Inflammation modifies the platelet reactivity among thrombocytopenia patients undergoing percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) patients combined with thrombocytopenia (TP) are usually considered to be at low ischemic risk, receiving less proper antiplatelet therapy. However, recent studies reported a paradoxical phenomenon that PCI patients with TP were prone to experience thrombotic events, while the mechanisms and future treatment remain unclear. We aim to investigate whether inflammation modifies platelet reactivity among these patients. Consecutive 10 724 patients undergoing PCI in Fuwai Hospital were enrolled throughout 2013. High-sensitivity C-reactive protein (hsCRP) ≥2 mg/L was considered inflammatory status. TP was defined as platelet count <150×109/L. High on-treatment platelet reactivity (HTPR) was defined as adenosine diphosphate-induced platelet maximum amplitude of thromboelastogram >47mm. Among 6617 patients finally included, 879 (13.3%) presented with TP. Multivariate logistic regression demonstrated that patients with TP were associated with a lower risk of HTPR (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.53-0.76) than those without TP in the overall cohort. In further analysis, among hsCRP <2 mg/L group, patients with TP exhibited a decreased risk of HTPR (OR 0.53, 95% CI 0.41-0.68); however, in hsCRP ≥2mg/L group, TP patients had a similar risk of HTPR as those without TP (OR 0.83, 95% CI 0.63-1.08). Additionally, these results remain consistent across subgroups, including patients presenting with acute coronary syndrome and chronic coronary syndrome. Inflammation modified the platelet reactivity of PCI patients with TP, providing new insights into the mechanisms of the increased thrombotic risk. Future management for this special population should pay more attention to inflammation status and timely adjustment of antiplatelet therapy in TP patients with inflammation.

What is the context? Recent studies reported a paradoxical phenomenon that percutaneous coronary intervention (PCI) patients with thrombocytopenia (TP) were prone to experience thrombotic events. The potential mechanisms underlying the increased thrombotic risk and how to manage antiplatelet therapy in PCI patients with TP remain unclear.Growing attention has been paid to immunothrombosis. Inflammation is closely associated with high-on treatment platelet reactivity (HTPR) and thrombotic risk.HTPR is an independent risk factor of thrombosis and can provide information for guiding antiplatelet therapy.What is new? This prospective cohort study enrolled 10 724 patients undergoing PCI in Fuwai Hospital (National Center for Cardiovascular Diseases, Beijing, China), with HTPR risk being the study endpoint of interest.We first reported that inflammation significantly modified the platelet reactivity of PCI patients with TP.When hsCRP level <2 mg/L, PCI patients with TP had a decreased risk of HTPR. However, when hsCRP ≥2 mg/L, TP patients had similar HTPR risk as those without TP.HsCRP levels could modify the relationship between TP and HTPR risks both in patients with acute coronary syndrome and chronic coronary syndrome.What is the impact? These results provide insights into potential mechanisms of the increased thrombotic risk in PCI patients with TP. Specifically, inflammation might be involved in the thrombotic risk of PCI patients with TP by modifying the platelet reactivity.As for future management, personalized antiplatelet therapy should be administrated to TP patients with inflammation status.

Renal function alters the association of lipoprotein(a) with cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a prospective cohort study.

Background and hypothesis: Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60-90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)]. Results: Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without. Conclusion: The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.

Baseline high-sensitivity C-reactive protein and glycosylated hemoglobinA1c predict adverse outcomes in patients with chronic coronary syndromes undergoing percutaneous coronary intervention.

Introduction: This study explored the ability of high-sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin A1c (HbA1c) to predict adverse cardiac and cerebrovascular outcomes in patients with chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Methods: In total, 4083 consecutive patients with CCS undergoing PCI were investigated throughout 2013 at a single center. The primary endpoint was all-cause death at the 5-year follow-up. Hs-CRP and HbA1c data were collected on admission. Results: The highest quartile of hs-CRP had a significantly increased the risk of all-cause death, with an adjusted HR of 1.747 (95 % CI 1.066-2.863), while, there was no difference in all-cause death among the groups of HbA1c after adjustment, with an adjusted HR of 1.383 (95 % CI 0.716-2.674). The highest quartiles for hs-CRP and HbA1c in the study population had a significantly increased risk of major adverse cardiac and cerebrovascular events (MACCE), with an adjusted hazard ratios (HR) of 1.263 (95 % confidence intervals [CI] 1.032-1.545) for hs-CRP and an adjusted HR of 1.417 (95 % CI 1.091-1.840) for HbA1c. Remarkably, the incidence of all-cause death and that of MACCE were significantly increased when both hs-CRP and HbA1c were elevated (HR 1.971, 95 % CI 1.079-3.601, P = 0.027 and HR 1.560, 95 % CI 1.191-2.042), P = 0.001, respectively). Addition of hs-CRP and HbA1c to conventional risk factors significantly improved prediction of the risk of all cause death (net reclassification index 0.492, P < 0.001; integrated discrimination improvement 0.007, P = 0.011) and MACCE (net reclassification index 0.160, P < 0.001; integrated discrimination improvement 0.006, P < 0.001). Conclusions: Hs-CRP and HbA1c can serve as independent predictors of MACCE in patients with CCS undergoing PCI. Furthermore, a combination of hs-CRP and HbA1c could predict all cause death and MACCE better than each component individually.

Mild Renal Function Impairment and Long-Term Outcomes in Patients with Three-Vessel Coronary Artery Disease: A Cohort Study.

INTRODUCTION: Limited data are available on the long-term impact of mild renal dysfunction (estimated glomerular filtration rate [eGFR] 60-89 mL/min/1.73 m2) in patients with three-vessel coronary disease (3VD). METHODS: A total of 5,272 patients with 3VD undergoing revascularization were included and were categorized into 3 groups: normal renal function (eGFR ≥90 mL/min/1.73 m2, n = 2,352), mild renal dysfunction (eGFR 60-89, n = 2,501), and moderate renal dysfunction (eGFR 30-59, n = 419). Primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke. RESULTS: During the median 7.6-year follow-up period, 555 (10.5%) deaths occurred. After multivariable adjustment, patients with mild and moderate renal dysfunction had significantly higher risks of all-cause death (adjusted hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.07-1.70; adjusted HR: 2.06, 95% CI: 1.53-2.78, respectively) compared with patients with normal renal function. Patients after coronary artery bypass grafting (CABG) had a lower rate of all-cause death and MACCE than those undergoing percutaneous coronary intervention (PCI) in the normal and mild renal dysfunction group but not in the moderate renal dysfunction group. Results were similar after propensity score matching. CONCLUSIONS: In patients with 3VD, even mild renal impairment was significantly associated with a higher risk of all-cause death. The superiority of CABG over PCI diminished in those with moderate renal dysfunction. Our study alerts clinicians to the early screening of mild renal impairment in patients with 3VD and provides real-world evidence on the optimal revascularization strategy in patients with renal impairment.

Prolonging dual antiplatelet therapy improves the long-term prognosis in patients with diabetes mellitus undergoing complex percutaneous coronary intervention.

OBJECTIVE: To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI). METHODS: A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581). RESULTS: Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371). CONCLUSIONS: For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

Association Between Free Fatty Acids and Cardiometabolic Risk in Coronary Artery Disease: Results From the PROMISE Study.

CONTEXT: The association between free fatty acids (FFAs) and unfavorable clinical outcomes has been reported in the general population. However, evidence in the secondary prevention population is relatively scarce. OBJECTIVE: We aimed to examine the relationship between FFA and cardiovascular risk in patients with coronary artery disease (CAD). METHODS: This study was based on a multicenter cohort of patients with CAD enrolled from January 2015 to May 2019. The primary outcome was all-cause death. Secondary outcomes included cardiac death and major adverse cardiovascular events (MACE), a composite of death, myocardial infarction, and unplanned revascularization. RESULTS: During a follow-up of 2 years, there were 468 (3.0%) all-cause deaths, 335 (2.1%) cardiac deaths, and 1279 (8.1%) MACE. Elevated FFA levels were independently associated with increased risks of all-cause death, cardiac death, and MACE (all P < .05). Moreover, When FFA were combined with an original model derived from the Cox regression, there were significant improvements in discrimination and reclassification for prediction of all-cause death (net reclassification improvement [NRI] 0.245, P < .001; integrated discrimination improvement [IDI] 0.004, P = .004), cardiac death (NRI 0.269, P < .001; IDI 0.003, P = .006), and MACE (NRI 0.268, P < .001; IDI 0.004, P < .001). Notably, when stratified by age, we found that the association between FFA with MACE risk appeared to be stronger in patients aged ≥60 years compared with those aged <60 years. CONCLUSION: In patients with CAD, FFAs are associated with all-cause death, cardiac death, and MACE. Combined evaluation of FFAs with other traditional risk factors could help identify high-risk individuals who may require closer monitoring and aggressive treatment.

Inverse Association of Lipoprotein(a) on Long-Term Bleeding Risk in Patients with Coronary Heart Disease: Insight from a Multicenter Cohort in Asia.

BACKGROUND: Lipoprotein(a), or Lp(a), has been recognized as a strong risk factor for atherosclerotic cardiovascular disease. However, the relationship between Lp(a) and bleeding remains indistinct, especially in the secondary prevention population of coronary artery disease (CAD). This investigation aimed to evaluate the association of Lp(a) with long-term bleeding among patients with CAD. METHODS: Based on a prospective multicenter cohort of patients with CAD consecutively enrolled from January 2015 to May 2019 in China, the current analysis included 16,150 participants. Thus, according to Lp(a) quintiles, all subjects were divided into five groups. The primary endpoint was bleeding at 2-year follow-up, and the secondary endpoint was major bleeding at 2-year follow-up. RESULTS: A total of 2,747 (17.0%) bleeding and 525 (3.3%) major bleeding were recorded during a median follow-up of 2.0 years. Kaplan-Meier survival analysis showed the highest bleeding incidence in Lp(a) quintile 1, compared with patients in Lp(a) quintiles 2 to 5 (p < 0.001), while the incidence of major bleeding seemed similar between the two groups. Moreover, restricted cubic spline analysis suggested that there was an L-shaped association between Lp(a) and 2-year bleeding after adjustment for potential confounding factors, whereas there was no significant association between Lp(a) and 2-year major bleeding. CONCLUSION: There was an inverse and L-shaped association of Lp(a) with bleeding at 2-year follow-up in patients with CAD. More attention and effort should be made to increase the clinician awareness of Lp(a)'s role, as a novel marker for bleeding risk to better guide shared-decision making in clinical practice.

Five-Year Prognostic Value of DAPT Score in Older Patients undergoing Percutaneous Coronary Intervention: A Large-Sample Study in the Real World.

AIM: The dual-antiplatelet therapy (DAPT) score is recommended for predicting the risk of ischemia and bleeding for patients undergoing percutaneous coronary intervention (PCI). This study aimed to investigate the long-term prognostic value of the DAPT score in older PCI patients. METHODS: This study enrolled 10,724 consecutive patients who underwent PCI from January 2013 to December 2013 in Fu Wai hospital, among whom 2,981 (27.8%) were aged ≥ 65 years. The ischemic endpoint was major adverse cardiovascular and cerebrovascular events (MACCE, including myocardial infarction, all-cause death, and stroke). The bleeding endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. RESULTS: After a 5-year follow-up, 256 (12.0%) MACCEs and 53 (2.5%) BARC 2, 3, or 5 bleeding occurred. The patients were divided into two groups according to the DAPT score: the low-score (＜2, n=1,646) and high-score (≥ 2, n=485) group. Multivariate Cox regression revealed that the risk of MACCE was similar between the two groups [hazard ratio (HR): 1.214, 95% confidence interval (CI): 0.916-1.609, P=0.178], whereas the risk of bleeding was significantly higher in the high-score group than in the low-score group (HR: 2.447, 95% CI: 1.407-4.257, P=0.002). The DAPT score did not show prognostic value in MACCE [area under the receiver operating characteristic curve (AUROC), 0.534; 95% CI: 0.496-0.572, P=0.079]; however, it demonstrated a certain prognostic value in BARC 2, 3, or 5 bleeding (AUROC, 0.646; 95% CI: 0.573-0.719, P＜0.001). CONCLUSION: This study suggested that in older PCI patients, the DAPT score did not show predictive value for MACCE; however, it had a certain predictive value for 5-year BARC 2, 3, or 5 bleeding.

For patients with prior coronary artery bypass grafting and recurrent myocardial ischemia, percutaneous coronary intervention on bypass graft or native coronary artery?-A 5-year follow-up cohort study.

BACKGROUND: Real-world data on target vessel of percutaneous coronary intervention (PCI) for patients with prior coronary artery bypass grafting (CABG) was still limited. HYPOTHESIS: A prospective cohort was examined to determine the frequency and outcomes of native coronary artery PCI versus bypass graft PCI in patients with prior CABG. METHODS: A large-sample observational study enrolled a total of 10 724 patients with coronary artery disease (CAD) underwent PCI in 2013. Two- and five-year clinical outcomes were compared between graft PCI group and native artery PCI group in patients with prior CABG. RESULTS: A total of 438 cases had CABG history in the total cohort. Graft PCI group and native artery PCI group accounted for 13.7% and 86.3%, respectively. The rates of 2- and 5-year all-cause death and major adverse cardiovascular and cerebral events (MACCE) showed no significant difference between the two groups (p > .05). Two-year revascularization risk was lower in graft PCI group than native artery PCI group (3.3% and 12.4%, p < .05), but 5-year myocardial infarction (MI) risk was higher (13.3% and 5.0%, p < .05). In multivariate COX regression models, graft PCI group was independently associated with lower 2-year revascularization risk (hazard ratio [HR]: 0.21; 95% confidence interval [CI]: 0.05-0.88; p = .033), but higher 5-year MI risk than native artery PCI group (HR: 2.61; 95% CI: 1.03-6.57; p = .042). Five-year all-cause death and MACCE risk showed no difference between the two groups in model. CONCLUSIONS: In patients with prior CABG underwent PCI, patients in graft PCI group had higher 5-year MI risk than patients received native artery PCI. But, 5-year mortality and MACCE was not significantly different between graft PCI group and native artery PCI group.

Association between cumulative lipoprotein(a) exposure and adverse cardiovascular outcomes in patients with prediabetes or diabetes.

Few studies have characterized long-term exposure to lipoprotein(a), or Lp(a), different glucose metabolism status, and their joint role in adverse cardiovascular outcomes risk. We consecutively enrolled 10,724 coronary heart disease (CAD) patients from January to December 2013 in Fuwai Hospital. Associations of cumulative lipoprotein(a) (CumLp(a)) exposure and different glucose metabolism status with major adverse cardiac and cerebrovascular events (MACCEs) risk were evaluated using Cox regression models. Compared with participants with normal glucose regulation and lower CumLp(a), those with type 2 diabetes and higher CumLp(a) were at the highest risk (HR 1.56, 95% CI 1.25-1.94), and those with prediabetes and higher CumLp(a) and those with type 2 diabetes and lower CumLp(a) were at relatively higher risk (HR 1.41, 95% CI 1.14-1.76; HR 1.37, 95% CI 1.11-1.69; respectively). Similar findings concerning the joint association were observed in sensitivity analyses. Cumulative lipoprotein(a) exposure and different glucose metabolism status were associated with 5-year MACCEs risk and may be useful concurrently for guiding secondary prevention therapy decisions.

Association of prognostic nutritional index level and diabetes status with the prognosis of coronary artery disease: a cohort study.

BACKGROUND: Malnutrition and inflammation are associated with adverse clinical outcomes in patients with diabetes or coronary artery disease (CAD). Prognostic nutritional index (PNI) is a comprehensive and simple indicator reflecting nutritional condition and immunological status. Whether there is a crosstalk between nutritional-immunological status and diabetes status for the impact on the prognosis of coronary artery disease (CAD) is unclear. METHODS: A total of 9429 consecutive CAD patients undergoing percutaneous coronary intervention were grouped by diabetes status [diabetes (DM) and non-diabetes (non-DM)] and preprocedural PNI level [high PNI (H-PNI) and low PNI (L-PNI)] categorized by the statistically optimal cut-off value of 48.49. The primary endpoint was all-cause death. RESULTS: During a median follow-up of 5.1 years (interquartile range: 5.0-5.1 years), 366 patients died. Compared with the non-DM/H-PNI group, the DM/L-PNI group yielded the highest risk of all-cause death (adjusted hazard ratio: 2.65, 95% confidence interval: 1.97-3.56, p < 0.001), followed by the non-DM/L-PNI group (adjusted hazard ratio: 1.44, 95% confidence interval: 1.05-1.98, p = 0.026), while DM/H-PNI was not associated with the risk of all-cause death. The negative effect of L-PNI on all-cause death was significantly stronger in diabetic patients than in nondiabetic patients (p for interaction = 0.037). Preprocedural PNI category significantly improved the Global Registry of Acute Coronary Events (GRACE) risk score for predicting all-cause death in patients with acute coronary syndrome, especially in those with diabetes. CONCLUSIONS: CAD patients with diabetes and L-PNI experienced the worst prognosis. The presence of diabetes amplifies the negative effect of L-PNI on all-cause death. Poor nutritional-immunological status outweighs diabetes in increasing the risk of all-cause death in CAD patients. Preprocedural PNI can serve as an assessment tool for nutritional and inflammatory risk and an independent prognostic factor in CAD patients, especially in those with diabetes.

Prolonged dual antiplatelet therapy after drug-eluting stent implantation improves long-term prognosis for acute coronary syndrome: five-year results from a large cohort study.

BACKGROUND: To investigate the most appropriate dual antiplatelet therapy (DAPT) duration for patients with acute coronary syndrome (ACS) after drug-eluting stent (DES) implantation in the largest cardiovascular center of China. METHODS: We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013. Patients were divided into four groups based on DAPT duration: standard DAPT group (11-13 months, n=1,568) and prolonged DAPT groups (13-18 months [n=308], 18-24 months [n=2,125], and >24 months [n=1,186]). Baseline characteristics and 5-year clinical outcomes were recorded. RESULTS: Baseline characteristics were similar across the four groups. Among the four groups, those with prolonged DAPT (18-24 months) had the lowest incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) (14.1% vs. 11.7% vs. 9.6% vs. 24.2%, P<0.001), all-cause death (4.8% vs. 3.9% vs. 2.1% vs. 2.6%, P<0.001), cardiac death (3.1% vs. 2.6% vs. 1.4% vs. 1.9%, P=0.004), and myocardial infarction (MI) (3.8% vs. 4.2% vs. 2.5% vs. 5.8%, P<0.001). The incidence of bleeding was not different among the four groups (9.9% vs. 9.4% vs. 11.0% vs. 9.4%, P=0.449). Cox multivariable analysis showed that prolonged DAPT (18-24 months) was an independent protective factor for MACCEs (hazard ratio [HR] 0.802, 95% confidence interval [CI] 0.729-0.882, P<0.001), all-cause death (HR 0.660, 95% CI 0.547-0.795, P<0.001), cardiac death (HR 0.663, 95% CI 0.526-0.835, P<0.001), MI (HR 0.796, 95% CI 0.662-0.957, P=0.015), and target vessel revascularization (HR 0.867, 95% CI 0.755-0.996, P=0.044). Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs. CONCLUSION: For patients with ACS after DES, appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.

Prognostic impact of lipoprotein(a) in patients undergoing percutaneous coronary intervention modified by low density lipoprotein cholesterol.

BACKGROUND: It is well established that lipoprotein(a)[Lp(a)] and low-density lipoprotein cholesterol (LDL-C) play a vital role in atherosclerosis. We investigated the prevalence and prognostic implications of increased Lp(a) in patients undergoing percutaneous coronary intervention (PCI) according to different LDL-C concentrations. METHODS: A total of 9,190 patients with CAD after PCI were consecutively enrolled in the study and subsequently divided into three groups according to baseline LDL-C at cut-off of 70 and 100 mg/dl. Increased Lp(a) was defined as > 30 mg/dl. The primary endpoint was all-cause death. Second endpoint was cardiac death. Cox regression, Kaplan-Meier and Sensitivity analysis were performed. RESULTS: During an average of 5.0 y of follow-up, 354 (3.9 %) patients experienced all-cause death with 213(2.3 %) of whom from cardiac death. Increased Lp(a) was present in 25.7 %, 34.2 %, and 40.6 % across the LDL-C < 70, 70-100 and≧100 mg/dl groups, respectively. After multivariate adjustment, Lp(a) elevation remained significantly associated with 5-y all-cause death (adjusted HR, 1.243; 95 % CI 1.001-1.544; p = 0.048) in the total cohort and only in those with LDL-C ≥ 100 mg/dl (adjusted HR, 1.642; 95 % CI 1.139-2.367; p = 0.008) when analyzed within each LDL-C category. Consistently with the results of associations between Lp(a) and cardiac death (adjusted HR, 1.534; 95 % CI 1.164-2.021; p = 0.002 for total cohort and adjusted HR, 2.404; 95 % CI 1.439-3.872; p < 0.001 for LDL-C ≥ 100 mg/dl). And this relationship holds after adjusting for LDL-Ccorr additionally. These findings are confirmed again in sensitivity analyses that excluded patients with Lp(a) concentrations in the top or the bottom 5 %. CONCLUSIONS: We confirmed that increased Lp(a) was associated with increased risk of long-term outcomes, and such an association was modified by the baseline LDL-C concentrations. Screening of high Lp(a) in individuals with elevations of LDL-C may enables risk stratification for poor prognosis.

Associations of lipid measures with total occlusion in patients with established coronary artery disease: a cross-sectional study.

BACKGROUND: Total occlusion is the most severe coronary lesion, indicating heavy ischemic burden and poor prognosis. The lipid profile is central to the development of atherosclerotic coronary lesions. Evidence on the optimal lipid measure to be monitored and managed in patients with established coronary artery disease (CAD) is inconclusive. METHODS: Total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), nonhigh-density lipoprotein cholesterol (non-HDL-c), lipoprotein (a) [Lp(a)], apolipoprotein B (apoB), non-HDL-c/HDL-c, and apoB/apoA-1 were analyzed in quintiles and as continuous variables. The associations of lipid measures with total occlusion were tested using logistic regression models, visualized with restricted cubic splines, and compared by areas under the receiver operating characteristic curves (AUROC). Discordance analysis was performed when apoB/apoA-1 and non-HDL-c/HDL-c were not in concordance. RESULTS: The prospective cohort study included 10,003 patients (mean age: 58 years; women: 22.96%), with 1879 patients having total occlusion. The risks of total occlusion significantly increased with quintiles of Lp(a), non-HDL-c/HDL-c, and apoB/apoA-1 (all p for trend < 0.001). TG had no association with total occlusion. Restricted cubic splines indicate significant positive linear relations between the two ratios and total occlusion [odds ratio per 1-standard deviation increase (95% confidence interval): non-HDL-c/HDL-c: 1.135 (1.095-1.176), p < 0.001; apoB/apoA-1: 2.590 (2.049-3.274), p < 0.001]. The AUROCs of apoB/apoA-1 and non-HDL-c/HDL-c were significantly greater than those of single lipid measures. Elevation in the apoB/apoA-1 tertile significantly increased the risk of total occlusion at a given non-HDL-c/HDL-c tertile but not vice versa. CONCLUSION: ApoB/apoA-1 confers better predictive power for total occlusion than non-HDL-c/HDL-c and single lipid measures in established CAD patients.

Association of high-sensitivity C-reactive protein and anemia with acute kidney injury in neonates.

Background: The association of high-sensitivity C-reactive protein (hsCRP) and anemia with postoperative acute kidney injury (AKI) in neonates with congenital heart disease (CHD) is still unclear. The purpose of this study was to examine whether anemia-associated AKI is modulated by hsCRP in neonates. Methods: This study included 253 consecutive neonatal patients who underwent CHD surgery in a national tertiary hospital. We investigated the association between postoperative AKI with baseline hsCRP, anemia, and their interaction by multivariable logistic regression analyses. Results: The incidence of AKI was 24.1% in the entire cohort. After being adjusted for covariates, hsCRP level was negatively correlated with AKI (P < 0.01 for 1 mg/L threshold), whereas anemia emerged as an independent risk factor of AKI (P = 0.02). In addition, there was a significant interaction between anemia and hsCRP level (P = 0.01). In neonates with hsCRP < 1 mg/L, anemia was positively associated with AKI (P = 0.03). However, no significant association was found between anemia and AKI in the context of hsCRP ≥ 1 mg/L. Combination of anemia and hsCRP < 1 mg/L was independently correlated with the risk of AKI (P < 0.01), while concomitant anemia and hsCRP ≥ 1 mg/L or hsCRP < 1 mg/L combined with non-anemia was not. Conclusions: In neonates with CHD, the risk of anemia-associated AKI may be modulated by hsCRP level. Attention should be paid to neonates with preoperative anemia and baseline hsCRP < 1 mg/L to reduce the risk of postoperative AKI.

Lipoprotein(a), high-sensitivity C-reactive protein, and cardiovascular risk in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), the effects of high-sensitivity C-reactive protein (hsCRP) on Lipoprotein(a) (Lp(a))-associated cardiovascular risk remains unclear. This study aimed to investigate the independent and combined association of Lp(a) and hsCRP with cardiovascular events in this specific population. METHODS: A total of 10,424 patients with measurements of both Lp(a) and hsCRP were included in this prospective cohort study. Cox proportional hazards models and Kaplan-Meier analysis were performed to evaluate the relationship between Lp(a), hsCRP and adverse cardiac and cerebrovascular events (MACCE; all-cause death, myocardial infarction, ischemic stroke and revascularization). RESULTS: During 5 years of follow-up, 2140 (20.5%) MACCE occurred. Elevated Lp(a) and hsCRP levels were associated with increased risks of MACCE (p<0.05). Notably, there might be a significant interaction between Lp(a) and hsCRP (P for interaction = 0.019). In the setting of hsCRP≥2 mg/L, significant higher risk of MACCE was observed with Lp(a) 15-29.9 mg/dL (HR: 1.18; 95% CI 1.01-1.39) and Lp(a) ≥30 mg/dL (HR: 1.20; 95% CI 1.04-1.39), whereas such association was attenuated when hsCRP was <2 mg/L with Lp(a) 15-29.9 mg/dL (HR: 0.94; 95% CI 0.80-1.10) and Lp(a) ≥30 mg/dL (HR: 1.12; 95% CI 0.98-1.28). Moreover, when Lp(a) and hsCRP were combined for risk stratification, patients with dual elevation of these two biomarkers had a significant higher risk of MACCE compared with the reference group (Lp(a) < 15 mg/dL and hsCRp<2 mg/L) (p<0.05). CONCLUSIONS: In patients with CAD undergoing PCI, high Lp(a) level was associated with worse outcomes, and this association might be stronger in those with elevated hsCRP concomitantly. Evaluation of Lp(a) and hsCRP together may help identify high-risk individuals for targeted intervention in clinical utility.

Big Endothelin-1 and long-term all-cause death in patients with coronary artery disease and prediabetes or diabetes after percutaneous coronary intervention.

BACKGROUND AND AIMS: The present study aimed to examine the association between big endothelin-1 (big ET-1) and long-term all-cause death in patients with coronary artery disease (CAD) and different glucose metabolism status. METHODS AND RESULTS: We consecutively enrolled 8550 patients from January 2013 to December 2013. Patients were categorized according to both status of glucose metabolism status [Diabetes Mellitus (DM), Pre-Diabetes (Pre-DM), Normoglycemia (NG)] and big ET-1 levels. Primary endpoint was all-cause death. During a median of 5.1-year follow-up periods, 301 all-cause deaths occurred. Elevated big ET-1 was significantly associated with long-term all-cause death (adjusted HR: 2.230, 95%CI 1.629-3.051; p < 0.001). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause death compared with NG group (p < 0.05). When patients were categorized by both status of glucose metabolism and big ET-1 levels, high big ET-1 were associated with significantly higher risk of all-cause death in Pre-DM (adjusted HR: 2.442, 95% CI 1.039-5.740; p = 0.041) and DM (adjusted HR: 3.162, 95% CI 1.376-7.269; p = 0.007). The Kaplan-Meier curve indicated that DM patients with the highest big ET-1 levels were associated with the greatest risk of all-cause death (p < 0.05). CONCLUSIONS: The present data indicate that baseline big ET-1 levels were independently associated with the long-term all-cause death in DM and Pre-DM patients with CAD undergoing PCI, suggesting that big ET-1 may be a valuable marker in patients with impaired glucose metabolism.

Long-term effects of baseline on-treatment platelet reactivity in patients with acute coronary syndrome and thrombocytopenia undergoing percutaneous coronary intervention.

OBJECTIVE: To analyse the association between on-treatment platelet reactivity (TPR) and long-term outcomes of patients with acute coronary syndrome (ACS) and thrombocytopenia (TP) in the real world. METHODS: This prospective observational study enrolled patients with coronary artery disease (CAD) that underwent percutaneous coronary intervention (PCI). Patients with ACS and TP under dual antiplatelet therapy were selected for analysis. The 2- and 5-year clinical outcomes were evaluated among patients with high on-treatment platelet reactivity (HTPR), low on-treatment platelet reactivity (LTPR) and normal on-treatment platelet reactivity (NTPR), as tested by thromboelastogram at baseline. RESULTS: A total of 10 724 patients with CAD that underwent PCI were identified. Of these, 474 patients with ACS and TP met the inclusion criteria: 124 (26.2%) with HTPR, 163 (34.4%) with LTPR and 187 (39.5%) with NTPR. The 5-year rates of all-cause death, major adverse cardiovascular and cerebrovascular events, cardiac death, myocardial infarction, revascularization, stroke and bleeding were not significantly different among the three groups. Multivariate Cox regression analysis demonstrated that patients with HTPR were not independently associated with any of the 5-year endpoints compared with patients with NTPR. CONCLUSIONS: TPR at baseline was not independently associated with long-term outcomes in patients with ACS and TP that underwent PCI.

High fibrinogen-to-albumin ratio with type 2 diabetes mellitus is associated with poor prognosis in patients undergoing percutaneous coronary intervention: 5-year findings from a large cohort.

BACKGROUND: Inflammation plays a crucial role in coronary atherosclerosis progression, and growing evidence has demonstrated that the fibrinogen-to-albumin ratio (FAR), as a novel inflammation biomarker, is associated with the severity of coronary artery disease (CAD). However, the long-term risk of cardiovascular events remains indistinct in patients with different level of FAR and different glycemic metabolism status. This study was to assess 5-year clinical outcomes of diabetic and non-diabetic patients who underwent percutaneous coronary intervention (PCI) with different level of FAR. METHODS: We consecutively enrolled 10,724 patients with CAD hospitalized for PCI and followed up for the major adverse cardiac and cerebrovascular events (MACCE) covering all-cause mortality, cardiac mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, and unplanned coronary revascularization. FAR was computed using the following formula: Fibrinogen (g/L)/Albumin (g/L). According to the optimal cut-off value of FAR for MACCE prediction, patients were divided into higher level of FAR (FAR-H) and lower level of FAR (FAR-L) subgroups, and were further categorized into four groups as FAR-H with DM and non-DM, and FAR-L with DM and non-DM. RESULTS: 5298 patients (58.36 ± 10.36 years, 77.7% male) were ultimately enrolled in the present study. A total of 1099 (20.7%) MACCEs were documented during the 5-year follow-up. The optimal cut-off value of FAR was 0.0783 by the surv_cutpoint function. Compared to ones with FAR-H and DM, patients with FAR-L and non-DM, FAR-H and non-DM, FAR-L and DM had decreased risk of MACCEs [adjusted hazard ratio (HR): 0.75, 95% confidence interval (CI) 0.64-0.89, P = 0.001; HR: 0.78, 95% CI 0.66-0.93, P = 0.006; HR: 0.81, 95% CI 0.68-0.97, P = 0.019; respectively]. Notably, non-diabetic patients with lower level of FAR also had lower all-cause mortality and cardiac mortality risk than those in the FAR-H/DM group (HR: 0.41, 95% CI 0.27-0.63, P < 0.001; HR: 0.30, 95% CI 0.17-0.53, P < 0.001; respectively). Multivariate Cox proportional hazards regression analysis also indicated the highest risk of MACCEs in patients with FAR-H and DM than others (P for trend = 0.005). In addition, post-hoc analysis revealed consistent effects on 5-year MACCE across various subgroups. CONCLUSION: In this real-world cohort study, higher level of FAR combined with DM was associated with worse 5-year outcomes among patients with CAD undergoing PCI. The level of FAR may help to identify high-risk individuals in this specific population, where more precise risk assessment should be performed.