ORIGINAL RESEARCH Hyperhomocysteinaemia in HIV-infected patients: determinants of variability and correlations with predictors of cardiovascular disease G Guaraldi, 1 P Ventura, 1 E Garlassi, 1 G Orlando, 1 N Squillace, 1 G Nardini, 1 C Stentarelli, 1 S Zona, 1 S Marchini, 1 V Moriondo 1 and P Tebas 2 1 Department of Medicine and Medical Specialties, Infectious Diseases Clinic, Emilia School of Medicine, University of Modena and Reggio Emilia, Modena, Italy and 2 University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, PA, USA Objective We evaluated hyperhomocysteinaemia (HHcy) in a cohort of HIV-infected patients in order to assess its relation to cardiovascular risk (CVR) and identify determinants of HHcy variability. Methods Cross-sectional observational study. HIV-infected patients on stable highly active antiretroviral therapy (ART) were evaluated for the presence of the metabolic syndrome, lipodystrophy and traditional CVR factors. Plasma homocysteine levels were measured using high-performance liquid chromatography. Results Five hundred and sixty-seven patients (38% female) with a median age of 44 years were included in the study. Homocysteine (Hcy) was significantly higher in patients with the metabolic syndrome and lipodystrophy. No significant association was found between Hcy levels and the use of ART. However, Hcy was associated with higher blood pressure, waist circumference and waist-to-hip ratio, total lean body mass, visceral adipose tissue (VAT), VAT/total adipose tissue, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, high-density lipoprotein cholesterol, apolipoprotein A1, B, and creatinine. All 10-year CVR assessment scores were significantly associated with Hcy. In a multivariate regression model, systolic blood pressure, vitamin supplementation and HOMA-IR were significantly and independently related to Hcy. Conclusions Hcy is elevated in HIV-infected patients and is significantly associated with increased CVR. Measurement of Hcy might be useful in identifying particularly high-risk populations at whom therapeutic interventions could be targeted. Keywords: cardiovascular disease, homocysteine, metabolic syndrome Accepted 17 July 2008 Introduction Hyperhomocysteinaemia (HHcy) has been recognised as an independent risk factor for ischaemic heart disease and strokes [1–4]. After adjustment for known cardiovascular risk (CVR) factors, a decrease of about 3 mmol/L in homocysteine (Hcy) level was associated with an 11% lower ischaemic heart disease risk and 19% lower stroke risk in a meta-analysis of more than 30 large studies [5]. The exact mechanism of the association between HHcy and increased CVR is still unclear. HHcy has been associated with hypertension [6] and (to a lesser degree) with insulin resistance [7–12]. Although in vivo and in vitro there is evidence that Hcy is pro-atherogenic, three prospective, randomized controlled trials failed to demonstrate that vitamin supplementation with folic acid, vitamin B6 and B12 – which are associated with decreases in circulating Hcy levels – resulted in a lower incidence of cardiovascular Correspondence: Giovanni Guaraldi, Department of Medicine and Medical Specialties, Infectious Diseases Clinic, Emilia School of Medicine, University of Modena and Reggio Via del Pozzo 71, 41100 Modena, Italy. Tel: 1 39 059 422 2799; fax: 1 39 059 422 3710; e-mail g.guaraldi@unimo.it DOI:10.1111/j.1468-1293.2008.00649.x HIV Medicine (2009), 10, 28–34 r 2008 British HIV Association 28