Analysis of KLF7 and KLF5 transcription factors gene variants in coronary artery disease.

INTRODUCTION AND OBJECTIVE: Genetic susceptibility has a key role in the pathogenesis of coronary artery disease (CAD). KLF5 and KLF7 are transcriptional factors essential to cell development and differentiation. Their genetic variants have been associated with the risk of metabolic disorders. The present study aimed to evaluate the possible correlation of KLF5 (rs3812852) and KLF7 (rs2302870) single nucleotide polymorphisms (SNPs) with the risk of CAD for the first time in the world. METHODS: The clinical trial study comprised 150 patients with CAD and 150 control subjects without CAD from the Iranian population. After blood sampling, deoxyribonucleic acid was extracted and genotyped using the Tetra Primer ARMS-PCR method and confirmed by Sanger sequencing. RESULTS: The KLF7 A/C genotypes and C allele frequency were meaningfully higher in the control group compared to the CAD+ group (p<0.05). No obvious association has been observed between KLF5 variants and CAD risk. However, the distribution of the AG genotype of KLF5 was statistically lower in CAD+ patients with diabetes than in CAD+ patients without diabetes (p<0.05). CONCLUSION: This study identified KLF7 SNP as a causative gene contributing to CAD, which presents novel insight into the molecular pathogenesis of the disease. It is, however, unlikely that KLF5 SNP has an essential role in the risk of CAD in the studied population.

Transcription factor 21 gene and prognosis in a coronary population.

INTRODUCTION AND OBJECTIVES: Transcription factor 21 (TCF21) is a member of the basic helix-loop-helix (bHLH) transcription factor family, and is critical for embryogenesis of the heart. It regulates differentiation of epicardium-derived cells into smooth muscle cell (SMC) and fibroblast lineages. The biological role of TCF21 in the progression of atherosclerosis is the subject of debate. The aim of this study was to investigate the impact of the TCF21 rs12190287 gene variant on the prognosis of coronary artery disease (CAD) in a Portuguese population from Madeira island. METHODS: We analyzed major adverse cardiovascular events (MACE) in 1713 CAD patients, mean age 53.3±7.8, 78.7% male, for 5.0±4.3 years. Genotype and allele distribution between groups with and without MACE was determined. The dominant genetic model (heterozygous GC plus homozygous CC) was used and compared with the wild GG to assess survival probability. Cox regression with risk factors and genetic models assessed variables associated with MACE. Kaplan-Meier analysis was used to estimate survival. RESULTS: The wild homozygous GG, heterozygous GC and risk CC genotypes were found in 9.5%, 43.2% and 47.3% of the population, respectively. The dominant genetic model remained in the equation as an independent risk factor for MACE (HR 1.41; p=0.033), together with multivessel disease, chronic kidney disease, low physical activity and type 2 diabetes. The C allele in the dominant genetic model showed worse survival (22.5% vs. 44.3%) at 15 years of follow-up. CONCLUSION: The TCF21 rs12190287 variant is a risk factor for CAD events. This gene may influence fundamental SMC processes in response to vascular stress, accelerating atherosclerosis progression, and may represent a target for future therapies.

Predictive value of a positive stress single-photon emission computed tomography or stress cardiac magnetic resonance for ruling in obstructive coronary artery disease in a real-world setting.

INTRODUCTION AND OBJECTIVES: Randomized controlled trials comparing stress cardiac magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) suggest similar diagnostic accuracy for detecting obstructive coronary artery disease (CAD). There are few data on whether this remains true in routine clinical practice. The aim of this study was to assess clinical and angiographic characteristics of patients undergoing invasive coronary angiography (ICA) after stress CMR or SPECT, and to compare their positive predictive value with published results from the CE-MARC trial. METHODS: In this retrospective tertiary-center analysis, we included 429 patients undergoing ICA after a positive stress CMR or positive SPECT performed within the previous 12 months. Obstructive CAD was defined as any coronary artery stenosis ≥50% in a vessel compatible with the ischemic territory on stress testing. RESULTS: Of the total 429 patients, 356 (83%) were referred after a positive SPECT, and 73 (17%) after a positive stress CMR. Patients did not differ according to age, cardiovascular risk factors, previous revascularization or left ventricular dysfunction, but patients with SPECT were more frequently male (p=0.046). The prevalence of obstructive CAD was similar in patients with positive SPECT vs. positive stress CMR (76.1% vs. 80.8%, respectively, p=0.385). The positive predictive values of both techniques were similar to those reported in the CE-MARC trial. CONCLUSION: In this tertiary center analysis, stress CMR and SPECT showed similar positive predictive values, comparable to those reported in the CE-MARC trial. This finding supports the emerging adoption of CMR in clinical practice for the diagnosis and management of CAD.

Coronary artery calcium score as a gatekeeper for further testing in patients with low pretest probability of obstructive coronary artery disease: A cost-effectiveness analysis.

INTRODUCTION AND OBJECTIVES: Current guidelines recommend not routinely testing patients with chest pain and low pretest probability (PTP <15%) of obstructive coronary artery disease (CAD), but envisage the use of risk modifiers, such as coronary artery calcium score (CACS), to refine patient selection for testing. We aimed to assess the cost-effectiveness (CE) of three different testing strategies in this population: (A) defer testing; (B) perform CACS, withholding further testing if CACS=0, and proceeding to coronary CT angiography (CCTA) if CACS>0; (C) CCTA in all. METHODS: We developed a CE model using data from a two-center cross-sectional study of 1385 patients with non-acute chest pain and PTP <15% undergoing CACS followed by CCTA. Key input data included the prevalence of obstructive CAD on CCTA (10.3%), the proportion with CACS=0 (57%), and the negative predictive value of CACS for obstructive CAD on CCTA (98.1%). RESULTS: Not testing would correctly classify 89.7% of cases and at a cost of €121433 per 1000 patients. Using CACS as a gatekeeper for CCTA would correctly diagnose 98.9% of cases and cost €247116/1000 patients. Employing first-line CCTA would correctly classify all patients, at a cost of €271007/1000 diagnosed patients. The added cost for an additional correct diagnosis was €1366 for CACS±CCTA vs. no testing, and €2172 for CCTA vs. CACS±CCTA. CONCLUSIONS: CACS as a gatekeeper for further testing is cost-effective between a threshold of €1366 and €2172 per additional correct diagnosis. CCTA yields the most correct diagnoses and is cost-effective above a threshold of €2172.

Coronary angiography and percutaneous coronary intervention after transcatheter aortic valve replacement: Feasibility in clinical practice.

INTRODUCTION AND OBJECTIVE: Coronary artery disease is highly prevalent among patients with severe aortic stenosis who undergo transcatheter aortic valve replacement (TAVR). As indications for TAVR are now expanding to younger and lower-risk patients, the need for coronary angiography (CA) and percutaneous coronary intervention (PCI) during their lifetime is expected to increase. The objective of our study was to assess the need for CA and the feasibility of re-engaging the coronary ostia after TAVR. METHODS: We performed a retrospective analysis of 853 consecutive patients undergoing TAVR between August 2007 and December 2020. Patients who needed CA after TAVR were selected. The primary endpoint was the rate of successful coronary ostia cannulation after TAVR. RESULTS: Of a total of 31 CAs in 28 patients (3.5% of 810 patients analyzed: 57% male, age 77.8±7.0 years) performed after TAVR, 28 (90%) met the primary endpoint and in three cannulation was semi-selective. All failed selective coronary ostia cannulations occurred in patients with a self-expanding valve. Sixteen (52%) also had indication for PCI, which was successfully performed in all. The main indication for CA was non-ST-elevation acute coronary syndrome (35%, n=11). Two cases of primary PCI occurred without delay. There were no complications reported during or after the procedure. CONCLUSION: Although CA was rarely needed in patients after TAVR, selective diagnostic CA was possible in the overwhelming majority of patients. PCI was performed successfully in all cases, without complications.

Predicting obstructive coronary artery disease in heart failure with reduced ejection fraction: A practical clinical score.

INTRODUCTION AND OBJECTIVES: Obstructive coronary artery disease (CAD) remains the most common etiology of heart failure with reduced ejection fraction (HFrEF). However, there is controversy whether invasive coronary angiography (ICA) should be used initially to exclude CAD in patients presenting with new-onset HFrEF of unknown etiology. Our study aimed to develop a clinical score to quantify the risk of obstructive CAD in these patients. METHODS: We performed a cross-sectional observational study of 452 consecutive patients presenting with new-onset HFrEF of unknown etiology undergoing elective ICA in one academic center, between January 2005 and December 2019. Independent predictors for obstructive CAD were identified. A risk score was developed using multivariate logistic regression of designated variables. The accuracy and discriminative power of the predictive model were assessed. RESULTS: A total of 109 patients (24.1%) presented obstructive CAD. Six independent predictors were identified and included in the score: male gender (2 points), diabetes (1 point), dyslipidemia (1 point), smoking (1 point), peripheral arterial disease (1 point), and regional wall motion abnormalities (3 points). Patients with a score ≤3 had less than 15% predicted probability of obstructive CAD. Our score showed good discriminative power (C-statistic 0.872; 95% CI 0.834-0.909: p<0.001) and calibration (p=0.333 from the goodness-of-fit test). CONCLUSIONS: A simple clinical score showed the ability to predict the risk of obstructive CAD in patients presenting with new-onset HFrEF of unknown etiology and may guide the clinician in selecting the most appropriate diagnostic modality for the assessment of obstructive CAD.

Impact of genetic information on coronary disease risk in Madeira: The GENEMACOR study.

INTRODUCTION: Coronary artery disease (CAD), characterized by an atherogenic process in the coronary arteries, is one of the leading causes of death in Madeira. The GENEMACOR (GENEs in MAdeira and CORonary Disease) study sought to investigate the main risk factors - environmental and genetic - and estimate whether a genetic risk score (GRS) improves CAD prediction, discrimination and reclassification. METHODS: Traditional risk factors and 33 CAD genetic variants were considered in a case-control study with 3139 individuals (1723 patients and 1416 controls). The multivariate analysis assessed the likelihood of CAD. A multiplicative GRS (mGRS) was created, and two models (with and without mGRS) were prepared. Two areas under receiver operating characteristic curve (area under curve (AUC)) were analyzed and compared to discriminate CAD likelihood. Net reclassification improvement (NRI) and integrated discrimination index (IDI) were used to reclassify the population. RESULTS: All traditional risk factors were strong and independent predictors of CAD, with smoking being the most significant (OR 3.25; p<0.0001). LPA rs3798220 showed a higher CAD likelihood (odds ratio 1.45; p<0.0001). Individuals in the fourth mGRS quartile had an increased CAD probability of 136% (p<0.0001). A traditional risk factor-based model estimated an AUC of 0.73, rising to 0.75 after mGRS inclusion (p<0.0001), revealing a better fit. Continuous NRI better reclassified 28.1% of the population, and categorical NRI mainly improved the reclassification of the intermediate risk group. CONCLUSIONS: CAD likelihood was influenced by traditional risk factors and genetic variants. Incorporating GRS into the traditional model improved CAD predictive capacity, discrimination and reclassification. These approaches may provide helpful diagnostic and therapeutic advances, especially in the intermediate risk group.

Doença coronariana em jovens: novas formas de detecção, prevenção e tratamento / Coronary heart disease in young individuals: novel ways to detect, prevent and treat

Apesar dos grandes avanços nas estratégias de manejo e prevenção da aterosclerose, a prevalência da doença arterial coronariana aumenta em todo o mundo, tendo início em idade precoce. As doenças cardiovasculares em adultos jovens caracterizam-se como um grupo heterogêneo de doenças que ocorrem por causas congênitas ou adquiridas. Múltiplos fatores de risco, como dislipidemia, doença coronária prematura, diabetes melito e tabagismo, potencializam o risco do paciente para a coronariopatia precoce. A avaliação precoce de pacientes com doença arterial coronariana pode ser feita por meio de vários métodos de imagem não invasivos, que facilitam a seleção precoce de condutas preventivas e terapêuticas efetivas para manejo da doença arterial coronariana; no entanto, ela está associada a várias dificuldades, devido às limitações dos escores de risco e à sensibilidade limitada de vários métodos de rastreamento. Neste manuscrito, discutimos sobre fisiopatologia, fatores de risco, métodos de imagem invasivos e não invasivos e várias estratégias de manejo na prevenção precoce da doença coronariana em adultos jovens e, mais importante, os rumos futuros e a prevenção de doenças e da morte súbita cardíaca.

In spite of major advancements in the management and prevention strategies of atherosclerosis, the prevalence of coronary artery disease has risen worldwide, and might start at an early age. Cardiovascular diseases among young adults are characterized as a heterogeneous group of disorders due to congenital or acquired causes. Multiple risk factors, such as dyslipidemia, premature coronary heart disease, diabetes mellitus and cigarette smoking potentiate the patient's risk for early coronary heart disease. Early assessment of patients with coronary artery disease can be performed using various non-invasive imaging methods, which facilitate early selection of effective and preventative therapies for coronary artery disease management; however, it is associated with several challenges due to limitations in risk calculators, and limited sensitivity of various screening methods. In this manuscript, we will discuss about pathophysiology, risk factors, invasive and non- invasive imaging methods, and various management strategies for the early prevention of coronary heart disease in young adults and, importantly, the future directions and preventing disease and sudden cardiac death.

Investigação da Relação entre Índice de Triglicerídeos-Glicose e Fluxo Lento Coronariano: Um Estudo Retrospectivo de Caso-Controle / Investigation of the Relationship Between Triglycerides-Glucose İndex and Coronary Slow Flow: A Retrospective Case-Control Study

Resumo Fundamento O fluxo lento coronariano (FLC) refere-se à opacificação retardada dos vasos distais na ausência de estenose da artéria coronária epicárdica. O mecanismo etiopatogênico do FLC ainda não está claro. Objetivos Este estudo investiga a relação entre o FLC e o índice de triglicerídeos-glicose (TyG). Métodos A amostra do estudo consistiu de 118 pacientes com FLC e 105 pacientes com fluxo coronariano normal (FCN). A taxa de fluxo coronariano foi medida por medio do método de contagem de quadros (TFC) Thrombolysis in Myocardial Infarction (TIMI) em todos os pacientes. O índice TyG foi calculado como o logaritmo do valor [triglicerídeos em jejum (mg/dL)×glicose em jejum (mg/dL)]/2. Adotou-se como estatisticamente significativo o nível de significância < 0,05. Resultados O índice TyG, lipoproteína de baixa densidade (LDL), índice de massa corporal (IMC), relação neutrófilo-linfócito (RNL) e valores de TFC, proporção masculina e proporção de fumantes foram maiores, enquanto os níveis de lipoproteína de alta densidade (HDL) foram significativamente menores no grupo FLC em comparação com o grupo FNC (p<0,05). A análise de correlação revelou que o FLC estava significativamente correlacionado com os valores do índice TyG, IMC, RNL e HDL. A mais forte dessas correlações foi entre o FLC e o índice TyG (r= 0,57, p<0,001). Além disso, a análise multivariada revelou que o índice TyG, IMC, razão RNL e sexo masculino foram preditores independentes para FLC (p<0,05). A análise da curva ROC (Receiver Operating Characteristic) indicou que um valor de corte ≥ 9,28 para o índice TyG previu FLC com sensibilidade de 78% e especificidade de 78,1% [Área sob a curva (AUC): 0,868 e 95% intervalo de confiança (IC): 0,823-0,914]. Conclusão Os achados deste estudo revelaram uma relação muito forte entre o FLC e o índice TyG.

Abstract Background Coronary slow flow (CSF) refers to delayed distal vessel opacification in the absence of epicardial coronary artery stenosis. The etiopathogenic mechanism of CSF is still unclear. Objectives This study investigates the relationship between CSF and the triglyceride-glucose (TyG) index. Methods The study sample consisted of 118 CSF patients and 105 patients with normal coronary flow (NCF). The coronary flow rate was measured via the Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) method in all patients. The TyG index was calculated as the logarithm of the [fasting triglyceride (mg/dL)×fasting glucose (mg/dL)]/2 value. A significance level of < 0.05 was adopted as statistically significant. Results The TyG index, low-density lipoprotein (LDL), body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR) and TFC values, male ratio, and the ratio of smokers were higher, whereas high-density lipoprotein (HDL) levels were significantly lower in the CSF group compared to the NCF group (p<0,05). The correlation analysis revealed that CSF was significantly correlated with TyG index, BMI, NLR, and HDL values. The strongest of these correlations was between CSF and TyG index (r= 0.57, p<0.001). Additionally, the multivariate analysis revealed that TyG index, BMI, NLR ratio, and male gender were independent predictors for CSF (p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that a cut-off value of ≥ 9.28 for the TyG index predicted CSF with a sensitivity of 78% and a specificity of 78.1% [Area under the curve (AUC): 0.868 and 95% Confidence Interval (CI): 0.823-0.914]. Conclusion The findings of this study revealed a very strong relationship between CSF and TyG index.

The updated pre-test probability model of the 2019 ESC guidelines improves prediction of obstructive coronary artery disease.

INTRODUCTION AND OBJECTIVES: The 2019 ESC guidelines on chronic coronary syndromes updated the method for estimating the pre-test probability (PTP) of obstructive coronary artery disease (CAD). We aimed to compare the performance of the new PTP method against the 2013 prediction model in patients with stable chest pain undergoing coronary computed tomography angiography (CCTA) for suspected CAD. METHODS: We conducted a single-center cross-sectional study enrolling 320 consecutive patients undergoing CCTA for suspected CAD. Obstructive CAD was defined as any ≥50% luminal stenosis on CCTA. Whenever invasive coronary angiography was subsequently performed, patients were reclassified accordingly. The two PTP prediction models were assessed for calibration, discrimination and the ability to change the downstream diagnostic pathway. RESULTS: The observed prevalence of obstructive CAD was 16.3% (n=52). The 2013 prediction model significantly overestimated the likelihood of obstructive CAD (relative overestimation of 130%, p=0.005), while the updated 2019 method showed good calibration (relative underestimation of 6.5%, p=0.712). The two approaches showed similar discriminative power, with C-statistics of 0.73 (95% CI: 0.66-0.80) and 0.74 (95% CI: 0.66-0.81) for the 2013 and 2019 methods, respectively (p=0.933). Reclassification of PTP using the new method resulted in a net reclassification improvement of 0.10 (p=0.001). CONCLUSIONS: The updated 2019 prediction model provides a more accurate estimation of pre-test probabilities of obstructive CAD than the previous model. Adoption of this new score may improve disease prediction and influence the selection of non-invasive testing.

Ejercicio aeróbico versus concurrente sobre la interleucina-6 en pacientes con enfermedad arterial coronaria: Una revisión sistemática / Aerobic Versus Concurrent Exercise on Interleukin-6 in Patients with Coronary Arterial Disease: A Systematic Review

Resumen El ejercicio aeróbico (EA) ha demostrado ser beneficioso para la supervivencia del paciente con enfermedad arterial coronaria (EAC) y la disminución de la interleucina 6 (IL-6). Sin embargo, hay poco evidencia del efecto del entrenamiento concurrente (EC). Propósito: Analizar el efecto del EA versus EC sobre la IL-6 en pacientes con EAC. Metodología: Se desarrolló con base en los acuerdos PRISMA, se realizó una búsqueda de los artículos científicos mediante bases de datos electrónicas. Los términos de búsqueda (frase booleana) fueron los siguientes: ("coronary artery disease" OR ''cardiac disease'' OR "cardiovascular disease") AND (''exercise'' OR ''training'' OR "cardiac rehabilitation") AND ("IL-6" OR "Interleukin-6" OR "inflammatory markers"). Las búsquedas se realizaron entre agosto y diciembre de 2019. Resultados: Se revisaron un total de 2516 estudios, de los cuales se incluyeron 10 estudios que cumplieron con los criterios de elegibilidad. Se analizaron un total de 413 pacientes. Se encontró una mejoría entre un 5% y un 74% con el EA y entre un 2.3% y 58.8% con el EC. Ambas modalidades disminuye significativamente la IL-6, independientemente de la edad, sesiones de entrenamiento semanales y de la etapa inicial de los pacientes con EAC, pero aquellos estudios que utilizaron una alta intensidad o un volumen superior a 30 minutos presentaron mayores beneficios. Conclusión: Tanto el EA como el EC son beneficiosos en la disminución de la IL-6 en pacientes con EAC. Esta revisión sistemática deja la posibilidad de continuar investigando el comportamiento de la alta intensidad en la disminución de la IL-6.

Abstract Aerobic exercise (AE) has been shown to be beneficial for the survival of patients with CAD and the decrease in interleukin 6 (IL-6). However, there is little evidence of the effect of concurrent training (CT). Purpose: To analyze the effect of AE versus CT on IL-6 in patients with CAD. Methodology: It was developed based on the PRISMA agreements; scientific articles were searched through electronic databases. The search terms (Boolean phrase) were the following: ("coronary artery disease" OR '' cardiac disease '' OR "cardiovascular disease") AND ('' exercise '' OR '' training '' OR "cardiac rehabilitation") AND ("IL-6" OR "Interleukin-6" OR "inflammatory markers") NOT ("animals" OR "rat"). The searches were conducted between August and December 2019. Results: A total of 2516 studies were reviewed, of which 10 studies that met the eligibility criteria were included. A total of 413 patients were analyzed. An improvement was found between 5% and 74% with the AE and between 2.3% and 58.8% with the CT. Both modalities significantly decrease IL-6, regardless of age, weekly training sessions, and the initial stage of patients with CAD; however, those studies that used a high intensity or a volume greater than 30 minutes showed greater benefits. Conclusion: Both EA and CT are beneficial in reducing IL-6 in patients with CAD. This systematic review leaves the possibility of continuing to investigate the behavior of high intensity in the decrease of IL-6.

Resumo O exercício aeróbio (EA) demonstrou beneficiar a sobrevivência dos pacientes com doença arterial coronária (DAC) e diminuir a interleucina 6 (IL-6). No entanto, há poucas evidências do efeito do treino simultâneo (TC). Objetivo: Analisar o efeito da EA versus TC na IL-6 em pacientes com DAC. Metodologia: Com base nos acordos PRISMA, foi realizada uma pesquisa de artigos científicos utilizando bases de dados eletrônicas. Os termos de busca (frase booleana) foram os seguintes: (''doença arterial coronária'' OU ''doença cardíaca'' OU ''doença cardiovascular'') E (''exercício'' OU ''treinamento'' OU ''reabilitação cardíaca'') E (''IL-6'' OU ''Interleucina-6'' OU ''marcadores inflamatórios''). As pesquisas foram realizadas entre agosto e dezembro de 2019. Resultados: Um total de 2516 estudos foram revistos, dos quais foram incluídos 10 estudos que preenchiam os critérios de elegibilidade. Foram analisados um total de 413 pacientes. A melhoria foi encontrada entre 5% e 74% com a EA e entre 2,3% e 58,8% com o TC. Ambas as modalidades diminuíram significativamente a IL-6, independentemente da idade, das sessões semanais de treinamento e do estágio inicial dos pacientes com DAC, mas os estudos que utilizaram alta intensidade ou volume superior a 30 minutos tiveram maiores benefícios. Conclusão: Tanto a EA como a TC são benéficas para a redução da IL-6 em pacientes com DAC. Esta revisão sistemática deixa espaço para uma investigação mais aprofundada sobre o comportamento de baixa intensidade da IL-6.

Coronary atherosclerotic burden in veteran male recreational athletes with low to intermediate cardiovascular risk.

INTRODUCTION: Although there is evidence that a significant proportion of veteran athletes have coronary atherosclerotic disease (CAD), its prevalence in recreational athletes with low to intermediate cardiovascular (CV) risk is not established. This study aimed to characterize the coronary atherosclerotic burden in veteran male recreational athletes with low to intermediate CV risk. METHODS: Asymptomatic male athletes aged ≥40 years with low to intermediate risk, who exercised >4 hours/week for >5 years, underwent cardiac computed tomography (CT) for coronary artery calcium (CAC) scoring and CT angiography. High coronary atherosclerotic burden was defined as at least one of the following: CAC score >100; CAC score ≥75th percentile; obstructive CAD; disease involving the left main, three vessels or two vessels including the proximal left anterior descending artery; segment involvement score >5; or CT Leaman score ≥5. Athletes were categorized by tertiles of exercise volume, calculated by metabolic equivalent of task (MET) scores. RESULTS: A total of 105 athletes were included, all with SCORE <4%, mainly engaged in high-dynamic sports. Median exercise volume was 66 (44-103) METs/hour/week, with 8±5 hours training/week and 17±10 years of exercise. A high coronary atherosclerotic burden was present in 27 (25.7%) athletes. Ten (9.5%) athletes had CAC score >100, 13 (12.4%) had CAC score ≥75th percentile and six (5.7%) had obstructive lesions. The extent and severity of coronary plaques did not differ according to exercise volume. CONCLUSIONS: The prevalence of subclinical CAD detected by cardiac CT in veteran male recreational athletes with low to intermediate CV risk was high. Up to a quarter of our cohort had a high coronary atherosclerotic burden.

Update on myocardial blood flow quantification by positron emission tomography. / Quantificação do fluxo sanguíneo miocárdico por tomografia por emissão de positrões ­ Atualização.

Cardiovascular disease is the leading cause of death worldwide and ischemic heart disease is the most frequent etiology, with high economic costs for both treatment and diagnosis. Over the past two decades, the assessment of patients with this disease has undergone various changes, with cardiac positron emission tomography (PET) emerging as a powerful and versatile imaging exam for diagnosis and risk stratification of these patients. This review aimed to assess the utility of this exam, particularly through quantification of myocardial blood flow and myocardial flow reserve in the diagnosis and risk stratification of coronary artery disease. Compared to other imaging methods, measurement of these parameters by cardiac PET provides a better characterization of coronary artery disease, with particular value in microvascular and balanced multivessel disease.

Whole blood viscosity in microvascular angina and coronary artery disease: Significance and utility.

INTRODUCTION AND OBJECTIVES: Whole blood viscosity (WBV) is the intrinsic resistance of blood flow in vessels, and when elevated induces endothelial shear stress and endothelial inflammation and can accelerate the atherosclerotic process. This study aims to compare WBV levels in patients with microvascular angina (MVA), patients with coronary artery disease (CAD), and normal controls, and to identify the relationship between WBV and high-sensitivity C-reactive protein as a marker of inflammation in MVA and CAD. METHODS: A total of 573 patients were studied. The MVA group consisted of 189 subjects, the CAD group consisted of 203 subjects, and the control group consisted of 181 age- and gender-matched individuals. WBV was calculated from hematocrit and plasma protein concentration at a low shear rate (0.5 s-1) and high shear rate (208 s-1) by a validated equation. RESULTS: Patients with CAD and MVA had significantly higher WBV at both low and high shear rates compared to the control group. Correlation analysis revealed a significant relationship between high-sensitivity C-reactive protein and WBV at low (r=0.556; p<0.001) and high shear rates (r=0.562) in the CAD group and at low (r=0.475) and high shear rates (r=0.493) in the MVA group. CONCLUSIONS: Overall, this study demonstrated a significant and independent association between blood viscosity and the existence of endothelial inflammation and the atherosclerotic process.

Validação de resultados de enfermagem e seus indicadores para pacientes com risco de perfusão tissular cardíaca diminuída secundário à doença arterial coronária / Validation of nursing outcomes and indicators for patients with risk of decreased cardiac tissue perfusion secondary to coronary artery disease

Introdução: Para analisar a efetividade das intervenções de enfermagem no cuidado de pacientes com Risco de perfusão tissular cardíaca diminuída (00200) (RPTCD) secundário à Doença arterial coronária (DAC) é necessária a seleção de Resultados do paciente sensíveis à enfermagem (RPSE) relevantes e capazes medir estado, percepção ou comportamento do paciente. Objetivo: Estimar a relevância clínica dos resultados e a sensibilidade de seus indicadores às intervenções de enfermagem para pacientes com RPTCD secundário à DAC em unidade de terapia intensiva (TI) e clínica médico-cirúrgica (CMC). Método: Estudo desenvolvido em três etapas. Na primeira, RPSE claramente não pertinentes foram descartados a priori. Os demais foram analisados quanto à pertinência por nove expertos, representantes de seis disciplinas da saúde por meio de escala de 3 pontos. Calculou-se o índice de concordância (IC); RPSE com IC 50% foram considerados pertinentes. Expertos enfermeiros participaram da segunda e terceira etapas. Na segunda, a relevância dos RPSE pertinentes foi determinada por meio de escala Likert de 5 pontos, variando de não relevante a extremamente relevante. Atribuiu-se pesos a cada ponto da escala Likert para o cálculo da média ponderada. RPSE com média 0,80 em pelo menos um cenário clínico foram considerados relevantes. Na terceira etapa, a sensibilidade dos indicadores dos RPSE pertinentes foi estimada por meio de escala de 3 pontos. Calculou-se o IC; indicadores com IC 0,80 foram considerados sensíveis. Todos os expertos forneceram dados de caracterização que foram descritos por medidas de tendência central e dispersão. Testes Wilcoxon-Mann-Whitney, exato de Fisher e Qui-quadrado de Pearson foram utilizados para comparar os expertos que participaram das etapas 2 e 3 com aqueles que não participaram da etapa 3. O estudo foi aprovado pelo Comitê de Ética da Escola de Enfermagem da Universidade de São Paulo. Resultados: Na primeira etapa, foram analisados 245 RPSE, dos quais 116 obtiveram IC > 50%. Na segunda etapa, 25 RPSE foram considerados relevantes, de modo que 509 indicadores foram analisados na terceira etapa. Recuperação cirúrgica: pós- operatório imediato (2305) foi considerado relevante apenas na TI e 80,6% de seus indicadores foram considerados sensíveis. RPSE do domínio IV foram considerados relevantes apenas na CMC. Dentre estes, o percentual de indicadores sensíveis variou de 13,3% para Participação nas decisões sobre cuidados de saúde (1606) a 100% para Conhecimento: regime de tratamento (1813). Em relação aos RPSE relevantes na TI e na CMC, Perfusão tissular (0422) apresentou o menor percentual (30,0% e 20,0%, respectivamente) e Sinais vitais (0802) o maior percentual (90,0% e 80,0%, respectivamente) de indicadores sensíveis concomitantemente. Houve indicadores considerados sensíveis em apenas um dos cenários. Conclusão: RPSE relevantes para pacientes com RPTCD secundário à DAC assistidos em TI e CMC pertencem aos domínios II-Saúde fisiológica, III-Saúde psicossocial, IV-Conhecimento em saúde e comportamento e V-Saúde percebida. Os indicadores sensíveis parecem refletir as especificidades do cuidado prestado em cada cenário de prática. Entretanto, é necessária a confirmação desses achados em estudos de validação clínica.

Introduction: Effectiveness analysis of nursing interventions in caring of patients with Risk of decreased cardiac tissue perfusion (00200) (RDCTP) secondary to Coronary artery disease (CAD), it is important to select relevant Nursing Sensitive Patient Outcomes (NSPO) and able to measure the patient's status, perception or behavior. Objective: To estimate the clinical relevance of the outcomes and the sensitivity of their indicators to nursing interventions for patients with RDCTP secondary to CAD in the intensive care (IC) and medical-surgical ward (MSW). Method: This study was developed in three steps. In the first, clearly non-pertinent NSPO were discarded. The others NSPO were analyzed by nine experts considering relevance, representing six health disciplines through a 3-point scale. The agreement index (AI) was calculated; NSPO with AI 50% were considered pertinent. Expert nurses participated in the second and third stages. In the second, the relevance of the pertinent NSPO was determined by a 5-point Likert scale, ranging from not relevant to extremely relevant. Scores were assigned to each point on the Likert scale for measure average calculation. NSPO with a mean 0.80 in at least one clinical setting were considered relevant. In the third stage, the indicators sensitivity of the relevant RPSE was estimated using a 3-point scale. AI was calculated; indicators scored 0.80 were considered sensitive. All of the experts provided characterization data that was described by measures of central tendency and dispersion. Wilcoxon-Mann-Whitney, Fisher's exact, and Pearson's chi-square tests were used to compare the experts who participated in steps 2 and 3 with those who did not participate in step 3. The study was approved by the School of Nursing Ethics Committee of University of Sao Paulo. Results: In the first stage, 245 NSPO were analyzed, of which 116 obtained AI 50%. In the second stage, 25 NSPO were considered relevant, then 509 indicators were analyzed in the third stage. Surgical recovery: immediate postoperative (2305) was considered relevant only in IC and 80.6% of its indicators were considered sensitive. NSPO of Domain IV were considered relevant only in MSW. Among these, the percentage of sensitive indicators ranged from 13.3% for Participation in Health Care Decisions (1606) to 100% for Knowledge: Treatment Regimen (1813). Regarding the relevant RPSE in IC and MSW, Tissue perfusion (0422) presented the lowest percentage (30.0% and 20.0%, respectively) and Vital signs (0802) the highest percentage of sensitive indicators (90.0% and 80.0%, respectively). There were indicators considered sensitive in only one of the scenarios. Conclusion: Relevant NSPO for patients with RDCTP secondary to CAD assisted in IC and MSW belong to Domains II-Physiological Health, III-Psychosocial Health, IV- Health Knowledge and Behavior, and V-Perceived Health. Sensitive indicators might reflect the specifics of care provided in each practice setting. However, confirmation of these findings is required in clinical validation studies.

Metabolismo e função das lipoproteínas de alta densidade (HDL) em indivíduos idosos: efeito da presença de diabetes mellitustipo 2 e doença coronária obstrutiva / Metabolism and function of high density lipoprotein (HDL) in the elderly: effects of type 2 diabetes mellitus and coronary artery disease

Introdução: A doença arterial coronária (DAC) decorrente da aterosclerose é uma das principais causas de comprometimento do envelhecimento saudável e sobrevida do idoso.Entre os principais fatores de risco da DAC estão o diabetes mellitus tipo 2 (DM) e as dislipidemias. O HDL-colesterol baixo é fator de risco importante, mas aspectos funcionais e metabólicos da HDL devem ser avaliados, já que esta lipoproteína tem várias ações anti-aterogênicas. Neste sentido, a transferência de lípides de outras lipoproteínas para a HDL, mediada pela proteína de transferência de ésteres de colesterol (CETP), é passo importante na formação e metabolismo da HDL e está relacionada com a presença de DAC. Objetivo: Avaliar o impacto da idade nas transferências de lípides para HDL e outros parâmetros relacionados com o metabolismo da HDL em indivíduos idosos e as mudanças nesses parâmetros em idosos com DAC e com DAC e DM. Métodos: Foram estudados 25 jovens (JOV), 35 idosos sem DAC e sem DM (IDS), 35 idosos com DAC (IDS-DAC) e 34 idosos com DAC e DM (IDS-DAC-DM). Foram determinados perfil lipídico e apolipoproteínas plasmáticas, concentração plasmática da CETP e da lecitina-colesterol aciltransferase (LCAT), composição lipídica e diâmetro da HDL e marcadores inflamatórios. A transferência de colesterol esterificado e livre, fosfolípides e triglicérides para a HDL foi realizada por ensaio "in vitro" com uma nanopartícula marcada com lípides radioativos como partícula doadora de lípides. Após a precipitação química das outras lipoproteínas e da nanopartícula doadora, o sobrenadante contendo HDL foi separadoe medida a radioatividade. Resultados: IDS apresentou IMC maior que JOV. LDL-colesterol e não-HDL-colesterol, IL-6 e IL-8 foram mais altos, IL-1ß mais baixo e a transferência de fosfolípides para a HDL foi maior em IDS do que em JOV, mas as diferenças desapareceram quando corrigidas pelo IMC. Entre IDS-DAC e IDS não houve diferenças nos lípides plasmáticos, mas no IDS-DAC a transferência de colesterol livre, triglicérides e fosfolípides foi menor e a de colesterol esterificado foi maior. A concentração de CETP foi maior no IDS-DAC, onde houve maior % de colesterol esterificado e triglicérides e menor % de fosfolípides na HDL. Em IDS-DAC-DM, apoB foi maior que em IDS-DAC, mas LDL-colesterol foi igual. Houve menor transferência de colesterol esterificado em IDS-DAC-DM comparado a IDS-DAC e maior de fosfolípides. IDS-DAC-DM teve CETP mais baixa e LCAT mais alta do que IDS-DAC. Em IDS-DAC-DM houve menor proporção de colesterol esterificado e livre e maior de fosfolípides na HDL. Marcadores inflamatórios não diferiram entre IDS-DAC-DM e IDS-DAC. Conclusões: As alterações nos parâmetros de transferência de lípides sinalizaram tanto a presença de DAC nos idosos quanto diferenciaram idosos com DAC associada a DM daqueles apenas com DAC. A redução da transferência de colesterol livre nos idosos com DAC é aterogênica, como foi mostrado em trabalho anteriorem indivíduos de 40-50 anos com DAC precoce. Esses dados podem ter aplicação tanto na prevenção quanto na terapêutica da DAC, por meio de medicamentos que modulem a transferência de lípides para a HDL e assim melhorem a função anti-aterogênica desta lipoproteína

Introduction: Coronary artery disease (CAD) resulting from atherosclerosis is one of the main causes of compromised healthy aging and lifespan in elderly people. Amongst the main risk factors for CAD are type 2 diabetes mellitus (DM) and dyslipidemias. Low HDL-cholesterol is an important risk factor, but functional and metabolic aspects of HDL must be evaluated, since this lipoprotein has several anti-atherogenic actions. In this regard, lipid transfer from other lipoproteins to HDL, mediated by cholesteryl ester transfer protein (CETP), is an important step towards the formation and metabolism of HDL and is related to the presence of CAD. Objective: To evaluate the impact of age in lipid transfer to HDL and other parameters related to HDL metabolism in elderly individuals and the changes in these parameters in elderly individuals with CAD and with CAD and DM. Methods: 25 young (YOUNG), 35 elderly without CAD and DM (ELDERLY), 35 elderly with CAD (ELDERLY-CAD) and 34 elderly with CAD and DM (ELDERLY-CAD-DM) subjects were studied. The lipid profile, the apolipoprotein, CETP and lecithin-cholesterol acyltransferase (LCAT) plasma concentration,theHDL lipid composition and diameter and inflammatory markers were evaluated.The transfer of esterified and free cholesterol, phospholipids and triglycerides to HDL was assayed in vitro with a donor lipid nanoparticle labeled with radioactive lipids.After chemical precipitation of the other lipoproteins and the donor lipid nanoparticle, the supernatant containing HDL was separated and the radioactivity was measured. Results: ELDERLY presented greater BMI than YOUNG. LDL-cholesterol and non-HDL-cholesterol, IL-6 and IL-8 were higher, IL-1ß was lower and phospholipid transfer to HDL was higher in ELDERLY than in YOUNG, but the differences disappeared when corrected by BMI. There were no differences in plasmatic lipids between ELDERLY-CAD and ELDERLY, but in ELDERLY-CAD the transfer of free cholesterol, triglycerides and phospholipids was lower and of esterified cholesterol was higher. CETP concentration was higher in ELDERLY-CAD, where there was higher % of esterified cholesterol and triglycerides and lower % of phospholipids in HDL. In ELDERLY-CAD-DM, apo B was higher than in ELDERLY-CAD, but LDL-cholesterol was equal. There was lower transfer of esterified cholesterol in ELDERLY-CAD-DM compared to ELDERLY-CAD and higher transfer of phospholipids. ELDERLY-CAD-DM had lower CETP and higher LCAT than ELDERLY-CAD. In ELDERLY-CAD-DM there was a smaller proportion of esterified and free cholesterol and greater proportion of phospholipids in HDL. Inflammatory markers did not differ between ELDERLY-CAD-DM and ELDERLY-CAD. Conclusions: The alterations in the parameters of lipid transfer not only signalled the presence of CAD in the elderly but also differentiated the elderly with CAD and DM from those with CAD only. The reduction of free cholesterol transfer in the elderly with CAD is atherogenic, as shown in a previous work on individuals of 40-50 years of agewith precocious CAD. This data may be applied both to the prevention and the therapeutics of CAD, by means of medicines that modulate lipid transfer to HDL and thus improve the anti-atherogenic function of this lipoprotein

Diretriz brasileira baseada em evidências sobre prevenção de doenças cardiovasculares em pacientes com diabetes: posicionamento da Sociedade Brasileira de Diabetes (SBD), da Sociedade Brasileira de Cardiologia (SBC) e da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) / Brazilian evidence-based guideline on cardiovascular disease prevention in patients with diabetes: positioning of the Brazilian Society of Diabetes (SBD), the Brazilian Society of Cardiology (SBC) and the Brazilian Society of Endocrinology and Metabology (SBEM)

Resumo Fundamentação: desde o primeiro posicionamento da Sociedade Brasileira de Diabetes (SBD) sobre diabetes e prevenção cardiovascular, em 2014,1 importantes estudos têm sido publicados na área de prevenção cardiovascular e tratamento do diabetes,2 os quais contribuíram para a evolução na prevenção primária e secundária nos pacientes com diabetes. Ferramentas de estratificação de risco mais precisas, novos fármacos hipolipemiantes e novos antidiabéticos com efeitos cardiovasculares e redução da mortalidade, são parte desta nova abordagem para os pacientes com diabetes. O reconhecimento de que o diabetes é uma doença heterogênea foi fundamental, sendo claramente demonstrado que nem todos os pacientes diabéticos pertencem a categorias de risco alto ou muito alto. Um porcentual elevado é composto por pacientes jovens, sem os fatores de risco clássicos, os quais podem ser classificados adequadamente em categorias de risco intermediário ou mesmo em baixo risco cardiovascular. O presente posicionamento revisa as melhores evidências atualmente disponíveis e propõe uma abordagem prática, baseada em risco, para o tratamento de pacientes com diabetes. Estruturação: perante este desafio e reconhecendo a natureza multifacetada da doença, a SBD uniu-se à Sociedade Brasileira de Cardiologia (SBC) e à Sociedade Brasileira de Endocrinologia e Metabolismo (SBEM), e formou um painel de especialistas, constituído por 28 cardiologistas e endocrinologistas, para revisar as melhores evidências disponíveis e elaborar uma diretriz contendo recomendações práticas para a estratificação de risco e prevenção da Doença Cardiovascular (DVC) no Diabetes Melito (DM). As principais inovações incluem: (1) considerações do impacto de novos hipolipemiantes e das novas medicações antidiabéticas no risco cardiovascular; (2) uma abordagem prática, baseada em fator de risco, para orientar o uso das estatinas, incluindo novas definições das metas da Lipoproteína de Baixa Densidade-colesterol (LDL-colesterol) e colesterol não Lipoproteína de Alta Densidade HDL; (3) uma abordagem baseada em evidências, para avaliar a isquemia miocárdica silenciosa (IMS) e a aterosclerose subclínica em pacientes com diabetes; (4) as abordagens mais atuais para o tratamento da hipertensão; e (5) recomendação de atualizações para o uso de terapia antiplaquetária. Esperamos que esta diretriz auxilie os médicos no cuidado dedicado aos pacientes com diabetes. Métodos: inicialmente, os membros do painel foram divididos em sete subcomitês para definirem os tópicos principais que necessitavam de uma posição atualizada das sociedades. Os membros do painel pesquisaram e buscaram no PubMed estudos clínicos randomizados e metanálises de estudos clínicos e estudos observacionais de boa qualidade, publicados entre 1997 e 2017, usando termos MeSH: [diabetes], [diabetes tipo 2], [doença cardiovascular], [estratificação de risco cardiovascular] [doença arterial coronária], [rastreamento], [isquemia silenciosa], [estatinas], [hipertensão], [ácido acetilsalicílico]. Estudos observacionais de baixa qualidade, metanálises com alta heterogeneidade e estudos transversais não foram incluídos, embora talvez tenham impactado no Nível de Evidência indicado. A opinião de especialistas foi usada quando os resultados das buscas não eram satisfatórios para um item específico. É importante salientar que este posicionamento não teve a intenção de incluir uma revisão sistemática rigorosa. Um manuscrito preliminar, destacando recomendações de graus e níveis de evidência (Quadro 1), foi esboçado. Este passo levou a várias discussões entre os membros dos subcomitês, que revisaram os achados e fizeram novas sugestões. O manuscrito foi, então, revisto pelo autor líder, encarregado da padronização do texto e da inclusão de pequenas alterações, sendo submetido à apreciação mais detalhada pelos membros dos comitês, buscando uma posição de consenso. Depois desta fase, o manuscrito foi enviado para a banca editorial e edição final, sendo encaminhado para publicação. Quadro 1 Graus de recomendações e níveis de evidências adotados nesta revisão Grau de recomendação Classe I A evidência é conclusiva ou, se não, existe consenso de que o procedimento ou tratamento é seguro e eficaz Classe II Há evidências contraditórias ou opiniões divergentes sobre segurança, eficácia, ou utilidade do tratamento ou procedimento Classe IIa As opiniões são favoráveis ao tratamento ou procedimento. A maioria dos especialistas aprova Classe IIb A eficácia é bem menos estabelecida, e as opiniões são divergentes Classe III Há evidências ou consenso de que o tratamento ou procedimento não é útil, eficaz, ou pode ser prejudicial Níveis de Evidência A Múltiplos estudos clínicos randomizados concordantes e bem elaborados ou metanálises robustas de estudos clínicos randomizados B Dados de metanálises menos robustas, um único estudo clínico randomizado ou estudos observacionais C Opinião dos especialistas