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.