Several studies have shown an increased risk of myocardial infarction (MI) in HIV-infected patients exposed to protease inhibitors, whereas the association with certain nucleoside reverse transcriptase inhibitors is more controversial [1,2]. The SMART study showed that antiretroviral treatment interruption significantly increased the risk of MI relative to continuous treatment . The incidence of MI is lower in France than in English-speaking and northern European countries . We estimated the incidence of MI in the HIV-infected population in France, on the basis of the data collected for the French Hospital Database on HIV (FHDH-ANRS CO4), by comparison with three population-based registries .
The FHDH-ANRS CO4 cohort and the methodology of this study are described in detail elsewhere . Between 2000 and 2006, 74 958 HIV-infected patients who had been examined at least once were included in the database, corresponding to a total follow-up of 298 156 person-years (207 300 person-years for men and 90 856 person-years for women). As part of a nested case–control study, we reviewed all reported cases of MI (code I21 of the International Disease Classification) . The diagnosis of MI was validated by a cardiologist, based on cardiac signs and symptoms, troponin and/or creatine kinase levels, and electrocardiographic findings collected in the medical records, using the American College of Cardiology/European Society of Cardiology definition .
The sex and age MI incidence rates were compared with the estimated rates in the general population aged from 35 to 64 years during the same period . In the three French regions covered by registries, MI was defined as lethal and nonlethal MI and coronary death according to MONICA protocol . Sex- and age-specific (per 5-year stratum) incidence rates in the HIV-infected and general populations were compared using standardized morbidity ratios (SMRs) .
There were 360 validated cases of MI (325 men, 35 women) among the HIV-infected patients, corresponding to an incidence rate of 1.24 per 1000 patient-years [95% confidence interval (CI) 1.11–1.36]. Of these 360 cases, 313 were diagnosed between 35 and 64 years of age (283 men, 30 women), corresponding to a total follow-up of 221 183 patient-years and an incidence of 1.42 per 1000 patient-years (95% CI 1.3–1.5). The incidence rates per age stratum are shown in Fig. 1(a) (men) and Fig. 1(b) (women). The risk of MI was higher in both HIV-infected men and women than in the general population, with respective SMRs of 1.4 (95% CI 1.3–1.6) and 2.7 (95% CI 1.8–3.9). The bulk of this increase concerned men up to 55 years of age and women up to 45. The overall SMR was 1.5 (95% CI 1.3–1.7).
The MI incidence rates in HIV-infected patients and in the general population have already been compared in English-speaking countries  and in northern Europe . Our results, obtained in a country with a low overall incidence of MI, are very similar to those of Triant et al. for the USA, who also found a higher relative risk in women (3.0) than in men (1.4) . Savès et al., who used the PRIME model to predict the risk of coronary disease in HIV-infected patients in France, based on smoking, systolic blood pressure and total and high-density lipoprotein cholesterol levels, also found a higher relative risk in women than in men, but the relative risks were smaller than in our study (1.2 versus 1.4 for men, 1.6 versus 2.7 for women). This suggests that the increase may be due not only to classical risk factors, accounted for in the PRIME model, but also to exposure to combined antiretroviral treatment, as shown by Obel et al., and to HIV infection itself. For example, Lo et al. recently reported that the risk of subclinical coronary arteriosclerosis correlated with the CD4/CD8 ratio and MCP1 level. The higher relative risks of MI found in younger men and women in our study raises the possibility of a premature aging effect of HIV infection on the cardiovascular system .
Thus, in France, a country with a low incidence of MI in the general population, the risk of MI is increased in HIV-infected patients, and this increase is unlikely to be explained only by classical cardiovascular risk factors.
The study was sponsored by Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (French National Agency for Research on AIDS and Viral Hepatitis). The full list of investigators participating in the MONICA project can be found at http://www.ktl.fi/monica/. Accessed 12 January 2010. The full list of investigators participating in the Clinical Epidemiology Group of the French Hospital Database on HIV can be found at http://www.ccde.fr. Accessed 12 January 2010. We thank all the cohort participants, and especially the research assistants, without whom this work would not have been possible. Special thanks to P. Ducimetière (Villejuif), P. Amouyel (Lille), D. Arveiler (Strasbourg) and J. Ferrières (Toulouse) for providing the MONICA-France incidence data.
1. Worm WS, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, et al
. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis 2009; 201:318–330.
2. Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, et al.Impact of individual antiretroviral drugs on the risk of myocardial infarction in HIV-infected patients: a case–control study nested within the FHDH ANRS Cohort CO4
. Arch Intern Med
3. Study Group SMART, Gordin F, Finley E, et al
. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355:2283–2296.
4. Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E, for the WHO MONICA Project. Geographical variation in the major risk factors of coronary heart disease in men and women aged 35–64 years. World Health Stat Q 1988; 41:115–140.
5. Arveiler D, Wagner A, Ducimetière P, Montaye M, Ruidavets JB, Bingham A, et al
. Trends in coronary heart disease in France during the second half of the 1990s. Eur J Cardiovasc Prev Rehabil 2005; 12:209–215.
6. World Health Organization. International statistical classification of diseases and related health problems
. 10th Revision. Geneva: World Health Organization; 1993.
7. Luepker RV, Apple FS, Christenson RH, Crow RS, Fortmann SP, Goff D, et al
. Case definitions for acute coronary heart disease in epidemiology and clinical research studies. Circulation 2003; 108:2543–2549.
8. Turnstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas AM, Pajak A. Myocardial infarction and coronary deaths in the World Health Organization MONICA project. Circulation 1994; 90–91:583–612.
9. Breslow NE, Day NE. Statistical methods in cancer research. Vol. 2. The design and analysis of cohort studies. Scientific Publication No. 82. Lyon, France: IARC; 1987. pp. 48–79.
10. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007; 92:2506–2512.
11. Obel N, Thomsen HF, Kronborg G, Larsen CS, Hildebrandt PR, Sørensen HT, et al
. Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study. CID 2007; 44:1625–1631.
12. Savès M, Chêne G, Ducimetière P, Leport C, Le Moal G, Amouyel P, et al
. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus compared with the general population. Clin Infect Dis 2003; 37:292–298.
13. Lo J, Abbara S, Shturman L, Soni A, Wei J, Rocha-Filho JA, et al
. Increased prevalence of subclinical coronary arteriosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS 2010; 24:243–253.
14. Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 2009; 338:a3172.