Age and gender dependency of baroreflex sensitivity in healthy subjects

Laitinen, Tomi, Juha Hartikainen, Esko Vanninen, LeoNiskanen, Ghislaine Geelen, and Esko Länsimies. Age andgender dependency of baroreflex sensitivity in healthy subjects.J. Appl. Physiol. 84(2): 576-583, 1998.We evaluated the correlates of baroreflex sensitivity (BRS) inhealthy subjects. The study consisted of 117 healthy, normal-weight,nonsmoking male and female subjects aged 23-77 yr. Baroreflexcontrol of heart rate was measured by using the phenylephrinebolus-injection technique. Frequency- and time-domain analysis of heartrate variability and an exercise test were performed. Plasmanorepinephrine, epinephrine, insulin, and arginine vasopressinconcentrations and plasma renin activity were measured. In theunivariate analysis, BRS correlated with age(r = 0.65,P < 0.001), diastolic blood pressure(r = 0.47, P < 0.001), exercise capacity(r = 0.60, P < 0.001), and the high-frequency component of heart rate variability (r = 0.64, P < 0.001). There was also asignificant correlation between BRS and plasma norepinephrine concentration (r = 0.22,P < 0.05) and plasma renin activity (r = 0.32, P < 0.001). According to themultivariate analysis, age and gender were the most importantphysiological correlates of BRS. They accounted for 52% ofinterindividual BRS variation. In addition, diastolic blood pressureand high-frequency component of heart rate variability were significantindependent correlates of BRS. BRS was significantly higher in men thanin women (15.0 ± 1.2 vs. 10.2 ± 1.1 ms/mmHg, respectively;P < 0.01). Twenty-four percent ofwomen >40 yr old and 18% of men >60 yr old had markedly depressedBRS (<3 ms/mmHg). We conclude that physiological factors, particularly age and gender, have significant impact on BRS in healthysubjects. In addition, we demonstrate that BRS values that have beenproposed to be useful in identifying postinfarction patients at highrisk of sudden death are frequently found in healthy subjects.

     

Increased Visceral Adipose Tissue as a Potential Risk Factor in Patients with Embolic Stroke of Undetermined Source (ESUS)

Purpose

The etiology of an ischemic stroke remains undetermined in 20–35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke.

Methods

Altogether 58 patients (mean age 57.7±10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered.

Results

Mean VAT area was significantly higher in stroke patients (205±103 cm² for men and 168±99 cm² for women) compared to all reference populations (P<0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors.

Conclusion

Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients.     

Preoperative Axillary Staging with 3.0-T Breast MRI: Clinical Value of Diffusion Imaging and Apparent Diffusion Coefficient

The axillary staging in newly diagnosed breast cancer is under major evolution. The aims of this study were to define the diagnostic performance of 3.0-T diffusion-weighted imaging (DWI) in the detection of axillary metastases in newly diagnosed breast cancer, to assess apparent diffusion coefficients (ADCs) for histopathologically confirmed metastatic lymph nodes in a clinical setting. Altogether 52 consecutive breast cancer patients underwent magnetic resonance imaging and DWI in addition to axillary ultrasound. ADCs of axillary lymph nodes were analysed by two breast radiologists and ultrasound-guided core biopsies were taken. In a separate reading by one radiologist two types of region of interests were used for a smaller group of patients. Altogether 56 axillae (121 lymph nodes) were included in the statistical analysis. Metastatic axillae (51.8%) had significantly lower ADCs (p<0.001). Mean ADCs were 0.663–0.676 x 10^-3 mm²/s for the histologically confirmed metastatic LNs and 1.100–1.225 x 10^-3 mm²/s for the benign. The sensitivity, specificity, and accuracy of DWI were 72.4%, 79.6%, and 75.9%, respectively with threshold ADC 0.812 x 10^-3 mm²/s. Region of interest with information on the minimum value increased the diagnostic performance (area under the curve 0.794 vs. 0.619). Even though ADCs are significantly associated with histopathologically confirmed axillary metastases the diagnostic performance of axillary DWI remains moderate and ultrasound-guided core biopsies or sentinel lymph node biopsies cannot be omitted.     

Acute Phase IL-10 Plasma Concentration Associates with the High Risk Sources of Cardiogenic Stroke

Background

Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.

Methods

A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit.

Results

Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment.

Conclusion

IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology.     

Role of genetic and environmental influences on heart rate variability in middle-aged men

Our aim was to estimate causal relationships of genetic factors and different specific environmental factors in determination of the level of cardiac autonomic modulation, i.e., heart rate variability (HRV), in healthy male twins and male twins with chronic diseases. The subjects were 208 monozygotic (MZ, 104 healthy) and 296 dizygotic (DZ, 173 healthy) male twins. A structured interview was used to obtain data on lifetime exposures of occupational loading, regularly performed leisure-time sport activities, coffee consumption, smoking history, and chronic diseases from 12 yr of age through the present. A 5-min ECG at supine rest was recorded for the HRV analyses. In univariate statistical analyses based on genetic models with additive genetic, dominance genetic, and unique environmental effects, genetic effects accounted for 31-57% of HRV variance. In multivariate statistical analysis, body mass index, percent body fat, coffee consumption, smoking, medication, and chronic diseases were associated with different HRV variables, accounting for 1-11% of their variance. Occupational physical loading and leisure-time sport activities did not account for variation in any HRV variable. However, in the subgroup analysis of healthy and diseased twins, occupational loading explained 4% of the variability in heart periods. Otherwise, the interaction between health status and genetic effects was significant for only two HRV variables. In conclusion, genetic factors accounted for a major portion of the interindividual differences in HRV, with no remarkable effect of health status. No single behavioral determinant appeared to have a major influence on HRV. The effects of medication and diseases may mask the minimal effect of occupational loading on HRV.     

Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

Background  

Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD.     

New insights into Alzheimer's disease progression: a combined TMS and structural MRI study

Background:

Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas.

Methodology and Principal Findings:

To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer''s disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness.

Conclusions:

In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD.     

Structural MRI in Frontotemporal Dementia: Comparisons between Hippocampal Volumetry,Tensor-Based Morphometry and Voxel-Based Morphometry

Background

MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods.

Objective

To compare FTD with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy.

Methods

Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups.

Results

We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55).

Conclusion

Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.