A multinational risk-evaluation and risk-modelling study suggests that non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease (CVD), and highlights the potential benefit of early lipid-lowering strategies. The study identified 398 846 individuals in 38 cohorts (48·7% women; median age 51·0 years, without prevalent CVD at baseline and with robust available data on CVD outcomes) from 19 countries across Europe, Australia, and North America. 199 415 individuals were included in a derivation cohort (48·4% women) and 199 431 (49·1% women) in a validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years), 54 542 cardiovascular endpoints (a composite of coronary heart disease event or ischaemic stroke) occurred. Incidence curve analyses showed progressively higher 30-year CVD event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and CVD for both sexes (from hazard ratio 1·1 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9 for ≥5·7 mmol/L in women and from 1·1 to 2·3 in men). A derived tool allowed the estimation of CVD event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of CVD. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a CVD event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. The findings extend current knowledge and highlight the impact of non-HDL cholesterol on long-term CVD outcomes, particularly in cases of modest increase at a young age. Source: https://www.thelancet.com/
