Association of inflammatory cytokines and endothelial adhesion molecules with immunological, virological, and cardiometabolic disease in HIV-infected individuals.

Elevated levels of inflammatory and endothelial biomarkers are related to chronic diseases, cancers, and cardiovascular disease. This study aimed at evaluating the association of inflammatory cytokines and endothelial adhesion molecules with immunological, virological, and cardiometabolic disease in HIV-infected individuals. A cross-sectional study was initiated to evaluate the association of CD4 lymphocyte count, viral load, antiretroviral therapy, and metabolic and cardiovascular disease with inflammatory cytokines [interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNF-α)], adhesion molecules [soluble intercellular Adhesion Molecule 1 (sICAM) and soluble Vascular Adhesion Molecule 1 (sVCAM)], and highsensitive C-reactive protein (hs-CRP) levels in 125 HIV-infected patients. The associations between independent variables and biomarkers were analyzed by means of multivariate logistic regression. A viral load ≥100,000 copies/mL had a stronger association with high levels of sVCAM-1 (P=0.026; OR=2.54; CI=1.12-5.78) and TNF-α (P=0.048; OR=2.42; CI=1.01-5.85) than the current viral load using a multivariate analysis. Antiretroviral treatment was associated with lower levels of sVCAM-1 (P=0.20; OR=0.20; CI=0.05-0.78), TNF-α (P=0.060; OR=0.22; CI=0.05-1.07), and hs-CRP (P=0.093; OR=0.44; CI=0.17-1.15). CD4 counts <200 cells/mm(3) were associated with high IL-6 levels (P=0.013; OR=3.17; CI=1.27-7.91); however, antiretroviral treatment was not associated with IL-6 levels. Metabolic syndrome was associated with high hs-CRP levels, systolic hypertension was associated with IL-6 levels, and family history of coronary disease was associated with TNF-α levels. High biomarker levels were associated not only with viral and immunological characteristics but also with cardiometabolic factors. The maximum viral load attained was an important risk factor for high levels of TNF-α and sVCAM-1. Treatment protected patients from high biomarker levels, except IL-6.

Risk factors for subclinical atherosclerosis in HIV-infected patients under and over 40 years: a case-control study.

BACKGROUND: Cardiovascular diseases (CVD) are a major cause of death in people with AIDS. Factors contributing to atherosclerosis include traditional risk factors, antiretrovirals and inflammatory factors related to HIV infection. This study set out to compare risk factors associated with subclinical atherosclerosis in individuals under and over 40 years of age. METHODS: Case-control study with 697 HIV/AIDS individuals without HAART or who remain on their first antiretroviral regimen. Of the total, 351 individuals under 40 years and 346 over 40 years were analyzed separately. Subclinical atherosclerosis was assessed by carotid intima-media thickness, using B-mode ultrasound. Multivariate logistic regression was performed to find predictors of subclinical atherosclerosis in the entire group. Subsequent analysis excluded patients with major risk factors for CVD. Magnitudes of associations were expressed by odds ratio (OR) statistical significance, using a 95% confidence interval and p-value <0.05. RESULTS: In the <40 years group subclinical atherosclerosis was associated with male gender (OR: 2.77, 95% CI: 1.43-5.34), nonwhite race (OR: 3.01, 95% CI: 1.23-6.53), obesity (OR: 5.13, 95% CI: 1.79-14.7) and metabolic syndrome (OR: 3.30, 95% CI: 1.44-7.58). In the group ≥40 years predictors of subclinical atherosclerosis were overweight and obesity (OR = 2.53, 95% CI, 0.85-7.54), current CD4 ≥350 cells/mL (OR: 2.81, 95% CI: 1.22-6.47) and NNRTI use ≥ 5 years (OR: 2.65, 95% CI: 1.10-6.37) or PI use >5 years (OR: 1.81, 95% CI: 0.38-8.59). In the multivariate model excluding patients with major risk factors for CVD, age, male sex and nonwhite race were associated with subclinical atherosclerosis in the <40 y group, while in the ≥40 y group, age, HIV viral load >10,000 copies and the use of NNRTI (OR: 7.60, 95% CI: 1.61-35.8) or PI ≥5 years (OR: 3.62, 95% CI: 0.48-26.8) were associated with subclinical atherosclerosis. CONCLUSIONS: In young people the fight against obesity and metabolic syndrome is the main aim in the prevention of CVD. In individuals aged ≥40 y, the prevention of obesity is also of great importance. Moreover, the effects of uncontrolled viremia and the prolonged use of HAART appear to be more harmful in the older group.

Associação dos biomarcadores com aterosclerose e risco para doença coronariana em portadores de HIV / Association of biomarkers with atherosclerosis and risk for coronary artery disease in patients with HIV

FUNDAMENTO: O uso maciço da Terapia Antirretroviral (TARV) na população com vírus da imunodeficiência adquirida (HIV) coincidiu com um aumento das doenças cardiovasculares, causa importante de morbimortalidade nesse grupo. OBJETIVO: Determinar a frequência de aterosclerose carotídea e avaliar a associação entre os níveis dos biomarcadores e o espessamento da camada médio-intimal carotídea em indivíduos HIV positivos, atendidos em serviços de referência para HIV em Pernambuco. MÉTODOS: Corte transversal com 122 pacientes HIV positivos. Considerou-se aterosclerose carotídea subclínica o aumento da espessura da camada média intimal da carótida comum > 0,8 milímetros ou placas no ultrassom de carótidas. Os biomarcadores inflamatórios analisados foram IL6, IL1-β, TNF-α, PCR-ultrassensível, sVCAM-1 e sICAM-1. RESULTADOS: Dos 122 pacientes analisados, a maioria era de homens (60,7%), com > 40 anos (57,4%), em uso de TARV (81,1%). A prevalência de aterosclerose foi de 42,6% (52 casos). Pacientes com idade acima de 40 anos e Framingham intermediário ou alto apresentaram maior chance de desenvolver aterosclerose na análise univariada. Idade acima de 40 anos (OR = 6,57 IC 2,66 -16,2; p = 0,000), sexo masculino (OR = 2,76 IC 1,12-6,79; p = 0,027) e a condição de síndrome metabólica (OR = 2,27 IC 0,94-5,50; p = 0,070) mostraram-se associados à aterosclerose na análise multivariada. Níveis elevados de citocinas inflamatórias e moléculas de adesão não mostraram associação com a presença de aterosclerose. CONCLUSÃO: Não houve associação entre os biomarcadores inflamatórios, moléculas de adesão e presença de aterosclerose carotídea. Entretanto, evidenciou-se em homens, pessoas com mais de 40 anos, portadores de escore de Framingham intermediário/alto ou síndrome metabólica maior chance de aterosclerose subclínica.

BACKGROUND: The massive use of Highly-Active Antiretroviral Therapy (HAART) in individuals with human immunodeficiency virus (HIV) coincided with an increase in cardiovascular disease, a major cause of morbidity and mortality in this group. OBJECTIVE: To determine the frequency of carotid atherosclerosis and the association between biomarker levels and carotid intimal-medial thickening in HIV-positive individuals treated for HIV at referral centers in Pernambuco. METHODS: This was a cross-sectional study of 122 HIV-positive patients. Subclinical carotid atherosclerosis was considered with the presence of increased intimal-medial thickness of the common carotid artery > 0.8 mm or plaques in the carotid ultrasound. The following inflammatory biomarkers were analyzed: IL6, IL1-β, TNF-α, high-sensitivity CRP, sVCAM-1 and sICAM-1. RESULTS: Of the 122 patients analyzed, most were men (60.7%) aged > 40 years (57.4%) receiving HAART (81.1%). The prevalence of atherosclerosis was 42.6% (52 cases). Patients older than 40 years and intermediate or high Framingham score were more likely to develop atherosclerosis at the univariate analysis. Age older than 40 years (OR = 6.57, 95%CI: 2.66 to 16.2, p = 0.000), male gender (OR = 2.76, 95%CI: 1.12 to 6.79, p = 0.027) and presence of syndrome metabolic (OR = 2.27, 95%CI: 0.94 to 5.50, p = 0.070) were associated with atherosclerosis at the multivariate analysis. Elevated levels of inflammatory cytokines and adhesion molecules were not associated with the presence of atherosclerosis. CONCLUSION: There was no association between inflammatory biomarkers, adhesion molecules and presence of carotid atherosclerosis. However, a higher chance of subclinical atherosclerosis was observed in men, those older than 40 years, with intermediate / high Framingham score or metabolic syndrome.

Association of biomarkers with atherosclerosis and risk for coronary artery disease in patients with HIV.

BACKGROUND: The massive use of Highly-Active Antiretroviral Therapy (HAART) in individuals with human immunodeficiency virus (HIV) coincided with an increase in cardiovascular disease, a major cause of morbidity and mortality in this group. OBJECTIVE: To determine the frequency of carotid atherosclerosis and the association between biomarker levels and carotid intimal-medial thickening in HIV-positive individuals treated for HIV at referral centers in Pernambuco. METHODS: This was a cross-sectional study of 122 HIV-positive patients. Subclinical carotid atherosclerosis was considered with the presence of increased intimal-medial thickness of the common carotid artery > 0.8 mm or plaques in the carotid ultrasound. The following inflammatory biomarkers were analyzed: IL6, IL1-ß, TNF-α, high-sensitivity CRP, sVCAM-1 and sICAM-1. RESULTS: Of the 122 patients analyzed, most were men (60.7%) aged > 40 years (57.4%) receiving HAART (81.1%). The prevalence of atherosclerosis was 42.6% (52 cases). Patients older than 40 years and intermediate or high Framingham score were more likely to develop atherosclerosis at the univariate analysis. Age older than 40 years (OR = 6.57, 95%CI: 2.66 to 16.2, p = 0.000), male gender (OR = 2.76, 95%CI: 1.12 to 6.79, p = 0.027) and presence of syndrome metabolic (OR = 2.27, 95%CI: 0.94 to 5.50, p = 0.070) were associated with atherosclerosis at the multivariate analysis. Elevated levels of inflammatory cytokines and adhesion molecules were not associated with the presence of atherosclerosis. CONCLUSION: There was no association between inflammatory biomarkers, adhesion molecules and presence of carotid atherosclerosis. However, a higher chance of subclinical atherosclerosis was observed in men, those older than 40 years, with intermediate / high Framingham score or metabolic syndrome.

Efeito da terapia antirretroviral e dos níveis de carga viral no complexo médio-intimal e no índice tornozelo-braço em pacientes infectados pelo HIV / Antirretroviral therapy effect in the intima-medio complex and ankle-brachial index in patients infected by HIV

OBJETIVOS: Identificar precocemente a prevalência de aterosclerose, por causa do espessamento do complexo médio-intimal das carótidas comuns e do índice tornozelo-braço. Essas medidas foram relacionadas com os fatores de risco clássicos de aterosclerose e os específicos dos infectados pelo HIV (tempo de doença, tempo de tratamento, tipo de tratamento, tipo de terapia antirretroviral utilizada, CD4 e carga viral). MÉTODOS: Setenta casos infectados com o HIV foram avaliados pela medida automática do complexo médio-intimal nas carótidas e do índice tornozelo-braço. Consideraram-se os fatores de risco clássicos de aterosclerose (idade, sexo, hipertensão arterial sistêmica, tabagismo, hipercolesterolemia, hipertrigliceridemia, obesidade e história familiar de evento cardiovascular), as medidas antropométricas e as variáveis relacionadas ao HIV. O nível de significância assumido foi de 5%. RESULTADOS: O tempo médio de diagnóstico do HIV foi de 104,9 meses e de tratamento foi de 97,9 meses. Quanto ao tipo de tratamento, 47 (67,1%) fizeram uso de inibidor de protease por mais de seis meses e 36 (51,4%) estão em uso atualmente. O índice tornozelo-braço estava aumentado em um único paciente (0,7%) e não se evidenciou espessamento do complexo médio-intimal em nenhum indivíduo. Não existiu associação significante da medida do complexo médio-intimal da carótida comum direita com nenhuma das variáveis analisadas. CONCLUSÕES: Indivíduos jovens, sob o uso de terapia antirretroviral por cinco anos ou mais, não apresentaram espessamento do complexo médio-intimal ou aumento do índice tornozelo-braço. Não houve diferença do espessamento do complexo médio-intimal associada ao tipo de esquema antirretroviral utilizado ou nível de carga viral.

OBJECTIVES: To precociously identify the prevalence of atherosclerosis caused by thickening of the intima-media complex of the common carotid arteries and of the ankle brachial index. These measurements were associated with the classical risk factors of atherosclerosis and the specific factors of those infected by HIV (duration of disease, length of treatment, kind of treatment, kind of antiretroviral therapy used, CD4 and viral load). METHODS: Seventy cases infected by HIV were assessed by automatic measurement of the intima-media complex in the carotids and of the ankle brachial index. The classical risk factors of atherosclerosis (age, gender, systemic arterial hypertension, smoking, hypercholesterolemia, hypertriglyceridemia, obesity, and family history of cardiovascular events), anthropometric measurements and the variables related to HIV were taken into consideration. The adopted level of significance was 5%. RESULTS: The mean time of HIV diagnosis was 104.9 months, mean duration of treatment was 97.9 months. As regard to the type of treatment, 47 (67.1%) used protease inhibitor for more than six months and 36 (51.4%) are using it recently. The ankle brachial index was increased in one patient (0.7%), and the intima-media complex was not thickened in any individual. There was no significant association of the measurement of the intima-media complex of the right common carotid with any of the variables analyzed. CONCLUSIONS: Young individuals under the use of antiretroviral therapy for five years or more did not show increase in thickness of the intima-media complex or increase in the ankle brachial index, and there was no difference in the intima-media complex thickness associated with the therapeutical scheme of antiretroviral used or the viral load level.

Angina pectoris in patients with HIV/AIDS: prevalence and risk factors.

INTRODUCTION: The incidence of ischemic heart disease is higher in patients with HIV/AIDS. However, the frequency of angina pectoris in these patients is still not known. Literature about this subject is still scarce. OBJECTIVE: To evaluate the prevalence of angina pectoris and risk factors for coronary disease and to examine the association between traditional risk factors and HIV-related risk factors and angina pectoris. METHOD: An epidemiological cross-sectional study, analyzed as case-control study, involving 584 patients with HIV/AIDS. Angina pectoris was identified by Rose questionnaire, classified as definite or possible. Information regarding risk factors was obtained through a questionnaire, biochemical laboratory tests, medical records and anthropometric measures taken during consultations at AIDS treatment clinics in Pernambuco, Brazil, from June 2007 to February 2008. To adjust the effect of each factor in relation to others, multiple logistic regression was used. RESULTS: There was a preponderance of men (63.2%); mean ages were 39.8 years for men, 36.8 years for women. The prevalence of definite and possible angina were 11% and 9.4%, respectively, totaling 20.4%, with independent associations between angina and smoking (OR = 2.88; 95% CI: 1.69-4.90), obesity (OR = 1.62; 95% CI: 0.97-2.70), family history of heart attack (OR = 1.70; 95% CI: 1.00-2.88), low schooling (OR = 2.11; 95% CI: 1.24-3.59), and low monthly income (OR = 2.93; 95% CI: 1.18-7.22), even after adjustment for age. CONCLUSION: This study suggests that angina pectoris is underdiagnosed, even in patients with medical monitoring, revealing lost opportunities in identification and prevention of cardiovascular morbidity.

Angina pectoris in patients with HIV/AIDS: prevalence and risk factors

INTRODUCTION: The incidence of ischemic heart disease is higher in patients with HIV/AIDS. However, the frequency of angina pectoris in these patients is still not known. Literature about this subject is still scarce. OBJECTIVE: To evaluate the prevalence of angina pectoris and risk factors for coronary disease and to examine the association between traditional risk factors and HIV-related risk factors and angina pectoris. METHOD: An epidemiological cross-sectional study, analyzed as case-control study, involving 584 patients with HIV/AIDS. Angina pectoris was identified by Rose questionnaire, classified as definite or possible. Information regarding risk factors was obtained through a questionnaire, biochemical laboratory tests, medical records and anthropometric measures taken during consultations at AIDS treatment clinics in Pernambuco, Brazil, from June 2007 to February 2008. To adjust the effect of each factor in relation to others, multiple logistic regression was used. RESULTS: There was a preponderance of men (63.2 percent); mean ages were 39.8 years for men, 36.8 years for women. The prevalence of definite and possible angina were 11 percent and 9.4 percent, respectively, totaling 20.4 percent, with independent associations between angina and smoking (OR = 2.88; 95 percent CI: 1.69-4.90), obesity (OR = 1.62; 95 percent CI: 0.97-2.70), family history of heart attack (OR = 1.70; 95 percent CI: 1.00-2.88), low schooling (OR = 2.11; 95 percent CI: 1.24-3.59), and low monthly income (OR = 2.93; 95 percent CI: 1.18-7.22), even after adjustment for age. CONCLUSION: This study suggests that angina pectoris is underdiagnosed, even in patients with medical monitoring, revealing lost opportunities in identification and prevention of cardiovascular morbidity.

Escore de cálcio na avaliação da aterosclerose em pacientes com HIV/AIDS / Calcium score in the evaluation of atherosclerosis in patients with HIV/Aids

FUNDAMENTO: A terapia antirretroviral aumentou drasticamente a expectativa de vida em pacientes com HIV/AIDS, embora a aterosclerose esteja associada a uma terapia de longo prazo. OBJETIVO: Investigar a prevalência de aterosclerose em pacientes com AIDS submetidos à terapia antirretroviral e a influência de tratamentos de diferentes regimes e durações. MÉTODOS: Pacientes com HIV/AIDS foram abordados durante consultas de rotina. Aqueles que estiveram em terapia antirretroviral por, pelo menos, dois anos tiveram o sangue coletado para análise do perfil lipídico e da glicemia em jejum e foram submetidos à tomografia computadorizada cardíaca para quantificação do escore de cálcio dentro de seis dias, no máximo. A aterosclerose foi definida como escore de cálcio maior que zero (CAC > 0). Fatores de risco tradicionais, síndrome metabólica e o escore de Framingham foram analisados. RESULTADOS: Cinquenta e três pacientes realizaram tomografia computadorizada cardíaca: 50,94 por cento eram do sexo masculino, com idade média de 43,4 anos; 20 por cento tinham hipertensão; 3,77 por cento tinham diabetes; 67,92 por cento tinham hipercolesterolemia; 37,74 por cento tinham hipertrigliceridemia; 47,17 por cento tinham HDL baixo; 24,53 por cento atenderam aos critérios para síndrome metabólica; 96,23 por cento foram classificados no escore de Framingham como "baixo risco"; e 18,87 por cento eram tabagistas. A duração média do tratamento antirretroviral foi de 58,98 meses. A aterosclerose coronária ocorreu em 11 pacientes (20,75 por cento). A duração da terapia antirretroviral não se relacionou à aterosclerose (p = 0,41), e não houve diferenças significativas entre os diferentes esquemas antirretrovirais (p = 0,71). Entre os fatores de risco tradicionais, o tabagismo (OR = 27,20; p = 0,023) e a idade (OR = 20,59; p = 0,033) foram significativos na presença de aterosclerose. Havia tendência para uma associação positiva da aterosclerose com a hipercolesterolemia (OR = 8,30; p = 0,0668). CONCLUSÃO: Os fatores associados à aterosclerose foram idade, tabagismo e hipercolesterolemia. A duração e o tipo de terapia antirretroviral não influenciaram a prevalência da aterosclerose.

BACKGROUND: Antiretroviral therapy has dramatically increased life expectancy in patients with HIV/AIDS although atherosclerosis has been associated with long-standing therapy. OBJECTIVE: To investigate the prevalence of atherosclerosis in patients with AIDS undergoing antiretroviral therapy and the influence of different schemes and duration of treatment. METHODS: HIV/AIDS patients were approached during routine consultations. Those who had been on antiretroviral therapy for at least two years had their blood collected for analysis of lipid profile and fasting glycemia and underwent cardiac CT for quantification of calcium score within six days at the most. Atherosclerosis was defined as calcium score greater than zero (CAC > 0). Traditional risk factors, metabolic syndrome and Framingham score were analyzed. RESULTS: Fifty-three patients performed cardiac CT. Twenty-seven (50.94 percent) were male, mean age 43.4 years; 20.00 percent had hypertension, 3.77 percent diabetes, 67.92 percent hypercholesterolemia, 37.74 percent hypertriglyceridemia and 47.17 percent low HDL. Thirteen (24.53 percent) met criteria for metabolic syndrome and 96.23 percent were classified in Framingham score as "low risk." Ten patients (18.87 percent) were smokers. Mean duration of antiretroviral treatment was 58.98 months. Coronary atherosclerosis occurred in 11 (20.75 percent) patients. Duration of antiretroviral therapy was not related to atherosclerosis (p = 0.41) and there were no significant differences between different antiretroviral regimens (p = 0.71). Among traditional risk factors, smoking (OR = 27.20; p = 0.023) and age (OR = 20.59; p = 0.033) were significant in the presence of atherosclerosis. There was a trend towards a positive association of atherosclerosis with hypercholesterolemia (OR = 8.30; p = 0.0668). CONCLUSION: Factors associated with atherosclerosis were age, smoking and hypercholesterolemia. Duration and type of antiretroviral therapy had no influence on the prevalence of atherosclerosis.

Calcium score in the evaluation of atherosclerosis in patients with HIV/AIDS.

BACKGROUND: Antiretroviral therapy has dramatically increased life expectancy in patients with HIV/AIDS although atherosclerosis has been associated with long-standing therapy. OBJECTIVE: To investigate the prevalence of atherosclerosis in patients with AIDS undergoing antiretroviral therapy and the influence of different schemes and duration of treatment. METHODS: HIV/AIDS patients were approached during routine consultations. Those who had been on antiretroviral therapy for at least two years had their blood collected for analysis of lipid profile and fasting glycemia and underwent cardiac CT for quantification of calcium score within six days at the most. Atherosclerosis was defined as calcium score greater than zero (CAC > 0). Traditional risk factors, metabolic syndrome and Framingham score were analyzed. RESULTS: Fifty-three patients performed cardiac CT. Twenty-seven (50.94%) were male, mean age 43.4 years; 20.00% had hypertension, 3.77% diabetes, 67.92% hypercholesterolemia, 37.74% hypertriglyceridemia and 47.17% low HDL. Thirteen (24.53%) met criteria for metabolic syndrome and 96.23% were classified in Framingham score as "low risk." Ten patients (18.87%) were smokers. Mean duration of antiretroviral treatment was 58.98 months. Coronary atherosclerosis occurred in 11 (20.75%) patients. Duration of antiretroviral therapy was not related to atherosclerosis (p = 0.41) and there were no significant differences between different antiretroviral regimens (p = 0.71). Among traditional risk factors, smoking (OR = 27.20; p = 0.023) and age (OR = 20.59; p = 0.033) were significant in the presence of atherosclerosis. There was a trend towards a positive association of atherosclerosis with hypercholesterolemia (OR = 8.30; p = 0.0668). CONCLUSION: Factors associated with atherosclerosis were age, smoking and hypercholesterolemia. Duration and type of antiretroviral therapy had no influence on the prevalence of atherosclerosis.