Background: To explore the association between blood pressure and cognition in older participants in the Shanghai Aging Study.Methods: Data were drawn from 3,327 participants at the baseline of Shanghai Aging Study. History of hypertension was inquired and confirmed from participants' medical records. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by research nurses in the early morning. Participants were diagnosed with “cognitive normal,” “mild cognitive impairment (MCI),” or “dementia” by neurologists using DSM-IV and Petersen criteria. Multivariate logistic regression was used to evaluate the association between history of hypertension, duration of hypertension, SBP, DBP, or classification of blood pressure and cognitive function. Generalized linear model was used to assess the relation between duration of hypertension, SBP, or DBP and Mini Mental State Examination (MMSE).Results: A significantly higher proportion of hypertension [78 (76.5%)] was found in participants with dementia than in those with MCI [347 (59.3%)] and cognitive normal  (P < 0.0001). Participants with dementia had significantly higher SBP [157.6 (26.1) mmHg] than those with MCI [149.0 (23.7) mmHg] and cognitive normal [143.7 (22.6) mmHg] (P < 0.0001). After adjusting for sex, age, education, living alone, body mass index, anxiety, depression, heart disease, diabetes, and stroke, the likelihood of having dementia was positively associated with history of hypertension , duration of hypertension , higher SBP , higher DBP , moderate hypertension , or severe hypertension . The MMSE score was inversely correlated to duration of hypertension , SBP , and DBP .Conclusion: Our results suggest that hypertension and high blood pressure may be potential risk factors for dementia. Blood pressure management for the elderly may be important for maintaining cognitive vitality. Cognitive impairment has a great impact on disability and mortality among the elderly, while it also reduces the quality of life for both patients and their caregivers. Approximately, there have been 24.3 million prevalent dementia cases, with 4.6 million new cases worldwide every year . China hHypertension is a highly prevalent condition, occurring in one-third of the world's adults and in two-thirds of adults over 65 years of age , 4. BothEpidemiological dementia research in China is still far behind developed countries. Only two epidemiological studies examined the relation between hypertension and cognitive impairment in the elderly in China, but it was inconclusive because of small sample size and simple neuropsychological assessments , 20. TheFrom January 2010 to December 2012, the Shanghai Aging Study recruited 3,836 permanent residents aged ≥50 years in the Jingansi community, Shanghai. Participants were excluded if they were (1) residing in nursing homes or other institutions; (2) suffering from severe schizophrenia or mental retardation, based on the data abstracted from their medical record or diagnosed by neurologists; or (3) suffering from severe vision, hearing, or verbal impairment and could not participate in the neuropsychological evaluation. Detailed process of the participant recruitment has been published elsewhere . In thisThis study was approved by the Medical Ethics Committee of Huashan Hospital, Fudan University, Shanghai, China. All the participants and/or their legal guardians provided their written informed consent to participate in the study.Participants were interviewed face-to-face by neurologists and research nurses to collect information on their demographic characteristics, including age, sex, and education. The participants' weight and height were measured and used to calculate the body mass index (BMI: the weight in kilograms divided by the square of the height in meters). We also obtained lifestyle factors, such as living alone, cigarette smoking, and alcohol drinking. Their history of chronic diseases, such as diabetes, stroke, and heart disease (including coronary artery disease and arrhythmia), was inquired and confirmed from their medical records.From 7:30 to 8:00 a.m., after at least 5 min of rest in a seated position blood pressure was measured twice, with a standard sized cuff placed on the right arm at heart level of the seated subject, by trained research nurses using a validated and calibrated digital electronic tensiometer  . We recoHypertension was defined as the reported physician-diagnosed hypertension, with or without treatment. Duration of hypertension was also inquired and confirmed from the participants' medical records , 23. AccCognitive function of each participant was assessed by a neuropsychological test battery, which covers domains of global cognition, executive function, spatial construction function, memory, attention, and language. The battery contained (1) Mini Mental State Examination (MMSE); (2) Conflicting Instructions Task (Go/No Go Task); (3) Stick Test; (4) Modified Common Objects Sorting Test; (5) Auditory Verbal Learning Test; (6) Modified Fuld Object Memory Evaluation; (7) Trail-making test A&B; and (8) RMB (Chinese currency) test. Neuropsychological tests were administered by study psychometrists according to the different education levels of each participant. Test 1, 2, 3, 4, 5, and 7 in the battery were used in participants with education ≥6 years; test 1, 2, 3, 4, 6, and 8 were used in those with education < 6 years. All tests were conducted in Chinese within 90 min. A pilot validation study was conducted for each cognitive measure using corrections for gender, age, and years of education in a community of healthy elderly people, and the normative data and the detailed description of these tests were reported elsewhere , 25.Neurologists examined each participant for their reflexes and motor responses. They also administered the Center for Epidemiologic Studies Depression Scale (CES-D)  and the After each clinical assessment, two study neurologists, one neuropsychologist, and one neuroepidemiologist reviewed the functional, medical, neurological, psychiatric, and neuropsychological data and reached a consensus regarding the presence or absence of dementia using DSM-IV criteria . Only thApolipoprotein E (APOE) genotyping was conducted by the TaqmanSNP method  or median , and categorical variables were expressed as frequencies (%). The analysis of variance (ANOVA) and Kruskal-Wallis test were used to compare the continuous variables; the Cochran-Mantel-Haenszel Chi-squared test was used to compare the categorical variables. Multivariate logistic regression model was used to detect the association between history of hypertension, duration of hypertension, SBP, DBP, or blood pressure categories and different clinical cognitive diagnoses, which were adjusted for confounders. Measurement of the association was presented as odds ratio (OR) and 95% confidence interval (CI). Generalized linear model was used to evaluate the relation between duration of hypertension, SBP, or DBP and MMSE, which were adjusted for confounders. Systolic and diastolic blood pressures were regarded as continuous variables and were expressed in units of 10 mmHg  in the multivariate logistic regression model and in the generalized linear model.P-values and 95% CIs were estimated in two-tailed tests. Differences were considered to be statistically significant at P < 0.05. The data analysis was conducted using SAS 9.4 .All the APOE-ε4 allele, history of heart disease, diabetes, stroke, anxiety, and depression were found to be significantly different across groups with different diagnosis of cognition  were males. The mean age of all the participants was 70.1 (SD 7.2) years, and the mean year of education was 11.7 (SD 4.2) years. Five hundred and eighty-five (17.6%) participants were diagnosed as MCI, while 102 (3.1%) were diagnosed as dementia. Age, education, MMSE score, alcohol drinking, P < 0.0001). Participants with dementia had significantly longer duration of hypertension (median 10 years) than those with MCI (median 4 years) and cognitive normal (median 1 year) (P < 0.0001). Participants with dementia had significantly higher SBP [157.6 mmHg (SD 26.1)] than those with MCI [149.0 mmHg (SD 23.7)] and cognitive normal [143.7 mmHg (SD 22.6)] (P < 0.0001). The distribution of blood pressure category was significantly different across the three groups (P < 0.001). More moderate and severe hypertension (47.0%) was seen in participants with dementia than those with MCI (33.4%) and cognitive normal (23.5%)  participants were suffering from hypertension. Participants with dementia had a significantly higher proportion of having hypertension (76.5%) than those with MCI (59.3%) and cognitive normal (51.1%) ( mmHg SD 6.1] thanP = 0.0132), SBP , and DBP , duration of hypertension , higher SBP , higher DBP , moderate hypertension , or severe hypertension , but it was not associated with mild hypertension . There was no significant association between MCI and hypertension or blood pressure  higher odds of cognitive impairment based on 6-Item Screener. No independent association was identified between impaired cognitive status and SBP  or pulse pressure  , and there was a 13% reduction in cognitive impairment  with every 10 mmHg increase in DBP; in the Monongahela Valley, America, a similar association between DBP and cognitive impairment was observed, but it did not remain significant after adjustment for confounders   . However65–1.06) .OR = 1.35 per 10 mmHg; 95% CI: 1.04–1.75; P = 0.025) and 50–59 years . The analysis turned out to be insignificant for patients aged 60–69 years  and ≥70 years . Results similar to those obtained for SBP were obtained for DBP, mean arterial blood pressure, and high blood pressure as well  in a rural area of Xi'an, stratified multivariate analysis revealed a positive relation between SBP (when regarded as continuous data) and cognitive impairment (MMSE) in patients aged 40–49 years  and ones' innate intelligence, which could also reflect cognitive reserve. Thirdly, spot blood pressure measurement might not represent the whole situation of blood pressure level. But for each participant, we measured the blood pressure at the same time in the early morning; therefore, it is better than those measured at other time points. Finally, our study site lies in the urban center of Shanghai, and the participants had higher education than most of the others in China. Therefore, the results could not be generalized to the whole Chinese population.Our results suggest that hypertension and high blood pressure may be potential risk factors for dementia. Blood pressure management for the elderly may be important for maintaining cognitive vitality. The association between blood pressure and risk of cognitive impairment needs to be further studied and validated by prospective studies with longer follow-up time in older population.This work was conceptualized by DD, YS, and ZH and all of them approved the protocol. Data collection was done by DD, QZ, QG, XL, and LZ. Statistical analysis was undertaken by XL, WD, and JL. XL, YS, LT, and DD prepared the manuscript. YS and DD are the guarantors of this paper.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.


Postoperative acute kidney injury is associated with a higher mortality, a more complicated hospital course with longer hospital stay. Urinary kidney injury molecule 1 may play an important role as an early predictor of acute kidney injury post-cardiopulmonary in open heart surgery. We evaluated 45 patients who underwent open heart surgery from January 2016 to June 2016. Both urinary kidney injury molecule 1 and serum creatinine were evaluated before operation and 3hs and 24hs after operation. Acute kidney injury was diagnosed according to Kidney Disease: Improving Global Outcomes, 2012 guidelines. In this study, 27 patients developed acute kidney injury. The three hour-post-surgery urinary kidney injury molecule 1 was significantly higher in the acute kidney injury group (P<0.015) and, at the same time, we did not find any significant difference in the serum creatinine levels between the two groups. Although serum creatinine is still the gold standard for diagnosis of acute kidney injury searching for other new markers is mandatory. Urinary kidney injury molecule 1 can be used as simple noninvasive and specific biomarker for early diagnosis of acute kidney injury. Postoperative acute kidney injury {AKI} is associated with a higher mortality, a more complicated hospital course with longer hospital stay, and a higher risk for hospital acquired infections . Even slThe risk of postsurgery AKI can be decreased by using less invasive approaches, such as off-pump coronary artery bypass grafting or transcatheter aortic valve implantation, but these options cannot be employed in all cases, as cardiac surgery remains the first and only option in many conditions such as severe coronary artery disease, valvular heart diseases, and complex interventions. Therefore, it is important to adopt strategies which help the clinician to prevent AKI or diagnose it early. Old age, preprocedural chronic kidney disease, obesity, some comorbidities, wide pulse pressure, and some pharmacological regimens represent risk factors for post-cardiopulmonary bypass {CPB} AKI, poor outcomes, and mortality –5.Acute kidney injury in patients undergoing cardiac surgery ranged from 7.7% to 28.1% in different studies, according to the criteria adopted to define AKI . Renal rImportant intraoperative factor such as use and duration of CPB is closely related to postoperative AKI . PostopeThe half-life of creatinine limits its use as a marker of renal function. As if the glomerular filtration rate {GFR} decreases, its half-life increases from 4 h to 24–72 h. Consequently, the serum concentration may increase after 24–36 h of a definite kidney injury. Moreover, in patients with sepsis, liver dysfunction, and muscle wasting, a true decrease in GFR may not be adequately assessed by serum creatinine .Kidney injury molecule 1 {KIM-1} is a promising marker for early detection of AKI, and its concentration is markedly increased within hours following kidney injury . It is aIn our study, we aimed to assess the role of urinary KIM-1 level for early detection of AKI in postoperative cardiac patients.The current study was approved by the Institutional Research Board of Mansoura Faculty of Medicine. Free voluntary informed consent was taken from all patients. Confidentiality and privacy were considered as regards personal, clinical, and laboratory data.In this prospective cohort study, 45 patients {23  males  and  22  females} who admitted to cardiothoracic surgery department in Mansoura University Hospital in Egypt and underwent cardiopulmonary bypass were enrolled in our study from January 2016 to June 2016.Patients with normal kidneys seen by pelvi-abdominal ultrasound and normal kidney functions approved by laboratory investigations and with estimated glomerular filtration rates higher than 90 ml/min by the Modification of Diet in Renal Disease MDRD equation were included.From all participants before operation and 3h and 24h after operation, 5ml of venous blood samples was withdrawn from each patient. Blood samples were allowed to clot for 15 minutes and then serum was separated by centrifugation for 10 minutes at 6000 rpm. Serum creatinine, sodium, and potassium were assessed immediately with daily follow-up of serum creatinine till the time of discharge on Dimension Xpand plus {Seimens Healthcare GmbH, Henkestr. 127- 91052 Erlangen, Germany} using its commercial kits.For urinary KIM-1, 10 ml of midflow urinary samples was collected in disposable urine cups without preservatives at the same time points of blood sampling, before operation and 3 hours after operation. Urine samples were centrifuged at 2000-3000 rpm for 20 min and then supernatant was kept in -20°C until KIM-1 will be analyzed.Quantitative determination of urinary KIM-1 was done using enzyme linked immunoassay {ELISA} kit supplied by Sun Red {Shangahi, China}.Duration of CPB, cross-clamping time and core temp were recorded for all the included patients.Increase in Serum creatinine {SCr} more than 0.3 mg/dl within 48 hours.Increase in SCr to more than 1.5 times of baseline SCr, which is known or presumed to have occurred within the previous 7 days.Urine volume less than 0.5 ml/kg/h for six hours.Use KDIGO criteria for AKI diagnosing {2012} which includePatients were divided into 2 groups: {1} AKI group included {27  patients}  {16  males  and  11  females} with cardiac disease that developed AKI after open heart surgery with cardiopulmonary bypass. {2} Non-AKI group included 18 individuals {7  males  and  11  females}.Data were verified. All statistical procedures were performed Using the Statistical Package of Social Sciences {SPSS} version 22 for Windows {SPSS, Inc., Chicago, IL, USA}. Using Kolmogorov-Smirnov test for normality, the distribution of tested variables was examined. Independent samples t- test was used to determine the significance of the differences between continuous variables with normal distribution. Mann-Whitney test was used to determine the significance of the differences between continuous variables which was not normally distributed. For comparison between qualitative variables, Chi- square or Fisher exact test was used. The mean differences between more than two groups normally distributed were analyzed by one-way analysis of variance {ANOVA}, while Kruskal Wallis test was used for nonparametric variables which were not normally distributed.ROC curve statistics were used to estimate specificity and sensitivity of the markers. Statistic results were considered statistically significant when p values were less than 0.05.Forty-five patients were included in this study. Diabetic patients represented 33.3% while hypertensive patients were 44.4%. Open heart surgery was indicated due to ischemic heart disease, valvular heart disease, and congenital heart diseases {In this study, 27 patients developed AKI according to KDIGO criteria, 2012, after 24 hours of cardiopulmonary bypass in open heart surgery.The mean cardiopulmonary bypass duration was 132.8 minutes ± 29.03, while the median cross-clamping time was 80 minutes with range {60-170}. On the other hand, the median core temperature of patients during operation was 33°C with range {32-35}°C {Comparison between AKI and non-AKI patients revealed no statistically significant finding as regards preoperative demographic, medical, and laboratory data {In this study, we did not find any significant difference between the AKI and the non-AKI patients as regards the indications and the characteristics of the open heart surgery {There was no significant difference between the two groups as regards preoperative serum creatinine and urinary KIM-1 levels while the non-AKI group showed significantly lower urine output in comparison to AKI group. The three hour-post-surgery urinary KIM-1 was significantly higher in the AKI group and, at the same time, we did not find any significant difference in the serum creatinine levels between the two groups. On the other hand, after 24h of surgery all the patients who developed AKI showed rising of serum creatinine in concordance with KDIGO criteria, 2012, for diagnosis of AKI and the 24h-post-surgical serum creatinine was significantly higher in the AKI group in comparison to the non-AKI group. Both groups showed significant increase in the postoperative urine output with no significant difference between them {ROC analysis of urinary KIM-1 for early detection of postoperative AKI {3 h  postoperative} was done. We found that, at cutoff value of 1.9 ng/mg of urinary KIM-1, its sensitivity was 48% and specificity was 94% with AUC 0.715, AKI is a frequent complication with cardiac surgery in both children and adult and it is related to poor outcomes and mortality after the operation . In the The unique characteristics of cardiac surgery as an AKI risk factor include CPB, aorta cross-clamping, and high doses of exogenous vasopressors. These factors alter renal perfusion, induce cycles of ischemia and reperfusion, increase oxidative damage, and increase renal and systemic inflammation resulting in higher AKI incidence after CPB . In the Han et al., 2009 , studiedIncidence of AKI varied depending on type of the operation with higher percentage in patients who underwent valvular replacement operation {64.7%} compared to {52%} in patients who underwent CABG but the difference was not statistically significant. Risk factors associated with the development of AKI after CPB include type of surgery, with valvular procedures associated with a higher risk . ReferenAccording to our results all patients had a statistically significant higher urine output 12 h after operation than before operation {p  0.001}. However, preoperative urine output was significantly higher in the AKI, while postoperative urine output showed no significance between AKI and non-AKI groups.Postoperative polyuria can be explained by plenty of fluid infusion during and after operation. Reference  suggesteThe median core temperature of patients who developed AKI was lower than that in non-AKI group with no statistical significance. Reference  reportedOn the other hand, the mean CPB time of patients who developed AKI was higher compared to those who did not develop AKI but with no statistical significance. Similar results were concluded by  that fouNone of the AKI patients needed renal replacement therapy within the 2 weeks of follow-up. This finding interestingly agreed with that of  which stIn the current study there was a statistically significant increase in the median level of 24 h after operation serum creatinine in AKI group. None of AKI patients showed an absolute increase in creatinine more than 0.3 mg/dl from baseline in the first 3 h after operation. These results were in concordance with Han et al., 2009 , and MisResults of the ROC analysis of the 3h-post-operative urinary KIM-1 level showed an AUC of 0.715. Multiple studies estimated the AUC for 3h-post-operative KIM-1 –30 and tIn the current study, it was found that at cutoff value 1.9 ng/mg, 3h-post-operative urinary KIM-1 had sensitivity {48%} and specificity {94%}.The current study is important for early detection of AKI in post-cardiopulmonary bypass {CPB} in Open Heart Surgery Egyptian Patients. However, it has its own limitations as other larger multicenter studies are recommended for more robustness of data and will check the data in different cardiothoracic surgery departments .Early diagnosis of AKI is still challenging and despite that serum creatinine is still the gold standard for diagnosis of AKI but searching for other new markers is mandatory. Urinary KIM-1 can be used as simple noninvasive and specific biomarker for early diagnosis of AKI.


A retrobulbar hemorrhage is a rapidly worsening emergent condition characteristically associated with significant orbital or facial trauma. Spontaneous hemorrhage into the retrobulbar compartment is rare. If not managed in a timely manner, it can lead to permanent vision loss. Rivaroxaban is a directly acting oral anticoagulant (DOAC) that inhibits factor Xa and is widely used for stroke prevention in patients with non-valvular atrial fibrillation (AFib). A spontaneous retrobulbar hemorrhage is a rare presentation. The accumulation of blood in the retrobulbar space leads to increased pressure within a closed space, causing orbital compartment syndrome (OCS), and any substantial rise in pressure displaces the eye forward (proptosis). The increased pressure stretches the optic nerve, resulting in the compression of the central retinal artery, which runs inferior to the nerve in its neural sheath; impeding blood flow to the eye and resulting in vision loss. As 90 minutes of elevated intraocular pressure (IOP) can lead to permanent loss of vision , a retroRivaroxaban is a directly acting oral anticoagulant (DOAC) that inhibits factor Xa; it is Food and Drug Administration (FDA) approved in patients with non-valvular atrial fibrillation (AFib). AFib causes stasis of blood in the left atrium and can lead to thrombus formation, which can embolize and cause an ischemic stroke. Rivaroxaban inhibits the formation of the thrombus by inhibiting factor Xa, and the adverse risk of bleeding is low with DOAC when compared to vitamin K antagonists (warfarin). Here, we present a case of a rivaroxaban-induced spontaneous retrobulbar hemorrhage, review the pathophysiology, and discuss the diagnosis and the medical emergency of timely treatment in order to prevent permanent visual damage.A 79-year-old male with a past medical history of atrial fibrillation presented with symptoms of left eye pain, loss of vision, swelling, and redness for one week. The patient went to his ophthalmologist, who believed his current symptoms were most likely from lacrimal duct blockage, and he was advised to follow up. An appointment was scheduled with the ophthalmologist, but the patient’s visual blurriness worsened, and he eventually developed complete loss of vision, proptosis, redness, and swelling of the left eye, which made him come to the hospital. The patient denied any history of trauma to the left eye.On examination, the left intraocular pressure was 47 mmHg, the pupil was mildly dilated, with no response to light, and vision was completely lost in the left eye, with redness and swelling around the left eye. Maxillofacial computed tomography (CT) scan Figure  demonstrIn a recent study, the incidence of retrobulbar hemorrhages among emergency department patients was reported to be 3%-4% with an incidence of permanent blindness of 0.14% -3. The uAtrial fibrillation accounts for up to 15% of strokes in persons of all ages and 30% in patients over the age of 80 years . The useA lot of patients in this era are on rivaroxaban and other novel oral anticoagulants, and this case highlights the importance of diagnosing spontaneous orbital hemorrhage in patients on anticoagulation and intervening timely to prevent permanent vision loss.


Transthyretin-mediated hereditary amyloidosis (hATTR amyloidosis) is a multisystemic disease with heterogeneous clinical presentation. Hallmarks of the disease are sensory-motor and autonomic neuropathy and cardiomyopathy. Two disease-modifying drugs, inotersen (an antisense oligonucleotide) and patisiran , were recently approved for the treatment of hATTR polyneuropathy. We here review the results of the RNA-targeted therapy clinical trials with special emphasis on the endpoints measuring autonomic symptoms and function.Literature review. We used the terms “autonomic neuropathy”, “dysautonomia”, “autonomic symptoms”, “oligonucleotides”, “inotersen” and “patisiran” in patients with hATTR amyloidosis.In the NEURO-TTR (inotersen) clinical trial, the modified NIS+7 score (mNIS+7) remained stable in 36% of the patients in the inotersen arm (defined as a change of less than 2 points), and 50% of patients had improved quality of life (Norfolk-QOL-DN score) after 15 months. In the APOLLO patisiran trial, 74% of the patients showed stabilization of the neuropathy, defined as a < 10 points increase on mNIS+7, and 51% of patients showed an improvement of quality of life (Norfolk QOL-DN), favoring patisiran at 18 months. Patients on patisiran had a reduced burden of autonomic dysfunction as measured by the COMPASS-31, and a stabilization of nutritional status, suggesting an effect on gastrointestinal autonomic function.Clinical trials of inotersen and patisiran showed that these agents were able to halt the progression of the disease, with some patients even reducing the burden of polyneuropathy, and improving qualify of life. The information on their impact on autonomic parameters is limited, warranting further dedicated studies. Transthyretin-mediated hereditary amyloidosis (hATTR amyloidosis) is a multisystemic debilitating, progressive and life-threatening disease, caused by the deposition of misfolded transthyretin protein as amyloid fibrils at the extracellular space of the somatic and autonomic peripheral nervous system, cardiac, renal, ocular and central nervous systems , 2. WorlhATTR amyloidosis is a highly heterogeneous disease with a broad genotype–phenotype presentation that may present with a wide range of clinical manifestations , 4. The Sensory motor and autonomic neuropathy is the hallmark of the early-onset hATTRV30M amyloidosis, although it is also reported in non-V30M hATTR amyloidosis . AutonomGastrointestinal (GI) manifestations are prominent in most cases, being one of the clinical manifestations mostly related to the poor quality of life of these patients. . GI invoCardiovascular autonomic involvement is an important autonomic manifestation in hATTR amyloidosis attributed to sympathetic and parasympathetic dysfunction that may induce reduced heart rate variability (HRV) , impairmParasympathetic dysfunction also contributes to genitourinary dysfunction, starting from urinary retention with incomplete bladder emptying and urinary urgency progressing to urinary incontinence , 12. UriEvaluating the autonomic function is an important issue in hATTR amyloidosis, acknowledging an early diagnosis, monitoring modifying disease therapeutics, and predicting the prognosis , 13.Recent studies have shown that TTR-specific oligonucleotides, either small interfering RNAs (patisiran) or antisense oligonucleotides (inotersen), can reduce TTR levels of the mutated and wild-type, with significant clinical efficacy in the progression of hATTR amyloid neuropathy over time , 15.In this review, we address the therapeutic value of the recently approved RNA-targeted therapies (inotersen and patisiran) on hATTR amyloidosis, with special emphasis on autonomic dysfunction.A 47-year-old Portuguese male, with a past history of tuberculosis and moderate alcoholic and smoking habits, was diagnosed as hATTRV30 amyloidosis 4 years after the first symptoms, characterized by diarrhea and unintentional weight loss of 20 kg, followed 2 years later by burning feet and sexual dysfunction. At the time of diagnosis, a length-dependent sensory-motor and autonomic neuropathy was confirmed and molecular testing disclosed a V30M TTR mutation .At the time of diagnosis, at age 42, the patient was able to walk unaided, but with bilateral foot drop , and had severe diarrhea (more than 8 times/day) with nocturnal fecal incontinence, urinary retention with effort incontinence, sexual dysfunction and renal involvement with a non-nephrotic proteinuria. An autonomic cardiac involvement was described with a 2nd degree AV block, decreased heart rate variability, and an inverted dipper pattern on ambulatory blood pressure monitoring. No amyloid load was seen at DPD scintigraphy score and there was a normal echocardiogram.The disease progressed to stage 2 with PNDs 3b, despite a TTR stabilizer treatment during 1.5 years. The stabilizer was withdrawn and the patient was enrolled on a double-blind clinical trial with an oligonucleotide. At the time of inclusion, besides the sensory motor neuropathy, a severe autonomic involvement was present, with sexual impotence, severe diarrhea  with fecal incontinence, a neurogenic bladder with recurrent urinary tract infections, urinary incontinence and symptomatic postural hypotension with syncope.GI manifestations improved gradually until the present, with a significant decrease in the frequency of diarrhea (3–4 times/day), particularly during the night period, which resulted in a meaningful improvement in sleep quality. Symptoms of neurogenic bladder and sexual dysfunction remain stable. The patient experienced the disappearance of syncope, maintaining some orthostatic dizziness but with no need for additional symptomatic therapy. The patient remains in stage 2 with a PNDs IIIb after 42 months of therapy.This case illustrates the typical clinical picture of an early-onset hATTR V30M amyloidosis patient whose symptomatology begins with autonomic dysfunction with marked gastrointestinal involvement, followed by somatic fiber dysfunction (sensory-motor neuropathy). In this case, the diagnostic delay had a significant impact on his functional status, conditioning a non-response to the first disease-modifying therapy instituted, due to the advanced stage of the disease. Oligonucleotide therapy allowed a significant reduction of gastrointestinal symptoms and stabilization of sensory-motor neuropathy, with a significant improvement in the quality of life throughout the treatment.Several tools have been used to evaluate the autonomic function in hATTR amyloidosis , 16, butThe modified Neuropathy Impairment Score Plus 7 (mNIS+7) is a score composed of signs of polyneuropathy and neurophysiological tests that has been validated as a metric of hATTR amyloidosis disease burden and neuropathy progression . The scoConcerning small fiber sensation, a quantitative sensory test (QST) assessment to estimate the touch-pressure (TP) and heat as pain (HP5) sensation loss over the surface of the body is used, with scoring based on percentile reference value at each time . The meaIn the Neuro-TTR trial (inotersen), progression of sensory-motor and autonomic neuropathy was assessed by the mNIS+7 total score with the maximum abnormality of 346 points. The mNIS+7 total score comprises eight components, four belonging to the total NIS  while the other four are heart rate deep breathing (3.7 points), nerve conduction tests (18.6 points), touch–pressure sensation (40 points), and heat–pain sensation (40 points). Scoring of HRDB is expressed as normal deviates (0–3.72) based on healthy-subject parameters, an increase in score indicating a decline in function .Neuropathy progression in the APOLLO trial was assessed by mNIS+7 score (max 304 points) with five subcomponents: mNIS+7 motor (192 points), QST (80 points), reflexes (20 points), NCS (10 points), and postural blood pressure BP (2 points). Scoring of the postural blood pressure is based on grading of function: normal (< 95th percentile) = 0 points; mildly reduced (≥ 95th– < 99th percentile) = 1 point; and very reduced (≥ 99th percentile) = 2 points , 18.The Norfolk Quality of Life Questionnaire diabetic neuropathy (Norfolk QOL-DN) is a 35-item patient self-reporting questionnaire of quality of life able to capture symptoms of both peripheral and autonomic neuropathy related to hATTR disease severity . A recenFive domains are grouped according to small fiber, large fiber, and autonomic nerve fiber function and symptoms and activities of daily living. Scoring was based on one composite score  and five subdomain scores: physical functioning/large fiber neuropathy (56 points), activities of daily living 20 points), symptoms (32 points), small fiber neuropathy (16 points), and autonomic neuropathy (12 points). Autonomic function is captured according to the patient’s prompt response and classified from always (5) to never (0) on a 5-point scale. Higher scores reflect a poorer quality of life  and the body mass index (BMI)  is an antisense oligonucleotide designed to bind to wild-type and mutant transthyretin RNA transcripts, resulting in their degradation in the nucleus of the hepatocyte by ribonuclease H, with subsequent reduction of the amount of mRNA available for translation. Inotersen is administered by a subcutaneous route once weekly. It has recently received marketing authorization approval from the European Medicines Agency (EMA) for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hATTR amyloidosis, and regulatory approval from the US FDA for the treatment of the polyneuropathy of hATTR amyloidosis in adults.These approvals were based on results from the phase III Neuro-TTR study in patients with hATTR amyloidosis with polyneuropathy during 15 months . PrimaryInotersen showed a slowing of the progression of polyneuropathy (assessed by the mNIS+7 score) relative to placebo, and stabilized neuropathy-related quality of life as measured by the Norfolk QOL-DN score.On average, patients who received inotersen had an increase of 5.8 points (95% CI = 1.6–10.0) from baseline in the mNIS+7 [vs. 25.5 points (95% CI = 20.2–30.8) with placebo] and of 1.0 point (95% CI = − 3.2–5.2) in the Norfolk QOL-DN score [vs. 12.7 points (95% CI = 7.4–17.9) with placebo] significantly favoring inotersen by the end of the intervention period .Concerning the efficacy of treatment in the mNIS+7 component and subcomponent scores, and in the Norfolk QOL-DN domains, the treatment effect favors inotersen in all domains, with a significantly smaller difference versus placebo for the autonomic and small fiber domains .In mNIS+7, the heat–pain domain showed a reduction of 3.54 points (95% CI = − 5.67–1.42) and the HRDB subcomponent only showed a decrease of 0.1 point (95% CI = 0.33–0.12) from baseline. In the Norfolk QOL-DN, the autonomic and small fiber domains are those with a minor evidence of therapeutic efficacy, with a small increase of 0.12 points in the small fiber domain (95% CI = − 0.95–1.19) from baseline, and a non-significant decrease of baseline of − 0.59 points (95% CI = − 1.37–0.18) in the autonomic domain . Thirty-P = 0.51) , gait speed , nutritional status (mBMI), and patient-reported autonomic symptoms (Composite Autonomic Symptom Score 31) were considered exploratory secondary endpoints .Seventy percent of patients on the patisiran arm reported stable or improved neuropathy stage , and 56% of patisiran patients showed neurological improvement by mNIS+7 score . The treatment effect was significant for all subgroups and components of the mNIS+7. The sensory domain measured by QST  showed a reduction of 13 points (95% CI = − 16.3 to − 9.8), and the postural BP subcomponent showed a decrease of 0.3 points (95% CI = − 0.5 to − 0.1) from baseline .The change from baseline in the Norfolk QOL-DN score was significantly lower with patisiran than with placebo at 18 months, indicating better quality of life in the drug arm. At 18 months, 51% of the patients who received patisiran had an improvement (decrease from baseline at 18 months) in the Norfolk QOL-DN score, as compared to 10% of those who received placebo . ConsistP < 0.001) at 18 months, indicating less autonomic involvement.The change from baseline in the COMPASS 31 score was significantly lower with patisiran, with a decrease of − 5.3 ± 1.3 points as compared to 2.2 ± 1.9 with placebo  favoring the patisiran arm [Patients on patisiran showed a decreased of 3.7 points of mBMI compared with a decreased of − 119.4 points in the placebo arm  in 54% of the patients in the drug arm versus 13% in the placebo arm, and three cases (3%) with glomerulonephritis. Five (4%) deaths were reported between patients in the Neuro-TTR trial, all of which occurred in the inotersen group; one death was considered possibly related to the drug [The frequency of adverse events was similar between patients who received patisiran (28%) and those who received placebo (36%), most of which were mild or moderate in severity. Peripheral edema (30% vs. 22%) and infusion-related reactions (19% vs. 9%) were the adverse events that occurred more frequently with patisiran than with placebo . The freAutonomic neuropathy is an important concern in hATTR amyloidosis patients, particularly in early-onset V30M patients, being non-negligible in late-onset cases or even in other mutations associated with different phenotypes . AutonomQuantification and assessment of autonomic dysfunction is a challenge to any physician, due to the low sensitivity of the available methods . CompounThe poor response to most of the drugs used in the symptomatic management of autonomic and GI manifestations raises the need for other therapeutic approaches, in particular, disease-modifying therapies .Stabilization of GI symptoms and improvement of nutritional status have been reported after liver transplantation , but notThe therapeutic scenario in hATTR amyloidosis changed recently with the approval of two new TTR gene-silencing drugs, namely inotersen and patisiran. Both drugs have shown therapeutic efficacy in all domains of neuropathy, whether somatic or autonomic, as well in quality of life, being consistent in all groups and TTR mutations , 15.Drug efficacy, as demonstrated by the results in the reported clinical trials, is undeniable, although the effectiveness cannot be compared directly between the two drugs due to the use of different polyneuropathy evaluation scales (mNIS+7). A good correlation between disease stage and mNIS+7 has been shown .Some measures used in mNIS+7, including HRDB used in the Neuro-TTR (inotersen) study, have been recognized as having some limitations in assessing disease progression, due to a ceiling effect that prevents the recognition of worsening in subsequent evaluations. HRDB was replaced on the mNIS+7 score in the APOLLO trial by the measurement of postural blood pressure, with the rationale that HRDB has limitations for patients with pacemakers or cardiac arrhythmias. In the two scales, HRDB or postural blood pressure have a minor weighting on the total mNIS+7 score of, respectively, 3.6% and 0.7%. Regarding the efficacy of treatment in the mNIS+7 component and subcomponent scores, and in the Norfolk QOL-DN domains, the treatment effect favors both drugs in all domains. Consistent effects in favor of patisiran and inotersen were noted in Norfolk QOL-DN scores across all individual domains, namely physical functioning/larger fiber, symptoms and autonomic domains. The improvement in quallity of life at 18 months in patients on patisiran was related to strength, digestive health, ability to perform everyday activities and steadiness on their feet .The nutritional status assessed by mBMI, an index of good prognosis and improved survival, evaluated in the APOLLO trial, demonstrated the efficacy of patisiran preserving nutritional status , 25. TheCOMPASS-31, an autonomic symptom assessment scale, was used as a secondary endpoint in the APOLLO trial, with results that showed a significant improvement of autonomic symptoms in the therapeutic arm, with a significant difference in relation to placebo .Autonomic dysfunction and gastrointestinal involvement are the main manifestations of the disease, responsible for poor quality of life and survival of hATTR amyloidosis patients. Besides the limitations presented by the different measurements used, both drugs were able to demonstrate effectiveness in halting disease progression and even offering potential improvement in the different domains of the neuropathy and quality of life.


Objective. This study aimed to determine the possible relationship between variability of diabetic macular edema associated with hypertension retinopathy in patients with type 2 diabetes mellitus and essential high blood pressure, in correlation with contrast sensitivity.Material and Methods. In order to accomplish the objective, this retrospective study evaluated the progression of diabetic macular edema in patients with high blood pressure during day time through measurements of the total macular volume and central macular thickness using optical coherence tomography and contrast sensitivity variations measured through Pelli Robson test, four times a day, along with glycemia and blood pressure measurements. Results. Our results showed a statistically significant correlation between the values of glycemia and central macular thickness, and between contrast sensitivity and macular thickness at every tested hour.Conclusions. The study revealed many statistically significant correlations involving blood pressure, blood glucose levels, Pelli Robson test and central macular thickness.Abbreviations: OCT = optical coherence tomography; DME = diabetic macula edema; SD-OCT = spectral domain optical coherence tomography; LOCS = lens opacities classification system; LE = left eye; ANOVA = analysis of variance Over time, high blood glucose levels lead to the development of diabetic retinopathy and high blood pressure might increase the risk of rapid progression and earlier onset of the disease [2].Worldwide it has been found that diabetes mellitus is an essential cause of blindness and represents the leading cause of severe loss of vision in people of working age in many countries [Optical coherence tomography (OCT) has made it possible to enlarge our knowlegde of diabetic retinopathy and to quantify the retinal edema.3].Fenwick et al. demonstrated that poor glucose and blood pressure control leads to a higher risk of developing diabetic retinopathy and macular edema than poor glycemic control alone [4]. An important objective of this paper was to highlight the physiological mechanisms of the progression of macular edema in patients with type 2 diabetes mellitus and essential hypertension, in correlation with contrast sensitivity using paraclinical imaging methods (OCT).Sometimes, patients with poor blood pressure and glucose control may have a fulminant evolution of their diabetic retinopathy .Within the study, statistical analysis and graphics were made with 20 SPSS . SPSS is a modular line of fully integrated products for the analytical process-planning, data collection, access, training, data management and analysis in the bargain for reports and presentation of the results. Statistical data analysis was done on a sample composed of 45 people - 85 eyes. Due to their type and formulated objectives, the cross table and Chi-square test were used in the research, in addition to the descriptive analysis of the variables  [In the study, 24 females (53.33%) and 21 males (46.66%) were included. The average age was 72.8 years.In terms of distribution by age groups, the majority of the patients, 14, 31.11%, was in the 70-79 years old group. In the group under the age of 50 years there were 2 patients, between 50-59 years old, 6 patients, between 60-69 years old, 12 patients, between 80-89 years old, 8 patients, and in the group over 90, 3 patients.Table 2.A table was made for each patient in the study with the obtained data. In the following table, the data for the first 15 patients is presented in Table 3 .In addition, for each eye that was included in the study, for each hour the measurements were made, macular thickness value in the central subfield was followed, in perifoveolar subfields  and in parafoveolar subfields , according to the example presented in The measurments were made at indicated times, with a significant difference of 30 minutes maximum.The thickening of the retina was defined as the difference between retinal thickness obtained at 9:00 am and the normal one, 202 microns. The relative difference was followed too, which was the proportion between retinal thickness at 15:00 pm and 9:00 am and retinal thickening. The relative and absolute mean change was calculated with a confidence interval of 95%, considering the correlation between the eyes of the subjects included in the study. The proportion of eyes with changes of retinal thickness over 25% was calculated between 9:00 am and 15:00 pm or between 9:00 am and 18:00 pm, and was considered to be statistically significant.The average blood sugar levels at 9:00 am was 171.4444 (+/ -14.1814) mg/ dl, range of confidence 95%. At 12:00 pm, the mean value was 182.3543 mg/ dl, at 15:00 pm it was 175.3322 mg/ dl and at 18:00 pm it was 170.4333 mg/ dl.The mean blood pressure at 9:00 am was 158.4444 (+/ -5.1542) mm Hg. At 12:00 pm it was 163.2333 (+/ -6.1773) mm Hg, at 15:00 pm it was 161.3222 (+/ -5.8233) mm Hg and at 18:00 pm it was 160.0666 (+/ -5.9561) mm Hg.There was a statistically significant difference (p = 0.044425) between the values of blood pressure and blood glucose at 9:00 am. This association was maintained at 15:00 am .Comparatively, analyzing blood pressure and central macular thickness values at 9:00 am the following results were obtained:A statistical significant difference between the values of blood glucose at 9:00 am and central macular thickness was obtained:Next, we analyzed comparatively central macular thickness from 9:00 am, 12:00, 15:00 and 18:00 pm, in patients who met the conditions for entering the study. After performing ANOVA , there were statistically significant differences between macular central thickness at 9:00 am and 15:00 am, and between 12:00 pm and 15:00 pm. There was no statistically significant difference between 9:00 am and 12:00 pm, and between 18:00 pm and other hours.The correlation between contrast sensitivity (test Pelli-Robson) and macular thickness was analyzed at each of the given hours. A significant statistic correlation between the Pelli Robson test and central macular thickness was obtained, at every tested hour.Average blood sugar levels at 9:00 am was 171.4444 (+/ -14.1814) mg/ dl, 95% interval of confidence. At 12:00 pm, the mean value was 182.3543 mg/ dl, at 15:00 pm it was 175.3322 mg/ dl and at 18:00 pm it was 170.4333 mg/ dl.The average blood pressure at 9:00 am was 158.4444 (+/ - 5.1542) mm Hg. At 12:00 it was 163.2333 (+/ - 6.1773) mm Hg, at 15:00 it was 161.3222 (+/ - 5.8233) mm Hg and at 18:00 it was 160.0666 (+/ - 5.9561) mm Hg.There was a statistically significant difference (p = 0.044425) between the blood pressure and blood glucose values at 9:00. This association was also maintained at 15:00 (p = 0.041275 and 18:00 (p = 0.042745), but not at 12:00.There was a statistically significant difference (p <0.0001) between the glycemic value at 9:00 and the central macular thickness values. On a comparative analysis of the central macular thickness at 9:00, 12:00, 15:00 and 18:00, following the ANOVA test, there were statistically significant differences between the central macular thickness at 9:00 and 15:00, and between 12:00 and 15:00. There were no significant statistical differences between 9:00 and 12:00 and between 18:00 and the other hours.A statistically significant correlation was obtained between the Pelli Robson test and the macular central thickness at each of the aforementioned time intervals.DisclosuresNone.AcknowledgmentAll authors have equal contribution to this paper.


In general population, resting heart rate (RHR) is associated with cardiovascular disease. However, its relation to chronic kidney disease (CKD) is debated. We therefore investigated the relationship between RHR and urinary albumin/creatinine ratio  in general population at different levels of blood pressure and blood glucose.  We screened out 32,885 subjects from the REACTION study after excluding the subjects with primary kidney disease, heart disease, tumor history, related drug application, and important data loss. The whole group was divided into four groups  according to the quartile of average resting heart rate. The renal function was evaluated by UACR . Ordinary logistic regression was carried out to explore the association between RHR and UACR at diverse blood pressure and blood glucose levels.  The subjects with higher RHR quartile tend to have a higher UACR, even multifactors were adjusted. After stratifying the subjects according to blood pressure and blood glucose, the positive relationship between RHR and UACR remained in the subjects with normal blood pressure and normal glucose tolerance, while in the hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg) group and the diabetic mellitus (FPG ≥ 7.0 mmol/L and/or PPG ≥ 11.1 mmol/L) group, the relationship disappeared. In the subjects without hypertension, compared with the Q1 group, the UACR is significant higher in the Q3 group (OR: 1.11) and the Q4 group (OR: 1.22). In the subjects with normal glucose tolerance (NGT), compared with the Q1 group, the UACR is significantly higher in the Q3 group (OR: 1.13) and the Q4 group (OR: 1.19).  The population with higher RHR tend to have a higher UACR in the normal blood pressure group and the normal glucose tolerance group. Resting heart rate (RHR) is a well-recognized marker of autonomic nervous system tone and has been found to be a significant correlate of blood pressure, increased body mass index, and metabolic disturbances in many studies; this association is particularly striking in patients with hypertension or diabetes . ElevateThe kidney is one of the important target organs of metabolic diseases. Chronic kidney disease (CKD), primarily caused by hypertension and diabetes , which cA raised RHR has been found to be an independent predictor for the prevalence of microalbuminuria in hypertensive patients with high cardiovascular risk . And peoAn early subanalysis of the randomized olmesartan and diabetes microalbuminuria prevention (ROADMAP) study on patients with type 2 diabetes has shown that a lower RHR was associated with a reduced risk of developing microalbuminuria, indicating that a lower RHR is an independent predictor for a lower risk of new-onset microalbuminuria in type 2 diabetes . Our stuA total of 53,639 participants from the Risk Evaluation of cAncers in Chinese diabeTic Individuals a lONgitudinal (REACTION) study gave written informed consent, and the protocols were reviewed and approved by the research ethics committee at each of the participating centers . After excluding the subjects with primary kidney disease, heart disease, tumor history, related drug application, and important data loss, 32,885 participants were investigated.2.The baseline data were collected by trained health workers via a standardized questionnaire during interviews, including the general situation, the past medical history, the current medication situation, lifestyle, physical exercise, smoking and drinking habits, family history, and other basic information. All involved investigators have been formally trained. Participants were asked to take off shoes, hats, and coats before measurements. Waist circumference (WC) was measured at the horizontal level of the midpoint of the ligature between anterior superior spine and inferior margin of the twelfth rib. Hip circumference (HC) was defined as the horizontal of the most protruding part of the hip. Body mass index (BMI) = weight (kg)/[height(m)]An automated electronic device  was used to measure blood pressure and resting heart rate in the nondominant arm of seated participants three times consecutively at 1-minute intervals after a ≥5-minute rest. The three readings were averaged for analysis. The subjects were stratified based on RHR quartiles .Urine samples were collected in the morning (midclean urine) for UACR measurements. Because the kits for measuring UACR in each center and the range of normal values are different, the value of UACR, divided by quartiles of all data in the center which the subject belonged to, was used to estimate albuminuria.Blood samples were drawn in the morning after subjects had an 8-hour fasting the previous night. Participants without a history of diabetes underwent a 75 g oral glucose tolerance test, and their venous blood samples were drawn at 0 and 120 minutes. Biochemical index included triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), creatinine (Cr), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transaminase (GGT), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycosylated hemoglobin (HbA1c), and fasting blood insulin was measured by the glucose oxidase-peroxidase method.2 by the formula eGFR = 186 × [serum creatinine × 0.011]‐1.154 × [age]‐0.203 × [0.742 if female] × 1.233, where serum creatinine was expressed as μmol/L and 1.233 was the adjusting coefficient for the Chinese population. This formula is according to the abbreviated Modification of Diet in Renal Disease (MDRD), which was recalibrated for Chinese population.The estimated glomerular filtration rate (eGFR) was expressed in mL/min per 1.73 mNormal glucose tolerance (NGT) was defined as FPG < 6.1 and PPG < 7.8; impaired glucose regulation (IGR) was defined as 6.1 ≤ FPG < 7.0 and/or 7.8 ≤ PPG < 11.1; diabetes mellitus (DM) was defined as FPG ≥ 7.8 and/or PPG ≥ 11.1. Normal blood pressure (NBP) was defined as 90 ≤ systolic blood pressure (SBP) < 140 and 60 ≤ diastolic blood pressure (DBP) < 90; hypertension was defined as SBP ≥ 140 and/or DBP ≥ 90.U test and the Kruskal-Wallis test were used, respectively, to compare the means of 2 and 3 or more groups of variables not normally distributed. The frequencies of categorical variables were compared using Pearson Chi-square or Fisher's exact test, when appropriate. A value of P < 0.05 was considered significant. Ordinary logistic regression was performed to explore the association between RHR and UACR.The data was analyzed by SPSS version 20.0 for Windows . The normality of distribution of continuous variables was tested by the one-sample Kolmogorov-Smirnov test. Continuous variables with normal distribution were presented as mean ± standard deviation (SD). The Mann-Whitney P < 0.001). The means of age, HC, SBP, Cr, and eGFR have a significant difference between RHR quartiles. The percentile of UACR > 75% is higher in the higher RHR group as A total of 32,885 participants, including 10,058 males and 22,827 females were accepted into the study. The general clinical characteristics of the study population are presented in P < 0.05). Ordinal logistic regression was performed to explore the association between UACR and RHR. P < 0.05). After adjusted for gender, age, BMI, WC, smoking, and alcohol drinking, the risk of having UACR increased progressively across the lowest to the highest quartiles of RHR with ORs of 1.07 (95% CI 1.01-1.13), 1.18 (95% CI 1.12-1.25), and 1.33 (95% CI 1.26-1.41), respectively . When adjusted for all factors, the third quartile  and the fourth quartile  still tend to have a higher UACR.Multiple factor analysis was carried out to screen out the risk factors related to UACR. The association between UACR and RHR at diverse blood pressure and blood glucose was analyzed by ordinal logistic regression. As Chronic kidney disease has insidious onset and slow progression and is easy to be ignored. UACR is a sensitive indicator reflecting early renal function injury. Resting heart rate is a reliable indicator of sympathetic nervous system excitation, and epidemiological studies , 20 showA previous study in Germany that included 4447 patients with type 2 diabetes showed that as the heart rate increases, the risk of microalbuminuria appearing increased ; this poThere was also a study extending the previous findings to a population with cardiovascular disease, showing that heart rate is associated with a renal disease risk and suggesting that a reduction in heart rate might be protective for kidney function . In thisOur study shows that hypertension (OR: 1.66) and diabetes (OR: 1.52) are more significant than RHR  related to UACR. In the general population, the positive relationship between RHR and UACR exists, while in the new diagnostic hypertension and diabetes group, it disappeared. In combination with previous results, we may guess that after effective hypoglycemic and antihypertensive therapy, the relationship between RHR and UACR will reoccur, but it remains further clinical trials. Anyhow, RHR may be a marker of UACR, which reflects early renal impairment.Several mechanisms may underlie these effects such as progression of atherosclerosis, and thus nephrosclerosis, due to changes in endothelial oxidative stress, which is sensitive to RHR reduction , 22. FurParticipants in our study belonged to 8 communities of mainland China, guaranteeing representative results. Compared to other studies, our participants included diverse blood pressure and blood glucose (after excluding the effects of related drugs). Therefore, we fully adjusted confounding such as gender, age, BMI, WC, liver function, and serum lipid. However, several deficiencies exist in this study. First, protein content intake in the previous day and the interval between last meal and sleep were not available; second, UACR levels were determined by a single measurement, but detection methods of the 8 centers were different; third, this is a cross-sectional study; we cannot get a cause-and-effect relationship. Its specific mechanism needs to be explored and confirmed by further basic experiments, but the conclusion still has a certain clinical sense in some aspect.Our study reported the association between RHR and UACR in general population. For the population with nonhypertension and normal glucose tolerance, higher RHR is associated with higher UACR. As for the population with hypertension and diabetes, the positive relationship disappeared. After adjusting blood pressure and blood glucose, people with higher RHR tend to have a higher UACR. That indicates RHR may represent an independent risk factor for chronic kidney disease.


The combination of chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) is associated with a higher prevalence of comorbidities and increased mortality. The impact of kidney function on patient-centered outcomes in COPD has not been evaluated.2 at study inclusion and six month later. The effect of CKD, on comorbidities, symptoms [modified British Medical Research Council dyspnoea scale], physical capacity  and St George’s Respiratory Questionnaire were analysed. Restricted cubic spline models were used to evaluate a nonlinear relationship between eGFR with patient-centered outcomes, cox survival analysis was applied to evaluate mortality.Patients from the German COPD and Systemic Consequences - Comorbidities Network (COSYCONET) cohort COPD were analysed. CKD was diagnosed if the estimated glomerular filtration rate (eGFR) measurements were < 60 mL/min/1.73m1 and cardiovascular comorbidities revealed independent associations between eGFR with modified British Medical Research Council dyspnoea scale, St George’s Respiratory Questionnaire, (p < 0.001 and p = 0.011), six-minute walk test (p = 0.015) and timed up and go (p < 0.001). CKD was associated with increased mortality, independently from for other cardiovascular comorbidities .2274 patients were analysed, with CKD diagnosed in 161 (7.1%). Spline models adjusted for age, gender, BMI, FEVThese data show that CKD is a relevant comorbidity in COPD patients which impacts on patient-centered outcomes and mortality.NCT01245933The online version of this article (10.1186/s12931-019-1107-x) contains supplementary material, which is available to authorized users. Chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) affect a large number of patients. The World Health Organization estimates COPD to become the 3rd leading cause of mortality worldwide in 2030 . CKD, deThe presence of a number of comorbidities has been shown to correlate with limitations of exercise capacity in COPD patients. Cardiovascular dysfunction is a well-known predictor of a limited functional capacity and health status . WhetherCOSYCONET recruited patients age ≥ 40 years and with a diagnosis of COPD or symptoms of chronic bronchitis who were available to attend repeated study visits up to 18 months. The characteristics of the cohort have been described previously . A total2 at study inclusion and at the six month visit were considered as having CKD, as per the Kidney Disease Outcome Quality Initiative (KDOQI) guidelines [2, respectively), reflecting normal or mildly decreased kidney function, were combined into the category ‘no CKD’. CKD categories were defined as follows: CKD category 3a (eGFR 45–59 mL/min/1.73 m2), category 3b (eGFR 30–44 mL/min/1.73 m2), category 4 (eGFR 15–29 mL/min/1.73 m2) and category 5 (eGFR < 15 mL/min/1.73 m2). Patients with missing laboratory values at one or both time points were excluded from the first part of the present analyses.CKD was diagnosed by the estimated glomerular filtration rate, based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation . PatientAll pulmonary function tests  were performed 45 min after inhalation of 400 μg salbutamol and 80 μg ipratropium bromide according to current recommendations –17.1/FVC ratio above 70% at baseline. These patients were described as GOLD Stage 0. This group was defined as having a FEV1/FVC ratio > 70% and (i) having a doctor’s diagnosis of chronic bronchitis and/or (ii) indicating a severity of cough of at least 3 in the respective COPD Assessment Test (CAT) item and/or (iii) indicating a severity of phlegm of at least 3 in the respective CAT item [Due to the above mentioned inclusion criteria there were also some patients with a FEVCAT item .All participants underwent structured interviews to identify other comorbidities. The overall comorbid burden was summarised in a main comorbidity index (MCI). The MCI depicts a non-weighted summary score of the 34 following conditions: allergic diseases, arrhythmia, asthma, cancer, cirrhosis of the liver, coronary artery disease, chronic bronchitis, epilepsy, gastritis, gastroesophageal reflux, gout, heart failure, hepatitis, hypertension, hypothyroidism, hyperthyroidism or hyperparathyroidism, mental disorders, insulin-dependent diabetes mellitus, multiple sclerosis, myocardial infarction, non-insulin-dependent diabetes mellitus, osteoarthrosis, osteoarthritis, osteoporosis, peptic ulcer, parkinson disease, peripheral artery disease, peripheral neuropathy, pulmonary fibrosis, renal colic or renal calculi, sarcoidosis, sleep apnea, stroke and venous thrombosis. The MCI was calculated by counting each item with 1 point. A summarised assessment of cardiovascular comorbidity was performed in a similar manner using the cardiovascular index (CVI), which includes the five cardiovascular items hypertension, coronary artery disease, myocardial infarction, arrhythmia and stroke. Patients with a CVI of ≥1 point were considered as having cardiovascular comorbidities.Severity of dyspnoea was assessed using the modified British Medical Research Council dyspnoea scale (mMRC) . The COP2 test, as appropriate in case of categorical variables, t-tests or Wilcoxon test were used for continuous variables as appropriate. Multivariate regression models with included established risk factors  were used for analysis of the impact of CKD for different numeric variables. Analysis was performed in SAS 9.3 and results were considered statistically significant for P values less than 0.05. Because of the non-linear association between mMRC, TuG, 6MWT, SGRQ, FEV1, BMI and eGFR, we analyzed non-linear associations between the aforementioned parameters and eGFR from the first visit by using restricted cubic splines of eGFR with three knots. Knots were placed at 59.6 ml/min, 84.8 ml/min, and 100.8 ml/min which corresponds to the 10th, 50th, and 90th percentile of the eGFR values. Analyses were adjusted for age, sex, BMI, FEV1 (% pred.) and CVI score, where appropriate. Analyses were performed using STATA IC 15. Multivariate adjusted restricted cubic spline analyses were performed using the STATA package ‘postrcspline’. Cox analysis was used to characterize the impact of CKD on mortality with additional independent variables: BMI, sex, CVI, and FEV1% pred. Analysis was performed using SPSS version 24 .The association of CKD with functional, laboratory values and other comorbidities were analyzed using group comparisons. We described categorical data using frequencies and percentages. For continuous data we used means (standard deviations), those values which were markedly different from normal distribution are presented as median (interquartile range). Comparisons between the “CKD and the ‘no CKD’ group were performed by Fisher’s exact test or X2 or on Dialysis. The distribution of chronic kidney disease categories in the study population is presented in Table After screening of all 2741 patients from the COSYCONET study cohort, 2274 were eligible for analysis of CKD. 467 patients with missing laboratory values at one or both of the two defined time points were excluded from the CKD part of the analysis. CKD was diagnosed in 161 of 2274 patients (7.1%). The majority of all patients (60.6%) were male, and the mean ± SD age was 65.0 ± 8.4 years. Among the 161 patients with CKD, 114 (70.8%) were category 3A, 43 (26.7%) were category 3B, and 4 (2.5%) were category 4. There were no patients with an eGRF < 15 mL/min/1.73 mPatients with CKD were significantly older and had a significantly higher BMI than those with normal or mildly reduced kidney function (i.e. the ‘no CKD’ group) Table . CompareSelf-reported comorbidities were more frequent in the CKD group, in particular cardio- and cerebrovascular disease, peripheral artery disease (PAD), diabetes, gout and malignancies Table . FurtherHaemoglobin was significant lower in patients with CKD compared with the ‘no CKD’ group. CKD patients presented significantly elevated blood glucose and glycosylated haemoglobin compared to the‘no CKD’ group. There were no differences between the two groups in term of leucocytes, C-reactive protein or cholesterol. Laboratory findings are summarized in the Additional file p < .0001).Patients with CKD had a significant higher mMRC values as compared to the ‘no CKD’ group. The COPD related symptom load as measured by the CAT showed no differences between the two groups Table . Functiop < 0.001) and SGRQ (p = 0.011) with j-shaped associations. Figure p = 0.015, Fig. P = 0.003 and 0.001 respectively)Spline models adjusted for age, sex, BMI, FEV1 (% pred.) and cardiovascular comorbidity (CVI score) were performed to analyse the non-linear association of eGFR with dyspnea, functional status (FS), exercise capacity (EC) and quality of life (QoL). These models revealed independent relationships of eGFR with mMRC, TuG, 6MWT, and SGRQ. Figure p value) were: CKD, 2.35 ; sex  1.49 , FEV1% pred. 0.96 ; age 1.09 . No significance was found for CVI and BMI.To investigate whether COPD patients with comorbid CKD have an increased risk of dying, we performed Cox regression analysis with age, BMI, sex, packyears, CVI, and FEV1% pred. as cofounders and found that CKD is significantly associated with increased mortality Fig. . This asThe present study characterized patients with comorbid COPD and CKD from the German COSYCONET study cohort. This is to our knowledge the first study analysing the effects of comorbid CKD on patient-centered outcomes in COPD. COPD Patients with CKD were more likely to have additional comorbidities, reported increased dyspnea, and had a significantly reduced exercise capacity compared with the ‘no CKD’ group. Spline models adjusted for age, gender, BMI, FEV1 (% pred.) and cardiovascular comorbidity revealed independent nonlinear associations of eGFR with dyspnoea, functional status, exercise capacity and health status. CKD was furthermore a predictor for mortality independently from other cardiovascular comorbidities.There are several studies focusing on the prevalence of CKD in patients with COPD, conducted in a range of populations –29. Most2. This relationship was also shown for eGFR and COPD specific health status measured by the SGRQ if kidney function were reduced. However those patients with normal kidney function showed mixed outcomes for mMRC, timed up and go, six minute walk test and SGRQ. Especially those patients with high eGFR (> 90 ml/min/1.73m2) values presented more symptoms and inferior performance. The combination of high eGFR values and unfavourable outcomes in apparently healthy subjects was described as renal hyperfiltratration (RH). The pathogenesis of RH is still poorly understood, but there are associations with hypertension, diabetes, obesity and smoking [1 and BMI were independently associated with high eGFR values in our cohort. COPD related inactivity and sarcopenia might be on explanation for these findings, however the BMI values were still in the normal range and the BMI includes no information on body composition.In the present study, mMRC scores were higher in patients with CKD and spline interpolations revealed an independent inverse association of eGFR with mMRC. Increased mMRC values in turn are linked with reduced physical activity levels in patients with COPD . The hig smoking . Renal h smoking . This isWe also assessed whether CKD is associated with increased mortality. CKD is closely associated with cardiovascular diseases and an independent risk factor for death , 35. ThiThe present study has some limitations: The presence of comorbidities was based on patients’ reports. Other limitations are mainly related to the limited sample size in the CKD categories. The majority of patients within this category had only moderate kidney impairment, probably because these are the ones that are more willing to participate into cohorts, which might lead to a selection bias.Our results from eGFR spline interpolations suggest that there is an increasing impact on dyspnoea, exercise capacity and health status with increasing kidney impairment. We therefore speculate that a higher proportion of CKD category 4 and 5 patients would have led to more pronounced differences between the two categories.CKD is a frequent finding in COPD patients and possibly an important contributor to the comorbidome of the disease as well as to many important disease outcomes, including mortality. Spline models showed a nonlinear association of eGFR on different patient-centered outcomes, CKD but also high eGFR values might be predictors for inactivity and progressive deconditioning in COPD. Interventions that increase physical activity levels might play a key role to improve outcomes in these special groups of patients. CKD is therefore a relevant COPD comorbidity, and there is an urgent need for more information to improve outcome in this high risk group of patients.Additional file 1:Table S1. Laboratory values. (DOCX 18 kb)


The beneficial effects of epidural analgesia (EDA) in terms of pain control and postoperative convalescence are widely known and led to a frequent use for patients who underwent living donor kidney nephrectomy. The objective of this study was to determine whether general anesthesia (GA) plus EDA compared to GA only, administered for living donor nephrectomy has effects on postoperative graft function in recipients.p < 0.05, respectively.In this monocentric, retrospective cohort analysis we analyzed the closed files of all consecutive donor- recipient pairs who underwent living donor kidney transplantations from 2008 to 2017. The outcome variable was delayed graft function (DGF), defined as at least one hemodialysis within seven days postoperatively, once hyperacute rejection, vascular or urinary tract complications were ruled out. Statistical analyses of continuous variables were calculated using the two-tail Student’s t test and Fisher exact test for categorical variables with a significance level of p = 0.031).The study enclosed 291 consecutive living donor kidney transplantations. 99 kidney donors received epidural analgesia whereas 192 had no epidural analgesia. The groups showed balanced pretransplantational characteristics and comparable donors´ and recipients’ risk factors. 9 out of all 291 recipients needed renal replacement therapy (RRT) during the first 7 days due to delayed graft function; none of these donors received EDA. The observed rate of DGF in recipients whose kidney donors received epidural analgesia was significantly lower (0% vs. 4.6%; In our cohort we observed a significantly lower rate of DGF when epidural analgesia for donor nephrectomy was administered. Due to restrictions of the study design this observation needs further confirmation by prospective studies. Living kidney transplantation showed superior results compared to deceased donor kidney transplantation in terms of graft survival, accessibility, waiting time and cost containment for public health services –3. For pIn numerous studies major outcome benefits like mortality of EDA could neither be confirmed nor denied , 5. HoweThis retrospective cohort study was approved by the local Institutional Review Board, University of Freiburg, Germany . The study was conducted at the Department of Anesthesiology and Critical Care and the Department of General and Visceral Surgery, Medical Center - University of Freiburg, Faculty of Medicine - University of Freiburg Germany. The study was planned and designed in accordance with the initiative for Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), using the suggested checklist for epidemiological cohort studies . The stuRecipient and donor evaluation were based on a check-up examination which lead to confirmation of donor suitability. Ahead of transplantation all donor- recipient pairs were evaluated by an ethics committee of the District Medical Association Suedbaden, Germany. A positive vote of this ethics committee was mandatory for transplantation.Surgical procedure was standardized to a maximum as only two different surgeons contributed to the transplantations in this cohort. The donor nephrectomy was performed in supine position over an open anterior extraperitoneal minimal incision laparotomy. Transplantations were performed in the established technique, to the right iliac fossa of the recipient.Decision on epidural analgesia was based on the patients´ preference. All patients that received epidural analgesia gave their informed consent on that procedure. Epidural analgesia was performed directly preoperatively according a specific departmental standard operating procedure: Epidural catheter was placed between the 7th and the 11th thoracic intervertebral space, followed by an application of 25 μg sufentanil and 10 ml ropivacaine 0.2%. After the initial dose a continuous epidural application of 45 ml ropivacaine 0.2% mixed with 25 μg sufentanil (= ropivacaine 0.18% and sufentanil 0.5 μg/ml) with an infusion rate of 8 ml/h during the surgery was established. Anesthesia procedures for donor nephrectomy with and without epidural analgesia followed a unique mandatory standard operating procedure (SOP) which differed only regarding the administration of EDA and was performed by a specialized transplantation team. Our transplantation team consists of 8 to 10 attending anesthesiologists, who underwent special training (transplant fellowship) and are used to perform anesthesiology for kidney transplantation in accordance to our mandatory in-house standard operating procedure. Over the years the attending anesthesiologists in charge changed, so that in total a number of 25 anesthesiologists took care of the patients. Postoperatively all donors were transferred to a transplantation ICU. Patients who received epidural analgesia were visited daily by the acute pain service of our department. Epidural catheters were removed between the second and the fifth postoperative day by the acute pain service.Anesthesia for transplantation was performed without epidural analgesia for the recipient and followed a departmental SOP which was established and revised where necessary in close collaboration between the responsible surgeons and anesthetists The SOP addresses the need for 250 mg prednisolone and 10 g mannitol ahead of reperfusion. With the onset of reperfusion of the transplant kidney 125 mg furosemide were administered. Intraoperative fluid and catecholamine management was performed by the attending anesthetist referring to the SOP.Renal replacement therapy (RRT) was initiated when patients were threatened by volume overload or increased serum potassium levels. Delayed graft function was defined as any renal replacement therapy in the first postoperative week, once hyperacute rejection, vascular or urinary tract complications were ruled out –21 .p < 0.05, respectively.The data was collected in a MS Excel™  datasheet. Further statistical processing was performed using SPSS™ . Statistical analyses of continuous variables were calculated using the two-tail Student’s t test and Fisher Exact test for categorical variables with a significance level of The study enclosed 291 consecutive living donor kidney transplantations between October 2008 and December 2017. 99 kidney donors received epidural analgesia whereas 192 had no epidural analgesia. Table p < 0.003). The intraoperative fluid consumption  and maximum dose of vasopressor  showed no statistically significant difference. None of the recipients´ pre- and intra-transplantation data showed a significant difference (Table p = 0.031) .The perioperative characteristics are shown in Table The benefits of EDA regarding pain control, ICU stay, intestinal motility and early mobilization are frequently reported –27. The In line with the significantly lower rate of DGF in EDA group, we found that serum creatinine level, as well as the maximum serum potassium level within 7 days, were significantly lower in the EDA group. Although these findings are statistically significant, their measured levels and differences in numbers are clinically not of relevance. Even when looking at the decline of the serum creatinine levels over the first two days postoperatively no significant or clinically relevant difference can be found. The recipients of the no-EDA group start at a slightly higher level of serum creatinine which should be taken into account. Further baseline characteristics of donors and recipients showed no statistically significant difference or clinically relevant imbalance between the donors and recipients of both groups. An increased intraoperative fluid and vasopressor consumption in the EDA group could be associated with the EDA mediated inhibition of the sympatho- adrenal response with consecutive vasodilatation. However, neither intraoperative fluid nor vasopressor consumption showed a statistically significant difference in our study.The standard surgical technique for donor nephrectomy in our institution is an open anterior extraperitoneal minimal incision laparotomy. Open surgical technique for donor nephrectomy is associated with inferior cosmetic result, longer hospitalization and more intra- and postoperative pain with consecutively increased need for pain medication , 37. HowThe reasons why kidney grafts fail to function immediately after transplantation when acute rejection, urological or vascular reasons are ruled out are associated with the transplanted kidney. DGF is modulated and caused by complex mechanisms of hypoxic and ischemic injuries and insufficient repair mechanisms . These cThe potential benefit of EDA performed for the transplantation could not be investigated by our study group. In our institution the transplantation itself is performed without EDA due to the mandatory immune suppressive therapy and the high incidence of platelet dysfunction in patients suffering from end stage renal disease , 53. HadFirst, the retrospective and non-randomized design implies that a study protocol which addresses randomization on who receives EDA is missing. It is speculative why patients opted for or against EDA, possibly the way whether EDA was offered by the visiting anesthesiologist or rather recommended plays an important role. Perhaps patients who opted for EDA were more trustful of their physicians and therefore had less anxiety or stress levels which may have influenced DGF of their donated kidney. The way EDA was offered to the donors might have been changed throughout the years. We have seen that EDA is more frequently performed in the last years of the program compared to the very early years of the observation period. However, this imbalance of EDA rates throughout the observational period was not associated with an accumulation of RRTs or DGF in the early or the late years of the observation. RRT was initiated by visiting nephrology specialists and the request of the attending ICU physician when patients were threatened by volume overload or increased serum potassium levels. We are fully aware that living donor kidney transplantation is a highly complex procedure. The outcome quality is affected by various confounding variables for which we have not adjusted in our study due to the limited number of cases with DGF.There are also several slightly different definitions on delayed graft function in literature. In our study DGF was defined as any renal replacement therapy in the first postoperative week, when hyperacute rejection, vascular and urinary tract complications were ruled out. More than 22 different definitions of DGF are described, the most common definition refers to any RRT within the first posttransplantational week , 19. DueIn this retrospective cohort study, we found an association between epidural analgesia for living kidney donors and significantly less delayed graft function in the corresponding kidney recipients. These results favor not only the beneficial analgesic effect of epidural analgesia for donors, but also show significant beneficial effects for kidney recipients. As our analysis depends on the authors’ experience, derived from a very low level of evidence with consecutive relevant shortcoming in terms of study design, number of index cases and adjustment of confounding variables, our findings have to be confirmed by prospective randomized trials.


Hypertension remains one of the leading causes of death in Nigeria. Appropriate and cost-effective treatment of the disease is necessary to reduce mortality. This study evaluates (i) the prescription patterns and quality (ii) blood pressure control and (iii) cost of medication among patients with hypertension uncomplicated by co-morbid diseases or compelling indications.Patients with uncomplicated hypertension attending three clinics in the University College Hospital, Ibadan in Nigeria were recruited into this study. Information on demographics, antihypertensive medication prescribed, blood pressure measurements, and cost of medications were collected for each patient. Antihypertensive medications were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and the Defined Daily Dose (DDD) system. The frequency of usage of each drug class and their prescribed doses per patient/day were calculated and compared with the DDD to assess the quality of prescription. Cost of antihypertensive medication was calculated for each patient and reported as cost per patient/day and cost per patient/month. Effect of variables on BP control was ascertained. Statistical analyses were done using SPSS, chi-square and correlation test was used to test for associations.2 = 33.618, p < 0.001; r = .18, p < 0.001). The most prescribed antihypertensive medication either as a single therapy or a fixed-dose combination was diuretic. About 54% of the prescribed daily doses of antihypertensive medication exceeded the DDD. The total monthly expenditure on antihypertensive drugs was approximately N3.2 million .A total number of 1050 hypertensive patients were included in this study. The mean age was 60 years, females made up 62% of the study population. A high level of polypharmacy (87%) and sub-optimal blood pressure control was observed. An increase in blood pressure was observed with increase in the number of medication prescribed , is recommended in hypertensive patients. This is necessary to control blood pressure while increasing treatment adherence. Hypertension is a global cause of morbidity and mortality . A largeThe quality of antihypertensive medication prescribed is vital to successful management of hypertension. Quality of prescription takes into consideration the rationality of medication use among patients . MedicinPrevious studies carried out on prescription quality included a limited number of patients , 11 and Hypertensive patients without compelling indications attending three clinics of the University College Hospital, Ibadan, Nigeria were included in the study. This cross-sectional study was conducted over a period of 6 months from November 2011 to April 2012. Patients above 30 years receiving treatment (including life style modification) for hypertension were included in the study. Patients with comorbid conditions such as diabetes mellitus, renal diseases and/or complications such as congestive heart failure, Ischemia were excluded from the study. Patient recruitment and enrolment was by convenient sampling. Medical records of consecutive patients were evaluated for completeness. Patient records containing more than 80% of information required for analysis were included in the study. The most recent information about patients was used for analysis. Patients’ age, sex, BMI, antihypertension medication prescribed with dosage and frequency of administration and blood pressure readings were collected from their records.Antihypertensive drugs prescribed were evaluated for quality and conformity with current guidelines. Drugs were classified according to the Anatomical Therapeutic Chemical classification (ATCC) and daily defined dose (DDD) system . AntihypSPSS statistical package version 24 was used for analysis. Socio-demographic and clinical variables of patients was presented as frequencies and percentage. Chi-square test was used to test for significance between the groups of variables . The effect of number of medication prescribed on blood pressure control was also tested by chi-square. Correlation between blood pressure control and age, sex, BMI and the number of antihypertensive medication prescribed was evaluated.F = 646 (61.5%), M = 404 (38.5%)). The mean age of patients was 59.9 years ±12.1 (range = 30–85), with most patients above 59 years. Blood pressure control was poor with only 35% of the patients achieving optimum blood pressure values  Table , beta-blr = .25, p < 0.001, n = 1043) and diastolic blood pressure . Age also correlated with blood pressure control . There was no correlation between blood pressure control and sex of patients.The proportion of patients with uncontrolled blood pressure increased with increasing number of antihypertensive medication prescribed Table . The numCost analysis of prescriptions showed that the total expenditure by study participants on antihypertensive medication per day was N 103,845.75_o103,845.8 ($519.4)  was commonly practiced in the management of hypertension. In Nigeria majority of people with hypertension are between 40 and 60 years , 18, 19,Lifestyle modifications are recommended as the first line of therapy in hypertension especially in black patients without compelling indications or co-morbid diseases . Where tIn blacks, diuretics and CCBs have been shown to reduce BP more effectively than ACEIs, ARBs and beta-blockers . They arDaily defined dose was exceeded in more than 50% of the prescriptions. This varies with a previous report in this institution . The DDDBlood pressure control was poor in this population with only about 35% of the patients achieving optimum blood pressure thresholds. Poor blood pressure control continues to be an issue in Nigeria. Previous studies carried out showed high rates of uncontrolled BP , 19. FacCost-effectiveness is an important determining factor in the success of therapy. Very low socio-economic status is prevalent among the Nigerian population with most people subsisting on below $1 . This prIn this study, the quality of antihypertensive medications prescribed was critically evaluated. There is scarce information comparing the prescribed daily dose with the DDD. Cost implication of prescribing patterns was also studied.This study was carried out at clinics in one tertiary level hospital and cannot be generalized to reflect the prescribing pattern and quality in Nigeria.The impact of duration of hypertension on blood pressure control was not assessed.For cost consideration, comparison is a challenge because the exchange rate at the time the study was conducted is quite different from the current rates. The purchasing power parity (PPP) at the time of study was 79.8. Presently, the PPP stands at 102.7. The % change in PPP is 28.7%.Blood pressure control was low in patients. Poly-pharmacy may have contributed to the low BP control. Prescription of FDC will reduce the number of medication prescription to improve adherence to treatment. Prescribed daily dose equal to the DDD should be prescribed. This will improve clinical outcome as well as reduce adverse effects of medication. Measures to improve blood pressure control and attain acceptable BP targets should be explored in further studies.