Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and nonresistant hypertension.

We sought to compare the risk of end-stage renal disease (ESRD), ischemic heart event (IHE), congestive heart failure (CHF), cerebrovascular accident (CVA), and all-cause mortality among 470,386 individuals with resistant and nonresistant hypertension (non-RH). Resistant hypertension (60,327 individuals) was subcategorized into two groups: 23,104 patients with cRH (controlled on four or more medicines) and 37,223 patients with uRH (uncontrolled on three or more medicines) in a 5-year retrospective cohort study. Cox proportional hazard modeling was used to estimate hazard ratios adjusting for age, gender, race, body mass index, chronic kidney disease (CKD), and comorbidities. Resistant hypertension (cRH and uRH), compared with non-RH, had multivariable adjusted hazard ratios (95% confidence intervals) of 1.32 (1.27-1.37), 1.24 (1.20-1.28), 1.46 (1.40-1.52), 1.14 (1.10-1.19), and 1.06 (1.03-1.08) for ESRD, IHE, CHF, CVA, and mortality, respectively. Comparison of uRH with cRH had hazard ratios of 1.25 (1.18-1.33), 1.04 (0.99-1.10), 0.94 (0.89-1.01), 1.23 (1.14-1.31), and 1.01 (0.97-1.05) for ESRD, IHE, CHF, CVA, and mortality, respectively. Men and Hispanics had a greater risk for ESRD within all three cohorts. Individuals with resistant hypertension had a greater risk for ESRD, IHE, CHF, CVA, and mortality. The risk of ESRD and CVA were 25% and 23% greater, respectively, in uRH compared with cRH, supporting the linkage between blood pressure and both outcomes

Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and nonresistant hypertension.

We sought to compare the risk of end-stage renal disease (ESRD), ischemic heart event (IHE), congestive heart failure (CHF), cerebrovascular accident (CVA), and all-cause mortality among 470,386 individuals with resistant and nonresistant hypertension (non-RH). Resistant hypertension (60,327 individuals) was subcategorized into two groups: 23,104 patients with cRH (controlled on four or more medicines) and 37,223 patients with uRH (uncontrolled on three or more medicines) in a 5-year retrospective cohort study. Cox proportional hazard modeling was used to estimate hazard ratios adjusting for age, gender, race, body mass index, chronic kidney disease (CKD), and comorbidities. Resistant hypertension (cRH and uRH), compared with non-RH, had multivariable adjusted hazard ratios (95% confidence intervals) of 1.32 (1.27-1.37), 1.24 (1.20-1.28), 1.46 (1.40-1.52), 1.14 (1.10-1.19), and 1.06 (1.03-1.08) for ESRD, IHE, CHF, CVA, and mortality, respectively. Comparison of uRH with cRH had hazard ratios of 1.25 (1.18-1.33), 1.04 (0.99-1.10), 0.94 (0.89-1.01), 1.23 (1.14-1.31), and 1.01 (0.97-1.05) for ESRD, IHE, CHF, CVA, and mortality, respectively. Men and Hispanics had a greater risk for ESRD within all three cohorts. Individuals with resistant hypertension had a greater risk for ESRD, IHE, CHF, CVA, and mortality. The risk of ESRD and CVA were 25% and 23% greater, respectively, in uRH compared with cRH, supporting the linkage between blood pressure and both outcomes

Phosphorus and risk of renal failure in subjects with normal renal function.

PurposeWhether higher serum phosphorus levels increase risk for kidney disease onset and progression to end-stage renal disease in those with normal renal function is largely unknown. We sought to determine whether higher serum phosphorus levels increase risk for end-stage renal disease within a large ethnically diverse population with normal kidney function.MethodsA retrospective longitudinal cohort study was performed in the period January 1, 1998 through December 31, 2008 of adults within a vertically integrated health plan (3.4 million members). The primary objective was to determine risk of incident end-stage renal disease. Baseline and time-averaged phosphorus were used for Cox regressions analyses to calculate hazard ratios (HR) adjusting for age, sex, race, pre-existing hypertension, and diabetes.ResultsA total of 94,989 subjects were identified in the 11-year observation period. Mean age of the cohort was 50 years, with 61% female, 38% white, 14% black, and 25% Hispanic. Population-based phosphorus quartile ranges were 1.9-3.0 mg/dL, 3.1-3.4 mg/dL, 3.5-3.8 mg/dL, and 3.9-5.7 mg/dL. End-stage renal disease occurred in 130 (0.1%) subjects. Every 0.5-mg/dL phosphorus increase demonstrated an adjusted HR of 1.40 (95% confidence interval [CI], 1.06-1.84) and HR for mortality of 1.09 (95% CI, 1.06-1.13). Adjusted HRs were 0.64 (95% CI, 0.37-1.11), 0.83 (95% CI, 0.50-1.39), and 1.48 (95% CI, 0.96-2.28) in the 2nd, 3rd, and 4th quartile, respectively, compared with the first phosphorus quartile. Time-averaged serum phosphorus demonstrated a similar relationship across quartiles and as a continuous variable.ConclusionIn our large, ethnically diverse cohort of non kidney disease subjects, higher serum phosphorus levels were associated with greater risk for end-stage renal disease and mortality

Plasma renin activity (PRA) levels and antihypertensive drug use in a large healthcare system.

BackgroundAlthough hypertension guidelines have utility in treating uncomplicated hypertension, they often overlook the pathophysiologic basis and heterogeneity of hypertension. This may explain the relatively poor hypertension control rates. A proposed approach is to guide addition and subtraction of medications using ambulatory plasma renin activity (PRA) values. To evaluate the heterogeneity of hypertension and the medication burden associated with it, we investigated medication usage in relation to PRA among hypertensive patients within a large ethnically diverse organization.MethodsA cross sectional data analysis was performed of hypertensive subjects with PRA measurements in the Kaiser Permanente Southern California database between 1 January 1998 and 31 October 2009.ResultsAmong 7,887 such patients 0, 1, 2, ≥3 medication usage was 16%, 20%, 24%, 40% respectively. PRA levels ranged 1000-fold. Across PRA quartiles (Q1 to Q4) ≥3 meds were prescribed to 50%, 40%, 34%, 37%. From low to high PRA quartiles there was no usage trend for angiotensin converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (71%), but diuretics increased (52%, 53%, 57%, 68%), calcium channel blocker's (CCB) fell (56%, 53%, 51%, 42%), and β-blockers fell (77%, 61%, 49%, 41%). Moreover, systolic BP fell (146, 142, 140, 135 mm Hg), blood urea nitrogen (BUN) rose (16, 17, 18, 20 mg/dl), serum uric acid rose (6.1, 6.3, 6.5, 6.9 mg/dl), and chronic kidney disease rose (22%, 22%, 23%, 27%).ConclusionsPolytherapy was the norm for treating hypertension. Lower PRAs were associated with higher blood pressures and more medications. Higher PRAs were associated with lower pressures and fewer medications. The results indicate that opportunities exist to simplify antihypertensive therapy by using current ambulatory PRA levels to guide drug selections and subtractions

Phosphorus and risk of renal failure in subjects with normal renal function.

PurposeWhether higher serum phosphorus levels increase risk for kidney disease onset and progression to end-stage renal disease in those with normal renal function is largely unknown. We sought to determine whether higher serum phosphorus levels increase risk for end-stage renal disease within a large ethnically diverse population with normal kidney function.MethodsA retrospective longitudinal cohort study was performed in the period January 1, 1998 through December 31, 2008 of adults within a vertically integrated health plan (3.4 million members). The primary objective was to determine risk of incident end-stage renal disease. Baseline and time-averaged phosphorus were used for Cox regressions analyses to calculate hazard ratios (HR) adjusting for age, sex, race, pre-existing hypertension, and diabetes.ResultsA total of 94,989 subjects were identified in the 11-year observation period. Mean age of the cohort was 50 years, with 61% female, 38% white, 14% black, and 25% Hispanic. Population-based phosphorus quartile ranges were 1.9-3.0 mg/dL, 3.1-3.4 mg/dL, 3.5-3.8 mg/dL, and 3.9-5.7 mg/dL. End-stage renal disease occurred in 130 (0.1%) subjects. Every 0.5-mg/dL phosphorus increase demonstrated an adjusted HR of 1.40 (95% confidence interval [CI], 1.06-1.84) and HR for mortality of 1.09 (95% CI, 1.06-1.13). Adjusted HRs were 0.64 (95% CI, 0.37-1.11), 0.83 (95% CI, 0.50-1.39), and 1.48 (95% CI, 0.96-2.28) in the 2nd, 3rd, and 4th quartile, respectively, compared with the first phosphorus quartile. Time-averaged serum phosphorus demonstrated a similar relationship across quartiles and as a continuous variable.ConclusionIn our large, ethnically diverse cohort of non kidney disease subjects, higher serum phosphorus levels were associated with greater risk for end-stage renal disease and mortality

Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system.

ObjectiveTo evaluate the prevalence of and characterize resistant hypertension in a large representative population with successful hypertension management and reliable health information.Patient and methodsWe performed a cross-sectional study using clinical encounter, laboratory, and administrative information from the Kaiser Permanente Southern California health system between January 1, 2006, and December 31, 2007. From individuals older than 17 years with hypertension, resistant hypertension was identified and prevalence was determined. Multivariable logistic regression was used to calculate odds ratios (ORs), with adjustments for demographic characteristics, clinical variables, and medication use.ResultsOf 470,386 hypertensive individuals, 60,327 (12.8%) were identified as having resistant disease, representing 15.3% of those taking medications. Overall, 37,061 patients (7.9%) had uncontrolled hypertension while taking 3 or more medicines. The ORs (95% CIs) for resistant hypertension were greater for black race (1.68 [1.62-1.75]), older age (1.11 [1.10-1.11] for every 5-year increase), male sex (1.06 [1.03-1.10]), and obesity (1.46 [1.42-1.51]). Medication adherence rates were higher in those with resistant hypertension (93% vs 89.8%; P<.001). Chronic kidney disease (OR, 1.84; 95% CI, 1.78-1.90), diabetes mellitus (OR, 1.58; 95% CI, 1.53-1.63), and cardiovascular disease (OR, 1.34; 95% CI, 1.30-1.39) were also associated with higher risk of resistant hypertension.ConclusionIn a more standardized hypertension treatment environment, we observed a rate of resistant hypertension comparable with that of previous studies using more fragmented data sources. Past observations have been limited due to nonrepresentative populations, reliability of the data, heterogeneity of the treatment environments, and less than ideal control rates. This cohort, which was established using an electronic medical record-based approach, has the potential to provide a better understanding of resistant hypertension and outcomes

Use of Phosphorus Binders among Non-Dialysis Chronic Kidney Disease Patients and Mortality Outcomes.

BackgroundWhether the benefits of phosphorus binders extend to those without end stage renal disease is uncertain. Among a large diverse non-dialysis chronic kidney disease (CKD) population with hyperphosphatemia, we sought to evaluate phosphorus binder use and compare mortality risk between patients prescribed and not prescribed binders.MethodsA retrospective cohort study within an integrated health system (January 1, 1998 - December 31, 2012) among CKD patients (age ≥18) was performed. Non-dialysis CKD patients with 2 separate estimated glomerular filtrate rate (eGFR) <30 mL/min/1.73 m2 and serum phosphorus ≥5.0 mg/dL within 180 days of eGFR were included. Multivariable cox proportional hazards and inverse probability of treatment-weighted models were used to estimate mortality hazard ratios (HRs) for patients who received phosphorus binders compared to no binders.ResultsAmong 10,165 study patients, 2,733 subjects (27%) received phosphorus binders. Compared to the no-phosphorus-binder group, the binder group had mortality HRs (95% CI) of 0.86 (0.79-0.94) and 0.86 (0.80-0.93) using traditional multivariable and inverse probability of treatment-weighted models respectively. Sensitivity analyses removing patients who were prescribed binders >180 days after index date revealed no difference in mortality between those with binders and with no binders.ConclusionOur findings from a real-world clinical environment revealed that 27% of hyperphosphatemic non-dialysis CKD patients were prescribed binders. They also had lower risk of mortality compared to those not prescribed phosphorus binders. However, the lower mortality risk was not observed when we accounted for immortal time bias. Whether phosphorus binder use in CKD improves survival remains to be determined

Use of Phosphorus Binders among Non-Dialysis Chronic Kidney Disease Patients and Mortality Outcomes.

BackgroundWhether the benefits of phosphorus binders extend to those without end stage renal disease is uncertain. Among a large diverse non-dialysis chronic kidney disease (CKD) population with hyperphosphatemia, we sought to evaluate phosphorus binder use and compare mortality risk between patients prescribed and not prescribed binders.MethodsA retrospective cohort study within an integrated health system (January 1, 1998 - December 31, 2012) among CKD patients (age ≥18) was performed. Non-dialysis CKD patients with 2 separate estimated glomerular filtrate rate (eGFR) <30 mL/min/1.73 m2 and serum phosphorus ≥5.0 mg/dL within 180 days of eGFR were included. Multivariable cox proportional hazards and inverse probability of treatment-weighted models were used to estimate mortality hazard ratios (HRs) for patients who received phosphorus binders compared to no binders.ResultsAmong 10,165 study patients, 2,733 subjects (27%) received phosphorus binders. Compared to the no-phosphorus-binder group, the binder group had mortality HRs (95% CI) of 0.86 (0.79-0.94) and 0.86 (0.80-0.93) using traditional multivariable and inverse probability of treatment-weighted models respectively. Sensitivity analyses removing patients who were prescribed binders >180 days after index date revealed no difference in mortality between those with binders and with no binders.ConclusionOur findings from a real-world clinical environment revealed that 27% of hyperphosphatemic non-dialysis CKD patients were prescribed binders. They also had lower risk of mortality compared to those not prescribed phosphorus binders. However, the lower mortality risk was not observed when we accounted for immortal time bias. Whether phosphorus binder use in CKD improves survival remains to be determined