An adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in familial hypercholesterolemia: A pilot study protocol

BACKGROUND AND AIMS: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. METHODS: A national, multicenter, factorial, and parallel placebocontrolled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICAFH) þ phytosterol placebo þ krill oil placebo; 2) DICA-FH þ phytosterol 2 g/day þ krill oil placebo; 3) DICA-FH þ phytosterol placebo þ krill oil 2 g/day; or 4) DICA-FH þ phytosterol 2 g/day þ krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. RESULTS: A total of 58 participants were enrolled between May e August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. CONCLUSIONS: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

Oxidative Stress Biomarkers, Nut-Related Antioxidants, and Cardiovascular Disease.

Atherosclerosis is related to fat accumulation in the arterial walls and vascular stiffening, and results in acute coronary syndrome which is commonly associated with acute myocardial infarction. Oxidative stress participates in the pathogenesis of atherosclerosis. Thus, the inclusion of food sources of dietary antioxidants, such as different kinds of nuts, may improve biomarkers related to oxidative stress, contributing to a possible reduction in atherosclerosis progression. This article has briefly highlighted the interaction between oxidative stress, atherosclerosis, and cardiovascular disease, in addition to the effect of the consumption of different nuts and related dietary antioxidants-like polyphenols and vitamin E-on biomarkers of oxidative stress in primary and secondary cardiovascular prevention. Studies in vitro suggest that nuts may exert antioxidant effects by DNA repair mechanisms, lipid peroxidation prevention, modulation of the signaling pathways, and inhibition of the MAPK pathways through the suppression of NF-κB and activation of the Nrf2 pathways. Studies conducted in animal models showed the ability of dietary nuts in improving biomarkers of oxidative stress, such as oxLDL and GPx. However, clinical trials in humans have not been conclusive, especially with regards to the secondary prevention of cardiovascular disease.

Correlations between Traditional and Nontraditional Indicators of Adiposity, Inflammation, and Monocyte Subtypes in Patients with Stable Coronary Artery Disease.

Background: Recruitment of monocytes and low-grade inflammation process are both involved in obesity and in atherosclerosis. Thus, the aim of this study was to evaluate the correlation among indicators of adiposity, monocyte subtypes, and inflammatory markers in patients with stable coronary artery disease (CAD). Methods: This was a cross-sectional study including 97 patients with stable CAD aged >40 years. Traditional anthropometric indicators of adiposity (body mass index (BMI); waist, hip, and neck circumferences; and waist-hip ratio) and nontraditional anthropometric indicators of adiposity (lipid accumulation product index (LAP), visceral adiposity index (VAI), and deep-abdominal-adipose-tissue index (DAAT)) were determined. Immunoprecipitation, turbidimetry, coagulometric method, and CBA were used for the evaluation of inflammatory markers (hs-CRP, IL-2, IL-4, IL-6, IL-10, and INF-γ). Monocyte subtypes were identified by flow cytometry and defined as CD14++ CD16- (Mon1), CD14++ CD16+ (Mon2), and CD14+ CD16++ (Mon3). Pearson's correlation coefficient and adjusted partial correlation were calculated. Results: Monocyte subtypes were correlated with inflammation regardless of nutritional status according to BMI. In overweight individuals, LAP was correlated with IL-4 and fibrinogen (P < 0.01 and P < 0.05, respectively) and VAI with IL-4 (P < 0.05). In obese patients, the BMI, waist, neck, and hip circumferences, and DAAT were correlated with IL-6 (P < 0.05), regardless of age and sex. The hip circumference was correlated positively with Mon1 (r = 0.40, P = 0.007) and negatively with Mon3 (r = -0.35, P = 0.02) in obese subjects. Conclusion: Monocyte subtypes are correlated with inflammation in patients with stable CAD independently of BMI, whereas traditional and nontraditional indicators of adiposity are correlated differently with inflammatory markers and monocytes, according to the nutritional status.

Applicability of two international risk scores in cardiac surgery in a reference center in Brazil.

BACKGROUND: The applicability of international risk scores in heart surgery (HS) is not well defined in centers outside of North America and Europe. OBJECTIVE: To evaluate the capacity of the Parsonnet Bernstein 2000 (BP) and EuroSCORE (ES) in predicting in-hospital mortality (IHM) in patients undergoing HS at a reference hospital in Brazil and to identify risk predictors (RP). METHODS: Retrospective cohort study of 1,065 patients, with 60.3% patients underwent coronary artery bypass grafting (CABG), 32.7%, valve surgery and 7.0%, CABG combined with valve surgery. Additive and logistic scores models, the area under the ROC (Receiver Operating Characteristic) curve (AUC) and the standardized mortality ratio (SMR) were calculated. Multivariate logistic regression was performed to identify the RP. RESULTS: Overall mortality was 7.8%. The baseline characteristics of the patients were significantly different in relation to BP and ES. AUCs of the logistic and additive BP were 0.72 (95% CI, from 0.66 to 0.78 p = 0.74), and of ES they were 0.73 (95% CI; 0.67 to 0.79 p = 0.80). The calculation of the SMR in BP was 1.59 (95% CI; 1.27 to 1.99) and in ES, 1.43 (95% CI; 1.14 to 1.79). Seven RP of IHM were identified: age, serum creatinine > 2.26 mg/dL, active endocarditis, systolic pulmonary arterial pressure > 60 mmHg, one or more previous HS, CABG combined with valve surgery and diabetes mellitus. CONCLUSION: Local scores, based on the real situation of local populations, must be developed for better assessment of risk in cardiac surgery.

Applicability of Two International Risk Scores in Cardiac Surgery in a Reference Center in Brazil / Aplicabilidade de Dois Escores de Risco Internacionais em Cirurgia Cardíaca em Centro de Referência Brasileiro

Background: The applicability of international risk scores in heart surgery (HS) is not well defined in centers outside of North America and Europe. Objective: To evaluate the capacity of the Parsonnet Bernstein 2000 (BP) and EuroSCORE (ES) in predicting in-hospital mortality (IHM) in patients undergoing HS at a reference hospital in Brazil and to identify risk predictors (RP). Methods: Retrospective cohort study of 1,065 patients, with 60.3% patients underwent coronary artery bypass grafting (CABG), 32.7%, valve surgery and 7.0%, CABG combined with valve surgery. Additive and logistic scores models, the area under the ROC (Receiver Operating Characteristic) curve (AUC) and the standardized mortality ratio (SMR) were calculated. Multivariate logistic regression was performed to identify the RP. Results: Overall mortality was 7.8%. The baseline characteristics of the patients were significantly different in relation to BP and ES. AUCs of the logistic and additive BP were 0.72 (95% CI, from 0.66 to 0.78 p = 0.74), and of ES they were 0.73 (95% CI; 0.67 to 0.79 p = 0.80). The calculation of the SMR in BP was 1.59 (95% CI; 1.27 to 1.99) and in ES, 1.43 (95% CI; 1.14 to 1.79). Seven RP of IHM were identified: age, serum creatinine > 2.26 mg/dL, active endocarditis, systolic pulmonary arterial pressure > 60 mmHg, one or more previous HS, CABG combined with valve surgery and diabetes mellitus. Conclusion: Local scores, based on the real situation of local populations, must be developed for better assessment of risk in cardiac surgery. .

Fundamento: A aplicabilidade de escores de risco (ER) internacionais em cirurgia cardíaca (CC) ainda não está bem definida em centros fora da América do Norte e Europa. Objetivo: Avaliar a capacidade do Berstein Parsonnet 2000 (BP) e do EuroSCORE (ES) em predizer mortalidade intra-hospitalar (MIH) em pacientes submetidos a CC em hospital de referência do Brasil e identificar os preditores de risco (PR). Métodos: Coorte retrospectiva de 1.065 pacientes. Foram incluídos dados de cirurgias realizadas entre janeiro de 2007 e julho de 2008, quando 60,3% dos pacientes realizaram CRM, 32,7%, cirurgia valvar, e 7,0%, CRM combinada com cirurgia valvar. Foram calculados os modelos aditivos e logísticos dos escores, a área sob a curva ROC (AUC) e a razão de mortalidade padronizada (RMP). Regressão logística multivariada foi realizada para identificar os PR. Resultados: A MIH da amostra foi de 7,8%. As características basais dos pacientes da amostra foram significativamente diferentes em relação ao BP e ao ES. As AUCs do BP aditivo e logístico foram 0,72 (IC95%; 0,66-0,78 p = 0,74) e as do ES foram 0,73 (IC95% 0,67-0,79 p = 0,80). O cálculo da RMP no BP foi 1,59 (IC95%; 1,27-1,99) e no ES foi 1,43 (IC95%; 1,14-1,79). Sete PR de MIH foram identificados: idade, creatinina sérica > 2,26 mg/dL, endocardite ativa, pressão arterial pulmonar > 60 mmHg, uma ou mais CC, CRM combinada com cirurgia valvar e diabetes melito. Conclusão: Ambos os ER mostraram-se inadequados na avaliação pré-operatória de pacientes submetidos a CC, reforçando a necessidade de se desenvolverem ER baseados na realidade local. .