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Prevalence of Cardiovascular Risk Factors in Hemodialysis Patients - The CORDIAL Study

Abstracts

Background:

There are scarce epidemiological data on cardiovascular risk profile of chronic hemodialysis patients in Brazil.

Objective:

The CORDIAL study was designed to evaluate cardiovascular risk factors and follow up a hemodialysis population in a Brazilian metropolitan city.

Methods:

All patients undergoing regular hemodialysis for chronic renal failure in all fifteen nephrology centers of Porto Alegre were considered for inclusion in the baseline phase of the CORDIAL study. Clinical, laboratory and demographic data were obtained in medical records and in structured individual interviews performed in all patients by trained researchers.

Results:

A total of 1215 patients were included (97.3% of all hemodialysis patients in the city of Porto Alegre). Their average age was 58.3 years old, 59.5% were male and 62.8% were white. The prevalence of cardiovascular risk factors observed was 87.5% for hypertension, 84.7% for dyslipidemia, 73.1% for sedentary lifestyle, 53.7% for tobacco use, and 35.8% for diabetes. In a multivariate adjusted analysis, we found that sedentary lifestyle (p = 0.032, PR 1.08 - 95%CI: 1.01-1.15), dyslipidemia (p = 0.019, PR 1.08 - 95%CI: 1.01-1.14), and obesity (p < 0.001, PR 1.96 - 95%CI: 1.45-2.63) were more frequent in women; and hypertension (p = 0.018, PR 1.06 - 95%CI: 1.01-1.11) and tobacco use (p = 0.006, PR 2.7 - 95%CI: 1.79-4.17) were more often found among patients under 65 years old. Sedentary lifestyle was independently associated with time in dialysis less than 12 months (p < 0.001, PR 1.23 - 95% CI: 1.14-1.33).

Conclusion:

Hemodialysis patients in this southern metropolitan Brazilian city have a high prevalence of cardiovascular risk factors resembling many northern countries.

Patients; Renal dialysis; Risk factors; Prevalence


Fundamentos:

Há uma carência de dados epidemiológicos sobre o perfil de risco cardiovascular nos pacientes renais crônicos em hemodiálise no Brasil.

Objetivo:

O estudo CORDIAL foi planejado para avaliar fatores de risco cardiovascular e acompanhar a evolução de uma população em programa de hemodiálise numa cidade metropolitana do Brasil.

Métodos:

Todos os pacientes em hemodiálise por doença renal crônica nos quinze centros de nefrologia de Porto Alegre foram considerados para inclusão na fase inicial do estudo CORDIAL. Dados clínicos, laboratoriais e demográficos foram obtidos nos registros médicos, e em entrevistas individuais estruturadas realizadas com todos os pacientes por pesquisadores treinados.

Resultados:

Foram incluídos 1215 pacientes (97,3% de todos os que estavam em hemodiálise na cidade de Porto Alegre). A média de idade era 58,3 anos, 59,5% eram homens e 62,8% eram brancos. A prevalência de fatores de risco cardiovascular encontrada foi 87,5% para hipertensão, 84,7% para dislipidemia, 73,1% para sedentarismo, 53,7% para tabagismo e 35,8% para diabetes. Em uma análise multivariada ajustada, sedentarismo (p = 0,032; RP 1,08 - IC95%: 1,01-1,15), dislipidemia (p = 0,019; RP 1,08 - IC95%: 1,01-1,14), e obesidade (p < 0,001; RP 1,96 - IC95%: 1,45-2,63) foram mais frequentes em mulheres; e hipertensão (p = 0,018; PR 1,06 - IC95%: 1,01-1,11) e tabagismo (p = 0,006; RP 2,7 - IC95%: 1,79-4,17) foram mais frequentes naqueles com menos de 65 anos. Sedentarismo apresentou uma associação independente com tempo em diálise inferior a 12 meses (p < 0,001; RP 1,23 - IC95%: 1,14-1,33).

Conclusão:

Pacientes em hemodiálise nesta metrópole do sul do Brasil apresentaram uma prevalência elevada de fatores de risco cardiovascular similar a diversos países do hemisfério norte.

Pacientes; Diálise renal; Fatores de risco; Prevalência


Introduction

Cardiovascular diseases (CVD) are the main cause of death in chronic kidney disease (CKD) patients on hemodialysis11. United States Renal Data System, Excerpts from USRDS 2009 Annual Data Report. U.S. Department of Health and Human Services. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Am J Kidney Dis. 2010;55(Suppl 1):S1-420.

2. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(Suppl.3):S112-9.
- 33. Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, et al. Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn, where do we go from here? Am J Kidney Dis. 1998;32(5):853-906.. In these patients, cardiovascular mortality is 10- to 20-fold higher when compared to individuals from the general population of the same sex, age and race22. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(Suppl.3):S112-9.

3. Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, et al. Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn, where do we go from here? Am J Kidney Dis. 1998;32(5):853-906.

4. Sarnak MJ, Coronado BE, Greene T, Wang SR, Kusek JW, Beck GJ, et al. Cardiovascular disease risk factors in chronic renal insufficiency. Clin Nephrol. 2002;57(5):327-35.
- 55. Weiner DE, Tabatabai S, Tighiouart H, Elsayed E, Bansal N, Griffith J, et al. Cardiovascular outcomes and all-cause mortality: exploring the interaction between CKD and cardiovascular disease. Am J Kidney Dis. 2006;48(3):392-401. and can be up to 44 times higher in the presence of diabetes66. Brown JH, Hunt LP, Vites NP, Short CD, Gokal R, Mallick NP. Comparative mortality from cardiovascular disease in patients with chronic renal failure. Nephrol Dial Transplant. 1994;9(8):1136-42.. CVD are present since the early stages of chronic kidney disease and reach around 30 to 44% of those beginning hemodialysis77. Ohtake T, Kobayashi S, Moriya H, Negishi K, Okamoto K, Maesato K, et al. High prevalence of occult coronary artery stenosis in patients with chronic kidney disease at the initiation of renal replacement therapy: an angiographic examination. J Am Soc Nephrol. 2005;16(4):1141-8.

8. Di Benedetto A, Marcelli D, D'Andrea A, Cice G, D'Isa S, Cappabianca S, et al. Risk factors and underlying cardiovascular diseases in incident ESRD patients. J Nephrol. 2005;18(5):592-8.

9. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88.
- 1010. Stack AG, Bloembergen W. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol. 2001;12(7):1516-23.. Strikingly, occult ischemic CVD are present in up to 50% of asymptomatic dialysis patients77. Ohtake T, Kobayashi S, Moriya H, Negishi K, Okamoto K, Maesato K, et al. High prevalence of occult coronary artery stenosis in patients with chronic kidney disease at the initiation of renal replacement therapy: an angiographic examination. J Am Soc Nephrol. 2005;16(4):1141-8. , 1111. Charytan D, Kuntz RE, Mauri L, DeFilippi C. Distribution of coronary artery disease and relation to mortality in asymptomatic hemodialysis patients. Am J Kidney Dis. 2007;48(3):409-16. , 1212. Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, et al. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. Nefrologia. 2010;30(3):342-8..

This high amount of CVD can be attributed to the high prevalence of cardiovascular risk factors1313. Levin A, Djurdjev O, Barrett B, Burgess E, Carlisle E, Ethier J, et al. Cardiovascular disease in patients with chronic kidney disease: getting to the heart of the matter. Am J Kidney Dis. 2001;38(6):1398-407.. Although traditional risk factors alone could not entirely explain such a high CVD burden44. Sarnak MJ, Coronado BE, Greene T, Wang SR, Kusek JW, Beck GJ, et al. Cardiovascular disease risk factors in chronic renal insufficiency. Clin Nephrol. 2002;57(5):327-35. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27., they seem to be highly predictive of cardiovascular events1212. Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, et al. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. Nefrologia. 2010;30(3):342-8., especially in the elderly1515. Shlipak MG, Fried LF, Cushman M, Manollo TA, Peterson D, Stehman-Breen C et al. Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors. JAMA. 2005;293(14):1737-45.. Likewise, cardiovascular profile seems to allow risk stratification in CKD1616. Shah DS, Polkinghorne KR, Pellicano R, Kerr PG. Are traditional risk factors valid for assessing cardiovascular risk in end-stage renal failure patients? Nephrology (Carlton). 2008;13(8):667-71..

A large percentage of patients entering dialysis have a clustering of non-controlled risk factors for CVD1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27. leading to an even higher chance of adverse outcomes1717. Xue JL, Frazier ET, Herzog CA, Collins AJ. Association of heart disease with diabetes and hypertension in patients with ESRD. Am J Kidney Dis. 2005;45(2):316-23..

This high prevalence of traditional CVD risk factors on chronic hemodialysis patients has been reported in several studies in different world countries88. Di Benedetto A, Marcelli D, D'Andrea A, Cice G, D'Isa S, Cappabianca S, et al. Risk factors and underlying cardiovascular diseases in incident ESRD patients. J Nephrol. 2005;18(5):592-8.

9. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88.
- 1010. Stack AG, Bloembergen W. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol. 2001;12(7):1516-23. , 1212. Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, et al. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. Nefrologia. 2010;30(3):342-8. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27. , 1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105.

19. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306.
- 2020. Furth S, Hermann J, Powe N. Cardiovascular risk factors, comorbidity and survival outcomes in black and white dialysis patients. Semin Dial. 1998;11(2):102-5.. However, there is a lack of consistent epidemiological data in our country for this population, both for methodological biases and the use of small samples restricted to a single hospital or clinic.

The main objective of this study was to evaluate the prevalence of traditional cardiovascular risk factors in the population of CKD outpatients on chronic hemodialysis in a southern metropolitan city of Brazil.

Methods

Study Design and Research Population

The CORDIAL (Cardiovascular Outcomes Registry in Dialysis Patients) study was designed to collect data on cardiovascular risk profile and carry out the follow-up of all CKD patients enrolled in a regular outpatient hemodialysis program in the city of Porto Alegre, Brazil. The present article describes the baseline phase data and reports a cross-sectional analysis of this population.

Eligibility criteria for enrollment included age 18 years or more, being in chronic outpatient dialysis for more than 30 days, and ability to provide informed consent for participation. The study complies with the Declaration of Helsinki and the protocol was approved by the Ethics Committee for Research of Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA) and by the review boards of the clinical centers included.

From August 2010 to March 2011, all CKD patients on hemodialysis in each of the fifteen dialysis centers of the city of Porto Alegre (Appendix 1 Appendix 1 - Dialysis clinical centers of Porto Alegre, Brazil Centro de Dialise e Transplante, CliniRim, Clinica Nefron, Clinica Vita Rim, Hospital das Clinicas de Porto Alegre, Hospital Divina Providência, Hospital Ernesto Dornelles, Hospital Mãe de Deus, Hospital Moinhos de Vento, Hospital N. Sra. da Conceição, Hospital Parque Belém, Hospital Santa Casa Porto Alegre, Hospital São Lucas, Hospital Vila Nova, Mãe de Deus Center. ) were considered for enrollment and 1215 (97.3% of all) matched the inclusion criteria and agreed to provide informed consent.

CORDIAL Data Collection

To collect the CORDIAL baseline data we used a standardized case report form adapted and extended to our needs from the REACH registry, a study performed in several countries including Brazil2121. Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, Mas JL, et al; REACH Registry Investigators. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA. 2006;295(2):180-9.. The form was comprehensively filled after visits to each center where patients, health care staff and electronic clinical records were accessed.

Weight, height and blood pressure measured before and after the dialysis session (mean of the last 3 sessions) were obtained from reviewing the patients' medical records. Prevalence of atherosclerotic cardiovascular disease, diabetes, and hypertension were established by reviewing all history and physical data in the dialysis clinic medical charts and other available medical documents. Furthermore, we considered as hypertensive any patient in use of antihypertensive drugs, or those with mean pre dialysis blood pressure in the stage 1 or up of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) classification2222. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. National Heart, Lung and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure:National Hoigh Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-72..

The definition of diabetes included both type 1 and type 2, with or without oral hypoglycemic medication or insulin. Tobacco use was registered as past or present. In accordance with the Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (K/DOQI-NKF)2323. Kidney Disease Outcomes Quality Initiative (K/DOQI) Group. K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis. 2003;41(Suppl 3):S1-92., dyslipidemia was defined as the presence of any of the following - total cholesterol > 200 mg/dL, low-density lipoprotein (LDL)-cholesterol > 100 mg/dL, high-density lipoprotein (HDL)-cholesterol < 40 mg/dL, triglycerides > 150 mg/dL, or the use of statin. Current physical activity was established by an inquiry asking about "any moderate activity (as light walking, bicycling, or gardening) or hard one (running, playing football - soccer, hard swimming) at least 30 min two times per week" and "how many minutes in a week".

Laboratory data were obtained from the medical chart as the most recent result in the six preceding months.

Data about gender were available for all CORDIAL participants, about age for 1213 (99.8%), and race, height and weight for 1206 (99.3%) each.

Information about hypertension status, cardiovascular disease, physical activity, smoking and lipid profile were available respectively for 1210 (99.6%), 1170 (96.3%), 1150 (94.7%), 1147 (94.4%), and 1121 (92.3%) of the individuals in the cohort.

Statistics

Statistical analyses were carried out in STATA 9.0. Descriptive statistics were used to characterize the sample. Unadjusted and adjusted prevalence ratios were calculated separately for each dependent variable (hypertension, diabetes, dyslipidemia, tobacco use, sedentary lifestyle, and obesity) with independent variables (gender, age, race, time in dialysis, and diagnosis of cardiovascular disease). All tests were two-tailed and the significance level used was 0.05.

Results

The present study included 1215 subjects (97.3% population on chronic outpatient hemodialysis) with a mean age of 58.3 years old, being 59.5% males and 62.8 % white.

Table 1 presents demographic and clinical data for all the patients in the CORDIAL study and also stratified by gender.

Table 1
Clinical and demographic data for the patients in the CORDIAL study

The prevalence of traditional cardiovascular risk factors displayed in Table 2 reaches almost 90% for hypertension and dyslipidemia, and about 75% of the subjects were sedentary. Diabetes has a prevalence of 35.8 % in the hemodialysis population of Porto Alegre (Table 2).

Table 2
Prevalence of cardiovascular risk factors in CORDIAL (%)

In a multivariate analysis (Table 3), older patients presented a higher prevalence of diabetes and sedentary lifestyle. Hypertension, tobacco use, and obesity, however, were more prevalent in the younger ones. Tobacco use was more prevalent in males, while obesity, dyslipidemia, and sedentary lifestyle were more common in females. Sedentary lifestyle was more prevalent in those who were on dialysis for less than 12 months (linear tendency). Hypertension, diabetes, dyslipidemia, and low physical activity were more prevalent among those with diagnosis of cardiovascular disease.

Table 3
Adjusted prevalence rates (PR) of each cardiovascular risk factor in CORDIAL study

Discussion

The 1215 individuals included in our study represent 97.3 % of all outpatients on hemodialysis for chronic renal failure during the collecting data period in Porto Alegre. The demographic characteristics of our study population were similar to other studies in several countries99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1010. Stack AG, Bloembergen W. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol. 2001;12(7):1516-23. , 1212. Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, et al. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. Nefrologia. 2010;30(3):342-8. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27. , 1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105. , 1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306.. The mean age was close to 60 years old (with 35% over 65 years old) and almost 60% of the participants were men. Overall, the baseline cross-sectional phase of the CORDIAL study describes a high prevalence of various traditional cardiovascular risk factors. Prevalence of hypertension (87.5%), dyslipidemia (84.7%), sedentary lifestyle (73.1%), smoking (53.7%) and diabetes (35.8%) were similar to recent studies developed all over the world99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1212. Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, et al. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. Nefrologia. 2010;30(3):342-8. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27. , 1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105. , 1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306. , 2424. Kronenberg F, Lingenhel A, Neyer U, Lhotta K, König P, Auinger M, et al. Prevalence of dyslipidemic risk factors in hemodialysis and CAPD patientes. Kidney Int. 2003;63(Suppl 84):S113-6. and also comparable to findings in pre-dialysis CKD patients44. Sarnak MJ, Coronado BE, Greene T, Wang SR, Kusek JW, Beck GJ, et al. Cardiovascular disease risk factors in chronic renal insufficiency. Clin Nephrol. 2002;57(5):327-35..

Hypertension

Hypertension was found in 87.5 % of our patients, a result higher than that found by Portolés et al. (the MAR study) in a multicenter cohort in Spain a decade ago (75.8 %)1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306., but similar to others, like 87.1 % in the study by Ohsawa et al. in Japan (KAREN Study, 2005)1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105., 86 % in a cohort of 2535 patients in the USA (Agarwal, 2003)2525. Agarwal R, NissensonAR, Battle D, Coyne DW, Trout JR, Warnock DG. Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States. Am J Med. 2003;115(4):291-7., and around 86 % in two studies in Spain99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1212. Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, et al. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. Nefrologia. 2010;30(3):342-8.. The CHOICE study found a higher prevalence (96.0 % among 1041 individuals)1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27.. Pre dialysis mean blood pressure in our population (about 147/82 mmHg) is similar to other studies (149/79 mmHg in CHOICE, and 147/80 mmHg in DMMS Wave2)1010. Stack AG, Bloembergen W. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol. 2001;12(7):1516-23. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27.. Uncontrolled blood pressure in the pre dialysis measurements is 72 % in our cohort (Table 1), similar to the 70 % in the study of Agarwal et al2525. Agarwal R, NissensonAR, Battle D, Coyne DW, Trout JR, Warnock DG. Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States. Am J Med. 2003;115(4):291-7. and to the 69 % in the CHOICE study1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27.. In CORDIAL, a multivariate adjusted analysis found that patients under 65 years-old presented a higher prevalence of hypertension.

Hypertension has been related to higher mortality in hemodialysis patients2626. Amar J, Vernier I, Rossignol E, Bongard V, Arnaud C, Conte JJ, et al. Nocturnal blood pressure and 24-hour pulse pressure are potent indicators of mortality in hemodialysis patients. Kidney Int. 2000;57(6):2485-91. and the importance of treating high blood pressure in these individuals was highlighted in two recent meta-analysis suggesting a reduction in cardiovascular events and all-cause mortality in those treated with antihypertensive drugs2727. Heerspink HJ, Ninomiya T, Zoungas S, de Zeeuw D, Grobbe DE, Jardine MJ, et al. Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2009;373(9668):1009-15. , 2828. Agarwal R, Sinha AD. Cardiovascular protection and antihypertensive drugs dialysis patients: a systematic review and meta-analysis. Hypertension. 2009;53(5):860-6..

Dyslipidemia

Among our patients, the prevalence of dyslipidemia was 84.7 %, a higher rate comparing to other studies like 50% in CHOICE1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27.. The different criteria in each study preclude a more accurate comparison. Our mean LDL-cholesterol (94.3 mg/L) was similar to others99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1212. Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, et al. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. Nefrologia. 2010;30(3):342-8. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27. , 1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105. , 1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306., with Kronnnenberg reporting a higher value (115 mg/dL)2424. Kronenberg F, Lingenhel A, Neyer U, Lhotta K, König P, Auinger M, et al. Prevalence of dyslipidemic risk factors in hemodialysis and CAPD patientes. Kidney Int. 2003;63(Suppl 84):S113-6..

The prevalence of elevated triglycerides was 45.2 % in our cohort, higher than the study by Collado et al1212. Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, et al. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. Nefrologia. 2010;30(3):342-8. and the CHOICE study (36.9 % over 200mg/dL)1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27.. Mean values were 171.7 mg/dL in CORDIAL, higher than in KAREN and ANSWER, similar to the MAR study and Kronenberg et al2424. Kronenberg F, Lingenhel A, Neyer U, Lhotta K, König P, Auinger M, et al. Prevalence of dyslipidemic risk factors in hemodialysis and CAPD patientes. Kidney Int. 2003;63(Suppl 84):S113-6., and lower than CHOICE (199mg/dL)99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27. , 1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105. , 1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306. , 2424. Kronenberg F, Lingenhel A, Neyer U, Lhotta K, König P, Auinger M, et al. Prevalence of dyslipidemic risk factors in hemodialysis and CAPD patientes. Kidney Int. 2003;63(Suppl 84):S113-6.. HDL-cholesterol under 40 mg/dL was more prevalent in our cohort (60.3 %) than in others99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27. , 1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105. , 1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306.. An exception was the 66 % reported by Kronenberg et al2424. Kronenberg F, Lingenhel A, Neyer U, Lhotta K, König P, Auinger M, et al. Prevalence of dyslipidemic risk factors in hemodialysis and CAPD patientes. Kidney Int. 2003;63(Suppl 84):S113-6..

In CORDIAL, there was a higher adjusted prevalence of dyslipidemia in female patients, while Ohsawa et al. reported an opposite finding1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105.. Although there is not a proven association between serum lipids and the development CVD outcomes in dialysis patients2929. Heymann EP, Kassimatis TI, Goldsmith DJ. Dyslipidemia, statins, and CKD patients' outcomes - review of the evidence in the post-sharp era. J Nephrol. 2012;25(4):460-72., lipid measurements and treatment remains a cornerstone approach to prevent CVD even in CKD patients2424. Kronenberg F, Lingenhel A, Neyer U, Lhotta K, König P, Auinger M, et al. Prevalence of dyslipidemic risk factors in hemodialysis and CAPD patientes. Kidney Int. 2003;63(Suppl 84):S113-6..

Smoking

Tobacco use is associated with a markedly increased risk of heart disease in dialysis patients88. Di Benedetto A, Marcelli D, D'Andrea A, Cice G, D'Isa S, Cappabianca S, et al. Risk factors and underlying cardiovascular diseases in incident ESRD patients. J Nephrol. 2005;18(5):592-8. , 1616. Shah DS, Polkinghorne KR, Pellicano R, Kerr PG. Are traditional risk factors valid for assessing cardiovascular risk in end-stage renal failure patients? Nephrology (Carlton). 2008;13(8):667-71.. Smoking (past or present) was described in 53.7 % of our patients, in accordance to others studies99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1010. Stack AG, Bloembergen W. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol. 2001;12(7):1516-23. , 1212. Collado S, Coll E, Deulofeu R, Guerrero L, Pons M, Cruzado JM, et al. Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors. Nefrologia. 2010;30(3):342-8. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27. , 1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306.. Thirteen percent of our patients were current smokers, similar to other authors99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27. , 1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306., except for the KAREN study, with 28.2%1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105.. In CORDIAL, the adjusted prevalence of tobacco use was higher in males and in those with less than 65 years.

Sedentary lifestyle

Sedentary lifestyle was identified in 73.1% of our patients. In the CHOICE study1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27., only 14 % reported physical activity to perspiration at least 3 times a week. Tentori et al. (2010)3030. Tentori F, Elder SJ, Thumma J, Pisoni RL, Bommer J, Fissell RB, et al. Physical exercise among participants in the Dialysis Outcomes and Practice Patterns Study (DOPPS): correlates and associated outcomes. Nephrol Dial Transplant. 2010;25(9):3050-62. described results of 20,920 patients in the DOPPS study with a self-reported regular physical activity of 47.4 %. Comorbidities and physical limitations could explain the low adherence of haemodialysis patients to exercise programs3131. Miller BW, Cress CL, Johnson ME, Nichols DH, Schnitzler MA. Exercise during hemodialysis decreases the use of antihypertensive medications. Am J Kidney Dis. 2002;39(4):828-33.. Besides, older age could represent another limitation to physical activity - among our patients, adjusted prevalence of physical inactivity was higher in those over 65 years than in younger patients (Table 3).

Diabetes

Diabetes prevalence among dialysis patients is already high and increasing3232. Van Dijk PC, Jager KJ, Stengel B, Grönhagen-Riska C, Feest TG, Briggs JD. Renal replacement therapy for diabetic end-stage renal disease: data from 10 registries in Europe (1991-2000). Kidney Int. 2005;67(4):1489-99.. The 5-year survival rate among diabetic patients on hemodialysis is worse than in non-diabetics. A recent study in Brazil found 41.1 versus 62.7 %, respectively3333. Matos JP, Almeida JR, Guinsburg A, Marelli C, Barra AB, Vasconcellos MS, et al. Assessment of a five-year survival on hemodialysis in Brazil: a cohort of 3,082 incident patients. J Bras Nefrol. 2011;33(4):436-41.. According to the 2009 United States Renal Data System (USRDS) database, only 30 % of the diabetic patients survived five years after beginning hemodialysis11. United States Renal Data System, Excerpts from USRDS 2009 Annual Data Report. U.S. Department of Health and Human Services. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Am J Kidney Dis. 2010;55(Suppl 1):S1-420..

In CORDIAL, diabetics were 35.8 % of the population, a lower rate than the one presented in CHOICE (54%)1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27., but similar to the 38.5% in the 2012 USRDS Annual Report3434. U. S. Renal Data System, USRDS 2012 Annual Data Report.: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD;2012., with others ranging from 26 to 43 %99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1010. Stack AG, Bloembergen W. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol. 2001;12(7):1516-23. , 1818. Ohsawa M, KatoK, Itai K, Onoda T, Konda R, Fujioka T, et al; KAREN Study Group. Cardiovascular risk factors in hemodialysis patients: results from baseline data of kaleidoscopic aproaches to patients with end-stage renal disease study. J Epidemiol. 2005;15(3):96-105.

19. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306.
- 2020. Furth S, Hermann J, Powe N. Cardiovascular risk factors, comorbidity and survival outcomes in black and white dialysis patients. Semin Dial. 1998;11(2):102-5..

Obesity

Obesity estimated by body mass index (BMI) was present in 12.4% of individuals in CORDIAL. The MAR study1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306. reported obesity in 14% of their patients, while in ANSWER and CHOICE the prevalence was higher (20 and 26%, respectively)99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1414. Longenecker JC, Coresh J, Powe NR, LeveyAS, FinkNE, Martin A et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol. 2002;13(7):1918-27.. Unlike the general population, overweight dialysis patients have better prognosis, supposedly due to a better nutritional status3535. Leavey SF, McCullough K, Hecking E, Goodkin D, Port FK, Young EW. Body mass index and mortality in "healthier" as compared with "sicker" haemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant. 2001;16(12):2386-94.. Recently, BMI has been considered a non-efficient tool in the assessment of excess body fat content and thereafter obesity3636. Okorodudu DO, Jumean MF, Montori VM, Romero-Corral A, Somers VK, Erwin PJ, et al. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes (Lond). 2010;34(5):791-9.. Reverse epidemiology and inadequate assessment of fat accumulation could explain the "obesity paradox" in CKD3737. Agarwal R, Bills JE, Light RP. Diagnosing obesity by body mass index in chronic kidney disease: an explanation for the "obesity paradox"? Hypertension. 2010,56(5):893-900..

Age

In CKD patients on hemodialysis, older age confers a cardiovascular risk that parallels the relationship described in the general population3838. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108(17):2154-69.. There is a growing prevalence of elderly in the hemodialysis population all-over the world99. Pérez-Garcia R, Martín-Malo A, Fort J, Cuevas X, Lladós F, Lozano J, et al. Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER - a multicentre, prospective, observational cohort study. Nephrol Dial Transplant. 2009;24(2):578-88. , 1010. Stack AG, Bloembergen W. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol. 2001;12(7):1516-23. , 1919. Portolés J, López-Gómez JM, Aljama P. Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study). Nefrología.2005;25(3):297-306.. In the Brazilian dialysis census of 2000, those with age 60 or more were 26 %3939. Sesso R. Inquérito epidemiológico em unidades de diálise do Brasil. J Bras Nefrol. 2000;22(3 Supl 2):23-6., while in 2011 there were 31.5 % with age 65 or more4040. Sesso RC, Lopes AA, Thomé FS, Lugon JR, Santos DR. Diálise crônica no Brasil - relatório do Censo Brasileiro de Diálise, 2011. J Bras Nefrol. 2012;34(3):272-7.. In CORDIAL, also in 2011, we found a rate of 34.9 %.

Limitations

Our data presents the usual drawbacks of cross-sectional studies limiting causal inferences. We had to rely on clinical laboratory measurements of 15 dialysis centers instead of using a core lab. We described similar rates observed in other studies, but our data cannot be generalized to other cities in our country. Our data, however, has the strength of having been acquired from a large population with few dropouts and double-checking structured individual interviews and clinical charts.

Conclusion

The population in chronic hemodialysis in this large metropolitan south-American city described in the CORDIAL study presents a high prevalence of cardiovascular risk factors. These findings confirm in Brazil what has been previously verified in northern hemisphere countries, the high-risk cardiovascular profile of hemodialysis patients. Prospective studies and clinical trials are needed to further clarify interventions that can be transformed in public health strategies to prevent cardiovascular death in hemodialysis patients.

Acknowledgement

The authors thank the medical directors of all dialysis units in the city of Porto Alegre for their consent and assistance to this study.

Appendix 1 - Dialysis clinical centers of Porto Alegre, Brazil

Centro de Dialise e Transplante, CliniRim, Clinica Nefron, Clinica Vita Rim, Hospital das Clinicas de Porto Alegre, Hospital Divina Providência, Hospital Ernesto Dornelles, Hospital Mãe de Deus, Hospital Moinhos de Vento, Hospital N. Sra. da Conceição, Hospital Parque Belém, Hospital Santa Casa Porto Alegre, Hospital São Lucas, Hospital Vila Nova, Mãe de Deus Center.

Appendix 2 - Associated researchers to the CORDIAL study

Amanda Galdino Macolmes, Camila Borges Mosmann, Daiane Jaqueline Nascimento, Debora Wassaf Youssef, Eduardo Hoffmann Miranda, Felipe Borsu Salles, Fernando Mendonça Alvares, Fernando Augusto Dannebrock, Gabriela Dotta Dornelles, Gisiane Munaro, Jaime Fracasso Jr, Japão Drose Pereira, Jean Pierre W. Youssef, Liana Pilau Abreu, Liz Lopes Sombrio, Luana Bringhenti, Luzia Gross Lague, Maikel Alf Klein, Mariano Feraboli Fontana, Mauricio Rodrigues, Natalia Fiorentin Caramori, Ramiro Tubino Saraiva, Renata Rech Grandi, Renato Budzyn David, Veridiana Borges Costa.

  • Author contributions
    Conception and design of the research: Burmeister JE, Rosito GA; Acquisition of data: Burmeister JE, Mosmann CB, Costa VB, Saraiva RT, Grandi RR, Bastos JP; Analysis and interpretation of the data: Burmeister JE, Mosmann CB, Costa VB, Bastos JP, Gonçalves LF, Rosito GA; Statistical analysis: Burmeister JE, Bastos JP, Gonçalves LF, Rosito GA; Writing of the manuscript: Burmeister JE, Mosmann CB, Costa VB, Saraiva RT, Grandi RR, Bastos JP, Rosito GA; Critical revision of the manuscript for intellectual content: Burmeister JE, Mosmann CB, Costa VB, Bastos JP, Gonçalves LF, Rosito GA; Coordination work of collecting and recording data: Burmeister JE; General Coordinator of the Project: Rosito GA.
  • Sources of Funding
    There were no external funding sources for this study.
  • Study Association
    This study is not associated with any thesis or dissertation work.

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Publication Dates

  • Publication in this collection
    17 Apr 2014
  • Date of issue
    10 June 2014

History

  • Received
    25 July 2013
  • Reviewed
    11 Nov 2013
  • Accepted
    29 Nov 2013
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