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Age, race, and sex differences in autonomic cardiac function measured by spectral analysis of heart rate variability--the ARIC study. Atherosclerosis Risk in Communities.

To investigate the distribution of heart rate variability (HRV) spectral power in an unselected sample of the population, and to ascertain the population correlates of HRV, we examined 1,984 healthy persons, aged 45 to 64 years, randomly selected from the Atherosclerosis Risk in Communities (ARIC) study cohort. Resting, supine, 2-minute, beat-to-beat heart rate data were collected between 7 A.M. and 12 noon. The race- and sex-adjusted geometric means of low-frequency component (LF, 0.025 to 0.15 Hz) were 4.00 and 3.13 (beats/min)2; of high-frequency component (HF, 0.16 to 0.35 Hz), 1.65 and 1.21 (beats/min)2; and of the HF/LF ratio, 0.41 and 0.39, for 45-to-54 and 55-to-64 years age groups, respectively (test of mean difference by age, p < 0.01, p < 0.01, and p = 0.11 for LF, HF, and HF/LF ratio, respectively). Comparing black with white examinees, the age- and sex-adjusted geometric means of LF were 3.06 and 3.70 (beats/min)2; of HF, 1.66 and 1.36 (beats/min)2; of HF/LF, 0.54 and 0.37, respectively (test of mean difference by race, p < 0.01, p < 0.01, and p < 0.01). The age- and race-adjusted geometric means of LF for women and men were 3.12 and 4.10 (beats/min)2; of HF, 1.46 and 1.38 (beats/min)2; and of HF/LF, 0.47 and 0.34, respectively (test of mean difference, p < 0.01, p = 0.34, and p < 0.01). We conclude that HRV spectral indexes are associated with age, race, and sex. With increasing age, the parasympathetic and sympathetic spectral power components decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Cardiac autonomic function during sleep of never-depressed borderline subjects: a pilot study.

In a controlled 48 h ambulatory polysomnographic study of never-depressed subjects with DSM-III-R borderline (BDL) personality disorder (PD) we obtained measures of tonic and phasic heart rate variability. Subjects with BDL PD showed a significantly smaller index of tonic heart rate decrease during NREM sleep than normal controls. This is unlikely to be a state-dependent finding and it may derive from relative augmentation of adrenergic function compared to cholinergic function between wakefulness and NREM sleep. Hyperadrenergic states in BDL PD have already been suggested by studies of other biological indicators: a smaller index of tonic heart rate decrease may be a further correlate of core psychobiological dimensions such as impulsivity and affective instability.

Adrenergic Fibers↗

Worsening of depressive symptoms 6 months after an acute coronary event in older adults is associated with impairment of cardiac autonomic function.

BACKGROUND: Depression increases mortality of coronary patients, and autonomic dysfunction has been proposed as an explanation for this association. METHODS: In a sample of 38 adults > or = 60 years with myocardial infarction or unstable angina, we studied depression (presence of a major depressive episode and 21-item Hamilton depression score) and heart rate variability (HRV) of 550 normal beats shortly after admission to the coronary care unit (CCU). Thirty patients were alive at 6 months and were studied at that time as well. Spectral HRV measurements included power in the high-frequency range (HF, 0.15-0.55 Hz, a measure of parasympathetic activity) and low-frequency range (LF, 0.03-0.15 Hz). Nonspectral HRV measurements included standard deviation of normal beats (SDNN) and two measures of vagal activity: percentage of adjacent cycles differing by >50 ms (pNN50) and the root-mean-square of differences in successive beats (rMSNN). RESULTS: Patients who died within 6 months (n=8) had a higher Hamilton-D score than survivors (13.9+/-6.5 vs. 18.4+/-5.6, P=0.039) and were more likely to have an episode of major depression upon admission to the CCU (71 vs. 27%, P=0.027). An increase in Hamilton-D score at 6 months correlated with a decrease in total (r=-0.48, P=0.014), high-frequency (r=-0.49, P=0.007), and low-frequency HRV (r=-0.46, P=0.014). LIMITATIONS: Patients belonged to a single institution and there was a small proportion of men. CONCLUSIONS: Progression of mood symptoms 6 months after an acute coronary event is associated with an impairment of autonomic control of the heart in elderly individuals.

Acute Disease↗

Effects of physical conditioning on cardiac autonomic function in healthy middle-aged women.

The purpose of this study was to determine whether moderate exercise training affects heart rate variability (HRV) and spontaneous baroreflex (SBR) function in healthy middle-aged women. Thirty-two sedentary women aged 40-59 yr were divided into four groups depending on reproductive state (premenopausal, PrM or postmenopausal, PoM, and training group (exercise or sedentary control group). The electrocardiographic R-R interval and systolic blood pressure (finger plethysmograph) were measured at rest during paced breathing at 16 breaths/min in the left lateral decubitus, sitting, and free standing postures, and during upright cycling at 40% maximal heart rate reserve (MHRR). After initial testing, the exercise groups underwent a 12 week walking program. After training, both exercise groups (PrM and PoM) had a longer R-R interval in all conditions, a higher SBR slope in the sitting and standing posture and lower sympathetic modulation in the standing posture, than the control groups and pre-training levels. During exercise, vagal modulation was higher and sympathetic modulation was lower in both exercise groups compared to pre-training values. Vagal modulation is increased following moderate intensity aerobic conditioning in middle-aged women.

Adult↗

Effects of human pregnancy on cardiac autonomic function above and below the ventilatory threshold.

This study examined the effects of human pregnancy on heart rate variability (HRV), spontaneous baroreflex (SBR) sensitivity, and plasma catecholamines at rest and during exercise. Subjects were 14 healthy, physically active pregnant women (PG; mean gestational age = 33.9 +/- 1.0 wk). Results were compared with an age-matched nonpregnant control group (NPG; n = 14) with similar characteristics. The electrocardiographic R-wave-R-wave interval and systolic blood pressure (via finger plethysmograph) were measured on a beat-to-beat basis at rest and during upright cycling at 60 and 110% of the ventilatory threshold (T(vent)). Parasympathetic nervous system (PNS) modulation (as reflected by HRV high-frequency/total power and SBR slope) was significantly reduced at rest in the PG vs. the NPG. During exercise, PNS modulation decreased significantly in both groups, but the magnitude of PNS withdrawal from rest to 110% T(vent) was smaller in the PG vs. NPG. Sympathetic nervous system (SNS) modulation (reflected by the low-frequency power-to-high-frequency power ratio) increased above resting values at 60 and 110% T(vent) in the NPG. SNS modulation at 110% T(vent) was significantly lower in the PG compared with the NPG. Plasma norepinephrine and epinephrine levels were also lower at 110% T(vent) in the PG. It was concluded that healthy pregnant women exhibit lower PNS modulation at rest and blunted SNS modulation during exercise above T(vent) in late gestation.

Adult↗

Adolescent pain sensitivity is associated with cardiac autonomic function and blood pressure over 8 years.

Low pain sensitivity has been reported in hypertensive subjects as well in groups deemed to be at increased risk of development of the disorder. However, it is uncertain whether individual differences in pain sensitivity are associated prospectively with increases in blood pressure. In the current study, 24-hour blood pressure and heart rate variability were recorded in 110, 22-year-old men previously assessed at age 14 years for casual blood pressure and pain sensitivity (mechanical finger pressure). Significant correlations were observed between pain tolerance in 14-year-olds and current 24-hour systolic blood pressure (r=0.37, P<0.01) and diastolic blood pressure (r=0.36, P<0.01). Hierarchical multiple regression analyses indicated that information regarding pain tolerance improved prediction of systolic and diastolic blood pressure at age 22 years beyond that afforded by differences in blood pressure, parental history of hypertension, and body mass index at age 14 years. Similar analyses revealed that average pain sensitivity at age 14 was also associated with 24-hour high-frequency heart rate variability (r=0.28, P<0.01) and low-frequency/high-frequency heart rate variability at age 22 (r=-0.35, P<0.01), suggesting increased sympathetic and reduced parasympathetic tone among individuals less sensitive to pain. These results provide further evidence that blood pressure related hypoalgesia might be related to processes involved in blood pressure regulation as well as in the development of sustained high blood pressure.

Adolescent↗

Cross correlation of heart rate and respiration versus deep breathing. Assessment of new test of cardiac autonomic function in diabetes.

Cross correlation is a mathematical function whereby spectral analysis is used to describe the relationship between heart-rate fluctuations (256 R-R intervals) and respiration (simultaneously obtained by pneumotacograph). To assess its usefulness for testing autonomic integrity, cross correlation and deep breathing were compared in 141 diabetic subjects (aged 39 +/- 14 yr) and in 77 control subjects (aged 33 +/- 13 yr). To characterize patients, Valsalva maneuver, 30:15 ratio, tilt, and handgrip tests were performed in 96 of these patients; 23 had two or more abnormal tests (group A), 28 had one (group B), and 45 had none (group C). Sensitivity to parasympathetic withdrawal was compared in 9 control subjects (aged 26 +/- 4 yr) by four sequential 0.01-mg/kg i.v. atropine administrations. Reproducibility was compared in 11 control subjects (aged 25 +/- 2 yr) by repeating the tests four times for 2 consecutive days. Considering all 141 patients, cross correlation and deep breathing were less than 2SD of the mean of control subjects in 64 and 36 subjects, respectively. Considering patients who also performed other tests of autonomic function, cross correlation and deep breathing were less than 2SD of the mean of controls in 42 and 30 subjects, respectively (group A, 20 and 15; group B, 12 and 9; group C, 10 and 6). Cross correlation had better reproducibility than deep breathing (C.V. 10.3 vs. 30.6% at 6 breaths/min) and greater sensitivity to atropine (after the 1st injection, cross correlation and deep breathing decreased to 34.6 and 48.2% of baseline values, respectively; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Blood pressure and cardiac autonomic function in relation to risk factors and treatment perspectives in Type 1 diabetes.

The cumulative incidence of diabetic nephropathy in Type 1 diabetes mellitus is in the order of 25 30%. The recognition that elevated blood pressure (BP) is a major factor in the progression of these patients to end-stage renal failure has led to the widespread use of antihypertensive therapy in order to preserve glomerular filtration rate and ultimately to reduce mortality. The routine measurement of microalbuminuria allows early identification of the subgroup of patients at increased risk of developing clinical nephropathy. Microalbuminuric Type 1 diabetic patients show a number of characteristic pathological abnormalities. In addition to elevated BP and abnormal circadian rhythm, there are also associated abnormalities of vagal function, lipid profile and endothelial function, as well as an increased prevalence of retinopathy. The first section of this two-part review focusses on the early changes associated with renal involvement in Type 1 diabetes. It addresses the associations between urinary albumin excretion, glycaemic control, smoking, BP, circadian BP variation, QT interval abnormalities and autonomic function in three groups of patients; those with normoalbuminuria, those progressing towards microalbuminuria and those with established low-grade microalbuminuria.

Albuminuria↗

An improved method for measuring heart-rate variability: assessment of cardiac autonomic function.

Heart rate oscillates in synchrony with respiration. Several methods have been employed to assess this 'sinus arrhythmia', as an index of autonomic nervous system function. This paper proposes a new, easily computed measure, R, which is relatively resistant to the major nonrespiratory sources of variation, including premature beats, heart-rate differences among subjects, and slow trends in heart rate over time within subjects. The method can also be used more generally in any context where individuals are associated with event processes (for example, with seizures), when one requires assessment of the extent to which a point process is periodic with a particular known period.

Arrhythmia, Sinus↗

Effect of propionyl-L-carnitine on motor nerve conduction, autonomic cardiac function, and nerve blood flow in rats with streptozotocin-induced diabetes: comparison with an aldose reductase inhibitor.

The effects of propionyl-L-carnitine (PCAL) on caudal motor nerve conduction velocity, the coefficient of variation of the R-R interval on the electrocardiogram, and sciatic nerve blood flow were compared with those of [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate, an aldose reductase inhibitor, in rats with streptozotocin-induced diabetes. Diabetic control rats showed significantly delayed nerve conduction (P < .05), decreased R-R variability (P < .05) and reduced sciatic nerve blood flow (P < .05). Oral administration of PCAL (0.5 g/kg/day) and [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (0.05% in the diet: 60 mg/kg/day) for 8 weeks significantly improved both nerve conduction (P < .05) and R-R variability (P < .05) in diabetic rats, along with the normalization of sciatic nerve blood flow. PCAL treatment increased the nerve tissue levels of carnitine and myo-inositol and reduced the serum triglyceride level in diabetic rats. Our results suggests that PCAL could have therapeutic potential for the treatment of diabetic neuropathy.

Aldehyde Reductase↗

Noninvasive assessment of the relationship between cardiac and autonomic function in diabetes.

In order to assess a possible relationship between left ventricular (LV) function and cardiac autonomic involvement in type-1 insulin dependent diabetes, we performed M-mode echocardiograms and autonomic function tests in 21 patients (mean age +/- SD, 38 +/- 11 years, range 18-55, 16 male and 5 female). In 7 patients and in 21 age-matched controls the echocardiogram was also recorded before and during handgrip. At rest, ventricular function abnormalities were found only in 4 subjects, and no significant correlation was found between echocardiographic parameters and autonomic function tests. Unlike controls, during handgrip diabetic subjects failed to increase peak Vcf and peak filling rate, and increased their left ventricular end-systolic diameter. The changes in LV parameters during handgrip were significantly correlated with resting autonomic function tests (p less than 0.025). Our results suggest that resting cardiac function may be normal in diabetics despite high incidence of abnormal autonomic tests. Latent abnormalities of left ventricular function can be unmasked by acute haemodynamic challenges such as handgrip, and are correlated with abnormalities in autonomic function tests.

Adolescent↗

Analysis of RR variability in drug-resistant epilepsy patients chronically treated with vagus nerve stimulation.

Vagus nerve stimulation (VNS) has been suggested as an adjunctive treatment for drug-resistant epilepsy when surgery is inadvisable. The overall safety profile of VNS seems to be favorable as only minor adverse effects have been described. The purpose of this study was to determine if cardiac vagal tone is eventually modified by short- and long-term VNS. The effects of short- and long-term VNS were evaluated in seven subjects with intractable epilepsy. Autonomic cardiac function has been carried out by means of a 24-h analysis of RR variability at baseline (t(0)), 1 month (t(1), short-term VNS) and 36 months after VNS initiation (t(2), long-term VNS). Frequency- and time-domain parameters were calculated. Periodic cardiological and neurological evaluations were performed.Clinically relevant cardiac effects were not observed throughout the study. Despite the limited number of patients and the variety of data among them, for all the patients, a common trend towards a nocturnal decrease in the high-frequency (HF) component of the spectrum was observed after long-term VNS (mean+/-S.D.: 40+/-18 normalized units (nu) at t(0), 38+/-17 nu at t(1), 18+/-10 nu at t(2); p<0.05 of t(2) vs. either t(0) or t(1)). The day-to-night changes in the power of low-frequency (LF) and HF components were significantly blunted after long-term VNS (LF day-to-night change: +16+/-13 nu at t(0) and +15+/-8 nu at t(1) vs. +3+/-13 nu at t(2), p<0.02; HF day-to-night change: -18+/-13 nu at t(0) and -13+/-11 nu at t(1) vs. +3+/-12 nu at t(2), p<0.003). No significant changes were observed with regard to the time-domain parameters of the heart rate variability. Throughout the neurological follow-up, one subject became seizure-free, three experienced a seizure reduction of >50%, two patients of <50% and one had no changes in his seizure frequency. Our findings suggest that long-term VNS might slightly affect cardiac autonomic function with a reduction of the HF component of the spectrum during night and a flattening of sympathovagal circadian changes, not inducing, however, clinically relevant cardiac side effects.

Adult↗

Diabetes, glucose, insulin, and heart rate variability: the Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVE: To describe the progression of autonomic impairment among individuals with diabetes and pre-diabetic metabolic impairments. RESEARCH DESIGN AND METHODS: We investigated the consequence of diabetes and pre-diabetic metabolic impairments on the 9-year change in heart rate variability (HRV) in a population-based cohort of 6,245 individuals aged 45-64 years at baseline and cross-sectional associations among 9,940 individuals. RESULTS: Diabetic subjects had a more rapid temporal decrease in HRV conditional on baseline HRV than nondiabetic subjects. Adjusted mean annual changes (95% CI) (ms/year) in the SD of all normal-to-normal R-R intervals were -0.65 (-0.69 to -0.61) for those with normal fasting glucose vs. -0.95 (-1.09 to -0.81) for diabetic subjects, in root mean square of successive differences in normal-to-normal R-R intervals -0.35 (-0.39 to -0.30) vs. -0.66 (-0.82 to -0.51), and in R-R interval 6.70 (6.37-7.04) vs. 3.89 (2.72-5.05). While we found cross-sectional associations between decreased HRV and diabetes and nondiabetic hyperinsulinemia and a weak inverse association with fasting glucose, neither impaired fasting glucose nor nondiabetic hyperinsulimenia was associated with a measurably more rapid decline in HRV than normal. CONCLUSIONS: Cardiac autonomic impairment appears to be present at early stages of diabetic metabolic impairment, and progressive worsening of autonomic cardiac function over 9 years was observed in diabetic subjects. The degree to which pre-diabetic metabolic impairments in insulin and glucose metabolism contribute to decreases in cardiac autonomic function remains to be determined.

Arteriosclerosis↗

Studies on the autonomic nervous function in Tsukuba emotional rats--with special reference to their cardiac function.

Autonomic nervous function in Tsukuba high (THE) and low (TLE) emotional rats as well as Wistar rats (control) was studied by means of electrocardiographical examination in addition to the runway test. In the runway test, locomotive activity differed significantly among the three strains, the greatest activity in TLE and the smallest in THE. Electrocardiogram (ECG) and locomotive activity were successively recorded for 24 hr using a small size of telemeter system. Though the locomotive activity showed a clear nocturnal rhythm, no significant difference was observed among the three strains. The mean value of R-R intervals in THE tended to be smaller than those in other two strains; showing a significant difference between THE and TLE. The mean value of standard deviation (SD) of R-R intervals in TLE tended to be larger than those in other two strains; showing a significant difference between TLE and Wistar in the light and dark periods, and also between TLE and THE in the light period. As regards coefficients of variation of R-R intervals (CV), there was no significant difference among the three strains. Autonomic nervous tone in THE and TLE was evaluated by means of autonomic blockades using atropine and/or propranolol. The sympathetic nervous tone represented 21.6% in THE and 16.8% in TLE, while the parasympathetic nervous tone -9.0% and -12.3% in THE and TLE, respectively. There was a significant difference in the net autonomic nervous tone between THE (10.7%) and TLE (-6.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗