G. Cornélissen

Arterial stiffness independently predicts cardiovascular events in an elderly community : Longitudinal Investigation for the Longevity and Aging in Hokkaido County (LILAC) study

We investigated the predictive value of arterial stiffness to assess cardiovascular risk in elderly community-dwelling people by means of a multivariate Cox model. In 298 people older than 75 years (120 men and 178 women, average age: 79.6 years), brachial-ankle pulse wave velocity (baPWV) was measured between the right arm and ankle in a supine position. The LILAC study started on July 25, 2000, consultation was repeated yearly, and the last follow-up ended on November 30, 2004. During this follow-up span of 1227 days, there were nine cardiovascular deaths, the cause of death being myocardial infarction for two men and three women or stroke for two men and two women. In Cox proportional hazard models, baPWV as well as age, Mini-Mental State Examination (MMSE), Hasegawa Dementia Scale Revised (HDSR) and the low-frequency/high-frequency (LF/HF) ratio showed a statistically significant association with the occurrence of cardiovascular death. A two-point increase in MMSE and HDSR score significantly protected against cardiovascular death, the relative risk (RR) being 0.776 (P = 0.0369) and 0.753 (P = 0.0029), respectively. The LF/HF ratio also was significant (P = 0.025), but the other indices of HRV were not. After adjustment for age and HDSR, a 200 cm/s increase in baPWV was associated with a 30.2% increase in risk (RR = 1.302, 95% CI: 1.110-1.525), and a 500 cm/s increase in baPWV with a 93.3% increase in risk (RR = 1.933, 95% CI: 1.300-2.874, P = 0.0011), whereas the LF/HF ratio was no longer associated with a statistically significant increase in cardiovascular mortality. In elderly community-dwelling people, arterial stiffness measured by means of baPWV predicted the occurrence of cardiovascular death beyond the prediction provided by age, gender, blood pressure and cognitive functions. baPWV should be added to the cardiovascular assessment in various clinical settings, including field medical surveys and preventive screening. The early detection of risk by chronomics allows the timely institution of prophylactic measures, thereby shifting the focus from rehabilitation to prehabilitation medicine, as a public service to several Japanese towns.

Excessive circadian amplitude of blood pressure increases risk of ischaemic stroke and nephropathy

After 48-h ambulatory blood pressure monitoring, the incidence of ischaemic stroke, nephropathy, coronary heart disease and retinopathy was prospectively assessed for 6 years in 297 subjects, including 176 treated patients with an elevated blood pressure mean (MESOR-hypertensives). The relative risk associated with an excessive circadian blood pressure amplitude is 8.2 (95% confidence interval 3.1 to 21.7; p < 0.001) for ischaemic stroke and 6.9 (2.9 to 16.3; p < 0.001) for nephropathy. In MESOR-hypertensives, the relative risk for ischaemic stroke and nephropathy is 6.3 (p < 0.005) and 4.0 (p < 0.05), respectively. In MESOR-normotensives as well, an excessive circadian blood pressure amplitude is associated with a large increase in risk for ischaemic stroke and nephropathy (p < 0.05). An excessive circadian blood pressure amplitude is an entity in its own right that increases the risk of adverse vascular events irrespective of the blood pressure MESOR, age and the presence of other known risk factors. The diagnosis of this condition requires around-the-clock monitoring of blood pressure. The treatment of patients with this condition should aim not only at lowering the blood pressure mean but also at reducing blood pressure variability within 24 h.

The circadian rhythm of cortisol in the saliva of young pigs

Single and population-mean cosinor analyses document a circadian rhythm in salivary cortisol of pigs (p < 0.001). The midline estimated statistic of rhythm, the MESOR (M), is 1.50 +/- 0.07 ng/ml. For the group of 14 pigs studied there was a predictable variation of 64% around this mean in salivary cortisol within a day: the double circadian amplitude, 2A, was 0.96 ng/ml, with a 95% confidence interval ranging from 0.60 to 1.32 ng/ml. A measure of timing, the acrophase, phi, was 10 h 52 min from the phase reference (0030, the middle of the daily dark span of the 24-h light-dark cycle in which the pigs were kept). The 95% confidence interval of phi extended from 9 h 48 min to 12 h 12 min from the reference time. The chronobiologic approach provides indispensable quantitive characteristics as reference standards for future basic or applied work.

Common carotid intima-media thickness is predictive of all-cause and cardiovascular mortality in elderly community-dwelling people: Longitudinal Investigation for the Longevity and Aging in Hokkaido County (LILAC) study

Several cohort studies have examined the association of carotid intima-media thickness (IMT) with the risk of stroke or myocardial infarction in apparently healthy persons. We investigated the predictive value of IMT of cardiovascular mortality in elderly community-dwelling people, beyond the prediction provided by age and MMSE, assessed by means of a multivariate Cox model. Carotid IMT and plaque were evaluated bilaterally with ultrasonography in 298 people older than 75 years (120 men and 178 women, average age: 79.6 years). The LILAC study started on July 25, 2000. Consultations were repeated every year. The follow-up ended on November 30, 2004. During the mean follow-up span of 1152 days, 30 subjects (21 men and nine women) died. Nine deaths were attributable to cardiovascular causes (myocardial infarction: two men and three women; stroke: two men and two women). The age- and MMSE-adjusted relative risk (RR) and 95% confidence interval (95% CI) of developing all-cause mortality was assessed. A 0.3 mm increase in left IMT was associated with a RR of predicted 1.647 (1.075-2.524), and a similar increase in right IMT with a RR of 3.327 (1.429-7.746). For cardiovascular mortality, the corresponding RR values were 2.351 (1.029-5.372) and 2.890 (1.059-7.891), respectively. Carotid IMT assessed by ultrasonography is positively associated with an increased risk of all-cause and cardiovascular death in elderly community-dwelling people.

Individual assessment of antihypertensive response by self-starting cumulative sums

A self-interpreted control chart, on an individualized basis, assesses the effect of a switch from beta-blockers to an angiotensin-converting enzyme (ACE)-inhibitor in a patient with occasional blood pressure (BP) excess. In dense and long data series, the BP and heart rate (HR) of this patient respond to the change in treatment by the test criterion of a self-starting Cumulative Sum (cusum), which reaches values outside a decision interval with a lowering of BP and an increase in HR and vice versa, at least for BP, after treatment cessation. Thereafter, minimal sampling requirements are sought in the same data by applying the same control chart approach to decimated data. Skeleton sampling schemes in a system of chronobiologic self-analysis and interpretation of manually recorded data obtained at strategically placed times (established on the basis of data decimations) could complement control charts that are used on a home computer or preferably would be built into the output of ambulatory monitors used at the outset as a minimum and routinely as an optimum.

The week, inherited in neonatal human twins, found also in geomagnetic pulsations in isolated Antarctica

About 7-day (circaseptan) components, found at different levels of organization, notably in relation to growth, regeneration, repair and development, are often viewed as reflecting no more than the 7-day societal schedule, ample evidence for a built-in feature notwithstanding. Herein, we resolve circaseptans in geomagnetic pulsations recorded by a stand-alone magnetometer residing in Antarctica, far away from societal influences. Human physiological data, collected in the neonatal intensive care unit, show by intra-class correlation analysis that the nonlinearly assessed circaseptan period of heart rate, diastolic blood pressure and body weight is more similar between same-gender twins than among twin pairs, lending additional support for the endogenicity of circaseptans. Like circadians, about-weekly features in environmental variables such as geomagnetic pulsations were genetically acquired in the course of evolution.

Chronobiologic blood pressure assessment with a cardiovascular summary, the sphygmochron

Chronobiology deals with rhythmic patters that occur in all forms of life [1–5, 7–33, 35–38, 40–44, 47]. Virtually all organisms exhibit approximately daily (circadian) cycles. In human beings, prominent rhythms are found in blood pressure, circulatory pulse, body core and surface temperature and in chemical variables of blood, urine, and tissues. (Fig. 1). The medical section of this new science explores the relationships of rhythms to prediction, prevention, diagnosis, and treatment of diseases. Several decades of research worldwide have established that medical diagnoses can be subject to a much higher proportion of false positives (e. g., “office hypertension”) and false negatives (e. g., “odd-hour” hypertension) when only single samples are taken at arbitrary times of the day instead of taking rhythms into account. Radiation, chemotherapy, and other treatments have been shown to have markedly different efficacy and safety depending upon the pattern of administration within the day. Without modern engineering tools, chronobiology had to rely on manual measurement series that were cumbersome to collect and required methods of analysis that were not generally available. Modern bioengineering with microcomputers can bring the findings of chronobiology on circadian and other rhythms into the mainstream of medicine. Chronobiology can thus provide new dimensions to an individualized, positive assessment of health complementing the current negative approach relying solely on the absence of unusual values or overt disease.

Multiple resonances among time structures, chronomes, around and in us. Is an about 1.3-year periodicity in solar wind built into the human cardiovascular chronome?

Aims: Velocity changes in the solar wind recorded by satellite (IMP8 and Wind) are characterized by a solar cycle–dependent ∼1.3-year component. The presence of any ∼1.3-year component in human blood pressure (BP) and heart rate (HR) and in mortality from myocardial infarction (MI) is tested and its relative prominence compared to the 1.0-year variation. Materials and Methods: Around-the-clock manual or automatic BP and HR measurements from four subjects recorded over 5–35 years and a 29-year record of mortality from MI in Minnesota were analyzed by linear–nonlinear rhythmometry. Point and 95% confidence interval (CI) estimates were obtained for the ∼1.3-year period and amplitude. The latter is compared with the 1.0-year amplitude for BP and HR records concurrent to the solar data provided by one of the authors (JDR). Results: An ∼1.3-year component is resolved nonlinearly for MI, with a period of 1.23 (95% CI: 1.21, 1.26) years. This component was invariably validated with statistical significance for BP and HR by linear rhythmometry. Nonlinearly, the 95% CI for the 1.3-year amplitude did not overlap zero in 11 of the 12 BP and HR series. Given the usually strong synchronizing role of light and temperature, it is surprising that 5 of the 12 cardiovascular series had a numerically larger amplitude of the 1.3-year versus the precise 1.0-year component. The beating of the ∼1.3-year and 1.0-year components was shown by gliding spectra on actual and simulated data. Discussion and Conclusion: The shortest 5-year record (1998–2003) revealed an ∼1.3-year component closer to the solar wind speed period characterizing the entire available record (1994–2003) than the value for the concurrent 5-year span. Physiological variables may resonate with nonphotic environmental cycles that may have entered the genetic code during evolution.

Impact of circadian amplitude and chronotherapy: relevance to prevention and treatment of stroke

The long-acting calcium antagonist nifedipine reduces the incidence of stroke in Eastern Asia, as shown by the Shanghai Trial Of Nifedipine in the Elderly (STONE) and the Systolic Hypertension in China (Syst-China) trials. Recent trials in Japan have shown that benidipine may be more efficient than the former drug in preventing strokes in the elderly. Benidipine, commonly prescribed in Japan for a definite depressor effect, reportedly without causing remarkable fluctuations in blood pressure (BP), is investigated herein from a chronobiological viewpoint. Eighteen subjects (nine women and nine men, 39 to 87 years of age) with essential hypertension (office and ambulatory systolic, S/diastolic, D BP values above 160/95 mm Hg and 130/80 mm Hg, respectively) were enrolled in this investigation. Ambulatory BP was monitored at 30-min intervals for at least 24 h (ABPM-630, Colin Medical) before and after 4 weeks of crossover treatment with nifedipine tablets (twice daily, 20 mg/d) and benidipine (once daily, 4 mg/d, in the morning). The results indicate that: 1) benidipine and nifedipine reduce 24-h daytime (10:00-20:00) and nighttime (00:00-06:00) averages of SBP and DBP (P < 0.001); 2) the circadian double amplitude of BP is decreased after treatment with benidipine (from 28.6 to 21.1 mm Hg SBP and from 19.7 to 15.2 mm Hg DBP; P< 0.05), while the day-night difference in SBP is increased after treatment with nifedipine (18.6 vs 27.9 mm Hg, P< 0.01); and 3) the increase in the day-night difference of heart rate (HR) is significant after treatment with benidipine (13.6 vs 18.8 beats per minute, bpm; P< 0.05), but not with nifedipine. We have previously evaluated the usefulness of the circadian amplitude of BP as a prognostic tool of cardiovascular outcome, and found that an excessive circadian SBP or DBP amplitude was associated with an increased risk of vascular disease. The fact that benidipine reduces the circadian BP amplitude may be one reason for the superiority of this treatment over nifedipine in preventing an adverse outcome. A reduced heart rate variability (HRV) also predicts adverse cardiovascular outcomes in patients with overt cardiovascular disease and in hypertensive subjects. The fact that benidipine increases the day-night difference in HR may be another reason for the positive effects of this treatment.

Geomagnetic disturbance associated with decrease in heart rate variability in a subarctic area

BACKGROUND Physical environmental variables, such as the natural variation in the geomagnetic field in and around the earth, influence biological processes and human health. The effect of geomagnetic disturbances on heart rate variability (HRV) in healthy students in a subarctic area is studied herein. SUBJECTS AND METHODS Seven-day records by Holter ECG were obtained from eight clinically healthy subjects in Alta, Norway (70 N). Frequency- and time-domain measures of HRV were compared between 24-hour spans of high geomagnetic disturbance versus quiet conditions. RESULTS A 5.9% increase in the 24-hour average of HR (P = 0.020) and a 25.2% decrease in HRV (P = 0.002) were documented on days of high geomagnetic disturbance. The decrease in spectral power was found primarily at frequencies lower than 0.04 Hz and was not statistically significant around 3.6 sec. CONCLUSIONS The physiological mechanism involved may be other than the parasympathetic, usually identified with spectral power centered around 3.6 sec, a spectral region wherein no statistically significant differences were found.