Hyperlipidemias: Fellström B

Holdaas H, Fellström B, Jardine AG, Anonymous00166. · No affiliation provided · Am J Transplant. · Pubmed #15888072 No free full text.

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Fellström B. · Uppsala University, Sweden. · Transplantation. · Pubmed #11583483 No free full text.

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Fellström B. · No affiliation provided · Transplantation. · Pubmed #11152232 No free full text.

Abstract: CVD morbidity and mortality is a major cause of premature death and allograft loss in recipients of renal and cardiac transplants, and hyperlipidemia--a major risk factor for CVD in the general population--may be a significant risk factor for CVD in transplant recipients. Hyperlipidemia is common after transplantation, and immunosuppression with corticosteroids, cyclosporine, or sirolimus causes posttransplantation hyperlipidemia. Posttransplantation hyperlipidemia can be treated in various ways, but statin therapy has thus far proved to be the most effective in lowering lipid levels in the transplant population. However, to date, no large solid end-point studies have demonstrated that lipid-lowering therapy with statins (or any other class of agents) significantly reduces CVD morbidity or mortality and improves allograft survival in transplant recipients, although some smaller studies point in that direction. The ongoing ALERT trial is currently studying whether early and later intervention with a statin (fluvastatin) can reduce chronic allograft dysfunction, decrease CVD, and improve patient survival in transplant recipients.

Fellström B. · Department of Medical Sciences, University Hospital, Uppsala, Sweden. · Transplant Proc. · Pubmed #10576035 No free full text.

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Holdaas H, Fellström B, Holme I, Nyberg G, Fauchald P, Jardine A, Grönhagen-Riska C, Madsen S, Neumayer HH, Cole E, Maes B, Weinreich T, Olsson AG, Pedersen TR, Benghozi R, Hartmann A, Anonymous00351. · Department of Medicine, National Hospital, N-0027 Oslo, Norway. · J Cardiovasc Risk. · Pubmed #11324372 No free full text.

Abstract: BACKGROUND: Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ('statins') reduces morbidity and mortality from coronary heart disease in diverse patient populations. STUDY AIMS: The aim of the present ALERT (Assessment of Lescol in Renal Transplantation) study is to determine whether renal transplant recipients would also benefit from statin therapy. ALERT is a multicentre, randomized, double-blind, placebo-controlled trial to assess the effect of fluvastatin in renal transplant recipients with mild-to-moderate hypercholesterolaemia. The primary objective is to investigate the effects of fluvastatin on major adverse cardiac events (MACE). In addition, the effects on cardiovascular and all-cause mortality, as well as renal function, will be addressed. STUDY POPULATION: The study population contains patients with functioning renal allografts of more than 6 months' duration, recruited from 75 centres in Northern Europe and Canada. Patients of both sexes, aged 30-75 years, with a total cholesterol level of 4.0-9.0 mmol/l (155-348 mg/dl) were included, except for those with a history of myocardial infarction, where the upper limit for inclusion was 7.0 mmol/l (270 mg/dl). STUDY DESIGN: A total of 2100 patients were recruited by the end of October 1997 and will be followed for up to 6 years. This report presents the design features of the study (recruitment, follow-up, sample size, data analysis and study organization), along with baseline results. ALERT is the first large-scale prospective, randomized, double-blind study to address the prevention of cardiovascular mortality in renal transplant patients receiving an HMGCoA reductase inhibitor.

Soveri I, Holdaas H, Jardine A, Gimpelewicz C, Staffler B, Fellström B. · Department of Medical Sciences, Uppsala University Hospital, entr 40, 75185, Uppsala, Sweden. · Nephrol Dial Transplant. · Pubmed #16574686 links to  free full text

Abstract: BACKGROUND: Renal transplant recipients (RTR) mainly die of premature cardiovascular disease. Traditional cardiovascular disease risk factors are prevalent in RTR. Additionally, non-traditional risk factors seem to contribute to the high risk. The impact of renal dysfunction was compared with traditional risk factors for cardiovascular morbidity and mortality in 1052 placebo-treated patients of the ALERT trial. METHODS: All patients were on cyclosporine-based immunosuppressive therapy, follow-up was 5-6 years and captured endpoints included cardiac death, non-cardiovascular death, all-cause mortality, major adverse cardiac event (MACE), non-fatal myocardial infarction (MI) and stroke. RESULTS: A calculated 84 micromol/l increase in serum creatinine was needed to double the risk for cardiac death, an increase of 104 micromol/l to double the risk for non-cardiovascular death and an increase of 92 micromol/l to double the risk for all-cause mortality. MACE risk was doubled if serum creatinine was elevated by 141 micromol/l, age was increased by 23 years, or LDL-cholesterol by 2 mmol/l. Diabetes increased the incidences of cardiac death, all-cause mortality, MACE, stroke and non-fatal MI. A serum creatinine increase of approximately 130 micromol/l, or approximately 20 years increase in age was calculated as similar in risk for cardiac death, all-cause mortality and MACE, and comparable to risk of diabetes in RTR. CONCLUSION: An increase in serum creatinine of 80-100 micromol/l doubles the risk for cardiac death, non-cardiovascular death and all-cause mortality in RTR. An increase of 130 micromol/l in serum creatinine or approximately 20 years increase in age is comparable to risk of diabetes.

Jardine AG, Fellström B, Logan JO, Cole E, Nyberg G, Grönhagen-Riska C, Madsen S, Neumayer HH, Maes B, Ambühl P, Olsson AG, Pedersen T, Holdaas H. · University of Glasgow, UK. · Am J Kidney Dis. · Pubmed #16129216 No free full text.

Abstract: BACKGROUND: Renal transplantation is associated with an increased risk for premature cardiovascular disease. We analyzed the data in the placebo arm of Assessment of Lescol in Renal Transplantation (ALERT) to improve our understanding of the relationship between cardiovascular risk factors and outcomes in this unique population. METHODS: We performed Cox survival analysis for myocardial infarction, cardiac death, and noncardiac death in 1,052 patients recruited to the placebo arm of ALERT. These subjects were aged 30 to 75 years, had stable graft function at least 6 months after transplantation, had a serum total cholesterol level between 155 and 348 mg/dL (4 and 9 mmol/L), and were receiving cyclosporine-based immunosuppression. RESULTS: The results confirm previous studies. In multivariate analysis, preexisting coronary heart disease (hazard ratio [HR], 3.69; P < 0.001), total cholesterol level (HR, 1.55 per 50 mg/dL; P = 0.0045), and prior acute rejection (HR, 2.36; P = 0.0023) were independent risk factors. Conversely, independent risk factors for cardiac death were age (HR, 1.58 per decade; P = 0.0033), diabetes (HR, 3.35; P = 0.0002), ST-T changes on the ECG (HR, 3.17; P = 0.0004), and serum creatinine level (HR, 2.65 per milligram per deciliter; P < 0.0001). CONCLUSION: This analysis confirms that renal transplant recipients share risk factors for myocardial infarction and cardiac death with the general population. However, the pattern of risk factors and their relationship with outcomes is atypical, highlighting the unique nature of cardiovascular risk in transplant recipients.

Fellström B, Larsson E, Zezina L. · Department of Medicine, Renal Unit, University Hospital, Uppsala, Sweden. · Transplant Proc. · Pubmed #11266827 No free full text.

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