Genetic background has a major impact on
the risk of coronary artery disease for people with HIV, results of a large
study published in the online edition of Clinical
Infectious Diseases show. An unfavourable genetic background increased the
risk of coronary artery disease more than some traditional risk factors such as
high cholesterol. Treatment with certain antiretroviral drugs
including abacavir (Ziagen, also in Kivexa) and lopinavir/ritonavir (Kaletra) also increased the risk.
“Genetic background explained a larger
proportion of CAD [coronary artery disease] variability than did diabetes,
hypertension or dyslipidemia,” comment the authors. “An unfavorable genetic
background had an effect on CAD comparable to certain antiretroviral agents
known to increase cardiovascular risk.”
The investigators believe their findings
are of clinical significance, and that genetic screening could help identify
HIV-positive people with an especially high risk of heart disease.
There is now convincing evidence that
HIV infection is associated with an increased risk of coronary artery disease.
The precise reasons for this are uncertain. However, traditional risk factors,
the inflammatory effects of untreated HIV, immune suppression and the
side-effects of some antiretroviral drugs all seem to be significant.
The importance of genetic background to the
risk of coronary artery disease in the context of HIV infection is, however,
An international team of investigators
therefore designed a study involving 1875 HIV-positive people enrolled in 24
separate observational studies in Europe, the US, Australia and Argentina.
Participants were screened for 23 common single nucleotide polymorphisms (SNPs) known
to be associated with an increased risk of coronary artery disease in the
general population. The impact of genetic factors on the risk of coronary heart
disease was assessed and compared to the contribution of other known risk
The investigators believe their study
“represents the most comprehensive genetics-CAD study undertaken in HIV-positive
The participants received care between 2000 and
2009 and a total of 571 individuals experienced a coronary artery disease
event. These people provided cases and the remaining participants were classified
The patients experiencing cardiovascular
events were older than the controls (50 vs 45), and more likely to be current or
past smokers (77 vs 69%), to have elevated cholesterol (46 vs 32%), to have diabetes
(19 vs 14%), to have a family history of coronary artery disease (28 vs 15%)
and to be taking antiretroviral therapy that included abacavir (26 vs 18%).
The investigators divided the participants into
four groups (quartiles) according to their number of SNPs associated with
coronary artery disease risk. Individuals experiencing a cardiovascular event
were significantly more likely to be in the third and fourth quartiles (i.e.,
greater number of SNPs) than the controls (p = 0.01).
Individuals with the highest number of
high-risk SNPs (quartile four) were approximately 50% more likely (p = 0.02) to
have experienced a coronary artery event than participants with the fewest
high-risk SNPs (quartile one).
The risk of coronary artery disease
associated with genetic factors exceeded that associated with hypertension and
therapy with abacavir or lopinavir.
The investigators then conducted an
analysis to determine the precise contribution of specific factors to the risk
of coronary artery disease among their patients.
Age made the single biggest contribution,
accounting for 7.5% of risk, followed by current smoking (3.1%), family history
(1.9%) and genetic score (0.9%).
However, genetic score made a larger
contribution to overall risk of coronary disease than some traditional and
HIV-related risk factors, including elevated cholesterol (0.7%), diabetes
(0.5%), hypertension (0.5%), current therapy with abacavir (0.5%) and long-term
treatment with lopinavir (0.5%).
Adjustment for family history did not
affect the association between genetic profile and risk of coronary artery
“Our findings suggest that genetic testing
may provide prognostic information complementary to that afforded by family
history, traditional risk factors, and antiretroviral regimen,” comment the
investigators. “Particularly in high risk patients, knowledge of a deleterious
genetic CAD predisposition might further emphasize the rationale for aggressive
risk factor modulation and selection of a CAD-neutral antiretroviral regimen to
achieve HIV control.”