Hemodynamic and central blood pressure differences between carvedilol and valsartan added to lisinopril at rest and during exercise stress

There is little information about the hemodynamic and exercise-response implications of renin-angiotensin system blocker combinations. After a 3-week lisinopril (L; 40 mg/day) run-in, carvedilol (C; 20 then 40 mg/day) or valsartan (V; 160 then 320 mg/day) was added to L for 4 weeks each in a forced-titration, random order-entry crossover study in 30 subjects. Arterial tonometry (central pressures and time-tension index, TTI); impedance cardiography (steady-state hemodynamics), and ultrasound (carotid flow) were performed at rest and during supine bicycle exercise at 30 and 60 watts. At rest, both V and C lowered TTI similarly (7% to 9%, P = .05 compared with L, in part because they lowered blood pressure (3 to 7/3 to 4 mm Hg). V lowered central systolic pressure, augmentation pressure (AP), and systemic vascular resistance (SVR, all P < .02); C lowered heart rate but not central systolic pressure or SVR. During exercise, V persistently lowered central systolic pressure, AP, and SVR, whereas C did not. Neither drug affected exercise responses or carotid blood flow. Adding V or C to an angiotensin-converting enzyme inhibitor reduced cardiac workload by different mechanisms: vasodilation and reduced central blood pressure with V and lower heart rate with C.     

Effect of age on mean heart rate and heart rate variability

Age-related changes in heart rate and in its variability might prove to be a suitable parameter to evaluate the physiological course of advancing age in human beings. We demonstrated higher mean heart rate values and increased heart rate variability in younger adult subjects. A significant direct relationship was demonstrated by linear regression equation between age and the product between mean heart rate and heart rate variability. We conclude that the analysis of these parameters may help assess the aging process of human beings.     

高血压患者静息心率、率压乘积及其临床意义

目的　探讨高血压患者静息心率及率压乘积的变化及其意义。方法　 40 5例高血压患者 ,平均年龄 5 6.8岁 ,男 2 2 8例 ,女 177例 ,测定其静息心率、血压、血脂及血糖 ,并与正常对照组 2 38例进行比较。结果　高血压组静息心率及率压乘积显著高于正常对照组 (P<0 .0 5 ) ,合并左心室肥厚者高于无左心室肥厚者 (P<0 .0 5 )。合并高血糖及高胆固醇者 ,其静息心率显著高于血糖及胆固醇正常者。结论　静息心率及率压乘积与高血压的发展、高血压靶器官损害左心室肥厚及高血压合并代谢异常有关。     

缬沙坦对高血压心率变异性的影响

目的　观察缬沙坦对高血压心率变异性的影响。方法　 70例原发性高血压患者服用缬沙坦 ,在治疗前与治疗 12周后行动态心电图及心率变异性检查 ,并与对照组 ( 30例 )比较。结果　治疗后连续 R-R间期标准差 ( SDNN ) ,相邻 R-R间期均方差( RMSSD) ,相邻 R-R间期大于 5 0 ms百分数 ( PNN5 0 ) ,高频功率 ( HF)值均明显上升 ,低频功率与高频功率比值 ( LF /HF )显著降低 ( P<0 .0 1)。结论　原发性高血压患者服用缬沙坦后使交感神经功能活动减退而继发引起迷走神经功能增强     

Resting and ambulatory heart rate variability in chronic anorexia nervosa

Heart rate variability was measured at rest and during ambulation in 6 women with anorexia nervosa. Compared with 10 nonanorexic women controls, resting and ambulatory measures of heart rate variability tended to be lower in patients, despite no differences in resting heart rate.     

Changes in heart rate and heart rate variability before ambulatory ischemic events(1)

OBJECTIVES: The aim of this study was to determine the time course of autonomic nervous system activity preceding ambulatory ischemic events. BACKGROUND: Vagal withdrawal can produce myocardial ischemia and may be involved in the genesis of ambulatory ischemic events. We analyzed trajectories of heart rate variability (HRV) 1 h before and after ischemic events, and we examined the role of exercise and mental stress in preischemic autonomic changes. METHODS: Male patients with stable coronary artery disease (n = 19; 62.1 +/- 9.3 years) underwent 48-h ambulatory electrocardiographic monitoring. Frequency domain HRV measures were assessed for 60 min before and after each of 68 ischemic events and during nonischemic heart rate-matched control periods. RESULTS: High-frequency HRV decreased from -60, -20 to -10 min before ischemic events (4.8 +/- 1.3; 4.6 +/- 1.3; 4.4 +/- 1.2 ln [ms(2)], respectively; p = 0.04) and further from -4, -2 min, until ischemia (4.4 +/- 1.3; 4.1 +/- 1.3; 3.7 +/- 1.2 ln [ms(2)]; p's < 0.01). Low frequency HRV decreases started at -4 min (p < 0.05). Ischemic events occurring at high mental activities were preceded by depressed high frequency HRV levels compared with events at low mental activity (p = 0.038 at -4 min, p = 0.045 at -2 min), whereas the effects of mental activities were not observed during nonischemic control periods. Heart rate variability measures remained significantly decreased for 20 min after recovery of ST-segment depression when events were triggered by high activity levels. CONCLUSIONS: Autonomic changes consistent with vagal withdrawal can act as a precipitating factor for daily life ischemia, particularly in episodes triggered by mental activities.     

Influence of age on ambulatory electrocardiogram-derived heart rate variability

OBJECTIVE: To evaluate the quantitative change in heart rate variability with age by using 24 h Holter ambulatory monitoring of electrocardiogram and to set the lower limit of heart rate variability depending on age. PARTICIPANTS: Eighty healthy subjects without any medication (male to female ratio 40:40, 45.6 +/- 14.1 years of age, range 16 to 68 years). METHODS: Holter monitoring was performed, and frequency and time domain heart rate variability was obtained. RESULTS: A significant inverse relationship was found between age and heart rate variability, especially in the frequency domain, and, in the time domain analysis, in the root mean square of the difference in the RR intervals of sinus rhythm (NN) between successive beats and in the portion of NN cycles greater than 50 ms apart. Except for the standard deviation of the mean of RR intervals taken every 5 mins and averaged over 24 h and the ratio of low frequency high frequency power spectra, all parameters decreased to a certain age and did not change thereafter, and the rate of decrease differed among the parameters of heart rate variability. Because age had a strong influence on heart rate variability, the lower limit of heart rate variability for a certain age was determined by using the polynomial curve fitting of the moving average minus 2 SD of 10 consecutive subjects. By using these equations, it could be determined whether heart rate variability was normal or abnormal depending on age.     

Relation of mean heart rate and heart rate variability in patients with left ventricular dysfunction.

The new finding was that mean heart rate and heart rate variability were more closely coupled in patients with more advanced LV dysfunction. Mean heart rate explained a larger portion of variance in heart rate variability in patients in the lowest LVEF quartile than in those in the highest one. These results support our hypothesis that sympathetic activation in patients with more severe LV dysfunction results in closer correlation between heart rate and heart rate variability. Generally, the correlation between mean heart rate and heart rate variability is weak because heart rate and heart rate variability represent different modalities of cardiovascular regulation. Mean heart rate is normally determined by the interactions of both the sympathetic and parasympathetic nervous systems, whereas modulation of these activities, with different gains, determines the magnitude of heart rate variability. This results in great complexity in control of the heart by the autonomic nervous system. However, heart rate is likely to be more dominantly regulated by the sympathetic nervous system because of vagal withdrawal in patients with more severe LV dysfunction. The effect of sympathetic cardiac modulation has been shown to be more sluggish than that of the parasympathetic nervous system in beat-to-beat regulation of heart rate. This may result in more blunted heart rate variability concomitantly with elevated mean heart rate. Thus, variation in heart rate variability in any given mean heart rate is likely to be lower than in patients with more preserved LV function, and hence with more complex cardiac autonomic regulation with involvement of the parasympathetic nervous system. Indeed, even the slopes of regression lines between mean heart rate and heart rate variability were similar in the first and fourth LVEF quartile; the intercept of the regression line was significantly higher in the fourth quartile than in the first one. This further supports our hypothesis.     

Relationships of heart rate and heart rate variability with conventional and ambulatory blood pressure in the population

BACKGROUND: Most studies on relationships between blood pressure and autonomic nervous function, assessed by power spectral analysis of heart rate variability, have used conventional or clinic blood pressure measurements in selected subjects, which may have influenced the results. OBJECTIVE: We aimed to investigate, in a population-based approach, associations of heart rate and heart rate variability, assessed in basal resting conditions and in response to standing, with conventional blood pressure measured by an investigator, and with ambulatory blood pressure monitored outside the laboratory. METHODS: RR interval and respiration were registered in 614 men and women, ages 25-89 years. After exclusion of subjects with myocardial infarction or diabetes and elimination of unsatisfactory recordings, 549 subjects remained for analyses at supine rest and 515 of these to assess the orthostatic responses. Hypertension was present in 39% of the subjects. The low-frequency (LF) and high-frequency (HF) components of heart rate variability were quantified by use of autoregressive modelling and expressed in absolute and normalized units. RESULTS: At supine rest, indices of heart rate variability were not independently related to 24 h systolic blood pressure, whereas some indices showed weak associations with diastolic 24 h pressure; the relationships were in general stronger for conventional blood pressure. For example, partial correlation coefficients of the relationships of the LF: HF ratio with systolic pressure were 0.12 (P < or = 0.01) for conventional pressure and 0.02 (NS) for 24 h pressure; these coefficients amounted to 0.20 (P < or = 0.001) and 0.11 (P < or = 0.01) for the diastolic pressures. The decrease of HF power and the increase of the LF:HF ratio on standing were significantly blunted at higher blood pressure, both when measured conventionally and by ambulatory monitoring (P < or = 0.001 for the LF: HF ratio). CONCLUSIONS: Relationships between autonomic nervous function at rest, assessed by use of power spectral analysis of heart rate variability, and conventional blood pressure, can at least partly be ascribed to the influence of the measurement conditions, whereas the orthostatic autonomic responses appear to be influenced by blood pressure per se.     

Effects of carvedilol on heart rate and blood pressure variability in subjects with chronic heart failure

In this study we observed that carvedilol administration to patients with heart failure improves hemodynamic function, baroreflex sensitivity, and heart rate variability. These findings contribute to improvement in survival in such patients.     

Ambulatory heart rate is underestimated when measured by an ambulatory blood pressure device.

OBJECTIVE: To test the validity of ambulatory heart rate (HR) assessment with a cuff ambulatory blood pressure (ABP) monitor. DESIGN: Cross-instrument comparison of HR measured intermittently by a cuff ABP monitor (SpaceLabs, Redmond, Washington, USA), with HR derived from continuous electrocardiogram (ECG) recordings (1) in a controlled laboratory experiment and (2) during long-term recording in a true naturalistic setting. PARTICIPANTS: Six normotensive subjects participated in the laboratory study. A total of 109 male white-collar workers underwent ambulatory monitoring, of which 30 were mildly hypertensive. METHODS: Four different laboratory conditions (postures: lying, sitting, standing, walking), repeated twice, were used to assess the short-term effects of cuff inflation on the HR. To test the actual ambulatory validity, participants simultaneously wore a continuous HR recorder and the ABP monitor from early morning to late evening on 2 workdays and one non-workday. Diary and vertical accelerometery information was used to obtain periods of fixed posture and (physical) activity across which HR from both devices was compared. RESULTS: Laboratory results showed that the ABP device reliably detected HR during blood pressure measurement, but that this HR was systematically lower than the HR directly before and after the blood pressure measurement. The ambulatory study confirmed this systematic underestimation of the ongoing HR, but additionally showed that its amount increased when subjects went from sitting to standing to light physical activity (2.9; 4.3 and 9.1 bpm (beats/min), respectively). In spite of this activity-dependent underestimation of HR, the correlation of continuous ECG and intermittent ABP-derived HR was high (median r= 0.81). Also, underestimation was not different for normotensives and mild hypertensives. CONCLUSIONS: A direct effect of cuff inflation leads to the underestimation of ongoing HR during cuff-based ABP measurement. Additional underestimation of HR occurs during periods with physical activity, probably due to behavioural freezing during blood pressure measurements. HR underestimation was not affected by hypertensive state. When its limitations are taken into account, ABP-derived ambulatory HR can be considered a reliable and valid measure.     

Effects of work stress on ambulatory blood pressure, heart rate, and heart rate variability

Work stress has repeatedly been associated with an increased risk for cardiovascular disease. This study tested whether this relationship could be explained by exaggerated cardiovascular reactivity to work or impaired recovery in leisure time. Vagal tone was assessed as a possible determinant of these work stress effects. Participants included 109 male white-collar workers (age, 47.2+/-5. 3) who were monitored on 2 workdays and 1 nonworkday for ambulatory blood pressure, heart rate, and heart rate variability. Chronic work stress was defined according to Siegrist's model as (1) high imbalance, a combination of high effort and low reward at work, or (2) high overcommitment, an exhaustive work-related coping style indexing the inability to unwind. All findings were adjusted for possible differences in posture and physical activity between the work stress groups. High imbalance was associated with a higher heart rate during work and directly after work, a higher systolic blood pressure during work and leisure time, and a lower 24-hour vagal tone on all 3 measurement days. Overcommitment was not associated with an unfavorable ambulatory profile. Logistic regression analysis revealed that heart rate [odds ratio 1-SD increase 1.95 (95% CI, 1.02 to 3.77)] and vagal tone [odds ratio 1-SD decrease 2.67 (95% CI, 1.24 to 5.75)] were independently associated with incident mild hypertension. Surprisingly, the values during sleep were more predictive for mild hypertension than the values during work. The results from the present study suggest that the detrimental effects of work stress are partly mediated by increased heart rate reactivity to a stressful workday, an increase in systolic blood pressure level, and lower vagal tone.     

Reproducibility and relation to mean heart rate of heart rate variability in normal subjects and in patients with congestive heart failure secondary to coronary artery disease

Before heart rate (HR) variability can be used for predictive purposes in the clinical setting, day-to-day variation and reproducibility need to be defined as do relations to mean HR. HR variability and mean HR were therefore determined in 2 successive 24-hour ambulatory electrocardiograms obtained from 33 normal subjects (age 34 ± 7 years, group I), and 22 patients with coronary disease and stable congestive heart failure (CHF) (age 59 ± 7 years, group II). Three measures were used: (1) SDANN (standard deviation of all mean 5-minute normal sinus RR intervals in successive 5-minute recording periods over 24 hours); (2) SD (the mean of the standard deviation of all normal sinus RR intervals in successive 5-minute recording periods over 24 hours); and (3) CV (coefficient of variation of the SD measure), a new measure that compensates for HR effects. Group mean HR was higher and HR variability lower in group II than in group I (80 ±10 vs 74 ± 9 beats/min, p < 0.04). Mean group values for HR and HR variability showed good correlations between days 1 and 2 (mean RR, R = 0.89, 0.97; SDANN, R = 0.87, 0.87; SD, R = 0.93, 0.97; CV, R = 0.95, 0.97 in groups I and II, respectively). In contrast, considerable individual day-to-day variation occurred (group I, 0 to 46%; group II, 0 to 51%). Low HR variability values were more consistent than high values. SDANN and SD correlated moderately with HR in both groups (r = 0.50 to 0.64). The CV measure minimizes HR effects on HR variability. In conclusion (1) mean group differences in HR variability between normal subjects and patients with CHF are highly reproducible, but considerable day-to-day variations may occur in some subjects, particularly normal persons with high HR variability; (2) mean HR is higher and HR variability lower in patients with CHF; and (3) mean HR must be considered when interpreting changes in HR variability. The CV measure minimizes this problem.     

Effects of alcohol restriction on ambulatory blood pressure,heart rate,and heart rate variability in Japanese men

We investigated the effects of alcohol restriction on ambulatory blood pressure (BP), heart rate, and heart rate variability in 33 Japanese male volunteers (37 ± 1 years, mean ± SE), who were all habitual drinkers. Subjects were told either to keep their usual drinking habits for 3 weeks (usual alcohol period), or to reduce alcohol intake by at least half of their usual drinking amount (reduced alcohol period). The ambulatory BP, heart rate, and electrocardiographic R-R intervals were measured during a 24-h period with a portable recorder on the last day of each period. A power spectral analysis of R-R intervals was performed to obtain the low-frequency (LF) and high-frequency (HF) components. The percentage of differences between adjacent normal R-R intervals >50 msec (pNN50) was also calculated. The amount of ethanol intake was significantly reduced from 70 ± 5 mL/day in the usual alcohol period to 19 ± 3 mL/day in the reduced alcohol period (P < .0001). The daytime systolic BP was significantly lower in the reduced alcohol period than in the usual alcohol period by 4 ± 1 mm Hg (P < .05). The daytime and nighttime heart rate was significantly lower in the reduced alcohol period than in the usual alcohol (P < .001 for each). The pNN50 and the HF component were significantly higher in the reduced alcohol period than in the usual alcohol period (P < .0001 for each). The LF/HF ratio was significantly lower in the reduced period than in the usual period (P < .01). These results demonstrate that 3-week alcohol restriction produced reductions in ambulatory systolic BP, heart rate, and the index of sympathovagal balance, and augmentations of parasympathetic indices of heart rate variability in Japanese male drinkers.     

Sometimes higher heart rate variability is not better heart rate variability: results of graphical and nonlinear analyses

OBJECTIVE: To determine the prevalence and effect on traditional heart rate variability (HRV) indices of abnormal HRV patterns in the elderly. METHODS: Hourly Poincaré plots and plots of spectral HRV from normal-to-normal interbeat intervals and hourly nonlinear HRV values were examined in a subset of 290 consecutive participants in the Cardiovascular Health Study. Only subjects in normal sinus rhythm with > or = 18 hours of usable data were included. Eligible subjects were 71 +/- 5 years. During 7 years of follow-up, 21.7% had died. Hours were scored as normal (0), borderline (0.5), or abnormal (1) from a combination of plot appearance and HRV. Summed scores were normalized to 100% to create an abnormality score (ABN). Short-term HRV versus each 5th percentile of ABN was plotted and a cutpoint for markedly increased HRV identified. The t-tests compared HRV for subjects above and below this cutpoint. Cox regression evaluated the association of ABN and mortality. RESULTS: Of 5,815 eligible hourly plots, 64.4% were normal, 14.5% borderline, and 21.1% abnormal. HR, SDNN, SDNNIDX, ln VLF and LF power, and power law slope did not differ by the cutpoint for increased short-term HRV, while SDANN and ln ULF power were significantly lower for those above the cutpoint. However, many HRV indices including LF/HF ratio and normalized LF and HF power were significantly different between groups (P < 0.001). Increased ABN was significantly associated with mortality (P = 0.019). Despite similar values for many HRV indices, being in the group above the cutpoint was significantly associated with mortality (P = 0.04). CONCLUSIONS: Abnormal HR patterns that elevate many HRV indices are prevalent among the elderly and associated with higher risk of mortality. Consideration of abnormal HRV may improve HRV-based risk stratification.     

高血压病左室肥厚患者心率变异及动态血压分析

观察高血压左室肥厚（ＬＶＨ）患者的心率变异（ＨＲＶ）及血压昼夜节律变化，以期了解三者之间的关系。选择伴有左心室肥厚的高血压病患者２１例，不伴有左心室肥厚的高血压患者２８例，选择年龄与患者可比的健康人２５例作为正常对照组，进行动态心电图及动态血压监测，分析２４ｈＨＲＶ时域指标及血压昼夜节律。结果:高血压伴左室肥厚患者ＨＲＶ各指标均显著低于对照组（Ｐ＜０．０５），也比不伴左室肥厚患者进一步降低。ＰＮＮ５０昼夜节律明显减弱。动态血压结果显示:不伴左室肥厚组与左室肥厚组血压昼夜节律消失者分别占各组总数的１７．９％及４７．６％，组间比较差异显著（Ｐ＜０．０５）。结论:副交感神经调节功能减弱可能与以上变化相关。高血压治疗应注意改善ＨＲＶ，重视恢复血压的昼夜节律     

老年高血压患者静息心率与心率变异性及动态血压的相关研究

目的探讨老年原发性高血压（EH）患者静息心率（RHR）与心率变异性（HRV）及动态血压的关系。方法106例老年EH患者根据RI-IR水平分为：A组60例,RHR〈80次／min;B组46例,RHR〉80次／min。对入选患者同步监测动态心电图及动态血压,对比分析HRV及动态血压参数的变化。结果B组HRV时域指标SDNN、SDANN、RMssd、PNN50及TI低于A组,而动态血压各参数均高于A组,差异有统计学意义（P〈0．05,P〈0．01）。RHR与HRV指标SDNN、SDANN及TI呈负相关,而与DBP呈正相关（P〈0．05,P〈0．01）。结论RHR增快是老年EH患者的一个危险因子,与HRV降低、血压增高相关密切。