The aim of this analysis was to determine whether racial differences exist in the prognostic value of cardiorespiratory fitness (CRF) in black and white patients undergoing stress testing. We included 53,876 patients (mean age 53 ± 13, 49% women) from the Henry Ford Exercise Testing project free of established coronary disease or heart failure who completed a maximal exercise test from 1991 to 2009. Patients were followed for a mean duration of 11.5 years for all-cause mortality, ascertained by linkage with the Death Master File. Follow-up over mean 6.2 years was also available for incident myocardial infarction. Multivariate Cox proportional hazards regression models were used adjusting for demographic variables, risk factors, medications, and reason for stress test referral, including formal interaction testing by race (black vs white). Black patients (n = 16,725) were younger (54 ± 13 vs 52 ± 13, p <0.001) but had higher prevalence of hypertension (73% vs 57%, p <0.001) and obesity (28% vs 21%, p <0.001). On average, black patients achieved a lower CRF compared with whites (8.4 vs 9.5 metabolic equivalents, p <0.0001). A graded increase in mortality risk was noted with decreasing CRF for both black and white patients. In multivariate Cox regression, CRF was a predictor of both myocardial infarction and mortality, with no significant interaction between race, fitness, and outcomes (all interaction terms p >0.10). CRF is a strong predictor of all-cause mortality in both white and black patients, with no significant interaction observed between race, fitness, and outcomes.
Cardiorespiratory fitness (CRF) is an important marker of cardiovascular heath in the general adult population. Reduced fitness is a risk factor for all-cause mortality and cardiovascular disease, independent of cardiovascular risk factors. In a meta-analysis of more than 80,000 subjects, an increase in CRF of one metabolic equivalent (MET) is associated with 13% decrease in cardiovascular mortality. Several studies have demonstrated consistent results; however, many of these studies are limited by lack of objectively defined measurements of CRF and small sample sizes. Although previous evidence demonstrated lower fitness in blacks, most of this evidence is based on physical activity measures and not treadmill based exercise testing. However, these studies used self-reported physical activity as a measure of CRF. It is also not known if the relation of CRF with cardiovascular outcomes is modified by race. Thus, the aim of this analysis is to determine whether racial differences exist in the prognostic value of CRF in black and white patients who underwent clinically indicated maximal exercise stress testing.
Methods
The methods of the Henry Ford Exercise Testing project (the FIT project) have been described previously. In summary, the FIT project is an investigator-initiated retrospective single-center cohort study aimed at describing the long-term association between CRF and clinical events in an ethnically diverse real-world population.
The FIT project used multiple data sources including directly measured exercise data and CRF, retrospective collection of medical history and medication treatment data taken at the time of the stress test, retrospective supplementation of supporting clinical data using the electronic medical record, as well as administrative databases including pharmacy and claims files. Epidemiologic follow-up for total mortality was accomplished through linkage with Social Security Administration Death Master File (DMF) and for myocardial infarction (MI) through linkage with administrative claims files. The FIT project was approved by the Henry Ford Health System Institutional Review Board.
The FIT project population consists of 69,885 consecutive patients who underwent physician-referred treadmill stress testing at Henry Ford Health System–affiliated hospitals and ambulatory care centers in metropolitan Detroit, Michigan from 1991 to 2009. We included patients undergoing routine, clinically referred, symptom-limited maximal treadmill stress testing after the standard Bruce protocol as described previously. Patients <18 years old at the time of stress testing, those undergoing pharmacologic stress testing, modified Bruce, and other non-Bruce protocol tests as well as patients with heart failure and known coronary artery disease (previous MI, percutaneous coronary intervention, coronary artery bypass graft, or documented coronary artery disease on a previous angiogram) were excluded from this analysis. In addition, patients with races other than black or white race (n = 4,181) were excluded from this analysis, and 53,876 patients were included.
Treadmill, medical history, and medication data were collected by exercise physiologists and nurses. Supporting clinical data and follow-up for cardiovascular outcomes were derived from the electronic medical record and administrative databases shared in common across system-affiliated subsidiaries. Heart rate and blood pressure at rest were manually assessed immediately before each test. All patients exercised according to the Bruce protocol. In addition to continuous heart rate monitoring, blood pressure was measured every 3 minutes during the test. The highest recorded heart rate and blood pressure were considered the peak heart rate and peak blood pressure. The tests were terminated at the discretion of the supervising clinician for reasons that included significant arrhythmias, abnormal hemodynamic responses, diagnostic ST-segment changes, exercise-limiting symptoms such as chest pain or shortness of breath, or if the patient was unable to continue. Otherwise, patients were allowed to reach their peak attainable workload independent of heart rate achieved. Peak exercise workload, expressed in estimated METs of task, was categorized into 4 groups: <6, 6 to 10, 10 to 12, >12 METs.
Race was exclusively defined by self-report and categorized by study investigators into common identifications (white, black, or other). Obesity was defined by self-report and/or assessment by the clinician historian as present or absent. Current smoking was defined as self-reported active smoking at the time of testing. Indication for stress testing was extracted from the stress test requisition provided by the referring physician and subsequently categorized by study investigators into common indications (e.g., ischemia evaluation/risk stratification, chest pain, shortness of breath, and preoperative evaluation).
Mortality ascertainment was conducted in April 2013 using an algorithm for searching the Social Security Death Index DMF using of social security number, first name, last name, and date of birth. Ascertainment was conducted after federal law changes in 2011 limiting reporting of certain deaths by state agencies. A complete algorithmic search of the Social Security Death Index DMF could be completed in more than 99.5% of patients. MIs were ascertained in May 2010 through linkage with administrative claims files from services delivered by the affiliated group practice and/or reimbursed by the health plan. Linkage was performed using appropriate International Statistical Classification of Diseases and Related Health Problems, Ninth revision (410.xx). Patients were censored at their last contact with the integrated Henry Ford Health System group practice when ongoing coverage with the health plan (and therefore serviced rendered) could no longer be confirmed.
Baseline characteristics between black and white races were compared using chi-squared testing or analysis of variances techniques as appropriate. Unadjusted Kaplan–Meier survival analysis was performed and compared through log-rank testing. The cumulative incidence for mortality and MI were evaluated using Kaplan–Meier’s method. We used Cox regression models to calculate hazard ratios for all-cause mortality, and MI, with adjustment for age, gender, race, obesity, heart rate at rest, systolic and diastolic blood pressures, a history of hypertension, dyslipidemia, smoking, diabetes mellitus, atrial fibrillation; heart failure; indication for stress testing, medications used to treat chronic obstructive pulmonary disease, hypertension or hyperlipidemia as well as aspirin, clopidogrel and beta blockers. Statistical analyses were performed using Stata, version 12.1, 2013 (StataCorp, College Station, Texas). Interactions were assessed both graphically and with formal interaction testing by adding interaction terms to the fully adjusted model. The p value of interaction term was reported. The model was also run separately in patients who achieved and did not achieve their target heart rate defined as 85% of 220-age.
Results
A total of 53,876 patients (mean age 53 ± 13 years, 49% women) met the inclusion criteria, of which 16,724 (31%) were black patients. The baseline characteristics of the study population are listed in Table 1 . Black patients were younger (52 vs 54 years, p <0.001) with a majority female (57% vs 45%, p <0.001). Black patients also had higher prevalence of coronary risk factors including hypertension, dyslipidemia, diabetes, and smoking (p <0.05 for all). Data on stress test performance are listed in Table 2 . The most common reason for the stress test was chest pain (51%), which was also more common in black patients. Most patients (80%) achieved their target heart rate, and 20% of the study cohort had chronotropic incompetence. The overall mean METs achieved were 9.1 ± 3.0 with significant racial variation (mean METs achieved by white patients 9.4 ± 3.0 vs 8.4 ± 2.9 achieved by black patients, p <0.001). Categories of METS for both races are shown in Figure 1 . After a mean follow-up duration of 8 ± 5 years, 6,382 patients (11.85%) died and 1,680 patients (3.12%) developed MI. The rate of mortality in black and white patients were 13.1 and 11.3 per 1,000 person-years, whereas the rate of MI in black and white patients were 2.6 and 4.3 per 1,000 person-years, respectively (p <0.0001). Graded increases in risks of mortality ( Figure 2 ) and MI ( Figure 2 ) were observed with a decrease in CRF. An unadjusted Kaplan–Meier curve (by fitness category) is shown in Figure 3 . After adjustment of covariates, CRF remained independently associated with all-cause mortality and MI. As shown in Figure 4 , patients with high CRF had similarly lower event rates in both white and black patients. No graphical interaction was noted in Figure 2 . We also did not detect any interaction of race with relation of CRF with all–cause mortality ( Table 3 ) or MI ( Table 4 ; independent whether fitness was included as continuous or categorical variable). This was also seen in patients with or without chronotropic incompetence.
| Variable | All Patients (N = 53,876) | White (N = 37,152) | Black (N= 16,724) | p-Value |
|---|---|---|---|---|
| Age (years) | 53.6 ± 12.6 | 54.3 ± 12.5 | 52.2 ± 12.6 | <0.001 |
| Female | 26425 (49%) | 16896 (45%) | 9529 (57%) | <0.001 |
| Hypertension | 33440 (62%) | 21304 (57%) | 12,136 (73%) | <0.001 |
| Anti-hypertensive medication use | 23413 (43%) | 14481 (39%) | 8932 (53%) | <0.001 |
| Lipid – lowering medication use | 23049 (43%) | 17212 (46%) | 5837 (35%) | <0.001 |
| Hyperlipidemia Medications | 10702 (20%) | 7900 (21%) | 2802 (17%) | <0.001 |
| Smoking | 22714 (42%) | 15774 (42%) | 6940 (42%) | 0.04 |
| Diabetes mellitus | 9632 (18%) | 5591 (15%) | 4041 (24%) | <0.001 |
| Family History of coronary heart disease | 27822 (52%) | 20194 (54%) | 7628 (46%) | <0.001 |
| Obesity ∗ | 12551 (23%) | 7829 (21%) | 4722 (28%) | <0.001 |
| Bronchodilator medication use | 4895 (9%) | 3288 (9%) | 1607 (10%) | 0.005 |
| Variable | All Patients (N= 53,876) | White (N= 37,152) | Black (N= 16,724) | p-Value |
|---|---|---|---|---|
| Reason For Stress Test | ||||
| Chest Pain | 27335 (51%) | 17598 (47%) | 9737 (58.2%) | <0.001 |
| Dyspnea | 4812 (8.9%) | 3774 (10%) | 1038 (6.2%) | <0.001 |
| Pre-operative evaluation | 1081 (2.0%) | 744 (2%) | 337 (2.0%) | 0.92 |
| Evaluate for Ischemia | 5973 (11.1%) | 4179 (11%) | 1,794 (10.7%) | 0.04 |
| Palpitations | 1918 (3.6%) | 1450 (4.0%) | 468 (2.8%) | <0.001 |
| Exercise stress test parameters | ||||
| Resting heart rate (bpm) | 73.1 ± 12.5 | 73.1 ± 12.4 | 73.1 ± 12.8 | 0.98 |
| Resting systolic blood pressure (mmHg) | 131.4 ± 18.9 | 130.9 ± 18.8 | 132.2± 19.1 | <0.001 |
| Resting diastolic blood pressure (mmHg) | 81.2± 10.4 | 80.8 ± 10.2 | 82.24 ± 10.8 | <0.001 |
| Peak heart rate (bpm) | 150.8 ± 20.3 | 151 ± 19.9 | 149.9 ± 21.1 | <0.001 |
| Peak systolic blood pressure (mmHg) | 180.4± 26.7 | 178.6± 25.8 | 184.3± 28.2 | <0.001 |
| Peak diastolic blood pressure (mmHg) | 84.4 ± 14.1 | 83.4± 13.4 | 86.6 ± 15.3 | <0.001 |
| Achieved Target Heart Rate ∗ | 43082 (80.2%) | 30503 (82.3%) | 12579 (75.5%) | <0.001 |
| Mean METS | 9.1± 3.0 | 9.4 ± 3.0 | 8.4 ± 2.9 | <0.001 |
∗ Achieved target heart rate was defined as 85% of calculated maximal heart rate (age–220).
