ABSTRACT. The incidence rate of end-stage renal disease hasincreased in many countries in the past 20 yr, including theUnited States and Singapore. The increase in ESRD incidencein the United States is primarily attributable to diabetes andto hypertension. In Singapore the major cause of ESRD is diabetes,however the prevalence of hypertension in the Singapore populationis rising rapidly, and renal complications of hypertension maybecome more common in the future. Information on the associationof hypertension with renal dysfunction and ESRD in the UnitedStates may be useful in predicting future trends in the incidenceof ESRD due to hypertension in Singapore. This paper describespublished and unpublished data presented at a conference toassist in developing plans for a comprehensive renal diseaseprevention program in Singapore. It compares recent data onthe reported prevalence of hypertension in the United Statesand Singapore; and presents information on the association ofhypertension with serum creatinine, urinary albumin excretion,and ESRD in the United States. E-mail: Cmele100@aol.com
The incidence rate of end-stage renal disease has increasedin many countries in the past 20 yr, including the United States(1) and Singapore (2). In 1997, Singapore had one of the highestincidence rates of ESRD in the world (158 cases per million),a rate that was comparable to the United States (296 cases permillion) and Japan (229 cases per million) (3). In the US population,the increase in ESRD incidence is primarily attributable todiabetes and to hypertension, whereas in Singapore the majorcause of ESRD is diabetes.
Comparison of trends in prevalence of hypertension in the UnitedStates and Singapore can be mutually useful. The associationof hypertension with renal dysfunction and ESRD in the UnitedStates may be useful to health planners in Singapore in predictingtrends in the incidence of ESRD due to hypertension, and inplanning a renal disease prevention program. Conversely, theperiodic National Health and Nutrition Examination Surveys (NHANES)in the United States have not been designed to provide subgroupanalyses for Asian ethnic subgroups, and data on the prevalenceof hypertension in Singapore may provide insight into diseasepatterns among US residents who are of Chinese, Asian Indian,and other Asian ethnic descent.
This paper describes published and unpublished data presentedat a conference to assist in developing plans for a comprehensiverenal disease prevention program in Singapore. It compares thereported prevalence of hypertension in the United States andSingapore, and presents information on the association of hypertensionwith serum creatinine, urinary albumin excretion, and ESRD inthe United States.
NHANES III is a cross-sectional examination survey of the UScivilian noninstitutionalized population that was implementedin two nationally representative phases (phase 1 in 1988 to1991, and phase 2 in 1992 to 1994) (4). Overall, more than 29,300persons aged 6 mo and older participated in NHANES III. Participantswere identified using a complex multistage probability samplesurvey design, and responses were statistically weighted toprovide estimated prevalence of diseases and risk factors. Race/ethnicity(non-Hispanic white, non-Hispanic black, and Mexican American)was based on a participant’s self-reported race and parentalcountries of origin. Non-Hispanic blacks, Mexican Americans,children, and elderly individuals were oversampled to allowmore precise estimates of prevalence of disease in these groups.A detailed health interview was conducted in the home, and anextensive examination was conducted in a mobile examinationcenter within several weeks of the interview. BP was measuredthree times in the home, and three times in the mobile examinationcenter, with the participant seated, and using an appropriatecuff size. All available measurements from an individual wereaveraged to obtain the BP value used in the analyses. Hypertensionwas defined as present if a participant reported both ever beingtold that she or he had high BP and current use of medicationsto treat high BP, or if the average measured BP was 140mmHg systolic, or 90 mmHg diastolic. Serum creatininewas measured by the modified kinetic Jaffe reaction, with acoefficient of variation that ranged between 0.2 to 1.4% duringthe study (5). Urinary albumin excretion was measured by solidphase fluorescence immunoassay, and urinary creatinine by themodified kinetic Jaffe reaction (6). Albumin excretion was expressedas urinary albumin (mg) to urinary creatinine (g) ratio (ACR).
Incidence counts of new cases with ESRD attributed to hypertension(1) and the estimated numbers of persons in the United Stateswith hypertension (7) for the years 1984 to 1996 were used tocalculate the age-specific ratios of the number of incidentcases of ESRD per 100,000 hypertensive individuals in the USpopulation.
SAS Proc SURVEYMEANS was used to estimate prevalence of albuminuria(ACR 30 mg/g) by level of BP (8).
Prevalence and Treatment of Hypertension in the United States and Singapore
The prevalence of hypertension in the United States in 1988to 1991 was reported for adults aged 18 yr and older, usingdata from NHANES III, phase 1 (9). Mean systolic BP increasedwith increasing age in both men and women, and in all threeof the racial/ethnic subgroups that were analyzed in NHANESIII (Figure 1). Mean diastolic BP rose with increasing decileof age until age 50 to 59, and declined with increasing agethereafter. Overall, 24% of the adults had hypertension, representing43.2 million individuals. The age-adjusted prevalence of hypertensionwas higher in non-Hispanic blacks compared with non-Hispanicwhites and Mexican Americans (Figure 2). Among all persons withhypertension in the United States, 69% were aware that theyhad the disease, and 53% were being treated with anti-hypertensivemedications. However, only 45% of the persons treated with antihypertensivemedications had BP controlled to <140/90 mmHg. This represents24% of the total hypertensive population in 1988 to 1991.
Figure 1. Mean systolic and diastolic BP in US adults aged 18+ by sex, age group and racial/ethnic group, National Health and Nutrition Examination Surveys (NHANES) III, 1988 to 1991. Non-Hispanic blacks (continuous line); non-Hispanic whites (slashed line); Mexican-Americans (dotted line). Adapted from Burt et al. (9).
Figure 2. Estimated percent prevalence of hypertension in the United States (based on NHANES III, with data presented for three major racial/ethnic groups) (9) and Singapore (based on the 1992 and 1998 National Health Survey) (11).
Another study, which compared hypertensive persons aged 18 to74 yr in NHANES II and NHANES III phase I, found that 32% versus55% were controlled to BP levels <140/90 mmHg in 1976 to1980 and 1988 to 1991, respectively (10). Note that the 1990US adult noninstitutionalized population aged 18 to 74 yr wasused to standardize the rates.
Singapore conducted a nationally representative National HealthSurvey in 1992 and in 1998 (11). BP was measured 2 to 3 timesusing a standardized protocol in persons aged 30 to 69 yr, andthe average of the two closest readings was calculated. Hypertensionwas defined as an average measured systolic or diastolic BP140 mmHg or 90 mmHg, respectively.In 1998, hypertension prevalence rates were 31.5% in the Malayethnic group, compared with 26.9% and 24.6% in the Chinese andthe Indian ethnic groups, respectively. Among all persons aged30 to 69 yr with hypertension in Singapore, 47% were aware thatthey had the disease. Only 30% of persons with known hypertensionhad measured BP values <140/90 mmHg. This represents 14%of the total hypertensive population. Comparing data from the1992 and 1998 surveys, the age standardized prevalence of hypertensionamong persons aged 30 to 69 yr rose significantly from 22.2%to 27.3% (Figure 2). Note that the 1990 Singapore resident populationwas used to standardize the rates.
Association of Hypertension with Indicators of Renal Disease Function in NHANES III
In NHANES III, among persons aged 17 yr or older, mean serumcreatinine was 1.2 mg/dl in men and 1.0 mg/dl in women (5).Elevated serum creatinine was defined as a serum creatininevalue 1.6 mg/dl in men and 1.4 mg/dlin women (based on serum creatinine cut points that were greaterthan the 99th percentile of serum creatinine for the subsetof the US population aged 20 to 39 who did not have hypertensionor diabetes). Three percent of persons aged 17 or more (5.6million people) had elevated serum creatinine. Elevated serumcreatinine was more common in persons with hypertension (9.1%)than in persons without hypertension (1.1%).
The Sixth Joint National Committee on Prevention, Detection,Evaluation and Treatment of High BP (JNC 6) defined six BP controlcategories ranging from optimal control (BP <120/80) andnormal control (BP 120 to 129/80 to 84) to severe stage 3 hypertension(BP 180/110) (12). As the JNC 6 BP control categoryworsened, the prevalence of elevated serum creatinine increasedin a dose response fashion (5). (Table 1).
Table 1. Mean serum creatinine level and prevalence of elevated serum creatinine levels, by blood pressure status, NHANES IIIa
In persons with hypertension and renal insufficiency, the JNC6 currently recommends BP treatment goals of <130/85 and<125/75 mmHg based on whether urine protein excretion is<1 g/day or 1 g/day, respectively (12). InNHANES III, these recommendations were rarely met; only 27%of persons with hypertension (diagnosed and undiagnosed) andelevated serum creatinine had measured BP <140/90 mmHg, andonly 11% had BP <130/85 mmHg (5).
This failure to achieve good control may be partially explainedby lack of aggressive treatment of high BP in persons with hypertension,even in persons who also have renal insufficiency. In an unweightedanalysis of NHANES III participants who had hypertension andelevated serum creatinine, 49% were receiving only one antihypertensivemedication (mean BP 151/77 mmHg), and 37% were receiving onlytwo antihypertensive medications (mean BP 148/77 mmHg) (5).
BP control can be achieved with aggressive therapy even in subgroupsconsidered to be difficult to control. The African AmericanStudy of Kidney Disease and Hypertension (AASK) enrolled 1094persons aged 18 to 70 yr with hypertension and renal insufficiencydue to hypertensive nephrosclerosis (GFR, 20 to 65 ml/min per1.73 m2) (13). Participants were randomized to one of two BPtreatment goals, a mean arterial pressure (MAP) <92 mmHg(similar to a BP goal <120/70 mmHg) or a MAP between 102to 107 mmHg; and to one of three blinded study medications;amlodipine, ramipril, or metoprolol. Furosemide, doxazosin,clonidine, hydralazine, and minoxidil were added in a steppedcare fashion if the BP was not at the goal level. At baseline,only 20% of those assigned to the low MAP goal had BP <140/90mmHg; however, 14 mo after randomization 79% had BP controlledto <140/90 mmHg and 48% had a MAP <92 mmHg, using a meanof 3.5 antihypertensive medications.
Albuminuria is a potential indicator of renal dysfunction andis associated with increased risk of renal and cardiovasculardisease morbidity and mortality in persons with hypertension(14). In NHANES III among adults aged 20 yr and older, the medianalbumin to creatinine ratio (ACR) was 5.0 mg/g in men, and 7.0mg/g in women (6), and the prevalence of microalbuminuria, definedas an ACR between 30 to 299 mg/g, was 7.8% (6.1% in men and9.7% in women). The prevalence of albuminuria (defined as ACR30 mg/g) was 9.3% (15).
Prevalence of albuminuria increased with increasing severityof the JNC 6 BP category in adult men and women in the UnitedStates (Figure 3). The association of albuminuria with BP wasalso studied in 189,117 adult participants in a screening programin Singapore (16). BP was measured 2 to 3 times, and the averageBP was calculated. Proteinuria was defined as a urine dipsticktest for protein that was 1+ (approximately 30 mg/dl) or higher.Most (88%) participants were 50 yr old. In the screened population,6.6% reported a history of hypertension, whereas 14.6% had systolicBP 140 mmHg and 11.4% had diastolic BP 90mmHg; 1% had proteinuria. Risk of proteinuria increased withsystolic and diastolic BP. Simultaneous statistical adjustmentwas done for gender, age, race, pre-existing history of diabetesor hypertension or renal disease, body mass index (BMI), diastolicand systolic BP, hematuria, glucosuria, and clustering of familyhistories of diabetes, hypertension, and/or renal disease. Theadjusted odds ratios (OR) for proteinuria compared with a systolicBP <110 mmHg were 1.2, 1.4, 1.7, 2.3, 3.3, and 3.8 for systolicBP levels of 110 to 129, 130 to 139, 140 to 159, 160 to 179,180 to 199, and 200+ mmHg, respectively. The adjusted OR forproteinuria compared with a diastolic BP <80 mmHg were 1.1,1.5, 1.7, 1.8, and 4.5 for diastolic BP levels of 80 to 89,90 to 99, 100 to 109, 110 to 119, and 120+ mmHg, respectively.All OR were statistically significant, except the OR for diastolicBP 80 to 89 mmHg.
Figure 3. Prevalence of albuminuria (albumin creatinine ratio [ACR] 30 mg/g) by increasing JNC 6 BP control category, in men and women, NHANES III.
ESRD Attributed to Hypertension
The age-, gender-, and race-adjusted incidence rates of treatedESRD in the total US population have increased from 89 per millionin 1981 to 218 per million in 1991 and 314 per million in 1999(17), mostly due to the increased incidence of ESRD attributedto diabetes and hypertension (1). Aging of the US populationcannot fully explain the increased incidence of ESRD due tohypertension, because the age-specific incidence rates of ESRDattributed to hypertension per 100,000 persons with hypertensionhave also increased, especially in persons aged 65 yr and older(Figure 4). The increasing incidence rates of ESRD attributedto hypertension have occurred despite a decrease in the prevalenceof hypertension from 1976 to 1980 and 1988 to 1994 (Figure 5)(10) and a shift to lower values of systolic and diastolic BPin the US population. In addition, despite the dramatic increasein obesity in the United States, a decrease in the mean systolicand diastolic BP has occurred in each quintile of BMI (basedon the BMI distribution in 1976 to 1980), from 1976 to 1980and 1988 to 1994 (Figure 6) (10).
Figure 4. Incidence ratio of ESRD attributed to hypertension per 100,000 persons with hypertension, by age group and calendar year from 1984 to 1996. Incidence ratios were determined using the United States Renal Data System (USRDS) counts of incident cases with ESRD attributed to hypertension in each calendar year as the numerator, and National Health Interview Survey estimates of the number of hypertensive persons in the US population for each year as the denominator.
Figure 5. Time trends in prevalence of hypertension in the United States between 1960 and 1994, among adults aged 18–74, by race. Data come from four nationally representative surveys, the Health Examination Survey (1960 to 1962), NHANES I (1970 to 1974), NHANES II (1976 to 1980), and NHANES III, phase 1 (1988 to 1991) (10).
Figure 6. Age adjusted mean systolic and diastolic BP by increasing quintile of body mass index (BMI, kg/m2), for adults aged 18 to 74 in NHANES II and NHANES III. Quintiles cut points were defined based on the NHANES II cohort (10).
Incidence rates of ESRD attributed to hypertension are rising.Prevalence of hypertension has decreased in the United States,but control of BP to optimal levels in persons with hypertensionis still a concern even after more than two decades of an extensiveBP education program. Less than optimal control of hypertensionmay be important, because increasing BP is associated with increasedprevalence of elevated serum creatinine and urinary albuminconcentrations, two markers for possible kidney disease. Themagnitude of the effect of other factors that could affect ESRDincidence rates, such as changes in the rate of premature mortalitydue to other complications of hypertension, is unclear.
These observations may be relevant to Singapore, which is experiencinga rapidly rising burden of both diabetes and hypertension. In1997, 41% of incident cases of ESRD in Singapore were attributedto diabetes (2). A prevention program is being developed todecrease the incidence of ESRD in Singapore by screening forundiagnosed hypertension and diabetes in the general population.Although this approach has the potential to affect the futureincidence rates of ESRD, the screening must be accompanied byan effective campaign to control BP to optimal levels in personswith both newly diagnosed and previously diagnosed hypertension.
Footnotes
The interpretation and reporting of data that have been suppliedby the United States Renal Data System are the responsibilityof the author and in no way should be seen as an official policyor interpretation of the US government.
US Renal Data System: USRDS 2002 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2002, http://www.usrds.org
Ramirez SPB, Hsu SIH, Nandakumar M, Friedman EA, Durai TT, Owen WF: Funding ESRD Care through charity: The paradigm of the National Kidney Foundation of Singapore. Semin Nephrol 21: 411–418, 2001[CrossRef][Medline]
US Renal Data System: USRDS 1999 Annual Data Report, Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 1999, http://www. usrds.org
National Center for Health Statistics: Plan and Operation of the Third National Health and Nutrition Examination Survey, 1988–94, National Center for Health Statistics, Vital and Health Statistics, Series 1, No. 32. DHHS Publication No. (PHS) 94–1308, 1994
Coresh J, Wei GL, McQuillan G, Brancati FL, Levey AS, Jones C, Klag MJ: Prevalence of high blood pressure and elevated serum creatinine level in the United States: Findings from the Third National Health and Nutrition Examination Survey (1988–1994). Arch Intern Med 161: 1207–1216, 2001[Abstract/Free Full Text]
Jones CA, Francis ME, Eberhardt MS, Chavers B, Coresh J, Engelgau M, Kusek JW, Byrd-Holt D, Narayan V, Herman WH, Jones CP, Salive M, Agodoa LY: Microalbuminuria in the US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 39: 445–459, 2002[Medline]
Office of Health Research, Statistics, and Technology. Current Estimates from the National Health Interview Survey, United States, Hyattsville, National Center for Health Statistics, Vital Health Statistics, Series 10, Nos. 156, 160, 164, 166, 173, 176, 181, 184, 189, 190, 193, 199, 200, for years 1984 through 1996
SAS Institute: SAS/STAT Users Guide,Version 8.0. Cary, NC, SAS Institute, 2001
Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, Horan MJ, Labarthe D: Prevalence of hypertension in the US adult population: Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension 25: 305–313, 1995[Abstract/Free Full Text]
Burt VL, Cutler JA, Higgins M, Horan MJ, Labarthe D, Whelton P, Brown C, Roccella EJ: Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population: Data from the Health Examination Surveys, 1960 to 1991. Hypertension 26: 60–69, 1995[Abstract/Free Full Text]
Epidemiology and Disease Control Department. 1998 National Health Survey of Singapore, Ministry of Health, Singapore, 1999, http://www.moh.gov.sg
Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure: The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 157: 2413–2446, 1997[Abstract]
Wright JT Jr, Agodoa L, Contreras G, Green T, Douglas JG, Lash J, Randall O, Rogers N, Smith MC, Massry S, African-American Study of Kidney Disease and Hypertension Study Group: Successful blood pressure control in the African-American study of kidney disease and hypertension. Arch Intern Med 162: 1636–1643, 2002[Abstract/Free Full Text]
National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative (K/DOQI) Advisory Board: K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 39 [2 Suppl 2]: S1–S246, 2002[CrossRef][Medline]
Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM: Albuminuria and renal insufficiency prevalence guides population screening: Results from the NHANES III. Kidney Int 61: 2165–2175, 2002[CrossRef][Medline]
Ramirez SPB, McClellan W, Port FK, Hsu SIH: Risk factors for proteinuria in a large, multiracial Southeast Asian population. J Am Soc Nephrol 13: 1907–1917, 2002[Abstract/Free Full Text]
Private communication from USRDS Data Request Service, usrds@usrds.gov
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Abstract
Introduction
140 mmHg systolic, or 
50 yr old. In the screened population, 6.6% reported a history of hypertension, whereas 14.6% had systolic BP 
