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.

Adipokines and Adipose Tissue-Related Metabolites, Nuts and Cardiovascular Disease.

Adipose tissue is a complex structure responsible for fat storage and releasing polypeptides (adipokines) and metabolites, with systemic actions including body weight balance, appetite regulation, glucose homeostasis, and blood pressure control. Signals sent from different tissues are generated and integrated in adipose tissue; thus, there is a close connection between this endocrine organ and different organs and systems such as the gut and the cardiovascular system. It is known that functional foods, especially different nuts, may be related to a net of molecular mechanisms contributing to cardiometabolic health. Despite being energy-dense foods, nut consumption has been associated with no weight gain, weight loss, and lower risk of becoming overweight or obese. Several studies have reported beneficial effects after nut consumption on glucose control, appetite suppression, metabolites related to adipose tissue and gut microbiota, and on adipokines due to their fatty acid profile, vegetable proteins, l-arginine, dietary fibers, vitamins, minerals, and phytosterols. The aim of this review is to briefly describe possible mechanisms implicated in weight homeostasis related to different nuts, as well as studies that have evaluated the effects of nut consumption on adipokines and metabolites related to adipose tissue and gut microbiota in animal models, healthy individuals, and primary and secondary cardiovascular prevention.

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.

Serious infections among unselected patients with ST-elevation myocardial infarction treated with contemporary primary percutaneous coronary intervention.

BACKGROUND: Contemporary studies assessing the frequency, characteristics, and outcomes of serious infections (SIs) in patients presenting a ST-elevation myocardial infarction are scarce. METHODS: Prospective cohort of consecutive patients undergoing primary percutaneous coronary intervention (pPCI). Serious infection was defined as the presence of infection that prolonged hospitalization. Community-acquired infection (CAI) was defined by SI diagnosed in the first 72 hours of hospitalization, whereas hospital-acquired infections (HAI) were those diagnosed after 72 hours of hospital admission. RESULTS: From December 2009 to November 2012, 1,486 patients were included in the analysis. Serious infection was present in 58 (3.9%) individuals; 30 (2%) patients had CAI and 28 (1.9%) patients had HAI. Respiratory tract infection was responsible for 82% of the SI. Patients with SI were older, had more comorbidities, and had worse angiographic results of the pPCI procedure when compared with those without SIs. After multivariable adjustment, SI was associated with an approximately 10-fold risk of 30-day death. Patients with CAI had more often a history of smoking, Killip III/IV on hospital admission, worse pPCI, and angiographic results than did patients with HAI. However, no differences were seen in 30-day major cardiovascular outcomes between patients with CAI and HAI. CONCLUSION: In a contemporary cohort of unselected ST-elevation myocardial infarction patients representative of the daily practice, SI was uncommon but associated with worse pPCI results and high risk of mortality. The occurrences of CAI or HAI were similar, but CAI patients presented distinctly worse angiographic outcomes than did patients with HAI.

Effect of polymorphisms in the CD36 and STAT3 genes on different dietary interventions among patients with coronary artery disease: study protocol for a randomized controlled trial.

BACKGROUND: Cardiovascular disease has become a major health problem, and it has been associated with both environmental and genetic factors. Studies have shown that the Mediterranean Diet (MeDiet), or its components such as nuts and olive oil, may be strongly associated with the improvement of cardiovascular risk factors in specific populations. The purpose of the GENUTRI study is to investigate the interaction of genetics with cardiovascular risk factors in a non-Mediterranean population with coronary artery disease (CAD) according to three different diets: rich in pecan nuts, in extra-virgin olive oil or a control diet. METHODS/DESIGN: The GENUTRI study is a single-center, randomized, open-label, parallel-group, 12-week pragmatic clinical trial conducted in patients aged 40 to 80 years and diagnosed with CAD. A standardized questionnaire will be applied to data collection and a blood sample will be obtained for lipid, glycemic and inflammatory profile evaluation. Polymorphisms in the CD36 and STAT3 genes will be detected using the TaqMan® SNP Genotyping Assay. Patients will be allocated in three groups: group 1: 30 g/day of pecan nuts; group 2: 30 ml/day of olive oil; and group 3: control diet. The primary outcome will consist of changes in LDL-cholesterol (in mg/dl) after 12 weeks of intervention. DISCUSSION: Studies have shown the beneficial effects of diets rich in nuts and olive oil mainly in the Mediterranean population. GENUTRI is a clinical trial focusing on the effects of nuts or olive oil supplementation in Brazilian individuals. Additionally, we will try to demonstrate that genetic polymorphisms linked to cardiovascular disease may modulate the effects of different diets on biochemical and inflammatory markers among these subjects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02202265 (registered on 18 July 2014: first version).

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. .

Society of Thoracic Surgeons Score: validação para pacientes submetidos à cirurgia cardíaca no Instituto de Cardiologia do RS – nota prévia / Society of Thoracic Surgeons Score: validation for patients undergoing surgery at the Cardiology Institute of RS - preview note

Objetivo: avaliar a acurácia clínica do Society of Thoracic Surgeons score em predizer mortalidade e complicações pósoperatóriasintra-hospitalares em pacientes submetidos à cirurgia cardíaca no Instituto de Cardiologia do RS/FundaçãoUniversitária de Cardiologia. Método: estudo de coorte com abordagem quantitativa. Serão analisadas, em prontuários,variáveis demográficas e clínicas de 1223 pacientes submetidos à cirurgia de revascularização miocárdica e/ou trocavalvar de dezembro de 2007 a dezembro de 2008. Para a análise dos dados será utilizado o programa Statistical Packagefor the Social Sciences, sendo que os resultados serão considerados estatisticamente significantes se p < 0,05, comintervalo de 95% de confiança. Resultados esperados: espera-se identificar a acurácia do STS score em predizermortalidade e complicações pós-operatórias e estabelecer a comparação entre o STS e os índices estudados na instituição:Parsonnet, EuroSCORE, NNE e SCTS para o desfecho mortalidade, quando aplicados à pacientes submetidos à cirurgiacardíaca no IC/FUC.