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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.