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.

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.

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.

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.

Prognostic value of fibrinogen in patients with coronary artery disease and prediabetes or diabetes following percutaneous coronary intervention: 5-year findings from a large cohort study.

BACKGROUND: Fibrinogen (FIB) is an independent risk factor for mortality and cardiovascular events in the general population. However, the relationship between FIB and long-term mortality among CAD patients undergoing PCI remains unclear, especially in individuals complicated with diabetes mellitus (DM) or prediabetes (Pre-DM). METHODS: 6,140 patients with CAD undergoing PCI were included in the study and subsequently divided into three groups according to FIB levels (FIB-L, FIB-M, FIB-H). These patients were further grouped by glycemic status [normoglycemia (NG), Pre-DM, DM]. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. RESULTS: FIB was positively associated with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in CAD patients with and without DM (P < 0.001). During a median follow-up of 5.1 years (interquartile range 5.0-5.2 years), elevated FIB was significantly associated with long-term all-cause mortality (adjusted HR: 1.86; 95% CI 1.28-2.69; P = 0.001) and cardiac mortality (adjusted HR: 1.82; 95% CI 1.15-2.89; P = 0.011). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause and cardiac mortality compared with NG group (all P < 0.05). When grouped by both FIB levels and glycemic status, diabetic patients with medium and high FIB levels had higher risk of mortality [(adjusted HR: 2.57; 95% CI 1.12-5.89), (adjusted HR: 3.04; 95% CI 1.35-6.82), all P < 0.05]. Notably, prediabetic patients with high FIB also had higher mortality risk (adjusted HR: 2.27; 95% CI 1.01-5.12). CONCLUSIONS: FIB was independently associated with long-term all-cause and cardiac mortality among CAD patients undergoing PCI, especially in those with DM and Pre-DM. FIB test may help to identify high-risk individuals in this specific population.

Real-world long-term outcomes based on three therapeutic strategies in very old patients with three-vessel disease.

BACKGROUND: There are relatively limited data regarding real-world outcomes in very old patients with three-vessel disease (3VD) receiving different therapeutic strategies. This study aimed to perform analysis of long-term clinical outcomes of medical therapy (MT), coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI) in this population. METHODS: We included 711 patients aged ≥ 75 years from a prospective cohort of patients with 3VD. Consecutive enrollment of these patients began from April 2004 to February 2011 at Fu Wai Hospital. Patients were categorized into three groups (MT, n = 296; CABG, n = 129; PCI, n = 286) on the basis of different treatment strategies. RESULTS: During a median follow-up of 7.25 years, 262 deaths and 354 major adverse cardiac and cerebrovascular events (MACCE) occurred. Multivariate Cox analysis showed that the risk of cardiac death was significantly lower for CABG compared with PCI (adjusted hazard ratio [HR] = 0.475, 95% confidence interval [CI] 0.232-0.974, P = 0.042). Additionally, MACCE appeared to show a trend towards a better outcome for CABG (adjusted HR = 0.759, 95% CI 0.536-1.074, P = 0.119). Furthermore, CABG was significantly superior in terms of unplanned revascularization (adjusted HR = 0.279, 95% CI 0.079-0.982, P = 0.047) and myocardial infarction (adjusted HR = 0.196, 95% CI 0.043-0.892, P = 0.035). No significant difference in all-cause death between CABG and PCI was observed. MT had a higher risk of cardiac death than PCI (adjusted HR = 1.636, 95% CI 1.092-2.449, P = 0.017). Subgroup analysis showed that there was a significant interaction between treatment strategy (PCI vs. CABG) and sex for MACCE (P = 0.026), with a lower risk in men for CABG compared with that of PCI, but not in women. CONCLUSIONS: CABG can be performed with reasonable results in very old patients with 3VD. Sex should be taken into consideration in therapeutic decision-making in this population.

Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease.

BACKGROUND AND AIMS: Whether routine assessment of FT3/FT4 ratio in euthyroid patients with three-vessel disease (3VD) could help identify high-risk individuals remains unclear. This study evaluated the relationship between FT3/FT4 ratio and long-term clinical outcomes in this specific population. METHODS AND RESULTS: This study included 2106 euthyroid patients with 3VD (stenoses of ≥50% in right coronary artery, left circumflex and left anterior descending). Patients were categorized into three groups according to tertiles of FT3/FT4 ratio (Q1>2.58,n = 704; 2.2 ≤ Q2<2.58, n = 706; Q3<2.22, n = 696). The median follow-up time was 5.3 years, during which 206 deaths and 332 MACCEs (consisting of all-cause death, myocardial infarction, and stroke) occurred. Compared with the other two groups, patients with low level of FT3/FT4 ratio tended to be female, older, diabetic, and had significantly higher incidences of all-cause death, cardiac death and MACCE (all P < 0.05). Cox regression analysis showed that patients with low level of FT3/FT4 ratio had higher risks of long-term cardiac death (adjusted HR = 1.87, 95% CI 1.06-3.28, P = 0.030) and MACCE (adjusted HR = 1.43, 95% CI 1.07-1.93, P = 0.017) than those with high level of FT3/FT4 ratio. Subgroup analysis showed there was a significant interaction between FT3/FT4 ratio and age (≥65 years vs.<65 years) for MACCE (P = 0.029). CONCLUSION: Low level of FT3/FT4 ratio is independently associated with an increased risk of long-term cardiac death and MACCE in euthyroid patients with 3VD. Routine assessment of FT3/FT4 ratio might be helpful to identify high-risk individuals in this specific population.

Long-Term Clinical Outcomes for Non-ST Elevation Acute Coronary Syndrome Patients with High-Risk Angiographic Findings Undergoing Percutaneous Coronary Intervention.

OBJECTIVE: We aim to evaluate the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with high-risk coronary anatomy (HRCA). BACKGROUND: Coronary disease severity is important for therapeutic decision-making and prognostication among patients presenting with NSTE-ACS. However, long-term outcome in patients undergoing percutaneous coronary intervention (PCI) with HRCA is still unknown. METHOD: NSTE-ACS patients undergoing PCI in Fuwai Hospital in 2013 were prospectively enrolled and subsequently divided into HRCA and low-risk coronary anatomy (LRCA) groups according to whether angiography complies with the HRCA definition. HRCA was defined as left main disease >50%, proximal LAD lesion >70%, or 2- to 3- vessel disease involving the LAD. Prognosis impact on 2-year and 5-year major adverse cardiovascular and cerebrovascular events (MACCE) is analyzed. RESULTS: Out of 4,984 enrolled patients with NSTE-ACS, 3,752 patients belonged to the HRCA group, while 1,232 patients belonged to the LRCA group. Compared with the LRCA group, patients in the HRCA group had worse baseline characteristics including higher age, more comorbidities, and worse angiographic findings. Patients in the HRCA group had higher incidence of unplanned revascularization (2 years: 9.7% vs. 5.1%, p < 0.001; 5 years: 15.4% vs. 10.3%, p < 0.001), 2-year MACCE (13.1% vs. 8.8%, p < 0.001), and 5-year death/MI/revascularization/stroke (23.0% vs. 18.4%, p = 0.001). Kaplan-Meier survival analysis showed similar results. After adjusting for confounding factors, HRCA is independently associated with higher risk of revascularization (2 years: HR = 1.636, 95% CI: 1.225-2.186; 5 years: HR = 1.460, 95% CI: 1.186-1.798), 2-year MACCE (HR = 1.275, 95% CI = 1.019-1.596) and 5-year death/MI/revascularization/stroke (HR = 1.183, 95% CI: 1.010-1.385). CONCLUSION: In our large cohort of Chinese patients, HRCA is an independent risk factor for long-term unplanned revascularization and MACCE.

Long-Term Prognosis of Moderate to Severe Coronary Artery Calcification in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Moderate/severe coronary artery calcification (CAC) predicts worse clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). However, to date most studies have been modest in size and with limited follow-up. We aimed to assess the association between calcification severity and long-term clinical outcomes in a large cohort undergoing PCI.Methods and Results:In total, 10,068 consecutive patients who underwent PCI at Fuwai Hospital were enrolled in this prospective observational study. Patients were categorized as none/mild or moderate/severe CAC according to the severity of the target lesion by visual assessment of coronary angiography. Major adverse cardiovascular events (MACE), a composite event of death, myocardial infarction and revascularization, at 5 years were assessed. None/mild CAC was observed in 8,229 (81.7%) patients, and moderate/severe CAC was observed in 1,839 (18.3%) patients. Patients with moderate/severe CAC had a significantly higher rate of 5-year unplanned revascularization (15.2% vs. 13.2%, P=0.022) and MACE (20.7% vs. 17.9%, P=0.005). After propensity score matching, the moderate/severe CAC group still had a higher rate of 5-year unplanned revascularization (15.2% vs. 12.6%, P=0.019). Cox regression analysis using clinically significant variables revealed moderate/severe calcification was independently associated with higher risk of 2-year unplanned target vessel revascularization (hazard ratio (HR)=1.287, 95% confidence interval (CI): 1.036-1.600, P=0.023) and MACE (HR=1.242, 95% CI: 1.039-1.484, P=0.017), but not 5-year unplanned revascularization and MACE. CONCLUSIONS: In patients undergoing PCI, moderate/severe coronary calcification increases the risk of long-term MACE.

Apolipoprotein B/A-I Ratio Predicts Lesion Severity and Clinical Outcomes in Diabetic Patients With Acute Coronary Syndrome.

BACKGROUND: Dyslipidemia plays a crucial role in acute coronary syndrome (ACS). Paucity of data is available concerning the effect of apolipoprotein (apo) B/A-I ratio on the severity and outcomes in diabetic patients with ACS. This study investigated these associations in a Chinese cohort undergoing percutaneous coronary intervention.Methods and Results:In 2013, a total of 2,563 diabetic patients concomitant with ACS were included. Patients were divided into 2 groups based on the apoB/apoA-I ratio on admission: <0.63 (n=1,279, 49.9%) and ≥0.63 (n=1,284, 50.1%). Angiographic complexity and severity were determined by SYNTAX score (SS). A higher apo ratio was significantly associated with higher proportions of acute myocardial infarction (MI) and intermediate-high SS. Multivariable logistic regression analysis showed that the apo ratio was an independent factor of complicated lesions (OR 1.341, 95% confidence interval 1.039-1.730, P=0.024). Moreover, consistent results were found in the subgroups of normal concentrations of conventional lipid parameters. During a median follow-up period of 878 days, significant differences were found in periprocedural MI (1.0% vs. 2.2%, P=0.019) and total events of MI (2.0% vs. 3.3%, P=0.028). After adjusting for confounders, a high apo ratio remained independently predictive of MI, the risk of which was doubled during the periprocedural period and in the long term. CONCLUSIONS: The ApoB/apoA-I ratio is an independent predictor for complicated lesions and future MI in patients with diabetes and ACS.

Antithrombotic Drugs-Pharmacology and Perspectives.

Thrombosis, the localized clotting of blood that affects arterial or venous circulation, is one of the leading causes of death worldwide. Arterial thrombosis is commonly initiated by vascular endothelial injury, while venous thrombosis mainly stems from blood stasis. Despite these differences, platelet adhesion, activation and aggregation, and fibrin formation as a result of coagulation constitute the fundamental processes of thrombus formation. Antithrombotic drugs permitted on the clinical currently can dramatically reduce major adverse cardiovascular events; however, they can also increase the bleeding risk. Discovery of antithrombotic drugs that can effectively prevent thrombosis while sparing bleeding side effects remains unmet medical need. In this chapter, we provide an overview on the pathophysiology of thrombosis, followed by introduction of each class of antithrombotic drugs including their pharmacology, clinical applications and limitations. Practical challenges and future perspectives of antithrombotic drugs are discussed in the last part of this chapter.

The association between glycated hemoglobin levels and long-term prognosis in patients with diabetes and triple-vessel coronary disease across different age groups: A cohort study.

AIM: Our study aimed to investigate the correlation between glycated hemoglobin (HbA1c) and adverse prognostic events in patients with diabetes and triple-vessel coronary disease (TVD). METHODS: This study ultimately included 2051 patients with TVD and diabetes. Patients were categorized into five groups based on their HbA1c levels: < 6.0 %, 6.0-6.4 %, 6.5-6.9 %, 7.0-7.9 %, and ≥ 8.0 %. The primary endpoint was all-cause death, and the secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: The median follow-up time was 5.88 years. During this period, a total of 323 (15.7 %) all-cause deaths and 537 (26.2 %) MACCEs were recorded. The relationship between HbA1c and the risk of endpoint events showed a J-shaped pattern, with the lowest risk observed between 6.0 % and 6.4 %. Further analysis revealed a significant interaction between HbA1c and age. In the subgroup with age < 70 years, as HbA1c increased, the risk of endpoint events gradually rose. While in the subgroup with age ≥70 years, there was an L-shaped relationship between HbA1c and endpoint events, with the highest risk observed in patients with HbA1c < 6.0 %. CONCLUSION: Our study revealed variations in the relationship between HbA1c levels and endpoint events among patients with TVD and diabetes of different ages. In younger patients, elevated HbA1c levels were associated with a higher risk of death and MACCE, while in older patients, excessively low HbA1c levels (HbA1c < 6 %) were linked to a higher risk of death and MACCE.

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.

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.

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.

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.

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.

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.