Long-term HIV infection
is the only significant factor associated with thickening of the
carotid intima media, a marker for atherosclerosis, a French
case-control study has reported.
anti-inflammatory response also appears to reduce the risk of carotid
intima media thickening, independent of the duration of HIV
infection. (The thickening of the wall of the carotid artery due to the accumulation of cholesterol, calcium and plaques is considered a reliable indicator of the progression of cardiovascular disease).
A number of studies have shown that people with HIV infection have a higher risk of cardiovascular disease than their HIV-negative counterparts. Various risk factors have been identified, including treatment with several protease inhibitors, with the NRTIs abacavir and with ddI, as well as the widely known risk factors for heart disease of age, smoking and high lipid levels.
However some studies suggest that HIV infection itself, and the inflammatory state that uncontrolled HIV infection creates, are important risk factors for cardiovascular disease.
The difficulty in assessing which of the major risk factors is most important lies in untangling the many confounding factors. For example, the majority of people with HIV in many cohort studies either smoke or have an extensive smoking history. Also, not all studies control for duration of infection, for immunodeficiency, for viral load or for duration of treatment.
The new findings, presented
last week at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston,
come from a study carefully designed to exclude biases, by some of
the leading international experts in the metabolic complications of
HIV infection, led by Dr Moise Desvarieux.
The study compared men
with long-term HIV infection who had been infected for a median of
more than 7.9 years with men who had been infected for less than 7.9
years, and to untreated men and to HIV-negative age-matched men.
The study recruited 100
men who had been infected for between 3.8 years (median period of
infection in the untreated group <7.9 years duration of infection)
to 14 years in the treated group with a median duration of infection
greater than 7.9 years.
There were no
significant differences in any cardiovascular indicators (total
cholesterol, LDL and HDL cholesterol or triglycerides) between the
groups. Nor was there any significant difference in age between the
groups recruited (the median age of the groups ranged from 38.9 to 43
The study only
recruited men who had never smoked in order to rule out any bias
introduced by smoking, which is common in men with HIV infection and
an independent risk factor for atherosclerosis (hardening of the
arteries). The analysis controlled for CD4 count, viral load and duration of treatment.
Carotid intima media
thickness (cIMT) was significantly associated with duration of infection,
after adjusting for nadir (lowest ever) CD4 count, regardless of antiretroviral
treatment. Greater cIMT was also associated with low levels of
anti-inflammatory cytokines. Declining levels of adiponectin, a
substance which regulates a number of metabolic pathways and which
has been associated with a reduced risk of cardiovascular disease,
was strongly correlated with cIMT thickness.
However, higher levels
of pro-inflammatory cytokines, suspected by some as a cause of
cardiovascular disease in people with HIV, were much less strongly
associated with greater cIMT.
Another study, which
looked at 235,000 patients receiving care through the Kaiser
Permanente network of clinics in California (20,775 HIV-positive),
found that individuals with HIV infection had a 40% higher risk of
myocardial infarction and 20% higher risk of any cardiovascular
disease than their HIV-negative counterparts after controlling for
age (both values p < 0.001).
patients on treatment, immunodeficiency had a significant impact on
cardiovascular risk: individuals with a current CD4 count below 500 cells/mm3
had a significantly higher risk of cardiovascular disease (risk
ratio 1.4 for CD4 200 to 499, risk ratio 1.7 for CD4 < 200, p < 0.001).
Those with nadir CD4 counts below 200 and now on treatment also had
an elevated risk (RR 1.4, p < 0.001).
A similar pattern for
myocardial infarction was observed in treated patients, although the
elevation in risk was marginally greater.
In untreated patients
the only elevation in risk was observed in the stratum of patients
with lowest CD4 counts between 200 and 499. This result may be
explained by duration of infection, since individuals would need to
pass through this stratum in order to reach one of the treated strata
study also found that among HIV-positive patients, age had the
strongest impact on a person's risk of cardiovascular disease, with
individuals aged 65 and over at 12-fold greater risk of a diagnosis
of coronary heart disease than individuals aged 18 to 39, even after
controlling for years since HIV diagnosis. Individuals aged 50 to 64 had
a sixfold greater risk, and 40 to 49 years a 2.5-fold greater risk when
compared to 18 to 39 year olds. Time since HIV diagnosis had no
significant impact on risk, and even smoking had a modest impact on
risk in comparison to age (RR 1.9, p < 0.001).
Although the authors
caution that the results may be less generalisable to women and
ethnic minorities, and note that they could not control for family
history of heart disease, they note that their findings support
earlier initiation of antiretroviral treatment.