No description available.

No description available.

Introduction: Rheumatoid arthritis (RA) is known to be associated with an increased risk of cardiovascular disease (CVD), resulting in excess mortality. Dyslipidaemia has been identified as a major CVD risk factor in the general population. Current evidence would suggest that lipid metabolism is altered in RA due to inflammation, and that use of anti-inflammatory therapy may reverse some of these changes. However, the impact of such lipid changes on CVD in RA remains unknown. Data regarding the effects of RA/drug therapy on lipid structure and function are sparse. Genetic factors are important in the pathogenesis of RA and play a central role in the regulation of lipid metabolism. To date, no studies have assessed the impact of genetic polymorphisms on lipids in RA.The aim of this thesis is to: 1) assess the prevalence of dyslipidaemia in RA and the CVD risk this confers 2) establish the effects of inflammation on lipid levels and lipid ratios 3) assess the impact of anti-inflammatory drug therapy (anti-TNF, rituximab and intravenous glucocorticoids) on lipid levels, structure and function 4) assess the prevalence and associations of particular genetic polymorphisms (RA susceptibility and lipid metabolism regulating genes) with lipids in RA.Methods: Data from 400 RA patients were used to address aims 1, 2 and 4 in cross-sectional studies. All patients had a clinical assessment and fasting blood taken. Blood was processed to provide data on the lipid profile, ESR, CRP and DNA was extracted for genotyping. Aim 2 and 4 also utilised a retrospective longitudinal cohort of 550 RA patients and the DNA from 400 healthy controls, respectively. Aim 3 was addressed using a longitudinal cohort including: patients due to commence anti-TNF (n=35), rituximab (n=10), intravenous glucocorticoids (n=12); 15 RA controls on stable therapy; and 40 healthy controls. Assessments and blood samples were taken at baseline, 2 weeks and 3 months. Results: Dyslipidaemia was highly prevalent (56.8%), but undertreated in many RA patients at risk of developing CVD. Systemic inflammation associated with many of the changes in lipid levels and structure. Lipid ratios were found to be less susceptible to fluctuations due to inflammation. The use of anti-inflammatory drug therapy produced changes in lipid structure and function through both generic suppression of inflammation and drug specific mechanisms (particularly in the case of glucocorticoids). The prevalence of cholesterol ester transfer protein (CETP) and Apolipoprotein C3 genetic polymorphisms differed between RA patients and local population controls. RA susceptibility genes (HLA-DRB1-SE and TRAF1C5) and several ’lipid metabolism genes’ (Apolipoprotein E, ATP-binding cassette transporter 1 (ABCA1) and CETP) were found to associate with lipid levels within the RA population. Conclusion: Dyslipidaemia is highly prevalent in RA and currently undertreated. Dyslipidaemia in RA is regulated by numerous factors including inflammation, drug therapy and genetic factors. Further longitudinal studies are required to assess whether these findings have an impact on hard CVD endpoints.

Apolipoproteins have important roles in the transport of lipids and the regulation of lipoprotein metabolism as cofactors for enzymes and ligands for receptor-binding. Their function and metabolism are closely related to the development of many diseases. This dissertation describes the investigation of the distribution and metabolism of apoE and glycated apoE in diabetes, obesity and hyperlipidaemia in comparison with healthy people. In order to carry out the research, I developed several robust laboratory methods and techniques for the isolation and measurement of apoE and glycated apoE. These included (1) a modified in-house ultracentrifugation for isolation of lipoprotein fractions (2) high sensitivity sandwich enzyme-linked immunosorbent assay (ELISA) for apoE and (3) m-aminophenylboronate affinity chromatography for the separation of glycated and non- glycated apoE.In healthy people the apoE concentration in different lipoprotein fractions is influenced by age, gender and apoE genotype. The effect of atorvastatin on serum apoE concentration in patients with type 2 diabetes with nephropathy was dependent on the dose of atorvastatin and apoE genotype and was strongly correlated with the reduction in triglycerides (TG) in very low density lipoprotein (VLDL).The effect of bariatric surgery on obese patients with and without diabetes demonstrated that after bariatric surgery, VLDL-apoE increased and apoE in low density lipoprotein (LDL), high density lipoprotein (HDL) and d>1.21g/ml fractions decreased; both glycated LDL-apoE and glycated HDL-apoE decreased. Total apoE and glycated apoE concentrations in plasma decreased to levels comparable to those of healthy controls. However, the distribution within the lipoprotein fractions was very different. The effect of niacin/laropiprant (LRPT) on lipoproteins in hyperlipidaemia patients was assessed in a blind crossover trial. Niacin/LRPT slightly decreased VLDL-apoE and LDL-apoE. It had no effect on apoE in HDL. Glycated apoE did not change in hyperlipidaemia. These results show that, compared with healthy people, the apoE distribution in obese and hyperlipidaemia patients is abnormal despite no change in total apoE concentration in some cases. The results also demonstrate that glycated apoE originates preferentially from VLDL. Various mechanisms for these results and relationships with other lipids are discussed. Furthermore, I suggest several potential directions, especially in vitro, for further research on apoE function and metabolism.

Abstract The aim of this study was to investigate the nature of the association between obesity and periodontal infection and the association of statin medication with periodontal infection. This study was based on the nationally representative Health 2000 Survey, conducted by the National Institute for Health and Welfare (former National Public Health Institute of Finland) in 2000–2001. Article I included 396 dentate, non-diabetic subjects, aged 30–59 years, who had never smoked and who participated in the Follow-up Study on Finnish Adults’ Oral Health about four years later. Article II included 2,784 dentate, non-diabetic subjects, aged 30–49 years. Article III included 425 dentate, non-diabetic, non-rheumatic subjects, aged 45–64 years, who had never smoked and who participated in the in-depth examinations of the Health 2000 Survey. Article IV included 1,297 dentate, non-diabetic subjects, aged 30–49 years, who had never smoked. Article V included 2,032 dentate, non-diabetic, non-rheumatic subjects, aged 40–69 years, who did not smoke. The data used in this study were collected via home-visit interviews, self-administered questionnaires, clinical health examinations and laboratory measurements. In this general population of Finnish adults, high BMI was found to be associated with the incidence of new teeth with pathologically deepened periodontal pockets during four-year follow-up. On the other hand, the presence of teeth with deepened periodontal pockets was found to be associated with obesity in an exposure-response manner. Serum IL-6 levels were found to be associated with the number of teeth with deepened periodontal pockets, but no consistent association was found between serum TNF-α, triglyceride, HDL-C or LDL-C levels and periodontal infection. Statin medication was found to be inversely associated with the number of teeth with deepened periodontal pockets among subjects with visible signs of gingival inflammation, whereas among subjects with no signs of inflammation, statin medication was associated with an increased likelihood of having periodontal infection. The results of this study support the view that obesity could be causally related to the development of periodontal infection, but does not provide evidence that high body weight could be considered a major risk factor. The present study also suggests that a bi-directional association between obesity and periodontal infection is possible. The present study suggests that elevated serum IL-6 could mediate the association of obesity with periodontal infection. The results of this study also suggest that statins could be beneficial as a part of periodontal treatment. / Tiivistelmä Tämän tutkimuksen tarkoituksena oli selvittää lihavuuden ja parodontaali-infektion välisen yhteyden luonnetta sekä statiinien käytön yhteyttä parodontaali-infektioon. Tutkimus perustui kansalliseen Terveys 2000 -tutkimukseen, jonka toteutti Terveyden ja hyvinvoinnin laitos (entinen Kansanterveyslaitos) vuosina 2000 ja 2001. Artikkeli I perustui 396 hampaalliseen henkilöön, jotka olivat ei-diabeetikkoja, 30–59-vuotiaita, eivät koskaan olleet tupakoineet sekä olivat osallistuneet suunterveyden seurantatutkimukseen neljä vuotta myöhemmin. Artikkeli II perustui 2784 hampaalliseen henkilöön, jotka olivat ei-diabeetikkoja, 30–49-vuotiaita eivätkä olleet koskaan tupakoineet. Artikkeli III perustui 425 hampaalliseen henkilöön, joilla ei ollut diabetesta tai reumaa, olivat 45–64-vuotiaita, eivät koskaan olleet tupakoineet ja olivat osallistuneet Terveys 2000 -tutkimuksen täydentäviin tutkimuksiin. Artikkeli IV perustui 1297 hampaalliseen henkilöön, jotka olivat ei-diabeetikkoja, 30–49-vuotiaita eivätkä olleet koskaan tupakoineet. Artikkeli V perustui 2032 hampaalliseen henkilöön, jotka olivat ei-diabeetikkoja, ei-reumaatikkoja, 40–69-vuotiaita, jotka olivat hampaallisia eivätkä tupakoineet. Tutkimuksen aineisto kerättiin kotihaastattelusta, kyselyistä, kliinisestä tutkimuksesta sekä laboratoriomittauksista. Korkean painoindeksin todettiin olevan yhteydessä uusien ientaskuhampaiden ilmaantumiseen seurannan aikana. Toisaalta ientaskuhampaiden esiintymisen todettiin olevan yhteydessä lihavuuteen altistus-vastesuhteen mukaisesti. Seerumin IL-6 pitoisuuden todettiin olevan yhteydessä ientaskuhampaiden lukumäärään, mutta seerumin TNF-α-, triglyseridi-, LDL-kolesteroli- tai HDL-kolesterolipitoisuudella ei todettu yhteyttä ientaskuhampaiden lukumäärään. Statiinien käytön todettiin olevan käänteisesti yhteydessä ientaskuhampaiden lukumäärään henkilöillä, joilla oli näkyviä merkkejä ikenen inflammaatiosta. Henkilöillä, joilla ei ollut näkyviä merkkejä inflammaatiosta, statiinien käyttö oli yhteydessä suurentuneeseen todennäköisyyteen ientaskuhampaiden esiintymiseen. Tämän tutkimuksen tulokset tukevat käsitystä, että lihavuus voi olla kausaalisesti yhteydessä parodontaali-infektion kehittymiseen, mutta ei puolla käsitystä, että sitä voitaisiin pitää merkittävänä riskitekijänä. On myös mahdollista, että lihavuuden ja parodontaali-infektion välillä on kaksisuuntainen yhteys. Tämän tutkimuksen tulosten mukaan on mahdollista, että kohonnut seerumin IL-6 pitoisuus voi välittää lihavuuden yhteyden parodontaali-infektioon. Tutkimuksen tulosten mukaan on myös mahdollista, että statiineista voi olla hyötyä osana parodontaalihoitoa.

Background: More than 5.5 million South Africans aged 30 years and older are at risk of chronic disease by virtue of their triglyceride levels (Maritz, 2006:101). Dyslipidaemia is common in westernized and industrialized communities (Steyn et al., 2000:720), especially so for South Africa, where burden of disease data show dyslipidaemia to be the second most prevalent of all the chronic conditions in the country (Council for Medical Schemes, 2006:48). It is therefore no surprise that at 3.3 per cent hipolipidaemics ranked second highest based on prevalence percentage per therapeutic group in the 2005 Mediscor medicines review on South African medical claims data (Bester et al., 2005:8-11). Hipolipidaemic drugs subsequently also ranked second highest for expenditure per therapeutic group, achieving a total expenditure of 5.8 per cent. Objective: The purpose of this study was to characterise the usage and cost of hipolipidaemic drugs in the private health care environment in South Africa based on various categories, including age, sex, prescriber type and generic indicator. Methods: A quantitative retrospective drug utilisation review was performed using dispensing records from a medicine claims database. Data for a two-year period (1 Jan. 2005 to 31 Dec. 2006) were used. Hipolipidaemic medicine usage was analysed according to five patient age strata: patients younger than 9 years, 10 ≤ 19 years, 20 ≤ 45 years, 46 ≤ 59 years and older than 59 years. Basic descriptive statistics such as frequencies and arithmetic mean (average) were used to characterise the study sample, and were calculated using the Statistical Analysis System (SAS®) for Windows 9.1® program (SAS Institute Inc., 2002-2003). Results: The database consisted of 19 860 593 and 21 473 062 medicine item claims for 2005 and 2006 respectively, at a total cost of R 1 893 376 921.00 (for 2005) and R2 046 944 383.00 (for 2006). Patients receiving hipolipidaemic medicine items represented about 7.2% of the total number of patients on the database in both 2005 and 2006. About 47% of the study population in both 2005 and 2006 was female, compared to 53% males. Hipolipidaemics represented between 3.1% (N = 19 860 593) and 3.3% (N = 21 473 062) of the total number of items claimed during the study period. The total cost of hipolipidaemics accounted for between 5.6% (N = R1 893 376 921.00) and 5.8% (N = R2 046 944 383.00) of the total cost of all medications claimed during the study period. The average cost per item of hipolipidaemics was R170.63 ± 70.19 in 2005 compared to R167.08 ± 71.93) in 2006. HMG-CoA reductase inhibitors formed the leading therapeutic class in hipolipidaemic medicine items in all age groups on the database, except for children aged 0 ≤ 9 years, where the “others” group, in particular cholestyramine (Questran Lite 4 mg) was claimed more frequently. Of the items claimed for both study periods, simvastatin was the most commonly claimed, accounting for 45.35% (n = 284 232) and 46.21% (n = 325 970) respectively of the number of hipolipidaemic items claimed, at a total cost of 30.97% (n = R33 119 294.18) and 31.38% (n = R36 983 938.41) for 2005 and 2006 respectively. Non-substitutable and generic hipolipidaemic medicine items carried the largest percentage of prevalence and cost in both study periods for both sex categories and all age groups. The majority of claims for hipolipidaemic medicine items were prescribed by general medical practitioners, followed by “other prescribers” and then by cardiologists. Only a small number of prescriptions claimed were prescribed by thoracic surgeons and even fewer by pharmacotherapists and pharmacists. Trade name products that were mostly prescribed were Lipitor and Adco-Simvastatin. Of all the hipolipidaemic drugs utilised on the database, only three active ingredients (bezafibrate, simvastatin and pravastatin) had generic equivalents available at the time of the study. With total substitution (100%) of these three drugs with the average price of the available generic hipolipidaemic equivalents on the database, a cost saving of R1 744 462.27 or 1.63% (N = R106 943 348.53) was possible in 2005. In 2006, a total cost saving of R1 526 985.79 or 1.30% (N = R117 862 631.87) was calculated. Conclusion: The study highlighted the most commonly prescribed hipolipidaemics within a sub-population of South African patients. The high average cost per prescription of hipolipidaemic drugs indicates that they are relatively expensive in comparison to other medications. Generic (and therapeutic) substitution should be investigated as potential cost-saving mechanisms in the private health care sector of South Africa. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2010.

With great appreciation, I would like to accentuate the substantial contributions of the following people who made this project possible: To Dr. CMT Fourie (my supervisor), Prof. JM van Rooyen (my co–supervisor) and Prof. AE Schutte (my co–supervisor) whose gracious advise, patient guidance, commitment and support have enabled me to plan, analyse, interpret and write this project in a scientific manner. It has been an educational experience for me, thank you. To Mr. LS Wyldbore for the language editing of this dissertation. I thank all the participants, researchers, field workers and supporting staff of the PURE study. The financial assistance of the National Research Foundation (DAAD–NRF) towards this research is hereby acknowledged. A special thanks to my parents, sister, Albert, family and friends, thank you for the never–ending love, support, patience and understanding that you gave me throughout this project. Last, but not the least, a special thank to God for giving me the opportunity, talent, determination and endurance to complete this project. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

Background: More than 5.5 million South Africans aged 30 years and older are at risk of chronic disease by virtue of their triglyceride levels (Maritz, 2006:101). Dyslipidaemia is common in westernized and industrialized communities (Steyn et al., 2000:720), especially so for South Africa, where burden of disease data show dyslipidaemia to be the second most prevalent of all the chronic conditions in the country (Council for Medical Schemes, 2006:48). It is therefore no surprise that at 3.3 per cent hipolipidaemics ranked second highest based on prevalence percentage per therapeutic group in the 2005 Mediscor medicines review on South African medical claims data (Bester et al., 2005:8-11). Hipolipidaemic drugs subsequently also ranked second highest for expenditure per therapeutic group, achieving a total expenditure of 5.8 per cent. Objective: The purpose of this study was to characterise the usage and cost of hipolipidaemic drugs in the private health care environment in South Africa based on various categories, including age, sex, prescriber type and generic indicator. Methods: A quantitative retrospective drug utilisation review was performed using dispensing records from a medicine claims database. Data for a two-year period (1 Jan. 2005 to 31 Dec. 2006) were used. Hipolipidaemic medicine usage was analysed according to five patient age strata: patients younger than 9 years, 10 ≤ 19 years, 20 ≤ 45 years, 46 ≤ 59 years and older than 59 years. Basic descriptive statistics such as frequencies and arithmetic mean (average) were used to characterise the study sample, and were calculated using the Statistical Analysis System (SAS®) for Windows 9.1® program (SAS Institute Inc., 2002-2003). Results: The database consisted of 19 860 593 and 21 473 062 medicine item claims for 2005 and 2006 respectively, at a total cost of R 1 893 376 921.00 (for 2005) and R2 046 944 383.00 (for 2006). Patients receiving hipolipidaemic medicine items represented about 7.2% of the total number of patients on the database in both 2005 and 2006. About 47% of the study population in both 2005 and 2006 was female, compared to 53% males. Hipolipidaemics represented between 3.1% (N = 19 860 593) and 3.3% (N = 21 473 062) of the total number of items claimed during the study period. The total cost of hipolipidaemics accounted for between 5.6% (N = R1 893 376 921.00) and 5.8% (N = R2 046 944 383.00) of the total cost of all medications claimed during the study period. The average cost per item of hipolipidaemics was R170.63 ± 70.19 in 2005 compared to R167.08 ± 71.93) in 2006. HMG-CoA reductase inhibitors formed the leading therapeutic class in hipolipidaemic medicine items in all age groups on the database, except for children aged 0 ≤ 9 years, where the “others” group, in particular cholestyramine (Questran Lite 4 mg) was claimed more frequently. Of the items claimed for both study periods, simvastatin was the most commonly claimed, accounting for 45.35% (n = 284 232) and 46.21% (n = 325 970) respectively of the number of hipolipidaemic items claimed, at a total cost of 30.97% (n = R33 119 294.18) and 31.38% (n = R36 983 938.41) for 2005 and 2006 respectively. Non-substitutable and generic hipolipidaemic medicine items carried the largest percentage of prevalence and cost in both study periods for both sex categories and all age groups. The majority of claims for hipolipidaemic medicine items were prescribed by general medical practitioners, followed by “other prescribers” and then by cardiologists. Only a small number of prescriptions claimed were prescribed by thoracic surgeons and even fewer by pharmacotherapists and pharmacists. Trade name products that were mostly prescribed were Lipitor and Adco-Simvastatin. Of all the hipolipidaemic drugs utilised on the database, only three active ingredients (bezafibrate, simvastatin and pravastatin) had generic equivalents available at the time of the study. With total substitution (100%) of these three drugs with the average price of the available generic hipolipidaemic equivalents on the database, a cost saving of R1 744 462.27 or 1.63% (N = R106 943 348.53) was possible in 2005. In 2006, a total cost saving of R1 526 985.79 or 1.30% (N = R117 862 631.87) was calculated. Conclusion: The study highlighted the most commonly prescribed hipolipidaemics within a sub-population of South African patients. The high average cost per prescription of hipolipidaemic drugs indicates that they are relatively expensive in comparison to other medications. Generic (and therapeutic) substitution should be investigated as potential cost-saving mechanisms in the private health care sector of South Africa. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2010.

With great appreciation, I would like to accentuate the substantial contributions of the following people who made this project possible: To Dr. CMT Fourie (my supervisor), Prof. JM van Rooyen (my co–supervisor) and Prof. AE Schutte (my co–supervisor) whose gracious advise, patient guidance, commitment and support have enabled me to plan, analyse, interpret and write this project in a scientific manner. It has been an educational experience for me, thank you. To Mr. LS Wyldbore for the language editing of this dissertation. I thank all the participants, researchers, field workers and supporting staff of the PURE study. The financial assistance of the National Research Foundation (DAAD–NRF) towards this research is hereby acknowledged. A special thanks to my parents, sister, Albert, family and friends, thank you for the never–ending love, support, patience and understanding that you gave me throughout this project. Last, but not the least, a special thank to God for giving me the opportunity, talent, determination and endurance to complete this project. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

Background. The incidence of starting renal replacement therapy (RRT) among young people (< 20 years of age) in 2013 in Scotland was 7.7 per million (age-related) population. Little knowledge exists about cardiovascular risk factors (CVRFs), long-term survival and cardiovascular disease (CVD) outcomes in patients who initiated RRT in childhood. The main source of routine data for these patients is available from the European Society of Paediatric Nephrology/European Renal Association- European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry. In Scotland nationally comprehensive data on patients receiving RRT is available from the Scottish Renal Registry (SRR). Aim and objectives. The overall aim of the thesis is to review relevant literature and conduct retrospective cohort studies describing CVRF prevalence, all-cause mortality and incidence of CVD outcomes in patients who initiated RRT in childhood. ESPN/ERA-EDTA registry data were used to describe the prevalence of anaemia, hypertension, dyslipidaemia and BMI categories and their association with all-cause and CV mortality. SRR data were used to describe all-cause mortality and CVD incidence and their association with age at start of RRT, sex, primary renal disease (PRD), type of RRT and period of start of RRT. Methods. Systematic searches were performed to identify relevant literature. For the ESPN/ERA-EDTA analyses patients who started RRT between 0 and 20 years of age and who had CVRF data were included. Patients were followed from date of first CVRF measurement until the earliest of death, loss to follow-up, reaching 20 years of age or the end of follow-up (December 31st 2012). Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality, comparing patients with and without each CVRF. For the SRR analyses, patients who started RRT under 18 years of age in the period from 1963 to 2013 were included in the analyses. To describe CVD incidence the SRR data were linked to national registers for death and CVD hospital admissions available from 1981 onwards. These analyses, therefore, included patients who started RRT between 1981 and 2013 with follow-up until first CVD event after start of RRT, end of follow-up period or censoring at death. Cox proportional hazard models were used to examine the association of age at initiation of RRT, sex, PRD, type of RRT and period of initiation of RRT with all-cause mortality and CVD incidence. Results. The systematic reviews revealed a gap in current knowledge about CVD incidence and the association of CVRFs with CVD outcomes in patients who initiated RRT in childhood. In total, 7,845 patients were included in the ESPN/ERA-EDTA registry analysis. The mean age of the patients was 9.5 (SE 0.06) years, 58.9% were male, and the most common PRD was congenital anomalies of kidney and urinary tract (CAKUT). The prevalence of dyslipidaemia, hypertension, anaemia overweight/obesity and underweight was 87.5%, 79.3%, 36.0%, 29.9% and 4.3%, respectively. During median follow-up of 3.7 (IQR 1.7-6.8) years 357 patients died. HRs for anaemia were 2.19 (95% CI 1.64-2.93) and 2.55 (95% CI 1.27-5.12) for all-cause and CVD mortality, respectively. The HR for all-cause mortality for underweight was 1.81 (95% CI 1.30-2.53). No other studied CVRFs were statistically significantly associated with all-cause and CVD mortality. In total, 479 patients were included in the SRR analyses of all-cause mortality. The most common PRD was CAKUT and 55.3% of patients were male. During a median follow-up of 18.3 (IQR 8.7-27.0 years) years 126 patients died. Twenty-year survival among patients initiated RRT in childhood was 77.6% (95% CI 73.8-81.3). Age at start of RRT, PRD and type of RRT were significantly associated with all-cause mortality. HR for all-cause mortality for patients who started RRT under 2 years of age was 2.50 (95% CI 1.19-5.25) compared to patients who started RRT at 12 to 18 years old. HR for all-cause mortality for patients with PRD other than CAKUT or glomerulonephritis (GN) was 1.58 (95% CI 1.05-2.39) compared to patients with CAKUT. HRs for all-cause mortality for patients who only received either HD or PD during follow-up were 19.4 (95% CI 10.4-36.4 and 19.5 (9.65-39.7), respectively, compared to patients who received a renal transplant. In total, 381 patients were included in the SRR analyses of CVD incidence. During a median of 12.9 (IQR 5.6-21.5) years of follow-up after initiation of RRT 134 patients (35.2%) developed CVD. The overall crude CVD incidence was 2.6 (95% CI 2.2-3.0) per 100 person-years. HRs for CVD were 1.69 (95% CI 1.05-2.74) for males compared to females, 1.72 (95% CI 1.02-2.91) for PRD other than CAKUT or GN compared to CAKUT and 8.38 (95% CI 3.31-21.23) and 7.30 (95% CI 2.30-23.16) for patients who only received either HD or PD during follow-up, respectively, compared to patients who received a renal transplant. Conclusions. This thesis has contributed to knowledge about CVRF prevalence, longer-term survival and CVD outcomes in patients who initiated RRT in childhood by identifying high prevalence of CVRFs and that CVD is a common complication. This study did not investigate whether anaemia, hypertension, dyslipidaemia and obesity are associated with a higher risk of developing CVD after start of RRT. Future research is needed to study whether treatment of anaemia, hypertension, dyslipidaemia and controlling body weight will reduce the risk of CVD and mortality in patients who initiated RRT in childhood.