Hozawa A, Folsom AR, Sharrett AR, Chambless LE. Absolute and Attributable Risks of Cardiovascular Disease Incidence in Relation to Optimal and Borderline Risk FactorsComparison of African American With White Subjects—Atherosclerosis Risk in Communities Study. Arch Intern Med. 2007;167(6):573-579. doi:10.1001/archinte.167.6.573
Copyright 2007 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2007
Among white Americans, a large proportion of cardiovascular disease (CVD) events is explained by borderline or any elevated CVD risk factor levels. The degree to which this is true among African American subjects is unclear.
The Atherosclerosis Risk in Communities Study included 14 162 middle-aged adults who were free of recognized stroke or coronary heart disease and had baseline information on risk factors. Based on national guidelines, we categorized risk factors (blood pressure, cholesterol levels, diabetes, and smoking) into 3 categories, ie, optimal, borderline, and elevated. Incidence of CVD (composite of stroke and coronary heart disease) (n = 1492) and CVD mortality (n = 612) were identified for a 13-year period.
The proportion of subjects with all optimal risk factor levels was lower in African American (3.8%) than in white (7.5%) subjects. Conversely, the proportion of subjects with at least 1 elevated risk factor was higher in African American (approximately 80%) than in white (approximately 60%) subjects. After adjustment for these risk factor differences and education level, African American and white subjects had virtually identical rates of CVD (relative hazard for African American subjects, 1.01; 95% confidence interval, 0.90-1.14). The proportion of CVD events explained by elevated risk factors was high in African American subjects (approximately 90%) compared with approximately 65% in white subjects.
The higher CVD incidence rate in African American than in white subjects seems largely attributable to a high frequency of elevated CVD risk factors in African American subjects. Primary prevention of elevated CVD risk factors in African American subjects might greatly reduce CVD occurrence as much as it has for white subjects.
Traditional risk factors for cardiovascular disease (CVD)—ie, age, high blood pressure (BP), high serum cholesterol level, cigarette smoking, and diabetes mellitus—explain most incident CVD events.1- 4 As a result, persons with multiple risk factors have high CVD event rates,5,6 whereas low-risk persons with no risk factors rarely develop CVD.7- 10 This underscores that maintaining a low risk lifelong is key to CVD prevention.
Much literature indicates that African American subjects have higher rates of CVD than do white subjects.11,12 The relations of risk factors to CVD are largely similar in white and African American subjects,13 so the excess CVD risk in African American subjects may be largely attributable to their higher prevalence of risk factors.10,14 After adjusting for education level and risk factors, there may be no excess risk of CVD in African American subjects, but only a few studies have demonstrated this.10
Most previous studies of low CVD risk unfortunately have not involved African American subjects8 or analyzed African American and white subjects together.7,9 Only 1 study10 separately analyzed the CVD mortality rate among low-risk white and African American subjects. However, that study did not show the population-attributable fraction for these risk profiles.
Because BP and total cholesterol levels have continuous positive associations with CVD events,15- 17 even borderline risk factors are detrimental. Some reports indicate that people with average risk factor levels (below recognized intervention thresholds) account for a sizable proportion of individuals who develop CVD.18,19 However, only 1 study has specifically examined the relative importance of borderline risk factors to CVD incidence,8 and its participants did not include African American subjects.
To further explore these issues in African American compared with white subjects, we calculated the absolute and attributable risks of CVD incidence in relation to optimal and borderline risk factors in the Atherosclerosis Risk in Communities (ARIC) Study.
The ARIC Study protocol was approved by the institutional review board of each participating university. The ARIC Study is a multicenter prospective cohort study investigating the natural history of atherosclerotic disease in the following 4 US communities: Forsyth County, North Carolina; Jackson, Miss; Washington County, Maryland; and the northwest suburbs of Minneapolis, Minn.20 At baseline in 1987 to 1989, the cohort consisted of 15 792 men and women aged 45 to 64 years who were selected by list or area probability sampling. Race or ethnicity was self-reported, and only African American subjects were recruited in the Jackson study center. The baseline home interview assessed the participants' sociodemographic characteristics, smoking and alcohol-drinking habits, medication use, and personal history of diseases. A clinic examination included measurement of various risk factors and CVD conditions, B-mode ultrasound examinations of the carotid and popliteal arteries, and a 12-lead electrocardiogram (ECG).
Sitting BP was measured 3 times using a random-zero sphygmomanometer after 5 minutes of rest.21 The mean of the last 2 measurements was used for analysis. Use of antihypertensives within the past 2 weeks of the baseline interview was self-reported.22 Methods for blood collection and processing in the ARIC Study have been described in detail.23 Fasting plasma total cholesterol level was measured by enzymatic methods.24 Serum glucose level was measured by a hexokinase–glucose-6-phosphate dehydrogenase method. Smoking status (current, former, or never smokers) and education (less than, equivalent to, or greater than high school) were derived from interviews.18 Preexisting coronary heart disease (CHD) at baseline was defined by a self-reported previous physician diagnosis of myocardial infarction (MI) or coronary revascularization, or by a prevalent MI by ARIC ECG.25 Preexisting stroke was defined by any self-reported previous physician diagnosis of stroke.
We classified CVD risk factors into optimal (low), borderline, or elevated categories according to national guidelines (Table 1).26- 28Because, in observational studies, participants under medical treatment typically have higher CVD risk than subjects with borderline risk, we included treated participants in the elevated category.
We followed up all participants from the baseline examination to the date of CVD incidence, death, or loss to follow-up or through December 31, 2002. Incidence of CHD in the ARIC Study was ascertained by contacting participants annually, identifying hospitalizations and deaths during the preceding year, and surveying discharge lists from local hospitals and death certificates from state vital statistics offices for potential CVD events.22,29,30 For patients hospitalized with a potential MI, trained abstractors recorded the presenting symptoms and related clinical information, including cardiac enzyme levels, and photocopied up to three 12-lead ECGs for Minnesota coding.25,31 Out-of-hospital deaths were investigated by means of death certificates and, in most cases, by an interview with 1 or more next of kin (98%) and a questionnaire completed by the patient's physician (85%). Coroner reports or autopsy reports, when available, were abstracted for use in validation.
A CHD event was defined as a validated definite or probable hospitalized MI or a definite CHD death. The criteria for definite or probable MI were based on combinations of chest pain symptoms, ECG changes, and cardiac enzyme levels.29,30 The criteria for definite fatal CHD were based on chest pain symptoms, history of CHD, underlying cause of death from the death certificate, and any other associated hospital information or medical history, including that from an ARIC clinic visit.29,30 Unstable angina, unrecognized MI determined by ECG,1 and coronary revascularization were not included in CHD events because of concerns about ethnic differences in diagnosis and use of procedures.
The diagnostic classification of stroke was described previously.32 In brief, for potential hospitalized strokes, the abstractors recorded signs and symptoms and photocopied neuroimaging studies (computed tomography or magnetic resonance imaging) and other diagnostic reports. According to criteria adopted from the National Survey of Stroke,33 strokes were classified by computer algorithm and categorized into 1 of the following 4 main types: subarachnoid hemorrhage, intracerebral hemorrhage, thrombotic brain infarction, or embolic brain infarction. Categories of possible stroke of undetermined type, out-of-hospital fatal stroke (based on underlying cause of death from the death certificate only), and no stroke were also assigned. Stroke events were defined as a definite or probable hospitalized embolic, thrombotic, or hemorrhagic stroke. Transient ischemic attacks and a small number of undocumented fatal strokes were also not included as stroke events. We defined incident CVD events as the first occurrence of CHD or stroke.
We also separately analyzed deaths ascertained through December 31, 2002. Deaths were identified through annual follow-up telephone calls, hospital surveillance, state vital statistics databases, and the National Death Index. The broader CVD death category was based on the death certificate and included any underlying cause-of-death codes of 390 through 459, or cause-of-death codes I00 through I99, as coded by state health departments according to the International Classification of Diseases, Ninth Revision, or the International Statistical Classification of Diseases, 10th Revision, respectively.
Of 15 792 ARIC Study participants at baseline, we excluded 1357 who had a history of CVD or who could not be classified by history of CVD. We further excluded, owing to small numbers, nonwhite and non–African American subjects (n = 43). Subjects who did not have complete information on plasma cholesterol level (n = 206), cigarette smoking (n = 9), BP value (n = 6), or serum glucose level (n = 9) were also excluded. In all, 14 162 participants were included in the analysis.
Age-adjusted incidence rates were calculated according to risk factor groups. To compare the prevalence of optimal risk factors only between African American and white subjects, we used age- and sex-adjusted or age-, sex-, and education-adjusted logistic regression models. The relative hazards (RHs) of CVD incidence, CVD mortality, and all-cause mortality in relation to risk factor groups were estimated from Cox proportional hazards models adjusted for age and education (less than, equivalent to, or greater than high school). We treated the participants with at least 1 elevated risk factor as the reference group. The population-attributable fraction was calculated using the following equation:
P × [(RH for Borderline or Elevated Risk Factor Category − RH for the Optimal Risk Category)/RH for Borderline or Elevated Risk Factor Category],
where P is the proportion of cases exposed in the risk factor category.34 In some analyses, we determined the relation between race and CVD incidence adjusted for individual risk factors, ie, systolic BP, use of antihypertensive drugs, total cholesterol level, use of lipid-lowering medication, smoking status, and diabetes mellitus, instead of risk factor categories.
The mean ± SD age of the ARIC Study participants at baseline was 54.0 ± 5.7 years. The proportions with hypertension, hypercholesterolemia, and diabetes and who currently smoked were sizable (36.9%, 25.9%, 10.9%, and 25.8%, respectively). The proportions with hypertension and diabetes were higher in African American than in white subjects, and the proportion of never smokers was higher in women than in men (Table 1).
Very few participants had only optimal risk factors. The percentages of participants with only borderline risk factors were nearly twice as high in white as in African American subjects. The percentage of subjects with 1 or more elevated risk factors was 66.5%, higher in African American subjects (men, 80.5%; women, 79.0%) than in white subjects (men, 60.5%; women, 62.9%). The percentage of African American subjects with 2 or more elevated risk factors was almost twice that of white subjects (Table 2).
Participants with elevated risk factors were older and less well educated compared with participants with lower risk factor profiles (Table 3), and the worse risk factor profile of African American subjects was partly explained by educational status. That is, the age- and sex-adjusted odds ratio of not having an optimal risk factor profile in African American vs white subjects was 0.44 (95% confidence interval [CI], 0.36-0.53), and the odds ratio was slightly attenuated (0.48; 95% CI, 0.40-0.58) when we further adjusted for education.
The mean duration of follow-up was 13.1 years (maximum, 16.1 years), during which 1492 incident CVD events occurred. Among white subjects, 71.3% of events were CHD and 28.7% were stroke; among African American subjects, these percentages were 54.1% and 45.9%, respectively. The age-adjusted CVD incidence rate was highest in participants with at least 1 elevated risk factor (10.13 per 1000 person-years), and was 3.28 per 1000 person-years among those with only borderline risk factors and 1.64 per 1000 person-years among those with all optimal risk factors. The age-adjusted CVD incidence rate in white subjects was 6.63 per 1000 person-years; in African American subjects, 10.38 per 1000 person-years.
The age- and education-adjusted RH for CVD incidence among participants with all optimal risk factors compared with participants with any elevated risk factor was 0.19 (95% CI, 0.12-0.29), and the RH among participants with only borderline risk factors was 0.37 (95% CI, 0.31-0.43). These findings were similar in ethnicity-sex subgroups. The range of RHs for CVD of participants with all optimal risk factors was 0.00 to 0.26, and the range of RHs of participants with only borderline risk factors was 0.20 to 0.40.
The population-attributable fraction suggested that having at least 1 elevated risk factor accounted for 70.2% of CVD events (Table 4). Borderline risk factors accounted for just 6.2% more. Elevated and borderline risk factors accounted for almost all CVD events in African American subjects (men, 100.0%; women, 87.7%), compared with approximately 70% in white subjects (men, 75.1%; women, 66.6%). To explore whether race-ethnicity predicts incident CVD independent of major risk factors, we conducted additional analyses. Compared with white subjects, African American subjects had a 65% (95% CI, 48%-84%) higher CVD incidence when adjusted for age and sex only and a 46% (95% CI, 30%-84%) higher CVD incidence with further adjustment for education. Further adjustment for major risk factors eliminated ethnicity as an independent risk factor (RHs for African American compared with white subjects were as follows: RH for both sexes, 1.01 [95% CI, 0.90-1.14]; RH for men, 0.96 [95% CI, 0.82-1.14]; and RH for women, 1.08 [95% CI, 0.90-1.29]).
We also performed analyses using CVD and all-cause mortality data (Table 5). The CVD mortality rate was consistently and markedly lower in participants with all optimal risk factors (RH, 0.12 [95% CI, 0.04-0.31]), and in those with borderline risk factors only (RH, 0.28 [95% CI, 0.21-0.37]), than in participants with at least 1 risk factor. The all-cause mortality rate was also lower in participants with all optimal risk factors (RH, 0.26 [95% CI, 0.17-0.38]) and in those with borderline risk factors only (RH, 0.48 [95% CI, 0.42-0.55]). No CVD death was observed in African American subjects with all optimal risk factors (Table 5).
In this prospective cohort study, we found that the low-risk participants with all optimal risk factors had very low CVD incidence rates. Our major finding was that more than 90% of CVD events in African American subjects, compared with approximately 70% in white subjects, were explained by elevated or borderline risk factors. Furthermore, the prevalence of participants with elevated risk factors, particularly 2 or more elevated risk factors, was higher in African American subjects; once we accounted for education and risk factors, the incidence of CVD was identical in African American and white subjects. Thus, the observed higher CVD incidence rate in African American subjects seems largely attributable to a greater prevalence of elevated risk factors. These findings demonstrated that preventing elevated CVD risk factors in the first place might largely eliminate CVD incidence, and these beneficial effects would be applicable not only for white but also for African American subjects.
Consistent with previous studies,7- 10 the prevalence of an optimal CVD risk profile was low (6.5%) in the ARIC Study. The CVD risk of participants with only borderline risk factors, who constituted 20% to 40% of the sample, was double that of those with all optimal risk factors. Still, borderline risk factors accounted for only 6.2% of all CVD events. Although the definition of CVD events was different, this proportion is in line with a report8 that borderline levels of risk factors probably account for a small proportion of hard CHD events in the Framingham Study and the Third National Health and Nutrition Examination Survey. Although previous studies clarified that people with no risk have low rates of all-cause mortality,7,9 CHD mortality,7,9 and hard CHD events,8 only 1 study had examined the impact of a low-risk profile on CVD mortality among African American subjects.10 Thomas et al10 demonstrated that, among African American subjects in the Multiple Risk Factor Intervention Trial, the age-adjusted CVD death rate per 10 000 person-years during a 25-year period was 25.1 for low-risk, 30.1 for intermediate-risk, 52.4 for high-risk, and 94.1 for very high-risk men. The respective rates in white men were 11.5, 21.2, 35.8, and 82.0. The Multiple Risk Factor Intervention Trial results were consistent with ours.
Thomas et al10 also reported that the prevalence of low, intermediate, and elevated CVD risk factors were 4.2%, 17.4%, and 88.4%, respectively, among black men and 6.9%, 26.2%, and 66.9%, respectively, among white men. Similarly, our data indicated that almost 40% of African American subjects in the ARIC Study had at least 2 risk factors, almost twice the percentage for white subjects. This is also similar to the Third National Health and Nutrition Examination Survey,14 which showed that non-Hispanic black subjects were twice as likely as the other ethnic groups to have 4 or 5 risk factors. Although the age-, sex-, and education-adjusted RH of CVD incidence was significantly higher in African American relative to white subjects, the relative risk of CVD incidence risk for African American compared with white subjects was approximately 1.0 after adjustment for CVD risk factors. This result was comparable to the findings of Thomas et al10 (age-, income-, and risk-adjusted black-to-white RH was 1.05 [95% CI, 1.01-1.10]). Thus, the higher CVD rate in African American subjects11,12 may be largely attributable to a higher frequency of elevated CVD risk factors in African American than in white subjects.
We estimated that borderline risk and elevated risk factors accounted for 76.4% of CVD incidence and 84.7% of CVD mortality in our sample. These percentages are similar to those from previous studies. From the results of Stamler et al,7 we calculated that approximately 71% to 75% of CVD mortality in 2 cohorts aged 40 to 59 years occurred in participants who were not low risk (defined by total cholesterol level of <200 mg/dL [<5.2 mmol/L], systolic BP of <120 mm Hg, diastolic BP of <80 mm Hg, not currently smoking, and no diabetes). Vasan et al8 reported that no hard CHD events occurred in Framingham participants with all optimal risk factors, using a strict definition of optimal risk factors (defined by systolic BP of <120 mm Hg and diastolic BP of <80 mm Hg, never smoked, and optimal glucose tolerance defined as fasting glucose level of <110 mg/dL [<6.1 mmol/L] or 2-hour glucose level of <140 mg/dL [<7.8 mmol/L], high-density lipoprotein cholesterol level of ≥60 mg/dL [≥2.3 mmol/L], and low-density lipoprotein cholesterol level of <100 mg/dL [<2.6 mmol/L]). Combinations of healthy lifestyle factors also yield similar conclusions. Stampfer et al35 reported that lack of adherence to low-risk behaviors (ie, healthy diet, nonsmoking, moderate-to-vigorous exercise ≥30 min/d, body mass index [calculated as weight in kilograms divided by the square of height in meters] of <25, and moderate alcohol consumption) could account for 82% of CHD incidence and 74% of CVD incidence. Similarly, Chiuve et al36 reported that not having a healthy lifestyle (ie, not currently smoking, healthy diet, exercise of ≥30 min/d, body mass index of <25, and moderate alcohol consumption) accounted for 62% of CHD.
In our study, participants with optimal or only borderline risk factors also had lower all-cause mortality rates than did participants with any elevated risk factors. This result corroborates the report by Stamler et al,7 which showed that the relative risk for all-cause mortality ranged from 0.42 to 0.60 in low-risk vs higher-risk participants. Lloyd-Jones et al37 also reported recently that the absence of established risk factors at 50 years of age is associated with very low lifetime risk for CVD and markedly increased survival. Thus, having optimal CVD risk factors yields not only lower CVD incidence and mortality but also lower risk for all-cause mortality.
The strengths of our study include careful assessment of CVD risk factors and incidence for an extended follow-up period. One limitation is that, although our sample size was large, few CVD events occurred in the low-risk group. A second is that our study does not provide information about whether careful control of elevated risk factors might reduce CVD incidence, because we grouped participants taking risk factor–lowering medications in the elevated risk group regardless of their current BP or cholesterol or glucose level.
In conclusion, the CVD incidence rate was very low in participants with optimal risk factors among white and African American subjects. Although participants with borderline risk factors only were frequent, their population-attributable fraction for CVD was not high. Our results suggest that primary prevention of elevated CVD risk factors might greatly reduce CVD occurrence.
Correspondence: Aaron R. Folsom, MD, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 S Second St, Suite 300, Minneapolis, MN 55454-1015 (email@example.com).
Accepted for Publication: October 6, 2006.
Author Contributions: Drs. Hozawa and Folsom had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hozawa and Folsom. Acquisition of data: Folsom. Analysis and interpretation of data: Hozawa and Chambless. Drafting of the manuscript: Hozawa. Critical revision of the manuscript for important intellectual content: Folsom, Sharrett, and Chambless. Statistical analysis: Chambless.
Financial Disclosure: None reported.
Funding/Support: This study was supported by a grant from the Banyu Fellowship Program sponsored by Banyu Life Science Foundation International (Dr Hozawa) and contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 from the National Heart, Lung, and Blood Institute (NHLBI) (ARIC Study).
Acknowledgment: We thank the staff and participants of the ARIC Study for their important contributions. The NHLBI staff helped design the ARIC Study and approved this manuscript.