1.1: Central Blood Pressure, Statins and LDL-Cholesterol: A Mediation Analysis

Abstract

Background

Central blood pressure (CBP) is a better predictor of cardiovascular burden than peripheral blood pressure (BP). While studies have suggested a reduction in peripheral BP with statins, it remains uncertain to what extent statins reduce CBP and whether this reduction is mediated through a decrease in LDL-cholesterol (LDL).

Methods

Of the 20,004 CARTaGENE participants, 17,011 had CBP and LDL measurements (n = 13,439 without, n = 3,133 with statins). Linear and logistic regression analyses were used to evaluate the association between CBP, LDL and statin use (after stratification for treatment indication for the latter). The impact of LDL on the association between statin use and CBP was determined by mediation analyses. All analyses were adjusted for age, sex, diabetes, cardiovascular disease, smoking, eGFR, BMI, uric acid, heart rate, anti-hypertensive agents and aspirin.

Results

Lower levels of LDL were associated with lower systolic and diastolic CBP in participants treated with (b = 0.098 and 0.125; p < 0.001)and without statins (b = 0.089 and 0.105; p < 0.001). Statin use as primary prevention (per ACC/AHA guidelines; n = 8,865) was also associated with lower systolic CBP, diastolic CBP and central pulse pressure (b = −0.091, −0.073 and −0.055; p < 0,001). Mediation analyses demonstrated that 15%, 46% and -22% of these effects were achieved through the concomitant changes in LDL (Table 1). In secondary prevention (n = 995), statins use was not associated with lower CBP, although the small sample size may lack power.

Conclusion

In this populational cohort, statin use as primary prevention is associated with lower CBP. These changes are mediated directly by statins but also indirectly through effects on LDL.