Low Achieved Systolic Blood Pressure Related to Kidney Protection in Diabetic and Non-Diabetic High-Risk Hypertensive Patients

Figures

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  Figure 1.. Flowchart showing that n = 15,245 patients with high-risk hypertension were investigated as intention to treat (ITT) for effects valsartan vs. amlodipine in the VALUE Trial. Further, n = 1442 patients were excluded from the current analysis either because they had endpoint during the first 6 months of up-titration of study drugs or they had less than 3 study visits with standardized office BP measurements after the first 6 months. A minimum of 3 visits was chosen a priori to be able to calculate an achieved average systolic BP during the trial. Then n = 13,803 patients were included in the analysis of incident kidney endpoints related to the achieved average systolic BP; n = 4,655 patients with diabetes mellitus and n = 9,148 patients without diabetes mellitus. These patients were then grouped according to their achieved average systolic BP ≥ 140 mmHg, 130-139 mmHg and < 130 mmHg.

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  Figure 2.. The Box plots show achieved average SBP in patients with diabetes (DM, n=4,655), non-DM (n=9,148) and in the total group (n=13,803) for ranges of achieved average SBP from 6 months and throughout. The patients were grouped according to their achieved average systolic BP ≥140 mmHg (mean values 150, 149 and 149 mmHg in the 3 groups, respectively), 130-139 mmHg (mean values 135 mmHg in all 3 groups) and <130 mmHg (125 mmHg in all 3 groups). Patients with DM are shown in orange Box plots, patients without DM in blue Box plots, and all patients are shown in green Box plots. Patients with achieved average systolic SP 130-139 mmHg have a minimal scatter as expected. The group who achieved average systolic BP ≥140 mmHg has a marked scatter towards high values for the 4th quartile of the distribution, whereas the group who achieved average systolic BP <130 mmHg has a marked scatter towards low values for the 1st quartile of the distribution. The patients were followed by 969 investigators in 31 countries in all parts of the world. Target systolic BP was <140 mmHg which was achieved by 70% of the patients. The main driver for the achieved systolic BP in individual patients, and thus in the…

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  Figure 3.. The Forest plots show Hazard ratios with 95% confidence intervals for the study protocol-defined kidney endpoints approved by the VALUE Trial endpoint committee during the trial. The kidney endpoints are presented related to ranges of achieved average systolic BP, 130–139 mmHg and < 130 mmHg, compared to ≥ 140 mmHg (defined as 1.0) in patients with diabetes (DM, n = 4,655), patients without (non) DM (n = 9,148) and in the total group of all patients (n = 13,803). The endpoint Worsened Kidney Function, detected in n = 420 patients, was defined as a 50% increase of serum creatinine at two occasions with a minimum of 4 weeks apart. The endpoint End Stage Kidney Disease (ESKD), detected in n = 82 patients, was defined as the need for dialysis or transplantation. Statistical analyses were done with adjusted Cox proportional hazards models. ESKD was stepwise lower with lower systolic BP for all groups though borderline significant (P = 0.05) for DM patients achieving an average of 130-139 mmHg and not significant for DM patients achieving average systolic BP < 130 mmHg (only one DM patient had ESKD at achieved average systolic BP < 130 mmHg). The number of patients with kidney…

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  Figure 4. The Forest plots show Hazard ratios with 95% confidence intervals for the study protocol-defined kidney endpoints approved by the VALUE Trial endpoint committee during the trial. The kidney endpoints, defined in legends to Figure 3, are presented related to quartiles of achieved average systolic BP with quartile 1 defined as 1.0. The Forest plots show the main findings from the continuous quartile trend analyses in patients with diabetes (DM, n = 4,655), non-DM (n = 9,148) and in the total group (n = 13,803). Statistical analyses were done with adjusted Cox proportional hazards models. The trend for less kidney endpoints with lower quartiles of achieved systolic BP is statistically highly significant for the analyses of both kidney endpoints (Worsened Kidney Function and ESKD) in patients with DM, in patients without (non-) DM and in the group of all patients. The number of patients with kidney endpoints (n and %) in the groups is shown inTable 3.