Natural variation in plasma CETP levels does not affect RAAS responsiveness or blood pressure reactivity in healthy men (Expert Opin Ther Targets 2008)

Background: The blood pressure increase associated with the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib is probably attributable to an off-target effect but it is unknown whether activation of the renin-angiotensin-aldosterone system (RAAS) may be related to variation in the plasma CETP level. We questioned whether the plasma CETP level would affect RAAS responsiveness to low sodium diet and the blood pressure response to angiotensin-II infusion in healthy subjects.

Methods: RAAS parameters and blood pressure were determined during liberal sodium diet (200 mmol/24 h) and low sodium diet (50 mmol/24 h) in 67 healthy men. Blood pressure response to incremental angiotensin-II infusion was assessed in 34 subjects during liberal sodium diet. Correlation analysis was performed to test whether RAAS responsiveness and blood pressure were related to plasma CETP mass, high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I measured during liberal sodium diet.

Results: CETP mass ranged from 1.29 to 2.95 mg/l. No significant differences in (changes) in mean arterial pressure, aldosterone and active plasma renin concentration in response to low sodium were observed between the lowest and highest tertiles of CETP mass, HDL-C and apolipoprotein A-I. These outcome variables were also not significantly correlated with CETP, HDL-C and apolipoprotein A-I, except for a modest relation of aldosterone measured during low sodium with apolipoprotein A-I (r = 0.28, p = 0.022). Blood pressure response to angiotensin-II was similar between CETP tertiles.

Conclusions: Mineralocorticoid and blood pressure responsiveness to dietary salt intake are not significantly related to physiological interindividual differences in plasma CETP. We suggest that a lower CETP mass does not exert adverse effects on blood pressure regulation.