|Year : 2017 | Volume
| Issue : 2 | Page : 52-57
Cardiovascular risk assessment in hemodialysis patients: relation to malnutrition, inflammation, and body fluid determined by bioelectrical impedance
Essam El Din Hassan El Kashef1, Sameh Morsi Arab2, Yasmine Salah Naga1, Shaimaa Elsayed Mohamed Mohamed3, Montasser Mohammed Hussein Zeid1
1 Department of Internal Medicine and Nephrology, Alexandria University, Alexandria, Egypt
2 Department of Cardiology and Angiology, Alexandria University, Alexandria, Egypt
3 Alexandria Fever Hospital, Alexandria, Egypt
|Date of Submission||15-Jan-2017|
|Date of Acceptance||07-Feb-2017|
|Date of Web Publication||21-Sep-2017|
Shaimaa Elsayed Mohamed Mohamed
Nephrologist at Alexandria Fever Hospital, Alexandria
Source of Support: None, Conflict of Interest: None
Background Cardiovascular disease prevalence increases as the renal function declines across the spectrum of chronic kidney disease. In end-stage renal disease (ESRD), cardiovascular mortality may even account for 50% of mortality. The coexistence of malnutrition, inflammation, and atherosclerosis (the so-called MIA syndrome) has been observed in hemodialysis (HD) patients and is considered one of the cardiovascular risk factors unique to this population. In addition, chronic fluid overload is frequently present in HD patients.
Objective The aim of the present study was to investigate the relationship between nutrition, inflammation, atherosclerosis, the presence of overhydration (OH) measured using multifrequency bioimpedance analysis, and the cardiac condition as assessed using echocardiography in HD patients.
Patients and methods Thirty HD patients (mean age: 41.13±12.77 years, 15 were male and 15 were female) were enrolled in the Dialysis Unit of the Alexandria Main University Hospital. Serum albumin was used as a nutritional marker, and serum C-reactive protein (CRP) was used as an inflammatory marker. Doppler ultrasonography was performed to measure the carotid artery intimamedia thickness (CA-IMT) to assess the presence of atherosclerosis. Extracellular water (ECW), OH, and OH/ECW were measured using multifrequency bioimpedance analysis to detect OH. Cardiac condition was determined by means of echocardiographic measurement of the left ventricular mass index and ejection fraction (EF).
Results Only two (6.6%) of the studied patients had a low albumin, 26 (86.6%) patients had a positive CRP, 23 (76.6%) patients had high carotid intimamedia thickness (CIMT), and nine (30%) patients had atherosclerotic plaques in the carotid artery. Bioimpedance showed OH in 15 (50%) patients, who had an OH/ECW ratio of more than 0.15. Echocardiography showed high left ventricular mass index in 55.5% and low EF in 16.6%. The presence of inflammation as indicated by CRP was associated with higher CIMT (r=0.520, P=0.003), higher interventricular wall thickness (IVWT) (r=0.469, P=0.007), and lower EF (r=−0.610, P<0.001). OH as assessed by OH/ECW was associated with higher CRP (r=0.553, P=0.002), higher CIMT (r=0.655, P<0.001), and lower EF (r=−0.742, P<0.001).
Conclusion Inflammation, atherosclerosis, and fluid overload are prevalent in ESRD patients on MHD. Both inflammation and OH are correlated with increased CIMT and low EF, implicating them in the cardiovascular diseases commonly found in ESRD patients.
Keywords: bioimpedance, cardiovascular risk, inflammation
|How to cite this article:|
El Kashef EH, Arab SM, Naga YS, Mohamed SM, Zeid MH. Cardiovascular risk assessment in hemodialysis patients: relation to malnutrition, inflammation, and body fluid determined by bioelectrical impedance. J Egypt Soc Nephrol Transplant 2017;17:52-7
|How to cite this URL:|
El Kashef EH, Arab SM, Naga YS, Mohamed SM, Zeid MH. Cardiovascular risk assessment in hemodialysis patients: relation to malnutrition, inflammation, and body fluid determined by bioelectrical impedance. J Egypt Soc Nephrol Transplant [serial online] 2017 [cited 2018 Feb 21];17:52-7. Available from: http://www.jesnt.eg.net/text.asp?2017/17/2/52/215228
| Introduction|| |
In patients with chronic kidney disease, the cardiovascular risk and mortality increase as the glomerular filtration rate decreases due to multiple traditional and nontraditional risk factors . The risk is highest in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD), at which stage cardiovascular disease (CVD) may be responsible for as much as 50% of mortality . The 1-year mortality may even rise to over 90% following a myocardial infarction in the dialysis population .
The coexistence of malnutrition, inflammation, and atherosclerosis (MIA) has been observed in HD patients and has been collectively referred to as the MIA syndrome. The MIA syndrome is considered one of the main risk factors for mortality in ESRD patients . In particular, inflammation, as indicated by serum C-reactive protein (CRP) levels, remains an integral risk factor for peripheral atherosclerosis and cardiac ischemia .
Another unique cardiovascular risk factor in the dialysis population is chronic fluid overload (FO) . FO can lead to hypertension as well as cardiac volume and pressure overload, which all contribute to the development of CVD, including left ventricular (LV) hypertrophy, heart failure, and pulmonary edema ,. However, chronic volume deficit can lead to intradialytic hypotension, muscle cramps, and shock . Therefore, good fluid balance is essential in dialysis patients to achieve ideal blood pressure control and cardiac health. The first step to reach that goal is to accurately assess the hydration state of the patients.
Despite its importance, patients’ volume status is most commonly clinically evaluated. Interdialytic weight changes, the degree of edema, and blood pressure are the most frequently used markers of hydration status in dialysis units, but they are largely unreliable . An objective tool to measure body fluid composition is the multifrequency bioelectrical impedance analysis (m-BIA) technique. This inexpensive, noninvasive method can accurately determine the degree of overhydration (OH) as well as the nutritional status of patients .
The objective of the present study was to examine how these different factors affect each other and affect the cardiac condition in HD patients.
| Patients and methods|| |
After obtaining the approval of the ethics committee of the Faculty of Medicine of the Alexandria University, 30 ESRD patients (50% male and 50% female) on maintenance HD for at least 6 months were recruited from the dialysis units of the Alexandria University Hospitals. Informed consent from the patients was taken before conducting the study. Patients with hypotension, known chronic inflammatory disease including systemic lupus erythematosis and vasculitis, malignancy, liver cirrhosis, gastrointestinal diseases, history of a systemic infection within 1 month before entry into the study, and patients with catheters such as vascular access were excluded.
Data including name, age, sex, past medical history, and data obtained from clinical examination were recorded at enrollment. Laboratory investigations included lipid profile, serum albumin, and CRP.
To detect atherosclerosis, the common carotid artery intimamedia thickness (CA-IMT) was assessed by using a high-resolution color Doppler ultrasound unit. After visualizing the double echogenic line of the arterial wall, the carotid intimamedia thickness (CIMT) was measured, including the inner echogenic line representing the lumen–intima interface and the adjacent hypoechoic and excluding the outer echogenic line, which represents the media–adventitia interface.
M-mode transthoracic echocardiography was performed according to the recommendations of the American Society of Echocardiography  just before performing the m-BIA, mainly to assess the left ventricular mass index (LVMI) and ejection fraction (EF).
Body fluid composition was assessed using m-BIA, which relies on measuring the flow of current through the body . The flow of current depends on the frequency applied. At low frequencies, the current cannot bridge the cellular membrane and will pass predominantly through the extracellular space. At higher frequencies, penetration of the cell membrane occurs and the current is conducted by both the extracellular water (ECW) and intracellular water. The impedance values were obtained at frequencies of 5, 50, 100, and 200 kHz. The following variables were measured: ECW, OH, and OH/ECW using a cutoff of greater than 0.15 as an indicator of OH ,.
SPSS version 20.0 (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. Data are presented as mean±SD. Proportions were compared using χ2 analysis. Student’s t-test, analysis of variance, and Mann–Whitney tests were used for group comparison. Correlation analysis was performed using Spearman’s correlation coefficient. A P value of less than 0.05 (two-sided) was regarded as statistically significant.
| Results|| |
The study included 30 ESRD patients on maintenance HD in the dialysis units of the Alexandria University Hospitals. In all, 50% of patients were male and 50% were female. The studied variables are summarized in [Table 1] and [Table 2]. The mean age of the patients was 41.13±12.77 years. Total cholesterol was high in only three (10%) patients and triglycerides were high in 16 (53.3%) patients, whereas the others had normal values.
Serum albumin as a marker of nutrition ranged from 3.40 to 4.90 g/dl with a mean of 4.03±0.39 g/dl, with only two (6.6%) patients having low serum albumin (<3.5 g/dl). CRP as a marker of inflammation ranged from 1.05 to 47.54 with a mean of 12.64±13.65. Twenty-six (86.6%) patients had a positive CRP. As for the lipid profile, total cholesterol was high in only three (10%) patients and triglycerides were high in 16 (53.3%) patients.
The common carotid intimamedia thickness ranged from 0.10 to 0.95 with a mean of 0.70±0.20 mm. Twenty-three (76.6%) patients had increased CIMT. Carotid Doppler also showed plaque in 30% of the examined patients. The EF ranged from 35 to 87% with a mean of 62.11±12.80%. Five (16.7%) patients had low EF. LVMI ranged from 63.0 to 178.0 with a mean of 118.40±31.49 g/m2, revealing that 20 (66.7%) patients had LV hypertrophy.
Bioimpedance measurements included the ECW, which ranged from 10.70 to 62.30 with a mean of 20.23±12.27 l, the OH, which ranged from 2.70 to 6.0 with a mean of 2.10±1.88 l, and the OH/ECW ranged from 0.17 to 0.28 with a mean of 0.11±0.10. According to the OH/ECW, 50% of the patients were overhydrated at an OH/ECW ratio of more than 0.15.
Because of the small number of patients with low albumin (6.6%), we could not analyze the effect of malnutrition on inflammation, CVD, and body composition.
CRP was positively correlated with IVWT (r=0.496, P=0.007), CIMT (r=0.408, P=0.025, [Figure 1]), and OH/ECW (r=0.553, P=0.002). It was negatively correlated with EF (r=−0.610, P=0.002). There was a significant positive correlation between CIMT ([Table 3] and [Table 4]) and OH/ECW (r=0.655, P<0.001), ECW (r=0.392, P=0.032), IVWT (r=0.499, P=0.007), and CRP (r=0.408, P=0.025). Patients with carotid plaque had significantly higher age (49.33±11.65 vs. 37.62±11.78, P=0.018) and higher low-density lipoprotein-cholesterol (127.67±22.54 vs. 100.0±28.58, P=0.016).
|Figure 1 Correlation between C-reactive protein and carotid artery intimamedia thickness.|
Click here to view
OH/ECW was positively correlated with CRP (r=0.553, P=0.002, [Figure 2]) and the CIMT (r=0.655, P<0.001) ([Figure 3]) and negatively with the EF of the heart (r=−0.742, P<0.001).
|Figure 2 Correlation between C-reactive protein and overhydration/extracellular water.|
Click here to view
|Figure 3 Correlation between overhydration/extracellular water and intimamedia thickness (n=30).|
Click here to view
| Discussion|| |
ESRD patients on maintenance HD are at increased cardiovascular risk secondary to the complex interplay of multiple traditional and nontraditional risk factors. The MIA syndrome and FO are among these factors ,. FO and OH are common in HD patients, yet basing its detection on clinical assessment is often unsuccessful. m-BIA to assess the body composition is a practical, objective method for assessment of the patients’ hydration status ,,,.
In this study, the number of malnourished patients was small and we could not analyze the effect of malnutrition on inflammation, CVD, and body composition. Other studies, however, found a link between hypoalbuminemia in dialysis patients and inflammation and CVDs . For example, Beddhu et al.  showed an association between serum albumin level and CVD in chronic HD patients. This link is believed to be secondary to albumin acting as a negative acute phase reactant rather than a marker of poor nutrition. Kaysen et al.  reported that albumin levels are mainly correlated with inflammation, better reflecting the presence of inflammation rather than nutritional status in dialysis patients.
In the present study, CRP was positive in 26 (86.6%) patients. CIMT assessment was used to detect atherosclerosis. CIMT was high in 23 (76.6%) patients and plaque was found in nine (30%) patients. CRP and CIMT were significantly correlated (r=0.408, P=0.025). Inflammation is a nontraditional risk factor believed to play a role in mediating cardiovascular risk in the general population as well as in different stages of CKD . Wanner et al.  further identified an increased overall and cardiovascular mortality in HD patients associated with inflammation.
CRP was also correlated to OH/ECW, a marker of FO (P=0.002, r=0.553). Other studies found a bidirectional relationship between inflammation and extracellular FO ,,. Inadequate water and sodium removal may act as a inflammatory stimulus, whereas inflammation may lead to further ECW accumulation ,.
An additional finding of the present study was the presence of a significant negative correlation between OH/ECW ratio and EF (r=−0.742, P<0.001). Other studies such as that by Schreiber and Collins reported that patients entering chronic dialysis display frank symptoms of heart failure and because as much as 48% of asymptomatic patients stabilized on dialysis have compromised LV function ,.
However, LVMI did not significantly change with the degree of OH (r=−0.214, P=0.256). In contrast, Fagugli et al.  observed an association between ECW and LV mass and hypertension in hemodialysis patients . Harnett et al.  reported that heart failure is a highly prevalent complication in long-term HD.
| Conclusion|| |
Inflammation, atherosclerosis, and FO are prevalent in ESRD patients on maintenance HD. FO as indicated by elevated OH/ECW measured by m-BIA was significantly correlated with markers of inflammation and atherosclerosis and negatively correlated with cardiac function in HD patients. The detection and appropriate management of OH, inflammation, and atherosclerosis may allow the reduction of cardiovascular risk in this high-risk population.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sarnak MJ, Levey AS. Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis 2000; 35(Suppl 1): S117–S131.
Drey N, Roderick P, Mullee M, Rogerson M. A population based study of the incidence and outcomes of diagnosed chronic kidney disease. Am J Kidney Dis 2003;42:677–684.
Herzog CA, Ma JZ, Collins AJ. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med. 1998; 339:799–805.
Kalantar-Zadeh K, Ikizler TA, Block G et al.
Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences. Am J Kidney Dis 2003; 42:864–881.
Zoccali C, Benedetto FA, Mallamaei F. Inflammation is associated with carotid atherosclerosis in dialysis patients. J Hypertens 2000; 18:1207–1213.
London GM, Marchais SJ, Metivier F, Guerin AP. Cardiovascular risk in end-stage renal disease: vascular aspects. Nephrol Dial Transplant 2000; 15(Suppl 5):97–104.
Koc M, Toprak A, Tezcan H, Bihorac A, Akoglu E, Ozener IC. Uncontrolled hypertension due to volume overload contributes to higher left ventricular mass index in CAPD patients. Nephrol Dial Transplant 2002; 17:1661–1666.
D’Amico M, Locatelli F. Hypertension in dialysis: pathophysiology and treatment. J Nephrol 2002; 15:438–445.
Leunissen KML, Kooman JP, Vander Sandle FM, van Kuijik WH. Hypotension and ultrafiltration physiology in dialysis. Blood Purif 2000; 18:251–254.
Daugirdas J. Chronic hemodialysis prescription. In: Daugirdas JT, Blake PG, Ing TS, editors. Handbook of dialysis. 4th ed. Sydney: Lippincott Williams & Wilkins; 2007. 146–169.
Kuhlmann MK, Zhu F, Seibert E, Levin NW. Bioimpedance, dry weight and blood pressure control: new methods and consequences. Curr Opin Nephrol Hypertens 2005; 14:543–549.
Lang RM, Bierig M, Devereux RB, Chamber Quantification Writing Group. Recommendations for chamber quantification: a report from the American Society of Echocardiograpliy Guidelines an standards committee and the chamber quantification writing group, developed in corfunction with the European Association of echocardiography, a branch of the European society of cardiology. J Am Soc Echocardiogr 2001; 18:1440–1463.
Lukaski HC. Validation of body composition assessment techniques in the dialysis population. ASAIOJ 1997; 43:261–265.
Wizemann V, Wabel P, Chamney P, Zaluska W, Moissl U, Rode C et al.
The mortality risk of overhydration in haemodialysis patients. Nephrol Dial Transplant 2009; 24:1574–1579.
Paniagua R, Ventura MD, Avila-Díaz M, Hinojosa-Heredia H, Méndez-Durán A, Cueto-Manzano A et al.
NT-proBNP, fluid volume overload and dialysis modality are independent predictors of mortality in ESRD patients. Nephrol Dial Transplant 2010; 25:551–557.
Konings CJ, Kooman JP, Schonck M et al.
Fluid status, blood pressure and cardiovascular abnormalities in patients on peritoneal dialysis. Perit Dial Int 2002; 22:477–487.
Wabel P, Chamney P, Moissl U, Jirka T. Importance of whole-body bioimpedance spectroscopy for the management of fluid balance. Blood Purif 2009; 27:75–80.
Moissl UM, Wabel P, Chamney PW, Bosaeus I, Levin NW, Bosy-Westphal A et al.
Body fluid volume determination via body composition spectroscopy in health and disease. Physiol Meas 2006; 27:921–933.
Crepaldi C, Soni S, Chionh CY, Wabel P, Cruz DN, Ronco C. Application of body composition monitoring to peritoneal dialysis patients. Contrib Nephrol 2009; 163:1–6.
Wizemann V, Rode C, Wabel P. Whole-body spectroscopy (BCM) in the assessment of normovolemia in hemodialysis patients. Contrib Nephrol 2008; 161:115–118.
Shah NR, Dumler F. Hypoalbuminaemia: a marker of cardiovascular disease in patients with chronic kidney disease stages II-IV. Int J Med Sci 2008; 5:366–370.
Beddhu S, Kaysen GA, Yan G, Sarnak M, Agodoa L, Ornt D et al.
HEMO Study Group. Association of serum albumin and atherosclerosis in chronic hemodialysis patients. Am J Kidney Dis 2002; 40:721–727.
Kaysen GA, Dubin JA, Muller HG, Rosales LM, Levin NW. The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients: The HEMO Study Group. Kidney Int 2000; 58:346–352.
Wanner C, Zimmermann J, Schwedler S, Metzger T. Inflammation and cardiovascular risk in dialysis patients. Kid Int 2002; 61(Suppl 80): S99–S102.
Vicenté-Martínez M, Martínez-Ramírez L, Muñoz R et al.
Inflammation in patients on peritoneal dialysis is associated with increased extracellular fluid volume. Arch Med Res 2004; 35:220–224.
Woodrow G, Oldroyd B, Wright A et al.
Abnormalities of body composition in peritoneal dialysis patients. Perit Dial Int 2004; 24:169–175.
Plum J, Schoenicke G, Kleophas W et al.
Comparison of body fluid distribution between chronic haemodialysis and peritoneal dialysis patients as assessed by biophysical and biochemical methods. Nephrol Dial Transplant 2001; 16:2378–2385.
Asghar RB, Green S, Engel B et al.
Relationship of demographic, dietary, and clinical factors to the hydration status of patients on peritoneal dialysis. Perit Dial Int 2004; 24:231–239.
Avila-Díaz M, Ventura MD, Valle D et al.
Inflammation and extracellular volume expansion are related to sodium and water removal in patients on peritoneal dialysis. Perit Dial Int 2006; 26:574–580.
Schreiber BD. Congestive heart failure in patients with chronic kidney disease and on dialysis. Am J Med Sci 2003; 325:179–193.
Fagugli RM, Pasini P, Quintaliani G, Pasticci F, Ciao G, Cicconi B et al.
Association between extracellular water, left ventricular mass and hypertension in haemodialysis patients. Nephrol Dial Transplant 2003; 18:2332–2338.
Collins AJ. Cardiovascular mortality in end-stage renal disease. Am J Med Sci 2003; 325:163–167.
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.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]