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Prognostic Value of Serum Creatinine and
Effect of Treatment of Hypertension
on Renal Function
Results From the Hypertension Detection
and Follow-up Program
Neil B. Shulman, Charles E. Ford, W. Dallas Hall, M. Donald Blaufox, David Simon,
Herbert G. Langford, and Kenneth A. Schneider on behalf of the Hypertension Detection
and Follow-up Program Cooperative Group
The Hypertension Detection and Follow-up Program followed up 10,940 persons for 5 years in
a community-based, randomized, controlled trial of treatment for hypertension. Participants
were randomized to one of two treatment groups, stepped care and referred care. The primary
end point of the study was all-cause mortality, with morbid events involving the heart, brain,
and kidney as secondary end points. Loss of renal function, ascertained by a change in serum
creatinine, was among these secondary events. Baseline serum creatinine concentration had a
significant prognostic value for 8-year mortality. For persons with a serum creatinine
concentration greater than or equal to 1.7 mg/dl, 8-year mortality was more than three times
that of all other participants. The estimated 5-year incidence of substantial decline in renal
function was 21.7/1,000 in the stepped-care group and 24.6/1,000 in the referred-care group.
Among persons with a baseline serum creatinine level between 1.5 and 1.7 mg/dl, the 5-year
incidence of decline was 113.3/1,000 (stepped care) and 226.6/1,000 (referred care) (p<0.01).
The incidence of decline in renal function was greater in men, blacks, and older adults, as well
as in those with higher entry diastolic blood pressure. Among persons with a baseline serum
creatinine level greater than or equal to 1.7 mg/dl, serum creatinine concentration declined by
25% or more in 28.6% of stepped-care and 25.2% of referred-care participants. Although the
incidence of clinically significant hypercreatininemia in a hypertensive population is low, an
elevated serum creatinine concentration is a very potent independent risk factor for mortality.
The slightly lower rate of development of hypercreatininemia and the higher rate of improve-
ment in stepped-care compared with referred-care participants is consistent with the belief that
aggressive treatment of hypertension may reduce renal damage and the associated increased
risk of death. (Hypertension 1989;13(suppl I):I-80-1-93)
H
ypertension is one of the most common
adult chronic diseases for which treatment
is available. The disease affects all race,
sex, and age groups but has a markedly higher
prevalence among blacks
1
and a concomitantly higher
mortality from its sequelae.
2
The risk associated with
hypertension includes fatal and nonfatal outcomes
From the Emory University School of Medicine, Atlanta, Geor- gia (N.B.S., W.D.H., and D.S.); The University of Texas Health Science Center at Houston, School of Public Health, Houston, Texas (C.E.F); The Albert Einstein College of Medicine, New York, New York (M.D.B.); The University of Mississippi Medical School, Jackson, Mississippi (H.G.L.); and the Duke University Medical Center Hospital, Durham, North Carolina (K.A.S.). Research on which this publication is based was performed
involving the brain, heart, and kidneys. Although the
development of cerebrovascular and cardiovascular
complications of hypertension have been described
frequently,
3
4
in recent years, less attention has been
directed toward concomitant renal disease.
The kidney is one of the principal target organs of
hypertension, and most diseases of the kidney are
pursuant to Contract Nos. NO1-HV-12433-42; NO1-HV-22931, 37-39 and 45; NO1-HV-32922; NO1-HV-72915 and NOI- HV-82915; and Grant No. 5-R01-HL-35528-02 with the National Heart, Lung, and Blood Institute, National Institutes of Health. Address for reprints: The University of Texas Health Science Center at Houston, School of Public Health, The Coordinating Center for Clinical Trials, 1200 Herman Pressler Street, Suite 801, Houston, TX 77030.
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Shulman et al Hypertension and Renal Function 1-
associated with blood pressure elevation.
5
9 The mechanism by which hypertension damages the kidney and the relative contribution of high blood pressure to the progression of renal insufficiency remain incompletely defined. In general, large- scale, prospective, randomized trials of treatment for hypertension have not focused on renal func- tion, possibly because of the relatively low inci- dence of renal disease in hypertensive subjects and because the lack of premonitory symptoms makes ascertainment of renal disease difficult even in the general population. Except for urinalysis and serum creatinine concentration, tests to accurately mea- sure renal function or detect new renal disease are often difficult to conduct.
The clinical quantification of renal function to provide early evidence of disease is usually thought to require determination of the plasma clearance rate of endogenous creatinine,
10 a procedure requir- ing a 24-hour urine collection. In general, it is difficult to obtain an accurate 24-hour urine collec- tion from patients being treated on an outpatient basis, thus making this procedure an impractical test for epidemiological evaluation. For this reason, elevated serum creatinine concentration has fre- quently been used as a criterion for renal morbidity in clinical trials of hypertension."-
15
This article reports the prevalence of hypercre- atininemia at baseline, its use as a prognostic marker, and the longitudinal change of serum creatinine concentration in participants of the Hypertension Detection and Follow-up Program (HDFP). The data base of the HDFP provides a source of infor- mation to examine renal function and its course during 5 years in a large cohort of persons with hypertension. The HDFP used a central laboratory and standardized procedures to routinely monitor serum creatinine in its stepped-care (SC) cohort during the 5-year treatment trial (1973-1979) and on three specific occasions in its referred-care (RC) cohort. In addition, the HDFP data base contains follow-up data on 8-year mortality, thereby provid- ing an opportunity to examine the mortality risk associated with serum creatinine.
Subjects and Methods
Trial Design
The design and methods of the HDFP have been described in detail in previous articles.
1617 Briefly, participants were recruited through a two-stage, community-based, screening program for high blood pressure that was performed in 14 US communities between 1973 and 1974.
18 From a base population of 159,000 people, aged 30-69 years, a cohort of 10,940 persons with hypertension was identified. (Only bedfast and institutionalized persons were excluded.) Each participant was randomly assigned to either the SC or the RC group; 5,485 persons to the SC group and 5,455 persons to the RC group. Randomization was stratified by clinical center and
by three ranges of diastolic blood pressure (DBP): 90-104 mm Hg (stratum 1), 105-114 mm Hg (stratum 2), and greater than or equal to 115 mm Hg (stratum 3). The two treatment groups were comparable with regard to age, race, sex, and risk factors at entry into the study.
17 The mean age was 50.8 years, and the percentages of white men, black men, white women, and black women were 34.3%, 21.4%, 19.6%, and 24.6%, respectively. The percentages of participants in the three DBP strata were 71.5%, 18.8%, and 9.7%, respectively. Participants with known primary parenchymal renal disease like chronic glomerulonephritis or diabetic nephropathy were not excluded, but the prevalence of such disease was less than 1%.
19
At entry into the study, a physical examination, chest X-ray, 12-lead electrocardiogram, and blood and urine tests were performed. A similar examina- tion in the clinic was repeated at the end of Years 2 and 5. In addition, all SC and RC participants were seen at home (or place of employment at one clinic) at the end of Years 1,2,4, and 5 for interval health history and blood pressure measurement. The SC participants were seen at intervals dictated by clin- ical judgment but at least every 4 months.
Stepped Care
The SC program was designed to treat hyperten- sion by a standardized drug protocol. Therapy was increased stepwise to achieve and maintain a reduc- tion of DBP to or below set goals. Goal DBP was defined as 90 mm Hg for those entering the trial with a DBP of 100 mm Hg or greater or who were already receiving antihypertensive drug therapy; goal DBP was defined as a 10 mm Hg decrease for those with a DBP of 90-99 mm Hg. Drug treatment included the use of diuretic agents, adrenergic receptor block- ing agents, and vasodilators. Seventy-five percent of SC participants received either the diuretic agent, chlorthalidone, alone or in combination with an antiadrenergic agent like reserpine or methyldopa.
17
Serum Creatinine Determination
Serum creatinine concentration was determined for each participant at baseline and at the end of Years 2 and 5. For SC participants, serum creatinine was determined at 4-month intervals throughout the 5 years of follow-up. Blood samples were analyzed at a central laboratory with consistent methodology throughout the course of the study. Frozen samples were shipped by priority mail or air freight to the central laboratory where the samples were thawed, remixed, and analyzed within 24 hours. The analysis of serum creatinine was performed with a Technicon SMA 12/60 multichannel analyzer (Technicon Corp., Tarrytown, New York) by Jaffe's reaction between alkaline picrate and creatinine.
20
After color development, the absorbance was mea- sured at 505 nm. The sensitivity for creatinine analysis was expanded by standardizing the SMA 12/60 for the
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Shulman et al Hypertension and Renal Function 1-
The tests of significance for the differences between SC and RC are based on the standard normal distribution for the comparison of two pro- portions (SC vs. RC). Because the subgroup analy- ses presented here involve multiple comparisons, a difference at the/?<0.05 level may have occurred by chance in one of 20 comparisons. No adjustment for multiple comparisons was done.
Results Baseline Distribution of Serum Creatinine Concentration
Table 1 presents baseline serum creatinine sam- ple means and standard deviations, overall and by selected baseline characteristics. Also shown are the respective percentages and numbers of partici- pants with concentrations greater than or equal to 1.5 mg/dl (132.6 yumol/l) and greater than or equal to 1.7 mg/dl (150.3 /imol/1) at baseline. In this sample of 10,768 persons with hypertension, the mean serum creatinine level was significantly higher for men than for women and for blacks than whites (p<0.01). These sex-race differences remained after adjustment for body mass index, age, level of blood pressure, use of antihypertensive medication at trial entry, an elevated fasting blood sugar level or a history of diabetes, a history of cancer, serum cholesterol level, and cigarette use. For the HDFP hypertensive population as a whole, 2.76% of the participants had a serum creatinine concentration greater than or equal to 1.7 mg/dl. Among black men, 5.17% had a serum creatinine concentration greater than or equal to 1.7 mg/dl compared with 2.53% of white men, 2.57% of black women, and 1.13% of white women. No differences in baseline mean creatinine levels were noted between the SC and RC groups, but a slightly higher percentage of SC participants had hypercreatininemia at trial entry. The frequency and cumulative distributions of serum creatinine concentration at entry into the HDFP are depicted in Figure 1 by race and sex.
As shown in Table 1, the baseline prevalence of serum creatinine concentrations greater than or equal to 1.5 mg/dl generally increased with age, blood pressure, serum uric acid, and proteinuria. Nearly 40% of all participants with a proteinuria level of 3+ or greater had a baseline serum creati- nine value in this range, and 24.3% had a concen- tration greater than or equal to 1.7 mg/dl.
Prognostic Value of Serum Creatinine Concentration
The baseline level of serum creatinine was an important and significant risk factor for 8-year mortality among HDFP participants. As shown in Figure 2, the risk of death increased progressively with the concentration of creatinine, starting with creatinine levels between 0.80 and 0.99 mg/dl. There was nearly a fivefold increase in the 8-year mortal- ity risk between the lowest and the highest risk
strata of creatinine. As depicted by the cumulative 8-year life table mortality curves in Figure 3, the absolute risk of death associated with hypercreat- ininemia began in the 1st year of the study and became more marked in those with higher baseline creatinine concentrations as time passed. The abso- lute mortality risk generally was higher in blacks than in whites at all levels of serum creatinine, but the relative increase in risk associated with higher concentrations was similar. The independent contribution of hypercreatinine- mia (creatinine s i .7 mg/dl) at baseline to the risk of 8-year mortality was examined by multiple logistic regression analysis. The results, summarized in Table 2, suggest that the risk associated with hyper- creatininemia was similar to the other variables considered except age and body mass index. The relative odds of dying in 8 years, after adjusting for all other factors examined, was more than twice as great for those with hypercreatininemia than for those with lower concentrations. When the analysis was restricted to those with mild hypertension (90- 104 mm Hg diastolic without drug therapy for hyper- tension at entry), the risk of death associated with hypercreatininemia remained two times greater than in its absence.
Cause-specific 8-year mortality among SC and RC participants is presented in Table 3. Overall, death from renal disease in this cohort was rare; only 43 (3.1%) of the 1,393 deaths with a known cause were attributed to renal disease. However, the mean annual death rate from renal disease was approximately 5/10,000 persons—roughly 10 times the 1976 rate for the general US population in this age range. Most frequently, the cause of death among those with hypercreatininemia was attrib- uted to cardiovascular rather than renal causes. Death from renal disease was much more likely in the presence of an elevated baseline serum creati- nine concentration than in its absence. The mortal- ity rates for neoplastic diseases were similar for those with and without hypercreatininemia.
Change in Serum Creatinine Concentration
Mean serum creatinine concentrations during the course of the HDFP trial are shown in Figure 4 by race-sex group. Throughout follow-up, the mean concentration of creatinine in women remained about 0.2 mg/dl (17.7 /u.mol/1) below that of men and remained higher in blacks than in whites for both sexes. For SC participants whose creatinine con- centration was measured every 4 months, there was a gradual rise of about 0.2 mg/dl (17.7 fimol/l) in the mean concentration of serum creatinine during the first 2 years, which was followed by a leveling off for the next 3 years. The mean and standard devi- ation of the paired difference between the 60-month and baseline serum creatinine concentrations was 0.20±0.40 mg/dl (17.7±35.4 /xmol/1) for SC black men, 0.16±0.35 mg/dl (14.1 ±30.9 /tmol/1) for SC white men, 0.17±0.41 mg/dl (15.0+36.2 /xmol/1) for
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1-84 Supplement I Hypertension Vol 13, No 5, May 1989
TABLE 1. Baseline Serum Creatinine of Hypertension and Detection Follow-up Program Participants, Overall and Stratified by Selected Baseline Characteristics
Baseline characteristic
Sample size Mean±SD
a 1. % _(n)_*
^1.
All randomized persons Treatment group Stepped care Referred care Sex-race Black men White men Black women White women Age (years) 30- 35- 40- 45- 50- 55- 60-. 65-
Diastolic BP (mm Hg) 90- 95- 100- 105- 110- 115- a 120 Systolic BP (mm Hg) < 120- 140- 160- 180- == Body mass index (kg/m^2 ) <23. 23.89-26. 26.43-28. 28.79-32. ^32. Entry BP medication status Untreated Treated History of diabetes or FBS No Yes Proteinuria Negative Trace 1 + 2+ 3 + 4+ Serum uric acid (mg/dl) <4. 4.90-5. 5.70-6. 6.50-7. S7.
140 mg/dl
10,768t
1, 1, 2, 1, 1, 980
2, 2, 1, 716 488 548
9, 1,
BP, blood pressure and FBS, fasting blood sugar. *Values denote percentage and number (n) of participants with values at or above specific levels. tThere were 172 participants who did not have serum creatinine measurements at baseline.
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1-86 Supplement I Hypertension Vol 13, No 5, May 1989
36 48 60 Months of Follow-up
FIGURE 3. Cumulative 8-year life table
mortality curves (% at months of follow-
up) for selected strata of baseline serum
creatinine. The sample size (n) and the
creatinine stratum limits (mgldl) are noted
to the right of each curve.
line creatinine level, this predicted pattern was observed in all strata except for those with concen- trations greater than or equal to 2.0 mg/dl (176. /*mol/l). This subgroup, 1.4% of the cohort, had the greatest increase over time despite a death rate of more than 30% in 5 years. In the regression analy- ses, age at entry had a significant positive relation with change in creatinine concentration for all race- sex groups as did baseline diastolic blood pressure; diabetes was positively associated in all but white men. A significant treatment group difference was found only among black women, a difference which is also apparent in Figure 5.
Development of Clinically Significant Hypercreatininemia
For the great majority of HDFP participants, the 5-year increase in serum creatinine concentration was relatively small for SC and RC groups. How- ever, among the 8,683 participants for whom the 5-year change in creatinine concentration was ascer- tained, 200 (2.3%) experienced a progressive rise in serum creatinine concentration to levels that were considered indicative of possible renal insufficiency and that posed considerable risk of future mortality. Table 5 presents data on the incidence and progres- sion of clinically significant hypercreatininemia,
TABLE 2. Multiple Logistic Analysis of Comparison of Relative Odds of Dying in 8 Years for Selected Baseline Variables
Rank
1 2 3 4 5 6 7 g 9
Baseline variable
Age Body mass index Hypercreatininemia* Diabetes or FBSS140 mg/dl Cigarette smoker ECG ischemia Left ventricular hypertrophy Systolic blood pressure Sex Myocardial infarction History' of stroke History of cancer Angina pectoris Uric acid High school education Pulse rate Antihypertensive drug use Treatment group Race
FBS, fasting blood sugar and ECG, electrocardiogram. There were 1,521 deaths among the 10,768 participants in *Serum creatinine concentration greater than or equal to
Risk (High/Low)
(65/40 years) (25/30 kg/m^2 ) (Present/Absent) (Yes/No) (Yes/No) (Present/Absent) (Present/Absent) (200/140 mm Hg) (Male/Female) (Yes/No) (Yes/No) (Yes/No) (Yes/No) (7.5/4.5 mg/dl) (No/Yes) (100/70 beats/min) (Yes/No) (Referred care/Stepped care) (Black/White)
the analysis. 1.7 mg/dl.
Relative odds ratio
. . . . . . . . . .
Z-score
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Shulman et al Hypertension and Renal Function 1-
TABLE 3. Age-Adjusted, Cause-Specific, 8-Year Mortality Rates per 1,000 for Participants Stratified by Baseline Serum Creatinine Concentration*
Cause of death (ICDA codes)t All causes
All cardiovascular causes (390-458, 746)
Cerebrovascular disease (430-438)
Ischemic heart disease (410-414)
Noncardiovascular causes
Renal disease (580-599)
Neoplastic diseases (140-239)
Treatment group
SC
RC
SC
RC
SC
RC
SC
RC
SC
RC
SC
RC
SC
RC
Serum creatinine concentration (mg/dl) <1.
(n=5,243 SC) («=5,228 RC) Rate±SEM/l,000(No.)
(n=l-59SC) (n=138RC) Rate+SEM/l,000(No.)
SC, stepped care and RC, referred care. *Rates have been adjusted for distributional differences in age between the SC and RC groups. The combined SC and RC population was used as the standard. •(•International Classification of Diseases, Adapted; eighth revision. lp<0.01, based on the approximate standard normal test of no difference between RC-SC rates.
O^ o i ..
O E
SC Black Womer
SC While Women
36 Months of Follow-up
FIGURE 4. Plot of change in mean serum
creatinine concentration (mg/dl) in Hyper-
tension Detection and Follow-up Program
black and white men and women during 60
months offollow-up. The mean values for
the stepped-care (SC) group, which had
serum creatinine determinations every 4
months, have been connected to give an
indication of trend. For the referred-care
(RC) group, which had serum creatinine
levels measured only at baseline and at 24
and 60 months, the means have been left
unconnected. The numbers of SC partici-
pants with creatinine measurements at
baseline, 24 months, and 60 months are as
follows: black men—1,046, 912, and 853;
white men—1,868, 1,696, and 1,643; black
women—1,318, 1,159, and 1,139; white
women—1,170, 1,007, and 998. Similarly
for RC, the numbers are': black men —
1,061, 850, and 774; white men—1,848,
1,561, and 1,486'; black women—1,323,
1,077, and 1,035; white women—1,134,
922, and 863.
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C ' c ra Q) O E
I
a) c ( .c O c o
Shulman et al Hypertension and Renal Function I-
WHITE WOMEN
0 75 (^1 00) 1.25 1.50 1.75 0 75 1 00 1.25 1 50 1 75
Baseline Serum Creatinine Concentration, mg/dL
FIGURE 5. Regression analysis curves of the 60-month change in serum creatinine concentration (mg/dl) in stepped-care
(SC) and referred-care (RC) participants by sex-race group. The predicted creatinine change (ordinate axis) has been
plotted against baseline serum creatinine concentration. The graphs were plotted from the regression functions in Table
4, with discrete variables other than treatment group set equal to -I, diastolic blood pressure (DBF) change set to -
mm Hg, baseline DBP deviation from the mean set to zero, age set to 50 years, and body mass index set to 27 kglm
2
(«=238), the incidence of clinically significant hyper- creatininemia was 113/1,000 among SC compared with 226/1,000 among RC participants. The subsequent 3-year mortality experience of participants who developed clinically significant loss of renal function during the 5-year trial period was four times that of other participants. There were 54 deaths among the 200 participants who developed possible renal insufficiency; 27.2% were from the SC group and 28.4% from the RC group. For partici- pants without evidence of clinically significant renal function loss, the adjusted 3-year mortality rates were 6.92% for SC and 7.83% for RC.
Regression of Hypercreatininemia
Regression of preexisting hypercreatininemia among 5-year survivors was greater in SC than in RC participants. Of 106 SC participants who had a baseline serum creatinine concentration greater than or equal to 1.7 mg/dl, 21.7% had a 5-year value that was below 1.7 mg/dl and that was at least 25% lower than their baseline level. Among the corresponding 71 RC participants, 16.9% experienced a similar improvement in serum creatinine concentration. (The difference between these percentages was not signif- icant.) Only two (5.9%) of the 34 participants with such improvement died during the succeeding 3 years compared with the deaths of 15 (31.3%) of the
48 whose condition worsened between baseline and their 5th-year examination, that is, those who had a 5th-year serum creatinine level 1.25 times greater than or equal to their baseline value.
Discussion
The risk factors for the development of cerebrovas- cular and cardiovascular complications of hyperten- sion have been well defined during the past 2 decades.
3427
29 However, there is a paucity of data on the natural history of the development and progression of renal disease in hypertensive patients. This lack of information is probably related to the relatively lower prevalence of renal disease com- pared with the prevalence of cardiovascular or cerebrovascular disease in hypertensive patients. In addition, progression of renal disease does not cause symptoms until late in its course. Large-scale, prospective, randomized trials have clearly shown the impact of antihypertensive treat- ment in significantly reducing the risk of death, stroke, congestive heart failure, left ventricular hypertrophy, worsening of the level of blood pres- sure, and possibly, of coronary heart disease. To demonstrate the effectiveness of antihypertensive drug therapy in reducing the incidence and progres- sion of renal disease would require a large study population and a long study period. In addition, the
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1-90 Supplement I Hypertension Vol 13, No 5, May 1989
TABLE 5. Five-Year Incidence and Progression of Clinically Significant Hypercreatininemia*
Subgroup
Total
Baseline DBP (mm Hg) 90-
Race-sex White men
White women
Black men
Black women
Age at entry (years) 30-
Treatment group
SC RC
SC
RC
SC
RC
SC
RC
SC
RC
SC
RC
SC
RC
SC
RC
SC
RC
SC
RC
SC
RC
Size
4, 4,
Sample cases
99 101
Rate/1,000±SEM
21.7±2. 24.6±2.
95% Confidence limits for RC-SC
(-3.40, 9.20) p=
p=0. (-16.75, 18.95) p=0. (-44.31,20.31) p=0.
p=0. (-6.18, 11.58) p=0. (-31.47, 7.27) p=0. (-0.15,26.75) p=0.
p=0. (-5.91, 16.11) p=0. (-13.96,26.96) p=0.
Values are reported for SC and RC participants with baseline and 5th-year serum creatinine concentration measurements. Rates have been adjusted for distributional differences between SC and RC in age, race, and sex. RC, referred care; SC, stepped care; and DBP, diastolic blood pressure. *Clinically significant hypercreatininemia is defined as a 5th-year serum creatinine concentration §2.0 mg/dl and at least 1.25 times the baseline concentration. SI units can be obtained from the metric units of creatinine by the conversion factor 88.4 /umol/l per mg/dl.
tests to monitor renal function meticulously or to detect new renal disease are often expensive and time-consuming for the physician and the patient. Hence, the level of serum creatinine has become the standard marker for renal function in the hyper- tensive population treated in office practice. How- ever, this measurement is imperfect because its level is also altered by muscle mass or age.
30
This analysis offers data on two topics, namely, elevated serum creatinine as a risk factor and the
natural history of the development and progression of hypercreatininemia in a hypertensive population. The conventional cardiovascular risk factors include high blood pressure, elevated serum cholesterol, and cigarette smoking. The risk markers include electrocardiogram abnormalities and cardiac enlarge- ment. The data presented here show that elevated serum creatinine should also be considered an equally important marker of risk. In the HDFP, hypercreatininemia was a potent predictor of mor-
TABLE 6. Five-Year Incidence and Progression of Clinically Significant Hypercreatininemia*
Baseline creatinine concentration < 1.50 mg/dl
1.50-1.69 mg/dl
< 1.70 mg/dl
a 1.70 mg/dl
Treatment group
SC RC SC RC SC RC SC RC
Sample size
4, 3, 121 117 4, 4, 106 71
Cases 55 55 15 27 70 82 29 19
Rate/1,000+SEM 12.7±1. 14.1±1. 113.3±25. 226.6+34. 15.7±1. 2O.3±2. 286.4±39. 252.2±51.
95% Confidence limits for RC-SC (-3.56, 6.36) p=0. (28.85, 197.75) p=0. (-1.05, 10.25) p=0. (-161.19,92.79) p=0.
Values are reported for SC and RC participants stratified by baseline serum creatinine concentration. Rates have been adjusted for distributional differences between SC and RC in age, race, and sex. "Clinically significant hypercreatininemia is defined as a 5th-year serum creatinine concentration §2.0 mg/dl and at least 1.25 times the baseline concentration. SI units can be obtained from the metric units of creatinine by the conversion factor 88.4 /umol/1 per mg/dl.
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1-92 Supplement I Hypertension Vol 13, No 5, May 1989
Albert Oberman, MD and Harold W. Schnaper, MD (Birmingham-University of Alabama); Edward H. Kass, MD, PhD; James O. Taylor, MD; and B. Frank Polk, MD (deceased) (Boston- Brigham and Women's Hospital and Harvard Med- ical School); Jeremiah Stamler, MD; Rose Stamler, MA; and Flora Gosch, MD (Chicago-Northwestern Univer- sity); Nemat O. Borhani, MD; Beth Newman, PhD; and Marshall Lee, MD (Davis-University of Cali- fornia); John W. Jones, MD and Sandra A. Daugherty, MD, PhD (East Lansing-Michigan State Univer- sity); H.A. Tyroler, MD and Curtis G. Hames, MD (Evans County Health Department-Georgia); Lawrence M. Slotkoff, MD, PhD (deceased) (Georgetown, DC-Georgetown University); Herbert G. Langford, MD and John Abernethy, MD (Jackson-University of Mississippi Medical School); Morton H. Maxwell, MD and Roger Detels, MD (Los Angeles-Cedars-Sinai and UCLA Medical Centers); Reuben Berman, MD and Ronald J. Prineas, MB, BS, PhD, (Minneapolis-Mt. Sinai Hospital and Uni- versity of Minnesota); M. Donald Blaufox, MD, PhD and Sylvia Wassertheil-Smoller, PhD (New York-Albert Ein- stein College of Medicine); C. Hilmon Castle, MD and Josephine Kasteller, PhD (Salt Lake City-University of Utah); C. Morton Hawkins, ScD; Charles E. Ford, PhD; and Barry R. Davis, MD, PhD (Coordinating Cen- ter, Houston-The University of Texas School of Public Health); Agostino Molteni, MD, PhD and Kenneth A. Schneider, MD (Central Laboratory, Chicago- Northwestern Memorial Hospital); Ronald J. Prineas, MB, BS, PhD (ECG Center, Minneapolis-University of Minnesota); Gerald H. Payne, MD, MPH; Thomas P. Blasz- kowski, PhD; and William J. Zukel, MD (National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland).
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KEY WORDS • cardiovascular risk factors • epidemiology renal insufficiency • prevalence • incidence • prognosis serum creatinine concentration
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