1 levels were associated with a greater risk of renal function decline in patients undergoing CAG, but were not associated independently with CIN.

InVestiGation of the Association of Physical Activity and Sedentary Behavior with tHe Occurrence of Future Cardiovascular Disease and Long Term Outcome in General Population Using the HEALTHCARE Database (VGH-HEALTHCARE).

BACKGROUND: Current evidence supports the beneficial effect of physical activity in reducing adverse events, however studies on Asian populations are limited and have reported inconsistent findings. The aim of this study was to investigate the association between physical activity and the development of cardiovascular disease, diabetes, hypertension and malignancy in a large Asian cohort. We also investigated interactions between the intensity of physical activity, environmental exposure and biochemical markers. METHODS: Subjects who received annual checkups at Taipei Veterans General Hospital were invited to join this study. Information on physical activity was evaluated using the International Physical Activity Questionnaire Short Form (IPAQ-SF). Associations between the occurrence of clinical events including cardiovascular events, diabetes and malignancies and the intensity of physical activity, biochemical markers, imaging findings, personality trait evaluations and nutrition were evaluated. RESULTS: In the initial stage of this study, a total of 1010 patients enrolled, 626 (62%) were male, 74 (7.4%) had diabetes, 183 (18.3%) had hypertension, and 220 (21.8%) were smokers. The total cholesterol was 202.1 ± 36.2 mg/dL and low-density lipoprotein-cholesterol was 125.7 ± 32.9 mg/dL, including 49.3 ± 13.1 mg/dL for serum high-density lipoprotein-cholesterol and 120.7 ± 70.7 mg/dL for triglycerides. The fasting glucose level was 93.8 ± 21.9 mg/dL, and HbA1c was 5.7 ± 0.7%. All information collected will be incorporated with future events to analyze the relationship between biochemical parameters, physical activity and future adverse events. CONCLUSIONS: These findings will contribute to the understanding of the value of physical activity in determining future cardiovascular and non-cardiovascular events in Asian populations.

Circulating TNFSF14 (Tumor Necrosis Factor Superfamily 14) Predicts Clinical Outcome in Patients With Stable Coronary Artery Disease.

Objective- Basic research indicates that TNFSF14 (tumor necrosis factor superfamily 14) may be involved in the pathogenesis of atherosclerosis. Given the requirements of new biomarkers for risk classification in coronary artery disease (CAD), we conducted a longitudinal analysis to investigate if TNFSF14 levels are associated with the risk of cardiovascular events among patients with stable CAD. Approach and Results- In total, 894 patients with CAD were enrolled in a multicenter prospective study. The primary outcome was the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome was the occurrence of all-cause death, nonfatal myocardial infarction, stroke, revascularization, and hospitalization because of angina or heart failure. During the mean follow-up period of 22±9 months, 32 patients reached the primary outcome and 166 patients reached the secondary outcome. Kaplan-Meier analysis showed that the event-free survival was significantly different in the first and fourth quartile groups in subjects categorized by TNFSF14 levels. In multivariate Cox proportional hazard regression analysis, TNFSF14 was independently associated with the risk of cardiovascular events after adjustment for various relevant factors (adjusted hazard ratio, 1.14; 95% CI, 1.04-1.25). In the validation cohort of 126 multivessel patients with CAD, TNFSF14 was confirmed to provide good prognostic predictive value for composite cardiovascular events (adjusted hazard ratio, 1.11; 95% CI, 1.04-1.19). Conclusions- This is the first study to demonstrate that increased TNFSF14 levels were independently associated with the occurrence of cardiovascular events in patients with stable CAD. Future studies are worthy to validate if TNFSF14 could be a novel prognostic biomarker for CAD outcomes over different populations.

Metabolic surgery ameliorates cardiovascular risk in obese diabetic patients: Influence of different surgical procedures.

BACKGROUND: In recent years, bariatric surgery was found to have therapeutic potential for the treatment of type 2 diabetes (T2D) in severely obese patients (body mass index [BMI] ≥35 kg/m2) and to reduce cardiovascular disease (CVD) risk and mortality. However, the benefit of CVD risk reduction after metabolic surgery in nonseverely obese T2D patients (BMI <35 kg/m2) remained to be proven. OBJECTIVE: To evaluate the CVD risk after metabolic surgery in T2D patients using The UK Prospective Diabetes Study score. SETTING: Tertiary referral general hospital, Taiwan, Republic of China. METHODS: Outcomes of 392 patients (235 women and 147 men) who had undergone sleeve gastrectomy (87) or gastric bypass (305) for treatment of T2D with 1-year follow-up were assessed. Data were prospectively collected for study, and cerebral and coronary heart disease risk was calculated by using The UK Prospective Diabetes Study risk engine. Outcomes of patients who had undergone different surgical procedures were assessed. RESULTS: One year after surgery, weight and glycemic control with complete and partial remission of T2D were significant in most of the patients. The 10-year coronary heart disease risk and fatal coronary heart disease risk were also reduced from 8.8% to 4.6% and from 4.6% to 2.1%, respectively (both P < .001). Similar CVD risk reduction was seen in both patients with BMI ≥35 and BMI <35. Multivariable analysis confirmed that surgical procedure of sleeve gastrectomy was a negative independent predictor of CVD risk reduction after metabolic surgery. CONCLUSION: The present study confirms the efficacy of metabolic surgery for the T2D treatment and reduction of CVD risk up to 50% 1 year after surgery. Gastric bypass surgery has more power on CVD risk reduction than sleeve gastrectomy.

Circulating Fibroblast Growth Factor 21 is Associated with Subsequent Renal Injury Events in Patients Undergoing Coronary Angiography.

Fibroblast growth factor 21 (FGF21) is a regulator of glucose homeostasis, and is suggested to have protective effect on diabetic nephropathy. Its impact on non-diabetic kidney disease is unclear. To investigate the impact of FGF21 on contrast-induced nephropathy (CIN), 531 subjects underwent elective coronary angiography (CAG) were enrolled. Baseline creatinine and FGF21 were obtained before CAG. Patients were grouped into tertiles according to their FGF21 concentration. Creatinine was obtained 48 hours after CAG, and every 6 months in the follow-up period. Renal function decline was defined as >30% reduction of eGFR from baseline. All subjects were followed up till December 2016, or till the occurrence of major adverse cardiovascular events (MACE). Patients with higher FGF21 concentration were older, had higher incidence of hypertension, diabetes, chronic kidney disease, and heart failure. Thirty-four cases of CIN and 111 cases of renal function decline were identified during mean follow-up of 2.3 ± 1.3 years. Circulating FGF21 level was independently associated with CIN (aOR: 4.66, 95% CI: 1.29-16.86, p = 0.019) and renal function decline (aHR: 7.98, 95% CI: 4.07-15.66, p < 0.001) whether diabetes was present or not. In conclusion, circulating FGF21 level is independently associated with the incidence of CIN and subsequent kidney injury in patients undergoing CAG.

Chronic hyperuricemia impairs blood flow recovery in the ischemic hindlimb through suppression of endothelial progenitor cells.

OBJECTIVE: Chronic hyperuricemia is associated with cardiovascular disease, but its impact on endothelial progenitor cells (EPC) and ischemia-induced neovascularization remains unclear. Herein we investigated whether chronic hyperuricemia could impede blood flow recovery in response to tissue ischemia by suppression of EPC. METHODS: Human EPC were isolated and cultured in a high-level uric acid medium for functional testing. Cell proliferation, nitric oxide (NO) production and apoptosis assay were examined. A chronic hyperuricemia mouse model was established by potassium oxonate treatment and/or a high-level uric acid diet to evaluate the actions of chronic hyperuricemia on ischemia-induced blood flow recovery. After 4 weeks of drug treatment, hindlimb ischemia surgery was performed in the control and hyperuricemia mice. Blood flow recovery was followed up every week before and after ischemic surgery using a laser Doppler Perfusion Imager System. The circulating EPC number in the peripheral blood was determined by flow cytometry (Sca-1+/Flk-1+). RESULTS: Incubation with a high-level uric acid medium (10 mg/dL) significantly suppressed EPC proliferation, reduced NO production, and lessened phosphorylation of Akt and eNOS. Moreover, EPC treated with high-level uric acid increased reactive oxygen species production, promoted cellular apoptosis and senescence, and also inhibited EPC tube formation. Four weeks after hindlimb ischemia surgery, the chronic hyperuricemia mice had significantly reduced tissue reperfusion, EPC mobilization, and impaired neovascularization in the ischemic hindlimbs compared with the control mice. CONCLUSIONS: Chronic hyperuricemia impaired blood flow recovery and EPC mobilization in response to tissue ischemia, and these effects could have occurred through suppression of EPC.

Circulating Fibroblast Growth Factor 21 is Associated with Diastolic Dysfunction in Heart Failure Patients with Preserved Ejection Fraction.

Fibroblast growth factor 21 (FGF21), a polypeptide ligand promoted glucose homeostasis and lipids metabolism, was recently reported to attenuate cardiac hypertrophy. The aim of this study was to investigate the impact of FGF21 in diastolic heart failure. Subjects admitted for coronary angiogram were screened for heart failure, and those with left ventricular (LV) ejection fraction < 45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Plasma levels of FGF21 and N-terminal Pro-Brain Natriuretic Peptide (NT-pro-BNP) were determined. All patients were followed up for 1 year, or till the occurrence of heart failure readmission or death. Totally 95 patients with diastolic dysfunction and 143 controls were enrolled. Circulating FGF21 level was correlated with echocardiographic parameters of diastolic function and LV end-diastolic pressure (LVEDP). In multivariate logistic analysis, FGF21 was significantly associated with diastolic dysfunction, either identified by echocardiographic criteria (odds ratio: 2.97, p = 0.012) or confirmed with LVEDP level (odds ratio: 3.73, p = 0.030). Both plasma FGF21 (log rank p < 0.0001) and NT-pro-BNP levels (log rank p = 0.0057) showed good predictive power to the 1-year adverse cardiac events. This finding suggested FGF21 could be involved in the pathophysiology of diastolic heart failure.

CHADS2 score predicts risk of contrast-induced nephropathy in stable coronary artery disease patients undergoing percutaneous coronary interventions.

BACKGROUND/PURPOSE: To investigate the correlation between the CHADS2 score and risk of contrast-induced nephropathy (CIN), we conducted a retrospective study in patients who underwent elective percutaneous coronary intervention (PCI) and compared its accuracy with previous scoring systems. METHODS: A total of 539 patients who underwent elective PCI were enrolled. Based on their underlying diseases, such as hypertension, diabetes, and kidney disease, CHADS2 score, R2CHADS2 score, and Mehran's risk score were calculated for each patient. Incidence of CIN was defined as a rise in serum creatinine >0.5 mg/dL or >25% increase in baseline within 48 hours after PCI. All study participants were followed up until October 2014, or until the occurrence of major adverse cardiovascular events (MACEs). RESULTS: Overall, 55 cases (10.2%) of CIN and 90 cases (16.7%) of MACEs were identified after participants were followed up for 1.57 ± 1.46 years. The study cohort was divided into three groups according to CHADS2 scores: score 0, score 1-2, and score 3-6. In multivariate analysis, an increase of 1 point in the CHADS2 score was independently associated with a 37% increase in the risk of CIN (odds ratio, 1.37; 95% confidence interval, 1.00-1.87; p = 0.048) and a 49% increase in MACEs (hazard ratio, 1.49; 95% confidence interval, 1.18-1.88, p = 0.001). In pairwise comparison, the discriminatory performance of CHADS2 score was not inferior to either R2CHADS2 score (p = 0.226) or Mehran's risk score (p = 0.075). CONCLUSION: CHADS2 score could be a simple and useful predictor for CIN in patients undergoing elective PCI.