Nicolae M Panduru1,2,3,4, Carol Forsblom2,3,4, Markku Saraheimo2,3,4, Lena M Thorn2,3,4, Daniel Gordin2,3,4, Nina Elonen2,3,4, Valma Harjusalo2,3,4,5, Angelika Bierhaus6, Per M Humpert6,7, Per-Henrik Groop8,9,10,11. 1. Second Clinical Department - Diabetes, Nutrition and Metabolic Disorders Unit, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania. 2. Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum 1 Helsinki, Haartmaninkatu 8, P.O. Box 63, University of Helsinki, FI-00014, Helsinki, Finland. 3. Research Programmes Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. 4. Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 5. Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland. 6. Department of Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany. 7. Stoffwechselzentrum Rhein Pfalz, Mannheim, Germany. 8. Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum 1 Helsinki, Haartmaninkatu 8, P.O. Box 63, University of Helsinki, FI-00014, Helsinki, Finland. per-henrik.groop@helsinki.fi. 9. Research Programmes Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. per-henrik.groop@helsinki.fi. 10. Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. per-henrik.groop@helsinki.fi. 11. Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. per-henrik.groop@helsinki.fi.
Abstract
AIMS/HYPOTHESIS: In type 1 diabetes, cardiovascular disease (CVD) and diabetic nephropathy progress in parallel, thereby potentiating the risk of premature death during their development. Since urinary liver-type fatty acid binding protein (L-FABP) predicts the progression of diabetic nephropathy, the aim of this study was to investigate whether urinary L-FABP also predicts cardiovascular outcomes and mortality. METHODS: We tested our hypothesis in a Finnish cohort of 2329 individuals with type 1 diabetes and a median follow-up of 14.1 years. The L-FABP to creatinine ratio was determined from baseline urine samples. The predictive value of urinary L-FABP was evaluated using Cox regression models, while its added predictive benefit for cardiovascular outcomes and mortality was evaluated using a panel of statistical indexes. RESULTS: Urinary L-FABP predicted incident stroke independently of traditional risk factors (HR 1.33 [95% CI 1.20, 1.49]) and after further adjustment for eGFR (HR 1.28 [95% CI 1.14, 1.44]) or AER (HR 1.24 [95% CI 1.06, 1.44]). In addition, it predicted mortality independently of traditional risk factors (HR 1.34 [95% CI 1.24, 1.45]), and after adjustment for eGFR (HR 1.29 [95% CI 1.18, 1.39]) or AER (HR 1.22 [95% CI 1.09, 1.36]). Urinary L-FABP was as good a predictor as eGFR or AER, and improved the AUC for both outcomes on top of traditional risk factors, with no reclassification benefit (integrated discrimination improvement/net reclassification improvement) for stroke or mortality when AER or eGFR were added to traditional risk factors. However, urinary L-FABP was not a predictor of other cardiovascular endpoints (coronary artery disease, peripheral vascular disease and overall CVD events) when adjusted for the AER. CONCLUSIONS/ INTERPRETATION: Urinary L-FABP is an independent predictor of stroke and mortality in individuals with type 1 diabetes.
AIMS/HYPOTHESIS: In type 1 diabetes, cardiovascular disease (CVD) and diabetic nephropathy progress in parallel, thereby potentiating the risk of premature death during their development. Since urinary liver-type fatty acid binding protein (L-FABP) predicts the progression of diabetic nephropathy, the aim of this study was to investigate whether urinary L-FABP also predicts cardiovascular outcomes and mortality. METHODS: We tested our hypothesis in a Finnish cohort of 2329 individuals with type 1 diabetes and a median follow-up of 14.1 years. The L-FABP to creatinine ratio was determined from baseline urine samples. The predictive value of urinary L-FABP was evaluated using Cox regression models, while its added predictive benefit for cardiovascular outcomes and mortality was evaluated using a panel of statistical indexes. RESULTS: Urinary L-FABP predicted incident stroke independently of traditional risk factors (HR 1.33 [95% CI 1.20, 1.49]) and after further adjustment for eGFR (HR 1.28 [95% CI 1.14, 1.44]) or AER (HR 1.24 [95% CI 1.06, 1.44]). In addition, it predicted mortality independently of traditional risk factors (HR 1.34 [95% CI 1.24, 1.45]), and after adjustment for eGFR (HR 1.29 [95% CI 1.18, 1.39]) or AER (HR 1.22 [95% CI 1.09, 1.36]). Urinary L-FABP was as good a predictor as eGFR or AER, and improved the AUC for both outcomes on top of traditional risk factors, with no reclassification benefit (integrated discrimination improvement/net reclassification improvement) for stroke or mortality when AER or eGFR were added to traditional risk factors. However, urinary L-FABP was not a predictor of other cardiovascular endpoints (coronary artery disease, peripheral vascular disease and overall CVD events) when adjusted for the AER. CONCLUSIONS/ INTERPRETATION: Urinary L-FABP is an independent predictor of stroke and mortality in individuals with type 1 diabetes.
Authors: Michael T Wunderlich; Thorsten Hanhoff; Michael Goertler; Friedrich Spener; Jane F C Glatz; Claus-W Wallesch; Maurice M A L Pelsers Journal: J Neurol Date: 2005-04-18 Impact factor: 4.849
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Authors: Susan P Laing; Anthony J Swerdlow; Lucy M Carpenter; Stefan D Slater; Andrew C Burden; Johannes L Botha; Andrew D Morris; Norman R Waugh; Wendy Gatling; Edwin A M Gale; Christopher C Patterson; Zongkai Qiao; Harry Keen Journal: Stroke Date: 2003-02 Impact factor: 7.914
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