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Doctoral Thesis
DOI
10.11606/T.5.2010.tde-09032010-174842
Document
Author
Full name
Margareth da Eira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Lotufo, Paulo Andrade (President)
Buchalla, Cassia Maria
Caramelli, Bruno
Gutierrez, Eliana Battaggia
Olmos, Rodrigo Diaz
Title in Portuguese
Avaliação de ateromatose subclínica em pacientes HIV/aids: determinação da velocidade de onda de pulso e da espessura média-íntima de carótidas
Keywords in Portuguese
Antiretrovirais/efeitos adversos
Aterosclerose
HIV
Pulso arterial/métodos
Risco
Síndrome da imunodeficiência adquirida
Síndrome metabólica
Ultra-sonografia/métodos
Abstract in Portuguese
A terapia anti-retroviral altamente potente (HAART), determinou uma melhora significativa do prognóstico dos pacientes vivendo com HIV/aids. Contudo, a presença de toxicidades agudas e crônicas, incluindo risco aumentado de doenças cardiovasculares, acarretou novas implicações para a qualidade e expectativa de vida destes pacientes. O objetivo deste estudo foi determinar o risco cardiovascular de pacientes HIV/aids tratados e nãotratados com esquema HAART. De 02/2008 a 07/2009 foram incluídos 118 indivíduos entre 18 e 70 anos, procedentes do Instituto de Infectologia Emílio Ribas e do Hospital Universitário da USP, além de voluntários saudáveis. Os indivíduos foram distribuídos em 4 grupos: (1) pacientes com infecção pelo HIV em uso de HAART; (2) pacientes com infecção pelo HIV sem tratamento (naïve); (3) pacientes diabéticos não insulino-dependentes (DM); (4) controle. Foram avaliados em todos os participantes: parâmetros bioquímicos, teste de tolerância oral à glicose, PCR ultra-sensível, microalbuminúria, sorologias para hepatite B e hepatite C, ECG, EMI, VOP, escore de risco de Framingham (ERF) e presença de síndrome metabólica (SM). Os pacientes DM tinham idade mais avançada (51,7 ± 9,7 anos) e 75, 8% eram do sexo feminino. Os dados foram ajustados para a idade (média ± erro-padrão). A relação cintura-quadril foi maior no grupo HAART que no controle (0,94 ± 0,01 vs. 0,88 ± 0,01, p< 0,0001); a pressão arterial sistólica média aferida no dia da visita foi maior no grupo HAART comparado ao grupo naive e controle (124,7 ± 2,3 vs. 118,1 ± 2,4 vs. 119,8 ± 2,2 mmHg, respectivamente; p= 0,001 e p= 0,005), e a pressão arterial diastólica média foi maior no grupo HAART que no naive (78,2 ± 1,8 vs. 75,9 ± 1,9 mmHg, respectivamente; p= 0,03); os níveis séricos de triglicérides estavam mais elevados no grupo HAART comparado aos grupos naive e controle (233,7 ± 193,4 vs. 137,3 ± 108,6 vs. 147,2 ± 87,3 mg/dL, respectivamente; p= 0,03 e p=0,04); microalbuminúria foi maior no grupo HAART que nos grupos naive e DM (86,2 ± 27,3 vs. 49,8 ± 30,5 vs. 30,8 ± 30,6 mg/dL, respectivamente; p= 0,01 e p= 0,009). A EMI da carótida direita foi maior no grupo naive comparado aos grupos HAART e controle (0,55 ± 0,02 vs. 0,52 ± 0,02 vs. 0,52 ± 0,02 mm, respectivamente; p< 0,0001), enquanto a EMI da carótida esquerda foi maior no grupo HAART comparado aos grupos naive e DM (0,64 ± 0,04 vs. 0,53 ± 0,04 vs. 0,52 ± 0,04, respectivamente; p< 0,0001). Houve diferença significativa em relação à VOP entre os grupos HAART e controle (9,7 ± 1,8 vs 8,7 ± 0,03 m/seg, p = 0,03). SM foi mais freqüente no grupo HAART que nos grupos naive e controle (41,4% vs. 25,0% vs. 28,1%, p= 0,0001). O ERF evidenciou risco alto em 27,6% dos pacientes do grupo HAART, o que foi significativo em relação aos grupos naive e controle (p=0,003). O nadir de CD4 foi menor nos pacientes do grupo HAART comparado ao grupo naive (208 ± 191 vs. 449 ± 176 células/L, p< 0,0001). A carga viral atual foi maior no grupo naive que no grupo HAART (13.633 ± 25.314 vs. 76 ± 61 cópias/ml, p= 0,005). Este estudo demonstra que pacientes com infecção pelo HIV em uso de HAART apresentam maior risco cardiovascular em relação aos pacientes não-tratados, evidenciado pela presença de maior freqüência de SM, maior ERF, maior rigidez arterial e presença de aterosclerose prematura mensurada pelo EMI da carótida esquerda. Isto ocorreu mesmo na ausência de viremia detectável, o que significa que devemos ter atenção para o risco de aterosclerose subclinica no seguimento de pacientes HIV/aids sob adequado tratamento antiretroviral, inclusive com eficaz controle imunológico e virológico.
Title in English
Evaluation of subclinical atheromatous disease in HIV/AIDS patients: assessment of pulse wave velocity (PWV) and carotid intimamedia thickness (IMT)
Keywords in English
Acquired immunodeficiency syndrome
Antiretroviral/adverse effects
Atherosclerosis
HIV
Metabolic syndorme
Pulse/methods
Risk
Ultrasonography/methods
Abstract in English
The highly active antiretroviral therapy (HAART), led to a significant improvement in the prognosis of patients living with HIV/AIDS. However, the presence of acute and chronic toxicities, including increased risk of cardiovascular disease, yielded further implications for the quality and life expectancy of these patients. The aim of this study was to determine the cardiovascular risk of HIV/AIDS patients treated and untreated with HAART. From february/2008 to july/2009 we enrolled 118 subjects between 18 and 70 years, attending at the Institute of Infectious Diseases Emilio Ribas and the University Hospital from USP, as well as healthy volunteers. The subjects were divided into 4 groups: (1) patients with HIV-infection on HAART; (2) patients with untreated HIV-infection (ART-naive); (3) diabetic patients not insulin-dependent (DM); (4) controls. Were evaluated in all participants: biochemical parameters, oral glucose tolerance test, high-sensitivity Creactive protein, microalbuminuria, serologies for hepatitis B and hepatitis C, ECG, carotid IMT, PWV, Framingham risk score (FRE) and the presence of metabolic syndrome (MS). The DM patients were older (51.7 ± 9.7 years) and 75.8% were female. The data were adjusted for age (mean ± standard error). The waist-to-hip ratio was higher in the HAART-treated patients than in the controls (0.94 ± 0.01 vs. 0.88 ± 0.01, p< 0.0001), the mean systolic blood pressure measured on the day of the visit was higher in the HAARTtreated patients compared to the ART-naive and controls (124.7 ± 2.3 vs. 118.1 ± 2.4 vs. 119.8 ± 2.2 mmHg, respectively, p= 0.001 and p= 0.005), and the mean diastolic blood pressure was higher in the HAART-treated patients than in the ART-naive (78.2 ± 1.8 vs. 75.9 ± 1.9 mmHg, respectively, p= 0.03); serum triglycerides were higher in the HAART-treated patients compared to the ART-naive subjects and controls (233.7 ± 193.4 vs. 137.3 ± 108.6 vs. 147.2 ± 87.3 mg/dL, respectively, p= 0.03 and p= 0.04); microalbuminuria was higher in the HAART-treated patients than in the ARTnaive and DM (86.2 ± 27.3 vs. 49.8 ± 30.5 vs. 30.8 ± 30.6 mg/dL, respectively, p=0.01 and p=0.009). The right carotid IMT was increased in the ART-naive compared to HAART-treated patients and controls (0.55 ± 0.02 vs. 0.52 ± 0.02 vs. 0.52 ± 0.02 mm, respectively, p< 0.0001), while the left carotid IMT was increased in the HAART-treated patients compared to the ART-naive and DM (0.64 ± 0.04 vs. 0.53 ± 0.04 vs. 0.52 ± 0.04, respectively, p< 0.0001). There was significant difference in PWV between the HAART-treated patients and controls (9.7 ± 1.8 vs. 8.7 ± 0.03 m/s, p= 0.03). MS was more prevalent in the HAART-treated patients than in the ART-naive and controls (41.4% vs. 25.0% vs. 28.1%, p= 0.0001). The FRE showed high risk in 27.6% of HAART-treated patients, which was significant compared to ART-naive and controls (p= 0.003). The nadir CD4 count was lower in HAART-treated patients compared to the ART-naive (208 ± 191 vs. 449 ± 176 cells/L, p<0.0001). Current viral load was higher in the ART-naive than in the HAART-treated patients (13,633 ± 25,314 vs. 76 ± 61 copies/ml, p= 0.005). This study shows that patients with HIV infection receiving HAART have a higher cardiovascular risk compared to untreated patients, as evidenced by the presence of a higher frequency of MS, higher ERF, increased arterial stiffness and the presence of early atherosclerosis measured by left carotid IMT. These abnormalities occurred even in the absence of detectable viremia, which means that physicians must pay attention to the risk of subclinical atherosclerosis as a result of HIV-infected patients under appropriate antiretroviral treatment, including effective virological and immunological control.
 
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Publishing Date
2010-03-11
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • BENSEñOR, Isabela M., et al. Heart Rate Variability in HIV Patients, Diabetics, and Controls : The AGATAA Study [doi:10.5402/2011/876864]. ISRN Vascular Medicine [online], 2011, vol. 2011, p. 1-8.
  • LOTUFO, Paulo, et al. Heart rate variability and human immudeficiency virus treatment [doi:10.1093/eurheartj/ehq287]. [online], .
  • MARGARETH, E., et al. Prevalence of metabolic syndrome and estimated Framingham risk score among Brazilian HIV-infected patients [doi:10.1016/j.ijid.2010.02.1658]. International Journal of Infectious Diseases [online], 2010, vol. 14, p. e76.
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