| |
Peripheral artery disease and physical
function in women with and without HIV
|
| |
| |
Download the PDF here
AIDS March 2022
In middle-aged women with and without HIV infection, greater PAD severity is associated with progressively slower gait speed. Early detection of subclinical PAD may decrease the risk of lower extremity functional impairment and its long-term health consequences
From October 2013 through October 2019, 2010 WIHS participants aged older than 40 years underwent ABI measurements. Among the 2010 participants, 1845 also had measured 4 m timed gait speed.
Of clinical concern is that lower extremity functional declines were noted even in those with early and subclinical PAD. Early detection of subclinical PAD using ABI measurements in women at high risk for PAD could have major implications for decreasing the risk of lower extremity functional impairment and its long-term health consequences.
As expected, we found that several vascular risk factors other than PAD were independently associated with lower extremity functional declines including smoking, waist circumference, and history of statin use, which could be a marker of dyslipidemia. These factors may contribute to reduced lower extremity vascular perfusion resulting from atherosclerosis. Being Black and of Hispanic ethnicity have also been associated with slower gait speed in men with and at risk for HIV, and with physical function declines in a general aging population cohort [23,34,35]. These studies have postulated that socioeconomic disparities may be a reason.
When we adjusted for metabolic risk factors, low-normal ABI values and borderline PAD remained independently associated with slower gait speed, suggesting that other unmeasured factors besides traditional cardiovascular risk factors may contribute to the association of subclinical PAD with lower extremity functional declines. PAD has been associated with skeletal muscle damage from ischemia-perfusion injury in microvascular beds, leading to lower calf muscle area and increased calf muscle fat [32]. Future investigation will examine whether factors such as lower extremity muscle volume might explain the association of subclinical PAD with lower extremity functional declines.
Our findings are notable for several reasons. First, we demonstrated that increasing PAD severity was associated with increasing lower extremity functional impairment in women who were relatively young in age. Second, this relationship was observed in those with early, subclinical PAD as measured by low ABI values. While one study also showed that low-normal values of ABI and borderline, mild, moderate, and severe PAD were associated with decreasing rates of mobility, the mean age of adults in that study was older than 70 years [7]. In other population studies among older adults, borderline ABI values have been associated with subclinical atherosclerosis and endothelial dysfunction [7,27].
Results
The 1839 women included in this study were median age 50 years, the majority were Black, and 51% were obese (BMI ≥ 30 kg/m2) (Table 1). Nearly half reported current smoking, approximately 25% had diabetes and 50% had hypertension. Among the women with HIV, the majority had well controlled HIV, with mean CD4+ cell count more than 500 cells/μl and undetectable HIV viral loads. Table 1 shows clinical characteristics by PAD severity. Over one-third had ABI values in the normal range (41%), about one-third had low-normal ABI values (36%), 15% had borderline PAD, 6% had mild PAD, and 1.3% had moderate-severe PAD. Smoking, physical inactivity, higher triglyceride levels, lower median HDL cholesterol and LDL cholesterol levels, statin use, diabetes, hypertension, peripheral neuropathy, and report of symptoms consistent with claudication were more common in women with moderate-severe PAD than those in the other ABI categories.
In multivariable analyses, PAD category was associated with slower gait speed: 6% slower for low-normal ABI (95% CI: 2, 9%), 9% slower for borderline PAD (95% CI: 5, 13%), 12% slower for mild PAD (95% CI: 6, 17%), and 11% slower for moderate-severe PAD (95% CI: -4, 24%), although the association in the latter group did not reach significance. Reporting a history of ART was associated with a 13% faster gait speed (95% CI: 2, 24%). There was little association of CD4+ cell nadir and HIV viral load with gait speed.
In this large cohort of middle-aged US women with and without HIV, we found that increasing PAD severity was associated with progressively slower gait speed, even after adjustment for HIV and HCV status, demographic, behavioral, and metabolic risk factors.
Another study of men and women without HIV infection found that increased physical activity improved ABI values in those with borderline ABI values who underwent a cardiovascular intervention [33]. Future study will evaluate the impact of ABI improvements on physical function. Whether ABI monitoring can be used as a tool for early detection and prevention of lower extremity functional declines in women at high risk for PAD needs further study.
-----------------
Peripheral artery disease (PAD) is common in persons living with HIV (PLWH). We previously reported a PAD prevalence of 7.7% in middle-aged women with and without HIV infection in the United States, on par with prevalence rates in general population studies of women a decade older [1]. These findings are of great clinical concern because PAD is associated with functional decline, decreased quality of life, and greater risk of disability and death [2-14]. Women with PAD may experience faster functional decline and higher prevalence of leg pain than men with PAD [15,16]. Therefore, women with and without HIV infection may experience adverse health consequences of PAD at earlier ages.
Gait speed (or walking speed at 'usual' pace) is a well established marker of lower extremity function and predicts disability and death in older adults without HIV infection [20-22]. The Multicenter AIDS Cohort Study (MACS) found that men living with HIV had earlier and faster declines in gait speed than HIV seronegative men [23]. Another study of mostly men who used injection drugs in Baltimore found an increased risk of poor functional performance including slower gait speed in PLWH compared with seronegative persons [24]. Studies to date have not examined the contribution of PAD to these functional declines among PLWH.
We aimed to examine the association of PAD severity, measured using ABI, with gait speed in a large nationally representative cohort of middle-aged women with and without HIV infection. Women with HIV are an understudied population that may be affected by PAD and functional decline in specific ways that could impact public health and clinical care.
Abstract
Objectives:
Peripheral artery disease (PAD) is associated with decreased physical function and increased mortality in the general population. We previously found that PAD is common in middle-aged women with and without HIV infection, but its association with functional decline is unclear. We examine the contribution of PAD to functional decline in the Women's Interagency HIV Study, controlling for traditional cardiovascular risk factors and HIV-related factors.
Methods:
Analysis included 1839 participants (72% with HIV) with measured ankle-brachial index (ABI) and 4 m gait speed. ABI values categorized PAD severity. Linear models with repeated measures estimated the association of PAD severity with log-transformed gait speed after controlling for demographic, behavioral, and metabolic risk factors, and HIV/hepatitis C virus status.
Results:
Median age was 50 years and more than 70% were Black. Compared with normal ABI, there was a dose-response relationship between increasing PAD severity and slower gait speed in univariable analyses: 6% slower gait speed for low-normal ABI [95% confidence interval (CI): 4-9%], 10% for borderline PAD (95% CI: 6-13%), 14% for mild PAD (95% CI: 9-18%), and 16% for moderate-severe PAD (95% CI: 5-25%). PAD severity remained associated with slower gait speed in multivariable analyses. HIV/hepatitis C virus co-infection was independently associated with 9% (95% CI: 4-14%) slower gait speed compared with those with neither infection. Among women with HIV, neither CD4+ cell count nor HIV-RNA level was associated with gait speed.
Conclusion:
In middle-aged women with and without HIV infection, greater PAD severity is associated with progressively slower gait speed. Early detection of subclinical PAD may decrease the risk of lower extremity functional impairment and its long-term health consequences.
|
|
| |
| |
|
|
|
