Article

PDF
Access to the PDF text
Advertising


Free Article !

Archives of cardiovascular diseases
Volume 105, n° 4
pages 211-217 (avril 2012)
Doi : 10.1016/j.acvd.2012.01.012
Received : 29 November 2011 ;  accepted : 31 January 2012
Metabolic syndrome is associated with better nutritional status, but not with cardiovascular disease or all-cause mortality in patients on haemodialysis
Le syndrome métabolique est associé à un meilleur statut nutritionnel, mais non avec la maladie cardiovasculaire ou la mortalité toute cause chez les patients hémodialysés
 

Qian Xie, Ai-Hua Zhang , Shao-Yan Chen, Xuan Lai, Feng Zhang, Lian He, Zhen Zhuang, Ning Zhu, Min-Hua Fan, Tao Wang
Division of Nephrology, Peking University Third Hospital, Beijing, China 

Corresponding author.
Summary
Background

Metabolic syndrome increases the risk of cardiovascular disease (CVD) and all-cause mortality in the general population.

Aims

To investigate whether metabolic syndrome affects CVD and all-cause mortality in chronic haemodialysis patients.

Methods

This prospective, observational cohort study was carried out at Peking university third hospital from June 2006 to June 2010. Baseline anthropometric and laboratory parameters were evaluated, and causes and times of mortality were documented. Nutritional status of the patients was assessed using subject global assessment (SGA) and serum albumin levels.

Results

Of 162 haemodialysis patients recruited, five were lost to follow-up, leaving 157 in the final cohort, who were followed for 36−42 months. Mean age was 62 ± 11 years and 55.4% were men. Forty-six patients (30%) had metabolic syndrome. In the metabolic syndrome versus the non-metabolic syndrome group, there were fewer patients with malnutrition (by SGA) (15.2% vs. 55.0%; P < 0.001), but there were no significant differences in CVD mortality (8.7% vs. 10.8%; P = 0.9) or all-cause mortality (15.2% vs. 22.5%; P = 0.39), nor in mean observed survival time (30.8 ± 7.3 vs. 29.8 ± 8.5 months; P = 0.49) or total survival time (67 ± 43 vs. 78 ± 48 months; P = 0.20). Cox regression analysis showed that independent mortality risk factors were pre-existing CVD, age more than or equal to 66 years and serum albumin less than 37g/L (indicating malnutrition).

Conclusion

Metabolic syndrome was associated with a better nutritional status, but not with CVD or all-cause mortality in the haemodialysis patients in this prospective cohort study.

The full text of this article is available in PDF format.
Résumé
Justification

Le syndrome métabolique augmente le risque d’affection cardiovasculaire et de mortalité toute cause dans la population générale.

Objectifs

Évaluer l’hypothèse que le syndrome métabolique pourrait retentir sur le risque cardiovasculaire de la mortalité globale chez des patients en hémodialyse chronique.

Méthode

Cette étude prospective, observationnelle de cohortes a été effectuée dans l’université de Pékin entre juin 2006 et juin 2010. Les caractéristiques anthropométriques et biologiques ont été évaluées ainsi que les causes et les modalités de survenue d’évènements dont la mortalité. Le statut nutritionnel des patients était évalué en utilisant l’échelle SGA ainsi que les concentrations sériques d’albumine.

Résultats

Parmi les 162 patients hémodialysés chroniques inclus, cinq ont été perdus de vue, permettant d’analyser au sein de la cohorte 157 patients, suivis de 36 à 42 mois. L’âge moyen était de 62±11ans et 55,4 % étaient des patients de sexe masculin. Quarante-six patients (30 %) présentaient un syndrome métabolique. En comparant les groupes avec et sans syndrome métabolique, il y avait un nombre moindre de patients souffrant de malnutrition évalués par SGA (15,2 % vs 55 %, p < 0,001), mais il n’y avait pas de différence significative en ce qui concerne la mortalité cardiovasculaire (8,7 % vs 10,8 %, p = 0,9) ou de mortalité totale (15,2 % vs 22,5 %, p = 0,39). Il n’y avait pas non plus de différence significative en ce qui concerne le délai de survenue (30,8 ± 7,3 vs 29,8 ± 8,5 mois, p = 0,49) ou la durée totale de survie au cours du suivi (67 ± 43 vs 78 ± 48 mois, p = 0,20) au sein de cette cohorte. L’analyse par régression de Cox a montré que les facteurs de risque indépendants de mortalité étaient la présence d’une pathologie cardiovasculaire préexistante, un âge supérieur ou égal à 66ans et un taux sérique d’albumine inférieur à 37g/L, synonyme de malnutrition.

Conclusion

Le syndrome métabolique est associé à un meilleur statut nutritionnel, mais pas avec un excès d’évènements cardiovasculaires ou de mortalité totale chez les patients hémodialysés, suivis au sein d’une cohorte prospective.

The full text of this article is available in PDF format.

Keywords : Metabolic syndrome, Nutrition, Risk factors, All-cause mortality, Cardiovascular disease

Mots clés : Syndrome métabolique, Nutrition, Facteurs de risque, Mortalité totale, Maladie cardiovasculaire

Abbreviations : BMI, CVD, DBP, FPG, HDL-C, IDF, MS, NCEP/ATPIII, PTH, SBP, SD, SGA, hs-CRP


Introduction

MS, which refers to a group of metabolic risk factors, has been found in recent meta-analyses to increase the risk of incident CVD and all-cause mortality in the general population [1, 2, 3]. Current literature most frequently cites the definitions of MS provided by the NCEP/ATP III [4] and the IDF (2005) [5].

CVD is the most common cause of hospitalization and death in chronic haemodialysis patients [6]. However, some risk factors for CVD in the general population (e.g. hyperlipidaemia, hypertension and obesity) have been associated with a relatively good prognosis among dialysis patients [7, 8, 9, 10, 11, 12]. This phenomenon is known as reverse epidemiology [13]. We therefore hypothesized that MS may not have a negative effect on mortality; particularly mortality associated with CVD, in haemodialysis patients.

Methods
Patients

Patients were recruited from the haemodialysis centre at Peking university third hospital from June 2006 to December 2007. Patients had to have received haemodialysis for more than or equal to 3 months; patients who started dialysis less than 3 months previously and irregular dialysis patients were not eligible for inclusion. All eligible regular dialysis patients in the centre were included, unless they did not agree to participate in the study. Dialysis lasts 4–5hours at each session and is conducted three times each week. The ethics committee of Peking university approved the study protocol.

Follow-up and endpoints

Patients were classified based on the presence or absence of MS, and were prospectively followed until June 2010 or until death, if this event occurred earlier. The dates of death were defined as endpoints.

Definitions

The 2006 IDF definition of MS was used: central obesity (waist circumference more than or equal to 80cm in Asian women or more than or equal to 90cm in Asian men) plus two of the following factors:

elevated triglycerides (more than or equal to 1.69 mmol/L) or specific treatment for this lipid abnormality;
reduced HCL-C (less than 1.03 mmol/L in men or less than 1.29 mmol/L in women) or specific treatment for this lipid abnormality;
elevated blood pressure (SBP more than or equal to 130mmHg or DBP more than or equal to 85mmHg) or treatment for previously diagnosed hypertension;
elevated fasting plasma glucose (more than or equal to 5.55 mmol/L) or a previous diagnosis of type 2 diabetes.

CVD was defined as coronary artery disease, arrhythmia, heart failure, peripheral vascular disease or cerebrovascular disease.

Laboratory and anthropometric variables

Biochemical data were collected at baseline and included haemoglobin, serum creatinine, serum triglycerides, HDL-C, FPG, serum albumin, hs-CRP and serum intact PTH levels. All tests were performed in the central laboratory of our hospital using standard methods. Blood pressure (taken with the patient in the sitting position), height, weight and waist circumference (at umbilical level in a standing position) were recorded. Each patient’s nutritional status was assessed by SGA methods (A = normal nutrition, B = mild malnutrition, C = severe malnutrition) according to the patient’s weight, food intake, symptoms (nausea, vomiting, diarrhoea and constipation), activities and function, disease and its relation to nutritional requirement, metabolic demand and physical findings [14].

Body composition measurement

Post-dialysis body composition was analysed by Bioelectrical Impedance (BIA, Tanita, Japan). The collected data included body fat (% and kg), lean body mass (kg), muscle mass (kg) and visceral fat rating (1–59 grade; where 1–12 is considered healthy while more than or equal to 13 corresponds to excessive abdominal fat and indicates central obesity). The measurements were performed by skilled staff who were experienced at collecting these measurements.

Statistical analysis

Continuous variables are expressed as the mean ± SD, while frequency variables are expressed as count (%). Continuous variables were compared using one-way analysis of variance or non-parameter testing between the two groups classified by the presence or absence of MS. Frequency variables were compared using the χ2 test. A Cox regression model was performed to determine risk factors for mortality. The assumption of proportionality was assessed through the analysis of partial residuals of the covariates introduced into the models. Survival between patients with and without MS was compared using Kaplan-Meier analysis and a log-rank test. A P -value < 0.05 was considered statistically significant. All statistical calculations were performed using SPSS 13.0 for Windows.

Results
Baseline characteristics

A total of 162 patients were recruited; five were transferred to other haemodialysis centres, leaving 157 in the final cohort, of whom 99 underwent post-dialysis body composition analysis. Of the 157 patients included, 46 patients (30%) had MS by the IDF criteria [5]. All patients were of Chinese origin. Other baseline characteristics are shown in Table 1. The dialysis vintage at baseline was significantly shorter among diabetic versus other haemodialysis patients (24 ± 23 vs. 50 ± 49 months, Z = –2.884; P = 0.004).

Not surprisingly, patients with MS had significantly higher BMI, body fat, visceral fat rating and waist circumference (Table 1). They also had significantly higher concentrations of haemoglobin, serum albumin and triglycerides; but significantly lower HDL-C (Table 1). More MS patients had normal nutrition (A, assessed by SGA) than those without MS (84.8% vs. 45.0%; P < 0.001; Table 1). There were no significant differences in sex or prevalence of pre-existing CVD between the two groups (Table 1).

Association between all-cause mortality and metabolic syndrome

All patients were followed for 36–42 months. During this time, seven patients with MS and 25 patients without MS died (15.2% vs. 22.5%; P = 0.39), most commonly of CVD (Table 2). There were no significant differences in observed or total survival times between the two groups (Table 2; Figure 1), although total survival was somewhat shorter among patients with MS (67 vs. 78 months; P = 0.20; Table 2). Total survival time was significantly shorter among patients with versus without diabetes (54 ± 23 vs. 80 ± 50 months; Z = –2.582; P = 0.01).



Figure 1


Figure 1. 

Kaplan-Meier survival analysis of all-cause mortality in patients with and without metabolic syndrome P = 0.30.

Zoom

Comparison of baseline characteristics by survival

To further analyse the risk factors for death, the 157 patients were reclassified according to survival and death and the baseline clinical characteristics compared between these two groups (Table 3). Compared with surviving patients, patients who died were older and had lower muscle mass and serum albumin levels (Table 3). Additionally, there were more patients with malnutrition (B, assessed by SGA) and pre-existing CVD in the all-cause mortality group (Table 3). However, there were no significant differences in SBP, BMI, waist circumference or percentage with diabetic nephropathy between the survival and mortality groups (Table 3). The percentage of patients with MS was higher among the group that died and their mean hs-CRP was lower, but these differences were not significant.

Cox regression analysis of mortality risk

Cox regression analysis was performed based on the risk factors that may lead to CVD or all-cause mortality. Based on the Table 3 results, the analysis was focused on age, serum albumin and pre-existing CVD. The effects of MS were also analysed. None of these factors were found to affect CVD-related mortality, but there were significant differences in all-cause mortality. The independent risk factors for all-cause mortality were: being more than or equal to 66 years old, having serum albumin less than 37g/L and having pre-existing CVD (Table 4) but MS was not the independent mortality risk factor.

Discussion

In this prospective, observational cohort study we collected data related to age, sex and BMI, as well as other basic information, and found that our data were distributed similarly to other studies of Asian patients [15]. However, patients with MS accounted for 30% of the cohort, which is lower than has been found in haemodialysis patients in other developed regions (44% in Asian American patients [16] and 46% in Taiwanese patients [17]). This may be due to the use of different definitions of MS.

In the general population, MS is well known to be associated with a higher risk of cardiovascular events [1, 18, 19]. Many studies, and the data presented here, suggest that CVD events account for approximately 50% of the mortality of haemodialysis patients [2, 3]. Meanwhile, a high proportion of haemodialysis patients have been found to have MS [8, 9]. Overall, the relationship between prognosis and the presence of MS in haemodialysis patients has not been resolved. Data from Taiwan have shown that haemodialysis patients with MS (as defined by the NCEP/ATP III Asian criteria [4]) had higher hospitalization rates than those without MS, although there were no significant differences in CVD or all-cause mortality [17].

In the present study, we used the IDF criteria for MS [5]. These criteria have been revised to define central obesity based on the core content to better predict CVD risk. According to the IDF criteria, patients who have central obesity and two other variables are defined as having MS. Currently, it is still inconclusive whether the IDF definition of MS can successfully predict high CVD risk in long-term haemodialysis patients.

In this study, we classified the patients into groups based on the IDF criteria and performed a prospective cohort study focusing on the relationship between MS and the risk of death in haemodialysis patients. Based on our results, we conclude that MS does not increase the risk of CVD or all-cause mortality in haemodialysis patients and is consistent with other authors’ reports [17]. Furthermore, CVD and all-cause mortality rates were actually numerically (though not significantly) lower among MS patients than among those without MS (CVD: 8.7% vs. 10.8%; all-cause: 15.2% vs. 22.5%). Whether this observation could have been significant with a larger sample size is not clear. Conversely, mean total survival time was shorter among patients with MS (67 vs. 78 months) although, again, this was not significant. This means that, using the IDF definition of MS, we did not find a firm link between MS and CVD or all-cause mortality in haemodialysis patients.

There may be certain factors that could weaken the effects of MS on CVD and all-cause mortality among long-term haemodialysis patients. Firstly, some patients with type 2 diabetes mellitus and MS were excluded from our study because they had a smaller waist circumference than that specified by the IDF [5]. Secondly, our follow-up time was relatively short and our sample size from only a single centre was relatively small. Moreover, our result that pre-existing CVD was strongly associated with all-cause mortality also means that pre-existing CVD affected patients’ survival over the shorter time whereas metabolic syndrome might affect patients’ survival over a longer time. These reasons may have masked any effect of MS on CVD and all-cause mortality in haemodialysis patients.

Conversely, there are some factors that may predispose haemodialysis patients to CVD and all-cause mortality, other than MS, most obviously, malnutrition. There were more patients with malnutrition (B, assessed by SGA) in the group without MS; and more patients with malnutrition in the mortality group than in the survival group. The Cox regression analysis also showed that serum albumin less than 37g/L was an independent risk factor for all-cause mortality in these haemodialysis patients. It should be noted that the ten patients who died of severe lung infection or severe malnutrition. To some extent, nutrition in patients with MS was found to be relatively better than in patients without MS. Previous studies have found that comorbid conditions in haemodialysis patients, such as hyperlipidaemia, hypertension and obesity, are often associated with a relatively good prognosis [10, 11, 12]. It is possible that these patients therefore have relatively good nutritional status. Stolic et al. have recently reported that haemodialysis patients with malnutrition had a lower rate of survival than those with MS, and that malnutrition increased the risk of mortality in haemodialysis patients compared with MS [20]. All of these factors suggest that the potential role of malnutrition in the mortality of haemodialysis patients should not be ignored.

Conclusions

In this prospective cohort study, 30% of haemodialysis patients had MS, defined according to the IDF criteria [5]. MS was associated with better nutritional status, while it was not associated with CVD or all-cause mortality in these haemodialysis patients. The independent risk factors for all-cause mortality were: pre-existing CVD, low albumin levels (indicating malnutrition) and older age (older than 66 years).

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

References

Ford E.S. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence Diabetes Care 2005 ;  28 : 1769-1778 [cross-ref]
Galassi A., Reynolds K., He J. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis Am J Med 2006 ;  119 : 812-819 [inter-ref]
Gami A.S., Witt B.J., Howard D.E., and al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta- analysis of longitudinal studies J Am Coll Cardiol 2007 ;  49 : 403-414 [cross-ref]
Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) JAMA 2001 ;  285 : 2486-2497
International diabetes federation. The IDF consensus worldwide definition of the metabolic syndrome. Available at: MetS_def_update2006.pdf. [accessed date: 21st December 2010].
Lindner A., Charra B., Sherrard D.J., Scribner B.H. Accelerated atherosclerosis in prolonged maintenance hemodialysis N Engl J Med 1974 ;  290 : 697-701 [cross-ref]
Iseki K., Yamazato M., Tozawa M., Takishita S. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients Kidney Int 2002 ;  61 : 1887-1893 [cross-ref]
Kalantar-Zadeh K., Kopple J.D., Block G., Humphreys M.H. A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients Am J Kidney Dis 2001 ;  38 : 1251-1263 [inter-ref]
Zager P.G., Nikolic J., Brown R.H., and al. U” curve association of blood pressure and mortality in hemodialysis patients Kidney Int 1998 ;  54 : 561-569 [cross-ref]
Port F.K., Hulbert-Shearon T.E., Wolfe R.A., and al. Predialysis blood pressure and mortality risk in a national sample of maintenance hemodialysis patients Am J Kidney Dis 1999 ;  33 : 507-517 [inter-ref]
Leavey S.F., Strawderman R.L., Jones C.A., Port F.K., Held P.J. Simple nutritional indicators as independent predictors of mortality in hemodialysis patients Am J Kidney Dis 1998 ;  31 : 997-1006 [inter-ref]
Fleischmann E., Teal N., Dudley J., May W., Bower J.D., Salahudeen A.K. Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients Kidney Int 1999 ;  55 : 1560-1567 [cross-ref]
Chiang C.K., Hsu S.P., Pai M.F., and al. Interleukin-18 is a strong indicator of hospitalization in hemodialysis patients Nephrol Dial Transplant 2004 ;  19 : 2810-2815 [cross-ref]
Koo H.M., Do H.M., Kim E.J., and al. Elevated osteoprotegerin is associated with inflammation, malnutrition and new onset cardiovascular events in peritoneal dialysis patients Atherosclerosis 2011 ;  219 : 925-930
Patient registration committee, Japanese society for dialysis therapy, Tokyo, Japan An overview of regular dialysis treatment in Japan as of 31 December 2003 Ther Apher Dial 2005 ;  9 : 431-458
Wong J.S., Port F.K., Hulbert-Shearon T.E., and al. Survival advantage in Asian American end-stage renal disease patients Kidney Int 1999 ;  55 : 2515-2523 [cross-ref]
Yang S.Y., Chiang C.K., Hsu S.P., and al. Metabolic syndrome predicts hospitalization in hemodialysis patients: a prospective Asian cohort study Blood Purif 2007 ;  25 : 252-259 [cross-ref]
Isomaa B., Almgren P., Tuomi T., and al. Cardiovascular morbidity and mortality associated with the metabolic syndrome Diabetes Care 2001 ;  24 : 683-689 [cross-ref]
Lakka H.M., Laaksonen D.E., Lakka T.A., and al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men JAMA 2002 ;  288 : 2709-2716 [cross-ref]
Stolic R.V., Trajkovic G.Z., Peric V.M., and al. Impact of metabolic syndrome and malnutrition on mortality in chronic hemodialysis patients J Ren Nutr 2010 ;  20 : 38-43 [cross-ref]



© 2012  Elsevier Masson SAS. All Rights Reserved.
EM-CONSULTE.COM is registrered at the CNIL, déclaration n° 1286925.
As per the Law relating to information storage and personal integrity, you have the right to oppose (art 26 of that law), access (art 34 of that law) and rectify (art 36 of that law) your personal data. You may thus request that your data, should it be inaccurate, incomplete, unclear, outdated, not be used or stored, be corrected, clarified, updated or deleted.
Personal information regarding our website's visitors, including their identity, is confidential.
The owners of this website hereby guarantee to respect the legal confidentiality conditions, applicable in France, and not to disclose this data to third parties.
Close
Article Outline