Effects of physical activity and exercise training on cardiovascular risk in coronary artery disease patients with and without type 2 diabetes.

OBJECTIVE: Leisure-time physical activity (LTPA) and exercise training are essential parts of current guidelines for patients with coronary artery disease (CAD). However, the contributions of LTPA and exercise training to cardiovascular (CV) risk in CAD patients with type 2 diabetes (T2D) are not well established. RESEARCH DESIGN AND METHODS: We examined the effects of LTPA (n = 539 and n = 507; with and without T2D, respectively) and 2-year controlled, home-based exercise training (n = 63 plus 64 control subjects with T2D and n = 72 plus 68 control subjects without T2D) on the CV risk profile and composite end point among CAD patients. RESULTS: During the 2-year follow-up, patients with reduced LTPA at baseline had an increased risk of CV events (adjusted hazard ratio 2.3 [95% CI 1.1-5.1; P = 0.033], 2.1 [1.1-4.2; P = 0.027], and 2.0 [1.0-3.9; P = 0.044] for no LTPA, LTPA irregularly, and LTPA two to three times weekly, respectively) compared with those with LTPA more than three times weekly. Among patients who completed the 2-year exercise intervention, exercise training resulted in favorable changes in exercise capacity both in CAD patients with T2D (+0.2 ± 0.8 vs. -0.1 ± 0.8 MET, P = 0.030) and without T2D (+0.3 ± 0.7 vs. -0.1 ± 0.5 MET, P = 0.002) as compared with the control group but did not have any significant effects on major metabolic or autonomic nervous system risk factors in CAD patients with or without T2D. CONCLUSIONS: There is an inverse association between habitual LTPA and short-term CV outcome, but controlled, home-based exercise training has only minor effects on the CV risk profile in CAD patients with T2D.

Acute post-exercise change in blood pressure and exercise training response in patients with coronary artery disease.

We tested the hypothesis that acute post-exercise change in blood pressure (BP) may predict exercise training responses in BP in patients with coronary artery disease (CAD). Patients with CAD (n = 116, age 62 ± 5 years, 85 men) underwent BP assessments at rest and during 10-min recovery following a symptom-limited exercise test before and after the 6-month training intervention (one strength and 3-4 aerobic moderate-intensity exercises weekly). Post-exercise change in systolic BP (SBP) was calculated by subtracting resting SBP from lowest post-exercise SBP. The training-induced change in resting SBP was -2 ± 13 mmHg (p = 0.064), ranging from -42 to 35 mmHg. Larger post-exercise decrease in SBP and baseline resting SBP predicted a larger training-induced decrement in SBP (ß = 0.46 and ß = -0.44, respectively, p < 0.001 for both). Acute post-exercise decrease in SBP provided additive value to baseline resting SBP in the prediction of training-induced change in resting SBP (R(2) from 0.20 to 0.26, p = 0.002). After further adjustments for other potential confounders (sex, age, baseline body mass index, realized training load), post-exercise decrease in SBP still predicted the training response in resting SBP (ß = 0.26, p = 0.015). Acute post-exercise change in SBP was associated with training-induced change in resting SBP in patients with CAD, providing significant predictive information beyond baseline resting SBP.

Effects of exercise rehabilitation on cardiac electrical instability assessed by T-wave alternans during ambulatory electrocardiogram monitoring in coronary artery disease patients without and with diabetes mellitus.

Effects of exercise rehabilitation on electrocardiographic markers of risk for sudden cardiac death have not been adequately studied. We examined effects of controlled exercise training on T-wave alternans (TWA) in 24-hour ambulatory electrocardiogram recordings in patients with stable coronary artery disease (CAD) without and with type 2 diabetes mellitus (DM). Consecutive patients with angiographically confirmed CAD were recruited to join the ARTEMIS (Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection) study. Exercise (n = 65) and control groups (n = 65) were matched on age, sex, DM, and previous myocardial infarction. Ambulatory electrocardiograms were recorded before and after a 2-year training period. TWA was assessed using time domain-modified moving average method by an investigator blinded to patients' clinical status. Average TWA values decreased in the rehabilitation group but not in control patients (rehabilitation [mean ± SEM]: 52.8 ± 1.7 µV vs 48.7 ± 1.5 µV, p <0.001; control: 53.7 ± 1.7 µV vs 54.3 ± 1.6 µV, p = 0.746). Changes in TWA differed between the groups (rehabilitation: -4.1 ± 1.2 µV vs controls: +0.6 ± 1.1 µV, p = 0.005). In CAD + DM patients, 50% (n = 9) of the 18 positive TWA cases were converted with exercise versus 10% (n = 2 of 20) of controls (p = 0.020). In CAD patients, 30% (n = 8 of 27) of positive TWA cases were converted with exercise versus 4% (n = 1 of 28) of controls (p = 0.012). In conclusion, this is the first report of the effectiveness of exercise rehabilitation to reduce TWA, a marker of sudden cardiac death risk, in patients with stable CAD.

Determinants and prognostic value of cardiovascular autonomic function in coronary artery disease patients with and without type 2 diabetes.

OBJECTIVE Cardiovascular autonomic dysfunction is a common finding among patients with coronary artery disease (CAD) and type 2 diabetes (T2D). The reasons and prognostic value of autonomic dysfunction in CAD patients with T2D are not well known. RESEARCH DESIGN AND METHODS We examined the association between heart rate recovery (HRR), 24-h heart rate (HR) variability (SD of normal R-R interval [SDNN]), and HR turbulence (HRT), and echocardiographic parameters, metabolic, inflammatory, and coronary risk variables, exercise capacity, and the presence of T2D among 1,060 patients with CAD (mean age 67 ± 8 years; 69% males; 50% patients with T2D). Second, we investigated how autonomic function predicts a composite end point of cardiovascular death, acute coronary event, stroke, and hospitalization for heart failure during a 2-year follow-up. RESULTS In multiple linear regression model, exercise capacity was a strong predictor of HRR (R = 0.34, P < 0.001), SDNN (R = 0.33, P < 0.001), and HRT (R = 0.13, P = 0.001). In univariate analyses, a composite end point was predicted by reduced HRR (hazard ratio 1.7 [95% CI 1.1-2.6]; P = 0.020), reduced SDNN (2.0 [95% CI 1.2-3.1]; P = 0.005), and blunted HRT (2.1 [1.3-3.4]; P = 0.003) only in patients with T2D. After multivariate adjustment, none of the autonomic markers predicted the end point, but high-sensitivity C-reactive protein (hs-CRP) remained an independent predictor. CONCLUSIONS Cardiovascular autonomic function in CAD patients is associated with several variables, including exercise capacity. Autonomic dysfunction predicts short-term cardiovascular events among CAD patients with T2D, but it is not as strong an independent predictor as hs-CRP.

Peak exercise capacity prediction from a submaximal exercise test in coronary artery disease patients.

The purpose of this study was to determine whether a rating of perceived exertion scale (RPE) obtained during submaximal exercise could be used to predict peak exercise capacity (METpeak) in coronary artery disease (CAD) patients. Angiographically documented CAD patients (n = 124, 87% on ß blockade) completed a symptom-limited peak exercise test on a bicycle ergometer, reporting RPE values at every second load on a scale of 6-20. Regression analysis was used to develop equations for predicting METpeak. We found that submaximal METs at a workload of 60/75 W (for women and men, respectively) and the corresponding RPE (METs/RPE ratio) was the most powerful predictor of METpeak (r = 0.67, p < 0.0001). The final model included the submaximal METs/RPE ratio, body mass index (BMI), sex, resting heart rate, smoking history, age, and use of a ß blockade (r = 0.86, p < 0.0001, SEE 0.98 METs). These data suggest that RPE at submaximal exercise intensity is related to METpeak in CAD patients. The model based on easily measured variables at rest and during "warm-up" exercise can reasonably predict absolute METpeak in patients with CAD.

Impact of type 2 diabetes on cardiac autonomic responses to sympathetic stimuli in patients with coronary artery disease.

Type 2 diabetes (T2D) has shown limited impact on cardiac autonomic function in patients with cardiac disease at rest. The effect of T2D on autonomic responses to sympathetic stimuli, such as passive tilt and static exercise, is not well known in patients with coronary artery disease (CAD). Heart rate, arterial pressure, and their variability along with baroreflex sensitivity (BRS) were analyzed at supine rest and during passive head-up tilt (TILT) and static handgrip exercise (HG) in CAD patients with (T2D+, n=68, 61±6 years, 14 women) and without T2D (T2D-, n=68, 62±6 years, 17 women). The effect of T2D at rest and in responses to TILT and HG was examined. In T2D+, the normalized low-frequency (0.04-0.15 Hz) power of R-R intervals was higher at rest (44±17 vs. 38±17 nu, p=0.015) and its response to TILT and HG was lower than that in T2D- (8±21 vs. 2±17 nu, p=0.041 and 3±18 vs. -4±15 nu, p=0.019, respectively). Vagally mediated heart rate variability indices and BRS were not different between T2D+ and T2D-. We concluded that T2D has a specific impact on low-frequency oscillation of R-R interval among patients with angiographically documented CAD. This may indicate increased basal sympathetic modulation of sinoatrial node and lower sympathetic responsiveness to sympathetic activation by baroreceptor unloading and exercise pressor response. Limited effects of T2D on vagally mediated heart rate variability and baroreflex were observed in the patients with CAD.

Determinants of heart rate recovery in coronary artery disease patients with and without type 2 diabetes.

Cardiovascular autonomic dysfunction, which is a common complication of diabetes, is associated with increased mortality in patients with coronary artery disease (CAD). However, the reasons of autonomic dysfunction in CAD patients with or without diabetes are not well known. We examine the association between heart rate recovery (HRR) and other potential factors among CAD patients with and without type 2 diabetes (T2D). Correlations between HRR 60s after exercise (HRR(60)), characteristics, laboratory and echocardiographic variables, exercise capacity and physical activity were assessed in 50 CAD patients with T2D and 55 patients with CAD alone. HRR(60) had the closest univariate correlation with physical activity and exercise capacity in patients with T2D (r=0.38, p=0.006 and r=0.37, p=0.008, respectively). Age, exercise capacity and high-density lipoprotein cholesterol level explained 30% of the HRR(60) in patients with T2D (p=0.001), while the high intensity physical activity was the only predictor of HRR(60) in CAD patients (12%, p=0.010). HRR(60) was reduced in patients with T2D as compared with those without (34±9 vs. 39±9bpm, p=0.005), but the difference was no longer significant after adjustments for physical activity, exercise capacity, body mass index and the use of calcium antagonists and nitrates (p=0.273). In conclusion, blunted HRR is more common among CAD patients with T2D than in those without, and this is more closely related to physical activity and obesity than to the duration of T2D or associated co-morbidities.

Effects of exercise prescription on daily physical activity and maximal exercise capacity in coronary artery disease patients with and without type 2 diabetes.

BACKGROUND: Promotion of and adherence to increased physical activity (PA) is an important part of the prevention and treatment of coronary artery disease (CAD). We hypothesized that individually tailored home-based exercise prescriptions will increase long-term PA and maximal exercise capacity among CAD patients without and with type 2 diabetes (CAD+T2D). METHODS: Physical activity of patients with CAD (n = 44) and CAD+T2D (n = 39), matched by age, sex and ejection fraction, was measured over 5 days with an accelerometer pre- and postexercise prescription. PA was assessed as the average time per day of moderate (METs = 2-5) and high (METs > 5) intensities. Six-month exercise prescriptions were introduced based on individual maximal heart rate reserve. RESULTS: At the baseline, patients with CAD+T2D engaged in less moderate-intensity PA (2:40 ± 1:23 versus 3:24 ± 1:17 h, P = 0·014) and exhibited a non-significant trend to reduced high-intensity PA (2:08 ± 2:57 versus 5:02 ± 9:19 min, P = 0·091) compared with patients with CAD. High-intensity PA increased markedly in CAD (5:02 ± 9:19 versus 9:59 ± 15:03 min) and patients with CAD+T2D (2:08 ± 2:57 versus 6:14 ± 10:18 min) after exercise prescription (main effect for time P = 0·001). Also maximal exercise capacity increased in both groups (main effect for time P< 0·001). CONCLUSION: Patients with CAD with T2D are physically less active than CAD patients without diabetes in their daily life. Individually tailored home-based exercise prescriptions are an effective way to promote more active lifestyles and improve fitness in both patient groups.