Poor kidney function associated with increased cardiovascular risk for people with HIV

Renal impairment is associated with an increased risk of cardiovascular disease (CVD) in HIV-positive individuals, according to data from a large observational cohort study published in the online edition of the Journal of Infectious Diseases.

Within five years of follow-up, over a fifth of people with severely impaired kidney function developed cardiovascular disease compared to less than 2% of individuals with competent kidney function. Even after taking into account age and the side-effects of antiretroviral drugs, severely impaired kidney function remained associated with cardiovascular disease, increasing rates between 30 and 40%.

“In this large heterogeneous cohort of HIV-positive individuals we found a strong association between centrally adjudicated CVD events and advanced levels of renal impairment,” write the authors. “The high rates of CVD observed in older individuals with mild to moderate renal impairment highlight the need for intensified monitoring and search for effective prophylactic measures for impaired renal function and CVD in the ageing HIV-population.”

The relationship between impaired renal function and cardiovascular disease is well established in the general population. However, studies examining the relationship between kidney and cardiovascular disease in people living with HIV have tended to be small, and the relationship between estimated glomerular filtration rate (eGFR) – a key marker of renal function – and cardiovascular disease has been little explored.

To remedy this knowledge gap, investigators from the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study, designed a substudy to determine the relationship between renal function measured by eGFR and cardiovascular disease. The D:A:D study involves eleven large observational cohorts in America, Europe and Australia.

People who had at least two eGFR measurements between 2004 and 2015 were eligible for inclusion. Cardiovascular disease was defined as validated heart attack, stroke, invasive cardiovascular procedures or sudden cardiac death.

The study population comprised 35,357 individuals. They were predominately white (48%), male (74%) and the median age at baseline was 41 years.

There was a reasonably high prevalence of cardiovascular risk factors: 42% were smokers, 4% had diabetes, 9% hypertension and a little under 1% had experienced a previous cardiovascular event. Median baseline overall five year risk of chronic kidney disease was just 0.3%, and median risk of a cardiovascular event was 2%.

There was a clear relationship at baseline between age and renal function. Of the participants aged younger than 40 years, 87% (n = 13,660) had normal (eGFR > 90ml/min/1.73m²) baseline kidney function and only 0.04% had advanced renal impairment (eGFR < 30/min/1.73m²). In contrast, only 16% of participants aged 60 and older had normal kidney function at baseline and 0.8% has confirmed advanced renal impairment.

Individuals were followed for a median of eight years. During this time, 1357 people experienced 1646 cardiovascular events, an incidence of 5.2 per 1000 person-years of follow-up.

The median eGFR prior to a cardiovascular disease event was significantly lower (eGFR 85ml/min/1.73m²) in people experiencing an event compared to those who remained event free (eGFR 94ml/min/1.73m²).

There was a clear relationship between baseline eGFR levels and incident cardiovascular disease events. Over five years of follow-up, 2% of people with eGFR above 90ml/min/1.73m² experienced an event, increasing to 4% of those with eGFR between 60-90ml/min/1.73m², 11% of those with baseline eGFR between 30-60ml/min/1.73m² and 21% of individuals with a baseline eGFR below 30ml/min/1.73m².

In the initial analysis there was a strong relationship between worsening baseline eGRF and the risk of cardiovascular disease, the incidence rate ratio (IRR) increasing from 1.00 at eGFR > 90ml/min/1.73m² to 14.09 at eGFR <  30ml/min/1.73m². However, adjustment for age explained most of the relationship between eGFR and cardiovascular risk at eGFR levels above 30ml/min/1.73m². Nevertheless, all eGRF levels below 80ml/min/1.73m² were associated with an increased incidence of cardiovascular disease of approximately 30 to 40%. This finding remained essentially unchanged after adjustment for use of anti-HIV drugs associated with impaired renal function.

Adjusting for Framingham risk score – ten-year risk of a cardiovascular event – explained some of the relationship between current eGFR and cardiovascular events, but not to the same extent as age alone. Further analysis showed that people with a higher five year kidney disease risk score had a more than two-fold increase in their five year risk of cardiovascular disease, compared to individuals with a modest medium term risk of kidney disease (IRR, 2.56, 95% CI, 2.22-2.95).

The proportion of people with a cardiovascular event who experienced a fatal cardiovascular event was strongly related to current eGFR score, increasing from 4% for individuals with a current eGFR > 90ml/min/1.73m² to 25% for those with a current eGFR < 30ml/min/1.73m².

“In a large, contemporary cohort of HIV-positive individuals we observed a strong relationship between confirmed impaired renal function and impaired CVD,” conclude the authors. “Our findings highlight the need for an intensified monitoring for emerging CVD, in particular in older individuals with continuously low eGFR levels.”