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Hypertension Awareness, Treatment, and Control in Chronic Kidney Disease
CLINICAL RESEARCH STUDY
Hypertension Awareness, Treatment, and Control in Chronic Kidney Disease Pantelis A. Sarafidis, MD, PhD,a Suying Li, PhD,b Shu-Cheng Chen, MS,b Allan J. Collins, MD,b Wendy W. Brown, MD, MPH,c Michael J. Klag, MD, MPH,d George L. Bakris, MDa a
Hypertensive Diseases Unit, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago-Pritzker School of Medicine, Chicago, Ill; bKidney Early Evaluation Program Data Coordinating Center, Minneapolis, Minn; cWest Side VA Medical Center, Chicago, Ill; dJohns Hopkins General Hospital, Baltimore, Md.
ABSTRACT BACKGROUND: Hypertension prevalence, awareness, treatment, and blood pressure control rates in the population with chronic kidney disease are limited. The objective of this study was to determine the state of blood pressure control in patients with chronic kidney disease. METHODS: This is a cross-sectional analysis of data of participants with chronic kidney disease from the Kidney Early Evaluation Program. The Kidney Early Evaluation Program is a national-based health screening program for individuals at high risk for kidney disease conducted in 49 states and the District of Columbia. Of 55,220 adults with kidney disease, 10,813 completed information for demographic and medical characteristics used in the analysis. Predictors of blood pressure control were assessed using multiple logistic regression analysis. RESULTS: Hypertension prevalence, awareness, and treatment proportions in the screened cohort were high (86.2%, 80.2%, and 70.0%, respectively), but blood pressure control rates were low (13.2%). These proportions increased with advancing stage of kidney disease. Elevated systolic blood pressure accounted for the majority of inadequate control. Male gender (odds ratio [OR] 0.86; 95% confidence interval [CI], 0.75-0.99), non-Hispanic black race (OR 0.76; 95% CI, 0.65-0.89), and body mass index of 30 kg/m2 or more (OR 0.83; 95% CI, 0.73-0.94) were inversely related with blood pressure control. Those with stage 3 kidney disease were more likely to have blood pressure at goal than those with stage 1 kidney disease (OR 2.08; 95% CI, 1.55-2.80). CONCLUSION: We conclude that despite increased awareness and treatment of hypertension, control rates in these participants are poor. This poor control rate centers around elevated systolic pressure in people who are obese, non-Hispanic black, or male. These data suggest that those who are aware of their kidney disease are more likely to achieve blood pressure control. © 2008 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2008) 121, 332-340 KEYWORDS: Awareness; Chronic kidney disease; Control; Hypertension; Treatment
Hypertension is the most common chronic disease in developed societies1,2 and accounts for an estimated 7.1 million deaths per year worldwide.3 Chronic kidney disease most commonly results from diabetes or poorly controlled blood pressure.4,5 The United States National Health and Nutrition Examination Survey (NHANES) 1999-2003 estimated the The authors declare no conflicts related to the present study. Requests for reprints should be addressed to George L. Bakris, MD, Hypertensive Diseases Unit, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago-Pritzker School of Medicine, 5841 S. Maryland Ave MC 1027, Chicago, IL 60637. E-mail address: [email protected]
0002-9343/$ -see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2007.11.025
prevalence of chronic kidney disease in the adult population at approximately 10%,6 whereas the incidence of end-stage renal disease, requiring dialysis, is increasing faster than expected according to data from the United States Renal Data Service.7 Kidney disease, defined by an estimated glomerular filtration rate of less than 60 mL/min, is an independent risk factor for cardiovascular events.8,9 Because of this increasing burden of chronic kidney disease, the National Kidney Foundation launched the Kidney Early Evaluation Program (KEEP) to increase public awareness and early detection of chronic kidney disease.10
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Poor control of blood pressure results in accelerated cluded questions on medical history, basic demographics, progression of chronic kidney disease11 but can also occur educational level, and use of medical services data. Trained as a consequence of kidney injury.12 Interventions that deaffiliate personnel or volunteers performed height, weight, crease blood pressure levels to less than 130/80 mm Hg in and blood pressure measurements. Blood samples were patients with chronic kidney disease and proteinuria have drawn for plasma glucose, lipid profile, serum creatinine, repeatedly demonstrated delayed and hemoglobin levels. A urine progression of kidney injury13 and sample was assayed for an albuthus are recommended by all mamin-to-creatinine ratio and tested CLINICAL SIGNIFICANCE jor guidelines.11,14 for pyuria, hematuria, and miBecause of the impact of elecroalbuminuria using dipsticks. ● Only 13.2% of hypertensive adults with vated blood pressure levels on the chronic kidney disease had adequately public health, the prevalence, levBlood Pressure controlled blood pressure (⬍130/80 els of awareness, treatment, and Measurement mm Hg). control of hypertension in the genBlood pressure was measured by ● Rates of adequate control of hyperteneral population have been astrained personnel using mercury sessed worldwide.1,2,15 Despite sion increased progressively with adsphygmomanometers and appropristudies in the general population, vancing kidney disease, as did hyperately sized cuffs following the data on individuals with chronic tension awareness and treatment. American Heart Association guidekidney disease are limited.16,17 lines for blood pressure measure● Other predictors of adequate control were The aim of the present study was ment.19 Participants remained at female gender, advanced age, diabetes, to determine the prevalence, awarerest in the sitting posture for at smoking, and having a physician. ness, treatment, and control of hyleast 5 minutes before blood prespertension, and to investigate possisure was measured. If the first ● Subgroups at high risk for kidney disble predictors of blood pressure blood pressure reading was eleease are an important target for better control in individuals with chronic vated, defined as a blood pressure blood pressure control. kidney disease from the KEEP of 140/90 mm Hg or more, the cohort. subject remained at rest for an-
MATERIALS AND METHODS Study Population The KEEP program is a nationwide effort by the National Kidney Foundation to evaluate and educate people at high risk for chronic kidney disease, that is, adult individuals with a history of diabetes or hypertension or a family history of these diseases. The program was officially launched in August of 2000, and by the end of 2005, some 55,220 individuals were screened in 49 states and the District of Columbia.10 The present study is a cross-sectional analysis including all KEEP participants with chronic kidney disease as of December 31, 2005, without missing information for race, education, smoking status, insurance, having a doctor, history of hypertension, diabetes, kidney disease, blood pressure levels, body mass index, and blood glucose levels.
Participant Evaluation Participant recruitment and screening protocols of the KEEP program are described elsewhere.10,18 Eligibility criteria for screening include age 18 years or more with a history of diabetes or hypertension or a family history of either diseases or chronic kidney disease. Recruitment efforts included local media (flyers, radio, television stations, and newspapers), with most of the screening sites located in community centers, schools, churches, health centers, and hospitals. Each subject was required to give informed consent before being allowed to participate in the program. All participants completed a standard questionnaire that in-
other 5 minutes and a second measurement was taken. For these participants, only the second blood pressure value was used in the analysis. If the participant was taking antihypertensive medications, blood pressure values were obtained without changing current drug dosing or regimen schedule.
Definitions Chronic kidney disease was defined as a glomerular filtration rate of less than 60 mL/min/1.73 m2 or the presence of kidney damage indicated by elevated urine albumin excretion.20 The glomerular filtration rate was estimated from serum creatinine using the Modification of Diet in Renal Disease equation.21 Stage 1 chronic kidney disease was defined as an estimated glomerular filtration rate of 90 mL/min/1.73 m2 or more and an elevated albumin-to-creatinine ratio of 30 mg/g or more. Stage 2 kidney disease was defined as an estimated glomerular filtration rate of 60 to 89 mL/min/1.73 m2 and albuminuria. Stages 3, 4, and 5 kidney disease were defined as an estimated glomerular filtration rate of 30 to 59 mL/min/1.73 m2, 15 to 29 mL/min/1.73 m2, and less than 15 mL/min/1.73 m2, respectively.20 Diabetes was defined per the American Diabetes Association guidelines as a fasting plasma glucose level greater than 126 mg/dL, nonfasting plasma glucose level greater than 200 mg/dL, or self-report of diabetes. Hypertension was defined as a blood pressure of 130/80 mm Hg or more or current treatment with antihypertensive drugs.11,14 Additional analyses using the general population
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Figure 1 Participant eligibility and recruitment. KEEP ⫽ Kidney Early Evaluation Program; eGFR ⫽ estimated glomerular filtration rate; ACR ⫽ albumin-to-creatinine ratio; BMI ⫽ body mass index.
threshold of 140/90 mm Hg was also performed. Awareness of hypertension or chronic kidney disease was defined as knowledge by the participant of having hypertension or chronic kidney disease according to a previous diagnosis by a physician. Treatment of hypertension was defined as current use of antihypertensive drugs. Control was defined as treated hypertension with blood pressure less than 130/80 mm Hg and less than 140/90 mm Hg in the secondary analysis. The proportions of awareness, treatment, and control of hypertension were calculated within the cohort of hypertensives for comparison. Participants with a positive history of hypertension and blood pressure less than 130/80 mm Hg receiving no treatment were classified as normotensive. Body mass index was calculated as weight divided by height squared.
Biochemical Analyses Plasma glucose was measured using Lifescan’s SureStep Pro test strips (Lifescan, Milpitas, Calif). Serum creatinine was assessed using a standardized method in all participants: the Olympus 5431 device (Olympus Optical, Tokyo, Japan). Albumin-to-creatinine ratio was assessed with Bayer Clinitek reagent strips (Bayer Diagnostics, Tarrytown, NY).
Statistical Analysis Analysis was performed with SAS version 9.1 for Windows (SAS Institute Inc, Cary, NC). Continuous variables are presented as mean ⫾ standard deviation. Categoric variables
are presented as absolute frequencies along with the relevant percentages. In univariate analysis we compared the characteristics of hypertensive individuals with controlled hypertension with those with uncontrolled hypertension. The chi-square test was used to compare frequencies between groups, and the Kruskal-Wallis test was used to compare the difference in the mean for continuous variables. In addition, multiple logistic regression analysis was performed and models were created to assess the association of several demographic and clinical characteristics with hypertension control. By using hypertension control as a dependent variable, we assessed the effect of age, gender, race, diabetes, obesity, smoking status, education, insurance status, having a doctor, and stage of chronic kidney disease, as well as awareness of hypertension and chronic kidney disease. We report adjusted odd ratios with 95% confidence intervals. Probability values of P less than .05 (2-tailed) were considered statistically significant.
RESULTS Demographic and Clinical Characteristics A total of 10,813 of 55,220 KEEP participants (19.6%) were included in the present study (Figure 1). A summary of demographic and clinical characteristics of KEEP participants who were evaluated for study selection is presented in Table 1. The demographic and clinical characteristics of the chronic kidney disease cohort evaluated are presented in Table 2. Awareness of chronic kidney disease in this cohort was as low as 6.5%.
Sarafidis et al Table 1
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335
Demographic and Clinical Characteristics of the Entire Kidney Early Evaluation Program Cohort Screened Total Without Missing Values
Those with Missing Values
N (43,130)
%
N (12,090)
Age, N (%) 18-30 y 31-45 y 46-60 y 61-75 y ⬎75 y
3594 9865 15,047 11,038 3586
8.3 22.9 34.9 25.6 8.3
1096 2916 4216 2938 924
9.1 24.1 34.9 24.3 7.6
Gender, N (%) Female Male
29,547 13,583
68.5 31.5
8205 3885
67.9 32.1
Race, N (%) Non-Hispanic white Non-Hispanic black Hispanic Other race
19,027 13,778 5221 5104
44.1 32.0 12.1 11.8
4171 5019 1555 1226
34.8 41.9 13.0 10.2
BMI, N (%) ⬍30 kg/m2 ⱖ30 kg/m2
23,970 19,160
55.6 44.4
6571 5339
55.2 44.8
Smoking status, N (%) Never smoke Used to smoke Current smoker
23,685 12,371 5136
57.5 30.0 12.5
6034 3070 1512
56.8 28.9 14.2
Education, N (%) ⬍ High school High school graduate ⫹
6521 36,609
15.1 84.9
2024 9872
17.0 83.0
Those with insurance, N (%)† Those who had a doctor, N (%)† Those with diabetes, N (%)† Awareness of blood pressure, N (%)† Receiving antihypertensive drugs, N (%)† Aware of chronic kidney disease, N (%)† Age (mean ⫾ SD) BMI (mean ⫾ SD) Systolic blood pressure (mean ⫾ SD) Diastolic blood pressure (mean ⫾ SD) Pulse pressure (mean ⫾ SD) eGFR (mean ⫾ SD)
35,309 37,606 14,508 21,893 17,649 1322 43,130 42,710 42,954 42,952 42,935 43,130
81.9 87.2 33.6 50.8 40.9 3.1 53.4 30.2 133.3 79.1 54.2 80.6
%
P Value* ⬍.0001
.18
⬍.0001
.43
⬍.0001
⬍.0001
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
15.8 6.8 20.1 11.5 16.6 23.7
9448 10,252 3954 5851 4616 337 12,090 11,756 11,780 11,779 11,769 9760
82.1 87.3 32.8 48.4 38.2 2.8 52.6 30.3 134.9 80.0 54.9 82.8
.52 .65 .07 ⬍.0001 ⬍.0001 .13 ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
15.8 6.9 21.2 12.2 17.3 25.4
⬍.0001 .27 ⬍.0001 ⬍.0001 ⬍.0001
BMI ⫽ body mass index; SD ⫽ standard deviation; eGFR ⫽ estimated glomerular filtration rate. *Population without chronic kidney disease, N ⫽ 32,317 ⫹ final population with chronic kidney disease, N ⫽ 10,813 versus KEEP participants who were excluded because of missing values (missing values for chronic kidney disease, N ⫽ 9909 ⫹ missing values for blood pressure, N ⫽ 77 ⫹ missing values for all the rest variables, N ⫽ 2104). †These statistical comparisons were relative to those who did not have insurance, a doctor, diabetes, and so forth.
Hypertension Awareness, Treatment, and Control Eighty-six percent of the study cohort were identified as hypertensive at the 130/80 mm Hg threshold (Figure 2). Hypertension prevalence gradually increased with advancing chronic kidney disease stages, increasing from approximately 79.1% in participants with stage 1 chronic kidney disease to 95.5% in participants with stages 4 and 5 chronic kidney disease. The blood pressure control rate was as low as 13.2%. Systolic blood pressure was more
difficult to control than diastolic blood pressure; only approximately 18% of the participants achieved control of systolic blood pressure compared with 33% for diastolic blood pressure. Both awareness and treatment of hypertension were increased with advancing kidney disease stages. This trend translated into a progressive increase in control rates from stage 1 to stages 4 and 5 (Figure 2). Because 93.5% of the individuals assessed were not aware of their kidney disease, a supplemental analysis was performed
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Table 2
Demographic and Clinical Characteristics of the Total Study Cohort
Total
Uncontrolled Hypertensives (ⱖ130/80 mm Hg)
Controlled Hypertensives (⬍130/80 mm Hg) N (1230)
N (10,813)
(%)
N (8089)
(%)
Age, N (%) 18-30 y 31-45 y 46-60 y 61-75 y ⬎75 y
355 1330 3134 4087 1907
(3.28) (12.30) (28.98) (37.80) (17.64)
188 859 2312 3218 1512
(2.32) (10.62) (28.58) (39.78) (18.69)
10 62 320 568 270
(0.81) (5.04) (26.02) (46.18) (21.95)
Gender, N (%) Female
7565
(69.96)
5514
(68.17)
876
(71.22)
Race, N (%) Non-Hispanic white Non-Hispanic black Hispanic Other race
5586 2989 895 1343
(51.66) (27.64) (8.28) (12.42)
4100 2387 652 950
(50.69) (29.51) (8.06) (11.74)
696 293 74 167
(56.59) (23.82) (6.02) (13.58)
BMI, N (%) ⱖ30 kg/m2
4947
(45.75)
4019
(49.68)
565
(45.93)
Smoking status, N (%) Never smoke Used to smoke Current smoker
5957 3730 1126
(55.10) (34.49) (10.41)
4465 2831 793
(55.2) (35.0) (9.80)
648 470 112
(52.68) (38.21) (9.11)
Education, N (%) ⬍ High school High school graduate ⫹
1992 8821
(18.42) (81.58)
1578 6511
(19.51) (80.49)
222 1008
(18.05) (81.95)
9278 9931 4838
(85.80) (91.84) (44.74)
6928 7465 3795 6252 5291
(85.65) (92.29) (46.92) (77.29) (65.41)
1122 1199 634 1230 1230
(91.22) (97.48) (51.54) (100.0) (100.0)
⬍.0001 ⬍.0001 .002 ⬍.0001 ⬍.0001
705
(6.52)
543
(6.71)
104
(8.46)
.02
Those with insurance, N (%) Those with a doctor, N (%) Those with diabetes, N (%) Aware of hypertension, N (%) Receiving antihypertensive medications, N (%) Those who were aware of chronic kidney disease, N (%) Age (mean ⫾ SD) BMI (mean ⫾ SD) Systolic blood pressure (mean ⫾ SD) Diastolic blood pressure (mean ⫾ SD) Pulse pressure (mean ⫾ SD) eGFR (mean ⫾ SD)
(%)
P Value* ⬍.0001
.03 ⬍.0001
.01 .09
.23
61.2 30.4 138.4 79.0 59.4 59.7
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
15.2 6.8 21.9 12.2 18.6 22.7
62.4 31.0 146.2 82.7 63.5 59.7
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
14.4 6.8 19.2 11.4 19.0 22.6
65.4 30.6 117.0 67.8 49.3 52.5
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
12.1 6.8 8.8 7.4 9.7 17.2
⬍.0001 .04 ⬍.0001 ⬍.0001 ⬍.0001 ⬍.0001
BMI ⫽ body mass index; SD ⫽ standard deviation; eGFR ⫽ estimated glomerular filtration rate. *P value for comparisons between uncontrolled and controlled hypertensives.
to identify the hypertension prevalence, awareness, treatment, and control with blood pressure threshold of the general population (ie, ⬎140/90 mm Hg). As shown in Figure 3, the prevalence is estimated to be approximately 10% lower than at 130/80 mm Hg. Awareness and treatment proportions, however, are approximately 10% higher than the 130/80 mm Hg goal, and control rates are more than doubled.
Predictors of Hypertension Control Blood pressure levels differed considerably between participants who achieved and did not achieve adequate
blood pressure control (117.0 ⫾ 8.8/67.8 ⫾ 7.4 mm Hg vs 146.2 ⫾ 19.2/82.7 ⫾ 11.4 mm Hg, respectively, P ⬍ .001 for each comparison). In a univariate analysis, individuals at the blood pressure goal of less than 130/80 mm Hg were older and less obese than those at higher levels (Table 2). Those at the blood pressure goal of less than 130/80 mm Hg were female, non-Hispanic white, and more likely to have insurance and access to a physician. Participants with adequate blood pressure control were more likely to have diabetes (51.5% vs 46.9%, P ⫽ .002) and a lower estimated glomerular filtration rate (52.5 ⫾ 17.2
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337 Table 3 Odds Ratios of Blood Pressure Control Among All Patients with Hypertension
Figure 2 Prevalence, awareness, treatment, and control of hypertension to recommended systolic goal (⬍130 mm Hg) by chronic kidney disease stage. Note total cohort has an N ⫽ 10,813. Prevalence is defined by systolic blood pressure ⱖ 130 mm Hg or diastolic blood pressure ⱖ 80 mm Hg or use of medication. All comparisons between stages for all categories at P ⬍ .0001.
vs 59.7 ⫾ 22.6, P ⬍ .001) than uncontrolled hypertensive participants. Participants with controlled hypertension also had a higher proportion of chronic kidney disease awareness (8.5% vs 6.7%, P ⫽ .025). Table 3 illustrates that male gender and non-Hispanic blacks had lower odds of being at blood pressure goal. Conversely, smoking, having a physician, or having a diagnosis of diabetes were independent predictors of having a blood pressure of less than 130/80 mm Hg.
OR
Lower
Upper
P Value
Age 18-45 y (ref) 46-60 y 61-75 y ⬎75 y
1.00 1.55 1.68 1.62
1.18 1.28 1.20
2.04 2.20 2.17
.002 ⬍.001 .001
Gender Female (ref) Male
1.00 0.87
0.76
0.99
.04
Race Non-Hispanic white (ref) Non-Hispanic black Hispanic Other race
1.00 0.85 0.93 1.23
0.73 0.71 1.02
0.99 1.21 1.49
.04 .57 .03
BMI BMI ⬍ 30 kg/m2 (ref) BMI ⱖ 30 kg/m2
1.00 0.91
0.80
1.03
.13
Smoking status Never smoked (ref) Used to smoke Current smoker
1.00 1.14 1.26
0.99 1.004
1.30 1.57
.06 .046
Education Less than high school (ref) High school graduate ⫹
1.00 1.15
0.98
1.35
.09
Insurance No (ref) Yes
1.00 1.18
0.94
1.48
.14
Had a physician No (ref) Yes
1.00 2.34
1.59
3.44
⬍.0001
Diabetes No (ref) Yes
1.00 1.20
1.06
1.37
.004
Chronic kidney disease stage Stage 1 (ref) Stage 2 Stage 3 Stages 4 and 5
1.00 1.18 2.22 2.67
0.85 1.66 1.83
1.64 2.98 3.91
.33 ⬍.0001 ⬍.0001
OR ⫽ odds ratio; BMI ⫽ body mass index.
Figure 3 Prevalence, awareness, treatment, and control of hypertension in total cohort by chronic kidney disease stage with ⬍ 140/90 mm Hg as a threshold. Note total cohort has an N ⫽ 10,813. Prevalence of systolic blood pressure ⱖ 140 mm Hg or diastolic blood pressure ⱖ 90 mm Hg or use of medication. All comparisons between stages are significant to a P ⬍ .0001. BP ⫽ blood pressure.
Patient awareness of chronic kidney disease was not associated with better blood pressure control (Table 4). Male gender, non-Hispanic black race, and obesity defined by a body mass index 30 kg/m2 or more were associated with a lower probability of being at blood pressure goal. Conversely, smoking, higher education, and having a doctor were independent predictors of being at blood pressure goal. Blood pressure control was also more likely to occur in kidney disease stages 3 to 5 (data not shown).
DISCUSSION Our data demonstrate that in a cohort of patients with chronic kidney disease the prevalence, awareness, and treat-
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Table 4 Odds Ratio of Hypertension Control Among Patients Who Were Aware They Had Chronic Kidney Disease OR
Lower
Upper
P Value
Age 18-45 y (ref) 46-60 y 61-75 y ⬎75 y
1.00 1.12 1.08 1.01
0.84 0.82 0.75
1.48 1.44 1.37
.45 .57 .95
Gender Female (ref) Male
1.00 0.86
0.75
0.99
.04
Race Non-Hispanic white (ref) Non-Hispanic black Hispanic Other race
1.00 0.76 0.87 1.15
0.65 0.66 0.95
0.89 1.14 1.39
⬍.001 .31 .16
BMI ⬍30 kg/m2 (ref) ⱖ30 kg/m2
1.00 0.83
0.73
0.94
.004
Smoking status Never smoked (ref) Used to smoke Current smoker
1.00 1.12 1.30
0.98 1.03
1.28 1.63
.10 .03
Education Less than high school (ref.) High school graduate ⫹
1.00 1.18
1.004
1.39
.04
1.00 1.20
0.96
1.51
.11
1.00 1.86
1.25
2.75
.002
Diabetes No (ref) Yes
1.00 1.11
0.98
1.26
.11
Chronic kidney disease stage Stage 1 (ref) Stage 2 Stage 3 Stage 4 and 5
1.00 1.14 2.08 2.14
0.81 1.55 1.44
1.59 2.80 3.17
.46 ⬍.0001 ⬍.001
Awareness of chronic kidney disease No (ref) Yes
1.00 1.11
0.88
1.40
.39
Insurance No (ref) Yes Having a physician No (ref) Yes
OR ⫽ odds ratio; BMI ⫽ body mass index.
ment of hypertension was comparable, if not better, than in NHANES 2003-2004,22 but that the blood pressure control rate was far worse than in NHANES. Elevated systolic blood pressure accounted for most of the cases of inadequate control. Male gender, non-Hispanic black race, and obesity were associated with a greater likelihood that blood pressure would not be controlled, whereas smoking, higher education, having a doctor, and increased chronic kidney disease stage were independent predictors of achieving blood pressure goals.
Hypertension prevalence, defined as greater than 140/90 mm Hg, in the KEEP cohort is higher than in the general population, which ranged from 28% in the United States to 44% in European countries.1,2,22 However, because hypertension was among the criteria to enter KEEP, those with hypertension were oversampled. Thus, hypertension prevalence in KEEP may be higher than in a sample of individuals with chronic kidney disease drawn from the general population. Oversampling may also account for increased awareness and treatment rates of hypertension, which were higher in KEEP than in the general population.1,22 Note, however, that hypertension prevalence did increase with advancing chronic kidney disease stage, a finding that corresponds with the natural history of hypertension and kidney injury.11 The overall control rate of less than 130/80 mm Hg was 13.2% in this cohort, a much lower rate than seen in NHANES 1999-2003, with 37% of 3213 subjects with chronic kidney disease being at blood pressure goal.16 One explanation for this difference is that the NHANES analysis included the total chronic kidney disease cohort in the denominator and provided no direct data for hypertension prevalence. Thus, the control rate among hypertensive individuals with chronic kidney disease cannot be estimated, and no direct comparisons with our study can be made. In a multicentered study of 1201 adult, nondialyzed patients with chronic kidney disease who were followed for a minimum of 6 months, 12.5% achieved the less than 130/80 mm Hg target,17 a finding closer to ours. In our analysis, systolic blood pressure accounted for the majority of patients not achieving control, a finding similar to both the aforementioned studies16,17 and those in the general population.23,24 Given that elevated systolic pressure provides the highest risk for decline in renal function,25 these data further support the need for aggressive systolic blood pressure reduction to slow nephropathy progression. If the less than 140/90 mm Hg threshold is used, the blood pressure control rate in our study increased to approximately 34%, a control rate similar to that in NHANES 2003-2004.22 A comparable 40.6% of patients with chronic kidney disease achieving this target is reported in the aforementioned Italian study.17 This finding may be associated with the lower awareness of chronic kidney disease in our cohort, as noted in other studies.6 This highlights the importance of undertaking strategies to increase awareness of chronic kidney disease. Perhaps the most important finding of this study is the progressive increase in control rates with advancing chronic kidney disease. Patients with stages 4 and 5 kidney disease had a 3-fold higher blood pressure control rate than those with stage 1 kidney disease. This may relate to the respective increases in hypertension awareness and treatment and highlights the importance of hypertension awareness. Our data demonstrate that older persons and those with diabetes were more likely to have hypertension control. These were rather peculiar observations, because both older age and diabetes are associated with a higher prevalence of
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and more difficult to control hypertension. In patients with chronic kidney disease16,17 and the general population,23 older age is associated with inadequate blood pressure control. These associations were no longer present when hypertension awareness was included in our model, a finding suggesting that increased hypertension awareness with advancing age or the presence of a major concomitant disease was responsible for the observation. Differences in control rates between sexes were largely attributed to respective differences in awareness and treatment. This could be related to women being more attentive to the risks of hypertension.1,15,23,26 Most data, including ours, support the notion of lower blood pressure control rates in non-Hispanic blacks compared with whites,27,28 although some studies do not support this observation23 and the respective time trends do not show a clear pattern.1 However, because hypertension management in black patients is more difficult29 and black patients have a much higher risk of kidney disease progression,30 particular attention should be given to aggressively lowering blood pressure in this group. Better blood pressure control was seen in those with a higher education. This may be due to a number of factors, including better appreciation of hypertension-associated risks, increased adherence to the prescribed regimen, and better access to health care. A similar association between educational level and hypertension control has been noted in the general population,27 but studies in cohorts with16 or without26,28 chronic kidney disease have not confirmed this observation. In the general population, current smoking was negatively associated27 or did not affect blood pressure control.23,28 In our study, smoking resulted in a higher likelihood of having blood pressure controlled. This unusual finding is unclear, although this group had much lower rates of obesity. There are several limitations associated with our analysis, which would include the cross-sectional design. In addition, although the collection of data was standardized, much of it was based on self-report; thus, recall bias exists for some of the variables (ie, hypertension treatment, history of diabetes). Also, blood pressure was measured on a single occasion; thus, recorded blood pressure levels could be higher than measured in clinical trials because of the “white coat” effect.31 We tried to minimize this bias by repeating the measurement if the first reading was elevated and having non-physician personnel performing the measurements, because the “white coat” phenomenon is more overt when a physician performs the readings.32 This limitation could have led to an overestimation of hypertension prevalence and an underestimation of hypertension control in our study. This is unlikely, however, because there was a high awareness of hypertension in this cohort. Finally, because urine albumin excretion is characterized by high intraindividual variation33 and was also measured once, it is not known whether the inclusion of participants with glomerular filtration rate levels greater than 60 mL/min/1.73 m2 and ele-
339 vated urinary albumin excretion in stages 1 and 2 chronic kidney disease led to overestimation of chronic kidney disease prevalence.
CONCLUSIONS This is the first study to provide data on the prevalence, awareness, and treatment of hypertension in a cohort with chronic kidney disease. Hypertension control rates were lower than in the general population, primarily driven by elevated systolic blood pressure. Achievement of blood pressure goals improves as awareness of advancing kidney disease stage is apparent. Because the presence of advanced kidney disease is the most common cause of medically treatable hypertension,34 current strategies to improve blood pressure control may rest on better knowledge of kidney disease awareness. Last, although we did not assess physician adherence to guidelines, it was clear that those whose physicians made patients aware of their chronic kidney disease stage had a higher likelihood of achieving blood pressure goal.
References 1. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. JAMA. 2003; 290:199-206. 2. Wolf-Maier K, Cooper RS, Banegas JR, et al. Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. JAMA. 2003;289:2363-2369. 3. World Health Organization. World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva, Switzerland: World Health Organization; 2002. 4. McCullough PA, Jurkovitz CT, Pergola PE, et al. Independent components of chronic kidney disease as a cardiovascular risk state: results from the Kidney Early Evaluation Program (KEEP). Arch Intern Med. 2007;167:1122-1129. 5. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis. 2007;49(2 Suppl 2):S12-S154. 6. Coresh J, Byrd-Holt D, Astor BC, et al. Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol. 2005;16:180-188. 7. Hsu CY, Vittinghoff E, Lin F, Shlipak MG. The incidence of end-stage renal disease is increasing faster than the prevalence of chronic renal insufficiency. Ann Intern Med. 2004;141:95-101. 8. Sarafidis PA, Bakris GL. Microalbuminuria and chronic kidney disease as risk factors for cardiovascular disease. Nephrol Dial Transplant. 2006;21:2366-2374. 9. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296-1305. 10. Kidney Early Evaluation Program. Annual Data Report 2006. Am J Kidney Dis. 2007;49;(Suppl 3):S1-S160. 11. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 Suppl 2):1-290. 12. Mailloux LU, Haley WE. Hypertension in the ESRD patient: pathophysiology, therapy, outcomes, and future directions. Am J Kidney Dis. 1998;32:705-719. 13. Sarafidis PA, Khosla N, Bakris GL. Antihypertensive therapy in the presence of proteinuria. Am J Kidney Dis. 2007;49:12-26. 14. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and
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Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572. Wolf-Maier K, Cooper RS, Kramer H, et al. Hypertension treatment and control in five European countries, Canada, and the United States. Hypertension. 2004;43:10-17. Peralta CA, Hicks LS, Chertow GM, et al. Control of hypertension in adults with chronic kidney disease in the United States. Hypertension. 2005;45:1119-1124. De Nicola L, Minutolo R, Gallo C, et al. Management of hypertension in chronic kidney disease: the Italian multicentric study. J Nephrol. 2005;18:397-404. Brown WW, Peters RM, Ohmit SE, et al. Early detection of kidney disease in community settings: the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis. 2003;42:22-35. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003; 289:2560-2572. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis. 2002;39(2 Suppl 2):S1-246. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461-470. Ong KL, Cheung BM, Man YB, Lau CP, Lam KS. Prevalence, awareness, treatment, and control of hypertension among United States adults 1999-2004. Hypertension. 2007;49:69-75. Hyman DJ, Pavlik VN. Characteristics of patients with uncontrolled hypertension in the United States. N Engl J Med. 2001;345:479-486. Lloyd-Jones DM, Evans JC, Larson MG, et al. Differential control of systolic and diastolic blood pressure: factors associated with lack of blood pressure control in the community. Hypertension. 2000;36:594-599.
The American Journal of Medicine, Vol 121, No 4, April 2008 25. Young JH, Klag MJ, Muntner P, et al. Blood pressure and decline in kidney function: findings from the Systolic Hypertension in the Elderly Program (SHEP). J Am Soc Nephrol. 2002;13:2776-2782. 26. Sarafidis PA, Lasaridis A, Gousopoulos S, et al. Prevalence, awareness, treatment and control of hypertension in employees of factories of Northern Greece: the Naoussa study. J Hum Hypertens. 2004;18:623-629. 27. Nieto FJ, Alonso J, Chambless LE, et al. Population awareness and control of hypertension and hypercholesterolemia. The Atherosclerosis Risk in Communities study. Arch Intern Med. 1995;155:677-684. 28. He J, Muntner P, Chen J, et al. Factors associated with hypertension control in the general population of the United States. Arch Intern Med. 2002;162:1051-1058. 29. Hebert LA, Kusek JW, Greene T, et al. Effects of blood pressure control on progressive renal disease in blacks and whites. Modification of Diet in Renal Disease Study Group. Hypertension. 1997;30(3 Pt 1): 428-435. 30. Hsu CY, Lin F, Vittinghoff E, Shlipak MG. Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States. J Am Soc Nephrol. 2003;14:2902-2907. 31. Verdecchia P, Schillaci G, Borgioni C, et al. White coat hypertension and white coat effect. Similarities and differences. Am J Hypertens. 1995;8:790-798. 32. La Batide-Alanore A, Chatellier G, Bobrie G, et al. Comparison of nurse- and physician-determined clinic blood pressure levels in patients referred to a hypertension clinic: implications for subsequent management. J Hypertens. 2000;18:391-398. 33. Khosla N, Sarafidis PA, Bakris GL. Microalbuminuria. Clin Lab Med. 2006;26:635-653. 34. Ruilope L, Kjeldsen SE, de la Sierra A, et al. The kidney and cardiovascular risk—implications for management: a consensus statement from the European Society of Hypertension. Blood Press. 2007;16: 72-79.
Hypertension Awareness, Treatment, and Control in Chronic Kidney Disease Pantelis A. Sarafidis, MD, PhD,a Suying Li, PhD,b Shu-Cheng Chen, MS,b Allan J. Collins, MD,b Wendy W. Brown, MD, MPH,c Michael J. Klag, MD, MPH,d George L. Bakris, MDa a
Hypertensive Diseases Unit, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago-Pritzker School of Medicine, Chicago, Ill; bKidney Early Evaluation Program Data Coordinating Center, Minneapolis, Minn; cWest Side VA Medical Center, Chicago, Ill; dJohns Hopkins General Hospital, Baltimore, Md.
ABSTRACT BACKGROUND: Hypertension prevalence, awareness, treatment, and blood pressure control rates in the population with chronic kidney disease are limited. The objective of this study was to determine the state of blood pressure control in patients with chronic kidney disease. METHODS: This is a cross-sectional analysis of data of participants with chronic kidney disease from the Kidney Early Evaluation Program. The Kidney Early Evaluation Program is a national-based health screening program for individuals at high risk for kidney disease conducted in 49 states and the District of Columbia. Of 55,220 adults with kidney disease, 10,813 completed information for demographic and medical characteristics used in the analysis. Predictors of blood pressure control were assessed using multiple logistic regression analysis. RESULTS: Hypertension prevalence, awareness, and treatment proportions in the screened cohort were high (86.2%, 80.2%, and 70.0%, respectively), but blood pressure control rates were low (13.2%). These proportions increased with advancing stage of kidney disease. Elevated systolic blood pressure accounted for the majority of inadequate control. Male gender (odds ratio [OR] 0.86; 95% confidence interval [CI], 0.75-0.99), non-Hispanic black race (OR 0.76; 95% CI, 0.65-0.89), and body mass index of 30 kg/m2 or more (OR 0.83; 95% CI, 0.73-0.94) were inversely related with blood pressure control. Those with stage 3 kidney disease were more likely to have blood pressure at goal than those with stage 1 kidney disease (OR 2.08; 95% CI, 1.55-2.80). CONCLUSION: We conclude that despite increased awareness and treatment of hypertension, control rates in these participants are poor. This poor control rate centers around elevated systolic pressure in people who are obese, non-Hispanic black, or male. These data suggest that those who are aware of their kidney disease are more likely to achieve blood pressure control. © 2008 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2008) 121, 332-340 KEYWORDS: Awareness; Chronic kidney disease; Control; Hypertension; Treatment
Hypertension is the most common chronic disease in developed societies1,2 and accounts for an estimated 7.1 million deaths per year worldwide.3 Chronic kidney disease most commonly results from diabetes or poorly controlled blood pressure.4,5 The United States National Health and Nutrition Examination Survey (NHANES) 1999-2003 estimated the The authors declare no conflicts related to the present study. Requests for reprints should be addressed to George L. Bakris, MD, Hypertensive Diseases Unit, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago-Pritzker School of Medicine, 5841 S. Maryland Ave MC 1027, Chicago, IL 60637. E-mail address: [email protected]
0002-9343/$ -see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2007.11.025
prevalence of chronic kidney disease in the adult population at approximately 10%,6 whereas the incidence of end-stage renal disease, requiring dialysis, is increasing faster than expected according to data from the United States Renal Data Service.7 Kidney disease, defined by an estimated glomerular filtration rate of less than 60 mL/min, is an independent risk factor for cardiovascular events.8,9 Because of this increasing burden of chronic kidney disease, the National Kidney Foundation launched the Kidney Early Evaluation Program (KEEP) to increase public awareness and early detection of chronic kidney disease.10
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Poor control of blood pressure results in accelerated cluded questions on medical history, basic demographics, progression of chronic kidney disease11 but can also occur educational level, and use of medical services data. Trained as a consequence of kidney injury.12 Interventions that deaffiliate personnel or volunteers performed height, weight, crease blood pressure levels to less than 130/80 mm Hg in and blood pressure measurements. Blood samples were patients with chronic kidney disease and proteinuria have drawn for plasma glucose, lipid profile, serum creatinine, repeatedly demonstrated delayed and hemoglobin levels. A urine progression of kidney injury13 and sample was assayed for an albuthus are recommended by all mamin-to-creatinine ratio and tested CLINICAL SIGNIFICANCE jor guidelines.11,14 for pyuria, hematuria, and miBecause of the impact of elecroalbuminuria using dipsticks. ● Only 13.2% of hypertensive adults with vated blood pressure levels on the chronic kidney disease had adequately public health, the prevalence, levBlood Pressure controlled blood pressure (⬍130/80 els of awareness, treatment, and Measurement mm Hg). control of hypertension in the genBlood pressure was measured by ● Rates of adequate control of hyperteneral population have been astrained personnel using mercury sessed worldwide.1,2,15 Despite sion increased progressively with adsphygmomanometers and appropristudies in the general population, vancing kidney disease, as did hyperately sized cuffs following the data on individuals with chronic tension awareness and treatment. American Heart Association guidekidney disease are limited.16,17 lines for blood pressure measure● Other predictors of adequate control were The aim of the present study was ment.19 Participants remained at female gender, advanced age, diabetes, to determine the prevalence, awarerest in the sitting posture for at smoking, and having a physician. ness, treatment, and control of hyleast 5 minutes before blood prespertension, and to investigate possisure was measured. If the first ● Subgroups at high risk for kidney disble predictors of blood pressure blood pressure reading was eleease are an important target for better control in individuals with chronic vated, defined as a blood pressure blood pressure control. kidney disease from the KEEP of 140/90 mm Hg or more, the cohort. subject remained at rest for an-
MATERIALS AND METHODS Study Population The KEEP program is a nationwide effort by the National Kidney Foundation to evaluate and educate people at high risk for chronic kidney disease, that is, adult individuals with a history of diabetes or hypertension or a family history of these diseases. The program was officially launched in August of 2000, and by the end of 2005, some 55,220 individuals were screened in 49 states and the District of Columbia.10 The present study is a cross-sectional analysis including all KEEP participants with chronic kidney disease as of December 31, 2005, without missing information for race, education, smoking status, insurance, having a doctor, history of hypertension, diabetes, kidney disease, blood pressure levels, body mass index, and blood glucose levels.
Participant Evaluation Participant recruitment and screening protocols of the KEEP program are described elsewhere.10,18 Eligibility criteria for screening include age 18 years or more with a history of diabetes or hypertension or a family history of either diseases or chronic kidney disease. Recruitment efforts included local media (flyers, radio, television stations, and newspapers), with most of the screening sites located in community centers, schools, churches, health centers, and hospitals. Each subject was required to give informed consent before being allowed to participate in the program. All participants completed a standard questionnaire that in-
other 5 minutes and a second measurement was taken. For these participants, only the second blood pressure value was used in the analysis. If the participant was taking antihypertensive medications, blood pressure values were obtained without changing current drug dosing or regimen schedule.
Definitions Chronic kidney disease was defined as a glomerular filtration rate of less than 60 mL/min/1.73 m2 or the presence of kidney damage indicated by elevated urine albumin excretion.20 The glomerular filtration rate was estimated from serum creatinine using the Modification of Diet in Renal Disease equation.21 Stage 1 chronic kidney disease was defined as an estimated glomerular filtration rate of 90 mL/min/1.73 m2 or more and an elevated albumin-to-creatinine ratio of 30 mg/g or more. Stage 2 kidney disease was defined as an estimated glomerular filtration rate of 60 to 89 mL/min/1.73 m2 and albuminuria. Stages 3, 4, and 5 kidney disease were defined as an estimated glomerular filtration rate of 30 to 59 mL/min/1.73 m2, 15 to 29 mL/min/1.73 m2, and less than 15 mL/min/1.73 m2, respectively.20 Diabetes was defined per the American Diabetes Association guidelines as a fasting plasma glucose level greater than 126 mg/dL, nonfasting plasma glucose level greater than 200 mg/dL, or self-report of diabetes. Hypertension was defined as a blood pressure of 130/80 mm Hg or more or current treatment with antihypertensive drugs.11,14 Additional analyses using the general population
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Figure 1 Participant eligibility and recruitment. KEEP ⫽ Kidney Early Evaluation Program; eGFR ⫽ estimated glomerular filtration rate; ACR ⫽ albumin-to-creatinine ratio; BMI ⫽ body mass index.
threshold of 140/90 mm Hg was also performed. Awareness of hypertension or chronic kidney disease was defined as knowledge by the participant of having hypertension or chronic kidney disease according to a previous diagnosis by a physician. Treatment of hypertension was defined as current use of antihypertensive drugs. Control was defined as treated hypertension with blood pressure less than 130/80 mm Hg and less than 140/90 mm Hg in the secondary analysis. The proportions of awareness, treatment, and control of hypertension were calculated within the cohort of hypertensives for comparison. Participants with a positive history of hypertension and blood pressure less than 130/80 mm Hg receiving no treatment were classified as normotensive. Body mass index was calculated as weight divided by height squared.
Biochemical Analyses Plasma glucose was measured using Lifescan’s SureStep Pro test strips (Lifescan, Milpitas, Calif). Serum creatinine was assessed using a standardized method in all participants: the Olympus 5431 device (Olympus Optical, Tokyo, Japan). Albumin-to-creatinine ratio was assessed with Bayer Clinitek reagent strips (Bayer Diagnostics, Tarrytown, NY).
Statistical Analysis Analysis was performed with SAS version 9.1 for Windows (SAS Institute Inc, Cary, NC). Continuous variables are presented as mean ⫾ standard deviation. Categoric variables
are presented as absolute frequencies along with the relevant percentages. In univariate analysis we compared the characteristics of hypertensive individuals with controlled hypertension with those with uncontrolled hypertension. The chi-square test was used to compare frequencies between groups, and the Kruskal-Wallis test was used to compare the difference in the mean for continuous variables. In addition, multiple logistic regression analysis was performed and models were created to assess the association of several demographic and clinical characteristics with hypertension control. By using hypertension control as a dependent variable, we assessed the effect of age, gender, race, diabetes, obesity, smoking status, education, insurance status, having a doctor, and stage of chronic kidney disease, as well as awareness of hypertension and chronic kidney disease. We report adjusted odd ratios with 95% confidence intervals. Probability values of P less than .05 (2-tailed) were considered statistically significant.
RESULTS Demographic and Clinical Characteristics A total of 10,813 of 55,220 KEEP participants (19.6%) were included in the present study (Figure 1). A summary of demographic and clinical characteristics of KEEP participants who were evaluated for study selection is presented in Table 1. The demographic and clinical characteristics of the chronic kidney disease cohort evaluated are presented in Table 2. Awareness of chronic kidney disease in this cohort was as low as 6.5%.
Sarafidis et al Table 1
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335
Demographic and Clinical Characteristics of the Entire Kidney Early Evaluation Program Cohort Screened Total Without Missing Values
Those with Missing Values
N (43,130)
%
N (12,090)
Age, N (%) 18-30 y 31-45 y 46-60 y 61-75 y ⬎75 y
3594 9865 15,047 11,038 3586
8.3 22.9 34.9 25.6 8.3
1096 2916 4216 2938 924
9.1 24.1 34.9 24.3 7.6
Gender, N (%) Female Male
29,547 13,583
68.5 31.5
8205 3885
67.9 32.1
Race, N (%) Non-Hispanic white Non-Hispanic black Hispanic Other race
19,027 13,778 5221 5104
44.1 32.0 12.1 11.8
4171 5019 1555 1226
34.8 41.9 13.0 10.2
BMI, N (%) ⬍30 kg/m2 ⱖ30 kg/m2
23,970 19,160
55.6 44.4
6571 5339
55.2 44.8
Smoking status, N (%) Never smoke Used to smoke Current smoker
23,685 12,371 5136
57.5 30.0 12.5
6034 3070 1512
56.8 28.9 14.2
Education, N (%) ⬍ High school High school graduate ⫹
6521 36,609
15.1 84.9
2024 9872
17.0 83.0
Those with insurance, N (%)† Those who had a doctor, N (%)† Those with diabetes, N (%)† Awareness of blood pressure, N (%)† Receiving antihypertensive drugs, N (%)† Aware of chronic kidney disease, N (%)† Age (mean ⫾ SD) BMI (mean ⫾ SD) Systolic blood pressure (mean ⫾ SD) Diastolic blood pressure (mean ⫾ SD) Pulse pressure (mean ⫾ SD) eGFR (mean ⫾ SD)
35,309 37,606 14,508 21,893 17,649 1322 43,130 42,710 42,954 42,952 42,935 43,130
81.9 87.2 33.6 50.8 40.9 3.1 53.4 30.2 133.3 79.1 54.2 80.6
%
P Value* ⬍.0001
.18
⬍.0001
.43
⬍.0001
⬍.0001
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
15.8 6.8 20.1 11.5 16.6 23.7
9448 10,252 3954 5851 4616 337 12,090 11,756 11,780 11,779 11,769 9760
82.1 87.3 32.8 48.4 38.2 2.8 52.6 30.3 134.9 80.0 54.9 82.8
.52 .65 .07 ⬍.0001 ⬍.0001 .13 ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
15.8 6.9 21.2 12.2 17.3 25.4
⬍.0001 .27 ⬍.0001 ⬍.0001 ⬍.0001
BMI ⫽ body mass index; SD ⫽ standard deviation; eGFR ⫽ estimated glomerular filtration rate. *Population without chronic kidney disease, N ⫽ 32,317 ⫹ final population with chronic kidney disease, N ⫽ 10,813 versus KEEP participants who were excluded because of missing values (missing values for chronic kidney disease, N ⫽ 9909 ⫹ missing values for blood pressure, N ⫽ 77 ⫹ missing values for all the rest variables, N ⫽ 2104). †These statistical comparisons were relative to those who did not have insurance, a doctor, diabetes, and so forth.
Hypertension Awareness, Treatment, and Control Eighty-six percent of the study cohort were identified as hypertensive at the 130/80 mm Hg threshold (Figure 2). Hypertension prevalence gradually increased with advancing chronic kidney disease stages, increasing from approximately 79.1% in participants with stage 1 chronic kidney disease to 95.5% in participants with stages 4 and 5 chronic kidney disease. The blood pressure control rate was as low as 13.2%. Systolic blood pressure was more
difficult to control than diastolic blood pressure; only approximately 18% of the participants achieved control of systolic blood pressure compared with 33% for diastolic blood pressure. Both awareness and treatment of hypertension were increased with advancing kidney disease stages. This trend translated into a progressive increase in control rates from stage 1 to stages 4 and 5 (Figure 2). Because 93.5% of the individuals assessed were not aware of their kidney disease, a supplemental analysis was performed
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Table 2
Demographic and Clinical Characteristics of the Total Study Cohort
Total
Uncontrolled Hypertensives (ⱖ130/80 mm Hg)
Controlled Hypertensives (⬍130/80 mm Hg) N (1230)
N (10,813)
(%)
N (8089)
(%)
Age, N (%) 18-30 y 31-45 y 46-60 y 61-75 y ⬎75 y
355 1330 3134 4087 1907
(3.28) (12.30) (28.98) (37.80) (17.64)
188 859 2312 3218 1512
(2.32) (10.62) (28.58) (39.78) (18.69)
10 62 320 568 270
(0.81) (5.04) (26.02) (46.18) (21.95)
Gender, N (%) Female
7565
(69.96)
5514
(68.17)
876
(71.22)
Race, N (%) Non-Hispanic white Non-Hispanic black Hispanic Other race
5586 2989 895 1343
(51.66) (27.64) (8.28) (12.42)
4100 2387 652 950
(50.69) (29.51) (8.06) (11.74)
696 293 74 167
(56.59) (23.82) (6.02) (13.58)
BMI, N (%) ⱖ30 kg/m2
4947
(45.75)
4019
(49.68)
565
(45.93)
Smoking status, N (%) Never smoke Used to smoke Current smoker
5957 3730 1126
(55.10) (34.49) (10.41)
4465 2831 793
(55.2) (35.0) (9.80)
648 470 112
(52.68) (38.21) (9.11)
Education, N (%) ⬍ High school High school graduate ⫹
1992 8821
(18.42) (81.58)
1578 6511
(19.51) (80.49)
222 1008
(18.05) (81.95)
9278 9931 4838
(85.80) (91.84) (44.74)
6928 7465 3795 6252 5291
(85.65) (92.29) (46.92) (77.29) (65.41)
1122 1199 634 1230 1230
(91.22) (97.48) (51.54) (100.0) (100.0)
⬍.0001 ⬍.0001 .002 ⬍.0001 ⬍.0001
705
(6.52)
543
(6.71)
104
(8.46)
.02
Those with insurance, N (%) Those with a doctor, N (%) Those with diabetes, N (%) Aware of hypertension, N (%) Receiving antihypertensive medications, N (%) Those who were aware of chronic kidney disease, N (%) Age (mean ⫾ SD) BMI (mean ⫾ SD) Systolic blood pressure (mean ⫾ SD) Diastolic blood pressure (mean ⫾ SD) Pulse pressure (mean ⫾ SD) eGFR (mean ⫾ SD)
(%)
P Value* ⬍.0001
.03 ⬍.0001
.01 .09
.23
61.2 30.4 138.4 79.0 59.4 59.7
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
15.2 6.8 21.9 12.2 18.6 22.7
62.4 31.0 146.2 82.7 63.5 59.7
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
14.4 6.8 19.2 11.4 19.0 22.6
65.4 30.6 117.0 67.8 49.3 52.5
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
12.1 6.8 8.8 7.4 9.7 17.2
⬍.0001 .04 ⬍.0001 ⬍.0001 ⬍.0001 ⬍.0001
BMI ⫽ body mass index; SD ⫽ standard deviation; eGFR ⫽ estimated glomerular filtration rate. *P value for comparisons between uncontrolled and controlled hypertensives.
to identify the hypertension prevalence, awareness, treatment, and control with blood pressure threshold of the general population (ie, ⬎140/90 mm Hg). As shown in Figure 3, the prevalence is estimated to be approximately 10% lower than at 130/80 mm Hg. Awareness and treatment proportions, however, are approximately 10% higher than the 130/80 mm Hg goal, and control rates are more than doubled.
Predictors of Hypertension Control Blood pressure levels differed considerably between participants who achieved and did not achieve adequate
blood pressure control (117.0 ⫾ 8.8/67.8 ⫾ 7.4 mm Hg vs 146.2 ⫾ 19.2/82.7 ⫾ 11.4 mm Hg, respectively, P ⬍ .001 for each comparison). In a univariate analysis, individuals at the blood pressure goal of less than 130/80 mm Hg were older and less obese than those at higher levels (Table 2). Those at the blood pressure goal of less than 130/80 mm Hg were female, non-Hispanic white, and more likely to have insurance and access to a physician. Participants with adequate blood pressure control were more likely to have diabetes (51.5% vs 46.9%, P ⫽ .002) and a lower estimated glomerular filtration rate (52.5 ⫾ 17.2
Sarafidis et al
Hypertension in Kidney Disease
337 Table 3 Odds Ratios of Blood Pressure Control Among All Patients with Hypertension
Figure 2 Prevalence, awareness, treatment, and control of hypertension to recommended systolic goal (⬍130 mm Hg) by chronic kidney disease stage. Note total cohort has an N ⫽ 10,813. Prevalence is defined by systolic blood pressure ⱖ 130 mm Hg or diastolic blood pressure ⱖ 80 mm Hg or use of medication. All comparisons between stages for all categories at P ⬍ .0001.
vs 59.7 ⫾ 22.6, P ⬍ .001) than uncontrolled hypertensive participants. Participants with controlled hypertension also had a higher proportion of chronic kidney disease awareness (8.5% vs 6.7%, P ⫽ .025). Table 3 illustrates that male gender and non-Hispanic blacks had lower odds of being at blood pressure goal. Conversely, smoking, having a physician, or having a diagnosis of diabetes were independent predictors of having a blood pressure of less than 130/80 mm Hg.
OR
Lower
Upper
P Value
Age 18-45 y (ref) 46-60 y 61-75 y ⬎75 y
1.00 1.55 1.68 1.62
1.18 1.28 1.20
2.04 2.20 2.17
.002 ⬍.001 .001
Gender Female (ref) Male
1.00 0.87
0.76
0.99
.04
Race Non-Hispanic white (ref) Non-Hispanic black Hispanic Other race
1.00 0.85 0.93 1.23
0.73 0.71 1.02
0.99 1.21 1.49
.04 .57 .03
BMI BMI ⬍ 30 kg/m2 (ref) BMI ⱖ 30 kg/m2
1.00 0.91
0.80
1.03
.13
Smoking status Never smoked (ref) Used to smoke Current smoker
1.00 1.14 1.26
0.99 1.004
1.30 1.57
.06 .046
Education Less than high school (ref) High school graduate ⫹
1.00 1.15
0.98
1.35
.09
Insurance No (ref) Yes
1.00 1.18
0.94
1.48
.14
Had a physician No (ref) Yes
1.00 2.34
1.59
3.44
⬍.0001
Diabetes No (ref) Yes
1.00 1.20
1.06
1.37
.004
Chronic kidney disease stage Stage 1 (ref) Stage 2 Stage 3 Stages 4 and 5
1.00 1.18 2.22 2.67
0.85 1.66 1.83
1.64 2.98 3.91
.33 ⬍.0001 ⬍.0001
OR ⫽ odds ratio; BMI ⫽ body mass index.
Figure 3 Prevalence, awareness, treatment, and control of hypertension in total cohort by chronic kidney disease stage with ⬍ 140/90 mm Hg as a threshold. Note total cohort has an N ⫽ 10,813. Prevalence of systolic blood pressure ⱖ 140 mm Hg or diastolic blood pressure ⱖ 90 mm Hg or use of medication. All comparisons between stages are significant to a P ⬍ .0001. BP ⫽ blood pressure.
Patient awareness of chronic kidney disease was not associated with better blood pressure control (Table 4). Male gender, non-Hispanic black race, and obesity defined by a body mass index 30 kg/m2 or more were associated with a lower probability of being at blood pressure goal. Conversely, smoking, higher education, and having a doctor were independent predictors of being at blood pressure goal. Blood pressure control was also more likely to occur in kidney disease stages 3 to 5 (data not shown).
DISCUSSION Our data demonstrate that in a cohort of patients with chronic kidney disease the prevalence, awareness, and treat-
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The American Journal of Medicine, Vol 121, No 4, April 2008
Table 4 Odds Ratio of Hypertension Control Among Patients Who Were Aware They Had Chronic Kidney Disease OR
Lower
Upper
P Value
Age 18-45 y (ref) 46-60 y 61-75 y ⬎75 y
1.00 1.12 1.08 1.01
0.84 0.82 0.75
1.48 1.44 1.37
.45 .57 .95
Gender Female (ref) Male
1.00 0.86
0.75
0.99
.04
Race Non-Hispanic white (ref) Non-Hispanic black Hispanic Other race
1.00 0.76 0.87 1.15
0.65 0.66 0.95
0.89 1.14 1.39
⬍.001 .31 .16
BMI ⬍30 kg/m2 (ref) ⱖ30 kg/m2
1.00 0.83
0.73
0.94
.004
Smoking status Never smoked (ref) Used to smoke Current smoker
1.00 1.12 1.30
0.98 1.03
1.28 1.63
.10 .03
Education Less than high school (ref.) High school graduate ⫹
1.00 1.18
1.004
1.39
.04
1.00 1.20
0.96
1.51
.11
1.00 1.86
1.25
2.75
.002
Diabetes No (ref) Yes
1.00 1.11
0.98
1.26
.11
Chronic kidney disease stage Stage 1 (ref) Stage 2 Stage 3 Stage 4 and 5
1.00 1.14 2.08 2.14
0.81 1.55 1.44
1.59 2.80 3.17
.46 ⬍.0001 ⬍.001
Awareness of chronic kidney disease No (ref) Yes
1.00 1.11
0.88
1.40
.39
Insurance No (ref) Yes Having a physician No (ref) Yes
OR ⫽ odds ratio; BMI ⫽ body mass index.
ment of hypertension was comparable, if not better, than in NHANES 2003-2004,22 but that the blood pressure control rate was far worse than in NHANES. Elevated systolic blood pressure accounted for most of the cases of inadequate control. Male gender, non-Hispanic black race, and obesity were associated with a greater likelihood that blood pressure would not be controlled, whereas smoking, higher education, having a doctor, and increased chronic kidney disease stage were independent predictors of achieving blood pressure goals.
Hypertension prevalence, defined as greater than 140/90 mm Hg, in the KEEP cohort is higher than in the general population, which ranged from 28% in the United States to 44% in European countries.1,2,22 However, because hypertension was among the criteria to enter KEEP, those with hypertension were oversampled. Thus, hypertension prevalence in KEEP may be higher than in a sample of individuals with chronic kidney disease drawn from the general population. Oversampling may also account for increased awareness and treatment rates of hypertension, which were higher in KEEP than in the general population.1,22 Note, however, that hypertension prevalence did increase with advancing chronic kidney disease stage, a finding that corresponds with the natural history of hypertension and kidney injury.11 The overall control rate of less than 130/80 mm Hg was 13.2% in this cohort, a much lower rate than seen in NHANES 1999-2003, with 37% of 3213 subjects with chronic kidney disease being at blood pressure goal.16 One explanation for this difference is that the NHANES analysis included the total chronic kidney disease cohort in the denominator and provided no direct data for hypertension prevalence. Thus, the control rate among hypertensive individuals with chronic kidney disease cannot be estimated, and no direct comparisons with our study can be made. In a multicentered study of 1201 adult, nondialyzed patients with chronic kidney disease who were followed for a minimum of 6 months, 12.5% achieved the less than 130/80 mm Hg target,17 a finding closer to ours. In our analysis, systolic blood pressure accounted for the majority of patients not achieving control, a finding similar to both the aforementioned studies16,17 and those in the general population.23,24 Given that elevated systolic pressure provides the highest risk for decline in renal function,25 these data further support the need for aggressive systolic blood pressure reduction to slow nephropathy progression. If the less than 140/90 mm Hg threshold is used, the blood pressure control rate in our study increased to approximately 34%, a control rate similar to that in NHANES 2003-2004.22 A comparable 40.6% of patients with chronic kidney disease achieving this target is reported in the aforementioned Italian study.17 This finding may be associated with the lower awareness of chronic kidney disease in our cohort, as noted in other studies.6 This highlights the importance of undertaking strategies to increase awareness of chronic kidney disease. Perhaps the most important finding of this study is the progressive increase in control rates with advancing chronic kidney disease. Patients with stages 4 and 5 kidney disease had a 3-fold higher blood pressure control rate than those with stage 1 kidney disease. This may relate to the respective increases in hypertension awareness and treatment and highlights the importance of hypertension awareness. Our data demonstrate that older persons and those with diabetes were more likely to have hypertension control. These were rather peculiar observations, because both older age and diabetes are associated with a higher prevalence of
Sarafidis et al
Hypertension in Kidney Disease
and more difficult to control hypertension. In patients with chronic kidney disease16,17 and the general population,23 older age is associated with inadequate blood pressure control. These associations were no longer present when hypertension awareness was included in our model, a finding suggesting that increased hypertension awareness with advancing age or the presence of a major concomitant disease was responsible for the observation. Differences in control rates between sexes were largely attributed to respective differences in awareness and treatment. This could be related to women being more attentive to the risks of hypertension.1,15,23,26 Most data, including ours, support the notion of lower blood pressure control rates in non-Hispanic blacks compared with whites,27,28 although some studies do not support this observation23 and the respective time trends do not show a clear pattern.1 However, because hypertension management in black patients is more difficult29 and black patients have a much higher risk of kidney disease progression,30 particular attention should be given to aggressively lowering blood pressure in this group. Better blood pressure control was seen in those with a higher education. This may be due to a number of factors, including better appreciation of hypertension-associated risks, increased adherence to the prescribed regimen, and better access to health care. A similar association between educational level and hypertension control has been noted in the general population,27 but studies in cohorts with16 or without26,28 chronic kidney disease have not confirmed this observation. In the general population, current smoking was negatively associated27 or did not affect blood pressure control.23,28 In our study, smoking resulted in a higher likelihood of having blood pressure controlled. This unusual finding is unclear, although this group had much lower rates of obesity. There are several limitations associated with our analysis, which would include the cross-sectional design. In addition, although the collection of data was standardized, much of it was based on self-report; thus, recall bias exists for some of the variables (ie, hypertension treatment, history of diabetes). Also, blood pressure was measured on a single occasion; thus, recorded blood pressure levels could be higher than measured in clinical trials because of the “white coat” effect.31 We tried to minimize this bias by repeating the measurement if the first reading was elevated and having non-physician personnel performing the measurements, because the “white coat” phenomenon is more overt when a physician performs the readings.32 This limitation could have led to an overestimation of hypertension prevalence and an underestimation of hypertension control in our study. This is unlikely, however, because there was a high awareness of hypertension in this cohort. Finally, because urine albumin excretion is characterized by high intraindividual variation33 and was also measured once, it is not known whether the inclusion of participants with glomerular filtration rate levels greater than 60 mL/min/1.73 m2 and ele-
339 vated urinary albumin excretion in stages 1 and 2 chronic kidney disease led to overestimation of chronic kidney disease prevalence.
CONCLUSIONS This is the first study to provide data on the prevalence, awareness, and treatment of hypertension in a cohort with chronic kidney disease. Hypertension control rates were lower than in the general population, primarily driven by elevated systolic blood pressure. Achievement of blood pressure goals improves as awareness of advancing kidney disease stage is apparent. Because the presence of advanced kidney disease is the most common cause of medically treatable hypertension,34 current strategies to improve blood pressure control may rest on better knowledge of kidney disease awareness. Last, although we did not assess physician adherence to guidelines, it was clear that those whose physicians made patients aware of their chronic kidney disease stage had a higher likelihood of achieving blood pressure goal.
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