| 1. |
- Abedini, Sadollah, et al.
(författare)
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Asymmetrical dimethylarginine is associated with renal and cardiovascular outcomes and all-cause mortality in renal transplant recipients
- 2010
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 77:1, s. 44-50
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Tidskriftsartikel (refereegranskat)abstract
- Increased plasma levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and predict the progression to dialysis and death in patients with chronic kidney disease. The effects of these increased ADMA levels in renal transplant recipients, however, are unknown. We used the data from ALERT, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients with stable graft function on enrollment. Patients who were initially randomized to fluvastatin or placebo in the 5- to 6-year trial were offered open-label fluvastatin in a 2-year extension of the original study. After adjustment for baseline values for established factors in this post hoc analysis, ADMA was found to be a significant risk factor for graft failure or doubling of serum creatinine (hazard ratio 2.78), major cardiac events (hazard ratio 2.61), cerebrovascular events (hazard ratio 6.63), and all-cause mortality (hazard ratio 4.87). In this trial extension, the number of end points increased with increasing quartiles of plasma ADMA levels. All end points were significantly increased in the fourth compared to the first quartile. Our study shows that elevated plasma levels of ADMA are associated with increased morbidity, mortality, and the deterioration of graft function in renal transplant recipients.
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| 2. |
- Abedini, Sadollah, et al.
(författare)
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Cerebrovascular events in renal transplant recipients
- 2009
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 87:1, s. 112-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The incidence of stroke and risk factors for different subtypes of cerebrovascular (CBV) events in renal transplant recipients have not been examined in any large prospective controlled trial. METHODS: The Assessment of Lescol in Renal Transplantation was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg) daily on cardiovascular, and renal outcomes in renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5 to 6 year trial was offered open-label fluvastatin in a 2-year extension to the original study. We investigated the incidence of stroke and risk factors for ischemic and hemorrhagic CBV events in 2102 renal graft recipients participating in the Assessment of Lescol in Renal Transplantation core and extension trial with a mean follow-up of 6.7 years. RESULTS: The incidence and type of CBV events did not differ between the lipid lowering arm and the placebo arm. A total of 184 (8.8%, 95% confidence interval 4.6-12.9) of 2102 patients experienced a CBV event during follow-up, corresponding to an incidence of 1.3% CBV event per year. The mortality for patients experiencing a hemorrhagic stroke was 48% (13 of 27), whereas the mortality for ischemic strokes was 6.0% (8 of 133). Diabetes mellitus, previous CBV event, age, and serum creatinine were independent risk factors for cerebral ischemic events. The risk of a hemorrhagic cerebral event was increased by diabetes mellitus, polycystic kidney disease, left ventricular hypertrophy, and systolic blood pressure. INTERPRETATION: Risk factors for CBV events in renal transplant recipients differ according to subtype.
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| 3. |
- Abedini, Sadollah, et al.
(författare)
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Inflammation in renal transplantation
- 2009
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 4:7, s. 1246-1254
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated. RESULTS: The baseline IL-6 value was 2.9 +/- 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 +/- 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049). CONCLUSIONS: The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.
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| 4. |
- Bugge, Anna, et al.
(författare)
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Effects of a 3-year intervention: The Copenhagen School Child Intervention Study.
- 2012
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Ingår i: Medicine & Science in Sports & Exercise. - 1530-0315. ; 44:7, s. 1310-1317
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: This study assessed short and long term effects of a 3-year controlled school-based physical activity (PA) intervention on fatness, cardiorespiratory fitness (VO2peak) and cardiovascular disease (CVD) risk factors in children. METHODS: The study involved 18 schools (10 intervention and 8 controls) and included a follow-up 4 years after the end of intervention. The analyses included 696, 6-7 yrs old children at baseline, 612 at post-intervention (age 9.5 yrs) and 441 at follow-up (age 13.4 yrs). The intervention consisted of a doubling of the amount of physical education (from 90 to 180 min/week), training of PE-teachers, and upgrading of physical education and playing facilities. Anthropometrics and systolic blood pressure (SBP) were measured. VO2peak was directly measured and PA assessed using accelerometry. Fasting blood samples were analyzed for CVD risk factors. A composite risk score was computed from z-scores of SBP, triglycerides, ratio of total cholesterol to high-density lipoproteins cholesterol, homeostatic model assessment (HOMA-score), skinfolds, and inverse VO2peak. RESULTS: The HOMA-score of intervention group boys had a smaller increase from baseline to post-intervention compared to control boys (p = 0.004). From baseline to follow-up intervention group boys had a smaller increase in SBP compared to control boys (p=0.010). There were no other significant differences between groups. CONCLUSION: This 3-years school-based PA intervention caused positive changes in SBP and HOMA-score in boys, but not in PA, VO2peak, fatness and the other measured CVD risk factors. Our results indicate that a doubling of physical education and providing training and equipment may not be sufficient to induce mayor improvements in CVD risk factors in a normal population.
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| 5. |
- Dahle, Dag Olav, et al.
(författare)
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Inflammation-associated graft loss in renal transplant recipients
- 2011
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 26:11, s. 3756-3761
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Tidskriftsartikel (refereegranskat)abstract
- Background. Although short-term graft survival has improved substantially in renal transplant recipients, long-term graft survival has not improved over the last decades. The lack of knowledge of specific causes and risk factors has hampered improvements in long-term allograft survival. There is an uncertainty if inflammation is associated with late graft loss. Methods. We examined, in a large prospective trial, the inflammation markers high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) and their association with chronic graft dysfunction. We collected data from the Assessment of Lescol in Renal Transplant trial, which recruited 2102 maintenance renal transplant recipients. Results. Baseline values were hsCRP 3.8 +/- 6.7 mg/L and IL-6 2.9 +/- 1.9 pg/mL. Adjusted for traditional risk factors, hsCRP and IL-6 were independently associated with death-censored graft loss, the composite end points graft loss or death and doubling of serum creatinine, graft loss or death. Conclusion. The inflammation markers hsCRP and IL-6 are associated with long-term graft outcomes in renal transplant recipients.
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| 6. |
- Dahle, Dag Olav, et al.
(författare)
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Uric acid and clinical correlates of endothelial function in kidney transplant recipients
- 2014
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 28:10, s. 1167-1176
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Tidskriftsartikel (refereegranskat)abstract
- Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores.METHODS: One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation (FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models.RESULTS: Uric acid was associated negatively with FMD% in an age- and gender-adjusted model, while not in the multivariable model. No association was shown between uric acid and LnRHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated negatively with risk scores in the latter model only (p < 0.05).CONCLUSIONS: Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores.
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| 7. |
- Faergeman, Ole, et al.
(författare)
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Plasma Triglycerides and Cardiovascular Events in the Treating to New Targets and Incremental Decrease in End-Points Through Aggressive Lipid Lowering Trials of Statins in Patients With Coronary Artery Disease
- 2009
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Ingår i: AMERICAN JOURNAL OF CARDIOLOGY. - : Elsevier BV. - 0002-9149. ; 104:4, s. 459-463
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Tidskriftsartikel (refereegranskat)abstract
- We determined the ability of in-trial measurements of triglycerides (TGs) to predict new cardiovascular events (CVEs) using data from the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) trials. The trials compared atorvastatin 80 mg/day with moderate-dose statin therapy (simvastatin 20 to 40 mg/day in IDEAL and atorvastatin 10 mg/day in TNT) in patients with clinically evident coronary heart disease or a history of myocardial infarction. The outcome measurement in the present research was CVE occurring after the first year of the trial. After adjusting for age, gender, and study, risk of CVEs increased with increasing TGs (p andlt;0.001 for trend across quintiles of TGs). Patients in the highest quintile had a 63% higher rate of CVEs than patients in the lowest quintile (hazard ratio 1.63, 95% confidence interval 1.46 to 1.81) and the relation of TGs to risk was apparent even within the normal range of TGs. The ability of TG measurements to predict risk decreased when high-density lipoprotein cholesterol and apolipoprotein B:apolipoprotein A-I were included in the statistical analysis, and it was abolished with inclusion of further variables (diabetes, body mass index, glucose, hypertension, and smoking; (p = 0.044 and 0.621, respectively, for trend across quintiles of TGs). Similar results were obtained in patients in whom low-density lipoprotein cholesterol had been lowered to guideline-recommended levels. In conclusion, even slightly increased TG levels are associated with higher risk of recurrence of CVEs in statin-treated patients and should be considered a useful marker of risk.
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| 8. |
- Fellström, Bengt, et al.
(författare)
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Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal Transplant (ALERT) trial
- 2004
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 66:4, s. 1549-1555
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transplant function and development of chronic allograft nephropathy in the ALERT (Assessment of Lescol in Renal Transplantation) study. METHODS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 mg and 80 mg daily, in renal transplant recipients. Patients were randomized to receive either fluvastatin (N= 1050) or placebo (N= 1052) and followed for five to six years. Renal end points included graft loss or doubling of serum creatinine or death; glomerular filtration rate (GFR) was also measured during follow-up in a subset of patients (N= 439). RESULTS: There were 283 patients (13.5%) with graft loss, mainly due to chronic rejection (82%), yielding an annual rate of 2.4%. Fluvastatin treatment significantly lowered mean low-density lipoprotein (LDL)-cholesterol levels by 32% (95% CI -33 to -30) compared with placebo, but had no significant effect on the incidence of renal graft loss or doubling of serum creatinine, or decline in GFR throughout follow-up in the whole study population. Neither was any treatment effect by fluvastatin found in any of the subgroups analyzed. CONCLUSION: Fluvastatin treatment significantly improves lipid values in renal transplant recipients but has no effect on graft loss or doubling of serum creatinine.
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| 9. |
- Gerdts, Eva, et al.
(författare)
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Impact of baseline severity of aortic valve stenosis on effect of intensive lipid lowering therapy (from the SEAS study)
- 2010
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Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 106:11, s. 1634-1639
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Tidskriftsartikel (refereegranskat)abstract
- Retrospective studies have suggested a beneficial effect of lipid-lowering treatment on the progression of aortic stenosis (AS) in milder stages of the disease. In the randomized, placebo-controlled Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, 4.3 years of combined treatment with simvastatin 40 mg and ezetimibe 10 mg did not reduce aortic valve events (AVEs), while ischemic cardiovascular events (ICEs) were significantly reduced in the overall study population. However, the impact of baseline AS severity on treatment effect has not been reported. Baseline and outcomes data in 1,763 SEAS patients (mean age 67 years, 39% women) were used. The study population was divided into tertiles of baseline peak aortic jet velocity (tertile 1: <= 2.8 m/s; tertile 2: >2.8 to 3.3 m/s; tertile 3: >3.3 m/s). Treatment effect and interaction were tested in Cox regression analyses. The rates of AVEs and ICEs increased with increasing baseline severity of AS. In Cox regression analyses, higher baseline peak aortic jet velocity predicted higher rates of AVEs and ICEs in all tertiles (all p values <0.05) and in the total study population (p <0.001). Simvastatin-ezetimibe treatment was not associated with a statistically significant reduction in AVEs in any individual tertile. A significant quantitative interaction between the severity of AS and simvastatin-ezetimibe treatment effect was demonstrated for ICEs (p <0.05) but not for AVEs (p = 0.10). In conclusion, the SEAS study results demonstrate a strong relation between baseline the severity of AS and the rate of cardiovascular events but no significant effect of lipid-lowering treatment on AVEs, even in the group with the mildest AS.
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| 10. |
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