How calculated LDL-cholesterol compares with direct measurement: performance and cost analysis from a large NHS service evaluation

Background and Aims: Hypertriglyceridaemia contributes to residual atherosclerotic cardiovascular disease (ASCVD) risk, but its association with recurrent events in real-world populations remains unclear.This study evaluated the relationship between triglyceride (TG) levels and subsequent ASCVD risk. Methods:We conducted a retrospective cohort study using linked primary and secondary care data from the United Kingdom Clinical Practice Research Datalink (CPRD).Adults with established ASCVD were identified using validated diagnostic codes.Cohort entry was defined by the first recorded TG measurement during the follow-up period (2010 -2020).Participants were categorised into four TG groups: <1.7, 1.7-5.6,5.7-10.0,and >10.0 mmol/L.The primary outcome was a composite of fatal and non-fatal ASCVD events.Secondary outcomes included coronary heart disease (CHD), cerebrovascular and peripheral vascular disease (PVD) events, and cardiovascular mortality.Cox Proportional Hazards models were used to estimate hazard ratios (HRs) with progressive adjustment for demographics, cardiometabolic factors, lipid parameters, and lipid-lowering therapies.Results: A total of 296,620 individuals were included (203,185 with TG <1.7 mmol/L; 90,654 with TG 1.7-5.6 mmol/L; 2,292 with TG 5.7-10.0mmol/L; and 489 with TG >10.0 mmol/L).Higher TG levels were associated with younger age, male predominance, higher body mass index, and increased prevalence of type 2 diabetes.Over a median follow-up of 2.4 years (0.9-4.9), increasing TG levels were associated with a higher risk of composite ASCVD outcomes.In fully adjusted models, compared with TG <1.7 mmol/L, HRs were 1.07 (95% CI 1.04-1.10;p<0.001) for TG 1.7-5.6 mmol/L and 1.28 (1.14-1.43;p<0.001) for TG 5.7-10.0mmol/L, while the association was not significant for TG >10.0 mmol/ L (HR 1.14, 0.88-1.48;p=0.30).Elevated TG levels were independently associated with higher risk of CHD [HR 1.12 (1.07-1.16)and 1.36 (1.16-1.58),respectively; both p<0.001] and PVD ; p<0.001), 1.22 (0.99-1.50; p=0.06), and 1.75 (1.19-2.56;p=0.005) across increasing TG strata].No independent associations were observed for cerebrovascular events or cardiovascular mortality in higher TG