Cholesteryl ester transfer protein (CETP) genotype and reduced CETP levels associated with decreased prevalence of hypertension.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Department of Family and Social Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. clyde.schechter@Einstein.y.edu
Clyde B
CB
Schechter
Nir
N
Barzilai
Jill P
JP
Crandall
Gil
G
Atzmon
D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects; D001794:Blood Pressure; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000453:epidemiology*; D008297:Male; D015995:Prevalence; D011804:Quinolines / Q000009:adverse effects
D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D011804:Quinolines; C483909:torcetrapib