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.

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.

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.

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.

Hemoglobin-to-Red-Cell Distribution Width Ratio Is a Novel Predictor of Long-Term Patient Outcomes After Percutaneous Coronary Intervention: A Retrospective Cohort Study.

BACKGROUND: The hemoglobin level and red cell distribution width (RDW) have been linked to the prognosis of coronary atherosclerotic heart disease (CAHD). However, the relationship between the ratio of hemoglobin to the RDW (HRR) and clinical outcomes after percutaneous coronary intervention (PCI) is not known. Here, we explored the impact of the HRR on clinical outcomes after PCI. METHODS: In our study, we selected 6,046 CAHD patients with PCI hospitalized in the First Affiliated Hospital of Xinjiang Medical University from 2008 to 2016. The patients were grouped according to their HRR ratio: group A (HRR < 10.25, n = 2,344) and group B (HRR ≥ 10.25, n = 3,702). The difference in clinical outcomes between the two groups was compared. Patients were followed up for 35.9 ± 22.6 months. RESULTS: Three hundred nine patients died during follow-up. These included 166 patients (7.1%) in the HRR < 10.25 group and 143 patients (3.9%) in the HRR ≥ 10.25 group (P < 0.001). The incidences of cardiogenic death (5.7 vs. 3.2%) and major cardiovascular adverse events (16.5 vs. 12.9%) also differed significantly between the groups (both Ps < 0.001). Analysis using the multivariate Cox proportional hazard model found a significant association between a decreased HRR and post-PCI mortality (all-cause death, adjusted HR: 1.479, 95% CI: 1.156-1.893, p = 0.002; cardiac death, adjusted HR: 1.470, 95% CI: 1.116-1.936, p = 0.006). CONCLUSION: The HRR is predictive of post-PCI mortality among CAHD patients.

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.

ALB-dNLR Score Predicts Mortality in Coronary Artery Disease Patients After Percutaneous Coronary Intervention.

Background: The influence of the albumin/derived neutrophil and lymphocyte ratio (ALB-dNLR) on the outcomes of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI) is not known. Here, we aimed to determine the association between the ALB-dNLR score and post-PCI CAD patient outcomes. Methods: A total of 6,050 patients from the First Affiliated Hospital of Xinjiang Medical University were enrolled between January 2008 and December 2016. These patients were divided into three groups according to their ALB-dNLR scores (0 points, n = 1,121; 1 point, n = 3,119; 2 points, n = 1,810). Mortality after PCI [all-cause (ACM) and cardiac (CM)] was taken as the primary endpoint. The prognostic value of the ALB-dNLR score was determined with the Cox proportional hazard model after adjustment for covariates. Results: The ACM and CM rates differed among participants in the three groups (P = 0.007 and P = 0.034, respectively). Multivariate Cox analysis showed that the ALB-dNLR score independently predicted both ACM [1 point vs. 0 points, HR = 1.249 (95% CI: 0.79-1.774), P = 0.215; 2 points vs. 0 points, HR = 1.777 (95% CI: 1.239-2.549), P = 0.002] and CM [1 point vs. 0 points, HR = 1.294 (95% CI: 0.871-1.922), P = 0.202; 2 points vs. 0 points, HR = 1.782 (95% CI: 1.185-1.782), P = 0.027]. We also found that among male patients in the three groups, both ACM and CM rates differed (P = 0.006 and P = 0.017, respectively). Multivariate Cox analysis showed that the ALB-dNLR score independently predicted both ACM [1 point vs. 0 points, HR = 1.237 (95% CI: 0.806-0.330), P = 0.330; 2 points vs. 0 points, HR = 1.790 (95% CI: 1.159-2.764), P = 0.009] and CM [1 point vs. 0 points HR = 1.472 (95% CI: 0.892-2.430), P = 0.130; 2 points vs. 0 points, HR = 1.792 (95% CI: 1.182-3.289), P = 0.009]. Conclusion: The ALB-dNLR score is a credible predictor for mortality in patients with CAD who have undergone PCI.

Characteristics of the Intestinal Microorganisms in Middle-Aged and Elderly Patients: Effects of Smoking.

Introduction: Smoking affects the occurrence and development of many diseases. We attempt to study the structure of intestinal flora in the middle-aged and elderly population as well as how smoking affects the intestinal flora. Methods: We collected population information, biochemical indicators, and patient feces from 188 middle-aged and elderly male patients, and their feces were tested for the 16S rRNA gene of intestinal flora. Results: We performed a cluster analysis on the intestinal structure of the included population and found that there was a significant difference in the number of smokers between each group (p = 0.011). Subsequently, the microbiological diversity analysis of current smokers and nonsmokers was carried out. The results indicated that there was a significant difference in species composition between the two groups (p = 0.029). Through the analysis on LEfSe differential bacteria, it was found that in current smoking patients, the abundances of the genus Bifidobacterium and the genus Coprobacillus were less, while the abundances of the genera Shigella, Paraprevotella, Burkholderia, Sutterella, Megamonas, and p-75-a5 under the family level of Erysipelotrichaceae were slightly high. We analyzed the correlation between the abundances of these eight different bacteria and clinical indicators. The results revealed the following: the abundance of the genus Bifidobacterium was negatively correlated with fasting blood glucose (r = -0.198, p = 0.006) and positively correlated with uric acid (r = 0.207, p = 0.004) and total bilirubin (r = 0.175, p = 0.017); Shigella bacteria were positively correlated with fasting blood glucose (r = 0.160, p = 0.028) and uric acid (r = 0.153, p = 0.036) levels; the genus Paraprevotella and BMI (r = -0.172, p = 0.018) are negatively correlated; the abundance of the genus Burkholderia was positively correlated with γ-glutamyltransferase (r = 0.146, p = 0.045) levels; Sutterella was correlated with fasting blood glucose (r = 0.143, p = 0.05) and creatinine level (r = -0.16, p = 0.027), which was positively correlated with fasting blood glucose and negatively correlated with creatinine. Conclusions: In middle-aged and elderly patients with cardiovascular disease, smoking can reduce the abundance of Bifidobacterium, while the abundances of some negative bacteria such as Burkholderia, Sutterella, and Megamonas increase.

Gut Microbiome-Based Diagnostic Model to Predict Diabetes Mellitus.

The aim of this study was to determine the diversity of intestinal microflora and its correlation with clinical parameters in diabetic patients and healthy subjects and to assess the importance of intestinal flora in patients with diabetes. Forty-four patients with diabetes were included. The control group included 47 healthy people. Their data, biochemical indicators and results from 16S rRNA sequencing of their fecal samples were collected. Compared with the healthy population, the intestinal flora of the diabetic patients was obviously abnormal. Within the diabetes group, the abundances of the genera Faecalibacterium, Prevotella, and Roseburia were higher, and the abundances of the genera Shigella and Bifidobacterium were lower. In the correlation analysis between bacteria and clinical indicators, it was found that the genera Veillonella and unclassified_Enterobacteriaceae were negatively related to blood glucose, while the genera Phascolarctobacterium, unidentified_Bacteroidales and Prevotella were significantly positively correlated with fasting blood glucose. Twelve microbial markers were detected in the random forest model, and the area under the curve (AUC) was 84.1%. This index was greater than the diagnostic effect of fasting blood glucose. This was also supported by the joint diagnostic model of microorganisms and clinical indicators. In addition, the intestinal flora significantly improved the diagnosis of diabetes. In conclusion, it can be concluded from these results that intestinal flora is essential for the occurrence and development of diabetes, which seems to be as important as blood glucose itself.Abbreviations: PCoA: principal coordinate analysis; NMDS: non econometric multidimensional scaling analysis; LEfSe: linear discriminant analysis effect size; LDA: linear discriminant analysis; POD: probability of disease; BMI: body mass index; DCA: decision curve analysis.

Gut Microbiota Characterization in Patients with Asymptomatic Hyperuricemia: probiotics increased.

Asymptomatic hyperuricemia (AH) is an early stage of gout. Emerging evidence shows that the intestinal microbiota is related to gout. However, the relationship between AH and the intestinal microbiota is poorly understood. Therefore, the aim of the current study was to explore the possible correlation between AH and intestinal flora. We compared the intestinal microbial communities of AH (45 cases) and healthy subjects (45 cases) by 16S rRNA gene sequencing and clustering analysis on the incorporated population. Intestinal-type clustering can be divided into two groups, and significant differences in the proportion of AH are found among different bowel types. Alpha diversity indices were higher in the AH group than in the control group, and beta diversity indices also showed significant differences. A total of 19 genera were found different between the AH group and the control group. Compared with the control group, some probiotics are increased in the AH population. Two groups were ranked by importance of bacteria. We found the different bacteria partially coincided with the important bacteria, and the joint diagnosis level of the important bacteria was good. Conclusion: There were significant differences in the composition of intestinal biota between AH patients and healthy subjects. Some probiotics increased in AH.