Predicting Significant Coronary Obstruction in a Population with Suspected Coronary Disease and Absence of Coronary Calcium: CORE-64 / CORE320 Studies. / Predição de Obstrução Coronariana Significativa em População com Suspeita de Doença Coronariana e Ausência de Cálcio Coronariano: CORE-64 e CORE320.

BACKGROUND: Coronary artery calcium (CAC) scanning can be performed using non-contrast computed tomography to predict cardiovascular events, but has less value for risk stratification in symptomatic patients. OBJECTIVE: To identify and validate predictors of significant coronary obstruction (SCO) in symptomatic patients without coronary artery calcification. METHODS: A total of 4,258 participants were screened from the CORE64 and CORE320 studies that enrolled patients referred for invasive angiography, and from the Quanta Registry that included patients referred for coronary computed tomography angiography (CTA). Logistic regression models evaluated associations between cardiovascular risk factors, CAC, and SCO. An algorithm to assess the risk of SCO was proposed for patients without CAC. Significance level of 5% was used in the analyses. RESULTS: Of the 509 participants of the CORE study, 117 (23%) had zero coronary calcium score; 13 (11%) patients without CAC had SCO. Zero calcium score was related to younger age, female gender, lower body mass index, no diabetes, and no dyslipidemia. Being a current smoker increased ~3.5 fold the probability of SCO and other CV risk factors were not significantly associated. Considering the clinical findings, an algorithm to further stratify zero calcium score patients was proposed and had a limited performance in the validation cohort (AUC 58; 95%CI 43, 72). CONCLUSION: A lower cardiovascular risk profile is associated with zero calcium score in a setting of high-risk patients. Smoking is the strongest predictor of SCO in patients without CAC.

FUNDAMENTO: A avaliação do Escore de Cálcio Coronariano (ECC) pode ser realizada por tomografia computadorizada sem contraste para prever eventos cardiovasculares, mas tem menor valor na estratificação de risco em pacientes sintomáticos. OBJETIVO: Identificar e validar preditores de obstrução coronariana significativa (OCS) em pacientes sintomáticos sem calcificação da artéria coronária. MÉTODOS: Um total de 4258 participantes foram rastreados dos estudos CORE64 e CORE 320, nos quais foram avaliados pacientes encaminhados para angiografia invasiva, e do Quanta Registry que incluiu pacientes encaminhados para angiotomografia. Modelos de regressão logística avaliaram associações entre fatores de risco cardiovascular, ECC e OCS. Um nível de significância de 5% foi usado nas análises. RESULTADOS: Dos 509 participantes do estudo CORE, 117 (23%) apresentaram um ECC igual a zero; 13 (11%) pacientes sem cálcio coronariano apresentaram OCS. A ausência de cálcio coronariano correlacionou-se com idade mais jovem, sexo feminino, índice de massa corporal mais baixo, ausência de diabetes, e ausência de dislipidemia. O fato de ser fumante atual aumentou em 3,5 vezes a probabilidade de OCS e outros fatores de risco cardiovasculares não apresentaram associação significativa. Considerando os achados clínicos, um algoritmo para estratificar os pacientes com ECC igual a zero foi proposto, e tiveram desempenho limitado na coorte de validação (AUC 58; IC95% 43, 72). CONCLUSÃO: Um perfil de risco cardiovascular mais baixo está associado a um ECC igual a zero em pacientes de alto risco. Tabagismo é o preditor mais forte de OCS em pacientes com ausência de cálcio coronariano.

Coronary computed tomography plaque-based scores predict long-term cardiovascular events.

OBJECTIVES: Coronary computed tomography angiography (coronary CTA) scores based on luminal obstruction, plaque burden, and characteristics are used for prognostication in coronary artery disease (CAD), such as segmental stenosis and plaque extent involvement and Gensini and Leaman scores. The use of coronary CTA scores for the long-term prognosis remains not completely defined. We sought to evaluate the long-term prognosis of CTA scores for cardiovascular events in symptomatic patients with suspected CAD. METHODS: The presence and extent of CAD were evaluated by coronary CTA in patients from two multicenter prospective studies, which were classified according to several coronary CTA scores. The primary endpoint was major adverse cardiac events (MACE). Two hundred and twenty-two patients were followed up for a median of 6.8 (6.3-9.1) years, and 73 patients met the composite endpoints of MACE. RESULTS: Compared to the clinical prediction model, the highest model improvement was observed when added obstructive CAD. After adjustment for the presence of obstructive CAD, the segment involvement score for non-calcified plaque (SISNoncalc) was independently associated with MACE, presenting incremental prognostic value over clinical data and CAD severity (χ2 39.5 vs 21.2, p < 0.001 for comparison with a clinical model; and χ2 39.5 vs 35.6, p = 0.04 for comparison with clinical + CAD severity). Patients with obstructive CAD and SISNoncalc > 3 were likely to experience events (HR 4.27, 95% CI 2.17-4.40, p < 0.001). CONCLUSIONS: Coronary CTA plaque-based scores provide incremental long-term prognostic value for up to 7 years. Among patients with obstructive CAD, the presence of extensive non-calcified disease (> 3 coronary segments) is associated with increased cardiovascular risk for late events independently of the presence of obstructive CAD. KEY POINTS: • Coronary CTA plaque-based scores are long-term prognostic markers in patients with stable CAD. • Besides obstructive CAD, the segment involvement score of non-calcified disease of 3 or more independently increased the risk of cardiovascular events.

Predição de Obstrução Coronariana Significativa em População com Suspeita de Doença Coronariana e Ausência de Cálcio Coronariano: CORE-64 e CORE320 / Predicting Significant Coronary Obstruction in a Population with Suspected Coronary Disease and Absence of Coronary Calcium: CORE-64 / CORE320 Studies

Resumo Fundamento A avaliação do Escore de Cálcio Coronariano (ECC) pode ser realizada por tomografia computadorizada sem contraste para prever eventos cardiovasculares, mas tem menor valor na estratificação de risco em pacientes sintomáticos. Objetivo Identificar e validar preditores de obstrução coronariana significativa (OCS) em pacientes sintomáticos sem calcificação da artéria coronária. Métodos Um total de 4258 participantes foram rastreados dos estudos CORE64 e CORE 320, nos quais foram avaliados pacientes encaminhados para angiografia invasiva, e do Quanta Registry que incluiu pacientes encaminhados para angiotomografia. Modelos de regressão logística avaliaram associações entre fatores de risco cardiovascular, ECC e OCS. Um nível de significância de 5% foi usado nas análises. Resultados Dos 509 participantes do estudo CORE, 117 (23%) apresentaram um ECC igual a zero; 13 (11%) pacientes sem cálcio coronariano apresentaram OCS. A ausência de cálcio coronariano correlacionou-se com idade mais jovem, sexo feminino, índice de massa corporal mais baixo, ausência de diabetes, e ausência de dislipidemia. O fato de ser fumante atual aumentou em 3,5 vezes a probabilidade de OCS e outros fatores de risco cardiovasculares não apresentaram associação significativa. Considerando os achados clínicos, um algoritmo para estratificar os pacientes com ECC igual a zero foi proposto, e tiveram desempenho limitado na coorte de validação (AUC 58; IC95% 43, 72). Conclusão Um perfil de risco cardiovascular mais baixo está associado a um ECC igual a zero em pacientes de alto risco. Tabagismo é o preditor mais forte de OCS em pacientes com ausência de cálcio coronariano.

Abstract Background Coronary artery calcium (CAC) scanning can be performed using non-contrast computed tomography to predict cardiovascular events, but has less value for risk stratification in symptomatic patients. Objective To identify and validate predictors of significant coronary obstruction (SCO) in symptomatic patients without coronary artery calcification. Methods A total of 4,258 participants were screened from the CORE64 and CORE320 studies that enrolled patients referred for invasive angiography, and from the Quanta Registry that included patients referred for coronary computed tomography angiography (CTA). Logistic regression models evaluated associations between cardiovascular risk factors, CAC, and SCO. An algorithm to assess the risk of SCO was proposed for patients without CAC. Significance level of 5% was used in the analyses. Results Of the 509 participants of the CORE study, 117 (23%) had zero coronary calcium score; 13 (11%) patients without CAC had SCO. Zero calcium score was related to younger age, female gender, lower body mass index, no diabetes, and no dyslipidemia. Being a current smoker increased ~3.5 fold the probability of SCO and other CV risk factors were not significantly associated. Considering the clinical findings, an algorithm to further stratify zero calcium score patients was proposed and had a limited performance in the validation cohort (AUC 58; 95%CI 43, 72). Conclusion A lower cardiovascular risk profile is associated with zero calcium score in a setting of high-risk patients. Smoking is the strongest predictor of SCO in patients without CAC.

Impact of non-pharmacological initiatives for COVID-19 on hospital admissions due to pediatric acute respiratory illnesses.

INTRODUCTION: Interventions to deal with the COVID-19 pandemic may impact the burden of other respiratory diseases. The aim of this study is to analyze the impact of non-pharmacological initiatives (NPI) against COVID-19 on the number of hospitalizations due to pediatric acute respiratory illnesses (ARIs). MATERIAL AND METHODS: This is a retrospective analysis of pediatric hospitalizations in Porto Alegre, Brazil. We analyzed the monthly incidence of hospital admissions from 2018 to 2020 due to ARIs included in the study. The time series was divided into the period before introducing NPI (2018 and 2019), and the period when NPI were running (2020). We compared means between the years with Student's t-test. The Dickey-Fuller test was used for secular trend analysis. For seasonality, Fischer's G test was performed. Dynamic linear univariate and multivariate models were used to estimate the association between the predictors (the introduction of NPI, secular trend, and seasonality) and outcome (the incidence of ARI admissions). For the statistical analysis, the cut-off probability for rejecting the null hypothesis was defined as <5%. RESULTS: From 2018 to 2020, 10,109 hospital admissions were due to the respiratory causes included in this study. There was a significant decrease in 2020 in the mean incidence of the ARIs studied compared with 2018 and 2019. The number of hospitalizations due to respiratory diseases in children decreased by 64% for asthma and 93% for bronchiolitis. A secular trend of monthly admissions rates due to ARIs was only observed in the laryngotracheitis data (p = 0.485), but seasonality was detected in all analyses. According to the univariate and multivariate analysis, the introduction of NPI was associated with a decrease in the incidence of ARI admissions. CONCLUSION: There was a significant reduction in hospital admissions due to ARIs in children. Our data suggest a significant impact of NPI on reducing the spread of viruses associated with ARIs in children. These results support respiratory illness prevention strategies.

Ecocardiografia e Análise de Doenças Cardiovasculares Subclínicas em Povos Indígenas que Vivem em Diferentes Graus de Urbanização: Projeto de Aterosclerose nas Populações Indígenas (Pai) / Echocardiography and Analysis of Subclinical Cardiovascular Diseases in Indigenous People Living in Different Degrees of Urbanization: Project of Atherosclerosis Among Indigenous Populations (Pai

Fundamento: O processo de urbanização tem impacto na carga de doenças cardiovasculares. As populações indígenas podem sofrer uma transição epidemiológica devastadora. Objetivos: Descrever o protocolo de estudo do Projeto de Aterosclerose nas Populações Indígenas (PAI) para avaliar a análise ecocardiográfica e as doenças cardiovasculares (CV) subclínicas em populações indígenas de acordo com o grau de urbanização e mostrar resultados preliminares do estudo piloto. Métodos: O PAI é um estudo transversal, com voluntários com idade entre 30 e 70 anos, em grupos indígenas brasileiros expostos a estágios baixos e avançados de urbanização (Fulni-ô e Truká, respectivamente) e um grupo controle urbano, excluindo indivíduos com doenças CV conhecidas ou em hemodiálise. O estudo piloto começou no território de Fulni-ô em setembro de 2016. Os participantes foram submetidos a avaliação clínica e laboratorial, eletrocardiograma (ECG), ultrassonografia de carótidas e um protocolo ecocardiográfico abrangente, incluindo strain longitudinal global (SLG) avaliado por speckle tracking. Os resultados preliminares são descritos de acordo com o sexo em uma análise univariada. Resultados: O estudo piloto avaliou o protocolo descrito em 55 indivíduos do grupo indígena Fulni-ô (48,7 ± 12,0 anos, 80% mulheres). Foram encontrados fatores de risco tradicionais como hipertensão, diabetes e dislipidemia em 40%, 36% e 54%, respectivamente, sem diferenças estatísticas significativas entre os sexos. O uso de tabaco mostrou-se extremamente prevalente, referido em 91% dos participantes. Os parâmetros derivados da ecocardiografia estavam, em média, dentro da faixa normal. No entanto, a média do SLG foi de 17,3 ± 3,4% (p 0,73 por sexo). Conclusão: Descrevemos o protocolo do estudo PAI para avaliar doenças cardiovasculares subclínicas e fatores de risco em populações indígenas de acordo com o estágio de urbanização. Resultados preliminares sugerem alta prevalência desses na população indígena em menor grau de urbanização.

Background: The urbanization process impacts the burden of cardiovascular disease (CVD). Indigenous populations can undergo a devastating epidemiological transition. Objective: The present study aimed to describe the Project of Atherosclerosis among Indigenous Populations (PAI) study protocol for assessing echocardiographic images and subclinical CVD in indigenous populations according to the degree of urbanization and report its preliminary results. Methods: The PAI is a cross-sectional study that includes volunteers aged 30­70 years among Brazilian indigenous groups exposed to low and advanced stages of urbanization (Fulni-ô and Truká, respectively) and an urban control group. Individuals with known CVD or who were on hemodialysis were excluded. The pilot study began in Fulni-ô territory in September 2016. The participants underwent clinical and laboratory

Pulmonary Artery Acceleration Time in Young Adulthood and Cardiovascular Outcomes Later in Life: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: Lower pulmonary artery acceleration time (PAcT) is correlated with higher pulmonary artery pressure. The aim of this study was to test the hypothesis that PAcT measured in young adulthood would be associated with future cardiovascular outcomes. METHODS: In the Coronary Artery Risk Development in Young Adults year 5 examination (1990-1991), PAcT was measured as the time interval from onset to peak flow velocity at the pulmonary valve annulus on Doppler echocardiography. The primary outcome was a composite of fatal or nonfatal cardiovascular disease events: myocardial infarction, non-myocardial infarction acute coronary syndrome, coronary revascularization, congestive heart failure, stroke, transient ischemic attack, carotid artery disease, and peripheral arterial disease. RESULTS: PAcT was obtained in 4,171 participants (mean age, 30 ± 4 years, 55% women, 51% white). PAcT groups obtained using linear spline methodology were as follows: group I, PAcT ≥ 196 msec (n = 122); group II, PAcT < 196 and ≥115 msec (n = 3,195); and group III, PAcT < 115 msec (n = 854). During follow-up (median, 24.9 years), the primary outcome occurred in 216 participants (5.2%); 66 of 854 (7.7%) of those with PAcT < 115 msec, 149 of 3,195 (4.7%) of those with intermediate PAcT level, and one of 122 (0.8%) of those with PAcT ≥ 196 msec. In a fully adjusted model, the lowest and intermediate PAcT groups had hazard ratios of 8.3 (95% CI, 1.1-62.1; P = .04) and 6.8 (95% CI, 0.9-50.5; P = .06), respectively, in comparison with the highest PAcT group. CONCLUSIONS: PAcT is useful for better identifying young adults at higher risk for cardiovascular events, who may benefit from a strict control of modifiable cardiovascular risk factors.

Left Ventricular Scar and Prognosis in Chronic Chagas Cardiomyopathy.

BACKGROUND: Patients with chronic Chagas cardiomyopathy (CCC) have pronounced myocardial fibrosis, which may predispose to sudden cardiac death, despite well-preserved global left ventricular (LV) systolic function. Cardiac magnetic resonance can assess myocardial fibrosis by late gadolinium enhancement (LGE) sequences. OBJECTIVES: This prospective study evaluated if the presence of scar by LGE predicted hard adverse outcomes in a cohort of patients with CCC. METHODS: A prospective cohort of 140 patients with CCC (52.1% female; median age 57 years [interquartile range: 45 to 67 years]) were included. Cardiac magnetic resonance cine and LGE imaging were performed at enrollment with a 1.5-T scanner. The primary endpoint was the combination of cardiovascular death and sustained ventricular tachycardia. The secondary endpoint was the combination of cardiovascular death, sustained ventricular tachycardia, or cardiovascular hospitalization during follow-up. RESULTS: After a median of 34 months (interquartile range: 24 to 49 months) of follow-up, 11 cardiovascular deaths, 3 episodes of sustained ventricular tachycardia, and 20 cardiovascular hospitalizations were recorded. LGE scar was present in 71.4% of the patients, with the lateral, inferolateral, and inferior walls most commonly affected. Patients with positive LGE had lower LV ejection fraction and higher LV end-diastolic volume and LV mass than patients without LGE. No difference in other cardiovascular risk factors was noted. Patients with scar had higher event rates compared with those without scar for the primary (p = 0.043) and the secondary (p = 0.016) endpoint. In multivariable analysis, age and LGE area were related to primary outcome; age and lower LV ejection fraction were related to the secondary outcome. The pattern of LGE myocardial fibrosis was transmural, focal, or diffuse scar in approximately one-third of patients with positive LGE, and no pattern was specifically related to outcomes. CONCLUSIONS: In patients with CCC, presence of scar by LGE is common and is strongly associated with major adverse outcomes.

Diagnostic accuracy of semi-automatic quantitative metrics as an alternative to expert reading of CT myocardial perfusion in the CORE320 study.

AIMS: To determine the diagnostic accuracy of semi-automatic quantitative metrics compared to expert reading for interpretation of computed tomography perfusion (CTP) imaging. METHODS: The CORE320 multicenter diagnostic accuracy clinical study enrolled patients between 45 and 85 years of age who were clinically referred for invasive coronary angiography (ICA). Computed tomography angiography (CTA), CTP, single photon emission computed tomography (SPECT), and ICA images were interpreted manually in blinded core laboratories by two experienced readers. Additionally, eight quantitative CTP metrics as continuous values were computed semi-automatically from myocardial and blood attenuation and were combined using logistic regression to derive a final quantitative CTP metric score. For the reference standard, hemodynamically significant coronary artery disease (CAD) was defined as a quantitative ICA stenosis of 50% or greater and a corresponding perfusion defect by SPECT. Diagnostic accuracy was determined by area under the receiver operating characteristic curve (AUC). RESULTS: Of the total 377 included patients, 66% were male, median age was 62 (IQR: 56, 68) years, and 27% had prior myocardial infarction. In patient based analysis, the AUC (95% CI) for combined CTA-CTP expert reading and combined CTA-CTP semi-automatic quantitative metrics was 0.87(0.84-0.91) and 0.86 (0.83-0.9), respectively. In vessel based analyses the AUC's were 0.85 (0.82-0.88) and 0.84 (0.81-0.87), respectively. No significant difference in AUC was found between combined CTA-CTP expert reading and CTA-CTP semi-automatic quantitative metrics in patient based or vessel based analyses(p > 0.05 for all). CONCLUSION: Combined CTA-CTP semi-automatic quantitative metrics is as accurate as CTA-CTP expert reading to detect hemodynamically significant CAD.

Urbanization is Associated with Increased Trends in Cardiovascular Mortality Among Indigenous Populations: the PAI Study / Urbanização Associa-se com Tendência a Maior Mortalidade Cardiovascular em Populações Indígenas: o Estudo PAI

Abstract Background: The cardiovascular risk burden among diverse indigenous populations is not totally known and may be influenced by lifestyle changes related to the urbanization process. Objectives: To investigate the cardiovascular (CV) mortality profile of indigenous populations during a rapid urbanization process largely influenced by governmental infrastructure interventions in Northeast Brazil. Methods: We assessed the mortality of indigenous populations (≥ 30 y/o) from 2007 to 2011 in Northeast Brazil (Bahia and Pernambuco states). Cardiovascular mortality was considered if the cause of death was in the ICD-10 CV disease group or if registered as sudden death. The indigenous populations were then divided into two groups according to the degree of urbanization based on anthropological criteria:9,10 Group 1 - less urbanized tribes (Funi-ô, Pankararu, Kiriri, and Pankararé); and Group 2 - more urbanized tribes (Tuxá, Truká, and Tumbalalá). Mortality rates of highly urbanized cities (Petrolina and Juazeiro) in the proximity of indigenous areas were also evaluated. The analysis explored trends in the percentage of CV mortality for each studied population. Statistical significance was established for p value < 0.05. Results: There were 1,333 indigenous deaths in tribes of Bahia and Pernambuco (2007-2011): 281 in Group 1 (1.8% of the 2012 group population) and 73 in Group 2 (3.7% of the 2012 group population), CV mortality of 24% and 37%, respectively (p = 0.02). In 2007-2009, there were 133 deaths in Group 1 and 44 in Group 2, CV mortality of 23% and 34%, respectively. In 2009-2010, there were 148 deaths in Group 1 and 29 in Group 2, CV mortality of 25% and 41%, respectively. Conclusions: Urbanization appears to influence increases in CV mortality of indigenous peoples living in traditional tribes. Lifestyle and environmental changes due to urbanization added to suboptimal health care may increase CV risk in this population.

Resumo Fundamento: O risco cardiovascular das diversas comunidades indígenas não está bem estabelecido e pode ser influenciado pelo processo de urbanização a que se submetem esses povos. Objetivos: Investigar o perfil da mortalidade cardiovascular (CV) das populações indígenas durante o rápido processo de urbanização altamente influenciado por intervenções governamentais de infraestrutura no Nordeste do Brasil. Métodos: Avaliamos a mortalidade de populações indígenas (≥ 30 anos) do Vale do São Francisco (Bahia e Pernambuco) no período de 2007-2011. Considerou-se mortalidade CV se a causa de morte constasse no grupo de doenças CV do CID-10 ou se tivesse sido registrada como morte súbita. As populações indígenas foram divididas em dois grupos conforme o grau de urbanização baseado em critérios antropológicos: Grupo 1 - menos urbanizadas (Funi-ô, Pankararu, Kiriri e Pankararé); e Grupo 2 - mais urbanizadas (Tuxá, Truká e Tumbalalá). Taxas de mortalidade de cidades altamente urbanizadas (Petrolina e Juazeiro) nas proximidades das áreas indígenas foram também avaliadas. A análise explorou tendências na porcentagem de mortalidade CV para cada população estudada. Adotou-se o valor de p < 0,05 como significância estatística. Resultados: Houve 1.333 mortes indígenas nas tribos da Bahia e de Pernambuco (2007-2011): 281 no Grupo 1 (1,8% da população de 2012) e 73 no Grupo 2 (3,7% da população de 2012), mortalidade CV de 24% e 37%, respectivamente (p = 0,02). Entre 2007 e 2009, houve 133 mortes no Grupo 1 e 44 no Grupo 2, mortalidade CV de 23% e 34%, respectivamente. Entre 2009 e 2010, houve 148 mortes no Grupo 1 e 29 no Grupo 2, mortalidade CV de 25% e 41%, respectivamente. Conclusões: A urbanização parece influenciar os aumentos de mortalidade CV dos povos indígenas vivendo de modo tradicional. Mudanças no estilo de vida e ambientais devidas à urbanização somadas à subótima atenção à saúde podem estar implicadas no aumento do risco CV nos povos indígenas.

Urbanization is Associated with Increased Trends in Cardiovascular Mortality Among Indigenous Populations: the PAI Study.

BACKGROUND: The cardiovascular risk burden among diverse indigenous populations is not totally known and may be influenced by lifestyle changes related to the urbanization process. OBJECTIVES: To investigate the cardiovascular (CV) mortality profile of indigenous populations during a rapid urbanization process largely influenced by governmental infrastructure interventions in Northeast Brazil. METHODS: We assessed the mortality of indigenous populations (≥ 30 y/o) from 2007 to 2011 in Northeast Brazil (Bahia and Pernambuco states). Cardiovascular mortality was considered if the cause of death was in the ICD-10 CV disease group or if registered as sudden death. The indigenous populations were then divided into two groups according to the degree of urbanization based on anthropological criteria:9,10 Group 1 - less urbanized tribes (Funi-ô, Pankararu, Kiriri, and Pankararé); and Group 2 - more urbanized tribes (Tuxá, Truká, and Tumbalalá). Mortality rates of highly urbanized cities (Petrolina and Juazeiro) in the proximity of indigenous areas were also evaluated. The analysis explored trends in the percentage of CV mortality for each studied population. Statistical significance was established for p value < 0.05. RESULTS: There were 1,333 indigenous deaths in tribes of Bahia and Pernambuco (2007-2011): 281 in Group 1 (1.8% of the 2012 group population) and 73 in Group 2 (3.7% of the 2012 group population), CV mortality of 24% and 37%, respectively (p = 0.02). In 2007-2009, there were 133 deaths in Group 1 and 44 in Group 2, CV mortality of 23% and 34%, respectively. In 2009-2010, there were 148 deaths in Group 1 and 29 in Group 2, CV mortality of 25% and 41%, respectively. CONCLUSIONS: Urbanization appears to influence increases in CV mortality of indigenous peoples living in traditional tribes. Lifestyle and environmental changes due to urbanization added to suboptimal health care may increase CV risk in this population.

Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study.

OBJECTIVES: To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function. STUDY DESIGN: TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10-17 years, and with 2-6 years of follow-up. Participants were 36% male, obese, and ethnically diverse. Annual serum concentrations of brain natriuretic peptide, troponin, tumor necrosis factor (TNF)-α, receptors 1 and 2 were related to blood pressure, body mass index, hemoglobin A1c, and left ventricular ejection fraction, diastolic function, relative wall thickness, and mass. RESULTS: Elevated concentrations of brain natriuretic peptide (≥100 pg/mL), TNF-α (≥5.6 pg/mL) and troponin (≥0.01 ng/mL), were present in 17.8%, 18.3%, and 34.2% of the cohort, respectively, at baseline, and in 15.4%, 17.1%, and 31.1% at the end of the study, with wide variability over time, without persistence in individuals or clear relationship to glycemia or cardiovascular structure/function. TNF receptors concentrations were increased at baseline and not significantly different from end-of-study concentrations. Adverse echocardiographic measures were more likely in the highest TNF receptor tertile (all P < .05): higher left ventricular mass (39.3 ± 9.0 g/m2.7), left atrial internal dimension (3.7 ± 0.4 cm) and E/Em ratio, a measure of diastolic dysfunction (6.2 ± 1.9). After adjustment for body mass index, these relationships were no longer significant. CONCLUSIONS: Elevated serum concentrations of cardiac biomarkers were common in youth with type 2 diabetes, but their clinical significance is unclear and will require further long-term study. TRIAL REGISTRATION: ClinicalTrials.govNCT00081328.

Reference Ranges and Regional Patterns of Left Ventricular Strain and Strain Rate Using Two-Dimensional Speckle-Tracking Echocardiography in a Healthy Middle-Aged Black and White Population: The CARDIA Study.

BACKGROUND: Strain and strain rate are sensitive markers of left ventricular (LV) myocardial function. The aim of this study was to assess reference ranges and regional patterns of LV strain and strain rate using two-dimensional speckle-tracking echocardiography in a large population of black and white subjects. METHODS: This study involved a retrospective review of prospectively collected images in 557 participants in the Coronary Artery Risk Development in Young Adults study who remained healthy at the year 25 examination. LV deformation parameters were measured in apical four-chamber, apical two-chamber, and parasternal short-axis views in 509, 391, and 521 subjects, respectively. RESULTS: Patients' mean age was 49.6 ± 3.6 years, 61.6% were women, and 69.5% were white. White women showed the highest LV systolic and diastolic deformation values, reflected by a more negative reference range for apical four-chamber longitudinal strain (-16.4%; 95% prediction interval [PI], -20.8% to -12.0%) and a higher positive reference range for early diastolic strain rate (0.93 1/sec; 95% PI, 0.41 to 1.46 1/sec), respectively. The lowest LV systolic and diastolic deformation values were found in black men, with apical four-chamber longitudinal strain (14.7%; 95% PI, -19.1% to -10.3%) and early diastolic strain rate (0.79 1/sec; 95% PI, 0.42 to 1.16 1/sec). Absolute strain increased from the epicardium toward the endocardium. A base-to-apex gradient of longitudinal strain toward the apex was exhibited in inferior and inferoseptal regions and, in contrast, in the opposite direction in anterior and anterolateral walls. Sex had the strongest influence on LV deformation variability. CONCLUSIONS: Strain and strain rate reference values were sex and race related. White women showed the highest reference ranges for LV deformation, while the lowest values were found in black men. Significant layer- and level-specific patterns in regional LV deformation were identified.

Factors Associated With Coronary Artery Disease Progression Assessed By Serial Coronary Computed Tomography Angiography.

Background: Coronary computed tomography angiography (CCTA) allows for noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable. Objective: To identify factors associated with CAD progression in patients undergoing sequential CCTA testing. Methods: We retrospectively analyzed 384 consecutive patients who had at least two CCTA studies between December 2005 and March 2013. Due to limitations in the quantification of CAD progression, we excluded patients who had undergone surgical revascularization previously or percutaneous coronary intervention (PCI) between studies. CAD progression was defined as any increase in the adapted segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stent (in-stent restenosis was excluded from the analysis). Stepwise logistic regression was used to assess variables associated with CAD progression. Results: From a final population of 234 patients, a total of 117 (50%) had CAD progression. In a model accounting for major CAD risk factors and other baseline characteristics, only age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07), interstudy interval (OR 1.03, 95%CI 1.01-1.04), and past PCI (OR 3.66, 95%CI 1.77-7.55) showed an independent relationship with CAD progression. Conclusions: A history of PCI with stent placement was independently associated with a 3.7-fold increase in the odds of CAD progression, excluding in-stent restenosis. Age and interstudy interval were also independent predictors of progression.

Objetivo: Angiografia coronariana por tomografia computadorizada (ACTC) permite fenotipagem não invasiva da doença arterial coronariana (DAC). Fatores relacionados à progressão da DAC têm valor epidemiológico. Métodos: Nós analisamos retrospectivamente 384 pacientes consecutivos que apresentavam pelo menos duas avaliações por ACTC entre dezembro de 2005 e março de 2013. Devido às limitações na quantificação da progressão da DAC, os pacientes que haviam sido submetidos previamente à revascularização cirúrgica ou intervenção coronariana percutânea (ICP) entre as avaliações foram excluídos. A progressão da DAC foi definida como qualquer aumento no escore adaptado de estenose segmentar (calculado com utilização do número de segmentos afetados e gravidade da estenose) em todos os segmentos coronarianos sem stent (restenose intra-stent foi excluída da análise). Regressão logística stepwise foi utilizada para avaliar as variáveis associadas com a progressão da DAC. Resultados: De uma população final de 234 pacientes, um total de 117 (50%) pacientes apresentaram progressão da DAC. Em um modelo considerando os principais fatores de risco para DAC e outras características basais, apenas a idade (odds ratio [OR] 1,04, intervalo de confiança de 95% [IC95%] 1,01-1,07), intervalo entre avaliações (OR 1,03, IC95% 1,01-1,04) e ICP prévia (OR 3,66, IC95% 1,77-7,55) mostraram uma relação independente com a progressão da DAC. Conclusões: Uma história de ICP com implante de stent esteve independentemente associada a um aumento de 3,7 vezes na chance de progressão da DAC, excluindo a restenose intra-stent. Idade e intervalo entre avaliações também foram preditores independentes de progressão.

Factors Associated With Coronary Artery Disease Progression Assessed By Serial Coronary Computed Tomography Angiography / Fatores Associados com Progressão da Doença Arterial Coronariana Avaliada por Angiografia Coronariana por Tomografia Computadorizada Seriada

Abstract Background: Coronary computed tomography angiography (CCTA) allows for noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable. Objective: To identify factors associated with CAD progression in patients undergoing sequential CCTA testing. Methods: We retrospectively analyzed 384 consecutive patients who had at least two CCTA studies between December 2005 and March 2013. Due to limitations in the quantification of CAD progression, we excluded patients who had undergone surgical revascularization previously or percutaneous coronary intervention (PCI) between studies. CAD progression was defined as any increase in the adapted segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stent (in-stent restenosis was excluded from the analysis). Stepwise logistic regression was used to assess variables associated with CAD progression. Results: From a final population of 234 patients, a total of 117 (50%) had CAD progression. In a model accounting for major CAD risk factors and other baseline characteristics, only age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07), interstudy interval (OR 1.03, 95%CI 1.01-1.04), and past PCI (OR 3.66, 95%CI 1.77-7.55) showed an independent relationship with CAD progression. Conclusions: A history of PCI with stent placement was independently associated with a 3.7-fold increase in the odds of CAD progression, excluding in-stent restenosis. Age and interstudy interval were also independent predictors of progression.

Resumo Fundamento: Angiografia coronariana por tomografia computadorizada (ACTC) permite fenotipagem não invasiva da doença arterial coronariana (DAC). Fatores relacionados à progressão da DAC têm valor epidemiológico. Objetivo: Identificar os fatores associados com a progressão da DAC em pacientes submetidos à avaliação sequencial por ACTC. Métodos: Nós analisamos retrospectivamente 384 pacientes consecutivos que apresentavam pelo menos duas avaliações por ACTC entre dezembro de 2005 e março de 2013. Devido às limitações na quantificação da progressão da DAC, os pacientes que haviam sido submetidos previamente à revascularização cirúrgica ou intervenção coronariana percutânea (ICP) entre as avaliações foram excluídos. A progressão da DAC foi definida como qualquer aumento no escore adaptado de estenose segmentar (calculado com utilização do número de segmentos afetados e gravidade da estenose) em todos os segmentos coronarianos sem stent (restenose intra-stent foi excluída da análise). Regressão logística stepwise foi utilizada para avaliar as variáveis associadas com a progressão da DAC. Resultados: De uma população final de 234 pacientes, um total de 117 (50%) pacientes apresentaram progressão da DAC. Em um modelo considerando os principais fatores de risco para DAC e outras características basais, apenas a idade (odds ratio [OR] 1,04, intervalo de confiança de 95% [IC95%] 1,01-1,07), intervalo entre avaliações (OR 1,03, IC95% 1,01-1,04) e ICP prévia (OR 3,66, IC95% 1,77-7,55) mostraram uma relação independente com a progressão da DAC. Conclusões: Uma história de ICP com implante de stent esteve independentemente associada a um aumento de 3,7 vezes na chance de progressão da DAC, excluindo a restenose intra-stent. Idade e intervalo entre avaliações também foram preditores independentes de progressão.

Relationship of Cardiac Structure and Function to Cardiorespiratory Fitness and Lean Body Mass in Adolescents and Young Adults with Type 2 Diabetes.

OBJECTIVE: To investigate the relationships of cardiac structure and function with body composition and cardiorespiratory fitness (CRF) among adolescents with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth study. STUDY DESIGN: Cross-sectional evaluation of 233 participants (median age 18.3 [min-max 12.4-24.2] years, 63% females, median hemoglobin A1c 6.8%) who had echocardiography measurements of left ventricular (LV) mass, ejection fraction, left atrial dimensions, LV diastolic function (early transmitral flow velocity to early mitral annular velocity ratio from tissue Doppler imaging), and right ventricular function (tricuspid annular plane systolic excursion [TAPSE]) and body composition (dual-energy x-ray absorptiometry) and CRF (cycle ergometry determination of physical work capacity at heart rate of 170 beats per minute). RESULTS: LV mass correlated positively with CRF (r = 0.5, P < .0001), lean body mass (LBM) (r = 0.7, P < .0001), and fat mass (FM) (r = 0.2, P = .00047); LV ejection fraction did not. Early transmitral flow velocity to early mitral annular velocity was positively related to FM (r = 0.14, P = .03) and % body fat (r = 0.18, P = .007), and left atrial internal diameter correlated with FM (r = 0.4, P < .0001), LBM (r = 0.3, P < .001), and CRF (r = 0.2, P = .0033). TAPSE weakly correlated with CRF (r = 0.2, P = .0014) and LBM (r = 0.13, P < .05) but not with FM. In multivariable regression analyses, LBM (ß = 2.13, P < .0001) and CRF (ß = 0.023, P = .008) were related to LV mass independent of race, sex, age, hemoglobin A1c, hypertension, smoking, and diabetes medications. CRF (ß = 0.0002, P = .0187) and hemoglobin A1c (ß = -0.022, P = .0142) were associated with TAPSE. CONCLUSIONS: In youth with type 2 diabetes, LV size is related to physical fitness. LV ejection fraction is within normal limits. LV diastolic function is inversely related to FM. Greater fitness may counteract adverse effects of poor glycemic control on right ventricular function. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00081328.

Lack of association between epicardial fat volume and extent of coronary artery calcification, severity of coronary artery disease, or presence of myocardial perfusion abnormalities in a diverse, symptomatic patient population: results from the CORE320 multicenter study.

BACKGROUND: Epicardial fat may play a role in the pathogenesis of coronary artery disease (CAD). We explored the relationship of epicardial fat volume (EFV) with the presence and severity of CAD or myocardial perfusion abnormalities in a diverse, symptomatic patient population. METHODS AND RESULTS: Patients (n=380) with known or suspected CAD who underwent 320-detector row computed tomographic angiography, nuclear stress perfusion imaging, and clinically driven invasive coronary angiography for the CORE320 international study were included. EFV was defined as adipose tissue within the pericardial borders as assessed by computed tomography using semiautomatic software. We used linear and logistic regression models to assess the relationship of EFV with coronary calcium score, stenosis severity by quantitative coronary angiography, and myocardial perfusion abnormalities by single photon emission computed tomography (SPECT). Median EFV among patients (median age, 62.6 years) was 102 cm(3) (interquartile range: 53). A coronary calcium score of ≥1 was present in 83% of patients. Fifty-nine percent of patients had ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography, and 49% had abnormal myocardial perfusion results by SPECT. There were no significant associations between EFV and coronary artery calcium scanning, presence severity of ≥50% stenosis by quantitative coronary angiography, or abnormal myocardial perfusion by SPECT. CONCLUSIONS: In a diverse population of symptomatic patients referred for invasive coronary angiography, we did not find associations of EFV with the presence and severity of CAD or with myocardial perfusion abnormalities. The clinical significance of quantifying EFV remains uncertain but may relate to the pathophysiology of acute coronary events rather than the presence of atherosclerotic disease.

Accuracy of multidetector computed tomography for detection of coronary artery stenosis in acute coronary syndrome compared with stable coronary disease: a CORE64 multicenter trial substudy.

BACKGROUND: Multi-detector computed tomography angiography (MDCTA) is a promising method for risk assessment of patients with acute chest pain. However, its diagnostic performance in higher-risk patients has not been investigated in a large international multicenter trial. Therefore, in the present study we sought to estimate the diagnostic accuracy of MDCTA to detect significant coronary stenosis in patients with acute coronary syndrome (ACS). METHODS: Patients included in the CORE64 study were categorized as suspected-ACS or non-ACS based on clinical data. A 64-row coronary MDCTA was performed before invasive coronary angiography (ICA) and both exams were evaluated by blinded, independent core laboratories. RESULTS: From 371 patients included, 94 were categorized as suspected ACS and 277 as non-ACS. Patient-based analysis showed an area under the receiver-operating-characteristic curve (AUC) for detecting ≥ 50% coronary stenosis of 0.95 (95% CI: 0.88-0.98) in ACS and 0.92 (95% CI: 0.88-0.95) in non-ACS group (P=0.29). The sensitivity, specificity, positive and negative predictive values of MDCTA were 0.90(0.80-0.96), 0.88(0.70-0.98), 0.95(0.87-0.99) and 0.77(0.58-0.90) in suspected ACS patients and 0.87(0.81-0.92), 0.86(0.79-0.92), 0.91(0.85-0.95) and 0.82(0.74-0.89) in non-ACS patients (P NS for all comparisons). The mean calcium scores (CS) were 282 ± 449 in suspected ACS and 435 ± 668 in non-ACS group. The accuracy of CS to detect significant coronary stenosis was only moderate and the absence or minimal coronary artery calcification could not exclude the presence of significant coronary stenosis, particularly in ACS patients. CONCLUSIONS: The diagnostic accuracy of MDCTA to detect significant coronary stenosis is high and comparable for both ACS and non-ACS patients.