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CETP genotype predicts increased mortality in statin-treated men with proven cardiovascular disease: an adverse
Jakub J Regieli1, J Wouter Jukema, Diederick E Grobbee
1Juliuscenter for Health Sciences and Primary Care, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
European Heart Journal
|October 30, 2008
Summary
Genetic variations linked to lower cholesteryl ester transfer protein (CETP) levels in patients with coronary artery disease (CAD) are associated with increased long-term mortality despite statin therapy. This highlights the importance of CETP genotype in cardiovascular risk management.
Area of Science:
- Pharmacogenetics
- Cardiovascular Medicine
- Lipid Metabolism
Background:
- Inhibition of cholesteryl ester transfer protein (CETP) raises HDL-cholesterol but may increase mortality when combined with statins.
- Previous research suggests patients with intrinsically low CETP levels (TaqIB-B2 allele carriers) may experience reduced statin benefits.
Purpose of the Study:
- To test the pharmacogenetic hypothesis that CETP genotype influences long-term outcomes in statin-treated coronary artery disease (CAD) patients.
- To investigate the association between CETP genetic variation and mortality risk over a 10-year period.
Main Methods:
- A 10-year follow-up analysis of 812 CAD patients from the REGRESS cohort, treated with statins.
- Analysis of TaqIB-B2 allele carriers for CETP levels, HDL-cholesterol, and mortality endpoints (atherosclerotic disease death, ischemic heart disease death, all-cause mortality).
- Haplotype-effects analysis to identify genetic risk factors.
Main Results:
- Carriers of the TaqIB-B2 allele had significantly lower CETP levels and higher HDL-cholesterol.
- Each copy of the B2 allele was associated with increased hazard ratios for atherosclerotic disease death (1.59), ischemic heart disease death (1.53), and all-cause mortality (1.30).
- A specific risk-haplotype was identified with strong association to these adverse outcomes.
Conclusions:
- In male CAD patients treated with statins, genetic variations associated with low CETP levels correlate with increased 10-year mortality.
- Statin efficacy in reducing cardiovascular risk appears dependent on CETP genotype and plasma levels.
- These findings warrant consideration for CETP genotype when administering CETP inhibition therapies to CAD patients.
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