Author + information
- Received January 12, 2013
- Revision received December 2, 2013
- Accepted December 3, 2013
- Published online April 29, 2014.
- Todd M. Brown, MD, MSPH∗∗ (, )
- Jenifer H. Voeks, PhD†,
- Vera Bittner, MD, MSPH∗,
- David A. Brenner, MD‡,
- Mary Cushman, MD, MSc§,
- David C. Goff Jr., MD, PhD‖,
- Stephen Glasser, MD∗,
- Paul Muntner, PhD¶,
- Paul B. Tabereaux, MD# and
- Monika M. Safford, MD∗
- ∗Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
- †Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina
- ‡Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama
- §Department of Medicine, University of Vermont, Burlington, Vermont
- ‖Colorado School of Public Health, Aurora, Colorado
- ¶Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama
- #Huntsville Hospital, Huntsville, Alabama
- ↵∗Reprint requests and correspondence:
Dr. Todd M. Brown, University of Alabama at Birmingham, LHRB 313, 701 19th Street South, Birmingham, Alabama 35294.
Objectives In a nonclinical trial setting, we sought to determine the proportion of individuals with coronary artery disease (CAD) with optimal risk factor levels based on the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation) trial.
Background In the COURAGE trial, the addition of percutaneous coronary intervention (PCI) to optimal medical therapy did not reduce the risk of death or myocardial infarction in stable CAD patients but resulted in more revascularization procedures.
Methods The REGARDS (REasons for Geographic And Racial Differences in Stroke) study is a national prospective cohort study of 30,239 African-American and white community-dwelling individuals older than 45 years of age who enrolled in 2003 through 2007. We calculated the proportion of 3,167 participants with self-reported CAD meeting 7 risk factor goals based on the COURAGE trial: 1) aspirin use; 2) systolic blood pressure <130 mm Hg and diastolic blood pressure <85 mm Hg (<80 mm Hg if diabetic); 3) low-density lipoprotein cholesterol <85 mg/dl, high-density lipoprotein cholesterol >40 mg/dl, and triglycerides <150 mg/dl; 4) fasting glucose <126 mg/dl; 5) nonsmoking status; 6) body mass index <25 kg/m2; and 7) exercise ≥4 days per week.
Results The mean age of participants was 69 ± 9 years; 33% were African American and 35% were female. Overall, the median number of goals met was 4. Less than one-fourth met ≥5 of the 7 goals, and 16% met all 3 goals for aspirin, blood pressure, and low-density lipoprotein cholesterol. Older age, white race, higher income, more education, and higher physical functioning were independently associated with meeting more goals.
Conclusions There is substantial room for improvement in risk factor reduction among U.S. individuals with CAD.
Coronary artery disease (CAD) is highly prevalent in the United States (1). The American Heart Association (AHA) estimates that 15,400,000 Americans have CAD and that CAD accounted for 1 in 6 deaths in the United States in 2009. The total estimated annual direct and indirect cost of CAD in the United States is $195.2 billion (1).
Current guideline recommendations for the management of patients with stable CAD involve intensive risk factor management and anti-ischemic therapies, with revascularization reserved for individuals whose symptoms persist or progress despite intensive medical therapy (2). Despite these recommendations, many patients undergo revascularization, often because of emotional or psychological factors on the part of both patients and physicians (3,4). More than 1 million percutaneous coronary interventions (PCIs) are performed annually in the United States (1). Although estimates vary, it appears that at least one-half of all PCIs in the United States are performed electively (5).
The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial recently demonstrated that, compared with a strategy of PCI plus optimal medical therapy, an initial strategy of optimal medical therapy alone, with PCI reserved for those with refractory angina, had similar rates of death or nonfatal myocardial infarction in individuals with stable CAD who had undergone coronary angiography before randomization (6). Also, over a median follow-up of 4.6 years, only 33% of individuals randomized to the optimal medical therapy group required revascularization (6), suggesting that two-thirds of individuals with stable CAD could potentially avoid PCI during this time period if treated initially with optimal medical therapy alone (7).
Because clinical trial populations tend to be more adherent and health conscious, it is not clear to what extent individuals with stable CAD in the United States achieve the risk factor goals used in the COURAGE trial. Therefore, using data on participants who reported a history of CAD at baseline in the national REGARDS (REasons for Geographic and Racial Differences in Stroke) study, we sought to examine the proportion of individuals with risk factor levels similar to the goals used in the COURAGE trial. Additionally, we examined sociodemographic factors associated with being at these risk factor goals.
The REGARDS study was described in detail previously (8). Briefly, the REGARDS study is a cohort of 30,239 community-dwelling individuals recruited between 2003 and 2007. Although the cohort is currently being followed longitudinally, this analysis uses data that were collected during the baseline examination. The cohort was designed to be balanced on race (white and African American) and sex; the final sample was 42% African Americans and 55% female. Because the primary goal of the REGARDS study is to elucidate regional and racial differences in stroke, residents of the Stroke Belt, located in the southeastern United States, were oversampled such that 20% of the overall cohort was selected from the “buckle” of the Stroke Belt (the coastal plain region of North Carolina, South Carolina, and Georgia), 30% from the rest of the Stroke Belt (the remaining parts of North Carolina, South Carolina, and Georgia plus Alabama, Mississippi, Louisiana, Arkansas, and Tennessee), and 50% from the remaining 40 contiguous states. Individuals were identified by commercially available lists and contacted by mail and telephone. Of those determined to be eligible, 49% agreed to paricipate. Upon enrollment, participants underwent a computer-assisted telephone interview followed by an in-home examination. During the telephone interview, demographic and self-reported medical information was obtained. During the in-home examination, the participant’s blood pressure, height, and weight were measured, and blood and urine samples were collected.
At enrollment, there were a total of 4,245 participants who reported a history of CAD, defined as a self-reported history of myocardial infarction, PCI, or coronary artery bypass graft surgery. Of these participants, 454 with missing data on blood pressure, glucose or lipid values, smoking status, height, weight, or physical activity were excluded. Additionally, 624 individuals who had not fasted for their blood draw were excluded from the primary analysis. This resulted in a final sample size for our primary analyses of 3,167 participants with a self-reported history of prevalent CAD. Individuals excluded from our primary analyses were more likely to be African American (39% vs. 33%, p < 0.001) and less likely to live in the Stroke Buckle (17% vs. 23%, p < 0.001) than those included. Female sex did not differ significantly between those excluded (38%) and those included (35%) (p = 0.16). We conducted additional secondary analyses as described in the following without excluding the 624 individuals who had not fasted for their blood draw (n = 3,791 for these analyses).
Risk factor treatment goals
The risk factor goals used for this analysis were based on those used at the beginning of the COURAGE trial (9,10) and are listed in Table 1. These goals were based on the American College of Cardiology (ACC) and AHA guidelines at the time that the COURAGE trial was designed (9,10) and do not vary significantly from current guideline recommendations (2,11) or the AHA 2020 goals for ideal cardiovascular health (12), as shown in Table 1. Because our intent was to estimate the degree to which optimal risk factor levels are achieved in the general U.S. population in individuals with stable CAD, for our primary analyses, we defined the blood pressure goal as achieving both the systolic and diastolic blood pressure goals, the lipid goal as achieving all 3 lipid goals, and an optimal body mass index as <25 kg/m2. Exercise was defined as intense physical activity, enough to work up a sweat. Aspirin use was determined by participant self-report. Because hemoglobin A1c was not measured in the REGARDS study, we substituted a fasting glucose of <126 mg/dl in place of a hemoglobin A1c of <7% (13). Because some of these goals have higher degrees of evidence to support their use and are easier to achieve than others, we also examined 3 goals in a secondary analysis: aspirin use, blood pressure control, and low-density lipoprotein cholesterol (LDL-C) control (LDL-C <85 mg/dl).
Urban residence was defined based on census tract categories (urban, rural, or mixed). Functional status was assessed by the physical component summary score of the Short Form-12 (14). Kidney function was estimated by the Modification of Diet in Renal Disease equation (15). The presence of depressive symptoms was defined as a score of ≥4 on the 4-item version of the Centers for Epidemiologic Study Depressive Scale (16). Finally, diabetes was defined as a self-reported history of diabetes, the use of diabetes medications, a fasting glucose ≥126 mg/dl, or a nonfasting glucose ≥200 mg/dl.
We first calculated the proportion of participants in the study sample who met each risk factor goal listed in Table 1. Then, we calculated a composite score for each participant reflecting the total number of risk factor goals reached. To determine factors associated with the total number of goals achieved, we constructed a multivariable linear regression model, adjusting for age, sex, race, region of residence, income, education, urban residence, functional status, kidney function, and depressive symptoms. Similar methodology was used for the analyses examining meeting the aspirin, blood pressure, and LDL-C goals.
Additionally, because we required optimal levels of 3 lipid values to achieve the cholesterol goal, a body mass index <25 kg/m2, and a fasting glucose of <126 mg/dl in all participants regardless of their diabetes status in our definition of optimal risk factor levels, we conducted a series of secondary analyses in the 3,167 fasting participants. First, to examine control LDL-C alone, we calculated the proportion of individuals who had an LDL-C level <100, <85, and <70 mg/dl, respectively. Second, we calculated the number of REGARDS participants with a body mass index <30 kg/m2. Third, to investigate glucose control in only those with diabetes, we calculated the proportion of individuals with diabetes at enrollment who had a fasting blood sugar <126 mg/dl. Also, because in our primary analyses, we excluded individuals who were not fasting at the time their blood was drawn, we calculated the number of total risk factor goals reached without excluding the 624 individuals who were nonfasting. For this portion of the analysis, we used a non–high-density lipoprotein cholesterol (HDL-C) level <100 mg/dl as the lipid criterion for all participants, and, for those who were nonfasting, we substituted a glucose level of <200 mg/dl for the glucose criterion in our definitions for risk factor goals (Table 1). All analyses were performed with SAS, version 9.2 (SAS Institute, Cary, North Carolina). All participants provided informed consent to participate, and this study was approved by the institutional review board of each participating university.
The demographic and clinical characteristics of the study sample are shown in Table 2. Participants were a mean 69 ± 9 years of age. Approximately one-third was female and one-third was African American.
The proportion of individuals meeting each risk factor goal is displayed in Figure 1. Nonsmoking status, fasting glucose <126 mg/dl, and the regular use of aspirin were the most frequently met risk factor goals. Overall, 50% of participants met the systolic and diastolic blood pressure goals and ≤25% participants met the physical activity, body mass index, or lipid goals. The total number of risk factor goals met is displayed in Figure 2. Overall, an average of 3.6 ± 1.2 of the 7 total possible risk factor goals was met, whereas the median number of goals met was 4. Nearly all participants met at least 1 risk factor goal. However, less than one-fourth met ≥5 goals, and only 17 of the 3,167 participants (0.5%) met all 7 goals. After multivariable adjustment, older age, white race, higher income, more education, and higher physical functioning were independently associated with meeting more treatment goals (Table 3). REGARDS participants enrolled in 2007 met slightly more risk factor goals (3.8 ± 1.2) than those in previous years (3.5 ± 1.2 in 2003 and 3.6 ± 1.2 in each of years 2004 through 2006, p < 0.01 for each comparison). When examining only the aspirin, blood pressure, and LDL-C goals, 91% of participants met at least 1 of these 3 goals, and 16% met all 3 goals. Male sex, white race, increased income, and more education were independently associated with meeting more treatment goals after multivariable adjustment (Table 4).
In secondary analyses evaluating LDL-C level as a separate goal rather than simply 1 of 3 components of the lipid goal, 57% of individuals had an LDL-C <100 mg/dl, 38% had an LDL-C <85 mg/dl, and 18% had an LDL-C <70 mg/dl. Additionally, 61% of individuals had a body mass index <30 kg/m2 at enrollment, and 44% of individuals with diabetes had a fasting glucose <126 mg/dl. After including individuals who had not fasted, the average number of risk factors goals met was still 3.6 ± 1.2 with a median number of goals met of 4. When evaluating non–HDL-C as a separate measure, 23% of individuals had a non–HDL-C <100 mg/dl.
In this analysis of community-dwelling individuals with self-reported CAD, we demonstrate that, on average, 4 of a possible 7 risk factor goals studied in the COURAGE trial were met, and <1% of individuals achieved all 7 risk factor goals. Our results expand on data recently published from the National Cardiovascular Data Registry that focused on the intensity of pharmacological management in patients undergoing elective PCI (17). Although risk factor levels were not reported, less than one-half of all patients undergoing elective PCI for stable angina were receiving pharmacological therapy with antiplatelet agents, beta-blockers, and statins before undergoing PCI both before and after publication of the COURAGE trial (17).
The achievement of risk factor goals that we observed in this population-based sample was considerably lower than what participants in the COURAGE trial achieved (10). At its conclusion, 96% of COURAGE trial participants were taking antiplatelet therapy compared with 77% of our study sample who reported regular aspirin use; 66% were exercising at least 150 min/week compared with 25% of our study sample who reported exercising ≥4 days/week; and approximately 60% reached the blood pressure goal compared with 50% of our study sample (10). Smoking rates were similar with 19% of COURAGE participants smoking at the end of the study compared with 15% of our study sample (10). This suggests that there is substantial opportunity to improve the risk factor profiles of individuals with CAD if optimal medical therapy, similar to that used in the COURAGE trial, were adopted on a wider scale. The COURAGE trial was not successful in reducing obesity, as the mean body mass index in the COURAGE trial increased from 28.8 ± 0.13 kg/m2 to 29.3 ± 0.23 kg/m2 during the course of the study, which was similar to the mean body mass index (29.4 ± 5.8 kg/m2) present in REGARDS participants with CAD (10). It is also noteworthy that in the COURAGE trial, not all participants achieved the study’s goals either. A recent analysis of risk factor control among diabetic participants in 3 clinical trials, including COURAGE, demonstrated that risk factor goal attainment was poor even in a clinical trial setting (18). These data suggest that although marked improvement can be made in risk factor control for U.S. adults with CAD, achieving all of these risk factor goals may be unrealistic for many people.
Similar to the findings in the COURAGE trial (9), multiple previous studies have demonstrated no reduction in death or myocardial infarction in stable CAD patients undergoing PCI compared with those medically managed (19–23). However, these studies all suggest that the frequency and severity of anginal symptoms are reduced with PCI (19–23). In the COURAGE trial, individuals randomized to the optimal medical therapy–only arm received PCI for angina refractory to medical treatment or objective evidence of worsening ischemia on noninvasive testing. With this strategy, one-third of individuals required PCI over a median follow-up of 4.6 years. In the COURAGE trial, the added cost of PCI was $10,000 without a significant increase in life-years or quality-adjusted life-years gained (24). Furthermore, PCI as an initial management strategy was associated with a cost of $206,229 per quality-adjusted life-year gained (24). A recent publication from 10 institutions in the Northeastern United States suggests that at least in this consortium, the number of PCIs performed for stable angina has decreased since the publication of the COURAGE trial (25). These authors were unable to determine whether the observed decline in PCI was related to changes in risk factor modification. However, given the low number of risk factor targets achieved in the current study, efforts targeted toward improving risk factor control in CAD patients may result in substantial reductions in healthcare costs.
Previous studies have examined compliance with secondary prevention recommendations but were limited to specific populations or the examination of a limited number of risk factors (26–30). Muntner et al. (28) demonstrated using data from 1999 through 2010 from the National Health and Nutrition Examination Survey that many high-risk individuals had not achieved lipid goals. Ho et al. (29) examined achievement of lipid and blood pressure goals in Veterans Affairs facilities; only approximately one-half of patients were at goal LDL-C levels and less than one-half were at goal blood pressures. In the Duke Databank for Cardiovascular Disease from 1995 to 2002, Newby et al. (30) reported on changes in adherence to pharmacological therapies but not actual risk factor goals. Use of aspirin therapy in 2002 was 83% in their study (30), similar to the rate in the REGARDS study. Our study extends these aforementioned findings by examining a wide range of risk factor treatment goals in a large, nationwide, biracial community-based population.
Our study also provides insight into which types of patients are not achieving these risk factor goals. Similar to Newby et al. (30), the African-American race was associated with achievement of fewer risk factor goals. For age, we saw varying results based on the analysis performed. In the analysis looking at simply aspirin use, blood pressure control, and LDL-C control, younger age was associated with meeting more targets. However, in our analysis looking at all 7 targets, including behavioral targets, older age was associated with meeting more targets, suggesting that younger individuals with CAD may have better access to medications but are less likely to reach behavioral goals. In addition to age and race, we also observed that low income, less education, and poor functional status were associated with achievement of fewer risk factor goals. However, our model of sociodemographic factors explains only a small amount of the variance in risk factor control. Although efforts should be concentrated on the vulnerable subgroups identified, achievement of risk factor goals was sufficiently low to justify a population-wide effort to identify and treat high-risk individuals.
We studied the achievement of risk factor goals to draw conclusions about implications of the COURAGE trial (6,9). Instead, had we chose to study achievement of the ACC/AHA secondary prevention guideline goals (2) or clinical performance measures for the management of patients with stable CAD (11), we might have found different results, although the risk factor goals used in the COURAGE trial are, in most cases, very similar to those recommended by the ACC/AHA secondary prevention guidelines (2) as well as clinical performance measures for stable CAD (11), as shown in Table 1. However, our intent was not to examine quality of care but rather to estimate how close the management of more average CAD patients is to the treatment goals used in the COURAGE trial (6,9). Additionally, unlike the goals used in the COURAGE trial, the secondary prevention guidelines and performance measures have never been prospectively studied. Based on the results of the COURAGE trial, a large percentage of individuals with stable CAD whose care is driven by these treatment goals can avoid PCI with good quality of life and no increased risk of myocardial infarction or death. As a result, given the significant number of PCIs performed annually in the United States, we were interested in studying the proportion of stable CAD patients who may not currently be achieving risk factor levels similar to those achieved in the COURAGE trial. The current results suggest that a large proportion of stable African-American and white adults with CAD in the United States do not achieve risk factor levels similar to those used in the COURAGE trial, potentially contributing to more chronic angina, impaired quality of life, and potentially avoidable PCIs.
First, the REGARDS participants were enrolled between 2003 and 2007, and the COURAGE trial was published in 2007. Therefore, we cannot evaluate whether increases in the proportion of CAD patients achieving these risk factor goals have occurred since the COURAGE trial was published. In addition, our mean age (69 years) is higher than the baseline age in COURAGE trial (61 years), and our sample included a higher proportion of African Americans (33% vs. 5%) and women (35% vs. 15%) than the COURAGE trial. However, the baseline values for the risk factors studied were very similar in our participants to those of the COURAGE trial participants at baseline, suggesting that similar improvements in quality of life and reductions in the need for revascularization could be achieved with more intensive risk factor modification. Last, as is the case for most epidemiological studies, we relied on self-report to identify individuals with CAD. Individuals with undiagnosed CAD or who failed to report a history of CAD were not included in this analysis.
On average, in the current study of U.S. black and white adults with a self-reported history of CAD, only one-half of the 7 possible modifiable risk factor goals were met. One strategy to enhance quality of life and reduce the number of PCIs performed may be to increase our focus on risk factor management for stable CAD patients.
The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at http://www.regardsstudy.org.
This research project is supported by cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke, grant R01 HL80477 from the National Heart, Lung, and Blood Institute, and grant 5KL2RR025776 from the UAB Center for Clinical and Translational Science with funding from the NIH National Center for Research Resources.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. Representatives of the funding agency have been involved in the review of the manuscript but not directly involved in the collection, management, analysis, or interpretation of the data. Dr. Brown has received salary support from a research grant from Amgen; and his position is supported in part by grant 5KL2RR025776 from the UAB Center for Clinical and Translational Science with funding from the NIH National Center for Research Resources. Dr. Goff was a DSMB member for a trial of a glucose-lowering drug marketed by Takeda; and has received travel reimbursement and speaker stipend for a CME program sponsored by Merck. Dr. Muntner has received consultant fees and research grants from Amgen. Dr. Safford is a consultant for and has received research grants from diaDexus; and has received salary support from Amgen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- American College of Cardiology
- American Heart Association
- coronary artery disease
- high-density lipoprotein cholesterol
- low-density lipoprotein cholesterol
- percutaneous coronary intervention
- Received January 12, 2013.
- Revision received December 2, 2013.
- Accepted December 3, 2013.
- American College of Cardiology Foundation
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