Sub-clinical cardiovascular disease in people with HIV is more strongly associated with traditional risk factors for heart disease rather than
inflammation or HIV-related parameters, US research published in the online
edition of AIDS suggests.
The cross-sectional study involved 331
participants who were about to start antiretroviral therapy (ART). Ultrasound
investigations were used to assess arterial structure and function, predictors
of future risk of cardiovascular disease (CVD).
“In a contemporary cohort of HIV-infected
ART-naive individuals without advanced HIV disease, ultrasonographic measures
of CVD risk were more strongly associated with traditional risk factors such as
aging, body size, and lipoprotein measurements, rather than CD4 cell count,
viral replication, inflammatory markers, and cytokines,” write the authors.
They believe their findings are “notable” and “important to the understanding
of CVD risk in contemporary patients with HIV infection.”
HIV infection is associated with an
increased risk of cardiovascular disease. The exact reasons are uncertain, but
they appear to include a combination of factors, including a high prevalence of
smoking and other traditional risks, the inflammatory effects of HIV and the
side-effects of some antiretroviral drugs.
“Given the complex interplay between HIV
infection and treatment on CVD risks factors and CVD risk, understanding the
associations with arterial disease prior to ART initiation is important for
understanding why patients with HIV infection appear to at increased CVD risk
compared to HIV-negative individuals,” explain the investigators.
They therefore designed a study involving
participants who were about to start HIV therapy. As part of their baseline
investigations they had ultrasounds monitoring carotid artery intima-media
thickness (CIMT) and flow-mediated vasodilation (FMD) in the brachial artery.
The investigators then conducted a series
of analyses to see if arterial structure and function were related to
traditional risk factors of cardiovascular disease (smoking, body composition,
lipid levels, Framingham risk score), markers of inflammation, or HIV-related
parameters (viral load and CD4 cell count).
Most (89%) of the participants were male, 44%
were white and the median age was 36 years.
Approximately a quarter had been diagnosed
with AIDS, median CD4 cell count was 349 cells/mm3 and median viral
load was in the region of 32,000 copies/ml.
None of the participants had a history of cardiovascular
disease or diabetes. Smoking (current or former) was reported by 60% of
participants. Median HDL cholesterol was mildly low at 38 mg/dl, but otherwise the
prevalence of traditional cardiovascular risk factors was typical of that
expected for a relatively young and healthy population. The median Framingham
risk score was just 1%, and only 13% were assessed as having a moderate to high
ten-year risk of cardiovascular disease.
Ultrasound examinations showed that
traditional risk factors were most strongly associated with arterial health and
Thickening of the carotid artery was
associated with older age, a median/high Framingham risk score, lipid levels,
longer history of smoking, body composition, poorer kidney function and the
presence of metabolic syndrome. There was also some evidence that a lower viral load was associated with
thickening of the carotid artery, as was an AIDS diagnosis and longer duration
of infection with HIV. However, there was no association with CD4 cell count.
After controlling for potential
confounders, older age (p < 0.001), increasing body weight (p < 0.001),
non-Hispanic race (p= 0.049) and LDL cholesterol (p = 0.001) remained
Lesions in the carotid artery were detected
in 8% of participants. The investigators’ preliminary analysis showed that these
were associated with older age, higher blood pressure, metabolic syndrome,
lipid levels, body composition, higher levels of the inflammatory marker IL-6
and a lower viral load.
In the adjusted analysis, age (p < 0.001),
metabolic syndrome (p < 0.001), lower viral load (p = 0.03) and IL-6 levels
(p = 0.006) all remained significant.
Higher blood flow through the brachial
artery (FMD), indicative of a lower risk of cardiovascular disease, was
associated with younger age, a lower Framingham risk score, diameter of the
brachial artery, weight, higher levels of IL-6 and higher viral load. A smaller
brachial artery diameter remained significant (p < 0.001) after controlling for
potential confounders, as did Framingham risk score (p = 0.035).
The investigators explored the factors
associated with brachial artery diameter in more detail. In their first
analysis, larger diameter – indicative of an increased risk of cardiovascular
disease – was associated with older age, male sex, body composition, lipid
levels, Framingham score, blood pressure and kidney function. Surprisingly, a
higher CD4 cell count was also a risk factor, as was a lower viral load.
In the multivariate analysis that
controlled for confounders, older age (p < 0.001), increasing weight (p <
0.001), male sex (p <0 .001), fasting
glucose (p = 0.004) and lower viral load (p = 0.006) remained significant.
The authors believe their findings show the
importance of encouraging HIV-positive people to make lifestyle changes, such
as eating a healthy diet, exercising regularly, and stopping smoking, to lower
their risk of cardiovascular disease. “By identifying that modifiable risk
factors such as increased body size and lipoprotein measures are major
associates of increased CIMT, carotid artery lesions and impaired FMD, these
parameters can be targeted for early preventative lifestyle and if necessary
pharmacological interventions to reduce future CVD risk in patients initiating