Serum 5'-Nucleotidase as a Novel Predictor of Adverse Clinical Outcomes after Percutaneous Coronary Intervention in Patients with Coronary Artery Disease.

Background: The correlation between 5 ' -Nucleotidase ( 5 ' -NT) and the clinical outcomes in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) is not clear. This study aims to clarify this relationship. Methods: The PRACTICE study enrolled 15,250 patients between December 2016 and October 2021. After filtering out those without 5 ' -NT data, a total of 6555 patients were analyzed with a median follow-up of 24 months. Based on the receiver operating characteristic (ROC) curve analysis, a 5 ' -NT level of 5.57 U/L was selected as the optimal cutoff value. All research samples were divided into high-value ( ≥ 5.57 U/L, n = 2346) and low-value groups ( < 5.57 U/L, n = 4209). Key clinical outcomes included all-cause death (ACD), cardiovascular death (CD), major adverse cardiovascular events (MACE), and major adverse cardiovascular and cerebrovascular events (MACCE). After separating patients into high and low value groups, multivariate Cox regression analysis was used to correct for potential confounding variables. Finally, risk ratios and their 95% confidence intervals (CIs) were calculated. Results: During the follow-up period, 129 instances of ACD were recorded-49 cases (1.2%) in the low-value group and 80 cases (3.4%) in the high-value group. Similarly, 102 CDs occurred, including 42 low-value group cases (1.0%) and 60 high-value group cases (2.6%). A total of 363 MACE occurred, including 198 low-value group cases (4.7%) and 165 high-value group cases (7%). A total of 397 cases of MACCE occurred, including 227 low-value group cases (5.4%) and 170 high-value group cases (7.2%). As serum 5 ' -NT increased, the incidence of ACD, CD, MACE and MACCE increased. After multivariate Cox regression, high 5 ' -NT levels were linked with a 1.63-fold increase in ACD risk (hazard ratio [HR] = 2.630, 95% CI: [1.770-3.908], p < 0.001) when compared to low 5 ' -NT patients. Similarly, the risk of CD, MACE, and MACCE increased by 1.298-fold (HR = 2.298, 95% CI: [1.477-3.573], p < 0.001), 41% (HR = 1.410, 95% CI: [1.124-1.768], p = 0.003) and 30.5% (HR = 1.305, 95% CI: [1.049-1.623], p = 0.017), respectively. Conclusions: high serum 5 ' -NT levels were independently correlated with adverse clinical outcomes in CAD patients following PCI, affirming its potential as a prognostic indicator.

Association between the C-Reactive Protein-Albumin-Lymphocyte (CALLY) Index and Adverse Clinical Outcomes in CAD Patients after PCI: Findings of a Real-World Study.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 10 4 ). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 ( ≤ 0.69, n = 950), Q2 (0.69-2.44, n = 950), Q3 (2.44-9.52, n = 950), and Q4 ( > 9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan-Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147-0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150-0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422-0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401-0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).

Cystatin C to Left Ventricular Ejection Fraction Ratio as a Novel Predictor of Adverse Outcomes in Patients with Coronary Artery Disease: A Prospective Cohort Study.

Background: While both cystatin C and left ventricular ejection fraction (LVEF) revealed established prognostic efficacy in coronary artery disease (CAD), the relationship between cystatin C/left ventricular ejection fraction ratio (CLR) and adverse clinical outcomes among patients with CAD following percutaneous coronary intervention (PCI) remains obscure, to date. Therefore, we sought to assess the predictive efficacy of CLR among CAD patients who underwent PCI in current study. Methods: A total of 14,733 participants, including 8622 patients with acute coronary syndrome (ACS) and 6111 patients with stable coronary artery disease (SCAD), were enrolled from a prospective cohort of 15,250 CAD patients who underwent PCI and were admitted to the First Affiliated Hospital of Xinjiang Medical University from 2016 to 2021. The primary outcome of this study was mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary outcomes were major adverse cardiovascular events (MACEs), major adverse cardiac and cerebrovascular events (MACCEs) and nonfatal myocardial infarction (NFMI). For CLR, the optimal cut-off value was determined by utilizing receiver operating characteristic curve analysis (ROC). Subsequently, patients were assigned into two groups: a high-CLR group (CLR ≥ 0.019, n = 3877) and a low-CLR group (CLR < 0.019, n = 10,856), based on optimal cut-off value of 0.019. Lastly, the incidence of outcomes between the two groups was compared. Results: The high-CLR group had a higher incidence of ACM (8.8% vs. 0.9%), CM (6.7% vs. 0.6%), MACEs (12.7% vs. 5.9%), MACCEs (13.3% vs. 6.7%), and NFMIs (3.3% vs. 0.9%). After adjusting for confounders, multivariate Cox regression analyses revealed that patients with high-CLR had an 8.163-fold increased risk of ACM (HR = 10.643, 95% CI: 5.525~20.501, p < 0.001), a 10.643-fold increased risk of CM (HR = 10.643, 95% CI: 5.525~20.501, p < 0.001), a 2.352-fold increased risk of MACE (HR = 2.352, 95% CI: 1.754~3.154, p < 0.001), a 2.137-fold increased risk of MACCEs (HR = 2.137, 95% CI: 1.611~2.834, p < 0.001), and a 1.580-fold increased risk of NFMI (HR = 1.580, 95% CI: 1.273~1.960, p < 0.001) compared to patients with low-CLR. Conclusions: The current study indicated that a high CLR is a novel and powerful predictor of adverse long-term outcomes in CAD patients who underwent PCI, and that, it is a better predictor for patients wtih SCAD and ACS. Clinical Trial Registration: NCT05174143, http://Clinicaltrials.gov.

Serum Globulin to Albumin Ratio as a Novel Predictor of Adverse Clinical Outcomes in Coronary Artery Disease Patients Who Underwent PCI.

Background: Coronary heart disease is one of the main causes of Mortality. Many biological indicators have been used to predict the prognosis of patients with coronary heart disease. The ratio of serum globulin to albumin (GAR) has been used to predict the prognosis of patients with various cancers. It has been proven that GAR is related to the prognosis of patients with stroke. However, GAR's role in cardiovascular disease remains unclear. Our purpose was to investigate the predictive value of GAR on clinical outcomes in post-percutaneous coronary intervention (PCI) patients with coronary artery disease (CAD). Methods: From Dec. 2016 to Oct. 2021, a total of 14,994 patients undergoing PCI patients admitted to the First Affiliated Hospital of Xinjiang Medical University were divided into high GAR group (GAR ≥ 0.76, n = 4087) and low GAR group (GAR < 0.76, n = 10,907). The incidence of adverse outcomes including all-cause mortality (ACM), cardiovascular mortality (CM), major adverse cardiovascular events (MACE) and major adverse cardiovascular and cerebrovascular events (MACCE) was compared between the two groups. Multivariate Cox regression was used to adjust for the effects of confounding factors, while hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated. Median follow-up time was 24 months. Results: Compared with the low GAR group, the high GAR group had significantly higher incidence of ACM (6.5% vs. 1.7%, p < 0.001); CM (4.9% vs. 1.2%, p < 0.001), MACE (10.5% vs. 6.7%, p < 0.001), and MACCE (11.3% vs. 7.5%, p < 0.001). Cox regression analysis showed the patients in the high GAR group had a 1.62-fold increased risk for ACM (HR = 2.622, 95% CI: 2.130-3.228, p < 0.01), a 1.782-fold increased risk for CM (HR = 2.782, 95% CI: 2.180-3.550, p < 0.01). There was a 37.2% increased risk for MACE (HR = 1.372, 95% CI: 1.204-1.564, p < 0.01), and 32.4% increased risk for MACCE (HR = 1.324, 95% CI: 1.169-1.500, p < 0.01), compared to the patients in the low GAR group. Conclusions: The present study suggested that post-PCI CAD patients with higher GAR presented significantly increased mortality and adverse events GAR level at admission may 296 be considered as part of risk stratification when PCI is possible in patients with coronary heart disease. Clinical Trial Registration: The detailed information of the PRACTICE study has been registered on http://Clinicaltrials.gov (Identifier: NCT05174143).

Mutated CYP17A1 promotes atherosclerosis and early-onset coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a multi-factor complex trait and is heritable, especially in early-onset families. However, the genetic factors affecting the susceptibility of early-onset CAD are not fully characterized. METHODS: In the present study, we identified a rare nonsense variant in the CYP17A1 gene from a Chinese Han family with CAD. To validate the effect of this variation on atherosclerosis and early-onset coronary artery disease, we conducted studies on population, cells, and mice. RESULTS: The mutation precisely congregated with the clinical syndrome in all the affected family members and was absent in unaffected family members and unrelated controls. Similar to the human phenotype, the CYP17A1-deficient mice present the phenotype of metabolic syndrome with hypertension, increased serum glucose concentration, and presentation of central obesity and fatty liver. Furthermore, CYP17A1 knockout mice or CYP17A1 + ApoE double knockout mice developed more atherosclerotic lesions than wild type (WT) with high fat diary. In cell models, CYP17A1 was found to be involved in glucose metabolism by increasing glucose intake and utilization, through activating IGF1/mTOR/HIF1-α signaling way, which was consistent in CYP17A1 knockout mice with impaired glucose tolerance and insulin resistance. CONCLUSIONS: Through our study of cells, mice and humans, we identified CYP17A1 as a key protein participating in the pathophysiology of the atherosclerotic process and the possible mechanism of CYP17A1 C987X mutation induced atherosclerosis and early-onset CAD involving glucose homeostasis regulation was revealed. Video Abstract.

Age and outcomes following personalized antiplatelet therapy in chronic coronary syndrome patients: a post hoc analysis of the randomized PATH-PCI trial.

It is particularly important to establish more effective and safer antiplatelet treatment strategies according to age. The present subanalysis of the PATH-PCI trial was to determine the safety and efficacy of any dual-antiplatelet therapy (DAPT) strategy in different age groups. We randomized 2285 chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) into a standard group or a personalized group from December 2016 to February 2018. The personalized group received personalized antiplatelet therapy (PAT) based on a novel platelet function test (PFT). The standard group received standard antiplatelet therapy (SAT). Then, all patients were divided according to age (under the age of 65 years and aged 65 years or over) to investigate the association and interaction of age on clinical outcomes at 180 days. In the patients under the age of 65 years, the incidence of NACEs was decreased in the personalized group compared to the standard group (5.1% vs. 8.8%, HR: 0.603, 95% CI: 0.409-0.888, P = .010). The rates of MACCEs (3.3% vs. 7.7%, HR: 0.450, 95% CI: 0.285-0.712, P = .001), MACEs (2.2% vs. 5.4%, HR: 0.423, 95% CI: 0.243-0.738, P = .002) also decreased. We did not find a significant difference in bleeding between the groups. In the patients aged 65 years or over, no difference in the primary endpoint was found (4.9% vs. 4.2%, P = .702), and comparable rates of survival were observed with the two strategies (all Ps > 0.05). The present study shows that PAT according to PFT was comparable to SAT at the 180-day follow-up for both ischemic and bleeding endpoints in CCS patients aged 65 years or over who underwent PCI. In patients under the age of 65 years, PAT can reduce ischemic events but does not increase bleeding, and it is an effective and safe treatment strategy. It may be necessary for young CCS patients after PCI to undergo PAT early after PCI.

What is the context? The PATH-PCI trial reported that personalized antiplatelet therapy (PAT) based on a novel platelet function test (PFT) can greatly reduce the incidence of ischemic events.Antiplatelet strategies may have very different effects on clinical outcomes in patients in China who are undergoing PCI at different ages.What is new? PL-12 is a new point-of-care platelet function analyzer that is used to test the platelet maximum aggregation rate (MAR).We explored the efficacy and safety of different antiplatelet strategies in chronic coronary syndrome (CCS) patients in different age groups.What is the impact? PAT according to PFT was comparable to standard antiplatelet therapy (SAT) at the 180-day follow-up for both ischemic and bleeding endpoints in CCS patients aged 65 years or over who underwent PCI.In patients under the age of 65 years, PAT can reduce ischemic events but not increase bleeding.PAT may be an effective and safe treatment strategy in CCS patients under the age of 65 years who underwent PCI.Abbreviation: PCI: percutaneous coronary intervention; CCS: chronic coronary syndrome; DAPT: dual antiplatelet therapy; PAT: personalized antiplatelet therapy; SAT: standard antiplatelet therapy; PFT: platelet function test; NACEs: net adverse clinical events; MACCEs: major adverse cardiac and cerebrovascular events; MACEs: major adverse cardiovascular events.

Gamma-glutamyl transferase to albumin ratio as a novel predictor of bleeding events and mortality in patients after percutaneous coronary intervention: A retrospective cohort study.

OBJECTIVES: To determine whether gamma-glutamyl transferase (GGT) to albumin ratio (GAR) independently predicts mortality and bleeding events in coronary artery disease (CAD) patients who undergo percutaneous coronary intervention (PCI). BACKGROUND: Serum GGT and albumin levels have been associated with CAD risk and mortality. However, more analysis is needed to determine their predictive relationship with adverse outcomes. METHODS: In total, 5,638 patients from a large retrospective cohort study were enrolled from January 2008 to December 2016 and divided into two groups (GAR <0.62, n = 2,712 and GAR ≥0.62, n = 2,926). The average follow-up time was 35.9 ± 22.6 months. Multivariate Cox regression analyses were performed to determine the risk of all-cause mortality and bleeding events associated with GAR. RESULTS: The low-GAR group had a significantly higher number of all-cause mortality (p = .016) and bleeding events (p = .010) than the high-GAR group. Multivariate Cox regression analyses showed that the risk of all-cause death and bleeding events decreased by 23.8% (hazard risk [HR] = 0.762 95% confidence interval [CI]: 0.601-0.966, p = .025) and 39.4% (HR = 00.616, 95% CI: 0.446-0.852, p = .003), respectively, in the high-GAR group. In patients with acute coronary syndrome, the risk of bleeding events decreased by 57.3% in the high-GAR group (HR = 0.427, 95% CI: 0.234-0.781, p = .006). In patients with stable coronary heart disease, the risk of all-cause death decreased 28.6% (HR = 0.714, 95% CI: 0.540-0.944, p = .018) in the high-GAR group. CONCLUSION: GAR was an independent and novel predictor of mortality and bleeding events in CAD patients who underwent PCI.

Baseline white blood cell count-to-apolipoprotein A1 ratio as a novel predictor of long-term adverse outcomes in patients who underwent percutaneous coronary intervention: a retrospective cohort study.

BACKGROUND: Previous studies suggested that baseline white blood cell count and apolipoprotein A1 levels were associated with clinical outcomes in patients with coronary heart disease (CAD) who underwent percutaneous coronary intervention (PCI). However, the ratio of baseline white blood cell count-to-apolipoprotein A1 level (WAR) and CAD after PCI have not been investigated. The present study investigated the effects of baseline WAR on long-term outcomes after PCI in patients with CAD. METHODS: A total of 6050 patients with CAD who underwent PCI were included in the study. Of these, 372 patients were excluded because no baseline white blood cell counts or apolipoprotein A1 (ApoA1) data was available or because of malignancies or other diseases. Finally, 5678 patients were enrolled in the present study and were divided into 3 groups according to WAR value: lower group - WAR< 5.25 (n = 1889); median group - 5.25 ≤ WAR≤7.15 (n = 1892); and higher group - WAR≥7.15 (n = 1897). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM), after PCI. The average follow-up time was 35.9 ± 22.6 months. RESULTS: A total of 293 patients developed ACM, including 85 (4.5%) patients in the lower group, 90 (4.8%) patients in the median group, and 118 (6.2%) patients in the higher group. The risk of ACM, cardiac mortality (CM), major adverse cardiovascular and cerebrovascular events (MACCEs), and major adverse cardiovascular events (MACEs) increased 62.6% (hazard risk [HR] =1.626, 95%CI: 1.214-2.179, P = 0.001), 45.5% (HR = 1.455, 95%CI: 1.051-2.014, P = 0.024), 21.2% (HR = 1.212, 95%CI: 1.011-1.454, P = 0.038), and 23.8% (HR = 1.238, 95%CI: 1.025-1.495, P = 0.027), respectively, as determined by multivariate Cox regression analyses comparing the patients in the higher group to patients in the lower group. Patients with a WAR≥4.635 had 92.3, 81.3, 58.1 and 58.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, compared to the patients with WAR< 4.635. Every 1 unit increase in WAR was associated with 3.4, 3.2, 2.0 and 2.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, at the 10-year follow-up. CONCLUSION: The present study indicated that baseline WAR is a novel and an independent predictor of adverse long-term outcomes in CAD patients who underwent PCI.

Red blood cell distribution width as long-term prognostic markers in patients with coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: The aim of this study was to assess the prognostic value of red blood cell distribution width (RDW) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). METHODS: A retrospective cohort study (CORFCHD-PCI, [Identifier: ChiCTR-INR-16010153]) of 6050 patients who were hospitalized with a diagnosis of coronary artery disease (CAD) and treated with PCI from January 2008 to December 2016 were enrolled in the study. The primary outcome was long-term mortality after PCI. Clinical follow-up data of participating patients were obtained during an outpatient examination 35.9 ± 22.6 months after PCI. Demographic and clinical data and admission laboratory parameters were recorded, and patients were categorized into two groups according to RDW level (high group ≥13.1%; low group < 13.1%). RESULTS: Multivariate Cox regression analysis revealed RDW as an independent prognosis factor for cardiac death. The incidence of cardiac death increased 1.33 times in patients in the high RDW group (HR, 1.331; 95% CI, 1.009-1.755, P = 0.043). Kaplan-Meier survival analysis suggested that patients with high RDW tended to have an increased accumulated risk of cardiac death. However, we did not found significant differences in the incidence of long-term mortality (adjusted HR = 1.203[0.941-1.537], P = 0.140), MACCE (adjusted HR = 1.128[0.979-1.301], P = 0.096), MACE (adjusted HR = 1.155[0.994-1.341], P = 0.059), stroke, bleeding events or readmission between the two groups. CONCLUSION: The baseline level of RDW is an independent predictor for cardiac death in post-PCI CAD patients.

Smoking and outcomes following personalized antiplatelet therapy in chronic coronary syndrome patients: A substudy from the randomized PATH-PCI trial.

BACKGROUND: This is a sub-analysis of the Personalized Antithrombotic Therapy for Coronary Heart Disease after PCI (PATH-PCI) trial in China to explore the relationship between smoking and outcomes following personalized antiplatelet therapy (PAT) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI). METHODS: As a single-center, prospective, randomized controlled and open-label trial, the PATH-PCI trial randomized CCS patients undergoing PCI into standard group or personalized group guided by a novel platelet function test (PFT), from December 2016 to February 2018. All patients were divided into smokers and nonsmokers according to their smoking status. Subsequently, we underwent a 180-day follow-up evaluation. The primary endpoint was the net adverse clinical events (NACE). RESULTS: Regardless of smoking status, in the incidence of NACE, there was a reduction with PAT but that the reductions are not statistically significant. In the incidence of bleeding events, we found no statistically significant difference between two groups (smokers: 2.0% vs. 1.4%, HR = 1.455, 95% confidence interval [CI]: 0.595-3.559, p = .412; nonsmokers: 2.2% vs. 1.8%, HR = 1.228, 95% CI: 0.530-2.842, p = .632). In smokers, PAT reduced major adverse cardiac and cerebrovascular events (MACCE) by 48.7% (3.0% vs. 5.9%, HR = 0.513, 95% CI: 0.290-0.908, p = .022), compared with standard antiplatelet therapy (SAT). PAT also reduced the major adverse cardiovascular events (MACE) but there was no statistically difference in the reductions (p > .05). In nonsmokers, PAT reduced MACCE and MACE by 51.5% (3.3% vs. 6.7%, HR = 0.485, 95% CI: 0.277-0.849, p = .011) and 63.5% (1.8% vs. 4.9%, HR = 0.365, 95% CI: 0.178-0.752, p = .006), respectively. When testing p-values for interaction, we found there was no significant interaction of smoking status with treatment effects of PAT (pint-NACE = .184, pint-bleeding = .660). CONCLUSION: Regardless of smoking, PAT reduced the MACE and MACCE, with no significant difference in bleeding. This suggests that PAT was an recommendable regimen to CCS patients after PCI, taking into consideration both ischemic and bleeding risk.

Association between extremely high prognostic nutritional index and all-cause mortality in patients with coronary artery disease: secondary analysis of a prospective cohort study in China.

OBJECTIVES: Decreased prognostic nutritional index (PNI) was associated with adverse outcomes in many clinical diseases. This study aimed to evaluate the relationship between baseline PNI value and adverse clinical outcomes in patients with coronary artery disease (CAD). DESIGN: The Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, a prospective cohort study of 15 250 patients with CAD, was performed from December 2016 to October 2021. The longest follow-up period was 5 years. This study was a secondary analysis of the PRACTICE study. SETTING: The study setting was Xinjiang Medical University Affiliated First Hospital in China. PARTICIPANTS: Using the 50th and 90th percentiles of the PNI in the total cohort as two cut-off limits, we divided all participants into three groups: Q1 (PNI <51.35, n = 7515), Q2 (51.35 ≤ PNI < 59.80, n = 5958) and Q3 (PNI ≥ 59.80, n = 1510). The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). PRIMARY OUTCOME: The primary outcome measure was mortality, including all-cause mortality (ACM) and cardiac mortality (CM). RESULTS: In 14 983 participants followed for a median of 24 months, a total of 448 ACM, 333 CM, 1162 major adverse cardiovascular events (MACE) and 1276 major adverse cardiovascular and cerebrovascular events (MACCE) were recorded. The incidence of adverse outcomes was significantly different among the three groups (p <0.001). There were 338 (4.5%), 77 (1.3%) and 33 (2.2%) ACM events in the three groups, respectively. A restricted cubic spline displayed a J-shaped relationship between the PNI and worse 5-year outcomes, including ACM, CM, MACE and MACCE. After adjusting for traditional cardiovascular risk factors, we found that only patients with extremely high PNI values in the Q3 subgroup or low PNI values in the Q1 subgroup had a greater risk of ACM (Q3 vs Q2, HR: 1.617, 95% CI 1.012 to 2.585, p=0.045; Q1 vs Q2, HR=1.995, 95% CI 1.532 to 2.598, p <0.001). CONCLUSION: This study revealed a J-shaped relationship between the baseline PNI and ACM in patients with CAD, with a greater risk of ACM at extremely high PNI values. TRIAL REGISTRATION NUMBER: NCT05174143.

Association of hemoglobin glycation index with clinical outcomes in patients with coronary artery disease: a prospective cohort study.

BACKGROUND: To analyze the association between the hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD). METHODS: HGI represented the difference between laboratory measured Hemoglobin A1c (HbA1c) and predicted HbA1c based on a liner regression between Hb1Ac and fasting plasma glucose (FPG). A total of 10 598 patients who treated with percutaneous coronary intervention (PCI) were stratified into three groups (low HGI group: HGI<-0.506, medium HGI group: -0.506 ≤ HGI < 0.179, and high HGI group: HGI ≥ 0.179). The primary endpoints includes all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: A total of 321 ACMs, 243 CMs, 774 MACEs, and 854 MACCEs were recorded during a 60-month follow-up period. After adjusting for confounders using a multivariate Cox regression analysis, the patients in the low HGI group had a significantly increased risk of ACM (adjusted HR = 1.683, 95%CI:1.179-2.404, P = 0.004) and CM (HR = 1.604, 95%CI:1.064-2.417, P = 0.024) as compared with patients in the medium HGI group. Similarly, the patients in the high HGI group had an increased risk of MACEs (HR = 1.247, 95% CI: 1.023-1.521, P = 0.029) as compared with patients in the medium HGI group. For ACM, CM, and MACEs, a U-shaped relation were found among these three groups. However, we did not find significant differences in the incidence of MACCEs among these three groups. CONCLUSION: The present study indicates that HGI could be an independent predictor for the risk of mortality and MACEs in patients with CAD.

Age-Bilirubin-International Normalized Ratio (INR)-Creatinine (ABIC) Score, a Potential Prognostic Model for Long-Term Mortality of CAD Patients After PCI.

Background: Given that age, international normalized ratio (INR), total bilirubin, and creatinine are reported to be independent risk factors for predicting outcome in patients with coronary artery disease (CAD), it is possible that the age-bilirubin-INR-creatinine (ABIC) score might be a potential prognostic model for patients with CAD. Methods: A total of 6046 CAD patients after percutaneous coronary intervention (PCI) from the retrospective cohort study (Identifier: ChiCTR-ORC-16010153) were evaluated finally. The primary outcome long-term mortality and secondary endpoints mainly major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded. Multivariate Cox regression models were used to determine risk factors for mortality and MACCEs. Results: The ABIC score was significantly higher in the death group than in the survival group. After adjusting for other CAD risk factors, the ABIC score was identified to be an independent risk factor for long-term mortality by multivariate Cox analysis. When in the high ABIC group, the incidence of all-cause mortality would increased 1.7 times (adjusted HR=1.729 (1.347-2.218), P<0.001), and 1.5 times for cardiac death (adjusted HR=1.482 (1.126-1.951), P=0.005). Conclusion: The present study indicated that ABIC score≥7.985 predicts high long-term mortality and cardiac death risk for PCI patients. The ABIC score might be a potential prognostic model for patients with PCI.

Decreased free fatty acid levels associated with adverse clinical outcomes in coronary artery disease patients with type 2 diabetes: findings from the PRACTICE study.

AIMS: Increased free fatty acid (FFA) levels are known to be strongly associated with mortality in coronary artery disease (CAD) patients and the development of type 2 diabetes (T2DM). However, few studies have been large enough to accurately examine the relationship between FFA levels and mortality in CAD patients with T2DM. METHODS AND RESULTS: From December 2016 to October 2021, 10 395 CAD patients enrolled in PRACTICE, a prospective cohort study in China, were divided into four groups according to baseline FFA concentration. We investigated mortality, including all-cause mortality (ACM) and cardiac mortality (CM), as the primary endpoint. The secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs) and major adverse cardiovascular events (MACEs). The median follow-up time was 24 months. In the total cohort, there were 222 ACMs, 164 CMs, 718 MACEs, and 803 MACCEs recorded. After controlling for baseline variables, the association between FFA levels and the risk of mortality presented a non-linear U-shaped curve, with the lowest risk at 310 µmol/L. We also identified a non-linear U-shaped relationship for ischaemic events (MACE or MACCE) with the lowest risk at 500 µmol/L. Subgroup analysis showed that a U-shaped relationship between FFA and mortality or ischaemic events was observed only in individuals with T2DM but not in non-diabetic CAD patients. CONCLUSIONS: A non-linear U-shaped association was identified between baseline FFA levels and mortality or ischaemic events in CAD patients with T2DM.

From December 2016 to October 2021, 10 395 coronary artery disease (CAD) patients enrolled in PRACTICE, a prospective cohort study in China, were divided into four groups according to baseline free fatty acid (FFA) concentration. We investigated mortality, including all-cause mortality (ACM), and cardiac mortality (CM), as the primary endpoints. The secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs) and major adverse cardiovascular events (MACEs). The median follow-up time was 24 months. Finally, we were surprised to find that high and low FFA levels were associated with a higher risk of mortality and ischaemic events in CAD patients with T2DM. Baseline plasma FFA levels may be a more powerful, effective, and easily detectable biomarker of adverse outcomes in CAD patients with T2DM. As the FFA increases, a U-shaped curve appears in the poor long-term prognosis.

The Fibrinogen-to-Albumin Ratio Is Associated with Poor Prognosis in Patients with Coronary Artery Disease: Findings from a Large Cohort.

We aimed to evaluate the association of the fibrinogen-to-albumin ratio (FAR) with the clinical outcomes of coronary artery disease (CAD). All 14,944 patients with CAD evaluated in the present study were from a prospective cohort that recruited 15,250 patients admitted in the First Affiliated Hospital of Xinjiang Medical University between December 2016 and October 2021. The all-cause mortality (ACM) and cardiac mortality (CM) were selected as the primary endpoints. The secondary endpoints were major adverse cardiovascular events (MACEs), major adverse cardiac and cerebrovascular events (MACCEs), and non-fatal myocardial infarction (NFMI). The optimal FAR cutoff value was determined by using a receiver operating characteristic (ROC) curve analysis. Using 0.1 as the cutoff value, all the patients were divided into two groups: a low-FAR group (FAR < 0.1, n = 10,076) and a high-FAR group (FAR ≥ 0.1, n = 4918). The incidence of outcomes between the two groups was compared. The high-FAR group exhibited a higher incidence of ACM (5.3% vs. 1.9%), CM (3.9% vs. 1.4%), MACEs (9.8% vs. 6.7%), MACCEs (10.4% vs. 7.6%), and NFMI (2.3% vs. 1.3%) than the low-FAR group. To adjust the confounders, multivariate Cox regression analyses showed that the risk in the high-FAR group was increased 2.182 fold in ACM (HR = 2.182, 95% CI: 1.761 ~ 2.704, P < 0.001), 2.116 fold in CM (HR = 2.116, 95% CI: 1.761 ~ 2.704, P < 0.001), 1.327 fold in MACEs (HR = 1.327, 95% CI: 1.166 ~ 1.510, P < 0.001), 1.280 fold in MACCEs (HR = 1.280, 95% CI: 1.131 ~ 1.448, P < 0.001), and 1.791 fold in NFMI (HR = 1.791, 95% CI:1.331 ~ 2.411, P < 0.001), compared to the low-FAR group. The present study suggested that the high-FAR group was an independent and powerful predictor of adverse outcomes in CAD patients.

The higher the serum albumin, the better? Findings from the PRACTICE study.

AIMS: The relation between hypoalbuminemia and coronary artery disease (CAD) has been established. However, the association of increased albumin level and outcomes of CAD has not been investigated. METHODS: There were 14 994 CAD patients from the PRACTICE study, which is a large, single center prospective cohort study based on case records and follow-up registry performed in the First Affiliated Hospital of Xinjiang Medical University from Dec. 2016 to Oct. 2021 in the present study. All the 14 994 patients were divided into five categories according albumin levels: <35 g/L group (n = 1 478), 35-40 g/L group (n = 5 007), 40-45 g/L group (n = 6 076), 45-50 g/L group (n = 1 835), and ≥50 g/L group (n = 598). RESULTS: A total of 448 all-cause deaths(ACD), 333 cardiac deaths (CD), 1 162 MACEs and 1 276 MACCEs were recorded during up to 60-months follow-up period. After adjusting for confounders, we observed a non-linear relation for either MACE or MACCE with the lowest risk at 45 g/L of albumin levels. A threshold value of albumin ≥50 g/L was associated with an increased risk for either MACE (adjusted HR=1.617, 95%CI:1.130-2.315, P = 0.009) or MACCE (adjusted HR= 1.439, 95%CI: 1.007-2.056, P = 0.045) in multivariable Cox regression model. For mortality, we only found decreased (<35 g/L) but not increased albumin level was associated with either ACD (HR=2.744, 95%CI: 1.631-4.617, P<0.001) or CD (HR=2.736, 95%CI: 1.484-5.045, P = 0.001). CONCLUSIONS: In the present study, a U-shaped curve relation was identified between albumin levels and MACE and MACCE in CAD patients, with the lowest risk at 45 g/L levels.

Serum a-1 antitrypsin as a novel biomarker in chronic heart failure.

AIMS: Chronic heart failure (CHF) remains a major health issue worldwide. In the present study, we aimed to identify novel circulating biomarkers for CHF using serum proteomics technology and to validate the biomarker in three independent cohorts. METHODS AND RESULTS: The isobaric tags for relative and absolute quantitation technology was utilized to identify the potential biomarkers of CHF. The validation was conducted in three independent cohort. Cohort A included 223 patients with ischaemic heart disease (IHD) and 321 patients with ischaemic heart failure (IHF) from the CORFCHD-PCI study. Cohort B recruited 817 patients with IHD and 1139 patients with IHF from the PRACTICE study. Cohort C enrolled 559 non-ischaemic heart disease patients with CHF (n = 316) or without CHF (n = 243). We found the expression of a-1 antitrypsin (AAT) was elevated significantly in patients with CHF compared with that in the patients with stable IHD using statistical and bioinformatics analyses. In a validation study, there was a significant difference between patients with stable IHD and patients with IHF in AAT concentration either in cohort A (1.35 ± 0.40 vs. 1.64 ± 0.56, P < 0.001) or in cohort B (1.37 ± 0.42 vs. 1.70 ± 0.48, P < 0.001). The area under the receiver operating characteristic curve was 0.70 [95% confidence interval (CI): 0.66 to 0.74, P < 0.001] in cohort A and 0.74 (95% CI: 0.72 to 0.76, P < 0.001) in cohort B. Furthermore, AAT was negative correlated with left ventricular ejection fraction (r = -0.261, P < 0.001). After adjusting for confounders using a multivariate logistic regression analysis, AAT remained an independent association with CHF in both cohort A (OR = 3.14, 95% CI: 1.667 to 5.90, P < 0.001) and cohort B (OR = 4.10, 95% CI: 2.97 to 5.65, P < 0.001). This association was also validated in cohort C (OR = 1.86, 95% CI: 1.02 to 3.38, P = 0.043). CONCLUSIONS: The present study suggests that serum AAT is a reliable biomarker for CHF in a Chinese population.

Effectiveness of lipid-lowering therapy on mortality and major adverse cardiovascular event outcomes in patients undergoing percutaneous coronary intervention: a network meta-analysis of randomised controlled trials.

BACKGROUND: Emergency percutaneous coronary intervention (PCI) can quickly restore myocardial perfusion after acute coronary syndrome. Whether and which lipid-lowering regimens are effective in reducing major adverse cardiovascular events (MACEs) and mortality risk after PCI remain unclear. OBJECTIVE: This study assessed the benefits of different lipid-lowering regimens on the risk of MACEs and mortality in the post-PCI population by network meta-analysis. METHODS: Public databases, including PubMed, Embase and the Cochrane Library, were searched from inception to August 2022. Randomised controlled trials (RCTs) on lipid-lowering regimens in post-PCI populations were included and analysed. The outcomes were the incidence of all-cause mortality and MACEs, whether reported as dichotomous variables or as HRs. RESULTS: Thirty-nine RCTs were included. For MACEs, alirocumab plus rosuvastatin (OR: 0.18; 95% CI: 0.07 to 0.44), evolocumab plus ezetimibe and statins (OR: 0.19; 95% CI: 0.06 to 0.59), eicosapentaenoic acid (EPA) plus pitavastatin (HR: 0.67; 95% CI: 0.49 to 0.96) and icosapent ethyl plus statins (HR: 0.73; 95% CI: 0.62 to 0.86) had significant advantages and relatively high rankings. For mortality, rosuvastatin (OR: 0.30; 95% CI: 0.11 to 0.84), ezetimibe plus statins (OR: 0.55; 95% CI: 0.43 to 0.89) and icosapent ethyl plus statins (OR: 0.66; 95% CI: 0.45 to 0.96) had significant advantages compared with the control. CONCLUSION: EPA, especially icosapent ethyl, plus statins had a beneficial effect on reducing the risk of MACEs and mortality in post-PCI patients. Proprotein convertase subtilisin/kexin type-9 inhibitors plus statins were able to reduce the risk of MACEs, but the risk of mortality remained unclear. PROSPERO REGISTRATION NUMBER: CRD42018099600.

Low HDL Cholesterol Is Associated with Reduced Bleeding Risk in Patients Who Underwent PCI: Findings from the PRACTICE Study.

BACKGROUND: We sought to examine the dose-response relationship between high-density lipoprotein cholesterol (HDL-C) and bleeds in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). METHODS: All the 15,250 participants were from the Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, which is a large, single-center, prospective cohort study based on case records and a follow-up registry performed in the First Affiliated Hospital of Xinjiang Medical University from December 2016 to October 2021. We divided all the patients into five groups according to their HDL-C levels: the ≤35 mg/dL group (n = 4,732), 35 to 45 mg/dL group (n = 6,049), 45 to 55 mg/dL group (n = 2,826), 55 and 65 mg/dL group (n = 1,117), and >65 mg/dL group (n = 526). The incidence of bleeds, mortality, ischemic events, and net adverse clinical events (NACEs) among the five groups was compared. RESULTS: A total of 713 bleeds, 1,180 ischemic events, 456 deaths, and 1,893 NACEs were recorded during the up to 60-month follow-up period. After adjusting for confounders, we observed a nonlinear relation for bleeds, with the highest risk at intermediate HDL-C levels (45-55 mg/dL). We also identified a dose-response relationship for ischemic events. A threshold value of HDL-C ≤35 mg/dL (adjusted hazard ratio = 0.560, 95% confidence interval: 0.360-0.872, p = 0.010) was associated with a decreased risk for bleeds in the multivariable Cox regression model. The results were consistent in multiple sensitivity analyses and propensity score-matching analysis. CONCLUSION: In the present study, a nonlinear association was identified between HDL-C levels and bleeds in CAD patients who underwent PCI, with a higher risk at intermediate levels. However, further multicenter studies are warranted.

Diabetes and Outcomes Following Personalized Antiplatelet Therapy in Coronary Artery Disease Patients Who Have Undergone PCI.

CONTEXT: A personalized antiplatelet therapy guided by a novel platelet function testing (PFT), PL-12, is considered an optimized treatment strategy in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, the safety and efficacy of any dual-antiplatelet therapy (DAPT) strategy may differ in relation to diabetes status. OBJECTIVE: The aim of this study was to compare the outcomes of PFT-guided personalized DAPT in stable CAD patients with and without diabetes mellitus. METHODS: The PATH-PCI trial randomly assigned 2285 stable CAD patients to either personalized antiplatelet therapy or standard antiplatelet treatment. We investigated the association and interaction of diabetes on clinical outcomes across 2 treatment groups. RESULTS: We did not find a significant difference between the personalized group and the standard group in net adverse clinical events in either diabetes patients (10.3% vs 13.4%, P = .224) or in the nondiabetic group (3.1% vs 5.0%, P = .064). In diabetes patients (n = 646, 28.3%), the overall ischemic event rates were significantly low (6.8% vs 11.3%, HR = 0.586, 95% CI, 0.344-0.999, P = .049) and the bleeding event rates did not differ between the 2 groups (3.5% vs 3.3%, HR = 1.066, 95% CI, 0.462-2.458, P = .882). Similarly, in nondiabetic patients, the overall ischemic event rates were significantly low (1.8% vs 4.2%, HR = 0.428, 95% CI, 0.233-0.758, P = .006) and the bleeding event rates did not differ between the 2 groups (1.6% vs 0.9%, HR = 1.802, 95% CI: 0.719-4.516, P = .209). CONCLUSION: The present study suggests that personalized antiplatelet therapy according to PFT can reduce ischemic events but not increase bleedings in stable CAD patients with or without diabetes who have undergone PCI.