Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.

AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.

In-Hospital influenza vaccination to prevent cardiorespiratory events in the first 45 days after acute coronary syndrome: A prespecified analysis of the VIP-ACS trial.

BACKGROUND: Influenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain. METHODS: The VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization). RESULTS: The trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70---1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71---1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48---1.39; P = 0.46). No serious adverse events were observed. CONCLUSION: In patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.

Primary Prevention of Cardiovascular Disease at Community Clinics in the State of Sao Paulo, Brazil: Results from the Epidemiological Information Study of Communities.

Background: Primary prevention of cardiovascular disease (CVD) remains a major challenge, especially in communities of low- and middle-income countries with poor medical assistance influenced by distinct local, financial, infrastructural, and resource-related factors. Objective: This a community-based study aimed to determine the proportion and prevalence of uncontrolled cardiovascular risk factors (CRF) in Brazilian communities. Methods: The EPICO study was an observational, cross-sectional, and community clinic-based study. Subjects were living in Brazilian communities and were of both sexes and ≥18 years old, without a history of a stroke or myocardial infarction but presenting at least one of the following cardiovascular risk factors: hypertension, diabetes mellitus and hypercholesterolemia. The study was carried out in Brazil, including 322 basic health units (BHU) in 32 cities. Results: A total of 7,724 subjects with at least one CRF were evaluated, and one clinical visit was performed. Mean age was 59.2 years-old (53.7% were >60 years old). A total of 66.7% were women. Of the total, 96.2% had hypertension, 78.8% had diabetes mellitus type II, 71.1% had dyslipidemia, and 76.6% of patients were overweight/obese. Controlled hypertension (defined by <130/80 mmHg or <140/90 mmHg) was observed in 34.9% and 55.5% patients among respective criteria, the rates of controlled blood glucose in patients taking antidiabetic medications was 29.5%, and among those with documented dyslipidemia who received any lipid-lowering medication, only 13.9% had LDL-c on target. For patients presenting three CRF less than 1.9% had LDL-c < 100 mg/dL once their BP and blood glucose were on target. High education level as associated with blood pressure (BP) target of less than 130 / 80mm Hg. The glucose and LDL-c levels on target were associated with the presence of hypertension and diabetes mellitus. Conclusion: In Brazilian community clinics, regarding most patients in primary prevention, the CRF such as BP, blood glucose, and lipid levels are poorly controlled, with a majority of patients not achieving guidelines/recommendations.

HIV-Infected Naïve Patients Exhibit Endothelial Dysfunction Concomitant with Decreased Natural Antibodies Against Defined Apolipoprotein B Autoantigens. / Pacientes Naïve Infectados por HIV Apresentam Disfunção Concomitante com Diminuição de Anticorpos Naturais contra Autoantígenos Derivados da Apolipoproteína B Definidos.

BACKGORUND: Traditional and HIV-defined risk factors may be associated with an increase in cardiovascular events. Recent studies have suggested that the humoral immune response to modified LDL may be associated with the process of atherosclerosis. OBJECTIVES: To evaluate the presence of anti-oxLDL and apolipoprotein B-derived peptides in the blood, and their association with the endothelial function in HIV-infection. METHODS: This study consecutively included subjects matched for age, gender, and demographic data in two groups: (1) HIV-infected and naïve for antiviral therapy and (2) uninfected individuals. Subclinical atherosclerosis was assessed by intimal-media thickness, using ultrasonography of the carotid arteries. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery by ultrasonography. Autoantibodies (IgM, IgG) anti-oxidized low-density lipoprotein (oxLDL), anti-apolipoprotein B-peptide fragments (ApoB-D and 0033G-Cys peptides), and cytokine levels were evaluated by ELISA. RESULTS: This study's results showed no difference in subclinical atherosclerosis between groups; however, HIV-infected subjects showed a lower FMD, when compared to non-infected subjects. Therefore, HIV-infected subjects showed higher levels of inflammatory cytokines, titers of IgG anti-oxLDL, and IgG anti-ApoB-D. In contrast, titers of IgM anti-ApoB-D were lower in HIV-infected individuals and associated with reduced endothelial functions. CONCLUSIONS: This study's results show that HIV infection, in naïve subjects, is associated with endothelial dysfunction and a decline of natural antibodies to apo-B antigens.

FUNDAMENTO: Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose. OBJETIVOS: Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV. MÉTODOS: Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA. RESULTADOS: Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas. CONCLUSÕES: Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.

COVID-19 Vaccination and Cardiopulmonary Events After Acute Coronary Syndromes: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial investigates the association of COVID-19 vaccination with incidence of cardiopulmonary events among patients who had experienced acute coronary syndromes.

Pacientes Naïve Infectados por HIV Apresentam Disfunção Concomitante com Diminuição de Anticorpos Naturais contra Autoantígenos Derivados da Apolipoproteína B Definidos / HIV-Infected Naïve Patients Exhibit Endothelial Dysfunction Concomitant with Decreased Natural Antibodies Against Defined Apolipoprotein B Autoantigens

Fundamento: Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose. Objetivos: Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV. Métodos: Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA. Resultados: Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas. Conclusões: Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.

Abstract Backgorund: Traditional and HIV-defined risk factors may be associated with an increase in cardiovascular events. Recent studies have suggested that the humoral immune response to modified LDL may be associated with the process of atherosclerosis. Objectives: To evaluate the presence of anti-oxLDL and apolipoprotein B-derived peptides in the blood, and their association with the endothelial function in HIV-infection. Methods: This study consecutively included subjects matched for age, gender, and demographic data in two groups: (1) HIV-infected and naïve for antiviral therapy and (2) uninfected individuals. Subclinical atherosclerosis was assessed by intimal-media thickness, using ultrasonography of the carotid arteries. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery by ultrasonography. Autoantibodies (IgM, IgG) anti-oxidized low-density lipoprotein (oxLDL), anti-apolipoprotein B-peptide fragments (ApoB-D and 0033G-Cys peptides), and cytokine levels were evaluated by ELISA. Results: This study's results showed no difference in subclinical atherosclerosis between groups; however, HIV-infected subjects showed a lower FMD, when compared to non-infected subjects. Therefore, HIV-infected subjects showed higher levels of inflammatory cytokines, titers of IgG anti-oxLDL, and IgG anti-ApoB-D. In contrast, titers of IgM anti-ApoB-D were lower in HIV-infected individuals and associated with reduced endothelial functions. Conclusions: This study's results show that HIV infection, in naïve subjects, is associated with endothelial dysfunction and a decline of natural antibodies to apo-B antigens.

Non-linear Optical Responses of Low-Density Lipoprotein are Associated with Intima-Media Thickness of Carotid Artery in Athletes.

We investigated the association between the degree of oxidative modification of LDL particles by non-linear optical response of LDL (Z-scan technique) and the presence of subclinical atherosclerosis in different segments of the carotid artery. We recruited high-intensity athlete runners (n = 44) and controls (n = 51) to participate in the study. The carotid intima-media thickness (cIMT), interleukin 10 (IL-10), TNF-alpha, and the non-linear optical responses of LDL particle (Z-scan) were assessed. In athletes, the mean cIMT differed between genders, with higher values observed in female athletes compared to male athletes (P < 0.05). Higher mean values for cIMT were seen in the right carotid arteries of female athletes as compared to female controls (P < 0.05). Higher levels of TNF-alpha and IL-10 were found in athletes (P < 0.05). Yet, ΔΓpv (transmittance curve) of Z-scan in athletes was higher than in the non-athletes, indicating less oxidation in LDL particles of athletes (P < 0.05). There was an inverse association between the ΔΓpv and cIMT in the right internal carotid segments (ß = -0.163, P < 0.05) in all subjects, and between the VO2max and the mean cIMT (ß = -0.003, P < 0.05) in male subjects. The present study shows that the Z-scan technique enabled to detect less oxidative modifications in LDL particles from athletes. This effect was associated with cIMT in a gender-dependent mode.

Antihypertensive therapy increases natural immunity response in hypertensive patients.

AIMS: The aim of this work was to evaluate the effects of treatment of hypertension on the autoantibodies to apolipoprotein B-derived peptides (anti-ApoB-D peptide Abs) response, inflammation markers and vascular function. MAIN METHODS: Eighty-eight patients with hypertension (stage 1 or 2) were recruited and advised to receive perindopril (4mg), hydrochlorothiazide (25mg), or indapamide (1.5mg) for 12weeks in a blinded fashion. Office and 24-h ambulatory blood pressure monitoring (24h ABPM), flow-mediated dilatation (FMD), nitrate-induced dilatation (NID), titers of IgG and IgM anti-ApoB-D peptide Abs, hsCRP, and interleukins (IL-8 and IL-10) were evaluated at baseline and 12weeks after therapies. KEY FINDINGS: All treatments reduced office BP, and improved FMD (P<0.05 vs. baseline). The NID was improved only in the perindopril arm (P<0.05 vs. baseline). The 24h-ABPM was reduced with perindopril and hydrochlorothiazide therapies (P<0.05 vs. baseline), but not with indapamide, and this effect was followed by increase in titers of IgM Anti-ApoB-D peptide Abs (P<0.05 vs. baseline), without modifications in titers IgG Anti-ApoB-D peptide Abs and interleukins. Multivariable regression analysis has shown that change in the titers of IgM anti-ApoB-D peptide was associated with the changes in FMD (ß -0.347; P<0.05). SIGNIFICANCE: These findings shed light to a possible modulator effect of the antihypertensive therapy on the natural immunity responses and vascular function.

Obesity modulates the immune response to oxidized LDL in hypertensive patients.

Obesity and hypertension have been recognized as inflammatory diseases capable of activating the immune system, thus contributing to an increased cardiovascular risk. However, the link between adaptive immunity, obesity, and hypertension is poorly understood. We investigated the relationship of the body mass index (BMI) on the inflammatory, vascular, and immune responses in patients with hypertension naïve of anti-hypertensive treatment. Hypertensive patients (N = 88) were divided into three groups: normal weight (NW), overweight (OW), and obese (OB) subjects. Anti-oxidized LDL autoantibodies (anti-oxLDL Abs), anti-ApoB-D peptide (anti-ApoB-D) Abs, interleukin (IL)-8 and IL-10, flow-mediated dilation (FMD) of the brachial artery, and 24-h ambulatory blood pressure monitoring (ABPM) were assessed. OB patients presented lower levels of anti-oxLDL Abs and IL-10, higher levels of IL-8, and impaired FMD, when compared to NW and OW (P < 0.05), without differences between groups regarding anti-ApoB-D Abs. After adjusting for age, systolic and diastolic blood pressure, anti-oxLDL Abs were inversely correlated with BMI and waist circumference (r = -0.24, P = 0.02 and r = -0.25, P = 0.02, respectively), whereas ApoB-D correlated with 24-h ABPM (r = 0.22, P = 0.05 for systolic, and r = 0.29, P = 0.01 for diastolic blood pressure). Regression analyses showed inverse associations of anti-oxLDL Abs with BMI (ß = -0.05, P = 0.01) and waist circumference (ß = -0.01, P = 0.02); anti-ApoB-D Abs were associated with systolic and diastolic 24-h ABPM (ß = 0.96, P = 0.04; ß = 1.02, P = 0.005, for systolic and diastolic 24-h ABPM, respectively). Among hypertensive patients, obesity modulates the immune and inflammatory milieu, determining an unfavorable balance of cytokines and reduction in titers of anti-oxLDL Abs. Twenty-four hour ABPM is associated with titers of anti-ApoB-D Abs.