Evidence is mounting regarding the clinically significant effect of temperature on blood pressure.In this cross-sectional study the authors obtained minimum and maximum temperatures and their respective previous week variances at the geographic locations of the self-reported residences of 26,018 participants from a national cohort of blacks and whites, aged 45+. Linear regression of data from 20,623 participants was used in final multivariable models to determine if these temperature measures were associated with levels of systolic or diastolic blood pressure, and whether these relations were modified by stroke-risk region, race, education, income, sex hypertensive medication status, or age.After adjustment for confounders, same-day maximum temperatures 20°F lower had significant associations with 1.4 mmHg  higher systolic and 0.5 mmHg  higher diastolic blood pressures. Same-day minimum temperatures 20°F lower had a significant association with 0.7 mmHg  higher systolic blood pressures but no significant association with diastolic blood pressure differences. Maximum and minimum previous-week temperature variabilities showed significant but weak relationships with blood pressures. Parameter estimates showed effect modification of negligible magnitude.This study found significant associations between outdoor temperature and blood pressure levels, which remained after adjustment for various confounders including season. This relationship showed negligible effect modification. Pathways contributing to the development of hypertension are complex, and blood pressure (BP) levels are affected by season ,2. ThereTemperatures may have differing effects on autonomic and cardiovascular systems of different racial and ethnic groups, introducing the possibility that temperature is a contributor to the higher cardiovascular mortality observed in African-Americans compared to whites -7. ThoseWe examined the relationship between outdoor temperature and seasonality with blood pressure by linking data from a national longitudinal study with weather information available from satellite and ground-level assessments. In addition, we examined whether these relationships are modified by stroke-risk region, race, education, income, sex, hypertensive medication status, or age. To our knowledge, this study is the first large cohort study that includes a substantial representation of both black and white participants from the United States to explore these relationships performed.The assessment of the temperature-BP relationship was performed using participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. In brief, REGARDS is a longitudinal study with the goal of understanding racial and regional health disparities in stroke mortality and incidence . The parhttp://www.geocode.com using the Haversine formula [The current residence from the original recruitment file plus updated information from the participant at the time of scheduling the in-home exam was used to establish each participant's address, which was then geocoded using SAS/GIS batch geocoding. Information obtained from SAS/GIS with 80% accuracy or greater was utilized in these analyses. The results from the SAS/GIS procedure were validated against a commercially available program  formula . A mean  formula .(NASA's) Marshall Space Flight Center. We obtained daily maximum and minimum temperatures for 2003 to 2006 from the North American Regional Reanalysis (NARR), a data product produced by the National Center for Environmental Prediction (NCEP), a division of the U.S. National Weather Service. The product includes data from satellites and ground observations and is composed of a 32 km resolution grid over North America. NARR daily maximum and minimum temperatures were matched to the latitude and longitude of each participant's geocoded residence. All temperature measures were indexed to the date that the in-home BP assessment was performed.Temperature values were prepared and provided by National Aeronautics and Space Administration's All temperature measurements were modeled as continuous variables. Maximum and minimum temperatures were characterized either as "same-day temperatures" taken solely from the day of the in-home visit or as "2-week temperatures" calculated as the average of the two weeks prior to the date of the in-home visit (inclusive).We also examined temperature fluctuation and variability to determine whether the body's physiological adjustment and acclimatization, or possible behavioral changes  could have been involved in a participant's response to temperature ,16. TempSystolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were determined from the REGARDS in-home visit. Blood pressure was measured by a trained technician using a standard protocol and regularly tested aneroid sphygmomanometer and was calculated as an average of two measurements taken after the participant was seated for five minutes.Data for the current analysis included 26,018 participants without previous stroke or TIA. Of these, 3,868 (14.9%) participants with unacceptable geocoding (less than 80% accuracy) were excluded from this analysis. An additional 11 (< 0.1%) participants were excluded because of an age under 45 years, and 245 (0.9%) because of implausible recorded blood pressure data (SBP not between 75 and 275 or DBP not between 50 and 150), reducing evaluable participants to 21,894. Missing values of any of the potential confounders (primarily glucose assessment missing 747 and BMI missing 279) eliminated an additional 1,271 (4.9%) during regression modeling. Although income data was missing for 2,652 participants, previous REGARDS methods were followed by creating a separate "refused" category in this variable so that fewer participants would be excluded during regression modeling.th grade or less), race (black or white), smoking , alcohol use (never used or ever used), Body Mass Index (BMI) , hyperlipidemia (cholesterol > 240), diabetes status , age in years, hypertensive medication status (currently taking vs. not currently taking), and astronomical season  . The final multivariable models included all potential covariates. Parameter estimates with 95% confidence intervals (CIs) and p-values were calculated to measure the magnitude and strength of the associations between all predictors with DBP or SBP. In the final model we assessed interactions between temperature and race, region, education, income, sex, hypertensive medication status, and age. Lastly, likelihood ratio chi-squared and t-tests were used to assess differences between the 5,245 excluded and 20,773 included subjects in the final model.Linear regression models were used to assess the association between temperature and BP and to adjust for potential confounding by geographic region , population density defined by census tract , individual income , community-based income status (percent of census tract under poverty), years of education ; we used same-day measurements in model building since we knew participants were at or near their homes during this day. Daily temperature range and 2-day maximum and minimum temperature changes all showed non-significant associations with BPs (P > 0.05).Table SBP and DBP showed significant univariate relationships with season; mean SBP was approximately 2 mmHg higher and mean DBP was about 1 mmHg higher in the winter than the summer ; spring was not significantly different (P = 0.39). In the final model assessing the relationship between minimum temperatures and DBP, compared to summer, fall had 0.7 mmHg, winter had 1.2 mmHg, and spring had 0.9 mmHg higher DBPs . This is shown in Figures interaction > 0.05), but did between same-day temperatures and SBP (Pmax temps = 0.02 and Pmintemps = 0.03). Figure Chi-square tests on interaction variables indicated that income did not significantly modify the relationships between same-day temperatures and DBP (Pinteraction > 0.05), with the exception that the association between high temperatures and DBP were stronger among females than males (Pinteraction = 0.001). However, a 20°F maximum temperature difference was associated with less than 1 mmHg DBP in both males and females (0.3 and 0.8 mmHg respectively).The associations between same-day temperatures and blood pressure did not significantly differ by sex (Pinteraction > 0.05). After accounting for any significant interactions, the associations between a standard deviation change in temperature variability and SBP or DBP still did not exceed 1 mmHg, so we did not display any of this data.Race, stroke-risk region, education, anti-hypertensive medication use, and age did not show effect modification on any of the relationships between same-day temperatures and BP  and 2-day change (previous day high minus current day high) were not found to be associated with BP.This study adds to the body of literature showing that blood pressure varies by season, but demonstrates that this relationship is likely driven by temperature, rather than other factors that vary with the time of year, such as exercise, stress levels, mood, cognitive function, and various health behaviors and biological processes -24. FurtOur results indicated that the relationship of temperature with SBP or DBP differed only negligibly by stroke-risk region, race, education, income, sex, hypertensive medication status, or age. Given the large sample size of the REGARDS study, we feel that there was good statistical power to detect such differences if they did exist. Previous studies gave rise to question of whether environmental stresses have differing effects on black populations compared to white populations, but there were no racial differences in the relationships explored in our study ,33-35. BThis study was one of the few large population-based studies looking at associations of directly measured outdoor temperature and blood pressure ,11. AlpéThese two previous studies also differed by population ages. Alpérovitch et al., 2009 had an age range of 65 years and older, and in cross-sectional analyses found no interaction between age and temperature, which agrees with our study . HoweverA limitation of these previous studies is that they did not account for racial or other demographic differences unique to U.S. populations and climates. REGARDS is representative of African-Americans and whites across the entire 48 conterminous United States, with regional and racial sampling biases. Cardiovascular risk factors and relationships differ by country and have been shown to be different between the US and both countries with both developed and emerging economies across the world ; this stDue to the high proportion of participants (21%) excluded for poor geocoding or missing covariate data, bias remains a possible limitation of this study. Table Our study indicates that future studies looking at environmental impacts on blood pressure might not only use absolute temperature measurements, but also temperature variances. However, if the researcher has model simplification as a priority, our results indicate that this relationship might be best captured by using daily maximum temperatures as the exposure and SBP as the outcome. While it is possible these relationships differ by region, race, education, income, sex, hypertensive medication status, or age, our study provides evidence that the differences are likely not large.BMI: Body Mass Index; BP: blood pressure; CI: confidence interval;DBP: Diastolic Blood Pressure; NARR: North American Regional Reanalysis; NASA: National Aeronautics and Space Administration; NCEP: National Center for Environmental Prediction; REGARDS: Reasons for Geographic And Racial Differences in Stroke; SBP: Systolic Blood Pressure;The authors declare that they have no competing interests.STK performed the analysis and wrote the manuscript. LAM provided statistical and GH provided epidemiological guidance and was involved in the generation of the hypothesis. WLC provided meteorological expertise and provided the NASA data. RJP provided epidemiological and medical expertise. All authors read and approved the final manuscript.


Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD). It has variable presentation, ranging from hyposthenuria to end-stage renal disease (ESRD). Management of ESRD in SCD patients is froth with multiple challenges which has potential to impact negatively the outcome of the patient. Kidney transplant is the preferred renal replacement therapy in these patients. The objective of this case study is to report kidney transplant in a Nigerian young man with sickle cell nephropathy and to highlight the outcome and the challenges to kidney transplant in this patient. The index case is a 26-years-old sickle cell disease patient with ESRD complicated with cardiovascular, pulmonary, immunological, and infective challenges. These conditions were controlled, and the patient had a successful live-related kidney transplant. Kidney transplant is a viable option for sickle cell disease patients with ESRD. Sickle cell disease (SCD) is a haematological disorder associated with multisystemic complications and manifestations . Sickle Mechanisms of SCN include fortuitous occurrence, iron overload and its subsequent deposition in the kidney parenchyma, immune complex formations, and focal segmental glomerulosclerosis (FSGS) associated with glomerular hyperfiltration and intrinsic glomerular capillary injury , 4.Treatment of sickle cell nephropathy is fraught with many challenges as a result of antecedent complications prevalent in sickle cell disease patients. The outcome of treatment is usually variable. Renal replacement therapy is inevitable in SCN patients with uraemia, circulatory overload including pulmonary oedema and ESRD. Kidney transplant is usually renal replacement therapy of choice for eligible patients with ESRD barring other challenges and limitations. SCD and prevailing complications worsen these challenges, further limiting the prevalence of kidney transplant in these patients. However, in Nigeria and most developing countries kidney transplant is not readily available as a result of some factors which include poverty, ignorance, lack of transplant centres, and lack of donors . There aThe aim of this paper is to report and highlight the outcome of kidney transplant in a 26-year-old Nigerian patient with sickle cell Nephropathy. Mr DJ is a 26-year-old student, a male, who was diagnosed with SCA in childhood. He was adherent to his routine medications and regular to follow up. He presented with 2 weeks history of oliguria and passage of frothy urine. This was preceded by swelling of the leg and face a week prior to presentation. This was associated with anorexia, weakness of the body, early satiety, abdominal fullness, and nausea. There was no fever, vomiting, jaundice, or change in bowel habit. He had cough productive of frothy sputum but no haemoptysis or chest pain; however, he had dyspnoea, orthopnoea, and paroxysmal nocturnal dyspnoea.He has had few bone pain crises, and these were usually treated with rehydration, opiate analgesic, antimalarial, and/or antibiotics. He was transfused on 2 occasions as a result of the crises and twice during the course of this illness. He is not a known hypertensive or diabetic and no family history of same or kidney disease. There no positive history of use of herbs, mercury, alcohol, or tobacco. He is the only sickler in a family of 3 siblings; both parents are alive and well. He was conscious but in respiratory distress. He had anasarca, pallor, and asterixis but no cyanosis. The pulse was 108 beats/minute, full volume, and regular, the blood pressure was 160/90 mmHg, the praecordium was hyperactive, and apex beat was displaced and heaving. The heart sound heard were S1, S2, and S3 gallop with pansystolic murmur maximal at the apex. He had bilateral basal fine crepitations, distended abdomen with firm smooth hepatomegaly and ascites. He was conscious and had no asterixis. He was admitted as a case of sickle cell cardiomyopathy in congestive cardiac failure, with sickle cell nephropathy as a differential diagnosis. μmol/L, urea was 35 mmol/L, calcium was 2.3 mmol/L, total protein was 59 mg/dL, albumin was 28 mg/dL, total cholesterol was 5.2 mmol/L, LDL was 3.2 mmol/L, and HDL was 1.1 mmol/L. Investigations results revealed that urinalysis showed proteinuria 3+. PCV was 14%, blood film hypochromia, polychromasia, anisocytosis, and fragmented cells. The total and differential white blood cell count was normal, and ESR was 94 mm/hr. The serum sodium was 132 mmol/L, potassium was 4.1 mmol/L, bicarbonate was 13 mmol/L, creatinine was 645 The abdominal ultrasound showed bilateral shrunken kidneys, hepatomegaly, and ascites. Other viscera were normal. Chest X-ray showed marked cardiomegaly, pulmonary oedema as abnormality.Echocardiography revealed marked 4-chamber dilatation and biventricular failure.The diagnosis was then changed to sickle cell nephropathy with congestive cardiac failure. He was comanaged with the cardiologist.He was advised on low salt diet, care on protein intake, and was commenced on tabs Ramipril, hydrochlorothiazide, frusemide, digoxin, erythropoietin, folic acid, proguanil, vasoprine, and erythropoietin. He was also on twice weekly haemodialysis. He was transfused with 2 units of packed red blood cell.The haemodialysis including ultrafiltration and medication was regular; however, the breathlessness and ascites persisted. Weekly therapeutic abdominal paracentesis for symptomatic relief was then instituted while awaiting result of other investigations.Results of further investigations revealed sterile exudative ascitic fluid. Chest CT scan revealed enlarged heart, mild pericardial effusion, and prominent main pulmonary artery. Abdominal CT scan revealed bilateral small kidneys, gross ascites, hepatomegaly, cholelithiasis, dilatation of the portal vein, and prominent collaterals seen at the porta hepatis. BACTEC blood culture was positive for tuberculosis. Other investigations were consistent with previous results as documented above.The managing team then was expanded and included nephrologists, infectious disease physician, cardiologist, gastroenterologist, and haematologist.The frequency of haemodialysis was increased to daily, antituberculous therapy was commenced, and tabs Sildenafil were added to the medications above. He improved remarkably within 2 weeks of these regimens. The patient improved progressively, and 4 weeks later he had a successful and live-related kidney transplant. There was no operative or immediate postoperative complication. He is 1-year posttransplant, there was complication, and he has remained stable clinically, biochemically, and haematologically. His present blood pressure was 120/70 mmHg, PCV was 25%, sodium was 137 mmol/L, potassium was 4.1 mmol/L, Serum creatinine was 96 umol/L, serum urea was 5.3 mmol/L, and tacrolimus level was 4.8 ng/L.Sickle cell disease (SCD) patients with end-stage renal disease (ESRD) can be treated with all forms of renal replacement therapy: hemodialysis, peritoneal dialysis, or kidney transplant. Our patient was treated initially with haemodialysis and later had kidney transplant. Earlier reports suggested poor allograft survival and other disease-specific problems in SCD patients who had kidney transplant . HoweverThere was a trend toward improved survival in those SCD patients who received transplants compared to those on chronic dialysis. One-year patient and graft survival were 87 and 67%, respectively . In an uOjo and colleagues  reportedOur patient had a remarkable improvement following the transplant. There was no operative, postoperative patient, or graft-related complication. He is a year posttransplant, and there had not been any notable complication. The graft is structurally and functionally normal. The patient is clinically stable, and the blood pressure and haematological parameters were normal. There was no sickle crisis since the kidney transplant. And the patient had recommenced his education. Despite encouraging results on survival advantage of renal transplantation over maintenance haemodialysis, renal transplantation in sickle cell disease is used less frequently, possibly reflecting the limited experience with renal transplantation and/or the various challenges associated with kidney transplant in this patient population. Although many SCD patients as documented above including our patient have done well after renal transplantation, several unique challenges and complications have been described . The priPatients with sickle cell nephropathy are at risk of developing various haematologic, cardiovascular, pulmonary, and immunologic complications. These influence and compromise the choice, fitness, and outcome of kidney transplant in these patients. The impact of these conditions could manifest during pretransplant work-up, surgery, or posttransplant management. Various authors , 11 haveOur patient presented with various challenging features which included pulmonary oedema, pulmonary hypertension, cardiomyopathy, pericardiac effusion, cardiac failure, portal hypertension, marked ascities, abdominal tuberculosis, autosplenectomy, and multiple blood transfusion. These challenges are worrisome; it ranges from anaesthetic/surgical risk, difficulty in controlling pre- and posttransplant infection, marked immunosuppression and alloimmunization, and its impact in obtaining compatible donor to poor wound healing. Various suggestions for risk reduction have been made, including correction of anemia by simple or exchange blood transfusion, attention to hydration and oxygenation, postoperative respiratory care, and selection of less aggressive or extensive surgical procedures. The protocol specified a minimum of 8 hours of preoperative hydration, with intraoperative monitoring of temperature, blood pressure, electrocardiographic features, and oxygenation. Postoperative care included the administration of oxygen, intravenous hydration, monitoring with pulse oximetry, and respiratory therapy . The patBone marrow transplantation has recently emerged as a novel treatment for SCD. Anecdotal reports suggest a beneficial effect of bone marrow transplantation in improving target organ damage, including chronic lung, bone, and central nervous system disease. Whether bone marrow transplantation in the early stage of the disease can reverse or halt the progression of established sickle cell nephropathy is unknown and awaits clinical studies. Further more experience in stem cell and kidney transplant is lacking; however, it may have potential in improving the long-term outcome of kidney transplant in sickle cell patients .As noted above, the patient reported improved significantly on management of the prevailing challenging clinical condition he presented with and had uneventful kidney transplant. This could be attributed to adequate interventions taken in this patient including the multidisciplinary approach to combat the challenges with daily haemodialysis, therapy for infection, reduction of pulmonary and portal hypertension, induction immunosuppression, and extended nursing in intensive care unit. Patients with sickle cell disease requiring kidney transplant are also prone to challenges experienced by their normal counterpart. This varies from universal challenges like scarcity of donor to challenges peculiar to resource poor nations like poverty, ignorance, lack of facilities, and personnel .In conclusion kidney transplant in patients with sickle cell nephropathy is plagued with multiplicity of challenges; however, outcome is encouraging and comparable to that of patients with normal haemoglobin AA. There is need for multidisciplinary and subspecialty coordination in management of these patients. Thus sickle cell disease or trait should not be regarded as a contraindication to transplantation, at least from the patient and allograft survival standpoint.


The effect of impaired kidney function on B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) is vague. This study was performed to examine the effect of kidney dysfunction on the afore-mentioned markers and determine appropriate cutoffs for systolic heart failure (SHF).In this cross sectional study adults with estimated glomerular filtration rate (eGFR) <60 ml/min for ≥3 months were identified in consulting clinics from June 2009 to March 2010. SHF was defined as documented by a cardiologist with ejection fraction of < 40% and assessed by New York Heart Association classification (NYHA). Plasma was assayed for creatinine (Cr), BNP and NT-proBNP.A total of 190 subjects were enrolled in the study, 95 with and 95 without SHF. The mean age of patients was 58 (±15) years, 67.4% being males. Mean BNP levels showed a 2.5 fold and 1.5 fold increase from chronic kidney disease (CKD) stage 3 to stage 5 in patients with and without SHF respectively. NT-proBNP levels in non-heart failure group were 3 fold higher in CKD stage 5 compared to stage 3. Mean NT-proBNP levels were 4 fold higher in CKD stage 5 compared to stage 3 in patients with SHF. Optimal BNP and NT-proBNP cutoffs of SHF diagnosis for the entire CKD group were 300 pg/ml and 4502 pg/ml respectively.BNP and NT-proBNP were elevated in kidney dysfunction even in the absence of SHF; however the magnitude of increase in NT-proBNP was greater than that of BNP. BNP and NT-proBNP can be useful in diagnosing SHF, nonetheless, by using higher cutoffs stratified according to kidney dysfunction. NT-proBNP appears to predict heart failure better than BNP. Literature from the United States, Australia and China report the prevalence of chronic kidney disease (CKD) as ranging from 11–13.1% . Communi1-108. This pro-hormone is released into the circulation and is proteolytically cleaved into the biologically active BNP1-32 and the inactive NT-proBNP1-76. The understanding of the cleavage of proBNP in circulation is most likely by the pro-protein convertases corin and furin [The source of BNP and NT-proBNP are mainly left ventricular myocytes. Distention of cardiac ventricle is considered the main stimulus for release of proBNPnd furin ,15. The nd furin . The synnd furin . The clend furin -20. Bothnd furin ,22.We presume that with declining kidney function. NT-proBNP would be affected more as compared to BNP. The ideal natriuretic peptide to diagnose heart failure in CKD remains undecided. This study was conducted to evaluate the effects of compromised kidney function on natriuretic peptides (BNP or NT-proBNP) and to determine optimal cutoffs predictable of systolic heart failure (SHF).A cross-sectional study was conducted in the Section of Chemical Pathology, Department of Pathology and Microbiology in collaboration with the nephrology and cardiac units of Aga Khan University, Karachi Pakistan. It was conducted over a period of 10 months from June 2009 to March 2010. The Aga Khan University’s Ethical Review Committee approved all investigational procedures involved in the study (reference number: 1054-Path-ERC-08). Recruitment of consecutive adult ambulatory subjects with impaired kidney function was carried out via non-probability quota sampling from the clinics. After taking informed consent a proforma was filled including patient demographics, clinical history, smoking history, history of alcohol intake and drug history. The patient’s body weight and height were recorded in order to determine the body mass index (BMI).2 were not included in this study. Both endogenous and exogenous hormones have shown to induce elevated levels of BNP/NT-proBNP in circulation therefore pregnant females, those on hormonal therapy or taking contraceptives were also not included in this study group [Impaired kidney function was taken as estimated glomerular filtration rate (eGFR) of ≤ 60 ml/min. The Cockcroft Gault equation was used to estimate the GFR of the study subjects from plasma creatinine (Cr), age and body weight of the subjects . The subdy group ,27. Six Plasma samples were collected after informed consent and centrifuged at 3000 g for 10 minutes, aliquoted, frozen and maintained at −80°C. All samples were run in batches for plasma BNP, NT-pro BNP and Cr. The BNP levels were measured by automated electrochemiluminescence immunoassay (ECLIA) on Axym analyzer (Abbott diagnostic). The NT-proBNP levels were measured by automated ECLIA on Elecsys analyzer (Roche diagnostic). Plasma Cr levels were assayed with the rate-Jaffe reaction  on Synchron analyzer (Beckman Coulter). To ensure quality, normal and abnormal controls were run with every batch of BNP, NT-proBNP and Cr analysis.th to 95th percentile for continuous variables were computed. Dichotomous variables were expressed in percentages. The differences between groups were tested using t-test, one way analysis of variance (ANOVA) or Chi square test, as applicable. Post-hoc comparisons of log BNP/NT-proBNP in different groups were carried out using Bonferroni method. Variables used in univariate analysis with p-value of < 0.2 were then entered in a multiple regression model using ENTER method. Results were reported as standardized ß-coefficient. Receiver operating characteristic (ROC) curves were constructed and areas under the curve (AUC) calculated for BNP and NT-proBNP to detect SHF. Compromising on sensitivity in order to improve the specificity the uppermost corner on the left side of the ROC curve was not used for calculating cutoffs. A p-value of < 0.05 was treated as significant in all above statistical analysis.Data analysis was performed using SPSS version 19. After checking for normality using the Kolomogorov-Smirnove test, BNP and NT-proBNP values were log transformed. Mean and ± standard deviation (SD) or median with 25p-value > 0.05). Statistically non-significant difference existed between mean log BNP/NT-proBNP amongst males and females in those with and without SHF .Table The following predictor variables were used in univariate analysis taking log BNP/log NT-proBNP as the dependent variables: age, gender, BMI, eGFR, ejection fraction, diabetes, hypertension, ischemic heart disease, cerebrovascular accident, dyslipidemia, anemia, smoking history, calcium channel blockers, beta-blockers, statins, digoxin, angiotensin converting enzyme inhibitor, angiotensin receptor blocker, diuretics and duration of kidney disease. Table p-value <0.05). A progressive decline in eGFR with a rise in NYHA class was noted .According to NYHA classification 35.8% were in NHYA 1, 19.5% in NYHA 2, 30% in NYHA 3 and 14.7% belonged to NYHA 4. Median BNP in these four classes were 80.8 (42.6-163.2), 200 (118.7-331), 478 (144.1 - 742.7), and 409.4 (285.8-720.3) pg/ml respectively. Post-hoc test was applied for multiple comparisons, using Bonferroni alpha (0.05), which revealed significant differences in log BNP between NYHA Class I, II and III whereas differences were non- significant between NYHA Class III and IV. Median log NT-proBNP in NYHA classes were 535.1 (191.9- 876.), 4192 (1505.8-7105), 13831 (4640.5-31230.5) and 22520 (9693.2-35000) pg/ml respectively. There was a significant mean difference in ANOVA results between log NT-proBNP levels amongst all the four classes of NYHA classification . The association of BNP with NT-proBNP was higher in those suffering from kidney dysfunction alone without SHF  compared to those suffering from kidney dysfunction and SHF . Non-significant correlation with each other was shown by both peptides in the group with SHF along with CKD 5.A continuous relationship of both peptides was revealed by head to head comparison of log BNP and log NT-proBNP in the total group of patients. Log transformed BNP levels correlated with log transformed NT-proBNP levels  and 0.86  respectively  and NT-proBNP (r = − 0.5) ,28-31. A2. Jae Wong Yang et al. stated that heart failure could be diagnosed in patients with kidney dysfunction using BNP cut-off 858.5 pg/ml with 77% sensitivity and 72% specificity [In this study group, plasma NT-proBNP levels were more affected by declining eGFR as compared to plasma BNP levels plus the optimal cut off for plasma NT-proBNP in the diagnosis of SHF was markedly influenced by the severity of kidney dysfunction. A great deal of controversy exists regarding the cut-off values of BNP and NT-proBNP levels in diagnosing SHF in patients with impaired kidney function. Generally the BNP and NT-proBNP values 100 pg/ml and 125 pg/ml are considered abnormal and suggestive of heart failure as per manufacturers’ product inserts. The strength of these markers is their capability to rule out the diagnosis of acute heart failure. In general, heart failure is unlikely at BNP values <100 pg/ml and is very likely at BNP values >500 pg/ml and, similarly, unlikely at NT-proBNP values < 300 pg/ml and very likely at NT-proBNP values >450 pg/ml -34. McCucificity . AnwarudKidney dysfunction represents a variable that complicates the interpretation of BNP and NT-proBNP. As reported previously ,30,37,38Our results show that NT-proBNP was more dependent on kidney function than BNP and but using a higher NT-proBNP cut-off had a better diagnostic accuracy than BNP. Given the high prevalence of left ventricular hypertrophy and left ventricular systolic dysfunction in patients with CKD, exclusion of heart failure becomes important in this population. In the present study half of the patients had SHF along with impaired kidney and has significant implications for use of natriuretic peptide assay. Both plasma BNP and NT-proBNP levels correlated with NYHA symptom severity in patients with impaired kidney function. It has been consistently found in a large number of studies that BNP and NT-proBNP are elevated in patients with heart failure, and values were found to be related to disease severity as assessed by NYHA functional class ,40. StroOvertly symptomatic patients (n = 28) in our study classified under NYHA class four had extremely high BNP and NT-proBNP levels (median 409.4 and 22520 pg/ml respectively). The biological activity of BNP includes diuresis, natriuresis, and inhibition of renin-angiotensin system, endothelin secretion, and systemic and renal sympathetic activity. Paradoxically, in congestive heart failure high BNP levels measured by conventional assays are associated with an absence of effect of this hormone . The pheThe studied population already suffered from impaired kidney function; hence duration of the disease may be a confounder in the current study. Ideally occult myocardial ischemia which raises BNP and NT-proBNP levels should have been excluded. Use of Cockcroft Gault equation to estimate GFR is controversial in Asians populations but good agreement between Cockcroft Gault and creatinine clearance has been observed in our setup . PatientProduct inserts by manufacturers of plasma BNP and NT-proBNP only have a single cut-off used in normal population and there is no mention of limitations of using them in patients with compromised renal function. The fact remains that many patients with heart failure also have renal insufficiency. Therefore, current study becomes very important in making clinicians aware of how to interpret the results in concomitant renal disease and also for kit manufacturers to include it in their product labeling. Both natriuretic peptides’ assays can be used in patients with impaired kidney function but by using higher cutoffs stratified according to kidney dysfunction. NT-proBNP appears to predict SHF better than BNP. Kidney dysfunction makes the interpretation of these natriuretic peptides complicated. To improve the quality of care and subsequent prognosis, plasma BNP and especially NT-proBNP values should be interpreted in relation to the severity of kidney dysfunction.The study was given approval by the Ethical Review Committee of the Aga Khan University Hospital. Reference number: 1054-Path-ERC-08).The authors declare that they have no competing interests.LJ was involved in planning, patient recruitment, biochemical analysis, data analysis and write up of the manuscript, WK participated in patient selection and recruitment and review of manuscript, JT contributed in patient selection and recruitment and review of manuscript, IS was involved in project execution, data analysis and manuscript review, IA participated in design of study and statistical analysis of data, HS was involved in patient recruitment and FG proposed the initial idea, participated in its design, project execution and manuscript review. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/14/117/prepub


The conventional sequence when using supraglottic airway devices is insertion, cuff inflation and fixation. Our hypothesis was that a tighter fit of the cuff and tip could be achieved with a consequently lower incidence of air leak, better separation of gastrointestinal and respiratory tracts and less airway morbidity if the device were first affixed and the cuff then inflated.2O. The patients’ lungs were ventilated in pressure-controlled mode with 5 cmH2O PEEP, Pmax to give 6 ml kg-1 tidal volume, and respiratory rate adjusted to end-tidal CO2 of 4.8 and 5.6 kPa. Correct cuff and tip position were determined by leak detection, capnometry trace, oropharyngeal leak pressure, suprasternal notch test, and lube-tube test. Bowl and cuff position and the presence of glottic narrowing were assessed by fiberscopic examination. Postoperative dysphagia, hoarseness and sore throat were assessed with a questionnaire. Ventilatory impairment was defined as a tidal volume < 6 ml kg-1 with Pmax at oropharyngeal leak pressure, glottic narrowing was defined as an angle between the vocal cords under 16 degrees.Our clinical review board approved the study (public registry number DRKS00003174). An LMA Supreme® was inserted into 184 patients undergoing lower limb arthroscopy in propofol-remifentanil anaesthesia who were randomly assigned to either the control  or study group . The cuff was inflated to 60 cmH2O, p = 0.63), failed lube-tube test (16.3% vs. 17.6%) and glottic narrowing  was similar in both groups . When glottic narrowing occurred, it was more frequently associated with ventilatory impairment in the control group . Airway morbidity was more common in the control group .The incidence of incorrect device position (18% vs. 21%), failed ventilation (10% vs. 9%), leak pressure (24.8 vs. 25.2 cmHAltering the sequence of cuff inflation and device fixation does not affect device position, oropharyngeal leak pressures or separation of gastrointestinal and respiratory tracts. It reduces the incidence of glottic narrowing with impaired ventilation and also perioperative airway morbidity. Supraglottic airways are now widely used in clinical anaesthesia, and although the limitations of the original model have been addressed and a wide variety of improved models are available, the incidence of perioperative complications associated with their use is still between 8% and 19% . These cBased on theoretical considerations, we hypothesised that the sequence of cuff inflation and tube fixation might influence both the seating of the cuff in the surrounding anatomical structures as well as the factors causing airway morbidity. To the best of our knowledge, in all published studies, the device was inserted, the cuff inflated and the device then fastened to the patient with tape. The increasing size of the cuff during inflation might force it out of an initially correct position causing an air leak. Friction between the cuff and the soft tissues of the pharynx and hypopharynx can cause airway morbidity. The concept was that by first fastening the device, the cuff would have to expand downward and force the tip into a tighter fit in the upper oesophageal sphincter.We tested the hypothesis that securing the device first and then inflating the cuff would reduce the incidence of an inadequate seal and of airway morbidity. We used a single model of supraglottic airway device to minimise confounding factors. We chose one with an integrated drainage channel (LMA-Supreme®) that allows one to assess tip position with simple clinical tests.This prospective, randomised study was approved by our institutional clinical study review board (Ethikkommission der Universitätsmedizin Göttingen) and registered in a publicly available registry under the number DRKS00003174. It was conducted in the period from June 2011 to May 2012. The participants were 18 to 75 year-old, ASA I-III patients scheduled for elective lower-limb arthroscopy in the supine position who had given written informed consent. Exclusion criteria were a history of radiation therapy or surgery of the neck or hypopharynx, a mouth opening less than 3 cm, a known or expected difficult airway, gastric reflux or a BMI over 35. Immediately before induction of anaesthesia, the patients were allotted to one of the two study groups using the computer-generated randomisation list described below. The groups were “conventional sequence”, i.e. cuff inflation then device fixation, and “study sequence”, i.e. device fixation then cuff inflation.in situ position, occurrence of glottic narrowing, impaired ventilation, evidence of airway morbidity.The primary endpoints were oropharygeal leak pressure and sufficient separation of gastrointestinal and respiratory tracts. Secondary endpoints were fibreoptically assessed On the patients’ arrival in the operating theatre, we inserted a peripheral venous cannula, established monitoring of ECG, non-invasive blood pressure, peripheral oxygen saturation and depth of anaesthesia , and gave intravenous midazolam for anxiolysis (1–3 mg titrated to effect).-1, continuous infusion at 0.2 μg.kg-1.min-1) and propofol. Propofol was administered initially at a rate of 1 mg.kg-1.min-1 until the state entropy value dropped below 60. We then adjusted the infusion rate to keep the SE value between 40 and 60. After the patient stopped breathing we manually ventilated the lungs by bag and mask.After a ten-minute rest period, we recorded the baseline values of blood pressure, heart rate, and state and response entropy  and then induced anaesthesia with remifentanil  inserted the lubricated  LMA-Supreme® device (LMA-S) according to the manufacturer’s instructions. We initially used a size 4 LMA-S in all patients, since this is the correct size for the majority of our patient population and because the manufacturer recommends it as the first choice. The distance between the lips and the fixation tab of the LMA-S was measured and recorded. According to the manufacturer’s criteria the mask size is correct if this distance is between 0 and 2.5 cm. The following steps were then performed according to the study protocol. In the control group, we inflated the cuff to 60 cm H2O and an initial maximal inspiratory pressure of 15 cmH2O. The pressure was increased step-wise until a tidal volume of 6 ml.kg-1 was achieved. We auscultated the anterolateral neck and the mouth to detect any audible leakage. The position of the device was accepted and graded as “adequate oropharyngeal seal” if there was no audible leak at this tidal volume, and if the capnography trace showed a normal plateau phase. If these criteria were not fulfilled, we allowed two attempts to improve the seating. The permitted corrective measures were adjusting the mask’s position without removing it, removing and reinserting the same device or exchanging it for one of a different size with the restriction that size change was never the first measure. The necessity of corrective measures was documented. If the functional seating criteria were not fulfilled after the second attempt, the LMA-S was removed, the trachea was intubated, and the patient was graded as “failed” and excluded from further evaluation. Oropharyngeal leak pressure was determined by slowly increasing the airway pressure with a constant fresh gas flow into the circuit in the closed manual mode until an audible leak was detected from the mouth and/or by ausculation over the larynx [Two investigators who were blinded to the patients’ group allocations (BB and HS) performed the following measures. They connected the LMA to the respirator in pressure-controlled mode with a PEEP of 5 cmHe larynx .We assessed the separation of the gastrointestinal and respiratory tracts with two further tests. In the suprasternal notch test a small amount of lubrication gel is introduced into the drainage channel, and pressure on the jugulum forces the gel upwards if the tip of the device is correctly positioned in the upper oesophageal sphincter. In the “lube-tube test” the gel in the drainage channel should show an oscillatory movement during ventilation but not leave the tube when the tip is correctly positioned and the oesophagus and the trachea are adequately separated . FailureAfter these tests had demonstrated that the position of the tip was correct, we inserted a 3.5 mm diameter fiberscope  through the ventilation tube in apnoea, with which we viewed and photographed the position of the bowl and tip, and the anatomy of hypopharyngeal structures. The correct position of the device’s tip is posterior to the arytenoid cartilage with the epiglottis visible and not reflected over the glottic opening. The vocal cords should be visible with no narrowing of the glottic opening . We defi2O, Pmax sufficient to give a tidal volume of at least 6 ml.kg body weight-1 and a respiratory rate adjusted to keep end-tidal CO2 between 4.8 and 5.6 kPa. Endoscopy was repeated whenever there was an unexpected increase in airway pressure or decrease in tidal volume to determine a possible cause. We defined ventilatory impairment as a reduction of tidal volume to less than 6 ml.kg-1 and/or a required Pmax greater than the oropharyngeal leak pressure. If glottic narrowing was identified as a possible cause, we deepened anaesthesia with bolus injections of propofol (50 mg) and remifentanil (50 μg) and then reassessed the glottis. If this did not improve the glottic narrowing, the LMA-S was removed and reinserted. If there was still no improvement the trachea was intubated.For surgery the respirator was in pressure-control mode with the following settings: PEEP 5 cmHThe propofol and remifentanil infusions were stopped when all instruments and sheaths were removed from the joint. We removed the LMA when the patient was breathing spontaneously and muscle tone had returned to the jaw. The attending personnel in the postanaesthetic care unit were blinded to the patients’ group allocations. When the patients were able to swallow, they were given 600 mg ibuprofen PO. One hour postoperatively they were evaluated with regard to swallowing difficulties, hoarseness and sore throat on a numeric rating scale of one to ten.The patients were discharged home with stable vital functions, absent or adequately controlled PONV and absent or adequately controlled pain. For pain control at home they were given ibuprofen (600 mg every 6 hours), metamizole (1 g every 6 hours) and tramadol as rescue medication for severe pain. A follow-up was scheduled for two days postoperatively, and airway morbidity was re-evaluated at that time.The primary end-point of this study was the incidence of a functionally inadequate oropharyngeal seal or incorrect tip position of the LMA-S with inadequate separation of the GI and respiratory tracts. Secondary end-points were the position of the LMA-S bowl and glottic anatomy determined by endoscopy, the incidence of intraoperative ventilatory complications, the incidence and severity of airway morbidity , and the presence of blood on the cuff of the LMA-S that indicated airway lesions.http://www.randomizer.org).All statistical calculations including calculations of power and sample size were performed with the program Statistica® . Sample size calculations showed that two groups of 90 patients each would be required to detect a clinically relevant reduction of the incidence of an seal from the previously observed 10% to 5% with a power of 80% and a p-value of less than 0.05. To compensate for dropouts we used two groups of 95 patients each. The randomisation list was created with an online randomisation program  but in only five of the 13 patients (39%) in the study group (p = 0.04). Increasing the depth of anaesthesia was generally unsuccessful; it resolved the difficulties in four of the 13 in the control group and none of the five in the study group (p = 0.06). Two patients in the control group and one in the study group required tracheal intubation to resolve the problem. Removing and reinserting the LMA was successful in the others.We observed glottic narrowing in 30 patients (17%); 13 in the study group and 17 in the control group. This caused impaired ventilation with tidal volumes of less than 6 ml.kgThe incidence and severity of postoperative airway morbidity is shown in Table In this study we investigated the influence of the sequence of cuff inflation and device fixation on functional, anatomical and clinical parameters as well as on perioperative airway morbidity when using an LMA-Supreme®.We were unable to confirm our hypothesis that the sequence of cuff inflation and device fixation influenced the incidence of inadequate ventilation or incorrect position of the device. Oropharyngeal leak pressures, functional tests of tip position or separation of gastrointestinal and respiratory tracts did not differ between the groups. Direct observation of the position of the device’s bowl showed similar incidences of the various types of malposition in the two groups.We did observe a greater incidence of blood on the cuff, indicating soft tissue damage, as well as an increased rate of sore throat and dysphagia in the control group. We can only speculate whether this resulted from a greater tendency of the cuff to shift its position and abrade surrounding tissues during surgery.The 1%, respectively 3.3% incidence of an incorrect tip position in the upper oesophageal sphincter seen through the fiberscope was much lower than the up to 40% incidence described for the classical laryngeal mask airway ,11. ThisGlottic narrowing occurred with equal frequency in both groups, and the observed incidence was similar to that described in previous studies ,7,12. HoGlottic narrowing associated with the use of a supraglottic device is an interesting phenomenon, the cause of which is not fully understood. It seems unlikely that it is due to an inadequate depth of anaesthesia, since deepening the anaesthetic rarely improved the condition. Russo et al. suggested that the tip of the device might compress the dorsal portion of the trachea and the cricoid cartilages , but thi-1 without air leak. But since this inter-individually differing pressure would have been a confounding factor we decided to use one standard pressure for all patients. We normally use this pressure for studies [Most studies describe an incidence of airway morbidity between 8 and 19% with varying degrees of severity -5. The i studies , since i2O. Any other method of inserting, affixing or otherwise using the device might, of course, affect the results in an unpredictable manner. The depth of intraoperative analgesia was not assessed  and we have shown that periods of insufficient analgesia can occur even with normal depth of hypnosis in BIS or entropy [The results of the present study apply to the LMA-Supreme® inserted as recommended by the manufacturer and blocked to a cuff pressure of 60 cmH entropy . This coChanging the sequence of inflation and fixation had no effect on oesophageal leak pressure, gastrointestinal and respiratory tract separation, total incidence of glottic narrowing, rate of failed ventilation, or the incidence of incorrect mask position. Securing the position of the LMA-S before inflating the cuff reduced the incidence of airway morbidity, and of impaired ventilation due to glottic narrowing.The study was financed by departmental funds, including the purchase of all devices and materials used in the study. During the past five years none of the authors have received any form of reimbursement or financial or non-financial support from a company that could gain or lose financially from the publication of this manuscript. None of the authors hold any stocks or shares in a company that would gain or lose financially from the publication of this manuscript. None of the authors are applying for any patents related to the content of the manuscript. There are no other competing financial or non-financial interests.IB initiated, designed and conducted the study, performed device insertion, analysed the data, and wrote the first manuscript draft. TAC analysed and interpreted the data and wrote the final manuscript. MR and MB were involved in study design and data analysis. HS and AM were involved in study design and were responsible for perioperative data acquisition. BB participated in study design and performed device insertions the study. JMH participated in the design of the study and was responsible for statistical analysis. All authors were funded by the department and agree to be accountable for all aspects of the work. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2253/14/2/prepub


Systemic hypertension is a prominent feature in humans with metabolic syndrome (MS) and this is partly caused by an enhanced endothelin-1 (ET-1) mediated vasoconstriction. There are indications that systemic hypertension might be a feature in equine metabolic syndrome (EMS) but if ET-1 is involved in the development of hypertension in horses is not known. Increased levels of cortisol have also been found in humans with MS but there are no reports of this in horses. Before blood pressure, plasma ET-1 and serum cortisol can be evaluated in horses with EMS, it is necessary to investigate the interday variation of these parameters on clinically healthy horses. The aims of the present study were therefore to evaluate the interday variation and influence of transportation on systemic blood pressure, plasma ET-1 and serum cortisol in healthy Standardbred and Icelandic horses, and to detect potential breed differences.Nine horses of each breed were included in the study. Blood pressure was measured and blood samples were collected between 6 and 9 am on two separate days. Eight of the horses (four of each breed) were transported to a new stable were they stayed overnight. The next morning, the sampling procedure was repeated.The interday variation was higher for plasma ET-1 (37%) than for indirect pressure measurements (8-21%) and serum cortisol (18%). There were no differences in systemic blood pressure between the two breeds. The Icelandic horses had significantly lower serum cortisol and significantly higher plasma ET-1 concentrations compared to the Standardbred horses. Plasma ET-1 was significantly elevated after transportation, but systemic blood pressure and serum cortisol did not differ from the values obtained in the home environment.Indirect blood pressure, plasma ET-1 and serum cortisol are of interest as markers for cardiovascular dysfunction in horses with EMS. The elevated plasma ET-1 concentrations recorded after transportation was likely caused by a stress response. This needs to be considered when evaluating plasma ET-1 in horses after transportation. The differences detected in plasma ET-1 and serum cortisol between the two breeds might be related to differences in genetic setup, training status as well as management conditions. Equine metabolic syndrome (EMS) was introduced in veterinary medicine in 2002 and is a clinical condition characterized by obesity, regional adiposity, insulin resistance (IR) and clinical or subclinical laminitis,2. A simIn humans, the similarities between MS and Cushings´s disease has raised the question if elevated cortisol levels are associated with the development MS,9. ThereThe aims of the present study were therefore to evaluate the interday variation and influence of transportation on systemic blood pressure, plasma ET-1 and serum cortisol in healthy Standardbred and Icelandic horses, and to detect potential breed differences. An additional aim was to compare two different oscillometeric blood pressure measurement devices, the Cardell Veterinary Vital Signs Monitor (Cardell) and the Memo Diagnostic High Definition Oscillometry Monitor (HDO).The study was sanctioned (C27/11) by the Ethical Committee for Animal Experiments, Uppsala, Sweden.Nine Standardbred  and nine Icelandic horses  were included in the study. The Standardbred horses were owned by the Department of Clinical Sciences and kept in box stalls with a daily turn out in a paddock. The horses were fed a standardized diet consisting of hay (three times/day) and concentrate (once daily) and provided water ad libitum. The Icelandic horses were privately owned and mainly in free range in a paddock but were also kept in box stalls on a regular basis. These horses were fed grass haylage (three times/day) and provided water ad libitum. All Standardbreds were sedentary horses whereas eight of the Icelandic horses performed lighter exercise three to five times a week and one was sedentary. Four of the Standardbred horses  and four of the Icelandic horses  were included in the transportation study. None of the horses included in the study showed any signs of disease on the clinical examination that was performed before the start of the study.Systolic, diastolic, and mean indirect arterial pressures were obtained with Cardell  and HDO  oscillometric monitors. For the transportation study only the HDO device was used. For each monitor, indirect blood pressure was obtained from cuffs placed at the base of the tail  according the manufacturer’s instructions. The cuff size for the Cardell device was 11 cm and 8 cm for the HDO device. Both devices automatically inflate an occluding cuff and use the oscillometric measurement technique for determination of systolic, diastolic, mean arterial blood pressure and heart rate. The cuffs were repositioned as needed to acquire data acceptable to the internal sensor of the monitor. The same cuff size accompanied each device through all measurements.The blood pressure measurements and the sample collection were performed between March and April 2011, before the horses had access to summer pasture. The arterial systemic blood pressure was measured between 6 and 9 am on two separate days (M1 and M2). The cuffs were placed on the base of the horse’s tail while the horse was standing in the box stall. Five consecutive determinations of systolic and diastolic blood pressure were performed on each horse, using both devices. On the first day of the study, the starting order in which of the two blood pressure measurement devices were used was randomized by raffle. The next day the starting orders of the devices were switched. In each horse, blood samples were drawn immediately after both blood pressure measurements had been completed.The horses were transported in a two-horse trailer for one hour to a new stable were they stayed overnight. The next morning, the blood pressure was measured (HDO) and blood samples collected (M3) in the same manner as previously described.g), plasma and serum subsequently harvested and stored in a −80°C freezer until analysis.Blood samples for analysis of plasma ET-1 and serum cortisol were drawn using vacutainer technique and collected in evacuated NaEDTA and serum glass tubes . In each horse, the blood samples were drawn immediately after the blood pressure measurements had been completed. All samples were kept on ice until centrifuged for 10 min  enzyme immunoassay, Biomedica Medizinprodukte GmbH & Co KG, Wien, Austria). Serum cortisol concentrations (hydrocortisone Compound F) were measured in duplicates with a radioimmunoassay-kit .In each horse, the lowest and highest recorded value of the five consecutive blood pressure determinations were excluded and the mean systolic and diastolic pressure was calculated from the three remaining determinations (triplicates). The statistical analysis was performed using SigmaPlot software version 11 .t-test (M1 and M2) or one way repeated measures analyses of variance . Differences between individual means for the three days were tested with a tukey test. Differences in the two breeds for measurement of indirect blood pressure measurement, plasma ET-1 and serum cortisol were compared by use of a t-test whereas differences between the blood pressure measurement devices were compared by use of a paired t-test. Measurement error, defined as the variation between measurement of the same quantity on the same animal, blood pressure device and ELISA- and radioimmunoassay-kit, was expressed as the coefficient of variation (CV). The standard deviation for duplicate or triplicate measurements was calculated according to Bland[P ≤ 0.05).The results of repeated tests for indirect blood pressure measurement, plasma ET-1 and serum cortisol were compared by use of a paired to Bland. The CV The mean systolic blood pressure differed significantly between the two devices , but not the mean diastolic blood pressure  (TableOne Icelandic horse had plasma ET-1 concentrations that were considered as unreasonably high (16.41 and 14.59 pg/ml) and another Icelandic horse showed a great variation in plasma ET-1 concentrations between measurements (3.09 and 14.54 pg/ml). These values were therefore excluded from the calculations of plasma ET-1. One of these horses took part in the transportation study, and the ET-1 values of this horse were excluded since it had concentrations above the detection limit. There was no significant difference between M1 and M2 in the mean concentration of plasma ET-1 and serum cortisol , the sample collection was carried out the same day as the transportation occurred and the time interval between transportation and sampling might have been too short for a reestablishment of the pulsatile secretion. The results of the present study indicate that serum cortisol and indirect blood pressure can be measured with reliable results if samples are collected at least 12 hours post-transportation. This is supported from findings from a study in donkeys were transportation altered the normal rhythm of resting cortisol to an increased rate of continuous secretion in both fed and fasted animals with a reestablishment of the circadian rhythm 8.5-10.5 hours later[After transportation and exposure to a new environment, plasma ET-1 concentrations differed significantly from the concentrations measured in the home environment. This is likely related to a stress reaction caused by the transportation and the new environment. No significant differences were detected in the cortisol concentrations measured after transportation compared to the measurements in the home environment. This is in contrast to findings from a previous study, were higher serum cortisol levels were found in horses that had been transported compared to a group of non-transported horses. The rears later.The significant difference in the concentrations of ET-1 and cortisol between the two breeds was not reflected in any differences in blood pressure. Previous studies have found that laminitis prone ponies have a different metabolic profile compared to non-laminitic ponies with significantly higher BCS, plasma insulin concentrations as well as decreased cortisol concentrations,35. The Both blood pressure measurement devices gave values that showed an acceptable interday variation. The indirect oscillometric blood pressure technique is known to overestimate the systolic blood pressure in dogs compared to the direct blood pressure technique-37. HoweIn conclusion, indirect blood pressure measurements, plasma ET-1 and serum cortisol all showed an acceptable interday variation and are candidates for further investigation in horses with Equine metabolic syndrome. Both the Cardell and the HDO device can be used for measurement of indirect blood pressure in horses, but the HDO was most practical to handle, especially in a field setting. There seem to exist a breed difference in the concentrations of plasma ET-1 and serum cortisol. Transportation and housing in a new environment seemed to influence the concentrations of plasma ET-1 but not serum cortisol. All of these factors need to be considered when indirect blood pressure, plasma ET-1 and serum cortisol are used in a clinical setting. Future studies that investigate the possible seasonal variation in blood pressure, ET-1 and cortisol on healthy horses of different breeds and of horses clinically affected of EMS are desirable.The authors declare that they have no competing interests.JBR and KNO took equal responsibility for designing the study as well as coordinating the project and apply for funding. The practical experiment was conducted with equal contribution from JS, JBR and KNO. JS drafted the manuscript and KN supervised the drafting. All authors commented on the manuscript. All authors read and approved the final manuscript.


Hypertension in Estonia (HYPEST) study represents the country's first hypertension-targeted sample collection aiming to examine the epidemiological and genetic determinants for hypertension (HTN) and related cardiovascular diseases (CVD) in Estonian population. The HYPEST subjects  were recruited across Estonia between 2004-2007 including clinically diagnosed HTN cases and population-based controls. The present report is focused on the clinical and epidemiological profile of HYPEST cases, and gender-specific effects on the pathophysiology of hypertension.More than one third of adult population in Estonia has problems with elevated blood pressure (BP). The Current analysis was performed on 1,007 clinically diagnosed HTN patients (617 women and 390 men) aged 18-85 years. The hypertensives were recruited to the study by BP specialists at the North Estonia Medical Center, Centre of Cardiology, Tallinn or at the Cardiology Clinic, Tartu University Hospital, Estonia. Longitudinal BP data was extracted retrospectively from clinical records. Current and retrospective data of patient's medical history, medication intake and lifestyle habits were derived from self-administrated questionnaire and each variable was examined separately for men and women. Eleven biochemical parameters were measured from fasting serum samples of 756 patients.2) and a total of 79% of patients had additional complications with cardiovascular system. In men, the hypertension started almost 5 years earlier than in women (40.5 ± 14.5 vs 46.1 ± 12.7 years), which led to earlier age of first myocardial infarction (MI) and overall higher incidence rate of MI among male patients . Heart arrhythmia, thyroid diseases, renal tubulo-intestinal diseases and hyperlipidemia were more prevalent in hypertensive women compared to men (P < 0.0001). An earlier age of HTN onset was significantly associated with smoking (P = 0.00007), obesity , increased stress (P = 0.0003) and alcohol consumption (P = 0.004).The distribution of recruited men and women was 39% and 61% respectively. Majority of Estonian HTN patients (85%) were overweight (BMI ≥ 25 kg/mUnderstanding the clinical profile of HTN patients contributes to CVD management. Estonian hypertension patients exhibited different disease and risk profiles of male and female patients. This well-characterized sample set provides a good resource for studying hypertension and other cardiovascular phenotypes. HYPertension in ESTonia).Hypertension is defined as a physiological condition characterized by consistently elevated blood pressure (BP). High BP affects approximately 20 - 30% of the adult population in modern societies and its prevalence has been predicted to increase as high as 60% in 2025 ,2. AmongThere is an increasing body of data showing gender-dependent effects of commonly accepted confounders  contributing to the determination of an individual's BP -12. For HYPertension in ESTonia) study has been approved by the Ethics Committee on Human Research of University of Tartu . The study was carried out in compliance with the Helsinki Declaration and all the participants have given their written informed consent. The HYPEST sample collections have been recruited to target the genetic-epidemiological component of essential hypertension and cardiovascular disease in Estonian population. The subjects  were recruited across Estonia between 2004-2007 including (i) patients with clinically diagnosed essential hypertension (HTN) (n = 1007) and (ii) a population controls of long-term blood donors (n = 959). All of the study participants are of Eastern European ancestry. Blood samples for DNA extraction and further genetic analysis were obtained from 1,823 HYPEST individuals . The genomic DNA of HYPEST participants are stored at -80°C at the laboratory of the Human molecular genetics research group (headed by Maris Laan), Institute of Molecular and Cell Biology, University of Tartu. Current report is only focused on the epidemiology of HYPEST patients with clinically diagnosed HTN.The HYPEST (th Revision (ICD-10) codes: essential (primary) hypertension (I10), hypertensive heart disease with (congestive) heart failure (I11.0) and/or hypertensive heart disease without (congestive) heart failure I11.9).Estonian HTN patients n = 1,007) were recruited by blood pressure (BP) specialists during patients' ambulatory visits or hospitalization at the North Estonia Medical Center, Centre of Cardiology, Tallinn or at the Cardiology Clinic, Tartu University Hospital, Estonia. These two main healthcare centers cover major part of Estonia with premium medical aid  readings (before and during antihypertensive treatment) of the HYPEST HTN patients were extracted retrospectively from clinical records. The average of each participant BP readings was used for the analyses in the current study. Blood pressure measures had been taken after a rest in sitting position using a conventional mercury column sphygmomanometer and size adjusted cuffs, and the procedures were performed by trained clinicians following the standardized protocol . Hyperte2. Additionally, self-reported data were documented for birth weight, birth height and weight at age 18 years. Physiological stress was rated based on self-reported information: (i) no stress or occasional short stress episodes during their life; (ii) exposure to regular stress.The HYPEST study participants filled out a self-administered epidemiological questionnaire recording their past and present health and lifestyle. The questionnaire included participants' general demographic data , lifestyle factors , physical activity, stress, health status and medical records of the subject. Additionally, self-reported familiar disposition to cardiovascular disease was recorded. Personal medication, including past and current prescription and over-the-counter drugs were collected based on self-reported data and available clinical records. Additionally, for female participants' data regarding their reproductive history  was collected. Information about smoking status included the previous and current smoking status as well as the amount of tobacco smoked , age of beginning and quitting (for former smokers). Data on alcohol consumption habits during lifetime included the drinking status and the volume of consumed alcohol  during the week. Body mass index was based on participant's body weight and height values during recruitment and was defined as weight/height® analytical platform, Roche Diagnostics, Inc. USA) applied at the accredited hospital laboratories in Tartu  and in Tallinn . The following parameters from serum were estimated: (1) Sodium (S-Na) [mmol/l], (2) Potassium (S-K) [mmol/l], (3) Urea (fS-Urea) [mmol/l], (4) Creatinine (fS-Crea) [μmol/l], (5) Uric acid (S-UA) [μmol/l], (6) Albumin (S-Alb) [g/l], (7) Cholesterol (fS-Chol) [g/l], (8) Triglycerides (fS-Trigl) [mmol/l], (9) HDL-Cholesterol (fS-HDL-C) [g/l], (10) LDL-Cholesterol (fS-LDL-C) [g/l] and (11) C-reactive protein (fS-CRP) [mg/L]. The tests of the serum biomarkers have been accredited by Estonian Accreditation Center [Among the enrolled HTN patients  756 individuals (484 women/272 men) agreed to provide blood samples for serum biomarker analysis. The venous blood samples for clinical chemistry analysis were drawn in the morning after an overnight fast. Clinical chemistry assays were performed using standardized assays  software (version 9.1) . Variables were estimated separately for men and women, and significance of gender differences was compared using Mann-Whitney U-test (two-sided) for quantitative  and categorical variables. Gender comparison of SBP and DBP without and under antihypertensive treatment was performed by analysis of covariance (ANCOVA) adjusted by median age of each patient at BP readings during pre-treatment or medication period, respectively. Fisher's exact test was used for calculating of frequency differences. Statistical significance was assessed for HYPertension in ESTonia (HYPEST) study by the cardiology centers at the University of Tartu Clinics, Tartu and North-Estonian Regional Hospital, Tallinn. Detailed information on recruitment stages and response rates is provided in Table vs. 43.4%, respectively). Eventually, 1,007 HTN patients returned filled self-administrated epidemiological questionnaires and 756 of them (75.1%) also agreed to provide blood samples for serum biomarker analysis. The recruited Estonian HTN patients covered a wide range of age groups  were invited to the vs. 54.5 ± 11.2 years; Table vs.162.9 cm; mean weight 94.2 vs. 80.6 kg, respectively) and for self-reported birth height and weight (Table 2), mean BMI was estimated as high as 30.4 ± 5.5 kg/m2 for women and 29.8 ± 5.0 kg/m2 for men.The final distribution of genders among HYPEST cases with self-administrated epidemiological data was 617 women/390 men (61.3%/38.7%). At the recruitment, an average female patient was 4 years older than a participating male patient . Retrospective BP readings (range 1-29 measurements/subject) had been documented for 708 HTN patients (248 men/460 women) during mean 2.3 years (range 1-17 years). BP values during antihypertensive treatment period were available for 528 (182 men/346 women) and the pre-diagnosis (without treatment) BP values were available for 344 patients (124 men/220 women). For 272 patients (101 men/171 women) both, pre-treatment and under medication BP values had been clinically recorded. BP records under antihypertensive treatment had been documented with ≥ 3 readings/subject for 328 patients and ≤ 2 readings/subject for 200 patients , whereas majority of available pre-treatment data (82% of patients) was represented by up to two BP readings/subject .At the recruitment, the mean duration of hypertension among in HYPEST male and female HTN patients was similar, 13.9 ± 12.5 and 13.1 ± 10.8 years, respectively Table . Howevervs. 140.5 ± 17.3 mmHg; P = 0.06; Table The mean baseline systolic (SBP) and diastolic blood pressure (DBP) of recruited patients regardless their antihypertensive treatment status, was 143.2 mmHg (range 131.8 - 156.7 mmHg) and 87.1 mmHg (range 80.3 - 94.6 mmHg), respectively. Recruited female patients exhibited a trend for higher SBP compared to men  588 individuals were knowledgeable about the details of their prescribed antihypertensive treatment. Majority of them (93%) was currently taking anti-hypertensive medication, 7% had temporarily quitted medication. Across all recruited HTN patients the mean period of antihypertensive treatment was 42.5 ± 40.6 months. The number of different prescribed medicines per patient during the treatment period was as high as 3.4 ± 1.7. The most frequent choice for the first prescribed medicine had been a β-blocker (33.6% of cases) followed by ACE-inhibitors (27.7%) and Ca-antagonists (24.5%). For 16.7% of the patients the antihypertensive treatment was launched by the prescription of several drugs.vs. 55.5 ± 8.0 years, respectively; P = 0.02). In total, the incidence of MI among hypertensive men was more than twice as high as in women . This may be related to earlier onset of hypertension in men in general (Table P < 0.01). The diagnosis of diabetes showed similar trend of earlier onset in male HTN patients , whereas no differences among sexes were estimated in disease prevalence . Hypertensive women suffered significantly more from heart arrhythmia . No gender effect was detected for the age of incidence of the first stroke as well as for the frequency of stroke  had complications in cardiovascular system. Among the Estonian HTN patients recruited to the HYPEST study , 119 individuals had experienced myocardial infarction (MI), 53 subjects had suffered from stroke and 120 had also diabetes  from renal tubulo-intestinal diseases (16.8% vs. 2.8%), thyroid diseases (22.1% vs. 4.2%) and hyperlipidemia (46.1% vs. 30.1%).Among other diseases, the HYPEST hypertensive men experienced 3-fold higher frequency of renal failure . Urea, uric acid, creatinin and albumin levels were higher in men compared to women. Conversely, women exhibited higher concentration of K+, total cholesterol and HDL-cholesterol levels.Majority of the HYPEST HTN patients  provided blood samples for the analyses of 11 serum biomarkers , whereas male patients invest more to regular exercise (P = 0.0091). The proportion of never-smokers (non-smokers at diagnosis of HTN excluding previous smokers) was substantially higher in women (75.5% vs. 24.9%) and there were more smokers among men at the diagnosis of hypertension  and at the recruitment  . The most significant effect was detected for smoking, which strongly enhanced the development of HTN. Among non/previous smokers (smoking status at the diagnosis of HTN), the age of the diagnosis of HTN (47.5 ± 13.8 years) was approximately 5 years later (P = 0.00007) compared to the subgroup of regular smokers (42.0 ± 12.3 years).We attempted to estimate the role of individual lifestyle risk factors  on the age of onset of hypertension Figure . All theIn Estonia, cardiovascular diseases (including hypertension) are the most common cause of death both in men and women . DespiteMen and women differ in the pathophysiology, risks and treatment of essential hypertension. The prevalence of hypertension increases with age and is higher among men than women before the age of 55 years, but slightly higher among women thereafter . Similar2 and non-obese < 30 kg/m2). In general, study participants appeared to be aware of the risk factors and seemed to consciously reduce them in their everyday life. For example, among hypertensive patients the number of current smokers is two times lower compared to general Estonian population [It is widely known that lifestyle behaviors such as reducing weight and alcohol intake, quitting smoking, increasing physical activity and eating a healthy diet are related to the prevention and control of elevated blood pressure ,23. Currpulation ,25. Furt2) and this proportion is approximately 20% higher than average in 40-70 years old Estonian people [2 for males; 30.4 ± 5.5 kg/m2 for females) than respective means of age and gender in general Estonian population  in age group 50-60 years [Unfortunately excessive weight gain shows increasing trend in general Estonian population, which is also reflected in HYPEST data ,24,26. Tn people . ObserveThe present study has certain limitations that should be taken into account for interpretation of the results. First, the retrospective self-reported epidemiological data may be biased and tend to exaggerate the occurrence of events. Second, the non-equal distribution of men/women patients as well as the age distribution among sexes might affect the gender-related differences and bias the estimate. In addition, the study sample is only representative of volunteers and findings may therefore not be generalized to all Estonian hypertension patients. Finally, the retrospective BP data extracted from patient's clinical records were measured with different clinical settings  and thus, certain undefined measurement variability could have been introduced into the estimates. Despite these limitations, the present study gives a profile of Estonian hypertensive patients by analyzing considerably larger number of subjects than earlier investigations ,7,24.In summary, the current study characterizes the profile of HTN patients in Estonia. We compared disease and lifestyle parameters of male and female hypertensive patients recruited for the HYPEST study. Our findings are in agreement with published studies, which have revealed gender-specific differences in (i) the age at HTN onset, (ii) HTN risk factors affecting males and females, and (iii) secondary complications of the disease. HYPEST sample collection, combining the clinically diagnosed HTN cases  and population-based controls across Estonia (n = 959) is a valuable source for further epidemiological as well as genetic studies of hypertension -37.The authors declare that they have no competing interests.ML initiated and directed the research, and EO, MV and ML designed jointly the study. All authors participated in the recruitment of study subjects and collection of epidemiological data. GV, EO, MV, MR and TU contributed to the collection of clinical data. GV, EO and ML designed, and GV performed the statistical analysis. EO, GV, PJ and ML drafted the first manuscript and MV, MP, MR, KT and TU revised the interpretation of the data and results, and contributed to the preparation of the final manuscript text. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/11/55/prepub


There is considerable evidence that impaired autonomic control may be associated with the etiology of coronary artery disease (CAD). We hypothesized that the autonomic imbalance as assessed by measuring heart rate variability (HRV) and biological parameters before and after coronary angiography (CAG) may predict the presence of CAD.® (Parama-Tec) is a novel, rapid, and simple method with which we can measure HRV within 5 min. We selected patients  who underwent CAG and analyzed their ambulatory ECGs and blood levels of neuropeptides at both 1 day and immediately before and after CAG. The patients were divided into the presence  and absence of CAD .Ambulatory electrocardiographic (ECG) examination using eHEARTAlthough the CAD group showed an increase in blood pressure immediately before CAG, the ratio of low-frequency to high-frequency (LF/HF) was significantly decreased in the CAD group, but not in the non-CAD group. On the other hand, there was no difference in a coefficient of variation of the R-R interval or pulse rate between the two groups. CAD was independently associated with hypertension (P = 0.011), dyslipidemia (P = 0.009), and LF/HF immediately before CAG (P = 0.046) by a logistic regression analysis.These findings suggest that LF/HF immediately before CAG in addition to hypertension and dyslipidemia might predict the presence of CAD. There is considerable evidence that impaired cardiac autonomic control may be associated with the etiology of coronary artery disease (CAD) , 2. Impa®  has become available for clinical use. This equipment offers a novel, rapid, and simple method with which we can measure HRV, such as the coefficient of variation of the R-R interval (CVRR), high-frequency (HF), low-frequency (LF), and the ratio of LF to HF (LF/HF), all within 5 min.Ambulatory electrocardiographic (ECG) monitoring for 24 h is generally used to assess HRV. Recently, however, an ambulatory ECG examination using eHEARTAutonomic control can also be evaluated by measuring blood levels of catecholamines , noradrenaline (NAd), and dopamine (DOA)) and neuropeptides, such as neuropeptide Y (NPY), pancreatic polypeptide (PP), and urinary L-type fatty acid binding protein (U-L-FABP). Catecholamines are highly sensitive to sympathetic activity , and PP Patients with suspected CAD need to receive coronary angiography (CAG) for the diagnosis of CAD, and CAG may affect the autonomic imbalance. We hypothesized that the autonomic response before and after CAG may predict the presence of CAD. Therefore, we enrolled patients who underwent CAG and analyzed their ambulatory ECG and blood levels of neuropeptides and U-L-FABP at both 1 day and immediately before and after CAG.From April 2012 to August 2012, we enrolled 115 consecutive patients who underwent CAG because of suspected CAD at Fukuoka University Hospital. After ECG examination, we checked the 5 min ECG recording in all patients. When the patients showed a poor ECG recording and had arrhythmias in more than 10% of their recordings, we excluded the patients from the study. The eHEART automatically calculated HRV after we manually deleted the ECG recording with arrhythmias. Thus, we excluded 37 patients including the patients who failed to provide blood and urine samples. Finally, we analyzed 78 patients and divided the patients into CAD (n = 64) and non-CAD (n = 14) groups. The presence of CAD was defined according to significant coronary stenosis  by CAG. The protocol in this study was approved by the ethics committee of Fukuoka University Hospital, and all subjects gave their written informed consent to participate. We collected and analyzed all data using the medical database of Fukuoka University Hospital.2. Medications included β-blocker, α-blocker, αβ-blocker, calcium channel blocker (CCB), angiotensin II receptor blocker (ARB), angiotensin converting enzyme inhibitor (ACE-I), and diuretic.We compared the CAD and non-CAD groups with regard to coronary risk factors based on fasting serum samples. Coronary risk factors included age, gender, obesity (body mass index (BMI)), HT, dyslipidemia (DL), DM, hyperuricemia (HU), smoking, and chronic kidney disease (CKD). Patients who had a current systolic blood pressure (SBP)/diastolic BP (DBP) ≥ 140/90 mmHg or who were receiving antihypertensive therapy were considered to have HT. DM was defined using the Japan Diabetes Society Criteria or if the patient was being treated with an oral hypoglycemic agent or insulin. Patients with LDL-C ≥ 140 mg/dL, TG ≥ 150 mg/dL, and/or HDL-C < 40 mg/dL, or who were receiving lipid-lowering therapy, were considered to have DL. Obesity was defined as a BMI > 25 kg/m® at 4 time-points (at both 1 day and immediately before and after CAG). We defined the time-point at 1 day before CAG as the baseline. We evaluated HRV, such as CVRR, HF, LF, and LF/HF. The fluctuations of R-R intervals were integrated on the HF band (0.15 - 0.40 Hz) and the LF band (0.05 - 0.15 Hz). HRV was expressed as the power of the LF and HF components and the LF/HF power ratio. Supine BP and HR were also measured at these 4 points.Beat-to-beat HR data in the supine positions were continuously recorded for 5 min using eHEARTBlood levels of catecholamines , NPY, PP, N terminal-pro brain natriuretic peptide (NT-proBNP), and U-L-FABP were measured at 2 points (at 1 day before and after CAG). All blood and urinary samples were drawn after the patients had fasted overnight. The concentrations of NPY and PP in plasma and L-FABP in urine were determined in duplicate by specific enzyme immunoassays  according to the manufacturer’s instructions. At our laboratory, the intra- and inter-assay coefficients of variation were each < 5%.2 test for non-continuous variables. Multivariate analysis was performed using a logistic regression analysis for independent variables that were related to the presence or absence of CAD. A value of P < 0.05 was considered significant.Statistical analysis was performed using the Stat View statistical software package . Data are expressed as the mean ± standard deviation (SD). The significance of differences was evaluated using the unpaired and paired t-test for continuous variables and the χAs shown in Blood levels of Ad, NAd, and NPY were significantly reduced at 1 day after CAG in the CAD and non-CAD groups . AlthougNext, we analyzed predictors of the presence of CAD using independent variables by a logistic regression analysis . We seleFirst, we found that LF/HF immediately before CAG was significantly decreased in the CAD group, but not in the non-CAD group, although the CAD group showed an increase in BP. Second, CAD was independently associated with HT, DL, and LF/HF immediately before CAG.RSA  has been shown to be significantly decreased with an increase in coronary angiographic severity [RSA, but not LF/HF, were associated with CAD according to previous reports. Moreover, since lower LF/HF was seen immediately before CAG in the CAD group, we considered the autonomic control immediately before and after CAG in both the CAD and non-CAD patients. The CAD group showed CAG-induced elevation of BP immediately before and after CAG, whereas there were no changes in BP in the non-CAD group. The percent of HT in the CAD group was significantly higher than that in the non-CAD group and the sympathetic nervous system both promotes and amplifies the hypertensive state [The presence of CAD was independently associated with LF/HF immediately before CAG, in addition to HT and DL. It is reasonable that CAD was independently associated with HT and DL in this study because it is well known that HT and DL are critical risk factors for the onset and progression of CAD . Surprisseverity . Thus, Sve state . Since t®. This equipment is convenient and both rapid and simple to use, and 5 min of recording was sufficient for an analysis. A previous report indicated that 5 min was sufficient for short-term HRV analysis [In this study, beat-to-beat HR data were continuously recorded for 5 min using eHEARTanalysis . In addianalysis . In factAlthough blood levels of catecholamine and neuropeptide were significantly decreased at 1 day after CAG, the levels in the CAD group did not differ from those in the non-CAD group. However, the differences between the groups were too small to cause a corresponding difference in sympathetic and/or parasympathetic activities. The blood levels significantly decreased after CAG, whereas LF, HF, and LF/HF at baseline were similar to those at 1 day after CAG. Changes in catecholamine and neuropeptide may not directly influence LF, HF, or LF/HF. In fact, catecholamine increased and LF/HF decreased at day 1 after the operation in a study on the role of the autonomic nervous system in the development of atrial fibrillation after coronary artery bypass surgery . In addiThis study has several limitations. First, the sample size was relatively small and this study was cross-sectional, so causal conclusions can be drawn. Second, the HRV measurements were performed under various medications. Although many of the patients were taking medications that may have influenced the measurements, we analyzed time-course of HRV in each patient and analyzed changes of HRV before and after CAG. In addition, there were no differences in % α-blocker, % β-blocker and % αβ-blocker between non-CAD and CAD groups, although sympathetic blocking agents influence HRV in particular. Third, respiratory rate (RR) may also influence the measurement, although we did not count RR. Fourth, the non-CAD group described in this study was a special group and was not considered to be a usual control group, since the patients underwent CAG because of suspected CAD. Prospective studies are needed to clarify the associations we identified.LF/HF immediately before CAG in addition to HT and DL might predict the presence of CAD, although the mechanism of the association between the increase in BP and the decrease in LF/HF is not yet clear.