CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 3, April 2012
176
AFRICA
Difficult-to-control blood pressure
Prof Henry Krum
Prof Krum used data from the National
Health and Nutrition Examination
Surveys (NHANES) 2003–2008 to
highlight the prevalence of childhood
hypertension. Uncontrolled and untreated
hypertension was evident in 30% of the
study population, 9% of the study subjects
displayed resistant hypertension; whereas
40% were controlled on less than two
drugs and 21% on less than three drugs.
Resistant hypertension
‘A significant proportion of the
hypertensive population has resistant
hypertension’, Prof Krum said. He
defined resistant hypertension as not
being able to reach a blood pressure target
of 140/90 mmHg (130/80 mmHg for
diabetic patients), despite full adherence
to triple hypertensive therapy, including
a diuretic.
Examination of causes of resistant
hypertension revealed non-adherence
(16%) and drug-related causes (58%)
as the predominant factors; with office
resistance or white-coat effect (6%),
psychological reasons (9%), secondary
hypertension (5%), interfering substances
(1%), and other factors of unknown
origin (5%) also resulting in resistant
hypertension.
Assessment and treatment of
resistant hypertension
Initial clinical assessment of the resistant
hypertensive patient should include
a history and physical examination,
urinalysis and blood chemistry. Prof
Krum advised to carefully consider
adherence issues, particularly the
medication schedule (dosing), and to look
for interacting drugs (taken regularly,
often or occasionally) that may raise
blood pressure. In the case of sub-optimal
therapy, investigatemedication intolerance
and drug–drug interactions.
Spironolactone, as an addition to
triple-therapy hypertensive agents, has
been found to be useful in refractory and
resistant hypertension. Prof Krum drew
attention to the ASPIRANT study, which
compared the effect of spironolactone vs
placebo on ambulatory and office blood
pressure. Spironolactone was shown to be
of therapeutic benefit.
Prof Krum also noted that there is a
well-established relationship between
both obesity and sleep apnoea (through
activation of the sympathetic nervous
system), and hypertension. Treatment
of both conditions will decrease the
hypertensive burden, with non-
pharmacological interventions including
weight loss and a reduction of sodium
intake.
Baroreflex activation therapy
Prof Krum then went on to discuss
baroreflex activation therapy, an invasive
procedure that requires the implantation
of leads and a pulse generator. This
sensitisation device exploits the
relationship between stimulation and
response to retrain the baroreflex and
improve sensitivity. Increasing voltage
results in a progressive reduction in blood
pressure and heart rate.
Renal denervation
Another invasive procedure entails
denervation of the renal sympathetic
nerves, which contribute considerably
to progressive hypertension. This
procedure targets the renal efferent nerves
(disrupting renin release and sodium
retention, and decreasing renal blood flow
and proteinuria) and the renal afferent
nerves (affecting the heart and smooth
muscle). These nerves follow the renal
artery to the kidney within the adventitia.
Denervation by radio frequency
catheter, via the endovascular femoral
approach, results in a progressive blood
pressure reduction. Typically, patients with
a systolic blood pressure higher than 160
mmHg despite three or more medications
are suitable candidates to benefit
from this procedure. This technique is
currently being used successfully in South
Africa.
Conclusion
In light of the hypertension epidemic
currently being faced, Prof Krum
concluded with three considerations: a
reminder that target blood pressure levels
are being continually revised downwards,
that evidence suggests existing therapeutic
agents are being sub-optimally utilised,
and that the need to explore novel agents,
novel procedures and devices is imperative
in these difficult-to-treat patients.
G Hardy
Prof Henry Krum
Head of the Clinical Pharmacology
Unit, chair of Medical Therapeutics
and director of the Monash University
Centre of Cardiovascular Research
and Education in Therapeutics,
Department of Epidemiology and
Preventive Medicine and Department
of Medicine, Melbourne, Australia
News from 2012 ACC congress
Prof Krum also reported on long-term
follow up in the Symplicity HTN-1 trial
using the Medtronic renal denervation
(RDN) catheter over a two-year period.
1
HTN-1 was an open-label cohort
study which enrolled 153 patients
with resistant hypertension at sites in
Australia, Europe and the United States.
The patients all had systolic blood
pressure
≥
160mmHg despite being on at
least three antihypertensive medications
including a diuretic, at target/maximum
tolerated doses. Patients with an eGFR
< 45 ml/min or those with type 1
diabetes were excluded.)
Importantly,
blood
pressure
progressively declined over the two
years in this cohort, suggesting that
functional re-innervation was unlikely
to be occurring, at least up to two years
post-RDN procedure. Only one case of
renal artery stenosis was reported in the
12 months.
In the same session, Dr Murray Esler
reported on a randomised, controlled
trial of RDN versus medical treatment
only (Symplicity HTN-2) at one year.
2
The primary endpoint was change in
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