EDITORIALS
Hypertension in the Hemodialysis Population?
High Time for Answers
Related Articles, pp. 498, 507
I
N VARIOUS series, approximately 90% of
patients starting dialysis are hypertensive.1
Hypertension is improved, but not eliminated by,
hemodialysis. Several recent reports from Europe2 and the United States3 have shown a hypertension prevalence of 70% to 90%. This high
prevalence is again shown in the article by Rahman et al4 in this issue of the American Journal
of Kidney Diseases. The prevalence of hypertension was 62%. Uncontrolled hypertensive patients were more likely to gain weight in between
dialyses, be black, and have hypertension as the
origin of their end-stage renal disease (ESRD).
Among hypertensive patients, a significant correlation existed between the level of blood pressure and interdialytic weight gain. This correlation did not exist for normotensive patients.
Perhaps hypertensive patients have less of a
vasodilatory response in the face of the inevitable volume overload in the interdialytic period.
This is supported by the clinical observation of
patients who are edematous and/or gain excessive weight between dialyses and do not develop
hypertension. Thus, effective vasodilatation,
rather than increased ultrafiltration, may be more
effective in dialysis patients.
The link between hypertension and vascular
disease is strong. Hypertension in the general
population is the most important predictor of
coronary artery disease.5 Ischemic heart disease
is the leading cause of death in the US dialysis
population.6 In Europe, the death rate caused by
myocardial ischemia in dialysis patients is 17
times that of the general population.2 Twentythree percent of the US dialysis population dies
every year. Would control of the blood pressure
in this population decrease this high mortality?
The article by Port et al7 in this issue tells us
that hypertension has no adverse effect on mortality. Indeed, a low predialysis systolic blood pres娀 1999 by the National Kidney Foundation, Inc.
0272-6386/99/3303-0021$3.00/0
592
sure (⬍109 mm Hg) was associated with an
astounding 86% increase in mortality over a
follow-up period of 2 to 3 years. There was also a
trend toward decreased mortality as predialysis
systolic blood pressure increased. The relative
risk (RR) of death decreased to 1.27 for those
with a predialysis systolic pressure of 110 to 119
mm Hg. The group with 120 to 149 pressure was
the reference group with an RR of 1.0. The
lowest RR of 0.98 was for those with a predialysis systolic greater than 180 mm Hg.
The data for the diastolic blood pressure were
not significant except for increased mortality
with postdialysis diastolic more than 110 in a
very small group of patients (n ⫽ 22). The use of
the postdialysis blood pressure is of doubtful
value because it is an artificial transient reading
that is dependent on the fluid removed and the
response of the vasculature. Blood pressure usually increases in the next few hours to the predialysis level. In an attempt to dissect the confounding variable of heart disease causing both
hypotension and increased mortality, the investigators analyzed the survival in the groups with
and without heart failure and/or coronary artery
disease. The trend toward increased mortality
with lower blood pressure persisted.
Similar conclusions have been reached by two
previous studies. In 1996, Salem and Bower8
reported that hypertensive patients have half the
RR of dying when compared with normotensive
patients in a prospective cohort followed for 1
year. Because only the treated hypertensive patients benefited, the survival advantage of hypertensive patients in that study may have been
related to the antihypertensive medication they
were taking. The untreated hypertensive patients
had a mortality rate that was no different than the
normotensive patients. Unfortunately, the Port et
al7 study does not tell us about the antihypertensive use.
In 1998, Zager et al9 reported a J-shaped
association of blood pressure and mortality in the
hemodialysis population with both low and high
blood pressure associated with reduced survival.
However, careful review of their article shows
American Journal of Kidney Diseases, Vol 33, No 3 (March), 1999: pp 592-594
EDITORIALS
no adverse effect of increased blood pressure on
survival (the stem of the J was missing). On the
contrary, those with hypertension as a cause of
their ESRD had an RR of 0.86. There was a 1%
decrease in risk of death for each 1 mm Hg
increase in the predialysis mean arterial pressure.
Even more interesting was the gradual continuous decline in mortality as blood pressure rose
from optimal to very severe in accordance with
the classification of the Fifth Joint National Committee Report on Detection, Evaluation, and
Treatment of High Blood Pressure (JNC V).10
The categories were defined as follows: optimal,
less than 120/80; normal but not optimal, less
than 130/84; high normal, less than 140/90; mild
hypertension less than 160/100; moderate hypertension less than 180/110; and severe/very severe hypertension, more than 180/110. The RR
of death at 2.5 years follow-up was considered 1
for the optimal reference group, 0.9 for the
optimal but not normal, 0.84 for the high normal,
0.75 for the mild hypertension, 0.74 for the
moderate hypertension, and 0.75 for the severe/
very severe hypertension. Zager et al9 also confirmed the observation of Salem and Bower8
regarding the survival benefit of antihypertensives.
Now, how can we interpret these data in view
of what we know about the effect of hypertension on the general population? There are several
possibilities. In the article by Port et al,7 a vital
piece of the puzzle is missing. The antihypertensives given or not given to these patients are not
known. Were patients with low blood pressure
overmedicated? Are we simply seeing the effect
of iatrogenesis? This may explain the harmful
effect of a low blood pressure, but it cannot
account for the better survival of the hypertensive patients.
Hypertension is a sign of diseased blood vessels; the higher the blood pressure, the more
severe the underlying vascular disease. The variability of the blood pressure in dialysis patients
from one session to the next and in the interdialytic period, depending on volume status and
other parameters, would tend to dissociate the
level of blood pressure elevation from its underlying vascular disease. It may be that hypertension in the general population is a better gauge of
the extent of the underlying vascular disease and,
consequently, is a better predictor of mortality.
593
The lack of association between blood pressure
and mortality may also reflect the overall poor
prognosis of the dialysis population in the United
States. Smoking, drinking, and high blood pressure are unlikely to kill you if you only have an
average life expectancy of 5 years. This may
explain that in a cohort of well-dialyzed patients
from France, where the annual death rate is low
and life expectancy is high, only those patients
with normotension were long-term survivors.
Another possibility is that malnourished older
patients have lower blood pressure. The Cox
proportional hazard may be inadequate to correct
for these factors. We need to know the average
ages and nutritional status of these patients who
belong to the different quintiles of blood pressure
in the article by Port et al.7
Morbidity of hypertension within the hemodialysis population is an issue worthy of further
consideration. Unfortunately, with only a few
exceptions (eg, Foley et al11 in Canada), little or
no data exist on the subject. The contribution of
hypertension to cerebrovascular accidents has
been documented in Japan12 and now in the
United States.7 Thus, the issue is not whether to
treat hypertension, but to what extent should
blood pressure be controlled in this population.
The other unanswered question concerns any
selective beneficial effect of one class of antihypertensives over the others. In a group of patients
with an average age of 64 years and a high
prevalence of atherosclerosis, it may not be advisable to lower the blood pressure less than 160/90.
This is a common-sense approach that requires
validation in a prospective randomized controlled study. This avalanche of retrospective
analysis of data is unlikely to lead to real advances in our understanding of hypertension in
the dialysis population. It is time for the US
Renal Data System and the National Institutes of
Health to go beyond statistical analysis of retrospective data and sponsor prospective studies of
the effect and treatment of hypertension in dialysis patients.
—Mahmoud Salem, MD
Assistant Professor of Medicine
University of Mississippi Medical Center
Department of Medicine
Section of Nephrology
Jackson, MS
594
EDITORIALS
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