OBJECTIVE: Clinical trials using cholesteryl ester transfer protein (CETP) inhibitors to raise high-density lipoprotein cholesterol (HDL-C) concentrations reported an 'off-target' blood pressure (BP) raising effect. We evaluated the relations of baseline plasma CETP activity and longitudinal BP change. METHODS AND RESULTS: One thousand, three hundred and seven Framingham Study participants free of cardiovascular disease attending consecutive examinations 4 years apart (mean age 48 years) had baseline plasma CETP activity related to change in BP over the 4-year interval, adjusting for standard risk factors. Systolic BP increased [median +2 mmHg, 95% confidence interval (CI) -16,+23 mmHg], whereas diastolic BP decreased (median -3 mmHg, 95% CI -15,+11 mmHg). Plasma CETP activity was not related to change in diastolic BP, but was inversely related to change in systolic BP that was borderline significant (P=0.09). On multivariable analyses, plasma CETP activity was inversely related to change in pulse pressure (PP; beta per SD increment= -0.71 mmHg, P=0.005). When dichotomized at the median, plasma CETP activity above the median was associated with a 1 mmHg lower PP on follow-up (P=0.045). CONCLUSION: Decreasing plasma CETP activity was modestly related to increasing PP on follow-up in our community-based sample, suggesting that inhibition of intrinsic CETP activity itself is likely associated with minimal changes in BP.
OBJECTIVE: Clinical trials using cholesteryl ester transfer protein (CETP) inhibitors to raise high-density lipoprotein cholesterol (HDL-C) concentrations reported an 'off-target' blood pressure (BP) raising effect. We evaluated the relations of baseline plasma CETP activity and longitudinal BP change. METHODS AND RESULTS: One thousand, three hundred and seven Framingham Study participants free of cardiovascular disease attending consecutive examinations 4 years apart (mean age 48 years) had baseline plasma CETP activity related to change in BP over the 4-year interval, adjusting for standard risk factors. Systolic BP increased [median +2 mmHg, 95% confidence interval (CI) -16,+23 mmHg], whereas diastolic BP decreased (median -3 mmHg, 95% CI -15,+11 mmHg). Plasma CETP activity was not related to change in diastolic BP, but was inversely related to change in systolic BP that was borderline significant (P=0.09). On multivariable analyses, plasma CETP activity was inversely related to change in pulse pressure (PP; beta per SD increment= -0.71 mmHg, P=0.005). When dichotomized at the median, plasma CETP activity above the median was associated with a 1 mmHg lower PP on follow-up (P=0.045). CONCLUSION: Decreasing plasma CETP activity was modestly related to increasing PP on follow-up in our community-based sample, suggesting that inhibition of intrinsic CETP activity itself is likely associated with minimal changes in BP.
Authors: Ian B Wilkinson; Ahmed Qasem; Carmel M McEniery; David J Webb; Albert P Avolio; John R Cockcroft Journal: Circulation Date: 2002-01-15 Impact factor: 29.690
Authors: D Levy; A L DeStefano; M G Larson; C J O'Donnell; R P Lifton; H Gavras; L A Cupples; R H Myers Journal: Hypertension Date: 2000-10 Impact factor: 10.190
Authors: Ramachandran S Vasan; Michael J Pencina; Sander J Robins; Justin P Zachariah; Guneet Kaur; Ralph B D'Agostino; Jose M Ordovas Journal: Circulation Date: 2009-12-15 Impact factor: 29.690
Authors: B R Winkelmann; M M Hoffmann; M Nauck; A M Kumar; K Nandabalan; R S Judson; B O Boehm; A R Tall; G Ruaño; W März Journal: Pharmacogenomics J Date: 2003 Impact factor: 3.550