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Changes Over Time in the Use of Antiretroviral Therapy and Risk Factors for Cardiovascular Disease in the D:A:D Study
Caroline Sabin*1, L Morfeldt2, N Friis-Moller3, M Rickenbach4, P Reiss5, A d'Arminio Monforte6, C Pradier7, O Kirk8, G Calvo9, M Law10, P Mercie11, W El-Sadr12, S De Wit13, J Lundgren3, and The D:A:D Study Group
1Royal Free and Univ Coll Med Sch, London, UK; 2HivBivus, Karolinska Hosp, Stockholm, Sweden; 3Copenhagen HIV Prgm, Hvidovre Univ Hosp, Denmark; 4Univ Hosp, Lausanne, Switzerland; 5ATHENA Cohort Study Group, HIV Monitoring Fndn, Academic Med Ctr, Univ of Amsterdam, The Netherlands; 6L Sacco Hosp, Univ of Milan, Italy; 7Ctr Hosp Univ Nice, Hosp de l'Archet, France; 8EuroSIDA, Copenhagen HIV Prgm, Hvidovre Univ Hosp, Denmark; 9BASS, Autonomous Univ of Barcelona, Spain; 10Australian HIV Observational Database, Natl Ctr in HIV Epidemiology and Clin Res, Sydney, Australia; 11Aquitaine Cohort, Bordeaux Univ Hosp, INSERM U593, France; 12Community Prgms for Clin Res on AIDS, Harlem Hosp, Columbia Univ, New York, NY, USA ; and 13St-Pierre Cohort, Ctr Hosp Univ St-Pierre, Brussels, Belgium
Background: The
growing recognition of the relationship between exposure to combination antiretroviral
therapy (ART) and an increased risk of myocardial infarction (MI) may have
influenced patients’ lifestyles.
Methods: We
analyzed data on 23,441 persons from 11 cohorts in Europe, the United States, and Australia. Changes in patient
characteristics and cardiovascular disease (CVD) risk factors were assessed.
High-risk individuals were those with a previous CVD
event (prior MI, stroke, or invasive procedure), diabetes, or ≥ 2 risk
factors for CVD (current smoker,
hypertension, total cholesterol ≥6.2 mmol/L or HDL-cholesterol ≤ 0.9
mmol/L or
total cholesterol:HDL ratio ≥6.5, family
history of CVD or age ≥ 45
in men or 55 in women). Poisson regression models compared MI incidence over
calendar time from December 1999 to January 2004, and were repeated after
controlling for changes in patient demographics, ART
use and CVD risk factors.
Results: CVD risk factors over time are shown in the table below. The proportion
of patients with ≥ 2 CVD
risk factors increased from 34.6 to 42.4% and the proportion at high risk
increased from 36.2 to 44.7%. Serum lipid levels remained stable (median total cholestserol, HDL, and triglyceride levels of 5.1, 1.1, and
1.7 mmol/L, respectively), although the proportion of
patients using lipid-lowering drugs increased from 4.0% to 8.1%. Changes in
risk factors were generally more pronounced in men and those who were older,
but were apparent in all. Although there was no univariable
effect of calendar time on MI incidence, adjustment for changes in CVD risk factors suggested that the risk of MI—all
else being equal—was lower in later years compared to 1999/2000 (rate ratio for
2001: 1.13 (0.79 to 1.61), 2002: 0.67 (0.45 to 1.00), 2003/2004: 0.62 (0.42 to 0.94); p = 0.002).
Conclusions: The CVD risk profile of
patients in D:A:D
has worsened over time, with an increase in the proportion of patients at high
risk of CVD. After
controlling for these changes, the risk of MI has decreased over the years,
possibly as a result of improved targeting of interventions to those at high
risk (e.g. use of lipid lowering drugs) or because of changes in the choice of ART.
Keywords: cardiovascular disease; risk factors; calendar time
