First degree relatives (FDRs) of subjects with early onset of coronary heart disease (CHD) have higher risk of developing cardiovascular disease. We verified early CHD by angiography in the index patients and extensively phenotyped their FDRs to investigate the relationship of traditional and non-traditional cardiovascular risk factors to carotid ultrasound and coronary calcium scoring findings. B-mode carotid ultrasound was used to assess the combined intima-media thickness and plaque burden in 111 FDRs. The biochemical and anthropometrical characteristics of the FDRs were compared with those of healthy controls matched for sex, age, ethnicity and BMI. Odds ratios indicate that FDRs are more likely to have positive carotid ultrasound findings compared to controls; 2.23 (95% CI 1.14 – 4.37) for intima-media thickness and 2.3 (95% CI 1.22 - 4.35) for average total thickness. In multivariate analysis positive carotid ultrasound findings were higher in FDRs independent of age, gender, total cholesterol over HDL-c ratio, systolic blood pressure and smoking but not homocysteine which had higher values in FDRs compared to controls. In conclusion FDRs of patients with angiographically confirmed CHD have higher burden of subclinical atherosclerosis even when considered in the context of traditional risk factors. Coronary artery calcium scoring (CAC), assessed by 64-slice multi-detector computed tomography (MDCT), was used to assess burden of subclinical atherosclerosis in 57 FDRs compared to controls. FDRs have a two-fold increase in risk of having CAC positive findings; odds ratios for the 75th percentile was 1.96 (95%CI 1.04 – 3.67, p<0.05) while for the 90th percentile odds ratio was 2.59 (95% 1.232 – 5.473, p<0.05). In summary, the risk of significant CAC findings, measured by 64-slice MDCT, is two-fold higher in FDRs than controls. These findings correlate highly with carotid ultrasound findings in the same cohort. Different thresholds for CAC may be appropriate when assessing male versus female FDRs. Together increased carotid ultrasound findings and CAC scoring results in FDRs of patients with validated early onset of CHD suggest these imaging techniques as potentially useful tools in cardiovascular risk assessment that will go above and beyond the current diagnostic algorithms.

First degree relatives (FDRs) of subjects with early onset of coronary heart disease (CHD) have higher risk of developing cardiovascular disease. We verified early CHD by angiography in the index patients and extensively phenotyped their FDRs to investigate the relationship of traditional and non-traditional cardiovascular risk factors to carotid ultrasound and coronary calcium scoring findings. B-mode carotid ultrasound was used to assess the combined intima-media thickness and plaque burden in 111 FDRs. The biochemical and anthropometrical characteristics of the FDRs were compared with those of healthy controls matched for sex, age, ethnicity and BMI. Odds ratios indicate that FDRs are more likely to have positive carotid ultrasound findings compared to controls; 2.23 (95% CI 1.14 – 4.37) for intima-media thickness and 2.3 (95% CI 1.22 - 4.35) for average total thickness. In multivariate analysis positive carotid ultrasound findings were higher in FDRs independent of age, gender, total cholesterol over HDL-c ratio, systolic blood pressure and smoking but not homocysteine which had higher values in FDRs compared to controls. In conclusion FDRs of patients with angiographically confirmed CHD have higher burden of subclinical atherosclerosis even when considered in the context of traditional risk factors. Coronary artery calcium scoring (CAC), assessed by 64-slice multi-detector computed tomography (MDCT), was used to assess burden of subclinical atherosclerosis in 57 FDRs compared to controls. FDRs have a two-fold increase in risk of having CAC positive findings; odds ratios for the 75th percentile was 1.96 (95%CI 1.04 – 3.67, p<0.05) while for the 90th percentile odds ratio was 2.59 (95% 1.232 – 5.473, p<0.05). In summary, the risk of significant CAC findings, measured by 64-slice MDCT, is two-fold higher in FDRs than controls. These findings correlate highly with carotid ultrasound findings in the same cohort. Different thresholds for CAC may be appropriate when assessing male versus female FDRs. Together increased carotid ultrasound findings and CAC scoring results in FDRs of patients with validated early onset of CHD suggest these imaging techniques as potentially useful tools in cardiovascular risk assessment that will go above and beyond the current diagnostic algorithms.

First degree relatives (FDRs) of subjects with early onset of coronary heart disease (CHD) have higher risk of developing cardiovascular disease. We verified early CHD by angiography in the index patients and extensively phenotyped their FDRs to investigate the relationship of traditional and non-traditional cardiovascular risk factors to carotid ultrasound and coronary calcium scoring findings. B-mode carotid ultrasound was used to assess the combined intima-media thickness and plaque burden in 111 FDRs. The biochemical and anthropometrical characteristics of the FDRs were compared with those of healthy controls matched for sex, age, ethnicity and BMI. Odds ratios indicate that FDRs are more likely to have positive carotid ultrasound findings compared to controls; 2.23 (95% CI 1.14 – 4.37) for intima-media thickness and 2.3 (95% CI 1.22 - 4.35) for average total thickness. In multivariate analysis positive carotid ultrasound findings were higher in FDRs independent of age, gender, total cholesterol over HDL-c ratio, systolic blood pressure and smoking but not homocysteine which had higher values in FDRs compared to controls. In conclusion FDRs of patients with angiographically confirmed CHD have higher burden of subclinical atherosclerosis even when considered in the context of traditional risk factors. Coronary artery calcium scoring (CAC), assessed by 64-slice multi-detector computed tomography (MDCT), was used to assess burden of subclinical atherosclerosis in 57 FDRs compared to controls. FDRs have a two-fold increase in risk of having CAC positive findings; odds ratios for the 75th percentile was 1.96 (95%CI 1.04 – 3.67, p<0.05) while for the 90th percentile odds ratio was 2.59 (95% 1.232 – 5.473, p<0.05). In summary, the risk of significant CAC findings, measured by 64-slice MDCT, is two-fold higher in FDRs than controls. These findings correlate highly with carotid ultrasound findings in the same cohort. Different thresholds for CAC may be appropriate when assessing male versus female FDRs. Together increased carotid ultrasound findings and CAC scoring results in FDRs of patients with validated early onset of CHD suggest these imaging techniques as potentially useful tools in cardiovascular risk assessment that will go above and beyond the current diagnostic algorithms. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-01-21T11:38:26Z No. of bitstreams: 1 thaizrubertischmal.pdf: 2268904 bytes, checksum: 877a1db5ed9f8d6d7c9869b75edccfc8 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-01-25T18:44:30Z (GMT) No. of bitstreams: 1 thaizrubertischmal.pdf: 2268904 bytes, checksum: 877a1db5ed9f8d6d7c9869b75edccfc8 (MD5) / Made available in DSpace on 2016-01-25T18:44:30Z (GMT). No. of bitstreams: 1 thaizrubertischmal.pdf: 2268904 bytes, checksum: 877a1db5ed9f8d6d7c9869b75edccfc8 (MD5) Previous issue date: 2014-05-22 / Doença aterosclerótica coronariana (DAC) ainda é a principal causa de morte nos países ocidentais, apesar dos grandes avanços no seu diagnóstico e terapêutica nas últimas décadas. No Brasil, cerca de 30% dos óbitos são por doença cardiovascular, sendo que 50% ocorrem em adultos entre 30 e 69 anos de idade. A elevada mortalidade e morbidade da doença coronariana implicam em alto impacto socioeconômico, visto que tais casos incidem em sua maioria, sobre indivíduos economicamente ativos. A faixa etária mais frequentemente acometida é dos 50 aos 65 anos. Porém, tem-se observado um aumento significativo no número de casos em pacientes mais jovens. Neste trabalho analisamos um banco de dados de pacientes jovens, abaixo de 45 anos, que foram encaminhados para realização de angiotomografia coronariana para esclarecimento de quadro de dor torácica ou de exames provocativos alterados. Os objetivos eram estimar a prevalência de doença coronariana obstrutiva e não obstrutiva nessa população jovem local; estimar a correlação dos achados anatômicos com os fatores de risco para doença cardiovascular; discutir a validade do escore de cálcio para o rastreio de doença coronariana desta população, comparando-o aos resultados da angiotomografia coronariana. Inicialmente 181 pacientes foram identificados, mas 6 deles foram excluídos por apresentarem diagnóstico prévio de DAC. Os 175 pacientes incluídos foram analisados para presença de placa aterosclerótica na angiotomografia e quantificação do escore de cálcio. Foi feita uma correlação dos achados anatômicos com os fatores de risco para doença cardiovascular, inicialmente em análise bivariada a partir de cada fator com o desfecho e, posteriormente, em análise multivariada controlando pelos fatores associados mais significativos. Desta forma pode-se chegar às estimativas de prevalência para diferentes perfis de pacientes. A idade média foi de 38 ± 7 anos, sendo 76% homens. A prevalência de DAC foi estimada em 37,7%, sendo o exame normal em 109 pacientes (p < 0,001). Placas obstrutivas foram detectadas em 3,4% dos casos. Os pacientes eram sintomáticos em 60,6% dos casos, sendo a tomografia normal em 70,8% deles (p < 0,001). A análise dos fatores de risco mostrou significância estatística para presença dos fatores dislipidemia, tabagismo e sexo masculino. O escore de cálcio foi igual a zero em 147 pacientes, porém 38 apresentavam DAC. A sensibilidade para o método foi estimada em 42%, especificidade 100%, valor preditivo positivo 100% e valor preditivo negativo 74%. Os tipos de placas foram identificados, sendo observada a predominância de placas não calcificadas (p = 0,04). Os dados apontam que a prevalência de DAC em indivíduos jovens e do sexo masculino com fatores de risco para DAC não é desprezível. Portanto, medidas preventivas e de rastreamento dos fatores de risco devem ser iniciadas mais precocemente do que é recomendado atualmente pelo sistema de saúde público. Além disso, o escore de cálcio mostrou ser uma ferramenta diagnóstica de baixa sensibilidade e baixo valor preditivo negativo para pacientes jovens. / Coronary artery disease (CAD) is the main cause of mortality in developed countries despite the great advances in the diagnosis and treatment in the last years. In Brazil, 30% of all-cause mortality is related to cardiovascular disease and 50% of these patients are adults between 30 and 69 years-old. The high morbity and mortality implies an important economic burden to the country. The most affected ages are between 50 to 65 years old, but an increasing number of younger patients have been noticed. We analized the data of patients under 45 years old that underwent coronary angiotomography evaluation due to chest pain or altered provocative tests. Objectives: estimate the prevalence of coronary artery disease, and its correlation to known cardiovascular risk-factors; discuss the use of coronary calcium scoring as a tool in the diagnosis of coronary artery disease in young patients. Methods: 181 patients were identified but 6 of them were excluded due to previous diagnosis of coronary disease. In our study, 175 patients we enrolled and analyzed for the presence of atheromatous plaques in the coronary arteries and quantification of calcium scoring. The plaques burdens were correlated to the known cardiovascular risk factors in bivariate and multivariate analyses. The prevalence of CAD was estimated and correlated to the different risk factors. Results: the mean age was 38 ± 7 years old, and 76% were men. The prevalence of CAD was estimated in 37.7%, and 109 patients had normal results at the coronary angiiotomography (p < 0.001). Obstructive plaques were identified in 3.4% of the cases. 60.6% of the patients had symptoms but the exam was normal in 70.8% of these cases (p < 0.001). The risk factors that had statistical significance were hypercholesterolemia, smoking and male sex. The calcium scoring was zero in 147 patients, but 38 of them had CAD. The sensitivity of calcium scoring was estimated in 42%, specificity 100%, positive predictive value 100% and negative predictive value 74%. Non-calcified plaques were the most common type of atheromatous plaque (p = 0.04). Conclusion: We conclude that the prevalence of CAD in young male individuals with coronary risk factors is not so low. Early diagnosis of risk factors and preventive actions are necessary, even before the recommended age by our health system. Also, the calcium scoring seems not to be an adequate diagnostic tool in young patients due its low sensitivity and negative predictive value.