The menopausal woman: The need for an individualized plan of care.

With life expectancy increasing, women will spend one-third of their lives in and beyond menopause. A collaborative discussion with the clinician facilitates informed decision-making and should include evidence-based discussion of physiologic changes, assessment of symptoms and treatment options, review of screening recommendations, and discussion of disease risk-reduction strategies and psychosocial issues.

Peripheral vasomotor activity assessment using a continuous wavelet analysis on webcam photoplethysmographic signals.

BACKGROUND: Vasoconstriction and vasodilation phenomena reflect the relative changes in the vascular bed. They induce particular modifications in the pulse wave magnitude. Webcams correspond to remote sensors that can be employed to measure the pulse wave in order to compute the pulse frequency. OBJECTIVE: Record and analyze pulse wave signal with a low-cost webcam to extract the amplitude information and assess the vasomotor activity of the participant. METHODS: Photoplethysmographic signals obtained from a webcam are analyzed through a continuous wavelet transform. The performance of the proposed filtering technique was evaluated using approved contact probes on a set of 12 healthy subjects after they perform a short but intense physical exercise. During the rest period, a cutaneous vasodilation is observable. RESULTS: High degrees of correlation between the webcam and a reference sensor were obtained. CONCLUSIONS: Webcams are low-cost and non-contact devices that can be used to reliably estimate both heart rate and peripheral vasomotor activity, notably during physical exertion.

Assessment of coronary vasoreactivity by multidetector computed tomography: feasibility study with rubidium-82 cardiac positron emission tomography.

BACKGROUND: Positron emission tomography (PET) during the cold pressor test (CPT) has been used to assess endothelium-dependent coronary vasoreactivity, a surrogate marker of cardiovascular events. However, its use remains limited by cardiac PET availability. As multidetector computed tomography (MDCT) is more widely available, we aimed to develop a measurement of endothelium-dependent coronary vasoreactivity with MDCT and similar radiation burden as with PET. METHODS AND RESULTS: A study group of 18 participants without known cardiovascular risk factor (9F/9M; age 60±6 years) underwent cardiac PET with (82)Rb and unenhanced ECG-gated MDCT within 4h, each time at rest and during CPT. The relation between absolute myocardial blood flow (MBF) response to CPT by PET (ml·min(-1)·g(1)) and relative changes in MDCT-measured coronary artery surface were assessed using linear regression analysis and Spearman's correlation. MDCT and PET/CT were analyzed in all participants. Hemodynamic conditions during CPT at MDCT and PET were similar (P>0.3). Relative changes in coronary artery surface because of CPT (2.0-21.2%) correlated to changes in MBF (-0.10-0.52ml·min(-1)·g(1)) (ρ=0.68, P=0.02). Effective dose was 1.3±0.2mSv for MDCT and 3.1mSv for PET/CT. CONCLUSIONS: Assessment of endothelium-dependent coronary vasoreactivity using MDCT CPT appears feasible. Because of its wider availability, shorter examination time and similar radiation burden, MDCT could be attractive in clinical research for coronary status assessment.

Undertreatment of menopausal symptoms and novel options for comprehensive management.

OBJECTIVE: There is currently a gap in treatment options for menopausal symptoms and a need for comprehensive therapies that are safe and effective for postmenopausal women. This review discusses challenges in the management of menopausal symptoms and the effect of the Women's Health Initiative (WHI) study findings on current treatment patterns. It also examines present and future therapies. RESEARCH DESIGN AND METHODS: A literature search was conducted using Medline, the Cochrane Database, and the National Heart Lung and Blood Institute WHI website with the following search terms: primary care, menopause, vasomotor symptoms, hormone therapy, osteoporosis, and vaginal atrophy. Searches were limited to articles published between 1995 and 2009. RESULTS: Comprehensive therapies that target several aspects of menopause, such as vasomotor symptoms and chronic disease prevention, are currently hormone based. These hormone-based approaches are considered more effective than currently available nonhormonal therapies for the relief of menopausal symptoms. However, hormone therapy is not recommended for women at high risk for venous thromboembolic events, cardiovascular disease, and/or breast cancer. A need exists for novel therapies that mitigate menopausal symptoms, provide protection from osteoporosis, and encourage patient compliance without promoting cancer, heart disease, or stroke. Emerging modalities and strategies, such as the tissue selective estrogen complex (TSEC), Org 50081, MF101, and desvenlafaxine, may provide improved options for postmenopausal women. CONCLUSIONS: Several new menopausal therapies that may help to address the ongoing unmet need for safe and effective therapies for postmenopausal women are currently in development. In particular, the TSEC, which provides the benefits of both a selective estrogen receptor modulator and conjugated estrogens with an improved tolerability profile, may offer advantages over currently available treatment options. Limitations of this review include the narrow search criteria and limited search period.

Novel measures of cardiovascular health and its association with prevalence and progression of age-related macular degeneration: the CHARM Study.

BACKGROUND: To determine if novel measures of cardiovascular health are associated with prevalence or progression of age-related macular degeneration (AMD). METHODS: Measures of the cardiovascular system: included intima media thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC), carotid augmentation index (AI). For the prevalence study, hospital-based AMD cases and population-based age- and gender-matched controls with no signs of AMD in either eye were enrolled. For the progression component, participants with early AMD were recruited from two previous studies; cases were defined as progression in one or both eyes and controls were defined as no progression in either eye. RESULTS: 160 cases and 160 controls were included in the prevalence component. The upper two quartiles of SAC, implying good cardiovascular health, were significantly associated with increased risk of AMD (OR = 2.54, 95% CL = 1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression was observed in 82 (32.3%) of the 254 subjects recruited for the progression component. Higher AI (worse cardiovascular function) was protective for AMD progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated with increased risk of AMD progression; the highest risk was seen with the second lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46). CONCLUSION: The results were unexpected in that better cardiovascular health was associated with increased risk of prevalent AMD and progression. Inconsistent findings between the prevalence and progression components could be due to truly different disease etiologies or to spurious findings, as can occur with inherent biases in case control studies of prevalence. Further investigation of these non-invasive methods of characterizing the cardiovascular system should be undertaken as they may help to further elucidate the role of the cardiovascular system in the etiology of prevalent AMD and progression.

Assessment of characteristic of the vasomotor control dynamics based on plethysmographic blood flow measurement.

Enhancing the knowledge about the characteristic of the vasomotor control can help physicians to improve the treatment of cardiovascular diseases and their consequences in people's daily activities. Vessels are generally evaluated from a static point of view, where some vascular features are obtained in a given space of time, or expressed as an average of some evaluation. The present study presents a method to assess some characteristics of the vasomotor control dynamics. Such a method is based on a mathematical description of the temporal profile of the blood flow observed during a reactive hyperemia condition induced by a protocol of 5 min of ischemia. The parameters for such a mathematical descriptive function were evaluated by searching for sensitivity to identify normal and vasomotor alterations induced by oral administration of ibuprofen (1200 mg) in ten healthy volunteers. The results indicated by the proposed mathematical description fitted appropriately experimental blood flow data (fitting-error of 0.18 ml/100 ml of tissue/min). Additionally, one parameter of the mentioned function was statistically different (P < 0.05) when one considers the normal and altered conditions of the vessel, even when the traditional peak and the basal flow values did not hint at the distinction.

Implantable cardioverter defibrillator algorithms: status review in terms of computational cost.

In recent decades, implantable cardioverter defibrillators (ICDs) have improved substantially, becoming the treatment of choice for patients at high risk of life-threatening arrhythmias. Nevertheless, inappropriate shock therapy for non-ventricular arrhythmias is still a problem. Extending the ICD battery lifetime demands very low power consumption, which is obtained at very low microprocessor clock frequencies. Currently, some high-performance algorithms remain beyond the computational capabilities of ICDs. Future ICDs with higher computing power will permit the implementation of computationally intensive algorithms, enhancing the discrimination performance and preventing inappropriate shock therapies. An ICD algorithm status review is presented from the point of view of signal processing techniques and their computational costs. Several examples of discrimination algorithms with increasing computational cost are analyzed. Whereas some of them are already used in commercial ICDs, other algorithms cannot be implemented yet in current ICDs. A solution based on dynamic adaptation of microprocessor power consumption to meet algorithm computational requirements is proposed. This solution allows implementation of complex discrimination algorithms in ICDs without significantly increasing the power consumption.

Clinical impact of vasomotor function assessment and the role of ACE-inhibitors and statins.

Impaired endothelial function is recognised as one of the earliest events of atherogenesis. Endothelium-dependent vasomotion has been the principal method to assess endothelial function. In this article, we will discuss the clinical value of the different techniques to evaluate endothelium-dependent vasomotion. To date, there seems not to be a simple and reliably endothelial function test to identify asymptomatic subjects at increased risk for cardiovascular disease in clinical practice. Recent studies indicate that pharmacological interventions, in particular with ACE-inhibitors and statins, might improve endothelial function. However, there is no solid evidence that improvement of endothelial function is a necessity for the observed reduction in cardiovascular events by these compounds. Overall, at this moment, there is no place in clinical practice for the use of endothelial function as a method for risk assessment or target of pharmacological interventions.

Lifestyle and demographic factors in relation to vasomotor symptoms: baseline results from the Study of Women's Health Across the Nation.

Results of recent trials highlight the risks of hormone therapy, increasing the importance of identifying preventive lifestyle factors related to menopausal symptoms. The authors examined the relation of such factors to vasomotor symptoms in the multiethnic sample of 3,302 women, aged 42-52 years at baseline (1995-1997), in the Study of Women's Health Across the Nation (SWAN). All lifestyle factors and symptoms were self-reported. Serum hormone and gonadotropin concentrations were measured once in days 2-7 of the menstrual cycle. After adjustment for covariates using multiple logistic regression, significantly more African-American and Hispanic and fewer Chinese and Japanese than Caucasian women reported vasomotor symptoms. Fewer women with postgraduate education reported vasomotor symptoms. Passive exposure to smoke, but not active smoking, higher body mass index, premenstrual symptoms, perceived stress, and age were also significantly associated with vasomotor symptoms, although a dose-response relation with hours of smoke exposure was not observed. No dietary nutrients were significantly associated with vasomotor symptoms. These cross-sectional findings require further longitudinal exploration to identify lifestyle changes for women that may help prevent vasomotor symptoms.

Psychometric properties of a menopausal symptom list.

OBJECTIVE: To determine psychometric properties of a brief menopause symptom list and its sensitivity to menopausal status in a population-based cohort of late reproductive-age women. DESIGN: A 12-item menopause symptom list (MSL) administered in a cohort of African American and Caucasian women aged 38 to 52 years (N = 350) was psychometrically evaluated. Menopausal status of the cohort was determined by menstrual cycle dates obtained in interviews and participants' daily symptom records. Results of factor analysis were applied to longitudinal assessments of the cohort over a 3-year period. Convergent validity with other standard measures of mood, stress, health, and quality of life was determined. RESULTS: Internal consistency was found for the MSL items. Item total correlations are reported. Factor analysis identified three dimensions (psychological, somatic, and vasomotor). Multivariate analysis of cohort data over a 3-year interval showed that the menopausal symptoms increased over time (P = 0.0004) and that the identified factors were differentially associated with menopausal status. Psychological symptoms increased in the premenopausal and early transition groups but decreased in the late menopausal-postmenopausal groups (P = 0.0046 for the interaction). Vasomotor symptoms increased in both the early transition and late menopausal-postmenopausal groups (P = 0.0309 and P = 0.0543, respectively). Psychological symptoms (factor 1) had high correlations with other standard symptom measures (Center for Epidemiologic Studies-Depression Scale, r = 0.59; Zung Anxiety Scale, r = 0.65), whereas factors 2 and 3 did not, suggesting that the somatic and vasomotor symptoms were not associated with mood or health problems. CONCLUSIONS: The MSL provides a brief questionnaire with acceptable psychometric properties for assessing three dimensions of menopause-related symptoms and demonstrated sensitivity to menopausal status in a population-based cohort.

Validation of Italian version of the Women's Health Questionnaire: assessment of quality of life of women from the general population and those attending menopause centers.

OBJECTIVES: The Women's Health Questionnaire has been developed and validated in Anglo-Saxon and Swedish populations. The purpose of this study was to evaluate the Italian version of the questionnaire to determine whether cross-cultural differences exist in the perception of quality of life, and to use it to compare the quality of life in women attending menopause centers with that of women in the general population. METHODS: An Italian version of the Women's Health Questionnaire (WHQ) was produced, using the forward-backward translation method to ensure conceptual equivalence, and approved by the originator. Women were recruited by random selection from the general population and from menopause centers, those taking hormone replacement therapy being ineligible. The questionnaire was completed anonymously at home and mailed to the co-ordinating center. Psychometric evaluation included tests of item convergent and discriminant validity, internal-consistency reliability, test-retest reliability, construct validity and the discriminative properties of the questionnaire. RESULTS: The completeness of the data was good, with missing-value rates consistently low for most items. Item-scale correlations, used to evaluate internal consistency, were also good and the scaling success rate, used to measure item discriminant validity, was high for all scales. Scale scores were reliable for seven out of nine scales and test-retest reliability was excellent. There were few significant differences between the two populations of women in most of the WHQ areas. A comparison of Italian data with published data on English women showed great similarity. CONCLUSION: The Italian version of the WHO is valid and reproducible. The subjective perception of the menopause and its related problems is similar in geographically and culturally different populations.

Non-invasive assessment of brachial artery endothelial vasomotor function: the effect of cuff position on level of discomfort and vasomotor responses.

Non-invasive assessment of brachial artery flow-mediated dilation using cuff occlusion of the arm above or below the elbow to stimulate flow is emerging as a highly useful technique to examine endothelial vasomotor function in human subjects. In anticipation of a large-scale investigation, an important issue is the acceptability of the technique to participants. The purpose of this study was to determine the level of discomfort associated with the technique and compare it to the commonly used procedure of venipuncture. Flow-mediated dilation was determined using cuff occlusion of the arm above the elbow and a blood sample was obtained by standard venipuncture from 54 subjects. The level of discomfort for each procedure was assessed and compared using a visual analogue scale and was found to be extremely low. When the occlusion cuff was positioned above the elbow, the discomfort was slightly more severe (1.9+/-1.9 cm) than venipuncture (1.0+/-1.3 cm, p = 0.003). In 27 subjects, the effect of cuff position (above or below the elbow) was compared: the below the elbow position was associated with a reduction in the percentage increase in flow (570+/-280% versus 900+/-560%, p = 0.005), flow-mediated dilation (6.8+/-3.8% versus 9.8+/-5.7%, p = 0.008) and discomfort (1.6+/-0.8 versus 3.7+/-2.2 cm, p = 0.008). When the cuff was located below the elbow, the level of discomfort was equivalent to that associated with venipuncture. Thus, non-invasive assessment of flow-mediated brachial artery dilation is well tolerated and appears to be suitable for a large-scale study of endothelial function.

Serial assessment of the cardiovascular system in normal pregnancy. Role of arterial compliance and pulsatile arterial load.

BACKGROUND: Temporal changes in systemic arterial compliance and wave propagation properties (pulsatile arterial load) and their role in ventricular-systemic arterial coupling during gestation have not been explored. Noninvasive methods combined with recently developed mathematical modeling techniques were used to characterize vascular and left ventricular (LV) mechanical adaptations during normal gestation. METHODS AND RESULTS: Fourteen healthy women were studied at each trimester of pregnancy and again postpartum. Experimental measurements included instantaneous aortic pressure (subclavian pulse tracings) and flow (aortic Doppler velocities) and echocardiographic imaging of the LV. A small increase in LV muscle mass and end-diastolic chamber dimension occurred by late gestation, with no significant alterations in myocardial contractility. Cardiac output increased and the steady component of arterial load (total vascular resistance) decreased during pregnancy. Several changes in pulsatile arterial load were noted: Global arterial compliance increased (approximately 30%) during the first trimester and remained elevated thereafter. The magnitude of peripheral wave reflections at the aorta was reduced. The mathematical model-based analysis revealed that peripheral wave reflections at the aorta were delayed and that both conduit and peripheral vessels contributed to the increased arterial compliance. Finally, coordinated changes in the pulsatile arterial load and LV properties were responsible for maintaining the efficiency of LV-to-arterial system energy transfer. CONCLUSIONS: The rapid time course of compliance changes and the involvement of both conduit and peripheral vessels are consistent with reduced vascular tone as being the main underlying mechanism. The pulsatile arterial load alterations during normal pregnancy are adaptive in that they help to accommodate the increased intravascular volume while maintaining the efficiency of ventricular-arterial coupling and diastolic perfusion pressure.

Method for assessment of vascular reactivity in bone: in vitro studies on resistance arteries isolated from porcine cancellous bone.

Knowledge about vascular regulation in bone is central to the understanding of both normal and pathological bone physiology. This article describes a new method for direct assessment of the reactivity of bone blood vessels. Resistance arteries (diameter approximately 250 microns) were isolated from epiphyseal cancellous bone (porcine femoral condyle). Arterial segments (2 mm long) were mounted as ring preparations on a myograph, and isometric force development was measured continuously. Fifty-nine vessels from 31 pigs were investigated. The active force development was maximal at 0.9 x L100 in nine of 12 investigated arteries (L100 corresponds to the circumference the vessel would have if relaxed and exposed to a luminal pressure of 100 mm Hg [13.3 kPa]). In all subsequent experiments, the vessels were stretched to 0.9 x L100. Noradrenaline (2 x 10(-8) to 10(-5) M) induced a concentration-dependent vasoconstriction; mean maximal tension development was 3.69 N/m. This force development would enable the arteries to contract against a pressure of more than 22 kPa (165 mm Hg), indicating preserved function of the media smooth muscle. Response to acetylcholine (10(-7) to 10(-5) M) was observed in only two of 12 arteries. Bradykinin (10(-11) to 10(-6) M) induced a concentration-dependent and reproducible relaxation in all vessels; the relaxation was endothelium-dependent, since no effect of bradykinin was detected after mechanical removal of the endothelium. Sodium nitroprusside (10(-4) M) induced a reproducible and endothelium-independent vasorelaxation. The results demonstrate preserved function of both smooth muscle and endothelium in this preparation. The model allows pharmacological investigations of bone arteries under well defined conditions and enables studies on focal bone lesions and human bone tissue.

Assessment of the CO2 response by means of non diffusible contrast media and angio-CT in patients with cluster headache.

We analyzed the possibility of assessing functional vasomotor changes by means of Arm-Brain Circulation Time (rABCT) and Vascular volume images (Vv) obtained with Angio-CT, in basal condition and following CO2 inhalation, in a sample of 48 patients with cluster headache. CO2 inhalation resulted in the appearance of local changes, which were detected in 28 regions. Analysis by indicator images of Vv-dependent rABCT distribution showed two main patterns: abnormal rABCT mostly evident at the smallest Vv pixels and abnormal rABCT dependent on abnormal Vv distribution. The former pattern was linked to abnormality at the circle of Willis; the latter to abnormal local vasomotor responses. Patients with cluster headache showed both patterns, which prompted us to conclude for the presence of low-degree stenosis in carotid arteries and vasomotor instability in peripheral brain vessels.

Assessment of noninvasive tests of cutaneous vascular control in the forearm using a laser Doppler meter and a Finapres blood pressure monitor.

The control of human forearm cutaneous vascular resistance was examined using a combination of laser Doppler perfusion measurement and continuous Finapres blood pressure measurement. Tests which provoke changes in blood flow via different control mechanisms (local and neural) were applied in a group of ten healthy subjects. The purpose was to select from them a suitable (i.e. statistically significant) group to apply in cases where a disease process is suspected of interfering with the control of the skin circulation. Deep inspiration, immersion of the feet in water at 15 degrees C (both eliciting sympathetic vasoconstrictor nerve activity) and arm dependency (eliciting the local veni-arteriolar response) produced statistically significant, symmetrical increases in cutaneous vascular resistance in both arms (p < 0.05, Wilcoxon's test for paired differences). Similarly, post-ischaemic reactive hyperaemia (mediated by local vasodilator mechanisms) and indirect heating of the body (eliciting increased sympathetic vasodilator nerve activity) resulted in significant decreases in cutaneous vascular resistance (p < 0.01). When deep inspiration was repeated from a vasodilated baseline after indirect heating, the increases in cutaneous vascular resistance were smaller than those obtained before heating. Isometric handgrip exercise failed to produce a significant change in contralateral cutaneous vascular resistance (p > 0.05). There were no differences between right and left arms for any test (p > 0.05). The successful tests were subjected to power analysis in order to predict likely patient sample sizes required to demonstrate altered responsiveness at sites of microcirculatory disturbance compared with normal skin.

Simultaneous assessment of vasoreactivity using transcranial Doppler ultrasound and cerebral blood flow in healthy subjects.

Blood flow velocities in both middle cerebral arteries and regional cerebral blood flow in their perfusion territories were measured simultaneously in 36 healthy subjects. In 20 subjects, the measurements were first performed under basal conditions and then repeated 15-20 min after an intravenous injection of 1 g of acetazolamide. Reproducibility of simultaneous blood flow and velocity measurements was tested by examining 16 subjects on two occasions under basal conditions with an interval of 20 min. Relatively good reproducibility was found for repeated measurements of velocity and blood flow, being best when side-to-side asymmetry was assessed. The increase in blood flow velocities after acetazolamide was symmetrical (right side, 34.2%; and left side, 35.5%), and the velocity increase was significantly correlated with basal values. The increase in cerebral blood flow was also symmetrical (right side, 29.8%; left side, 30.1%) but not correlated with basal flow values. No significant relationship was found between velocity increase and increase in regional cerebral blood flow. This finding is probably not only due to methodological inaccuracies but may suggest that acetazolamide has an effect on the diameter of the middle cerebral artery or on the magnitude of this artery's perfusion territory. This study supports the use of acetazolamide for assessing cerebral vasoreactivity following the definition of lower limits for velocity and flow increase and for asymmetry of the response.

Assessment of coronary vasomotor tone in humans.

The assessment of endothelium-mediated modulation of coronary vasomotor tone in the intact human circulation under physiologic conditions requires very precise determination of both epicardial artery diameters, reflecting effects within the conduit vessels, as well as coronary blood flow, reflecting effects within the resistance vasculature during cardiac catheterization. In the present report, the accuracy and limitations of quantitative approaches to assess arterial dimensions from coronary angiograms are discussed. Using state-of-the-art image-processing techniques and x-ray imaging, epicardial artery diameter changes within the range of 8-10% can be reliably detected by quantitative coronary angiography. In addition, advances in interventional techniques do provide a means to selectively assess intracoronary blood-flow velocities using intracoronary Doppler catheters. Combining epicardial artery diameter measurements and intracoronary blood-flow velocity parameters allows for a reasonably accurate instantaneous estimate of coronary arterial blood flow. The advantages and limitations of the intracoronary Doppler technique compared to other techniques are discussed.