JAIDS Journal of Acquired Immune Deficiency Syndromes:
Letters to the Editor
*I Divisione di Malattie Infettive, Ospedale Luigi Sacco, Milano; †Clinica di Malattie Infettive, Ospedale di Perugia; ‡Divisione A di Malattie Infettive, Ospedale Amedeo di Savoia Torino; §Divisione di Malattie Infettive, Ospedale di Ferrara, Ferrara; ∥Divisione di Malattie Infettive, Ospedale Galliera, Genova; ¶Divisione di Malattie Infettive, Ospedale di Pescara, Pescara; #Divisione di Malattie Infettive, Ospedale di Cesena, Cesena; **Clinica di Malattie Infettive, Ospedale di Sassari, Sassari; ††Divisione di Malattie Infettive, Ospedale Santa Maria Annunziata, Firenze; ‡‡Clinica Mallattie Infettive, Ospedale Luigi Sacco, Milano; and §§Divisione di Malattie Infettive, Ospedale Careggi-Firenze; and ∥∥Divisione di Malattie Infettive, Ospedale di Busto Arsizio, Busto Arsizio
To the Editor:
Morphological and metabolic alterations are the main clinical manifestations in HIV-infected patients under treatment.1,2 The Metabolic Syndrome (MS) ranks high among the metabolic reactions. Metabolic Syndrome involves a cluster in the same patient of several metabolic disorders, each of which alone is a cardiovascular risk factor. Figures on the prevalence of MS among HIV-infected patients tend to vary, with reports ranging from 17% to 39.8%.3-5
The SIMONE study (SIndrome Metabolica ONE) was a cross-sectional survey designed to assess the prevalence and characteristics of MS in a population of Italian HIV-infected patients, employing the National Education Cholesterol Program criteria.6 The study started in February and was completed in April 2005, conducted by the CISAI group (Coordinamento Italiano Studio Allergia e Infezione da HIV), an Italian coordination group for the study of allergies and HIV infection. All patients attending scheduled visits in this period at the hospitals were eligible. Exclusion criteria were as follows: age younger than 18 years, hepatic cirrhosis, non-white origin, pregnancy, unscheduled visit. These criteria were applied to eliminate confounding factors. Using a standard data collection form, we recorded each patient's sex, age, weight and height, smoking habit, blood pressure, waist measurement, diagnosis of diabetes or lipodystrophy, and treatment of hypertension or lipid-lowering drugs. A targeted pharmacological history was taken to obtain information on current treatments (by drug) and previous ones (by drug classes). Laboratory tests included total and high-density lipoprotein (HDL) cholesterol, fasting triglycerides, fasting blood glucose, and absolute CD4+ lymphocyte count. Metabolic Syndrome was diagnosed when a subject met 3 or more of the following National Education Cholesterol Program criteria 7: waist measurement >102 cm for men and >88 cm for women, high triglycerides (≥150 mg/dL), low HDL cholesterol (<40 mg/dL for men, <50 mg/mL for women), hypertension (≥135/≥85 mm Hg), and high blood glucose (≥110 mg/mL). Diabetic patients on treatment with normal blood glucose were classified as higher than 110 mg/dL; patients whose blood pressure was normal under antihypertensive therapy were classified as hypertensive. Subjects met the criterion of elevated fasting triglyceride level if they had normal fasting triglyceride level and were currently treated with lipid-lowering drugs.
To assess the association between categorical variables, we used the χ2 test or Fisher exact test, as appropriate, introducing age in the Cochrane-Mantel-Hanszel method. Means were compared using analysis of variance, adjusting for age. Odds ratios (ORs) as estimates of risk of MS, with their 95% confidence intervals (CI), were calculated using unconditional multiple logistic regression.
A total of 1243 subjects were enrolled, with mean age of 43.2 years (SD ± 9.2); 71.8% of them were male. Table 1 sets out their main characteristics. The prevalence of MS was 22.0% (CI 95% 19.7-24.3), 17.4% (CI 13.4-21.4) for women and 23.8% (CI 21.0-26.6) for men. Table 2 sets out, one by one, the prevalence of the criteria used to define MS: high serum triglycerides was the most frequent abnormality (52.2%); 80.5% of patients met at least 1 criterion, 51.2% met 2, 22.4% met 3, 6.4% met 4, and 1.1% met all 5. The most frequent trio of abnormalities that led to the diagnosis of MS was blood pressure, triglycerides, and HDL cholesterol. Univariate analysis to establish which variables were associated with MS considered the following: age, sex, body mass index (BMI), smoking habit, CD4+ lymphocytes, lipodystrophy, total serum cholesterol, current antiretroviral therapy, previous treatment with protease inhibitors (PI), or nonnucleoside reverse transcriptase inhibitors (NNRTI), zidovudine (AZT), or stavudine (d4T). Significant associations were found with older age, BMI >25, high CD4+ lymphocyte count, lipodystrophic syndrome, abnormal serum total cholesterol (>240 mg/dL), and previous PI treatment.
We also did multivariate analysis using the single antiretroviral drugs patients were taking at the time of the survey. Indinavir was the only drug that gave a significant association with MS (OR 4.3, CI 95% 1.7-11.0).
To our knowledge, the SIMONE study comprises the largest series yet of HIV-infected patients assessed for the prevalence of MS. Unlike previous studies, this was a multicenter investigation which should give a more realistic picture of the situation in the HIV-infected population. The prevalence of MS in this series seems closer to that reported for the Italian general population 7,8 than earlier, more alarming reports.4,5 The most frequent abnormality, high triglycerides, is clearly related to the widespread use of PI -approximately 50%-in these patients. It should therefore come as no surprise that there was also an association with lipodystrophy, which is marked, in the accumulation forms, by increased visceral fat, and metabolic alterations. Likewise, the association with high serum total cholesterol was largely to be expected., as it is also often seen together with other metabolic abnormalities, such as low HDL cholesterol and high triglycerides.
One last question regards the comparison with the prevalence of MS in the general population. We are not convinced by comparisons based solely on the literature because the prevalence in a general population can vary widely depending on the geographical region studied and the population's age. A correct approach would be to design a case-control study aimed at "matching" the populations being compared for sex and age.
This study is supported by an ISS grant from Ministry of Health, Rome, Italy (project no. 30F.43)
Giuseppe de Socio†
For the CISA1 study group
*I Divisione di Malattie Infettive
Ospedale Luigi Sacco, Milano
†Clinica di Malattie Infettive
Ospedale di Perugia
‡Divisione A di Malattie Infettive
Ospedale Amedeo di Savoia Torino
§Divisione di Malattie Infettive
Ospedale di Ferrara, Ferrara
∥Divisione di Malattie Infettive
Ospedale Galliera, Genova
∥Divisione di Malattie Infettive
Ospedale di Pescara, Pescara
#Divisione di Malattie Infettive
Ospedale di Cesena, Cesena
**Clinica di Malattie Infettive,
Ospedale di Sassari, Sassari
††Divisione di Malattie Infettive
Ospedale Santa Maria Annunziata
‡‡Clinica Mallattie Infettive
Ospedale Luigi Sacco, Milano
and §§Divisione di Malattie Infettive
and ∥∥Divisione di Malattie Infettive
Ospedale di Busto Arsizio
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2. Nolan D. Metabolic complications associated with HIV protease inhibitor therapy. Drugs
3. Jericó C, Knobel H, Montero M, et al. Metabolic syndrome among HIV-infected patients: prevalence, characteristics, and related factors. Diabetes Care
4. Bruno R, Gazzaruso C, Sacchi P, et al. High prevalence of metabolic syndrome among HIV-infected patients: link with the cardiovascular risk. J Acquir Immune Defic Syndr
5. Gazzaruso C, Sacchi P, Garzaniti A, et al. Prevalence of metabolic syndrome among HIV patients. Diabetes Care
6. Executive Summary of the Third Report of the National Cholesterol Educational Programme (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA
7. Bo S, Gentile L, Ciccone G, et al. The metabolic syndrome and high C-reactive protein: prevalence and differences by sex in a southern-European population-based cohort. Diabetes Metab Res Rev
© 2006 Lippincott Williams & Wilkins, Inc.
8. Bonora E, Kiechl S, Willeit J, et al. Metabolic syndrome: epidemiology and more extensive phenotypic description. Cross-sectional data from the Bruneck Study. Int J Obes Relat Metab Disord