Traditional risk factors strongest predictors of sub-clinical cardiovascular disease in people about to start HIV therapy

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 function.

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 significant.

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 ART.”

Stein JH et al. Ultrasonographic measures of cardiovascular disease risk in antiretroviral treatment-naive individuals with HIV infection. AIDS 26, online edition. DOI: 0. 1097/QAD.0b013e32835ce27e, 2012.