Abstract
Background Assessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes. Methods We used linked data from primary and secondary care for 15 M people, to explore the association between triglyceride concentration and risk of acute pancreatitis, chronic pancreatitis, new onset diabetes, myocardial infarction and all-cause mortality, over a median of 6-7 years follow up. Results Triglyceride concentration was available for 1,530,411 individuals (mean age 56 center dot 6 +/- 15 center dot 6 years, 51 center dot 4% female), with a median of 1 center dot 3 mmol/L (IQR: 0.9.to 1.9). Severe hypertriglyceridemia, defined as > 10 mmol/L, was identified in 3289 (0 center dot 21%) individuals including 620 with > 20 mmol/L. In multivariable analyses, a triglyceride concentration > 20 mmol/L was associated with very high risk for acute pancreatitis (Hazard ratio (HR) 13 center dot 55 (95% CI 9 center dot 15-20 center dot 06)); chronic pancreatitis (HR 25 center dot 19 (14 center dot 91-42 center dot 55)); and high risk for diabetes (HR 5 center dot 28 (4 center dot 51-6 center dot 18)) and all-cause mortality (HR 3 center dot 62 (2 center dot 82-4 center dot 65)) when compared to the reference category of <= 1 center dot 7 mmol/L. An association with myocardial infarction, however, was only observed for more moderate hypertriglyceridaemia between 1.7 and 10 mmol/L. We found a risk interaction with age, with higher risks for all outcomes including mortality among those <= 40 years compared to > 40 years. Conclusions We highlight an exponential association between severe hypertriglyceridaemia and risk of incident acute and chronic pancreatitis, new diabetes, and mortality, especially at younger ages, but not for myocardial infarction for which only moderate hypertriglyceridemia conferred risk.