Cardiac interbeat interval dynamics from childhood to senescence : comparison of conventional and new measures based on fractals and chaos theory.

BACKGROUND: New methods of R-R interval variability based on fractal scaling and nonlinear dynamics ("chaos theory") may give new insights into heart rate dynamics. The aims of this study were to (1) systematically characterize and quantify the effects of aging from early childhood to advanced age on 24-hour heart rate dynamics in healthy subjects; (2) compare age-related changes in conventional time- and frequency-domain measures with changes in newly derived measures based on fractal scaling and complexity (chaos) theory; and (3) further test the hypothesis that there is loss of complexity and altered fractal scaling of heart rate dynamics with advanced age. METHODS AND RESULTS: The relationship between age and cardiac interbeat (R-R) interval dynamics from childhood to senescence was studied in 114 healthy subjects (age range, 1 to 82 years) by measurement of the slope, beta, of the power-law regression line (log power-log frequency) of R-R interval variability (10(-4) to 10(-2) Hz), approximate entropy (ApEn), short-term (alpha(1)) and intermediate-term (alpha(2)) fractal scaling exponents obtained by detrended fluctuation analysis, and traditional time- and frequency-domain measures from 24-hour ECG recordings. Compared with young adults (<40 years old, n=29), children (<15 years old, n=27) showed similar complexity (ApEn) and fractal correlation properties (alpha(1), alpha(2), beta) of R-R interval dynamics despite lower spectral and time-domain measures. Progressive loss of complexity (decreased ApEn, r=-0.69, P<0.001) and alterations of long-term fractal-like heart rate behavior (increased alpha(2), r=0.63, decreased beta, r=-0.60, P<0.001 for both) were observed thereafter from middle age (40 to 60 years, n=29) to old age (>60 years, n=29). CONCLUSIONS: Cardiac interbeat interval dynamics change markedly from childhood to old age in healthy subjects. Children show complexity and fractal correlation properties of R-R interval time series comparable to those of young adults, despite lower overall heart rate variability. Healthy aging is associated with R-R interval dynamics showing higher regularity and altered fractal scaling consistent with a loss of complex variability.

Prevalence and characteristics of symptomatic gastroesophageal reflux disease in the elderly.

OBJECTIVE: To study prevalence and characteristics of symptomatic gastroesophageal reflux disease in the elderly. DESIGN: Survey by questionnaire of stratified random sample. SETTING: City of Turku, Finland. SUBJECTS: Population-based random sample consisting of non-institutionalized subjects aged 65 years or over. A questionnaire was sent to 559 subjects. The response rate was 92%. Twenty-nine incompletely filled forms were rejected. Thus, the questionnaires from 487 subjects, representing 87% of the original number, constitute the basis for the study. MEASUREMENTS: The questionnaire inquired about the following symptoms: heartburn, regurgitation, chest pain, dysphagia, dyspepsia, respiratory symptoms, vomiting, and belching. RESULTS: The age-adjusted prevalence of daily symptoms suggestive of gastroesophageal reflux disease was 8% in men and 15% in women (P < 0.05). Fifty-four percent of men and 66% of women reported that they had symptoms at least once a month (P < 0.05). The prevalence of symptoms was roughly the same across age groups. The occurrence of chest pain, dyspepsia, vomiting, belching, dysphagia, chronic cough, hoarseness, and wheezing were associated with symptoms suggestive of gastroesophageal reflux disease. CONCLUSIONS: Symptoms suggestive of gastroesophageal reflux disease are common in elderly subjects. Women suffer from these symptoms more frequently than men. Typical reflux symptoms are often associated with atypical complaints, such as abdominal symptoms, chest pain, or respiratory symptoms.

Predictive value of continuous ambulatory electrocardiographic monitoring in elderly people.

OBJECTIVE: To determine the predictive value of findings on continuous ambulatory electrocardiographic monitoring in elderly subjects. DESIGN: Retrospective cohort study. Ten year follow up of randomly selected elderly subjects who participated in ambulatory electrocardiography study in 1982. Mortality data derived from official registers. SETTING: Turku, Finland. SUBJECTS: 480 people aged 65 or older in 1982 who were living in the community, of whom 72% agreed to participate. MAIN OUTCOME MEASURES: Mortality from cardiac and non-cardiac causes during 10 year follow up. RESULTS: In the univariate analysis adjusted for age, risk of death from cardiac causes was increased among those with ventricular ectopy of more than 100 beats during the day (odds ratio 2.6; 99% confidence interval 1.4 to 6.1) or at night (3.3; 1.1 to 9.8) and in those with multifocal ventricular ectopic beats during the day (2.3; 1.0 to 5.0) or night (3.0; 1.3 to 7.1) compared with those with no ventricular ectopy. Sinoatrial pauses exceeding 1.5 seconds during the day (4.5; 1.8 to 11.1) were also associated with excess mortality from cardiac causes. None of the findings on ambulatory electrocardiography predicted death from non-cardiac causes. A further study of explanatory variables in the stepwise logistic regression analysis showed that sinoatrial pauses exceeding 1.5 seconds (4.0; 95% confidence interval 1.8 to 8.9) and night time multifocal ventricular ectopy (2.7; 1.2 to 5.9) predicted excess mortality from cardiac causes independently of age or clinically evident heart disease. CONCLUSION: Daytime sinoatrial pauses exceeding 1.5 seconds and night time multifocal ventricular ectopy in the ambulatory electrocardiogram predict increased mortality from cardiac causes independently of clinically evident cardiac diseases in unselected elderly subjects.

Pulmonary function in gastro-oesophageal reflux disease of elderly people.

An effect of gastro-oesophageal reflux disease (GORD) on respiratory function was studied in elderly patients. Twenty-seven patients with, and 29 patients without, abnormal gastro-oesophageal reflux (GOR) in 24-hour pH monitoring were included in the study. Symptoms suggestive of gastrooesophageal reflux disease were recorded and spirometry was performed in all the patients. Patients with abnormal GOR had lower vital capacity (percentage of predicted value) (VC%) than those with normal pH monitoring result (92 vs 102, p = 0.032). Forced vital capacity (FVC%) and forced expiratory volume in one second (FEV1%) did not differ between these two groups. Thirty-two per cent of patients with slight and 73% of patients with moderate or severe reflux in pH monitoring had abnormal VC%, FVC%, or FEV1% (less than 80% of predicted value) at spirometry (vs 30% of patients without reflux, p = 0.039). When patients were divided according to their symptoms suggestive of GORD, lower VC%, FVC%, and FEV1% were found in patients with than in those without symptoms (87 vs 102, p = 0.0018; 76 vs 91, p = 0.0099; 80 vs 93, p = 0.0026). In conclusion, mainly a restrictive ventilatory defect was associated with GORD in elderly patients.

The effect of calcium channel blocking on immune capacity of cardiovascular patients.

Calcium channel blocking drugs are widely used in the treatment of cardiovascular diseases. In vitro these drugs have been shown to block mitogen-induced lymphocyte proliferation. Their possible immunosuppressive effect has been tested especially in combination with cyclosporine A. In the present work, the effect of the calcium channel blocking drug verapamil on immune functions of cardiovascular patients was studied. The changes in leukocyte subpopulations, mitogenic responses and immunoglobulin production were determined during a three-month therapy. A significant increase in suppressor/cytotoxic cell number was detected and a decrease in the CD4/CD8 ratio, although the values were still within normal range. The responses to T and B cell mitogens remained unchanged. No significant decrease could be detected in immunoglobulin production either, despite minor changes in IgM. Our results indicate that the immunologic effects of verapamil at therapeutic doses are of little clinical significance.

Qt dispersion and mortality in the elderly.

BACKGROUND: The prognostic value of QT interval dispersion measured from a standard 12-lead electrocardiogram (ECG) in the general population is not well established. The purpose of the present study was primarily to assess the value of QT interval dispersion obtained from 12-lead ECG in the prediction of total, cardiac, stroke, and cancer mortality in the elderly. METHODS: A random population sample of community-living elderly people (n = 330, age > or = 65 years, mean 74 +/- 6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 12-lead ECG recordings. RESULTS: By the end of the 10-year follow-up, 180 subjects (55%) had died and 150 (45%) were still alive. Heart rate corrected QT (QTc) dispersion had been longer in those who had died than in the survivors (75 +/- 32 ms vs 63 +/- 35 ms, P = 0.01). After adjustment for age and sex in the Cox proportional hazards model, prolonged QTc dispersion (> or = 70 msec) predicted all-cause mortality (relative risk [RR] 1.38, 95% confidence interval [CI] 1.02-1.86) and particularly stroke mortality (RR 2.7, 95% CI 1.29-5.73), but not cardiac (RR 1.38, 95% CI 0.87-2.18) or cancer (RR 1.51, 95% CI 0.91-2.50) mortality. After adjustment for age, sex, body mass index, blood pressure, blood glucose and cholesterol concentrations, functional class, history of cerebrovascular disease, diabetes, smoking, previous myocardial infarction, angina pectoris, congestive heart failure, medication, left ventricular hypertrophy on ECG, presence of atrial fibrillation and R-R interval, increased QTc dispersion still predicted stroke mortality (RR 3.21, 95% CI 1.09-9.47), but not total mortality or mortality from other causes. The combination of increased QTc dispersion and left ventricular hypertrophy on ECG was a powerful independent predictor of stroke mortality in the present elderly population (RR 16.52, 95% CI 3.37-80.89). QTcmin (the shortest QTc interval among the 12 leads of ECG) independently predicted total mortality (RR 1.0082, 95% CI 1.0028-1.0136, P = 0.003), cardiac mortality (RR 1.0191, 95% CI 1.0102-1.0281, P < 0.0001) and cancer mortality (RR 1.0162, 95% CI 1.0049-1.0277, P = 0.005). CONCLUSIONS: Increased QTc dispersion yields independent information on the risk of dying from stroke among the elderly and its component, QTcmin, from the other causes of death.

Power-law relationship of heart rate variability as a predictor of mortality in the elderly.

BACKGROUND: The prognostic role of heart rate (HR) variability analyzed from 24-hour ECG recordings in the general population is not well known. We studied whether analysis of 24-hour HR behavior is able to predict mortality in a random population of elderly subjects. METHODS AND RESULTS: A random sample of 347 subjects of > or =65 years of age (mean, 73+/-6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 24-hour ECG recordings and were subsequently followed up for 10 years. Various spectral and nonspectral measures of HR variability were analyzed from the baseline 24-hour ECG recordings. Risk factors for all-cause, cardiac, cerebrovascular, cancer, and other causes of death were assessed. By the end of 10-year follow-up, 184 subjects (53%) had died and 163 (47%) were still alive. Seventy-four subjects (21%) had died of cardiac disease, 37 of cancer (11%), 25 of cerebrovascular disease (7%), and 48 (14%) of various other causes. Among all analyzed variables, a steep slope of the power-law regression line of HR variability (< -1.50) was the best univariate predictor of all-cause mortality (odds ratio, 7.9; 95% confidence interval [CI], 3.7 to 17.0; P<.0001). After adjusting for age and sex and including all univariate predictors of mortality in the proportional hazards analysis, ie, measures of HR variability, history of heart disease, functional class, smoking, medication, and blood cholesterol and glucose concentrations, all-cause mortality was predicted only by the slope of HR variability (adjusted relative risk, 1.74; 95% CI, 1.42 to 2.13; P<.0001) and a history of congestive heart failure (adjusted relative risk, 1.70; P=.0002). The slope of HR variability predicted both cardiac (adjusted relative risk, 2.05; P=.0002) and cerebrovascular death (adjusted relative risk, 2.84; P=.0001) but not cancer or other causes of death. CONCLUSIONS: Power-law relationship of 24-hour HR variability is a more powerful predictor of death than the traditional risk markers in elderly subjects. Altered long-term behavior of HR implies an increased risk of vascular causes of death rather than being a marker of any disease or frailty leading to death.