Abstract
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.
In the United States, African Americans living in low‐resource 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, 8, 9, 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 nonadherence, suggesting that the expansion of insurance coverage may narrow the gap in mortality disparities.11, 12, 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.
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.
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, 17, 18, 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 pill‐taking behavior. Table 1 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 pill‐taking 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.
Table 1.
Survey Questions, Variable Labels, and Definition of Nonadherence
| Variable Label | Survey Question | Answer Indicating Nonadherence |
|---|---|---|
| Adherence measures | ||
| Missed medication prior to admission | “Had you missed taking your blood pressure pills before you came into the hospital?” | Yes |
| Nonadherent: prescription refill | “On average, how many times a year do you run out of your pills for at least a day or two?” | Three or more times |
| Nonadherent: pill taking | “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 | “Do you ever miss your blood pressure pills because of side effects?” | Yes |
| Forget to take medicine | “Do you ever forget to take your medicine?” | Yes |
| Blood pressure pills don't help | “Do you ever miss your medication because you don't think that they are helping you?” | Yes |
| Can't find doctor to prescribe | “Do you ever miss your medication because you can't find a doctor to prescribe it?” | 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 |
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 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 log‐rank 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 3). 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).
Table 3.
Baseline Characteristics Among 187 African Americans Admitted to an Urban Hospital With Severe, Poorly Controlled Hypertension
| Characteristics | Overall (N=187) |
|---|---|
| Died | 89 (47.6) |
| Demographics | |
| Age, mean (SD), y | 51.0 (12.1) |
| Women | 102 (54.6) |
| Finished high school or equivalenta | 99 (53.2) |
| Currently employed full or part‐time | 55 (29.4) |
| Currently married | 47 (25.1) |
| Uninsuredb | 64 (34.2) |
| Self‐reported per‐capita monthly income, mean (SD), $c | 562.4 (754.9) |
| Disease characteristics | |
| Duration of hypertension diagnosis, mean (SD), yd | 14.5 (11.9) |
| Systolic blood pressure, mean (SD), mm Hg | 201.8 (18.7) |
| Diastolic blood pressure, mean (SD), mm Hg | 122.9 (13.9) |
| Comorbidities | |
| End‐stage renal disease | 28 (15.0) |
| HIV | 11 (5.9) |
| APR‐DRG risk of mortality | |
| Level 1 “minor” | 79 (42.3) |
| Level 2 “moderate” | 68 (36.4) |
| Level 3 “major” | 36 (19.3) |
| Level 4 “extreme” | 4 (2.1) |
| APR‐DRG disease complexity scores | |
| Level 1 “minor” | 17 (9.1) |
| Level 2 “moderate” | 95 (50.8) |
| Level 3 “major” | 66 (35.3) |
| Level 4 “extreme” | 9 (4.8) |
| Substance use | |
| Current tobacco use | 97 (51.9) |
| Current heavy alcohol usee | 24 (12.8) |
| Current heroin and/or cocaine usef | 59 (31.6) |
| Adherenceg | |
| Missed medications prior to admission | 136 (72.7) |
| Nonadherent: prescription refill | 60 (32.1) |
| Nonadherent: pill taking | 80 (42.8) |
Abbreviations: APR‐DRG, All Patient Refined Diagnostic Related Groups; HIV, human immunodeficiency virus; SD, standard deviation. Values are expressed as number (percentage) unless otherwise indicated. aPercentage was calculated for 186 participants since high‐school status was missing in one person (<1%). bInsurance status defined through a combination of self‐report, chart review, and hospital billing data. cSelf‐reported per‐capita monthly income based on 169 participants (18 missing, <10%). dSelf‐reported duration of hypertension diagnosis based on 185 participants (2 missing, 1%). eCurrent heavy alcohol use defined as greater than one drink per day for women and two drinks per day for men by self‐report. fCurrent heroin and/or cocaine used defined as use of either substance within 2 weeks of hospital admission by self‐report or positive urine toxicology. gSee Table 1 for survey questions and definitions.
Factors related to nonadherence were assessed using logistic regression with separate models fit for each outcome (ie, the three nonadherence variables) (Table 5). 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.
Table 5.
Reasons for Medication Nonadherence by Adherence Status Among 187 African Americans Admitted to an Urban Hospital With Severe, Poorly Controlled Hypertension a
| Characteristics | Missed Medication Prior to Admission, No. (%) | Prescription Refill, No. (%) | Pill Taking, No. (%) | |||
|---|---|---|---|---|---|---|
| No | Yes | Adherent | Nonadherent | Adherent | Nonadherent | |
| Access to care variables | ||||||
| Medical insuranceb | ||||||
| None | 8 (15.7) | 56 (41.2) | 30 (23.6) | 34 (56.7) | 33 (30.8) | 31 (38.8) |
| No medication coverage | 3 (5.9) | 12 (8.8) | 11 (8.7) | 4 (6.7) | 7 (6.5) | 8 (10.0) |
| Medication coverage with copays | 21 (41.2) | 35 (25.7) | 46 (36.2) | 10 (16.7) | 40 (37.4) | 16 (20.0) |
| Full medication coverage | 19 (37.3) | 33 (24.3) | 40 (31.5) | 12 (20.0) | 27 (25.2) | 25 (31.3) |
| Can't afford medicationsc | 8 (15.7) | 64 (51.6) | 40 (31.5) | 32 (66.7) | 41 (38.3) | 31 (45.6) |
| Can't find doctor to prescribed | 3 (5.9) | 22 (17.9) | 17 (13.4) | 8 (17.0) | 12 (11.3) | 13 (19.1) |
| Can't get to pharmacyc | 8 (15.7) | 24 (19.4) | 20 (15.8) | 12 (25.0) | 18 (16.8) | 14 (20.6) |
| Knowledge, attitudes, and beliefs | ||||||
| Hypertension knowledge, <80% correcte | 13 (25.5) | 37 (27.2) | 32 (25.2) | 18 (30.0) | 21 (19.6) | 29 (36.3) |
| Experience side effectsd | 9 (17.7) | 23 (18.7) | 23 (18.1) | 9 (19.2) | 12 (11.3) | 20 (29.4) |
| Forget to take medicinec | 16 (31.4) | 55 (44.5) | 56 (44.1) | 15 (31.3) | 33 (30.8) | 38 (55.9) |
| Blood pressure pills don't helpf | 6 (11.8) | 19 (15.6) | 16 (12.7) | 9 (19.2) | 10 (9.4) | 15 (22.4) |
| Take pills too many times per dayc | 1 (2.0) | 15 (12.1) | 12 (9.5) | 4 (8.3) | 5 (4.7) | 11 (16.2) |
aSee Table 1 for survey questions and definitions. bInsurance status defined through a combination of self‐report, chart review, and review of hospital billing data. cPercentages were calculated for 175 participants because variables were missing in 12 persons (6.4%). dPercentages were calculated for 174 participants because variables were missing in 13 persons (7.0%). eHypertension knowledge defined via a set of eight true/false questions. fPercentage was calculated for 173 participants because variable was missing in 14 persons (7.5%).
Sixteen participants (8.6%) were missing data for at least one of the seven variables describing reasons for nonadherence and one person (<1%) was missing high‐school status (Tables 2 and 4). In order to reduce bias associated with missing data, we used multiple imputation to generate estimates of missing values.23, 24 The missing variables were treated as the outcome and all nonmissing variables in Table 2 were used as predictors. The outcome was modeled by the combination of mortality status and time to censoring, which was represented by the standard estimate of the cumulative hazard function.25 Based on this model, 10 datasets were generated with imputed values for the missing data.23 Cox proportional hazards regression and logistic regression were then performed in each imputed dataset and combined using standardized statistical methods for multiple imputation.23 In order to assess the impact of imputation on these estimates, we also analyzed a complete case dataset, excluding all participants missing data in any of the covariates. These results were similar to those obtained using the imputed data and are not reported.
Table 2.
Distribution of Combinations of Adherence Variables
| Missed Medications Prior to Admission, 72% (136) | Nonadherence: Prescription Refill, 32% (60) | Nonadherence: Pill Taking, 43% (80) | No. (%), Total: 187 |
|---|---|---|---|
| O | O | O | 36 (19) |
| X | O | O | 52 (28) |
| O | X | O | 2 (1) |
| O | O | X | 7 (4) |
| X | X | O | 17 (9) |
| O | X | X | 6 (3) |
| X | O | X | 32 (17) |
| X | X | X | 35 (19) |
Table 4.
Medication Nonadherence a and Mortality Among 187 African Americans Admitted to an Urban Hospital With Severe, Poorly Controlled Hypertension b
| Type of Nonadherence | Modelc | |||
|---|---|---|---|---|
| 1 | 2 | 3 | 4 | |
| Missed medication prior to admission | 1.17 (0.73, 1.87) | 1.21 (0.75, 1.94) | 1.14 (0.71, 1.84) | 1.26 (0.78, 2.06) |
| Nonadherence: prescriptions | 1.42 (0.92, 2.20) | 1.51 (0.97, 2.35) | 1.43 (0.91, 2.23) | 1.63 (1.02, 2.59) |
| Nonadherence: pill taking | 1.66 (1.09, 2.54) | 1.77 (1.15, 2.70) | 1.77 (1.16, 2.71) | 1.80 (1.18, 2.76) |
aSee Table 1 for definitions. bValues are presented as hazard ratios (95% confidence intervals) and Columns represent statistical models. cModel 1 adjusted for age, sex, and disease severity (mortality risk and disease complexity). Model 2 further adjusts for completion of high school and employment status. Model 3 further adjusts for heroin and/or cocaine use. Model 4 further adjusts for insurance status. Bold values indicate P<.05.
All statistical analyses were performed using Stata 11 (StataCorp 2009, Stata: Release 11, Statistical Software, College Station, TX).
Results
A total of 187 African Americans with poorly controlled hypertension were recruited into the study. The median age at study entry was 48.4 years (interquartile range [IQR], 43.1–57.9; Table 3). Among participants, 54.6% were women, 53.5% had finished high school or equivalent, and only 29% were employed full‐ or part‐time. Mean SBP and DBP were 201.9 (standard deviation [SD] 18.6) and 122.3 (SD 12.9) mm Hg, respectively. Fifteen percent had end‐stage renal disease and 6% were positive for the human immunodeficiency virus (HIV). The APR‐DRG risk of mortality score was greater than level 1 in 57.7% of patients and disease complexity score was greater than level 1 in 90.9% of patients. More than one third were uninsured. Substance use was common, with 51.9% of patients being current smokers and a third who had used heroin, cocaine, or both within 2 weeks of admission. Adherence levels were poor, as 72.7% had missed their medication prior to admission, 42.8% reported missing at least one dose of medication in a typical week, and almost a third reported having run out of their medications for a day or more at least three times per year. About 19% of patients reported all three nonadherence measures and another 19% did not report nonadherence of any kind (Table 5).
There were 89 deaths during 1053 observed patient‐years from the time of the index discharge (median, 6.1 years/patient), yielding a 47.6% mortality rate. Median age at death was 54.4 years (IQR, 45.4–63.5). The two leading causes of death were CVD (38 deaths, 42.7%) and end‐stage renal disease (ESRD; 16 deaths, 18.0%).
Nonadherence was associated with increased risk of death. Those who reported missing their BP pills at least once per week were nearly twice as likely to die over follow‐up in models adjusted for age, sex, disease severity, completion of high school, employment status, heroin and/or cocaine use, and insurance status (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.18–2.76; Figure, Table 4). Those who ran out of their medications three or more times per year tended to have a higher risk of death, and this association was significant in the fully adjusted model (HR, 1.63; 95% CI, 1.08–2.73; Table 3, model 4). Having missed medications prior to admission was not significantly associated with increased mortality risk. In separate analyses, adjustment for a diagnosis of ESRD had no appreciable effect on the risk estimates. In analyses excluding patients with ESRD, there was only modest attenuation of the estimates (data not shown).
Figure 1.
Survival by medication adherence status among 187 African Americans admitted to an urban hospital with severe, poorly controlled hypertension.
The prevalence of factors related to poor access to care and to treatment ambivalence is described in Table 5. With regard to access to care, 34% were uninsured and 41% had difficulty in affording medications. Fewer study participants had difficulty in finding a doctor (14%) or getting to the pharmacy (18%). With regard to hypertension knowledge, attitudes, and beliefs, 27% answered fewer than 80% of standard hypertension knowledge questions correctly, 41% reported forgetting to take their medication, 18% reported experiencing side effects, 15% felt that the pills were not helping, and 9% felt that they were taking too many pills per day.
Factors related to nonadherence depended on the type of nonadherence. Sicker patients (disease severity level 3 and 4) tended to be less likely to have missed medications prior to admission (OR, 0.36; 95% CI, 0.12–1.11; Table 6), suggesting that disease severity, rather than nonadherence, was responsible for a portion of the admissions. However, disease severity was not associated with the tendency to run out of medications or to miss medications in a typical week. Poor access to care was strongly associated with nonadherence (Table 6). Specifically, those who were uninsured were more likely to have missed medications prior to admission (OR, 2.90; 95% CI, 1.05–8.00) and to have run out of medications (OR, 4.51; 95% CI, 1.76–11.5). Those with self‐reported difficulty in affording medications were also more likely to have missed medications prior to admission (OR, 4.90; 95% CI, 2.01–12.0) and to run out of medications (OR, 4.12; 95% CI, 1.88–9.03). In contrast, access measures such as difficulty in affording medications were not associated with the tendency to miss medications in a typical week or with mortality (Table 6 and Table S1).
Table 6.
Factors Associated With Medication Nonadherence Among 187 African Americans Admitted to an Urban Hospital With Severe, Poorly Controlled Hypertension a
| Missed Medication Prior to Admission, OR (95% CI) | Nonadherence: Prescription Refill, OR (95% CI) | Nonadherence: Pill Taking, OR (95% CI) | |
|---|---|---|---|
| Age (per 10 y) | 0.83 (0.63, 1.10) | 1.11 (0.83, 1.47) | 0.99 (0.76, 1.30) |
| Men (women as reference) | 1.19 (0.59, 2.40) | 1.57 (0.79, 3.11) | 0.54 (0.28, 1.04) |
| Disease characteristics | |||
| Heroin and/or cocaine use | 1.69 (0.77, 3.69) | 1.50 (0.72, 3.11) | 0.72 (0.36, 1.47) |
| Mortality risk category | |||
| Level 1 “minor” | Reference | Reference | Reference |
| Level 2 “moderate” | 0.59 (0.25, 1.40) | 0.99 (0.43, 2.29) | 1.00 (0.46, 2.21) |
| Level 3/4 “major” and “extreme” | 0.36 (0.12, 1.11) | 1.04 (0.32, 3.37) | 0.73 (0.24, 2.16) |
| P value for trend | .202 | .994 | .797 |
| Disease complexity category | |||
| Level 1 “minor” | Reference | Reference | Reference |
| Level 2 “moderate” | 0.40 (0.08, 2.03) | 0.70 (0.21, 2.37) | 2.35 (0.68, 8.16) |
| Level 3/4 “major” and “extreme” | 0.45 (0.08, 2.64) | 0.79 (0.19, 3.29) | 3.37 (0.82, 13.9) |
| P value for trend | .537 | .833 | .242 |
| Access to care variables | |||
| Insurance status | |||
| Insured with full medication coverage | Reference | Reference | Reference |
| Insured with medication copay | 1.04 (0.44, 2.44) | 1.05 (0.38, 2.96) | 0.40 (0.17, 0.98) |
| Insured without medication coverage | 2.48 (0.59, 10.4) | 1.01 (0.24, 4.17) | 1.09 (0.31, 3.79) |
| Uninsured | 2.90 (1.05, 8.00) | 4.51 (1.76, 11.5) | 0.52 (0.21, 1.29) |
| P value for trend | .103 | .002 | .169 |
| Can't afford medications | 4.90 (2.01, 12.0) | 4.12 (1.88, 9.03) | 0.77 (0.37, 1.59) |
| Can't find doctor to prescribe | 2.41 (0.66, 8.73) | 1.02 (0.40, 2.59) | 1.67 (0.66, 4.21) |
| Can't get to pharmacy | 1.10 (0.43, 2.78) | 1.64 (0.70, 3.86) | 0.94 (0.40, 2.18) |
| Knowledge, attitudes, and beliefs | |||
| Hypertension knowledge (fewer than 80% correct) | 0.78 (0.35, 1.77) | 0.91 (0.42, 1.95) | 2.97 (1.39, 6.32) |
| Experience side effects | 0.86 (0.34, 2.17) | 0.68 (0.28, 1.64) | 3.44 (1.47, 8.03) |
| Forget to take medicine | 1.66 (0.78, 3.52) | 0.32 (1.44, 0.71) | 3.62 (1.78, 7.34) |
| Blood pressure pills don't help | 1.19 (0.41, 3.48) | 1.26 (0.50, 3.16) | 2.78 (1.09, 7.09) |
| Take pills too many times per day | 7.15 (0.86, 59.7) | 0.42 (0.12, 1.46) | 3.82 (1.16, 12.5) |
aAdjusting for disease severity and other adherence factors. Bold values indicates P<.05.
In contrast, hypertension knowledge, attitudes, and beliefs were not associated with missing medications prior to admission or with the tendency to run out of medications. However, hypertension knowledge, attitudes, and beliefs were associated with usual pill‐taking behavior (Table 6). Missing medications in a typical week was strongly associated with low hypertension knowledge (OR, 2.97; 95% CI, 1.39–6.32), the experience of side effects (OR, 3.44; 95% CI, 1.47–8.03), forgetting to take medications (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) or that they have to be taken too many times per day (OR, 3.82; 95% CI, 1.16–12.5). Although nonsignificant, the experience of side effects and feeling that medications needed to be taken too many times per day were also associated with mortality (HR, 1.59; 95% CI, 0.92–2.73; and 1.67; 95% CI, 0.86–3.21; respectively; Table S1).
Discussion
Among urban African Americans admitted with severe, poorly controlled hypertension, missing medications prior to admission was common (70%) and long‐term mortality was high, approaching 50% at 5 years. Nonadherence to medications was a strong predictor of long‐term mortality independent of disease severity and other risk factors.
Hypertension is the primary cause of disparities in CVD mortality between African Americans and European Americans in the United States and a major cause of the disparity in all‐cause mortality.4, 8 Insufficient treatment of hypertension, due in part to nonadherence, may be responsible for a major portion of this disparity.3 Few data are available, however, linking medication nonadherence with health outcomes in hypertensive patients. Recently, Muntner and colleagues found that low medication adherence was associated with incident stroke symptoms among hypertensive patients.26 In addition, Bailey and colleagues27 found an association between nonadherence and increased CVD mortality among hypertensive Medicaid beneficiaries using administrative data. Greater adherence by one pill per day per week for a once‐a‐day dosing schedule was associated with a 7% lower hazard of death. Recently, Chowdhury and colleagues28 performed a systematic review and meta‐analysis of prospective studies demonstrating a strong and consistent association of nonadherence with mortality for both antihypertensive agents and statins. Our findings support the notion that nonadherence is a major risk factor for cardiovascular mortality in African American patients with hypertension. Furthermore, we examined dimensions of nonadherence that cannot be assessed using administrative data and found that both the tendency to miss medication doses and the tendency to run out of prescriptions increase the risk of dying by 1.6 to 1.8 times. In contrast, missing medications prior to admission was not associated with mortality, likely reflecting the stronger effect of daily adherence behaviors relative to nonadherence at one point in time.
We next examined factors related to nonadherence, specifically measures of access to care, hypertension knowledge, forgetfulness, the experience of side effects, and attitudes about medications. Poor access to medications, as reflected by lower levels of insurance coverage and self‐reported difficulty in paying for medications, was common and associated with higher odds of missing medications prior to admission and with running out of prescriptions. These findings are congruent with prior work demonstrating the strong and consistent association of poor access with nonadherence.29, 30, 31, 32 Moreover, these studies demonstrate that in low‐resource communities, even modest copays can have a large and important impact on medication adherence.11, 33, 34, 35, 36 We recently showed that under‐insurance is associated with death among patients with CVD discharged from one of three Maryland hospitals, independent of ethnicity and neighborhood‐level income.22 A portion of this increased risk may be mediated through nonadherence because of inability to afford care. Therefore, a key implication for health reform is to maximize medication coverage and to minimize copays, which may be particularly important for residents of low resource communities.
Measures of access to care were not associated with the tendency to miss medication doses in a typical week, the measure of nonadherence most strongly associated with death. Factors related to missing medication doses included lower hypertension knowledge, forgetfulness, the experience of side effects, and attitudes about medications. These attitudes included feeling that the medications were not helping or that one has to take too many pills per day. These results are consistent with prior work demonstrating the strong association between adherence and familiarity with hypertension etiology, consequences, and approaches to management.37, 38, 39, 40 Other studies support the relationship between pill‐taking nonadherence and forgetfulness,41 the experience of side effects,42 and attitudes and beliefs regarding the effectiveness and burden of medications.31, 38 The confluence of these factors may lead to treatment ambivalence and, therefore, incomplete adherence to medications, even among patients with sufficient access to care. These results are important since improved access to care may not be a sufficient remedy for mortality disparities caused by hypertension.
Study Limitations
There are several important limitations to this study. First, self‐reported adherence data are inherently imperfect. Our adherence measures, however, were based on previously validated instruments and performed well relative to biological markers of adherence in a subgroup of patients. Moreover, the specificity of the association between types of risk factors for nonadherence and dimensions of nonadherence support the validity of the measures and findings. Second, we measured adherence at only one point in time and, therefore, could not account for changing level of adherence over time. It is notable, however, that a single measure of adherence was strongly associated with mortality years out from the index assessment. Third, missing data could have biased our results. This bias was mitigated, however, through the use of multiple imputation methods, which provides conservative, nonbiased estimates of missing values. Fourth, our study focused on a previously understudied and severely affected segment of the US population admitted to one urban hospital with poorly controlled hypertension. Therefore, these results may not generalize to other populations. Fifth, our sample size was small, which decreased the precision of our estimates and decreased our power to detect associations. Finally, while nonadherence to medications is associated with mortality, a portion of its impact is likely caused by other health‐related behaviors, including adherence to nonpharmacologic measures such as lifestyle modification and self‐management of other illnesses such as diabetes. Efforts to improve medication ambivalence may also have a positive impact on these correlated health behaviors.
Conclusions
Given the higher prevalence and greater impact of hypertension on mortality in African Americans, improved BP control could greatly reduce the disparity in survival attributed to CVD.43, 44 We found that hypertensive, low‐income African Americans from urban centers are at high risk of death after admission for severe, poorly controlled hypertension. Nonadherence, particularly pill‐taking behavior, was a strong, independent predictor of mortality. Measures of access to care, as well as factors related to treatment ambivalence, were associated with dimensions of medication nonadherence. Specifically, the tendency to run out of medications was related to access but was not related to factors contributing to ambivalence. In contrast, missing medications, a strong predictor of mortality, was not related to access but was closely associated with treatment ambivalence. Taken together, these data suggest that the greater access to care afforded by health care reform is a necessary but insufficient remedy to the disparities in cardiovascular mortality experienced by urban African Americans. To achieve its full promise, health reform must also address treatment ambivalence among urban African Americans with hypertension. The Affordable Care Act, through the Centers for Medicare and Medicaid Services Health Innovation Award mechanism, is enabling many groups including ours to develop novel care delivery approaches addressing these long‐standing disparities among low‐income urban populations. The combination of improved access to care and attention to factors related to treatment ambivalence may help reduce the seemingly intractable burden of early mortality among low‐income urban residents.
Funding
Funding for this study was provided by the National Institutes of Health, the American Heart Association, and by the Johns Hopkins Medical Institution General Clinical Research Center. The funding source had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Supporting information
Table S1. Association of access and ambivalence factors with mortality among 187 African Americans admitted to an urban hospital with severe, poorly controlled hypertension, adjusting for age, sex, and disease severity.
J Clin Hypertens (Greenwich). 2015;17:614–621. DOI: 10.1111/jch.12562. © 2015 Wiley Periodicals, Inc.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1. Association of access and ambivalence factors with mortality among 187 African Americans admitted to an urban hospital with severe, poorly controlled hypertension, adjusting for age, sex, and disease severity.