This discussion is presented here to showcase the role the modern social media plays in enhancing the academic exchange and learning experience on the international stage. Some minor edits were performed for clarity purposes.The anesthesiologists from both the United States and China had an open and engaging discussion on intraoperative monitoring of cerebral perfusion and ischemia at the social media – WeChat International Chinese Academy of Anesthesiology  monitoring during aneurysm clipping. The surgeon normally request burst suppression. For brain tumor cases, we do not normally monitor bispectral index (BIS), etc. However, the surgeon may perform cortical and subcortical mapping if the tumor is adjacent to eloquent brain in order to maximize the extent of resection. For brain trauma, I personally do not think anesthesia depth monitoring is useful. What matters in traumatic injury cases is to decrease intracranial pressure (ICP) and maintain cerebral perfusion and oxygenation.Dr. Meng, what types of anesthesia monitoring are used during neurosurgical procedures in the United States?Dr. Guo, how to monitor neurosurgical patients is institution and surgeon dependent. Now, as anesthesiologists, we would like to monitor intravascular volume status, tissue perfusion, etc. This is important because mannitol that is almost routinely given to patients causes large urine output and volume depletion as a consequence. Also, hyperventilation if adopted can cause vasoconstriction, especially the brain, i.e., cerebral vasoconstriction.I have a different school of thought. EEG monitoring is very valuable in anesthetized patients. The target of general anesthesia is the brain. The electrophysiological activity of the brain is what the anesthesiologists can rely on, especially when the clinical picture is confusing. The patient complains dizziness when the blood pressure is decreased by epidural or spinal anesthesia. The awake elderly patient will complain dizziness and sickness if the systolic blood pressure is less than 100 mmHg. The patient who is under general anesthesia is unable to tell his/her feeling. The individualized index of cerebral perfusion is the percentage of the Delta wave on EEG tracing that can tell when the blood pressure cannot be further lowered. Cerebral perfusion pressure (CPP) equals mean arterial pressure minus ICP. CPP needs to be maintained above 70 mmHg. It cannot be less than 55 mmHg in patients with traumatic brain injury. Therefore, we should be able to tell how the mean arterial pressure should be maintained under various scenarios. As anesthesiologists, we did not pay the needed attention to hypotension. Therefore, I recommend EEG monitoring for blood pressure care.Dr. Huang, thank you for sharing your thought! Where is the relationship between blood pressure and EEG coming from? Would you please share with us the evidence, not just personal opinion?2) monitoring more valuable?Dr. Huang and Dr. Meng, what are the effects of anesthetic agents on EEG? Is cerebral tissue oxygen saturation . Therefore, non-invasive cardiac output monitoring is probably more valuable to tell how the tissue is perfused. A fixed number of cerebral perfusion pressure (CPP) cannot be used to tell if the brain is adequately perfused. A mean arterial pressure of 80 mmHg may not be adequate for cerebral perfusion in a hypertensive patient [2 monitoring is a valuable surrogate of cerebral blood flow. In addition, the brain is a vital and prioritized organ. Even if it is perfused okay, the other organs like the gut and the muscle may not (be well perfused). Tissue hypoxia or desaturation, even if not the brain, may be one of the root causes of adverse outcomes.Dr. Gao and Dr. Huang, in our institution, we do not use EEG monitoring to guide blood pressure management. Neither do we use BIS for blood pressure care. SctO patient . SctO2 m2 is indeed complex. It may vary at varying cerebral autoregulatory ranges. Therefore, caution is needed when using a “normal” value (or a fixed number) to guide blood pressure care. Relevant and recent studies are available, including the work by Dr. Hogue and Brady (from Johns Hopkins).Dr. Meng, the relationship between blood pressure and SctODr. Meng, thank you for sharing your opinion. The cerebral blood flow is 50 ml/100g/min in adults. Slow wave appears on EEG monitoring when the cerebral blood flow is less than 20 ml/100g/min (please refer to Miller’s Anesthesia book chapter). There is a close relationship between CPP and blood pressure. This is similar to the change in ST segment on electrocardiogram monitoring that is used to monitor myocardial ischemia. In patients with acute ischemic stroke, the treatment goal is to maintain blood pressure in addition to prompt thrombolysis.Dr. Meng, when you say the cardiac output is likely more important to cerebral oxygenation (than blood pressure), do you suggest that a faster heart rate is less problematic to cerebral oxygenation even though the blood pressure is relatively low after cardiopulmonary bypass? Or, can you tell which physiological status  is safer ? It seems that these newer findings do not agree well with the lower limit of cerebral autoregulation.Dr. Huang, your points of view are very unique. They are refreshing to me. I am not prepared to respond your queries at the moment. These are just friendly reminders. Critical thinking is needed during reading. Different issues or questions need to be treated differently. A conclusion can be stated in one direction; however, it cannot be applied in clinical practice in a reverse direction (because the cause-effect relationship is changed). Textbooks cannot be used without distinction. Dr. Miller’s office (the editor of the most popular anesthesia textbook) is 50 meters away from my desk. Views can be discussed, but cannot be imposed. Otherwise, it causes more harm than good. It is well known that CPP depends on blood pressure. This is the knowledge a medical student who wants to be a pediatrician in the future knows. Nonetheless, I really enjoyed the exchanges with you. Thank you for your courage and candor.Dr. Sun, thank you for your interest. We are drafting a review to address this issue at the moment. We believe that tissue perfusion and oxygenation are probably better when cardiac output is ideal even though blood pressure is low compared with that when cardiac output is low while blood pressure high.Dr. Meng, thank you! The increased incidence of stroke in the POISE study may have something to do with the reduced cardiac output in addition to hypotension .2) and Q10) is 10 times less than euthermia (normothermia). However, irreversible brain injury occurs if the cerebral blood flow is less than 12~15 ml/100g/min and the body temperature is normal. The EEG monitoring during surgery provides valuable information for blood pressure and ventilation management.Dr. Sun, the mean arterial pressure should be maintained at 60~80 mmHg when the temperature is 34°~35° during cardiopulmonary bypass. The incidence of brain injury is increased if the blood pressure is fluctuating during euthermic (normothermic) cardiopulmonary bypass that emphasizes the importance of intraoperative blood pressure care. However, the brain is not injured when its perfusion is stopped for 30~40 minutes as long as the core temperature is decreased to be less than 17° when the cerebral metabolic rate  and the adequacy of cerebral perfusion is trustworthy.Special thanks to Dr. Huang and Dr. Dong! The opinions from both of you are making this open discussion more meaningful. Cerebral blood flow stays relatively stable when the blood pressure fluctuates, as long as the cerebral perfusion pressure is higher than the lower limit, according to cerebral autoregulation. The cerebral perfusion pressure-cerebral blood flow relationship is not passive, meaning that, even though the blood pressure is decreased, the cerebral circulation stays the same. The challenge during surgery is to know if the cerebral autoregulation is still functional and where the lower limit is. We definitely need to maintain the CPP above the lower limit. However, this lower limit may change during surgery .2 based on near-infrared spectroscopy (NIRS) as a surrogate of cerebral blood flow.Dr. Huang, during cardiopulmonary bypass, it is well accepted that mean blood pressure be maintained at 60–80 mmHg and this range has been used in most hospitals. But, this range is largely based on the well-known cerebral autoregulation curve. Recent studies have shown that the range of cerebral autoregulation, especially in patients with hypertension and advanced age, is different from person to person. Therefore, post-cardiopulmonary bypass brain complications are common, likely due to the inaccurate blood pressure management during bypass. The most rigorous and scientific way to do is to find the cerebral autoregulation range of the patient and manage blood pressure based on this range. Unfortunately, no hospitals are doing it (monitoring autoregulatory range) at present. This is why it is necessary to conduct clinical studies in perioperative monitoring of cerebral oxygenation during open-heart surgery. The most straightforward way to find cerebral autoregulation range is measure blood pressure and cerebral blood flow directly, but direct measurement of cerebral blood flow is not practical during surgery. This is why Drs. Brady and Hogue discovered using SctOI always see perfusion pressure decreased to 20–30 mmHg as soon as the cardiopulmonary bypass initiates. Please advise !This range of blood pressure is too low. What about postoperative complications?I had a few patients with severe cerebrovascular stenotic lesions when I was working at Xuanwu Hospital. I used the mean blood pressure when the patients were hospitalized (before surgery), in addition to the symptoms of cerebral ischemia (before surgery), as the blood pressure management goal during cardiopulmonary bypass.I agree. The emphasis on blood pressure maintenance can leads to overuse of vasoactive drugs, which is good for the brain but may be bad for the heart.This is a more practical approach.Postoperative cognitive impairment increases as the mechanical ventilation time increases!2 was decreased when the blood pressure increased (by phenylephrine) [2 (and the tissue oxygenation monitoring on the leg). One of the potential explanations for this observation is cerebral autoregulation.Dr. Wei, here is the problem. I agree that inadequate cerebral perfusion leads to EEG change. However, a change in EEG does not necessarily mean the cerebral perfusion is becoming inadequate. For example, the change in anesthesia depth is probably the most common cause of EEG change. Low cerebral perfusion is just one of the potential causes of an EEG change. In addition, the cause of insufficient cerebral perfusion is also multifactorial. For example, both a decrease in cardiac output and hypocapnia secondary to hyperventilation can result in a decrease in cerebral blood flow. Interestingly, it was observed that SctOephrine) . Our recBoth brain and heart should be protected. It is therefore emphasized to employ a scientific and reliable monitoring method during (open heart surgery). I really hope colleagues in China to conduct more research using NIRS, because there is a lot of potential of conducting clinical studies in China.Dr. Meng, if a patient’s baseline blood pressure (mean) is 90 mmHg and assuming the autoregulatory range is 60–160 mmHg, should his blood pressure (mean) be maintained at 60 mmHg instead of his baseline (90 mmHg)? Will maintaining his blood pressure at baseline (90 mmHg) facilitate regional blood flow and metabolic substrate exchange?Dr. Cai, this is a great question. Dr. Gao, I meant both cerebral and muscular oxygenation. The manuscript was submitted recently.Perfusion pressure does affect cerebral blood flow. However, these are two different entities and their relationship should be treated carefully.Dr. Cai, if the autoregulation range is accurate, it means cerebral blood flow does not change as blood pressure changes. Local metabolism should not be expected to change as well.Dr. Meng, it (the results of your recent study) makes sense.The major problem (in daily practice) is that we do not know the autoregulatory range (under various conditions). Therefore, we use the strategy to keep the intraoperative blood pressure at the patient’s baseline. However, the use of vasopressor can lead to a decreased cardiac output secondary to decreased heart rate and increased afterload (if using pure α-agonist) even though the blood pressure is increased to the baseline level.Dr. Cai and Dr. Gao, different perfusion pressure leads to different cerebral vasomotor tones within the autoregulatory range because, in order to keep the flow stable when the perfusion pressure is changed, the flow resistance (vasomotor tone) needs to change accordingly. Therefore, I speculate this (different vasomotor tone under different perfusion pressure) may lead to different outcome. Maintaining the intraoperative blood pressure around the baseline is a great guess (for better outcome).Dr. Cai, this depends on the situation. If blood pressure is low enough to decrease blood supply to the heart, increasing blood pressure can increase cardiac contractility and cardiac output. Blood supply to cardiac tissue mostly occurs during diastole.Dr. Meng, here is a thought that may deserve attention. The surgical stimulation and anesthetic depth are relative constant during cardiac surgery; therefore, I believe the change in EEG monitoring is more meaningful (during cardiac surgery).Will the outcome be different between two different managements in which the blood pressure (mean) is maintained at 90 and 60 mmHg, respectively? The cerebral blood flow should be the same if the autoregulation is functional.We had studies on how the monitoring of the middle cerebral artery flow velocity using transcranial Doppler affects postoperative outcome.Dr. Ye, this is essentially the same as monitoring cerebral oxygenation.Yes. However, this is not as sensitive as EEG. Unfortunately, there are not many hospitals in China that use intraoperative EEG monitoring.2 monitoring and EEG monitoring are different. Based on current evidence, monitoring cerebral oxygenation is relatively clinically more significant because it seems associated with a better clinical outcome. Unless someone can show that EEG monitoring can also lead to a beneficial outcome: i.e., postoperative  neurological complications.One should realize that SctOWe routinely monitor EEG (during aneurysm clipping). However, we use it to guide the care of anesthesia depth (burst-suppression), not cerebral perfusion, and for sure not blood pressure.We had used cerebral oximetry. My personal experience is that it only measures the hemisphere and does not precisely measure the brain region that has the potential of ischemia. EEG has better precision by monitoring the brain area with ischemic risk secondary to, for example, cerebrovascular stenotic lesions.I am fascinated by the discussion. To my knowledge, the current blood pressure range for cerebral blood flow autoregulation in the textbook was reported in late 1950s. This value may not be very accurate. However, as the rule of thumb, it is important to keep the blood pressure within the 20–30% of the baseline value. This raised another question, what is the baseline blood pressure? Is the blood pressure we obtained right before surgery is the baseline blood pressure or the blood pressure recorded in the patient medical record 3 months ago is the baseline blood pressure? Is EEG a good indicator for intraoperative cerebral perfusion? I personally do not think EEG is, because it could be affected by too many factors, such as: anesthetic agents just to name one. Because there is no single good cerebral perfusion monitoring method available, the cerebral oxygen saturation is the best alternative that is currently available.Dr. Ye, in order to achieve the precision you mentioned, how many needles do you need to put on the scalp? There is no gold standard to diagnose cerebral ischemia. Otherwise, we will have to go to the court if, as a doctor, you do not use the gold standard for patient care .Dr. Kuang, there is a transit decrease in perfusion pressure when the cardiopulmonary bypass was initiated. It is important to communicate with the perfusionist when it occurs. It is necessary to use vasoactive medications if the perfusion pressure is still low and the cerebral oxygen saturation below the baseline.The BIS value changes when the cerebral perfusion pressure changes during cardiopulmonary bypass. This can be an important warning sign. However, large scale studies are needed to determine its threshold.2 may decrease even if the cerebral perfusion is increased or stable when the core temperature in increased at the end of cardiopulmonary bypass.Cerebral oximetry was applied in cardiopulmonary bypass surgery when it was first introduced to clinical practice in 1990s. However, it represents regional cerebral oxygenation that is determined by the balance between cerebral oxygen consumption and supply, and is affected by various factors. It does not represent cerebral blood flow or cerebral function. It cannot be used reliably to monitor regional cerebral ischemia. For example, SctO2) is more informative if the relevant factors (determining) are kept stable.It (SctO2) is the “trend of change” that is meaningful.Agree. It  is limited, I usually only use cerebral oxygen saturation monitoring during cardiac surgery. I actually never used BIS monitoring in cardiac surgical patients.Intraoperative awareness should not occur if enough midazolam plus inhalational anesthetics are used.I agree with Dr. Liu. EEG and BIS may be able to tell cerebral perfusion and metabolism depending on the aspects we are referring to. However, it may be proven unreliable by future research. That is why the evidence-based medicine is forever changing.I agree with Dr. Sun. There currently no monitoring or management strategy that can prevent intra-operative awareness.I practice enhanced recovery after surgery (ERAS) protocol; therefore, I rarely use midazolam. I have not encountered any case with intraoperative awareness yet.Awareness is a confusing concept. It is awareness in English. It is often confused with recall.I never saw a case of awareness even though the textbook says it has high incidence. This may due to the fact that, when I decrease the anesthesia depth during hypotension, I have a bottom line in addition to referring to the monitoring data. The management of hypotension is made much easier with the help of transesophageal echocardiogram (TEE).I had an idea before. The lowest tolerable blood pressure in patients undergoing carotid endarterectomy can be determined by gradually decreasing the blood pressure in a controlled manner until the symptoms of cerebral ischemia occur. At the same time, we monitor transcranial Doppler. This approach (maintaining a lower blood pressure) can increase cerebral oxygenation, decrease cerebral metabolic activity , and decrease cardiac work load (by avoiding vasopressor?).The key is to precisely tell when the brain is undergoing ischemia.Dr. Ye, the idea you just mentioned is risky! A study from Columbia University (published in Neurosurgery) showed that the outcome is better if the intraoperative blood pressure is maintained 20% above the patients’ baseline value during carotid endarterectomy. It is crucial not to let the blood pressure decrease in this patient population.I meant to do it before surgery. Yes, the protocol did not go through due to the concern of severe adverse outcome.2 monitoring and postoperative outcomes [2, not SctO2); however, there are no convincing studies showing that it is beneficial to outcomes. We believe SctO2 monitors a crucial cerebral circulation regulation mechanism that is neurovascular coupling [vice versa. SctO2 is essentially determined by the balance between cerebral oxygen consumption and supply. Therefore, we argue that it assesses the functional status of neurovascular coupling. If the mechanism of neurovascular coupling is intact during anesthesia, the cerebral perfusion and oxygenation will be regulated based on the cerebral metabolic activity. This would be great! Neurovascular coupling is different to cerebral autoregulation. They are both important mechanisms regulating cerebral hemodynamics. These distinctive mechanisms clearly demonstrate the importance of the brain as a vital organ.There are many published studies showing the relationship between intraoperative SctOoutcomes . One shocoupling . NeurovaDr. Meng, this is indeed complicated. It is complex when trying to understand the effect of vasopressor  when there are both change in blood pressure and consequential change in cardiac output. In addition, the outcome may differ between two management strategies that use vasoactive drugs during hypotension and normotension, respectively. The BJA paper showed vasopressor (like norepinephrine and phenylephrine) can decrease cardiac output during euvolemia; however, it may guarantee the blood supply to the brain and hear during hypovolemia via vasoconstriction of peripheral organs .2 represents the dissolved oxygen content in the blood ; therefore, cerebral blood flow is a better indicator of cerebral metabolic demand. Inhaled anesthetics, when it is used in a large dose, can alter cerebral autoregulation, that means that the cerebral blood flow will not stay stable at the perfusion pressure range of 60~150 mmHg and an increase in blood pressure can lead to an increase in cerebral blood flow. In addition, the main problem during stroke is not vasospasm, but the flow stoppage caused by the embolus coming from the broken atherosclerotic plaques. Briefly, we should first pay attention to blood pressure  when intraoperative EEG is changed (decreased), followed by adjustment of anesthetic dose. A deep EEG if it is not caused by hypotension is featured by slow eye movement sleep that helps brain resting.Dr. Meng, the cerebral oxygen supply equals to hemoglobin times 1.36 times cerebral blood flow. SctO2) should correlate with the cerebral blood flow because the oxygen is carried by the blood. Why bothered to study it? It is simply self-evidenced. This may be one of the key reasons that the scientists in China are more difficult to obtain Nobel Prize than these in the West.The difference between the West and the East is typically demonstrated by the exploration of the relationship between two different entities. The West insists to use study to test the hypothesis. They first measure these two entities, followed by statistical analysis and p-value to either accept or refute the hypothesis. This is an example of modern science based on statistics. In comparison, the East does it differently by using logical philosophy. This is one of the examples. If the cerebral oxygen consumption is constant, the cerebral oxygenation (SctOMany thanks to Dr. Yu for his participation in this discussion from a philosophical point of view. Philosophy is the flower of wisdom. Philosophical thinking is crucial for academic advancement. They supplement and benefit each other. After all, we all benefit from this open and wide-range discussion and would like to thank those who had participated in this forum!The brain constitutes only 2% of the body weight; however, it disproportionately receives 12% of the cardiac output . The wel


Objective. To analyze changes in vital signs (heart rate (HR), systolic (SBP), and diastolic blood pressure (DBP)) during and after intravenous methylprednisolone (IVMP) and any other adverse effects. Methods. Retrospective review of charts of patients who received IVMP as treatment regime for thyroid eye disease. All subjects had vital signs charted during and after infusions. Results. This study included 38 subjects and a total of 242 infusions administered. IVMP resulted in a small but significant percentage drop in mean SBP at 30 min (p < 0.001) and 60 min (p = 0.03) but no difference at 90 min. There was also small but significant percentage drop in mean DBP and HR . There were no cumulative effects on change of blood pressure or HR. There were 6 episodes of bradycardia (2.5%) and 12 episodes of moderate to severe hypertension (5%). No significant cardiovascular or hepatic toxicity was found. Conclusion. IVMP is relatively safe and efficacious. IVMP demonstrated mild and noncumulative effects on vital signs. Severe hypertension may occur in susceptible individuals such as those with underlying hypertension and uncontrolled thyroid dysfunction, whereas bradycardia may be more likely in those on beta-blockers. Thyroid eye disease (TED) is an autoimmune process which involves abnormal proliferation and activation of orbital fibroblasts, increased glycosaminoglycans, and proinflammatory cytokine production. Cytokines can modulate the immune reaction in TED by increasing major histocompatibility complex class II, adhesion molecules, prostaglandin, and heat shock protein expression in the orbit , 2. GlucPulsed intravenous methylprednisolone (IVMP) therapy is an established treatment of active moderate to severe TED and sight-threatening dysthyroid optic neuropathy . IVMP thHowever, there are concerns regarding the safety profile of pulsed IVMP, especially on the cardiovascular system. There are many known adverse effects of pulsed IVMP therapy. Minor effects include flushing, mild hypertension, gastritis, weight gain, depression, hyperglycemia, insomnia, palpitations, sinusitis, and urinary tract infections , 9–12. MThe purpose of this study is to analyze the changes in vital signs (including heart rate (HR), systolic (SBP), and diastolic blood pressure (DBP)) during and after IVMP infusion , as well as changes in electrocardiogram (ECG), potassium levels, glucose levels, and any other adverse effects.We performed a retrospective review of the charts of TED patients who underwent pulsed methylprednisolone therapy from 2004 to 2010 in Singapore National Eye Centre. Numerous different parenteral regimes for IVMP have been reported, with no clear consensus on the optimum dosage, dosing intervals, and duration of treatment , 22. TheAll subjects were examined for best correctable visual acuity (BCVA), colour vision, VISA scoring, and slit-lamp examination prior to pulsed methylprednisolone therapy. An inflammatory score of 4 or more on VISA was considered as active TED . BaselinAll subjects had their vital signs  charted before infusion (0 min), at 30 min (during infusion) and 60 min (end of infusion), and after infusion (90 min). ECG and capillary glucose level were checked at 60 min. Serum potassium was measured before and after each infusion for all subjects before discharge. All subjects had to complete a questionnaire at the end of infusion which documented any subjective complications experienced.Subjects were reviewed after each cycle of 3 doses of IVMP for BCVA, colour vision, VISA score, and full slit-lamp examination. Full blood count, liver function test, and renal panel were performed. Subjects were reviewed at interval of 1 to 3 months after treatment depending on their condition and physician's discretion. Subjects may undergo repeated cycles of IVMP if the TED was considered active or patients developed signs of compressive optic neuropathy. Subjects may also be given adjuvant methotrexate or radiotherapy after IVMP treatments were completed.t-test. A linear mixed model was utilized to analyze and account for the cumulative effect of the multiple doses of each cycle of methylprednisolone. Three candidate covariance structures were checked for minimizing the mean squared error of predictions, first-order autoregressive [AR(1)], compound symmetry (CS), and unstructured (UN), to estimate the fixed effects and we have selected the structure with the smallest Akaike's Information Criterion (AIC) and Bayesian's Information Criterion (BIC). Linear mixed models were fitted and compared using restricted maximum likelihood methods. A statistical significance level of 0.05 was used for this study.Statistical analysis was performed with SPSS software . Parametric data was analyzed using paired The study included 38 subjects who underwent a total of 242 infusions of IVMP . The meap < 0.001, and −2.25 ± 12.18%, p = 0.03, resp.) but no significant difference after stopping infusion at 90 min . There was also small but statistically significant drop in mean percentage change DBP at 30 min, 60 min, and 90 min compared to baseline DBP  (p < 0.001) from 0 min to 30 min (−5.73 ± 10.14%), 60 min (−5.58 ± 11.36%), and 90 min (−5.92 ± 12.12%)  SBP at 30 min and 60 min compared to baseline SBP  . The IVM 12.12%) . After cp = 0.045) in mean (SD) potassium levels from 4.14 ± 0.36 mmol/L to 4.08 ± 0.37 mmol/L, but all were within normal clinical range. There was no significant cumulative effect on potassium levels between each dose of the cycle (p = 0.837). The mean (SD) random capillary glucose level was significantly increased from 7.76 ± 3.28 mmol/g to 11.87 ± 5.87 mmol/g after infusion (p < 0.001). There was also no significant cumulative effect on glucose levels between each dose (p = 0.563). There were 4 patients (10.5%) who required subcutaneous insulin therapy to correct the hyperglycemia, and all these subjects had preexisting type 2 diabetes mellitus.There was a significant decrease . However, if only the subjects with compressive optic neuropathy were analyzed, there was a significant improvement in both visual acuity and colour vision (p < 0.001) of VISA inflammatory score from mean score (SD) of 4.29 ± 1.14 before treatment to 1.92 ± 1.12 after treatment.Overall, there was improvement in both BCVA and colour vision after treatment after each cycle of 3 doses of 1 g IVMP, although it was not statistically significant  episodes of bradycardia (HR less than 50 bpm), 8 (3.3%) episodes of tachycardia (HR more than 100 bpm), and 12 (5%) episodes of moderate to severe hypertension or stage 2 hypertension (SBP > 160 mmHg or DBP > 100 mmHg) . These 1Pulsed methylprednisolone infusion for treatment of active TED has been shown to be relatively safe and effective. IVMP therapy is established to be effective in improving inflammation in active TED, more efficacious than oral steroids with less adverse events , 27. ConThe mechanisms by which steroids lead to hypertension may be multifactorial. Steroids result in sodium retention and volume expansion  and act There were three patients with thyroid dysfunction at baseline who developed moderate to severe hypertension during IVMP infusion. Both hyperthyroidism and hypothyroidism are associated with increased blood pressure; hypothyroidism is a recognised cause of secondary hypertension , and hypIVMP administration has been associated with cardiac arrhythmias in some studies , 36. AltIVMP may also cause hyperglycemia, especially in diabetic patients and transient deranged liver enzymes; thus careful screening of patient's glucose levels and liver function should be performed prior to IVMP administration , 38. In Hypertension and hyperglycemia may also result in pathophysiological changes in the retina, such as arteriolar narrowing, retinal haemorrhages, microaneurysms, exudates, and optic disc swelling , 42. AltMarinó et al. estimated acute liver damage in 0.8% of TED patients who underwent IVMP . They poDespite demonstrating a decrease in potassium levels after IVMP infusion, all the subjects' potassium levels were within normal clinical range. This may suggest that in relatively well patients with normal potassium at baseline, there is no need to recheck their potassium levels after IVMP administration. The caveat is that these patients should not have any underlying medical conditions that may result in them having electrolyte abnormalities, such as renal failure or use of medications such as diuretics.The main strengths of our study were the large number of 242 infusions analyzed and recorded patients who had multiple infusions administered with the long follow-up duration. The main limitations were the small number of study subjects and the large variance of dosage administered (cumulative dose: 1 g to 21 g) instead of a fixed cumulative dosage administered. However, such variation is expected in the management of patients with active TED where response to IVMP may be variable and other forms of second-line treatment may be required at different time points during the course of treatment.IVMP is a relatively safe and efficacious therapy for active moderate to severe TED and optic neuropathy. Overall, IVMP administration resulted in mild and noncumulative effects on heart rate and blood pressure. However, patients with poorly controlled hypertension, diabetes, or active liver disease should have their underlying conditions optimised before undergoing pulsed methylprednisolone therapy. Severe hypertension may occur during IVMP treatment in susceptible individuals such as those with underlying hypertension and uncontrolled thyroid dysfunction, whereas bradycardia may be more likely in those on beta-blockers. Patients whose potassium levels are normal at baseline and are not predisposed to hypokalemia from drugs or medical conditions may not require close monitoring of their potassium levels after every dose.


The purpose of the study was to verify the efficacy of using internal jugular vein (IJV) size and distensibility as a reliable index of fluid responsiveness in mechanically ventilated patients with sepsis.2), heart rate (beats/min), mean arterial pressure (MAP) (mmHg), central venous pressure (CVP) (mmHg) and arterial pulse pressure variation (PPV), coupled with ultrasound evaluation of IJV distensibility (%), defined as a ratio of the difference between IJV maximal antero-posterior diameter during inspiration and minimum expiratory diameter to minimum expiratory diameter x100. Patients were retrospectively divided into two groups; fluid responders (R), if CI increase of more than or equal to 15% after a 7 ml/kg crystalloid infusion, and non-responders (NR) if CI increased more than 15%. We compared differences in measured variables between R and NR groups and calculated receiver-operator-characteristic (ROC) curves of optimal IJV distensibility and PPV sensitivity and specificity to predicting R. We also calculated a combined inferior vena cava distensibility-PPV ROC curve to predict R.Hemodynamic data of mechanically ventilated patients with sepsis were collected through a radial arterial indwelling catheter connected to continuous hemodynamic monitoring system , including cardiac index (CI) (L/min/MP <0.05). An IJV distensibility more than 18% prior to volume challenge had an 80% sensitivity and 85% specificity to predict R. Pairwise comparison between IJV distensibility and PPV ROC curves revealed similar ROC area under the curve results. Interestingly, combining IJV distensibility more than 9.7% and PPV more than 12% predicted fluid responsiveness with a sensitivity of 100% and specificity of 95%.We enrolled 50 patients, of these, 30 were R. Responders presented higher IJV distensibility and PPV before fluid challenge than NR  contains supplementary material, which is available to authorized users. Fluid resuscitation is performed because it is assumed that the heart is operating of the steep ascending portion of the Frank-Starling curve (preload-responsive). However, fluid resuscitation in the non-preload-responsive patient may be deleterious if it promotes al edema . It is tSeveral studies have emphasized the reduced clinical value of static hemodynamic parameters, such as central venous pressure (CVP) and pulmonary artery occluding pressure, as compared with dynamic parameters in predicting fluid responsiveness ,3. Such Many clinical examples, from tricuspid regurgitation to heart failure, from right heart failure to both hypo- and hypervolemia illustrate that any time pressure and volume change within the intrathoracic systemic venous compartment a change also occurs in extrathoracic veins, such as in the intra-abdominal IVC or extra-thoracic internal jugular vein (IJV) -10. BaseSince IJV imaging does not require transesophageal echocardiography and is technically easier to perform than IVC visualization, we tested the hypothesis that respiratory changes in IJV diameter in mechanically ventilated patients would also predict fluid responsiveness.After approval from the ethical committee for human biomedical of Azienda Ospedaliero Universitaria Pisana and the University of Pittsburgh, a prospective study was established elaborating hemodynamic data obtained from patients presenting sepsis, according to the definition of, and treated following the indications of the Surviving Sepsis Campaign . Patient2O , PCO2 <40 mmHg , SaO2 >96%, with a tidal volume of 6 to 8 ml/kg, positive end-expiratory pressure (PEEP) of 6 cmH2O  and inspired oxygen fraction (FiO2) of 0.4.All enrolled patients older than 18 years were mechanically ventilated in mandatory minute ventilation (MMV) modality in supine position with the head elevated to 30°, and with ventilatory parameters adjusted to maintain Pplat <30 cmH2), heart rate (beats/minute), mean arterial pressure (MAP) (mmHg), CVP (mmHg) and pulse pressure variation (PPV) using the the Most Care®  continuous hemodynamic monitoring system based on the pressure recording analytical method (PRAM) algorithm [We analyzed a series of measured hemodynamic variables from an indwelling radial arterial catheter in septic patients. These data included cardiac index (CI)  examination of the IJV by the same operator. The ultrasound examination was performed with a 12-MHz linear transducer  and ultrasound system (MyLab™ 50 XVision). The IJV was visualized with two-dimensional echo at the level of the cricoid cartilage and recognized by compression, color Doppler and pulse wave Doppler sampling. As the patient position can influence IJV, all measurements were performed in the semi-recumbent position (head elevated 30°).The antero-posterior (AP) IJV diameter was measured using M-mode during a respiratory cycle. In order to avoid changes in vein diameter unrelated to respiratory variation, gentle pressure by the US probe was used to collapse the IJV in order to distinguish it from the carotid artery, then the pressure was relieved to the US probe-skin interface and attention was given to avoid influence of probe compression on IJV dimensions  during t0) and immediately after (T1) 30-minute volume expansion with a 7-ml/kg crystalloid infusion. IJV distensibility was evaluated offline by an investigator blinded to the results of the fluid challenge on CI. Two consecutive measures of IJV diameters were obtained before and after fluid challenge on the first 15 patients to evaluate intraobserver variability.All ultrasound measurements were performed before  if an increase in CI (ΔCI) ≥15% was obtained after volume expansion, and non-responders (NR) if ΔCI was <15%.P-value <0.05. Comparison between ROC curves was made using the De Long method.Data were expressed as median and IQR. The non-parametric Mann-Whitney and Wilcoxon test was used. The concordance correlation coefficient was obtained to assess intraobserver variability. Receiver operator characteristic (ROC) curves were built to obtain maximal sensitivity and specificity of PPV and IJV distensibility to predict fluid responsiveness . Furthermore, we analyzed the sensitivity and specificity of the combination of PPV and IJV distensibility in predicting fluid responsiveness. We classified patients in cases R or NR according to two criteria  using thresholds c1 and c2. In order to compute the ROC curve, we then quantified the number of observed true positive and true negative when we classified patients to be cases if y1 < = c1 and y2 < = c2, for a variety of c1 and c2 . Significance was defined by a From October 2012 to December 2013, we enrolled fifty septic patients . None of them suffered from acute respiratory distress syndrome (ARDS) at the time of enrollment. Hemodynamic and US evaluation data are reported in Table P = 0.01) and mean (P = 0.05) arterial pressure, and a decrease in HR (P = 0.0001), with no change in diastolic arterial pressure. No significant changes in arterial pressure and no variation in HR were observed in NR group. CI increased in both groups . Despite a significant increase in CVP after fluid challenge in all patients , there was no difference in CVP between R and NR before (P = 0.15) or after volume expansion (P = 0.49). R displayed a higher variation of CVP than NR (P = 0.01).Basal heart rate (HR) was not different between the R and NR groups either before or after the volume challenge, though HR tended to decrease with volume challenge in R. Responders displayed an increase of systolic (P = 0.0001) . Responders had a significant reduction of IJV distensibility from baseline to post-volume expansion (P = 0.0001) not seen in NR (P = 0.26). Responders showed a higher initial PPV than NR (P = 0.0001). This difference was lost following volume challenge (P = 0.2). Both R and NR displayed a decrease in PPV with volume expansion , though the decrease in PPV was greater in R (P = 0.0001).Responders presented higher IJV distensibility before volume expansion Figure  than NR ) Figure . This diROC curves were constructed to establish the sensitivity and specificity of CVP, PPV and IJV distensibility in predicting fluid responsiveness. No value of CVP discriminated between R and NR with good sensitivity and specificity (area under the curve (AUC) 0,68. CI 0,45, 0,75) (see Additional file The main finding of this study is that US assessment of IJV distensibility during positive-pressure ventilation can discriminate R from NR in critically ill septic patients. Furthermore, the combination of both IJV distensibility and PPV markedly increased the reliability of these predictive indices.The use of respiratory variations of arterial pressure and aortic flow are accepted bedside parameters of fluid responsiveness and are incorporated into the display screens of many monitoring devices and used to drive resuscitation algorithms . Static Although each dynamic measure may independently predict fluid responsiveness, combining several independently affected physiological parameters, like PPV and IJV distensibility, improves the sensitivity and specificity of these parameters to predict volume responsiveness. The improved performance of the combined measure is due, most likely, to the ability to assess both right and left sided volume responsiveness. IJV distensibility assesses venous return and right ventricular reserve while PPV assesses left ventricular response, both of which are central to controlling overall cardiovascular homeostasis.et al. used a gray-zone approach evidencing that when PPV decreases into a gray zone between 9 and 13%, uncertainty exists and clinicians should attempt to define volume responsiveness using additional measures [Most of the studies evaluating the ability of functional parameters to predict the CI response to volume challenge use ROC-curve analysis to define the optimal threshold, allowing for maximum sensitivity and specificity. Recently Cannesson measures . By combOur new measure of IJV diameter change is easily seen with US with minimal training, as this approach is frequently used for US-guided central vein catheterization. We demonstrated the reliability of IJV distensibility on detecting fluid responsiveness of ventilated patients with a value of 16.4% IJV distensibility having a sensitivity of 80% and a specificity of 85% in mechanically ventilated septic patients. Similarly, PPV threshold values of 12.5% have been reported in the literature to discriminate between R and NR with similar sensitivity and specificity. Thus, both PPV and IJV distensibility can be used to assess fluid responsiveness. Perhaps more interesting, the combination of both PPV and IJV distensibility improves the sensitivity and specificity of fluid responsiveness prediction with best results for values of IJV >9.9% and PPV of >12%. These data suggest that combining right- and left-sided dynamic parameters should improve their predictive values.cor pulmonale markedly alters other dynamic indices, often making them appear positive when not, we chose to also exclude these patients from our study. However, this patient cohort had a wide range of baseline cardiac reserve, as manifested by having only 30 of 50 patients being volume responsive. Therefore, in this initial validation study, any confounding condition, such as cardiac disease, jugular vein thrombosis or atrial fibrillation was excluded. Sixth, our only cardiovascular challenge was fluid loading. It is not clear if the use of vasoactive drugs, which may independently alter both CVP and the effective circulating blood volume, would independently affect the IJV distensibility index. This interaction and its interpretation remain to be assessed. Finally, as all measurements were performed by a single operator, inter-observer variability in IJV diameter measurement remains to be assessed in future studies.Our study has several limitations. First, all subjects were on mechanical ventilation and fully adapted to the ventilator. However, IVC collapse analysis remains predictive of fluid responsiveness in spontaneously breathing subjects, suggesting that the IJV distensibility index may remain valid as well. Still, the IJV distensibility index needs to be studied in spontaneously breathing subjects. Second, we did not also measure IVC collapse or stroke-volume variation, both measures of volume responsiveness similar in quality to our IJV distensibility and PPV measures, respectively. Still, PPV should be an acceptable surrogate for stroke-volume variation in this type of comparison. Third, changes in CVP influence the IJV pressure and diameter and may decrease relative distensibility. Conditions associated with increased intra-abdominal or intrathoracic pressure may potentially increase CVP and can lead to a reduced IJV distensibility index independent of preload responsiveness. We did not study the effect of high CVP on IJV distensibility. However, this process would have similar effects on both SVC and IVC collapse parameters. Accordingly, right-sided US indices, using large-vein collapsibility to predict volume responsiveness, require careful awareness of these potential limitations. Again, these specific clinical conditions may also minimize the predictive values of PPV as well. Fourth, patients’ position can influence IJV size. The supine position leads to increased IJV diameter, which is further increased in the Trendelenburg position, whereas sitting or standing can reduce the IJV filling and IJV diameter. Therefore, we made all our measurements from a standard 30° head of the bed elevated semi-recumbent position. However, since this is the recommended position for supine ventilated patients, to minimize aspiration, this limitation needs to be understood and positioning standardized in clinical practice if IJV distensibility index is used for clinical decision-making. Fifth, we did not include patients with cardiac disease, who would particularly benefit from functional hemodynamic monitoring. However, in this initial clinical study we did not aim to evaluate the effectiveness of such methods in those patients, because of the potential confounding effect that right heart failure would impose on venous pressures. As Ultrasound evaluation of IJV distensibility is a simple, easy, and readily accessible bedside measure that predicts volume responsiveness in critically ill ventilator-dependent septic patients. Importantly, the combined use of IJV distensibility with PPV increases the predictive value of these two volume-responsiveness parameters. Such right- and left-sided dynamic-measure predictor combinations need to be prospectively studied in future clinical trials.Internal jugular vein distensibility is a reliable index of fluid responsiveness in mechanically ventilated septic patients and is not inferior to pulse pressure variationThe combined use of Internal Jugular Vein and PPV could enhance the ability to discriminate fluid responsiveness during mechanical ventilationWritten informed consent was obtained from the patient in Figure


Although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure in adults with hypertension, how kidney function impacts this effect is not known. We evaluated whether Estimated Glomerular Filtration Rate (eGFR) modifies the effect of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function.Secondary analysis of the DASH-Sodium trial, a multicenter, randomized, controlled human feeding study that evaluated the blood pressure lowering effect of the DASH diet at three levels of sodium intake. Data from 92 participants with pre-hypertension or stage 1 hypertension during the 3450 mg /day sodium diet assignment contributed to this analysis. Stored frozen plasma and urine specimens were used to measure kidney related laboratory outcomes.2, range 44.1 to 138.6 ml/min/1.73 m2) or the presence of chronic kidney disease (N=13%).Effects of the DASH diet on blood pressure, phosphorus, intact parathyroid hormone, creatinine, and albuminuria were not modified by baseline eGFR (mean 84.5 ± 18.0 ml/min/1.73 mThe impact of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function does not appear to be modified by eGFR in this small subset of DASH-Sodium trial participants with relatively preserved kidney function. Whether greater reduction in eGFR modifies the effects of DASH on kidney related measures is yet to be determined. A larger study in individuals with more advanced kidney disease is needed to establish the efficacy and safety of the DASH diet in this patient population. Although often underemphasized in clinical practice, a mainstay of therapy for all individuals with hypertension is lifestyle modification . One suc2)  <60 ml/min/1.73 m2) ,9. It is2) -13. HencIn this secondary analysis of the DASH-Sodium trial, which includes participants with preserved or mildly reduced kidney function, we evaluated whether the BP lowering effect of the DASH diet is modified by eGFR. We also evaluated whether the DASH diet negatively impacted kidney-related laboratory measures as eGFR declined.The DASH-Sodium trial was a multi-center, randomized, controlled human feeding study that evaluated the effects of the DASH diet at three levels of sodium intake on BP in adults with pre-hypertension or untreated stage I hypertension. Detailed descriptions of trial methods and main results have been previously published ,4. An In2, consumption of >14 alcoholic beverages per week, pregnancy or breast-feeding, and kidney disease. Kidney disease was defined as either a serum creatinine >1.2 mg/dl for women and >1.5 mg/dl for men (unless eGFR was ≥60 ml/min per Cockcroft-Gault equation) [DASH-Sodium participants were ≥22 years old with mean Systolic BP (SBP) of 120-159 mmHg and mean Diastolic BP (DBP) of 80-95 mmHg. Exclusion criteria were use of antihypertensive medications or nutritional supplements, history of cardiovascular disease, type 1 or poorly controlled type 2 diabetes mellitus, poorly controlled hyperlipidemia, Body Mass Index (BMI) >40 kg/mAfter a 2 week run-in period, participants were randomized to receive either the DASH diet or a control diet in parallel group design. The composition of each diet is shown in Our analyses included only those participants for whom both stored pre-intervention plasma and urine specimens were available, which allowed us to measure necessary labs to assess baseline eGFR, albuminuria and CKD status. We used DASH-Sodium trial data to evaluate change in BP from the beginning to the end of the 30-day high sodium (3450 mg/d) feeding period, which was the sodium intake typical of most Americans at the time and equivalent to the sodium level provided in the original DASH trial . Weight Detailed description of the BP measurement protocol has been previously published . BP measFasting plasma specimens and 24-hour urine collections were obtained during screening and the last week of each intervention period and subsequently frozen at −70°C. We retrieved and thawed available frozen plasma specimens to measure phosphorus (colorimetric method), intact parathyroid hormone , and creatinine (kinetic Jaffe method). Urine specimens were thawed to measure albumin (immunoturbidimetric method) and creatinine concentrations . Frozen specimens had no prior freeze-thaw cycles. We were unable to measure plasma potassium and calcium concentrations because blood was collected into vacutainers containing Ethylenediaminetetraacetic Acid (EDTA), an anticoagulant that contains potassium salts and chelates calcium, resulting in inaccurate potassium and calcium measurements.2 or if albuminuria was present at any eGFR. Participants with CKD were classified into the following standard stages: Stage 1=eGFR ≥ 90 ml/min/1.73 m2 with albuminuria, Stage 2=eGFR of 60-89 ml/min/1.73 m2 with albuminuria, and Stage 3=eGFR of 30-59 ml/min/1.73 m2.Estimated GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation . ParticiPrimary outcomes were change in SBP and DBP during the 30 day high sodium intervention period, comparing DASH to control by level of kidney function. Secondary outcomes were changes in phosphorus and iPTH  and changes in creatinine, eGFR, and UACR (measures kidney function) from the screening period to the end of the high sodium intervention period.Standard descriptive statistics were used to determine baseline demographics, physical measures, and laboratory data. Means, standard deviations, and ranges were computed for continuous variables and frequency counts with percentages were computed for categorical variables. Between group differences in continuous variables were compared using student’s t-test and categorical variables using chi-square test. Difference in between group changes in outcome variables was compared using general linear models. The relationship between eGFR and change in outcome variables were determined using multiple linear regressions. All models were adjusted for site, intervention period, baseline eGFR, and each respective baseline variable. Additionally, SBP and DBP were adjusted for race, gender, age and BMI. Regression models included an assessment for interaction between diet and baseline eGFR. Interactions between diet and the following variables were also assessed: evenly distributed eGFR quartiles , CKD stages (1-3), and CKD status . Goodness-of-fit of the models were assessed. These were exploratory analysis and no adjustment is made for multiple testing. A significance level of 0.05 was used for all tests. Statistical analysis was performed using SAS 9.3 .2; p<0.01). All other demographic and baseline physical measurements were similar. 2 with a wide range from 44.1 to 138.6 ml/min/1.73 m2 and 70% had a baseline eGFR >75 ml/min/1.73 m2. A total of 12 (13%) participants had CKD . Compared to those with normal kidney function, participants with CKD had a higher mean baseline plasma creatinine concentration , lower eGFR , greater albuminuria , and higher mean SBP  at study entry. Participants with CKD also tended to be older than those with normal kidney function but this was not statistically significant .There were a total of 412 participants enrolled in the DASH-Sodium trial. After exclusion of participants with missing baseline plasma or baseline urine samples, 92 (22%) individuals were included in our analysis. Compared to those who were excluded, our subset of participants were younger  and had a higher mean BMI  but not the control group  in both the unadjusted (data not shown) and adjusted models . BetweenPlasma phosphorus did not change after the 4-week feeding intervention within or between the two diet groups . In the Plasma creatinine and eGFR did not change significantly in either the DASH or control groups after the 4-week feeding intervention in both unadjusted and adjusted models . BetweenAdjusted multiple linear regression models were performed to determine if the relationship between diet and change in each outcome variable was altered by kidney function. Separate models were performed to evaluate kidney function by baseline eGFR, eGFR quartiles (Q1-Q4), CKD stage (1-3) and CKD status (yes or no). For each of these models, the effect of the DASH diet on change in SBP, DBP, phosphorus, iPTH, creatinine, eGFR, or UACR did not vary by level of kidney function. In this secondary analysis of the DASH-Sodium trial, we were able to evaluate the impact of the DASH diet on BP, markers of mineral metabolism, and kidney function as well as how these relationships may be influenced by level of kidney function. After a 4-week feeding intervention in adults with pre-hypertension and untreated stage 1 hypertension, we confirmed previous findings from the DASH-Sodium trial and other feeding studies that the DASH diet lowers SBP, even in a subpopulation with mildly decreased kidney function ,3,17. AlOur aim was to determine if kidney function modified the effect of the DASH diet on BP. Current knowledge about the management of hypertension in patients with CKD, as well as the effects of the DASH diet in various patient subgroups, could lead to two opposing hypotheses. On one hand, the DASH diet may be hypothesized to have a smaller BP lowering effect as eGFR declines because patients with CKD tend to have more difficult to control hypertension than those with preserved kidney function. For example, patients with CKD have a higher prevalence of uncontrolled hypertension and require a greater number of medications to achieve BP goals when compared to those without CKD ,18,19. OEvidence that the DASH diet reduces BP is insufficient alone to recommend it to patients with CKD because evidence of its safety is also required. Unfortunately, we were unable to directly measure serum concentrations of key electrolytes, such as potassium and calcium. Our small sample size of participants with CKD further limits or ability to compare those with reduced and preserved kidney function. Presumably at a certain eGFR, the DASH diet could in fact cause a rise in these serum electrolytes; the “safe range” of eGFR is yet to be determined.To our knowledge, an association between the DASH diet and changes in plasma iPTH or phosphorus has not been demonstrated. Under normal conditions, serum calcium and phosphorus are tightly regulated by interplay between both vitamin D and parathyroid hormones which act on bone, the intestines, and the kidneys to maintain physiologic balance. A previous study demonstrated urinary excretion of both calcium and phosphorus to be higher for participants on the DASH diet compared to the control diet, reflecting higher dietary intake . UnexpecEstimates of renal function were not altered by the DASH diet, despite its higher protein content. Restricting protein for individuals with reduced kidney function remains controversial since important clinical trials that evaluated whether protein restriction slows disease progression were inconclusive or showed only modest benefit ,23. Our 2) suggesting that this difference may not necessarily influence the expected impact of DASH on BP in our study [2, none less than 44 ml/min/1.73 m2, and only 13% were classified as having CKD. A larger study in patients with lower kidney function is clearly needed to definitively establish the efficacy and safety of the DASH diet in this population, albeit with caution due to risk of hyperkalemia.We acknowledge that our study has some limitations. Inclusion of a small subset (22%) of participants who were enrolled in the DASH-Sodium trial potentially introduces bias from unbalanced comparison groups. Compared to participants who were excluded, our subset was younger and had a higher BMI. However, in a subgroup analysis of the DASH-Sodium trial the effect of the DASH diet did not vary by age (>45 years) or BMI (≥30 kg/mur study . AnotherIn this small subset of DASH-Sodium participants, our findings suggest that kidney function, as measured by eGFR, does not modify the effect of the DASH diet on blood pressure or markers of mineral metabolism and kidney function. If confirmed in a larger population of patients with less preserved kidney function, the DASH diet may be a valuable, nonpharmacologic strategy for BP control in individuals with CKD.


Objective. The present study aimed to examine the association between serum BPA and hypertension and evaluated whether it was influenced by estradiol level. Methods. A subsample of 2588 sera randomly selected from the Thai National Health Examination Survey IV, 2009, was measured for serum BPA and estradiol. Logistic regression was used to examine the association controlling for age, sex, diabetes, body mass index, and estradiol level. Results. Compared with the lowest quartile, the adjusted odds ratio (AOR) of hypertension for the fourth quartile of serum BPA was 2.16  in women and 1.44  in men. There was no interaction between serum BPA and estradiol level. For analysis using log(BPA) as a continuous variable, the AOR per unit change in log(BPA) was 1.09 . Among postmenopausal women, the AOR for the fourth quartile of BPA was 2.33  and, for premenopausal women, it was 2.12 . Conclusion. Serum BPA was independently associated with hypertension in women and was not likely to be affected by estrogen; however, its mechanism related to blood pressure needs further investigation. Bisphenol A (BPA) is a widely used chemical in the production of plastic food containers in many consumer products and of epoxy resins in dental fillings. Exposure to BPA is very common in almost all US adults , Asian pGlobally, high blood pressure is the most common risk factor for cardiovascular diseases death. It contributed to 40% of cardiovascular deaths in 2010 . AlthougData were from Thai National Health Examination Survey (NHES) 2009. Details of sampling methods were described previously elsewhere . In brieThe NHES was approved by the Ethics Committee of Ministry of Public Health, and written informed consent was obtained from all participants. This study was also approved by the Ethics Committee of Ramathibodi Hospital, Faculty of Medicine, Mahidol University.β-estradiol (E2) were determined by electrochemiluminescence immunoassay on a Cobase 411 analyzer (Roche Diagnostics GmbH). The intra-assay precision was 4.3%.Demographic data such as age and sex were included. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. Serum BPA levels were measured by competitive ELISA  with an intra-assay and interassay precision of 11.8% and 13.6%, respectively. Serum levels of 17Measurements of blood pressure were performed by trained field research assistants using automatic sphygmomanometer Microlife model A100  with appropriate arm cuffs. Prior to measurement, participants rested for 5 min in a sitting position according to the standard protocol . Three mAlcohol drinking is defined as self-reported alcohol beverage consumption in the past 12 months. Smoking is defined as follows: current cigarette smokers were defined as individuals who had smoked ≥100 cigarettes during their lifetime and at the time of interview responded that they smoked every day or some days .Hypertension is defined as mean systolic blood pressure (SBP) equal to or greater than 140 mmHg or mean diastolic blood pressure (DBP) equal to or greater than 90 mmHg or on medication to lower blood pressure in the past two weeks. Unaware hypertension is defined as individuals with hypertension, who have never been told by health professionals that they had hypertension. In the analysis, we also examined the association with those who treated hypertension in the past two weeks and for those who were diagnosed but did not receive medication to lower their blood pressure.t-test was used to compare means between groups. Geometric mean of BPA was calculated and used due to the skewness of BPA distribution. BPA level was categorized into quartile. Means and proportions of several clinical variables including pulse pressure, SBP, DBP, fasting plasma glucose, serum estrogen level, diabetes, and several hypertension status variables were calculated according to quartile of BPA and then compared. Logistic regression was used to examine the association between BPA and blood pressure and hypertension status. First, each hypertension status variable was regressed on the log(BPA) as a continuous variable in the model. Potential confounding variables that were adjusted included age, sex, BMI, alcohol drinking, smoking and diabetes status, and estradiol level. We tested for the interaction between BPA and estrogen level by adding an interaction term between log(BPA) and estradiol level in the model. To handle the problem of missing values of log(BPA) for undetected BPA level as zero, individuals with zero BPA level were assigned to 0.005 . We also ran logistic regression using quartile of BPA as categorical variable in the model. To determine whether the effects of BPA or hypertension status varied by menopausal status, an additional stratified analysis for the association of BPA and hypertension was performed separately for premenopausal and postmenopausal status. There were 19 postmenopausal women having history of taking hormone supplement; however, excluding this group of women did not change the results, so we did not exclude them from the analysis. All the analyses were performed using Stata software version 10.1 . Statistical significance was set at a P value of <0.05.All analyses took into account the complex survey design by weighting for the total population. Descriptive statistical analyses of percentages, means, and standard variation (SD) were performed. Student's unpaired P < 0.001). Women had a higher BMI compared with men.P < 0.01), especially in women (P < 0.01). Geometric means of BPA were also higher among other hypertension variables designated for high blood pressure such as those with unaware hypertension and among those with high SBP ≥ 140 mmHg. There were no significant differences in BPA levels between smokers and nonsmokers as well as between alcohol drinkers and nondrinkers.P = 0.03 and 0.04, resp.), but not in men.The present study revealed that serum BPA was independently associated with hypertension. The positive association was found for all hypertension and unaware HT among women. The association was not likely to be confounded by age, sex, BMI, diabetes, and estrogen level. Although there was no clear interaction between BPA and estrogen level, the association between BPA and hypertension appeared to be stronger among postmenopausal women. The positive association between serum BPA and hypertension was consistent with studies using urinary BPA as surrogate. Bae and colleagues reported that urinary BPA was positively associated with blood pressure but negatively associated with heart rate variability . Shankarβ can reduce systematic arterial pressure via autonomic influence [β knockout mice [Mechanism of action of BPA on cardiovascular system is complex and the mode of action on blood pressure is unclear; however, there are several pathways that might be possible. A study suggests that exposure to BPA is related to insulin resistance and its role in weight gain and obesity . Activatnfluence . Hyperteout mice , 28. BPAout mice , and hypout mice . Endotheout mice . Insulinout mice .α) but acts only as an agonist for estrogen receptor beta (ERβ) [α through increase in eNOS and cyclooxygenase resulting in vasorelaxation [Effects of BPA binding to estrogen receptors on cardiovascular system might be different from those of estrogen. BPA has dual actions as an agonist and antagonist of estrogen for estrogen receptor alpha (ERta (ERβ) . Estrogelaxation , 21. TheThe different degrees of association according to criteria for hypertension were observed. The association was strongest for all hypertension but was weaker for high SBP and high DBP. This could be due to the fact that some individuals with hypertension were treated medically to lower BP level leading to an attenuated magnitude of association. For treated or untreated hypertension, the associations were relatively consistent suggesting that the medication for hypertension was not likely to affect the association.There are some limitations in the present study. First, the present study used serum BPA as surrogate for BPA exposure which may have low sensitivity to reflect the burden of BPA in the body compared to urine BPA . HoweverIn conclusion, the present study revealed that exposure to BPA was positively associated with hypertension and the results were not confounded by common risk factors. Effect of BPA on high blood pressure might be stronger in postmenopausal women; however, its mechanism related to estrogen on blood pressure needs further investigation.


Halotherapy (HT), derived from speleotherapy in salt mines, is also a drug-free therapeutic method. HT effects vary depending on the therapeutic method and the structure of halotherapy environment.The purpose of this article is to show the HT effects of “halotherapy chamber with artificial salt-mine environment” of the National Institute of Rehabilitation, Physical Medicine and Balneoclimatology (INRMFB), on patients with bronchial asthma and other chronic, infectious-inflammatory and allergic respiratory diseases, describing the clinical effects on certain nonspecific resistance factors, on markers of inflammatory processes and on certain immunological changes.Patients were clinically assessed, with the application of hematologic investigations, analysis of nonspecific resistance to infection and of inflammatory process markers, immunologic assessments, analysis of sodium and potassium concentrations, of mineralocorticoid function and other biochemical tests. For the experimental HT therapy performed in the “halotherapy chamber with artificial salt-mine environment” of INRMFB, 15 patients suffering from bronchial asthma, allergic rhinitis, chronic bronchitis, chronic obstructive bronchopneumopathy were selected, based on specific medical indications and contraindications and applying ethical principles, as well as 4 patients with similar pathologies for the control group, who underwent in-home drug treatment. After the specific halotherapy treatment on patients with bronchial asthma, chronic bronchitis and chronic obstructive bronchopneumopathy, which also showed other chronic, infectious-inflammatory and allergic respiratory pathologies, triggering of anti-inflammatory  mechanisms and healing effects on inflammatory process were noted. Data acquired also proved the halo therapeutic effect causing the reduction of sensitiveness of body in patients with bronchial asthma. Abbreviations: HT=Halotherapy, INRMFB=National Institute of Rehabilitation, Physical Medicine and Balneoclimatology Halotherapy, derived from speleotherapy in salt mines, is also a drug-free therapeutic method, applied especially on patients with bronchial asthma and chronic bronchitis. Following the “survey for the innovative use of potentially therapeutic salt-mine environment factors, in health and balneoclimateric tourism; modeling solutions”, the conceptual model was elaborated, subsequently converted into an experimental functional model entitled “halotherapy chamber with artificial salt-mine environment”, destined for surface halotherapy and built within the National Institute of Rehabilitation, Physical Medicine and Balneoclimatology. This model was followed by surveys in the underground salt-mine environment, destined to assess the presence and quality of factors with speleotherapeutic / halotherapeutic potential, medical-biological multi-discipline surveys, including organismic and cellular-level analysis, before and after the experimental halotherapy treatment, on lab animals – Wistar rats with pathology experimentally induced by sensitization with ovalbumin.1,2], the “Inception medical indications for the selection of patients with certain chronic respiratory pathologies for experimental halotherapy treatment” were elaborated.Based on the experimental results acquired .The phagocytosis process is one of the promptest defensive mechanisms against infection. The phagocytic cells are generated from precursor cells of bone marrow and they divide into macrophagous and microphagous cells. In blood, macrophagous cells are represented by monocytes, and microphagous cells – by polymorphonuclear neutrophils (PMN), which account for app. 60% of leukocytes and which are also the most significant phagocytic cells [The selection of patients intended for the application of experimental HT treatment in the “halotherapy chamber with artificial salt-mine environment” of INRMFB was made based on medical indications and contraindications obtained, including: I. Indications1. Patient age: 7-60 years old; infants under 10 years must be accompanied by parents. 2. Gender: female or male.3. Non-allergic / intrinsic / non-atopic asthma, allergic / extrinsic / atopic asthma, asthmatic bronchitis:(1) With negative allergological tests or atopic skin tests  or positive tests ;(2) eosinophils (Eo) – high or normal count in blood and ∕ or in expectorated sputum;(3) relatively non-severe clinical evolution;(4) asymptomatic period with or without bronchial obstruction, without asthmatic seizures; (5) symptomatic period with proven bronchial obstruction, without asthmatic seizures or severe asthmatic conditions; 4. intermittent bronchial asthma, without medication or with symptomatic medication (patient’s medication):(1) with no asthmatic seizures or severe asthmatic conditions; (2) with no negative evolution (frequent seizures or severe asthmatic conditions) caused by physical stress (Exercise-Induced Asthma);(3) with no negative evolution (frequent seizures or severe asthmatic conditions) caused by humidity, changes in air temperature, gases of other microclimatic parameters (Airways Asthma);(4) with or without non-allergic rhinitis;(5) with or without nasal polyposis; (6) with or without sensitiveness to aspirin or other drugs;5. chronic bronchitis, asymptomatic or symptomatic period without a negative evolution, without medication or with symptomatic medication (patient’s medication);6. chronic obstructive bronchopneumopathy (BPOC), asymptomatic or symptomatic period without a negative evolution , without medication or with symptomatic medication (patient’s medication);7. allergic and chronic, infectious-inflammatory rhinitis and sinusitis, intermittent or slightly persistent, asymptomatic or symptomatic period without a negative evolution, without medication or with symptomatic medication (patient’s medication);II. Contraindications:1. Complications of asthmatic seizures .2. Severe persistent form of bronchial asthma, with no drug control.3. Asthma with continuous dyspnea and severe asthmatic conditions with violent, subintrant seizures, with a duration of 12-48 hours, treatment-resistant, no cough and expectoration, with: polypnea, asphyxia, cyanosis, vascular collapse, drowsiness. 4. Bronchial asthma with negative evolution (frequent seizures or severe asthmatic conditions) caused by physical stress (Exercise-Induced Asthma). 5. Bronchial asthma negative evolution (frequent seizures or severe asthmatic conditions) caused by humidity, changes in air temperature, gases of other microclimatic parameters (Airways Asthma).6. Severe medication-related complications .7. Acute bronchitis. 8. Heart failure II – III.9. Tuberculosis. 10. Sub-compensated and decompensated cardiopathies. 11. Cardiosclerosis. 12. Hypertonia II-III.13. Acute renal diseases, lithiasis, enuresis. 14. Acute hyperacid gastritis.15. Hepatitis or acute cholecystitis. 16. Diabetes, severe form.17. Colagenosis, acute rheumatic diseases. 18. Cerebral trauma, neuroinfections, cerebral dysfunctions / central or peripheral neurologic diseases, epilepsy. 19. Otitis, acute internal ear diseases.20. Claustrophobia, depressions, neurosis. 21. Emphysema and BPOC complications .22. Post-surgery period up to 2 months. 23. General contraindications for referral to balneary treatment and physiotherapy.When patients for the experimental HT treatment were selected, 18 patients were investigated (16 adults and 2 infants with ages between 6–13 years) with bronchial asthma and chronic bronchitis, chronic obstructive bronchopneumopathy, of whom 14 had bronchial asthma with therapeutic control and partial control , also suffering from other pathologies like allergic rhinitis (including moderate persistence), rhinosinusitis, respiratory virosis, viral post-pneumonia condition, chronic gastritis, duodenal ulcer, ischemic coronary disease, light mitral failure, atopic dermatitis, chronic bronchitis, hypertensive cardiomyopathy, HTAE 1-2 degree, lumbar discopathy, cervical spondylosis, osteoporosis, hypothyreosis, hemorrhoid disease, dyslipidemia, obesity III degree, urinary infection; 4 patients with chronic bronchitis or chronic obstructive bronchopneumopathy (II and III) with acute exacerbation of GOLD (1 case), showing arrhythmia, tachycardia, dyslipidemia. Subsequently, all the patients underwent medical-biological investigations. Fig. 1). After medical and medical-biological investigations, 15 patients  were chosen for the experimental halotherapy (HT) treatment in the “halotherapy chamber with artificial salt-mine environment” of INRMFB  out of the 15 patients from the group subjected to HT treatment. The clinical adaptation of patients to the underground environment condition was found after 5–10 days of HT procedures, depending on the pathology and clinical progress of illness. After 10 days of HT procedures, a scarceness of cases and significant reduction in severity – until full regress – of irritative dry cough was seen in investigated patients, and after 12–15 of specific HT treatment – absence of dry cough and wheezing, and also for 2/3 of investigated patients  – rare cases of cough with viscous expectoration (1–3 expectorations in the last HT treatment procedures), and also cough with liquid expectoration and increase of expectorated sputum volume was noticed . During the treatment period, no severe asthmatic conditions or additional infections occurred. ¼ of the investigated patients were characterized after 15 days of HT procedures, or 5–10 days after the HT treatment was ceased, or after gradually reducing the dose of specific medications  to 20-30%. The patient with bronchial asthma and duodenal ulcer ceased the halotherapeutic treatment during the 3rd HT procedure, upon recommendation of the INRMFB physician, due to duodenal pains, and another patient with chronic bronchitis – during the 7th HT procedure, due to digestive issues occurred at home before the HT procedure, and resumed treatment after three days. The halotherapeutic treatment was also interrupted in one patient with bronchial asthma, during the 10th HT procedure, on the family doctor’s recommendation, due to acute exacerbation of cervical spondylosis pains. The data gathered proved the need for additional specific surveys on patients with chronic infectious-inflammatory and allergic respiratory diseases accompanied by other pathologies.The average blood count of phagocytes – neutrophils PMN in patients with bronchial asthma and other respiratory allergies, as well as in patients with chronic bronchitis or chronic obstructive bronchopneumopathy was found to be lower compared to the lower limit of “normal (“reference”) values”, cases with lower test values being noted in 9 of 13 patients with bronchial asthma and other allergies  and in patients with infectious-inflammatory bronchopulmonary diseases . The relative count of formasan-positive PMN neutrophil cells (in nitroblue tetrazolium test) was found to be high in blood for most investigated patients  and for patients with chronic bronchitis or chronic obstructive bronchopneumopathy. Thus, most of the investigated patients showed a deficit in the phagocytosis activity prior to the halotherapeutic treatment and also a decrease in the oxidative metabolism of phagocytes – granulocytes PMN in blood being noted. Based on data acquired after the experimental halotherapy (HT) treatment, the triggering of non-specific resistance parameters of the body was noted  in patients (including infants) subjected to specific halotherapy treatment, compared to “normal values” and to values found in control patients, respectively with chronic respiratory pathology and drug treatment .The results obtained showed the positive effect of experimental halotherapeutic treatment related to the stimulation of phagocytosis process and the increase in non-specific anti-infection resistance of the body, a fact noted based on the ascendant trend of phagocytes PMN in blood and the activation of oxygen-dependent bactericide action of granulocytes PMN (nitroblue-tetrazolium test) in patients with bronchial asthma and allergic rhinitis and in those with chronic bronchitis, chronic obstructive bronchopneumopathy . Still, the fact that the low number of patients with chronic bronchitis and chronic obstructive bronchopneumopathy did not allow the mentioning of significant positive changes should be mentioned, and, therefore, in this case, the extension of the respective surveys is needed.The assessment of results achieved in the investigated patients with bronchial asthma, chronic bronchitis and chronic obstructive bronchopneumopathy, after a specific halotherapy treatment, indicates the triggering of an anti-inflammatory  mechanism and a decreasing trend of the inflammatory process.Data acquired indicate a decrease in the body’s sensitiveness and in infectious-inflammatory process in patients with bronchial asthma after HT treatment, and it also proves the need to extend the period or to repeat the halotherapeutic treatment.


Different from many other species, human beings spend nearly two-thirds of the day in an upright posture. Due to gravity, about 700 to 900 ml of blood shift into the lower body during quiet standing. As a result, central blood volume decreases and this leads to a series of neural-humoral adjustments that aim to maintain the mean arterial pressure during orthostasis. Both the sympathetic nervous system and the renin-angiotensin-aldosterone system contribute importantly to the arterial pressure maintenance in upright humans. There is a growing interest in the blood pressure regulation during orthostasis in healthy individuals and patient populations. This e-book provides some updates on sympathetic neural control and renal-adrenal function in health and disease.Sympathetic neural activity regulates blood pressure mainly through the baroreflex-mediated vasoconstriction during orthostasis. The baroreflex is a closed-loop feedback system, but requires open-loop experiments to identify its characteristics, which is impossible in human research. Kamiya et al. demonstrated that system identification based analysis and numerical simulation using baroreflex subsystem characteristics identified in animal models may contribute to our understanding of human sympathetic physiology under orthostasis syncopal symptoms. Arnold et al. showed that ergotamine combined with caffeine could be used as an alternate treatment in carefully selected patients without comorbid coronary artery disease (Arnold et al., Taken together, this e-book highlights only a small portion of the recent advances in neural-humoral control during orthostasis in humans. More research is needed to better understand the role of the sympathetic nervous system and the renin-angiotensin-aldosterone system in the regulation of blood pressure in health and disease.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Aim. Increased aortic stiffness might adversely affect cardiac structure, function, and perfusion. Release of biomarkers of hemodynamic stress is thought to be enhanced by these alterations. We aimed to evaluate the association between biomarkers of hemodynamic stress and aortic stiffness assessed at a chronic stage after ST-segment elevation myocardial infarction (STEMI). Methods. Fifty-four patients four months after STEMI were enrolled in this cross-sectional, single-center study. N-terminal pro–B-type natriuretic peptide (NT-proBNP), mid-regional pro–A-type natriuretic peptide (MR-proANP), and mid-regional proadrenomedullin (MR-proADM) levels were measured by established assays. Aortic stiffness was assessed by the measurement of pulse wave velocity using phase-contrast cardiovascular magnetic resonance. Results. NT-proBNP, MR-proANP, and MR-proADM concentrations were all correlated with aortic stiffness in univariate analysis . In multiple linear regression analysis, NT-proBNP  and MR-proADM  levels were associated with increased aortic stiffness independently of age, blood pressure, and renal function. NT-proBNP was the strongest predictor for high aortic stiffness . Conclusion. At a chronic stage after STEMI, concentrations of biomarkers for hemodynamic stress, especially NT-proBNP, are positively correlated with aortic stiffness. These biomarkers might also be useful as predictors of high aortic stiffness after STEMI. In the last two decades, multiple studies have shown that increased arterial stiffness is independently associated with cardiovascular morbidity and mortality –4. A recNatriuretic peptides (NPs), such as N-terminal pro–B-type natriuretic peptide (NT-proBNP) and mid-regional pro–A-type natriuretic peptide (MR-proANP), are synthesised and secreted by cardiomyocytes . AlthougFrom November 2010 to March 2012, 54 eligible patients with first STEMI admitted to University Hospital of Innsbruck were included in this cross-sectional, single-centre study. STEMI was diagnosed according to the redefined ESC/ACC committee criteria [Heparinized blood samples were collected from all patients 4 months following STEMI by peripheral venipuncture. Samples for NT-proBNP were promptly analysed at the central laboratory of the University Hospital of Innsbruck by personnel blinded to study data. MR-proANP and MR-proADM were measured in batches after storage at −80°C. Assays used for the determination of NT-proBNP, MR-proANP and MR-proADM have previously been described , 21. BriWe used velocity-encoded, phase-contrast CMR imaging for the determination of PWV as described in detail previously , 11, 22. P value < 0.05 in univariate analysis were included into the models. Differences in continuous variables between groups were determined by ANOVA test. To calculate the predictive utility of biomarkers  for increased PWV, receiver operating characteristic (ROC) analysis was applied. For all data, a two-tailed P value of <0.05 was considered to indicate statistical significance.Statistical analysis was performed with SPSS Statistics 19  as well as MedCalc Version 13.1.2.0 . Kolmogorov-Smirnov test was applied to test for normal distribution. Results for continuous variables are all expressed as mean ± standard deviation or as median with interquartile range if not normally distributed. Pearson or Spearman-Rho correlations were performed as indicated. To determine whether there is an independent relation between PWV and biomarker levels multiple linear regression analysis was used. Nonnormally distributed variables were log-transformed for multiple regression analysis. Variables with aP = 0.468, resp.). PWV was similar in patients with anterior STEMI and nonanterior STEMI (P = 0.547). There was no relationship between PWV and pain-to-balloon time . PWV was strongly correlated to patients' age . No significant correlation was found between PWV and blood pressure, body mass index, total cholesterol, creatinine, and estimated glomerular filtration rate . There was no significant difference in PWV between patients with or without diabetes (P > 0.05). Correlations between PWV and biomarkers of myocardial wall stress are shown in r = 0.378, r = 0.425, and r = 0.532; all P < 0.005, resp.). Partial correlation analysis revealed that NT-proBNP, log MR-proANP, and MR-proADM remained significantly correlated with PWV when adjusting for gender . In multivariate analysis, each marker was examined separately because of the close correlation between them . In the first model, age, eGFR, systolic blood pressure, diastolic blood pressure, and log NT-proBNP were taken as independent variables. This model revealed that NT-proBNP levels  and age  remained significantly associated with PWV . In the second model, age, eGFR, systolic blood pressure, and log MR-proANP were taken as independent variables. In this model age , but not MR-proANP , correlated with PWV . In the third model, age, eGFR, systolic blood pressure, and MR-proADM were taken as independent variables. Along with age , MR-proADM  remained significantly associated with PWV . Patients were also stratified in those with a PWV below  and above  the third quartile of PWV (=8.6 m/sec). The area under the curve (AUC) of NT-proBNP  with the optimal cut-off level of 270 ng/L revealed 86% sensitivity and 75% specificity for the prediction of an increased PWV. The AUCs of MR-proANP and MR-proADM for the prediction of an increased PWV  were lower compared with that of NT-proBNP, but the difference was not significant  (P > 0.300).= 0.284) . The comIn this cross-sectional study of fifty-four patients after first STEMI, we evaluated the association between a 4-month concentration of biomarkers for hemodynamic stress  and aortic stiffness. We found significant, positive correlations between these biomarkers and CMR-derived aortic stiffness. Our results suggest that these biomarkers, especially NT-proBNP, might be useful for identifying patients with elevated aortic stiffness as well.The association between arterial stiffness and cardiovascular risk has been well proven for a long time . IncreasOf note, there is enough evidence to show that central arteries stiffen with advancing age , 33, 34.The cross-sectional design of the study precludes conclusions on a potential causal and temporal relationship between aortic stiffness and the reported biomarkers. Mean PWV was similar to that of mean PWV reported in a previous study assessing PWV in the acute phase after STEMI . Hence, A major limitation of this work is the relative small sample size and the fact that females represent only 13% of the study cohort. In partial correlation analysis, the association between biomarkers and PWV remained significant when considering gender. Nevertheless, conclusions regarding gender related differences cannot be drawn from this study. Investigations with a higher patient number as well as a higher percentage of women are necessary to confirm our data and to characterize possible gender differences in detail.This is the first study showing that, at a chronic stage after STEMI, levels of NT-proBNP, MR-proANP, and MR-proADM are significantly associated with increased aortic stiffness. Among these biomarkers, especially NT-proBNP might be useful for predicting high aortic stiffness after STEMI. Larger investigations are needed to confirm the results of this study.