(VP096) SEVERE HYPERTRIGLYCERIDEMIA IS ASSOCIATED WITH INCREASED CAROTID INTIMA-MEDIA THICKNESS

Background: Unlike the established causal role of low-density lipoprotein (LDL) particles, the role of triglycerides (TG) in atherosclerotic cardiovascular disease (ASCVD) is controversial. Some studies have demonstrated associations between hypertriglyceridemia and coronary heart disease risk. However, clinical trials of TG-lowering therapies have been inconsistent. The REDUCE-IT study demonstrated cardiovascular outcomes benefit of icosapent ethyl, but most other randomized controlled trials have not. To evaluate the relationship between elevated TG and ASCVD, we used carotid intima-media thickness (cIMT) as a measure of preclinical atherosclerosis. cIMT is a non-invasive test with proven predictive value in assessing risk for ASCVD. Previous investigations examining an association between TG and cIMT have been equivocal and have never reported specifically in patients with severe hypertriglyceridemia.

METHODS AND RESULTS: Our study includes three patient cohorts: 1) 89 patients with severe hypertriglyceridemia, defined as TG >10 mmol/L; 2) 274 patients with genetically confirmed heterozygous familial hypercholesterolemia (FH) and untreated LDL-cholesterol >5 mmol/L; and 3) 70 normolipidemic control individuals. All participants were outpatients at London Health Sciences Centre (University Hospital) Lipid Clinic and all provided informed consent. The study was approved by the Western University Institutional Review Board, protocol number 0379E.

A single sonographer obtained images of the cIMT at the referral visit for each participant utilizing the Philips HD11 ultrasound device and L12-5 transducer. The posterior wall of each common carotid artery was measured by averaging 10 one-millimetre segments, starting 10 millimetres away from the bifurcation point. These measurements were analyzed using the QLAB Advanced Quantification software's standard IMT extension. cIMT measurements were converted from millimetres to age- and sex-adjusted percentile scores.

Statistical analyses were performed using R Statistical Software. Normality of cIMT percentile for each group was assessed using Shapiro-Wilk test and differences between groups were assessed using Student’s t-tests.

Clinical and demographic features of the patients are shown in Table 1. The age- and sex-normalized cIMT percentiles ± standard deviations showed a stepwise gradient across FH, severe HTG and normolipidemic groups: 62.6 ± 27.0; 56.4 ± 28.0, , and 48.2 ± 20.8, respectively, with both FH and severe HTG groups significantly different from the normolipidemic group but not from each other (p = 0.067).

Conclusion: Our findings indicate that atherosclerosis risk as indexed by cIMT is significantly greater in severe HTG patients than in controls, but lower than in FH patients with genetically elevated LDL cholesterol. Thus, severe HTG may play a role in pre-clinical atherosclerosis and possibly ASCVD risk generally.