People with HIV have a high incidence of peripheral artery disease, a signal of future cardiovascular disease and circulation problems, a Danish study published in the journal AIDS has found. Diabetes and a low CD4 count each raised the risk of ‘silent’ peripheral artery disease that could lead to more serious problems in later life.
Peripheral artery disease can become a chronic problem in older people, leading to leg pain, poor circulation and ulcers on the legs that are difficult to heal. Peripheral artery disease can lead to weakness in the legs and reduced mobility. It is also a strong signal that you are at increased risk of a heart attack or stroke. Even sub-clinical peripheral artery disease, where the symptoms are not noticeable, is associated with a doubling of the risk of a cardiovascular event.
Early symptoms include cramping pains in the calves when exercising (claudication) and a heavy feeling in the legs.
Peripheral artery disease is diagnosed by measuring the blood flow in the legs, using a blood pressure cuff to measure flow at the ankle. Blood pressure at the ankle – the ankle-brachial index or ABI - should be at least 90% of the pressure measured in the arm. Pressure any lower than this indicates that peripheral artery disease is probably present.
In the general population, the major risk factors are older age, smoking and diabetes.
Danish researchers investigated the incidence of the condition in people with HIV to see whether people with HIV are at higher risk than others, whether risk factors differ and if the condition is occurring at a younger age in people with HIV.
They studied these questions in the Copenhagen Comorbidity in HIV Infection cohort, a prospective cohort study set up to monitor non-HIV comorbidities in people with HIV. Participants were recruited in 2015 and 2016 and attended follow-up visits two years later. Participants were included in this analysis if they had a normal ABI measurement at baseline and a follow-up measurement two years later.
The study included 844 people with a median age of 50, 86% male, almost all on antiretroviral treatment and 95% with undetectable viral load. Just over one in four were current smokers (26%) and 35% were former smokers. Forty percent had high blood pressure, 45% had raised cholesterol, 34% were overweight and 10% were obese.
The median baseline CD4 count was 667, 7% had a CD4 count below 350 and 15% had a history of an AIDS-defining condition. Participants had been living with HIV for a median of 13 years and taking antiretroviral treatment for a median of ten years.
The study measured the incidence of clinical and sub-clinical peripheral artery disease during the follow-up period.
In this study a clinical case was defined as an ABI below 90 and pain in the calves on walking that required a break from walking and pain relief. A sub-clinical case was defined as an ABI below 90 without symptoms.
During a median follow-up period of 2.3 years, 30 participants (3.6%) developed peripheral artery disease, all without symptoms.
"Even peripheral artery disease without symptoms is associated with a doubling of the risk of a cardiovascular event."
In a multivariable analysis which adjusted for age, sex and smoking history, a new diagnosis of peripheral artery disease was associated with diabetes (relative risk 4.90, p = 0.001), a CD4 count below 350 at study entry (RR 2.66, p=0.038) and higher concentrations of the inflammatory markers hsCRP (RR 1.30 per doubling in level, p=0.011) and IL-6 (1.32 per doubling, p=0.047).
The analysis also found a trend towards higher risk of disease with each decade of antiretroviral treatment. After adjusting for duration of HIV infection, each decade of antiretroviral treatment was associated with a threefold increase in risk (RR 3.40, p=0.058), but this finding was of borderline statistical significance. No specific antiretroviral drugs showed an association with developing peripheral artery disease.
The study authors say that the two-year incidence is high compared to studies in the general population and higher than the incidence reported in people with HIV in the US Veterans Ageing Cohort Study (2%). However, those studies did not test ABI systematically or look for asymptomatic disease.
But reinforcing their findings, they note that the baseline prevalence of peripheral artery disease in this cohort was approximately twice as high in people with HIV (12%) as in age- and sex-matched general population controls (6%). Further studies are needed with HIV-negative controls to clarify the contribution of HIV-related risk factors, especially inflammation. Although the prevalence of traditional risk factors was high in this cohort, these factors did not prove significant in this analysis, with the exception of diabetes. But the investigators say that smoking cessation counselling should nevertheless be prioritised.
Suarez-Zdunek M et al. High incidence of subclinical peripheral artery disease in people with HIV. AIDS, published online, 24 May 2022.