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Title: Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community

Author
item Zachariah, Justin - Children'S Hospital - Boston, Massachusetts
item Pencina, Michael - Boston University
item Lyass, Asya - Boston University
item Kaur, Guneet - Boston University
item D'agostino, Ralph - Boston University
item Ordovas, Jose - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Vasan, Ramachandran - Boston University

Submitted to: Journal of Hypertension
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2010
Publication Date: 5/1/2011
Citation: Zachariah, J.P., Pencina, M.J., Lyass, A., Kaur, G., D'Agostino, R.B., Ordovas, J.M., Vasan, R.S. 2011. Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community. Journal of Hypertension. 29(5):863-868.

Interpretive Summary: Cholesteryl ester transfer protein (CETP) is a blood protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. Its activity is inversely related with high density lipoprotein (HDL) levels. As HDL can alleviate atherosclerosis and other cardiovascular diseases, pharmacological inhibition of CETP has been studied as a method of improving HDL levels. However, clinical trials using CETP inhibitors to raise high-density lipoprotein cholesterol (HDL-C) concentrations reported an 'off-target' blood pressure (BP) raising effect. To shed some light into this negative effect, we evaluated the relations of baseline blood CETP activity and longitudinal blood pressure change in 1307 Framingham Study participants free of cardiovascular disease. Inhibition of CETP was moderately associated with decrease in blood pressure. Therefore, our data suggest that inhibition of intrinsic CETP activity itself is likely associated with minimal changes in BP.

Technical Abstract: 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. 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). 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.