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Poor kidney function associated with increased cardiovascular risk for people with HIV
Michael Carter, 2016-08-18 10:00:00
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 patients 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%-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.”
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 HIV-positive patients 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
To remedy this
knowledge gap, investigators from the Data Collection on Adverse events of
Anti-HIV Drugs (D:A:D) study, designed a sub-study 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.
Patients 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.
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 patients 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 patients aged 60 and
older had normal kidney function at baseline and 0.8% has confirmed advanced
followed for a median of eight years. During this time, 1,357 patients
experienced 1,646 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 patients experiencing an event compared to
patients 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 patients with eGFR above
90ml/min/1.73m2 experienced an event, increasing to 4% of patients
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 30-40%.
This finding remained essentially unchanged after adjustment fur use of
anti-HIV drugs associated with impaired renal function.
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 patients 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
patients with a cardiovascular event who experienced a fatal cardiovascular
event was strongly related to current eGFR score, increasing from 4% for
patients 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.”