Contribution of remnant cholesterol to cardiovascular risk

Background Remnant cholesterol in triglyceride-rich lipoproteins is associated observationally and genetic, causally with increased risk of atherosclerotic cardiovascular disease in healthy individuals. Objectives We tested the hypothesis that an unmet medical need exists in individuals with high nonfasting remnant cholesterol and prior atherosclerotic cardiovascular disease. Methods From amongst 109 574 individuals in a prospective cohort study of the Danish general population, we included 2973 individuals aged 20-80 with baseline diagnoses of myocardial infarction/ischaemic stroke ascertained from national Danish health registries. Results The recurrent major cardiovascular event (MACE) incidence rates per 1000 person-years were 39 (95% confidence interval: 30-50) for individuals with remnant cholesterol levels >= 1.5 mmol L-1 (>= 58 mg dL(-1)), 31 (26-37) for 1-1.49 mmol L-1 (39-57 mg dL(-1)), 27 (24-31) for 0.5-0.99 mmol L-1 (19-38 mg dL(-1)) and 23 (19-27) for individuals with remnant cholesterol < 0.5 mmol L-1 (<19 mg dL(-1)). Compared to individuals with remnant cholesterol < 0.5 mmol L-1 (<19 mg dL(-1)), the subhazard ratio for recurrent MACE was 1.23 (95% CI: 0.98-1.55) for individuals with remnant cholesterol levels of 0.5-0.99 mmol L-1 (19-38 mg dL(-1)), 1.48 (1.14-1.92) for 1-1.49 mmol L-1 (39-57 mg dL(-1)) and 1.79 (1.28-2.49) for >= 1.5 mmol L-1 (>= 58 mg dL(-1)). The recurrent MACE incidence rates per 1000 person-years for individuals with remnant cholesterol levels < 0.5 mmol L-1 (<19 mg dL(-1)) and >= 1.5 mmol L-1 (>= 58 mg dL(-1)) were 10 (6.6-15) and 31 (21-47) for those below age 65 and correspondingly 25 (21-30) and 43 (32-59) for those with LDL cholesterol levels < 3 mmol L-1 (<116 mg dL(-1)), respectively. For a 20% recurrent MACE risk reduction in secondary prevention, an estimated remnant cholesterol lowering of 0.83 mmol L-1 (32 mg dL(-1)) would be needed. Conclusions In individuals with a diagnosis of myocardial infarction/ischaemic stroke, a lower remnant cholesterol of 0.8 mmol L-1 (32 mg dL(-1)) was estimated to reduce recurrent MACE by 20% in secondary prevention. Our data indicate an unmet medical need for secondary prevention in individuals with high nonfasting remnant cholesterol levels.