Ten years after becoming infected with HIV, a person living
with HIV has approximately twice the risk of heart attack compared to
someone who has just acquired HIV, regardless of the age at which they seroconvert,
and after taking into account the effects of ageing, an analysis of 18,468 people living with HIV has shown.
The findings were presented at the 15th European
AIDS Conference in Barcelona last week.
The duration of HIV infection was one of the strongest
predictors of heart attack, and it did not matter whether a person had a fully
suppressed viral load or very high viral load. Severe
immune suppression did raise the risk however. Having a current CD4 cell count
below 100 was associated with an approximate four-fold increase in risk
compared with having a CD4 cell count above 100.
The study was designed to determine which factors are most
strongly linked with a raised risk of heart attack in people living with HIV,
and specifically, how HIV infection might contribute to the risk of heart
attack. Previous analyses of the Data
Collection on Adverse events of Anti-HIV Drugs (D:A:D) cohort, established in order to analyse
the long-term effects of antiretroviral therapy, have suggested that several
antiretroviral drugs are associated with an increased risk of heart attack,
including abacavir (Ziagen, also in Kivexa), indinavir (Crixivan) and lopinavir/ritonavir (Kaletra).
The most
recent report from the D:A:D cohort continues to show an
association between the nucleoside analogue abacavir and a raised risk of heart
attack. A meta-analysis
of 23 studies carried out before 2010 found that both HIV infection
and exposure to antiretroviral therapy were associated with an increased risk
of heart attack. This meta-analysis found that a greater duration of treatment
with protease inhibitors, especially lopinavir/ritonavir modestly increased the
risk of heart attack, as did current abacavir treatment.
Although that meta-analysis found an association between HIV
infection and a risk of heart attack, it didn’t examine duration of infection,
immune suppression, HIV viremia or other factors that have been proposed as
possible contributors to a raised risk of heart attack. All these factors might
contribute to the burden of inflammation.
Uncontrolled HIV replication causes inflammation, and even
when viral load is fully suppressed on treatment, some studies have found
evidence of chronic low-level inflammation. Inflammatory chemicals seem to
contribute to the process of atherosclerosis – the hardening and narrowing of
arteries – that leads up to a heart attack.
The analysis presented
at the European AIDS Conference, by Alexandra Lyons of University College
London, looked at the association between heart attack and the duration of HIV
infection; latest CD4 count and HIV viral load (VL); nadir (lowest-ever) CD4
count; duration of immune-suppression below a CD4 count of 200 cells/mm3, and
prior AIDS diagnosis.
The study analysed data from eight cohorts comprising
18,468 people living with HIV in Europe and North America as part of the
CASCADE collaboration in EuroCoord, a network which pools data on HIV in order
to answer questions about patient outcomes. 80% of participants were male, with
a median age of 32 years at the time of infection (interquartile range 26-39).
The eight cohorts accumulated a total of 128,249 person-years
(PY) of follow-up on 18,468 people. During this follow-up period a total of 116
people had a heart attack.
An important limitation of this study is that owing to the
quality of record-keeping by physicians, it was not possible to distinguish
between a first and subsequent heart attack. People who have had a first attack
are at higher risk of a subsequent heart attack regardless of any other risk
factors, and the inclusion of these cases may have biased the results somewhat.
After adjusting for the effects of age, and exposure to
indinavir, lopinavir/ritonavir or current abacavir use, the analysis showed a
substantial increase in the risk of heart attack for every ten- year duration
of HIV infection.
The rate of heart attack increased with duration of
infection, from 0.43 per 1000 person-years in people infected for five years or
less, to 0.86 per 1000 person-years in those infected for five to ten years,
1.06 per 1000 person-years in those infected for ten to fifteen years and 2.65
per 1000 person years of follow-up in those infected for more than 15
years.
To put these figures into everyday terms, in a clinic with
1000 patients who had all been living with HIV for at least 15 years, two
to three patients could be expected to have a heart attack each year. This rate
is in fact fairly low in comparison with some other studies of heart attack
risk, and Alexandra Lyons said that it was possible that heart attacks had been
under-reported.
The analysis also found that people with current CD4 counts
below 100 had a much greater rate of heart attack (4.52 per 1000 person-years)
compared to those with higher CD4 cell counts.
Multivariable analysis showed that after adjusting for age,
antiretroviral treatment exposure and current and nadir CD4 cell count, each
ten years of HIV infection had a similar impact to ten years of ageing on heart
attack risk. In other words, a person living with HIV aged 40, infected with
HIV for ten years, might have a similar risk of heart attack to a person
without HIV aged 50.
She concluded that guidelines for cardiovascular risk
management in people living with HIV may need to consider duration of HIV
infection as an independent risk factor, and that particular emphasis needs to
be placed on addressing risk factors like diet, smoking and exercise in people
who have been infected with HIV for a long time, regardless of their age.