Kidney Impairment Linked to Higher Risk of Cardiovascular Events in People with HIV

		SUMMARY: HIV positive individuals with signs of impaired kidney function -- including low glomerular filtration rate and protein in the urine -- had a significantly higher risk of cardiovascular events such as heart attacks, even after controlling for other traditional risk factors, according to a study published in the January 28, 2010 issue of AIDS.

By Liz Highleyman

Several observational studies have shown that people with HIV are at higher risk of heart disease, but whether this is due to HIV infection itself, antiretroviral therapy (ART), traditional risk factors such as smoking, or some combination of factors is not fully understood.

Elizabeth George from All India Institute of Medical Sciences in New Delhi and colleagues from Johns Hopkins designed a study to assess the correlation between kidney function and risk of cardiovascular events in HIV positive individuals.

An extensive body of literature demonstrates strong associations between impaired kidney function and cardiovascular events and mortality in HIV negative people, the researchers noted as background. However, many studies of heart problems in people with HIV -- including the large D:A:D and SMART studies -- have not collected extensive data on kidney function.

This case-control study included 315 HIV positive participants in the Johns Hopkins HIV Clinical Cohort, 63 of whom had experienced cardiovascular events and 252 control subjects. The case and control groups were demographically similar (most were men), and had comparable rates of obesity, cigarette smoking, family history of heart disease, and ART use.

However, patients with cardiovascular events had significantly more advanced HIV disease than those without (49% vs 25% with CD4 count < 200 cells/mm3), and were more likely to have diabetes (32% vs 11%), high blood pressure (64% vs 37%), abnormal blood lipids (71% vs 48%), and history of previous cardiovascular events (41% vs 7%).

Kidney function was assessed by estimated glomerular filtration rate (eGFR), calculated using both the Chronic Kidney Disease Epidemiology Collaboration (CKDEC) formula and the Modification of Diet in Renal Disease (MDRD) equation; lower scores indicate poorer function. They also looked at presence of protein in the urine (proteinuria).

Results

	Mean eGFR was significantly lower in patients who experienced cardiovascular events compared with control subjects:
	68.4 vs 103.2 ml/min per 1.73 m2 by CKDEC (P < 0.001); 69.0 vs. 103.1 ml/min per 1.73 m2 by MDRD (P < 0.001).
	In a univariate analysis, eGFR < 60 ml/min per 1.73 m (CKDEC) was associated with a 15.9-fold increase in the risk of cardiovascular events (P < 0.001).
	Mean serum creatinine was also significantly higher in case patients compared with control subjects (2.4 vs 1.1 mg/dL; P < 0.001).
	In a multivariate analysis controlling for other factors, an eGFR decrease of 10 ml/min per 1.73 m2 was associated with a 20% increase in cardiovascular event risk (odds ratio [OR] 1.2).
	Patients who experienced cardiovascular events were approximately twice as likely to have protein in their urine compared with control subjects (51% vs 25%; P < 0.001).
	Proteinuria was associated with increased cardiovascular event risk in both univariate and multivariate analyses (OR 3.6 and 2.2, respectively).
	Participants with both eGFR < 60 ml/min per 1.73 m2 (CKDEC) and proteinuria had a 41-fold increased risk of cardiovascular events compared to those with eGFR 90 ml/min per 1.73 m2 and no proteinuria (OR 41.4; P < 0.001).
	CD4 cell count < 200 cells/mm3 was also a significant predictor of increased cardiovascular risk.
	In the adjusted analysis, the traditional risk factors of diabetes, abnormal blood lipids, and previous cardiovascular events remained significant predictors, but not high blood pressure, obesity, family history, or HIV viral load.

Based on these findings, the study authors wrote, "Our study shows a significant independent association between decreased kidney function and increased risk of cardiovascular events in HIV-1-infected patients."

"In an HIV clinic-based population, decreasing eGFR was associated with a significantly increased risk of cardiovascular events independent of traditional cardiovascular risk factors and HAART," they elaborated in their discussion. "Whereas an eGFR of 60-89 ml/min per 1.73 m2 was associated with a marginally increased risk, which became non-statistically significant after adjustment for other factors, an eGFR of less than 60 ml/min per 1.73 m2 was associated with a significant 5-fold to 6-fold increase in odds of cardiovascular events."

The researchers noted that they found no significant associations between cardiovascular events and use of ART overall, individual antiretroviral drug classes, or abacavir (Ziagen; also in the Epzicom and Trizivir coformulations) or didanosine (ddI; Videx), as seen in some -- but not all -- previous studies.

At the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention this past summer, researchers reported that kidney disease was a confounding factor that might help explain the observed association between use of abacavir and elevated heart attack risk.

"Our study highlights the existence of a strong link between kidney function and cardiovascular disease risk in HIV-infected individuals, an association that is at least as strong, if not stronger, than that reported in the general population," the authors of the present study stated. "This finding is important because the prevalence of kidney disease has been found to be 3-fold to 5-fold higher in HIV-infected than in HIV-negative persons..."

In conclusion, they wrote, "Our findings require further confirmation but suggest the potential value of early screening and treatment of chronic kidney disease in HIV-1-infected patients, particularly those with other cardiovascular risk factors."

All India Institute of Medical Sciences, New Delhi, India; Division of Infectious Diseases, Division of Nephrology & Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Medicine, St. Luke's Roosevelt Hospital Center, New York, NY.

1/29/10

Reference
E George, GM Lucas, GN Nadkarni, and others. Kidney function and the risk of cardiovascular events in HIV-1-infected patients. AIDS 24(3): 387-394 (Abstract). January 28, 2010.