Journal of Gerontology: MEDICAL SCIENCES
2000, Vol. 55A, No. 11, M649–M657
Copyright 2000 by The Gerontological Society of America
Age, Functional Status, and Racial Differences in
Plasma D-Dimer Levels in Community-Dwelling
Elderly Persons
Carl F. Pieper,1,2,3 K. Murali K. Rao,4 Mark S. Currie,4,5 Tamara B. Harris,6 and Harvey J. Cohen1,3,4
1Center
for the Study of Aging and Human Development; 2Department of Community and Family Health, Division of
Biometry; and 3Claude D. Pepper Older Americans Independence Center, Duke University Medical Center,
Durham, North Carolina.
4Duke University Medical Center, and Geriatric Research, Education, and Clinical Center,
VA Medical Center, Durham, North Carolina.
5Lewis-Gale Clinic, Salem, Virginia.
6The National Institute on Aging, National Institutes of Health, Washington, DC.
Background. Dysregulation of immunologic and coagulation systems is common in elderly persons and is associated with many diseases of aging. Thrombotic events are a major cause of morbidity and mortality in the elderly population. This study assesses whether D-dimer, a marker of fibrinolytic activity, varies systematically by demographic,
health, and functional measures, and derives a prediction model for factors related to D-dimer in a sample of community-dwelling elderly persons.
Methods. D-dimer levels were assessed in a random sample of 1,727 community-dwelling elderly persons from five
rural and urban counties in North Carolina in 1992, as part of the Established Populations for the Epidemiologic Studies
of the Elderly (Duke University). All subjects were 72 years or older at the time of the blood draw. In addition, all subjects were surveyed yearly by telephone or in person each year from 1986 to 1992 for a variety of health, functional, and
social factors. Levels of D-dimer in 1992 were related cross-sectionally to demographics (age, race, education, income,
gender, smoking), function (Nagi, Rosow-Breslau, Katz, Older Americans Resources and Services procedures instrumental activities of daily living), life satisfaction and self-rated health, self-reported diseases (heart attack, cancer,
stroke, diabetes, and hypertension), and weight change from 1986 to 1992.
Results. D-dimer levels increased with increasing age and functional disability. Among the health variables, only
high blood pressure was predictive of D-dimer level. D-dimer levels were dramatically higher in blacks. Blacks were
nearly four times more likely to have an extreme value of D-dimer (⬎600 ␮g/l) than whites when high D-dimer (yes/no)
was analyzed, and blacks had an average level that was nearly 40% higher than whites in analyses of the continuous version of the outcome. This racial effect was not substantively affected in multivariable analyses with demographic and socioeconomic variables controlled. Race, age, functional status, current smoking, high blood pressure, and weight loss
were related to level of D-dimer, and race, age, and functional status were related to the presence of a high D-dimer level
(in the top 10% of the sample).
Conclusions. Black, older, and functionally impaired persons had significantly higher levels of D-dimer in this
sample of community-dwelling elderly persons. The findings for race were particularly striking and persisted even after
controlling for smoking and other factors known to be related to thrombosis and were not mediated by social factors.
This result may contribute to our understanding of the increased levels of thrombotic events found in these groups.
I
MMUNOLOGIC processes and coagulation play an important role in the genesis of thrombosis and atherosclerosis
(1,2). Thrombotic events are a major cause of morbidity in
the elderly population. In epidemiologic studies of atherosclerotic patients, as well as healthy subjects, baseline abnormalities of fibrinogen (3–5), antithrombin III (6,7), coagulation factor VII (8), and platelet reactivity (9) have been
associated with increased risk of acute thrombotic disorders,
and there have been numerous studies demonstrating aging
effects for hemostatic and inflammatory variables in elderly
populations (10–14).
D-dimer is the primary degradation product of crosslinked fibrin. The assay was originally developed to assess
the presence and/or risk of thrombosis. Plasma D-dimer levels remain stable over long periods in individual subjects,
and a single measurement may be adequate to assess the fibrinolytic status (15). In a limited sample of communitydwelling elderly persons, we have shown that racial/ethnic
differences in plasma D-dimer levels are related to age and
functional status, with some suggestion of a racial association
(16,17). Such changes may also be a harbinger of future adverse events, as suggested by a recent study that demonstrated
that activation of the endogenous fibrinolytic system occurs
many years in advance of coronary arterial occlusion (18).
In this study, we had the opportunity to measure D-dimer
levels in over 1,700 subjects in a community-based populaM649
M650
PIEPER ET AL.
tion of diverse racial composition, Duke University’s Established Populations for Epidemiologic Studies of the Elderly
(EPESE). In addition to D-dimer, there was an extensive
collection of survey information on demographics, social,
health, and functional conditions. We assessed the correlates to D-dimer in this sample of community-dwelling subjects measured across a range of functional, health, racial,
social, and demographic factors.
(1986). At the time of the third in-person interview in 1992,
current smoking status and marital status were assessed.
Body mass index and change in weight.—Height and
weight were measured at the baseline and third in-person interviews to derive body mass index (BMI) (kg/m2). Change
in weight was defined as the percentage change in weight
over the 6-year period between interviews. Weight loss was
defined as loss of more than 5% of body weight since 1986.
METHODS
Subject Population
Our subjects were obtained from Duke University’s component of the National Institute on Aging–funded EPESE.
The populations for the four sites—for the Duke University
study and for the subpopulation sampled for the blood
draw—have been described elsewhere in detail (19,20). The
study enrolled 4,162 subjects, aged 65 years and older in
1986, selected as a random household sample in a fivecounty area, including and adjacent to Durham, North Carolina. Blacks were oversampled in the sample to allow for
comparison by racial group. The initial in-person survey,
conducted in 1986, included extensive information on a variety of health status indicators including cognitive and
functional status, nutrition, depression, life satisfaction, exercise, social interaction and functioning, presence of
chronic health conditions, and drug and medical use. The
group was followed up in each subsequent year by telephone (1986–1987, 1990–1991) or in-person (1986, 1989,
1992) interview. In year 6 of the study, at the third in-person
interview in 1992, blood samples were drawn on all subjects
who were able to consent and who agreed to the blood draw,
with the purpose of assessing a variety of routine hematologic and blood chemistry variables, including D-dimer.
This was the only blood draw obtained in all waves of the
sample. In addition, at the point of this follow-up interview,
information on functioning, health status, cognitive status,
and quality of life was obtained again.
At the time of the blood draw, there were 2,569 interviews conducted with the remaining members of the cohort
(or their proxies). All subjects were older than 70 years at
the time of this interview. Among those interviewed, 67%
(1,727) had a successful blood draw for D-dimer and are the
subject of this report. Those not having a blood draw were,
in general, either unable to give consent, usually due to cognitive impairment (n ⫽ 269); were able to give consent, but
refused to have blood drawn; were residing too distant for
an in-person interview; or had technical difficulties in blood
draw (n ⫽ 573).
Measures
Variables that did not change over time were collected at
the baseline in-person interview (1986). Time-varying measures were re-collected at the time of the third in-person interview (1992). Information was collected on variables in
the following domains.
Demographics and smoking status.—Information on
self-reported age, race, marital status, urban status, education, income, and smoking status were collected at baseline
Activities of daily living and instrumental activities of
daily living.—Activities of daily living (ADLs) and instrumental activities of daily living (IADLs) measure the ability
of the individual to perform generally required tasks (e.g.,
stooping, walking, lifting, dressing, toileting). Three ADL
tasks were measured at the third in-person interview: Nagi
(21), Rosow-Breslau (22), and Katz (23). IADLs were assessed by the Older Americans Resources and Services procedures (OARS) (24).
Cognitive impairment and depression.—Cognitive impairment was assessed at the third in-person interview by
the Short Portable Mental Status Questionnaire (25). Depression was assessed by the Center for Epidemiologic
Studies–Depression Scale (26). Both of these scales have
extensive use in epidemiologic settings as screens for dementia and depression.
Life satisfaction and self-rated health.—Life satisfaction
and self-rated health were assessed by single questions
(“How would you say you find life” and “Overall, how
would you rate your health”) at the third in-person interview.
Prevalent diseases.—The third in-person interview obtained self-reported diseases (“Did a doctor ever tell you
that you had . . .”) for six comorbidities: cancer, arthritis,
heart disease, stroke, diabetes, and hypertension.
Laboratory methods.—Blood was collected in ethylenediaminetetraacetic acid-containing vacutainer tubes, placed
on ice and taken to the laboratory and centrifuged, and
plasma was stored at –70°C in 0.5 mL aliquots. D-dimers
were measured by an enzyme-linked immunosorbent assay
(ELISA; Dimertest Tripwell EIA kit, American Diagnostica,
Greenwich, CT) according to the instructions provided with
the kit as previously described (15,16). We have also previously reported the characteristics and reliability of the assay
(15,16).
Statistical Analyses
The relationship of D-dimer with demographics, health
status, health behaviors, and level of function was assessed.
Analyses proceeded in several stages. In the first set of analyses, the distribution of D-dimer was assessed in an attempt
to develop a transformation for the data, which could affect
approximate normality, and to discover multiple modes that
would be possibly indicative of increased risk. In the presence of unimodality, the data were then assessed to discern
some reasonable threshold in order to define an “at-risk”
group. As in our previous work with interleukin-6 (IL-6)
D-DIMER IN COMMUNITY-DWELLING ELDERLY PERSONS
(20), we chose the highest 10% to represent this high-risk
group.
Second, the bivariate relationship of D-dimer with demographics, level of functioning, health behaviors, and health
status variables was assessed. For each indicator, two statistics are reported: (i) for each independent variable, the mean
of the logarithm of D-dimer level is calculated at each level
of the independent variable; and (ii) the percent of subjects
above some threshold level at each level of the independent
variable is reported. Statistical significance is reported by
analysis of variance, the Kruskall-Wallis test, or the chisquared test of association. For variables measured at the ordinal level, a Spearman rank order correlation was calculated.
Finally, to arrive at a final multivariable model, we performed a forward stepwise regression for logarithm of D-dimer
and a forward stepwise logistic regression for the D-dimer
threshold variable. Because of their potential importance as
covariates, age (in decades), gender, and race were forced
into each of these final models. In addition, in an effort to
unconfound the effects of race from the social effects that
are correlated with race, education and income were also
forced into these models. For the nearly one third of subjects who did not answer the income question (mostly because of refusal), we imputed the mean income value and
computed an indicator variable for missing or not missing
into the equation. This allowed us to analyze the effect of
income and the effect of refusal on the outcome. The remaining variables were assessed individually as potential
entry variables ( p ⬍ .05 to enter, p ⬍ .05 to stay).
RESULTS
As shown in Table 1, there were significant differences
between the subjects for whom we obtained blood samples,
M651
for those requiring a proxy, and those for whom a blood
draw did not occur. It was known that subjects with proxy
interviews would be older, more cognitively impaired, more
functionally impaired, have lower education, would more
likely be black, and more diseased than their nonproxy
counterparts. Of interest for the generalizability of the results was to assess if, relative to the group with valid blood
samples, the nonproxy subjects who did not have a blood
sample (refusers) were different. As shown in Table 1, refusers were older on average (72.5 vs 71.6 years, p ⬍ .01),
were more likely to be women (78.0% vs 65.0%, p ⬍ .001),
had greater functional impairment ( p ⬍ .01 for Nagi,
Rosow-Breslau, Katz, and IADLs), and were more likely to
be black (57.8% vs 52.3%, p ⬍ .05). However, the two
groups did not differ statistically on percent urban, years of
education, percent depressed, and presence of chronic diseases. We concluded that those unable to give blood for reasons of consent were older, sicker, and more impaired than
those not having blood drawn and were, on average, somewhat older and more impaired than those for whom blood
was sampled and studied. This result may impose some ceiling effect on the generalizability of the results to be reported, relative to the general population of over-70 year
olds. Although the entire sample was randomly selected, the
sample who had a blood draw were younger and healthier
than the total population of over-70 year olds.
D-Dimer Distribution
D-dimer levels were measured in 1,727 subjects ranging
in age from 72 to 101 years. The minimum and maximum
values in this population were 13.8 and 6,831 ␮g/l. The
mean value was 300 ␮g/l and the median was 202 ␮g/l. The
data showed a non-Gaussian distribution. Because D-dimer
Table 1. Distribution of Demographic, Health, Functional, Cognitive Impairment, and Depression Variables: Comparison of Refusals,
Proxy, and Blood Draw Sample Groups (mean [SD] or percentage)
Variable
Age
% Women
% Black
% Urban
Years of education
Body mass index (kg/m2)
Katz (1–5)
Instrumental ADLs (1–7)
Rosow-Breslau (1–3)
Nagi (1–5)
% Cognitively impaired (SPMSQ)
% Depressed (CES-D)
Life satisfaction (1–26)
Self-rated health (1–5)
% Heart attack
% Stroke
% Cancer
% Diabetes
% Broken hip
I. Drawn Blood
(n ⫽ 1727)
71.6 (5.4)
65.0
52.3
53.7
9.0 (4.1)
25.8 (4.5)
0.3 (0.9)
1.7 (1.5)
1.0 (1.1)
1.8 (1.0)
12.4
8.8
18.6 (4.9)
2.4 (1.0)
21.7
11.8
18.1
23.6
4.6
II. Nonproxy Refusal
(n ⫽ 573)
III. Proxy
(n ⫽ 269)
p-Value Group
I. vs II.
72.5 (5.9)
78.0
57.8
57.4
8.8 (3.9)
25.7 (4.1)
0.5 (1.1)
1.8 (1.6)
1.3 (1.2)
2.0 (1.1)
15.0
10.2
17.8 (5.0)
2.9 (1.5)
20.2
10.3
18.0
24.3
6.6
77.0 (6.7)
72.1
61.7
52.4
7.0 (3.9)
24.1 (3.4)
3.1 (1.9)
5.6 (2.3)
2.6 (0.8)
1.3 (0)
78.8
Missing
Missing
Missing
23.1
35.7
16.0
21.2
19.0
**
***
*
**
**
***
***
**
***
***
Notes: Proxy interviews obtained from deceased subjects not included. North Carolina Established Populations for Epidemiologic Studies of the Elderly subjects
alive at time of interview (n ⫽ 2569) (1992). ADLs ⫽ activities of daily living; SPMSQ ⫽ Short Portable Mental Status Questionnaire; CES-D ⫽ Center for Epidemiologic Studies–Depression.
*p ⬍ .05; **p ⬍ .01; ***p ⬍ .001.
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PIEPER ET AL.
demonstrated a strong right skew and appeared to be distributed approximately log normal, the D-dimer was transformed by the natural log, which brought about approximate
normality (see Figure 1). As can be seen, this transformation brought the data to near perfect normality and allowed
the use of parametric statistics without the use of trimming
or nonparametric techniques.
D-dimer did not show evidence of bimodality, the right
skew could indicate extreme levels being associated with
deleterious outcomes. We chose 600 ␮g/l as the cut point
for a “high level,” because this value demarcated approximately the highest 10% D-dimer level for the sample.
D-Dimer Associations With Demographic Variables
Table 2 shows the D-dimer values in this age group, divided on the basis of race, gender, age, rural-urban residence, smoking status, and weight change over 6 years. Age
was positively correlated with high D-dimer levels ( p ⫽
.0001) by the Kruskall-Wallis test. In a set of follow-up
analyses (not shown), the age correlation appeared to be applicable across the races and gender. D-dimer values were
significantly higher in blacks (median value ⫽ 242 ␮g/l)
compared with whites (164 ␮g/l) and showed a trend towards statistical difference by gender (median value ⫽ 188
for men and 210 for women, p ⫽ .04 for levels of D-dimer).
D-dimer levels were not related to smoking status, but were
highly related to loss of 5% or more of body weight in the
preceding 6 years. The relationship of D-dimer with race,
gender, and age, simultaneously, is shown in Figure 2.
D-Dimer Associations With Measures of
General Health
Table 3 lists a number of health indicators that show a high
degree of correlation with D-dimer level. High D-dimer levels were associated with increasing functional disability, as
measured by ADL with Nagi, Katz, and Rosow-Breslau instruments. This was also reflected in the correlation (Spearman’s rho ⫽ 0.112) between high D-dimer levels and total
IADL. In concordance with the above correlations, high
D-dimers levels were associated with lower life satisfaction
and poor self-rated health.
D-Dimer Associations With Disease States
Table 4 shows the relationship of D-dimer with disease
states. Among this aged population, 1,207 subjects had high
blood pressure, determined by intake of antihypertensive
medicines or a blood pressure greater than 160/90 mm Hg.
There was a strong association between high blood pressure and high D-dimer values. The differences were significant when comparisons were made between mean log
levels, median levels, or percent greater than 600 ␮g/l. Similarly, a correlation was found between a history of stroke
Figure 1. Distribution of log (D-dimer) values for the North Carolina Established Populations for Epidemiologic Studies of the Elderly
(EPESE; n ⫽ 1727).
D-DIMER IN COMMUNITY-DWELLING ELDERLY PERSONS
Table 2. Mean Log D-Dimer and Percentage Above 600 (␮g/l)
D-Dimer With Demographic, Smoking, and Weight
Change Variables
Value
Race
Non-black
Black
No. of
Cases
812
915
Mean Log
(D-Dimer)
Level
Percentage With
D-Dimer
Level ⬎600
5.14
5.53
p ⬍ .0001
3.82
13.99
p ⬍ .0001
Sex
Male
Female
603
1124
5.29
5.37
p ⫽ .04
8.12
9.78
p ⫽ .255
Age (years)
70–79
80–89
90–99⫹
1155
517
55
5.23
5.56
5.81
p ⬍ .0001
6.73
13.16
23.64
p ⫽ .001
801
926
5.36
5.33
p ⫽ .45
8.24
10.04
p ⫽ .20
Current smoker
No
Yes
1517
205
5.34
5.39
p ⫽ .92
9.49
7.32
p ⫽ .17
Weight change 1986–1992
Lost ⱖ5% of 1986 weight
Lost ⬍5% or gained weight
536
1191
5.48
5.28
p ⫽ .0001
12.13
7.89
p ⫽ .005
Rural/urban status
Rural
Urban
Note: North Carolina Established Populations for Epidemiologic Studies of
the Elderly subjects with a valid blood draw at time of interview (n ⫽ 1727)
(1992).
and high D-dimer values. In this case, the difference was
significant only when median values were compared, indicating either a generalized effect of stroke on D-dimer or,
possibly, statistical vagaries in the findings. No correlation
was found between D-dimer levels and a history of arthritis,
heart attack, broken hip or bone, diabetes, or arthritis. There
was a weak association with history of cancer. These findings held true when “in the last year” variables were utilized
rather than “ever” (data not shown), indicating a lack of
both an acute and chronic effect of D-dimer for these variables.
Final Model
When the set of independent variables was used to predict log (D-dimer) using ordinary least squares regression
(Table 5) and D-dimer ⬎600 ␮g/l by logistic regression
(Table 6), controlling for age, gender and race, both models
revealed the importance of race and age in the association
with D-dimers. The parameter estimates indicate that, in
this sample, each decade of age was associated with a
25.9% elevation in level of D-dimer or a 1.8 increased odds
of having a D-dimer ⬎600 ␮g/l. Similarly, blacks had a
greater than 30% increase (␤ ⫽ 0.306) in level of D-dimer
relative to whites and a 3.94 increased odds of having an elevated D-dimer relative to whites. Because education and
income were entered into the model, these race effects are
independent of two of the common measures of socioeco-
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nomic status. Gender was a nonsignificant predictor in both
models, but women demonstrated slightly lower values.
For the log (D-dimer) model, four additional variables
were significantly related to D-dimer. Increased functional
impairment as measured by the Rosow-Breslau instrument
was related to elevated D-dimer level (p ⫽ .0001). In addition, weight loss in the previous 6 years was related to increased D-dimer (p ⫽ .002), and high blood pressure and
current smoking were related to increased levels (p ⫽ .04)
for both variables. For the prediction of D-dimer above 600
␮g/l, only ADL functioning, as measured by Rosow-Breslau, was related to D-dimer (p ⫽ .0001).
DISCUSSION
Aging is associated with increased morbidity due to a
number of autoimmune, degenerative, and vascular diseases. Efforts are being focused to determine the biological
markers that may show a correlation with functional status
of elderly individuals. With this in mind, we measured two
biological markers, namely, D-dimer and plasma IL-6 levels in a subpopulation of the Duke University’s EPESE cohort. In this report, we present the associations between
plasma D-dimer levels and a number of health parameters
that are a part of the Duke University’s EPESE database.
The IL-6 analyses have been presented previously (20).
We found age is associated with high D-dimer values, even
in this elderly cohort. This is consistent with several previous
reports showing high D-dimer levels in elderly subjects
(16,27–29). In a previous study, we measured D-dimer levels
in 315 elderly donors who were participants in the Duke University component of the MacArthur Foundation Network
in Successful Aging Study of Community-dwelling Elderly
(16). A majority of that group (89%) were in the upper third of
health status and functional abilities for community-dwelling
elderly persons, with no significant limitations in ability to
perform routine physical tasks. The average D-dimer levels in
that group were 153 ␮g/l, which are significantly lower than
in the current group (300 ␮g/l). Several factors account for
this difference in the mean D-dimer levels in the two cohorts:
(i) the age range in the MacArthur cohort was restricted to
70–79 years; (ii) blacks constituted 43% of the population
compared to 53% in the current cohort; and (iii) in the current
cohort, 608 subjects (35%) had some functional defect as
measured by OARS ADLs. As indicated by the current
analysis, all these factors might have contributed to the high
D-dimer levels in this population.
Thrombotic events are a major cause of morbidity in the
elderly population. The risk factors associated with thrombotic events include age, smoking, and a history of high
blood pressure. Several studies have examined relationships
between these risk factors and assays of coagulation activity. Smoking has been shown to increase levels of both fibrinogen and platelets in plasma (3). An increased risk of
ischemic disease and thrombotic events has been associated
with elevated plasma levels of fibrinogen (3,4), factor VII
(7), and plasminogen activator inhibitor (30,31). Increased
D-dimer levels have been documented in patients experiencing unstable angina (32), and the D fragment may stimulate increased fibrinogen production (33,34). Fibrin fragments also modulate function of neutrophils, monocyte/
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PIEPER ET AL.
Figure 2. Distribution of median D-dimer level by age group, race, and gender. From the North Carolina Established Populations for Epidemiologic Studies of the Elderly (EPESE; n ⫽ 1727).
macrophages, and lymphocytes in vitro (35–37). Thus, the
correlation between D-dimer levels and functional activity
may indicate subclinical activation of coagulation and inflammatory cascades, which may lead to functional disability.
The link between activation of coagulation and inflammatory process has been noted many other times in the literature
(38–41). In correlating disease associations with D-dimer levels, we found no association between high D-dimer levels
and a history of heart disease. This is consistent with the report that, although D-dimers are associated with increased
risk of future myocardial infarction, it did not appear to be
an independent predictor when other risk factors were considered (18). In contrast, we found a strong correlation between high D-dimer levels and another marker of heart disease, high blood pressure. A strong correlation was also
observed between D-dimer levels and a history or diagnosis
of stroke in bivariate analyses. It may be speculated that
high blood pressure leads to endothelial cell damage and
chronic activation of the fibrinolytic system, which might
contribute to the incidence of stroke.
Because our subjects reflected a full spectrum of functional capacity, we had the ability to assess the contributions
of this relationship with D-dimer levels by functional status,
disease, and other demographic variables. This observation
confirms our earlier report on the MacArthur cohort, where
we found high D-dimer levels were associated with func-
tional impairment (16). As a result, it was not unexpected to
find that the self-rated health and life satisfaction indices
were poorer in those subjects with high D-dimer levels, because these indices are associated with health and functional
status. Thus, a consistent picture of poor health being associated with high D-dimer levels emerges from these data. It
is worth noting that these same parameters were also highly
associated with increased IL-6 levels in this data set (20),
suggesting that the interface of inflammatory and coagulation factors may play an important role in these age and agerelated phenomena. However, in this sample, D-dimer and
IL-6 were only moderately correlated (Spearman’s rank order correlation ⫽ 0.24, p ⫽ .0001), indicating potentially
different pathways to pathogenesis.
One area in which there was discordance between the coagulation marker and our previous description of the inflammatory marker IL-6 was with respect to race. The Duke
University’s EPESE population is uniquely suited to establish such a relation, because African Americans were oversampled to ensure adequate numbers to address such issues.
We have shown a striking relationship of race with D-dimer
levels, with blacks having an average value nearly 40%
greater than whites and nearly four times the odds of having
a high D-dimer level. This racial effect was not mediated by
any of the standard socioeconomic factors (education and
income) commonly associated with race, was independent
D-DIMER IN COMMUNITY-DWELLING ELDERLY PERSONS
Table 3. Mean and Percentage Above 600 (␮g/l) D-Dimer With
Functional Status Variables
Variable and Value
Katz ADLs
0
1
2
3
4
5
Rosow-Breslau ADLs
0
1
2
3
Nagi ADLs
0
1
2
3
4
5
IADLs total
0
1
2
3
4
5
6
7
Life satisfaction
Very satisfying
Fairly
Not satisfying
Missing
Self-rated health
Excellent
Good
Fair
Poor
No. of
Cases
Mean Log Percentage With
(D-Dimer)
D-Dimer
Spearman
Level
Level ⬎600
Correlation*
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Table 4. Mean Log D-Dimer, Median D-Dimer and Percentage
Above 600 (␮g/l) D-Dimer With “Ever” Disease Variables
Variable
Mean Log
(D-Dimer)
Level
Percentage With
D-Dimer
Level ⬎600
Value
No. of
Cases
No
Yes
1415
312
5.36
5.24
p ⫽ .026
9.68
7.05
p ⫽ .146
No
Yes
1352
375
5.34
5.36
p ⫽ .82
9.02
9.87
p ⫽ .62
No
Yes
520
1207
5.22
5.40
p ⫽ .0006
6.54
10.36
p ⫽ .012
No
Yes
1524
203
5.32
5.47
p ⫽ .23
8.85
11.82
p ⫽ .17
No
Yes
1320
407
5.33
5.38
p ⫽ .26
8.71
10.81
p ⫽ .20
No
Yes
1647
80
5.34
5.35
p ⫽ .21
9.22
8.75
p ⫽ .88
No
Yes
1214
513
5.36
5.30
p ⫽ .24
10.13
7.02
p ⫽ .41
No
Yes
471
1256
5.30
5.36
p ⫽ .83
7.86
9.71
p ⫽ .23
All cancer
1491
92
44
35
44
17
5.30
5.51
5.43
5.83
5.78
5.82
p ⫽ .0024
7.78
13.04
11.36
25.71
29.54
23.53
p ⫽ .0005
820
385
217
305
5.18
5.34
5.45
5.71
p ⫽ .0001
4.63
8.05
11.98
20.98
p ⫽ .0005
5.22
5.34
5.54
5.42
5.61
5.79
p ⫽ .0001
5.69
8.74
12.77
2.05
18.69
22.92
p ⫽ .0001
1065
273
111
72
62
47
47
50
5.23
5.42
5.35
5.65
5.54
5.79
5.78
5.74
p ⫽ .0001
6.57
8.42
11.71
16.67
17.74
23.40
19.15
20.00
p ⫽ .0001
980
651
49
47
5.32
5.36
5.40
5.71
p ⫽ .39
8.57
9.52
12.24
14.89
p ⫽ .41
0.060
p ⫽ .012
5.22
5.29
5.37
5.65
p ⫽ .0001
7.04
7.83
9.28
17.09
p ⫽ .0001
0.144
p ⫽ .0001
Heart attack
0.155
p ⫽ .0001
High blood pressure
826
309
188
249
107
48
270
741
517
199
0.245
p ⫽ .0001
Stroke
Diabetes
0.132
p ⫽ .0001
Broken hip
Broken bone
Arthritis
0.112
p ⫽ .0001
Note: North Carolina Established Populations for Epidemiologic Studies of
the Elderly subjects with a valid blood draw at time of interview (n ⫽ 1727)
(1992).
Notes: ADLs ⫽ activities of daily living; IADLs ⫽ instrumental activities of
daily living. North Carolina Established Populations for Epidemiologic Studies
of the Elderly subjects with a valid blood draw at time of interview (n ⫽ 1727)
(1992).
*Adjusted for age group.
of hypertension status, and was unchanged in multivariable
models that controlled for these factors as well as level of
functioning. Thus, although it is true that blacks have lower
levels of socioeconomic variables and higher levels of hypertension, our study suggests that there are factors independent of hypertension and class that result in blacks having higher D-dimer levels.
To what can we attribute this increase in D-dimer levels?
The possibilities include intrinsically higher levels of reactivity in blacks because of stress (42), altered responsiveness of
the coagulation system per se (43–45), including the possibil-
ity of enhanced production of tissue factor (TF) to a given
level of cytokine stimulus from endothelial cells (46–48).
Future studies will be needed to assess TF gene expression in older subjects in samples with differing racial compositions. It would also be of interest to determine prospecTable 5. Stepwise Ordinary Least Squares Regression Estimates
Log (D-Dimer) (␮g/l)
Variable
Age (per 10 years)
Women
Black
Years of school
Income (in 1,000s of dollars)
Income missing
Rosow-Breslau ADLs (0–3)
Weight change (1986 to 1992)
High blood pressure
Current smoker
Estimate (␤)
p Value
0.259
⫺0.042
0.306
0.001
⫺0.019
⫺0.073
0.091
⫺0.006
0.082
0.113
.0001
.30
.0001
.91
.078
.416
.0001
.002
.040
.043
Notes: Age, gender, race, income, education forced into model. All other
variables entered by stepwise regression. North Carolina Established Populations for Epidemiologic Studies of the Elderly (1992); n ⫽ 1727. ADLS = activities of daily living.
M656
PIEPER ET AL.
Table 6. Stepwise Logistic Regression Odds Ratios
(D-Dimer ⬎600 ␮g/l)
Variable
Age (per 10 years)
Women
Black
Years of school
Income (in 1,000s of dollars)
Income missing
Rosow-Breslau (0–3)
Odds Ratio 95% Confidence Interval p Value
1.83
0.89
3.94
1.02
1.06
0.96
1.54
1.35, 2.48
0.60, 1.33
2.54, 6.10
0.97, 1.07
0.95, 1.19
0.39, 2.35
1.38, 1.90
.0001
.57
.0001
.40
.29
.93
.0001
Notes: Age, gender, race, income, education forced into model. All other
variables entered by stepwise regression. North Carolina Established Populations for Epidemiologic Studies of the Elderly (1992); n ⫽ 1727. ADLs ⫽ activities of daily living.
tively the impact of control of vascular phenomena, such as
hypertension, on the level of D-dimers in blacks and whites.
Regardless, our work suggests that one adverse risk factor
for subsequent vascular events, D-dimer, is remarkably increased in elderly community-dwelling subjects and, especially, in older black subjects. In future studies, we plan to
determine whether this risk factor is correlated with increased mortality, changes in function, and cardiovascular
events. If so, it could serve an important role in the overall
approach to geriatric assessment.
Acknowledgments
The research was performed pursuant to contract NO1-AG1-2102, with
the National Institute of Aging, and the Duke University Claude D. Pepper
Older American Independence Center Grant NIH AG112618. The content
of this publication does not necessarily reflect the views of the U.S. Department of Health and Human Services.
Address correspondence to Dr. Carl Pieper, Box 3003, Center for Aging and Human Development, DUMC, Durham, NC 27710. E-mail:
[email protected]
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Received April 26, 1999
Accepted February 8, 2000
Decision Editor: William B. Ershler, MD
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