Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes: Analysis of SURPASS-AP-Combo by Different Subgroups.

INTRODUCTION: Tirzepatide is a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist. In the SURPASS-AP-Combo trial, once-weekly tirzepatide was associated with improved glycemic control and weight loss versus insulin glargine and was generally well tolerated in an Asia-Pacific, predominately Chinese, population with type 2 diabetes (T2D). This post hoc subgroup analysis of SURPASS-AP-Combo assessed the potential influence of patient baseline characteristics on the efficacy and safety of tirzepatide. METHODS: Changes from baseline to week 40 in HbA1c, body weight, fasting serum glucose (FSG), and daily glucose average from self-measured blood glucose profiles were analyzed by potential influential factors including age (< 65, ≥ 65 years), sex, baseline HbA1c (≤ 8.5, > 8.5%), body mass index (BMI) (< 25, ≥ 25 kg/m2), body weight (< 75, ≥ 75 kg), duration of diabetes (< 10, ≥ 10 years), and concomitant oral antihyperglycemic medications (metformin, metformin plus sulphonylurea). Gastrointestinal adverse events and hypoglycemia were also evaluated. RESULTS: At week 40, all tirzepatide doses were associated with reduced HbA1c, body weight, FSG, and daily glucose average from baseline in all subgroups. Greater HbA1c reductions were achieved in patients with higher baseline HbA1c across all tirzepatide doses, higher body weight with 10 mg and younger age with 15 mg tirzepatide. Greater reductions in body weight were observed in patients with higher body weight across all tirzepatide doses, lower baseline HbA1c with 5 mg and higher BMI with 5 mg tirzepatide. CONCLUSIONS: In this post hoc analysis, tirzepatide was associated with reduced blood glucose and body weight in a predominantly Chinese population with T2D across different subgroups, consistent with previous reports for tirzepatide. CLINICAL TRIAL REGISTRATION: NCT04093752.

Echocardiographic Evaluation of the Effect on Left Ventricular Function Between Left Bundle Branch Pacing and Right Ventricular Pacing.

Purpose: The purpose of this study was to assess the left ventricular function effects of permanent left bundle branch pacing (LBBP) versus traditional right ventricular pacing (RVP). Patients and Methods: Consecutive patients receiving pacemaker implantation were included and divided into left bundle branch block (LBBB) group and right ventricular pacing (RVP) group. Baseline characteristics were collected, and they received 1-year follow-up. Electrocardiogram (ECG) characteristics and pacing parameters were assessed before and after implantation. Cardiac function parameters such as left ventricular ejection fraction (LVEF) and tricuspid regurgitation (TR) were recorded and compared. Results: Of 78 patients included, 45 patients received LBBP (mean age, 72.7 ± 12.2 years; male, 55.6%) and 33 patients underwent RVP (mean age 72.9 ± 11.8 years; male, 63.6%). The pacing parameters were satisfactory during the implantation and remained stable during mid-term follow-up. During the follow-up period, LBBP patients had a greater decrease in LVEDD and LVESD. The TR in the LBBP group was significantly improved as compared to the RVP group (P=0.016). Conclusion: Permanent LBBP achieves favorable cardiac hemodynamic effects with good stability and safety. LBBP may reduce severe TR at 1-year follow-up, and LBBP may be an option for patients with severe TR.

Near-infrared rhodol dyes bearing salicylaldehyde moieties for ratiometric pH sensing in live cells during mitophagy and under hypoxia conditions.

We describe a simple but efficient approach to make fluorescent probes A and B based on rhodol dyes incorporated with salicyaldehyde moiety for monitoring pH changes in mitochondria under oxidative stresses and hypoxia conditions, and for tracking mitophagy processes. Probes A and B possess pKa values (pKa ≈ 6.41 and 6.83 respectively) near physiological pH and exhibit decent mitochondria-targeted capabilities, low cytotoxicity, and useful ratiometric and reversible pH responses, which make the probes appropriate for monitoring pH fluctuations of mitochondria in living cells with built-in calibration feature for quantitative analysis. The probes have been effectively useful for the ratiometric determination of pH variations of mitochondria under the stimuli of carbonyl cyanide-4(trifluoromethoxy)phenylhydrazone (FCCP), hydrogen peroxide (H2O2), and N-acetyl cysteine (NAC), and during mitophagy triggered by cell nutrient deprivation, and under hypoxia conditions with cobalt chloride (CoCl2) treatment in living cells. In addition, probe A was efficient in visualizing pH changes in the larvae of fruit flies.

Prediction of Fetal Growth Restriction for Fetal Umbilical Arterial/Venous Blood Flow Index Evaluated by Ultrasonic Doppler under Intelligent Algorithm.

The empirical wavelet transform (EWT) algorithm was applied in ultrasound to explore the predictive value for fetal growth restriction (FGR) in fetal arteriovenous indexes. 142 pregnant women who received prenatal ultrasonic examination and delivered were selected. They were classified into control group and FGR group. There were 102 patients with normal pregnancy in the control group, and 40 patients with delayed fetal growth in the FGR group. The extended triple collocation (ETC) algorithm was employed to divide the Fourier spectrum of signals adaptively, and the constructed small filter banks were classified into corresponding intervals. The instantaneous frequency was analyzed, and the arterial blood flow indexes of the two groups were compared. The results showed that the time-frequency analysis method under EWT had lower normalization error and higher accuracy. The inner diameter and cross-sectional area of FGR were remarkably smaller than those of the control group, and the differences were statistically significant (P < 0.05). There were no significant differences in mean blood flow and mean blood velocity between the control group and FGR group (P > 0.05). The arterial blood flow parameters of the systolic flow velocity (VS) and the diastolic flow velocity (VD) in the FGR group were notably lower than those in the control group, and the differences were significant (P < 0.05). In conclusion, the frequency principal component extracted by EWT algorithm was less disturbed by noise, which could accurately and effectively evaluate fetal arteriovenous blood flow indexes and predict FGR.

Clinical implication of quantitative flow ratio to predict clinical events after drug-coated balloon angioplasty in patients with in-stent restenosis.

BACKGROUND: The association between the quantitative flow ratio (QFR) and adverse events after drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR) lesions has not been investigated. HYPOTHESIS: Post-procedural QFR is related to adverse events in patients undergoing DCB angioplasty for ISR lesions. METHODS: This retrospective study included data from patients undergoing DCB angioplasty for drug-eluting stent (DES) ISR between January 2016 and February 2019. The QFR was measured at baseline and after DCB angioplasty. The endpoint was the vessel-oriented composite endpoint (VOCE), defined as a composite of cardiac death, vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. RESULTS: Overall, 177 patients with 185 DES-ISR lesions were included. During 1-year follow-up, 27 VOCEs occurred in 26 patients. The area under curve (AUC) of the post-procedural QFR was statistically greater than that of the in-stent percent diameter stenosis (0.77, 95% confidence interval [CI] 0.67-0.87 vs. 0.64, 95% CI 0.53-0.75; p = .032). Final QFR cutoff of 0.94 has the best predictive accuracy for VOCE. A QFR > 0.94 was associated with a lower risk of VOCE compared to a QFR ≤ 0.94 (log-rank test, p < .0001). Survival analysis using the multivariable Cox model showed that a post-procedural QFR ≤ 0.94 was an independent predictor of 1-year VOCE (hazard ratio 6.53, 95% CI 2.70-15.8, p < .001). CONCLUSIONS: A lower QFR value was associated with worse clinical outcomes at 1 year after DCB angioplasty for DES-ISR.

A predictive nomogram of bleeding risk in patients with atrial fibrillation after drug-eluting stent implantation.

BACKGROUND: The use of anticoagulants and antiplatelet therapies is associated with a higher risk of bleeding in atrial fibrillation (AF) patients after percutaneous coronary intervention, especially after stent implantation. However, no accurate bleeding risk prediction tool has been developed for these patients. The aim of this study was thus to establish a bleeding risk prediction model (predictive nomogram) for patients with AF after stent implantation. METHODS: Construction of the predictive nomogram was based on a retrospective study, which enrolled 943 AF patients who underwent drug-eluting stent implantation between May 2012 and September 2016. A range of factors, including demographics, comorbidities, medication strategies, arterial access, and laboratory tests, were collected as baseline data. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis were used to identify the key clinical features for construction of the predictive nomogram. The concordance index (C-index) and internal validation were used to evaluate the efficacy of the nomogram. RESULTS: Of the 943 AF patients that underwent stent implantation, the occurrence of bleeding events was 8.2% (77 out of 943). Key predictors included the number of antiplatelet drugs, peptic ulcer, cerebral infarction, type 2 diabetes, thrombocytopenia, anemia, prior myocardial infarction, sex (male), use of anticoagulant drugs, liver dysfunction, hypertension, and acute myocardial infarction. These predictors were used to construct the nomogram. The C-index for the prediction of bleeding risk by the nomogram was 0.841 (95% CI: 0.79-0.89), which indicated good discrimination and calibration. The C-index of internal validation was 0.795, which demonstrated good efficacy of the model. CONCLUSIONS: This study suggests that our novel nomogram can accurately predict bleeding risk in AF patients after stent implantation during hospitalization, thereby helping to avoid complications. The nomogram may also be helpful for the creation of individualized post-discharge medication strategies.

Clinical implication of QFR in patients with ST-segment elevation myocardial infarction after drug-eluting stent implantation.

The feasibility and prognostic value of quantitative flow ratio (QFR) after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients have not been assessed. The aim of this study was to investigate the prognostic utility of post-PCI QFR to predict outcomes in STEMI and determine the influence of functional results, in both culprit and nonculprit lesions, after PCI. Patients undergoing PCI of culprit lesions and receiving staged procedures of nonculprit lesions after 7 days were enrolled from 2 centers and underwent post-PCI QFR. The primary outcome was the vessel-oriented composite endpoints (VOCEs), defined as vessel-related cardiovascular death, vessel-related myocardial infarction, and target vessel revascularization. Four hundred fifteen vessels (186 culprit lesions and 219 nonculprit lesions) in 186 patients were analyzed. Measured at staged PCI, the post-PCI QFR of culprit lesions was significantly lower than that of nonculprit lesions (0.92 ± 0.10 versus 0.95 ± 0.08, p < 0.001). The multivariable model demonstrated that low post-PCI QFR was an independent predictor of 2-year VOCE (20.8% versus 5.7%; hazard ratio 2.718; 95% CI 1.347-5.486; p = 0.005). In STEMI patients with a low angiography-derived index of microcirculatory resistance (≤ 40U), a good correlation and agreement between post-PCI QFR value of culprit lesions at primary and staged procedures (r = 0.942; mean difference: - 0.0017 [- 0.074 to 0.070]) was identified. In conclusion, culprit lesions suffered from suboptimal functional results more frequently compared to nonculprit lesions after PCI in STEMI patients. Low post-PCI QFR was associated with subsequent adverse clinical outcomes. After stenting, culprit lesions may feasibly be assessed through QFR without significant microvascular dysfunction.

MiR-125b participates in the occurrence of preeclampsia by regulating the migration and invasion of extravillous trophoblastic cells through STAT3 signaling pathway.

Preeclampsia (PE) is a major risk factor for maternal and fetal mortality. Studies showed that microRNAs (miRNAs) play important roles in PE, and are closely related to extra-villous trophoblastic proliferation and invasion. The current study determined miR-125b expression in PE patients, and explored the role of miR-125b in the occurrence and development of PE and its possible mechanism, aiming to provide a novel basis for the diagnosis and treatment of PE. The level of miR-125b in serum derived from pregnant women was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, invasion and migration of HTR-8/SVneo were determined by Cell Counting Kit-8 (CCK-8), Transwell and scratch assay, respectively. The target gene of miR-125b was predicted by Targetscan, and verified by luciferase reporter assay. The expressions of related proteins were determined by Western Blotting. The miR-125b level in the serum of PE patients was up-regulated as compared with normal pregnant women, and high level of miR-125b reduced cell proliferation, inhibited invasion and migration of HTR-8/SVneo as well as the expressions of STAT3, p-STAT3 and SOCS3, while low level of miR-125b produced the opposite results. STAT3 was predicted as the target gene of miR-125b, and the high level of miR-125b inhibited STAT3 signaling pathway. High expression of miR-125b may be involved in the occurrence of PE through inhibiting STAT3 pathway to inhibit the migration and invasion of extra-villous trophoblastic cells.

Quantitative flow ratio-guided residual functional SYNTAX score for risk assessment in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Functional incomplete revascularisation (IR) is associated with a higher risk of major adverse cardiac events (MACE) during long-term follow-up in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). AIMS: This study aimed to investigate the prognostic ability of quantitative flow ratio (QFR)-guided residual functional SYNTAX score (Q-rFSS) and functional IR in STEMI patients undergoing PCI. METHODS: In total, 354 consecutive STEMI patients who successfully underwent PCI were included. Q-rFSS was defined as residual SYNTAX score (rSS) measured only in vessels with QFR ≤0.8. The primary outcome was MACE (a composite of all-cause mortality, myocardial infarction, and ischaemia-driven revascularisation) at 2 years. RESULTS: At two-year follow-up, functional IR (Q-rFSS ≥1) showed significantly higher risk for MACE than functional complete revascularisation (CR) (Q-rFSS=0) (functional IR vs CR, 22.0% vs 7.4%; hazard ratio [HR] 3.21; 95% confidence interval [Cl]: 1.74 to 5.91; p<0.001). The area under the curve (AUC) of Q-rFSS (0.738, 95% CI: 0.659 to 0.817) was significantly greater than that of rSS (0.648, 95% CI: 0.547 to 0.749). The C-statistic for MACE also increased after the addition of Q-rFSS to the clinical risk factors. Q-rFSS significantly improved risk classification compared with rSS (net reclassification improvement 0.439, 95% CI: 0.201 to 0.548; p<0.001). CONCLUSIONS: Functional IR is associated with higher risk of MACE during long-term follow-up in STEMI patients undergoing PCI. Q-rFSS has a better prognostic ability for the risk of MACE.

Association of stress hyperglycemia ratio with intracoronary thrombus burden in diabetic patients with ST-segment elevation myocardial infarction.

BACKGROUND: Large intracoronary thrombus burden is not rare during primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Stress hyperglycemia is independently associated with poor prognosis. However, the underlying relationship between stress hyperglycemia and thrombus burden remains unknown. This study aims to investigate the association of stress hyperglycemia, evaluated by the combination of acute and chronic glycemic levels, with intracoronary thrombus burden in diabetic patients with STEMI. METHODS: We enrolled 227 consecutive diabetic patients with STEMI undergoing primary PCI within 12 hours after symptom onset. Stress hyperglycemia was estimated using the stress hyperglycemia ratio (SHR), which was calculated as admission glycemia divided by estimated average glucose derived from glycosylated hemoglobin. Based on reclassified angiographic thrombolysis in myocardial infarction (TIMI) thrombus grades, patients were divided into small thrombus burden (STB) group (TIMI thrombus grades <4) and large thrombus burden (LTB) group (TIMI thrombus grades 4 or 5). RESULTS: Of the entire study population, 77 (33.9%) patients were categorized as LTB group, whereas 150 (66.1%) patients presented with STB. The mean age was 64.1 years, and 80.6% of the patients were male. The SHR levels were significantly higher in patients with LTB than in those with STB [1.31; interquartile range (IQR): 1.13-1.48 versus 1.11; IQR: 0.96-1.32; P<0.001]. The predictive performance of SHR for LTB was moderate (area under the curve: 0.669; 95% confidence interval: 0.604-0.730; P<0.001), with the best cut-off value 1.19 (sensitivity 71.4%, specificity 64.7%). The incidence of LTB with SHR ≥1.19 was significantly higher compared with SHR <1.19 (50.9% versus 18.5%; P<0.001). Based on the multivariable logistic regression analysis, the high SHR (≥1.19) was found to be an independent predictor of LTB following adjustment for baseline clinical confounders. CONCLUSIONS: A high SHR value was independently associated with large thrombus burden and has a better predictive value than glycemia at admission in diabetic patients with STEMI undergoing primary PCI. Stress hyperglycemia may play an important role on the intracoronary thrombus formation.

MicroRNA-92a Inhibits the Cell Viability and Metastasis of Prostate Cancer by Targeting SOX4.

MicroRNAs (miRNAs) was confirmed to play an active role in the pathogenesis of prostate cancer (PCa). The expression and biological function for miR-92a in PCa remains unknown. In this study, we demonstrated that miR-92a expression was decreased in PCa tissues and cells lines. Overexpression miR-92a inhibited the cell viability, migration and invasion of PC-3 while inhibition of miR-92a led to opposite alteration of cell viability and metastasis of DU-145 cells. Mechanically, we confirmed that miR-92a interacted with 3'-UTR of SOX4 through the complementary sequences by luciferase reporter assay. qRT-PCR and western blot confirmed that miR-92a inhibited the expression of SOX4 in PCa cells. Moreover, overexpression of SOX4 reversed the inhibitory effects of miR-92a overexpression on PC-3 cell viability, migration and invasion, while knockdown of SOX4 suppressed the promoting effects of miR-92a knockdown on these biological functions of DU-145 cells. Therefore, our study indicates that miR-92a inhibits the growth and metastasis of prostate cancer by targeting SOX4, and can potentially serve as a biomarker and treatment target for PCa patients.

Pharmacological inhibition of CXCR2 alleviates neuropathic pain by inactivating microglia in a rat L5 spinal nerve ligation model.

Peripheral nerve injury (PNI)-induced neuropathic pain is a prevalent and severe clinical problem. It has been shown that microglia-mediated neuroinflammation plays a crucial role in neuropathic pain. The present study investigated the abnormal expression of C-X-C motif chemokine receptor type 2 (CXCR2) in a rat L5 spinal nerve ligation (SNL) model and evaluated the role of SB225002, a specific antagonist of CXCR2, in repressing neuroinflammation and neuropathic pain. It was found that CXCR2 expression was significantly upregulated in the dorsal horn of L5-SNL rats compared with sham control. Moreover, CXCR2 expression was increased in spinal microglia of rats after L5-SNL. Based on these results, the present study further examined whether pharmacological inhibition of CXCR2 suppressed microglial activation and neuropathic pain. It was demonstrated that SB225002 treatment inhibited L5-SNL-induced microglia proliferation and activation. Furthermore, SB225002 also significantly suppressed the L5-SNL-induced pro-inflammatory response, as indicated by decreased production of tumor necrosis factor-α, interleukin (IL)-1ß and IL-6 in spinal cord tissues. The results indicated that SB225002 also significantly inhibited microglial cell viability and lipopolysaccharide-induced production of pro-inflammatory cytokines in cultured microglia. Functionally, SB225002 treatment effectively repressed mechanical and cold hypersensitivity after peripheral nerve injury. Collectively, the present results suggested that pharmacological inhibition of CXCR2 by SB225002 suppressed L5-SNL-induced neuroinflammation and neuropathic pain, thus offering a potential therapeutic strategy for neuropathic pain treatment.

MiR-301a Promotes Cell Proliferation by Repressing PTEN in Renal Cell Carcinoma.

OBJECTIVE: Renal cell carcinoma (RCC) displays an increasing incidence and mortality rate worldwide in recent years. More and more evidence demonstrated microRNAs function as positive or negative regulatory factors in many cancers, while the role of miR-301a in RCC is still unclear. MATERIAL AND METHODS: The expression and clinical significance of miR-301a were assessed via bioinformatic software on open microarray datasets of the Cancer Genome Atlas (TCGA) and then confirmed by quantitative real-time PCR (qRT-PCR) in RCC cell lines. Loss of function assays were performed in RCC cell lines both in vitro and in vivo. Cell Counting Kit-8 (CCK-8), flow cytometry, luciferase reporter assays, Western blotting, and immunohistochemistry were employed to explore the mechanisms of the effect of miR-301a on RCC. RESULTS: By analyzing RCC clinical specimens and cell lines, we found a uniform increased miR-301a in expression in comparison with normal renal tissue or normal human proximal tubule epithelial cell line (HK-2). In addition, miR-301a upregulation correlated advanced stage and poor prognosis of clear cell RCC (ccRCC). Anti-miR-301a could inhibit growth and cell cycle G1/S transition in RCC cell lines. Moreover, we found that PTEN was identified as a direct target of miR-301a that might partially interrupt miR-301a-induced G1/S transition. Importantly, nude-mouse models revealed that knockdown of miR-301a delayed tumor growth. CONCLUSION: These results indicate that miR-301a functions as a tumor-promoting miRNA through regulating PTEN expression, representing a novel therapeutic target for RCC.

Selenium nanoparticles (SeNPs) have potent antitumor activity against prostate cancer cells through the upregulation of miR-16.

OBJECTIVES: This research aimed to examine the antitumor mechanisms of selenium nanoparticles (SeNPs) specifically against prostate cancers. METHODS: The antitumor activities of SeNPs against cancer cells were determined via MTT assay. The cell cycle was determined by detecting the DNA content, and apoptosis was determined via annexin V-Fluos staining kit. The microRNA expressions in cancer cells were analyzed via microarray and qRT-PCR. The potential targets of miR-16 were identified via luciferase analysis and mRNA expression determination. miR-16 functions in cancer cells were explored via the transient transfection of miR-16 mimic or inhibitor. RESULTS: SeNPs were most potent in prostate cancer cells, regardless of whether or not they were androgen-dependent. Furthermore, SeNP stimulation can induce cell cycle arrest and the apoptosis enhancement of prostate cancer cells. Microarray and molecular mechanism studies demonstrated that miR-16 could directly target cyclin D1 and BCL-2 to mediate SeNP apoptosis enhancement. Results show that the serum selenium levels positively correlate with miR-16 expressions, and they correlate with the overall and disease-free survival rates. CONCLUSION: These results signify the cytotoxic potential of SeNPs in prostate cancer treatment.

Coronary Artery Aneurysm Differs From Coronary Artery Ectasia: Angiographic Characteristics and Cardiovascular Risk Factor Analysis in Patients Referred for Coronary Angiography.

The differences in angiographic characteristics and cardiovascular (CV) risk factors between coronary artery aneurysm (CAA) and coronary artery ectasia (CAE) have not been compared systematically. Of 10 876 patients undergoing coronary angiography, patients with CAA (n = 85) and CAE (n = 51) were screened. The prevalence of CAA was greater than that of CAE ( P < .05). The right coronary artery was the most involved (70.6%) in CAE compared with left circumflex (52.9%) and left anterior descending (41.2%). Coronary artery aneurysm coexisted with coronary artery disease (CAD) more frequently than CAE ( P = .002), and the modified Gensini score of CAA was also higher than that of CAE ( P < .001). The average maximum diameter was smaller, and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count was lower in CAA than CAE in all 3 coronary arteries ( P < .001). Multivariate analysis showed that hyperlipidemia ( P = .02), smoking ( P = .04), and family history of CAD ( P = .02) were the independent variables most strongly associated with CAA, but not CAE. This study suggests that there are significant differences in coronary angiographic characteristics and CV risk factors between CAA and CAE.

Relationship between clopidogrel-related polymorphisms and variable platelet reactivity at 1 year: A cohort study from Han Chinese.

BACKGROUND: This study was designed to investigate the effect of clopidogrel-related gene polymorphisms on platelet reactivity and clinical outcome in Chinese Han patients. MATERIALS AND METHODS: Three hundred and thirty-six percutaneous coronary intervention - treated patients were recruited and followed for 1 year. Blood samples were collected from all patients for DNA genotyping. The platelet reactivity unit was measured by the VerifyNow technique. The CYP2C19*2, CYP2C19*3, CYP2C19*17, ATP-binding cassette subfamily B member 1, ITGB3, CYP2C9*3, CYP2B6*9, and P2Y12 alleles were assessed. RESULTS: The clinical endpoints were related to previous heart disease history (11.90% vs. 28.57%, P = 0.017), stroke (12.24% vs. 16.67%, P = 0.039), and diabetes (27.55% vs. 52.38%, P = 0.047). High on-treatment platelet reactivity (HTPR) was frequent in advanced age (P = 0.019), male gender (P = 0.016), hypertension (P = 0.033), and chronic renal failure (P = 0.040). There were more endpoints in the CYP2C19*2 and P2Y12 mutant carriers (76.19% vs. 43.20%, P < 0.001; 50.00% vs. 35.71%, P = 0.001, respectively), whereas fewer in the CYP2C19*17 mutant carriers (11.90% vs. 56.46%, P = 0.001). CYP2C19*2 and P2Y12 polymorphism manifested HTPR (194.25 ± 45.91 vs. 151.38 ± 58.14, P < 0.001; 180.33 ± 67.25 vs. 161.89 ± 56.49, P = 0.008, respectively), whereas CYP2C19*17 mutant improved platelet reactivity (97.17 ± 45.38 vs. 169.08 ± 57.15, P = 0.003). However, there were no further cardiovascular deaths in endpoint patients. CONCLUSION: In Han Chinese people of mainland China, clopidogrel-related gene polymorphisms are related to variable platelet reactivity after clopidogrel maintenance dosing, which influences major adverse cardiovascular events, without an effect on cardiac death.