Dissertations / Theses on the topic 'Chronic heart and renal failures'

Background-Heart failure is common in patients with chronic kidney disease. We studied risk factors for incident heart failure among 3557 participants in the CRIC (Chronic Renal Insufficiency Cohort) Study. Methods and Results-Kidney function was assessed by estimated glomerular filtration rate (eGFR) using serum creatinine, cystatin C, or both, and 24-hour urine albumin excretion. During an average of 6.3 years of follow-up, 452 participants developed incident heart failure. After adjustment for age, sex, race, and clinical site, hazard ratio (95% CI) for heart failure associated with 1 SD lower creatinine-based eGFR was 1.67 (1.49, 1.89), 1 SD lower cystatin C-based-eGFR was 2.43 (2.10, 2.80), and 1 SD higher log-albuminuria was 1.65 (1.53, 1.78), all P< 0.001. When all 3 kidney function measures were simultaneously included in the model, lower cystatin C-based eGFR and higher log-albuminuria remained significantly and directly associated with incidence of heart failure. After adjusting for eGFR, albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95% CI 1.09, 1.72, P= 0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P= 0.006), hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P< 0.001), interleukin-6 (1.15, 95% CI 1.05, 1.25, P= 0.002), and tumor necrosis factor-a (1.10, 95% CI 1.00, 1.21, P= 0.05) were all significantly and directly associated with incidence of heart failure. Conclusions-Our study indicates that cystatin C-based eGFR and albuminuria are better predictors for risk of heart failure compared to creatinine-based eGFR. Furthermore, anemia, insulin resistance, inflammation, and poor glycemic control are independent risk factors for the development of heart failure among patients with chronic kidney disease.

Thesis (Ph.D.) - University of Glasgow, 2008.
Ph.D. thesis submitted to the Faculty of Medicine, Division of Cardiovascular and Medical Sciences, University of Glasgow, 2007. Includes bibliographical references. Print version also available.

Limited data exists describing the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to currently recommended ejection fraction (EF) findings. In addition, little is known about the magnitude of, and factors associated with, long-term prognosis for these patients. Based on previously validated and clinically relevant criteria, we defined HF-REF as patients with an EF value ≤40%, HF-PEF was defined as an EF value > 50%, and HF-BREF was defined as patients with an EF value during their index hospitalization between 41 and 49%. The hospital medical records of residents of the Worcester (MA) metropolitan area who were discharged after ADHF from all 11 medical centers in central Massachusetts during the 5 study years of 1995, 2000, 2002, 2004, and 2006 were reviewed. Follow-up was completed through 2011 for all patient cohorts. The average age of this population was 75 years, the majority was white, and 44% were men. Patients with HF-PEF experienced higher post discharge survival rates than patients with either HF-REF or HF-BREF at 1, 2, and 5-years after discharge. Advanced age and lower estimated glomerular filtration rate findings at the time of hospital admission were important predictors of 1-year death rates, irrespective of EF findings. Previously diagnosed chronic obstructive pulmonary disease, chronic kidney disease, and atrial fibrillation were associated with a poor prognosis in patients with PEF and REF whereas a history of diabetes was an important prognostic factor for patients with REF and BREF. In conclusion, although improvements in 1-year post-discharge survival were observed for patients in each of the 3 EF groups examined to varying degrees, the post- 7 discharge prognosis of all patients with ADHF remains guarded. In addition, we observed differences in several prognostic factors between patients with ADHF with varying EF findings, which have implications for more refined treatment and surveillance plans for these patients.

Limited data exists describing the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to currently recommended ejection fraction (EF) findings. In addition, little is known about the magnitude of, and factors associated with, long-term prognosis for these patients. Based on previously validated and clinically relevant criteria, we defined HF-REF as patients with an EF value ≤40%, HF-PEF was defined as an EF value > 50%, and HF-BREF was defined as patients with an EF value during their index hospitalization between 41 and 49%. The hospital medical records of residents of the Worcester (MA) metropolitan area who were discharged after ADHF from all 11 medical centers in central Massachusetts during the 5 study years of 1995, 2000, 2002, 2004, and 2006 were reviewed. Follow-up was completed through 2011 for all patient cohorts. The average age of this population was 75 years, the majority was white, and 44% were men. Patients with HF-PEF experienced higher post discharge survival rates than patients with either HF-REF or HF-BREF at 1, 2, and 5-years after discharge. Advanced age and lower estimated glomerular filtration rate findings at the time of hospital admission were important predictors of 1-year death rates, irrespective of EF findings. Previously diagnosed chronic obstructive pulmonary disease, chronic kidney disease, and atrial fibrillation were associated with a poor prognosis in patients with PEF and REF whereas a history of diabetes was an important prognostic factor for patients with REF and BREF. In conclusion, although improvements in 1-year post-discharge survival were observed for patients in each of the 3 EF groups examined to varying degrees, the post- 7 discharge prognosis of all patients with ADHF remains guarded. In addition, we observed differences in several prognostic factors between patients with ADHF with varying EF findings, which have implications for more refined treatment and surveillance plans for these patients.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-10-13T18:19:07Z No. of bitstreams: 1 arisegarciadesiqueiragalil.pdf: 700408 bytes, checksum: bda59712c26407e09b49f3dd136c52b2 (MD5)
Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-10-22T13:00:41Z (GMT) No. of bitstreams: 1 arisegarciadesiqueiragalil.pdf: 700408 bytes, checksum: bda59712c26407e09b49f3dd136c52b2 (MD5)
Made available in DSpace on 2016-10-22T13:00:41Z (GMT). No. of bitstreams: 1 arisegarciadesiqueiragalil.pdf: 700408 bytes, checksum: bda59712c26407e09b49f3dd136c52b2 (MD5) Previous issue date: 2008-02-15
Introdução: A insuficiência cardíaca (IC) tem alta morbimortalidade que decorre de fatores causais e refratariedade ao tratamento. A doença renal crônica (DRC) e a anemia têm se associado a pior prognóstico em pacientes com IC grave, especialmente os hospitalizados. Há, porém, poucos estudos que avaliem a prevalência e as conseqüências da DRC e da anemia em pacientes com IC acompanhados ambulatorialmente. Objetivos: Avaliar a prevalência da DRC e anemia e o impacto de desfechos cardiovasculares em portadores de IC sistólica estágios B e C. Pacientes e Métodos: Foram estudados pacientes adultos, com idade >18 anos e diagnóstico de IC sistólica e com fração de ejeção (EF) ≤45%, selecionados do ambulatório do Serviço de Hipertensão, Diabetes e Obesidade do SUS de Juiz de Fora e acompanhados por 12 meses. A anemia foi definida como hemoglobina <12,0g/dl nas mulheres e <13,0g/dl nos homens. A reserva de ferro foi considerada adequada quando índice de saturação da transferrina encontrava-se ≥20% e a ferritina ≥100ηg/dl. A filtração glomerular foi estimada pela fórmula do estudo MDRD e a DRC foi definida como proposto pelo K/DOQI da National Kidney Foundation americana. Considerou-se com desfechos cardiovasculares (CV) a ocorrência de hospitalização e/ou morte decorrente da IC. Os dados demográficos, de exame físico e laboratorial foram obtidos do prontuário dos pacientes. Resultados: Foram avaliados 83 pacientes, com idade média de 62,7±12 anos, sendo 56,6% do sexo feminino. A média da fração de ejeção (FE) foi de 37,8+7,9% e a maioria dos indivíduos (60,2%) estava no estágio C. A prevalência de anemia foi de 24,09%; 30,30% no estágio B e 20% no estágio C. A prevalência de DRC foi elevada, presente em 49,4% da amostra, 42,4% no estágio B da IC e 54% no estágio C. Todos os pacientes com anemia tinham reserva de ferro normal e 68,6% apresentavam DRC concomitante. Os desfechos CV ocorreram em 26,5% da amostra. Na estratificação dos pacientes nos estágios B e C da IC e presença ou não de DRC, evidenciou que 100% e 64,7% apresentaram desfechos, respectivamente. Na análise multivariada, após ajustes para fatores prognósticos no período basal, o diagnóstico de DRC aumentou em 3,6 vezes a possibilidade de desfechos (IC 95%1,04-12,67, p=0,04), enquanto os níveis mais elevados de sódio sérico (R 0,807, IC95%0,862-0,992, p=0,03) e da fração de ejeção (R 0,925, IC95% 0,862-0,942, p= 0,03) se mostraram protetores. Conclusão: Na coorte de pacientes estudada, composta de pacientes com IC estágios B e C, a ocorrência de anemia foi compatível com a observada em outros estudos e com tendência de se associar com menor filtração glomerular. A DRC foi prevalente e independentemente se associou a maior risco de hospitalizações e mortes secundárias à descompensação cardíaca, especialmente nos pacientes assintomáticos.
Introduction: Chronic heart failure (CHF) has a high morbidity and mortality which are consequent to etiologic factors and no response to treatment. Anemia and chronic kidney disease (CKD) have been associated to worse outcome in patients with severe hospitalized CHF. So far, there is few studies that assessed the prevalence and the consequences of anemia and CKD in outpatients with CHF. Aim: To study the prevalence of CKD and anemia and the impact of CV end points in patients with systolic CHF followed in an outpatient clinic. Methods: This is prospective cohort study, dealing with adult patients older than 18 years of age and diagnosis of systolic CHF and ejection fraction (EF) ≤45%, selected from the Hypertension, Diabetes and Obesity Outpatient Clinic of SUS of Juiz de Fora. Anemia was defined as hemoglobin <12,0g/dL in women and <13g/dL in men and women after the menopause. Normal iron store was defined when transferring saturation index was >20% and/or ferritin >100ηg/dL. The glomerular filtration rate was estimated from serum creatinine usinf the MDRD study formula, and CKD was defined as suggested by the K/DOQI of National Kidney Foundation. CV endpoints were defined as death or hospitalization due to CHF, in 12 months follow up. Demographic and clinical date were obtained from the patients’ charts. Results: Eight three patients were studied, the mean age was 62.7±12 years, and 56.6% were female. The EF was 37,8+7,9%, and the majority of the patients had stage C CHF (60,2%). The prevalence of anemia was 24,1%; 30,3% in stage B and 50% in stage C. CKD was diagnosed in 49.4% of the patients, 42,4% of the stage B and 54% in the stage C. All patients with anemia had normal iron storage, and 68,6% had concomitant CKD. Cardiovascular endpoints were observed in 26.5% of the patients. When the sample was stratified in stages B and C of CHF and presence or absence of CKD, it was found that 100% and 64.7% had CV endpoints, respectively. After adjustments for all other prognostic factors at baseline, it was observed that the diagnosis of CKD increased in 3.6 folds the hazard of CV endpoints (CI 95% 1,04-12,67, p=0,04), whereas higher ejection fraction (R 0,925, IC 95% 0,862-0,942, p= 0,03) and serum sodium (R 0,807, IC 95% 0,862-0,992, p=0,03) were protectors. Conclusion: In this cohort of outpatients with CHF stages B and C, the occurrence of anemia was low and frequently associated with concomitant CKD. On the other hand, CKD was prevalent and independently associated with heightened risk for hospitalization and death secondary of cardiovascular causes, mainly in asymptomatic patients.

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2018-02-27T14:13:48Z No. of bitstreams: 1 marciogatti_dissert.pdf: 2240052 bytes, checksum: 38cfe0f95ee7d8c6d51f09ffe75f33ba (MD5)
Made available in DSpace on 2018-02-27T14:13:48Z (GMT). No. of bitstreams: 1 marciogatti_dissert.pdf: 2240052 bytes, checksum: 38cfe0f95ee7d8c6d51f09ffe75f33ba (MD5) Previous issue date: 2015-11-17
Introduction: Chronic Renal Failure (CRF) is a metabolic syndrome resulting in progressive loss of ability to renal excretion. In advanced stages dialysis is necessary. The introduction of new technological advances in hemodialysis made this procedure safe and able to maintain patients' lives for long periods. However, in 30% of the hemodialysis, may occur some kind of complication. The heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system and reflects the balance between the sympathetic and parasympathetic branches of the same. HRV analysis have been proposed as a component of the clinical evaluation for risk stratification of patients. HRV can be studied by linear methods, time domain and frequency and nonlinear methods in the field of chaos. Objective: Assess whether or not there is an association between lower HRV immediately preceding the hemodialysis and the occurrence of complications during or after the same period. Casuistic and Method: 44 unselected patients were included in the study, regardless of sex and age being 15 (34.1%) were female and 29 patients (65.9%) males, with 61.7 ± 14.5 years. Inclusion criteria were considered just the fact of having IRC, be in regular program of performing hemodialysis in the dialysis unit at Hospital de Base (HB) of São José do Rio Preto. The methodology consisted of the assessment of HRV in the time, frequency and chaos, using registration electrocardiographic time series with the aid of equipment Polar RS800CX for 20 minutes moments before initiating hemodialysis session. The 44 patients were followed throughout the dialysis period by verifying the occurrence of complications. Results: 35 patients (NC) had no complications during hemodialysis, while 9 patients (C) had complications, such as hypotension, hypoglycemia, and cramps. The results showed no association between lower HRV with the occurrence of complications during or after hemodialysis. But it was evident that the diabetic patients had a higher probability of complications, because it was the only variable that showed a statistically significant difference. Comparing the results of HRV in diabetic patients with nondiabetic patients, we found lower values for the variables that represent the sympathetic autonomic activity, such as SDNN, LF, SD2 and alpha 1. Conclusions: HRV in the time, frequency and chaos was not characterized as a predictor of the occurrence of complications during or after hemodialysis. However, in diabetic patients there is a significant reduction in the sympathetic component associated with the occurrence of complications, highlighting the possibility of using a simple, noninvasive method for determining prognosis by studying HRV.
Introdução: Insuficiência Renal Crônica (IRC) é uma síndrome metabólica decorrente de perda progressiva da capacidade de excreção renal. Em fases avançadas é necessário o tratamento dialítico. A introdução de novos avanços tecnológicos no tratamento hemodialítico tornou esse procedimento seguro e capaz de manter a vida dos pacientes por longos períodos. Entretanto, em 30% das sessões de hemodiálise, pode ocorrer algum tipo de complicação. A variabilidade da freqüência cardíaca (VFC) revela informações do estado funcional do sistema nervoso autônomo e reflete o balanço entre os ramos parassimpático e simpático do mesmo. Análises da VFC têm sido propostas como um componente da avaliação clínica para a estratificação do risco dos pacientes. A VFC pode ser estudada por meio de métodos lineares, no domínio do tempo e da frequência e métodos não lineares, no domínio do caos. Objetivo: Avaliar se há ou não associação entre menor VFC no período imediatamente precedente à realização de hemodiálise e a ocorrência de complicações durante ou logo após a mesma. Casuística e Método: Foram incluídos no estudo 44 pacientes não selecionados, independente do sexo e idade sendo 15 (34,1%) do sexo feminino e 29 (65,9%) do sexo masculino, com 61,7±14,5 anos. Os critérios de inclusão foram considerados apenas o fato de ser portador de IRC, estar em programa regular de realização de hemodiálise na Unidade de Terapia Dialítica do HB de São José do Rio Preto. A metodologia consistiu na avaliação da VFC nos domínios do tempo, frequência e caos, utilizando-se de registro de series temporais eletrocardiográficas com auxilio do equipamento Polar RS800CX, por 20 minutos instantes antes de iniciarem a sessão de hemodiálise. Os 44 pacientes foram acompanhados durante todo o período dialítico com a verificação da ocorrência de complicações. Resultados: 35 pacientes (NC) não tiveram complicações durante a hemodiálise, enquanto que 9 pacientes (C) apresentaram complicações, como hipotensão, hipoglicemia e câimbras. Os resultados obtidos mostraram que não houve associação entre uma menor VFC com a ocorrência de complicações durante ou logo após a hemodiálise. Porém foi evidente que os pacientes diabéticos apresentaram maior probabilidade de complicações, pois foi a única variável que apresentou diferença estatisticamente significativa. Comparando os resultados da VFC nos pacientes diabéticos com os não diabéticos, encontramos menores valores para as variáveis que representam a atividade autonômica simpática, como SDNN, LF, SD2 e alfa 1. Conclusões: A VFC nos domínios do tempo, freqüência e caos não se caracterizou como preditivo da ocorrência de complicações durante ou logo após a hemodiálise. Entretanto, em pacientes diabéticos há uma redução significante do componente simpático associado à ocorrência de complicações, ressaltando-se a possibilidade de utilização de um método simples e não invasivo para determinação de prognóstico por meio do estudo da VFC.

Made available in DSpace on 2016-01-26T12:51:32Z (GMT). No. of bitstreams: 1 sabrinaqueirozardito_dissert.pdf: 404181 bytes, checksum: cc58335cbd6ac86952c065cd2a36213e (MD5) Previous issue date: 2011-12-16
This study aimed at determining the prevalence and the prognostic significance of chronic renal impairment in patients with chronic systolic heart failure secondary to Chagas cardiomyopathy. A total of 245 patients followed at the Cardiomyopathy Outpatient service from January, 2000 to December, 2008 with the diagnosis of chronic systolic heart failure secondary to Chagas cardiomyopathy were included. Chronic renal impairment was diagnosed in 42 (17%) patients. A Cox proportional hazards model was used to evaluate the role of chronic renal impairment as a prognostic index, and a Kaplan-Meier survival curve to study its association with all-cause mortality. Baseline characteristics of patients with and without chronic renal impairment were similar. Beta-Blocker therapy (Hazard ratio=0,42; 95% Confidence Interval 0,27 to 0,63, p value <0,005), left ventricular ejection fraction (Hazard Ratio=0,97; 95% Confidence Interval 0,95 to 0,99; p value=0,005), serum sodium levels (Hazard ratio=0,94; 95% Confidence Interval 0,90 to 0,98; p value=0,004), inotropic support (Hazard Ratio= 1,85; 95% Confidence Interval 1,21 to 2,64; p value= 0,03), and digoxin use (Hazard ratio=2,35; 95% Confidence Interval 1,15 to 4,81; p value=0,02) were independent predictors of all- cause mortality. Survival probability at 12, 24, 36, and 60 months was 74%, 60%, 52%, and 37%, respectively, in patients with chronic renal impairment, and 84%, 70%, 70%, and 35% ,respectively, in patients without (p>0,05). Chronic renal impairment has a low prevalence and no prognostic significance in patients with chronic systolic heart failure secondary to Chagas Cardiomyopathy.
Este estudo tem por objetivo determinar a prevalência e a significância prognóstica da disfunção renal crônica em pacientes com insuficiência cardíaca crônica sistólica secundária à cardiomiopatia chagásica. Duzentos e quarenta e cinco pacientes seguidos no Ambulatório de Cardiomiopatia de Janeiro de 2000 a Dezembro de 2008 com o diagnóstico de insuficiência cardíaca crônica secundária a cardiomiopatia Chagásica foram incluídos no estudo. Disfunção renal crônica foi diagnósticada em 42 (17%) pacientes. Um modelo proporcional de Cox foi usado para avaliar a evolução da disfunção renal crônica como um indice prognóstico, e uma curva de sobrevida de Kaplan-Meier para estudar sua associação com todas as causas de mortalidade. As características basais dos pacientes com e sem disfunção renal crônica foram semelhantes. Terapia com betabloqueador (Razão de Risco=0,42; Intervalo de Confiança 95% de 0,27 a 0,63, p<0,005)], fração de ejeção ventricular esquerda(Razão de Risco=0,97; Intervalo de Confiança 95% de 0,95 a 0,99; p=0,005), nível sérico de sódio(Razão de Risco=0,94; Intervalo de Confiança 95% de 0,90 a 0,98; p=0,004), suporte inotrópico(Razão de risco = 1,85; Intervalo de Confiança 95% de 1,21 a 2,64; p= 0,03) e uso de digoxina(Razão de Risco =2,35; Intervalo de Confiança 95% de 1,15 a 4,81; p=0,02) foram fatores de predição independentes de mortalidade geral. A probabilidade de sobrevida em 12, 24, 36, e 60 meses foi 74%, 60%, 52%, e 37%, respectivamente, em pacientes com disfunção renal crônica e 84%, 70%, 70% e 35%, respectivamente, em pacientes sem disfunção renal crônica(p>0,05). A disfunção renal crônica tem baixa prevalência e não tem significância prognóstica em pacientes com insuficiência cardíaca crônica sistólica secundária a cardiomiopatia chagásica.

En France, environ un million de personnes seraient touchées par l’insuffisance cardiaque (IC) ; on recense près de 70 000 décès liés à l’IC, et plus de 150 000 hospitalisations et cela, malgré une prise en charge thérapeutique bien codifiée. Ces chiffres devraient s’accroitre dans les années futures du fait notamment du vieillissement de la population.L’objectif de ce travail était d’étudier l’utilisation des traitements pharmacologiques indiqués dans le traitement de l’IC (beta bloquant, inhibiteur de l’enzyme de conversion, anti-aldostérone, antagoniste des récepteurs à l’angiotensine II, diurétiques, digoxine, ivabradine) en situation réelle de soin, et d’identifier les facteurs cliniques ou pharmacologiques associés à la survenue d’un épisode de décompensation cardiaque.Un premier travail a permis de mesurer la fiabilité des bases de données médico-administratives françaises pour identifier des patients IC.Une deuxième étude a permis d’estimer que 17 à 37% de patients IC n’étaient exposés à aucun traitement de l’IC dans l’année suivant une première hospitalisation pour IC.Les troisième et quatrième parties de cette thèse ont mis en évidence qu’environ un quart des patients IC étaient réhospitalisés dans les 2 ans suivant une première hospitalisation. Les principaux facteurs cliniques prédictifs de cette réhospitalisation étaient l’âge, l’hypertension artérielle, la fibrillation auriculaire et le diabète. L’association retrouvée entre l’utilisation de fer bivalent et la réhospitalisation pour IC, souligne l’importance du risque lié à la présence d’une anémie ou d’une déficience en fer dans la survenue d’un épisode de décompensation cardiaque.Ces résultats permettent de reconsidérer la prise en charge thérapeutique chez les patients IC et mettent en avant la nécessité de renforcer la surveillance des patients les plus à risque de décompenser leur IC
In France, around one million persons would be affected by heart failure (HF); there are nearly 70 000 deaths related to HF and more than 150 000 hospitalizations despite a well defined treatment management. These numbers should increase in the next years due in particular to the ageing of the population.The objective of this work was to study the use of the pharmacological treatments indicated in HF (beta-blocker, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone antagonist, diuretics, digoxin, ivabradine) in real-world setting and to identify the clinical or pharmacological predictors associated with a new episode of cardiac decompensation.A first work has enabled to estimate the accuracy of French claims databases in identifying HF patients.A second study estimated that 17 to 37% HF patients were not exposed to any HF treatment in the year following an incident HF hospitalization.The third and fourth parts of this thesis showed that almost one forth of HF patients was rehospitalized within the 2 years following a first hospitalization. The main clinical predictors of rehospitalization were age, high blood pressure, atrial fibrillation and diabetes. The association found between bivalent iron use and HF rehospitalization underlines the importance of the risk related to anemia or iron deficiency in the occurrence of a cardiac exacerbation episode.These results allow to reconsider the treatment management of HF patients and highlight the need to reinforce the surveillance of patients with a highest risk of cardiac exacerbation

Periodic breathing (PB) is common in chronic heart failure (CHF) and has poor prognosis. The most commonly used therapy option involve continuous positive airway pressure, which is not acceptable to all patients. In this thesis I present a mathematical model providing a novel approach to treat PB with carefully controlled dynamic administration of supplementary CO2. I explored the consequences of phasic CO2 administration, with different timing and dosing algorithms. I found an optimal time window within the ventilatory cycle in which therapy reduces ventilation oscillations by more than 95%. Outside this window therapy increases ventilatory oscillations by more than 30%. A quadratic grading of CO2 dose (combined gradation of both concentration and duration) increased treatment efficiency. The undesired increase in mean CO2 caused by dynamic therapy was negligible compared with static therapy, to achieve the same degree of ventilatory stabilisation. Similarly, the increase in average ventilation was much smaller with dynamic than static therapy. In collaboration with my clinical and engineering colleagues we tested my model findings on seven healthy subjects simulating voluntary PB and seven heart failure (HF) patients with day time spontaneous PB. Dynamic CO2 administered at hyperventilation phase achieved the greatest reduction in ETCO2 oscillations caused by voluntary PB, and practically abolished spontaneous PB in the HF patients. During dynamic CO2 administration the mean ETCO2 and ventilation levels were not different to baseline and much lower than during continuous CO2 administration, in both groups of subjects. I developed the model further to investigate the effect of random physiological fluctuations on dynamic CO2 therapy and investigated, which is the best single parameter to guide dynamic CO2 therapy. I found that if alveolar CO2 could be measured to guide therapy, it would be as effective as using ventilation. However ETCO2, the clinically observable variable, is less effective because during severe hypopnoea it markedly diverges from alveolar CO2. Dynamic CO2 therapy ameliorated both sustained PB in unstable systems and intermittent PB in stable systems, although both guidance methods became less effective with a large noise component, regardless of the underlying system stability. I investigated further the emergence of intermittent ventilatory periodic patterns, on normally stable systems (loop gain < 1), following the introduction of random physiological fluctuations into the model. This was due to the amplification of the added noise by the delay feedback system, at its natural frequency. The development of this intermittent periodic breathing pattern is dependent on the proximity of the feedback system's loop gain to its tipping point (loop gain=1.0). To investigate the possibility of modulating heart rate by using implantable pacemaker in HF patients with PB, as a tool to manipulate ETCO2 and subsequently ventilation, I devised a novel analytical model equation that demonstrated how a change in cardiac output alters alveolar CO2. We implemented this model equation and found that ETCO2 and ventilation developed consistent oscillations with period 60s during the heart rate alternations. Furthermore, we verified the mathematical prediction that the amplitude of these oscillations would depend on those in cardiac output.

Purpose: To evaluate the diagnostic performance of Coronary Computed Tomography Angiography (CCTA) in predicting Myocardial Perfusion Scintigraphy (MPS) perfusion defects in low likelihood patients with End Stage Renal Disease (ESRD) awaiting transplant. Materials and Methods: In total, 131 consecutive patients with ESRD awaiting transplant were prospectively enrolled in this study (86 men; 54±9years). All patients underwent MPS as per standard of care and in addition non-enhanced CT for calcium scoring (CAC score) and Coronary Computed Tomography Angiography (CCTA). Results: The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CAC score in predicting MPS perfusion defects were 88%, 35%, 28% and 92%, respectively. The sensitivity, specificity, PPV and NPV of CCTA in predicting MPS perfusion defects at the patient level were 55%, 87%, 57% and 87%, respectively, and 48%, 92%, 41% and 94% at the vessel level. The diagnostic performance of CCTA in predicting MPS perfusion defects improved when patients with CAC score higher than 1000 (15/70, 21%) were excluded from the analysis. In patients with positive CAC score up to 1000 sensitivity, specificity, PPV and NPV at the patient level were 60%, 93%, 75% and 86% respectively. These were 53%, 91%, 36% and 95%, respectively, at the vessel level. Conclusion: Non-enhanced CT for CAC score and CCTA can be considered useful diagnostic tools in the ESRD population, particularly in identifying patients without coronary artery disease. This approach however had limitations in the presence of high CAC score.

Anemia is common in patients with chronic kidney disease (CDK), contributes to reduced Quality of Life (QoL) and is associated with cardiovascular disease, morbidity and mortality. Epoetin raises hemoglobin (Hb) and increases QoL and physical exercise capacity. Because of concerns about safety and economics, current anemia treatment with epoetin aims to achieve subnormal Hb (110-120 g/l). Normalization of Hb may be of additional benefit regarding QoL and cardiovascular effects. The present study examines the effects of Hb normalization with epoetin on safety variables, QoL, graft function after kidney transplantation, dialysis adequacy, hemorheology, hemodynamics and cardiac autonomic function in CKD patients.

In a randomized, multicenter study comprising 416 pre-dialysis and dialysis patients no difference was observed between patients treated to a normal or a subnormal Hb level on mortality, thrombovascular events, serious adverse events, vascular access thrombosis and residual renal function. QoL was enhanced in a subgroup of hemodialysis patients. Pretransplant epoetin treatment directed toward normal Hb levels did not result in worse graft function during 6 postoperative months. Dialysis adequacy was reduced in a subgroup of hemodialysis patients after normalization of Hb. The blood flow properties of pre-dialysis patients were altered. The hemorheological investigation demonstrated that Hb normalization caused a parallel increase in hematocrit and blood viscosity without other hemorheological changes. While the total peripheral resistance index increased, the cardiac index (CI) decreased. In a separate study cardiac autonomic function, measured by heart rate variability, was decreased in pre-dialysis patients. It was improved, but not fully normalized, by Hb normalization.

On the basis of this study, Hb normalization with epoetin appears to be safe and increases QoL in hemodialysis patients though may result in lower dialysis adequacy and increased blood pressure. A reduction in CI and improved cardiac autonomic function indicate a positive effect on cardiovascular function.

Submitted by Cristiane Chim (cristiane.chim@ucpel.edu.br) on 2018-05-07T11:51:08Z No. of bitstreams: 1 LARISSA RIBAS RIBEIRO.pdf: 853387 bytes, checksum: b07d078ec1ece03014fcfd9275152a65 (MD5)
Made available in DSpace on 2018-05-07T11:51:08Z (GMT). No. of bitstreams: 1 LARISSA RIBAS RIBEIRO.pdf: 853387 bytes, checksum: b07d078ec1ece03014fcfd9275152a65 (MD5) Previous issue date: 2017-11-28
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES#
#2075167498588264571#
#600
Introduction: Chronic kidney disease (CKD) is characterized by progressive decrease in glomerular filtration rate (GFR), eventually reaching the end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). The decrease in GFR is associated with a gradual and linear increase in cardiovascular mortality. Dysfunction of the autonomic nervous system (ANS) with sympathetic overactivity has been well documented in patients with CKD, especially in people with ESRD. The renal ischemia causes both the excessive activation of the renin-angiotensin-aldosterone system (RAAS) by increasing renin release, as sympathetic ANS, through the afferent sympathetic nerves. The overactivated RAAS and sympathetic SNA feedback each other, which contributes to cardiovascular disease (CVD) in CKD. Despite the clear involvement of these systems in the pathogenesis of CVD in CKD, randomized clinical trials using drugs that block the RAAS or sympathetic SNA have not shown significant effects in the frequency of cardiovascular events in this population. A possible explanation for these negative findings is the genetic heterogeneity, such as the polymorphism in the gene for angiotensin converting enzyme (ACE). Objectives: To investigate the correlation between polymorphisms in the ACE gene and heart rate variability (HRV), a noninvasive tool used to assess ANS activity, in patients with CKD on hemodialysis treatment. Hypotheses: The D allele of the ACE gene, associated with increased activity of the RAAS, would be associated with increased sympathetic activity, which is reflected in lower HRV. If confirmed, the finding could point the subgroup of patients that may get additional benefit of drugs that act on the sympathetic and RAAS systems. Methodology: quantitative and cross-sectional study. The sample will consist of at least 129 adult patients with CKD on hemodialysis treatment (HD) for more than 90 days. It wil be obtained sociodemographic data, previous medical history and medications used. HRV analysis will be conducted through Micromed® ECG machine with registration pulse interval variance, root mean square of squared differences between consecutive intervals (RMSSD) and the percentage of intervals greater than 50 milliseconds (pNN50), a low frequency band (LF) and high frequency (HF), at a time of normovolemia after a midweek HD session. Analysis of hydration status will be made through multi-Frequency bioimpedance device. Polymorphism of the ACE gene will be assessed by polymerase chain reaction method in peripheral blood sample. Data analysis will be performed by ANOVA with comparison of the LF / HF ratio, a component of HRV analysis, between polymorphisms II, ID and DD of the ACE gene. Multivariate analysis with linear regression will be applied using as dependent variables the HRV parameters, and as independent variables the polymorphisms of ACE gene and all variables known to influence HRV, for adjustment purposes. The data will be analyzed using the statistical package STATA 14.0.
Introdução: A doença renal crônica (DRC) caracteriza-se pela redução progressiva da taxa de filtração glomerular (TFG), eventualmente alcançando o estágio de doença renal crônica terminal (DRCT) com necessidade de terapia renal substitutiva (TRS). A diminuição da TFG está associada a um aumento progressivo e linear na mortalidade cardiovascular. A disfunção do sistema nervoso autônomo (SNA) com hiperatividade simpática tem sido bem documentada em pacientes portadores de DRC, especialmente na população com DRCT. A isquemia renal provoca tanto a ativação exagerada do sistema renina-angiotensina-aldosterona (SRAA), através do aumento da liberação de renina, quanto do SNA simpático, por meio dos nervos simpáticos aferentes. O SRAA e o SNA simpático, ambos hiperativados, se retroalimentam mutuamente, o que contribui para a doença cardiovascular (DCV) na DRC. Apesar da clara participação destes sistemas na gênese da DCV da DRC, ensaios clínicos randomizados utilizando drogas que bloqueiam o SRAA ou SNA simpático não têm mostrado efeitos significativos na redução de eventos nessa população. Uma possível explicação para esses resultados negativos seria a heterogeneidade genética, como por exemplo, o polimorfismo no gene da enzima conversora da angiotensina (ECA). Objetivos: Investigar a associação entre polimorfismos no gene da ECA e a variabilidade da frequência cardíaca (VFC), uma ferramenta não invasiva utilizada na avaliação da atividade do SNA, em pacientes portadores de DRC em tratamento por hemodiálise. Metodologia: Estudo quasi experimental do tipo antes e depois. A amostra foi composta por 114 pacientes adultos portadores de DRC em tratamento por hemodiálise (HD) há mais de 90 dias. Foram obtidos dados sociodemográficos, história clínica pregressa e medicamentos em uso. A análise da VFC foi realizada através de aparelho de eletrocardiograma Micromed® com registro do desvio padrão de todos os intervalos normais (SDNN), raiz quadrada da média dos quadrados das diferenças entre intervalos consecutivos (RMSSD), banda de baixa frequência (LF) e de alta frequência (HF), em momento de normovolemia, após uma sessão de HD do meio da semana. A análise do estado de hidratação foi realizada através de aparelho de bioimpedância multi-frequencial. O polimorfismo do gene da ECA foi avaliado por método de reação em cadeia da polimerase em amostra de DNA de sangue periférico. A análise dos dados foi realizada por ANOVA, com comparação da razão LF/HF, componente da análise da VFC, entre os polimorfismos II, ID e DD do gene da ECA. Análise multivariada com regressão linear foi aplicada utilizando como variáveis dependentes os parâmetros da VFC e como variáveis independentes foram incluídos os polimorfismos do gene da ECA juntamente com variáveis que sabidamente influenciam a VFC, para efeito de ajuste. Os dados foram analisados através do pacote estatístico STATA 15.0.

A doença renal crônica (DRC) se associa com a hiperatividade dos sistemas nervoso simpático e renina-angiotensina-aldosterona, o que leva e aumento da pressão arterial. O exercício aeróbico pode ser utilizado para prevenir as doenças cardiovasculares associadas à DRC, em especial a hipertensão arterial porque uma única sessão de exercício aeróbico promove redução da pressão arterial após a sua execução e esse fenômeno é denominado hipotensão pós-exercício. Este efeito do exercício é mediado pela redução da atividade nervosa simpática periférica e diminuição da atividade do sistema renina-angiotensina-aldosterona. Entretanto, a presença de polimorfismos do gene da enzima conversora de angiotensina I (ECA) pode modificar a resposta aguda ao exercício aeróbico. Outro benefício descrito do exercício é seu efeito anti-inflamatório observado pela redução de marcadores inflamatórios cuja presença na DRC é marcante. Desta forma, este estudo avaliou o efeito de uma sessão de exercício aeróbico na pressão arterial, na variabilidade da frequência cardíaca e nos marcadores inflamatórios em pacientes com DRC no estágio 3, portadores de polimorfismo do gene da ECA. Para isso, 12 pacientes com DRC (estágios 3A e 3B) e 12 indivíduos saudáveis realizaram duas sessões experimentais conduzidas em ordem aleatória de exercício aeróbico (cicloergômetro, 45 min, 50% VO2pico) e repouso (repouso sentado no cicloergômetro por 45 min). Antes e após as sessões foi coletada amostra de sangue para a análise dos marcadores inflamatórios, foi registrada a variabilidade da frequência cardíaca e da pressão arterial (Finometer) e a pressão arterial. Para a análise estatística dos dados, a normalidade da distribuição foi testada pelo teste de Shapiro-Wilk e transformações matemáticas foram feitas quando necessário. Os dados foram comparados através do teste T de Student para amostras repetidas e não repetidas e pela ANOVA de dois fatores, utilizando-se como pós-teste de contraste o teste de Newman-Keuls. O exercício promoveu maior redução da PAS no grupo com DRC (-14 ± 7 vs. -4 ± 1 mmHg), na PAD o resultado foi semelhante, no qual o grupo com DRC apresentou reduções maiores que o grupo controle (-4 ± 4 vs -1 ± 1 mmHg). A FC não apresentou diferença significativa nos dois grupos pós exercício (5 ± 3 vs. 9 ± 7 bpm). As variáveis hemodinâmicas não foram diferentes entre os portadores das variações DD e II. O exercício promoveu modulação autonômica cardíaca semelhante nos dois grupos, na BFR-R e AFR-R os resultados foram semelhantes (69 ± 13 vs. 74 ± 16 un) (28 ± 20 vs. 19 ± 12 un). A variância total apresentou aumento pós exercício nos dois grupos (884 ± 837 vs. 3139 ± 2521 ms²). A modulação vasomotora (BFPAS) aumentou nos dois grupos (14 ± 4 vs. 43 ± 36) e a sensibilidade barorreflexa reduziu nos dois grupos após o exercício. Os genótipos não influenciaram as respostas neurais. Entre os marcadores inflamatórios, o TNF-alfa pós-exercício se manteve inalterado nos dois grupos estudados, mantendo apenas a diferença encontrada no pré (7,62 ± 1,21 vs. 5,59 ± 0,96). Houve redução da IL-6 nos dois grupos, porém a redução foi maior no grupo com DRC, aproximando-se dos níveis do grupo controle (1,9 ± 0,4 vs. 1,51 ± 0,45). Houve aumento da IL-10 nos dois grupos no período pós exercício, porém sem diferença significativa entre si. Não houve interação entre as variantes genotípicas e as respostas dos marcadores inflamatórios ao exercício. Concluímos que o exercício aeróbico agudo reduziu os níveis de pressão arterial de forma mais efetiva no grupo com DRC, melhorou a modulação autonômica cardíaca, reduziu as concentrações de marcadores pró-inflamatórios e aumentou as concentrações de marcadores anti-inflamatórios nos pacientes com DRC. Os polimorfismos genotípicos não influenciaram as respostas das variáveis estudadas
Chronic kidney disease (CKD) is associated with hyperactivity of the sympathetic nervous system and renin-angiotensin-aldosterone, which leads to increased blood pressure. Aerobic exercise can be used to prevent cardiovascular diseases associated with CKD, especially arterial hypertension because a single aerobic exercise session promotes blood pressure reduction after its execution and this phenomenon is called post-exercise hypotension. This effect of exercise is mediated by the reduction of peripheral sympathetic nerve activity and decreased activity of the renin-angiotensin-aldosterone system. However, the presence of angiotensin I converting enzyme (ACE) gene polymorphisms may modify the acute response to aerobic exercise. Another benefit of exercise described is its anti-inflammatory effect observed by the reduction of inflammatory markers whose presence in CKD is marked. Thus, this study evaluated the effect of an aerobic exercise session on blood pressure, heart rate variability and inflammatory markers in stage 3 CKD patients with ACE gene polymorphism. To do this, 12 patients with CKD (stages 3A and 3B) and 12 healthy subjects performed two experimental sessions conducted in a random order of aerobic exercise (cycle ergometer, 45 min, 50% VO2peak) and rest (sitting on cycle ergometer for 45 min). Before and after the sessions a blood sample was collected for the analysis of inflammatory markers, the variability of heart rate and blood pressure (Finometer) and blood pressure were recorded. For the statistical analysis of the data, the normality of the distribution was tested by the Shapiro-Wilk test and mathematical transformations were done when necessary. The data were compared by Student\'s t test for repeated and non-repeated samples and by two-way ANOVA, using the Newman-Keuls test as contrast test. The exercise promoted a greater reduction of SBP in the group with CKD (-14 ± 7 vs. -4 ± 1 mmHg), in the DBP the result was similar, in which the group with CKD presented reductions larger than the control group (-4 ± 4 vs -1 ± 1 mmHg). HR did not present a significant difference in the two post exercise groups (5 ± 3 vs. 9 ± 7 bpm). Hemodynamic variables were not different between patients with DD and II. The exercise promoted similar cardiac autonomic modulation in both groups, in the BFR-R and AFR-R the results were similar (69 ± 13 vs. 74 ± 16 un) (28 ± 20 vs. 19 ± 12 un). The total variance presented increase after exercise in both groups (884 ± 837 vs. 3139 ± 2521 ms²). Vasomotor modulation (BFPAS) increased in both groups (14 ± 4 vs. 43 ± 36) and baroreflex sensitivity decreased in both groups after exercise. Genotypes did not influence neural responses. Among the inflammatory markers, post-exercise TNF-alpha remained unchanged in the two groups, maintaining only the difference found in the pre (7.62 ± 1.21 vs. 5.59 ± 0.96). There was a reduction in IL-6 in both groups, but the reduction was greater in the CKD group, approaching the levels of the control group (1.9 ± 0.4 vs. 1.51 ± 0.45). There was an increase in IL-10 in the two groups in the post-exercise period, but without significant difference between them. There was no interaction between the genotypic variants and the responses of the inflammatory markers to exercise. We concluded that acute aerobic exercise reduced blood pressure levels more effectively in the CKD group, improved cardiac autonomic modulation, reduced proinflammatory markers concentrations, and increased concentrations of anti-inflammatory markers in CKD patients. Genotypic polymorphisms did not influence the responses of the studied variables

碩士
台北醫學院
醫學資訊研究所
90
Purpose This study is aimed to explore the relationship between heart rate variability (HRV) parameters and electrolyte concentrations in both pre- and post-dialysis. Method 26 chronic renal failure patients (13 women, 13 men, 56.7±13.8 years) receiving maintenance hemodialysis therapy and 62 normal subjects (47 men，15 women，24.08±7.71 years) were included in this study. Patients were measured 5-minute ECG at rest. Calcium, phosphate, sodium, potassium, and chloride concentrations were collected before and after hemodialysis. ECGs were digitized by microcomputer. The next step was calculating the RR interval duration, then measuring average of RR intervals and standard deviation of all RR intervals. The short-term frequency domain HRV parameters are computed using fast Fourier transform (FFT). Five frequency domain and two time domain parameters of HRV are calculated: (1) LF: power in LF (low-frequency), range (0.04~0.15Hz); (2) LF norm: LF power in normalized units; (3) HF: power in HF (high-frequency), range (0.15~0.4 Hz); (4) HF norm: HF power in normalized units; (5) LF/HF: Ratio LF /HF; (6) MeanRR: average of RR intervals; (7) SDRR: standard deviation of all RR intervals. Statistical Analysis Wilcoxon signed rank test was used to compare HRV parameters and electrolyte levels before and after hemodialysis. Linear regression was performed to correlate HRV parameters with electrolyte concentrations before and after hemodialysis. Two-sample t-test was used to compare pre- and postdialysis HRV parameters with normal subjects. p<0.05 was considered significant. Result The longer duration of hemodialysis may increase SDRR, LF, and HF before hemodialysis. There is no significant relationship between electrolyte concentrations and HRV parameters before hemodialysis. Reduced phosphate level decreases sympathetic activity after hemodialysis. Increased calcium concentration is result in vagal modulation reduction. Decreased sympathovagal interaction is due to potassium level reduction. Calcium, phosphate, sodium, potassium, and chloride concentrations change significantly between before and after hemodialysis. There is no significant relationship on HRV parameters, except LF/HF ratio, before and after hemodialysis.

碩士
中原大學
醫學工程學系
87
Impairment of autonomic control of the cardiovascular system is frequency complication in chronic renal failure patients. Procedures based on changes in either blood pressure or heart rate in response to standard stimuli have been used to locate the defective part of the autonomic nervous system in patients undergoing regular hemodialysis(HD).Heart rate variability (HRV) is a recently introduced method for the quantitative description of the rhythmical components of cardiovascular variability. To purpose of this investigation was to determine non-invasively the alteration in autonomic cardiovascular control observed in chronic renal failure. Amplitude spectral of heart rate rhythmicity were estimated and integrated amplitudes of the low (0.04-0.15 Hz) and high frequency (0.15-0.4 Hz) component were computed. The normalized low-frequency spectral power was used as the index of sympathetic activity, the normalized high-frequency spectral power as the index of vagal activity and the low/high frequency power ratio as the index of sympathovagal balance of the study subjects.The study population consisted of 48 uremic patients without clear and obvious arrhythmia and 9 healthy controls were analyzed, and compared with before and after HD in postural change. The principle are as follows: (1)Heart rate increased significantly both healthy controls and patients in postural changed from supine to upright. (2)After HD, the low, high frequency power and low/high ratio were statistically significantly (P<0.05) in postural change, relatively before HD wasn''t. Take together, these findings suggest that volume depletion in chromic renal patients during a dialysis treatment is responsible for the improvement of HRV and its spectral components.

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, 2017.
Background: In spite of the contributions of cardiovascular disease (CVD) to morbidity and mortality in chronic kidney disease (CKD) worldwide, there are no studies that have looked at cardiovascular risk factors (CVRFs) and their association with cardiovascular changes in African children with CKD. Several CVRFs have been implicated in the initiation and progression of cardiovascular changes in children with CKD, and these changes have been reported even in early CKD. This study investigated CVRFs and their association with cardiovascular changes in South African children with CKD. Method: This comparative cross sectional study recruited children (5-18 years) with CKD being followed up at the Division of Paediatric Nephrology of the Charlotte Maxeke Johannesburg Hospital and the Chris Hani Baragwanath Academic Hospital. One hundred and six children with a spectrum of CKD including those on chronic dialysis (34 CKD I, 36 CKD II-IV and 36 CKD V-dialysis) were enrolled over a 12 month study period. All patients had a short history taken along with a physical examination. Blood samples for serum creatinine, urea, albumin, calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphatase, total cholesterol, haemoglobin and C-reactive protein, Vitamin D, Fibroblast growth factor-23 (FGF-23), Fetuin-A and genomic DNA studies were taken. Where feasible, transthoracic echocardiography and high resolution ultrasonography of the common carotid artery was performed. Results: The overall median age of the patients was 11 years (8-14 years), with a male female ratio of 2.1:1. Several CVRFs detected include hypertension, proteinuria, anaemia, hypercholesterolaemia and dysregulated mineral bone metabolism. The most common CVRF detected was anaemia (39.6%) and its prevalence was highest in the dialysis group when compared with the other CKD groups. The overall median (range) cIMT was 0.505mm (0.380-0.675), and was highest in patients with dialysis dependant CKD (p=0.003). The distribution of left atrial diameter (LAD) and left ventricular mass (LVM) differed significantly (p<0.05) across the different CKD groups. Abnormal LAD was seen in 10% of patients; left ventricular hypertrophy (LVH) in 27%; left ventricular systolic dysfunction in 6% and diastolic dysfunction in one patient. Mean arterial pressure and haemoglobin levels were independently associated with cIMT; hypertension was independently associated with concentric LVH; and age and hypoalbuminaemia were independently associated with eccentric LVH. Overall, the dialysis group had the highest prevalence of vascular changes, cardiac changes and associated risk factors. A skewed pattern of Fetuin-A and FGF-23 levels with medians (range) of 57.7 (0.9-225.2) mg/dL and 28.9 (0-3893.0) pg/ml respectively, were observed. The levels of these two biomarkers varied significantly between the different CKD groups (p<0.05). Fetuin-A was independently associated with abnormal LAD but no similar relationship with other cardiovascular changes and plasma levels of Fetuin-A and FGF-23 was found. Plasma FGF-23 levels correlated better with markers of bone mineralization than Fetuin-A. Eight Fetuin-A SNPs were analysed; rs2248690, rs6787344, rs4831, rs4917, rs4918, rs2070633, rs2070634 and rs2070635. We found an association between log-transformed Fetuin-A levels and the SNP rs4918 G-allele compared to the rs4918 C-allele (p=0.046) and the rs2070633 T-allele when compared to the rs2070633 C-allele (p=0.015). Markers of MBD such as phosphate and PTH levels were associated with Fetuin-A SNPs. The rs6787344 G-allele was significantly associated with phosphate levels (0.042), and the rs4918 G-allele with PTH (p=0.044). Seven deaths were recorded in the dialysis group during the study period and severe hypertension and intracranial bleed were the most common causes of death. Modifiable risk factors such as increased total cholesterol (TC) and decreased albumin levels were more commonly seen among the deceased dialysis patients. Conclusion: A high prevalence of CVRFs and cardiovascular changes were observed in the study groups, even in those with mild to moderate disease. Information obtained from the study highlights the need to address modifiable CVRFs such as hypertension, anaemia and hypoalbuminaemia in children with CKD and also the need to determine new, population specific, paediatric reference values for cIMT in healthy African children. Finally, the study was able to demonstrate differences in the relationship between Fetuin A SNPs and Fetuin-A levels and cardiovascular changes in our study population when compared with previously published data. We postulate that these differences may be due to genetic differences between our population and other population groups previously studied.
LG2018

ABSTRACT IMPORTANCE: Age-related macular degeneration (AMD) is a leading cause of low vision in elderly population. The association of vascular and renal conditions has been reported inconsistently. Unfolding the association may provide the insight to eye care providers to take account general health management into eye care. OBJECTIVES: To investigate the prevalence of the vascular and renal comorbidities with AMD, examine the association of a single or combination of these comorbidities with AMD. DSIGN AND PARTICIPANTS: Population-base cross-sectional study involved the adults aged 40 years or older (N=4596) who participated in the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES), a national representative population-based survey of non-institutionalized US residents. MAIN OUTCOMES AND MEASURES: AMD was defined by the presence of drusen and presence of pigmental abnormality. Angina pectoris (AP), coronary heart disease (CHD), congestive heart failure (CHF) and myocardial infarction (MI), and stroke, assessed by self-report by the questionnaire of medical conditions, Chronic kidney disease (CKD), assessed by self-report and estimation of glomerular filtration rate (GFR) and the level of urine albumin. Heart disease (HD) was defined as having AP or CHF or CHD or MI. RESULTS: Among individuals with AMD, 6% had AP, 10% had CHD, 7% had CHF, 10% had MI, 13% had stroke, and 29% had CKD. The weighted prevalence of these conditions were significantly higher than those without AMD (All P-values CONCLUSION AND RELEVANCE: These findings from the nationally-representative sample of the US population highlight the prevalence of vascular and renal comorbidities associated with AMD, the modest evidence of relationship of each single comorbidity, and strong association of combination of stroke and CKD to AMD independent of age, gender, and other factors. Because of the cross-sectional design, the results of this study can not address a causal relationship between AMD and the examined comorbidities. It is unclear whether AMD and comorbidities arise from individual predisposition to vascular and renal diseases or whether complications from these morbidities increase the risk of AMD. However, the important caveat is that preventive and care management for the examined comorbidities may lessen the severity of symptoms or prevent AMD.