Background Several factors that could affect survival and clinical outcomes of COVID-19 patients require larger studies and closer attention. Objective To investigate the impact of factors including whether COVID-19 was clinically or laboratory-diagnosed, influenza vaccination, former or current tuberculosis, HIV, and other comorbidities on the hospitalized patients' outcomes. Design Observational nationwide cohort study. Patients All subjects, regardless of age, admitted to 4,251 Russian hospitals indexed in the Federal Register of COVID-19 patients between March 26, 2020, and June 3, 2020. All included patients for which complete clinical data were available were divided into two cohorts, with laboratory- and clinically verified COVID-19. Measurements We analyzed patients' age and sex, COVID-19 ICD-10 code, the length of the hospital stay, and whether they required ICU treatment or invasive mechanical ventilation. The other variables for analysis were: verified diagnosis of pulmonary disease, cardiovascular disease, diseases of the endocrine system, cancer/malignancy, HIV, tuberculosis, and the data on influenza vaccination in the previous six months. Results This study enrolled 705,572 COVID-19 patients aged from 0 to 121 years, 50.4% females. 164,195 patients were excluded due to no confirmed COVID-19 (n=143,357) or insufficient and invalid clinical data (n=20,831). 541,377 participants were included in the study, 413,950 (76.5%) of them had laboratory-verified COVID-19, and 127,427 patients (23.5%) with the clinical verification. Influenza vaccination reduced the risk of transfer to the ICU (OR 0.76), mechanical ventilation requirement (OR 0.74), and the risk of death (HR 0.77). TB increased the mortality risk (HR 1.74) but reduced the likelihood of transfer to the ICU (OR 0.27). HIV comorbidity significantly increased the risks of transfer to the ICU (OR 2.46) and death (HR 1.60). Patients with the clinically verified COVID-19 had a shorter duration of hospital stay (HR 1.45) but a higher risk of mortality (HR 1.08) and the likelihood of being ventilated (OR 1.36). According to the previously published data, age, male sex, endocrine disorders, and cardiovascular diseases increased the length of hospital stay, the risk of death, and transfer to the ICU. Limitations The study did not include a control group of subjects with no COVID-19. Because of that, some of the identified factors could not be specific for COVID-19. Conclusions Influenza vaccination could reduce the severity of the hospitalized patients' clinical outcomes, including mortality, regardless of age, social, and economic group. The other factors considered in the study did not reduce the assessed risks, but we observed several non-trivial associations that may optimize the management of COVID-19 patients.
Background: High residual platelet reactivity (HRPR) during dual antiplatelet therapy (DAPT) may impact clinical outcomes following percutaneous coronary interventions (PCI). However, whether any biomarkers assessed before PCI at DAPT loading may predict delayed maintenance HRPR is not clear. Objective: The aim of this study was to determine whether conventional clinical or laboratory indices at loading before stenting may predict HRPR at 6 months of maintenance DAPT. Methods: The study was designed on a single-center prospective cohort, and included 94 pre-PCI patients. All patients underwent elective PCI with drug-eluting stent implantation, and received DAPT with aspirin and clopidogrel. Platelet reactivity was assessed with 5 μmol/L of adenosine diphosphate-induced light transmission aggregometry before PCI, but after 24 h of DAPT loading, and repeated at 6 months. Baseline clinical characteristics, CYP2C19 polymorphism, C-reactive protein, soluble P-selectin, CD40L, interleukin-6, PAI-1 levels, and von Willebrand factor activity were analyzed. Results: The incidence (light transmission aggregometry <50%) of prestent HRPR was 16%. By univariate regression, body mass index (BMI; p = 0.02), total cholesterol (p = 0.01), low-density lipoproteins (p = 0.004), CYP2C19*2 allele carriage (p = 0.006), soluble P-selectin (p = 0.009), and von Willebrand factor (p = 0.04) were linked to future HRPR. However, multivariate regression analysis suggested that only BMI and P-selectin were independent predictors of HRPR. Conclusions: Platelet reactivity before elective stenting is associated with numerous biomarkers; however, only BMI and soluble P-selectin were independent predictors of future HRPR during maintenance-phase DAPT. This may be important for future tailored antiplatelet strategies in patients with metabolic syndrome and diabetics.
The aim of this study was to triage platelet reactivity and adverse vascular outcomes after dual antiplatelet therapy due to percutaneous coronary intervention (PCI) dependent on CYP2C19*2 and CYP2C19*3 genotypes in patients with coronary artery disease. Fifty-five patients with coronary artery disease were studied serially pre-PCI and post-PCI. Platelet reactivity was assessed by conventional light transmission aggregometry, VerifyNow Analyzer, and thromboelastography with platelet mapping. Genetic testing was performed with allele-specific real-time polymerase chain reaction. Adverse events included vascular death, acute myocardial infarction, repeated PCI, definite stent thrombosis, and angina recurrence. The common genotype (GG) was found in 39 patients, heterozygous polymorphism CYP2C19 (GA) G681A allele was detected in 14 patients, and the rare homozygous polymorphism CYP2C19 (AA) G681A allele was exhibited in 2 patients. There were no CYP2C19*3 (Trp212Ter) carriers among index patients. The platelet reactivity was higher in patients with heterozygous and homozygous carriers compared with GG genotype. The largest differences were observed among GG, GA, and AA genotypes, which correlated with the average values of platelet aggregation (P = 0.02). There was a significant link between adverse events and high platelet reactivity assessed by light transmission aggregometry (P = 0.002). We found a trend between different genotype and VerifyNow readings (P = 0.057); moreover, their cumulative impact on adverse events was significant (P = 0.041). Platelet reactivity is higher in patients with heterozygous and homozygous carriers of CYP2C19*2 versus common genotype and may predict an increased risk of clopidogrel response variability and/or experiencing adverse cardiac events.
Background: Despite recent advances in stent design and constantly improving protective pharmacological strategies, complications and adverse events following percutaneous coronary interventions (PCI) are still major factors influencing morbidity and mortality. Therefore, predicting secondary vascular occlusions represents an unmet medical need. Objective: The aim of our study was to triage clinical and laboratory predictors of major adverse clinical events (MACE) following coronary stenting. Methods: This was a prospective, case-controlled, single-center study, which included 94 consecutive patients with documented coronary disease who underwent PCI with drug-eluting stent (DES) implantation. All patients received dual antiplatelet therapy with aspirin and clopidogrel. Numerous clinical characteristics and laboratory biomarkers were assessed before stenting and were correlated with poststenting MACE over the mean follow-up of 28 months. MACE included death, nonfatal myocardial infarction, target vessel revascularisation, stroke, stent thrombosis, angina recurrence and instent restenosis. Results: Twenty-three patients experienced MACE. Independent MACE predictors after PCI with DES implantation were antecedent diabetes mellitus (RR = 0.45; 95% CI 0.20-0.97; p = 0.045), prior thrombolytic therapy (RR = 0.42; 95% CI 0.27-0.83; p = 0.039), baseline plasminogen activator inhibitor -1 (PAI-1; p = 0.008) and plasma von Willebrand factor (vWF) activity (p = 0.007). Other clinical characteristics and laboratory indices showed no correlation with MACE. Conclusions: Background diabetes mellitus, prior thrombolytic therapy, PAI-1 and vWF prestenting activity may be useful for MACE prediction over 28 months of follow-up.
Научный центр сердечно-сосудистой хирургии имени А.Н. Бакулева Россия, 121552, Москва, Рублевское шоссе, 135 Предпосылки. Несмотря на значительные достижения в области разработки стентов и совершенствующиеся подходы к медикаментозному сопровождению, осложнения после чрескожного коронарного вмешательства (ЧКВ) по-прежнему остаются основными факторами, опре-деляющими развитие «больших кардиальных событий» (КС) после интервенционных вмешательств. Поэтому прогнозирование процессов рестенозирования, развития нефатального инфаркта миокарда и тромбоза стента имеет важнейшее значение. Цель. Выявить клинические и лабораторные предикторы неблагоприятных КС после стентирования коронарных артерий. Материал и методы. В одноцентровое проспективное исследование «случай-контроль» были включены 94 пациента с документирован-ным поражениями коронарного русла, требующими проведения ЧКВ с имплантацией стентов с лекарственным покрытием. Все пациенты на-ходились на двойной антиагрегантной терапии ацетилсалициловой кислотой и клопидогрелом. Оценивались различные клинические ха-рактеристики и лабораторные биомаркеры до проведения ЧКВ. После выписки из стационара всем 94 пациентам было проведено геноти-пирование CYP2C19 по аллелю *2. Комбинированная конечная точка включала в себя «большие кардиальные события» (смерть, нефатальный инфаркт миокарда, реваскуляризация целевого сосуда, инсульт, тромбоз стента), а также возврат стенокардии и in-stent рестеноз. Средний период наблюдения составил 28,2 мес (±15,5 мес). Результаты. Неблагоприятные КС были зарегистрированы у 23 пациентов. По данным однофакторного регрессионного анализа установлено, что сахарный диабет (р=0,049), уровень единиц реакции P2Y12-рецепторов (P2Y12 Reaction Units, PRU) по данным VerifyNow ® (р=0,01), число стентированных артерий более 2-х (р=0,01), число имплантированных стентов более 2-х (р=0,01), исходный уровень ингибитора активатора плазминогена-1 (PAI-1) (р=0,03) и активность фактора фон Виллебранда (ФВ) (р=0,01) являются предикторами развития не-благоприятных КС после планового ЧКВ с имплантацией стентов с лекарственным покрытием. По данным многофакторного анализа неза-висимыми предикторами КС после ЧКВ явились сопутствующий сахарный диабет, уровень PRU (по данным VerifyNow ® ) ≥202, исходный уро-вень PAI-1 ≥75.95 нг/мл и активности ФВ в плазме ≥155,15%. Другие включенные в анализ факторы не показали достоверного независи-мого влияния на исходы после ЧКВ, включая носительство аллеля CYP2C19*2. Заключение. Сопутствующий сахарный диабет, высокая реактивность тромбоцитов (по данным VerifyNow ® ), а также значения исходного уровня PAI-1 и активности фактора фон Виллебранда являются независимыми предикторами неблагоприятных кардиальных событий после проведения ЧКВ с имплантацией стентов с лекарственным покрытием.Ключевые слова: двойная антиагрегантная терапия, агрегация тромбоцитов, стентирование коронарных артерий, тромбоз стента, ресте-ноз стента, провоспалительные маркеры, ингибитор активатора плазминогена-1, фактор фон Виллебранда.Для цитирования: Голухова Е.З., Г...
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