Predictive Value of Plasma PCSK9 Levels for Degree of Atherosclerosis and Major Adverse Cardiovascular and Cerebrovascular Events in Older Adult Patients with Non-Alcoholic Fatty Liver Disease.

Purpose: This study investigated the influence of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) levels on the degree of atherosclerosis and major adverse cardiovascular and cerebrovascular events (MACCE) in older adults with non-alcoholic fatty liver disease. Methods: The degree of atherosclerosis severity was assessed by the standard Gensini score quartile method. According to the degree of atherosclerosis, patients were divided into mild (0-24 points; n=84), moderate (25-53 points; n=86), and severe groups (≥54 points; n=84) and then categorized as MACCE (n=30) or non-MACCE (n=224) according to 6-month follow-up data. The patients' age, sex, smoking history, medical history, and early morning fasting venous blood, for measuring biochemical indexes, were collected. Clinical data were compared between groups and the relationship between Gensini scores and PCSK9 was evaluated. Results: Compared with the mild group, the moderate and severe groups had higher high-sensitivity C-reactive protein(hs-CRP), PCSK9, triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a)[Lp(a)] levels and lower high-density lipoprotein cholesterol(HDL-C) levels (all P<0.05). Moreover, PCSK9 positively correlated with Gensini scores (r=0.657, P<0.01). The MACCE and non-MACCE groups had significantly different ages, statin use, Gensini scores, PCSK9, and LDL-C (all P<0.05). Multi-factorial Cox risk regression analysis showed the Gensini score (HR=1.018, 95% CI: 1.006~1.029) and PCSK9 (HR=1.147, 95% CI: 1.038~1.287) were independent risk factors for MACCE. Conclusion: The Gensini score and PCSK9 levels can be used as predictive indicators for the degree of illness and occurrence of MACCE in older NAFLD patients.

Effects of early PCSK9 inhibitor application on inflammation levels and microcirculatory function after PCI in patients with NSTE-ACS.

OBJECTIVE: To investigate inflammation levels and microcirculatory function following the early application of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor after percutaneous coronary intervention (PCI) in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS). METHODS: This is a retrospective study. Between December 2019 and December 2021, 120 patients with NSTE-ACS admitted to the People's Hospital of Henan University of Traditional Chinese Medicine for PCI were randomized via a web-based randomization system into a control group (60 cases) treated with atorvastatin or a PCSK9 inhibitor group (60 cases) treated with atorvastatin + evolocumab. After 6 months of treatment, between-group differences were assessed for the following measures: triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), index of microcirculatory resistance (IMR), Thrombosis in Myocardial Infarction myocardial perfusion grading (TMPG), major adverse cardiovascular events (MACEs), and adverse reactions. RESULTS: After 6 months of treatment, TG (P=0.037), TC (P<0.001), LDL-C (P<0.001), Lp(a) (P<0.001), hs-CRP (P<0.001), TNF-α (P<0.001), and IL-6 (P<0.001) levels and IMR values (P<0.001) were significantly lower in the PCSK9 inhibitor group than in the control group. TMPG grade 3 (P=0.04) was noted to occur significantly more frequently in the PCSK9 inhibitor group than in the control group. No significant between-group differences in MACEs (P>0.05) or adverse reactions (P>0.05) were observed. CONCLUSIONS: Compared with statins alone, a PCSK9 inhibitor combined with statins improves inflammation levels and microcirculatory function after PCI in patients with NSTE-ACS, and this strategy deserves clinical attention.

Efeitos Terapêuticos da Tripla Antiagregação Plaquetária em Pacientes Femininas Idosas com Diabetes e Infarto Agudo do Miocárdio / Therapeutic Effects of Triple Antiplatelet Therapy in Elderly Female Patients with Diabetes and Acute Myocardial Infarction

Resumo Fundamento A dupla antiagregação plaquetária (DAP) é o tratamento fundamental do infarto agudo do miocárdio (IAM). Objetivo O presente estudo visou investigar a eficácia e a segurança da tripla antiagregação plaquetária (TAP) em pacientes femininas idosas com diabetes e infarto agudo do miocárdio com supradesnível do segmento ST (IAMCSST), que foram submetidas à intervenção coronária percutânea ICP. Métodos Trata-se se de um estudo randomizado e mono-cego. O grupo controle A (97 pacientes idosos do sexo masculino com diabetes e STEMI, cujos escores CRUSADE foram < 30) recebeu aspirina, ticagrelor e tirofibana. Um total de 162 pacientes femininas idosas com diabetes e IAMCSST foram divididas aleatoriamente em dois grupos de acordo com o escore CRUSADE. O grupo B (69 pacientes com escore CRUSADE > 31) recebeu aspirina e ticagrelor. O grupo C (93 pacientes com escore CRUSADE < 30) recebeu aspirina, ticagrelor e tirofibana. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados Após a PCI, o fluxo sanguíneo grau 3 Thrombolysis in Myocardial Infarction (TIMI) e a perfusão miocárdica TIMI grau 3 foram significativamente menos prevalentes no grupo B, em comparação com o grupo A (p < 0,05). Quando comparada aos grupos A e C, a incidência de complicações adversas maiores foi significativamente maior no grupo B (p < 0,05). Conclusão A TAP pode efetivamente reduzir a incidência de complicações maiores em pacientes idosas com diabetes e IAMCSST. No entanto, atenção cuidadosa deve ser dada à hemorragia em pacientes que recebem TAP. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Dual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI). Objective The present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI). Methods We designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant. Results Compared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05). Conclusion TAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Therapeutic Effects of Triple Antiplatelet Therapy in Elderly Female Patients with Diabetes and Acute Myocardial Infarction. / Efeitos Terapêuticos da Tripla Antiagregação Plaquetária em Pacientes Femininas Idosas com Diabetes e Infarto Agudo do Miocárdio.

BACKGROUND: Dual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI). OBJECTIVE: The present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI). METHODS: We designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant. RESULTS: Compared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05). CONCLUSION: TAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

FUNDAMENTO: A dupla antiagregação plaquetária (DAP) é o tratamento fundamental do infarto agudo do miocárdio (IAM). OBJETIVO: O presente estudo visou investigar a eficácia e a segurança da tripla antiagregação plaquetária (TAP) em pacientes femininas idosas com diabetes e infarto agudo do miocárdio com supradesnível do segmento ST (IAMCSST), que foram submetidas à intervenção coronária percutânea ICP. MÉTODOS: Trata-se se de um estudo randomizado e mono-cego. O grupo controle A (97 pacientes idosos do sexo masculino com diabetes e STEMI, cujos escores CRUSADE foram < 30) recebeu aspirina, ticagrelor e tirofibana. Um total de 162 pacientes femininas idosas com diabetes e IAMCSST foram divididas aleatoriamente em dois grupos de acordo com o escore CRUSADE. O grupo B (69 pacientes com escore CRUSADE > 31) recebeu aspirina e ticagrelor. O grupo C (93 pacientes com escore CRUSADE < 30) recebeu aspirina, ticagrelor e tirofibana. Valores de p < 0,05 foram considerados estatisticamente significativos. RESULTADOS: Após a PCI, o fluxo sanguíneo grau 3 Thrombolysis in Myocardial Infarction (TIMI) e a perfusão miocárdica TIMI grau 3 foram significativamente menos prevalentes no grupo B, em comparação com o grupo A (p < 0,05). Quando comparada aos grupos A e C, a incidência de complicações adversas maiores foi significativamente maior no grupo B (p < 0,05). CONCLUSÃO: A TAP pode efetivamente reduzir a incidência de complicações maiores em pacientes idosas com diabetes e IAMCSST. No entanto, atenção cuidadosa deve ser dada à hemorragia em pacientes que recebem TAP. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Effect of KNDC1 overexpression on the senescence of human umbilical vein endothelial cells.

Kinase non-catalytic C-lobe domain containing 1 (KNDC1) exists in dendrites, guanine nucleotide exchange factor complexes and neuronal cell bodies as a putative protein­protein interaction module that regulates a number of signaling pathways. Previous studies have demonstrated that the knockdown of KNDC1 delays human umbilical vein endothelial cell (HUVEC) senescence. However, the effect of KNDC1 overexpression on HUVEC function remains unclear. In the present study, an adenovirus vector carrying KNDC1 was constructed and then transfected into endothelial cells to observe cell senescence. Furthermore, the effect of KNDC1 overexpression on HUVEC senescence was investigated in vitro and the underlying molecular mechanism was investigated. Senescence­associated ß­galactosidase staining was used to determine cellular senescence and reactive oxygen species (ROS) were monitored to detect the level of cell oxidative stress. The mRNA transcription level and protein expression were analyzed by reverse transcription­quantitative polymerase chain reaction and western blot analysis, respectively. The results demonstrated that KNDC1 overexpression possibly inhibited HUVEC activity and function and promoted HUVEC senescence. Mechanistic studies demonstrated that KNDC1 triggered a p53­ROS positive feedback loop, which serves a crucial role in regulating senescence. In conclusion, to the best of the authors' knowledge, this is the first time that KNDC1­adenovirus vector inhibition of HUVEC proliferation by activating the p53 signaling pathway has been reported. Theoretically, the results of the present study also support KNDC1 as a therapeutic target for future anti-senescence.