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Nadir CD4 Count Under 350 Predicts Arterial Stiffness in Case-Control Study
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
from Priscila Hsue also presented at CROI in a poster that worse levels of inflammation predicted arterial stiffness more than traditional risk factors in a separate study. Robert Kaplan reported in a study that activation & senescence in a WIHS analysis predicted premature onset of CVD CROI:
T-cell Senescence and T-cell Activation Predict Carotid Atherosclerosis in HIV-infected Women - (02/22/10) and in an oral Hsue reported that elite controllers with or without viremiahave more rapid IMT progression compared to HIB-uninfected controls
- - CROI: Rapid Progression of Atherosclerosis at the Carotid Bifurcation Is Linked to Inflammation in HIV-infected Patients -
"These data strongly suggest that inflammation contributes to the higher risk of atherosclerosis noted in HIV-infected persons." - (02/22/10).
In addition it was reported inflammation was increased in HIV+ individuals, even when viral load is undetectable, and associated with increased CVD risk.
Mark Mascolini
- Hsue and colleagues believe their findings "suggest that cardiovascular risk among HIV-infected individuals could be reduced through early initiation of antiretroviral therapy, before CD4 T-cell counts are depressed." They called for prospective studies to test this hypothesis. -
A nadir (lowest-ever) CD4 count, as well as traditional cardiovascular risk factors, independently predicted greater arterial stiffness, a signal of cardiovascular disease, in a cross-sectional study of 80 people with an undetectable viral load while taking antiretrovirals [1].
Priscilla Hsue and colleagues at the University of California, San Francisco (UCSF) compared people from two cohorts--the SCOPE cohort, in which people start antiretrovirals during chronic infection, and the OPTIONS study, in which people start treatment within 6 months of HIV infection. The investigators measured arterial stiffness noninvasively to assess augmentation index and carotid-femoral pulse wave velocity. A single observer performed all measurements. In the general population, arterial stiffness is associated with atherosclerotic disease and the risk of cardiovascular disease [2-4]. An earlier study by other investigators found worse arterial stiffness in people with untreated HIV infection than in people without HIV [5].
The UCSF study involved 65 people with a nadir CD4 count below 350 and 15 with a nadir above 350. The median nadir was 85 (interquartile range [IQR] 14 to 216) in the first group and 494 (IQR 400 to 540) in the second (P < 0.001). Current CD4 count was also significantly lower in the first group (median 459, IQR 316 to 621) than in the second (785, IQR 684 to 1190) (P < 0.001). The sub-350 group was older (median 48 versus 44 years, P = 0.06). The group with a low nadir also differed significantly from the other group in HIV duration (median 17 versus 6 years, P < 0.00) and tended to have a longer duration of protease inhibitor (PI) therapy (median 4 versus 2 years, P = 0.07), higher diastolic blood pressure (median 72 versus 70 mm Hg, P = 0.07), and faster heart rate (median 65 versus 59 beats per minute, P = 0.09).
In measures of arterial stiffness, augmentation index was significantly higher (worse) in people with a nadir under 350 (median 20% versus 11% in the comparison group, P = 0.008), as was augmentation index normalized for a heart rate of 75 beats per minute (median 17% versus 4%, P < 0.001). Time to return of the reflected wave was significantly lower in the sub-350 nadir group (148 versus 158 msec, P = 0.02), and carotid-femoral pulse wave velocity was worse in low-nadir group (5.5 versus 5.0 m/s, P = 0.009).
To identify risk factors for augmentation index normalized for a heart rate of 75, Hsue and colleagues devised a multivariate model that weighed systolic blood pressure, diabetes mellitus, hyperlipidemia, family history of heart disease, injection drug use, high-sensitivity C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), current CD4 count, and duration of HIV infection, antiretroviral therapy, and PI therapy. In that model a nadir CD4 count below 350 was independently associated with 7.2% higher normalized augmentation index, and four traditional risk factors were also independently associated with a higher normalized augmentation index:
· Age: 3.8% higher, 95% confidence interval [CI] 2.0 to 5.6, P < 0.001
· Diastolic blood pressure: 2.9% higher, 95% CI 1.1 to 4.7, P = 0.002
· Hypertension: 4.7% higher, 95% CI 1.9 to 8.5, P = 0.02
· Tobacco use, ever: 4.7% higher, 95% CI 1.2 to 8.1, P = 0.009
· Nadir CD4 below 350: 7.2% higher, 95% CI 2.6 to 11.8, P = 0.002
A model to identify predictors of pulse wave velocity considered hyperlipidemia, hypertension, cigarette smoking, family history of cardiovascular disease, injection drug use, current CD4 count, hsCRP, eGFR, and duration of HIV infection, antiretroviral therapy, and PI therapy. In this analysis, a CD4 nadir below 350 was independently associated with a 0.58 m/s increase in pulse wave velocity, while four traditional risk factors also had independent associations:
· Age: 0.48 m/s increase, 95% CI 0.26 to 0.70, P < 0.001
· Systolic blood pressure: 0.44 m/s increase, 95% CI 0.12 to 0.76, P = 0.007
· Diastolic blood pressure: 0.29 m/s decrease, 95% CI -0.53 to -0.04, P = 0.03
· Diabetes mellitus: 2.38 m/s increase, 95% CI 1.38 to 3.38, P < 0.001
· Nadir CD4 below 350: 0.58 m/s increase, 95% CI 0.15 to 1.01, P = 0.008
Hsue and colleagues believe their findings "suggest that cardiovascular risk among HIV-infected individuals could be reduced through early initiation of antiretroviral therapy, before CD4 T-cell counts are depressed." They called for prospective studies to test this hypothesis.
Full poster report:
CROI: Early Initiation of Antiretroviral Therapy in HIV-Infected Individuals Is Associated with Reduced Arterial Stiffness: a low nadir CD4+ T-cell counts are associated with arterial stiffness as assessed by Aix and PWV - (02/26/10)
References
1. Ho J, Deeks S, Hecht F, et al. Earlier initiation of ART in HIV-infected individuals is associated with reduced arterial stiffness. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 707.
2. Nair N, Oka RK, Waring LD, et al. Vascular compliance versus flow-mediated vasodilation: correlation with cardiovascular risk factors. Vasc Med. 2005;10:275-283.
3. Duprez D, Cohen J. Arterial stiffness as a risk factor for coronary atherosclerosis. Curr Atheroscler Rep. 2007;9:139-144.
4. Grey E, Bratteli C, Glasser SP, et al. Reduced small artery but not large artery elasticity is an independent risk marker for cardiovascular events. Am J Hypertens. 2003;16:265-269.
5. Baker JV, Duprez D, Rapkin J, et al. Untreated HIV infection and large and small artery elasticity. J Acquir Immune Defic Syndr. 2009;52:25-31.
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