Brain near-infrared spectroscopy (NIRS) is an emerging neurophysiological tool that combines straightforward activity localization with cost–economy, portability and patient compatibility. NIRS is proving its empirical utility across specific cognitive and emotional paradigms. However, a potential limitation is that it is not only sensitive to haemodynamic changes taking place in the cortex, and task-related cardiovascular responses expressed in the perfusion of extracranial layers may be confounding. Existing literature reports correlations between brain NIRS and systemic blood pressure, yet it falls short of establishing whether in normal participants the blood pressure changes encountered in experimental settings can have confounding effects. Here, we tested this hypothesis by performing two experimental manipulations while recording from superficial occipital cortex, encompassing striate and extrastriate regions. Visual stimulation with reversing chequerboards evoked cortical haemodynamic responses. Simultaneously and independently, transient systemic blood pressure changes were generated through rapid arm-raising. Shallow-penetration NIRS recordings, probing only extra-cerebral tissues, highlighted close haemodynamic coupling with blood pressure. A different coupling pattern was observed in deep-penetration recordings directed at haemodynamic signals from visual cortex. In absence of blood-pressure changes, NIRS signals tracked differences in visual stimulus duration. However when blood pressure was actively manipulated, this effect was absent and replaced by a very large pressure-related response. Our observations demonstrate that blood pressure fluctuations can exert confounding effects on brain NIRS, through expression in extracranial tissues and within the brain itself. We highlight the necessity for continuous blood pressure monitoring alongside brain NIRS, and for further research on methods to correct for physiological confounds. NIRS devices emit one or more incident beams via transmitting optodes through the scalp and skull. The light is back-scattered and follows a ‘banana-shaped’ wavepath through superficial cortical regions towards the receiving optodes. Using appropriate wavelengths, it is possible to quantify changes in the concentrations of oxy- and deoxyhaemoglobin, which have distinct absorption spectra. While brain NIRS shares a common physiological basis to fMRI, it offers several potential advantages in terms of logistics  and data quality . In contrast with EEG, the source localization problem is not ill-posed, as the recording regions are straightforwardly determined by the optode positions. A variety of NIRS devices are available, ranging from inexpensive wearable implementations based on light-emitting diodes and photodiodes, to large multichannel systems employing pulsed laser sources and photomultiplier detectors .Brain NIIn brain NIRS, the incident and backscattered beams cross skin, subcutaneous fat and scalp muscles, which are heavily vascularised. As a consequence, measurements are sensitive to haemodynamic changes occurring in these extracerebral tissues. Within the brain, haemodynamic parameters are closely regulated through tight neurovascular coupling and partial autonomic control . HoweverCoupling is observed between blood pressure and the haemodynamic responses measured using NIRS. For example, in one recent study, NIRS was used to record visually evoked haemodynamic responses during the processing of affective pictures carrying distinct valences: the emotional content modulated response amplitudes measured in the early visual areas but, in parallel, engendered changes in systemic blood pressure. These two effects were significantly correlated such that entering mean arterial pressure (MAP) as a nuisance covariate in the NIRS analysis reduced the significance of differences between picture types . AnotherThese observations of correlations do not necessarily imply causative effects of transient blood pressure changes on the recorded brain NIRS responses. Systemic and cortical haemodynamic effects may be highly correlated because they share a common effector, for example activation of the amygdala by emotionally valenced stimuli may trigger systemic autonomic cardiovascular responses while also enhancing activity within early visual cortical regions . The twoIt is well established that in patients with autonomic failure postural changes such as standing up or the table tilt-test produce cerebral oxygenation changes which are strongly coupled with systemic blood pressure. In healthy controls, the association between the two variables is not as strong . It rema22.1Sixteen participants , age 25 ± 7 (range 19–42) years were enrolled after providing written informed consent. The study was approved by the Brighton and Sussex Medical School Research Governance and Ethics Committee (BSMS-RGEC). All participants had normal or corrected-to-normal vision, and all but one were right handed. None was taking psychoactive or cardiovascular medication. A ‘deep-penetration’ optode configuration was used to record data from nine participants and a ‘shallow-penetration’ optode configuration from the remaining seven (see below).2.2The study was conducted with participants seated in the psychophysiological laboratory. Ambient lighting was darkened after positioning the NIRS optodes, and data were recorded in two 15 min-long sessions .Participants fixated on the centre of visual stimuli consisting of radial black/white chequerboards reversing at a rate of 5 Hz and presented for either 1500 or 3000 ms. The centre was marked by a red cross, which persisted between stimuli. The surrounding chequerboard occupied 80% of a 19 in. CRT screen positioned 1 m away from the head. The resting condition consisted of fixating the cross superimposed to a black screen.Transient blood pressure increases were induced through a motor act, i.e. by laterally raising a straight arm  while the rest of the body remained still. This action was performed as rapidly as possible with gaze remaining fixated on the central. For half the visual stimuli, 1 s prior to onset an upwards arrow was presented for 500 ms to prompt arm lifting . Twelve seconds after visual stimulus onset, a downwards arrow signalled to lower the arm slowly, until completely relaxed with the hand hanging towards the floor. For the other half of the visual stimuli , horizontal arrows were displayed for visual matching. Participants practiced the task, i.e. rapid arm-lifting with minimal movement of the rest of the body, several times prior to data acquisition. They were observed throughout the whole session by the experimenter, who ensured that movement of the head and contralateral arm was minimized.Each stimulus was presented 15 times, yielding a total of 60 stimuli which were delivered in randomized order. The inter-trial interval was jittered, with 19.2 ± 2.9 s.2.3NIRS measurements were acquired by means of a continuous wave device emitting at 764 ± 20 nm and 859 ± 20 nm, and recording at 50 Hz . Four channels were used, positioning two receiver optodes above and below the Oz site (as defined by the 10/20 system), and two transmitter optodes left and right of Oz.For the 9 participants from whom data were recorded in deep-penetration mode, the transmitter–receiver distance was 4 cm. This was implemented positioning the optodes approximately 2.8 cm away from Oz. The resulting ‘banana-shaped’ wavepath, penetrating a depth of about 2 cm, traversed a combination of striate and extrastriate regions, principally lying within the expected localization of visual areas V1 and V2 . When reThe optodes holder consisted of a tightly fitting modified silicone swimming cap , to which a nylon screw insulator and two nylon washers (RS no. 178-800 and 280-521) had been secured corresponding to the intended optode positions. The optodes were firmly held in place by a 5 cm-thick sponge secured with Velcro straps. In order to avoid weight loading, the optical fibres were supported by a flexible metal arm positioned placed close to the back of the head. The fibres did not touch the body to minimize the possibility of optode movement.2Hb) and deoxyhaemoglobin (HHb) concentration were calculated through the modified Beer–Lambert law, including the differential path length factor as given by the age-dependence formula introduced by Duncan and co-workers , on the side contralateral to the arm-movement. A height reference sensor was used to remove confounds related to arm position. Calibrations were synchronized with stimulus presentation through an RS232 serial link, and programmed to occur automatically before each trial.2.4All raw NIRS traces were visually inspected to confirm the absence of transient changes synchronous with arm-movement, which would suggest motion contamination.Recorded NIRS signals were low-pass filtered at 1 Hz, then detrended by fitting the baseline with a 5th degree polynomial which was subsequently subtracted. The resulting time-courses were epoched between −0.5 and 12 s with respect to visual stimulus onset, and the average pre-stimulus (0.5 s) baseline was subtracted. After rejection of outlier epochs (using a ±3 SD criterion), the remaining data were averaged according to the two experimental factors. Haemodynamic response amplitude and latency  were thereafter determined.For blood pressure, the volume clamping pressure signal was low-pass filtered at 10 Hz and pre-processed by means of a peak-picking algorithm to yield time-courses for systolic, diastolic and mean arterial pressure. As above, these were detrended polynomially, then epoched between −0.5 and 10 s to compute, for each trial, response amplitude and latency as above.t-tests with respect to zero were performed to confirm whether arm-raising induced significant changes in systolic, diastolic and mean arterial pressure. Linear regression was used to determine correlations between systolic and diastolic pressure. O2Hb and HHb responses following arm-raising recorded in shallow-penetration mode were similarly evaluated using one-sample t-tests, and linear regressions were performed between these signals and MAP.One sample t-tests separately for response amplitude and latency: (1) contrasting 1500 ms- with 3000 ms-persistency visual stimuli in the absence of arm-raising, (2) contrasting the same for arm-raised trials and (3) contrasting all arm-raised vs. all no-movement trials. Correcting for multiple comparisons, we set pCRIT = 0.05/3 = 0.017 for these tests. As above, linear regressions were performed to test for correlations between the O2Hb and HHb responses and MAP, separately for arm-raised and no-movement trials.For the deep-penetration measurements, three planned comparisons were considered, using two-sample 3t(15) = 7.7, p < 0.001), peaking at 5.8 ± 0.9 s (t(15) = 9.4, p < 0.001; peaking at 5.1 ± 0.8 s) and MAP  = 9.4, p < 0.001; peaking at 5.3 ± 0.8 s). Systolic and diastolic pressure changes were significantly correlated , yet diastolic pressure returned to baseline more rapidly.Arm-raising produced a transient increase in systolic blood pressure over pre-stimulus level  = 4.7, p = 0.003; peaking at 6.0 ± 0.9 s; 2Hb and HHb signals during arm-raised trials .In shallow-penetration NIRS recordings from the occipital region, arm-raising produced a transient increase in O2Hb and negative HHb responses  = 3, p = 0.01). Arm-raising abolished this differential effect , and markedly reduced latency  = 3.7, p = 0.006). The O2Hb response amplitude was not sensitive to the duration of visual stimulation , but it was significantly larger for arm-raised trials  = 4.4, p = 0.002). In the absence of arm-raising, the HHb response latency was not sensitive to the duration of visual stimulation , and there was no additional effect of arm-raising . The HHb response amplitude was not sensitive to the duration of visual stimulation , however there was a borderline effect of arm-raising, which did not survive correction for multiple comparisons  = 2.3, p = 0.04).In deep-penetration recordings, both visual stimulation and arm-rising generated positive Oesponses . In the 2Hb response and MAP . There was a looser correspondence between HHb and MAP, reflected in different slopes of the rising and falling parts of the response .For arm-raised trials, there was a strongly significant positive correlation between Oresponse , with a 4The key findings of this study are that (1) transient systemic blood pressure changes are reflected in brain NIRS measurements, and (2) the coupling appears to take place in both extracranial tissues and the brain itself, with different patterns. These results signal the need to monitor and correct for blood pressure effects when brain NIRS is used to investigate cortical haemodynamics.Arm-raising generated transient increases in systemic blood pressure. There are a number of possible mechanisms for this including the central command driving local and systemic facilitatory cardiovascular responses in anticipation and in response to effort , and the2Hb concentration which significantly correlate with MAP. These clearly demonstrate that transient blood pressure manipulation affects the oxygenation and perfusion of subcutaneous extracranial tissues. Since O2Hb was increased in the absence of a corresponding HHb decrease, the observed effect most likely reflects enlarged blood volume, consequential to vascular elasticity, rather than increased blood flow  NIRS recordings showed increases in Oculature . The finesponses . This deesponses . Accordi2Hb responses were flattened, suggesting that increased systemic MAP does not additively enhance neurally driven haemodynamic activation. Our observations are in line with empirical data regarding non-linearity and time-dependence of cerebrovascular responses and support the notion of multiple interacting systems involved in the control of regional cerebral perfusion (In arm-raising trials, the response latency difference observed between 1500 and 3000 ms visual stimuli was not detectable and interestingly, the stimulus-evoked Oerfusion .This study has several limitations that need to be considered. First, as with most other NIRS studies the wavepath and penetration depth were assumed a priori, on the basis of existing literature. More solid indication of the attained penetration depth would need to be obtained using Monte Carlo photon diffusion simulations, based on the segmentation of the individual structural scans e.g., . Second,k-means clustering to isolate task-related from physiology-related activity components, purely on the basis of the fNIRS or fMRI time series.In spite of these limitations, these results extend previous correlational findings by unequivocally demonstrating that blood pressure changes can exert strong confounding effects on brain NIRS measurements. Our findings have specific relevance to the implementation of NIRS as a functional neuroscience method. Moreover, since autonomically mediated neurovascular effects are also present within the brain itself , they ma2Hb and HHb concentrations. This will enable inclusion of blood pressure-derived measurements as nuisance covariate in statistical analyses. Our findings do not definitively clarify the relative contribution of extra- vs. intra-cranial coupling, and the experiment needs to be replicated with time-resolved spectroscopy. Relevant confirmation of our findings should also be obtained simultaneously recording from deep- and shallow-separation optodes, through a NIRS system with a larger number of channels. Further investigations are necessary to clarify to what extent MAP changes may affect tasks structured in longer blocks rather than individual events. Even before such data becomes available, in light of our observations blood pressure effects should always be characterized during functional NIRS experiments.More work is needed to explore the effect of smaller blood pressure manipulations and to characterize the response function mapping different magnitudes of blood pressure change to their effects on OAll authors declare that they do not have any real or perceived conflicts of interest pertaining to the present study.


Aim: To investigate the association of uncontrolled hypertension with psychological factors associated with high cardiovascular morbidity and mortality . Methods: 205 consecutive outpatient hypertensives completed three questionnaires evaluating Type D personality (DS 16), post traumatic symptoms , symptoms of anxiety, hostility, depression and obsessive-compulsive traits . Uncontrolled hypertension was diagnosed when clinic sitting blood pressure was above 140/90 mmHg (130/80 in the presence of diabetes or nephropathy), despite reported adherence to treatment with at least three antihypertensive medications, including a diuretic. Results: Uncontrolled hypertension (39%), was predicted by lower scores at Symptom Checklist obsessive-compulsive subscale and higher number of post traumatic avoidance symptoms, older age, diabetes, higher systolic pressure at first visit and longstanding hypertension. Type D personality correlated with depression, hostility, anxiety, compulsiveness, history of malignancy, and older age, but not with uncontrolled hypertension. Conclusions: Uncontrolled hypertension is associated with low obsessionality and avoidance symptoms, which reduce compliance to treatment. On the contrary, type D personality is not correlated with uncontrolled hypertension, as it includes compulsiveness, which improves compliance. A multidisciplinary approach to the hypertensive patient is mandatory to establish if the psychological profile affects compliance. Resistant hypertension is becoming a clinical entity due to its large prevalence and high associated cardiovascular risk ,2,3. It The inability to lower blood pressure stems from secondary hypertension, lifestyle factors and ingestion of substances that elevate blood pressure. White coat effect, poor compliance, inadequate dose or blood pressure measurement, physician selection of inappropriate drugs all affect blood pressure control and may cause what should be better named as “pseudoresistant” hypertension ,3. RecenMany studies have pointed out the role of psychological factors in hypertension, such as defensiveness, alexithymia, negative affectivity, expression of anger, anxiety and depression ,6, but vIn the whole sample (205 patients), 184 (90%) were diagnosed as having essential hypertension and 21 (10%) as secondary hypertension . The two groups did not differ for clinical and demographic characteristics , but the number of cardiovascular events  was more frequent among the patients with secondary hypertension . One hundred and twenty six hypertensives were classified as controlled (61.5%), and 79 as uncontrolled (38.5%). Uncontrolled hypertensives were older, had higher baseline systolic blood pressure, longer duration of hypertension, greater number of outpatient consultations, larger prevalence of diabetes and cardiovascular events than responders . By defiOne hundred and sixty six patients returned the questionnaires (81%). The clinical and demographic characteristics  were similar between the patients who returned the questionnaire and those who did not (data not shown). However, those who returned the questionnaires had fewer total vascular events , history of malignancy  and use of benzodiazepine . Another 19 subjects were excluded from subsequent analyses because they returned incomplete questionnaires. In the final sample (n = 147), the prevalence of type D personality was 37 % (n = 54). Type D patients were significantly older than non-type D patients , but did not differ for gender, blood pressure at first and last visit, number of consultations, duration of hypertension, number of drugs, BMI, type of hypertension, blood pressure response to antihypertensive treatment, history of diabetes, previous cardiovascular events, use of benzodiazepines or antidepressants. Type D personality was associated with history of malignancy .Type D patients scored significantly higher than non Type D patients at H-SCL obsessive-compulsive , depression , anxiety  and hostility  subscales. The presence of recent stressful and traumatic life events and of posttraumatic stress-related symptoms was not different between the two groups.The psychological characteristics, by response to antihypertensive therapy, are reported in Personality profile was similar in uncontrolled and controlled hypertensives, except for higher IES avoidance symptoms, and trends towards lower H-SCL obsessive-compulsion and H-SCL hostility in uncontrolled hypertensive patients. We, then, performed a series of logistic regression analyses to identify the predictors of blood pressure control. In a first model, we included only medical and demographic variables , model 1The present study shows that uncontrolled hypertension is associated with low obsessionality and a large number of post-traumatic avoidance symptoms. The association remained significant after controlling for the other well known risk factors of uncontrolled hypertension, such as old age, diabetes, secondary hypertension, and isolated systolic hypertension. On the contrary, type D personality, an independent predictor of cardiovascular morbidity and mortality in patients with cardiovascular diseases, does not play any role in uncontrolled hypertension.Anger, hostility, alexithymia, anxiety, negative affectivity and depression have been associated with hypertension ,6. MoreoThe combination of low obsessionality and post-traumatic avoidance symptoms among uncontrolled hypertensives suggests poor compliance to treatment. In fact, an old study showed that non compliant hypertensives had a lower average score of obsessionality than compliant patients . It is nPoor adherence to medication regimes is one of most important factor influencing poor blood pressure control . DiffereThe compliance was assessed by direct questioning by the physicians during each visit  and, acci.e., primary vs secondary).To improve compliance it may be necessary to increase patient motivation and understanding of the disease and of the antihypertensive treatment but also to identify psychological characteristics of those patients who probably don’t remember unconsciously to take their medications or psychological factors that could bring to a distorted perceived severity of illness. This approach is probably more cost effective than an extensive work up for secondary hypertension in uncontrolled patients, as the psychological profile was more strongly associated with uncontrolled hypertension than the type of hypertension  were invited to participate to the study, which had been approved by the local Ethical Committee, and 205 (38 coming for the first time) gave an informed written consent to use their data in a confidential form. All patients received follow up visits until October 2006. The study design was explorative, observational and longitudinal.Screening for secondary hypertension  and tests to define the cardiovascular risk were performed at the first visit. The patients were classified as “essential” or “secondary”, according to the results of the diagnostic work up, which had to be completed by the end of the study. In each visit blood pressure was measured three times in the sitting position with a mercury sphygmomanometer, with a properly-sized cuff and after the patient had been sitting quietly for five minutes. The mean of the three readings was used for the analysis of the results.Antihypertensive drugs were prescribed according to the 2003 European Society of Hypertension / European Society of Cardiology guidelines . CompliaThe following data were collected for each patient: Blood pressure at first and last visit, number of outpatient consultations, body mass index (BMI), duration of hypertension, type and number of antihypertensive drugs, chronic use of benzodiazepine or antidepressant, presence of diabetes, previous cardiovascular or cerebrovascular events, and history of malignancy.A series of self-reported questionnaires to investigate the psychological factors was self administered at the time of the outpatient visit. Type D personality was assessed with the 16-item DS16 which was developed and validated in Belgian cardiac patients ,18. The The other self-reported questionnaires included: a) the short version of the Hopkins Symptoms Check List (H-SCL)  to measure general psychopathology; b) a life event questionnaire, an inventory developed for this study that investigates the occurrence of stressful life events in the previous 6 months; c) the revised version of the Impact of Events Scale (IES), designed to assess current subjective distress for any specific life event  for those subjects who reported a stressful life event (n = 106). To assess life events, we used a modified version of the Life Experiences Survey, consisting of 14 items that investigate the occurrence of: serious illness, accident, physical aggression, serious illness or physical aggression of a loved one, loss of a loved one, separation or divorce, interpersonal conflicts, loss of work, economical problems, problems with law . PatientPearson’s chi-squared test and Student’s t-test were used to compare groups. A logistic regression analysis was used to derive a multivariate model of the risk of uncontrolled hypertension, while taking into account potential confounder variables. The results are given as mean ± SD. The significant level was set at p < 0.05. In conclusion, the present study, showing unforeseen psychological factors in uncontrolled hypertension, strongly supports a multidimensional approach to the patients with hypertension to focus not only the cardiovascular risk factors, but also the psychological characteristics that enhance the cardiovascular risk through emotional stress and poor compliance to treatment.


Cerebral autoregulation (CA) is integral to the delicate process of maintaining stable cerebral perfusion and brain tissue oxygenation against changes in arterial blood pressure. The last four decades has seen dramatic advances in understanding CA physiology, and the role that CA might play in the causation and progression of disease processes that affect the cerebral circulation such as stroke. However, the translation of these basic scientific advances into clinical practice has been limited by the maintenance of old constructs and because there are persistent gaps in our understanding of how this vital vascular mechanism should be quantified. In this review, we re-evaluate relevant studies that challenge established paradigms about how the cerebral perfusion pressure and blood flow are related. In the context of blood pressure being a major haemodynamic challenge to the cerebral circulation, we conclude that: (1) the physiological properties of CA remain inconclusive, (2) many extant methods for CA characterisation are based on simplistic assumptions that can give rise to misleading interpretations, and (3) robust evaluation of CA requires thorough consideration not only of active vasomotor function, but also the unique properties of the intracranial environment. The brain is one of the most metabolically active organs in the human body, accounting for 20 % of the body’s resting energy consumption despite weighing only 2 % of the total body mass  is thought to play a dominant role in CBF homeostasis. The classic description of CA is that CBF is maintained at a constant level across a wide range of mean arterial blood pressure 60–150 mmHg) Lassen . Based o50 mmHg LDespite developments of new method and models of dynamic CA quantification, the translation of findings into clinical practice has been limited. On the one hand, old dogmatic paradigms are being maintained due to inadequate comprehension of the limitations of existing data that support established constructs. On the other hand, adoption of new concepts about CA has been hampered by the fact that much still remains uncertain about the fundamental physiology of CA regulation and quantification. As discussed in volume I of this thematic series, blood pressure is not a static variable but varies in magnitude across a range of time scales Fig. . ObserveDo these rhythmic and non-rhythmic aspects of blood pressure challenge cerebral perfusion homeostasis? While research into the disease associations between blood pressure and cerebrovascular outcomes has primarily focused on average absolute blood pressure, clinical studies suggest that elevated short (minutes) and long-term (hours to days) blood pressure variability increases the likelihood of adverse cerebrovascular outcomes  are still frequently considered in the time domain summarised as averages (i.e. point estimates) even where continuous recordings are available. However, because blood pressure and blood flow exhibit dynamic fluctuations, it is beneficial to consider their relationships not only in terms of time-domain averages, but also in terms of different oscillatory components where progressively longer periodicities and trends correspond to progressively lower frequency components Fig. . These aThe focus of this paper is not to reiterate recent reviews in this area  using intravenous infusions of phenylephrine and nitroprusside are accompanied by more or less linear changes in middle cerebral artery velocity within the autoregulatory region  individual relationships. Unfortunately, efforts to define the ‘correct’ static CA curve have been somewhat hindered by normal physiologic responses. For example, the baroreflex limits the blood pressure range that can be systematically explored without using vasoactive drugs, or shifting central blood volume. Further, changes in alveolar ventilation secondary to hypertension/hypotension can alter the partial pressure of arterial COBecause it is difficult to distinguish CA from the vascular effects of drugs and other physiologic mechanisms, some studies have circumvented the use of drugs by studying the relationship between blood pressure and surrogates of cerebral perfusion averaged over relatively long durations using statistical techniques. Studies employing empirical , cerebral perfusion in clinical studies is still generally evaluated indirectly by measures of cerebral perfusion pressure or by internal jugular venous oxygen saturation. Because average blood pressure is a major clinical indicator and widely considered in clinical practice, clarifications of concepts such as the lower and upper limits of static CA are required if these concepts are to serve the management of haemodynamically compromised individuals. Here matters are further complicated by the fact that anaesthesia is often used in conjunction with surgery in many critical scenarios and many anaesthetic agents have direct cerebral vasodilatory effects that can alter the fundamental characteristics of static CA . Although this terminology only came into popular use in the 1980s, recognition that cerebral arterioles are capable of responding dynamically over relatively short time scales to blood pressure transients dates back to animal experiments showing that pial pre-capillary arterioles under direct observation undergo autoregulatory changes in vessel calibre with dynamic changes in blood pressure Fog , b.Several important factors were subsequently found to modulate the development and characteristics of this vascular response. First, significant vessel calibre changes typically did not occur until blood pressure had reached a certain threshold (MAP ~90 mmHg)  may influence our interpretation of pressure–flow relationships.An important technical consideration that applies to studies employing transcranial Doppler is that blood velocity measurements reflect volumetric blood flow only if the cross-sectional area of the insonated vessel remains constant. Any changes in vascular diameter will introduce errors in the estimation of flow  MAP-driven resistive flow through resistance vessels, (2) capacitive flow through compliant vessels driven by the rate of change in MAP, and (3) a residual component that reflects non-linear processes including CA. We found that Ca2+ channel blockade enhanced the resistive flow component without altering capacitive flow, and that steady-state vasodilation explained the vast majority (~90 %) of middle cerebral artery blood velocity variance. These findings provided the first quantitative illustration of how transfer function metrics do not necessarily reflect dynamic CA. Interestingly, Ca2+ channel blockade reduced middle cerebral artery blood velocity in all subjects even though Nimodipine is a potent cerebral vasodilator  maybe more adept at compensating for transient hypertension than for hypotension , ongoing analytical innovations that enable multivariate quantification of both linear as well as non-linear properties of the cerebral circulation are needed.In this review, we have deliberately highlighted important but often ignored discrepancies in the literature surrounding the characterisation of CA. These discrepancies point to a need to formulate new studies and measurement strategies that overcome those methodological limitations. Such work is crucial because our ability to understand how the cerebral circulation responds to blood pressure challenges rests on robust methods of assessment. Given that dynamic CA is frequently characterised indirectly by inference, close scrutiny needs to be applied to the methodological and conceptual assumptions we adopt. Some of these are outlined in “Finally, it is important to reiterate that the challenges discussed in this review do not preclude the use of existing techniques in clinical investigations. Whilst the elucidation of underlying control mechanisms is a principal focus, characterisation of the endpoint parameters that regulatory systems purportedly control (e.g. blood pressure and CBF variability) may yield equally important information. Indeed, many endpoint parameters, including the time-honoured average blood pressure, have proven clinical utility despite the incomplete understanding of their underlying physiology. Considering there is ready access to a range of technologies for quantifying blood pressure and CBF variability, clinical research that is focused on risk factor identification and monitoring can and must continue despite the physiological complexities we have sought to highlight.


N-acetyl-β-D-glucosaminidase (NAG) for the prediction of acute kidney injury (AKI) in patients after percutaneous nephrolithotripsy (PNL). Pre- and post-operative patient data were collected for 90 patients who underwent PNL between September 2008 and December 2010. The patients included 64 males and 26 females with an average age of 52.8±9.7 years. Pre- and post-operative urinary NAG was measured by colorimetric assay and serum creatinine levels were determined for comparative analysis. Urinary NAG levels significantly increased after PNL compared to pre-operative levels (P<0.05). AKI occurred in 11 cases after surgery. A comparison of the AKI and non-AKI groups revealed no significant differences in age, gender ratio or baseline creatinine levels (P>0.05); however, there were significant differences between the groups as regards surgical duration, post-operative infection rate, C-reactive protein levels and number of hospital days (P<0.05). NAG levels were significantly higher in the AKI compared to the non-AKI group after surgery (P<0.05). The diagnostic utility of the increase in urinary NAG 24 h after surgery was assessed by receiver operating characteristic (ROC) analysis. For an increase in NAG of 235.44%, the area under the ROC curve was 0.878 (P<0.01) and the sensitivity and specificity for AKI diagnosis were 81.8 and 91.1%, respectively. Urinary NAG significantly increased in patients suffering from AKI after surgery. This parameter is more sensitive than serum creatinine and can reflect the impairment of kidney function at an earlier stage. The surgical duration and post-operative infection rate are possible risk factors for AKI. Urinary NAG may have some clinical value in the early diagnosis of AKI after surgery.The present observational study was undertaken in order to evaluate the diagnostic value of urinary  Percutaneous nephrolithotripsy (PNL) is replacing open surgery as the preferred treatment for kidney and upper ureter stones due to its minimal invasiveness, high probability of success, and low probability of mortality. However, retrospective analysis has revealed that certain patients undergoing unilateral PNL suffer from acute kidney injury (AKI) after surgery. AKI can lead to a series of clinical problems; if not found and treated in a timely manner, it can extend the length of hospital stay, affect recovery of kidney function, increase mortality and morbidity –3 and inN-acetyl-β-D-glucosaminidase (NAG) activity, neutrophil gelatinase-associated lipocalin, interleukin-18 and kidney injury molecule-1  clear diagnosis of a kidney stone; ii) normal results for kidney function, routine blood parameters, electrolytes, routine urine analysis and midstream urine culture; and iii) suitability for PNL, with no hypertension, diabetes or coronary heart disease and no recent intake of drugs that affect renal function. Patients with serious hydronephrosis, a serious disease, renal insufficiency, obesity, emaciation, renal ectopia, a horseshoe kidney or a functional or organic solitary kidney, or for whom incomplete clinical data or incomplete samples were available, were excluded from this study. The research was carried out according to the principles of the Declaration of Helsinki. Informed consent was obtained and the Shanghai Renji Hospital Ethics Committee approved the study. The patient data, which are contained within this article, were obtained by a hospital-based doctor at Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine. Permission to use these data in this report has been obtained from all the subjects who participated in this study .All patients underwent unilateral PNL using an F18 channel. After successful air-intravenous anesthesia with the patient in a prone lithotomy position, a ureteroscope (Storz or Wolf) was inserted into the bladder and advanced into the ureter on the surgical side, led by a zebra wire. An F5 ureteral catheter was then inserted.A puncture was made in the pelvis guided by B ultrasound and a 10 ml pre-operative urine sample was collected and stored at 4°C. The channel was expanded to F18 with a fascial dilator led by a guide wire. After the percutaneous-nephro passage was established, the kidney stone was located using the ureteroscope and was broken up using a holmium laser. The majority of broken stones can be washed out by the filling pump through the working sheath. Consistent filling pump flow and pressure were maintained and recorded.The stones were removed from the pelvis. When the procedure was complete, the pressure measurement equipment was removed, and a retrograde guide wire and double-J pipe were inserted. A F16 nephrostomy tube was sutured in place to drain urine from the surgical side after surgery.At 2, 4, 6, 12, 24, 48 and 72 h after surgery, 10 ml urine samples were collected from the kidney on the surgical side.All urine samples were stored at 4°C and centrifuged for 3 min at 2,000 rpm within 1 week. The supernatant was used for NAG measurement.Urinary NAG activity was measured using the kinetic rate assay  with 2-cSerum creatinine (Scr) levels were measured in a single laboratory on a Hitachi 7600 analyzer using Jaffe’s kinetic method, reference range 40–140 μmol/l.Serum C-reactive protein (CRP) levels were measured by latex agglutination immunoassay using the Nanopia CRP kit . Normal values provided by the manufacturer were ≤0.30 mg/dl, and therefore patients with a serum CRP of ≤0.30 mg/dl were considered the ‘normal CRP’ cohort.The SPSS 11.5 package was used for all statistical analyses. For parametric variables with a normal distribution, the results are presented as the means ± SD and comparisons between two groups were carried out using a t-test. For parametric variables with a non-normal distribution, the results are presented as the median (interquartile range), and comparisons between groups were carried out using a rank test. The sensitivity and specificity of AKI diagnosis according to NAG levels were assessed by receiver operating characteristic (ROC) analysis. A value of P<0.05 was considered to indicate a statistically significant difference.Data were collected for 115 patients. Of these, 25 were excluded due to incomplete samples or medical history. Thus, 90 patients were included in this study. They ranged in age from 35 to 72 years (52.8±9.7) and included 64 males and 26 females.For all patients, urinary NAG increased 2 h after surgery to reach a peak at 6 h at twice the level prior to surgery, and then gradually decreased. Post-operative NAG levels were significantly higher at various time-points compared to pre-operative levels P<0.05; .Patients were categorized as AKI or non-AKI according to the AKI diagnosis criterion of a sudden decrease in kidney function over 48–72 h, evident as an absolute increase in Scr levels ≥0.3 mg/dl (≥26.4 mmol/l) or a percentage increase of ≥50%. Parameters for the groups are compared in There were no significant differences between the groups as regards age, gender ratio or baseline creatinine levels; however, there were significant differences in surgical duration, post-operative infection rate, CRP levels and number of hospital days P<0.01; . For theTo assess the utility of the extent of the increase in urinary NAG at 24 h after surgery for AKI prediction, ROC analysis was carried out. The area under the curve was 0.878  for a NAG increase of 235.44%, with diagnostic sensitivity and specificity of 81.8 and 91.1%, respectively .PNL as a surgical technique is minimally invasive; however, retrospective evaluation of a large amount of clinical data revealed that AKI occurs in some patients after unilateral PNL. Without timely adequate treatment, AKI can lead to an unfavorable prognosis. Early diagnosis and therapy are of great importance to reduce the risk of serious AKI complications.The main index currently used in clinical practice for AKI diagnosis is Scr; however, its sensitivity and specificity are relatively low. Scr levels are only altered when renal function decreases by approximately 50% and Scr cannot reflect changes in renal function over time until the body reaches a stable condition, which often takes several days. Scr levels are influenced by other factors, such as age, race, blood volume, muscle metabolism, drugs and nutritional condition. These limitations mean that Scr is not an ideal index for AKI and cannot provide early clues for AKI diagnosis, so early clinical therapy may be delayed –14. TherIn recent years, research on urine biomarkers has provided strong evidence that these are suitable for the early diagnosis and therapy of AKI . NAG hasOur results show that post-operative urinary NAG levels increased to different extents in 90 PNL patients, among whom 11 developed AKI. There were no significant differences between the non-AKI and AKI groups as regards age, gender ratio and baseline creatinine levels; however, the AKI group had a significantly longer surgical duration and a greater post-operative infection rate, CRP levels and number of hospital days. Thus, a longer surgical duration may increase the infection rate and AKI risk and prolong the hospital duration. If the surgical duration can be controlled to a certain extent, the risk of post-operative complications may be reduced.In addition, NAG levels were higher in the AKI than in the non-AKI group within 24 h after surgery. Thus, NAG indicates the occurrence of AKI earlier and is a more sensitive biomarker than Scr. ROC analysis was carried out to assess the diagnostic utility of the increase in urinary NAG 24 h after surgery in predicting AKI. The area under the curve was 0.878  for a post-operative increase in NAG of 235.44%, and the sensitivity and specificity of AKI diagnosis were 81.8 and 91.1%, respectively. Thus, the extent of any increase in urinary NAG levels may be an efficient marker for predicting AKI.et al found that urinary NAG positively correlated with the degree of acute renal failure (Currently AKI is divided into 3 phases . In phas failure . AKI detIn conclusion, our results demonstrate that urinary NAG activity significantly increases in AKI. This parameter is more sensitive than Scr and can reflect impairment of renal function at an earlier stage. The surgical duration and post-operation infection rate are possible risk factors for AKI. Urinary NAG may have some clinical value in the early diagnosis of AKI after surgery.


Effusive constrictive pericarditis (ECP) is visceral constriction in conjunction with compressive pericardial effusion. The prevalence of proven tuberculous ECP is unknown. Whilst ECP is distinguished from effusive disease on hemodynamic grounds, it is unknown whether effusive-constrictive physiology has a distinct cytokine profile. We conducted a prospective study of prevalence and cytokine profile of effusive-constrictive disease in patients with tuberculous pericardial effusion.From July 2006 through July 2009, the prevalence of ECP and serum and pericardial levels of inflammatory cytokines were determined in adults with tuberculous pericardial effusion. The diagnosis of ECP was made by combined pericardiocentesis and cardiac catheterization.Of 91 patients evaluated, 68 had tuberculous pericarditis. The 36/68 patients  with ECP were younger , had a higher pre-pericardiocentesis right atrial pressure , serum concentration of interleukin-10 (IL-10)  and transforming growth factor-beta , pericardial concentration of IL-10  and interferon-gamma  than effusive non-constrictive cases. In multivariable regression analysis, right atrial pressure > 15 mmHg  and IL-10 > 200 pg/ml  were independently associated with ECP.Effusive-constrictive disease occurs in half of cases of tuberculous pericardial effusion, and is characterized by greater elevation in the pre-pericardiocentesis right atrial pressure and pericardial and serum IL-10 levels compared to patients with effusive non-constrictive tuberculous pericarditis. Effusive-constrictive pericarditis (ECP) is a clinical syndrome in which compressive pericardial fluid and a constricting visceral pericardium occur simultaneously . The defECP is recognized as an important manifestation of pericardial tuberculosis , a diseaInvestigation of Management of Pericarditis in Africa (IMPI Africa) registry of patients with suspected tuberculous pericarditis which was approved by the University of Cape Town Human Research Ethics Committee (HREC REF: 402/2005) [This is a single center sub-study of the ongoing 02/2005) . This suMycobacterium tuberculosis (M. tuberculosis) was identified on pericardial fluid microscopy, culture or by polymerase chain reaction ; and/or the pericardial fluid was a lymphocytic exudate with an elevated interferon-gamma (IFN-γ) (>50pg/ml) or adenosine deaminase (ADA) (>40U/L) level  [Pericarditis was deemed to be tuberculous if one or more of the following criteria were met: arditis) . ECP was established on the basis of the following hemodynamic findings during combined pericardiocentesis and cardiac catheterization: a) a pre-pericardiocentesis mean pericardial pressure of > 8 mmHg, b) a pre-pericardiocentesis transmural filling pressure gradient of ≤ 4 mmHg , c) a post pericardiocentesis mean pericardial pressure of 0±4 mmHg, and d) failure of the post-pericardiocentesis mean right atrial pressure to fall below 11 mmHg or to fall by 50% of the pre-pericardiocentesis level. Participants were considered to have hemodynamic tamponade where there was a difference between the pre-pericardiocentesis right atrial pressure and intra-pericardial pressure of < 4 mmHg, i.e., the transmural pressure approached zero [From July 2006 through July 2009, 91 consecutive adults with suspected tuberculous pericarditis underwent simultaneous measurement of intra-pericardial and right heart pressures, and estimation of transmural filling pressures with 6 French multipurpose catheters before and after sub-xiphisternal pericardiocentesis using standard methods. Participants were enrolled if they were ≥18 years of age, had echocardiographic evidence of a pericardial effusion with at least 1 cm of echo-free space anterior to the heart in telediastole, and probable or definite tuberculous pericarditis as indicated under definitions above . They weThe 68 patients with tuberculous pericarditis who met the inclusion criteria underwent clinical evaluation by history, physical examination, echocardiography and laboratory analysis of cytokines in serum and pericardial fluid. Blood was collected prior to pericardiocentesis in BD Vacutainer SSTTM Advance vials  and pericardial fluid was decanted into BD Vacutainer vials . Both tubes were centrifuged at 3000 rpm for 10 minutes using a Sigma 4K15 laboratory centrifuge with a swing-out rotor. Serum and cell free pericardial fluid were collected and stored in NUNC cryotube vials at -80°C until batch analysis was performed. The following cytokines that are involved in the regulation of inflammation and fibrosis were measured by enzyme linked immunosorbent assay according to the manufacturers’ instructions: eBioscience, USA: interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) ; Mabtech2 test or, where appropriate, the Fisher exact test.  The sample size required to provide adequate power to estimate the prevalence rate of ECP with a precision of 5% was 54, based on the anticipated 15% prevalence rate of tuberculous ECP from published literature . The ShaM. tuberculosis culture, and PCR), and invasive cardiac hemodynamic findings . Variables found to be non-normally distributed were modeled as binary categorical variables using the first or the third quartile as a cut-off. Factors found significantly associated with ECP in univariable models were included in the final multivariable model. All tests were two-sided, and a p-value <0.05 was considered significant. Data analysis was performed with SPSS (version 17.0). Logistic regression models were fitted to determine factors associated with ECP. The following variables that were tested: age, gender, history of tuberculosis, duration of symptoms, New York Heart Association Functional Class, HIV status, clinical signs of heart failure , electrocardiographic changes , chest radiograph abnormalities , serum analysis (creatinine phosphokinase (CK), CK-MB fraction, NT-pro brain natriuretic peptide level, CD4 T cell count , lactate dehydrogenase (LDH), and total protein), pericardial fluid analysis  and probable tuberculous pericarditis  and had complete information on combined pericardiocentesis and cardiac catheterization to enter the study. The prevalence of ECP in patients with tuberculous pericardial effusion was 52.9% (95% CI: 41.2-65.4). The mean (±SD) volume of pericardial fluid drained was 917±414 ml for the whole group. Tuberculosis was confirmed by pericardial fluid culture in 60%  and established by ADA or IFN-γ level in the remainder . There was no difference in gender, HIV seroprevalence, use of anti-retroviral drugs and adjunctive corticosteroids, volume of pericardial fluid drained, proportion with definite tuberculous pericarditis, and frequency of pericardial tamponade between the two groups . M. tuberculosis. IFN-γ was not detected in the serum probably because ex-vivo levels tend to be lower than the detection threshold of the assay of 50 pg/ml[ 50 pg/ml. Likewis 50 pg/ml-16.In a multivariate regression model of factors associated with ECP, only opening right atrial pressure > 15 mmHg  and IL-10 > 200 pg/ml  were independently associated with the syndrome . We have described the first prospective study of the prevalence and cytokine profile of hemodynamically proven effusive-constrictive disease in tuberculous pericardial effusion. We show that, contrary to non-tuberculous forms of pericardial disease where effusive-constrictive disease is uncommon, ECP occurs in half of cases of tuberculous pericardial effusion. In addition, we demonstrate that tuberculous ECP has a unique clinical, hemodynamic, and cytokine profile that is characterized by a younger age of onset (about a decade earlier than effusive non-constrictive disease), a high pre-pericardiocentesis right atrial pressure on cardiac catheterization, elevated serum and pericardial levels of IL-10, serum TGF-β and pericardial IFN-γ compared to effusive non-constrictive disease. Finally, we demonstrate for the first time that pre-pericardiocentesis right atrial pressure and IL-10 level were independently associated with effusive-constrictive disease in patients with tuberculous pericardial effusion. Previous studies of ECP have suggested that it is an uncommon pericardial syndrome with a prevalence ranging from 2.4% to 14.8%, possibly because they were conducted in countries with a low prevalence of tuberculosis . SubsequThe finding that there was a relationship between the height of the pre-pericardiocentesis right atrial pressures and the diagnosis ECP was consistent with a similar observation by Hancock in the original case series on ECP . The expM. tuberculosis [There have been no studies hitherto of the pathogenesis of ECP. We have studied the levels of cytokines that play a role in inflammation and fibrosis to shed light on the immunological basis of tuberculous ECP. We have found that tuberculous ECP differs from effusive non-constrictive disease, having a distinctive cytokine profile characterized by elevated serum IL-10 and TGF-β and high pericardial fluid IL-10 and IFN-γ. IL-10 plays a role in the regulation of the immune response to rculosis , while Irculosis ,21. Furtrculosis -25. WhilThis pattern of cytokine expression may not only establish effusive-constrictive syndrome as biologically distinct in addition to the hemodynamic profile, but may have pathophysiological significance for pericardial remodeling following injury. The distensible visceral pericardium makes a vital contribution to cardiac compliance during diastole . DisruptThis study has a number of limitations. First, we enrolled patients with a moderate to a large pericardial effusion that was amenable to safe pericardiocentesis. This strategy may have introduced a degree of selection bias, and therefore the findings of this study apply to patients with moderate to large pericardial effusions with a probable and a definite diagnosis of tuberculous pericarditis. Second, a proven diagnosis of tuberculosis was made in 60% of cases. It is possible therefore that the 40% of participants with a presumed diagnosis may have had other inflammatory causes of pericarditis such as viral infection and autoimmune disease. The proportion of proven cases of tuberculosis is however typical of experience in tuberculosis endemic regions of the world . FinallyIn conclusion, this report provides new information on the prevalence, hemodynamics, clinical and cytokine profile of cases of proven and presumptive tuberculous ECP. We show that effusive-constrictive disease is a common form of tuberculous pericardial effusion that affects younger patients with an extremely high pre-pericardiocentesis right atrial pressure and markedly elevated pericardial and serum IL-10 levels. The cytokine profile is consistent with chronic unresolving inflammation and fibrosis. These observations lay the basis for studies of outcome and management of effusive-constrictive tuberculous pericarditis, a clinical entity that has hitherto not been addressed in guidelines for the management of pericardial disease .


Objectives. The aim of this study was to evaluate the prevalence and the risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes. Methods. The retrospective study included 3156 outpatients from the Diabetes Centre, the 306th Hospital of PLA, during the period from September 2003 to June 2010. QT interval was measured manually in the 12-lead conventional electrocardiogram. The QT interval corrected for heart rate (QTc) was calculated using Bazett's formula. Additional demographic and laboratory data were also collected. Potential risk factors of prolonged QTc interval were assessed using multivariable regression. Results. The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes was 30.1%. Height , waist circumference , diastolic blood pressure , postprandial glucose , fasting insulin , and presence of microalbuminuria  were significant risk factors. Conclusions. The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes is high. Risk factors for prolongation of QTc interval were low height, high waist circumference, increasing diastolic blood pressure levels, high postprandial glucose levels, high fasting insulin levels, and presence of microalbuminuria. Cardiac autonomic neuropathy (CAN) is a serious and common complication of diabetes. It is associated with a variety of adverse outcomes including cardiovascular death , 2. Howe The QT interval reflects the duration of the ventricular myocardial depolarization and repolarization. Prolongation of the corrected QT interval (QTc) has been demonstrated to be a specific indicator of CAN in most studies –7. MoreoA total of 3156 patients with type 2 diabetes who had standard ECGs record from September 2003 to June 2010 were recruited. Type 2 diabetes was diagnosed according to the 1999 WHO criteria . InclusiMedical documentations of all the patients were systematically reviewed with respect to age, sex, body weight, height, waist circumference, hip circumference, smoking habits, diabetes duration, and presence of diabetic complications including retinopathy, nephropathy, and peripheral neuropathy. Baseline laboratory data including fasting and postprandial blood glucose and plasma insulin, HbA1c, creatinine, lipids , low-density lipoprotein cholesterol (LDL-C), and triglycerides), and urine albumin-to-creatinine ratio (UACR) were also collected.Blood pressure was measured two consecutive times 1 min apart in the sitting position using an appropriate cuff size. The mean value of the two measurements was used in the statistical analysis. Hypertension was diagnosed as systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg or the current use of antihypertensive drugs.Diabetic retinopathy was evaluated by an ophthalmologist; normoalbuminuria was defined as UACR <30 mg/g, microalbuminuria as UACR between 30 and 300 mg/g, and macroalbuminuria as UACR >300 mg/g. Clinical nephropathy was diagnosed as the patient had persistent proteinuria of 500 mg/24 h, serum creatinine above 1.5 mg/dL, or UACR above 300 mg/g for at least twice. Peripheral neuropathy was diagnosed on the basis of neuropathic symptoms and signs or objectively abnormal results including insensitivity to a 10 g monofilament and abnormal vibration perception threshold based on the biothesiometer and without other significant disease.1/2. The QTc interval >0.44 s was considered abnormally prolonged.QT intervals and the preceding RR intervals were measured on the resting ECG tracing in lead II. The QT interval was measured manually from the starting point of QRS complex to the terminal point of the downslope of the T wave. QTc was calculated according to Bazett's formula : QTc = Qt-test was used to assess the differences. Data with skewed distribution were expressed as median (quartile) and Mann-Whitney U test was used. Categorical variables were presented as number and percentage and Chi-square test was used to test for group difference. Variables that were found to have a significant association in univariate analyses were entered in the multivariate analyses models (stepwise backward method). Entry and removal probabilities for stepwise were 0.05 and 0.1, respectively. All analyses were performed using SPSS 17.0 software . P values less than 0.05 were considered significant.The normality of the distribution of each continuous variable was assessed using the Kolmogorov-Smirnov test. If normality was established, continuous variables are presented as means ± SD and student's The 3156 patients with type 2 diabetes included 1425 (45.2%) females and 1731 (54.8%) males. The mean age (SD) was 54.9 (10.8) years. The median duration of diabetes was 3.0 years . Of the study population, 1121 (35.5%) were smokers; 2035 (38.5%) had hypertension. Retinopathy, neuropathy, and microalbuminuria were present in 422 (13.4%), 1159 (36.7%), and 718 (22.8%) patients, respectively.n = 951) of patients. Sex difference was evident, with higher prevalence in females than in males. Patients with prolonged QTc interval had more often lower height, higher waist and hip circumferences, higher systolic and diastolic blood pressure levels, longer diabetes duration, worse glycemic control , worse lipid profile , and higher UACR. Additionally, patients with prolonged QTc interval had microalbuminuria more often than patients with normal QTc interval. No differences in prevalence of either retinopathy or neuropathy were observed between the two groups , and that prolongation of QTc interval is associated with height, waist circumference, diastolic blood pressure, postprandial glucose levels, fasting insulin levels and presence of microalbuminuria. These findings have both epidemiological and clinical relevances. They support that patients with type 2 diabetes and prolonged QTc intervals have excess cardiovascular risk and should be treated to reduce the mortality risk.


Large artery stiffening and wave reflections are independent predictors of adverse events. To date, their assessment has been limited to specialised techniques and settings. A new, more practical method allowing assessment of central blood pressure from waveforms recorded using a conventional automated oscillometric monitor has recently been validated in laboratory settings. However, the feasibility of this method in a community based setting has not been assessed.>80 years in the whole population and a subset with a systolic BP < 140 mmHg.One-off peripheral and central haemodynamic (systolic and diastolic blood pressure (BP) and pulse pressure) and wave reflection parameters (augmentation pressure (AP) and index, AIx) were obtained from 1,903 volunteers in an Austrian community setting using a transfer-function like method  and from waveforms recorded with a regular oscillometric cuff. We assessed these parameters for known differences and associations according to gender and age deciles from <30 years to We obtained 1,793 measures of peripheral and central BP, PP and augmentation parameters. Age and gender associations with central haemodynamic and augmentation parameters reflected those previously established from reference standard non-invasive techniques under specialised settings. Findings were the same for patients with a systolic BP below 140 mmHg (i.e. normotensive). Lower values for AIx in the current study are possibly due to differences in sampling rates, detection frequency and/or averaging procedures and to lower numbers of volunteers in younger age groups.A novel transfer-function like algorithm, using brachial cuff-based waveform recordings, provides robust and feasible estimates of central systolic pressure and augmentation in community-based settings. Hypertension remains the most prevalent chronic disease in primary care, yet a considerable disease burden is attributable to inadequate blood pressure control . As a reAugmentation of blood pressure is related to changes in central haemodynamics and pressure wave characteristics resulting from increased aortic wall stiffening and aortic remodelling -12. The Despite the growing evidence base, pulse wave analysis assessment is yet to be adopted into clinical practice. This is most likely due to the lack of a pragmatic means in which to perform this analysis in real world settings. The evidence base to date has been provided from studies using non-invasive techniques (such as applanation tonomotry or mechanotransducers) that apply the current gold-standard methods for non-invasive pressure waveform analysis . Indeed,To counter this, a number of devices offering more accessible arterial assessment have become available. These devices use an ordinary blood pressure cuff and automated blood pressure monitor with specialist software. The ARCSolver method  provides estimates of central systolic and diastolic BP and augmentation index using a validated oscillometric device  to record pressure waves and the application of a general transfer function. Under controlled laboratory settings the device demonstrates realistic and valid estimates of central BP and augmentation index and performance equals that of current reference non-invasive techniques (SphygmoCor) when compared with measures derived invasively ,21]. Th. Th21]. The aim of this study was therefore to perform an initial assessment of ARCSolver derived arterial and central haemodynamic parameters in an unselected general population away from the usual “laboratory” setting. Further validation of the device was sought by evaluating estimated parameters for the known age and gender related associations previously established for non-invasive reference methods .Participation in the study was voluntary and the study was approved by the Austrian Society for Clinical Pharmacology and Therapeutics and institute for hypertension patients.We obtained estimates of central haemodynamics, including central systolic and diastolic BP and pulse pressure (PP), augmentation pressure (AP) and index (AIx) from 1,903 members of the general public during the period March – October 2007. Estimates were obtained in various public locations  in the city of Vienna, Austria. This formed part of the annual “Wiener Herz-Kreislauf (A Heart for Vienna) Event”, an annual initiative since 2003 for cardiovascular prevention and awareness building. Participants were approached and asked if they would be willing to have their blood pressure assessed using the ARCSolver method. Age was restricted to >14 years with no upper limit. Informed consent was obtained from all participants and parents where necessary (<16 years). Consent was given for the use of anonymised data for subsequent analysis and relevant dissemination. The study protocol adhered to the Declaration of Helsinki.The ARCSolver method is commercially available in the oscillometric Mobil-O-Graph NG® 24-hour ambulatory BP and PWA monitor . The device is Food and Drug Administration and Conformité Européenne approved and its blood pressure detection unit is validated according to British Hypertension Society  and EuroAll recordings were performed in seclusion within a Red Cross “medics” tent by trained paramedics familiarised with the ARCSolver method and standard oscillometric BP measurement procedures. Trained staff instructed each volunteer to sit on a chair with legs uncrossed and feet flat on the floor, and their back resting against the chair backrest. An appropriately-sized blood pressure cuff was then attached to the volunteer’s left or right arm. The volunteers arm was then rested on a table placing the cuff at approximately heart level. Participants were given a short rest (~5 minutes) prior to commencement of BP recordings during which time resting heart rate (HR) was recorded. The Mobil-O-Graph first performed a brachial BP recording to determine systolic and diastolic BP. This was followed by a 10-second PWA recording with the cuff inflated at the diastolic BP level.Mean arterial pressure (MAP) and pulse pressure (PP) were calculated from peripheral systolic and diastolic BP as MAP = diastolic BP + 0.4(systolic BP – diastolic BP)  and PP =>120/80 to <130/85; high normal, >130/85 to <140/90; Grade I hypertension, >140/90 to <160/100; and Grade II/III hypertension, >160/100 mmHg), accommodating those used in comparative studies [We performed descriptive analyses using PASW  statistics software (Version 18) and present data graphically, analysed according to age-specific and gender groups. We compared data in the present study with published data obtained from non-invasive reference methods (e.g. SphygmoCor). We categorised the sample into age deciles  and BP categories  as in previous studies [All parameter values in categories according to age and grade of hypertension are given as mean and standard deviation. We assessed differences between and within groups using analysis of variance (ANOVA) and independent  studies ,25.The average values for seated haemodynamic parameters in all volunteers  are presented in Table Men and women demonstrated a similar increase in peripheral systolic blood pressure with age, whereas diastolic blood pressure increased to approximately 50 years and then plateaued. As a result, peripheral PP widened from 50 years onward with differences between men and women in the manner  but not magnitude  of change. Central systolic blood pressure demonstrated similar changes with age as those observed for peripheral systolic blood pressure Figures . There wPerforming the above analysis in volunteers with a peripheral systolic BP <140 (i.e. normotensive) revealed similar findings except increases with age were not as marked and women demonstrated a marginally greater increase in central PP compared with men  and women , with values higher in women compared with men on average  and in each decile of age  [Similar outcomes were observed when analysis was performed in normotensive (systolic BP < 140 mmHg) participants only Table  and indig aorta) , the oscth derivative rule, the algorithm for the SphygmoCor is not in the public domain). It is also likely that the two methods adopt differing averaging procedures. It is important to note, however, that the reference non-invasive methods themselves (e.g. SphygmoCor) display a degree of error when compared to invasive measures [Our study is not without its limitations and many questions remain unanswered. Whilst we have demonstrated known age and gender associations for parameters derived from the oscillometric device, we have not demonstrated similar values for all parameters across all age groups compared with those from reference standard and other non-invasive techniques. This is particularly true for measures of augmentation index in younger participants (e.g. < 30 years of age). We were not able to assess statistically the nature of the systematic overestimation of augmentation index. Validation studies have demonstrated the ARCSolver method provides accurate estimates that are within recommended acceptable limits when compared to gold-standard invasive  and refemeasures  and therMore pragmatic factors offer additional explanation for the observed discrepancies. The smaller sample size of the present study meant small group sizes in some cases . For this reason we decided not to include certain groups that were presented in the comparison studies. For example, McEniery et al [Comparison studies included only “healthy” subjects in their reference group, identified as those with no concomitant medical conditions  . Whilst We report missing/erroneous values for 110 participants (5.8 %). However, we do not feel that this number reflects the true error rate with the device but is a reflection of our protocol design. Participants were approached in a community setting (shopping centre) and assessed in that same setting within 10-minutes of volunteering for the study. As a result, we believe that for some patients the scenario in which they were placed may have resulted in a raised BP and produced an erroneous diastolic BP of over 120 mmHg. This occurred in 29 participants or 1.5 % of the sample. Missing readings for cBP and AIx were reported in a further 81 participants (4.3 %). These reflected an inability to record a suitable quality pressure wave on the first attempt and where a second attempt was not possible . In practice, however, a repeat attempt is likely to be possible and therefore the missing readings observed here are unlikely to be as high in other settings . For reasons described we performed only one peripheral BP assessment prior to pulse wave assessments. In clinical practice it is recommended the average of two measures is used to determine office BP . In our Normotensive individuals were identified based on their peripheral BP as measured within the study and using the systolic BP determined from the oscillometric device. Thus, it is likely that a number of individuals presenting with a BP > 140 mmHg could have had artificially inflated values (white coat hypertension). It is also possible that a number of individuals with hypertension would have been missed (masked hypertension). The fact that only one peripheral BP assessment per participant was performed may also further confound these two factors. This may therefore present a markedly different population to the “normotensive” cohort of McEniery et al, in which all participants underwent a clinical diagnosis of hypertension.We present for the first-time non-invasive estimation of central blood pressure and arterial stiffness parameters from a commercially available, validated automated oscillometric device in a large community-based population and under deliberately robust settings. Measures of central blood pressure and pressure wave augmentation comply with known age and sex associations previously observed from reference non-invasive techniques. Estimates from more controlled settings (e.g. primary care) and with additional demographic parameters is warranted, particular to identify those factors influencing central haemodynamic and arterial stiffness parameters. Whilst the utility of arterial assessment at the primary care level becomes realised, this must be accompanied by concomitant clinician knowledge and understanding of their meaning and clinical significance.SW and CCM are inventors of a patent which is partly used in ARCSolver. There are no other competing of interest.DN constructed the concept of the study, performed the analysis, interpreted the data, drafted the manuscript and approved the final manuscript to be published. SW and BH performed data collection, participated in data analysis and interpretation of data, revised the manuscript for important intellectual content and approved the final manuscript to be published. DL, SF, AW and CH participated in data analysis and interpretation of data, revised the manuscript for important intellectual content and approved the final manuscript to be published. All authors’ read and approved the final manuscript.This work and its publication was partly supported by a grant of the government of Lower Austria and EFRE, contract number WST3-T-81/015-2008.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/12/48/prepub


This cross-sectional study aimed at estimating prevalence, awareness, treatment, control, and predictors of hypertension among Saudi adult population. Multistage stratified sampling was used to select 4758 adult participants. Three blood pressure measurements using an automatic sphygmomanometer, sociodemographics, and antihypertensive modalities were obtained. The overall prevalence of hypertension was 25.5%. Only 44.7% of hypertensives were aware, 71.8% of them received pharmacotherapy, and only 37.0% were controlled. Awareness was significantly associated with gender, age, geographical location, occupation, and comorbidity. Applying drug treatment was significantly more among older patients, but control was significantly higher among younger patients and patients with higher level of physical activity. Significant predictors of hypertension included male gender, urbanization, low education, low physical activity, obesity, diabetes, and hypercholesterolemia. In conclusion prevalence is high, but awareness, treatment, and control levels are low indicating a need to develop a national program for prevention, early detection, and control of hypertension. The importance of high blood pressure as a major cause of common serious diseases and deaths has been recognized in most countries particularly Western countries . HyperteThis is a cross-sectional community-based study covering the whole of KSA in 2005. The WHO STEPwise approach to Surveillance of Noncommunicable Disease (NCD) risk factors (STEPS) was the basis for conducting the survey and for collecting the data , 9.All Saudi population from all the 20 health regions of the country aged 15–64 years was included.A multistage stratified cluster random sampling technique was used to recruit the study subjects. Stratification was based on age , gender , and health regions of the country (20 regions). Based upon proposed methodology of the STEPS approach, a sample size of 196 was calculated for each of these ten strata. A list of all Primary Health Care Centers (PHCCs) in each region was prepared, and 10% of these PHCCs were randomly chosen and allocated regional sample proportionate to the size of their catchment population in sampled PHCCs. To identify the households, a map of the health center coverage area was used to choose the houses. Each house was assigned a number, and a simple random draw was made.Data was collected using the STEPS approach which includes a questionnaire and physical measurements plus biochemical measurements covering hypertension and other chronic diseases and risk factors. The questionnaire was translated into Arabic by a team of physicians and was back translated to ensure the accuracy of translation. Arabic instrument was pretested on 51 eligible respondents for wording and understanding of the questions. Necessary adjustments and corrections were made in the instrument in light of the pretest before using it. The questionnaire included sociodemographic data and history of blood pressure and blood pressure measurements in addition to other chronic diseases and risk factors.Data was collected by 54 male and 54 female collectors who work in teams. Each field team was made up of four persons: a male data collector, a female data collector, a driver, and a female assistant. Data collection teams were supervised by a hierarchy of local supervisor, regional coordinators, and national coordinator.All individuals involved in data collection attended a comprehensive training workshop that included interview techniques, data collection tools, practical applications, and field guidelines.The measurements of blood pressure (BP) were taken using a digital sphygmomanometer. Before taking the measurements, the respondent was advised to sit quietly and rest for 5 min with the legs uncrossed and the right arm free of clothing. Then, the right arm was placed on the table with the palm facing upwards. The appropriate cuff size was selected. The artery position mark (ART) was aligned with the brachial artery. The cuff was wrapped snugly and fastened securely. The cuff was kept at the same level as the heart during measurement. Taking measurement involved the following steps: pushing the “START” button enabled automatic inflation of the cuff and display of the reading of systolic blood pressure and diastolic blood pressure readings, which were recorded. A second reading was taken after five minutes from the first, and a third reading was taken after five minutes from the second one.The subject is labeled hypertensive if the average of the 3 BP measurements was 140 mmHg or above for systolic and/or 90 mmHg or above for diastolic blood pressure or the subject is a known hypertensive diagnosed previously by a health professional.P value was set to <0.05 throughout the study.Questionnaires collected from the field were reviewed by team leaders assigned to each team before submitting them to the headquarters for data entry. Double entry of the questionnaires was performed using EPI-INFO 2000 software and EpiData software developed by the Menzies centre for validation. After data entry, data cleaning was conducted. New variables were defined by adopting the standard Steps variables . Data analysis was conducted using SPSS (Version 17) software. The number of participants' responses used in the discrete statistical analyses varied due to missing data for certain variables. Descriptive statistics and univariate and multivariate analysis were performed for associations and risk factors for hypertension prevalence, awareness, treatment, and control. Chi squared test was used to find if there is any association between each of hypertensive, aware hypertensive, on drug treatment, and controlled subjects with different demographic variables and other associated risk factors. Logistic regression model was used to predict hypertension from the associated risk factors. Odds ration and its 95% confidence intervals were done. Chi squared test and logistic regression were used as appropriate, and The protocol and the instrument of the surveillance were approved by the Ministry of Health, Center of Biomedical Ethics and the concerned authorities in the Kingdom. Informed consent of all subjects was obtained. Confidentiality of data was assured and that data will be used only for the stated purpose of the survey. Further details of the method used and sampling procedures can be found in STEPS documents , 9.P < 0.001). The prevalence of hypertensive males was significantly higher than hypertensive females. As age increases, the prevalence of hypertension significantly increases. People in the central region of the KSA have higher prevalence than other regions. Uneducated participants showed higher prevalence than others. Retired participants showed the highest prevalence compared to other occupations. For smoked tobacco products, there is a significant association (P = 0.002) between hypertension and current smoking status where nonsmokers have significantly higher hypertension prevalence. Among current smokers themselves, nondaily smokers have lower hypertension prevalence compared to daily smokers, but differences were not significant. Further analysis showed no significant association between hypertension and smokeless tobacco product use currently or in the past. Subjects classified as having high physical activity level have significantly lower prevalence than others (P < 0.001). As body mass index increases, prevalence of hypertension increases (P < 0.0001). Diabetics and hypercholesteremic subjects have significantly higher hypertension prevalence (P < 0.001). Higher awareness of hypertension was significantly more among females, older subjects, residents of Eastern Region, housekeepers, and, with the presence of diabetes mellitus and an increasing level of physical activity. Applying drug treatment was significantly more among older patients, but control was significantly higher among younger patients and patients with higher level of physical activity. Of the total 4758 subjects who participated in the study, about 51% were females. A total of 1213 were hypertensives giving a prevalence of 25.5% . Of all hypertensives, 542 (44.7%) were known patients confirmed by health professionals and 671 (55.3%) were unaware of their disease. They were newly detected during the survey. Of the aware hypertensives, 389 (71.8%) were under drug treatment and 144 (37.0%) of them were controlled (BP under 140/90 mmHg). Tables This study, to the best of our knowledge, is the first to present authentic nationwide current data about prevalence, awareness, treatment, and control of hypertension among adults in one report. It is hoped that findings can be of help in efforts to control the disease.This study found that hypertension affects more than a quarter of the adult population in agreement with a previous national study . A similA worrying finding in this study is that less than half of the hypertensives were aware of their disease at the time of the survey in agreement with a previous study . In otheThis study found that of all aware hypertensives about 72% were on drug treatment but only 37.0% of them were adequately controlled. These findings, although not satisfactory, are better than the findings of another study which found that of the 28.2% who were receiving treatment, only 3.7% had their blood pressure adequately controlled . This inIn summary this study highlighted a disturbing situation with hypertension affecting more than a quarter of the adult population, more than half of them were unaware of their disease, and less than 40% of those under drug treatment were controlled as judged by their blood pressure measurement of less than 140/90 mmHg. Despite the availability of a large number of effective and well-tolerated antihypertensive drugs and other modalities, blood pressure control rates are not satisfactory on a national and global scale . The lowComparisons of prevalence of hypertension among population groups in different countries are hindered by the different methodologies and definitions used. Information bias may have been present with respect to both recall of hypertension diagnosis and treatment and the validity of some of the predictor variables. We hope that the extent of the bias is minimal due to the confidentiality assured, proper training of all manpower involved in the survey, and the health objectives of the survey. Three measurements of BP were taken during one diurnal visit. Nocturnal variations and white-coat effect were not ascertained as no home monitoring of BP measurements was available.The high prevalence of hypertension and the low prevalence of awareness, treatment, and control all are of high importance for all health professionals and politicians. There is a need for further research to document the impact of dealing with the modifiable risk factors and predictors of hypertension in reducing the burden of hypertension and its consequences. These results underscore the urgent need for developing a high blood pressure screening and education program to coordinate the effort of early detection, prevention, and treatment of hypertension in KSA.


The present study tested the hypothesis that the exercise protocol (continuous vs. intermittent) would affect the physiological response and the perception of effort during aquatic cycling. Each protocol was divided on four stages. Heart rate, arterial blood pressure, blood lactate concentration, central and peripheral rate of perceived exertion were collected in both protocols in aquatic cycling in 10 women : age=32.8 ± 4.8 years; height=1.62 ± 0.05 cm; body mass=61.60 ± 5.19 kg; estimated body fat=27.13 ± 4.92%. Protocols were compared through two way ANOVA with Scheffé’s post-hoc test and the test of Mann- Whitney for rate of perceived exertion with α=0.05. No systematic and consistent differences in heart rate, arterial blood pressure, double product and blood lactate concentration were found between protocols. On the other hand, central rate of perceived exertion was significantly higher at stage four during continuous protocol compared with intermittent protocol (p=0.01), while the peripheral rate of perceived exertion presented higher values at stages three (p=0.02) and four (p=0.00) in the continuous protocol when compared to the results found in intermittent protocol. These findings suggest that although the aquatic cycling induces similar physiologic demands in both protocols, the rate of perceived exertion may vary according to the continuous vs. intermittent nature of the exercise. Physical training is often based on continuous and/or intermittent methods with the purpose of improving cardio respiratory ability . StudiesAccording to In water, resting or exercising induces different physiological responses when compared with those achieved in dry-land conditions  and are Ten women  of low risk, practicing regular classes of cycling in water for at least six months, participated in the study. All of them signed a written informed consent to participate in the study and in accordance with the norms for accomplishment of research with humans established in the Helsinki Declaration of 1975. The experimental procedures were approved by the Ethics Committee of the Institution.All volunteers attended the test venue on three different days, with an interval of seven days. The volunteers were instructed not to workout exhaustively in the previous 24 hours; to remain well hydrated in the previous 24 hours and to avoid eating, smoking, drinking alcohol or caffeine three hours before the tests, as well as to sleep between 6 and 8 hours in the night before testing.The volunteers were submitted to an anthropometrical evaluation, consisting of body mass and height measures . The same technician obtained all anthropometric measurements, on the right side of the subject’s body. Skinfold thickness was obtained with a Lange skinfold caliper. A 3-site skin fold equation for woman was used to estimate body density  and bodyTo evaluate the cardio respiratory capacity, the individuals were submitted to the The exercise protocols had a total duration of 31 minutes and were divided in five stages. Absolute heart rate (HR) was continuously measured with a cardio-frequency meter  device and Rate of Perceived Exertion (RPE) was measured at the end of each minute of exercise . Blood pressure (BP) and blood Lactate concentration (BLC) were also assessed in the last minute of each stage. For BP, was measured by auscultation technique, non-invasive, using a sphygmomanometer  and professional stethoscope . Capillary (finger) blood sample were collected for BLC with an YSI 1500 analyzer . Prior to each testing, the lactate analyzer was calibrated with standard lactate solutions of 2.5, 5.0, 10.0 and 15.0 mmol·L-1 .After identification of data normality (Shapiro-Wilk test), a two-way analysis of variance  was applied to check the effect in the variables selected. A post-hoc Scheffé test was used to describe possible differences among the variables. The Mann-Whitney test was used to compare the rate of perceived exertion between the respective stages. The study admitted a significance level α= 0.05. The data were processed using Statistical software . Data s presented as mean ± standard deviation (SD).The P < 0.05). The double product showed few significant differences between protocols. In the Intermittent Protocol significantly higher values were recorded in Stage I (19229.00 ± 3046.21 mmHg.bpm) when compared with Stage IV (22702.00 ± 232.05 mmHg.bpm). In the Continuous Protocol mean values observed in Stage I (18810.00 ± 2993.71 mmHg.bpm) were statistically different from those in Stage III (22408 ± 3687.04 mmHg.bpm) and in Stage IV (24345 ± 4641.42 mmHg.bpm). Significant differences were found in systolic blood pressure when comparing the mean values in Stage V of the IP (110.40 ± 13.78 mmHg) and of the CP (114.80 ± 13.70 mmHg) with the foregoing stages. The diastolic blood pressure, in the IP, Stage I (74.60 ± 6.11mmHg) presented a significant difference when compared with Stage II (66.40 ± 7.22 mmHg), with Stage IV (65.60 ± 8.04 mmHg) and with Stage V (64.60± 9.38 mmHg). Additionally, in the IP, Stage I (97.46± 7.54 mmHg) recorded mean values significantly higher than Stage V (79.86 ± 8.10 mmHg). Finally, in the CP, Stage I (94.13± 10.86 mmHg) showed a significant difference relatively to Stage V (82.93 ± 13.88 mmHg) (vs. 4.00± 1.33). However, the Stages I , Stage II  and Stage V , all of them didn’t show significant values.We have hypothesized that the short recovery periods in the IP combined with the aquatic environment would lower the physiological stress and perception of effort when compared with CP. The findings in this investigation demonstrated that heart rate (HR), double product (DP) and rate pf perceived exertion (RPE) were higher during the CP when compared with IP. However, blood pressure (both systolic and diastolic) and blood lactate presented higher mean values in IP when compared with CP. The RPE tended to be higher at the continuous protocol.The HR response can be influenced by factors as: mechanical distension of the atrium, entailed by venous return, body temperature  blood acIn the present study the values of the BP, both systolic and diastolic, tended to be higher in IP, which could be justified by the fact that the individuals remained in the seated position during one and a half minute (corresponding to the recovery period), thereby probably increasing the hydrostatic pressure and stimulating the outlying baroreceptors, which could have facilitated the blood distribution and stimulated the venous return. Other than the position of the body, also buoyancy phenomena could have influenced our results . These fThe RPE was also addressed in the study by The hypothesis that the intermittent protocol would offer a lower physiologic demand was only partially confirmed. HR, DP and RPE were higher during the CP. Plus, SBP and DBP and BLC presented higher mean values in the IP. The IP induced a more pronounced HR reduction and BLC during the recovery periods, suggesting a faster recovery in the intermittent protocol. More studies are recommended with other possible exercise intensity and volume combinations, as well as with different gender and conditioning level of the individuals.