Peripheral artery disease more common with lower CD4 counts

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Peripheral artery disease occurs more frequently in people with HIV who have CD4 cell counts below 500, regardless of whether they smoke or have other risk factors for cardiovascular disease, a large US analysis found. Peripheral artery disease, one of the most common forms of cardiovascular disease, occurs more frequently in people with HIV who have CD4 cell counts below 500, regardless of whether they smoke or have other risk factors for cardiovascular disease, an analysis of the large US Veterans Aging Cohort Study has shown. The findings were presented by Matthew Freiberg of Vanderbilt University Medical Centre, Nashville, at the 9th International AIDS Society Conference on HIV Science (IAS 2017) in Paris last month.

Peripheral artery disease is the second most common form of cardiovascular disease after coronary artery disease. Arteries in the lower limbs or supplying major organs become narrowed as a result of deposits of cholesterol. Blood supply to the limbs is reduced, leading to cramping or pain in the leg and hip muscles during activity. As peripheral artery disease progresses, pain may become more persistent. In its most advanced form, peripheral artery disease can lead to tissue damage and gangrene in the limbs, possibly requiring amputation.

Numbness in the limbs, sores on the legs or feet, pale or blue skin on the legs or hair loss on the legs and feet are also symptoms of peripheral artery disease. The condition is more common in men and may progress for a long time without symptoms. Peripheral artery disease can be diagnosed by comparing the blood pressure at the ankle and the arm; lower blood pressure at the ankle, caused by a restricted blood supply, indicates peripheral artery disease.

People who develop peripheral artery disease are at high risk for a stroke or heart attack. Peripheral artery disease is already present in around one in twenty people in the 45-50 age group and the risk increases with age and in people with other risk factors for cardiovascular disease, especially smoking or diabetes.

Stopping smoking and taking regular exercise can improve the condition, as can reduction of cholesterol, blood sugar and blood pressure through lifestyle and dietary changes and medication.

To determine whether HIV infection is a risk factor for peripheral artery disease, researchers from the Veterans Aging Cohort Study (VACS) looked at the incidence of peripheral artery disease in over 90,000 participants in VACS from January 2003 to September 2012. VACS consists of US military veterans receiving care through the Veterans Health Administration; it follows the health of people living with HIV with a control group of HIV-negative people matched by age, race and sex.

This analysis included 29,291 people with HIV and 62,996 controls. Approximately 97% were male, the median age was 48 years, 48% of participants were African American, 38% were white and 7% were Hispanic. Risk factors for cardiovascular disease were common in both groups; 50% of people with HIV and 63% of HIV-negative controls had hypertension, 9% of people with HIV and 13% of the control group had diabetes and over half of each group smoked (56% and 50%).

In the HIV-positive population, the median CD4 cell count was 383 cells/mm3 at baseline and 56% were not taking antiretroviral treatment at the beginning of the follow-up period.

After adjusting for age, sex, race and cardiovascular risk factors including LDL cholesterol, triglycerides, diabetes, smoking, hypertension, obesity, impaired kidney function, hepatitis C infection, and alcohol or cocaine abuse, the investigators found an increased risk of peripheral artery disease in people with HIV with CD4 cell counts below 500 cells/mm3.

The risk of peripheral artery disease was 24% higher in people with CD4 counts in the range 200-499 cells/mm3 (hazard ratio 1.24, 95% CI 1.14-1.35, p < 0.001) and 73% higher in people with CD4 cell counts below 200 cells/mm3 (HR 1.72, 95% CI 1.53-1.91, p < 0.001) when compared to HIV-negative people but was not significantly higher than the control group in people with HIV who had CD4 cell counts above 500 cells/mm3. In this analysis the risk of peripheral artery disease was calculated using the most recent CD4 measurement prior to the diagnosis of peripheral artery disease.

The relationship between lower CD4 cell count and increased risk of peripheral artery disease persisted after adjusting for the absence of detectable viral load (which would indicate the use of effective antiretroviral treatment).

If people developed peripheral artery disease, their subsequent survival was strongly associated with their CD4 cell count at the time of diagnosis of peripheral artery disease. Four years after diagnosis, less than half of people with a CD4 cell count below 200 cells/mm3 at the time of diagnosis of peripheral artery disease were still alive compared to around three-quarters of those with CD4 cell counts above 500 at the time of their diagnosis.

The authors concluded that among a population of HIV-positive military veterans with a high prevalence of risk factors for cardiovascular disease, immunodeficiency – a CD4 cell count below 500 cells/mm3 – or a detectable viral load each raised the risk of developing peripheral artery disease and of dying after a diagnosis of peripheral artery disease.

Abstract
Background: Peripheral arterial disease (PAD) affects ~8 to 10 million U.S. adults annually and is the second most common clinical manifestation of atherosclerosis after acute myocardial infarction (AMI). While the increased risk of AMI and ischemic stroke among HIV infected (HIV+) compared to uninfected people is well documented, data linking HIV to incident PAD events are sparse. We, therefore, compared PAD risk among HIV+ and uninfected veterans.
Methods: We analyzed data on 91,457 veterans (33% HIV+) without prevalent cardiovascular disease from the Veterans Aging Cohort Study (VACS). VACS is an observational, longitudinal cohort of HIV+ veterans matched 1:2 with uninfected veterans on age, gender, race/ethnicity, and clinical site. Participants were followed from their first clinical encounter on or after 4/1/2003 until a PAD event, death, their last follow-up date, or 9/30/2012. We used ICD-9 and CPT codes to identify participants with incident PAD. Cox proportional hazard regression models were utilized to assess the association between HIV, CD4+ T cell count, and PAD adjusting for atherosclerotic risk factors (Table). Finally, we constructed cumulative incidence curves to examine PAD risk stratified by HIV status and CD4 + T cell count.
Results: During a median follow-up of 7 years, there were 5091 PAD events. See Table and Figure for rates and risk of PAD stratified by HIV status and CD4+ T cell count.
Conclusions: Conclusions and Relevance: HIV+ veterans have a significantly higher risk of PAD than uninfected veterans.

Authors
M Freiberg, M Duncan, A Justice, J Beckman

Aidsmap material
IAS 2017 abstract


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