editorial - Advances in Clinical and Experimental Medicine
Transkrypt
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. References [1] National Kidney Foundation, K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classi− fication, and stratification. Am J Kidney Dis 2002, 39, Suppl 1, S170–S266. [2] Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998, 32, Suppl 3, S112–S119. [3] Weiner DE, Tighiouart H, Stark PC, Amin MG, MacLeod B, Griffith JL, Salem DN, Levey AS, Sarnak MJ: Kidney disease as a risk factor for recurrent cardiovascular disease and mortality. Am J Kidney Dis 2004, 44, 198–206. [4] Segall L, Covic A: Cardiovascular disease in haemodialysis and peritoneal dialysis: arguments pro haemodialy− sis. Nephrol Dial Transplant 2007, 22, 59–63. [5] The Criteria Committee for the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. Little, Brown & Co. Boston 1994, 9th ed., 253–256. [6] Goldman L, Hashimoto B, Cook EF, Loscalzo A: Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale. Circulation 1981, 64, 1227–1234. [7] Parfrey PS, Foley RN, Harnett JD, Kent GM, Murray D, Barre PE: Outcome and risk factors of ischemic heart disease in chronic uremia. Kidney Int 1996, 49, 1428–1434. [8] Harnett JD, Foley RN, Kent GM, Barre PE, Murray D, Parfrey PS: Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors. Kidney Int 1995, 47, 884–890. [9] Stack AG, Bloembergen WE: A cross−sectional study of the prevalence and clinical correlates of congestive heart failure among incident US dialysis patients. Am J Kidney Dis 2001, 38, 992–1000. Heart Failure in Dialyzed Patients 13 [10] Postorino M, Marino C, Tripepi G, Zoccali C on the behalf of the Calabrian Registry of Dialysis and Transplantation. Prognostic value of the New York Heart Association classification in end−stage renal disease. Nephrol Dial Transplant 2007, 22, 1377–1382. [11] Foley RN, Culleton BF, Parfray PS, Harnett JD, Kent GM, Murray DC, Barre PE: Cardiac disease in dia− betic end−stage renal disease. Diabetologia 1997, 40, 1307–1312. [12] Huang JW, Yen CJ, Chiang HW, Hung KY, Tsai TJ, Wu KD: Adiponectin in peritoneal dialysis patients: a comparison with hemodialysis patients and subjects with normal renal function. Am J Kidney Dis 2004, 43, 1047–1055. [13] Prichard S: Cardiovascular risk in peritoneal dialysis. Contrib Nephrol 2003, 140, 82–90. [14] Foley RN, Herzog CA, Collins AJ: Smoking and cardiovascular outcomes in dialysis patients: the United States Renal Data System Wave 2 study. Kidney Int Suppl 2003, 63, 1462–1467. [15] Pawlaczyk K, Simachowicz A, Czekalski S: Is uric acid or it is not the uremic toxin? Abstr. O−2. 5th Intl. Con. of Uremic Research and Toxicity. Gdańsk/Sopot, 18–20.05.2007. [16] Weijenberg MP, Feskens EJ, Kromhout D: White blood cell count and the risk of coronary heart disease and all−cause mortality in elderly men. Arterioscler Thromb Vasc Biol 1996, 16, 499–503. [17] Furman MI, Becker RC, Yarzebski J, Savegeau J, Gore JM, Goldberg RJ: Effect of elevated leukocyte count on in−hospital mortality following acute myocardial infarction. Am J Cardiol 1996, 78, 945–948. [18] Fuster V, Lewis A: Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from stud− ies of vascular biology. Circulation 1994, 90, 2126–2146. [19] Friedman EA: Death on Dialysis: Preventable or Inevitable? Kluwer Academic Publishers, Dordrecht–Boston –London 1994. [20] Jones CH, Wells L, Stoves JJ, Farquhar F, Woodrow G: Can reduction in extracellular fluid result in increased serum albumin in peritoneal dialysis patients? Am J Kidney Dis 2002, 39, 872–875. [21] Yeun JY, Levine RA, Mantadilok V, Kaysen GA: C−reactive protein predicts all−cause and cardiovascular mor− tality in hemodialysis patients. Am J Kidney Dis 2000, 35, 469–476. [22] Bayes B, Pastor MC, Bonal J, Foraster A, Romero R: Oxidative stress, inflammation and cardiovascular mor− tality in haemodialysis – role of seniority and intravenous ferrotherapy: analysis at 4 years of follow−up. Nephrol Dial Transplant 2006, 21, 984–990. [23] Noordzij M, Korevaar JC, Bos WJ, Boeschoten EW, Dekker FW, Bossuvt PM, Krediet RT: For the NECOSAD Study Group: Mineral metabolism and cardiovascular morbidity and mortality risk: peritoneal dialy− sis compared with haemodialysis patients. Nephrol Dial Transplant 2006, 21, 2513–2520. [24] Block GA, Hulbert−Shearon TE, Levin NW, Port FK: Association of serum phosphorus and calcium x phos− phate product with mortality risk in chronic haemodialysis patients: a national study. Am J Kidney Dis 1998, 31, 607–617. [25] Kronenberg F, Lingenhel A, Neyer U, Lhotta K, Konig P, Auinger M, Wiesholzer M, Andersson H, Dieplinger H: Prevalence of dislipidemic risk factors in hemodialysis and CAPD patients. Kidney Int Suppl 2003, 84, S113–S116. [26] Habib AN, Baird BC, Leypold JK, Cheung AK, Goldfarb−Rumyantzev AS: The association of lipid levels with mortality in patients on chronic peritoneal dialysis. Nephrol Dial Transplant 2006, 21, 2881–2892. [27] Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, Kannel WB, Vasan RS: Obesity and the risk of heart failure. N Eng J Med 2002, 347, 305–313. [28] Lameire N, van Biesen W: Importance of blood pressure and volume control in peritoneal dialysis patients. Perit Dial Int 2001, 21, 206–211. [29] Konings CJ, Koeman JP, Schonck M, Cox−Reijven PL, van Krell B, Gladziwa U, Wirtz J, Gerlag PG, Hoorntje SJ, Wolters J, Heidendal GA, van der Sande FM, Leunissen KM: Assessment of fluid statement in peritoneal dialysis patients. Perit Dial Int 2002, 22, 683–692. [30] Jones CH, Newstead CG: The ratio of extracellular fluid to total body water and technique survival in peritoneal dialysis patients. Perit Dial Int 2004, 24, 363–369. [31] Asghar RB, Green S, Engel B, Davies SJ: Relationship of demographic, dietary, and clinical factors to the hydra− tion status of patients on peritoneal dialysis. Perit Dial Int 2004, 24, 231–239. [32] Ávila−Díaz M, Ventura MJ, Valle D, Vicenté−Martinez M, Garcia−González Z, Cisneros A, Furlong MD, Gómez AM, Prado−Uribe MD, Amato D, Paniagua R: Inflammation and extracellular volume expansion are related to sodium and water removal in patients on peritoneal dialysis. Perit Dial Int 2006, 26, 574–580. [33] Grzegorzewska AE, Młot−Michalska M: Influence of age and gender on bone mineral density in dialysis patients. Adv Perit Dial 2007, 23, 77–81. [34] Grzegorzewska AE, Młot−Michalska M: Assessment of selected factors as influencing bone mineral density in dialysis patients. 8th Eur Perit Dial Meeting, Helsinki, 7–10.07.2007, Book of Abstracts, 13. [35] Shane E, Mancini D, Aaronson K, Silverberg SJ, Seibel MJ, Addesso U, McMahon DJ: Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med 1997, 103, 197–207. [36] Mazess RB: Osteoporosis overestimated in congestive heart failure. Am J Med 1998, 105, 358. 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