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Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community
Justin P Zachariah1, Michael J Pencina, Asya Lyass
1Framingham Heart Study, Framingham, MA 01702-5803, USA.
Insights
Lower cholesteryl ester transfer protein (CETP) activity was linked to increased pulse pressure, suggesting CETP inhibition has minimal blood pressure effects. This impacts understanding of CETP inhibitors and cardiovascular risk.
Area of Science:
- Cardiovascular Science
- Biochemistry
- Clinical Pharmacology
Background:
- Cholesteryl ester transfer protein (CETP) inhibitors aim to increase HDL-C.
- Previous trials noted an 'off-target' blood pressure (BP) raising effect with CETP inhibitors.
Purpose of the Study:
- To investigate the relationship between baseline plasma CETP activity and longitudinal changes in blood pressure.
- To determine if intrinsic CETP activity influences blood pressure regulation.
Main Methods:
- Analysis of 1,307 Framingham Study participants over a 4-year interval.
- Assessed baseline plasma CETP activity and its correlation with changes in systolic BP, diastolic BP, and pulse pressure (PP).
- Adjusted for standard cardiovascular risk factors in multivariable analyses.
Main Results:
- Systolic BP increased (+2 mmHg), and diastolic BP decreased (-3 mmHg) over 4 years.
- Plasma CETP activity was inversely related to systolic BP change (P=0.09) and significantly inversely related to PP change (P=0.005).
- Higher baseline CETP activity was associated with a modest decrease in PP over time.
Conclusions:
- Decreasing plasma CETP activity was modestly associated with increasing pulse pressure.
- Findings suggest that inhibiting intrinsic CETP activity may be associated with minimal blood pressure changes.
- Further research is needed to fully elucidate the cardiovascular implications of CETP inhibition.
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.
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