Background: While the association between impaired kidney function and cardiovascular disease (CVD) is well established in the general population, this association remains poorly elucidated in HIV-positive individuals. As prior studies in HIV have focused on unconfirmed measures of kidney function, which are subject to random variation and acute illness, the influence of sustained kidney impairment is less clear.
Methods: D:A:D study participants with >2 eGFRs (Cockcroft Gault) measured after 1/1/2004 were followed until the earliest of CVD, last visit plus 6 months or 1/2/2013. CVD was defined as centrally validated (fatal and non-fatal) myocardial infarction, stroke, angioplasty, bypass, or carotid endarterectomy. Poisson regression stratified according to confirmed current eGFR level was used to model the incidence rate ratios of CVD, while adjusting for demographics, antiretroviral treatment, traditional HIV, cardiovascular and renal risk factors.
Results: During a median follow-up of 6.3 years (IQR 4.1-7.9) 1,033 of 34,793 included persons developed CVD (incidence 5.1/1000 PYFU [95% CI 4.8-5.4]). Those included were predominantly Caucasian (48%), male (74%), had homosexual HIV transmission (46%), a median age of 41 years (IQR 35-48), CD4 count of 440 cells/mm3 (IQR 290-623) and a median time between eGFRs of 3.8 months (IQR 2.8-5.7). There was a clear relationship between confirmed eGFR at baseline and incident CVD with 1.7% [95% CI 1.5-1.9] estimated to have progressed to CVD at 5 years among those with eGFR >90 ml/min/1.73m2, increasing to 23.4% [95% CI 6.9-39.8%] among those with eGFR <30 ml/min/1.73m2. The strong relationship between a low confirmed current eGFR and CVD in unadjusted analyses was primarily explained by increasing age in adjusted analyses, although a strong trend for increased CVD rates with decreasing eGFR levels remained, largely driven by high rates in those with eGFR <30 ml/min/1.73m2 (figure). This finding was consistent in different age groups (p=0.43, test for interaction). Analyses were consistent after accounting for death as a competing risk for CVD.
Conclusions: In a large contemporary cohort of HIV-positive individuals we observed a strong relation between confirmed impaired kidney function and incident CVD. This finding highlights the need for an intensified monitoring for emerging CVD, in particular in older individuals with continuously low eGFR levels, and an increased focus on renal preventive measures.