ORIGINAL
PAPER
Access to Care, Treatment Ambivalence, Medication Nonadherence, and Long-Term Mortality Among Severely Hypertensive African Americans: A Prospective Cohort Study J. Hunter Young, MD, MHS;1,2 Derek Ng, MHS;2 Chidinma Ibe, PhD;3 Kristina Weeks, MS;4 Daniel J. Brotman, MD;1 Sydney Morss Dy, MD, MSc;3 Frederick L. Brancati, MD, MHS;† David M. Levine, MD, ScD;1,5 Michael J. Klag, MD, MPH1,2,3 From the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD;1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;2 Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;3 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD;4 and Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD5
African Americans living in poor neighborhoods bear a high burden of illness and early mortality. Nonadherence may contribute to this burden. In a prospective cohort study of urban African Americans with poorly controlled hypertension, mortality was 47.6% over a median follow-up of 6.1 years. Patients with pill-taking nonadherence were more likely to die (hazard ratio, 1.80; 95% confidence interval [CI], 1.18–2.76) after adjustment for potential confounders. With regard to factors related to nonadherence, poor access to care such as difficulty paying for medications was associated with prescription refill nonadherence (odds ratio [OR], 4.12; 95% CI, 1.88–9.03). Pill-taking nonadherence was not
associated with poor access to care; however, it was associated with factors related to treatment ambivalence including lower hypertension knowledge (OR, 2.97; 95% CI, 1.39–6.32), side effects (OR, 3.44; 95% CI, 1.47–8.03), forgetfulness (OR, 3.62; 95% CI, 1.78–7.34), and feeling that the medications do not help (OR, 2.78; 95% CI, 1.09–7.09). These data suggest that greater access to care is a necessary but insufficient remedy to the disparities experienced by urban African Americans with hypertension. To achieve its full promise, health reform must also address treatment ambivalence. J Clin Hypertens (Greenwich). 2015;17:614–621. ª 2015 Wiley Periodicals, Inc.
In the United States, African Americans living in lowresource communities bear a high burden of illness and early death. By one estimate, life expectancy in these communities is 14 to 18 years less than that of other ethnic groups living in healthier neighborhoods.1,2 A major portion of this disparity is attributed to hypertension-related cardiovascular disease (CVD).3,4 Hypertension is the predominant cause of disparity in CVD mortality and is a major source of disparities in all-cause mortality.5,6 Hypertension’s earlier onset, higher prevalence, greater severity, and higher rate of insufficient treatment among African Americans contribute to its impact on this disparity.7–10 This greater burden of CVD mortality among African Americans is not inevitable. Effective treatment of hypertension can delay and potentially prevent premature deaths caused by CVD, thereby narrowing the mortality gap between African Americans in high-risk urban neighborhoods and other Americans. Nonadherence to antihypertensive regimens poses a considerable barrier to the effective control of high blood pressure (BP). Poor access to care is strongly related to nonad-
herence, suggesting that the expansion of insurance coverage may narrow the gap in mortality disparities.11– 13 Improved access to care may be insufficient, however, if patients are ambivalent about taking antihypertensive medication in the first place. The relative impact of access to care and treatment ambivalence, which is influenced by a person’s knowledge, attitudes, and beliefs about hypertension and its treatment, is poorly understood. In order to better understand the factors responsible for hypertension mortality and nonadherence among African Americans living in low-resource, urban communities, we examined the relationship of nonadherence with mortality among low-income African Americans who were initially identified during hospitalization with poorly controlled high BP. We further examined the relationship of access to care and treatment ambivalence with types of medication nonadherence.
†
Deceased.
Address for correspondence: J. Hunter Young, MD, MHS, 2024 East Monument Street, Room 2-625, Baltimore, MD 21212 E-mail: [email protected] Manuscript received: June 11, 2014; revised: January 26, 2015; accepted: January 29, 2015 DOI: 10.1111/jch.12562
614
The Journal of Clinical Hypertension
Vol 17 | No 8 | August 2015
METHODS Study Design, Setting, Participants, and Sampling We investigated the prospective association of adherence with mortality among African Americans with severe, poorly controlled hypertension enrolled in the Inner City Hypertension and Body Organ Damage (ICHABOD) study.14,15 We also assessed factors related to nonadherence utilizing data obtained at the time of enrollment.
Nonadherence and Mortality Among African Americans | Young et al.
We screened all patients admitted to the general medicine wards at the Johns Hopkins Hospital in Baltimore, Maryland, from August 1999 to June 2001 and from February 2002 to December 2004. We identified patients with severe, uncontrolled hypertension, defined as a systolic BP (SBP) ≥180 and a diastolic BP (SBP) ≥110 mm Hg as measured using an automatic oscillatory device on two occasions in the emergency department. Patients were excluded from the study for the following reasons: (1) elevated BP from known secondary causes, (2) age younger than 18 years, (3) nonresidence in Baltimore City, and (4) ethnicity other than African American. Of the 485 patients identified with severe, uncontrolled hypertension, 196 (40%) were excluded because they had an identifiable cause of elevated BP, no previous diagnosis of hypertension, or inability to give consent. Twenty-one patients (4%) died in the hospital prior to discharge. Of the 268 eligible patients, 81 (30%) patients refused, withdrew, never completed the questionnaire, or were discharged prior to contact. Thus, of the eligible patients, 187 were included in this analysis (70% response rate). Measurements Trained interviewers administered a structured questionnaire on admission and reviewed the admission history and physical examination. After discharge, they also reviewed the discharge summary. The questionnaire was modeled after those used in trials conducted in inner-city populations to improve the control of hypertension and diabetes, and was further refined through a pilot study.16–19 The questionnaire assessed history of hypertension, socioeconomic factors, adherence patterns, reasons for nonadherence (if nonadherence was reported), access to care, and knowledge of hypertension and its consequences. Other measurements included insurance coverage (self-reported combined with medical records and hospital billing data) and self-
reported difficulty in obtaining medications. Mortality data, including cause of death, were obtained from the National Death Index. We examined three dimensions of self-reported medication adherence representing distinct aspects of adherence behaviors: missing medications prior to admission (“acute” nonadherence), failure to refill prescription prior to running out of medications, and typical pilltaking behavior. Table I lists the questions and responses indicating nonadherence. Adherence at the time of admission (evaluated by the question “Had you missed taking your BP pills before you came into the hospital?”) was validated by detecting medication in urine utilizing high-performance liquid chromatography in a sample of the study population, as previously reported.15 The question was 90% sensitive and 88% specific for detecting the presence of the antihypertensive medication, indicating that it is a reasonable measure of adherence. The question, “On average, how many times per year do you run out of your pills for at least a day or two?” assessed the failure to refill prescriptions prior to running out of medications. Participants were considered nonadherent if they reported running out of medications, for at least a day or two, three or more times per year. To assess pilltaking behavior, we asked, “On average, how many times per week do you miss taking your BP pills?” A participant was considered nonadherent if he or she reported missing one or more pills per week or if the participant was not currently taking previously prescribed antihypertensive medication. Current illicit drug use was obtained from self-report and biochemical tests of urine. Participants were considered active users of a specific drug if they reported using that drug during the 2 weeks prior to admission or if the urine toxicology test was positive for that drug. Disease severity is an important potential confounder for this analysis given the possible relationship between
TABLE I. Survey Questions, Variable Labels, and Definition of Nonadherence Answer Indicating Variable Label Adherence measures Missed medication prior to
Survey Question
Nonadherence
“Had you missed taking your blood pressure pills before you came into the hospital?”
Yes
admission Nonadherent: prescription refill
“On average, how many times a year do you run out of your pills for at least
Three or more times
Nonadherent: pill taking
a day or two?” “On average, how many times a week do you miss taking your blood pressure pills?”
One or more times
Reasons for nonadherence Can’t afford medications
“Do you ever miss your pills because you can’t afford them?”
Yes
Side effects Forget to take medicine
“Do you ever miss your blood pressure pills because of side effects?” “Do you ever forget to take your medicine?”
Yes Yes
Blood pressure pills don’t help Can’t find doctor to prescribe
“Do you ever miss your medication because you don’t think that they are helping you?” “Do you ever miss your medication because you can’t find a doctor to prescribe it?”
Yes Yes
Can’t get to a pharmacy
“Do you ever miss your medicine because you have trouble getting to the pharmacy to get it?”
Yes
Take pills too many times per day
“Do you ever miss your medicine because you have to take it too many times a day?”
Yes
The Journal of Clinical Hypertension
Vol 17 | No 8 | August 2015
615
Nonadherence and Mortality Among African Americans | Young et al.
disease severity and adherence. Consequently, comorbid illness was assessed through self-report, chart review, and the discharge diagnoses (coded using the International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM]). Disease severity was quantified by two variables, risk of mortality score, and disease complexity score, from the 3M All Patient Refined Diagnostic Related Groups (APR-DRGs) scoring system, V20.20 The APR-DRG risk of mortality scores and disease complexity scores have four categories on an ordinal scale (1=minor, 2=moderate, 3=major, and 4=extreme).21 APR-DRG risk of mortality and disease complexity categories three and four were combined because of the small number of participants in the highest-risk groups. Both complexity and risk of mortality were included for risk adjustment as categorical variables.22 Statistical Analysis There were two stages to the analysis: the first, to examine the relationship between nonadherence and mortality and the second, to identify factors related to nonadherence. Kaplan-Meier survival analyses and logrank tests were performed using data from participants with complete records to compare survival by adherence status. Cox proportional hazards models adjusted for age, sex, and severity of disease were conducted to assess the relative hazard of death associated with nonadherence at the time of admission, nonadherence with refilling prescriptions, and nonadherence with pill taking (Table III). We assessed their relationship with mortality adjusted for age, sex, disease severity represented by disease complexity, and risk of mortality (model 1) and then further adjusted for completion of high school and employment status (model 2), heroin and/or cocaine use (model 3), and insurance status (model 4). Factors related to nonadherence were assessed using logistic regression with separate models fit for each outcome (ie, the three nonadherence variables) (Table V). These models were adjusted for disease severity as well as the other two nonadherence variables. Insurance status was defined as insured with full medication coverage, insured with medication copay, insured without medication coverage, and uninsured. A sensitivity analysis was conducted adjusting for disease severity only and yielded similar results. Sixteen participants (8.6%) were missing data for at least one of the seven variables describing reasons for nonadherence and one person (
PAPER
Access to Care, Treatment Ambivalence, Medication Nonadherence, and Long-Term Mortality Among Severely Hypertensive African Americans: A Prospective Cohort Study J. Hunter Young, MD, MHS;1,2 Derek Ng, MHS;2 Chidinma Ibe, PhD;3 Kristina Weeks, MS;4 Daniel J. Brotman, MD;1 Sydney Morss Dy, MD, MSc;3 Frederick L. Brancati, MD, MHS;† David M. Levine, MD, ScD;1,5 Michael J. Klag, MD, MPH1,2,3 From the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD;1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;2 Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;3 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD;4 and Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD5
African Americans living in poor neighborhoods bear a high burden of illness and early mortality. Nonadherence may contribute to this burden. In a prospective cohort study of urban African Americans with poorly controlled hypertension, mortality was 47.6% over a median follow-up of 6.1 years. Patients with pill-taking nonadherence were more likely to die (hazard ratio, 1.80; 95% confidence interval [CI], 1.18–2.76) after adjustment for potential confounders. With regard to factors related to nonadherence, poor access to care such as difficulty paying for medications was associated with prescription refill nonadherence (odds ratio [OR], 4.12; 95% CI, 1.88–9.03). Pill-taking nonadherence was not
associated with poor access to care; however, it was associated with factors related to treatment ambivalence including lower hypertension knowledge (OR, 2.97; 95% CI, 1.39–6.32), side effects (OR, 3.44; 95% CI, 1.47–8.03), forgetfulness (OR, 3.62; 95% CI, 1.78–7.34), and feeling that the medications do not help (OR, 2.78; 95% CI, 1.09–7.09). These data suggest that greater access to care is a necessary but insufficient remedy to the disparities experienced by urban African Americans with hypertension. To achieve its full promise, health reform must also address treatment ambivalence. J Clin Hypertens (Greenwich). 2015;17:614–621. ª 2015 Wiley Periodicals, Inc.
In the United States, African Americans living in lowresource communities bear a high burden of illness and early death. By one estimate, life expectancy in these communities is 14 to 18 years less than that of other ethnic groups living in healthier neighborhoods.1,2 A major portion of this disparity is attributed to hypertension-related cardiovascular disease (CVD).3,4 Hypertension is the predominant cause of disparity in CVD mortality and is a major source of disparities in all-cause mortality.5,6 Hypertension’s earlier onset, higher prevalence, greater severity, and higher rate of insufficient treatment among African Americans contribute to its impact on this disparity.7–10 This greater burden of CVD mortality among African Americans is not inevitable. Effective treatment of hypertension can delay and potentially prevent premature deaths caused by CVD, thereby narrowing the mortality gap between African Americans in high-risk urban neighborhoods and other Americans. Nonadherence to antihypertensive regimens poses a considerable barrier to the effective control of high blood pressure (BP). Poor access to care is strongly related to nonad-
herence, suggesting that the expansion of insurance coverage may narrow the gap in mortality disparities.11– 13 Improved access to care may be insufficient, however, if patients are ambivalent about taking antihypertensive medication in the first place. The relative impact of access to care and treatment ambivalence, which is influenced by a person’s knowledge, attitudes, and beliefs about hypertension and its treatment, is poorly understood. In order to better understand the factors responsible for hypertension mortality and nonadherence among African Americans living in low-resource, urban communities, we examined the relationship of nonadherence with mortality among low-income African Americans who were initially identified during hospitalization with poorly controlled high BP. We further examined the relationship of access to care and treatment ambivalence with types of medication nonadherence.
†
Deceased.
Address for correspondence: J. Hunter Young, MD, MHS, 2024 East Monument Street, Room 2-625, Baltimore, MD 21212 E-mail: [email protected] Manuscript received: June 11, 2014; revised: January 26, 2015; accepted: January 29, 2015 DOI: 10.1111/jch.12562
614
The Journal of Clinical Hypertension
Vol 17 | No 8 | August 2015
METHODS Study Design, Setting, Participants, and Sampling We investigated the prospective association of adherence with mortality among African Americans with severe, poorly controlled hypertension enrolled in the Inner City Hypertension and Body Organ Damage (ICHABOD) study.14,15 We also assessed factors related to nonadherence utilizing data obtained at the time of enrollment.
Nonadherence and Mortality Among African Americans | Young et al.
We screened all patients admitted to the general medicine wards at the Johns Hopkins Hospital in Baltimore, Maryland, from August 1999 to June 2001 and from February 2002 to December 2004. We identified patients with severe, uncontrolled hypertension, defined as a systolic BP (SBP) ≥180 and a diastolic BP (SBP) ≥110 mm Hg as measured using an automatic oscillatory device on two occasions in the emergency department. Patients were excluded from the study for the following reasons: (1) elevated BP from known secondary causes, (2) age younger than 18 years, (3) nonresidence in Baltimore City, and (4) ethnicity other than African American. Of the 485 patients identified with severe, uncontrolled hypertension, 196 (40%) were excluded because they had an identifiable cause of elevated BP, no previous diagnosis of hypertension, or inability to give consent. Twenty-one patients (4%) died in the hospital prior to discharge. Of the 268 eligible patients, 81 (30%) patients refused, withdrew, never completed the questionnaire, or were discharged prior to contact. Thus, of the eligible patients, 187 were included in this analysis (70% response rate). Measurements Trained interviewers administered a structured questionnaire on admission and reviewed the admission history and physical examination. After discharge, they also reviewed the discharge summary. The questionnaire was modeled after those used in trials conducted in inner-city populations to improve the control of hypertension and diabetes, and was further refined through a pilot study.16–19 The questionnaire assessed history of hypertension, socioeconomic factors, adherence patterns, reasons for nonadherence (if nonadherence was reported), access to care, and knowledge of hypertension and its consequences. Other measurements included insurance coverage (self-reported combined with medical records and hospital billing data) and self-
reported difficulty in obtaining medications. Mortality data, including cause of death, were obtained from the National Death Index. We examined three dimensions of self-reported medication adherence representing distinct aspects of adherence behaviors: missing medications prior to admission (“acute” nonadherence), failure to refill prescription prior to running out of medications, and typical pilltaking behavior. Table I lists the questions and responses indicating nonadherence. Adherence at the time of admission (evaluated by the question “Had you missed taking your BP pills before you came into the hospital?”) was validated by detecting medication in urine utilizing high-performance liquid chromatography in a sample of the study population, as previously reported.15 The question was 90% sensitive and 88% specific for detecting the presence of the antihypertensive medication, indicating that it is a reasonable measure of adherence. The question, “On average, how many times per year do you run out of your pills for at least a day or two?” assessed the failure to refill prescriptions prior to running out of medications. Participants were considered nonadherent if they reported running out of medications, for at least a day or two, three or more times per year. To assess pilltaking behavior, we asked, “On average, how many times per week do you miss taking your BP pills?” A participant was considered nonadherent if he or she reported missing one or more pills per week or if the participant was not currently taking previously prescribed antihypertensive medication. Current illicit drug use was obtained from self-report and biochemical tests of urine. Participants were considered active users of a specific drug if they reported using that drug during the 2 weeks prior to admission or if the urine toxicology test was positive for that drug. Disease severity is an important potential confounder for this analysis given the possible relationship between
TABLE I. Survey Questions, Variable Labels, and Definition of Nonadherence Answer Indicating Variable Label Adherence measures Missed medication prior to
Survey Question
Nonadherence
“Had you missed taking your blood pressure pills before you came into the hospital?”
Yes
admission Nonadherent: prescription refill
“On average, how many times a year do you run out of your pills for at least
Three or more times
Nonadherent: pill taking
a day or two?” “On average, how many times a week do you miss taking your blood pressure pills?”
One or more times
Reasons for nonadherence Can’t afford medications
“Do you ever miss your pills because you can’t afford them?”
Yes
Side effects Forget to take medicine
“Do you ever miss your blood pressure pills because of side effects?” “Do you ever forget to take your medicine?”
Yes Yes
Blood pressure pills don’t help Can’t find doctor to prescribe
“Do you ever miss your medication because you don’t think that they are helping you?” “Do you ever miss your medication because you can’t find a doctor to prescribe it?”
Yes Yes
Can’t get to a pharmacy
“Do you ever miss your medicine because you have trouble getting to the pharmacy to get it?”
Yes
Take pills too many times per day
“Do you ever miss your medicine because you have to take it too many times a day?”
Yes
The Journal of Clinical Hypertension
Vol 17 | No 8 | August 2015
615
Nonadherence and Mortality Among African Americans | Young et al.
disease severity and adherence. Consequently, comorbid illness was assessed through self-report, chart review, and the discharge diagnoses (coded using the International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM]). Disease severity was quantified by two variables, risk of mortality score, and disease complexity score, from the 3M All Patient Refined Diagnostic Related Groups (APR-DRGs) scoring system, V20.20 The APR-DRG risk of mortality scores and disease complexity scores have four categories on an ordinal scale (1=minor, 2=moderate, 3=major, and 4=extreme).21 APR-DRG risk of mortality and disease complexity categories three and four were combined because of the small number of participants in the highest-risk groups. Both complexity and risk of mortality were included for risk adjustment as categorical variables.22 Statistical Analysis There were two stages to the analysis: the first, to examine the relationship between nonadherence and mortality and the second, to identify factors related to nonadherence. Kaplan-Meier survival analyses and logrank tests were performed using data from participants with complete records to compare survival by adherence status. Cox proportional hazards models adjusted for age, sex, and severity of disease were conducted to assess the relative hazard of death associated with nonadherence at the time of admission, nonadherence with refilling prescriptions, and nonadherence with pill taking (Table III). We assessed their relationship with mortality adjusted for age, sex, disease severity represented by disease complexity, and risk of mortality (model 1) and then further adjusted for completion of high school and employment status (model 2), heroin and/or cocaine use (model 3), and insurance status (model 4). Factors related to nonadherence were assessed using logistic regression with separate models fit for each outcome (ie, the three nonadherence variables) (Table V). These models were adjusted for disease severity as well as the other two nonadherence variables. Insurance status was defined as insured with full medication coverage, insured with medication copay, insured without medication coverage, and uninsured. A sensitivity analysis was conducted adjusting for disease severity only and yielded similar results. Sixteen participants (8.6%) were missing data for at least one of the seven variables describing reasons for nonadherence and one person (
