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Background: The Duke treadmill score, a widely used treadmill testing tool, is a weighted index combining exercise time or capacity, maximum ST-segment deviation and exercise-induced angina. No previous studies have investigated whether the Duke treadmill score and its individual components based on bicycle exercise testing predict cardiovascular death., Design: Two populations with a standard bicycle testing were used: 3936 patients referred for exercise testing (2371 men, age 56 ± 13 years) from the Finnish Cardiovascular Study (FINCAVAS) and a population-based sample of 2683 men (age 53 ± 5.1 years) from the Kuopio Ischaemic Heart Disease study (KIHD)., Methods: Cox regression was applied for risk prediction with cardiovascular mortality as the primary endpoint., Results: In FINCAVAS, during a median 6.3-year (interquartile range (IQR) 4.5-8.2) follow-up period, 180 patients (4.6%) experienced cardiovascular mortality. In KIHD, 562 patients (21.0%) died from cardiovascular causes during the median follow-up of 24.1 (IQR 18.0-26.2) years. The Duke treadmill score was associated with cardiovascular mortality in both populations (FINCAVAS, adjusted hazard ratio (HR) 3.15 for highest vs. lowest Duke treadmill score tertile, 95% confidence interval (CI) 1.83-5.42, P < 0.001; KIHD, adjusted HR 1.71, 95% CI 1.34-2.18, P < 0.001). However, after progressive adjustment for the Duke treadmill score components, the score was not associated with cardiovascular mortality in either study population, as exercise capacity in metabolic equivalents of task was the dominant harbinger of poor prognosis., Conclusions: The Duke treadmill score is associated with cardiovascular mortality among patients who have undergone bicycle exercise testing, but metabolic equivalents of task, a component of the Duke treadmill score, proved to be a superior predictor.

Background: Exercise capacity, heart rate recovery and T-wave alternans are independent predictors of cardiovascular mortality. We tested whether these parameters contain supplementary prognostic information., Methods: A total of 3609 consecutive patients (2157 men) referred for a routine, clinically indicated bicycle exercise test were enrolled in the Finnish Cardiovascular Study (FINCAVAS). Exercise capacity was measured in metabolic equivalents, heart rate recovery as the decrease in heart rate from maximum to one minute post-exercise, and T-wave alternans by time-domain Modified Moving Average method., Results: During 57-month median follow-up (interquartile range 35-78 months), 96 patients died of cardiovascular causes (primary endpoint) and 233 from any cause. All three parameters were independent predictors of cardiovascular mortality when analysed as continuous variables. Adding metabolic equivalents (p < 0.001), heart rate recovery (p = 0.002) or T-wave alternans (p = 0.01) to the linear model improved its predictive power for cardiovascular mortality. The combination of low exercise capacity (<6 metabolic equivalents), reduced heart rate recovery (≤12 beats/min) and elevated T-wave alternans (≥60 μV) yielded the highest hazard ratio for cardiovascular mortality of 16.5 (95% confidence interval 4.0-67.7, p < 0.001). Harrell's C index was 0.719 (confidence interval 0.665-0.772) for cardiovascular mortality with previously defined cutpoints (<8 units for metabolic equivalents, ≤18 beats/min for heart rate recovery and ≥60 μV for T-wave alternans)., Conclusion: The prognostic capacity of the clinical exercise test is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans., (© The European Society of Cardiology 2014.)

Background: Psychosocial factors have been associated with cardiovascular outcomes, but few studies have examined the association between psychosocial function and natriuretic peptides., Purpose: The purpose of this study is to determine the predictive value of hostility, anger, and social support in relation to atrial natriuretic peptide (ANP), a marker of vascular health, among middle-aged men., Methods: One hundred twenty-one men (mean age = 39.8 years, SD = 4.1) underwent assessments of ANP and completed the Cook-Medley Hostility Scale, the Spielberger State-Trait Anger Scale, and the Interview Schedule for Social Interaction., Results: Higher levels of hostility (β = 0.22 [95 % CI 0.04, 0.40], P = 0.032) and trait anger (β = 0.18 [95 % CI 0.01, 0.37], P = 0.044) were associated with greater ANP levels. In contrast, higher perceived social support was also associated with lower ANP levels, (β = -0.19 [95 % CI -0.05, -0.41], P = 0.010)., Conclusions: Psychosocial factors, including hostility, anger, and social support, are associated with varying ANP levels among middle-aged men, independent of cardiovascular and behavioral risk factors.

Aims: As a part of the Finnish Cardiovascular Study, we tested the hypothesis that T-wave alternans (TWA) predicts mortality in a general population of patients referred for a clinical exercise test., Methods and Results: A total of 1037 consecutive patients (mean age+/-SD of 58+/-13 years, 673 men and 364 women) with a clinically indicated exercise test and with technically successful electrocardiographic (ECG) data during a bicycle ergometer test were included in the study. Digital ECGs were recorded and TWA was analysed continuously with the time-domain modified moving average method. The maximum TWA value at heart rate (HR)<125 b.p.m. was derived and its capacity to stratify risk for all-cause death, cardiovascular death, and sudden cardiac death (SCD) was tested. During a follow-up of 44+/-7 months (mean+/-SD), 59 patients died; 34 were due to cardiovascular causes and 20 were due to SCD. In multivariate analysis after adjustment for age, sex, use of beta-blockers, functional class, maximal HR during exercise, previous myocardial infarction, and other common coronary risk factors, the relative risk of TWA>or=65 microV for SCD was 7.4 (95% CI, 2.8-19.4; P<0.001), for cardiovascular mortality 6.0 (95% CI, 2.8-12.8; P<0.001), and for all-cause mortality 3.3 (95% CI, 1.8-6.3; P=0.001)., Conclusion: Time-domain TWA analysis powerfully predicts mortality in a general population undergoing a clinical exercise test.

Electrocardiogram and intraarterial blood pressure (BP) were recorded in 35 normotensive (NT), 29 borderline hypertensive (BHT), and 30 mildly hypertensive (HT) men (aged 35 to 45 years) by the Oxford method over a 24-h period. Consecutive data segments of 5 min were extracted from the recordings for frequency domain analysis. Heart rate (HR) and BP variability was calculated for oscillations between 0.05 and 0.12 Hz, usually referred to as Mayer waves. Power and median frequency of the oscillations were determined. Some 10% of the segments were excluded from the analysis because of artifacts and transients. The results were averaged for 5-h periods in the evening, at night, and during the day. In the BHT subjects, the median frequency of the Mayer waves was shifted to lower frequencies as compared with the NT subjects. This was seen at night and during the day. The phenomenon presumably reflects an increased latency in the sympathetic vasomotor control of the baroreceptor reflex. No between-group differences were found in the normalized spectral power values. Five years later, 24 NT, 22 BHT, and 19 HT subjects were reassessed using casual BP and noninvasive ambulatory 24-h monitoring. In the initial phase, the median frequencies for the 5-h periods showed no evident linear relationship with the corresponding BP levels. However, the median frequencies showed high inverse correlations with the follow-up ambulatory BP levels. In the evening and during the day, the median frequency showed a significant inverse correlation also with the increment in BP. No clear relationship was found between power estimates and BP levels or future increments in BP. In conclusion, the frequency shift of Mayer waves to lower frequencies is associated with an increased risk of developing established hypertension.

The aim of this study was to quantify the frequency shift in vasomotor oscillations in blood pressure we observed in borderline hypertensive individuals in our previous study. Electrocardiogram and intraarterial blood pressure were recorded in 33 normotensive, 29 borderline hypertensive, and 33 mildly hypertensive men (aged 35 to 45 years). Five-minute stationary periods in supine, sitting, and standing positions, and during sleep were extracted from the recordings for autoregressive frequency domain analysis. In borderline hypertensive subjects vasomotor oscillations in the range of 0.05 to 0.12 Hz in blood pressure and heart rate, assumed to be associated with baroreceptor activity, were shifted to lower values as compared with the other two groups. The frequency shift was assessed by median frequency of the oscillations. Significant between-group differences were observed in the supine and sitting positions. No significant between-group differences were seen in normalized spectral power estimates. Further studies are required to determine whether the frequency shift provides prognostic information on cardiovascular morbidity.

There is considerable disagreement in the literature on the clinical usefulness of exercise testing as a tool for prediction of future hypertension. Much of the discrepancy between various reports is attributable to the difficulties of blood pressure (BP) measurement during exercise. Therefore, we investigated whether accurate intraarterial BP measurement will increase the predictive power of exercise testing. The BP responses to dynamic and isometric exercise were evaluated in 97 healthy, unmedicated men, of whom 34 were normotensive (NT), 29 borderline (BHT), and 34 mildly hypertensive (HT) using three criteria: 1) achieved BP during the test, 2) the change of the BP from baseline to exercise, and 3) the group was divided into high responders (HIGH, n = 19, systolic BP > or = 220 and diastolic BP > or = 105 mm Hg) and normal responders (n = 60). Five years later the BP was reassessed by casual measurements and noninvasive ambulatory 24-h monitoring (NAMB) in 79 (81%; 27 NT, 24 BHT, and 28 HT) subjects. The achieved isometric BP correlated well with the follow-up BP (casual systolic BP r = 0.43, diastolic BP r = 0.45, and NAMB systolic BP r = 0.44, diastolic BP r = 0.58, P < .001). However, achieved dynamic BP showed a poorer relationship to future BP (r range, 0.09 to 31, P = NS to P < .01). Because the intraarterial preexercise sitting BP also correlated well with follow-up BP (r range, 0.33 to 0.48, P < .01 to P < .001), and the r values were close to those of achieved isometric BP we used multiple regressions (including all resting and exercise BP values as independent variables) to evaluate the contributions of the baseline and exercise values for prediction of the follow-up BP. The baseline value explained 12% to 23% (from casual diastolic BP to NAMB diastolic BP, systolic BP values) of future BP variance, whereas achieved isometric BP ranged an additional 1% to 11% (from casual systolic BP to NAMB diastolic BP) of variance. In general, BP change from baseline with stressors did not correlate with follow-up measurements. In the high responder group the achieved dynamic BP did not correlate significantly with the follow-up BP, whereas the achieved isometric diastolic BP did correlate (casual diastolic BP r = 0.56, P < .05, NAMB systolic BP and diastolic BP r = 0.52, P < .05). Both groups had similar future BP levels. In conclusion, even with very accurate BP readings the reactivity to dynamic exercise is a weak predictor of future BP, and does not improve the prediction compared to resting BP values. Intraarterial BP response to isometric exercise marginally improves the prediction of future BP levels.

The aims of this study were to determine the importance of ambulatory blood pressure measurement, diurnal blood pressure (BP) profile, and variability in the evaluation of left ventricular (LV) parameters, and the impact of smoking on these factors. We performed intraarterial ambulatory BP (IAMB) recording and echocardiography in 80 healthy, unmedicated men aged 35 to 45 years. Based on repeated casual (CAS) readings before the study, the subjects were classified as normotensive (NT, n = 32), borderline hypertensive (BHT, n = 21), or mildly hypertensive (HT, n = 27) according to WHO criteria. There were 19 (8 NT/5 BHT/6 HT) smokers and 48 (18 NT/13 BHT/17 HT) nonsmokers. Both BHT and HT had significantly greater LV mass index (LVMI) than NT, but LVMI did not differ between nonsmokers and smokers. For the whole group, 24-h BP correlated somewhat better with LVMI than CAS BP (24-h IAMB SBP r = 0.44, P < .001, DBP r = 0.36, P < .001, and CAS SBP r = 0.35, P < .01, DBP r = 0.37, P < .001). Casual SBP alone explained 12% of LVMI variance (F = 10.7, P < .01), whereas 24-h IAMB SBP alone explained 19% of LVMI variance (F = 18.4, P < .001). When comparing day and night SBP and DBP levels, night SBP showed the closest correlation with LVMI (r = 0.43, P < .001), and this alone explained 18% of LVMI variance (F = 18.1, P < .001). Smokers had higher correlations between night BP and LVMI (SBP and DBP r = 0.56, P < .05) than nonsmokers (SBP r = 0.37, P < .01 and DBP r = 0.30, P < .05). In a multiple linear regression including all BP variables, for smokers, night DBP (although only marginally better than night SBP) was the best predictor, explaining 32% of LVMI variance (F = 10.6, P < .01) and additionally night DBP standard deviation (SD) added 18% to the prediction of LVMI (F = 5.8, P < .05). For nonsmokers, day SBP had closest correlation with LVMI (r = .43, P < .01), but explained only 19% of LVMI variance (F = 10.5, P < .01), and other measures did not increase the explanation. We conclude that ambulatory BP was slightly better than CAS BP in predicting LVMI, but BP level, also when measured with the best method available, explained only a moderate fraction of LVMI variance in mild hypertension. However, among smokers, BP, especially nighttime and BP variability, explained LV changes better than among nonsmokers. Thus smoking may have an impact on the interaction of ambulatory BP and LVMI, and in future studies more attention should be paid to this toxic factor.

The diagnostic value of 123I-phenylpentadecanoic acid (IPPA) metabolic cardiac imaging was studied in a group (n = 29) of patients with angiographically confirmed CAD using single photon emission computed tomography (SPECT). A symptom-limited exercise test was first done with IPPA, and 2 days later with thallium. Medications were not withheld during testing. Fourteen healthy control subjects participated in parallel IPPA and 15 in thallium tests. Data acquisition and output were comparable in the two imaging modalities. By testing various relatively simple criteria for abnormality we found that the semiquantitative interpretation was more accurate than the visual readings. The best compromise of accuracy with the scored criteria consisted of a sensitivity of 86% and a specificity of 86%, obtained with IPPA polar tomograms (mild exercise defect) and a sensitivity of 86% and a specificity of 80% obtained with thallium (regionally decreased washout). With visual interpretation alone, a sensitivity of 83% and a specificity of 71% was detected with IPPA (mild exercise defect) and 72% and 73%, respectively, with thallium (partial reversibility). The sensitivity of the exercise ECG alone was 62%. The results of this study imply that IPPA imaging could be a rational, uncomplicated clinical method for non-invasive diagnosis of CAD. The diagnostic ability of IPPA is at least as good as that of thallium, and it is possible to use them in succession.