Disclosures: The authors report no relevant financial disclosures.
December 17, 2020
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Relationship of HIV severity, endothelial function may predict additional CVD risk

Disclosures: The authors report no relevant financial disclosures.
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The relationship between HIV and arterial endothelial function may imply CVD risk among infected patients, particularly if they also have kidney disease, according to a study published in Arteriosclerosis, Thrombosis, and Vascular Biology.

“People living with HIV infection have endothelial dysfunction, suggesting that HIV infection increases CV risk beyond associated risk factors,” James H. Stein, MD, Robert Turell Professor in Cardiovascular Research, vice chair for faculty development, department of medicine at the University of Wisconsin School of Medicine and Public Health in Madison, told Healio. “The effect of HIV-positive serostatus on endothelial function is influenced by even mild reductions in kidney function, which had a greater effect in people living with HIV infection than in people without HIV disease. These findings suggest that endothelial function related to even mild kidney disease may play a role in HIV-associated CVD risk.”

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Utilizing participant-level data from nine studies of 2,533 patients (986 with HIV [mean age, 44 years]; 1,547 without HIV [mean age, 43 years]), researchers evaluated the impact of HIV serostatus, disease severity and CVD risk factors on endothelial function. Brachial artery flow-mediated dilation was measured using a standardized ultrasound imaging protocol with central reading.

HIV, risk factors and endothelial function

The effect of HIV serostatus on flow-mediated dilation was not statistically significant, even after adjustment (beta = 0.22; P = .558).

Researchers observed that larger brachial artery diameter, age, female sex and lower BMI were the strongest factors associated with flow-mediated dilation (P for all < .0001).

After adjusting for creatinine levels, HIV-positive serostatus was associated with lower flow-mediated dilation (beta = 0.89%; 95% CI, 1.61 to 0.17; P = .015) and the association remained strong even after adjustment for use of antihypertensive, lipid-lowering and anti-glycemic drugs, lipoprotein particle sizes and interleukin-6 levels.

According to the study, subsequent adjustment with the addition of C-reactive protein level further strengthened the association between HIV positivity with lower flow-mediated dilation (beta = 1.2%; 95% CI, 1.85 to 0.55; P < .0001).

“Identifying the contributors to CVD in people living with HIV infection has been challenging because the HIV epidemic has evolved over the past 30 years in ways that affect CVD risk,” Stein said in an interview. “Today, people living with HIV infection are diagnosed younger, treated earlier, use antiretroviral therapies regimens with less metabolic toxicities, live longer and to older ages, use more lipid-lowering medications and have a lower prevalence of cigarette smoking.”

Kidney function, HIV and endothelial function

According to the study, creatinine levels were higher among patients living with HIV compared with HIV-negative participants (P < .001), and the inverse association between creatinine level and flow-mediated dilation was greater among patients living with HIV (r = 0.14) compared with those without it (r = 0.05).

“We expected that the risk of HIV on cardiovascular disease would differ by age, markers of HIV disease severity and use of antiretroviral therapies,” Stein told Healio. “We were surprised that the effect of HIV infection and kidney disease on arterial function was not modified by those factors.”

In analyses that included HIV serostatus, age, race and creatinine, researchers found that only HIV serostatus (beta = 1.25; P = .001) and creatinine (beta = 0.72; P = .024) were independently associated with flow-mediated dilation.

In addition, the association of creatinine and HIV-positive serostatus with flow-mediated dilation in the highest tertile of creatinine was strong and relatively unaffected by subsequent adjustment (1 mg/dL; beta = 1.59%; 95% CI, 2.58 to 0.6; P = .002).

“What is it about kidney disease that increases CVD risk, especially in people living with HIV infection?” Stein said about remaining areas for further research. “Is the relationship between HIV infection, CVD and kidney disease affected by antiretroviral therapy?”

For more information:

James H. Stein, MD, can be reached at jhs@medicine.wisc.edu.