Incidence of Myocardial Infarction or Stroke or Death at 47-Month Follow-Up in Patients With Diabetes and a Predicted Exercise Capacity ≤85% vs >85% During an Exercise Treadmill Sestamibi Stress Test

Authors


  • Presented at the Annual Scientific Meeting of the American Heart Association on November 18, 2009.

Wilbert S. Aronow, MD, FACC, FAHA, Cardiology Division, New York Medical College, Macy Pavilion, Room 138, Valhalla, NY 10595
E-mail: wsaronow@aol.com

Abstract

A treadmill exercise sestamibi stress test (TESST) was performed in 609 consecutive diabetic persons with a mean age of 70 years and no history of coronary artery disease (CAD) who were referred for a TESST because of chest pain or dyspnea. Of 609 patients, 301 (49%) had a predicted exercise capacity ≤85% (group A) and 308 (51%) had a predicted exercise capacity >85% (group B). Group A patients had a higher prevalence of myocardial ischemia (43% vs 30%, P=.0005), 2- or 3-vessel obstructive CAD (38% vs 18%, P=.001), myocardial infarction (17% vs 9%, P=.004), death (10% vs 4%, P=.008), and myocardial infarction or stroke or death at 47-month follow-up (21% vs 12%, P=.001). Stepwise Cox regression analysis showed that the only significant independent predictor for the time to development of myocardial infarction or stroke or death was a predicted exercise capacity >85% (hazard ratio, 0.52; 95% confidence interval, 0.34–0.78; P=.002). Diabetic persons with a predicted exercise capacity >85% had a 48% lower chance of myocardial infarction, stroke, or death than those with a predicted exercise capacity ≤85%.

Prev Cardiol. 2010;13:14–17.©2009 Wiley Periodicals, Inc.

A decrease in exercise capacity has been associated with an increased risk of all-cause mortality and cardiovascular events.1–6 The mechanism by which reduced exercise capacity increases mortality and cardiovascular events is unknown.

Diabetic persons have a higher prevalence of silent myocardial ischemia detected during treadmill exercise testing or myocardial perfusion imaging than do nondiabetics.7–10 We performed a study in 609 patients with diabetes and no history of coronary artery disease (CAD) investigating the association of decreased exercise capacity during an exercise treadmill sestamibi stress test (TESST) with the prevalence of myocardial ischemia; the prevalence of obstructive CAD in the 241 patients (40%) who had coronary angiography; and the incidence of myocardial infarction, stroke, death, and myocardial infarction, stroke, or death at 47-month follow-up in the 609 diabetics. These data are presented in this article.

Methods

A TESST was performed as previously described10 in 609 consecutive unselected patients with diabetes with no history of CAD, peripheral vascular disease, diabetic neuropathy, chronic obstructive pulmonary disease, or other pulmonary disease that could limit exercise capacity who were referred for a TESST by a primary care physician because of chest pain or dyspnea. All TESSTs were symptom-limited. Peak exercise capacity was measured as the percentage of age- and sex-predicted metabolic equivalents (METs). The maximal (100%) predicted exercise capacity for each patient was calculated using previously validated models of functional capacity for women2 and for men.11 Achieved METs were determined from the final speed and grade of the treadmill. The percentage of predicted exercise capacity achieved by each patient was calculated by dividing the METs achieved during exercise by the predicted METs. A predicted exercise capacity <85% has been associated with mortality1,3,6 and was considered decreased. Patients with a decreased exercise capacity were included in group A, and patients with a predicted exercise capacity ≥85% were included in group B.

Two board-certified nuclear cardiologists reviewed the TESSTs for myocardial ischemia. Of the 609 diabetics, 241 (40%) underwent coronary angiography because of the TESST showing myocardial ischemia in 221 of the 241 patients (92%) and because of persistent disabling chest pain in 20 patients (8%). The coronary angiograms were interpreted by 3 board-certified interventional cardiologists for the presence of obstructive CAD. Obstructive CAD was diagnosed if there was >50% narrowing of at least 1 major coronary artery. The patients were followed for the incidence of myocardial infarction, stroke, and death.

Student t tests were performed to compare continuous variables between groups A and B. Chi-square tests and Fisher exact tests were used to compare dichotomous variables between groups A and B. Stepwise Cox regression analysis was performed to identify significant prognostic risk factors for the time to myocardial infarction or stroke or death using the variables listed in Table I.

Table I.   Baseline Characteristics of Patients With Diabetes Mellitus and Reduced Exercise Capacity (Group A) vs Normal Exercise Capacity (Group B)
VariableGroup A (n=301)Group B (n=308)P Value
  1. Abbreviations: ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; COPD, chronic obstructive pulmonary disease; GFR, glomerular filtration rate; NS, not significant; PVD, peripheral vascular disease.

Men174 (58%)177 (57%)NS
Women127 (42%)131 (43%)NS
Age, y70±1070±10NS
Whites213 (71%)239 (78%)NS
Nonwhites88 (29%)69 (22%)NS
Smoking32 (11%)35 (11%)NS
Hypertension296 (98%)302 (98%)NS
Dyslipidemia296 (98%)302 (98%)NS
Body mass index >30 kg/m287 (29%)83 (27%)NS
GFR ≥60 mL/min/1.73 m2189 (63%)182 (59%)NS
GFR 30–59 mL/min/1.73 m294 (31%)104 (34%)NS
GFR <30 mL/min/1.73 m218 (6%)22 (7%)NS
Aspirin298 (99%)303 (98%)NS
Statins296 (98%)302 (98%)NS
β-Blockers296 (98%)302 (98%)NS
ACE inhibitors/ARBs298 (99%)305 (99%)NS
Follow-up, mo47±1247±12NS
Duration of diabetes, y8.2±3.9 8.7±4.6NS
Insulin-dependent diabetes102 (34%)113 (37%)NS
PVD or diabetic neuropathy or COPD or other pulmonary disorders limiting activity0 (0%)0 (0%)NS

The institutional review boards of Westchester Medical Center and of New York Medical College approved this study.

Results

All patients stopped exercise because of dyspnea. No studies were terminated because of deconditioning, arrhythmias, intermittent claudication, or symptoms other than dyspnea.

Table I shows the baseline characteristics of group A and group B. No significant differences were found between the 2 groups.

Table II shows the incidence of myocardial ischemia, obstructive CAD, multivessel CAD, myocardial infarction, stroke, death, and myocardial infarction or stroke or death in group A vs group B. Table II also lists levels of statistical significance.

Table II.   Incidence of Myocardial Ischemia, Obstructive Coronary Artery Disease, Multivessel Obstructive Coronary Artery Disease, Myocardial Infarction, Stroke, Death, and Myocardial Infarction or Stroke or Death in Patients With Diabetes Mellitus and Reduced Exercise Capacity (Group A) vs Normal Exercise Capacity (Group B)
VariableGroup A (n=301)Group B (n=308)P Value
  1. Abbreviations: CAD, coronary artery disease; NS, not significant.

Myocardial ischemia130 (43%)91 (30%).0005
Normal coronary arteries22/128 (17%)47/113 (42%)<.0001
Nonobstructive CAD9/128 (7%)16/113 (14%)NS
1-Vessel obstructive CAD49/128 (38%)29/113 (26%).037
2-Vessel obstructive CAD31/128 (24%)15/113 (13%).031
3-Vessel obstructive CAD17/128 (13%)6/113 (5%).036
2- or 3-vessel obstructive CAD48/128 (38%)21/113 (18%).001
Myocardial infarction51 (17%)28 (9%).004
Stroke5 (2%)2 (1%)NS
Death29 (10%)13 (4%).008
Myocardial infarction, stroke, or death64 (21%)36 (12%).001

Table III shows the stepwise Cox regression analysis for the time to the development of myocardial infarction or stroke or death. A predicted exercise capacity >85% was the only significant independent predictor for the time to the development of myocardial infarction or stroke or death. Diabetics with a predicted exercise capacity >85% had a 48% lower chance of myocardial infarction or stroke or death than those with a predicted exercise capacity ≤85%.

Table III.   Stepwise Cox Regression Analysis for the Time to the Development of Myocardial Infarction, Stroke, or Death
Prognostic FactorParameter EstimateStandard Error P ValueHazard Ratio95% Confidence Interval
Exercise capacity >85% of predicted metabolic equivalents achieved−0.6550.210.0020.5200.344–0.784

Discussion

At 6.2-year follow-up of 6213 men referred for treadmill exercise testing, each 1-MET increase in exercise capacity conferred a 12% improvement in survival.1 At 8-year follow-up of 5721 asymptomatic women undergoing treadmill exercise testing, Framingham risk score-adjusted hazards ratios of death associated with MET levels of <5, 5 to 8, and >8 were 3.1, 1.9, and 1.0, respectively.2 At 2.7-year follow-up of 9191 patients referred for treadmill exercise testing, a predicted exercise capacity <85% was associated with an increased risk of myocardial infarction (hazard ratio, 2.4), unstable angina (hazard ratio, 2.4), coronary revascularization (hazard ratio, 1.8), and death (hazard ratio, 2.9) compared with a predicted exercise capacity >100%.3

At 7.5-year follow-up of 8911 white men and 6749 black men who underwent a treadmill exercise test, exercise capacity was the strongest predictor of mortality.4 The adjusted risk of mortality was reduced by 13% for each 1-MET increase in exercise capacity.4 A meta-analysis of 33 studies involving 102,980 persons for mortality and 84,323 persons for CAD/cardiovascular disease events showed that the relative risk of mortality and of CAD/cardiovascular disease events per 1-MET higher level of maximal aerobic capacity were 0.87 and 0.85, respectively.5 At 8.4-year follow-up of 5721 asymptomatic women who had a treadmill exercise test, women with a predicted exercise capacity <85% had a hazard ratio for death of 2.0 and for cardiac death of 2.4 compared with women with a predicted exercise capacity ≥85%.6

In 104 patients with abnormal treadmill exercise test results with ischemic ST-segment depression achieved after exercising for ≥10 METs, death occurred at 7.2-year follow-up in 1 of 104 patients (1%).12 The investigators concluded that patients with ischemic ST-segment depression on a treadmill exercise test who achieved workloads of ≥10 METs infrequently require additional noninvasive or invasive evaluation.12

The present study of 609 diabetics with no history of CAD who had a TESST because of chest pain or dyspnea showed that diabetic persons with a predicted exercise capacity ≤85% had a higher prevalence of myocardial ischemia (43%) than those with a predicted exercise capacity >85% (30%; P=.0005). Of the 241 diabetics who underwent coronary angiography because of myocardial ischemia (92%) or persistent disabling chest pain (8%), the prevalence of 2- or 3-vessel obstructive CAD was 38% in those with a predicted exercise capacity ≤85% vs 18% in those with a predicted exercise capacity >85% (P=.001). At 47-month follow-up, the incidence of myocardial infarction, stroke, or death was 21% in those with a predicted exercise capacity ≤85% vs 12% in those with a predicted exercise capacity >85% (P=.001).

Stepwise Cox regression analysis showed that a predicted exercise capacity ≤85% was the only significant independent predictor of the time to the development of myocardial infarction, stroke, or death (P=.002). Diabetics with a predicted exercise capacity >85% had a 48% lower chance of myocardial infarction, stroke, or death than those with a predicted exercise capacity ≤85%.

The mechanism for increased mortality and cardiovascular events in patients with a reduced exercise capacity is unknown. Myocardial ischemia and multivessel obstructive CAD as shown in our study may have caused the increase in mortality and in myocardial infarction in diabetics with a predicted exercise capacity ≤85%. Diabetics with a predicted exercise capacity ≤85% are at increased risk for all-cause mortality and for cardiovascular events and should be treated with intensive risk factor modification including exercise training.13,14 Whether increasing physical activity in patients with a decreased exercise capacity will reduce mortality and cardiovascular events needs to be investigated by controlled clinical trials.

Conclusions

To the best of our knowledge, this is the first study showing that diabetic persons without a history of CAD undergoing a TESST because of chest pain or dyspnea with a predicted exercise capacity ≤85% had a significantly higher prevalence of myocardial ischemia and of 2- or 3-vessel obstructive CAD and a significantly higher incidence at long-term follow-up of myocardial infarction, death, and myocardial infarction or stroke or death than diabetics with a predicted exercise capacity >85%. Diabetics with a predicted exercise capacity ≤85% are at increased risk for mortality and cardiovascular events and should be treated with intensive risk factor modification including exercise training.13,14

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