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Atherogenic Lipid Profile and Cardiovascular Risk Factors in HIV- Infected Patients (Ntar Study)

Posted on: Saturday, 29 October 2005, 03:01 CDT

By Santos, J; Palacios, R; Gonzlez, M; Ruiz, J; Mrquez, M

Summary: We undertook a transverse study of 603 HIV outpatients to determine their atherogenic lipid profile (ALP) and cardiovascular risk (CVR) factors. CVR was estimated from the Framingham score. ALP was defined as a total cholesterol to high density lipoprotein (HDL)-cholesterol ratio ≥5 plus triglycerides ≥150 mg/dL and a CVR >10% at 10 years was considered high. The most frequent CVR factor was smoking. ALP was diagnosed in 26.9% and was related to sex (odds ratio [OR] 2.6; 95% confidence interval [CI], 1.3-5.0; P=0.0047), protease inhibitor use (OR 3.8; 95% CI, 1.8-7.8; P=0.0002) and sexual HIV risk (OR 2.4; 95% CI, 1.4.0; P=0.0004). The mean 10-year CVR was 6.2%, was high in 20.4% and was related to sexual HIV-risk (OR 3.8; 95% CI, 2.1-6.8; P<0.00001) and nadir cell differentiation factor (CD4) (OR 1.0; 95% CI, 1.0-1.003; P=0.0026). Although the current CVR of our patients is not high, the contribution to the lipid profile of highly active antiretroviral therapy (HAART)-associated factors and the high prevalence of some risk factors may lead to an increased future CVR.

Keywords: cardiovascular risk, atherogenic lipid profile, HAART, HIV

Introduction

Metabolic abnormalities associated with HIV infection and highly active antiretroviral therapy (HAART) are increasingly prevalent and there is concern about the possibility of an association with accelerated cardiovascular disease.1'2 While several reports have hinted at an increased risk of coronary heart disease among HIV- infected patients, not all authors agree.3 In this study, we determined the atherogenic lipid profile (ALP) and cardiovascular risk (CVR) factors in HIV-positive patients attending our clinic. We estimated the 10-year CVR and determined those factors associated with a high CVR.

Patients and methods

We undertook a transverse study of all HIV-infected outpatients from a single institution from May to September 2002. The catchment area of our hospital, in southern Spain, includes about 450,000 inhabitants. Each patient answered a detailed questionnaire focusing on CVR factors and underwent a physical examination, which included measurements of blood pressure and anthropometric data. Smokers were considered to be those who smoked one or more cigarettes a day; family history was considered positive if ischaemic heart disease had been present in the patient's father or brothers when they were younger than 55 years of age or the patient's mother or sisters when they were younger than 65 years. Blood was drawn after a 12 h fast. Diagnosis of dyslipidaemia, diabetes mellitus and hypertension was based on international criteria.4-6 Patients with a total cholesterol to high density lipoprotein (HDD-cholesterol ratio ≥5 plus triglycerides ≥150mg/dL were considered to have an ALP. The 10-year CVR was calculated from the Framingham equation.7 Patients with a CVR above 10% were considered to have a high risk. Patient data were collected in a computerized database for later statistical analysis with SPSS version 8.0 for Windows. Qualitative variables were studied with the χ^sup 2^ test and Yates correction or Fischer's exact test when necessary, and quantitative variables were studied with the Student's f-test or the Mann-Whitney U-test for variables that did not follow a normal distribution. Multiple logistic regression analysis was used to identify possible factors related to the ALP or a high CVR.

Results

The study included 603 patients with a mean age of 41.5 years (19- 80 years); 80.8% were men and the mean duration of HIV infection was 7.4 years (0-17.5 years). The mean cell differentiation factor (CD4) cell count was 499/mL (2-2.348 mL) and 81.4% of patients were receiving antiretroviral therapy, with a mean treatment duration of 4.9 years (0-12.4 years). Table 1 shows the CVR factors. The lipid profile fulfilled criteria for ALP in 162 (26.9%) patients. The mean 10-year CVR of the whole sample was 6.2% (95% confidence interval [CI], 0.5-20). The 10-year CVR was above 10% in 111 (20.4%) patients and equal to or above 20% in 41 (6.7%). Although an ALP was related to sex, age, sexual HIV risk, aids diagnosis, body mass index, blood pressure, the presence of diabetes mellitus, nadir CD4 cell count and antiretroviral and protease inhibitor (PI) use, in multivariate analysis only sex, sexual HIV-risk and PI use remained significant (Table 2). Univariate analysis showed a high CVR to be associated with sex, age, sexual HIV risk, body mass index, nadir CD4 cell count and antiretroviral use; however, multivariate analysis showed just sexual HIV risk and nadir CD4 cell count to be the only significant factors related to CVR (Table 3).

Table 1 Cardiovascular risk factors

Table 2 Univariate and multivariate analysis of patients with an atherogenic lipid profile (n=162) versus patients without an atherogenic lipid profile (n=441)

Discussion

The Ntar Study includes HIV-positive patients who have had their infection for a long time and most have been receiving antiretroviral therapy for some time. Although the mean 10-year likelihood of CVR in the whole cohort was not very high, a significant proportion did have a high CVR. Not only is the literature controversial as to whether patients with HIV infection are at increased risk for coronary heart disease, but the specific roles in this risk for the HIV infection itself, its treatment and HAART-associated metabolism disorders have not yet been defined.3'8

The prevalence in the Netar Study of known CVR factors, such as smoking and dyslipidaemia, was considerable. Smoking was the most frequent CVR factor in our patients. Previous studies of CVR factors in HIV-positive patients showed that a high percentage of these subjects smoke.9-13 Savs et al.11, suggest that smoking makes a major contribution to the risk for coronary heart disease in HIV- infected patients, independently of other risk factors, which may or may not be linked to the use of PIs. We found a high prevalence of an ALP among our HIV patients, which is consistent with previous studies.9-13 Dyslipidaemia is a known CVR factor which has been related to HAART.14-17 Although PIs are the group of drugs most commonly involved in HAART-associated lipid disorders, reverse transcriptase inhibitors may also play an important role in their development.18-21 Bearing in mind that the study cohort was composed of patients who had been receiving antiretroviral therapy for some time, it is not surprising that lipid profile disorders were present in a high percentage of patients. Use of PIs was related to the ALP, as were male sex and sexual HIV risk. Other CVR factors related to HAART, such as glucose metabolism disorders, diabetes and hypertension,14'15'17'22"24 were also relatively frequent in our patients. The study reported herein was also designed to determine the risk of coronary heart disease among our clinic HIV population. We used the Framingham risk equation to estimate the 10-year coronary heart disease risk.7 Although the Framingham equation has been validated in other patient populations,25 the reliability of this equation to predict coronary events among HIV-infected patiente remains unknown. Although some studies9"11'13'26'27 suggest an increase in coronary heart disease risk among these patients, others refute this.28'29 Thus, Bozette et al.29 found no increase in the number of hospitalizations for cerebrovascular or cardiovascular evente or in the mortality rate from 1993 to 2001 in a large cohort of HIV-infected patiente. On the other hand, in a recent prospective study with over 20,000 patients, factors predicting cardiovascular events included time of exposure to HAART, age, sex, smoking, prior coronary heart disease and metabolic disorders.13 Although the mean coronary heart disease risk of our series was not very high, over 20% of the patients had a high 10-year risk of coronary heart disease (>10%) according to the Framingham equation. If we consider the high prevalence in our patients of some classic CVR factors, mainly smoking, a progressively increasing age and the duration of HAART, with its associated risk of developing metabolic disorders, the CVR of these patients can be expected to increase over time, with the possible rise in the number of cardiovascular events.

Table 3 Univariate and multivariate analysis of patients with a high cardiovascular risk (n=111) versus those without a high cardiovascular risk (n=492)

In summary, although the current overall CVR of our patients is not high, if we consider the contribution of HAART-associated factors to the lipid profile and the high prevalence of some CVR factors, such as smoking, the CVR may well increase in the future. Although use of PIs may play a role, it may be more important to address traditional CVR factors as the primary concern for reducing coronary heart disease. Longitudinal studies with a longer follow- up are needed to determine the evolution of the risk of coronary heart disease and to demonstrate that the Framingham score is a good method to estimate this risk in HIV-positive patients.

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(Accepted 1 August 2004)

J Santos MD PhD, R Palacios MD PhD, M Gonzlez MD, J Ruiz MD and M Mrquez MD

Infectious Diseases Unit, Hospital Virgen de Ia Victoria, Campus Teatinus s/n, Mlaga 29010, Spain

Correspondence to: Dr Jess Santos

Email: med000854@saludalia.com

Copyright Royal Society of Medicine Press Ltd. Oct 2005

Source: International Journal of STD & AIDS

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