Evidence for Reverse Causality in the Association Between Blood Pressure and Cardiovascular Risk in Patients With Chronic Kidney Disease

Abstract

Among those with moderate-to-advanced chronic kidney disease, the relationship between blood pressure (BP) and cardiovascular disease seems U shaped but is loglinear in apparently healthy adults. The SHARP (Study of Heart and Renal Protection) randomized 9270 patients with chronic kidney disease to ezetimibe/simvastatin versus matching placebo and measured BP at each follow-up visit. Cox regression was used to assess the association between BP and risk of cardiovascular disease among (1) those with a self-reported history of cardiovascular disease and (2) those with no such history and, based on plasma troponin-I concentration, a low probability of subclinical cardiac disease. A total of 8666 participants had a valid baseline BP and troponin-I measurement, and 2188 had at least 1 cardiovascular event during follow-up. After adjustment for relevant confounders, the association between systolic BP and cardiovascular events was U shaped, but among participants without evidence of previous cardiovascular disease, there was a positive loglinear association throughout the range of values studied. Among those with the lowest probability of subclinical cardiac disease, each 10 mm Hg higher systolic BP corresponded to a 27% increased risk of cardiovascular disease (hazard ratio, 1.27; 95% confidence interval, 1.11–1.44). In contrast, the relationship between diastolic BP and cardiovascular risk remained U shaped irrespective of cardiovascular disease history or risk of subclinical disease. In conclusion, the lack of a clear association between systolic BP and cardiovascular risk in this population seems attributable to confounding, suggesting that more intensive systolic BP reduction may be beneficial in such patients. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00125593.

Estimated glomerular filtration rate and the risk–benefit profile of intensive blood pressure control amongst nondiabetic patients: a post hoc analysis of a randomized clinical trial

“…One suggested pathophysiological mechanism for the risk associated with lowering BP is altered cardiac structure and function amongst patients with cardiovascular disease due to long‐standing hypertension . A recent observational study of patients with advanced CKD showed that the association between SBP and cardiovascular risk was linearly incremental when patients did not have cardiovascular disease history , supporting intensive BP control for such patients. However, there remained a U‐shaped association for DBP irrespective of cardiovascular disease history, which has made the interpretation of these associations difficult because currently available BP‐lowering interventions decrease both SBP and DBP.…”

Blood pressure parameters are associated with all-cause and cause-specific mortality in chronic kidney disease

“…This association appeared to be consistent across various categories of eGFR and in those with and without albuminuria(15). A secondary analysis of the Study of Heart and Renal Protection trial noted that the U-shaped associations of blood pressure with mortality was noted only among CKD patients with underlying cardiovascular disease but not in those with pre-existing cardiovascular disease(16). The present study adds important information, in that it provided further insights into the potential reasons for the increased risks for death (both cardiovascular and non-cardiovascular) in those with lower BP.…”

Atrial Fibrillation and Hypertension

“…For example, the optimal BP for high-risk populations, such as the elderly or those with chronic kidney disease, requires further research. 8 Although AF patients were not specifically studied, they would be high risk from the cardiovascular perspective, and some insights from recent trials may be of interest.…”