Elevated uric acid is related to the no-/slow-reflow phenomenon in STEMI undergoing primary PCI.

BACKGROUND: No-/slow-reflow phenomenon (NRP) is a severe complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). This study aimed to explore the relationship between elevated serum uric acid (SUA) and NRP in patients with STEMI undergoing pPCI, focusing on inflammation and angiographic findings. METHODS: A total of 610 patients who received pPCI for STEMI were retrospectively enrolled. Patients were divided into a hyperuricaemia group and a non-hyperuricaemia group according to SUA levels. Clinical information and angiographic indicators were compared between the two groups. Thrombolysis in myocardial infarction (TIMI) flow and TIMI myocardial perfusion grade (TMPG) <3 after stent implantation were defined as TIMI-NRP and TMPG-NRP, respectively. A logistic model was used to analyse the relationship between hyperuricaemia and NRP. RESULTS: The hyperuricaemia group had a higher incidence of TIMI-NRP (24.9% vs 14.0%, p < .001) and TMPG-NRP (33.0% vs 24.9%, p = .03), higher levels of C-reactive protein (7.2 vs 4.1 mg/L, p < .001) and worse left ventricular ejection fraction (51.5% vs 54.0%, p = .002) than the non-hyperuricaemia group. As for angiographic findings, there was no significant difference between the two groups in terms of lesion characteristics measured by quantitative coronary angiography. After multivariable adjustment, elevated SUA was significantly associated with TIMI-NRP (odds ratio: 1.94, 95% confidence interval: 1.24-3.01, p = .003). Subgroup analysis showed that the effect of hyperuricaemia in TIMI-NRP was more pronounced in patients with delayed perfusion as well as in patients with diabetes mellitus. CONCLUSIONS: Elevated SUA is associated with severe inflammation and has higher incidence of TIMI-NRP in patients with STEMI undergoing pPCI, especially in those with delayed perfusion or diabetes mellitus.

Lipoprotein (a) as a residual risk factor for atherosclerotic renal artery stenosis in hypertensive patients: a hospital-based cross-sectional study.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-c) has been proven to be a risk factor for atherosclerotic cardiovascular disease (CVD), while lipoprotein (a) (Lp(a)) is a residual risk factor for CVD, even though LDL-c is well controlled by statin use. Importantly, the role of Lp(a) in atherosclerotic renal artery stenosis (ARAS) is still unknown. METHODS: For this hospital-based cross-sectional study, patients who simultaneously underwent coronary and renal angiography were examined. ARAS was defined as a 50% reduction in the cross-sectional (two-dimensional plane) area of the renal artery. Data were collected and compared between ARAS and non-ARAS groups, including clinical history and metabolite profiles. Univariate analysis, three tertile LDL-c-based stratified analysis, and multivariate-adjusted logistic analysis were conducted, revealing a correlation between Lp(a) and ARAS. RESULTS: A total of 170 hypertensive patients were included in this study, 85 with ARAS and 85 with non-RAS. Baseline information indicated comparability between the two groups. In the univariate and multivariate analysis, common risk factors for atherosclerosis were not significantly different. Stratified analysis of LDL-c revealed a significant increase in the incidence of ARAS in patients who had high Lp(a) concentrations at low LDL-c levels (odds ratio (OR): 4.77, 95% confidence interval (CI): 1.04-21.79, P = 0.044). Further logistic analysis with adjusted covariates also confirmed the result, indicating that high Lp(a) levels were independently associated with ARAS (adjusted OR (aOR): 6.14, 95%CI: 1.03-36.47, P = 0.046). This relationship increased with increasing Lp(a) concentration based on a curve fitting graph. These results were not present in the low and intermediate LDL-c-level groups. CONCLUSION: In hypertensive patients who present low LDL-c, high Lp(a) was significantly associated with atherosclerotic renal artery stenosis and thus is a residual risk factor.

Increased serum level of Lp-PLA2 is independently associated with the severity of coronary artery diseases: a cross-sectional study of Chinese population.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays complex and adverse roles on atherosclerosis. Current study was to investigate whether increased plasma Lp-PLA2 level is independently associated with the severity of coronary artery diseases (CAD). METHODS: Totally 781 participants were enrolled and performed coronary angiography (CAG) to figure out the number of coronary artery stenosis. According to clinical presentation, electrocardiography, cardiac biomarker, and CAG result, participants were divided into control (excluded CAD), stable angina (SA), unstable angina (UA) and acute myocardial infarction (AMI) groups. Baseline characteristics were recorded. Statistical analyses were performed to evaluate the relationship between Lp-PLA2 level and CAD severity. RESULTS: Plasma levels of Lp-PLA2 in control, SA, UA and AMI groups were 7.38(3.33-9.26) µg/L, 5.94(2.89-8.55) µg/L, 8.56(5.34-11.95) µg/L and 8.68(5.56-13.27) µg/L respectively (P < 0.001). After adjusted for age, gender, smoking, diabetes mellitus, hypertension, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apoprotein A (apoA) and statins, Lp-PLA2 level was still independently associated with CAD severity, with odd ratio (OR) of 1.055 (AMI group versus control group, 95% confidence interval (CI) 1.021-1.090, P < 0.05). Additionally, the relationship between Lp-PLA2 level and the number of stenosis coronary artery was also assessed. Lp-PLA2 levels in control, single-vessel, and multiple-vessels stenosis groups were 7.38(3.33-9.26) µg/L, 7.80 (4.05-10.76) µg/L and 8.29(5.18-11.76) µg/L respectively (P for trend < 0.001). After adjusted for age, gender, smoking, diabetes mellitus, hypertension, LDL-C and HDL-C, apoA and statins, Lp-PLA2 level remained independently associated with the number of coronary artery stenosis, with OR of 1.053 (multiple-vessels stenosis group versus control group, 95% CI 1.025-1.069, P < 0.05). CONCLUSION: Increased Lp-PLA2 level is independently associated with CAD severity, and Lp-PLA2 level may be used to discriminate those who are at increased risk of cardiovascular events.

Glycated hemoglobin level is significantly associated with the severity of coronary artery disease in non-diabetic adults.

BACKGROUND: To investigate relationship between glycated hemoglobin (HbA1c) level and coronary artery disease (CAD) severity. METHODS: Observational study was conducted and 573 participants were enrolled and baseline characteristics were collected. Clinical presentations in terms of stable angina, unstable angina or acute myocardial infarction were diagnosed. All participants were performed coronary angiography to figure out the numbers of coronary artery stenosis in terms of none-stenosis (< 50% stenosis), single or multiple vessels stenoses (≥ 50% stenosis). All participants were divided into subgroups according to two categories in terms of severity of clinical presentation (stable angina, unstable angina, or acute myocardial infarction) and the number of coronary artery stenosis (none, single, and multiple vessels). Primary endpoint was to evaluate relationship between baseline HbA1c value and CAD severity. RESULTS: Consistent to previous studies, participants with CAD had more risk factors such as elderly, smoking, low HDL-C and high CRP levels. Notably, HbA1c level was more prominent in CAD group than that without CAD. As compared to stable angina subgroup, HbA1c levels were gradually increased in unstable angina and acute myocardial infarction groups. Similar trend was identified in another category in terms of higher HbA1c level corresponding to more vessels stenoses. Multivariate regression analyses showed that after adjusted for traditional risk factors as well as fasting blood glucose, HbA1c remained strongly associated with the severity of CAD. Nonetheless, there was no significant association when CRP was accounted for. CONCLUSION: HbA1c may be a useful indicator for CAD risk evaluation in non-diabetic adults.

Association between the insufficient improvement of the quantitative flow ratio and worsening outcomes in ST-segment elevated myocardial infarction: a multicentre prospective cohort study.

Background: Improved coronary physiological function after percutaneous coronary intervention (PCI) has been shown to improve prognosis in stable ischaemic heart disease, but has not yet been explored in ST-segment elevated myocardial infarction (STEMI). The study sought to determine whether an improvement in the quantitative flow ratio (QFR) could improve the prognosis of STEMI patients undergoing primary PCI. Methods: Patients diagnosed with STEMI who were receiving primary PCI were recruited for the study. Those with thrombolysis in myocardial infarction (TIMI) flow <2 after wiring were excluded. The ΔQFR was calculated using the following formula: ΔQFR = post-PCI QFR - pre-stent QFR. The primary endpoint was the composite event, including recurrent myocardial infarction (MI) and acute heart failure (AHF). Results: In total, 515 STEMI patients with a median follow-up of 364 days were enrolled in the study. Based on the cut-off value from the receiver operator characteristic (ROC) curve, the patients were divided into the following two groups: the lower ΔQFR group (≤0.25, N=332); and the normal ΔQFR group (>0.25, N=183). Patients with a lower ΔQFR had a relatively higher rate of MI/AHF (10.5% vs. 4.4%, P=0.019) and AHF (7.2% vs. 2.7%, P=0.044). A lower ΔQFR was significantly associated with a higher incidence of MI/AHF [hazard ratio (HR) =2.962, 95% confidence interval (CI): 1.358-6.459, P=0.006, respectively] after adjusting for potential confounders. Pre-stent angiographic microvascular resistance [odds ratio (OR) =1.027, 95% CI: 1.022-1.033, P<0.001] and the stent-to-vessel diameter ratio <1.13 (OR =1.766, 95% CI: 1.027-3.071, P=0.04) were independent predictors of a lower ΔQFR. Conclusions: An insufficient improvement in the QFR contributes to worsening outcomes and might be a useful tool for risk stratification in STEMI.

Microvascular and Prognostic Effect in Lesions With Different Stent Expansion During Primary PCI for STEMI: Insights From Coronary Physiology and Intravascular Ultrasound.

Background: While coronary stent implantation in ST-elevation myocardial infarction (STEMI) can mechanically revascularize culprit epicardial vessels, it might also cause distal embolization. The relationship between geometrical and functional results of stent expansion during the primary percutaneous coronary intervention (pPCI) is unclear. Objective: We sought to determine the optimal stent expansion strategy in pPCI using novel angiography-based approaches including angiography-derived quantitative flow ratio (QFR)/microcirculatory resistance (MR) and intravascular ultrasound (IVUS). Methods: Post-hoc analysis was performed in patients with acute STEMI and high thrombus burden from our prior multicenter, prospective cohort study (ChiCTR1800019923). Patients aged 18 years or older with STEMI were eligible. IVUS imaging, QFR, and MR were performed during pPCI, while stent expansion was quantified on IVUS images. The patients were divided into three subgroups depending on the degree of stent expansion as follows: overexpansion (>100%), optimal expansion (80%-100%), and underexpansion (<80%). The patients were followed up for 12 months after PCI. The primary endpoint included sudden cardiac death, myocardial infarction, stroke, unexpected hospitalization or unplanned revascularization, and all-cause death. Results: A total of 87 patients were enrolled. The average stent expansion degree was 82% (in all patients), 117% (in overexpansion group), 88% (in optimal expansion), and 75% (in under-expansion). QFR, MR, and flow speed increased in all groups after stenting. The overall stent expansion did not affect the final QFR (p = 0.08) or MR (p = 0.09), but it reduced the final flow speed (-0.14 cm/s per 1%, p = 0.02). Under- and overexpansion did not affect final QFR (p = 0.17), MR (p = 0.16), and flow speed (p = 0.10). Multivariable Cox analysis showed that stent expansion was not the risk factor for MACE (hazard ratio, HR = 0.97, p = 0.13); however, stent expansion reduced the risk of MACE (HR = 0.95, p = 0.03) after excluding overexpansion patients. Overexpansion was an independent risk factor for no-reflow (HR = 1.27, p = 0.02) and MACE (HR = 1.45, p = 0.007). Subgroup analysis shows that mild underexpansion of 70%-80% was not a risk factor for MACE (HR = 1.11, p = 0.08) and no-reflow (HR = 1.4, p = 0.08); however, stent expansion <70% increased the risk of MACE (HR = 1.36, p = 0.04). Conclusions: Stent expansion does not affect final QFR and MR, but it reduces flow speed in STEMI. Appropriate stent underexpansion of 70-80% does not seem to be associated with short-term prognosis, so it may be tolerable as noninferior compared with optimal expansion. Meanwhile, overexpansion and underexpansion of <70% should be avoided due to the independent risk of MACEs and no-reflow events.

Association of systolic blood pressure and pulse pressure with microalbuminuria in treatment-naïve hypertensive patients.

INTRODUCTION: To investigate the association between blood pressure components and microalbuminuria (MAU) in newly diagnosed and treatment-naïve hypertensive patients. MATERIAL AND METHODS: A total of 1858 newly diagnosed and treatment-naïve hypertensive patients were enrolled. Based on 24 h urine albumin concentration, all patients were divided into MAU and normo-albuminuria groups. The associations between blood pressure (BP) components, namely systolic/diastolic BP (SBP/DBP) and pulse pressure (PP) and MAU, as well as the sensitivity and specificity of each BP component in predicting MAU, were evaluated. RESULTS: Compared to the normo-albuminuria group, patients in the MAU group were older and had significantly higher SBP and PP (p < 0.05). Serum levels of fasting blood glucose, total protein and creatinine were significantly higher in the MAU group (p < 0.05). 24-hour urine albumin excretion was significantly higher in the MAU group than the normo-albuminuria group (182.5 ±156.5 mg vs. 17.6 ±7.1 mg, p < 0.001). Logistic regression analyses revealed that SBP and PP were significantly associated with MAU, with an odds ratio (OR) of 1.010 (95% confidence interval (CI): 1.005-1.016, p < 0.001) in SBP and OR of 1.009 (95% CI: 1.003-1.015, p = 0.003) in PP. The receiver operating characteristic curve showed that the area under the curve for SBP to predict MAU was 0.541 ±0.013, and PP was 0.536 ±0.013. The difference in predicting MAU by SBP or PP was non-significant. CONCLUSIONS: In newly diagnosed and treatment-naïve hypertensive patients, increased SBP and PP were independently associated with MAU.

Ambulatory blood pressure is superior to clinic blood pressure in relation to ischemic stroke in both diabetic and nondiabetic patients.

AIM: The pressure study was carried out to evaluate the hypotheses that ambulatory blood pressure (ABP) is superior to clinic blood pressure for ischemic stroke and that ABP is important to refine risk stratification. PATIENTS AND METHODS: A total of 889 hospitalized patients who had undergone ABP monitoring were enrolled. Baseline data were compared between diabetic and nondiabetic subgroups. Area under receiver operating characteristics curve for each blood pressure (BP) component with ischemic stroke was evaluated. Each BP component was entered separately into a logistic regression basic model. The predictive performance of each model was compared using the Akaike Information Criterion and Schwartz's Bayesian Information Criterion, and a lower value indicated better performance. RESULTS: The mean age of the patients was 58 years, 56.2% were men, and 63.0, 30.6, and 27.7% had hypertension, diabetes, and ischemic stroke, respectively. The diabetic subgroup had significantly higher systolic blood pressure (SBP) profiles than the nondiabetic subgroup. Compared with patients without ischemic stroke, those with ischemic stroke had significantly higher 24-h SBP and daytime-SBP, whereas no differences in clinic-SBP were observed in both subgroups. Compared with clinic-SBP, the area under receiver operating characteristics curve values for predicting ischemic stroke were significantly higher for 24-h SBP and daytime-SBP in both subgroups. The results of predictive performance showed that logistic regression models including 24-h SBP and daytime-SBP had lower Akaike Information Criterion and Schwartz's Bayesian Information Criterion values than that with clinic-SBP in both subgroups. However, no significant improvement in predictive performance was observed when the BP variable was added to the basic model. CONCLUSION: Our study showed that in a hospital setting, 24-h SBP and daytime-SBP were superior to clinic-SBP in relation to ischemic stroke.

Association of lipoprotein(a) with long-term mortality following coronary angiography or percutaneous coronary intervention.

BACKGROUND: There is no consistent evidence to suggest the association of plasma lipoprotein(a) (Lp[a]) with long-term mortality in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). HYPOTHESIS: Level of Lp(a) is associated with long-term mortality following CAG or PCI. METHODS: We enrolled 1684 patients with plasma Lp(a) data undergoing CAG or PCI between April 2009 and December 2013. The patients were divided into 2 groups: a low-Lp(a) group (Lp[a] <16.0 mg/dL; n = 842) and a high-Lp(a) group (Lp[a] ≥16.0 mg/dL; n = 842). RESULTS: In-hospital mortality was not significantly different between the high and low Lp(a) groups (0.8% vs 0.5%, respectively; P = 0.364). During the median follow-up period of 1.95 years, the high-Lp(a) group had a higher long-term mortality than did the low-Lp(a) group (5.8% vs 2.5%, respectively; P = 0.003). After adjustment of confounders, multivariate Cox regression analysis revealed that a higher Lp(a) level was an independent predictor of long-term mortality (hazard ratio: 1.96, 95% confidence interval: 1.07-3.59, P = 0.029). CONCLUSIONS: Our data suggested that an elevated Lp(a) level was significantly associated with long-term mortality following CAG or PCI. However, additional larger multicenter studies will be required to investigate the predictive value of Lp(a) levels and evaluate the benefit of controlling Lp(a) levels for patients undergoing CAG or PCI.

Associations of systolic and diastolic blood pressure night-to-day ratios with atherosclerotic cardiovascular diseases.

Our objective was to evaluate the associations of the systolic and diastolic blood pressure night-to-day ratios (SBP-NDR and DBP-NDR) with composite atherosclerotic cardiovascular diseases (ASCVDs) comprising coronary heart disease (CHD) and ischemic stroke (IS) cases, respectively. The clinical conditions associated with SBP-NDR and DBP-NDR were also evaluated. A total of 401 patients who underwent 24-h ambulatory BP monitoring were enrolled. In general, the mean age was 59.7±14.7 years and male subjects accounted for 59.1% of the study subjects. Regarding the ASCVD risk factors, 17.0% of the study subjects smoked, 5.2% abused alcohol, 2.0% had a family history of ASCVD, 23.3% had diabetes and 96.0% had dyslipidemia. Fifty (12.5%) and 128 (31.9%) study subjects had a previous diagnosis of CHD and IS, respectively. Dipper and non-dipper pattern-specific differences in clinical characteristics between the SBP-NDR and DBP-NDR categories were observed. The multiple linear regression analysis showed that advanced age, smoking, CHD and IS were positively associated with SBP-NDR and statins were inversely associated with SBP-NDR; only IS was positively associated with DBP-NDR. The logistic regression analysis showed that after adjusting for the covariates of age, smoking, alcohol abuse, diabetes, hypertension, dyslipidemia, and SBP and DBP at admission, only DBP-NDR remained significantly associated with composite ASCVD, with an odds ratio of 1.029 (95% confidence interval 1.002-1.056, P=0.038). There were significant differences in the associations of SBP-NDR and DBP-NDR with composite ASCVD. Clinical conditions independently associated with SBP-NDR and DBP-NDR were also somewhat different. In a specific population group, DBP-NDR may be superior to SBP-NDR with respect to screening for ASCVD.

Associations of high HDL cholesterol level with all-cause mortality in patients with heart failure complicating coronary heart disease.

The aim of the present study was to evaluate the association between HDL cholesterol level and all-cause mortality in patients with ejection fraction reduced heart failure (EFrHF) complicating coronary heart disease (CHD).A total of 323 patients were retrospectively recruited. Patients were divided into low and high HDL cholesterol groups. Between-group differences and associations between HDL cholesterol level and all-cause mortality were assessed.Patients in the high HDL cholesterol group had higher HDL cholesterol level and other lipid components (P <0.05 for all comparison). Lower levels of alanine aminotransferase (ALT), high-sensitivity C-reactive protein (Hs-CRP), and higher albumin (ALB) level were observed in the high HDL cholesterol group (P <0.05 for all comparison). Although left ventricular ejection fraction (LVEF) were comparable (28.8 ±â€Š4.5% vs 28.4 ±â€Š4.6%, P = 0.358), mean mortality rate in the high HDL cholesterol group was significantly lower (43.5% vs 59.1%, P = 0.007). HDL cholesterol level was positively correlated with ALB level, while inversely correlated with ALT, Hs-CRP, and NYHA classification. Logistic regression analysis revealed that after extensively adjusted for confounding variates, HDL cholesterol level remained significantly associated with all-cause mortality although the magnitude of association was gradually attenuated with odds ratio of 0.007 (95% confidence interval 0.001-0.327, P = 0.012).Higher HDL cholesterol level is associated with better survival in patients with EFrHF complicating CHD, and future studies are necessary to demonstrate whether increasing HDL cholesterol level will confer survival benefit in these populations of patients.

Arg97² insulin receptor substrate-1 inhibits endothelial nitric oxide synthase expression in human endothelial cells by upregulating microRNA-155.

The dysregulation of nitric oxide (NO) synthesis attributable to the abnormal expression/activity of endothelial NO synthase (eNOS) is considered to be a major characteristic of insulin-resistant states, as well as an essential contributor to the pathogenesis of cardiovascular diseases. The Arg972 insulin receptor substrate-1 (IRS-1) is associated with insulin resistance. In the present study, we investigated the association between Arg972 IRS-1 and eNOS expression/activity in human subjects and in primary cultures of human endothelial cells. Data from 832 human subjects revealed that heterozygous and homozygous Arg972 IRS-1 carriers had significantly lower levels of plasma eNOS and nitrite/nitrate than the homozygous wild-type (WT) IRS-1 carriers. Human umbilical vein endothelial cells (HUVECs) established from delivering mothers expressing heterozygous Arg972 IRS-1 had significantly lower eNOS expression/activity and higher miR-155 levels than those expressing WT homozygous IRS-1. The overexpression of IRS-1 and Arg972 IRS-1 in the HUVECs, respectively, decreased and increased the miR-155 expression level. In addition, the overexpression of IRS-1 in the HUVECs significantly increased eNOS expression; this effect was reversed by transfection with mature miR-155 mimic or treatment with the selective phosphatidylinositol-3 kinase (PI3K) inhibitor, BKM120. On the other hand, the overexpression of Arg972 IRS-1 markedly decreased eNOS expression and this effect was reversed by transfection with antagomir-155. On the whole, our in vivo data demonstrate that Arg972 IRS-1 is associated with decreased plasma eNOS and nitrite/nitrate levels in human subjects. Our in vitro data demonstrate that Arg972 IRS-1 inhibits eNOS expression in human endothelial cells by upregulating miR-155 expression through the impairment of PI3K signaling. The present study provides new insight into the pathophysiological role of Arg972 IRS-1 in cardiovascular diseases.