Perceiving autonomy support—or encouragement to be oneself—from a romantic partner or other close relationship partners has been shown to yield a variety of psychological health benefits, but it is less clear how perceiving autonomy support from partners is linked to physical health. In two studies we examine the associations between receiving autonomy support in romantic relationships and diastolic blood pressure, an important indicator of cardiovascular health. Results of a longitudinal study found support for a model in which autonomy supportive romantic relationships are linked with lower diastolic blood pressure. Whereas Study 1 showed general longitudinal effects, Study 2 revealed the importance of receiving autonomy support from partners during times of conflict. Implications of the findings will be discussed in the context of self-determination theory. Close relationships, and romantic relationships in particular, offer significant opportunities for promoting or undermining well-being and health. Indeed, a large body of evidence has linked highly supportive relationships with physical health .Study 2 asked participants in the lab to reflect on a conflict with partners in order to examine the role of conflict in linking global autonomy support and blood pressure. Based on the research discussed above we expected that recalling autonomy-supportive behaviors during conflict would explain some of the variability shared between global perceived autonomy support and changes in blood pressure. Specifically, we hypothesized that:Global perceived autonomy support from one’s partner would be linked to lower blood pressure after reflecting on a conflict with one’s partner.duringconflict would be linked to lower blood pressure after conflict and would mediate links with global autonomy support.Recalling autonomy-supportive behaviors In both studies, we controlled for the potential effects of attachment style as insecure attachment negatively affects responses to interpersonal conflicts (Carpenter and Kirkpatrick support provider) own report on providing autonomy support to partner B  was controlled for to account for the possibility that being in autonomy-supportive relationships in general, rather than receiving autonomy support, specifically, accounted for changes in blood pressure  changes in diastolic blood pressure as a function of perceiving autonomy support from romantic relationship partners. Assessing changes across time allows us to control for the high level of natural variability between individuals’ blood pressure . At the start of the study, 187 couples took part in the project , with the number of couples dropping to 139 and 98 at the respective subsequent readings (1 year in and 2 years in). The number of completed sessions correlated with perceived partner autonomy support, do not agree at all) to 8 .During Time 1, at the start of the study, both individuals reported on the extent to which their partner provided autonomy support. Perceived autonomy support from one’s partner was measured with three items adapted from La Guardia et al. . Items ido not agree at all) to 8 (agree completely). Reliability across all items was high, α = .94, and so the items were averaged to create an overall insecure attachment score, similar to those used by La Guardia et al. (The Experiences in Close Relationships-Revised (ECR-R) Questionnaire .Relationship commitment at Time 1 was assessed using a 15-item scale . The ‘yes’ responses were given a score of 1, and the 33 items were summed to create an overall physical symptoms index .Physical health was controlled for at all three time points using a modified version of the Choen-Hoberman Inventory of Physical Symptoms (CHIPS), which is a 33-item scale that asks participants to check yes if they experienced each of the physical health symptoms over the last 6 years , but because diastolic blood pressure and partner autonomy support showed somewhat non-normal distributions  we analyzed models using log-transformed data; findings were consistent across models using both raw and transformed data.The data were non-independent across both longitudinal measurements and within couples. Given this, the general analytic strategy involved a two-level multilevel model in which effects for each of the two partners were initially modeled separately at Level 1  at Level 1. At Level 2 we also tested the main effects of gender on blood pressure, recipient’s and support provider’s commitment at Time 1, recipient’s attachment style at Time 1, and recipient’s and support provider’s perceived autonomy support at Time 1. Furthermore, at Level 2 we tested for moderation of time by: recipient’s and support provider’s commitment, recipient’s attachment style, and recipient’s and support provider’s autonomy support. All variables except for gender were grand-centered per recommendations by Bryk and Raudenbush .2 = .161, p > .50; systolic: χ2 = .758, p > .50. A second model including the four lesbian couples found nearly identical results; χ2 = .162, p > .50; systolic: χ2 = .753, p > .50. As such, the model was pooled across both partners of the couple and included the lesbian couples.Tests of model fit examined whether partners were distinguishable by constraining an effect to be equal across both spouses and examining change in model fit  = −2.41, p = .02, d = .08, and blood pressure at baseline showing significant positive associations to blood pressure across the 2 years, b = 0.004, t(348) = 16.93, p < .001, d = 1.90. None of the other Level 2 main effects were significant, ts < 1.60, ps > .10  = −0.07, p = .95, d = .01. Recipients’ insecure attachment did not influence this trajectory, b = −0.00, t(328) = −1.59, p = .11, d = .17. Recipients’ commitment was marginally linked to a relative decrease in blood pressure over time , b = −0.003, t(328) = −1.97, p = .05, d = .22, though there was no interaction with support providers’ commitment, b = 0.001, t(328) = 0.54, p = .59, d = .06. Although the support providers’ autonomy support (presumably reflecting one’s giving of support) did not moderate this relation, b = 0.001, t(328) = 0.87, p = .39, d = .10, recipients’ perceived autonomy support from his or her partner  interacted with time, b = −0.004, t(328) = −2.35, p = .02, d = .34. Follow-up analyses  from their partners, b = −0.57, t = −2.87, p = .005, d = .45, whereas those who initially perceived their partners to be low in autonomy support (−1SD) demonstrated moderately higher blood pressure across the 2-year period, b = 1.00 t = 2.74, p = .007, d = .43  = −0.13, p = .90, d = .02, and did not further moderate the interaction between attachment style and perceived autonomy support, b = 0.000, t(327) = 0.36, p = .72, d = .04.As shown in Table b = −0.032, t(348) = −7.90, p < .001, d = .87. A main effect was also found for systolic blood pressure at baseline, which was linked to higher systolic blood pressure at Level 1, b = 0.000, t(348) = 12.13, p < .001, d = 1.34. There were no other significant main effects, ts < −1.43, ps > .15  = −3.59, p < .001, d = .40. Time was not moderated by recipients’ perceived autonomy support, b = 0.000, t(328) = −0.17, p = .87, d = .02, support providers’ perceived autonomy support, b = −0.001, t(328) = −0.13, p = .26, d = .13, recipients’ insecure attachment, b = −0.001, t(685) = −0.93, p = .35, d = .10, recipients’ commitment, b = 0.001, t(328) = 0.96, p = .34, d = .11, or providers’ commitment, b = −0.001, t(328) = 0.62, p = .54, d = .07. Attachment style did not moderate the main effect of perceived autonomy support, b = 0.001, t(347) = 1.22, p = .23, d = .13, and did not further moderate the interaction between attachment style and perceived autonomy support, b = 0.002, t(327) = 1.18, p = .24, d = .13Findings indicated a main effect for gender, in that women had lower systolic blood pressure than men across the 2 years, Study 1 supported the hypothesized relation between perceived partner autonomy support and diastolic blood pressure over time (our H1 above), though there were no relations with systolic blood pressure. Results showed that individuals who perceived their romantic partners to be autonomy supportive showed significant decreases in diastolic blood pressure across 2 years, whereas those who perceived their partners to be less supportive (less than the mean level of support) significantly increased in diastolic blood pressure across a 2-year period. Effect sizes for these changes in diastolic blood pressure as a function of perceived autonomy support were moderate. Moreover, this effect seemed to be independent of gender, attachment style, commitment to the relationship, and physical health. It appears to be that the autonomy support perceived from one’s partner that matters; one’s own provision of autonomy support did not show an impact on blood pressure trajectories.Findings from this study led to the question: what is it about autonomy-supportive partners that relates to lower diastolic blood pressure? Notably, diastolic blood pressure in younger people is most affected by situations that are low or high in stress , relative to those who perceived their partners to be less supportive in these ways. We further hypothesized that recalling partners as autonomy supportive during the conflict would mediate this effect (H2b).M = 28.22, SD = 13.64). Only one member of the couple participated in this study. Of participants, 22 were women, and 20 were U.K. nationals . Seven participants were married, and participants were in the relationship for an average of 67.61 months (SD = 137.71 months), or 5.63 years. The number of months in a relationship did not relate to changes in blood pressure across the study, r = −.05, p = .78.Forty-two participants who were in a romantic relationship took part in the study, with ages ranging from 19 to 74  to 5 (completely true). The two scales were averaged (after negative items were reversed) to create a composite of partner autonomy support, with higher scores on the overall measure reflecting more autonomy support. Alpha for all items was acceptable, α = .77.For this study, we measured perceptions of partner autonomy support with the three items used in Study 1  to 7 (extremely true). Reliability for the five averaged items (none were reversed) was α = .94.Recalled autonomy support during conflict was measured with five items adopted from the perceived autonomy support climate questionnaires . Hierarchical regression analyses predicted the criterion variables—post-task blood pressure and recalled partner autonomy support during conflict—from covariates, namely: baseline blood pressure (when predicting post-task blood pressure only), gender, and attachment style at Step 1, global perceived partner autonomy support at Step 2, and two-way interactions between attachment and global partner autonomy support at Step 3. Mediation analyses were conducted using the Process procedure Hayes  to obtait(37) = 11.78, p < .001, d = 3.87, though there were no associations with gender, β = −.01, t(37) = −0.14, p = .89, d = .05 or attachment style, β = -.08, t(37) = 1.12, p = .27, d = .37. At Step 2, global perceived partner autonomy support related to lower diastolic blood pressure, β = −.15, t(36) = −2.10, p = .04, d = .69  = 0.16, p = .88, d = .05.At Step 1, baseline diastolic blood pressure was linked to blood pressure after the task, β = .90, t(37) = 10.83, p < .001, d = 3.56, though there were no associations with gender, β = −.01, t(37) = −1.22, p = .23, d = .40 or attachment style, β = .04, t(37) = 0.59, p = .56, d = .20. At Step 2, there was no link between global autonomy support and systolic blood pressure, β = −.02, t(36) = −0.24, p = .82, d = .08. At Step 3, global perceived autonomy support and attachment style did not interact, β = .17, t(35) = 0.69, p = .50, d = .23.At Step 1, baseline systolic blood pressure was linked to systolic blood pressure after the task, β = .86, t(38) = −1.30, p = .20, d = .42, nor attachment style, β = .15, t(38) = 0.97, p = .34, d = .31, were associated with recalled autonomy support during conflict. At Step 2, global perceived partner autonomy support moderately related to recalled autonomy support during the conflict, β = .33, t(37) = 2.18, p = .04, d = .71. At Step 3, there was no interaction between global perceived autonomy support and attachment style in predicting recalled autonomy support during conflict, β = −.15, t(35) = 0.42, p = .68, d = .14.At Step 1, neither gender, β = −.21, t(37) = −2.09, p = .04, d = .69. When taking this moderate effect of recalled autonomy support during conflict into account, the effect of global perceived partner autonomy support fell to non-significance, β = −.10, t(36) = −1.31, p = .20, d = .44, suggesting the presence of mediation. This mediation hypothesis was tested using the Process procedure  had lower diastolic blood pressure following the conflict, controlling for baseline blood pressure, β = −.15, re Hayes  to obtaiStudy 2 supported findings from Study 1 showing potential benefits of perceiving one’s partner as being autonomy supportive on blood pressure, and identified one factor that may contribute to this relation. Specifically, mediation analyses indicated that recalling autonomy support from a partner during a conflict may partially buffer the harmful effects of the conflict on blood pressure , and a second study highlighted the importance of recalling autonomy support during conflict for lower blood pressure.Study 1 utilized a longitudinal design to show the long-term health relations of being with an autonomy-supportive romantic partner. Specifically, findings indicated that blood pressure dropped over time among people who perceived their partners to support their autonomy needs, whereas blood pressure rose over time for people who experienced their partners as low in providing autonomy support. This is consistent with the high importance of romantic partners to wellness  were consistent in both studies for these relatively young adult samples. Psychosocial stress has powerful effects on diastolic blood pressure in particular  recently showed that an intervention that enhanced autonomy support provided by spousal and partner caregivers predicted healthier and more rapid changes in patients’ diets after cardiovascular incidents. Working with couples to increase the autonomy support they provide each other, especially during times of conflict, appears to not only improve relationship functioning, but may also have positive effects on physical health.


Epidemiological studies suggest the existence of a relationship between aircraft noise exposure and increased risk for myocardial infarction and stroke. Patients with established coronary artery disease and endothelial dysfunction are known to have more future cardiovascular events. We therefore tested the effects of nocturnal aircraft noise on endothelial function in patients with or at high risk for coronary artery disease.60 Patients  were exposed in random and blinded order to aircraft noise and no noise conditions. Noise was simulated in the patients’ bedroom and consisted of 60 events during one night. Polygraphy was recorded during study nights, endothelial function , questionnaires and blood sampling were performed on the morning after each study night.Leq(3) measured were 46.9 ± 2.0 dB(A) in the Noise 60 nights and 39.2 ± 3.1 dB(A) in the control nights. Subjective sleep quality was markedly reduced by noise from 5.8 ± 2.0 to 3.7 ± 2.2 (p < 0.001). FMD was significantly reduced  and systolic blood pressure was increased  by noise. The adverse vascular effects of noise were independent from sleep quality and self-reported noise sensitivity.The mean sound pressure levels Nighttime aircraft noise markedly impairs endothelial function in patients with or at risk for cardiovascular disease. These vascular effects appear to be independent from annoyance and attitude towards noise and may explain in part the cardiovascular side effects of nighttime aircraft noise. The role of noise as an environmental pollutant affecting health has been increasingly recognized. While acute noise interferes with communication, disturbs sleep and causes annoyance, chronic noise exposure has been demonstrated to be associated with negative health outcomes (for review ). StudieA recent investigator-blinded field study (The FLIGHT-Study) from our group demonstrated that simulated nighttime aircraft noise leads to endothelial dysfunction, worsening of sleep quality and increased vascular stiffness but no significant changes in blood pressure in young healthy volunteers .In an accompanying editorial Charakido and Deanfield emphasized that when considering the relevance of the findings for long-term clinical outcomes as well as for the causal pathways to cardiovascular disease and complications, that it would be highly important to examine the effects of noise on endothelial function of patients with already established cardiovascular disease .Thus, the FLIGHT-RISK study was set out to test the effect of nocturnal aircraft noise on endothelial function, stress hormone levels, blood pressure and inflammatory markers, sleeping quality, annoyance levels and coagulation markers in patients with established coronary artery disease or at high risk for developing coronary artery disease based on the Framingham score.LA,eq,22-6h > 40 dB for aircraft noise and LA,eq,22-6h > 45 dB for road and rail traffic noise).The study was approved by the local ethics committee. All volunteers signed informed consent. Anti-aircraft noise activists and airport employees were excluded from the study as were persons with high nighttime traffic noise exposure at home as determined by noise maps available from municipal online resources  and heart rate > 120 bpm were excluded.Persons with sleeping disorders , sleep disordered breathing, hearing loss >30 dB(A) and shift workers were also excluded. All blood pressure agents except for nitrates were allowed, calcium-antagonists had to be stopped 48 h prior to testing.Patients were mainly recruited via flyers and posters at the clinic and cardiologists offices.After initial screening and baseline data collection, subjects were exposed to simulated aircraft noise and no noise conditions in a randomized, cross-over and investigator-blinded fashion. The noise simulation took place in the familiar surroundings of the participants’ own bedrooms, thereby minimizing effects of an artificial laboratory situation.The aircraft noise consisted of 60 repetitive noise events, which had been recorded near Düsseldorf airport (window tilted open) have been used in our previous study [Study participants were instructed to refrain from the consumption of coffee, tea, alcohol, sleep altering medications and nicotine on the day prior to the study night.Participants attitude towards air traffic, aircraft noise and airport expansion was assessed with a dedicated questionnaire consisting of 19 items contributing to a total score between 0–64 with higher values denoting a more negative attitude.n = 19), citrated whole blood was centrifuged and frozen according to standard protocol for later analysis of coagulation factors.In a subset of patients , sleep related noise sensitivity, attitude towards aircraft noise, and morningness-eveningness questionnaire (MEQ).The level of significance for the primary endpoint (FMD) was set to 5 %. The analyses of secondary outcomes were regarded as explorative without adjustment for multiple testing. Differences between baseline characteristics were analyzed using paired p < 0.001 between visits [An interim analysis was scheduled at 60 patients; the stopping rule was based on the Haybittle-Peto boundary, i.e. it was predefined that the trial should be stopped early for a n visits , 10. Sta.60 patients m:w = 44:16) with a mean age of 61.8 ± 9.2 years were analyzed. The average calculated Framingham risk score was 26 %, (range 3–59 %). 50 patients had an established diagnosis of coronary artery disease (CAD) based on coronary angiograms (Table 6 with a p = 0.411) or humidity (p = 0.815 between the study nights). Participants’ blood pressure before the start of noise simulation were 137/74 mmHg (control night) and 136/75 mmHg .There was no evidence for differences in outside temperatures (eq(3) were 46.9 ± 2.0 dB(A) in the noise nights and 39.2 ± 3.1 dB(A) in the control nights.Averaged sound pressure levels Lp < 0.001; Fig. p = 0.442) nor velocity time integral (p = 0.348) changed significantly between control and noise nights.Compared to study nights without noise simulation, FMD of the brachial artery was markedly reduced after nighttime aircraft noise exposure .The randomization sequence had no impact on the blunting in FMD induced by noise  and those at lower risk.p = 0.001) and for the higher risk group FMD was reduced from 9.1 ± 4.4 to 7.8 ± 4.2 % (p = 0.023).For the lower risk group, FMD changed from 10.1 ± 4.3 to 8.0 ± 3.2 % , sleep related noise sensitivity or attitude towards aircraft noise Fig. .Fig. 2InAlthough subjective sleep quality was markedly impaired by the noise simulation, sleep quality  did not predict the blunting in endothelial responses on an individual level Fig. .p = 0.030) . The pNN50 index of heart rate variability did not change significantly.Heart rate was not different between control and noise nights . Likewise, there was no evidence for a difference in neurohormonal parameters  and inflammatory markers  (Table The mean pulse transit time did not show any change after noise exposure (6) Table .p < 0.001)  demonstrated just with respect Factor XII activity a significant reduction after noise exposure . All other coagulation factors remained unchanged .In particular, recently published studies clearly substantiate the cardiovascular side effects of aircraft noise. In a multi-airport retrospective study in more than 6 Million people aged >65 years residing near airports, Correia et al.  reportedAnother study in 3.6 million residents living close to Heathrow airport revealed that aircraft noise increased hospital admissions in a significant linear trend with increased risk with higher levels of both daytime and nighttime aircraft noise . When arLikewise, Floud et al.  reportedMore recently, we provided some insight into potential mechanisms leading to vascular dysfunction and subsequently cardiovascular disease in response to nighttime aircraft noise. In a field study, we showed that nighttime aircraft noise simulation caused endothelial dysfunction and tended to increase blood pressure . This paThe present studies provide several important new information concerning cardiovascular risk and nighttime aircraft noise.1. For the first time we demonstrate that nighttime noise substantially reduces FMD in patients with -or at risk for- coronary artery disease despite optimal, guideline conform concomitant cardiovascular medication including ACE-Inhibitors, AT-1 receptor blocker, statins and antiplatelet agents.Importantly, endothelial dysfunction of forearm vessels has been shown to correlate well with endothelial dysfunction (and with the presence of atherosclerosis) in coronary vessels  and it h2. In addition, there was evidence that nighttime aircraft noise simulation increased systolic blood pressure during the night by approximately 4 mmHg in patients with CAD. The observed 4 mmHg increase in systolic blood pressure is considered clinically relevant if sustained in the long-term, since recent studies have demonstrated that every 1 mmHg increase in systolic blood pressure in elderly with isolated systolic hypertension is associated with a 1 % increase new onset heart failure .In the present studies, the increase in blood pressure was not associated with a change in plasma adrenaline concentration, possibly due to the background therapy with beta receptor-blocker or ACE/inhibitors and AT1 receptor blockers, substances that are known to have substantial inhibitory actions on the activity of the adrenergic and the renin angiotensin system , 18.3. These data also demonstrate for the first time that detrimental vascular consequences in response to nighttime aircraft noise occur independently of the conscious perception of noise and the subject´s cognitive awareness Fig. .4. With regard to influence of noise on coagulation we detected a notable reduction in the level of Coagulation Factor XII (Hageman-Factor). While the role of factor XII in vivo remains controversial, associations of mildly reduced levels with increased coronary risk have been reported , 20.The FMD measured in our patient group with cardiovascular disease was just slightly reduced compared to the FMD measured in healthy subjects , which mIt is important to note that our previous study clearly demonstrated that vessels are getting sensitized to noise-induced vascular damage rather than getting habituated since the blunting in FMD was in particular evident, when subjects were exposed first to 30 and then to 60 night noise events [As in the previous study, noise exposure had a negative influence on subjective sleep quality of study participants. This finding may be regarded as clinically important, since self reported sleep quality is closely related to vascular calcification  and endoIn the current study, we could not detect changes in measures of immune function like cortisol levels, CRP, IL-6 or neutrophil count.The protocol was designed as a field study. While this limits the confounding influence of environment and equipment, thus creating ecologically valid conditions, ambient conditions, background sound levels and external stimuli could not be controlled for. Further, as only short-term effects of an environmental exposure were investigated here, conclusions on the long-term sequelae of such an exposure cannot be drawn from the present results.FMD was chosen as surrogate endpoint for several reasons: as a functional measure, it is ideally suited to quantify functional changes of the vasculature to short-term exposure to noxious stimuli and it has shown to be predictive for future cardiovascular events in patients with hypertension, coronary and peripheral artery disease and stroke. FMD of forearm conductance vessels has also been demonstrated in a multicenter trial to have a high reproducibility . In addiThe question whether a threshold of sound pressure levels beyond which the negative effects of noise appear, and what the best indicator of noise is, is often raised. Admittedly, our study setup cannot provide a definite answer to that. Nevertheless, there is now considerable evidence that a mean sound level of about 47 dB(A) such as that achieved in the present study consistently leads to moderate impairment of endothelial function in healthy controls  and to aThe presented results demonstrate that nocturnal aircraft noise exposure causes severe endothelial dysfunction, raises systolic blood pressure in patients at high risk for cardiovascular events despite guideline oriented medical therapy. Taking into account the prognostic importance of endothelial function in patients with CAD, it is reasonable to conclude that nighttime aircraft noise-induced deterioration of vascular function may contribute at least in part to the observed increased incidence of arterial hypertension, MI and stroke in nighttime aircraft noise exposed people.The present studies also stress the fact that more noise effect research has to be implemented and intensified. Important topics for the future may be to determine to what extent nighttime noise is able to modify the amount of circulating progenitor cells , whetherImportantly, when decisions concerning the location and/or activity volume of airports are taken, the impact of aircraft noise on the health of the surrounding population should be considered. While many of the traditional risk factors  can be modified by the patients´ behavior and attitudes, nighttime aircraft noise can be considered as the only risk factor, which can only be changed by politicians and not by the patient himself.


A variety of factors have been linked to perioperative visual loss during or directly after nonocular and ocular surgeries. Prolonged immobilization, biochemical factors and hemodynamic instability have been discussed as factors in the pathogenesis of this devastating complication. Perioperative visual loss in four consecutive patients, all featuring Flammer syndrome, is reported herein. To our knowledge, we present the first case series, which associates perioperative visual loss with Flammer syndrome. We assume that a low perfusion pressure, disturbed autoregulation of the ocular blood flow and altered drug sensitivity in such subjects, play significant role in the pathogenesis of this dreaded complication.We analysed the medical records of four consecutive patients with permanent perioperative visual loss and complemented our findings with additional history taking and clinical examinations. A variety of tests was performed, including colour Doppler ultrasonography of the retroocular vessels, static and dynamic retinal vessel analysis. The visual loss was unilateral in three patients and bilateral in one. An extensive review of published perioperative vision loss cases was conducted.All four patients were male Caucasians, and exhibited prominent signs and symptoms of Flammer syndrome. The visual loss originated from a propensity for unstable ocular blood flow, combined with hyperreactivity toward pharmacological stimuli, leading together to disturbed autoregulation of the blood supply, and subsequently - to ocular hypoxia. An identified intrinsic hypoperfusion diathesis was a crucial pathophysiologic link in all of the patients. Other, yet unknown systemic or local factors may also be involved in this process.A review of numerous publications of perioperative visual loss and our data, support our hypothesis for a novel pathophysiologic model and incorporate Flammer syndrome as a distinct risk factor for paradoxical visual loss, during nonocular and ocular surgeries, or invasive procedures. To prevent the complications produced by disturbed blood flow autoregulation in such patients, guidelines for screening and tailored preoperative approach are given. Presumed pathogenic factors for perioperative visual loss, reported with a variety of nonocular surgeries, thus far include prolonged immobilization in prone position, external pressure on the eye, significant blood loss and hypotension, or excessive hydration with systemic hypertension and/or hemodilution, systemic hypothermia, as well as hyperlipidemia, most of which occurring usually in adults –3.Our work highlights Flammer syndrome (FS) as a risk factor for visual loss during nonocular surgery in one adolescent patient and one adult patient, and during ocular interventions in two adult patients.We conducted a retrospective study on four consecutive patients, presenting in our clinic, between December 2006 and December 2015, with persistent perioperative visual loss not explained by prevailing ophthalmic diseases.The patients’ cases were indentified through thorough search in our multidisciplinary clinical meeting reports, produced in this nine-year period. In the files thus examined, we reviewed all data, along with the questionnaire used in cases of suspicion for disturbed vascular autoregulation. The questionnaire identifies signs and symptoms associated with FS. The inclusion criteria for our study were: positive answers to at least four out of ten signs or symptoms, and/or identified increased sensitivity toward medication. The exclusion criteria were: inclusion criteria not satisfied or a visual loss unequivocally due to purely ophthalmologic genesis.In each case, a comprehensive evaluation, including extensive file review, history taking, full general and ophthalmologic examinations, and complete vascular and pharmacological workup were performed. Appropriate follow up was made and the findings were recorded each time.Visual field examination, Dynamic Colour Doppler imaging of the orbital vessels and retinal vessel analysis were essential tools in the investigative process.Plasma Endothelin-1  level was investigated at the time when a common profile of our group of patients began to point toward vascular dysregulation in the context of Flammer syndrome. The ET-1 measurement was obtained according to our standard protocol: the blood sample was drawn at room temperature through a venesection, following 30 minute rest in supine position, then the blood was immediately transferred to an EDTA containing tube and was centrifuged for 5 minutes at 4 degree Celsius (°C). The plasma was separated from the blood cells at 4 °C and kept at −80 °C until the essay was performed. The ET-1 plasma level was determined by radioimmunoassay with synthetic human/porcine ET-1 , a rabbit antibody against synthetic ET (Peninsula Laboratories) and 125I-ET-1 (Amersham) [2 and unremarkable preoperative circulatory status, underwent 8 hour corrective scoliosis surgery, with 1400 ml blood loss. Upon awakening he noted blindness in his left eye. A profound visual loss, visual field constriction . Nailfold capillary microscopy with a cold-provocation test yielded blood flow cessation in one out of four capillaries for 57 seconds , while the patient was also positive for nine out of ten criteria for FS . Mepivacaine is a known vasoconstrictor of retrobulbar vessels ; promineA 75-year-old gentleman suffered from reduced visual acuity (0.1) due to a persistent macular edema in the context of a chronic uveitis in his left eye. Peribulbar injection of betamethasone acetate - betamethasone sodium phosphate was performed to treat the condition. Unfortunately, immediately following the uncomplicated peribulbar injection, the patient reported “seeing only white”. His visual acuity was reduced to light perception. The ultrasound examination of the involved eye and the optic nerve showed neither signs of compartment syndrome, nor a direct injury of the eye or the optic nerve. Dynamic Colour Doppler-Ultrasound revealed reduced flow velocity in the left central retinal artery, whereas the flow in the ophthalmic- and cilioretinal arteries was symmetrically normal Fig. . This paA 55 year-old male had bilateral visual loss, following surgery for aortic valve insufficiency. His previous ophthalmological check-up, revealed no pathology. During a mini-sternotomy the mammary artery has been injured, leading to hemodynamic shock. His visual acuity four days postoperatively was accessed as no light perception, with afferent pupillary defect bilaterally, and dilated pupils to 5.1 and 5.4 mm Fig. , with seWe describe four patients with acute visual loss, noticed by the patients immediately after a surgery or a drug application. The literature reports visual loss after a variety of nonocular surgeries, among which spinal surgery, cardiac surgery and radical neck dissection held the greatest risk for this devastating complication , 9, 10.The final steps in the pathogenetic chain of events of perioperative visual loss in adults are mainly retinal vascular occlusion, ischemic optic neuropathy and ischemic cerebral lesions , 11. HigThe roles of intraoperative arterial hypotension/hypertension or increased IOP with consecutive reduction of the ocular perfusion pressure have also been discussed.In our case series, low perfusion pressure, combined with disturbed autoregulation of the ocular blood flow, together with increased drug sensitivity seem to have played a central role in the pathogenesis of ocular hypoxia. The perfusion pressure (PP) of the eye depends on the difference between the mean arterial pressure and the retinal venous pressure (RVP). In healthy subjects, RVP is equal or slightly above the IOP. However, in patients with Flammer syndrome RVP is often distinctly above the IOP . TherefoAs it is now well established, and further exemplified in our case series, that subjects with Flammer syndrome have intrinsically insufficient and unstable blood flow autoregulation.Flammer syndrome subjects tend to react to a number of stimuli, such as cold, physical or emotional stress, and systemic medication, like adrenalin, with marked vasoconstriction , 15. TheSubjects with FS often suffer from systemic hypotension , partly Subjects with FS often exhibit further blood pressure dips; therefore they have a lower perfusion pressure.Subjects with FS have impaired autoregulation of their ocular blood flow, in which vascular endotheliopathy plays an important role .Subjects with FS have, on average, higher retinal venous pressure , 19. ThiSubjects with FS have altered drug sensitivity, which is linked to altered expression of the ABC transport proteins . This inAll four patients reported visual loss immediately after systemic surgery, ophthalmic surgery, or ocular interventions, while all of them suffered simultaneously from Flammer syndrome. Our hypothesis is that FS may increase the risk for perioperative visual loss, and is based on the following facts:To note well, the complete vascular workup in our patients was positive for history of cold extremities, increased reactivity to cold , and findings of increased plasma Endothelin-1 levels (Patient 1). Furthermore, the capillary blood flow cessation, registered through Nailfold Capillaroscopy with cold provocation test   and the We will summarise here some prominent signs and symptoms, in order to complete the profile of such patients. Subjects with FS tend to have cold extremities  and reduIn all of the presented patients the vascular dysregulation dynamics were supposedly influenced by pharmaceuticals, with known side effects.The pharmacological agents used during the surgery of Patient 1 were: Fentanyl, Remifentanil, Morphine, Thiopental, Atracurium, Ketamine, Propofol, Ringer’s lactate, HAES, Cefazolin, Paracetamol and Oxygen. Hypotension is observed after Morphine and Remifentanil medication. Thiopental and Atracurium may have hypotonic effect, mediated by histamine release , 28. KetRaynaud-like phenomenon has been described in a 14-year-old girl after Propofol medication . CerebraIn Patient 2 the anaesthetic protocol comprised Meperidine, Propofol, Ringer’s lactate, Hydroxyethyl Starch (HAES), Cefazolin, Paracetamol and Oxygen. Here the medications given to an individual with pre-existing Flammer syndrome and normal tension glaucoma produced the so dreaded outcome of visual loss. On the contrary, to our knowledge, a betamethasone-vascular dysregulation interaction (patient 3) has not been reported so far , 30.Regarding Patient 4, during cardiac surgery a catecholamine (Norepinephrine) is routinely used to preserve the vessel tonus under open-air conditions. However, Norepinephrine is known to produce peripheral vasoconstriction .Studying four patients with Flammer syndrome, in which seemingly different influences exacerbated the vascular disturbance, increased our understanding of this condition and the precautions to be taken, if a surgery or an invasive treatment, such as peribulbar or retrobulbar medication is to be performed.Our findings shed new light on the pathogenesis of perioperative visual loss, while we ought to point out the limitations of our study, stemming from the small number of observed patients. While thankfully this complication is quite rare, further reports and observational prospective studies would be necessary, in order to establish the rate of perioperative visual loss among subject with FS, compared to the general population undergoing anaesthesia and surgery, and how the perioperative management of such subjects can promote a more favourable outcome in terms of vision preservation.In Summary, we observed perioperative visual loss in four consecutive patients, and all data pointed toward episodes of ocular hypoxia. All four patients also had Flammer syndrome, therefore we presume that the syndrome may distinctly increase the risk for this devastating complication. A preoperative screening for FS would identify the patients in need of preventive measures. The screening can be done through thorough history taking, sensitive for data pointing toward probability for Flammer syndrome, such as prominent cold sensitivity, increased sleep latency, low blood pressure and other features of the syndrome Table .Identifying patients with FS may allow undertaking preventive measures, such as avoidance of: low blood pressure, cold provocation and vasoconstrictors, while implementing pre-treatment with magnesium  and low Finally, in our case series, we assume a disturbed blood flow autoregulation, and a hyperreactivity toward pharmacological stimuli, to be the etiological bases of the unstable blood supply during the respective interventions. This process leads to significant and rapid increase of free radicals and enormous oxidative stress in individuals with Flammer syndrome. In our patients, based on all presented findings, we also hypothesise a hyperactivity of the sympathetic nervous system during or immediately after the surgery, or procedure, which resulted in massive vasospasm of the retinal, choroidal and/or peribulbar vessels, thus producing a visual loss.The presented herein in-depth analysis of vascular dysregulation factors in a diverse group of patients, including an adolescent individual, has promoted our understanding of the pathological mechanisms leading to visual loss after uncomplicated (from systemic point of view) anesthesia or surgery, and was crucial for identifying effective preventive strategies.The study and data accumulation were in conformity with our institutional requirements  and in accordance with the Declaration of Helsinki, and all governmental regulations. A detailed explanation was given to the patients before each procedure and test, and the procedure or test was performed only after they gave their consent.Written consent was obtained from the patients (and the parents of Patient 1) for publication of these Case reports and any accompanying images. Copies of the written consents are available for review by the Editor of this journal. The presented herein material preserves the anonymity of the patients.


Use of serum creatinine to estimate GFR may lead to underestimation of the association between self-reported frailty and kidney function. Our objectives were to evaluate the association of measured GFR (mGFR) with self-reported frailty among patients with CKD and to determine whether self-reported frailty was associated with death after adjusting for mGFR.Participants in the Modification of Diet in Renal Disease study (1989–1993) had GFR measured using iothalamate clearance (mGFR), and GFR was estimated based on the CKD-EPI creatinine (eGFRcr) and cystatin C (eGFRcys) equations. We defined self-reported frailty as three or more of: exhaustion, poor physical function, low physical activity, and low body weight. Death was ascertained through 2007 using the National Death Index and the United States Renal Data System.N = 130) and mGFR (mean (SD) 33.1 ± 11.7 ml/min/1.73 m2). Higher GFR was associated with lower odds of self-reported frailty based on mGFR, , eGFRcr , and eGFRcys . Median follow-up was 17 (IQR 11–18) years, with 371 deaths. Self-reported frailty was associated with a higher risk of death , which was attenuated to a similar degree when mGFR , eGFRcr , or eGFRcys  was included as an indicator of kidney function.Eight hundred twelve MDRD participants (97 %) had complete data on self-reported frailty (16 % prevalence, We found an inverse association between kidney function and self-reported frailty that was similar for mGFR, eGFR and eGFRcys. In this relatively healthy cohort of clinical trial participants with CKD, using serum creatinine to estimate GFR did not substantially alter the association of GFR with self-reported frailty or of self-reported frailty with death. Frailty is more prevalent among patients with CKD than among individuals with normal kidney function –4, and fThe use of serum creatinine to estimate kidney function could also complicate the problem of assessing the association of kidney function with frailty. Because muscle wasting associated with frailty, there is a potential for bias using creatinine based estimates of glomerular filtration rate (eGFR). To our knowledge there have been no evaluations of the relationship of frailty with kidney disease using direct measurement of GFR. The Modification of Diet in Renal Disease (MDRD) study affords a unique opportunity to study frailty by self-report among a cohort of healthier patients who have stage 3 to 5 CKD not on dialysis. Within this cohort there is a wide range of directly-measured GFR to assess the association of kidney function with frailty. The purpose of this study was twofold; first to examine the association of kidney function with self-reported frailty, using a direct measure of kidney function and estimated GFR as a comparison, and second, to determine whether self-reported frailty was associated with death in this cohort with few comorbidities.n = 812; 97 %). Informed consent was obtained from all participants as part of the original study. The Committee on Human Research at the University of California - San Francisco and the Research and Development Committee of the San Francisco Veterans Affairs Medical Center deemed this study exempt.The MDRD Study was a multicenter cooperative clinical trial designed to determine whether restriction of dietary protein and a low target blood pressure ) reduced the rate of progression of CKD, irrespective of the nature of the primary underlying process. Patients with diabetes requiring insulin were excluded . At base mmHg) reOur frailty definition was an adaptation of the Fried Frailty Index that substituted patients’ self-report of physical function for the direct measures of physical performance (gait speed and grip strength) that are part of the original definition. This approach is similar to that originally developed by Woods et al.  and subs125I-iothalamate was completed twice during the baseline period for all participants. We used the average of the 2 baseline 125I-iothalamate clearance measures in our analyses . We modeled GFR as a continuous variable and as categories . To compare the association of the direct measurement of kidney function with self-reported frailty to the association of a creatinine-based estimate (eGFRcr) and cystatin C-based estimate (eGFRcys) of GFR with self-reported frailty, we used the Chronic Kidney Disease Epidemiology Collaboration  42–61), and a history of hypertension was common (84 %)  and poor physical function (23 %), whereas a smaller proportion of individuals met the criteria for underweight/weight loss 17 %) and exhaustion (13 %). There was a graded association of the prevalence of the components of self-reported frailty with GFR category such that individuals in the lowest GFR category had a higher prevalence of each of the components of self-reported frailty  (Table 2 were more likely to be frail by self-report compared to mGFR ≥45 ml/min/1.73 m2 (OR 2.10 95 % CI 1.09–3.60). In fully adjusted modelling, this association was attenuated. Individuals with mGFR ≤29 ml/min/1.73 m2 were more likely to be frail by self-report than those with mGFR ≥ 45 ml/min/1.73 m2 (OR 3.40 95 % CI 1.77–6.50) in multivariable analysis.In univariate analysis, higher mGFR was associated with lower odds of self-reported frailty Table . C-react2 (95 % CI 0.67–0.94) in multivariable analysis) (Table 2 were more likely to be frail by self-report (OR 3.20 95 % CI 1.61–6.40).Associations of eGFRcr with self-reported frailty were similar to those observed with mGFR. Higher eGFRcr was associated with lower odds of self-reported frailty in univariate and multivariable analysis (OR 0.80 per 10 ml/min/1.73 m2 were more likely to be frail by self-report (OR 2.30 95 % CI 1.11–4.70).Associations of eGFRcys and covariates with self-reported frailty were slightly lower compared to those observed with both mGFR and eGFRcr. Higher eGFRcys was associated with lower odds of self-reported frailty in univariate and multivariable analysis Table . When eGp-values for interactions >0.05). The potential for non-linearity of the association of GFR with frailty was examined using a quadratic term in the above models and by examining cubic splines, neither of which differed from the linear models presented. The concordance c statistic (area under the receiver operating characteristics [ROC] curve) for predicting frailty by self-report for the base model was 0. 66   Fig. , Table 4Three hundred seventy-one (45 %) patients died before the end of 2007 (median follow-up 17 years (IQR 11–18)). Self-reported frailty was associated with a higher risk of death in multivariable modeling (HR 1.71 95 % CI 1.26–2.30) when kidney function was not included as a covariate  and different definitions of frailty. Specifically, the prevalence of frailty is higher using definitions based on self-reported physical function compared to frailty defined by direct measures of physical performance . NeverthThe association of the severity of CKD with frailty has been previously evaluated using estimates of renal function. Similar to our findings with GFR modeled continuously, these studies have shown patients with more severe renal disease to have a higher likelihood of frailty , 13, 17.The expectation that frailty would be associated with a higher risk of death was based on a conceptual framework in which frailty is a marker of accelerated loss of functional reserve above and beyond what occurs as a result of kidney disease. Although other cohort studies have evaluated the association of frailty with risk of death among patients with CKD , 4, 16, A number of limitations of our study should be acknowledged. Our definition of frailty was based on patients’ self-reported physical function rather than direct measures of physical performance. We and others have shown that use of self-reported function identifies more individuals as frail, but such definitions have been associated with mortality as in this report –5, 8. WeIn summary, we found that worse kidney function was associated with higher prevalence of self-reported frailty in a cohort with a smaller burden of comorbidities than is generally present among patients with advanced CKD. Furthermore, the inverse association between kidney function and self-reported frailty was similar when kidney function was measured or estimated. Self-reported frailty was associated with higher risk of death even after adjusting for kidney function. There is a need for longitudinal and interventional studies to determine whether intervening on frailty can improve outcomes among patients with CKD.


Our hypothesis was that telehealth in combination with an optimised care program coordinated amongst care professionals in primary, secondary and tertiary care can achieve beneficial outcomes in heart failure. The objective was to evaluate the clinical effects of introduction of telehealth in an optimised care program in a community hospital in the north of the Netherlands.We compared the number of unplanned admissions for heart failure in the year before and after adding telehealth to the optimised care program. Furthermore, blood pressure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were evaluated at baseline and 3, 6 and 12 months after telehealth. Quality of life and knowledge about the disease were regularly evaluated via surveys on the telehealth system.The number of unplanned admissions for heart failure decreased from on average 1.29 to 0.31 admissions per year after telehealth introduction. Blood pressure decreased independent of medication and NT-proBNP levels improved as well. Quality of life increased during the telehealth intervention and disease knowledge remained high throughout the follow-up period. Unplanned admissions that remained after telehealth introduction could be accurately predicted at baseline by a multivariate regression model. Congestive heart failure (CHF) is a complex clinical syndrome, which represents an increasingly common health problem for patients, healthcare providers and reimbursing agencies. The continuing ageing of the population is expected to increase the prevalence of heart failure in the Netherlands from 120,000 (~ 1 % of the population) in 2008 to approximately 200,000 in the coming decade [Guidelines of the European Society of Cardiology (ESC) recommend a multidisciplinary approach that coordinates care along the continuum of CHF, often implemented as in-person follow-up visits . RecentlTelehealth for heart failure has had mixed and heterogeneous effects across studies, necessitating further evaluation within specific healthcare systems and patient populations. A systematic review on telehealth efficacy in RCTs concluded that telehealth reduced all-cause mortality by 34 % and CHF-related hospitalisations by 21 % and improvements in secondary endpoints such as quality of life and disease knowledge were also observed . HoweverThe first objective of this study was to assess the impact of telehealth-based disease management on unplanned admissions, disease severity and quality of life in CHF patients. The unique aspect of this study was its setting: a single community hospital in the north of the Netherlands, where cardiologists and nurse practitioners collaborate within the hospital outpatient heart failure unit. Furthermore, primary care, local home care agencies and nursing homes play a key role in the care protocol of CHF patients through their general practitioners, home care nurses and physicians. The second objective was to determine, which patient characteristics were predictive of unplanned admissions in a telehealth program. As unplanned readmissions are costly, a predictive score to quantify the risk of readmission would help clinicians to identify patients who might benefit from more intensive post-discharge care, even beyond telemonitoring.In this prospective study, 102 CHF patients were enrolled in an optimised care program with telehealth between 3 April 2011 and 10 May 2013. A pre-post study design was used to evaluate the effect of the telehealth intervention without the use of a control group. The primary outcome, number of unplanned hospitalisations for heart failure, was measured 1 year before and 1 year after introduction of the program. Unplanned admissions were considered admissions that could not be delayed beyond 24 h because of symptoms ascribed to heart failure by the attending physician or nurse practitioner. Secondary outcomes, blood pressure and NT-proBNP levels, were measured at enrolment and after 3, 6 and 12 months. Blood pressure was measured using an automatic upper arm cuff . NT-proBNP analysis was performed with an immunoassay .Patients discharged after an admission with the primary diagnosis of heart failure or outpatients after an episode of new or worsening heart failure, as judged by the attending cardiologist because of clinical symptoms and NT-proBNP levels elevated above normal limits, were recruited to participate in the study. Patients who were in New York Heart Association (NYHA) class II–IV, were in a stable condition, had good command of the Dutch language and were in possession of a television set were eligible for inclusion. Patients who were unable to provide informed consent were excluded from the study. Out of 105 patients who were asked to participate in the study, 102 (97 %) gave their informed consent.The study was conducted in a CHF outpatient unit of a local community hospital in the north of the Netherlands . The unit’s cardiologists and nurse practitioners provide care to heart failure patients in the region, involving the patient’s general practitioner, nurses from a local home care agency and physicians at the nursing home, if patients reside at such facilities. This structured service was already in place before patients were enrolled in the telehealth program. A detailed schematic diagram of the optimised care pathway including telehealth can be found elsewhere .Staff had prescription and treatment authorisation, preventing delay in response-treatment times and preventing burden on the workload of the cardiologist. The telemonitoring system was used to obtain and check patient vital sign measurements  on a daily basis. All members of the cardiology department had access to the telemonitoring system, allowing them to check vital sign measurements at every moment and react accordingly.Retrospective data of 1 year on CHF-related admissions were gathered as well as demographics, clinical status and treatment and physical examination data. All patients were followed up for a period of 1 year with additional visits as required in case of deterioration. Follow-up visits at the outpatient unit took place 3, 6 and 12 months (study end) after enrolment. The nurse practitioners and cardiologists participating in the study were the same as those involved in the patients’ everyday care before the study. During the study period, all patients continued to receive the standard care provided to patients at the CHF outpatient unit. Patients received primary care from their own general practitioner.The study was approved by the hospital ethics committee. All participants gave informed written consent.The Motiva telehealth system  was used and included a secured broadband home TV channel providing educational material, reminders of medication, health-related surveys and motivational messages to encourage the prescribed lifestyle regimen. Patients were given automated devices for daily measurements of blood pressure, heart rate and weight at home. A nurse practitioner evaluated the measurements every day using a dedicated clinical user interface. With tailored alarm settings, the nurse practitioner could identify which patients exceeded the alarm limits and needed extra attention. The situation was evaluated with a phone call or extra visit and if necessary the nurse practitioner altered the treatment.Patients also received scheduled educational videos covering topics such as symptoms, daily care, aetiology, medication, compliance, relapse prevention, cholesterol management, hypertension, lifestyle, nutrition, vaccinations and alcohol consumption. Questionnaires on quality of life  and disease knowledge  were sent every 8 and 12 weeks, respectively. MLHF measures the effects of symptoms, functional limitations and psychological distress on an individual’s quality of life due to heart failure and its treatment . DHFKS cThe number of unplanned admissions for heart failure in the period of 12 months before telemonitoring (the index admissions were not included in the counts) was compared with the number of admissions in the period of 12 months after telemonitoring was introduced with a rate ratio test . The incRepeated measures analysis of variance (ANOVA) followed by Tukey’s post-hoc comparison of means using α = 0.05 was used to determine significant deviations in blood pressure, NT-proBNP levels, knowledge level and quality of life from baseline. The method by Cousineau  was usedIt was further determined that patient characteristics at baseline could be used to provide a prediction of unplanned admission for heart failure within 12 months. A multivariate logistic regression model was developed on data from 80 patients chosen at random. The model variables were chosen using a forward selection approach, where the criterion used was to maximise the area under the receiver operator characteristic curve (AUC). Furthermore, to more accurately account for the non-linear relation between age and outcome, both age and age squared were included as predictors in the model. A cut-off level for NT-proBNP of 2500 pg/l was used to model the increased outcome in patients with NT-proBNP levels beyond 2500 pg/l. The model was evaluated using the AUC on the hold-out set of 22 patients.Out of 105 heart failure patients considered eligible, 102 patients (97 %) gave informed consent. Patients were on average 75 ± 12 years and 60 % were female patients (Table p < 0.001). In the pre-phase, 87 patients (85 %) had one or more unplanned admissions for heart failure, while only 31 patients (30 %) had one or more admissions in the post-phase. The number of days spent in hospital for all-cause admissions decreased from 975 in the 12 months before telehealth enrolment to 662 in the 12 months after telehealth introduction.There were 132 unplanned admissions for heart failure in the 12 months before telehealth enrolment, or an average of 1.29 admissions per patient in the pre-phase. In the 12 months after telehealth introduction, there were 32 unplanned heart failure admissions, or on average 0.31 per patient, i.e. a reduction of 76 % in unplanned heart failure admissions. The incidence rate ratio was found to be statistically significantly different from 1 , while diastolic blood pressure decreased significantly by 5.0 mmHg  = 22.6, p < 0.001) after 12 months in the telehealth program as compared with baseline. For NT-proBNP level, a significant decrease over time was found from 4433 ± 5720 at baseline to 2877 ± 3128 pg/l at 12 months, a reduction of 35 %  = 10.9, p < 0.001).Clinical effects of the telehealth program were determined by measuring systolic and diastolic blood pressure and NT-proBNP levels at baseline and after 3, 6 and 12 months in the program (Table p < 0.05), but diastolic blood pressure was not  = 1.2, p = 0.28). Repeated measures ANOVA including the interaction between use of both medications and time on the telehealth program demonstrated that the combination of β-blockers with ACE inhibitors did not have a statistically significant effect on the decrease in systolic blood pressure  = 1.2, p = 0.31) or diastolic pressure  = 1.1, p = 0.33) over time  were prescribed both β-blockers and ACE inhibitors. In patients using both medications, systolic blood pressure was significantly lower than in other patients  = 10.2, ,93 = 10.p < 0.001). Disease knowledge was assessed by the DHFKS survey with complete observations in 88 patients. The reported knowledge level was found to be consistently high across all follow-up times from 12.2 ± 0.5 at baseline to 11.5 ± 0.4 at 48 weeks . There were no significant differences with baseline at the other follow-up times.Quality of life was assessed by the MLHF survey with complete observations in 86 patients; a higher MLHF score corresponds to a lower quality of life. Mean total MLHF scores decreased over time Fig. , which wA total of 31 patients (30 %) had one or more admissions for heart failure. Odds ratios for the multivariate logistic regression model are given in Table In line with previous findings , the numInterventions using telehealth technology have the potential to reduce avoidable readmissions, and the evidence base for its beneficial effect is growing , 21. HowBy providing education to promote change in patient behaviour for proper self-management, telehealth may have improved clinical indicators and quality of life . Blood pPredicting admissions in heart failure patients is difficult ; howeverMain limitation of the current study is the pre-post design without a control group. Therefore, one needs to be cautious when interpreting these results as being brought about by the telehealth program. The number of admissions on remeasurement is likely to be lower due to the statistical phenomenon of regression to the mean. An estimation of this effect  led us tIn the Netherlands, virtually all hospitals work with a CHF clinic staffed with either nurses or nurse practitioners, as it is a performance indicator monitored by the Dutch Healthcare Inspectorate . ProvideIn future, we are looking to further expand the current optimised care program with telehealth to other hospitals in the region. However, the inadequacy of reimbursing systems in the Netherlands to pay for this type of coordinated care constitutes a potential threat to its wider implementation, thereby possibly withholding improved chronic care from patients who could benefit and missing the opportunity to reduce overall costs of the care for CHF patients.None.Jorn op den Buijs, Steffen Pauws and Murk Westerterp are employed by Royal Philips.


Despite the large differences in the epidemiology of hypertension across Europe, treatment strategies are similar for national populations of white European descent. However, hypertensive patients of African or South Asian ethnicity may require ethnic-specific approaches, as these population subgroups tend to have higher blood pressure at an earlier age that is more difficult to control, a higher occurrence of diabetes, and more target organ damage with earlier cardiovascular mortality. Therefore, we systematically reviewed the evidence on antihypertensive drug treatment in South Asian and African ethnicity patients. We used the Cochrane systematic review methodology to retrieve trials in electronic databases including CENTRAL, PubMed, and Embase from their inception through November 2015; and with handsearch. We retrieved 4596 reports that yielded 35 trials with 7 classes of antihypertensive drugs in 25,540 African ethnicity patients. Aside from the well-known blood pressure efficacy of calcium channel blockers and diuretics, with lesser effect of ACE inhibitors and beta-blockers, nebivolol was not more effective than placebo in reducing systolic blood pressure levels. Trials with morbidity and mortality outcomes indicated that lisinopril and losartan-based therapy were associated with a greater incidence of stroke and sudden death. Furthermore, 1581 reports yielded 16 randomized controlled trials with blood pressure outcomes in 1719 South Asian hypertensive patients. In contrast with the studies in African ethnicity patients, there were no significant differences in blood pressure lowering efficacy between drugs, and no trials available with mortality outcomes. In conclusion, in patients of African ethnicity, treatment initiated with ACE inhibitor or angiotensin II receptor blocker monotherapy was associated with adverse cardiovascular outcomes. We found no evidence of different efficacy of antihypertensive drugs in South Asians, but there is a need for trials with morbidity and mortality outcomes. Screening for cardiovascular risk at a younger age, treating hypertension at lower thresholds, and new delivery models to find, treat and follow hypertensives in the community may help reduce the excess cardiovascular mortality in these high-risk groups. The increasing ethnic diversity of the European population is likely to bring a greater diversity in disease and disease patterns to the doctor’s office. Around 33 million immigrants live in the European Union. It is estimated that a third of these immigrants are from other European countries, while immigrants from non-European countries are mainly African , or Asian 21 %) [ % [1].Despite the large differences in the epidemiology of hypertension across Europe , treatmeWhile little is reported regarding the pathophysiology of hypertension in South Asian patients, abundant data in patients of African descent indicate there is greater salt sensitivity, blunted nocturnal dipping, and enhanced vasoconstriction in this group , 16–21. In patients of all ethnicity groups, non-pharmacological intervention to reduce hypertension and cardiovascular risk, including dietary adjustments, physical exercise, weight reduction, smoking cessation, and reduction of excessive alcohol intake should be part of hypertension management. In addition, stress reduction and relaxation exercise might aid in reducing blood pressure . In partHowever, most patients with hypertension will need drug therapy aside life style measures. Therefore, in this paper, we review the evidence on randomized trials of antihypertensive drug treatment in African and South Asian ethnicity patients, and propose practical approaches for the European situation.The participation of patients of ethnic minority groups in major, international clinical trials is generally too low to calculate the primary outcome with sufficient power . TherefoSystematic searches were conducted in November 2015, with our previous systematic review on patients of African ethnicity , 17 updaWe included only trials with major drug classes in adults, men and non-pregnant women, with uncomplicated primary hypertension . Trials that considered oral antihypertensive treatment with thiazide and thiazide-like diuretics, calcium-channel blockers, centrally acting agents, peripheral adrenergic neuron antagonists, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin II receptor blockers were eligible for inclusion.We conducted separate searches and data analysis for these two ethnic groups. Searches were performed in electronic databases , African Index Medicus, and for South Asian patients, IndMED) from their inception through November 2015, without language restriction.These databases have different software and therefore different search languages, but a typical search strategy for trials in patients of African ethnicity was, “(Black* OR Afri* OR AFRO* OR Creole OR Carribean OR Caribbean OR negr* OR ethnic* OR blacks) AND (hypertension OR antihypertensive) AND randomized”; and for South Asians: the first step was “”.Search yields from all databases were considered and analysed separately to prevent merging errors and to enhance trial retrieval. Furthermore, we contacted experts and performed hand search. We did not include trials in diabetics only, with experimental drugs, or with complementary medicines.We used data extraction forms to collect trial data. With pilot searches, we retrieved very few placebo controlled trials in South Asians, and decided to review drug vs drug trials in this group. For drug vs drug trials with multiple treatment arms, we followed the Cochrane handbook methodology and combined the comparison groups into one group of “other drugs” . AfricanQuantitative analysis of outcomes was based on intention-to-treat results (primary) and per protocol analysis (secondary). We included data from the first part of crossover studies when such data were available; if not, we included the data these studies provided. Our measure of effect for each study was difference in means (in mmHg) for systemic arterial blood pressure (continuous measure) and relative risk (RR) for dichotomous data. In addition, we calculated achievement of target diastolic blood pressure  as the weighted mean of placebo-corrected results per drug class, or in South Asians, vs other drug types.I2 statistics to quantify the proportion of total variation in the estimates of treatment effect that was due to heterogeneity. We planned to not aggregate results with a high variation across studies (I2 ≥ 75 %)  (I2 = 0 %). With the addition of these relatively large trials to the pooled analysis  ,–66,36–66 = 50 %) , and witAchievement of target DBP differed by drug class, calcium-channel blockers 46 % ; with a RR of >1.0 indicating a beneficial effect.Thus, the aggregated data show a greater effect of calcium blockers and diuretics, while beta-adrenergic blockers and ACE inhibitors are the least effective drugs to lower SBP and DBP, respectively. The cause of these differences in drug responses is largely unknown. Our findings are in accord with the suppressed activity of the renin-angiotensin-aldosterone system in hypertensive patients of African ethnicity, and the high activity of creatine kinase, promoting vasoconstriction and salt retention , 16. As N = 146 patients), and this was not further analysed  , similarlosartan . These dCYP3A4 A392G, were more likely to reach a target MAP of 107 mmHg [adjusted hazard ratio of AA/AG compared to GG 3.41 ]. Among participants randomized to a lower MAP goal, men and women with the C allele at CYP3A4 T16090C were more likely to reach the target MAP of 107 mmHg [adjusted hazard ratio 2.04 ]. In addition, the polymorphisms Arg65Leu, Ala142Val, and Ala486Val of the G protein-coupled receptor kinase gene, GRK4, were studied in the AASK Study. Only in men randomized to the usual blood pressure goal , the adjusted “hazard” ratio to reach the goal blood pressure with metoprolol was 1.54  with Ala142Val. There was no association between GRK4 polymorphisms and blood pressure response to metoprolol in women ). In other outcomes, the relative risk for atherosclerotic coronary heart disease events with pravastatin was lower in patients of African descent than in other patients . However, there was a significantly greater stroke risk with pravastatin in patients of African descent . As a result, there was no significant effect of pravastatin treatment on combined cardiovascular disease outcomes in hypertensive patients of African ethnicity .Tab.Tab35].TOther effects described included that lisinopril reduced micro-albuminuria (−33 vs −10 % in amlodipine) , while dThe WHO Global Monitoring Framework has set a target of 25 % reduction in premature mortality from non-communicable diseases by 2025, including a 25 % reduction in the prevalence of hypertension . HyperteAntihypertensive drugs are the first cardiovascular therapy for which there was wide recognition of differences in clinical efficacy related to ethno-geographical ancestry . PatientThe existing evidence provides ample evidence of higher risk of premature cardiovascular mortality in South Asian and African ancestry groups –22. HoweAlso, we need data on whether lower thresholds to start treatment and lower therapeutic goal blood pressures need to be applied . The SysThe strength of this work is that we systematically review the available evidence of antihypertensive drug treatment with monotherapy for uncomplicated hypertension, and combination therapy for morbidity and mortality outcomes in hypertensive patients of African and South Asian ethnicity. The aggregated evidence should facilitate guideline development to reduce premature adverse outcomes in these high-risk population subgroups, but many questions remain. We are not well informed regarding the socio-economic circumstances of trial participants, which may have affected treatment failure . Also, tHowever, since there are ample effective drugs available, reducing hypertension and risk of end organ damage in these ethnic groups may predominantly involve different health management strategies. Public health approaches have been suggested to combat hypertension in all ethnic groups, with better models of screening, delivery of care , the use of a registry to treat and follow all hypertensives, and initial low dose combination therapy to increase compliance and blood pressure lowering efficacy, while reducing adverse effects , 116. HyIn summary, hypertension in persons of African or South Asian ethnicity occurs more frequently, and is associated with more therapy failure and more severe and earlier end organ damage. European guidelines for cardiovascular risk management should take this high risk into account. Persons of African or South Asian ethnicity need to be screened at a younger age, and treatment should potentially start at lower thresholds with early use of combination therapy and intensive treatment monitoring to reduce the high premature mortality.


The article summarizes current information on blood pressure changes in children during clinic visit. White coat as a general dressing of physicians and health care personnel has been widely accepted at the end of the 19th century. Two problems can be associated with the use of white coat: white coat phenomenon and white coat hypertension. Children often attribute pain and other unpleasant experience to the white coat and refuse afterwards cooperation with examinations. Definition of white coat hypertension in the literature is not uniform. It has been defined as elevated blood pressure in the hospital or clinic with normal blood pressure at home measured during the day by ambulatory blood pressure monitoring system. White coat effect is defined as temporary increase in blood pressure before and during visit in the clinic, regardless what the average daily ambulatory blood pressure values are. Clinical importance of white coat hypertension is mainly because of higher risk for cardiovascular accidents that are dependent on end organ damage . Current data do not allow any clear recommendations for the treatment. Pharmacological therapy is usually started in the presence of hypertrophic left ventricle, changes in intimal/medial wall thickness of carotic arteries, microalbuminuria and other cardiovascular risk factors. Nonpharmacological therapy is less controversial and certainly more appropriate. Patients have to change their life style, need to eliminate as much cardiovascular risk factors as possible and sustain a regular blood pressure monitoring. White coat as a general dressing of physicians and health care personnel has been widely accepted at the end of the 19th century. It should represent a protection and feeling of cleanliness for the doctors and patients. Children often attribute pain and other unpleasant experience to the white coat and refuse afterwards cooperation with examinations. Significant number of pediatricians and pediatric nurses are therefore replacing white coat with casual dress in an attempt to improve patient’s cooperation. Still the majority of health care personnel are retaining white coat as traditional clothing. Two problems can be associated with the use of white coat: white coat phenomenon and white coat hypertension.The exact definition of white coat hypertension has been source of debates for a long time. White coat hypertension was described for the first time by Riva-Rocci more than 100 years ago. Initially, it has been considered as an abnormally elevated blood pressure in hospital or clinic with personnel wearing white coats. Later on, it has been shown that elevation of blood pressure can also be seen in an environment with health care personnel dressed casually . It is aDiscussion about white coat hypertension in children has been going on since 1990 . SimilarWhite coat hypertension in children has also been considered as hypertension documented in clinic and concomitantly when both levels of systolic and diastolic pressures on daily ambulatory blood pressure monitoring were lower than the 95th percentile for height and sex or less than 135/85 mmHg for children older than 15 years .Diagnosis of white coat hypertension can be made only after defining normal levels of blood pressure in the clinic. Arterial hypertension in children is defined as blood pressure equal or higher than the 95th percentile for age, sex and height recorded at 3 different measurements several weeks or months apart .Because of the variability of high blood pressure in children it may be difficult to distinguish between physiologic and pathologic values. In order to avoid incorrect interpretation of blood pressure it is necessary to use percentile method and assess measured values according to age, height and sex . Blood pThe most common mistake in ambulatory blood pressure results interpretation is the use of percentile graphs specified for single measurement or even values for adults .With an increase in children obesity there is also increase in hypertension in children and adolescents. While prevalence of white coat hypertension in adults is between 11 and 57 % in dependence of criteria used, data on its prevalence in children are much more variable in literature. Prevalence in children with hypertension has been reported 47 % . The higAmbulatory blood pressure monitoring confirmed that patient’s blood pressure in clinic may not represent his/her true blood pressure . Ambulatuse only internationally approved equipmentuse appropriate cuff sizeset up automatic measurement to maximum of 30 minute intervals to achieve adequate number of measurementscuff pressure release should not be faster than 2 mmHg/secpatient should maintain daily routine activities, avoid strenuous physical exercise and should remain quite during measurementspatient or parents should take written notes of unusual events and provide information on the quality of sleepImportant considerations during ambulatory blood pressure monitoring are :use onlyThe results should be evaluated by personnel with sufficient experience in pediatric hypertension .White coat effect and white coat hypertension are different in their definition, physiological mechanisms and clinical significance. White coat effect similarly to white coat hypertension depends on the stress response associated with visit in doctor’s office. In general it is blood pressure response to health care environment. It is defined as temporary increase in blood pressure before and during visit in the clinic, regardless what the average daily ambulatory blood pressure values are . Some auhas been already observed before actual BP measurementis more pronounced when taken by physician than by nurseis not observed during automatic measurementThere is a theory that it is not only a direct response to blood pressure measurements . This isExact pathophysiological mechanisms linking blood pressure response to stress factors are still not complexly explained.White coat effect prevalence varies in different countries. Some authors consider it as a universal response occurring in majority, if not all, normotensive or hypertensive patients . It is mSeveral authors have tried to identify clinical, psychological a demographic predictors for white coat hypertension . The resFemale gender is considered significant independent predictive factor for white coat hypertension , 23. SimPositive family history is a significant risk factor for white coat hypertension . It is sWhite coat hypertension in adults is associated with higher age. Some studies report five times higher incidence in elderly people . Adult pObesity or high body mass index is considered a single correctable factor associated with primary hypertension . ObesitySome authors consider prehypertension detected in clinic as a predictor of white coat hypertension , 27. HigThe frequency of clinic visits has been associated with prevalence of white coat hypertension in some studies. Less frequent clinic visits increase its prevalence . In accoOther risk factors under consideration are smoking, prenatal malnutrition and low birth weight .In the past, it has been considered benign condition. It may not have as significant sequelae as systemic hypertension but it should not be viewed as an unimportant issue . ClinicaIt has been shown in echocardiographic studies that left ventricular hypertrophy depends more on degree of blood pressure increase than on prevalence of high blood pressure . When syImportant marker of cardiovascular risks associated with end organ damage is intimal/medial wall thickness of carotic arteries that can be measured by ultrasound. In one study it has been found that in normotensive people intimal/medial wall thickness was 0.76 mm, in patients with white coat hypertension 0.84 mm and in hypertensive patients 0.98 mm . These rCardiovascular risk factors are hypertriglycerinemia, hyperinsuilnemia and low HDL cholesterol levels.Some authors speculate that white coat hypertension may be the initial stage in the development of systemic hypertension but this would require long term follow-up studies , 7, 34.Current information suggests that it has better long term prognosis than systemic hypertension but is not completely harmless. In children it could represent an initial step to permanent systemic hypertension, so called prehypertensive stage . IncidenApproach to pharmacological treatment varies in different studies. Majority of authors do not recommend regular therapy . On the Nonpharmacological therapy is less controversial and certainly more appropriate. Patients have to change the life style and eliminate as much cardiovascular risk factors as possible with regular blood pressure monitoring. They are recommended dietary salt restriction and weight reduction in case of overweight or obesity. Very important is regular physical activity, stopping smoking and restriction in use of alcoholic beverages. Appropriate education of children and their parents about medical complications of obesity is necessary. Diet should contain low fat and cholesterol products and include cereals, fruits and vegetables. Short term diets and exercises with rapid weight loss should be avoided. Appropriate measures are regular physical activity lasting 30 to 60 minutes 3 times weekly. Very helpful may be cooperation with pediatric psychologist. Blood pressure has to be regularly monitored every 6 to 12 months in order to detect development of permanent hypertension , 10.Clinical importance of white coat hypertension is mainly because of higher risk for cardiovascular accidents that are dependent on end organ damage . Current data do not allow any clear recommendations for the treatment. Pharmacological therapy is usually started in the presence of hypertrophic left ventricle, changes in intimal/medial wall thickness of carotic arteries, microalbuminuria and other cardiovascular risk factors. Nonpharmacological therapy is less controversial and certainly more appropriate. Patients have to change the life style and eliminate as much cardiovascular risk factors as possible with regular blood pressure monitoring.