Numerous
studies have shown that antiretroviral drugs -- in particular the protease inhibitor
class -- are associated with metabolic abnormalities that may raise the risk of
heart disease. Further, more recent research (such as the SMART
treatment interruption study suggests that chronic HIV infection itself contributes
to heart and other major organ disease, perhaps due to persistent inflammation.
Yet
while risk factors for cardiovascular disease are increasingly common among HIV
positive people (largely attributable to aging), the rate of myocardial infarction
(heart attack) has remained stable, according to a new analysis from the D:A:D
(Data Collection on Adverse Events of Anti-HIV Drugs) study.
D:A:D is a
large ongoing cohort study that has been gathering data on side effects associated
with antiretroviral therapy among more than 33,000 HIV positive participants in
11 cohorts, mostly in the U.S. and Europe.
In
the latest analysis, reported in the April 1, 2008 issue of Clinical Infectious
Diseases, the large international team of investigators evaluated changes
in risk factors for cardiovascular disease and the use of lipid-lowering therapy,
and assessed the impact of changes on the incidence of myocardial infarction.
The analysis included data from 33,389 participants collected between December
1999 and February 2006.
Results
•
Overall, the
proportion of patients at high risk for cardiovascular disease increased from
35.3% during 1999-2000 to 41.3% during 2005-2006.
•
The increase
in risk was more pronounced among men (from 40.1% to 47.8%) than among women (from
0.4% to 22.9%). •
The proportion
of patients for whom older age was a risk factor rose from 25% to 37%. •
However, the
proportion of smokers dropped, from 47% to 38%.
•
Overall, 9.7%
of study participants started lipid-lowering therapy (such as statin drugs).
•
The use of
lipid-lowering drugs rose from 6% to 15% over the follow-up period.
•
Not surprisingly,
lipid-lowering therapy was more common among patients with abnormal lipid values
and those with traditional cardiovascular risk factors (male sex, older age, higher
body mass index, diabetes, and family and personal history of cardiovascular disease).
•
After controlling
for these risk factors, however, use of lipid-lowering drugs became relatively
less common over time.
•
A total of
445 myocardial infarctions were reported over 137,310 person-years (PY) follow-up,
for an incidence rate of 0.32 cases per 100 person- PY.
•
Incidence rates
appeared to remain stable over the study period: o 1999-2000: 0.32 episodes
per 100 PY;
•
2001: 0.43
per 100 PY;
•
2002: 0.31
per 100 PY;
•
2003: 0.34
per 100 PY;
•
2004: 0.33
per 100 PY;
•
2005-2006:
0.22 per 100 PY.
•
After controlling
for changes in cardiovascular risk factors, however, the myocardial infarction
incidence rate decreased over time:
•
Relative rate
in 2003 compared with 1999-2000: 0.73 cases per 100 PY;
•
Relative rate
in 2004: 0.64 cases per 100 PY;
•
Relative rate
in 2005-2006: 0.36 cases per 100 PY.
•
Further adjustment
for lipid levels attenuated the relative rates towards unity (i.e., no change):
•
Relative rate
in 2003 compared with 1999-2000: 1.06 cases per 100 PY;
•
Relative rate
in 2004: 1.02 cases per 100 PY;
•
Relative rate
in 2005-2006: 0.63 cases per 100 PY.
Conclusion
In
conclusion, the study authors wrote, "[O]ur findings suggest that, although
the cardiovascular disease risk profile among patients observed in the D:A:D study
has deteriorated since 1999, myocardial infarction incidence rates have remained
relatively stable."
They added that, "This is possibly a result
of a more aggressive targeted approach to managing the risk of cardiovascular
disease" in the HIV positive population.
5/13/08
Reference CA
Sabin, A d'Arminio Monforte, N Friis-Moller, and others (D:A:D Study Group). Changes
over time in risk factors for cardiovascular disease and use of lipid-lowering
drugs in HIV-infected individuals and impact on myocardial infarction. Clinical
Infectious Diseases 46(7):1101-10. April 1, 2008.
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