Advertisement

Trends in Comorbidity, Disability, and Polypharmacy in Heart Failure

  • Catherine Y. Wong
    Affiliations
    Weill Cornell Medical College, New York, NY
    Search for articles by this author
  • Sarwat I. Chaudhry
    Affiliations
    Section of General Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn
    Search for articles by this author
  • Mayur M. Desai
    Affiliations
    Division of Chronic Disease Epidemiology, School of Public Health, Yale University School of Medicine, New Haven, Conn
    Search for articles by this author
  • Harlan M. Krumholz
    Correspondence
    Requests for reprints should be addressed to Harlan M. Krumholz, MD, SM, Section of Cardiovascular Medicine, Yale University School of Medicine, 1 Church Street, Suite 200, New Haven, CT 06510
    Affiliations
    Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn

    Robert Wood Johnson Clinical Scholars Program, Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn

    Division of Health Policy and Administration, School of Public Health, Yale University School of Medicine, New Haven, Conn

    Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Conn
    Search for articles by this author

      Abstract

      Background

      Comorbidity, disability, and polypharmacy commonly complicate the care of patients with heart failure. These factors can change biological response to therapy, reduce patient ability to adhere to recommendations, and alter patient preference for treatment and outcome. Yet, a comprehensive understanding of the complexity of patients with heart failure is lacking. Our objective was to assess trends in demographics, comorbidity, physical function, and medication use in a nationally representative, community-based heart failure population.

      Methods

      Using data from the National Health and Nutrition Examination Survey, we analyzed trends across 3 survey periods (1988-1994, 1999-2002, 2003-2008).

      Results

      We identified 1395 participants with self-reported heart failure (n=581 in 1988-1994, n=280 in 1999-2002, n=534 in 2003-2008). The proportion of patients with heart failure who were ≥80 years old increased from 13.3% in 1988-1994 to 22.4% in 2003-2008 (P <.01). The proportion of patients with heart failure who had 5 or more comorbid chronic conditions increased from 42.1% to 58.0% (P <.01). The mean number of prescription medications increased from 4.1 to 6.4 prescriptions (P <.01). The prevalence of disability did not increase but was substantial across all years.

      Conclusion

      The phenotype of patients with heart failure changed substantially over the last 2 decades. Most notably, more recent patients have a higher percentage of very old individuals, and the number of comorbidities and medications increased markedly. Functional disability is prevalent, although it has not changed. These changes suggest a need for new research and practice strategies that accommodate the increasing complexity of this population.

      Keywords

      There is growing concern that clinical practice guidelines fail to adequately address the care of complex patients.
      • Tinetti M.E.
      • Bogardus Jr, S.T.
      • Agostini J.V.
      Potential pitfalls of disease-specific guidelines for patients with multiple conditions.
      • Boyd C.M.
      • Darer J.
      • Boult C.
      • et al.
      Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance.
      • O'Connor P.J.
      Adding value to evidence-based clinical guidelines.
      Patients with heart failure are particularly complex. They are generally older,
      • Levy D.
      • Kenchaiah S.
      • Larson M.G.
      • et al.
      Long-term trends in the incidence of and survival with heart failure.
      • Roger V.L.
      • Weston S.A.
      • Redfield M.M.
      • et al.
      Trends in heart failure incidence and survival in a community-based population.
      and their care is commonly complicated by comorbidity, disability, and polypharmacy. These factors can change biological response to therapy,
      • Gurwitz J.H.
      • Field T.S.
      • Judge J.
      • et al.
      The incidence of adverse drug events in two large academic long-term care facilities.
      reduce patient ability to adhere to recommendations,
      • Briesacher B.A.
      • Gurwitz J.H.
      • Soumerai S.B.
      Patients at-risk for cost-related medication nonadherence: a review of the literature.
      and alter patient preference for treatment and outcome. Yet, a comprehensive understanding of the complexity of patients with heart failure is lacking.
      • Patients with heart failure have grown substantially more complex over the last 2 decades.
      • In a nationally representative community-dwelling sample, the proportion that was very old (aged ≥80 years) increased 2-fold.
      • Several comorbid conditions—hypercholesterolemia, diabetes, obesity, kidney disease, thyroid disease, and osteoporosis—became significantly more prevalent.
      • Mean prescription drug use increased more than 50%.
      Existing studies characterizing patients with heart failure have had various limitations. Hospital-based studies examine patients in the acute setting and cannot be generalized to the community.
      • Fonarow G.C.
      • Heywood J.T.
      • Heidenreich P.A.
      • et al.
      Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE).
      • Kosiborod M.
      • Lichtman J.H.
      • Heidenreich P.A.
      • et al.
      National trends in outcomes among elderly patients with heart failure.
      • Baker D.W.
      • Einstadter D.
      • Thomas C.
      • Cebul R.D.
      Mortality trends for 23,505 Medicare patients hospitalized with heart failure in Northeast Ohio, 1991 to 1997.
      • Barker W.H.
      • Mullooly J.P.
      • Getchell W.
      Changing incidence and survival for heart failure in a well-defined older population, 1970-1974 and 1990-1994.
      • Polanczyk C.A.
      • Rohde L.E.
      • Dec G.W.
      • DiSalvo T.
      Ten-year trends in hospital care for congestive heart failure: improved outcomes and increased use of resources.
      • Havranek E.P.
      • Masoudi F.A.
      • Westfall K.A.
      • et al.
      Spectrum of heart failure in older patients: results from the National Heart Failure project.
      • Masoudi F.A.
      • Baillie C.A.
      • Wang Y.
      • et al.
      The complexity and cost of drug regimens of older patients hospitalized with heart failure in the United States, 1998-2001.
      Population-based studies have focused mainly on risk factors and survival.
      • Levy D.
      • Kenchaiah S.
      • Larson M.G.
      • et al.
      Long-term trends in the incidence of and survival with heart failure.
      • Roger V.L.
      • Weston S.A.
      • Redfield M.M.
      • et al.
      Trends in heart failure incidence and survival in a community-based population.
      • McCullough P.A.
      • Philbin E.F.
      • Spertus J.A.
      • et al.
      Confirmation of a heart failure epidemic: findings from the Resource Utilization Among Congestive Heart Failure (REACH) study.
      • Dunlay S.M.
      • Weston S.A.
      • Jacobsen S.J.
      • Roger V.L.
      Risk factors for heart failure: a population-based case-control study.
      • Dunlay S.M.
      • Weston S.A.
      • Redfield M.M.
      • et al.
      Anemia and heart failure: a community study.
      • From A.M.
      • Leibson C.L.
      • Bursi F.
      • et al.
      Diabetes in heart failure: prevalence and impact on outcome in the population.
      • Owan T.E.
      • Hodge D.O.
      • Herges R.M.
      • et al.
      Trends in prevalence and outcome of heart failure with preserved ejection fraction.
      • Senni M.
      • Tribouilloy C.M.
      • Rodeheffer R.J.
      • et al.
      Congestive heart failure in the community: trends in incidence and survival in a 10-year period.
      • Kannel W.B.
      • Ho K.
      • Thom T.
      Changing epidemiological features of cardiac failure.
      No national survey has comprehensively characterized the complexity of patients with heart failure or determined whether the complexity is changing over time.
      To assess the complexity of patients with heart failure, we analyzed data from the National Health and Nutrition Examination Survey (NHANES). Our objective was to describe trends in demographics, comorbidity, physical function, and medication use among adults with heart failure in nationally representative, community-based samples over time. We hypothesize that the proportion of patients who are elderly is substantial and growing, and the prevalence of comorbidity, disability, and polypharmacy is large and increasing.

      Materials and Methods

      Data Source

      We used data from NHANES III (1988 to 1994) and NHANES 1999 to 2008. The plan and operation of NHANES has been described in detail elsewhere.
      Plan and operation of the Third National Health and Nutrition Examination Survey, 1988-94
      Series 1: programs and collection procedures.
      Centers for Disease Control and Prevention
      National Health and Nutrition Examination Survey.
      Briefly, the NHANES are cross-sectional, multistage probability sample surveys conducted by the National Center for Health Statistics. Participants undergo both interview and clinical examination. With the use of sampling weights, each survey produces statistics that are representative of the noninstitutionalized, civilian US population.
      Beginning in 1999, NHANES transitioned from being a periodic survey to a continuous survey with data release every 2 years. For our analysis we combined 1999-2000 and 2001-2002 data releases into a 1999-2002 cohort. We similarly combined data releases to create a 2003-2008 cohort.

      Study Sample

      From an overall 25,679 NHANES participants aged ≥40 years who underwent examination, we excluded 20 participants who were pregnant and 133 participants with missing data regarding the presence of heart failure. Participants were identified as having heart failure if they answered “yes” to the interview question “Has a doctor or other health professional ever told you that you had congestive heart failure?”

      Measurements

      Trends were assessed for variables in 4 general domains: demographics, comorbidity, physical function, and medication use. Demographic variables included age, sex, race/ethnicity, education, and socioeconomic status. Participants that were eligible for federal food assistance programs, based on income and household size, were categorized as having low socioeconomic status.
      Centers for Disease Control and Prevention
      National Health and Nutrition Examination Survey Analytic Guidelines.
      United States Department of Agriculture
      Food and Nutrition Service.
      We evaluated trends in the prevalence of several comorbidities common in older patients and in patients with heart failure.
      • Anderson G.
      • Horvath J.
      The growing burden of chronic disease in America.
      • Braunstein J.B.
      • Anderson G.F.
      • Gerstenblith G.
      • et al.
      Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure.
      The presence of myocardial infarction, angina, stroke, diabetes (excluding gestational diabetes only), asthma, chronic obstructive pulmonary disease, arthritis, cancer, thyroid disease, and osteoporosis were determined by self-report. Analysis of the subsample of participants who underwent fasting blood draw showed substantial agreement between self-reported diabetes and diabetes based on medication use and fasting blood glucose levels (κ=.79).
      • Landis J.R.
      • Koch G.G.
      The measurement of observer agreement for categorical data.
      Participants were considered to have high cholesterol if they self-reported that they were taking medication for cholesterol or if their total cholesterol was ≥240 mg/dL.
      National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
      Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
      Participants were considered to have hypertension if their mean systolic blood pressure was ≥140 mm Hg, their mean diastolic blood pressure was ≥90 mm Hg, or they self-reported that they were taking medication for high blood pressure. According to World Health Organization standards, anemia was defined as having a hemoglobin level of <12 g/dL for women or <13 g/dL for men,
      World Health Organization (WHO)
      Nutritional anemias: report of a WHO scientific group.
      and obesity was defined as body mass index ≥30 kg/m2.
      Obesity: preventing and managing the global epidemic Report of a WHO consultation.
      Waist circumference was assessed to supplement body mass index as a measure of obesity. As recommended by the National Institutes of Heath, high-risk waist circumference was defined as ≥88 cm and ≥102 cm for women and men, respectively.
      Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report National Institutes of Health.
      Kidney function was determined using serum creatinine and the abbreviated Modification of Diet in Renal Disease formula to calculate glomerular filtration rates.
      • Levey A.S.
      • Coresh J.
      • Greene T.
      • et al.
      Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.
      Kidney disease was defined as a glomerular filtration rate <60 mL/min per 1.73 m2, which corresponds to clinically significant, stage 3 kidney disease as set forth by the National Kidney Foundation.
      • Levey A.S.
      • Coresh J.
      • Balk E.
      • et al.
      National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.
      A composite indicator of disease burden was calculated by tallying the number of chronic conditions for each patient. The following conditions were included in this composite measure: myocardial infarction, asthma, diabetes, chronic obstructive pulmonary disease, arthritis, cancer, thyroid disease, osteoporosis, hypercholesterolemia, hypertension, anemia, obesity, and kidney disease. Stroke, an acute event that may not result in chronic deficits, was not included. Angina was not included because data were unavailable for years 1988-1994. Although myocardial infarction is not a chronic condition, it was included as a proxy for coronary artery disease. In summing the number of chronic conditions, conditions with missing values were treated as if the condition were not present; 11% of participants had one or more chronic conditions with missing values.
      Two measures of disability and one measure of impairment were used to assess function: activities of daily living disability, mobility disability, and vision impairment. Participants were considered to have activities of daily living disability if they reported having much difficulty with or being unable to perform any of the following 3 tasks: dressing, eating, or getting in and out of bed. Participants were considered to have mobility disability if they reported having much difficulty with or being unable to walk 2 to 3 blocks or walk up 10 steps. Participants were considered vision impaired if they were unable to read ordinary newspaper print even with the help of contacts/glasses. Disability measures were assessed only for participants aged ≥60 years.
      Medication use was ascertained during home interviews. NHANES participants were asked to list names and dosages of all current medications and to show available medication containers for verification. NHANES classified medications according to Lexicon Plus, a proprietary database of Cerner Multum, Inc. (Denver, Colo).
      Cerner Multum, Inc.
      Lexicon.
      In calculating the total number of prescription medications, medications taken for <2 weeks were excluded.

      Statistical Analysis

      We analyzed trends across time periods (1988-1994, 1999-2002, 2003-2008). All analyses were performed using SAS-callable SUDAAN statistical software (Research Triangle Institute, Research Triangle Park, NC).
      Research Triangle Institute
      SUDAAN Language Manual, Release 10.0.
      Data were weighted according to NHANES analytical guidelines. The weighting methodology adjusts for bias that may arise from total nonresponse to examination.
      Centers for Disease Control and Prevention
      National Health and Nutrition Examination Survey Analytic Guidelines.
      Prevalence and mean estimates were age-adjusted by the direct method to the 2003-2008 heart failure population based on 40-59, 60-69, 70-79, and 80+ years age groups. Linear trends across time periods were determined based on the method of Fisher and Yates;
      Research Triangle Institute
      SUDAAN Language Manual, Release 10.0.
      the test for linear trend is the same as the comparison of first and last survey periods. In accordance with NHANES analytical guidelines, estimates with a coefficient of variation >0.30 were considered unreliable.
      Centers for Disease Control and Prevention
      National Health and Nutrition Examination Survey Analytic Guidelines.
      To account for multiple comparisons, we used a cutoff of α=0.01.

      Results

      Demographics

      We identified 1395 participants with heart failure (n=581 in 1988-1994, n=280 in 1999-2002, n=534 in 2003-2008). The mean age was 67.7 years. The proportion ≥80 years old significantly increased from 13% in 1988-1994 to 22% in 2003-2008 (Table 1). Overall, 49% of participants with heart failure were female and 76% were non-Hispanic white. These figures were consistent over time. A large proportion of patients with heart failure are poorly educated, living in poverty, or living alone. In 2003-2008, 36% had not completed high school, 23% had low socioeconomic status, and 26% were living alone.
      Table 1Trends in Demographics among Patients with Heart Failure
      Variable1988-1994 (n = 581)1999-2002 (n = 280)2003-2008 (n=534)Change, 1988-2008 (95% CI)P Value
      Age-specific data
       Age (years)67.4 (0.7)67.3 (1.1)68.4 (0.6)1.0 (−0.7-2.8).24
       Age group
        40-5923.7 (3.4)31.3 (3.9)23.1 (2.3)0.5 (−8.8-7.8).90
        60-6928.9 (2.5)17.0 (2.7)28.2 (2.7)0.7 (−8.0-6.6).85
        70-7934.1 (2.7)30.9 (3.2)26.2 (2.1)−7.9 (−14.5-−1.2).02
        80+13.3 (1.7)20.8 (3.6)22.4 (2.4)9.1 (3.4-14.8).002
      Age-adjusted data
       Demographics
        Female51.4 (3.2)48.8 (3.6)45.6 (2.5)−5.7 (−14.3-2.8).18
        Non-Hispanic white73.5 (2.9)75.8 (4.2)76.6 (2.5)3.1 (−4.9-11.0).44
        < High school education53.8 (2.7)47.7 (3.4)36.1 (3.1)−17.7 (−26.1-−9.3)<.001
        Low socioeconomic status
      See “Materials and Methods” for definition.
      28.3 (2.9)38.9 (4.9)22.6 (2.3)−5.7 (−13.0-1.6).12
        Lives alone25.4 (1.9)27.6 (2.5)25.8 (2.2)0.4 (−5.5-6.4).89
        Ever smoker62.2 (2.9)59.0 (2.8)63.0 (2.7)0.8 (−7.0-9.3).86
        Current smoker21.1 (2.6)18.5 (3.6)17.3 (1.6)−3.7 (−9.5-2.1).20
      CI=confidence interval.
      All variables are in weighted % or mean (standard error).
      a See “Materials and Methods” for definition.

      Comorbid Conditions

      Comorbidity was common. In 2003-2008, more than half of patients with heart failure had hypertension (73%), hypercholesterolemia (54%), or arthritis (62%) (Table 2). Nearly half had a history of myocardial infarction (48%) or were obese (47%).
      Table 2Trends in Comorbid Conditions among Patients with Heart Failure
      Variable1988-1994 (n=581)1999-2002 (n=280)2003-2008 (n=534)Change, 1988-2008 (95% CI)P Value
      MI58.8 (3.3)46.5 (3.3)47.7 (3.1)−11.2 (−20.3-−2.0).02
      AnginaNA
      Data not available because data collection methods differed substantially from methods in subsequent years.
      38.7 (3.8)26.9 (2.7)−11.9 (−12.1-−2.6)
      Comparison is for 1999-2002 vs 2003-2008.
      .01
      Comparison is for 1999-2002 vs 2003-2008.
      Stroke17.6 (2.1)16.6 (2.6)19.4 (2.4)1.8 (−4.8-8.4).59
      Diabetes
      See “Materials and Methods” for definitions.
      24.7 (2.7)29.3 (2.9)38.3 (2.3)13.6 (6.4-20.7)<.001
      Blood pressure (BP)
       Hypertension
      See “Materials and Methods” for definitions.
      67.8 (2.5)71.2 (3.7)73.3 (2.2)5.5 (−1.1-12.1).10
       Systolic BP (mm Hg)141.7 (1.1)131.7 (1.8)130.6 (1.3)−11.2 (−14.5-−7.8)<.001
       Diastolic BP (mm Hg)73.1 (1.1)66.9 (1.5)65.9 (0.7)−7.2 (−9.9-−4.5)<.001
      Cholesterol
       Hypercholesterolemia
      See “Materials and Methods” for definitions.
      41.3 (3.0)49.3 (3.9)53.5 (2.8)12.2 (5.0-19.4).001
       LDL cholesterol
      Calculated for fasting subsample only (n=271 in 1988-1994, n=105 in 1999-2002, n=136 in 2003-2008).
      (mg/dL)
      139.2 (3.1)116.7 (5.1)105.3 (4.6)−33.9 (−44.9-−22.8)<.001
       HDL cholesterol <40 mg/dL35.1 (2.9)34.0 (3.8)25.8 (2.2)−9.2 (−16.6-−1.8).02
      Obesity
       Obesity
      See “Materials and Methods” for definitions.
      32.8 (2.5)40.3 (4.7)46.8 (2.5)13.9 (7.5-20.4)<.001
       BMI (kg/m2)28.3 (0.3)30.0 (0.8)31.1 (0.4)2.8 (1.8-3.7)<.001
       Waist circumference (cm)
        Women95.9 (1.2)102.6 (1.9)105.5 (1.2)9.6 (6.1-12.1)<.001
        Men102.0 (1.0)105.1 (1.2)109.2 (1.4)7.2 (3.7-10.7)<.001
       High-risk waist circumference
      See “Materials and Methods” for definitions.
      57.6 (3.4)73.0 (2.9)75.7 (2.7)18.0 (8.5-27.6)<.001
      Kidney function
       Kidney disease
      See “Materials and Methods” for definitions.
      34.7 (2.9)41.2 (3.6)45.9 (2.1)11.2 (4.2-18.3).002
       Creatinine (mg/dL)1.10 (0.06)1.29 (0.09)1.23 (0.04)0.13 (0.00-0.26).06
       Creatinine >2 mg/dL4.6 (1.8)6.9 (1.8)7.4 (1.0)2.8 (−1.2-6.7).17
      Anemia
      See “Materials and Methods” for definitions.
      15.3 (2.7)15.0 (1.8)22.2 (2.7)6.9 (−0.6-14.5).07
      Asthma18.0 (2.5)16.8 (2.7)24.6 (1.9)6.6 (0.3-12.9).04
      Arthritis60.4 (2.9)68.5 (3.3)62.0 (2.4)1.6 (−5.4-8.6).65
      COPD26.2 (2.8)26.8 (2.9)30.9 (2.3)4.8 (−2.5-12.1).20
      Cancer21.5 (2.5)29.3 (2.8)24.4 (2.0)2.9 (−3.6-9.4).38
      Thyroid disease9.9 (1.5)15.2 (2.8)22.9 (1.9)13.0 (8.3-17.7).001
      Osteoporosis4.9 (1.2)13.6 (3.1)16.4 (2.5)11.5 (5.9-17.1).001
      BMI=body mass index; CI=confidence interval; COPD=chronic obstructive pulmonary disease; HDL=high-density lipoprotein; LDL=low-density lipoprotein; MI=myocardial infarction.
      All variables are in weighted % or mean (standard error).
      a See “Materials and Methods” for definitions.
      b Data not available because data collection methods differed substantially from methods in subsequent years.
      c Comparison is for 1999-2002 vs 2003-2008.
      d Calculated for fasting subsample only (n=271 in 1988-1994, n=105 in 1999-2002, n=136 in 2003-2008).
      Comorbidity was not only common, but also grew increasingly prevalent over the last decades. The age-adjusted proportion of patients with heart failure who had 5 or more comorbid chronic conditions increased from 42% in 1988-1994 to 58% in 2003-2008 (Figure) . The main conditions driving this increase included hypercholesterolemia (41% to 54%), diabetes (25% to 38%), obesity (33% to 47%), kidney disease (35% to 46%), thyroid disease (10% to 23%), and osteoporosis (5% to 16%) (Table 2).
      Figure thumbnail gr1
      FigureTrends in number of comorbid chronic conditions among patients with heart failure.
      The prevalence of myocardial infarction and angina trended downward, but these changes were not statistically significant. There was improved control of blood pressure and lipid levels.

      Disability and Impairment

      Age-adjusted levels of disability did not change over time, but were high throughout all periods. In 2003-2008, 57% of patients ≥60 years old with heart failure were mobility disabled; 11% were activities of daily living disabled; and 12% were vision impaired (Table 3).
      Table 3Trends in Disability and Impairment among Patients with Heart Failure
      Variable1988-1994 (n=480)1999-2002 (n=224)2003-2008 (n=441)Change, 1988-2008 (95% CI)P Value
      Mobility disabled
      See “Materials and Methods” for definitions.
      52.6 (3.2)57.6 (4.2)56.9 (2.8)4.3 (−4.1-12.7).31
      Activities of daily living disabled
      See “Materials and Methods” for definitions.
      12.5 (1.9)13.8 (2.1)11.1 (1.5)−1.4 (−6.2-3.4).57
      Vision impaired
      See “Materials and Methods” for definitions.
      11.8 (1.7)11.1 (2.8)11.7 (1.8)−0.1 (−4.9-4.7).97
      CI=confidence interval.
      All variables are in weighted % (standard error).
      a See “Materials and Methods” for definitions.

      Medication Use

      Table 4 shows trends in medication use, with drugs listed in order of decreasing frequency of use in 2003-2008. Prescription drug use in patients with heart failure increased from a mean of 4.1 prescriptions to 6.4 prescriptions. In 2003-2008, the highest decile managed more than 11 prescriptions. Although the use of digoxin and calcium channel blockers decreased, most medications experienced a sharp increase in use, including cardiovascular and noncardiovascular drugs. Potassium supplementation and aspirin use did not change significantly over time but were quite common, 20% and 28%, respectively, in the period 2003-2008.
      Table 4Trends in Prescription Medication Use among Patients with Heart Failure
      Variable1988-1994 (n=581)1999-2002 (n=280)2003-2008 (n=534)Change, 1988-2008 (95% CI)P Value
      No. of prescription medications4.1 (0.2)5.1 (0.3)6.4 (0.2)2.4 (1.8-2.9)<.001
      Cardiovascular medications
       Diuretic44.8 (2.9)51.2 (3.6)57.6 (2.3)12.8 (5.7-19.9)<.001
       ACE or ARB24.0 (2.7)47.1 (3.5)55.0 (2.6)31.1 (23.9-38.3)<.001
       β-blocker15.4 (2.2)36.0 (4.5)51.8 (2.5)36.3 (30.1-42.6)<.001
       HMG-CoA reductase inhibitors6.4 (2.1)36.0 (3.8)45.5 (2.7)39.1 (32.3-45.9)<.001
       Aspirin34.4 (2.8)36.5 (3.2)28.3 (3.1)
      Data available only for 2003-2004.
      −6.0 (−13.9-1.9).13
       Calcium channel blocker38.8 (3.3)28.1 (4.5)22.9 (2.0)−15.9 (−23.3-−8.4)<.001
       Potassium chloride15.9 (2.3)19.5 (2.7)19.5 (2.3)3.6 (−3.0-10.2).28
       Warfarin9.7 (1.7)20.6 (2.7)17.9 (2.1)8.2 (2.9-13.6).003
       Digoxin30.0 (2.9)20.0 (1.7)14.7 (2.1)−15.3 (−22.2-−8.4)<.001
       Antianginal agent30.7 (2.6)24.3 (2.4)12.5 (1.4)−18.2 (−24.0-−12.3)<.001
       Antiarrhythmic agent11.9 (2.1)2.5 (1.2)
      Statistically unreliable.
      5.7 (1.0)−6.1 (−10.7-−1.6).009
      Noncardiovascular medications
       Antidiabetic agent18.2 (2.2)24.5 (3.1)31.1 (2.2)12.9 (6.6-19.3)<.001
       PPI or H2 Antagonist13.8 (2.0)23.0 (2.7)32.3 (3.3)18.5 (10.7-26.2)<.001
       Levothyroxine4.8 (1.4)10.8 (2.2)18.2 (1.8)13.5 (9.2-17.7)<.001
       Bronchodilator11.1 (2.4)9.3 (2.2)14.2 (1.7)3.1 (−1.9-8.1).22
      ACE=angiotensin-converting enzyme; ARB=angiotensin receptor blocker; CI=confidence interval; HMG-CoA=3-hydroxy-3-methylglutaryl-coenzyme A; PPI=proton pump inhibitor.
      All variables are in weighted % or mean (standard error).
      a Data available only for 2003-2004.
      b Statistically unreliable.

      Discussion

      Patients with heart failure are remarkably complex. Specifically, in a nationally representative sample, patients with heart failure are very old with high rates of comorbidity, disability, and polypharmacy. Furthermore, not only are patients complex, but, even after adjusting for age, they have become increasingly complex over the last decades. In 2003-2008, nearly a quarter of community-dwelling patients with heart failure were ≥80 years old; more than half had 5 or more comorbid chronic conditions; more than half were mobility disabled; and on average, a patient with heart failure managed more than 6 prescription medications.
      Our study furthers previous research by comprehensively and representatively describing the complexity of patients with heart failure. In a nationally representative sample, we report on demographics, comorbidity, disability, and polypharmacy. In describing comorbidity and polypharmacy, we included a broad range of cardiac and noncardiac conditions. Prior studies have focused primarily on cardiovascular conditions.
      We found similar or higher rates of comorbidity than previously have been reported. Compared with a study by Braunstein et al,
      • Braunstein J.B.
      • Anderson G.F.
      • Gerstenblith G.
      • et al.
      Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure.
      which used inpatient and outpatient Medicare data from 1999, we found (in 1999-2002) higher rates of hypercholesterolemia (49% vs 21%), kidney disease (38% vs 11%), arthritis (68% vs 16%), and osteoporosis (14% vs 5%). Compared with 1997-2002 data from a population-based study from Olmsted County,
      • Dunlay S.M.
      • Weston S.A.
      • Jacobsen S.J.
      • Roger V.L.
      Risk factors for heart failure: a population-based case-control study.
      we found (in 1999-2002) higher rates of diabetes (29% vs 19%) and obesity (40% vs 30%). Differences in data type and patient demographics may explain some of these differences. Whereas Braunstein et al
      • Braunstein J.B.
      • Anderson G.F.
      • Gerstenblith G.
      • et al.
      Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure.
      and the Olmsted County study
      • Dunlay S.M.
      • Weston S.A.
      • Jacobsen S.J.
      • Roger V.L.
      Risk factors for heart failure: a population-based case-control study.
      used administrative data (medical records or medical claims) to determine comorbidity, we used a combination of self-report and standardized examination. Administrative data may underreport comorbidity as not all patient conditions are recorded at each encounter. Differences in patient demographics also could explain our higher estimates of comorbidity. Our study population was comparatively young. Whereas most prior studies have been limited to patients ≥65 years old and have included patients in nursing homes, our study looked at noninstitutionalized subjects ≥40 years old. Younger patients with heart failure have higher rates of coronary artery disease, hypercholesterolemia, diabetes, and chronic obstructive pulmonary disease.
      • Havranek E.P.
      • Masoudi F.A.
      • Westfall K.A.
      • et al.
      Spectrum of heart failure in older patients: results from the National Heart Failure project.
      • Bouchard J.L.
      • Aurigemma G.P.
      • Goldberg R.J.
      • et al.
      Heart failure in the “oldest old”: clinical and echocardiographic insights.
      Our findings corroborate prior studies, both community-based and hospital-based, which have shown that rates of diabetes and obesity have increased in patients with heart failure.
      • Kosiborod M.
      • Lichtman J.H.
      • Heidenreich P.A.
      • et al.
      National trends in outcomes among elderly patients with heart failure.
      • Polanczyk C.A.
      • Rohde L.E.
      • Dec G.W.
      • DiSalvo T.
      Ten-year trends in hospital care for congestive heart failure: improved outcomes and increased use of resources.
      • Dunlay S.M.
      • Weston S.A.
      • Jacobsen S.J.
      • Roger V.L.
      Risk factors for heart failure: a population-based case-control study.
      • From A.M.
      • Leibson C.L.
      • Bursi F.
      • et al.
      Diabetes in heart failure: prevalence and impact on outcome in the population.
      A strength of NHANES is that it allowed trending of various other complicating conditions. We found significant increases in the rates of hypercholesterolemia, kidney disease, thyroid disease, and osteoporosis. To our knowledge, we are the first to clearly examine long-term trends in noncardiac conditions in patients with heart failure.
      To our knowledge, we also are the first to examine long-term trends in the use of noncardiovascular medications in patients with heart failure. Over the last decades, the use of antidiabetic agents, levothyroxine, and proton pump inhibitors has significantly increased. Regarding trends in the use of cardiovascular medications, our findings are in line with previous studies.
      • Fonarow G.C.
      • Heywood J.T.
      • Heidenreich P.A.
      • et al.
      Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE).
      • Barker W.H.
      • Mullooly J.P.
      • Getchell W.
      Changing incidence and survival for heart failure in a well-defined older population, 1970-1974 and 1990-1994.
      • Masoudi F.A.
      • Baillie C.A.
      • Wang Y.
      • et al.
      The complexity and cost of drug regimens of older patients hospitalized with heart failure in the United States, 1998-2001.
      • Lee D.S.
      • Mamdani M.M.
      • Austin P.C.
      • et al.
      Trends in heart failure outcomes and pharmacotherapy: 1992 to 2000.
      There has been increased use of drugs with demonstrated survival advantage (angiotensin-converting enzyme inhibitors and beta-blockers) and decreased use of drugs with demonstrated lack of survival advantage (digoxin, calcium channel blockers, and anti-arrhythmics). Previously, Masoudi et al
      • Masoudi F.A.
      • Baillie C.A.
      • Wang Y.
      • et al.
      The complexity and cost of drug regimens of older patients hospitalized with heart failure in the United States, 1998-2001.
      described an increase in overall prescription medication use from 6.8 prescriptions in 1998-1999 to 7.5 in 2000-2001 in recently hospitalized Medicare beneficiaries with heart failure. Current findings show that this trend holds true over a longer time period and in the outpatient setting.
      In addition to polypharmacy and comorbidity, we were interested in describing the prevalence of disability in patients with heart failure. In the community setting, rates of disability did not change over time, but were nevertheless substantial throughout all study periods. Our ability to detect change in disability may have been limited because our measurement only captured severe disability in noninstitutionalized subjects. It is difficult to compare our findings with prior studies
      • Zhang J.X.
      • Rathouz P.J.
      • Chin M.H.
      Comorbidity and the concentration of healthcare expenditures in older patients with heart failure.
      • Gure T.R.
      • Kabeto M.U.
      • Blaum C.S.
      • Langa K.M.
      Degree of disability and patterns of caregiving among older Americans with congestive heart failure.
      because of differences in measure definitions.
      The growing complexity that we have demonstrated suggests a need to fundamentally change the way we research and care for patients with heart failure. The proportion of patients with heart failure who are very elderly is increasing. This figure will likely continue to increase as the elderly are expected to comprise a growing and substantial portion of the US population.
      • Foot D.K.
      • Lewis R.P.
      • Pearson T.A.
      • Beller G.A.
      Demographics and cardiology, 1950-2050.
      Yet, the very elderly are inadequately studied in clinical trials. They are often under-enrolled, and those that are enrolled tend to have less comorbidity.
      • Heiat A.
      • Gross C.P.
      • Krumholz H.M.
      Representation of the elderly, women, and minorities in heart failure clinical trials.
      Furthermore, analyses rarely evaluate safety and effectiveness in the very elderly separately, although evidence suggests that they experience higher rates of adverse drug events and may have distinct pathophysiology.
      • Duncan A.K.
      • Vittone J.
      • Fleming K.C.
      • Smith H.C.
      Cardiovascular disease in elderly patients.
      • Masoudi F.A.
      • Gross C.P.
      • Wang Y.
      • et al.
      Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States, 1998-2001.
      Our study emphasizes the need for future clinical trials to evaluate safety and effectiveness in older patients and in patients with multiple comorbidities.
      Our study also emphasizes the need for physicians to be careful and judicious when caring for patients with heart failure. With such high prevalence of comorbidity, disability, and polypharmacy, physicians need to be mindful of possible adverse drug events and nonadherence. Nonadherence could be a particularly salient issue given that a large proportion of patients with heart failure are poorly educated, have low socioeconomic status, or live alone. As patients with heart failure grow increasingly complex, physicians will need to better their ability to prioritize treatment recommendations based on relative benefits and harms and in the context of patient preferences.

      Limitations

      A significant limitation of our study is that the presence of heart failure and several comorbid conditions were determined by self-report. Self-report—a measure that reflects a combination of true prevalence, diagnosis, and patient awareness—can lead to both overestimation and underestimation. Prior studies have shown that agreement between self-report and clinical diagnosis varies by disease. Asthma and chronic obstructive pulmonary disease are commonly over-reported; thyroid disease and cancer are often under-reported; diabetes and heart disease are relatively accurately reported.
      • Desai M.M.
      • Bruce M.L.
      • Desai R.A.
      • Druss B.G.
      Validity of self-reported cancer history: a comparison of health interview data and cancer registry records.
      • Harlow S.D.
      • Linet M.S.
      Agreement between questionnaire data and medical records The evidence for accuracy of recall.
      • Okura Y.
      • Urban L.H.
      • Mahoney D.W.
      • et al.
      Agreement between self-report questionnaires and medical record data was substantial for diabetes, hypertension, myocardial infarction and stroke but not for heart failure.
      A prior NHANES study showed that self-report underestimates the presence of heart failure as compared with identification by clinical characteristics.
      • Schocken D.D.
      • Arrieta M.I.
      • Leaverton P.E.
      • Ross E.A.
      Prevalence and mortality rate of congestive heart failure in the United States.
      Our study has other limitations. First, even though our data come from large national surveys, our sample sizes are limited because the prevalence of heart failure is low. As a result, we had power to detect only large trends. Second, because our data come from cross-sectional surveys, we could not comment as to whether comorbid conditions preceded or followed the diagnosis of heart failure.

      Conclusion

      The phenotype of patients with heart failure has changed substantially over the last 2 decades. Most notably, more recent patients have a higher percentage of very old individuals, and the number of comorbidities and medications increased markedly. Severe functional disability is prevalent, although it has not changed. These changes suggest a need for new research and practice strategies that accommodate the increasing complexity of this population.

      Acknowledgment

      The authors wish to thank Dr. Elena Kuklina from the Centers for Disease Control and Prevention for biostatistical guidance.

      References

        • Tinetti M.E.
        • Bogardus Jr, S.T.
        • Agostini J.V.
        Potential pitfalls of disease-specific guidelines for patients with multiple conditions.
        N Engl J Med. 2004; 351: 2870-2874
        • Boyd C.M.
        • Darer J.
        • Boult C.
        • et al.
        Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance.
        JAMA. 2005; 294: 716-724
        • O'Connor P.J.
        Adding value to evidence-based clinical guidelines.
        JAMA. 2005; 294: 741-743
        • Levy D.
        • Kenchaiah S.
        • Larson M.G.
        • et al.
        Long-term trends in the incidence of and survival with heart failure.
        N Engl J Med. 2002; 347: 1397-1402
        • Roger V.L.
        • Weston S.A.
        • Redfield M.M.
        • et al.
        Trends in heart failure incidence and survival in a community-based population.
        JAMA. 2004; 292: 344-350
        • Gurwitz J.H.
        • Field T.S.
        • Judge J.
        • et al.
        The incidence of adverse drug events in two large academic long-term care facilities.
        Am J Med. 2005; 118: 251-258
        • Briesacher B.A.
        • Gurwitz J.H.
        • Soumerai S.B.
        Patients at-risk for cost-related medication nonadherence: a review of the literature.
        J Gen Intern Med. 2007; 22: 864-871
        • Fonarow G.C.
        • Heywood J.T.
        • Heidenreich P.A.
        • et al.
        Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE).
        Am Heart J. 2007; 153: 1021-1028
        • Kosiborod M.
        • Lichtman J.H.
        • Heidenreich P.A.
        • et al.
        National trends in outcomes among elderly patients with heart failure.
        Am J Med. 2006; 119: 616.e1-616.e7
        • Baker D.W.
        • Einstadter D.
        • Thomas C.
        • Cebul R.D.
        Mortality trends for 23,505 Medicare patients hospitalized with heart failure in Northeast Ohio, 1991 to 1997.
        Am Heart J. 2003; 146: 258-264
        • Barker W.H.
        • Mullooly J.P.
        • Getchell W.
        Changing incidence and survival for heart failure in a well-defined older population, 1970-1974 and 1990-1994.
        Circulation. 2006; 113: 799-805
        • Polanczyk C.A.
        • Rohde L.E.
        • Dec G.W.
        • DiSalvo T.
        Ten-year trends in hospital care for congestive heart failure: improved outcomes and increased use of resources.
        Arch Intern Med. 2000; 160: 325-332
        • Havranek E.P.
        • Masoudi F.A.
        • Westfall K.A.
        • et al.
        Spectrum of heart failure in older patients: results from the National Heart Failure project.
        Am Heart J. 2002; 143: 412-417
        • Masoudi F.A.
        • Baillie C.A.
        • Wang Y.
        • et al.
        The complexity and cost of drug regimens of older patients hospitalized with heart failure in the United States, 1998-2001.
        Arch Intern Med. 2005; 165: 2069-2076
        • McCullough P.A.
        • Philbin E.F.
        • Spertus J.A.
        • et al.
        Confirmation of a heart failure epidemic: findings from the Resource Utilization Among Congestive Heart Failure (REACH) study.
        J Am Coll Cardiol. 2002; 39: 60-69
        • Dunlay S.M.
        • Weston S.A.
        • Jacobsen S.J.
        • Roger V.L.
        Risk factors for heart failure: a population-based case-control study.
        Am J Med. 2009; 122: 1023-1028
        • Dunlay S.M.
        • Weston S.A.
        • Redfield M.M.
        • et al.
        Anemia and heart failure: a community study.
        Am J Med. 2008; 121: 726-732
        • From A.M.
        • Leibson C.L.
        • Bursi F.
        • et al.
        Diabetes in heart failure: prevalence and impact on outcome in the population.
        Am J Med. 2006; 119: 591-599
        • Owan T.E.
        • Hodge D.O.
        • Herges R.M.
        • et al.
        Trends in prevalence and outcome of heart failure with preserved ejection fraction.
        N Engl J Med. 2006; 355: 251-259
        • Senni M.
        • Tribouilloy C.M.
        • Rodeheffer R.J.
        • et al.
        Congestive heart failure in the community: trends in incidence and survival in a 10-year period.
        Arch Intern Med. 1999; 159: 29-34
        • Kannel W.B.
        • Ho K.
        • Thom T.
        Changing epidemiological features of cardiac failure.
        Br Heart J. 1994; 72: S3-S9
        • Plan and operation of the Third National Health and Nutrition Examination Survey, 1988-94
        Series 1: programs and collection procedures.
        Vital Health Stat 1. 1994; : 1-407
        • Centers for Disease Control and Prevention
        National Health and Nutrition Examination Survey.
        (Accessed March 4, 2010)
        • Centers for Disease Control and Prevention
        National Health and Nutrition Examination Survey Analytic Guidelines.
        (Accessed March 12, 2010)
        • United States Department of Agriculture
        Food and Nutrition Service.
        (Accessed March 12, 2010)
        • Anderson G.
        • Horvath J.
        The growing burden of chronic disease in America.
        Public Health Rep. 2004; 119: 263-270
        • Braunstein J.B.
        • Anderson G.F.
        • Gerstenblith G.
        • et al.
        Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure.
        J Am Coll Cardiol. 2003; 42: 1226-1233
        • Landis J.R.
        • Koch G.G.
        The measurement of observer agreement for categorical data.
        Biometrics. 1977; 33: 159-174
        • National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
        Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
        Circulation. 2002; 106: 3143-3421
        • World Health Organization (WHO)
        Nutritional anemias: report of a WHO scientific group.
        World Health Organ Tech Rep Ser. 1968; 405: 1
      1. Obesity: preventing and managing the global epidemic.
        World Health Organ Tech Rep Ser. 2000; 894 (1-253): i-xii
      2. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report.
        Obes Res. 1998; 6: 51S-209S
        • Levey A.S.
        • Coresh J.
        • Greene T.
        • et al.
        Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.
        Ann Intern Med. 2006; 145: 247-254
        • Levey A.S.
        • Coresh J.
        • Balk E.
        • et al.
        National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.
        Ann Intern Med. 2003; 139: 137-147
        • Cerner Multum, Inc.
        Lexicon.
        (Accessed March 12, 2010)
        • Research Triangle Institute
        SUDAAN Language Manual, Release 10.0.
        Research Triangle Institute, Research Triangle Park, NC2008
        • Bouchard J.L.
        • Aurigemma G.P.
        • Goldberg R.J.
        • et al.
        Heart failure in the “oldest old”: clinical and echocardiographic insights.
        Am J Geriatr Cardiol. 2007; 16: 236-242
        • Lee D.S.
        • Mamdani M.M.
        • Austin P.C.
        • et al.
        Trends in heart failure outcomes and pharmacotherapy: 1992 to 2000.
        Am J Med. 2004; 116: 581-589
        • Zhang J.X.
        • Rathouz P.J.
        • Chin M.H.
        Comorbidity and the concentration of healthcare expenditures in older patients with heart failure.
        J Am Geriatr Soc. 2003; 51: 476-482
        • Gure T.R.
        • Kabeto M.U.
        • Blaum C.S.
        • Langa K.M.
        Degree of disability and patterns of caregiving among older Americans with congestive heart failure.
        J Gen Intern Med. 2008; 23: 70-76
        • Foot D.K.
        • Lewis R.P.
        • Pearson T.A.
        • Beller G.A.
        Demographics and cardiology, 1950-2050.
        J Am Coll Cardiol. 2000; 35: 66B-80B
        • Heiat A.
        • Gross C.P.
        • Krumholz H.M.
        Representation of the elderly, women, and minorities in heart failure clinical trials.
        Arch Intern Med. 2002; 162: 1682-1688
        • Duncan A.K.
        • Vittone J.
        • Fleming K.C.
        • Smith H.C.
        Cardiovascular disease in elderly patients.
        Mayo Clin Proc. 1996; 71: 184-196
        • Masoudi F.A.
        • Gross C.P.
        • Wang Y.
        • et al.
        Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States, 1998-2001.
        Circulation. 2005; 112: 39-47
        • Desai M.M.
        • Bruce M.L.
        • Desai R.A.
        • Druss B.G.
        Validity of self-reported cancer history: a comparison of health interview data and cancer registry records.
        Am J Epidemiol. 2001; 153: 299-306
        • Harlow S.D.
        • Linet M.S.
        Agreement between questionnaire data and medical records.
        Am J Epidemiol. 1989; 129: 233-248
        • Okura Y.
        • Urban L.H.
        • Mahoney D.W.
        • et al.
        Agreement between self-report questionnaires and medical record data was substantial for diabetes, hypertension, myocardial infarction and stroke but not for heart failure.
        J Clin Epidemiol. 2004; 57: 1096-1103
        • Schocken D.D.
        • Arrieta M.I.
        • Leaverton P.E.
        • Ross E.A.
        Prevalence and mortality rate of congestive heart failure in the United States.
        J Am Coll Cardiol. 1992; 20: 301-306