黎嘉雯
中国医学科学院阜外医院
BACKGROUND:Coronary artery calcification (CAC) is a highly specific marker of atherosclerosis. Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are the therapeutic targets of ezetimibe and statins, respectively, which are important for the progression of atherosclerosis. However, CAC's genetic susceptibility with above targets is still unknown. We aimed to investigate the association of NPC1L1 and HMGCR gene polymorphisms with CAC in patients with premature triple-vessel disease (PTVD).METHODS:Four single nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, rs2073547) of NPC1L1, and three SNPs (rs12916, rs2303151, rs4629571) of HMGCR were genotyped in 872 PTVD patients. According to the coronary angiography results, patients were divided into low-degree CAC group and high-degree CAC group.RESULTS:A total of 872 PTVD patients (mean age, 47.71 ± 6.12; male, 72.8%) were finally included for analysis. Multivariate logistic regression analysis showed no significant association between the SNPs of NPC1L1 and HMGCR genes and high-degree CAC in the total population (P > 0.05). Subgroup analysis by gender revealed that the variant genotype (TT/CT) of rs4720470 on NPC1L1 gene was associated with increased risk for high-degree CAC in male patients only (OR = 1.505, 95% CI: 1.008-2.249, P = 0.046) in dominant model, but no significant association was found in female population, other SNPs of NPC1L1 and HMGCR genes (all P > 0.05).CONCLUSIONS:We reported for the first time that the rs4720470 on NPC1L1 gene was associated with high-degree CAC in male patients with PTVD. In the future, whether therapies related to this target could reduce CAC and cardiovascular events deserves further investigation.
BMC medical genomics 2024
BACKGROUND AND AIM:Remnant cholesterol (RC) has garnered increasing attention recently due to its association with adverse cardiovascular events. However, the relationship between RC levels and inflammation remains unclear. The goal of this study was to investigate and compare the predictive value of multiple inflammatory biomarkers for high RC in patients with percutaneous coronary intervention (PCI).METHODS AND RESULTS:Initially, a total of 10,724 consecutive individuals hospitalized for PCI at Fu Wai Hospital in 2013 were enrolled. Finally, 9983 patients receiving dual antiplatelet therapy and drug-eluting stent were selected for analysis. The inflammatory biomarkers included high-sensitivity C-reactive protein (hs-CRP), hs-CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lymphocyte-to-hs-CRP ratio (LCR), and systemic immune-inflammation index (SII). Patients were divided into higher RC and lower RC groups based on the median RC level. Multivariate logistic regression showed that hs-CRP (OR per SD: 1.254), CAR (OR per SD: 1.245), PLR (OR per SD: 1.139), and SII (OR per SD: 1.077) were associated with high RC (≥median), while LCR (OR per SD: 0.792) was associated with low RC ( Nutrition, metabolism, and cardiovascular diseases : NMCD 2024
BACKGROUND:Patients with diabetes and coronary artery disease have a higher risk of bleeding and thrombotic events. However, data on the safety and efficacy of bivalirudin in these patients undergoing elective percutaneous coronary intervention (PCI) are lacking.METHODS:1152 patients undergoing elective PCI anticoagulated with bivalirudin and 10,250 patients anticoagulated with unfractionated heparin (UFH) (with or without glycoprotein IIb/IIIa inhibitors [GPI]) were performed propensity-score matching method. The thrombotic endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The bleeding endpoint was according to the Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding.RESULTS:Finally, 376 (bivalirudin group) and 878 (UFH group) patients with type 2 diabetes (T2D) were enrolled. After one-year follow-up, there were 130 (10.4%) MACCE and 27 (2.2%) bleeding events occurred. Multivariate COX regression analysis showed no significant difference for MACCE between bivalirudin group and UFH group (P > 0.05). Further analysis showed that there was a reduction in the risk of myocardial infarction (MI) between two groups (Hazard ratio [HR] = 0.199, 95% confidence interval [CI]: 0.047-0.845, P = 0.029), but not in the risk of death, revascularization, stent thrombosis or stroke (all P > 0.05). As for BARC 2, 3 or 5 bleeding, no significant difference was found between two groups (P > 0.05).CONCLUSIONS:Although diabetes is considered a high-risk factor for poor prognosis, compared with UFH (with or without GPI), bivalirudin did not increase the risk of MACCE and even decreased the risk of MI in patients with T2D undergoing elective PCI, while the risk of bleeding was similar between two groups.
Diabetes & metabolic syndrome 2023
To reduce cardiovascular risk in patients with established coronary heart disease, the present study investigated the combined effect of D-dimer, high-sensitivity C-reactive protein (hs-CRP), and lipoprotein(a) [Lp(a)] on long-term cardiovascular outcomes from the perspectives of thrombosis, inflammation, and lipid risk simultaneously. Consecutive 10,724 patients with percutaneous coronary intervention (PCI) were enrolled throughout 2013. Over a median follow-up of 5.1 years, each individual elevation of D-dimer, hs-CRP, and Lp(a) was associated with poor ischemic outcomes but not bleeding. Concurrent high D-dimer, hs-CRP, and Lp(a) had even greater risks of all-cause death (hazard ratio [HR] 2.714, 95% confidence interval [CI] 1.742-4.231) and cardiac death (HR 4.152, 95% CI 2.207-7.812) and had incremental value beyond the traditional risk factors model. Concurrent high D-dimer, hs-CRP, and Lp(a) levels had a synergistic effect on adverse 5-year ischemic outcomes, highlighting that the potential utility of simultaneous assessment of multiple cardiovascular risk biomarkers may help to identify high-risk patients after PCI.
iScience 2023
AIM:The dual-antiplatelet therapy (DAPT) score is recommended for predicting the risk of ischemia and bleeding for patients undergoing percutaneous coronary intervention (PCI). This study aimed to investigate the long-term prognostic value of the DAPT score in older PCI patients.METHODS:This study enrolled 10,724 consecutive patients who underwent PCI from January 2013 to December 2013 in Fu Wai hospital, among whom 2,981 (27.8%) were aged ≥ 65 years. The ischemic endpoint was major adverse cardiovascular and cerebrovascular events (MACCE, including myocardial infarction, all-cause death, and stroke). The bleeding endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding.RESULTS:After a 5-year follow-up, 256 (12.0%) MACCEs and 53 (2.5%) BARC 2, 3, or 5 bleeding occurred. The patients were divided into two groups according to the DAPT score: the low-score (＜2, n=1,646) and high-score (≥ 2, n=485) group. Multivariate Cox regression revealed that the risk of MACCE was similar between the two groups [hazard ratio (HR): 1.214, 95% confidence interval (CI): 0.916-1.609, P=0.178], whereas the risk of bleeding was significantly higher in the high-score group than in the low-score group (HR: 2.447, 95% CI: 1.407-4.257, P=0.002). The DAPT score did not show prognostic value in MACCE [area under the receiver operating characteristic curve (AUROC), 0.534; 95% CI: 0.496-0.572, P=0.079]; however, it demonstrated a certain prognostic value in BARC 2, 3, or 5 bleeding (AUROC, 0.646; 95% CI: 0.573-0.719, P＜0.001).CONCLUSION:This study suggested that in older PCI patients, the DAPT score did not show predictive value for MACCE; however, it had a certain predictive value for 5-year BARC 2, 3, or 5 bleeding.
Journal of atherosclerosis and thrombosis 2023
BACKGROUND:Patients with coronary artery disease (CAD) combined with diabetes have a higher risk of cardiovascular events, and high-sensitivity C-reactive protein (hs-CRP)-to-albumin ratio (CAR) is a novel inflammatory biomarker. However, whether the CAR can identify high-risk patients with CAD and type 2 diabetes (T2DM) remains unclear.METHODS:The present study was based on a prospective and observational cohort with 10,724 individuals who undergo percutaneous coronary intervention (PCI) in Fu Wai Hospital throughout the year 2013 consecutively enrolled. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. CAR was calculated with the formula: hs-CRP (mg/L)/albumin (g/L). According to the optimal cut-off value of CAR for all-cause mortality, patients were divided into higher CAR (CAR-H) and lower CAR (CAR-L) groups.RESULTS:A total of 2755 patients with T2DM who underwent PCI and received dual antiplatelet therapy were finally enrolled. During a follow-up of 5 years (interquartile range: 5.0-5.1 years), 126 (4.6%) all-cause mortalities and 74 (2.7%) cardiac mortalities were recorded. In the multivariable Cox model, CAR-H was associated with a higher risk of all-cause mortality (hazard ratio [HR]: 1.634, 95% confidence interval [CI] 1.121-2.380, p = 0.011) and cardiac mortality (HR: 1.733, 95% CI 1.059-2.835, p = 0.029) compared with CAR-L. When comparing the predictive value, CAR was superior to hs-CRP for all-cause mortality (area under the curve [AUC] 0.588 vs. 0.580, p = 0.002) and cardiac mortality (AUC 0.602 vs. 0.593, p = 0.004).CONCLUSION:In this real-world cohort study, a higher level of CAR was associated with worse 5-year outcomes among diabetic patients with PCI.
Diabetology & metabolic syndrome 2023
BACKGROUND:To investigate the association of HMGCR and NPC1L1 gene polymorphisms with residual cholesterol risk (RCR) in patients with premature triple-vessel disease (PTVD).METHODS:Three SNPs within HMGCR including rs12916, rs2303151, and rs4629571, and four SNPs within NPC1L1 including rs11763759, rs4720470, rs2072183, and rs2073547 were genotyped. RCR was defined as achieved low-density lipoprotein cholesterol (LDL-C) concentrations after statins higher than 1.8 mmol/L (70 mg/dL).RESULTS:Finally, a total of 609 PTVD patients treated with moderate-intensity statins were included who were divided into two groups: non-RCR group (n = 88) and RCR group (n = 521) according to LDL-C concentrations. Multivariate logistic regression showed the homozygotes for the minor allele of rs12916 within HMGCR gene (CC) were associated with a 2.08 times higher risk of RCR in recessive model [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.16-3.75]. In codominant model, the individuals homozygous for the minor allele of rs12916 (CC) were associated with a 2.26 times higher risk of RCR (OR: 2.26, 95% CI: 1.16-4.43) while the heterozygous individuals (CT) were not, compared with the individuals homozygous for the major allele of rs12916 (TT). There was no significant association between the SNPs within NPC1L1 gene and RCR in various models.CONCLUSIONS:We first reported that the variant homozygous CC of rs12916 within HMGCR gene may incur a significantly higher risk of RCR in PTVD patients treated with statins, providing new insights into early individualized guidance of precise lipid-lowering treatment.
BMC cardiovascular disorders 2023
This study was aimed to investigate the association between remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) concentrations and long-term bleeding. A total of 10,724 consecutive patients who underwent percutaneous coronary intervention in 2013 were prospectively enrolled. During a median follow-up of 5.1 years, 411 bleeding events and 42 intracranial hemorrhages (ICH) were recorded. The findings revealed that lower RC concentrations were independently associated with an increased risk of long-term bleeding events (continuous RC hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.26-0.85; Q4 vs. Q1 HR: 0.66, 95% CI: 0.45-0.98), whereas lower LDL-C concentrations did not show a similar association. Additionally, a non-linear relationship was observed between RC concentrations and the risk of ICH (P for non-linear trend = 0.014), but no such relationship was found for LDL-C concentrations. These results provided insights into the safety of LDL-C-lowering therapy and emphasized the significance of RC concentrations in lipid management.
iScience 2023
BACKGROUND:Coronary heart disease and diabetes are highly interrelated and complex diseases. We proposed to investigate the association of genetic polymorphisms of the lipoprotein important regulatory genes Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with premature triple-vessel coronary disease (PTVD) with diabetes, blood glucose and body mass index.METHODS:Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183 and rs2073547) of NPC1L1 and three SNPs (rs12916, rs2303151 and rs4629571) of HMGCR were genotyped in 872 PTVD patients.RESULTS:After performing logistic regression analysis adjusted for age and sex, rs2303151 of HMGCR was related to the risk of diabetes in the dominance model (odds ratio = 1.35, 95% confidence interval = 1.01-1.80, p = 0.04). However, the four SNPs of NPC1L1 were not associated with the risk of diabetes. Further analyses showed that neither the above SNPs of NPC1L1, nor the SNPs of HMGCR were related to blood glucose and body mass index (all p > 0.05).CONCLUSIONS:We report that rs2303151 is a novel polymorphism of the HMGCR gene related to the risk of diabetes in PTVD patients, which suggests HMGCR may be a potential common targeted pathogenic pathways between coronary heart disease and diabetes.
The journal of gene medicine 2022
Background: Patients with diabetes mellitus (DM) are considered to increase the risk of thrombosis and bleeding. However, whether DM is an independent risk factor for events in patients anticoagulated with bivalirudin during elective percutaneous coronary intervention (PCI) is not clear. Methods: Patients anticoagulated with bivalirudin during elective PCI from January 2017 to August 2018 in 3 centers were enrolled. The primary endpoint of thrombotic events was major adverse cardiac and cerebrovascular events (MACCE, including all-cause death, myocardial infarction, ischemic revascularization, stent thrombosis, and stroke); the primary endpoint of bleeding events was Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding. Results: 1152 patients were finally enrolled. After one-year follow-up, 89 (7.7%) MACCE and 21 (1.8%) BARC 2, 3 or 5 bleeding occurred. Multivariate Cox regression analysis showed DM was not an independent risk factor for MACCE (hazard ratio [HR]: 1.029, 95% confidence interval [CI]: 0.674-1.573, P = .893), but peripheral artery disease (PAD) history (HR: 2.200, 95%CI: 1.290-3.751, P = .004) was an independent risk factor for MACCE. DM was not an independent risk factor for BARC 2, 3 or 5 bleeding (HR: 0.732, 95%CI: 0.293-1.831, P = .505), but PAD history (HR: 3.029, 95%CI: 1.102-8.332, P = .032) and low hemoglobin level (HR = 0.972, 95%CI: 0.947-0.998, P = .036) were independent risk factors for BARC 2, 3 or 5 bleeding. Conclusions: DM was not an independent risk factor for one-year thrombotic and bleeding events in patients anticoagulated with bivalirudin during elective PCI. More attention should be paid to PAD history and hemoglobin level to identify high-risk patients.
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 2022
