JAGS 51 (Suppl) S10–S13, 2003© 2003 by the American Geriatrics Society 0002-8614/03/$15.00

Medical and Functional Consequences of Anemia in the Elderly

David Lipschitz, MD, PhD

Anemia is a common problem in the elderly, accountingfor significant morbidity and mortality in this population.It also has a negative effect on quality of life. Recent find-ings have shown that anemia can lead to cardiovascularand neurological complications, such as congestive heartfailure and impaired cognitive function. In addition, ane-mia has been implicated in functional impairment andfalls. Available data have shown that the successful man-agement of this condition will not only improve patients’quality of life, but may also prevent the anemia fromworsening.

J Am Geriatr Soc 51:S10–S13, 2003.Key words: anemia; mortality; cardiovascular complica-

tions; neurological function; quality of life; aging

system is eventually affected. Regardless of the causes orpathophysiological mechanisms underlying anemia in theelderly, it is apparent that this disorder accounts for signif-icant morbidity and mortality in these patients and can re-duce quality of life.

ANEMIA AS AN INDEPENDENT RISK FACTORFOR DEATH

Studies have indicated that the presence of anemia in theelderly significantly increases the risk of mortality.

3,14

In alarge, community-based study conducted in Leiden, theNetherlands, hemoglobin concentrations were assessed in755 patients aged 85 and older over a period of 10 years.

14

Anemia was found in men (

�

13 g/dL) and women (

�

12 g/dL) (28% and 17%, respectively) at baseline. The risk ofmortality was significantly increased in the patients withanemia (mortality risk was 2.29% in men and 1.6% in

women;

P

�

.001) compared with their healthy counter-parts. Furthermore, an inverse relationship between mor-tality risk and hemoglobin concentration was observed.

Similar findings were reported in an earlier study,where survival of older patients (

�

65) with anemia wassignificantly less than that expected for the U.S. white pop-ulation when matched for age and sex (

P

�

.001; Figure1).

3

In this study, survival was significantly better (

P

�

.001) in those patients whose anemia was caused by bloodloss than in patients with anemia of some other knowncause, such as anemia due to acute infection or chronic in-flammatory disease.

3

CARDIOVASCULAR COMPLICATIONS OF ANEMIA

Cardiovascular disease is the major cause of morbidity andmortality in patients with renal failure. Multiple factors areinvolved in the development of cardiovascular disease inpatients with chronic kidney disease, including anemia.

In the absence of underlying cardiovascular disorders,severe anemia (hemoglobin concentration

�

4–5 g/dL) canlead to congestive heart failure.

15

In the presence of heartdisease, especially coronary artery disease, anemia canworsen angina pectoris and can contribute to a high inci-dence of other cardiovascular complications.

4

It is well known that anemia reduces the oxygen-carryingcapacity of blood; the body has several mechanisms that

interact to compensate and maintain adequate tissue oxygen-ation. Broadly, these can be classified as nonhemodynamicmechanisms (e.g., increased erythropoietin production and

From the Donald W. Reynolds Center on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Address correspondence to David Lipschitz, MD, PhD, Donald W. Reynolds Center on Aging, Second Floor, 4301 West Markham, Slot 547–13, Little Rock, AR 72205. E-mail: stewartwandaf@exchange.uams.edu

A

nemia is an increasingly common medical disorder inthe elderly, affecting approximately 12% of people

aged 60 and older.

1

Its prevalence is known to increasewith age, the highest prevalence occurring in men aged 85and older.

2,3

Thus, as the elderly population increasesworldwide, it is predicted that anemia will become a sig-nificant healthcare burden.

Anemia has been associated with a number of comor-bidities, such as cardiovascular disease

4

and cognitive andfunctional impairments. It is also associated with lowerfunctional ability, self-care deficits, and depression.

5–7

Inaddition, patients with chronic renal disease; cancer (diseaseor chemotherapy induced); and other chronic diseases, suchas rheumatoid arthritis, human immunodeficiency virus/acquired immunodeficiency diseases, and inflammatorybowel disease, are also susceptible to anemia.

8–13

Differen-tiating the effects of anemia from those of other, concur-rent disorders can prove challenging.

The symptoms and severity of anemia depend on vari-ous factors, including the degree of anemia, the rapidity ofits onset, and the age and physiological status of the pa-tient. Although the body tries to counterbalance the effectsof anemia using various mechanisms, almost every organ

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CONSEQUENCES OF ANEMIA IN THE ELDERLY

S11

increased oxygen extraction) and hemodynamic mecha-nisms, which lead to increased cardiac output.

Nonhemodynamic mechanisms can only compensatefor anemia to a limited degree, and, therefore, it is the he-modynamic mechanisms that are important. These mecha-nisms are complex and involve a decrease in afterload dueto vasodilation, an increase in preload because of increasedvenous return, and an increase in left ventricular function(Figure 2). Although these mechanisms improve tissue oxy-genation, they subsequently lead to tachypnea, palpitations,and throbbing headache. In the long term, the increasedcardiac output caused by compensatory mechanisms canlead to the gradual development of left ventricular hyper-trophy (LVH), which is characterized by increased leftventricular internal dimensions and a normal ratio of wallthickness to cavity diameter.

4

In patients with chronic re-nal impairment (mean age 51.5), low levels of hemoglobinhave been found to be associated with an increased risk ofLVH; each 1 g/dL decrease in hemoglobin concentrationwas associated with a 6% increased risk of LVH.

16

Ane-mia has been shown to have an independent role in thegenesis of LVH and subsequent cardiovascular disease.

Early intervention and better correction of anemia wouldbe important in the prevention and management of cardio-vascular disease and chronic kidney disease.

17

EFFECTS OF ANEMIA ONNEUROLOGICAL FUNCTION

Headache, loss of concentration, and depression are neu-rological symptoms that are commonly reported in elderlypatients with anemia.

7

Although data on the specific neu-rological effects of anemia are limited, some studies con-ducted in renal dialysis patients have shown that the pres-ence of anemia appears to contribute to impaired cognitivefunction and that patients with chronic renal failure fre-quently suffer from confusion, inability to concentrate, de-creased mental alertness, and impaired memory.

5

Acute iso-volemic anemia results in subtle slowing of data processingability of humans and degrades memory. It also decreasesself-assessed energy level.

18

Delirium is a sign of deteriora-tion in the homeostasis and physical status of the patient.In an investigation by the authors of the predisposing fac-tors for delirium in a surgical intensive care unit setting, itwas determined that anemia was among the conditionsthat were predictive factors for delirium.

19

There appearsto be an association between Alzheimer’s disease and ane-mia in elderly patients. For example, a Greek study

20

found that vitamin B

12

and anemia had significant inde-pendent associations with possible cognitive impairment.The study also found that anemia is a frequent finding inelderly, which may be a risk factor for dementia, but theextent of the associated deterioration of cognitive impair-ment or the relationship with Alzheimer’s disease is notknown.

20

The exact mechanisms behind the specific neurologi-cal effects of anemia are not yet fully understood, but ithas been postulated that the increased cerebral blood flowinduced by anemia may result in an increased delivery ofuremic toxins to the brain or that the impaired oxygen de-livery to the brain may affect a number of important meta-bolic processes within the brain.

12

EFFECT OF ANEMIA ON PHYSICAL FUNCTION AND HEALTH-RELATED QUALITY OF LIFE

Anemia can lead to a decline in physical function; for ex-ample, it can cause functional impairment and falls.

6,21

In astudy in elderly patients between the ages of 65 and 90, asignificant correlation was observed between hemoglobinconcentrations and functional state as measured by func-tional independence measure (FIM).

6

In this study, theFIM score was lower (demonstrating low functional abil-ity) in elderly patients with mild anemia (hemoglobin con-centration

�

12 g/dL) than in elderly subjects with normalhemoglobin levels (controls; hemoglobin concentration

�

12 g/dL). Furthermore, functional impairment caused byanemia has also been reported in patients with chronicrenal failure and cancer.

22

In a study of older women, the relationship betweenhemoglobin concentration, prevalent mobility difficulty,and summary performance score was evaluated. The prev-alence of difficulty in mobility was not constant within theWorld Health Organization’s normal range (12.0–16.0 g/dL). A hemoglobin concentration of 13 g/dL was associ-ated with a significant lower prevalence of difficulty in

Figure 1. Observed and expected survival among anemic pa-tients residing in Olmstead County.3 (Reprinted by permissionof Blackwell Publishing, Inc.)

Figure 2. Schematic representation of hemodynamic mecha-nisms to compensate for anemia. (Adapted from Metivier F., etal.4)

S12

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MARCH 2003–VOL. 51, NO. 3 SUPPLEMENT JAGS

mobility than was a hemoglobin concentration of 12.0 g/dL. The results suggest that hemoglobin currently per-ceived as mildly low and even low normal might have anindependent, adverse affect on mobility function. There-fore, a hemoglobin concentration of 12.0 g/dL might be asuboptimal criterion for defining anemia in older women.

23

It has been reported that anemia can lead to falls inthe elderly and that falls are a major cause of death and asignificant source of morbidity in this population.

24,25

Find-ings from a community-based study, where the relation-ship between falls in patients aged 65 and older andchronic medical conditions was assessed, showed that ane-mia was significantly associated with falls, even after ad-justing for demographic variables and recognized risk fac-tors.

21

The exact mechanism by which anemia can lead tofalls is not yet fully understood, but it is suggested that theassociated weakness or dizziness makes the person moresusceptible to falls.

21

It is expected that a decline in physical function as aresult of anemia will have an effect on the patient’s qualityof life. For example, several clinical trials in young pa-tients with renal disease or undergoing chemotherapy forvarious malignancies have reported a strong positive cor-relation between quality of life scores and hemoglobinconcentration.

26,27

Furthermore, Valderrabano reported thatanemia has a negative influence on quality of life.

27

Various instruments are available to analyze patients’perceptions of the physical, psychological, and social do-mains of health. Nonspecific instruments, such as theMedical Outcomes Study 36-Item Short-Form Health Sur-vey, have been widely used in evaluating quality of life invarious chronic diseases, including end-stage renal disease.These instruments should be used to provide a clearer as-sessment of the effects of anemia on health-related qualityof life in elderly patients.

Fatigue is a common symptom of anemia that canhave detrimental effects on patients’ quality of life.

28

Studiesof cancer patients with anemia have shown that low he-moglobin levels are associated with greater fatigue, poorerquality of life, and decreased ability to work.

22

BENEFITS OF EARLY DIAGNOSISAND TREATMENT OF ANEMIA

Although the prevalence of anemia is high in the elderly, itshould not be perceived as an inevitable consequence ofaging. An underlying cause is usually found in approxi-mately 80% of patients.

29–31

Therefore, it is important toidentify the cause and initiate relevant treatment to pre-vent the anemia from worsening, slow disease progression,and improve patient prognosis.

29

The benefits of early diagnosis and treatment of ane-mia have been shown in patients with chronic heart failureor renal failure, where improvements were observed in theadverse outcomes associated with these disorders.

15,32

Forexample, clinical studies have shown that partial correc-tion of anemia is associated with improvements in left ven-tricular ejection fraction.

15

In addition, during the past 10years, clinical studies in patients with end-stage renal dis-ease, who are highly susceptible to developing cardiaccomplications, have shown that correction of anemia im-proved cardiac function and other factors, such as cogni-tive function and exercise capacity.

12,15

It has also been

noted that successful treatment of anemia in congestiveheart failure patients not only improved cardiac function,but also reduced the need for diuretics and hospitaliza-tion.

15

Furthermore, it has been suggested that treatmentsthat reduce fatigue and other anemia-related symptomsmay have a positive effect on quality of life.

22

All this evi-dence indicates that identifying and treating patients withanemia is beneficial in reducing the incidence of cardiovas-cular complications and associated mortality.

CONCLUSION

Anemia is a common problem in the elderly and is associ-ated with significant morbidity and mortality. Because anincreasing proportion of the world’s population is aged 65and older, it is inevitable that the prevalence of anemiawill increase in the future. Therefore, early diagnosis ofanemia is important to prevent the condition from wors-ening, slow disease progression, and improve outcomes inpatients.

Available data have shown that overall prognosis isimproved by successfully managing and correcting anemiain patients with chronic diseases such as congestive heartfailure and end-stage renal disease;

15,32

this could have asignificant effect on patients’ quality of life.

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