editorial - Advances in Clinical and Experimental Medicine

EDITORIAL
Adv Clin Exp Med 2008, 17, 1, 5–14
ISSN 1230−025X
© Copyright by Silesian Piasts
University of Medicine in Wrocław
ALICJA E. GRZEGORZEWSKA, MONIKA MŁOT−MICHALSKA
Differences in Clinical Evaluation of Dialyzed Patients
with or Without Congestive Heart Failure*
Różnice w ocenie klinicznej dializowanych chorych
z zastoinową niewydolnością serca lub bez niej
Chair and Department of Nephrology, Transplantology and Internal Diseases, Karol Marcinkowski University
of Medical Sciences, Poznań, Poland
Abstract
Objectives. To look for clinical and laboratory parameters which might be different in dialysis patients with con−
gestive heart failure (CHF) from those without CHF.
Material and Methods. The CHF group (NYHA I–III) included 13 patients (mean ± SD age: 63.9 ± 13.5 years, medi−
an dialysis vintage: 15.2, range: 7.0–59.6 months). The group without CHF consisted of 17 persons (age: 50.3 ± 18.7
years, dialysis vintage: 24.7, range: 6.3–45.5 months). Clinical and laboratory parameters were compared in both groups.
Results. The CHF patients were older (p = 0.035) and had higher white blood cell counts (8.05±1.87 vs. 6.50 ± 1.89
× 109/l, p = 0.034), serum glucose (141 ± 61 vs. 95.1 ± 14.6 mg/dl, p = 0.022), total body mass (TBM: 77.7 ± 13.8
vs. 68.0 ± 8.8 kg, p = 0.035), body mass index (BMI: 29.5 ± 8.2 vs. 24.5 ± 3.1 kg/m2, p = 0.035), and extracellular
water (ECW) as the percentage of total body water (TBW) (46.5 ± 5.9 vs. 42.7 ± 2.8, p = 0.026). Serum albumin
was lower in the CHF patients (3.38 ± 0.44 vs. 3.69 ± 0.45 g/dl, p = 0.045) and negatively correlated with ECW in
all patients (r = –0.485, p = 0.007). After adjustment for gender and age, only differences in serum glucose, TBM,
and BMI remained significant. There were no significant differences in the other examined parameters.
Conclusions. CHF in dialysis patients is associated with advanced age, glucose intolerance/diabetes, and over−
weight/obesity. Severity of uremic toxicity, hyperlidemia, hyperparathyroidism, inflammation, hypertension, and cig−
arette smoking may not be more evident in this group than in that without CHF (Adv Clin Exp Med 2008, 17, 1, 5–14).
Key words: dialysis, congestive heart failure, age, glucose, obesity.
Streszczenie
Cel pracy. Poszukiwanie klinicznych i laboratoryjnych wskaźników, które mogą różnić dializowanych chorych
z zastoinową niewydolnością serca (z.n.s.) od chorych bez z.n.s.
Materiał i metody. Grupa chorych z z.n.s. (NYHA I–III) obejmowała 13 osób (63,9 ± 13,5 lat, długość dializowa−
nia 15,2; 7,0–59,6 miesięcy). Grupa chorych bez z.n.s. składała się z 17 osób (50,3 ± 18,7 lat, długość dializowa−
nia 24,7; 6,3–45,5 miesięcy). W obu grupach porównywano wskaźniki kliniczne i laboratoryjne.
Wyniki. Chorzy z z.n.s. byli starsi (63,9 ± 13,5 vs 50,3 ± 18,7 lat; p = 0,035), wykazywali większą liczbę białych
komórek krwi (8,05 ± 1,87 vs 6,50 ± 1,89 G/l; p = 0,034), większe stężenie glukozy w surowicy (141 ± 61 vs 95,1
± 14,6 mg/dl; p = 0,022), większą całkowitą masę ciała (TBM: 77,7 ± 13,8 vs 68,0 ± 8,8 kg, p = 0,035), większy
wskaźnik masy ciała (BMI: 29,5 ± 8,2 vs 24,5 ± 3,1 kg/m2; p = 0,035) i większą objętość wody pozakomórkowej
(ECW) wyrażoną jako % całkowitej objętości wody (TBW) (46,5 ± 5,9 vs 42,7 ± 2,8; p = 0,026). Stężenie albu−
miny było mniejsze u chorych z z.n.s. (3,38 ± 0,44 vs 3,69 ± 0,45 g/dl; p = 0,045). U wszystkich chorych stężenie
albuminy ujemnie korelowało z ECW (r = –0,485; p = 0,007). Po uwzględnieniu w analizie statystycznej wpływu
płci i wieku, statystycznie istotne pozostały jedynie różnice w stężeniu glukozy w surowicy, TBM i BMI. Nie by−
ło znamiennych różnic w innych badanych wskaźnikach.
Wnioski. Z.n.s. u dializowanych chorych wiąże się z bardziej zaawansowanym wiekiem, nietolerancją glukozy/cu−
krzycą i nadwagą/otyłością. Ciężkość toksemii mocznicowej, hiperlipidemia, nadczynność przytarczyc, stan zapal−
ny, nadciśnienie tętnicze lub palenie papierosów mogą wyraźnie nie różnić tej grupy od chorych bez z.n.s. (Adv
Clin Exp Med 2008, 17, 1, 5–14).
Słowa kluczowe: dializa, zastoinowa niewydolność serca, wiek, glukoza, otyłość.
* This paper was an oral presentation at the 34th ESAO Conference, Krems, Austria, Aug. 5–8, 2007.
6
A.E. GRZEGORZEWSKA, M. MŁOT−MICHALSKA
Cardiovascular disease is the leading cause of
premature mortality and disability of dialyzed
patients. In end−stage renal failure, cardiovascular
disease accounts for 40–50% of mortality in the
Caucasian adult dialysis population [1] and the
mortality rate due to vascular disease is 15 times
higher than in the general population [2]. Many of
the well−documented (“traditional”) cardiovascular
risk factors in the general population (older age,
obesity, elevated blood pressure, physical inactivi−
ty, cigarette smoking, dyslipidemia, glucose intol−
erance, hyperuricemia, hyperfibrinogenemia) are
also present in end−stage renal disease. The pres−
ence of chronic kidney disease independently pre−
dicts risk for the onset or progression of cardiovas−
cular disease and mortality, even after adjustment
for traditional cardiovascular risk factors [3].
“Uremic” risk factors are related to salt or volume
overload with consequent hypertension, anemia,
increased oxidative tress, chronic inflammatory
process, deranged calcium−phosphate metabolism,
loss of residual renal function, accumulation of
specific uremic toxins, malnutrition, metabolic aci−
dosis, and hemodialysis arterio−venous fistula. All
these risk factors of uremic cardiomyopathy, coro−
nary artery disease, and valvular disease lead to
myocardial damage that may eventually result in
congestive heart failure (CHF) [7]. The aim of the
present study was to look for clinical and laborato−
ry parameters which might be different in patients
with CHF from those without CHF.
Material and Methods
Uremic patients older than 18 years being
treated with peritoneal dialysis (PD) or intermit−
tent hemodialysis (HD) were qualified for the
study. Patients that met at least one of the follow−
ing conditions were excluded: dialysis treatment
less than 6 months, parathyroidectomy during the
last 6 months, a recognized disease which was not
a complication of dialysis treatment and could
influence bone metabolism except for diabetes
mellitus (e.g. gout, rheumatoid arthritis, unbal−
anced thyroid gland diseases, tumors), implanted
medical devices (e.g. pacemaker, infusion pump),
medication with drugs which influence bone
metabolism (e.g. glucocorticosteroids, estrogens,
androgens) currently and within two months
before examination, and acute infection or inflam−
mation during the last month before examination.
The exclusion criteria were introduced in order to
have stable patients during examination and to
diminish possible influences on bone mineral den−
sity (BMD), the measurement of which was
planned in these patients.
The study was performed in 30 uremic
patients. Four patients were treated with HD (3 dial−
ysis sessions per week lasting 4 hours each, dia−
lyzers not reused) and 26 with PD (continuous
ambulatory PD or automated PD). The medical
histories of all the patients were carefully evaluat−
ed with regard to evidence of a diagnosis of car−
diac disease and CHF. Additionally, attention was
paid to cigarette smoking, treatment with corticos−
teroids, sedatives, anticoagulants, anticonvulsive
drugs, and non−steroid anti−inflammatory drugs as
well as coffee intake.
Thirteen of the patients had documented heart
disease with subsequent CHF. This group consisted
of 8 women and 5 men aged 63.9 ± 13.5 years, one
patient on HD and 12 patients on PD, the duration
of dialysis treatment being 15.2 months (range:
7.0–59.6 months). The underlying disorders leading
to end−stage renal failure in this group were diabet−
ic nephropathy (7 cases), chronic tubulointerstitial
nephritis (2 cases), polycystic kidney disease (one
case), hypertensive nephropathy (one case), and
obstructive nephropathy (one case). In one case the
reason for end−stage renal disease was unknown.
Ischemic heart disease was shown in 10 persons
(myocardial infarction in the past was diagnosed in
one case, one patient had undergone a revascular−
ization procedure), atherosclerotic cardiomyopathy
in 2 cases (one with persistent and one with parox−
ysmal atrial fibrillation), hypertrophic cardiomy−
opathy in 1 case, and mitral insufficiency in 1 case.
Arterial hypertension contributed to the develop−
ment of CHF in all 13 patients. Cigarette smoking
was declared by 7 patients.
The dialysis patients with CHF were evaluat−
ed using the New York Heart Association (NYHA)
functional classification of CHF patients (class I:
patients with documented heart disease of any type
who are completely symptom free, class II: slight
limitation in physical activity, symptoms of short−
ness of breath, chest pain, class III: marked limita−
tion in physical activity, symptoms occurring even
with ordinary physical activity, e.g. eating meals,
and class IV: severe limitation of physical activity,
symptoms occurring even at rest, e.g. in a sitting or
lying position) [5]. The examined group included
one patient with NYHA class I, 8 with class II, and
4 with class III. There were no patients with
NYHA class IV.
In the group without CHF were 17 persons
(10 women and 7 men aged 50.3 ± 18.7 years, 3 pa−
tients on HD and 14 patients on PD, duration of
dialysis treatment: 24.7 months, range: 6.3–45.5
months). The underlying disorders leading to end−
stage renal failure in this group were chronic tubu−
lointerstitial nephritis (6 cases), chronic glomeru−
lonephritis (5 cases), and polycystic kidney dis−
7
Heart Failure in Dialyzed Patients
ease (3 cases). In 3 cases the reason for end−stage
renal disease remained unknown. In this group,
13 patients suffered from hypertension, one from
ischemic cardiac disease, and one from diabetes
mellitus without diabetic nephropathy. The patient
with ischemic cardiac disease did not develop
CHF and demonstrated class I according to the
Canadian Cardiovascular Society functional clas−
sification of patients with angina pectoris [6].
Cigarette smoking was declared by 3 patients.
The patients with CHF were analyzed with
respect to their clinical and laboratory parameters
and the obtained data were compared with those of
the patients without CHF. In all patients, fasting
blood samples were drawn to evaluate the serum
concentration of intact parathyroid hormone (iPTH),
total calcium, inorganic phosphate, urea, creatinine,
uric acid, glucose, blood count, serum activity of
total alkaline phosphatase, blood pH, C−reactive pro−
tein (CRP), sedimentation rate, ferritin, total protein,
albumin, and the serum lipid profile. Laboratory
markers were determined using standard methods.
The examined anthropometric markers of nutrition−
al state included total body mass (TBM), body mass
index (BMI), waist circumference, hip circumfer−
ence, and skinfold thickness at four sites (biceps, tri−
ceps, suprailliac and subscapular). All anthropomet−
ric measurements were performed by the younger
co−author according to standard techniques.
Impedance measurements were performed
with the patient in a supine position according to
standard, tetrapolar, whole−body techniques using
a single−frequency (50−kHz) analyzer (Akern−Srl
Systems, Florence, Italy) by the younger co−author.
The electrodes were placed in the standard tetrap−
olar positions (hand−foot). A current of 800 µA
was introduced at the distal electrodes and the
voltage drop was detected by the proximal elec−
trodes. Total body resistance and reactance values
were collected and used in specific formulas sup−
plied by the manufacturer to determine body com−
position, i.e. (total body water (TBW), body cell
mass, extracellular water (ECW), intracellular
water (ICW), lean body mass (LBM), and fat body
mass. BMD was examined by dual−energy X−ray
absorptiometry (DEXA). Assessment of BMD
was performed at two sites, i.e. the femoral neck
(FN) and lumbar spine from the second to the
fourth lumbar vertebra (L2–L4). Blood pressure
was measured after 30 minutes of rest.
In the PD patients the study measurements
were performed with a “dry” peritoneal cavity after
drainage of the dialysate, which was not replaced
until completion of all the study procedures. In the
HD patients a blood sample was taken before the
midweek HD session; other examinations were
started 30 minutes after an HD session.
The normality of the data distribution was
assessed using the Kolmogorov−Smirnov test and
the values are presented as the mean and standard
deviation or as the median and range. Comparisons
were performed for the unadjusted results, those
adjusted for gender and age, and those adjusted for
gender, age, coffee intake, and treatment with cor−
ticosteroids, sedatives, anticoagulants, anticonvul−
sive drugs, and non−steroid anti−inflammatory
drugs. The latter selection was done to avoid the
influence of the mentioned factors on an evaluation
of changes in BMD as possibly related to CHF.
ANCOVA methodology was used for comparisons.
Correlations were checked using the Spearman
correlation coefficient. Comparisons of prevalence
in different groups were assessed by the chi−
squared test with the Yates correction. A p value
below 0.05 was judged to be significant.
Results
The patients with CHF were significantly
older than those without (p = 0.035). The two
groups were not different with respect to gender
distribution, dialysis modality, dialysis vintage,
hypertension diagnosis, and cigarette smoking.
Diabetes mellitus (p = 0.001), diabetic nephropa−
thy (p = 0.003), and ischemic cardiac disease (p =
= 0.001) were shown more frequently in the
patients with CHF.
Significant differences in the examined para−
meters in the dialyzed patients with CHF compared
with the group without CHF are presented in Table 1.
In the entire group of patients, serum albumin con−
centration correlated with ECW (r = –0.485, p =
0.007). After adjustment of the results for gender
and age, significance was maintained for serum glu−
cose concentration, TBM, thickness of the triceps
skinfold and the subscapular skinfold, BMI, and
ECW. Additionally, TBW was significantly higher
in the patients with CHF. After adjustment of the
results for gender, age, coffee intake, and treatment
with corticosteroids, sedatives, anticoagulants, anti−
convulsive drugs, and non−steroid anti−inflammato−
ry drugs, significant differences remained for white
blood cell (WBC) count, serum glucose concentra−
tion, TBM, thickness of the triceps skinfold and the
subscapular skinfold, BMI, and ECW.
There were no significant differences between
the groups in blood pressure, serum lipid profile,
total protein, hemoglobin, platelets, iPTH, calci−
um, phosphate, total alkaline phosphatase, blood
pH, urea, creatinine, uric acid, ferritin, CRP, and
sedimentation rate (Table 2). BMD assessed at the
FN and L2–L4 was similar in the two groups
(Table 3).
8
A.E. GRZEGORZEWSKA, M. MŁOT−MICHALSKA
Table 1. Significant differences (p < 0.05) in results obtained in dialyzed patients with and without congestive heart failure
(CHF)
Tabela 1. Znamienne różnice (p < 0,05) w wynikach stwierdzonych u dializowanych chorych z lub bez zastoinowej
niewydolności serca (z.n.s.)
Parameter
(Wskaźnik)
Patients with CHF
(Chorzy z z.n.s.)
Patients without CHF
(Chorzy bez z.n.s.)
Total body mass – kg
(Całkowita masa ciała – kg)
77.7 ± 13.8
68.0 ± 8.8 a, c
Triceps skinfold thickness – mm
(Grubość fałdu skórnego nad mięśniem trójgłowym – mm)
14.8 ± 6.0
9.9 ± 5.5 a, c
Subscapular skinfold thickness – mm
(Grubość fałdu skórnego pod łopatką – mm)
21.2 ± 8.5
12.9 ± 5.6 a, c
Waist circumference – cm
(Obwód talii – cm)
103 ± 14
91.4 ± 9.1
Hip circumference – cm
(Obwód bioder – cm)
107 ± 11
96.8 ± 8.0
Body mass index – kg/m2
(Wskaźnik masy ciała BMI – kg/m2)
29.5 ± 8.2
24.5 ± 3.1a, c
Fat body mass – kg
(Tłuszczowa masa ciała – kg)
25.2 ± 8.2
19.4 ± 6.2
TBW – l
40.9 ± 8.3
36.2 ± 6.5 b
ECW – l
19.1 ± 5.1
15.1 ± 2.3 a, c
ECW as TBW – %
46.5 ± 5.9
42.7 ± 2.8
ICW as TBW – %
53.5 ± 5.9
57.3 ± 2.7
ECW/ICW
0.89 ± 0.23
0.74 ± 0.10
Serum albumin – g/dl
(Albumina w surowicy – g/dl)
3.38 ± 0.44
3.69 ± 0.45
Serum glucose – mg/dl
(Glukoza w surowicy – mg/dl)
141 ± 61
95.1 ± 14.6
White blood cells – 109/l
(Białe komórki krwi – 109/l)
8.05 ± 1.87
6.50 ± 1.89c
ECW – extracellular water (woda pozakomórkowa).
ICW – intracellular water (woda wewnątrzkomórkowa).
TBW – total body water (całkowita ilość wody w ustroju).
As compared with the unadjusted results:
a – differences remained significant after adjustment for age and gender,
b – difference became significant after adjustment for age and gender,
c – differences remained significant after adjustment for age, gender, and treatment with corticosteroids, sedatives, anti−
coagulants, anticonvulsive drugs and non−steroid anti−inflammatory drugs as well as coffee intake.
ECW – woda pozakomórkowa.
ICW – woda wewnątrzkomórkowa.
TBW – całkowita ilość wody w ustroju.
W porównaniu do wyników nieweryfikowanych:
a – różnice pozostały znamienne po zweryfikowaniu względem wieku i płci,
b – różnica stała się znamienna po zweryfikowaniu względem wieku i płci,
c – różnice pozostały znamienne po zweryfikowaniu względem wieku, płci, leczenia kortykosteroidami, lekami sedatywny−
mi, antykoagulantami, lekami przeciwdrgawkowymi, niesteroidowymi lekami przeciwzapalnymi oraz picia kawy.
Discussion
Patients’ Characteristics
and CHF
In dialysis patients, older age was a significant
and independent predictor of development of
ischemic cardiac disease [7], it was independently
associated with CHF at baseline, and was a risk fac−
tor for its development during dialysis therapy [8].
A cross−sectional study of incident US dialysis
patients showed that age and female sex were signif−
icantly associated with the presence of CHF [9]. The
Calabrian Registry of Dialysis and Transplantation
showed that dialyzed patients with more severe CHF
were older and had a higher proportion of females
9
Heart Failure in Dialyzed Patients
Table 2. Selected results obtained in dialyzed patients with and without congestive heart failure (CHF) which were not sta−
tistically different (p ≥ 0.05)
Tabela 2. Wybrane wyniki stwierdzone u dializowanych chorych z lub bez zastoinowej niewydolności serca (z.n.s.), które
nie różniły się znamiennie (p ≥ 0.05)
Parameter
(Wskaźnik)
Patients with CHF
(Chorzy z z.n.s.)
Patients without CHF
(Chorzy bez z.n.s.)
Hemoglobin – g/dl
(Hemoglobina – g/dl)
11.4 ± 1.1
11.5 ± 1.2
C−reactive protein – mg/l
(Białko C−reaktywne – mg/l)
0.87 (0.00 – 31.3)
2.00 (0.00 – 17.6)
Sedimentation rate – mm/h
(Odczyn opadania – mm/godz.)
69.2 ± 37.3
49.9 ± 21.9
Parathyroid hormone – pg/ml
(Parathormon – pg/ml
155 (12.3 – 913)
272 (80.1 – 1967)
Total calcium – mg/dl
(Wapń całkowity – mg/dl)
8.73 ± 0.95
9.08 ± 0.81
Phosphate – mg/dl
(Fosforany – mg/dl)
5.34 ± 1.40
5.35 ± 1.36
Alkaline phosphatase – IU/l)
(Fosfataza zasadowa – IU/l)
76.7 ± 23.1
88.5 ± 41.3
Creatinine – mg/dl
(Kreatynina – mg/dl)
7.57 ± 2.67
8.58 ± 2.98
Uric acid – mg/dl
(Kwas moczowy – mg/dl)
5.98 ± 0.85
5.78 ± 0.73
Total cholesterol – mg/dl
(Cholesterol całkowity – mg/dl)
207 ± 37
212 ± 53
Triglycerides – mg/l
(Triglicerydy – mg/l)
193 ± 103
175 ± 74
LDL−cholesterol – mg/dl
128 ± 34
124 ± 41
HDL−cholesterol – mg/dl
37.4 ± 7.5
42.8 ± 11.0
Total protein – g/dl)
(Białko całkowite – g/dl)
6.91 ± 0.76
6.93 ± 0.50
Blood pH
(pH krwi)
7.37 ± 0.04
7.38 ± 0.05
HCO3− – mmol/l
23.3 ± 3.0
23.5 ± 3.9
Ferritin – ng/ml
(Ferrytyna – ng/ml)
451 ± 263
304 ± 198
143 ± 19
132 ± 21
82.7 ± 13.1
83.1 ± 17.0
67.9 ± 8.5
71.4 ± 8.8
Blood pressure – mm Hg
(Ciśnienie krwi – mm Hg)
• systolic (skurczowe)
• diastolic (rozkurczowe)
LBM/TBM (%)
LBM – lean body mass.
TBM – total body mass.
LBM – beztłuszczowa masa ciała.
TBM – całkowita masa ciała.
[10]. In the present study, CHF in dialyzed patients
was also associated with older age, but the gender
distributions were similar in the examined groups.
Diabetes mellitus in dialysis patients was inde−
pendently associated with the development of
ischemic cardiac disease [7] and CHF at baseline
[8]. In incident US dialysis patients, diabetes was
also significantly associated with the occurrence
of CHF [9]. In the examined patients, diabetes
mellitus, subsequent diabetic nephropathy, and
elevated serum glucose levels were observed with
significantly higher prevalence in the CHF group.
In diabetic patients on dialysis, concentric left ven−
tricular hypertrophy, ischemic heart disease, and
CHF were found in 50, 32, and 48% of patients,
respectively, whereas these cardiac findings were
significantly less common in the non−diabetic
patients (38, 18, and 24%, respectively) [11].
10
A.E. GRZEGORZEWSKA, M. MŁOT−MICHALSKA
Table 3. Bone mineral density (BMD) in dialyzed patients with and without congestive heart failure (CHF)
Tabela 3. Mineralna gęstość kości (BMD) u dializowanych chorych z lub bez zastoinowej niewydolności serca (z.n.s.)
Parameter
(Wskaźnik)
Femoral neck
(Szyjka kości udowej)
Lumbar spine
(Odcinek lędźwiowy kręgosłupa)
BMD (g/cm2)
0.771 ± 0.106
1.154 ± 0.280
% YA
77.8 ± 12.1
97.4 ± 21.7
% AM
89.0 ± 14.3
105.5 ± 22.9
T−score
–2.110 (–3.390 – –0.170)
–0.860 (–3.950 – 4.070)
Z−score
–1.010 (–2.360 – 1.400)
0.550 (–4.410 – 4.490)
BMD (g/cm2)
0.847 ± 0.170
1.013 ± 0.236
% YA
86.2 ± 21.9
86.2 ± 17.6
% AM
96.1 ± 21.0
90.4 ± 17.2
T−score
–1.290 (–4.060 – 2.370)
–1.570 (–3.130 – 1.730)
Z−score
–0.505 (–2.360 – 2.970)
–1.095 (–2.600 – 2.180)
Patients with CHF (Chorzy z z.n.s.)
Patients without CHF (Chorzy bez z.n.s.)
AM – BMD of age matched.
YA – BMD of young adults.
AM – BMD odniesiona do wieku chorego.
YA – BMD odniesiona do młodych dorosłych.
PD patients are exposed to much greater
amounts of glucose than HD patients, potentially
leading to metabolic disturbances, insulin resis−
tance [12], and hyperlipidemia [13], also in non−
diabetic persons. It is a matter of controversy how
dialysis modality and duration of dialysis treatment
influence heart disease and cardiac outcome [4]. In
the present study, statistical analysis could not sup−
port any opinion on this subject due to the small
number of HD patients in the entire examined
group. Patients with CHF and those without this
complication were, however, affected by dialysis
glucose uptake in a similar manner and duration.
Arterial hypertension, like peritoneal glucose
absorption, was shown in both groups with com−
parable prevalence; however, with coexisting car−
diac diseases, both could be more dangerous than
in the absence of such co−morbidity. Additionally,
although there were no significant differences in
systolic and diastolic pressures between the
groups, the patients with CHF showed a mean sys−
tolic blood pressure of over 140 mm Hg. Thus,
hypertension as a risk factor for cardiovascular
disease was more pronounced in this group. This
finding is compatible with results indicating
hypertension during follow−up on dialysis as a fac−
tor associated with the development of chronic
cardiac disease [7] and CHF [8, 9] in dialyzed
patients. On the other hand, blood pressure in the
group with CHF in the present study was still not
as low as one can see in advanced heart failure.
Ischemic cardiac disease was the most fre−
quently diagnosed heart disease in the dialyzed
patients of the present study. It was independently
associated with CHF at baseline and was a signif−
icant risk factor for recurrence of CHF in dialyzed
patients [8].
As in the general population, cigarette smok−
ing was also shown to be associated with an
increased cardiovascular risk in dialysis patients
[14]. In the present study, smoking was declared
by 33% of all patients and its prevalence did not
reach statistical significance when the patients
with and without CHF were compared.
Laboratory Parameters
and CHF
Uremic retention products add to cardiovascu−
lar damage, but exactly which of these substances
are cardiotoxic and due to what mechanisms is
largely unclear [4]. Advanced oxidation protein
products, advanced glycation end−products, asym−
metric dimethyl arginine and homocysteine are
usually considered as uremic toxins that may
influence cardiac function. Routinely examined
small−molecule uremic toxins (urea, creatinine,
uric acid) do not seem to influence cardiac func−
tion [15]. In the present study, small uremic toxin
concentrations were also not significantly different
in the two examined groups.
In dialyzed patients with a mean hemoglobin
level of 8.8 ± 1.5 g/dl, each 1 g/dl decrease in
11
Heart Failure in Dialyzed Patients
mean hemoglobin was independently associated
with the presence of left ventricular dilatation [8].
Anemia during dialysis therapy was a risk factor
for the development and recurrence of CHF [8],
but it had no independent association with the
development of ischemic heart disease [7].
However, in the era of erythropoiesis−stimulating
agents there is no justified reason to find such low
mean levels of hemoglobin in the entire group of
patients. In the present study, differences in hemo−
globin level in patients with or without CHF were
not observed, so they could not influence cardiac
function.
In the general population, increased total
WBC count has been found to correlate with
increased cardiovascular mortality in elderly men
[16] and with increased mortality following
myocardial infarction in general [17]. Increased
total WBC count has also been implicated as a bio−
marker of atherosclerosis [18]. An association
between WBC count and mortality in end−stage
renal disease has also been suggested in the past
[19]. The present study showed that CHF in dia−
lyzed patients is associated with higher WBC
count (but usually not increased) compared with
values observed in dialyzed persons without CHF.
Low serum albumin concentration was shown
as a factor associated with the development of
ischemic heart disease [7] and CHF in HD and PD
patients [8, 9]. In the present study, lower serum
concentration of albumin in patients with CHF
may be at least partially explained by a dilution−
concentration effect because there was a signifi−
cant negative correlation between serum albumin
level and volume of ECW in the entire group of
dialyzed patients. A dilutional component of
hypoalbuminemia was also noted in PD patients,
irrespective of heart failure [20].
Inflammation is a commonly accepted cardio−
vascular risk factor. However, CRP predicts not
only cardiovascular, but all−cause mortality in dia−
lyzed patients [21]. Moreover, in a study by Baýes
et al. [22], serum concentration of CRP was not
a good predictive factor of cardiovascular mortali−
ty during a four−year follow−up, possibly because
of the slight positive correlation that existed
between CRP and age. In the present study, adjust−
ment of the results for age did not reveal a signifi−
cant difference in serum CRP level between
patients with and without CHF. Thus, inflammato−
ry state, at least expressed by serum CRP concen−
tration, was not a predictor of occurrence of CHF
in dialyzed patients in the present study.
Significantly elevated serum phosphate level
(≥ 6.8 mg/dl vs. < 6.8 mg/dl) and serum calcium
concentration (≥ 8.0 mg/dl vs. < 8.0 mg/dl) were
associated with more CHF in dialyzed patients
(HD and PD) [9]. Moreover, plasma serum con−
centrations of phosphate and iPTH above the
K/DOQI threshold increased the relative risk of
cardiovascular disease−related hospitalization in
HD patients [23] and elevated serum phosphate
and iPTH levels as well as Ca x P increased car−
diovascular mortality risk both in HD [24] and PD
[23] patients. In the present study, the management
of calcium−phosphate disturbances was as intensive
as possible in both groups, so differences in the
serum concentrations of calcium, phosphate, and
iPTH as well as total alkaline phosphatase activity
could not be observed. Their influence on dialyzed
patients was probably similar in both groups.
The examined patients showed hyperlipi−
demia, but it was not significantly different
between the two groups. Abnormal serum lipid
profile is frequently seen, especially in patients
treated with PD [25]. There is, however, evidence
that with PD neither total cholesterol levels nor
hypertriglyceridemia are related to worse outcome
in patients with good nutritional status (serum
albumin above 3.5 g/dl). Moreover, low serum
cholesterol levels were associated with more CHF
in both incident HD and PD US patients [9].
Aggressive lowering of plasma cholesterol in PD
patients is not supported by clinical analyses,
although treatment of hypertriglyceridemia may
be warranted with triglyceride levels > 200 mg/dl
[26]. In the opinion of the present authors, the lat−
ter should always be clinically recommended in
dialyzed patients with cardiac diseases.
Anthropometric Parameters
and CHF
The LBM/TBM ratio, as an additional marker
to serum albumin concentration in evaluating pro−
tein nutrition, was not significantly different in the
two examined groups. Other anthropometric para−
meters (TBM, thickness of the triceps and sub−
scapular skinfolds, BMI) indicated a greater fat
mass in patients with CHF. It should be kept in
mind that this group consisted mainly of patients
with diabetes mellitus, who are usually over−
weight. A recent report from the Framingham
Heart Study indicates that increased body mass in
itself is an independent risk factor for developing
heart failure [27].
Bioimpedance Records and CHF
An increase in ECW due to ineffective ultra−
filtration provided by dialysis treatment is an
important factor in the pathogenesis of cardiovas−
cular disease in dialyzed patients. The adverse car−
12
A.E. GRZEGORZEWSKA, M. MŁOT−MICHALSKA
diac effects of fluid overload may be mediated
through both hypertension and the direct hemody−
namic effects of ECW volume expansion on the
heart [28]. It was shown that ECW measured by
bioelectric impedance does not correlate with left
atrial diameter and left ventricular end diastolic
diameter in PD patients [29]. On the other hand,
cardiac failure may contribute to overhydration in
these patients.
The results of the present study indicate higher
water content in patients with CHF than in those
without this disorder. Jones et al. [30] suggested that
patients with cardiac failure would be expected to
have an increased ECW/TBW ratio. The results of
the present study showed higher ECW/TBW,
ICW/TBW, and ECW/ICW ratios in dialysis
patients with CHF than in those without it, which is
in agreement with the above concept. However, it is
a well−known phenomenon that ECW expansion is
related to gender and age, also in dialyzed patients
[31]. Although there were no significant differences
in the gender distributions between the examined
groups, the results with adjustment for both gender
and age were compared. Using such a procedure,
the differences in body−water parameters became
insignificant, indicating a poor relation to CHF, at
least to NYHA classes I–III.
A coincidence of higher ECW as %TBW,
lower serum albumin concentration, and higher
serum glucose level was shown in PD patients
with serum CRP concentrations ≥ 3 mg/l com−
pared with those with CRP < 3 mg/l [32]. It has to
be noted that patients with clinical data of coro−
nary artery disease, CHF, or peripheral artery dis−
ease were not considered for inclusion in that
study [32]. The data of the present study indicate
that concomitant occurrence of greater body mass
and CHF in dialyzed patients is also associated
with these aforementioned symptoms, even if the
serum CRP concentration is similar to that shown
in patients without CHF and with lower anthropo−
metric indices.
Bone Mineral Density and CHF
Earlier studies by the present authors revealed
influences of age, gender, coffee abuse, and anti−
coagulation on BMD in examined patients [33,
34]. No significant differences in BMD could be
shown in these patients grouped by occurrence of
CHF when the analysis was performed with
adjustment for the mentioned factors which were
known to influence BMD. In a study by Shane et
al. [35], osteopenia or osteoporosis were observed
in approximately half of the patients with severe
CHF (NYHA functional class III or IV). Abnormal
calciotropic hormone concentrations were associ−
ated with evidence of increased bone resorption,
but were not related to BMD in this cross−section−
al study [35]. According to other authors [36], the
prevalence of bone loss could, however, be over−
estimated in the above−mentioned study.
The authors conclude that the results of the
present study suggest that CHF (NYHA function−
al classes I–III) is significantly associated with
advanced age, glucose intolerance/diabetes, and
overweight/obesity in dialysis patients. Severity of
uremic toxicity, hyperlidemia, hyperparathy−
roidism, inflammation, hypertension, or cigarette
smoking may not be more evident in this group
than in that without CHF. BMD is similar in dia−
lyzed patients with or without CHF.
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14
A.E. GRZEGORZEWSKA, M. MŁOT−MICHALSKA
Address for correspondence:
Alicja E. Grzegorzewska
Chair and Department of Nephrology, Transplantology and Internal Diseases
Karol Marcinkowski University of Medical Sciences
Przybyszewskiego 49
60−355 Poznań
Poland
Tel.: +48 61 869 17 00
Mobile phone: (+48) 696 084 487
E−mail: [email protected]
Conflict of interest: None declared
Received: 8.11.2007
Accepted: 7.02.2008