CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 6, July 2012
348
AFRICA
Conference Report
Hypertension, chronic kidney disease, atrial fibrillation and the
newer anticoagulants: Prof Brian Rayner comments
Prof Brian Rayner, head of Nephrology
at Groote Schuur Hospital and the
University of Cape Town, presented this
Bayer-sponsored lecture. He began by
stating that it is highly likely that the
practitioner will encounter older patients
with atrial fibrillation (AF), concomitant
hypertension and chronic kidney disease
(CKD), requiring anticoagulation therapy.
A sophisticated inter-relationship exists
between these clinical conditions.
AF is commonly associated with
increased morbidity and mortality,
primarily related to embolic stroke. In
the absence of mitral valve disease,
the dominant risk factors for AF are
hypertension and older age; both of which
are CHADS
2
determinants in assessing
the need for anticoagulation. Additionally,
hypertension and ageing are risk factors
for the development of CKD, which in
itself is a risk factor for AF.
Atrial fibrillation
The co-existence of AF and hypertension
doubles the risk of overall mortality,
stroke, heart failure and hospitalisation;
in addition to affecting quality of life and
impairing cognitive function. In these
patients, the primary clinical goal is to
reduce blood pressure.
There is some evidence that drugs
blocking
the
renin-angiotensin-
aldosterone system reduce the risk of
new-onset AF, particularly in high-risk
patients (those with left ventricular
dysfunction, left ventricular hypertrophy
and post-myocardial infarction). Beta-
blockers are effective for rate control
but there is a dearth of evidence for the
use of beta-blockers and other agents in
new-onset AF.
Chronic kidney disease
Prof Rayner expressed the opinion that
South Africa is in the early stages of
an escalating CKD epidemic, fuelled
by the high prevalence of hypertension
and diabetes mellitus. CKD is defined
by glomerular filtration rate (GFR);
usually estimated from serum creatinine
level. The Modification of Diet in Renal
Disease (MDRD) equation is usually used
in South Africa. Prof Rayner emphasised
that CKD classification (Table 1) is an
epidemiological tool and not a gold
standard, and that the need to consider
the individual patient should not be
overlooked.
Relationship with cardiovascular
disease
The relationship between cardiovascular
disease (CVD) and CKD is a complex
one. In dialysis patients, 52% of deaths
are due to non-vascular causes. The
remainder of deaths are attributable to
acute myocardial infarction (8%), stroke
(5%), cardiac arrest/arrhythmia (27%),
other cardiovascular diseases (3%), and
other cardiac complications (5%).
CVD and CKD share traditional risk
factors including hypertension and ageing;
however, a number of ‘uraemia-specific’
risk factors contribute to CVD. These
are anaemia, phosphate retention, hyper-
parathyroidism, vascular calcification,
uraemic toxins, hyperhomocysteinaemia
and volume overload. The combination
of volume and pressure overload, as well
as sympathetic overactivity result in left
ventricular hypertrophy.
CKD (stages 3 to 5) is an independent
risk factor for new-onset AF in
hypertensive patients (8.3% with and
3.4% without CKD). The worse the GFR,
the greater the AF risk. Similarly, the
presence of proteinuria also increases
AF risk.
CKD results in altered cytokine
production, manifesting increased levels
of pro-inflammatory cytokines and
decreased levels of anti-inflammatory
cytokines, which may promote accelerated
atherosclerosis. As opposed to traditional
atherosclerosis, medial calcification
results in vascular thickening. Prof Rayner
recommended lateral lumbar X-ray for
assessment.
Anticoagulation in patients with
AF, hypertension and CKD
Kidney function is an important
determinant of the pharmacokinetics of
a variety of drugs. This is of particular
concern with the use of anticoagulants,
which have a narrow therapeutic/toxic
range.
Anticoagulants are potent therapies
used to prevent thromboembolism; as
a result, all anticoagulants may cause
potentially life-threatening bleeds.
Patients at a higher risk of bleeding
include those with renal and hepatic
impairment and those concomitantly
receiving systemic azole-antimycotics,
HIV protease inhibitors, drugs affecting
haemostasis, and agents that are strong
inhibitors of the CYP3A4 and P-GP
pathways.
Care also needs to be taken in the
anticoagulation of patients with other
haemorrhagic risk factors such as
uncontrolled severe arterial hypertension,
active or recent gastrointestinal ulceration,
recent intracranial or intracerebral
haemorrhage, and bronchiectasis or
a history of pulmonary bleeding. It is
therefore essential for the practitioner
to understand the risks and benefits of
TABLE 1. UPDATED CKD
CLASSIFICATION
Stage
GFR
(ml/min/
1.73 m
2
) Description
1
≥
90 Normal or increased GFR,
with other evidence of
kidney damage present for
≥
three months
2
60–89 Slight decrease in GFR,
with other evidence of
kidney damage present for
≥
three months
3a
3b
45–59
30–44
Moderate decrease in GFR
for
≥
three months with or
without other evidence of
kidney damage
4
15–29 Severe decrease in GFR,
with or without other
evidence of kidney damage
5
<
15 Established renal failure
