RESIDUAL VASCULAR RISK AFTER STATIN THERAPY: THE PROMISE OF NOVEL LIPOPROTEIN BIOMARKERS


Samia Mora, M.D., M.H.S., Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

Objectives: Statins are the most widely used lipid-lowering agents and the standard of care for individuals with dyslipidemia, prior CVD, or at high-risk for CVD. However, the risk among statin-treated individuals remains high and has been termed “residual risk”. The rate of a major CVD event occurring during 5 years of follow-up among statin-treated patients in randomized clinical trials was 1 in 5 for individuals with prior CVD and 1 in 10 for those without prior CVD.

Methods and Results: The Treating to New Targets study (N=9251) showed that clinical risk factors account for a substantial proportion of residual risk in individuals with prior CVD. However, the c-index of 0.679 suggested that other factors are determinants of residual risk. In the JUPITER trial of individuals without prior CVD or diabetes who were recruited based on low LDL-cholesterol and elevated high-sensitivity C-reactive protein, we examined whether two promising lipoprotein biomarkers are significant determinants of residual risk: 1) lipoprotein(a), and 2) HDL particle number (HDL-P). In approximately 10,000 JUPITER participants with baseline and one-year levels of lipoprotein(a), on-statin concentrations were associated with residual risk (adjusted hazard ratio per 1-standard deviation: 1.27, 95% CI 1.01-1.59, p=0.04),which was independent of LDL-cholesterol and other risk factors. In another analysis from JUPITER, on-statin concentrations of HDL-P were also significant determinants (inversely) of residual risk (adjusted hazard ratio per 1-standard deviation: 0.73, 95% CI 0.57-0.93, p=0.01), stronger than the association of on-statin HDL-cholesterol (0.82, 95% CI 0.63-1.08, p=0.16) or apolipoprotein A-I (0.86, 95% CI 0.67-1.10, p=0.22) with residual risk.

Conclusions: Thus, a multi-faceted prevention approach targeting modifiable risk factors should be underscored as the cornerstone of optimal residual risk assessment and prevention. In addition, future studies are needed to directly assess the impact of specifically modifying lipoprotein(a) or HDL-P concentrations for potentially reducing residual risk.