Observational Modeling of Strict vs Conventional Blood Pressure Control in Patients With Chronic Kidney Disease

Hypertension is a major, reversible cause of morbidity and mortality worldwide, and there have been many retrospective studies and prospective trials that have examined blood pressure1. Early retrospective studies initially showed that high blood pressure was asociated with heart disease and stroke2. Subsequent prospective clinical trials have sought to determine how agressively to treat elevated blood pressure3, and have attempted to lower systolic blood pressure to lower and lower levels 4. Retrospective studies also identified a J-curve of mortality for both systolic and diastolic blood pressure in certain groups of patients5, raising concerns about the safety of excessive blood pressure lowering in these populations. Prospective randomized clinical trials have the ability to establish a cause-effect relationship between a clinical intervention (e.g. the lowering of blood pressure to various predefined targets). Disadvantages of randomized clinical trials include their immense cost, and the fact that study participants may not be representative of the general population (limited external validity)6. Retrospective cohort studies and clinical trials are complementary in the knowledge they provide, and observational studies can examine populations that were excluded from clinical trials and treatments which cannot be tested in clinical trials, and hence they can offer valuable practical information. It is also true that retrospective studies often are in agreement with the results of prospective clinical trials7. Patients with chronic kidney disease (CKD) represent a large population with a high prevalence of cardiovascular morbidity and mortality8, which has been excluded from most clinical trials of blood pressure lowering. The few trials that have examined different blood pressure treatment goals in patients with CKD9–11 were unable to unequivocally establish the benefit vs. risk of stricter blood pressure control, due to limitations in which end-points they were powered to examine (primarily progression of kidney disease, with mortality or cardiovascular events either not examined, or examined as part of composite secondary outcomes), and due to discrepancies between results from primary and secondary or post-hoc analyses12–15. Therefore, current guidelines about the ideal target blood pressure in patients with CKD are based on extrapolations from trials done in healthier populations and on expert opinion. A growing body of observational studies suggests that the association of blood pressure with clinical events in patients with CKD is fundamentally different from the general population16. The implication is that strict BP control may not be advantageous in patients with CKD, and it could even be deleterious8. The Systlic Blood Pressure Interventional Trial (SPRINT) trial17 is the first major clinical trial of blood pressure lowering with a primary aim to prevent cardiovascular events and mortality that specifically enrolled patients with CKD, but its results will not be available for several years, and its strict inclusion/exclusion criteria may limit the generalizability of its findings to a narrow spectrum of the CKD population. Using a large database of United States Veterans with a wide spectrum of patients with CKD, we examined outcomes associated with stricter (systolic blood pressure (SBP) <120 mmHg) and conventional (SBP 120–139 mmHg) treated blood pressure in patients with baseline uncontrolled hypertension.