Pulse pressure should be maintained at low range for renal protection, study says

Pulse pressure (PP), a measure of arterial stiffness, is strongly related to the risk of developing end-stage renal disease (ESRD), as shown in a recent study from Singapore.

“Our findings provide novel evidence that supports the recommendations that the management of hypertension may require not only reducing SBP and diastolic (D)BP but also maintaining PP within a low range for renal protection,” the investigators said.

The analysis included 30,517 individuals (mean age, 63.0 years) who had their BP measured at ages 46–85 years during follow‐up interviews. There were 463 ESRD cases that occurred over an average 11.3 years of follow‐up, according to linked data from the nationwide Singapore Renal Registry Information.

Multivariable Cox proportional hazards regression models revealed each BP index to have a positive association with ESRD when studied individually. The respective hazard ratios (HRs) in the highest vs lowest categories of SBP, DBP, PP and mean arterial pressure (MAP) were 2.50 (95 percent confidence interval [CI], 1.76–3.55), 1.58 (95 percent CI, 1.05–2.39), 5.25 (95 percent CI, 3.52–7.84) and 2.66 (95 percent CI, 1.90–3.72; p-trend≤0.001). [J Am Heart Assoc 2019;doi:10.1161/JAHA.119.013282]

However, the associations for SBP, DBP and MAP were attenuated and no longer significant—except for a borderline significance for SBP 150–159 mm Hg—when adjusted for PP. On the other hand, PP remained significantly associated with ESRD risk, with an apparent dose‐dependent pattern (p-trend<0.001) after adjusting for SBP or DBP.

“Our findings suggest that the positive association between SBP and ESRD risk might be mediated through the widening of PP with increasing SBP, and this explains why the association became inverse and nonsignificant after controlling for PP in the same model,” the investigators pointed out.

In stratified analyses, ESRD associations with PP categories were generally stronger in participants aged <65 years vs their older counterparts (p-interaction=0.002) and in those who were not using antihypertensive medication vs those on such medication (p-interaction=0.005).

“In addition to the protective effect on renal function by reducing BP, antihypertensive drugs may also have beneficial effects on intrarenal mechanisms directly. This hypothesis is supported by a meta‐analysis of 15 randomized controlled trials that have suggested antihypertensive medication could reduce arterial stiffness beyond the effect on BP control,” they pointed out. [Drugs 2005;65(suppl 2):29-39; J Hypertens 2011;29:1034-1042]

Overall, the present data are in line the results of other studies reporting that PP is related to lower glomerular filtration rate independent of MAP and to faster kidney function decline independent of SBP. [Hypertension 2005;45:586-591; Am J Kidney Dis 2012;59:41-49]

“PP is a measure that has acquired a central position as an effective and technically simple surrogate measure of aortic stiffness that is dependent on cardiac output, the stiffness of elastic central arteries like the aorta, and wave reflection… Arterial stiffness and increased PP could lead to glomerular hypertrophy, hyperfiltration and segmental glomerular sclerosis, which would eventually cause nephrosclerosis and fibrosis,” the investigators said.

“Future studies are needed to evaluate potential therapies that target reduction of arterial stiffness to decrease the risk of ESRD,” they added.