Triglyceride-rich lipoproteins cholesterol, 10-years atherosclerotic cardiovascular disease risk, and risk of myocardial infarction and ischemic stroke

Triglyceride-rich lipoproteins cholesterol (TRLs-C) has been associated with atherosclerotic cardiovascular disease (ASCVD), even among individuals with low-density lipoprotein cholesterol in the targeted range. We assessed the associations of TRLs-C with myocardial infarction (MI) and ischemic stroke (IS) and compared the associations with those for other traditional lipids (i.e., triglycerides and non-high-density lipoprotein cholesterol [non-HDL-C]). Included were 327,899 participants from the UK Biobank who were free of MI or IS and did not receive lipid-lowering treatment at baseline. Ten-year risk for ASCVD was estimated by the Pooled Cohort Equations and was grouped as low (<7.5%), intermediate (7.5% to <20%), and high risk (≥20%). Multivariable Cox regression models were used to examine the associations of TRLs-C, triglycerides, and non-HDL-C with risk of MI and IS, overall and by the 10-years risk categories. During a median of 12.3 years of follow-up, 8,358 incident MI and 4,400 incident IS cases were identified. After multivariable adjustment, higher TRLs-C was associated with a higher risk of MI (p-trend <0.0001) but not IS (p-trend = 0.074), with similar associations for triglycerides and non-HDL-C. There were interactions between TRLs-C and 10-years ASCVD risk on risk of MI (p-interaction <0.0001) and IS (p-interaction = 0.0003). Hazard ratios (95% CIs) of MI comparing the highest with the lowest quartiles of TRLs-C were 2.10 (1.23-1.30) in the low-risk group, 1.52 (1.38-1.69) in the intermediate-risk group, and 1.22 (1.03-1.45) in the high-risk group. The corresponding estimates for IS were 1.24 (1.05-1.45), 0.94 (0.83-1.07), and 0.83 (0.67-1.04), respectively. Similar interactions with the 10-years ASCVD risk were observed for triglycerides and non-HDL-C on risk of MI and for triglycerides on risk of IS. Elevated levels of TRLs-C (or triglycerides or non-HDL-C) are associated with a higher risk of developing MI and IS (except non-HDL-C) predominantly among individuals who are typically classified as being low-risk. These findings may have implications for more detailed risk stratification and early intervention.