Heart Rate Turbulence and T-Wave Alternans in Patients with Coronary Artery Disease: The Influence of Diabetes.

BACKGROUND: Patients with diabetes mellitus (DM) have a higher risk of sudden cardiac death. Factors associated with the risk profiles of coronary artery disease (CAD) patients with DM are not well established. Heart rate turbulence (HRT) and T-wave alternans (TWA) are often used to predict arrhythmia events. METHODS AND RESULTS: HRT and TWA were measured in two independent groups: the ARTEMIS cohort study and the REFINE-ICD randomized trial. ARTEMIS assesses risk 3-12 months after coronary angiography in patients with CAD. The initial 1001 patients in ARTEMIS, 526 with and 475 without DM, are included in this analysis. REFINE-ICD compares usual care versus usual care plus ICD therapy in patients with left ventricular (LV) ejection fraction (EF) values of 36-50% assessed 2-15 months after myocardial infarction. The initial 275 patients screened in REFINE ICD are included in this analysis. Abnormal HRT plus TWA was more common in patients with versus without DM in ARTEMIS (125/526, 24% vs 63/475, 13%; P < 0.001) and REFINE-ICD (43/55, 78% vs 55/220, 25%; P < 0.001), respectively. Abnormal HRT plus TWA was also more common in patients with LVEF values < 50% (28%) vs ≥ 50% (18%; P < 0.001) in ARTEMIS and LVEF values below the population median of 42% (60/138, 43%) versus above the median (38/137, 28%; P < 0.01) in REFINE-ICD. CONCLUSIONS: Abnormal HRT plus TWA is more common in CAD patients with DM compared with the patients without DM and is related to the severity of LV dysfunction. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov, NCT01426685; http://www.clinicaltrials.gov, NCT00673842.

Exercise capacity is associated with endothelin-1 release during emotional excitement in coronary artery disease patients.

Endothelin-1 (ET-1), a potent vasoconstrictor, IL-6, and catecholamines are increased and heart rate variability [SD of normal to normal R-R intervals (SDNN)] decreased during emotional excitement, but individual responses vary. We tested the hypothesis that exercise capacity is associated with physiological responses caused by real-life emotional excitement. We measured the plasma levels of ET-1, IL-6, catecholamines, heart rate, and SDNN in enthusiastic male ice hockey spectators (n = 51; age, 59 ± 9 years) with stable coronary artery disease (CAD) at baseline and during the Finnish National Ice Hockey League's final play-off matches. Maximal exercise capacity (METs) by bicycle exercise test and left ventricular ejection fraction (LVEF) were measured on a separate day. ET-1 response from baseline to emotional excitement correlated with maximal METs (r = -0.30; P = 0.040). In a linear stepwise regression analysis age, body mass index (BMI), METs, LVEF, basal ET-1, and subjective experience of excitement were entered the model as independent variables to explain ET-1 response. This model explained 27% of ET-1 response (P = 0.003). Maximal METs were most strongly correlated with ET-1 response (ß = -0.45; partial correlation r = -0.43; P = 0.002), followed by BMI (ß = -0.31; partial correlation r = -0.31; P = 0.033) and LVEF (ß = -0.30; partial correlation r = -0.33; P = 0.023). Exercise capacity may protect against further cardiovascular events in CAD patients, because it is associated with reduced ET-1 release during emotional excitement.

Leisure time emotional excitement increases endothelin-1 and interleukin-6 in cardiac patients.

OBJECTIVES. Emotional excitement may trigger serious cardiovascular (CV) events. Our objective was to compare the changes in potential surrogate markers of CV events in patients with coronary artery disease (CAD) during emotional excitement and exercise. DESIGN. Fifty-three enthusiastic ice-hockey spectators with stable CAD attended the Finnish national ice-hockey play-off matches and a maximal bicycle exercise. Plasma catecholamines, endothelin-1, interleukin-6, and markers of platelet activation and blood coagulation were determined before and during the match and before and after the exercise. RESULTS. Plasma endothelin-1 (2.82 ± 0.21 vs. 2.94 ± 0.25 pg/mL, p < 0.0001), noradrenaline (4.38 ± 1.79 vs. 4.77 ± 1.75 nmol/L, p = 0.009) and interleukin-6 (2.04 ± 1.98 vs. 2.90 ± 2.41 pg/mL, p < 0.0001) increased during the match, but markers of platelet activation and coagulation remained unchanged. Endothelin-1 did not change during exercise (2.73 ± 0.17 vs. 2.72 ± 0.19 pg/mL, p = 0.593) but noradrenaline (2.70 ± 1.08 vs.10.6 ± 5.5 nmol/L), adrenaline (0.23 ± 0.13 vs. 0.52 ± 0.37 nmol/L), interleukin-6 (1.77 ± 1.59 vs. 2.43 ± 1.78 pg/mL) and markers of platelet activation and blood coagulation increased significantly (p < 0.0001 for all). CONCLUSIONS. The responses of surrogate markers of acute CV events to emotional excitement and physical exercise are partly different. Emotional excitement causes concomitant increases in markers reflecting vulnerability to atherosclerotic plaque complications while physical exercise causes more prominent changes in markers of coagulation.

Recovery of rate-pressure product and cardiac mortality in coronary artery disease patients with type 2 diabetes.

AIMS: To investigate prognostic significance of post-exercise recovery of rate-pressure product (RPP) in patients with stable coronary artery disease (CAD) and type 2 diabetes (T2D). METHODS: Patients with angiographically documented CAD and T2D (n = 697) underwent symptom-limited bicycle exercise test. Exercise capacity (EC), heart rate, blood pressure and RPP responses to peak exercise and recovery (2' and 5' after cessation of exercise) were analyzed. Cardiac death was the primary and sudden cardiac death (SCD) secondary endpoint. RESULTS: During a median follow-up of 76 months, 49 cardiac deaths (7.0%) and 28 SCDs (4.0%) were observed. The recovery of RPP at 5' was the strongest univariate predictor of cardiac death (hazard ratio [HR]: 2.55 per SD decrease, 95%CI: 1.82-3.58, p < 0.001) and SCD (HR: 2.34, 95%CI: 1.51-3.62, p < 0.001). In multivariate analysis, it remained significantly associated to cardiac death and SCD without (HR: 1.66, 95%CI: 1.14-2.41, p < 0.01 and HR: 1.75, 95%CI: 1.08-2.85, p < 0.05, respectively) and with additional adjustment for EC and peak RPP (HR: 1.45, 95%CI: 1.09-1.92, p < 0.05 and HR: 1.52, 95%CI: 1.01-2.27, p < 0.05, respectively). CONCLUSIONS: The recovery of RPP after exercise is a potent predictor of cardiac death in patients with CAD and T2D. It provides significant prognostic information beyond EC and peak RPP.

Prediabetes and Risk for Cardiac Death Among Patients With Coronary Artery Disease: The ARTEMIS Study.

OBJECTIVE: To compare cardiac mortality in patients with CAD and prediabetes with that in CAD patients with normal glycemic status and type 2 diabetes. RESEARCH DESIGN AND METHODS: The Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included patients with CAD after revascularization (79%), optimal medical therapy, or both. Patients had type 2 diabetes (n = 834), impaired glucose tolerance (IGT; n = 314), impaired fasting glucose (IFG; n = 103), or normal glycemic status (n = 697) as defined on the basis of the results of an oral glucose tolerance test. The primary end point was cardiac death. Major adverse cardiac event (MACE: cardiac death, heart failure, or acute coronary syndrome) and all-cause mortality were secondary end points. RESULTS: During a mean ± SD follow-up of 6.3 ± 1.6 years, 101 cardiac deaths, 385 MACEs, and 208 deaths occurred. Patients with IGT tended to have 49% lower adjusted risk for cardiac death (P = 0.069), 32% lower adjusted risk for all-cause mortality (P = 0.076), and 36% lower adjusted risk for MACE (P = 0.011) than patients with type 2 diabetes. The patients with IFG had 82% lower adjusted risk for all-cause mortality (P = 0.015) than the patients with type 2 diabetes, whereas risks for cardiac death and MACE did not differ significantly between the two groups. The adjusted risks for cardiac death, MACE, and all-cause mortality among patients with IGT and IFG did not significantly differ from those risks among patients with normal glycemic status. CONCLUSIONS: Cardiac mortality or incidence of MACE in patients with CAD with prediabetes (i.e., IGT or IFG after revascularization, optimal medical therapy, or both) does not differ from those values in patients with normal glycemic status.

Biomarkers as predictors of sudden cardiac death in coronary artery disease patients with preserved left ventricular function (ARTEMIS study).

AIMS: Biomarkers have shown promising results in risk assessment of cardiovascular events. Their role in predicting the risk of sudden cardiac death (SCD) is not well established. We tested the performance of several biomarkers in risk assessment for SCD in patients with coronary artery disease (CAD) and preserved left ventricular function. METHODS AND RESULTS: The study population consisted of 1,946 CAD patients (68% male; mean age 66.9±8.6 yrs; type 2 diabetes (T2D) 43%) enrolled in the ARTEMIS study. The study subjects underwent examinations with echocardiography and measurement of several biomarkers. The primary endpoint of the study was SCD. During the mean follow up of 76±20 months 50 patients experienced SCD. Elevated high sensitive CRP (hs-CRP, p = 0.001), soluble ST2 (sST2, p<0.001), B-type natriuretic peptide (BNP, p<0.001), and highly sensitive TroponinT (hs-TnT, p<0.001) predicted the occurrence of SCD in univariate analysis. Using the optimal cutoff points, elevated sST2 (≥27.45ng/mL; hazard ratio [HR] 2.7; 95%CI 1.4-5.1, p = 0.003) and hs-TnT (≥15 ng/mL; HR 2.9; 95% CI 1.5-5.6, p = 0.002) were the strongest predictors of SCD followed by hs-CRP (HR 2.4; 95% CI 1.3-4.4, p = 0.004) and BNP (HR 1.9; 95% CI 1.0-3.7, p = 0.046) in adjusted analysis. Combination of elevated hs-TnT and sST2 resulted in adjusted HR of 6.4 (95% CI 2.6-15.5, p<0.001). CONCLUSION: Elevated sST2 and hs-TnT predict the occurrence of SCD among patients with CAD and preserved left ventricular function. The association between sST2, hs-TnT and SCD may be explained by an ongoing myocardial apoptosis followed by fibrosis leading to vulnerability to malignant arrhythmias.

Type 2 diabetes and coronary artery disease: Preserved ejection fraction and sudden cardiac death.

BACKGROUND: Previous studies have shown that type 2 diabetes (DM2) is associated with sudden cardiac death (SCD) risk in post-myocardial infarction patients. The treatment of coronary artery disease (CAD) as well as DM2 has changed over time. OBJECTIVE: The purpose of this study was to compare the incidence of SCD in DM2 and nondiabetic patients with CAD and preserved ejection fraction (EF) in a prospective observational study (ARTEMIS study). METHODS: In 834 DM2 patients and 1112 nondiabetic patients with CAD enrolled, the EF measured ≥3 months after qualifying was 63% ± 10% in DM2 patients and 65% ± 8% in nondiabetic patients (P < .01). The primary end point was SCD or resuscitation from sudden cardiac arrest (SCA). All-cause mortality, cardiac mortality, non-SCD, hospitalization for heart failure, and acute coronary syndrome were secondary end points. RESULTS: During a mean follow-up of 6.3 ± 1.6 years, SCDs/SCAs occurred in 50 patients. The prevalence of SCD/SCA was higher in DM2 patients (4.1%) than in nondiabetic patients (1.4%) (adjusted hazard ratio 2.6; 95% confidence interval 1.3-5.3; P < .01). However, the non-SCD component of cardiac mortality was not significantly different between DM2 and nondiabetic patients. In addition, heart failure hospitalizations were more common in DM2 patients (8.4%) than in nondiabetic patients (2.9%) (P < .001). The annual cardiac mortality in nondiabetic patients with CAD was 0.50%, which was lower than the 0.59% reported in the general Finnish population. CONCLUSION: DM2 is an independent risk factor for SCD/SCA in CAD patients with preserved EF. Cardiac mortality in nondiabetic CAD patients is slightly lower than that in the general population in the present treatment era.

Effect of Changes in Physical Activity on Risk for Cardiac Death in Patients With Coronary Artery Disease.

Leisure-time physical activity (LTPA) is associated with longevity in patients with coronary artery disease (CAD). However, less is known about prognostic significance of longitudinally assessed LTPA in patients with stable CAD. The present study assessed the relationship between changes in LTPA and cardiac mortality in patients with CAD. Patients with angiographically documented CAD (n = 1,746) underwent clinical examination and echocardiography at the baseline. Lifestyle factors, including LTPA (inactive, irregularly active, active, highly active), were surveyed at baseline and after 2 years' follow-up. Thereafter, the patients entered the follow-up (median: 4.5 years; first to third quartile: 3.4 to 5.8 years) during which cardiac deaths were registered (n = 68, 3.9%). The patients who remained inactive (n = 114, 18 events, 16%) and became inactive (n = 228, 18 events, 8%) had 7.6- (95% confidence interval [CI] 4.2 to 13.6) and 3.7-fold (95% CI 2.1 to 6.7) univariate risk for cardiac death compared with those who remained at least irregularly active (n = 1,351, 30 events, 2%), respectively. After adjustment for age, gender, body mass index, diabetes, previous myocardial infarction, left ventricular ejection fraction, angina pectoris grading, cardiovascular event during initial 2-year follow-up, smoking and alcohol consumption, the patients who remained inactive and became inactive still had 4.9- (95% CI 2.4 to 9.8, p <0.001) and 2.4-fold (95% CI 1.3 to 4.5, p <0.01) risk for cardiac death, respectively, compared with patients remaining at least irregularly active. In conclusion, LTPA has important prognostic value for cardiac death in patients with stable CAD. Even minor changes in LTPA over 2 years were related to the subsequent risk for cardiac death.

MANTA versus ProGlide vascular closure devices in transfemoral transcatheter aortic valve implantation.

BACKGROUND: The MANTA system is a novel vascular closure device (VCD) and its safety and efficacy were compared to the ProGlide VCD in patients undergoing transfemoral transcatheter aortic valve implantation (TAVI). METHODS: This is a retrospective study including 222 patients who underwent transfemoral TAVI at three Finnish University Hospitals. The MANTA VCD was used in 107 patients and their outcome was compared with that of 115 patients in whom the arterial access was closed with the ProGlide VCD. RESULTS: VARC-2 VCD failure occurred less frequently in the MANTA cohort (3.7% vs. 7.8%, p = 0.378), but the difference did not reach statistical significance. When adjusted for the introducer outer diameter, the MANTA cohort had similar rates of VARC-2 major vascular complications (9.3% vs. 12.2%, adjusted: p = 0.456), VARC-2 life-threatening/disabling bleeding (9.3% vs. 6.1%, adjusted: p = 0.296) and need of invasive treatment of bleeding (4.7% vs. 7.0%, adjusted: p = 0.416) compared to the ProGlide cohort. Additional VCDs were more frequently needed in the ProGlide cohort (58.3% vs. 1.9%, p < 0.0001). CONCLUSIONS: In patients undergoing transfemoral TAVI, the MANTA VCD showed a similar risk of VARC-2 vascular and bleeding complications compared to the ProGlide VCD, but it reduced significantly the need of additional VCDs for completion of hemostasis.

Leptin predicts short-term major adverse cardiac events in patients with coronary artery disease.

INTRODUCTION: Leptin is an adipose tissue-derived hormone associated with cardiovascular risk factors. We examined whether leptin predicts major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. METHODS: Fasting plasma leptin levels were measured in 1327 male and 619 female CAD patients. The patients were followed up for two years. The primary endpoint (MACE) was the composite of a hospitalisation for congestive heart failure (CHF) or a cardiac death. The secondary endpoint was the composite of an acute coronary syndrome (ACS) or a stroke. RESULTS: In regression analysis including established risk variables, high leptin levels were associated with a significantly increased risk of MACE (HR 3.37; 95%CI 1.64-6.90; p = 0.001) and ACS or stroke (HR 1.95; 95%CI 1.29-2.96; p = 0.002). Adding leptin to the risk model for MACE increased the C-index from 0.78 (95%CI 0.71-0.85) to 0.81 (0.74-0.88) and improved classification (NRI 0.36; 95%CI 0.13-0.60; p = 0.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001-0.030; p = 0.031). CONCLUSIONS: High plasma leptin levels predict short-term occurrence of CHF or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible harmful effects of leptin should be thoroughly investigated. Key messages Leptin is a peptide hormone secreted mainly by adipose tissue. It has been associated with several cardiovascular risk factors. High leptin levels predict the short-term occurrence of congestive heart failure or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible detrimental effects of leptin on the cardiovascular system should be thoroughly investigated.

Usefulness of Highly Sensitive Troponin as a Predictor of Short-Term Outcome in Patients With Diabetes Mellitus and Stable Coronary Artery Disease (from the ARTEMIS Study).

The aim of this study was to test the hypothesis that novel biomarkers may predict cardiac events in diabetic patients with stable coronary artery disease (CAD). Serum levels of highly sensitive troponin T (hs-TnT), B-type natriuretic peptide, highly sensitive C-reactive protein (hs-CRP), galectin-3, and soluble suppressor of tumorigenicity-2 (sST2) were analyzed in 1,137 patients with CAD and with type 2 diabetes, impaired glucose tolerance, or fasting glycaemia (diabetic group) and in 649 patients with normal glucose state. Cardiac death or hospitalization for congestive heart failure was the major end point during the follow-up of 2 years. Forty patients in the diabetic group (3.5%) and 9 patients in the nondiabetic group (1.4%) reached the primary end point. High hs-TnT level (≥14 ng/l) was the strongest predictor of the primary end point with hazard ratio of 24.5 (95% confidence interval 8.7 to 69.0; p <0.001) and remained so when adjusted for clinical variables, ejection fraction, renal, lipid, and glycemic status and other biomarkers (hazard ratio 9.9, 95% confidence interval 3.2 to 30.8; p <0.001). In the multivariate model, hs-CRP, B-type natriuretic peptide, and sST2 also predicted the primary end point in the diabetic group (p <0.01 for all). Only sST2 (p <0.001) and hs-CRP (p = 0.02) predicted the primary end point in nondiabetic group. The inclusion of hs-TnT in the model significantly improved discrimination (integrated discrimination improvement 0.050) and reclassification of the patients (net reclassification index 0.21). In conclusion, hs-TnT is a strong predictor of cardiac death or hospitalization for heart failure independently from traditional risk markers or other biomarkers in diabetic patients with stable CAD.

Serum PINP, PIIINP, galectin-3, and ST2 as surrogates of myocardial fibrosis and echocardiographic left venticular diastolic filling properties.

OBJECTIVES AND BACKGROUND: Serum biomarkers have been proposed to reflect fibrosis of several human tissues, but their specific role in the detection of myocardial fibrosis has not been well-established. We studied the association between N-terminal propeptide of type I and III procollagen (PINP, PIIINP, respectively), galectin-3 (gal-3), soluble ST2 (ST2), and myocardial fibrosis measured by late gadolinium enhanced cardiac magnetic resonance imaging (LGE CMR) and their relation to left ventricular diastolic filling properties measured by tissue Doppler echocardiography (E/e') in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: We determined the PINP, PIIINP, gal-3, and ST2 serum levels and performed LGE CMR and echocardiography on 63 patients with stable CAD without a history of prior myocardial infarction. Myocardial late gadolinium enhancement T1 relaxation time was defined as a specific marker of myocardial fibrosis. ST2, PINP, and PIIINP did not have a significant correlation with the post-LGE T1 relaxation time tertiles (NS for all), but the lowest post-LGE T1 relaxation time tertile had significantly higher gal-3 values than the other two tertiles (p = 0.002 and 0.002) and higher E/é-values (p = 0.009) compared to the highest T1 relaxation time tertile. ST2 (p = 0.025 and 0.029), gal-3 (p = 0.003 and < 0.001) and PIIINP (p = 0.001 and 0.007) levels were also significantly higher in the highest E/é tertile, compared to the other two tertiles. CONCLUSIONS: Elevated serum levels of gal-3 reflect the degree of myocardial fibrosis assessed by LGE CMR. Gal-3, ST2, and PIIINP are also elevated in patients with impaired LV diastolic function, suggesting that these biomarkers are useful surrogates of structural and functional abnormality of the myocardium.

Exercise capacity and heart rate responses to exercise as predictors of short-term outcome among patients with stable coronary artery disease.

Although exercise capacity (EC) and autonomic responses to exercise predict clinical outcomes in various populations, they are not routinely applied in patients with coronary artery disease (CAD). We hypothesized that the composite index of EC and exercise heart rate responses would be a powerful determinant of short-term risk in CAD. Patients with angiographically documented stable CAD and treated with ß blockers (n = 1,531) underwent exercise testing to allow the calculation of age- and gender-adjusted EC, maximal chronotropic response index (CRI), and 2-minute postexercise heart rate recovery (HRR, percentage of maximal heart rate). Cardiovascular deaths and hospitalization due to heart failure, registered during a 2-year follow-up (n = 39, 2.5%), were defined as the composite primary end point. An exercise test risk score was calculated as the sum of hazard ratios related to abnormal (lowest tertile) EC, CRI, and HRR. Abnormal EC, CRI, and HRR predicted the primary end point, involving 4.5-, 2.2-, and 6.2-fold risk, respectively, independently of each other. The patients with intermediate and high exercise test risk score had 11.1-fold (95% confidence interval 2.4 to 51.1, p = 0.002) and 25.4-fold (95% confidence interval 5.5 to 116.8, p <0.001) adjusted risk for the primary end point in comparison with the low-risk group, respectively. The addition of this risk score to the established risk model enhanced discrimination by integrated discrimination index and reclassification by categorical and continuous net reclassification index (p <0.001 for all). In conclusion, the composite index of EC and heart rate responses to exercise and recovery is a powerful predictor of short-term outcome in patients with stable CAD.

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.

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.

Physiological responses to emotional excitement in healthy subjects and patients with coronary artery disease.

Emotional excitement may trigger cardiovascular (CV) events, particularly in patients with coronary artery disease (CAD). Our aim was to compare changes in various biomarkers in CAD patients and age-matched healthy male subjects during "real-life" emotional excitement. Enthusiastic male ice hockey spectators (CAD n = 18, healthy subjects n = 16) attended Finnish national ice hockey play-off matches. Heart rate variability, plasma catecholamines, endothelin-1 (ET-1) and interleukin-6 (IL-6) were determined at the baseline and during the match. A significantly more marked increase in both ET-1 and IL-6 was observed in CAD patients compared with healthy subjects during the match (time × group interaction p = 0.009 and p = 0.018 for ET-1 and IL-6, respectively). The high-frequency power of R-R intervals decreased in CAD patients (p<0.001) but did not change in healthy subjects (p = ns, time × group interaction p<0.001). Changes in adrenaline and noradrenaline did not differ between the groups. Emotional excitement causes more marked increases of markers of vasoconstriction and acute inflammation and withdrawal of cardiac vagal regulation in patients with CAD.

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.

Total testosterone levels, metabolic parameters, cardiac remodeling and exercise capacity in coronary artery disease patients with different stages of glucose tolerance.

OBJECTIVE AND METHODS: The correlation between total testosterone levels, exercise capacity, and metabolic and echocardiographic parameters was studied in 1097 male subjects with coronary artery disease (CAD) and different stages of glucose tolerance. RESULTS: Testosterone level was the lowest among diabetics as compared to prediabetics or controls (P < 0.001). Total and abdominal adiposity were the highest in the subjects with the lowest testosterone. Independent of adiposity, fasting glucose, insulin, and leptin were higher (P < 0.03 to < 0.001) among diabetic and control groups in the lowest, and HbA1c values (P < 0.001) higher among diabetics in the lowest, than in the highest testosterone tertile. Controls and prediabetic subjects with the lowest testosterone levels had the lowest HDL-cholesterol levels, and controls also the highest triglycerides. An association between low testosterone level and low maximal exercise capacity was observed in diabetics (P < 0.001) and controls (P < 0.03). Independent of adiposity and metabolic parameters, low testosterone levels were associated with the highest septal wall thickness (P < 0.03) among diabetics. CONCLUSION: A negative correlation between low testosterone and dysmetabolic features was observed. Independent of metabolic status, low plasma testosterone seems to be an indicator of impaired maximal exercise capacity and cardiac hypertrophy among CAD patients with type II diabetes.

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.