Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy.

OBJECTIVES: The aim of this study was to evaluate the role of coronary artery calcium (CAC) as a predictor of atherosclerotic cardiovascular disease (ASCVD) (fatal or not myocardial infarction, stroke, unstable angina requiring revascularization, and elective myocardial revascularization) events in asymptomatic primary prevention molecularly proven heterozygous familial hypercholesterolemia (FH) subjects receiving standard lipid-lowering therapy. BACKGROUND: FH is associated with premature ASCVD. However, the clinical course of ASCVD in subjects with FH is heterogeneous. CAC score, a marker of subclinical atherosclerosis burden, may optimize ASCVD risk stratification in FH. METHODS: Subjects with FH underwent CAC measurement and were followed prospectively. The association of CAC with ASCVD was evaluated using multivariate analysis. RESULTS: A total of 206 subjects (mean age 45 ± 14 years, 36.4% men, baseline and on-treatment low-density lipoprotein cholesterol 269 ± 70 mg/dl and 150 ± 56 mg/dl, respectively) were followed for a median of 3.7 years (interquartile range: 2.7 to 6.8 years). CAC was present in 105 (51%), and 15 ASCVD events (7.2%) were documented. Almost one-half of events were hard outcomes, and the others were elective myocardial revascularizations. The annualized rates of events per 1,000 patients for CAC scores of 0 (n = 101 [49%]), 1 to 100 (n = 62 [30%]) and >100 (n = 43 [21%]) were, respectively, 0, 26.4 (95% confidence interval: 12.9 to 51.8), and 44.1 (95% confidence interval, 26.0 to 104.1). In multivariate Cox regression analysis, log(CAC score + 1) was independently associated with incident ASCVD events (hazard ratio: 3.33; 95% CI: 1.635 to 6.790; p = 0.001). CONCLUSIONS: CAC was independently associated with ASCVD events in patients with FH receiving standard lipid-lowering therapy. This may help further stratify near-term risk in patients who might be candidates for further treatment with newer therapies.

Evaluation of clinical and laboratory parameters used in the identification of index cases for genetic screening of familial hypercholesterolemia in Brazil.

BACKGROUND AND AIMS: There is controversy on the accuracy of different diagnostic criteria for familial hypercholesterolemia (FH). The aim of this study is to assess the performance of different clinical criteria used to identify individuals for FH genetic cascade screening in Brazil. METHODS: All index cases (IC) registered in the Hipercol Brasil program between 2011 and 2016 were analyzed. Inclusion criteria were age ≥18 years and elevated LDL-cholesterol (LDL-C) levels, with a conclusive result in the genetic test, whether positive or negative. Initially, we tested the multivariable association between clinical and laboratory markers and the presence of an FH causing mutation. Then, we analyzed sensitivity, specificity, positive and negative predictive values for the LDL-C quartile distribution, LDL-C as a continuous variable, as well as the performance measures for the Dutch Lipid Clinic Network (DLCN) score to identify a mutation. RESULTS: Overall, 753 ICs were included and an FH causing mutation was found in 34% (n = 257) of the subjects. After multivariable analysis, LDL-C as a continuous variable, tendon xanthomas and corneal arcus were independently associated with the presence of FH mutations. LDL-C values ≥ 230 mg/dL (5.9 mmol/L) had the best tradeoff between sensitivity and specificity to diagnose a mutation. The DLCN score presented a better performance than LDL-C to identify a mutation, area under the ROC curve were 0.744 (95% CI: 0.704-0.784) and 0.730 (95% CI: 0.687-0.774), respectively, p=0.014. CONCLUSIONS: In our population, LDL ≥230 mg/dL is a feasible criterion to indicate ICs to genetic testing.

Achilles tendon xanthomas are associated with the presence and burden of subclinical coronary atherosclerosis in heterozygous familial hypercholesterolemia: A pilot study.

BACKGROUND AND AIMS: Achilles tendon xanthomas (ATX) are a sign of long-term exposure to high blood cholesterol in familial hypercholesterolemia (FH) patients, which have been associated with cardiovascular disease. We evaluated the ATX association with the presence and extent of subclinical coronary atherosclerosis in heterozygous FH patients. METHODS: 102 FH patients diagnosed by US-MEDPED criteria (67% with genetically proven FH), with median LDL-C 279 mg/dL (interquartile range: 240; 313), asymptomatic for cardiovascular disease, underwent computed tomography angiography and coronary artery calcium (CAC) quantification. Subclinical coronary atherosclerosis was quantified by CAC, segment-stenosis (SSS) and segment-involvement (SIS) scores. Adjusted Poisson regression was used to assess the association of ATX with subclinical atherosclerosis burden as continuous variables. RESULTS: Patients with ATX (n = 21, 21%) had higher LDL-C and lipoprotein(a) [Lp(a)] concentrations as well as greater CAC scores, SIS and SSS (p < 0.05). After adjusting for age, sex, smoking, hypertension, previous statin use, HDL-C, LDL-C and Lp(a) concentrations, there was an independent positive association of ATX presence with CAC scores (ß = 1.017, p < 0.001), SSS (ß = 0.809, p < 0.001) and SIS (ß = 0.640, p < 0.001). CONCLUSIONS: ATX are independently associated with the extension of subclinical coronary atherosclerosis quantified by tomographic scores in FH patients.

Predictors of cardiovascular events after one year of molecular screening for Familial hypercholesterolemia.

BACKGROUND AND AIMS: This study reports the first year follow-up of individuals enrolled in Brazil's genetic cascade screening program for Familial Hypercholesterolemia (FH), Hipercol Brasil. Predictors for the occurrence of cardiovascular (CV) events in individuals screened for FH were studied. METHODS: This is an open prospective cohort of individuals who were included in a cascade genetic screening program for FH. The first prospective follow-up was carried out one year after patients received their genetic test result. Individuals included in this study were index cases (probands) and relatives with identified (M +) or not genetic mutations (M -). Logistic regression analysis was performed to determine predictive variables for the occurrence of CV events censored at one-year of follow-up. RESULTS: A total of 818 subjects were included, 47 first CV events were ascertained, with 14 (29.7%) being fatal. For index cases, the only factor independently associated with increased risk of CV events was the presence of corneal arcus (OR: 9.39; 95% CI: 2.46-35.82). There was an inverse association of CV events with higher HDL-cholesterol levels (OR: 0.95; 95% CI: 0.90-0.99). For M+ relatives, risk factors associated with increased CV events risk were diabetes mellitus (OR: 7.97; 95% CI: 2.07-30.66) and tobacco consumption (OR: 3.70; 95% CI: 1.09-12.50). CONCLUSIONS: A high one-year incidence of CV events was found in this cascade-screening cohort. Predictors of events differed between index cases and relatives and can be useful for the development of preventive efforts in this highly susceptible group of individuals.

Hospitalization of children for asthma in the Brazilian Amazon: trend and spatial distribution.

OBJECTIVE: To analyze the distribution of hospitalizations of children for asthma in the states comprising the Brazilian Amazon, as well as the variations of hospitalization according to climatic seasonality. METHODS: A descriptive study of the distribution of hospitalizations for asthma of individuals aged 0 to 14 years living in the Brazilian Amazon, according to trend, spatial distribution, and climatic seasonality over the period from 2001 to 2007. We used the database of authorizations for hospitalizations (AIH) of the Hospital Information System (SIH/SUS) of the Brazilian Ministry of Health. RESULTS: The spatial distribution of hospitalizations for asthma resembles the configuration of the "arc of deforestation," mainly in the states of Rondônia and Maranhão. The distribution of annual hospitalizations for asthma decreased from 8.1 to 2.6 hospitalizations/1,000 inhabitants during the period. There was a peak of hospitalizations in March and May in all states. The seasonal differences were on average 10%, with the highest rates during the rainy season. CONCLUSION: We concluded that hospitalizations for asthma are more frequent in the months of more intense rainfall, with greater magnitude in the states comprising the "arc of deforestation" in the Brazilian Amazon, especially Rondônia and Maranhão.

Hospitalização de crianças por asma na Amazônia brasileira: tendência e distribuição espacial / Hospitalization of children for asthma in the Brazilian Amazon: trend and spatial distribution

OBJETIVO: Analisar a distribuição das internações hospitalares por asma em crianças nos estados que compõem a Amazônia brasileira e as variações das internações segundo a sazonalidade climática. MÉTODOS: Estudo descritivo de distribuição das hospitalizações por asma em indivíduos de 0 a 14 anos de idade residentes na Amazônia brasileira segundo tendência, distribuição espacial e sazonalidade climática no período de 2001 a 2007. Utilizou-se a base de dados das autorizações de internações hospitalares do Sistema de Informações Hospitalares do Ministério da Saúde. RESULTADOS: A distribuição espacial das hospitalizações por asma assemelha-se à configuração do arco do desmatamento, com destaque para os estados de Maranhão e Rondônia. As hospitalizações anuais por asma decresceram de 8,1 para 2,6 internações por mil habitantes no decorrer do período estudado. Verifica-se um pico de internações nos meses de março e maio em todos os estados. As diferenças sazonais alcançaram em média 10 por cento do conjunto das unidades da federação, com as maiores taxas no período chuvoso. CONCLUSÃO: Conclui-se que as hospitalizações por asma em crianças são mais frequentes nos meses chuvosos, com maior magnitude nos estados que compõem o arco do desmatamento da Amazônia brasileira, especialmente Rondônia e Maranhão.

OBJECTIVE: To analyze the distribution of hospitalizations of children for asthma in the states comprising the Brazilian Amazon, as well as the variations of hospitalization according to climatic seasonality. METHODS: A descriptive study of the distribution of hospitalizations for asthma of individuals aged 0 to 14 years living in the Brazilian Amazon, according to trend, spatial distribution, and climatic seasonality over the period from 2001 to 2007. We used the database of authorizations for hospitalizations (AIH) of the Hospital Information System (SIH/SUS) of the Brazilian Ministry of Health. RESULTS: The spatial distribution of hospitalizations for asthma resembles the configuration of the "arc of deforestation," mainly in the states of Rondônia and Maranhão. The distribution of annual hospitalizations for asthma decreased from 8.1 to 2.6 hospitalizations/1,000 inhabitants during the period. There was a peak of hospitalizations in March and May in all states. The seasonal differences were on average 10 percent, with the highest rates during the rainy season. CONCLUSION: We concluded that hospitalizations for asthma are more frequent in the months of more intense rainfall, with greater magnitude in the states comprising the "arc of deforestation" in the Brazilian Amazon, especially Rondônia and Maranhão.