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.
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.
Authors: Steven E Nissen; Jean-Claude Tardif; Stephen J Nicholls; James H Revkin; Charles L Shear; William T Duggan; Witold Ruzyllo; William B Bachinsky; Gabriel P Lasala; Gregory P Lasala; E Murat Tuzcu Journal: N Engl J Med Date: 2007-03-26 Impact factor: 91.245
Authors: Philip J Barter; Mark Caulfield; Mats Eriksson; Scott M Grundy; John J P Kastelein; Michel Komajda; Jose Lopez-Sendon; Lori Mosca; Jean-Claude Tardif; David D Waters; Charles L Shear; James H Revkin; Kevin A Buhr; Marian R Fisher; Alan R Tall; Bryan Brewer Journal: N Engl J Med Date: 2007-11-05 Impact factor: 91.245
Authors: Nir Barzilai; Gil Atzmon; Clyde Schechter; Ernst J Schaefer; Adrienne L Cupples; Richard Lipton; Suzanne Cheng; Alan R Shuldiner Journal: JAMA Date: 2003-10-15 Impact factor: 56.272
Authors: Rajesh Krishna; Matt S Anderson; Arthur J Bergman; Bo Jin; Marissa Fallon; Josee Cote; Kim Rosko; Cynthia Chavez-Eng; Ryan Lutz; Daniel M Bloomfield; Maria Gutierrez; James Doherty; Fredrick Bieberdorf; Jeffrey Chodakewitz; Keith M Gottesdiener; John A Wagner Journal: Lancet Date: 2007-12-08 Impact factor: 79.321
Authors: D J Gordon; J L Probstfield; R J Garrison; J D Neaton; W P Castelli; J D Knoke; D R Jacobs; S Bangdiwala; H A Tyroler Journal: Circulation Date: 1989-01 Impact factor: 29.690
Authors: M J Forrest; D Bloomfield; R J Briscoe; P N Brown; A-M Cumiskey; J Ehrhart; J C Hershey; W J Keller; X Ma; H E McPherson; E Messina; L B Peterson; W Sharif-Rodriguez; P K S Siegl; P J Sinclair; C P Sparrow; A S Stevenson; S-Y Sun; C Tsai; H Vargas; M Walker; S H West; V White; R F Woltmann Journal: Br J Pharmacol Date: 2008-06-09 Impact factor: 8.739
Authors: Kristen Fortney; Edgar Dobriban; Paolo Garagnani; Chiara Pirazzini; Daniela Monti; Daniela Mari; Gil Atzmon; Nir Barzilai; Claudio Franceschi; Art B Owen; Stuart K Kim Journal: PLoS Genet Date: 2015-12-17 Impact factor: 5.917