People with genetically reduced CETP levels have lower, not higher, blood pressure, arguing against a CETP class effect behind the hypertension seen with torcetrapib (Mayo Clin Proc 2010)

Original title: Cholesteryl ester transfer protein (CETP) genotype and reduced CETP levels associated with decreased prevalence of hypertension

Mayo Clin Proc · 1 June 2010 · 7

Schechter CB, Barzilai N, Crandall JP, Atzmon G

To determine whether reduced CETP activity inherently carries blood pressure risk, and whether the elevated blood pressure and mortality seen with torcetrapib are drug-specific or characteristic of the whole CETP-inhibitor class, researchers examined CETP genotype, phenotype, and blood pressure in 521 older adults from longevity studies enriched for a reduced-activity CETP variant. The prevalence of hypertension was actually lower among homozygotes for the variant CETP (48%) than among wild-type (60%) or heterozygous (65%) individuals (p = .03). Low CETP levels were associated with reduced hypertension prevalence across tertiles (65%, 59%, 55% from highest to lowest CETP tertile, p = .04) and with lower systolic blood pressure (140.8, 138.1, and 136.2 mmHg respectively, p = .03). The findings show that reduced CETP levels are linked to lower, not higher, blood pressure, suggesting the adverse blood pressure effects of torcetrapib reflect a drug-specific liability rather than a consequence of lower CETP levels generally.

Original abstract

Objectives: To clarify whether reduced cholesteryl ester transfer protein (CETP) activity carries inherent blood pressure risks and to infer whether the increased blood pressure and elevated mortality associated with torcetrapib are idiosyncratic or characteristic of this class of drugs.

Patients And Methods: We examined the associations among CETP genotype, phenotype, and blood pressure in a cohort of 521 older adults (who have complete data for the variables required in our primary analysis) enrolled between November 1, 1998, and June 30, 2003, in our ongoing studies of genes associated with longevity, including a cohort with a high prevalence of a genotype coding for a reduced activity variant of CETP and low levels of CETP.

Results: The prevalence of hypertension was actually lower among homozygotes for the variant CETP (48% vs 60% among those with wild-type and 65% among heterozygotes; P=.03). Low levels of CETP were associated with reduced prevalence of hypertension (65% in highest tertile, 59% in middle tertile, and 55% in lowest tertile; P=.04) and lower systolic blood pressure (140.8, 138.1, 136.2 mm Hg, respectively; P=.03).

Conclusion: Reduced levels of CETP are associated with lower, not higher, blood pressure. The adverse results with torcetrapib, if mediated through blood pressure, are likely to represent effects of this specific drug, rather than a result of lower CETP levels.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.