Long-Term Outcomes in Patients with Severe Hypertriglyceridemia—Simulation Using the Archimedes Model

Background: Individuals with elevated triglyceride (TG) levels are at higher risk for coronary heart disease (CHD). However, there is a lack of long-term data to quantitatively demonstrate the risk in patients with severe (≥500 mg/dl) hypertriglyceridemia (SHTG). Objective: The objective of this study was to simulate health outcomes and associated costs up to 20 years in SHTG individuals using the Archimedes Model. Methods: The Archimedes Model is a physiologically based mathematical model that is clinically and administratively detailed and has been rigorously validated using clinical trial data. To help simulate outcomes in SHTG individuals, the lipid component of the Archimedes Model was made more robust using data from individuals with TG>500mg/dl from a managed care plan. The risk of a myocardial infarction (MI), stroke, CHD death, cardiovascular disease (CVD) death, and composite major adverse cardiovascular event (MACE) was determined from simulations using the Model. Results: The simulation randomly selected SHTG individuals from NHANES 1999-2006 and used these individuals as the basis for a simulated population of 5000 individuals. The average age at baseline was 45 years, with 68% males, 27% diabetics, mean BMI of 30.6 kg/m2, blood pressure of 129/79 mmHg, total cholesterol of 265 mg/dl, HDL of 36.1 mg/dl, LDL of 85 mg/dl, TG of 881 mg/dl, FPG of 126 mg/dl, and HbA1c of 6.1%. At 10 years and 20 years respectively, the rate per individual at baseline of total MIs was 14.6% and 32.5%, the rate of ischemic stroke was 3.5% and 7.9%, CHD death was 5% and 11.8%, CVD death was 7.1% and 16.7%, and cumulative fraction of people with MACE was 16.2% and 31.5%. Conclusion: This simulation demonstrates a significant increase in the risk of future MI, stroke, CHD death, CVD death, and MACE associated with SHTG. More precisely, SHTG individuals are more than twice as likely to suffer an adverse cardiac outcome as compared with individuals with normal TG levels as based on published census data. Physicians should be aware of the need to treat SHTG levels to reduce the risk of long-term cardiovascular (CV) events.