Prevalent Left Ventricular Hypertrophy in the Predialysis

Population: Identifying Opportunities for Intervention

Adeera Levin, MD, FRCP(C), Joel Singer, PhD, Christopher R. Thompson, MD, FRCP(C),
Heather Ross, MD, FRCP(C), and Mary Lewis, RN
Left ventricular hypertrophy (LVH) is present in over 70% of patients commencing dialysis. It is an independent
risk factor for cardiac death, which is the cause of death in approximately 45% of patients on dialysis. The
prevalence of LVH in patients earlier in the course of renal insufficiency is unknown. As part of a prospective
longitudinal study evaluating the progression of comorbid diseases in patients with progressive renal disease, we
evaluated LVH. In 175 consecutive patients attending a renal insufficiency clinic we obtained technically adequate
echocardiograms and estimated left ventricular mass index (LVMI) using two-dimensional targeted M-mode echo-
cardiography. We calculated LVMI using the American Society of Echocardiography cube formula method re-
gressed to anatomic validation. The population consisted of 115 men and 60 women ranging in age from 20 to
82 years (mean age, 51.5 years). The mean creatinine was 403 _+ 207 /~mol/L (_+SD), representing a creatinine
clearance (Ccr) of 25.5 _+ 17 mL/min. Left ventricular hypertrophy was defined as LVMI greater than 131 g/m 2 in
men and greater than 100 g/m 2 in women, and was present in 38.9% of the population studied. We demonstrate
that the prevalence of LVH increases with progressive renal decline: 26.7% of patients with Ccr greater than 50
mL/min had LVH, 30.8% of those with Ccr between 25 and 49 mL/min had LVH, and 45.2% of patients with severe
renal impairment (Ccr <25 mL/min) had LVH (P = 0.05). The mean LVMI was significantly different among the
three groups (97.5 g/m 2 v 100.8 g/m 2 v 114.4 g/m 2, respectively; P < 0.001). Univariate analyses revealed that age,
hemoglobin, systolic blood pressure, and Ccr were significantly different between the groups with and without
LVH. The logistic regression model confirmed the findings of the univariate analysis: an increase in age of 5 years
was associated with an increase of 3% in risk of LVH (P = 0.0094), as was an increase in systolic blood pressure
of 5 mm Hg (P -- 0.0018). For each 10 g/L decrease in hemoglobin, the risk of LVH increased by 6 % (P = 0,0062),
and for each 5 mL/min decline in Ccr the risk increased by 3% (P = 0.0168). We demonstrate the high prevalence
of LVH in patients with renal insufficiency prior to the need for dialysis, which is associated with severity of renal
impairment, and identify two modifiable factors (systolic blood pressure and anemia) as important predictors of
LVH. We suggest that future studies should focus on interventions aimed at attenuating the impact of these
factors.
1996 by the National Kidney Foundation, Inc.

INDEX WORDS: Progressive renal insufficiency; left ventricular hypertrophy; cardiovascular risk.

ARDIOVASCULAR disease remains the PATIENTS AND METHODS

C leading cause of morbidity and mortality in
end-stage renal failure (ESRF) patients. Ischemic
All patients were referred to our nephrology division for
assessment and follow-up of renal insufficiency (serum creat-

heart disease, cerebrovascular disease, and left

ventricular hypertrophy (LVH) all occur with
high frequency in the dialysis population. 1,2 Ca-
nadian Organ Replacement Registry data demon-
strate that 45% of all deaths in the ESRF popula-
tion are due to cardiovascular causes. There has
been no change in these rates in the last decade. 2
Left ventricular hypertrophy is an independent
predictor of survival, present in approximately
70% of patients at the initiation of dialysis) -5 It
is obvious that cardiovascular disease must be
present in a significant proportion of patients
long before the initiation of dialysis. Despite this,
little is known about the prevalence and progres-
sion of LVH in patients in the interval between
onset of renal insufficiency and the initiation of
dialysis. We describe the prevalence of LVH in
a group of patients with renal insufficiency prior
to the onset of renal replacement therapy.
From The Divisions of Nephrology and Cardiology, the
Departments of Medicine and Health Care and Epidemiol-
ogy, St Paul's Hospital and the University of British Colum-
bia, Vancouver BC, Canada.
Received December 8, 1994; accepted in revised form No-
vember 14, 1995.
Supported by grants to Dr Levin from the BC Medical
Research/Vancouver Foundation, Vancouver, British Colum-
bia, Canada, and Ortho Biotech Canada, Toronto, Canada,
and to Dr Thompson from the Heart and Stroke Foundation
of British Columbia and the Yukon. Dr Levin is a St Paul's
Hospital Foundation Scholar.
Presented in part at the Annual Meeting of the Royal Col-
lege of Physicians and Surgeons of Canada, Quebec City,
Quebec, Canada, 1992, and at the Annual Meeting of the
American Society of Echocardiography, San Francisco, CA,
May 1994.
Address reprint requests to Adeera Levin, MD, FRCP(C),
Renal Insufficiency Clinic, #602--1160 Burrard St, Vancou-
ver BC, Canada V6Z 1Y6.
1996 by the National Kidney Foundation, Inc.
0272-6386/96/2 703-000753.00/0

American Journal of Kidney Diseases, Vol 27, No 3 (March), 1996: pp 347-354 347
348
inine > 150 #mol/L). As part of a prospective study evaluat-
ing the prevalence and progression of comorbid conditions
associated with renal insufficiency, we collected demo-
graphic, clinical, and biochemical data and attempted to ob-
tain echocardiographic data in 197 consecutive patients eval-
uated in the renal insufficiency clinic between February 1990
and March 1993.
Of the 197 patients, 22 (11%) did not have evaluable echo-
cardiograms; three of the studies were technically inadequate
and 19 patients failed to keep their appointments. The results
of 175 consecutive patients who had echocardiograms techni-
cally adequate for the determination of left ventricular mass
are presented.
All patients had two-dimensional targeted M-mode echo-
cardiograms recorded in the left lateral decubitus position
interpreted by an experienced echocardiographer. Measure-
ments of the thickness of the ventricular septum (IVS), the
thickness of the posterior wall (PW), and the internal diameter
of the left ventricle at end diastole (LVIDD) were taken using
American Society of Echocardiography techniques. Left ven-
tricular mass was calculated using the American Society of
Ecbocardiography cube formula regressed to anatomic vali-
dation6:
LV mass = 0.8 {1.04 x [(LVIDD + IVS + P W ) 3
- LVIDD3]} + 0.6 g
Left ventricular mass index (LVMI) was calculated by divid-
ing the left ventricular mass by body surface area. Left ven-
tricular hypertrophy was defined as 2 SD above the mean
LVMI found in the Framingham Study population as de-
scribed by Levy et al.v Left ventricular hypertrophy was de-
fined in absolute terms as more than 131 g/m2 in men and
more than 100 g/m2 in women. Further characterization of
LVH into concentric and eccentric hypertrophy was depen-
dent on measurements of relative wall thickness (RWT = [(2
x PW)/LVIDD]) according to American Society of Echocar-
diography criteria. Concentric hypertrophy was present if the
RWT was greater than 0.45 in the presence of LVH and
eccentric hypertrophy was present if the RWT was less than
0.45 in the presence of LVH; concentric remodelling was
present if the RWT was more than 0.45 in the absence of
LVH.
Blood pressure was measured in the supine position after
the patient had rested in the clinic for 5 minutes. The mean
of three blood pressure determinations obtained within 3
months of the echocardiogram is reported. Antihypertensive
medications were tabulated and medications were classified
by type into angiotensin-converting enzyme inhibitors, cal-
cium channel blockers, beta adrenergic blocking agents, and
other. Hypertension was defined as a mean arterial pressure
greater than 105 mm Hg or systolic or diastolic pressure
greater than 140 mm Hg or greater than 90 mm Hg, respec-
tively.
Fasting laboratory determinations of hemoglobin, intact
parathyroid hormone (iPTH; normal range, <5 pmol/L), and
serum creatinine were obtained during the same time period.
Anemia was defined as hemoglobin less than 110 g/L, and
hyperparathyroidism was present if the iPTH was above 15
pmol/L The Gault-Cockcroft formula was used to calculate
creatinine clearance (Ccr) as follows:
LEVIN ET AL
Males = Ccr(males) = (140 - age)
X weight (kg)/serum creatinine (#mol/L) x 0.81
Females = Ccr(females) = Ccr(males) X 0.85
The calculation of Ccr by this method correlates highly with
measured Ccr techniques.8 Renal insufficiency was classified
as mild (Ccr >50 mL/min), moderate (Ccr 25 to 49 mL/
min), or severe (Ccr <24 mL/min).
Statistical Methods
For normally distributed continuous variables, mean values
and standard deviations were calculated and the means com-
pared using the two sample t-test or ANOVA. For variables
with skewed distribution, median values and ranges were
determined and Wilcoxon rank sum test was used for com-
parisons. Categorical variables were compared using the
cbi-square test or Fisher's exact test. The Mantel-Haenszel
chi-square statistic for linear trends was used to test for the
association between Ccr categories (according to severity)
and the presence or absence of LVH and other variables
described in categorical terms, including the use of specific
classes of antihypertensive medications (angiotensin-con-
verting enzyme inhibitors, calcium channel blockers, beta-
blockers, and others). All tests were two-tailed, with P
< 0.05 taken to indicate statistical significance.
Logistic regression was used to identify the associations
between the presence of LVH and the following explanatory
variables: age, Ccr, blood pressure (systolic and diastolic),
hemoglobin, and iPTH. From the logistic model the adjusted
odds ratios and 95% confidence intervals were calculated
for each covariate. A second multivariate logistic regression
model was also fitted, which included only those covariates
with P < 0.05 (age, Ccr, systolic blood pressure, and hemo-
globin).
A multivariate linear regression analysis with the same
variables was performed to determine correlations with
LVMI; the partial r 2 value calculated for each variable was
the percentage of variance in the model explained indepen-
dently of other variables. For both linear and logistic regres-
sion procedures variables were retained only if they met the
P < 0.05 significance levels. All data were analyzed using
SAS software (Cary, NC).
RESULTS
Demographics
Table 1 describes the population studied. Age,
p r i m a r y r e n a l d i s e a s e , c r e a t i n i n e , a n d C c r are
p r e s e n t e d . P a t i e n t s w e r e b e t w e e n 2 0 a n d 82 y e a r s
old, a n d 6 6 % w e r e m a l e . T h e p r e d o m i n a n t c a u s e s
of renal insufficiency were glomerulonephritis
(29%), diabetic nephropathy (22%), and hyper-
tension (20%). Reflux nephropathy, polycystic
kidney disease, and pyelonephritis were the other
predominant causes of renal insufficiency. Creat-
i n i n e r a n g e d f r o m 169 to 850 # m o l / L ( m e a n ,
4 0 3 . 6 # m o l / L ) , c o r r e s p o n d i n g to c a l c u l a t e d C c r
LVH IN EARLY RENAL INSUFFICIENCY
Table 1. Demographics of the Population With
Evaluable Echocardiograms
Total Group
(N = 175)
Age, yr (mean _+ SD) 51.6 _+ 15.3
Range 20-82
Renal disease
Glomerulonephritis (%) 51 (29.1)
Hypertensive nephrosclerosis (%) 35 (20.0)
Diabetes mellitus (%) 39 (22.3)
Creatinine, #mol/L (mean _+ SD) 403.6 _+ 207.0
Calculated CrCI, mL/min
Median (Q1-Q2) 19.6 (13.4-34.1)
Mean +_ SD 25.5 _+ 17.0
levels between 5 and 90 mL/min (normal range,
100 to 120 mL/min). Nine percent of the study
population had mild renal insufficiency, 31% had
moderate renal insufficiency, and 60% had se-
vere renal insufficiency as determined by these
criteria. No patients had arteriovenous fistulas or
grafts at the time of echocardiographic study.
Left Ventricular Hypertrophy, Renal Function,
and Predictive Variables
The prevalence of LVH in this predialysis popu-
lation was 38.9% of patients. The prevalence of
LVH was higher at lower Ccr levels (P = 0.05;
Fig 1). Age, Ccr, systolic blood pressure, and he-
moglobin were significantly different between
those patients with and without LVH (Table 2).
Systolic hypertension, anemia, and hyperparathy-
roidism were more prevalent in patients with LVH.
Mean values of LVMI, age, hemoglobin, and
iPTH levels, but not blood pressure, were sig-
nificantly different at each level of renal function
(P < 0.001). The prevalence of systolic hyper-
tension was not different between the groups
with mild, moderate, or severe renal impairment,
but the prevalence of anemia and hyperparathy-
roidism was significantly higher with declining
renal function (P < 0.001) (Table 3).
We explored the relationship between these
clinical and laboratory values and the geometry
of LVH (Table 4). Those with eccentric hypertro-
phy were more likely to have hemoglobin levels
lower than 110 g/L and iPTH levels higher than
15 pmol/L. More patients with LVH had eccen-
tric hypertrophy (79.6%) than concentric hyper-
trophy (29.4%) (P < 0.001).
349
The logistic regression model confirmed the
findings of the univariate analysis; the adjusted
odds ratios are presented in Table 5. An increase
in age of 5 years was associated with an increase
of 3% in risk of LVH (P = 0.0094), as was an
increase in systolic blood pressure of 5 mm Hg
(P = 0.0018); for each 10 g/L decrease in hemo-
globin, the risk of LVH increased by 6% (P
= 0.0062), and for each 5 mL/min decrease in
Ccr the risk increased by 3% (P = 0.0168). The
second model was fitted using only variables that
were significant; systolic blood pressure (beta
= 0.0208, P = 0.0068) and hemoglobin (beta
= -0.0194, P = 0.023) emerged as predictors
of LVH in this predialysis population.
The multivariate linear regression was used to
determine independent correlations of age, Ccr,
systolic blood pressure, and hemoglobin with
LVMI. The portion of the total variation of
LVMI attributable to the effect was 10%:
L V M I = 4 4 . 5 0 + 0.38(age) + 0.37(systolic blood pressure [in mm Hg])
Thus, systolic blood pressure and age (r 2 = 7.2%
and 2.4%, respectively; P < 0.005 and P < 0.04,
respectively) were the only variables indepen-
dently and significantly associated with increased
LVMI in this multivariate model.
50
45
40
35
30
% 25
20
15
10
p = .05
5
0
CGR>50 CCR 25-49 CCR <25
Categories of Renal Function
(Creatinine clearance in ml/rn]n}
Fig 1. Prevalence of LVH (>2 SD above the mean
in the Framingham study) in patients with mild (Ccr
> 5 0 mL/min; n -- 16), moderate (Ccr 25 to 49 mL/min;
n = 54), and severe (Ccr < 2 5 mL/min; n = 105) renal
insufficiency. The prevalence of LVH increases as re-
nal function declines. There is a significant difference
between the prevalence of LVH in patients with mild
renal insufficiency compared with those with severe
renal insufficiency (P = 0.05).
350 LEVIN ET AL

Table 2. Mean Values and Prevalence of Abnormalities of Variables in Those With and Without
Left Ventricular Hypertrophy

No LVH LVH Present Probability Value

No. (%) 107 (61) 68 (38.9)

Age (yr) 49.2 +_ 14.5 55.4 _+ 15.9 0.0082
Males (%) 68.2 61.8 0.42
Creatinine clearance (mL/min) 22.5 ___15-36.7 17.3 _+ 12.3-27.9 0.017
SBP (mm Hg) 139.3 + 22.3 150.9 + 22.2 0.0012
DBP (mm Hg) 86.6 ___11.8 86.6 _+ 11.3 0.99
MAP (mm Hg) 104.0 13.7 108.0 _+ 12.5 0.07
Hgb (g/L) 119.0 19.7 110.1 + 20.7 0.0049
iPTH (pmol/L)* 13.3 ___6.4-29.1 20.9 _+ 9.6-39 0.13
SBP > 140 56.2% 71.2% 0.05
DBP > 90 41.9% 45.4% 0.75
MAP > 105 53.0% 60.4% 0.43
Hgb < 110 35.0% 60.0% 0.001
iPTH > 15" 44.0% 63.0% 0.04

NOTE. The upper portion of the table demonstrates the mean values _ SD for variables in those with and without LVH;
the lower portion demonstrates the proportion of patients with hypertension, anemia, and hyperaparathyroidism in those
with and without LVH. Note that patients with LVH have lower creatinine clearance, higher systolic blood pressure, and
lower hemoglobin than those without.
Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; Hgb, hemoglo-
bin; iPTH, intact parathyroid hormone.
* Missing data (29%).

Hypertension prior to enrollment in the study, but only 20%

The mean blood pressure of this group was
within the normal range (143/70 mm Hg). How-
ever, 56% of the population had hypertension,
defined as a mean arterial pressure of greater than
105 mm Hg. Eighty percent of the patients had
documented hypertension for at least 3 years
of the total population had a renal diagnosis of
hypertensive nephrosclerosis. There was no dif-
ference in the prevalence of hypertension be-
tween those with mild, moderate, or severe renal
impairment (P = 0.87). The use of angiotensin-
converting enzyme inhibitors, either alone or in

Table 3. Severity of Renal Dysfunction and Mean Values of Clinical and Laboratory Variables

Mild RD Moderate RD Severe RD

(Ccr > 50 mL/min) (Cor25-49 mL/min) (Ccr < 25 mL/min) Probability Value

No. (%) 16 (9.0) 54 (31.0) 105 (60.0)

Age (yr) 41.0 11.1 46.1 _+ 12.5 55.9 -4- 15.8 0.001
Males (%) 60.0 67.3 66.4 0.87
SBP (mm Hg) 141.9 20.8 140.6 _+ 23.3 146.1 _+ 22.7 0.36
DBP (mm Hg) 90.7 10.7 87.2 _+ 13.6 85.8 _ 10.6 0.28
MAP (mm Hg) 107.8 12.9 105.0 +_ 15.0 105.9 _+ 12.5 0.78
Hgb (g/L) 137.6 +__22.7 122.8 _+ 20.2 108.6 + 16.5 0.001
iPTH (pmol/L) 5.15 (3,45-6.45) 10.4 (6.2-9.5) 25.9 (12.7-39.2) 0.001
LVMI (g/m 2) 97.5 (84.6-113) 100.8 (88.8-130) 114.4 (97.6-139.8) 0.019

NOTE. The table demonstrates the mean values _+ SD, or the median values and ranges (as indicated), of each of the
variables examined by severity of renal dysfunction. Note that blood pressure is not different between the groups, but
that the mean values for hemoglobin decrease as a function of renal impairment and both the median and range of values
of LVMI are significantly different between the groups.
Abbreviations: RD, renal dysfunction; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial
pressure; Hgb, hemoglobin; iPTH, intact parathyroid hormone; LVMI, left ventricular mass index.
LVH IN EARLY RENAL INSUFFICIENCY 351

Table 4. Characterization of Left Ventricular Geometry in Relation to Renal Function, Blood Pressure,
Parathyroid Hormone, and Hemoglobin

Mild RD Moderate RD Severe

Total Group (Cc, > 50 mL/min) (Ccr 25-49 mL/min) (Cot < 25 mL/min) Probability Value

LVMI (g/m 2) 107.8 97.5 100.8 114.4 0.019

Range 94.7-133,4 84.7-113 88.4-130 97.6-139.4
LVlDD (mm) 53.4 + 6.9 52.5 -+ 6.1 52.3 _+ 7.1 54.2 _+ 6.9 0.24
PWT (mm) 10.7 + 1.8 10.7 + 1.8 10.5 +_ 1.6 10.5 _+ 2.0 0.93
IVS (mm) 10.7 _+ 1.8 10.6 _+ 1.9 10.6 _+ 1.5 10.6 _+ 2.0 0.97
Eccentric 57.8% 40.0% 47.8% 63.0% 0.107
Concentric 24.0% 40.0% 21.7% 24.0%
C-Remodel 18.0% 20.0% 30.4% 13.0%

C-Remodel Concentric Eccentric

SBP > 140 mm Hg 16.1% 30.4% 53.6% 0.0194

PTH > 15 pmol/L 11.8% 29.4% 58.8% 0.046
Hgb < 110 g/L 7.0% 27.9% 65.1% 0.017

NOTE. In patients with severe renal insufficiency, eccentric hypertrophy is the most prevalent, and in patients with
anemia and hyperparathyroidism, eccentric hypertrophy is the most prevalent.
Abbreviations: RD, renal dysfunction; LVMI, left ventricular mass index; SBP, systolic blood pressure; PTH, parathyroid
hormone; Hgb, hemoglobin.

combination with other medication, was not dif- tion prior to the institution of dialysis. This popu-
ferent between those who did and did not have lation is representative of the ESRF population
LVH. Interestingly, calcium channel blocker use in Canada, as demonstrated by the demographics
either alone or in combination was significantly of the group when compared with Canadian Or-
greater in patients with LVH. There was no dif- gan Replacement Registry data. Furthermore, we
ference in the use of specific classes of antihyper- have described the relationship between the pres-
tensive agents (angiotensin-converting enzyme ence of LVH and impaired renal function, ane-
inhibitors, calcium channel blockers, or beta mia, and systolic blood pressure in this predial-
blockers) at each level of renal impairment. ysis population. Our findings are concordant with
those of similar, but smaller, studies in predial-
DISCUSSION
ysis patients, 9 as well as with those of studies
In this cross-sectional study, we have de- from the dialysis t-14 and general 6'15 populations.
scribed a high prevalence of LVH in the popula- The importance of LVH in both the general
and dialysis populations in predicting morbidity
and mortality has been previously described in de-
Table 5. Adjusted Odds Ratios of Covariates tail. 3-5'7'~1The presence of LVH in dialysis patients
Associated With Presence of Left leads to an independent relative risk of death of
Ventricular Hypertrophy 2.9 for mortality related to all causes and 2.7 for
Associations Odds Ratio Probability Value
cardiac-related mortality. 3-5 Furthermore, Parfrey
et al have demonstrated both the progression of
Age (1 yr) 1.03 .009 LVH over a 30-month period in a cohort of pa-
Creatinine clearance 0.97 .01 tients followed on dialysis 5'jl and that those pa-
(1 mlJmin)
tients with more severe LVH had more episodes
Systolic blood pressure 1.02 .0018
(1 mm Hg) of congestive heart failure and a lowersurvival
Diastolic blood pressure 1.00 .99 rate than those with mild LVH. In the Framing-
(1 mm Hg) ham study, the normal population prevalence of
Hemoglobin (1 g/L) 0.98 .0062 LVH was 17%, and higher LV mass predicted a
iPTH (1 pmol/L) 1.0 .31
higher incidence of clinical events, including
352
death attributable to cardiovascular disease. 7 Left
ventricular hypertrophy is clearly an important
contributor to cardiovascular morbidity and mor-
tality in all populations, and in those with renal
failure, the institution of dialysis therapy does not
improve pre-existing LVH.
We have demonstrated that the prevalence of
LVH is higher with worsening renal insuffi-
ciency, prior to dialysis. As Foley et al4 have
documented a prevalence of LVH in patients
starting dialysis that is almost double that which
we report in this population (74% v 38%), the
information in the current study provides an op-
portunity to identify the critical period during
which it is possible to prevent the development
of or delay the progression of LVH.
Systolic blood pressure is consistently associ-
ated with LVH in studies in the general and dial-
ysis populations. 4'6'~1'15 Interestingly, the level of
blood pressure is often lower than one might ex-
pect to account for the dramatic increase in the
prevalence of LVH; the differences in mean sys-
tolic blood pressure that predict severity of LVH
are small (approximately 10 mm Hg), but consis-
tent with other reports in the literature. 6'7'14')5Our
study demonstrates similar small but statistically
significant differences in systolic blood pressure
between those with and without LVH. The multi-
variate analysis results are concordant with those
of other researchers ~ in that systolic hyperten-
sion appears to be related to LVMI, but they do
not explain a large amount of the variability in
LVMI.
The use of angiotensin-converting enzyme in-
hibitors alone and in combination with calcium
channel blockers was not different between those
with and without LVH; however, more patients
on calcium channel blockers alone had LVH.
This may be a function of severity of hyperten-
sion and clinical reluctance to use angiotensin-
converting enzyme inhibitors in patients with
severe renal dysfunction rather than truly a con-
sequence of calcium channel blocker use. How-
ever, there is ample evidence in the literature to
suggest that both angiotensin-converting enzyme
inhibitors and calcium channel blockers can limit
LV growth or cause regression. 16The descriptive
nature of this study does not allow us to deter-
mine the reasons for differential drug class use,
nor to infer that the use of calcium channel block-
ers causes LVH. Interestingly, in our study we
LEVIN ET AL
did not demonstrate any difference in systolic,
diastolic, or mean arterial blood pressure as a
function of severity of renal impairment. These
data serve to corroborate the notion that blood
pressure and renal impairment (or factors associ-
ated with renal impairment) may be independent
contributors to LVH.
Anemia has been consistently associated with
cardiovascular morbidity and LVH in the ESRF
populations, 1'~3 and the results of this study are
consistent with those in the literature. Anemia
leads to an increase in cardiac workload due to
relative tissue ischemia, which subsequently
leads to the development of LVH. Interestingly,
sustained anemia is often associated with eccen-
tric hypertrophy, whereas hypertension is associ-
ated with concentric hypertrophy. Our results
demonstrate a high prevalence of eccentric hy-
pertrophy in those patients with LVH and an in-
creased prevalence of anemia in those patients
with eccentric hypertrophy relative to concentric
hypertrophy. Thus, our data are consistent with
known physiologic processes. Studies have dem-
onstrated that the reversal of anemia using eryth-
ropoietin therapy has led to partial regression of
LVH j3'16'17 in the dialysis population. This study
identifies an opportunity to study the impact of
correction of anemia on LVH in the predialysis
population.
We were unable to consistently demonstrate
the importance of PTH as a predictor of LVH in
our model. The relationship between PTH and
LVH has been inconsistently demonstrated in
previous studies. 9'~'j8 We were able to demon-
strate a trend toward higher absolute PTH levels
in those patients with LVH, but it did not reach
statistical significance. It may be that with a
larger sample size and serial measurements over
time, the true nature of the relationship between
PTH and LVH can be demonstrated.
The progressive increase in the prevalence of
LVH as a function of declining renal function is
important information for planning the timing of
interventions. We hypothesize that an opportu-
nity to intervene prior to dialysis to limit the
extent and prevalence of LVH in this population
exists. Due to the sample size and heterogeneity
of the population, as well as the cross-sectional
nature of the data, we are unable to make firm
recommendations, but this is obviously an oppor-
tunity for further research. Solitary measure-
LVH IN EARLY RENAL INSUFFICIENCY
ments o f these variables do not accurately reflect
the dynamic impact that they m a y have on L V H
over time; thus, longitudinal data will be of tre-
mendous importance. Blood pressure control pre-
viously has been thought to be a significant con-
tributor to LVH, but our data highlight the need
for intensive exploration of alternative factors re-
sponsible for the m y o c y t e growth in this popula-
tion. The similarity in the pathogenesis of m y o -
cyte hypertrophy and glomerular hypertrophy
seen in progressive renal insufficiency suggests
a possible role for growth factors] 9-z~ Angioten-
sin II, catecholamines, epinephrine, insulin-de-
rived growth factor, endothelin-derived growth
factors, and P T H have all been shown to affect
m y o c y t e growth, zl'z2 These same factors have
been demonstrated to foster glomerular hypertro-
phy. z3,z4 It may be that renal insufficiency results
in higher circulating levels o f these factors be-
cause o f increased production, decreased clear-
ance, or lack of counterregulatory inhibitory fac-
tors. Indirect evidence for this key role that the
kidney plays in the development of L V H is con-
firmed by the demonstration of L V H regression
after renal transplantation, z5'26 Delineation o f the
factors associated with the progression of L V H
will be important for the future selection o f po-
tential therapeutic interventions.
The results o f the stepwise logistic regression
model and multivariate analyses underscore the
complex relationship between anemia, systolic
hypertension, impaired renal function, and LVH,
which reflects the biologic complexity of the
pathophysiology of L V growth.
Cardiovascular disease remains an important
cause of morbidity and mortality in E S R F pa-
tients. It is not known whether pharmacologically
induced regression o f established L V H would be
o f benefit, since there is evidence that the in-
crease in left ventricular mass observed in this
population is due to both hypertrophy of myo-
cytes and myocardial fibrosis, z7 Thus, strategies
to prevent the development and progression of
L V H with its associated morbidity in the renal
population at this early stage m a y prove to be
more effective than attempts to induce regression
of established severe LVH. The demonstration
of the high prevalence of L V H in a population
representative of the E S R F population, and the
systematic evaluation of factors known to con-
tribute to LVH, are the initial steps in improving
353
our understanding o f this disease process. Ulti-
mately, this understanding will improve our abil-
ity to identify strategies most likely to reduce the
burden of illness in this population.
ACKNOWLEDGMENT
The authors gratefully acknowledge the willing collabora-
tion of the nephrologists at St Paul's Hospital, the patients
in the clinic, the excellent echocardiograms produced by Roz
Gillis and Kitty Perry, and the outstanding statistical assis-
tance and collaboration of Ognjenka Djurdjev, from the
Health Research Centre at St Paul's Hospital.
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