Dose-response effects of physical activity on all-cause mortality and major cardiorenal outcomes in chronic kidney disease.

AIMS: Physical activity has a protective effect against mortality and cardiovascular events in chronic kidney disease (CKD) patients. Nonetheless, how different levels of physical activity affect the health benefits in CKD remains unclear. This study aimed to investigate the dose-response effects of physical activity on mortality and major cardiorenal events in CKD. METHODS AND RESULTS: We evaluated a longitudinal cohort of 4508 Taiwanese CKD patients between 2004 and 2017. Physical activity was assessed by the NHANES questionnaire and quantified in metabolic equivalent-hours per week (MET-hour/week). Patients were categorized into highly active (≥7.5 MET-h/week), low-active (0.1 to <7.5 MET-h/week), or inactive (0 MET-h/week) groups. Cox regression and restricted cubic spline models were utilized to explore the association between physical activity and the risks of study outcomes, including all-cause mortality, end-stage renal disease (ESRD), and major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, ischaemic stroke, and hospitalized heart failure). During a median follow-up of 686 days, 739 death, 1059 ESRD, and 521 MACE events occurred. Highly active group had the lowest chance of all study outcomes, followed by low-active and inactive groups (P < 0.001). Multivariable Cox regression showed that only highly active group was independently associated with lower risks for all-cause mortality [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.53-0.74], ESRD (HR 0.83, 95% CI 0.72-0.96), and MACE (HR 0.63, 95% CI 0.51-0.76) compared to the inactive group. The risks of MACE did not further decrease once physical activity surpassed 15 MET-h/week, indicating a U-shaped association. The results were consistent in the subgroup and sensitivity analyses. CONCLUSION: Physical activity of 7.5 to <15 MET-h/week is associated with lower risks of adverse cardiorenal outcomes and should be integrated into the care of CKD.

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.

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).

Hemoglobin A1C Levels are Independently Associated with the Risk of Coronary Atherosclerotic Plaques in Patients without Diabetes: A Cross-Sectional Study.

AIM: Coronary atherosclerotic plaques can be detected in asymptomatic subjects and are related to low-density lipoprotein cholesterol (LDL) levels in patients with coronary artery disease. However, researchers have not yet determined the associations between various plaque characteristics and other lipid parameters, such as HDL-C and TG levels, in low-risk populations. METHODS: One thousand sixty-four non-diabetic subjects (age, 57.86±9.73 years; 752 males) who underwent coronary computed tomography angiography (CCTA) were enrolled and the severity and patterns of atherosclerotic plaques were analyzed. RESULTS: Statin use was reported by 25% of the study population, and subjects with greater coronary plaque involvement (segment involvement score, SIS) were older and had a higher body mass index (BMI), blood pressure, unfavorable lipid profiles and comorbidities. After adjusting for comorbidities, only age (ß=0.085, p＜0.001), the male gender (ß=1.384, p＜0.001), BMI (ß=0.055, p=0.019) and HbA1C levels (ß=0.894, p＜0.001) were independent factors predicting the greater coronary plaque involvement in non-diabetic subjects. In the analysis of significantly different (＞50%) stenosis plaque patterns, age (OR: 1.082, 95% CI: 10.47-1.118) and a former smoking status (OR: 2.061, 95% CI: 1.013-4.193) were independently associated with calcified plaques. For partial calcified (mixed type) plaques, only age (OR: 1.085, 95% CI: 1.052-1.119), the male gender (OR: 7.082, 95% CI: 2.638-19.018), HbA1C levels (OR: 2.074, 95% CI: 1.036-4.151), and current smoking status (OR: 1.848, 95% CI: 1.089-3.138) were independently associated with the risk of the presence of significant stenosis in mixed plaques. CONCLUSIONS: A higher HbA1c levels is independently associated with the presence and severity of coronary artery atherosclerosis in non-diabetic subjects, even when LDL-C levels are tightly controlled.

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.

Long-term results of stenting versus coronary artery bypass surgery for left main coronary artery disease-A single-center experience.

BACKGROUND: Percutaneous coronary intervention (PCI) has emerged as an alternative treatment to coronary artery bypass grafting (CABG) for unprotected left main (LM) coronary artery disease, but the results of both treatments are less clear in real-world practice. We aimed to assess the long-term outcomes of unprotected LM disease treated with CABG or PCI with stenting in high-risk population from a single center. METHODS: We collected 478 consecutive patients with unprotected LM disease (PCI/CABG: 208/270; mean age: 70 ± 11 years; 85% male), and 252 patients were considered to be at high risk (European System for Cardiac Operative Risk Evaluation ≥6). The median follow-up was 4.3 years (interquartile range: 2.7-6.5 years). RESULTS: All-cause death (PCI/CABG: 27.4%/31.5%; p = 0.36) and all-cause death/myocardial infarction (MI)/stroke (PCI/CABG: 30.8%/35.9%; p = 0.49) were comparable between the two groups, whereas the repeat revascularization rate was significantly higher in the PCI group (PCI/CABG: 22.6%/11.0%; p < 0.01). These results remained similar after adjustment with the propensity score. Notably, CABG tended to be associated with higher periprocedural mortality (adjusted p = 0.08) and long-term stroke (adjusted p = 0.05), while PCI was associated with higher long-term MI (adjusted p = 0.09). Analyses of the diabetic subgroup (PCI/CABG: 98/124) yielded similar results. CONCLUSION: PCI was a comparable alternative to CABG for high-risk patients with unprotected LM disease in terms of long-term risks of all-cause death/MI/stroke, but with a significantly higher repeat revascularization rate.

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.

Serum bilirubin levels predict future development of metabolic syndrome in healthy middle-aged nonsmoking men.

BACKGROUND: Despite epidemiologic research demonstrating an inverse relationship between serum bilirubin levels and the prevalence of metabolic syndrome, prospective data on serum bilirubin as a predictor of incident metabolic syndrome are limited. METHODS: Serum bilirubin was examined as a risk marker for incident metabolic syndrome in a prospective study of 468 Taiwanese middle-aged men who were free of metabolic syndrome and other systemic diseases at baseline. These subjects were followed up in annual health examinations between 2001 and 2009 for the development of metabolic syndrome, which was defined according to unified criteria set by several major organizations. RESULTS: Among the study subjects, 377 were nonsmokers and 91 were current smokers. All individuals were then stratified into 3 groups according to their baseline serum bilirubin levels (low, normal, and high). During a mean follow-up period of 7.58 years, 66 subjects developed metabolic syndrome. The incidence of metabolic syndrome was significantly reduced in the high-bilirubin group compared with the low-bilirubin group (6.4% vs 22.4%, P < .001). Multivariate Cox regression analysis revealed that the hazard ratio for incident metabolic syndrome between the highest and lowest tertiles of serum bilirubin levels was 0.246 (95% confidence interval 0.120-0.503). However, although it remained clearly evident in nonsmokers, the inverse correlation was attenuated in current smokers. CONCLUSIONS: Increased serum bilirubin was associated with a reduced future risk of metabolic syndrome in apparently healthy middle-aged, nonsmoking men. Our findings support the predictive role of serum total bilirubin for future development of metabolic syndrome.

Association of central pulse pressure with contrast-induced nephropathy and clinical outcomes in patients undergoing coronary intervention.

OBJECTIVE: The increase in pulse pressure (PP) may be transmitted to the glomerulus and thus impair renal blood flow autoregulation. This subtle change could predispose patients to the detrimental effect of contrast media. We sought to determine whether elevated central PP is associated with increased contrast-induced nephropathy (CIN) and future cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). METHODS: In total, 448 consecutive patients receiving PCI were enrolled. In each patient, central and peripheral blood pressures were measured before PCI. The occurrence of CIN was identified and 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 then followed up for at least 3 years or until the occurrence of a major adverse cardiovascular event (MACE) including death, nonfatal myocardial infarction, and ischemic stroke after coronary intervention. RESULTS: Overall, CIN occurred in 52 (11.6%) patients. Patients developing CIN had higher baseline central PP (P = 0.004). Patients were then stratified into three groups (low/intermediate/high) according to baseline central PP. Compared to that with the lowest tertile of central PP, patients with the highest tertile of central PP had a significantly increased incidence of CIN after PCI (odds ratio, 2.94; 95% confidence interval, CI 1.02-8.51). By Cox regression analysis, elevated central PP was an independent predictor of future MACE in all patients undergoing PCI (hazard ratio, 2.07; 95% CI 1.04-4.12). CONCLUSION: Elevated baseline central PP was associated with an increased risk of CIN and future cardiovascular events in patients with PCI. Further clinical study may be indicated to determine whether pharmacological modulation on baseline central PP could prevent CIN and future MACE after PCI.

Association of serum bilirubin with contrast-induced nephropathy and future cardiovascular events in patients undergoing coronary intervention.

OBJECTIVES: Enhanced reactive oxygen species formation within the kidney following the administration of contrast media may play a key role in the development of contrast-induced nephropathy (CIN). Bilirubin has emerged as an important endogenous antioxidant molecule. This study was undertaken to determine whether bilirubin is associated with CIN and future cardiovascular events in patients undergoing coronary intervention. METHODS: Totally, 544 consecutive patients received coronary intervention were enrolled. All patients were followed up for at least 3 years or until the occurrence of a major event. The primary endpoint was CIN, defined as a rise in serum creatinine (SCr) of 0.5 mg/dl or a 25% increase from the baseline value within 48 hours after the procedure. The secondary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including death, nonfatal myocardial infarction, and ischemic stroke. RESULTS: Overall, CIN occurred in 85 (15.6%) patients. All patients were stratified into 3 groups (low/normal/high) according to the serum bilirubin levels. In a multivariate logistic analysis, the odds ratio for CIN with low-bilirubin levels relative to high-bilirubin levels was 11.82 (95% CI, 3.25-43.03). By Cox regression analysis, serum bilirubin levels was an independent predictor of MACE in patients undergoing coronary intervention (low vs. high hazard ratio 2.26; 95% CI, 1.05-4.90). CONCLUSIONS: CIN is a serious complication of coronary intervention. Higher serum bilirubin concentrations were associated with lower risk of CIN and fewer cardiovascular events. The development of interventions that promote bilirubin levels may be a potential target to reduce CIN and future MACE in patients undergoing coronary intervention.

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.

Decreased circulating endothelial progenitor cell levels and function in essential hypertensive patients with electrocardiographic left ventricular hypertrophy.

The aim of this study was to explore the role of circulating endothelial progenitor cells (EPCs) and endothelial apoptotic microparticles in hypertensive patients with and without electrocardiographic left ventricular hypertrophy (LVH). Flow cytometry was used to assess endothelial cell apoptosis and circulating EPC level by quantification of circulating EPC markers (defined as CD34(+)CD133(+), CD34(+)KDR(+)) and endothelial apoptotic microparticles (defined as CD31(+)/annexin V(+)) in peripheral blood samples. The LVH was defined by ECG with the Cornell voltage criteria. In total, 128 hypertensive patients (83 men and 45 women, aged 59±14 years) were enrolled in this study, in which 107 patients (84%) showed no electrocardiographic evidence of LVH, and 21 patients (16%) fulfilled the LVH criteria by ECG. There were no significant differences in basic characteristics between the two groups, but hypertensive patients with LVH had a higher urine albumin excretion rate than those without LVH (P=0.027). Furthermore, hypertensive patients with LVH were shown to have decreased circulating EPC numbers (all P<0.05) and adhesive function compared with those without LVH (LVH vs. no LVH: 14±6 vs. 30±6 cells per high-power field, P<0.001). Increased numbers of endothelial apoptotic microparticles were noted in hypertensive patients with LVH (4.2±4.9 vs. 2.4±3.4%, P=0.115), although the difference was not significant. This study showed that essential hypertensive patients with electrocardiographic LVH evidence have decreased circulating EPC numbers and adhesive function compared with those without LVH. These findings may explain the pathogenetic processes that link hypertensive LVH and endothelial injury in cardiovascular disease.

Association of adiponectin with future cardiovascular events in patients after acute myocardial infarction.

AIM: There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease risk, particularly in patients after acute myocardial infarction (AMI). The goal of this study was to determine whether plasma adiponectin levels could predict future cardiovascular events in patients after AMI, and to elucidate the role of adiponectin in cardioprotection. METHODS: A total of 102 patients with AMI were enrolled. Plasma adiponectin levels were examined from blood samples collected 18 months after AMI. All subjects were followed-up for 43+/-12 months. The primary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization due to unstable angina, nonfatal MI, revascularization with percutaneous coronary intervention or coronary artery bypass grafting, ischemic stroke, and cardiovascular death. RESULTS: A total of 30 MACE occurred, including one case of cardiovascular death, five cases of nonfatal MI, and nine cases of ischemic stroke. Patients with MACE had lower plasma adiponectin levels (p=0.013). In addition, adiponectin was positively associated with changes in left ventricular ejection fraction (p=0.005). All patients were divided into a high-adiponectin group (>or=6.46 microg/mL) and a low-adiponectin group (<6.46 microg/mL). The incidence of MACE was significantly reduced in the high-adiponectin group (p=0.021). In multivariate Cox regression analysis that included adiponectin, classical risk factors, and medications, adiponectin was an independent predictor of MACE in patients after AMI (HR, 0.821; 95% CI, 0.691 to 0.974; p=0.024). CONCLUSIONS: The results indicate a potential association between plasma adiponectin levels and future cardiovascular events in patients after AMI. Moreover, plasma adiponectin concentrations appear to play a pivotal role in atherothrombosis and cardioprotection.

Plasma heparin cofactor II activity is an independent predictor of future cardiovascular events in patients after acute myocardial infarction.

OBJECTIVES: This study tested the hypothesis that plasma heparin cofactor II (HCII) activity independently predicts cardiovascular events in patients after acute myocardial infarction (AMI) and attempted to elucidate the role of HCII in atherothrombosis. BACKGROUND: HCII inhibits thrombin activity by binding to dermatan sulfate and has been shown to be a novel and independent risk factor for atherosclerosis. However, there is limited data on the relation between plasma levels of HCII after AMI and future cardiovascular events. METHODS: A total of 110 consecutive patients (aged 63+/-11 years) with AMI were followed up for 42+/-12 months. Plasma HCII activity was determined from blood samples collected immediately after hospitalization. The primary end point was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization because of unstable angina, nonfatal MI, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting, ischemic stroke, and cardiovascular death. RESULTS: All patients were divided into three groups: a high-HCII group (>122%, n=35), a normal-HCII group (>98% and