Signe E J Hansen1,2,3, Christian M Madsen1,2,3, Anette Varbo1,2,4, Børge G Nordestgaard5,2,3,6. 1. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. 2. The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. 3. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 4. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 5. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; boerge.nordestgaard@regionh.dk. 6. The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark.
Abstract
BACKGROUND: How mild-to-moderate hypertriglyceridemia (2-10 mmol/L; 177-886 mg/dL) potentially causes acute pancreatitis is unknown; however, cellular studies indicate that inflammation might be a driver of disease progression. We tested the hypotheses that (a) mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and that (b) the association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis depends on low-grade inflammation. METHODS: From the Copenhagen General Population Study and the Copenhagen City Heart Study, 117865 men and women 20-100+ years of age with measurements of nonfasting plasma triglycerides at baseline were followed prospectively for development of acute pancreatitis. RESULTS: After multivariable adjustment, a 1 mmol/L (89 mg/dL) higher nonfasting triglyceride concentration was associated with 17% (95% CI, 16%-18%, P = 3 × 10-17) higher plasma C-reactive protein (CRP) and a 4.2% (4.0%-4.4%, P = 6 × 10-17) higher blood leukocyte count. Higher concentrations of nonfasting triglycerides were associated almost linearly with higher risk of acute pancreatitis (P for trend = 5 × 10-6), with hazard ratios of 1.5 (95% CI, 0.9-2.5), 2.0 (95% CI, 1.1-3.6), 2.2 (95% CI, 1.0-4.7), 4.2 (95% CI, 1.6-11.5), and 7.7 (95% CI, 3.0-19.8) in individuals with nonfasting triglycerides of 1.00-1.99 mmol/L (89-176 mg/dL; 46% of the population), 2.00-2.99 mmol/L (177-265 mg/dL; 17%), 3.00-3.99 mmol/L (266-353 mg/dL; 6%), 4.00-4.99 mmol/L (354-442 mg/dL; 2%), and ≥5mmol/L(443 mg/dL; 2%), respectively, vs individuals with <1 mmol/L (89 mg/dL; 27%). The association with risk of acute pancreatitis appeared more pronounced in individuals with CRP of ≥1.39 mg/L (P for trend = 0.001) and leukocytes of ≥7 × 109/L (P = 2 × 10-4) than in those with CRP <1.39 mg/L (P = 0.03) and leukocytes <7 × 109/L (P = 0.04); however, there was no formal evidence of statistical interaction (P = 0.38 for CRP and P = 0.41 for leukocytes). CONCLUSIONS: Mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and higher risk of acute pancreatitis. The association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis is possibly partly mediated by low-grade inflammation.
BACKGROUND: How mild-to-moderate hypertriglyceridemia (2-10 mmol/L; 177-886 mg/dL) potentially causes acute pancreatitis is unknown; however, cellular studies indicate that inflammation might be a driver of disease progression. We tested the hypotheses that (a) mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and that (b) the association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis depends on low-grade inflammation. METHODS: From the Copenhagen General Population Study and the Copenhagen City Heart Study, 117865 men and women 20-100+ years of age with measurements of nonfasting plasma triglycerides at baseline were followed prospectively for development of acute pancreatitis. RESULTS: After multivariable adjustment, a 1 mmol/L (89 mg/dL) higher nonfasting triglyceride concentration was associated with 17% (95% CI, 16%-18%, P = 3 × 10-17) higher plasma C-reactive protein (CRP) and a 4.2% (4.0%-4.4%, P = 6 × 10-17) higher blood leukocyte count. Higher concentrations of nonfasting triglycerides were associated almost linearly with higher risk of acute pancreatitis (P for trend = 5 × 10-6), with hazard ratios of 1.5 (95% CI, 0.9-2.5), 2.0 (95% CI, 1.1-3.6), 2.2 (95% CI, 1.0-4.7), 4.2 (95% CI, 1.6-11.5), and 7.7 (95% CI, 3.0-19.8) in individuals with nonfasting triglycerides of 1.00-1.99 mmol/L (89-176 mg/dL; 46% of the population), 2.00-2.99 mmol/L (177-265 mg/dL; 17%), 3.00-3.99 mmol/L (266-353 mg/dL; 6%), 4.00-4.99 mmol/L (354-442 mg/dL; 2%), and ≥5mmol/L(443 mg/dL; 2%), respectively, vs individuals with <1 mmol/L (89 mg/dL; 27%). The association with risk of acute pancreatitis appeared more pronounced in individuals with CRP of ≥1.39 mg/L (P for trend = 0.001) and leukocytes of ≥7 × 109/L (P = 2 × 10-4) than in those with CRP <1.39 mg/L (P = 0.03) and leukocytes <7 × 109/L (P = 0.04); however, there was no formal evidence of statistical interaction (P = 0.38 for CRP and P = 0.41 for leukocytes). CONCLUSIONS: Mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and higher risk of acute pancreatitis. The association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis is possibly partly mediated by low-grade inflammation.
Authors: Edward K Duran; Aaron W Aday; Nancy R Cook; Julie E Buring; Paul M Ridker; Aruna D Pradhan Journal: J Am Coll Cardiol Date: 2020-05-05 Impact factor: 24.094
Authors: Jean-Charles Fruchart; Raul D Santos; Carlos Aguilar-Salinas; Masanori Aikawa; Khalid Al Rasadi; Pierre Amarenco; Philip J Barter; Richard Ceska; Alberto Corsini; Jean-Pierre Després; Patrick Duriez; Robert H Eckel; Marat V Ezhov; Michel Farnier; Henry N Ginsberg; Michel P Hermans; Shun Ishibashi; Fredrik Karpe; Tatsuhiko Kodama; Wolfgang Koenig; Michel Krempf; Soo Lim; Alberto J Lorenzatti; Ruth McPherson; Jesus Millan Nuñez-Cortes; Børge G Nordestgaard; Hisao Ogawa; Chris J Packard; Jorge Plutzky; Carlos I Ponte-Negretti; Aruna Pradhan; Kausik K Ray; Željko Reiner; Paul M Ridker; Massimiliano Ruscica; Shaukat Sadikot; Hitoshi Shimano; Piyamitr Sritara; Jane K Stock; Ta-Chen Su; Andrey V Susekov; André Tartar; Marja-Riitta Taskinen; Alexander Tenenbaum; Lale S Tokgözoğlu; Brian Tomlinson; Anne Tybjærg-Hansen; Paul Valensi; Michal Vrablík; Walter Wahli; Gerald F Watts; Shizuya Yamashita; Koutaro Yokote; Alberto Zambon; Peter Libby Journal: Cardiovasc Diabetol Date: 2019-06-04 Impact factor: 9.951