Arto Uusitalo

Short-term variability of blood pressure and heart rate in borderline and mildly hypertensive subjects.

Electrocardiogram and intra-arterial blood pressure were recorded in 96 men (aged 35 to 45 years) by the Oxford method over a 30-hour period. The study involved 33 normotensive, 29 borderline hypertensive, and 34 mildly hypertensive individuals, as assessed by the cuff method. Five-minute periods during sleep and with subjects in supine, sitting, and standing positions were extracted from the recordings for frequency domain analysis. Power spectrum density estimates of systolic blood pressure, diastolic blood pressure, and heart rate were calculated by an autoregressive method over the bandwidths of 0.02 to 0.075 (low-frequency), 0.075 to 0.15 (midfrequency), and 0.15 to 0.35 Hz (high-frequency), attributable to thermoregulatory, baroreceptor, and respiratory activity. No significant intergroup differences were observed at nighttime, but in different body positions the borderline hypertensive subjects frequently had either greater low-frequency variability or smaller midfrequency variability than the other groups. In this respect, the power spectra for systolic and diastolic blood pressures provided better statistical differentiation between the groups than those for heart rate. Furthermore, the borderline hypertensive subjects exhibited attenuated night-day changes in the low-frequency band for all time series. The results suggest that in borderline hypertension the baroreceptor oscillations are shifted to lower frequencies, presumably reflecting altered function of the sympathetic nervous system. In conclusion, spectral analysis of blood pressure variability for controlled test situations made it possible to detect differences in the cardiovascular regulatory systems between normotensive, borderline hypertensive, and mildly hypertensive individuals.

Blood pressure and heart rate variability and reactivity as related to daily activities in normotensive men measured with 24-h intra-arterial recording.

The effect of blood pressure and heart rate reactivity on respective variability in everyday life conditions was studied in a group of middle-aged, normotensive men (n = 22, mean age 39.3 years, range 35-45 years). Continuous intra-arterial tape recording was used to measure 24-h blood pressure and heart rate and the subjects completed a 24-h behavioural diary. The variability of blood pressure and heart rate was analysed using 30-s averages and cumulative distribution curves. The overall blood pressure and heart rate variability was calculated as the difference between the 90 and 10% levels of the cumulative distribution curves. Reactivity caused by different daily activities was calculated as the change from baseline level, defined as the 10% level determined from the cumulative distribution curve of waking hours. All regular activities were monitored. Large interindividual differences were found in variability and reactivity. The mean reactivity to different activities varied from 3.3 to 44.7 mmHg for systolic blood pressure, from 1.8 to 16.3 mmHg for diastolic blood pressure and from 2.0 to 46.0 beats/min for heart rate. The mean contribution of reactivity to variability varied between 21 and 74% for systolic blood pressure, from 19 to 58% for diastolic blood pressure and from 20 to 82% for heart rate. As expected, blood pressure and heart rate levels were significantly higher at work than at home. We conclude that the reactivity caused by daily activities has a pronounced influence on blood pressure level and variability during waking hours.

Blood Pressure Responses to Exercise as Predictors of Blood Pressure Level After 5 Years

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.

Performance characteristics of various exercise ECG classifiers in different clinical populations

To improve the diagnostic power of the exercise electrocardiographic test in detecting myocardial ischemia, the authors have recently developed a diagnostic method called multivariate ST-segment/heart rate (ST/HR) analysis (MUSTA). The goal of this study was to evaluate the validity of MUSTA in different clinical populations and to compare its performance characteristics with ST-segment depression, the ST/HR slope, and the delta ST/HR index in these populations. The computerized exercise electrocardiographic measurements were performed on 1,507 cases, and 382 patients were selected as the study population: 161 with significant coronary artery disease according to coronary angiography and 221 with a low likelihood of coronary artery disease. The diagnostic accuracy of MUSTA in the pooled population was 77.7% (297 out of 382 patients), which was clearly better than the accuracy of 69.6% (266 out of 382 patients) using the conventional ST-segment depression criterion of 0.10 mV in detecting coronary artery disease and exercise-induced myocardial ischemia. According to receiver operating characteristics analysis, MUSTA had significantly better diagnostic power than the other classifiers. These findings suggest that multivariate and compartmental analysis methods like MUSTA can further improve the clinical importance of the exercise electrocardiogram.

Blood Pressure Levels and Variability, Smoking, and Left Ventricular Structure in Normotension and in Borderline and Mild Hypertension

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.

Frequency Shift in Baroregulatory Oscillation in Borderline Hypertensive Subjects

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.

Blood pressure level changes caused by posture change and physical exercise: can they be determined accurately using a standard cuff method?

The accuracy of the indirect standard cuff method of measurement was tested against intra-arterial blood pressure readings (Oxford method) in a series of simple clinical tests: in the sitting, supine and standing positions, during bicycle ergometer test and during recovery. The mean discrepancy between methods varied in tests from −2.3 to 12.9 mmHg for systolic blood pressure level and from −4.3 to 18.2 mmHg for diastolic blood pressure level. Blood pressure responses to other tests were analysed using the value measured in the sitting position as the reference. The. mean discrepancy between the methods in test responses varied from −6.3 to 8.9 mmHg for systolic responses and from −2.3 to 20.3 mmHg for diastolic responses. The data analysis indicates that the accuracy of the indirect method varies considerably between tests and also between subjects. We conclude that at present the standard cuff method cannot replace the direct method for determining blood pressure responses and reactivity.

Inhomogeneous exercise uptake and accelerated washout of a radioiodinated fatty acid analogue in syndromeX A SPECT study of the left ventricle

Myocardial metabolism in exercise was determined by studying 21 syndromeX patients and 14 healthy volunteers with an aromatic fatty acid analogue IPPA and a gamma camera. We developed criteria for visual semiquantitative assessment of relative segmental radiotracer uptake and washout, and tested a new computer program for quantitative evaluation. One volunteer (7%) and 12 patients (57%) showed visually inhomogeneous uptake (p=0.006, χ2-test) in SPECT polar tomograms after a maximal ergometry test. Images in none of the volunteers and seven patients (33%) gave the impression of a slowed regional washout (p=0.057). Only six patients (29%) had a normal radial polarogram. Patients with irregular coronary angiograms (showing ‘slow flow’ or minor sclerosis) and those with chest pain during the IPPA exercise test had a very low frequency of normalcy, but this was not significant.Total washout was higher in patients than in the reference population, as the exercise to rest activity ratio was 1.36 SD 0.13 versus 1.25 SD 0.11 in computerized quantitation (p=0.015, t-test). Washout did not correlate with age, sex or exercise heart rate. Regarding computerized analysis of uptake and slow washout, the number of deviant segments was not significantly higher in patients than in reference population. Semiquantitative and quantitative analysis correlated in the assessment of uptake, but not in the assessment of washout. Possible reasons for the discrepancy are discussed.Conclusions of this study are not straightforward. SyndromeX was associated with inhomogeneous IPPA uptake, which is not at variance with the theory of microvascular dysfunction. On the other hand, the analysis of washout presumably implies higher fatty acid utilization in patients than in normal controls, which is not a characteristic phenomenon in myocardial ischemia.

Plasma ANP and cyclic GMP after physical exercise in patients with mitral valve disease and in healthy subjects

Plasma levels of both atrial natriuretic peptide (ANP) and cyclic GMP are elevated in patients with various heart diseases as compared to healthy subjects. In this study patients with advanced mitral valve disease (Group A) and healthy subjects (Group B) were exposed to symptom-limited upright stepwise physical exercise on a cycle ergometer. Concentrations of ANP and cyclic GMP were measured in plasma at rest (20 min in supine position) or 5 min after physical exercise by specific radioimmunoassays. Here we show that short dynamic exercise caused a significant increase in plasma levels of ANP and cyclic GMP, in both groups. In Group A strong correlation between plasma ANP and cyclic GMP was found at rest (r = 0.91, P < 0.001, n = 11) and after physical exercise (r = 0.85, P < 0.001, n = 11). In contrast, there was no correlation between plasma concentrations of ANP and cyclic GMP in Group B at rest (r = -0.16, P > 0.05, n = 10) or after exercise loading (r = 0.14, P > 0.05, n = 10). Absolute increases in circulating levels of both substances were not found to correlate in either group. These data suggest that exercise-induced elevations in plasma cyclic GMP may be due not only to ANP release but also to an as yet undetermined factor, possibly EDRF/NO.

Patency of the infarct-related coronary artery — a pertinent factor in late recovery of myocardial fatty acid metabolism among patients receiving thrombolytic therapy?

The decrease in mortality among patients receiving thrombolytic therapy for myocardial infarction is greater than would be expected from the improvement in left ventricular contractile function alone; thus some additional advantage of recanalization of the infarctrelated coronary artery probably exists. Changes in the post-infarction myocardial metabolic state with respect to artery patency have not been studied with a gamma camera previously. A single-photon emission tomography scan using the fatty acid analogue para-123I-iodophenylpentadecanoic acid was performed at rest before hospital discharge on nine patients with first anterior myocardial infarction. All patients had received intravenous thrombolytic therapy at the beginning of the insult. The semiquantitative analysis of the left ventricle included a total of 44 segments in each patient. The test was repeated 3 months later, with the patients divided into two groups: six patients had an angiographically patent left anterior descending coronary artery (group A), and three an occluded artery (group B). In group A the number of myocardial segments with abnormal (<70% of maximum) fatty acid uptake was initially 20.2±4.7 (mean±SD) and was reduced to 11.3±6.1 during the follow-up (95% confidence interval of the decrease 16.0–1.7 segments). In group B the number of these aberrant segments was fairly constant (21.7±13.1, initial test, and 21.3±13.3, retest). Our preliminary results suggest that even when thrombolytic therapy fails to prevent myocardial infarction, myocardial fatty acid metabolism has a better change of recovering if the relevant coronary artery has regained its patency. This finding emphasizes the need for further study to establish whether a direct link exists between myocardial metabolic state and patient survival after infarction.