To study prevalence and determinants of pulmonary hypertension (PH) in a group of Cameroonian patients without chronic lung disease. We conducted a cross-sectional study conducted between April and December 2011 in a private cardiology clinic in Bafoussam, Cameroon. We included consenting participants aged ≥ 18, who underwent a Doppler echocardiography. Patients with chronic lung disease were excluded.A total of 178 participants were enrolled, of whom 44.4% were males with a mean age of 63.1 ± 17.3 years. The prevalence of PH was 25.3%. Among patients with PH 44.4% had severe disease, (11.2% of study population). Age ≥ 55 years, systolic blood pressure ≥ 140 mmHg, low left ventricular ejection fraction (< 55%), left atrial enlargement, left ventricular hypertrophy and presence of left heart disease  were predictors of echocardiography PH. Obesity was negatively associated with pulmonary hypertension. Pulmonary hypertension is found in a quarter of the participants. Age, systolic hypertension, and any left heart disease were strongly associated to pulmonary hypertension.The online version of this article (10.1186/s13104-017-2903-3) contains supplementary material, which is available to authorized users. Pulmonary hypertension (PH) is a condition characterized by an increase in pulmonary vascular resistance, or pulmonary venous pressure, pulmonary blood flow or both . It is dThis study is reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines .We conducted a cross-sectional study from April to December 2011 in a private cardiologic clinic, “Centre Médical de la Trinité”, located in a semi-urban setting in Bafoussam, Cameroon. Considering that data on the topic are very scarce in our setting and context, despite the still ongoing PAPUCO, there is a need of epidemiological data for a better understanding of this condition in sub Saharan Africa. Given that, these data collected in 2011 (6 years ago) remain of great importance in order to provide a picture of the situation of this pathology in a sub Saharan African setting such as Cameroon. We included all patients aged 18 years or more seen at the clinic, consenting to participate and who underwent a Doppler echocardiography. Though pulmonary artery catheterization is the gold standard for the diagnosis of pulmonary hypertension, a doppler echocardiography was used to this purpose in the present study since a strong correlation between the two tests has been reported. In addition echocardiography is non-invasive, therefore, it is more suitable for epidemiological investigations such as this latter.We excluded patients presenting chronic lung disease such as chronic obstructive pulmonary disease or asthma, and all factors that could influence the estimate of left ventricular mass such as septal dyskinesia on echocardiography, asymmetric septal hypertrophy  as well as large pericardial effusion or chest deformity.® scale balance; height was measured in the upright position to the nearest 0.5 cm. Finally, trans-thoracic echocardiography was performed with the patient in the left lateral decubitus position by an experienced cardiologist (PK) with a commercially available echocardiography equipment  and using a 4–7 MHz transducer.Consenting participants rested for 10 min during which a brief history was obtained. Then, their blood pressure was measured on both arms using a mercury sphygmomanometer with a standard cuff. A second blood pressure measurement was made in the arm with the highest reading after a further 5 min of rest, and the average of the measurements from this arm was considered. Secondly, anthropometric measurements were carried out. Weight was measured in light clothed subjects to the nearest 0.5 kg with a clinical Seca2 was calculated as 2 were classified as obese.Systolic blood pressure measurements ≥ 140 mmHg and/or diastolic blood pressure measurements ≥ 90 mmHg were considered diagnostic of hypertension [Left ventricular measurements were done on long parasternal long axis 2-D guided M-mode using the ASE recommendations . The LVM2 of BSA or LVM/m2.7 of height) > 115 g/m2 (BSA) or > 48 g/m2.7 (height in case of obesity) in men and Indexed LVM > 95 g/m2 or > 44 g/m2.7 in women [LVH was defined based on ASE recommendations as Indexed LVM  was calculated using the gradient across the regurgitant tricuspid valve plus the right atria pressure. This was estimated from the peak velocity of the trans-tricuspid jet recorded by CW Doppler ultrasound. Pulmonary arterial systolic pressure is equal to right ventricular systolic pressure in the absence of pulmonary stenosis. This was estimated by calculating the right ventricular to right atrial pressure gradient during systole, approximated by the modified Bernoulli equation as 4vulations .p value less than 0.05 was considered statistically significant.A sample size of 138 participants was required, assuming the prevalence of 10% of pulmonary hypertension among patients in Cameroon , a 5% map = 0.014), SBP ≥ 140 mmHg , low LV ejection fraction (< 55%) , left atrial enlargement , left ventricular hypertrophy , and the presence of any left heart disease (LVH with systolic dysfunction and LAE)  were predictors of echocardiography PH. Obesity (BMI ≥ 30 kg/m2) was negatively associated with  echocardiography PH. The differences in the prevalence and determinants of pulmonary hypertension in young and old female and male patients and the determinants of pulmonary hypertension in the whole population are summarized in Additional file One hundred and seventy-eight 178) participants were enrolled, of whom 79 (44.4%) were males. Their mean age was 62.8 ± 15.9 years, and the age group greater than 70 years was the most frequent 37.1%). The clinical and echocardiography characteristics of the study population are summarized in Tables 78 partic7.1%. TheThis study shown that pulmonary hypertension (PH) is found in a quarter of the participants without chronic lung disease in this group of sub-Saharan Africans. Age > 55 years, systolic hypertension, and any left heart disease were predictors of PH.The evidence from the few reports on PH in SSA showed that PH is more prevalent and carries a poor disease course . We haveIn conclusion, PH was seen in a quarter of the participants without chronic lung disease in this group of sub-Saharan Africans. Age ≥ 55 years, systolic hypertension, and any left heart disease were strongly associated with PH. This underscores the need for screening for PH in hypertensive patients in SSA age ≥ 55 years.An important limitation of this study was the used of clinical information to exclude chronic lung disease. Also, the data presented in this article were collected in 2011 (6 years ago) what makes them a bit outdated. However, despite the still ongoing PAPUCO, data on the topic are scarce especially in our setting and context and there is a need of epidemiological data for a better understanding of this condition in sub Saharan Africa. Given that, our report remain of high importance. Another limitation is the used of echocardiography which is not the gold standard for the diagnosis of pulmonary hypertension.Additional file 1: Table S1. Prevalence and risk factors of pulmonary hypertension in males and females.Additional file 2: Table S2. Prevalence and risk factors (unadjusted and adjusted) of pulmonary hypertension in the general population.Additional file 3: Table S3. Determinants of pulmonary hypertension without chronic lung disease.


The surge in prevalence of chronic noncommunicable diseases like hypertension and chronic kidney disease has been linked with modifiable lifestyle practices and increased body fat. This study sought to compare the association between different modifiable lifestyle practices, adiposity indices, renal function parameters, and hypertension as well as the predictive implications for levels of these parameters in target cardiac organ damage among an urban Ghanaian hypertensive population. Using a hospital-based case-control study design, 241 Ghanaian indigenes from the Kumasi metropolis were recruited for this study. The case group was made up of 180 hypertensives and 61 normotensives served as controls. In addition to sociodemographic data, standard haemodynamic, anthropometric, renal function, and cardiac organ damage assessments were done. The prevalence of chronic kidney disease (CKD) ranged from 13.3% to 16.6% depending on the equation used in estimating the glomerular filtration rate (eGFR). Percentage cluster distribution by chronic kidney disease was observed to be significantly tilted toward the upper quartiles (3rd and 4th) of the haemodynamic parameters measured. Chronic kidney disease was significantly higher among self-reported smokers and alcoholic hypertensives. In this urban population, adiposity was associated with hypertension and renal insufficiency. Chronic kidney disease was associated with hypertension and cardiac abnormalities. High blood pressure is a major health problem all over the world . Ghana aThe upsurge in chronic noncommunicable diseases has been attributed to modifiable lifestyle practices characterized by sedentary lifestyle and a resultant obesity –13. EvidThis study sought to compare the association between different modifiable lifestyle practices, adiposity indices, renal function parameters, and hypertension as well as the predictive implications for levels of these parameters in target cardiac organ damage among an urban Ghanaian hypertensive population.A hospital-based case-control study was conducted between November 2012 and September 2013. Two hundred and forty-one participants were involved in this study. One hundred and eighty (108) nondiabetic hypertensive patients were attending clinic at the Komfo Anokye Teaching Hospital (KATH) and the Precise Specialist Clinic, all in Kumasi, Ghana, and sixty-one (61) age-matched normotensive controls were from the Kumasi metropolis. The study participants were recruited from a population of adult individuals between the ages of 22 and 87 years. Criteria for the case group were patients diagnosed with hypertension who were not suffering from diabetes and were of consent age. The control group were normotensive age-matched healthy individuals with no past history of diabetes, cardiac, renal, and hepatic dysfunction, or dyslipidaemia, living in the Kumasi metropolis, who consented to participate in this study. The detailed characteristics of study participants have been published in an earlier work .Self-reported structured questionnaire was administered to determine duration of hypertension and treatment status, smoking status, alcohol intake, educational level, physical activity levels, occupation, the usage of nonprescribed orthodox and herbal medications, family history of hypertension, current and past symptoms of cerebrovascular disease, and peripheral vascular and coronary heart diseases.Blood pressure (BP) and pulse rate measurements were done using the Omron M5-I digital fully automatic blood pressure monitor . After participants had sat quietly for at least ten minutes, three measurements were taken at one-minute intervals on the right arm in a seated position, with arm supported at heart level and feet flat on the floor using an appropriate sized cuff. Hypertension was diagnosed when the mean of the second and third blood pressure (BP) measurements was equal or above 140/90 mmHg or when participants reported use of antihypertensive medication which was verified from their hospital files , 28.2). The waist-to-hip ratio (WHR) was calculated by dividing the waist circumference (cm) by the hip circumference (cm). Waist-to-height ratio was calculated by dividing the waist circumference (cm) by the height circumference (cm). Other calculated adiposity indices were as follows:(1)Conicity index (CI) :(1)CI=Wa(2)Abdominal volume index (AVI) :(2)AVI=2(3)Body Adiposity Index (BAI) :(3)BAI=HAnthropometric measurements included height to the nearest millimeter without shoes and weight to the nearest 0.1 kg in light clothing. Subjects were weighed on a bathroom scale  and their height was measured with a Seca stadiometer with the participant standing erect with back straight, heels together, and feet slightly apart at a 60-degree angle. Waist circumference (to the nearest centimeter) was measured with a Gulick II spring-loaded measuring tape  midway between the inferior angles of the ribs and the suprailiac crests. The hip circumference was measured as the maximal circumference over the hip circumference (HC) at the level of the widest diameter around the gluteal protuberance in centimeters. Body mass index (BMI) was calculated by dividing weight (kg) by height squared (mhttp://www.roche.com/index.htm) at the Komfo Anokye Teaching Hospital in Kumasi. All other biochemical analytical investigations were carried out at the Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR) located at the Kwame Nkrumah University of Science and Technology, Kumasi.Venous blood samples were collected after an overnight fast (12–16 hours) between 7 am and 10 am. About 5 mL of venous blood was drawn from the antecubital vein of which four mL was dispensed into vacutainer® plain tubes and one mL was dispensed into fluoride oxalate tubes. After centrifugation at 500 ×g for 15 minutes, the serum and plasma were stored at −80°C until assayed. Parameters that were determined include fasting blood glucose (FBG) to exclude participants with diabetes, urea, creatinine, uric acid, potassium, sodium, and chloride. The methods adopted for the determination of the urea, creatinine, and uric acid were predetermined by the reagent manufacturer . Ion Selective Electrode (ISE) method was used to assay electrolytes , and transthoracic echocardiogram (ECHO) were done. All diagnoses and interpretation were performed by consultant radiologists and cardiologists.Estimate glomerular filtration rate (GFR) was calculated from serum creatinine according to Cockcroft-Gault 2  tests, or Fisher exact tests where appropriate. Analysis of variance (ANOVA) and Bonferroni post hoc test were used to compare more than two means, whilst a post hoc linear contrast test was used for trend analysis of continuous variables. A level of p < 0.05 was considered as statistically significant for all analyses. IBM Statistical Package for the Social Sciences  version 20.00) and GraphPad Prism version 6.00 GraphPad software, San Diego, California, USA (http://www.graphpad.com/), for windows were used for statistical analysis where appropriate.Normality of all continuous variables was tested. All nonparametric variables were normalized by log transformation before analysis. Results obtained after analysis of log transformed variables were converted by antilog. Continuous variables were expressed as their mean ± SEM, whereas categorical variables were presented as count and proportion. Comparisons of the general characteristics of the hypertensive group against the normotensive group were performed using unpairedTwo hundred and forty-one (241) adult Ghanaians were recruited for the study. The sociodemographic characteristics of the participants, as shown in Among all the parameters evaluated as shown in +, Na+, Cl−, urea, creatinine, and UA) as well as renal insufficiency. With the exception of pulse, no significant correlation was observed between the anthropometric measures and the haemodynamic measures among the hypertensive subpopulation.Among the general study population after adjusting for age and gender, positive additive changes in waist-to-height ratio (WHtR) as well as both the abdominal body frame factors (waist circumference (WC); hip circumference (HC)), the abdominal body region volumetric models for central obesity (conicity index (CI); abdominal volume index (AVI)) and body fat deposition (body adiposity index (BAI)) were associated with corresponding incremental changes in the haemodynamic measures (hypertension), the serum biochemical kidney profile measures, and renal insufficiency (decreasing eGFR). Among the hypertensive subpopulation, positive association was observed between the anthropometric measures and the serum biochemical kidney profile  when assessed by the four-variable modification of diet in renal disease Among the hypertensive patients who were newly diagnosed and thus treatment-naïve and those who were on therapy irrespective of the equation used in assessing glomerular filtration rate, the group on therapy recorded a greater percentage of end-stage chronic kidney disease (CKD) than their naïve counterparts; however, with the exception of the chronic kidney disease epidemiology collaboration (CKD-EPI) equation see , this diIrrespective of the equation used in estimating the glomerular filtration rate (GFR), self-reported nonalcoholics presented with significantly higher percentage of chronic kidney disease (CKD) than the alcoholics  for chronic kidney disease epidemiology collaboration (CKD-EPI), Cockcroft-Gault From Almost all participants presenting with chronic kidney disease (CKD) clustered at the upper quartiles (3rd and 4th) of systolic blood pressure. The exception included 10% of CKD subjects who clustered at the lower quartiles  of systolic blood pressure when Cockcroft-Gault The prevalence of microalbuminuria among the alcoholic subjects was 32.4% compared to 27.8% among the nonalcoholics. Study participants who smoked recorded a higher percentage of microalbuminuria compared to nonsmokers and also a higher number of smokers were found to cluster at increasing levels of microalbuminuria compared to nonsmokers. Patients using herbal medicine had higher microalbuminuria (32.7%) than those who were not using herbal medications (27.6%). Even though higher microalbuminuria was observed among the physically active group, severity of microalbuminuria was more profound in their nonactive counterparts see .In general, significant additive linear relationship was observed for all serum renal biochemical parameters assayed with progressive quartile increment of haemodynamic indices. The exception was observed with the average levels of uric acid among the diastolic quartile cluster distribution, where no significant linearity was observed.Irrespective of the renal function equation used in the estimation of the glomerular filtration rate among the study population, participants presenting with cardiac abnormalities  recorded significant prevalence of chronic kidney disease compared to their counterparts who were without the specific abnormal heart condition see .2; stages 3, 4, and 5) among different hypertensive populations in Accra Ghana at 4.1% and 27.8%, respectively. The estimates of hypertensive kidney target organ damage burden for the present study (17.80%–22.22%) compared to the earlier records in the previous studies but were higher than the former and lower than the latter. The difference in CKD burden for the hypertensive cohort was perhaps due to differences in study population characteristics; thus, the work of Addo et al. [Earlier reports by Addo et al.  and Osafo et al.  involvedo et al.  and the o et al.  includedo et al.  in an edThe incidence of CKD was higher among the hypertensive study participants on treatment than the treatment-naïve group. The increased duration of chronic diseases like hypertension has usually been linked with deterioration of sequelae and survival. Also the institution of drug therapy in the management of hypertension is usually associated with advancing disease state and this may account for the higher target kidney organ damage observed among the hypertensives on treatment.p = 0.0337) among females (57.5%) compared to the males (40.5%).Gender differences in health vary according to differential vulnerabilities in males and females, which may be as a result of biological or sociodemographic differences , 39. In The raging debate of alcohol consumption as a modifiable lifestyle trait influencing both hypertension and kidney outcomes in the scientific literature has become even more intense in recent times because of the great importance it confers due to the seemingly large numbers of the population any prognostic outcome may affect. In the current study, self-reported alcohol consumption was recorded among more than half of the study population (130 (53.9%)) with a significantly higher presence among the hypertensives than the normotensives see . DeleterThe findings of the current study are consistent with those of Renaud et al.  and ReynDespite the recent report from the HUNT study suggesting smoking is not a major determinant of adverse blood pressure and other component cardiovascular disease risk factors  and the In the present study, self-reported smoking was 13.3% among the total study population and significantly higher among the hypertensives compared to normotensives (16.1% versus 4.9%). In agreement with the findings of adverse renal events associated with cigarette smoking among various study populations , 60–63, Excess weight gain is a major risk factor for essential hypertension and end-stage renal disease (ESRD) , 66. In There is an accumulating body of clinical and experimental data implicating obesity as an important causative factor in renal disease –76. SeveThere is intense debate as to whether hypertension causes kidney disease or vice versa . High blSerum elevation of kidney excretory products like electrolytes and metabolites of purine and amino acid catabolism (uric acid and urea) in hypertensives has traditionally been attributed to decreased glomerular filtration rate (GFR) as a result of the effect of hypertension on renal function. A reduction in renal blood flow as a consequence of increasing renal vascular resistance leads to decreased distal tubular flow rate which leads to increased reabsorption and decreased excretion , 79, 80.Linear additive relationship was observed for all serum electrolytes as well as urea and uric acid with progressive quartile increment of haemodynamic indices measured in this study. After adjusting for age and gender in the present study, surfeit urea and uric acid were significantly associated with renal insufficiency see . Often cIn this urban population, chronic kidney disease was associated with hypertension and cardiac abnormalities. Adiposity was associated with hypertension and renal insufficiency. Modifiable lifestyle practices  increased the risk of hypertension, whilst smoking increased kidney target organ damage among hypertensives.


In Europe more than 50% of asthmatic treated patients have not well-controlled asthma. Asthma affects about 2.5 million of patients in Italy.The present survey aims at investigating how Italian allergists approach asthmatic patients, in order to highlight pitfalls and unmet needs concerning real-life asthma management.An anonymous 16 item web questionnaire was available (April–October 2015) to all allergists who visited the web site of SIAAIC . Those who wished to give their contribution had the opportunity to answer about epidemiology, risk factors, treatment approaches, and adherence to therapy.One hundred and seventy four allergists answered the survey. 54% of them reported up to 10 patient visits per week and 35.3% between 10 and 30. The most frequent reasons of follow up visits are routine check-up , and worsening of symptoms . Nocturnal apnoeas, gastro-esophageal reflux and obesity are the most important comorbidities/risk factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO levels and reduced exercise tolerance are the most important indicators of asthma severity. Concerning therapy, ICS combined with LABA is the treatment of choice suitable for the majority of patients. A rapid onset of action and a flexible ICS dosage are indicated as the optimal characteristics for achieving the therapeutic goals. Poor adherence to therapy is an important reason for symptom worsening for the majority of allergists. Complex dosage regimens and economic aspects are considered the most important factors impacting on adherence.Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities are frequent in asthmatic patients and may impact negatively on disease control, thus identifying patients who need a more careful and strict monitoring. Airway hyper-responsiveness to methacholine challenge test and nitric oxide are considered important indicators of asthma severity. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals.The online version of this article (doi:10.1186/s12948-017-0067-2) contains supplementary material, which is available to authorized users. Asthma is one of the most prevalent chronic conditions, affecting approximately 300 million people worldwide . In deveAsthma cannot be cured, but appropriate management can control the disorder and enable people to enjoy a good quality of life. However, despite the advances in therapeutic approaches and the dissemination of guidelines , observaThe cornerstone of asthma management is to achieve and maintain the control of the disease  and seveA board of experts belonging to Società Italiana di Allergologia, Asma Immunologia Clinica (SIAAIC) developed a questionnaire composed of 16 multiple choice questions covering epidemiological (number of patients assisted) and clinical (presence of co-morbidities or risk factors) aspects about asthma, and exploring the overall management strategies  adopted by the Italian allergists .Ninety allergists (54%) reported to see up to 10 asthma patients per week and 60 (35.3%) between 10 and 30 patients Fig. .Fig. 1PeThe most frequent reasons of follow up visits were routine checkup for 91 allergists (56.5%), and worsening of symptoms for 66 allergists (41%), whereas the percentage of visits due to drug adverse effects was negligible (3%).Around 70% of allergists declared to assess their patients regularly with scheduled follow up visits: 25–50% of patients according to 54 allergists (35.5%) and >50–75% of patients according to 50 allergists (33.8%).For the assessment of patient’s condition in the follow up, airway hyper-responsiveness by methacholine challenge testing was considered the most important indicator, followed by nitric oxide (NO) levels and home PEF monitoring Fig. a. AccordNocturnal apneas and obesity were rated as the most important co-morbidities/risk factors of poorly controlled asthma, followed by gastro-esophageal reflux and smoking habits and lastly by rhinitis and rhino-sinusitis Fig. .Fig. 4AvConcerning therapy, regular use of inhaled corticosteroids (ICS) combined with long acting beta agonists (LABA) was considered the treatment of choice suitable for the majority of patients Fig. . A rapidPoor adherence to therapy was considered an important cause of symptom worsening for the majority of allergists, and 37% of them (n. 56) believed that it was the prevalent cause. Notably, complex dosing regimens and cost of therapy were rated as the most important factors impacting on adherence Fig. a.Fig. 8FAs regards the inhaler, consistency of the released dose and low number of critical errors were considered the most important characteristics impacting on adherence Fig. b.Allergists are involved in the management of asthma, seeing their patients more frequently, but not exclusively, in the pollen season. Interestingly, they rely on airway hyper-responsiveness and inflammation for classification of asthma severity and monitoring of asthma control during follow-up visits, as indicated by the high rate attributed to methacholine challenge testing and NO levels. Indeed, the degree of airway hyper-responsiveness and inflammation are usually in proportion to the severity of the underlying asthma and may reflect the response to the treatment . Of noteConsistently with international reports –10, alleFor allergists the combination of LABA and ICS is the treatment of choice for most asthmatic patients. This is consistent with broad literature evidence indicating that that combination therapy is the most effective strategy in preventing clinical manifestations and gaining rapid asthma control than ICS alone . FurtherLike in every chronic disease, adherence to medication regimens is considered of essence to achieve and maintain asthma control . Indeed,In regards to inhaler preferred features, allergists give high importance to inhaler efficiency in terms of consistency in dose delivery across different flow rates, making the device suitable and reliable also in patients with severe airflow limitation. Another important feature is the low risk of critical errors that impair the delivery of medication to the lung.Our survey has some limitations: (1) it has been addressed only to allergists, and we are aware that it would be of interest to compare the responses of different kinds of specialists  on the management of asthma; (2) the questionnaire did not investigate the knowledge of severe asthma, thus information is missing about the management of this kind of patients by allergists; (3) like in all surveys, the responses from physicians may not always correspond to their daily clinical practice, but rather reflect their opinions and insights on optimal disease management.Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities may identify patients who need a more careful and strict monitoring to achieve asthma control. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad literature evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals. Complex dosing regimens and poor inhalation technique may negatively impact on adherence.


Few reports have described the significance of viral respiratory infections (VRIs) in exacerbation of asthma in adult patients. The aim of this study was to elucidate the profiles of VRIs in adult patients with asthma along with their molecular epidemiology.A cross-sectional observational study was conducted at Kyorin University Hospital from August 2012 to May 2015. To identify respiratory pathogens in inpatients and outpatients suffering from asthma attacks, RT-PCR/sequencing/phylogenetic analysis methods were applied alongside conventional microbiological methods. Phylogenetic and pairwise distance analyses of 10 viruses were performed.A total of 106 asthma attack patients enrolled in this study in both inpatient (n = 49) and outpatient (n = 57) settings. The total 106 respiratory samples were obtained from nasopharyngeal swab (n = 68) or sputum (n = 38). Among these, patients with virus alone (n = 39), virus and bacterial (n = 5), and bacterial alone (n = 5) were identified. The ratio of virus-positive patients in inpatient or outpatient to the total cases were 31.1% (n = 33) and 10.4% (n = 11), respectively. The frequency of virus-positive patients was significantly higher in inpatients  than in outpatients . Major VRIs included human rhinovirus (HRV) (n = 24), human metapneumovirus (hMPV) (n = 9), influenza virus (Inf-V) (n = 8), and respiratory syncytial virus (RSV) (n = 3) infections with seasonal variations. HRV-A and HRV-C were the most commonly detected viruses, with wide genetic divergence on phylogenetic analysis.Asthmatic exacerbations in adults are highly associated with VRIs such as HRV-A or HRV-C, hMPV, RSV, and Inf-V infections with seasonal variations and genetic divergence, but similar frequencies of VRIs occurred in asthma attack patients throughout the seasons. Furthermore, Jackson et al demonstrated that children had an increased risk of asthma at 6 years of age if they experience wheezing in the first 3 years of life, with RSV [odds ratio (OR): 2.6], HRV (OR: 9.8), or both HRV and RSV (OR: 10). Regarding adult asthma patients, previous reports showed that respiratory tract infections associated with asthma exacerbation ranged from 10% to 21% to 45%,–6 of which 60% are HRV. However, especially in Japan, few epidemiological data exist on the correlation between VRIs and asthma attacks in adult patients,8 from studies conducted within the year.Risk factors relating to the development of asthma attacks are multiple and complex. The frequency of viral respiratory infections (VRIs) in asthma attack patients is now recognized as having a major impact on asthma pathogenesis in children. and Kraft et al described the correlation between Mycoplasma pneumoniae infection and asthma attacks in adult patients; however, the preliminary findings could not confirm the evidence of M. pneumoniae infection in those patients.,12 Therefore, we prospectively studied adult patients with asthma attacks to clarify the role of VRIs and/or bacterial infection, including M. pneumonia, and their molecular epidemiology.Moreover, Martin et al22.1In this cross-sectional observational study, we prospectively enrolled adult patients suffering from asthma attacks visiting Kyorin University Hospital (a 1100-bed tertiary center in Tokyo) in both inpatient and outpatient settings from August 2012 to May 2015.2.2American Thoracic Society (ATS)/European Respiratory Society (ERS) statement.Eligible patients were aged over 18 years and had a clinical diagnosis of asthma in addition to one or more of the following characteristics: variability in peak expiratory flow of more than 20%; airway reversibility by inhaled β2 agonist; hyper-responsiveness to methacholine challenge; and recurrent dyspnea episodes with wheezing. Asthma attack patients were enrolled in this study if they had acute or subacute episodes of progressively worsening shortness of breath, cough, wheezing, and chest tightness, or some combination of these symptoms, characterized by decreases in expiratory air-flow and objective measures of lung functions according to the latest National Institute of Health (NIH) National Asthma Education and Prevention (NAEP) guidelines/Global Initiative for Asthma (GINA) guideline 2012 or satisfied the moderate to severe exacerbation of asthma based on the 2.3We excluded the patients who had chronic obstructive lung disease, pneumonia, interstitial lung diseases, acute heart failure, and respiratory symptoms that were possibly due to infections in the last month.2.4M. pneumoniae, and Chlamydophila pneumoniae were collected separately from those intended for bacterial cultures and were stored at -80°C until use. Gram stain was performed on a purulent portion of each sputum specimen and examined by trained personnel. Sputum samples were considered as good quality for evaluation if they were classified as Geckler 4 or 5. Positive bacterial culture was based on acceptable sputum samples with predominant species and compatible results from Gram staining.Respiratory samples included sputum or nasopharyngeal swab collected at inpatient admission or at the outpatient setting at the time patients were diagnosed of asthma attacks. Clinical data were also obtained at the same time. Respiratory samples for PCR-based detection of respiratory viruses, 2.5M. pneumoniae and C. pneumoniae as previously described.,14 We used specific primer sets for the amplifications of these viruses as we also previously described.,14 PCR products were purified using MonoFas DNA Purification Kit I . The purified products were sequenced with a BigDye Terminator v3.1 Cycle Sequencing Kit  using the above primers. Sequence analysis was performed on an ABI 3130 Genetic Analyzer (Applied Biosystems). The nucleotide sequences thus obtained were given GenBank accession numbers from LC020476 to LC020488. 2.7.Samples were centrifuged at 3000 g at 41°C for 30 minutes. Viral RNA and DNA were extracted from supernatants using the QIAamp Viral RNA Mini Kit . Reverse transcription was performed using PrimeScript RT reagent Kit , according to the manufacturer's instructions. We used reverse transcription polymerase chain reaction [(RT)-PCR] to try to detect both DNA and RNA viruses, including human metapneumovirus (hMPV), human rhinovirus (HRV), enterovirus, respiratory syncytial virus (RSV), influenza viruses A, B, and C , human parainfluenza viruses, human coronavirus, adenovirus, cytomegalovirus, human parvovirus B19, varicella zoster virus, and human bocavirus together with 2.6F gene (317 bp), G gene , and VP4/VP2 coding region (390 bp), respectively.We performed phylogenetic analyses using Molecular Evolutionary Genetics Analysis (MEGA) software, version 5.0. Phylogenetic analysis of hMPV, RSV, and HRV was based on parts of the  Evolutionary distances were estimated using the Kimura 2-parameter method and phylogenetic trees were constructed using the neighbor-joining (NJ) method. Reliability of the trees was estimated using 1,000 bootstrap replications. We calculated pairwise distances (p-distance) of the respiratory viruses detected in this study, hMPV, RSV, Inf-V, and HRV, using MEGA software, version 5.0. Calculations were based on the nucleotide sequences of each virus.The species of the viruses were estimated using the basic local alignment search tool (BLAST).2.7Samples were collected after written informed consent was obtained from the subjects or their legal representatives. The study protocol was approved by the Ethics Committee on Human Research of Kyorin University Hospital (H24-021) on July 31, 2012. The protocols were carried out in accordance with the approved guidelines.2.8P < .05 was considered statistically significant. Data were analyzed using IBM SPSS version 20.0 software for Windows .Statistical comparisons of nonparametric data were performed using the Mann–Whitney test or Wilcoxon signed-rank test. Comparisons of categorical data were made using Pearson Chi-squared test. All tests were 2-sided. A value of 33.12 ≤88%), wheezes, and patients classified as severe or serious asthma attack according to Japanese guideline and/or ATS/ERS statement were significantly higher in the inpatient group than in the outpatient group (Table P = .054) between inpatients [median 37.0°C, interquartile range (IQR) 36.6–37.9) and outpatients  count and C-reactive protein (CRP), were also comparable in both groups.We examined a total of 106 asthma attack patients in the study period, in both inpatient (n = 49) and outpatient (n = 57) settings. Among these, patients with virus alone (n = 39), virus and bacterial (n = 5), and bacterial alone (n = 5) were identified. The ratio of virus-positive patients in inpatient or outpatient to the total cases were 31.1% (n = 33) and 10.4% (n = 11), respectively. The frequency of virus-positive patients was significantly higher in the inpatient group  than in the outpatient group  (Table 3.2P = .08) and the proportion of smokers  were not significantly different in virus-positive and negative inpatients. In addition, the proportion of the patients with hypercapnia (PaCO2 ≥45 Torr) was not significantly higher in virus-positive inpatients than in virus-negative inpatients .Of the 49 inpatients, 33 (67.3%) were virus positive Table . The ageDuration of respiratory failure (days), wheezes (days), steroid treatment (days), and hospital stays (days) did not differ significantly in virus-positive and negative inpatients Table . Further3.3The total 106 respiratory samples were obtained from the nasopharyngeal swab (n = 68) or sputum n = 38). Among the 38 sputum samples, good quality samples (Geckler classification of 4 or 5) were only 19 samples, out of which 10 samples were positive for bacteria , hMPV (n = 9), Inf-V (n = 8), and RSV n = 3) (Table  (Table 33.4During the study period (approximately 3 years), respiratory virus infection was more common in the spring (March to May) and autumn (September to November) Fig. . Of note3.5We performed phylogenetic analysis of HRV, hMPV, Inf-V, and RSV as a major cause of asthma attack in this study. HRV was the most commonly detected virus and consisted of diverse genotypes on phylogenetic analysis Fig. . This tr4This study was the first to show that various respiratory viruses such as HRV, hMPV, Inf-V, and RSV were associated with asthma attacks in Japanese adult patients.HRV was the most common cause of asthma attacks in autumn, Inf-V was predominantly seen in winter to spring, and VRIs seemed to equally affect asthma attacks in every season in Japan during the 3-year study period. Moreover, the molecular epidemiological data suggested that the detected viruses had a wide genetic divergence (particularly HRV-A and HRV-C) with seasonal variations. showed that a majority of Japanese children with acute wheezing illness during a 17-month period had an RSV, HRV, or RSV and HRV infections. They also found that RSV was dominantly detected in patients with no history of wheezing and/or asthma, while HRV was dominant in patients with a history of wheezing and/or asthma. Indeed, the present study demonstrates that HRV is an important cause of asthma attacks, even in adult patients.Fujitsuka et al Miller et al found that HRV-C has a stronger association with virus-induced asthma than HRV-A and HRV-B in hospitalized children younger than 5 years with acute respiratory illness. However, the epidemiological data of HRV associated asthma attacks in adults were scarcely reported in Japan. In this regard, the present study showed that HRV-A or HRV-C has a potential role in asthma attacks among Japanese adult patients, with a wide genetic divergence. As shown in Fig.  Furthermore, previous reports described other respiratory viruses, such as hMPV, RSV, parainfluenza virus, Inf-V, and coronavirus, as a cause of asthma attack in adults, and the present study clearly demonstrated the main causative viruses are HRV, hMPV, RSV, and Inf-V.The molecular epidemiology of each HRV species associated with asthma attacks may not be completely known, because the HRV-C was recently recovered or nonculturable.What is more important is the finding in our study that the various VRIs can cause asthma attacks with a seasonal predilection in each virus; however, the frequency of VRIs in asthma attack patients seem to be equal throughout the seasons.M. pneumoniae or C. pneumoniae, which is contrary to the findings described in previous reports.,11Interestingly, there was no infection or coinfection with 2 ≥45 Torr) and the duration of asthma (years), but the severity of wheezing and/or bronchial epithelial damage differed among respiratory viruses, thereby furthering the accumulation of index cases required to independently demonstrate the pathogenesis of asthma attacks or the clinical characteristics of each virus. The limitations of our study include lack of data for the severity of bronchoconstriction or inflammation in the lower respiratory tract and paucity of data about the different mechanisms of asthma attacks resulting from each virus infections, which might lead to the diverse respiratory symptoms or the development of airway remodeling.Of note, regarding inpatients, virus infection seemed to be associated with hypercapnia (PaCOHowever, the present study reports the first evidence of VRIs in asthmatic adult Japanese patients with a clear molecular epidemiology in a single-center cohort.5Asthmatic exacerbations in adults are highly associated with VRIs, such as HRV-A or HRV-C, hMPV, RSV, and Inf-V infections with seasonal variations and genetic divergence, but the frequency of VRIs in asthma attacks seemed to be equal throughout the seasons.


We investigated whether and to what extent stenosis of predominant collateral donor artery (PCDA) affects coronary collateral flow in relation to blood pressure (BP) in type 2 diabetic patients with chronic total occlusion (CTO).Collateral flow index (CFI) as derived from intracoronary pressure distal to occluded segment and mean aortic pressure in 220 type 2 diabetic patients and 220 propensity score matched non-diabetic controls undergoing percutaneous coronary intervention for CTO. The severity of PCDA stenosis was graded according to lumen diameter narrowing.CFI decreased stepwise from mild to severe stenosis of the PCDA and was lower in diabetic patients with moderate or severe PCDA stenosis than in non-diabetic controls . When the PCDA was mildly stenotic, CFI increased initially along with a reduction in diastolic BP, and decreased when diastolic BP was below 60 mmHg in diabetic patients . In the presence of moderate PCDA stenosis, diabetic patients had significantly lower CFI compared to non-diabetic controls, with a relative reduction of 19.8% at diastolic BP 70–79 mmHg, 28.2% at 60–69 mmHg and 38.2% below 60 mmHg . A severe PCDA stenosis resulted in a more pronounced decrease in CFI, with a relative reduction of 37.3% for diabetics compared to non-diabetics when diastolic BP was below 60 mmHg (P = 0.050).In the setting of CTO, donor artery stenosis confers greater risk for reduced coronary collateral flow when diastolic BP is decreased. Even a moderate stenosis in the PCDA may be associated with lower collateral flow as diastolic BP decreases below 80 mmHg in type 2 diabetic than in non-diabetic patients. In patients with stable coronary artery disease, a gradual development of complete coronary obstruction may lead to a sufficient compensation of blood supply via collateral circulation to prevent myocardial damage from ischemic insults . ProtectIn total, 1147 consecutive patients with stable coronary artery disease and CTO (> 3 months) of at least one major epicardial coronary artery between October 2010 and December 2016 were screened from the database of Shanghai Rui Jin Hospital PCI Outcome Program , 18. We The duration of CTO was estimated based on information obtained from a previous angiogram, a history of myocardial infarction in the target vessel territory, or the first onset of an abrupt worsening of existing angina. The diagnosis of type 2 diabetes was made according to the criteria of the American diabetes association, including glycosylated hemoglobin (HbA1c) ≥ 6.5%, fasting plasma glucose concentration ≥ 7.0 mmol/L, 2-h postprandial glucose concentration ≥ 11.1 mmol/L, or a random plasma glucose ≥ 11.1 mmol/L in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis . HyperteEPI (mL/min/1.73 m2) = 141 × min α × max −1.209 × 0.993age × 1.018 [if female], where k is 0.7 for females and 0.9 for males, α is − 0.329 for females and − 0.411 for males, min indicates the minimum of creatinine/k or 1, and max indicates the maximum of creatinine/k or 1 [We obtained blood samples at the day of angiography in all patients after an overnight fasting. Assessment of serum levels of creatinine, blood urea nitrogen, uric acid, lipid profiles, glucose, and glycosylated hemoglobin (HbA1c), was made with standard laboratory techniques. Glomerular filtration rate (GFR) was estimated using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation: GFRe/k or 1 . Serum hCoronary angiography was performed via femoral or radial access with 6Fr diagnostic catheters. Quantitative angiographic assessment was done independently by two blinded interventional cardiologists according to lesion classification scheme of the American College of Cardiology/American Heart Association . The PCDElective PCI for CTO was performed through an antegrade approach in all patients. After crossing the occluded segment with various types of guide wire, a microcatheter was advanced distal to the occlusion. Sometimes, a low-profile balloon catheter was passed initially, and then was exchanged for a microcatheter. Meticulous care was taken to ensure complete obstruction of the coronary artery by lack of contrast passage during proximal contrast injection through the guiding catheter while the microcatheter was in place. Intracoronary pressure distal to an occluded segment measured through a microcatheter  and central aortic pressure determined from a 6Fr guiding catheter were simultaneously recorded using a fluid-filled manometer system . The transducer was kept at the level of mid axillary line, and zero calibrated to atmosphere before measurement . DespiteWe have validated the accuracy of intracoronary pressure-derived collateral flow measurement using a microcatheter against the standard pressure wire technique  with RadiAnalyzer™ Xpress System . Bland–Altman analysis revealed that in 40 consecutive patients, Pd and CFI determined with a microcatheter correlated significantly with those by a pressure wire , with an absolute difference in Pd and CFI between the two techniques of 1.68 mmHg  and 0.019 , respectively.For patient selection, a propensity score matching analysis was performed in advance with a match tolerance of 0.02 and a ratio of 1:1 for diabetic and non-diabetic patients using a logistic regression model with age, sex and risk factors for coronary artery disease (smoking and history of hypertension or dyslipidemia). Continuous variables are presented as mean ± standard deviation (SD), and categorical data are summarized as frequencies (percentages). For categorical clinical variables, differences between groups were evaluated with the Chi square test. For continuous variables, the existence of a normal distribution was evaluated with the Kolmogorov–Smirnov test, and differences among groups were analyzed by one-way analysis of variance (ANOVA) followed by post hoc analysis with the Fisher’s least significant difference (LSD) test. Pearson’s or Spearman’s correlation analysis was run to determine the relationship between CFI and Pd or different levels of aortic BP. Multivariate linear regressions were used to explore the independent determinants for CFI, and the covariates chosen to enter the multivariate analysis model included diabetes and aortic systolic, diastolic and mean BP, respectively, as well as gender, age, body mass index (BMI), risk factors for coronary artery disease (history of hypertension and dyslipidemia and smoking), history of myocardial infarction, severity of coronary artery disease, GFR, total to high-density lipoprotein (HDL) cholesterol ratio, log-transferred hsCRP and left ventricular ejection fraction. All analyses used 2-sided tests with an overall significance level of alpha = 0.05, and were performed with the SPSS 20.0 for Windows .Mild, moderate and severe stenosis of the PCDA was observed in 99, 75 and 46 diabetic patients and 132, 60 and 28 non-diabetic patients, respectively. For diabetic and non-diabetic patients, age, proportion of male gender, dyslipidemia and prior myocardial infarction, and serum levels of creatinine and hsCRP increased whereas GFR, left ventricular ejection fraction and proportion of hypertension decreased stepwise from mild to severe stenosis of the PDCA . Multivessel coronary disease was more prevalent in patients with moderate or severe PDCA stenosis. Medications were similar irrespective of stenosis severity of the PDCA  and non-diabetic  patients whereas other medications such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, statins, oral hypoglycemic agents and insulin did not significantly affect CFI in both groups .Multivariable linear regression models with systolic (per 20 mmHg), diastolic (per 10 mmHg) and mean (per 10 mmHg) BP as well as potential confounding variables such as gender, age, body mass index, history of hypertension and dyslipidemia, smoking, prior myocardial infarction, severity of coronary artery disease, GFR, total-to-HDL cholesterol ratio, log-transferred hsCRP and left ventricular ejection fraction, revealed that after multiple adjustments, CFI correlated negatively with systolic, diastolic, and mean BP in diabetic and non-diabetic patients with mild PCDA stenosis (P ≤ 0.001), was inversely related to diastolic BP in non-diabetic patients with moderate PCDA stenosis (P = 0.011), but correlated positively with diastolic BP in diabetic patients with severe PCDA stenosis (P = 0.001).Further analysis showed an interaction between diabetes and diastolic BP in patients with moderate (P interaction = 0.008) and severe (P interaction = 0.032) stenosis of the PCDA  for the majority of patients. This may be because CFI was determined on an assumption of central venous pressure. Obviously, the accuracy of CFI measurement could be significantly affected by minor variation in actual central venous pressure. Likewise, measurement of left ventricular end-diastolic pressure (LVEDP) in these patients was also important as compressive forces of the ventricle can influence collateral support via septal collaterals. It is possible that diabetic patients have stiffer left ventricle and increased LVEDP that impairs collateral support.In patients with stable coronary artery disease and CTO, donor artery stenosis confers greater risk for reduced coronary collateral flow when diastolic BP is decreased. For type 2 diabetic patients, even a moderate stenosis in the PCDA is associated with more reduced collateral flow as diastolic BP decreases below 80 mmHg compared with non-diabetic patients. These findings may provide clinical insight into the management of patients with coronary artery disease.


Changes during the puerperium are still unclear, particularly in women with hypertension. The choice of antihypertensives, both to control very high blood pressure episodes and to keep blood pressure stable, also requires further elucidation. Currently, there are no clear data to guide the decision for the choice of postpartum antihypertensives. Captopril plays an important role in the treatment of very high blood pressure episodes and may be used postpartum. Clonidine has been used as an alternative in pregnant or postpartum women with contraindications to captopril, with satisfactory effect. The objective of the present study was to evaluate the effectiveness and safety of clonidine compared to captopril for treating severe postpartum hypertension.A randomized, drug-controlled, triple-blind clinical trial evaluating postpartum women receiving captopril or clonidine. Inclusion criteria consisted of: women with hypertensive disorders of pregnancy systolic blood pressure (SBP) ≥180 mmHg and/or diastolic blood pressure (DBP) ≥110 mmHg], requiring magnesium sulfate. Exclusion criteria were: heart disease, smoking, illicit drug use, contraindications to captopril, clonidine or oral medication, and having used captopril/clonidine previously. The primary outcome was the frequency of very high blood pressure episodes while in the obstetric intensive care unit. A total of 90 postpartum women met the study inclusion criteria, with 45 randomized to each group. There were fewer very high blood pressure episodes during hospitalization , greater percentage reduction in SBP  and fewer women requiring sodium nitroprusside  in the clonidine group compared to the captopril group; however, these differences were not significant. The groups were similar regarding daily mean SBP or DBP; however, on the third postpartum day, mean SBP was lower in the clonidine compared to the captopril group . Although not statistically significant, adverse reactions were more common in the captopril group (28.8%) compared to the clonidine group (18.6%).Clonidine and captopril represent safe, effective treatments for severe postpartum hypertension.www.clinicaltrial.gov, NCT01761916.clinicaltrials.gov:  Pregnancy induces changes that not only permit the fetus to develop adequately, but also prepare the woman’s body for childbirth, breastfeeding and the reestablishment of pre-pregnancy conditions . These aThe choice of antihypertensives, both to control very high blood pressure episodes and to keep blood pressure stable, also requires further elucidation ,5. CurreCaptopril, angiotensin-converting enzyme (ACE) inhibitors, plays an important role in the treatment of very high blood pressure episodes  and may Clonidine has been used as an alternative in pregnant or postpartum women with contraindications to captopril, with satisfactory effects . It is aThe objective of the present study was to determine the effectiveness of clonidine compared to captopril for treating severe postpartum hypertension. There are no clinical trials evaluating these aspects in this specific group of postpartum patients.www.clinicltrials.gov), reference NCT01761916 and published in Reproductive Health . If the dose required exceeded the maximum daily dose, then another antihypertensive drug  was selected to treat very high blood pressure episodes . Sodium The primary outcome was the frequency of very high blood pressure episodes while in the obstetric ICU. At the time of the protocol we intended to evaluate mean arterial blood pressure , but aftThe secondary outcomes were: daily mean SBP and DBP levels, the number of days with very high blood pressure episodes, number of days until blood pressure was controlled, percentage reduction in SBP, percentage reduction in DBP, number of doses used to control blood pressure, need to associate another hypertensive agent to control hypertension, number of antihypertensives associated, need for sodium nitroprusside, maternal complications associated with very high blood pressure episodes , maternal complications unrelated to very high blood pressure episodes , adverse effects of the use of the antihypertensives, number of days in the obstetric ICU and death.Sample size was calculated using the OpenEpi software program . A pilot study was conducted with an initial sample of 30 postpartum women with hypertensive disorders of pregnancy, 15 in each group. The mean number of very high blood pressure episodes during hospitalization in IMIP’s obstetric ICU (2.8 ± 2.0 in the clonidine group and 6.2 ± 6.2 in the captopril group) was then used to calculate sample size, for a power of 90% and a 95% confidence level (two sided t-test). It was found that 78 patients would be required to show this difference; however, it was decided to increase this number to 90 to compensate for any losses or differences between the groups.Statistical analysis was conducted using the Medcalc software program , version 12.7.0. Student’s t-test was used for continuous variables with normal distribution. The categorical variables were compared using the Pearson chi-square test of association or Fisher’s exact test, as appropriate. Risk ratios (RR) and their respective 95% confidence intervals were calculated.Repeated measures analysis of variance was used to compare daily mean SBP and DBP levels in both groups in the first four days postpartum. Sphericity was assumed, and p-values were calculated for the time-by-intervention interaction. Analysis was conducted on an intention-to-treat basis. All p-values were two-tailed and a significance level of 5% was adopted throughout the analysis.During the study period, 522 postpartum women with hypertensive disorders of pregnancy were admitted to IMIP’s obstetric ICU. Of these, 14 women declined to participate in the study. Other reasons for exclusion: 384 women had used captopril and/or clonidine previously, six were smokers, five had heart disease, one used illicit drugs, two had contraindications to oral medication, 17 had contraindications to captopril and three had contraindications to clonidine .A total of 90 postpartum women met the study inclusion criteria, with 45 randomized to each group. There were two exclusions during follow-up, both in the clonidine group after captopril was inadvertently administered by the attending physician. Therefore, 43 women were analyzed in the clonidine group and 45 in the captopril group .The baseline characteristics of the women in the two groups were similar, with no statistically significant differences. Severe preeclampsia was the most common hypertensive disorder (64.4%) .The frequency of the clinical parameters was also similar in the two groups; however, there were fewer very high blood pressure episodes during hospitalization , a greater percentage reduction in systolic pressure  and less need for sodium nitroprusside  in the clonidine group compared to the captopril group .Repeated measures analysis of variance for the first four days of hospitalization showed no differences between the groups with respect to mean daily SBP (p = 0.20)  or DBP lDuring hospitalization, HELLP syndrome was the most frequently diagnosed postpartum complication, both in the clonidine group (30.2%) and in the captopril group (28.8%). Although not statistically significant, adverse reactions  were more common in the captopril group (28.8%) compared to the clonidine group (18.6%) .None of the women needed to interrupt antihypertensive treatment because of adverse effects and all fulfilled the necessary criteria for discharge from the obstetric ICU. No cases of maternal death were recorded.No significant differences were found in the clinical parameters of these postpartum women with very high blood pressure episodes. To the best of our knowledge, there are no systematic reviews or clinical trials evaluating these aspects in which oral captopril (25 mg) is compared with oral clonidine (0.1 mg) in this specific group of postpartum patients.The effects of these drugs alone  or in coAlthough the routes of administration of the antihypertensives were different, the mean number of very high blood pressure episodes was similar to that found in the present study for the clonidine group, but different from that found for the captopril group . This difference may be due to the different route of administration of the clonidine . In that clinical trial, four patients in the transdermal clonidine group and one in the oral captopril group were discontinued due to adverse effects . In the As with all angiotensin-converting enzyme (ACE) inhibitors, captopril should not be used in pregnancy . HoweverCaptopril is contraindicated in cases of acute renal failure, a complication that is relatively common in postpartum women with severe preeclampsia or eclampsia , and cloBased on the present data, blood pressure control was similar in both groups, suggesting that both drugs are effective for the treatment of very high blood pressure episodes in postpartum women with hypertensive disorders of pregnancy. However, mean SBP was lower in the clonidine group on the third day. In these patients, the reduction in blood pressure levels could possibly be explained by the resolution of the endothelial lesion and vasospasm following delivery, and also by diuresis of the fluid extravasated to the third space, which would be potentiated by the pharmacokinetics of clonidine and its vascular effect .The need for other antihypertensive drugs was high, and similar (around 80%) in both groups. Nevertheless, it is debatable whether or not there is any need to maintain treatment in postpartum women with preeclampsia or eclampsia, and a Cochrane systematic review failed to find any evidence supporting the use of medication to control postpartum hypertension .The frequencies of complications were similar in both groups, with the most common complication being the HELLP syndrome. Although the difference between the two groups regarding the need for other antihypertensive drugs was slight, the need for sodium nitroprusside was greater in the captopril group compared to the clonidine group. There were also fewer very high blood pressure episodes per day in this group, although this difference was not statistically significant. It is possible that with larger sample sizes differences may be identified.In relation to the cost of the drugs, a 30-tablet package of captopril 25 mg) is sold in Brazil for US$50–80  mg is so. Taking This study is important because it investigates another option for the treatment of hypertensive emergency during the postpartum period. It was a well-designed randomized clinical trial and to the best of our knowledge, there are no systematic reviews or clinical trials evaluating these aspects in which oral captopril (25 mg) is compared with oral clonidine (0.1mg) in this specific group of postpartum patients.The sample size is still small, and maybe a grater sample would be necessary to show more differences in the effect of the two drugs. An analysis of the level of clonidine in breast milk of the patients was also not conducted. It would also have been interesting in conducting a longer observation of the women and evaluating blood pressure levels after discharge from ICU.External validity is still limited since this was a very selected population of patients, and in a very specific setting and new studies is different hospitals with different populations are still necessary.We consider that antihypertensive treatment with clonidine may constitute a safe, effective alternative for avoiding postpartum very high blood pressure episodes, with certain advantages such as a lower treatment costs. To define whether this antihypertensive should be adopted in different services and regions, each hospital should take into consideration the characteristics of the population, the frequency of very high blood pressure episodes in postpartum women and the confidence and ease of the medical team with the use of this drug.Although no studies of this type have yet been conducted with this particular group of postpartum patients, a systematic review including a metaanalysis of future studies should also be carried out to evaluate outcomes such as the duration of postpartum hospital stay, the occurrence of other complications related to very high blood pressure episodes, the behavior and control of blood pressure postpartum and patient satisfaction.S1 FileDOI: 10.1186/1742-4755-10-37.(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(PDF)Click here for additional data file.S1 Data(XLSX)Click here for additional data file.S2 Data(XLSX)Click here for additional data file.


BP) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed.To clarify the influence of hypertension and blood pressure  but not for thromboembolism . When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up , odds ratios for both events were significantly higher in Q4 than in Q1  after adjustment for components of CHA2DS2‐VASc score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage.A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation  were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation.URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000001569. Thromboembolism included symptomatic ischemic stroke, transient ischemic attack, and systemic embolic events. Major hemorrhage included intracranial hemorrhage (ICH), gastrointestinal hemorrhage, and other hemorrhages requiring hospitalization. If any event occurred during the follow‐up period, BP values at the time prior to and closest to the event were obtained.Patients were divided into 2 groups based on the presence of hypertension at the time of enrollment (Hypertension and No‐hypertension) and event incidence rates between the 2 groups were compared. In addition, patients were divided into 4 groups according to the quartiles of their systolic BP at baseline  and at the time prior to and closest to an event or at the end of follow‐up . Patients were also divided into quartiles based on their diastolic BP.t test or analysis of variance, as appropriate. Frequencies of parameters or events were compared using the χ2 test or Fisher's exact test, as appropriate. Trend among the quartiles was tested by Cochran‐Armitage test for categorical variables or Jonckheere‐Terpstra test for continuous variables, as appropriate. Kaplan–Meier curves between 2 groups were compared with log‐rank tests. A Cox proportional hazards model was used to investigate the influence of hypertension and baseline BP values on events. Odds ratios (ORs) of BP quartiles at the time closest to the event or at the end of the follow‐up period were calculated with multivariate logistic regression analysis. Explanatory variables for multivariate analysis were adopted from well‐known risk factors, i.e., unadjusted model (Model 1) and adjusted models for other components (except hypertension) of CHADS2 score (Model 2), other components (except hypertension) of CHA2DS2‐VASc score (Model 3), and Model 3 plus use of warfarin and antiplatelet (Model 4). The use of antihypertensive drugs was not included as an explanatory variable for multivariate analysis to avoid multicollinearity. Additionally, ORs of BP quartiles for major hemorrhage and ICH were determined after adjustment for other components (except hypertension) of HAS‐BLED score2+[1−specificity]2). Two‐tailed P‐values of <0.05 were considered to be statistically significant. All statistical analyses were performed with SPSS software version 23.0 .Data are presented as mean±SD. The statistical significance of differences in mean values was analyzed using Student Of 7937 patients with AF enrolled in the J‐RHYTHM Registry,2 score, and the prevalence of diabetes mellitus, use of warfarin or antiplatelet, coadministration of warfarin and antiplatelet, and use of antihypertensive drugs were all higher in the Hypertension group (Table Baseline patient characteristics and medications of the 2 groups are shown in Table up Table . Mean INup Table . Althougup Table . PatientP=0.540), whereas the rate of major hemorrhage was higher in the Hypertension group than in the No‐hypertension group  (Table P=0.478 by log‐rank test)   and major hemorrhagic events occurred in 140 patients (1.9%), including ICH in 50 patients (0.7%). The unadjusted 2‐year incidence rate of thromboembolism was similar between the 2 groups  was not different from that in event‐free patients (126±16 mm Hg). Diastolic BP at the time of enrollment in patients complicated with these events during the follow‐up period (74±13 and 73±11 mm Hg) was also similar to that in event‐free patients (74±17 mm Hg).P=0.724 for thromboembolism and HR 1.09, 95% CI 0.98–1.21, P=0.098 for major hemorrhage), although not statistically significant either.When patients were divided into quartiles of systolic BP at the time of enrollment, HRs for thromboembolism or major hemorrhage did not differ among the quartiles in any model; this was also true for quartiles of diastolic BP at the time of enrollment Table . When baP<0.001 for each). Diastolic BP was significantly higher in patients with thromboembolism (78±15 mm Hg) than in event‐free patients , but did not differ between patients with major hemorrhage (75±17 mm Hg) and event‐free patients (P=0.108).Systolic BP at the time prior to and closest to the event  in patients who were complicated with thromboembolism or major hemorrhage  was significantly higher than that at the end of follow‐up in event‐free patients  Figure . The ORsP=0.124). By contrast, the OR for ICH in Q4 was markedly higher than that in Q1   Figure .P<0.001), 0.556 , and 0.708 , respectively. Cutoff BP values were determined to be 137/79 mm Hg (with a sensitivity of 55.6% and a specificity of 77.0% for systolic BP), 130/73 mm Hg (53.0% and 58.8%), and 138/78 mm Hg (57.7% and 77.6%), for thromboembolism, major hemorrhage, and ICH, respectively.Areas under the curve of the receiver operating characteristic analysis for thromboembolism, major hemorrhage, and ICH were 0.663  nor the BP value at the time of enrollment was an independent risk factor for thromboembolism. By contrast, the highest quartile of systolic BP (≥136 mm Hg) at the time closest to the event was detected as a significant risk factor for thromboembolism. Since 94.8% of patients received antihypertensive drugs and the mean BP was controlled <130 mm Hg at the time of enrollment, even in the Hypertension group, these results appear reasonable.Hypertension is a well‐known risk factor for stroke. In the INTERSTROKE study, a large‐scale case–control study from 22 countries, self‐reported history of hypertension was the strongest risk factor for stroke of all types . History of hypertension also had the highest OR for ischemic stroke  compared with any other risk factors except for AF.P=0.100). However, it was not statistically significant when factors with P<0.25 in the antecedent univariate analysis were included as explanatory variables in the multivariate analysis. Consequently, the adopted explanatory variables differed from those in the present study. In the latter study, which aimed to assess the significance of each risk factor comprising the HAS‐BLED score in NVAF patients treated with warfarin,P=0.54), when the definition of hypertension was a systolic BP ≥140 mm Hg at the time of enrollment. By contrast, hypertension was detected as a significant risk factor for major hemorrhage in the present study, even after adjustment for other components of CHA2DS2‐VASc score, warfarin use, and antiplatelet use  in the present analyses were comparable to those in previous recommendations.The present study had several limitations. First, this study was a post hoc analysis of data from the J‐RHYTHM RegistryA systolic BP of ≥136 mm Hg at the time closest to the event was an independent risk for thromboembolism and major hemorrhage. BP control appeared to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with NVAF.The following persons participated in the J‐RHYTHM Registry: Executive Committee: H. Inoue, K. Okumura, H. Atarashi, and T. Yamashita. Local Executive Committee: M. Sakurai, Y. Kawamura (Hokkaido); K. Okumura, I. Kubota (Tohoku); Y. Kaneko, K. Matsumoto (North Kanto); S. Ogawa, H. Atarashi, T. Yamashita (South Kanto); H. Inoue, Y. Aizawa (Hokuetsu); I. Kodama, E. Watanabe (Chubu); Y. Koretsune, Y. Okuyama (Kansai); A. Shimizu, O. Igawa (Chugoku); S. Bando, M. Fukatani (Shikoku); T. Saikawa, A. Chishaki (Kyushu). Statistical Advisor: H. Origasa. Participating Investigators: N. Kato, K. Kanda, J. Kato, H. Obata, M. Aoki, H. Honda (Hokkaido); Y. Konta, T. Hatayama, Y. Abe, K. Terata, T. Yagi, A. Ishida, T. Komatsu, H. Tachibana, H. Suzuki, Y. Kamiyama, T. Watanabe, M. Oguma, M. Itoh, O. Hirono, Y. Tsunoda, K. Ikeda, T. Kanaya, K. Sakurai, H. Sukekawa, S. Nakada (Tohoku); T. Itoh, S. Tange, M. Manita, M. Ohta, H. Eguma, R. Kato, Y. Endo, T. Ogino, M. Yamazaki, H. Kanki, M. Uchida, S. Miyanaga, K. Shibayama, N. Toratani, T. Kojima, M. Ichikawa, M. Saito, Y. Umeda, T. Sawanobori, H. Sohara, S. Okubo, T. Okubo, T. Tokunaga, O. Kuboyama, H. Ito, Y. Kitahara (North Kanto); K. Sagara, T. Satoh, E. Kodani, K. Sugi, Y. Kobayashi, Y. Higashi, T. Katoh, Y. Hirayama, N. Matsumoto, M. Takano, T. Ikeda, S. Yusu, S. Niwano, Y. Nakazato, Y. Kawano, M. Sumiyoshi, N. Hagiwara, K. Murasaki, H. Mitamura, S. Nakagawa, K. Okishige, K. Azegami, H. Aoyagi, K. Sugiyama, M. Nishizaki, N. Yamawake, I. Watanabe, K. Ohkubo, H. Sakurada, S. Fukamizu, M. Suzuki, W. Nagahori, T. Nakamura, Y. Murakawa, N. Hayami, K. Yoshioka, M. Amino, K. Hirao, A. Yagishita, K. Ajiki, K. Fujiu, Y. Imai, A. Yamashina, T. Ishiyama (South Kanto); M. Sakabe, K. Nishida, H. Asanoi, H. Ueno, J. D. Lee, Y. Mitsuke, H. Furushima, K. Ebe, M. Tagawa, M. Sato, M. Morikawa (Hokuetsu); K. Yamashiro, K. Takami, T. Ozawa, M. Watarai, M. Yamauchi, H. Kamiya, H. Hirayama, Y. Yoshida, T. Murohara, Y. Inden, H. Osanai, N. Ohte, T. Goto, I. Morishima, T. Yamamoto, E. Fujii, M. Senga, H. Hayashi, T. Urushida, Y. Takada, R. Kato, N. Tsuboi, T. Noda, T. Hirose, T. Onodera, S. Kageyama, T. Osaka, T. Tomita, K. Shimada, M. Nomura, H. Izawa, A. Sugiura, T. Arakawa, K. Kimura (Chubu); T. Mine, T. Makita, H. Mizuno, A. Kobori, T. Haruna, M. Takagi, T. Watanabe, N. Tanaka, H. Shimizu, T. Kurita, K. Motoki, N. Takeda, Y. Kijima, M. Ito, A. Nakata, Y. Ueda, A. Hirata, S. Kamakura, K. Satomi, T. Noda, Y. Yamada (Kansai); Y. Yoshiga, H. Ogawa, M. Kimura, T. Hayano, T. Kinbara, H. Tatsuno, M. Harada, K. F. Kusano, M. Adachi, A. Yano, M. Sawaguchi, J. Yamasaki, T. Matsuura, Y. Tanaka, H. Moritani, T. Maki, S. Okada, M. Takechi, T. Hamada (Chugoku); A. Nishikado, Y. Takagi, I. Matsumoto, T. Yamamoto, T. Soeki, Y. Doi, M. Okawa, H. Seo, S. Kitamura, K. Yamamoto, M. Akizawa, N. Kaname (Shikoku); S. Ando, S. Narita, T. Nakamura, T. Inou, Y. Fukuizumi, K. Saku, M. Ogawa, Y. Urabe, M. Ikeuchi, S. Harada, H. Yamabe, Y. Imamura, Y. Yamanouchi, K. Sadamatsu, K. Yoshida, T. Kubota, N. Takahashi, N. Makino, Y. Higuchi, T. Ooie, T. Iwao, K. Kitamura, T. Imamura, K. Maemura, N. Komiya, M. Hayano, H. Yoshida, K. Yamashiro, K. Kumagai (Kyushu).The J‐RHYTHM Registry is registered at University hospital Medicine Information Network (UMIN) Clinical Trials Registry (UMIN000001569) and was supported by a grant from the Japan Heart Foundation (12080025). This research was partially supported by the Practical Research Project for Life‐Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development (AMED) (15656344).Dr Atarashi received research funding from Boehringer Ingelheim, and remuneration from Bayer Healthcare, Boehringer Ingelheim, and Daiichi‐Sankyo; Dr Inoue received remuneration from Daiichi‐Sankyo, Bayer Healthcare, and Bristol‐Myers Squibb; Dr Okumura received research funding from Boehringer Ingelheim and Daiichi‐Sankyo and remuneration from Boehringer Ingelheim, Bayer Healthcare, Daiichi‐Sankyo, and Pfizer; Dr Yamashita received research funding from Daiichi‐Sankyo, Bayer Healthcare, Tanabe‐Mitsubishi, Ono Pharmaceutical, and Bristol‐Myers Squibb and remuneration from Daiichi‐Sankyo, Pfizer, Bayer Healthcare, Bristol‐Myers Squibb, Boehringer Ingelheim, Eisai, and Ono Pharmaceutical; Dr Origasa received remuneration from Daiichi‐Sankyo and Bayer Healthcare.


Chronic low blood pressure and orthostatic hypotension remain challenging clinical issues after severe spinal cord injury (SCI), affecting health, rehabilitation, and quality of life. We previously reported that targeted lumbosacral spinal cord epidural stimulation (scES) could promote stand and step functions and restore voluntary movement in patients with chronic motor complete SCI. This study addresses the effects of targeted scES for cardiovascular function (CV-scES) in individuals with severe SCI who suffer from chronic hypotension. We tested the hypothesis that CV-scES can increase resting blood pressure and attenuate chronic hypotension in individuals with chronic cervical SCI. Four research participants with chronic cervical SCI received an implant of a 16-electrode array on the dura . Individual-specific CV-scES configurations  were identified to maintain systolic blood pressure within targeted normative ranges without skeletal muscle activity of the lower extremities as assessed by electromyography. These individuals completed five 2-h sessions using CV-scES in an upright, seated position during measurement of blood pressure and heart rate. Noninvasive continuous blood pressure was measured from a finger cuff by plethysmograph technique. For each research participant there were statistically significant increases in mean arterial pressure in response to CV-scES that was maintained within normative ranges. This result was reproducible over the five sessions with concomitant decreases or no changes in heart rate using individual-specific CV-scES that was modulated with modest amplitude changes throughout the session. Our study shows that stimulating dorsal lumbosacral spinal cord can effectively and safely activate mechanisms to elevate blood pressures to normal ranges from a chronic hypotensive state in humans with severe SCI with individual-specific CV-scES. Cardiovascular dysfunction is a leading cause of death in individuals with spinal cord injury (SCI) and has a significant negative impact throughout their lifetime. Individuals with chronic SCI above T6 experience persistent hypotension and bradycardia, with orthostatic hypotension and severe increases in blood pressure during autonomic dysreflexia resulting in drastic daily fluctuations in cardiovascular activity . This dyThe management of chronic hypotension in SCI is a challenging clinical issue as there is no standard or fully successful management strategy. Pharmacological interventions use agents that increase the sympathetic stimulation of the cardiovascular system or increase the blood volume in circulation . UndesirIn studies of motor behavior in individuals with motor complete SCI, we observed modulation of cardiovascular parameters when using scES at spinal segments L1–S1 (vertebrae T11–L1) that allows a direct modulation of the spinal neural networks below the level of injury. Targeted scES optimized for standing (stand-scES) enabled four individuals with chronic motor complete SCI to achieve full weight-bearing standing with minimal assistance , 2017. TThere have been animal studies  and a prTable 1). All individuals were clinically stable, presented with orthostatic hypotension, persistent low resting blood pressure, and routine symptoms of autonomic dysreflexia with no cardiovascular disease unrelated to SCI. The research participants signed an informed consent prior to participating in the study. The study protocol and informed consent were approved by the University of Louisville Institutional Review Board in accordance with the Declaration of Helsinki. A 16-electrode array  was implanted to span the spinal cord segments L1–S1 (vertebrae T11–L1) in all research participants , as previously described . This usually took two to three sessions that were limited to 2 h. Then five 2-h stimulation sessions occurred where the CV-scES stimulation voltage and frequency would have been adjusted as needed throughout the session in order to target systolic blood pressure within the 110–120 mmHg range  and 105–115 mmHg range (for participant A80). Pulse width was 450 μs in all sessions for all participants. Diastolic blood pressure and heart rate were also monitored to assure that they were maintained within normative ranges. Resting data were obtained for 15 min before and after the 2-h stimulation period. Data from the first five cardiovascular sessions obtained within 2 weeks are presented.Research participants were resting in a seated position for 2 h with continuous blood pressure and heart rate monitoring. CV-scES configurations  were identified to maintain systolic blood pressure within the range of 110–120 mmHg for research participants A41, A68, and B21 and 105–115 mmHg for research participant A80, without skeletal muscle activity of the lower extremities as assessed by electromyography in mapping experiments  was calibrated  and recoy represent the outcome , the equation of the model was specified as follows: log(yij) = β0 + β1 ∗ timeij + β2 phasej + 𝜀ij with 𝜀ij = α0 + α1 ∗ 𝜀i-1,j, where i represents the time and j represents the experimental phase rank . The three two-by-two comparisons were obtained by constructing linear contrasts from the model.Data were summarized graphically using box plots. The box represents the interquartile range values  and the whiskers extend to non-outliers minimum and maximum data points. Data points 1.5× IQR above the 75th percentile or below the 25th percentile were considered outliers. For each research participant and for the first session, we performed three comparisons for mean arterial pressure, systolic blood pressure, diastolic blood pressure, and heart rate: CV-scES (during stimulation) vs. pre-CV-scES (before stimulation); post-CV-scES (after stimulation) vs. CV-scES (during stimulation); and post-CV-scES (after stimulation) vs. pre-CV-scES (before stimulation). To perform these comparisons, we used linear mixed models on logged values including the experimental phase  as fixed effect and the minutes as random effect nested within period phase, adjusted for the longitudinal nature of the data and the autoregressive nature of the data. Let p-value of serial correlation < 0.05). To test whether delta mean arterial pressure, delta systolic blood pressure, delta diastolic blood pressure, and delta heart rate are different from 0, we hence used the signed rank test (comparing medians) adjusted for serial correlation using the method of effective sample size . We collected EMG at 2,000 Hz using a 24-channel hard-wired AD board and custom-written acquisition software . EMG  from the soleus, medial gastrocnemius, tibialis anterior, medial hamstrings, rectus femoris, and vastus lateralis using bipolar surface electrodes with fixed inter electrode distance . This typically occurs is response to yawning or involuntary muscle activation. Systolic blood pressure was gradually increased to the 110–120 or 105–115 mmHg range using the participant-specific CV-scES configuration and could be maintained with minimal modulations in the stimulation amplitude. The stimulation amplitude was increased to increase systolic blood pressure and decreased to reduce systolic blood pressure to maintain the systolic blood pressure within the target range for 60 min. Generally, heart rate was inversely related to systolic blood pressure with some variability over time.Cardiovascular parameters were normalized consistently in four individuals with chronic cervical SCI using participant-specific CV-scES. Prior to stimulation there is often variability in the systolic blood pressure especially when below 90 mmHg as exemplified in participant A68 . The mean arterial pressure changes represented concomitant increases in both systolic and diastolic blood pressures as detailed in Table 2. This rise in blood pressure returned near or below each participant’s baseline values within 15 min of CV-scES cessation. Three individuals had no significant change in heart rate while A41 had a significant decrease during stimulation. After the CV-scES was turned off heart rate was significantly greater than the baseline for each participant . The average increases in mean arterial pressure during CV-scES for all four participants were reproducible as shown from five sessions over a 2-week period with similar responses among the participants . Individuals reported physical changes during these sessions including: (1) a feeling of alertness or heightened awareness; (2) increased ability to project their voice and carry on conversations; (3) increased capacity to breathe and cough; and (4) overall improved sense of well-being.For each research participant there were statistically significant increases in mean arterial pressure in response to CV-scES . All four individuals had different configurations that maintained their systolic blood pressure stable within normal limits . Also, those configurations were specific and the anode–cathode selection as well as the frequency interaction is important in enabling the consistent control of blood pressure as shown when comparing configurations that were not successful even when continually modulating stimulation amplitude .Each individual required a specific and unique CV-scES configuration  to consistently maintain normalized cardiovascular parameters . Heart rates decreased in one individual and remained relatively stable in the other three during stimulation. These individuals reported that they were invigorated, had better voice projection, were able to communicate more effectively, and could breathe and cough better during these stimulation periods. The normotensive pressures were maintained for 2 h with minor adjustments in amplitude or frequency and without activation of skeletal muscles. This effect was reproducible over multiple sessions , and returned to low blood pressures when the stimulation ceased. Our study shows that stimulating dorsal lumbosacral spinal cord can effectively and safely activate mechanisms to elevate blood pressures to a normal range from a chronic hypotensive state in humans with severe SCI with individual-specific CV-scES for a limited time period when the stimulation is present .Persistent hypotension was resolved in four individuals with chronic cervical SCI within normal blood pressure ranges using lumbosacral scES with customized targeted configurations for cardiovascular function (CV-scES). In all four individuals there were significant and reproducible increases in systolic and diastolic blood pressures  in a small cohort human study  stimulatThe current study, when also taken in context with other recent studies of epidural stimulation, demonstrates that individuals diagnosed with motor complete SCI may have significant potential for recovery. In the presence of epidural stimulation of spinal networks there now is evidence that individuals who have been diagnosed with motor complete SCI can regain volitional movement  and the Epidural stimulation directly activated the spinal circuitry and immediately improved blood pressure in these individuals with SCI. There are other non-invasive modalities that can access the spinal circuitry such as transcutaneous stimulation , 2016. LThe availability of implantable scES devices provides a novel treatment for chronic SCI patients to improve symptomatic resting and orthostatic hypotension. Longer term studies are needed to assess cardiovascular effects of CV-scES on myocardial structure and function, vascular biology, and clinical outcomes in this population. Development of vascular pressure sensing devices that can activate appropriate CV-scES as a closed feedback system is essential for home and community use and could ameliorate this major impairment to quality of life in the SCI population. These findings are important not only to the chronic SCI population with substantial morbidity and mortality related to excess cardiovascular disease including extreme instability and liability of blood pressure control, but also to other disease states with significant morbidity from orthostatic hypotension such as multiple system atrophy  or baroreceptor-deafferentiated states such as those that occurs after carotid sinus disruption from trauma, vascular surgery, or tumor involvement. Other dietary treatments such as salt loading or pharmacologic therapy with adrenergic agonists do not consistently prevent orthostatic hypotension and can lead to supine hypertension. CV-scES provides a potential unique treatment option for SCI patients to normalize blood pressure and alleviates the adverse impacts of chronic low blood pressure and orthostatic hypotension on physical, emotional, and social well-being .This study was limited to four individuals and needs to be repeated in a larger number of people with chronic SCI over longer periods of time to understand the broader application and to continue to understand the human spinal circuitry and the capacity of recovery after SCI. Further analyses of mechanisms focused on heart rate and blood pressure variability and post-stimulation effects are needed. Larger, prolonged studies of this potential approach as a therapy are warranted to assess additional cardiovascular effects and whether it can improve symptoms or outcomes in other diseases characterized by low blood pressure and orthostatic hypotension. Closed-looped control systems need to be developed to allow monitoring and usability in real-life environments and in varied situations that will induce challenges to the cardiovascular system. Long-term effects of scES on autonomic dysreflexia and the respiratory system both related to these cardiovascular deficits also need to be studied.SH and CA designed the study. GH and MB provided the medical oversight. MB performed the implant procedure with SH, CA, and YC, providing the physiological data during the surgical procedure. SH identified the configurations for the cardiovascular stimulation, provided oversight for data acquisition and analyses, and performed cardiovascular sessions. SW and BU performed the data acquisition and analyses. All authors were involved in data interpretation and manuscript preparation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.