On-treatment lipoprotein components and risk of cerebrovascular events in the Treating to New Targets study


Bas van den Bogaard, Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Room F4-142, 1105 AZ, Amsterdam, the Netherlands. Tel.: +31 20 5668675; fax: +31 20 5669343; e-mail: b.vandenbogaard@amc.nl


Eur J Clin Invest 2011; 41 (2): 134–142


Background  The Treating to New Targets (TNT) study has recently provided evidence that reduction in LDL-C levels below 2·6 mmol L−1 lowers the risk of cerebrovascular events by an additional 20% to 25%, thereby confirming the value of statin therapy in preventing transient ischaemic attacks and stroke. Despite the protective effects of statin therapy, the epidemiological association between lipid components and cerebrovascular events is less clear. We therefore assessed the strength of association between in-trial lipoprotein components and cerebrovascular disease in patients receiving intensive lipid-lowering therapy.

Methods  In 9247 patients (mean age 61·0 years, 81·2% males), the association between lipoprotein components and the risk of cerebrovascular events after the first year into the TNT trial was assessed after stratification of lipoprotein components into approximate quartiles. Cox proportional hazards models were used to explore the association between lipoprotein components and time to first cerebrovascular event after adjustment for potential confounding variables.

Results  All lipoprotein components, except LDL-C, showed a significant gradient for incidence of cerebrovascular events with increasing quartiles of the lipoprotein component. If the lipoprotein components were treated as continuous variables, the adjusted hazard ratios (95% CI) for cerebrovascular events for 1 SD difference in 1-year lipoprotein components were 1·13 (1·02–1·25) for LDL-C, 0·86 (0·76–0·97) for HDL-C, 1·17 (1·04–1·28) for apoB, 0·83 (0·74–0·94) for apoA-1, 1·22 (1·10–1·34) for TC/HDL-C and 1·24 (1·12–1·37) for apoB/apoA-1.

Conclusions  In coronary heart disease patients receiving intensive lipid-lowering treatment, the on-treatment apoB/apoA-1 ratio provides the strongest association with incidence of cerebrovascular events followed by TC/HDL-C.