P = 0.006). Multivariate regression analysis identified old age, female gender, visceral fat area, and low residual urine volume as independent determinants of MRA. As compared with reference values from a healthy population, patients with kidney failure had lower MRA , independently of age, gender, and body-mass index. The subset of patients who underwent kidney transplantation showed a significant increase in MRA after restoration of kidney function. These observations expand the association between ectopic fat accumulation and CVD to the population on dialysis, and suggest that kidney failure is reversibly associated with fatty muscle infiltration.Fat accumulation in skeletal muscle was recently established as a major risk factor for cardiovascular disease (CVD) in the general population, but its relevance for patients with kidney failure is unknown. Here we examined the potential association between muscle radiation attenuation (MRA), a non-invasive indicator of fat deposits in muscle, and cardiovascular events in patients with kidney failure treated with peritoneal dialysis (PD) and investigated dynamic changes and determinants of MRA in this population. We retrospectively assessed MRA on computed tomography images collected yearly in 101 incident patients with kidney failure starting PD between January 2006 and December 2015. After a median of 21 months on dialysis, 34 patients had 58 non-fatal cardiovascular events, and 22 patients had died. Baseline MRA was associated with cardiovascular events during time on dialysis, and patients with higher MRA (reflecting lower amounts of fat in muscle) showed a reduced incidence of CVD, independently of traditional risk factors (adjusted HR, 0.91; 95% CI, 0.86–0.97,  Chronic kidney disease (CKD) dramatically increases the risk of cardiovascular disease (CVD), which culminates in patients with kidney failure in a 10- to 20-fold increased hazard as compared with age- and gender-matched controls . Among pEctopic fat accumulation, which refers to an increased amount of lipids around and within non-adipose tissue organs such as the skeletal muscle, liver, and heart, is now recognized as a major risk factor for metabolic alterations and CVD. It results from either an inappropriate and sustained positive energy balance, leading to the spill over of energy storage from subcutaneous adipose tissue; from impaired storage of energy in fat deposits ; or from defects in adipocyte metabolism . The devTo date, no study investigated the association between fat distribution and clinical outcomes among patients with ESKD, who are at risk for both metabolic alterations and CVD. We therefore tested the hypothesis that non-invasive quantification of fat accumulation in muscle may help identifying ESKD patients at risk for CVD. We also investigated dynamic changes and determinants of MRA in this population.The cohort included all consecutive adult ESKD individuals starting peritoneal dialysis (PD) between January 2006 and December 2015 at Saint-Luc Academic Hospital, Brussels, Belgium. Patients were followed during time on PD, until death, kidney transplantation, transfer to hemodialysis, or end of study on 31 December 2017. Only four out of 101 patients enrolled in this study were lost to follow-up. None of the relevant baseline characteristics differed between the four patients who were lost to follow-up from those who remained in the study. Time-independent variables were collected for each patient at study entry. Time-dependent variables, including parameters of fat distribution and body composition, were collected at dialysis initiation then yearly.The primary outcome was the occurrence of at least one non-fatal CVD event during time on dialysis, including myocardial infarction or coronary revascularization; ischemic stroke, transient ischemic attack, or cerebrovascular revascularization; lower limb necrosis or peripheral arterial revascularization . ResiduaThe study was in accordance with the World Medical Association’s Declaration of Helsinki, the Belgian law related to experiments in humans dated 7 May 2004, the General Data Protection Regulation 2016/679 and the Belgian law of 30 July 2018 regarding the protection of personal data. The Ethical Review Board of Cliniques universitaires Saint-Luc and UCLouvain approved the study  and waived the requirement to obtain informed consent based on the observational and retrospective design of the study. Patients for whom individual data are shown have provided written informed consent to the use of anonymized pictures or results of biological analyses.Body composition was assessed by secondary analysis of electronically stored CT images, obtained at dialysis start, then yearly in every patient, as part of routine clinical practice. The goal of the procedure, initiated in January 2006 for all patients starting PD, was to identify patients at risk for or with early encapsulating peritoneal sclerosis, a dramatic complication of PD . At the 2/m2) (The third lumbar vertebra (L3) was chosen as a standard landmark to assess parameters of body composition and fat distribution, as previously described . Skeleta2/m2) . Mean MR2/m2) . Values 2/m2) , b. A si2/m2) .–1. Total run time was 8 min. Detection was performed using a Xevo TQS tandem mass spectrometer , with alternated positive and negative electrospray ionization.Total serum levels of uremic retention solutes were assessed on serum using a highly sensitive ultra-performance liquid chromatography–tandem mass spectrometry method, as previously described . Brieflyt-test, or χ2 test, as appropriate. Time to event analyses were performed by Cox regression and competing risk survival analyses, using the Fine and Gray method to correct for competing risk outcomes. For multivariable analyses, the following pre-specified covariates were included in the model: age at dialysis start, HDL-cholesterol level, presence of hypertension and diabetes, history of coronary heart disease, body-mass index, residual urine volume, plasma level of high-sensitivity C-reactive protein, and MRA. Collinearity between variables was quantified using variance inflation factors and condition numbers. Variance inflation factors > 10 or condition numbers > 30 suggested excessive correlation between variables. Because collinearity diagnostics showed high condition numbers due to significant correlations between age and MRA, sensitivity analyses were performed after exclusion of the variable age. Although MRA also modestly correlated with body-mass index, condition numbers were less than 30 and, therefore, body-mass index was included in all analyses. The likelihood ratio test was also used in nested models to determine whether exclusion of variable age or body-mass index altered model performance as compared with a model with MRA alone. To avoid overfitting, we limited the number of explanatory variables to achieve a ratio of at least 20 observations per coefficient whenever possible, and validated models using shrinkage statistics ] for continuous variables and as numbers and proportions for categorical variables. Age was defined at start of PD; hypertension, diabetes, and history of coronary heart disease were constructed as binary presence/absence variables. Continuous variables were expressed in their natural units without standardization. Univariate comparisons between the CVD and non-CVD groups were performed using unpaired atistics . Linear 2. Thirty-one percent had diabetes; 81%, hypertension; 12%, coronary heart disease; and 96%, RKF at dialysis start, with a mean daily urine output of 1539 (±695) ml. Eighty-five percent received angiotensin converting enzyme inhibitors or angiotensin receptor blockers; 57%, statins; and 19% and 7%, insulin and oral antidiabetic agents, respectively. A total of 215 CT scans performed at dialysis start  and during therapy were analyzed  cm2; and SMI 51 (±9) cm2/m2, and MRA 36 (±12) HUs  HUs .Patients were followed on PD until death, transplantation, transfer to hemodialysis, or end of study period. After a median of 21 months on dialysis, 31% of patients had received a kidney transplant; 31% had been transferred to hemodialysis; 22% had died; 12% were still on PD; and 5% had been lost to follow-up or experienced recovery of kidney function. During follow-up, 34 patients presented 58 CVD events , includivs. 38 ± 12 HU; P = 0.006)  .Based on the strong association between MRA and CVD observed in non-CKD individuals , we testP = 0.004) (P = 0.006), or in sensitivity analyses (P = 0.007).Survival analyses using Cox regressions identified higher baseline MRA  as a strong negative predictor of CVD events during follow-up  . The assanalyses , S4. TheThus, low values of MRA at dialysis initiation represent a valuable and non-invasive indicator of increased risk of CVD in patients with kidney failure, independently of traditional risk factors.vs. baseline, at 12 and 24 months, respectively  in parallel to declining residual urine volume in long-term PD patients.Based on these observations, we compared values of MRA in our cohort of incident patients with kidney failure to previously reported reference values from healthy controls with normal kidney function. Irrespective of gender, age, and body-mass index, patients with ESKD consistently had lower MRA than healthy controls, supporting the hypothesis that severely altered kidney function associates with fat accumulation in skeletal muscle .2 (P < 0.001) (P = 0.009).Next, we examined the longitudinal changes in MRA after transplantation and restoration of kidney function. We screened medical records and identified 12 patients from this cohort  who received a kidney transplant after dialysis, and in whom an abdominal non-contrast enhanced CT scanning was also performed after transplantation for an unrelated clinical indication. All patients received a standard immunosuppression regimen containing mycophenolate mofetil, tacrolimus, and rapidly tapered doses of corticosteroids. After a median time [IQR] from transplantation to CT scanning of 169 days [82–803], MDRD-estimated glomerular filtration rate had increased from 6 [5–12] to 55 [38–76] ml/min/1.73 m< 0.001) . In para< 0.001) . OverallAltogether, these data showed in a small number of patients that kidney transplantation is associated with a rapid increase in MRA, supporting the hypothesis that kidney failure contributes to lipid redistribution and ectopic fat deposition in skeletal muscle.In a cohort of incident ESKD patients, our study shows, for the first time, a strong and independent association between low values of MRA—a surrogate for ectopic fat accumulation in skeletal muscle—and an increased risk for CVD. A low MRA at dialysis initiation is a reliable predictor of CVD, independently of traditional risk factors, suggesting its potential to identify high risk ESKD patients. Several observations also suggest that ESKD may promote ectopic fat redistribution, which in turn could be reversed by restoration of kidney function.The worldwide obesity epidemic has emerged as a major cause of insulin resistance and type 2 diabetes, and such metabolic alterations now represent the leading risk factors for CVD. Classically defined by body-mass index, overweight and obesity are heterogeneous conditions, with important inter-individual differences in risk factor profiles despite similar amounts of total body fat, including in the CKD population . Anthropvia defects in insulin signaling and reduced insulin-stimulated glucose-transport activity  and waived the requirement to obtain informed consent based on the observational and retrospective design of the study.MK, TM, and JM contributed to research idea, study design, and drafting of the manuscript. MK, TM, EC, PT, MN, RC, CC, BB, and JM contributed to data acquisition, analysis, and interpretation. EC, RC, and JM contributed to statistical analysis. EC, MN, RC, CC, BB, MJ, and EG contributed to critical revision of the manuscript for important intellectual content. RC, MJ, EG, and JM contributed to study supervision or mentorship. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.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.


Background and Purpose: Recent findings suggested that non-stenosing atherosclerosis (NSA) may play an important pathogenic role, especially in cryptogenic strokes. Furthermore, arterial stiffness has been suggested to be a useful tool in identifying patients with embolic stroke of undetermined source (ESUS) with poor neurological prognosis. In this view, the aim of our study was to assess the association between carotid NSA and arterial stiffness in ESUS patients, in order to better define the cardiovascular risk profile of this subgroup of patients.Methods: We enrolled 100 patients with ESUS  and 48 patients with ischemic stroke from atherosclerosis. All patients underwent clinical and neuroimaging examination. A 24-h heart rate and blood pressure monitoring was performed in order to evaluate systolic, diastolic and mean blood pressure, pulse pressure, and arterial stiffness index (ASI).Results: NSA was present in 48 patients. In comparison with non-NSA-ESUS, in NSA-ESUS the mean age was higher, neurological deficit was more severe, hypertension, and diabetes were more common; systolic blood pressure, pulse pressure, and ASI were higher. In particular NSA-ESUS had ASI levels similar to strokes due to atherosclerosis.Conclusions: Our findings shed light on specific cardiovascular risk profiles underlying different subtypes of ESUS, suggesting the presence of increased arterial stiffness in NSA-ESUS patients with a risk factors profile similar to strokes due to atherosclerosis. Embolic strokes of undetermined source (ESUS) represent one-third of ischemic strokes. Although embolism is presumably the underlying mechanism of these strokes, the current definition of ESUS seems to be too broad , includiIt is well-known that arterial stiffness is associated with atherosclerotic burden and incident cardiovascular events  and may In this view, the aim of our study was to assess the presence of the common cardiovascular risk factors and especially arterial stiffness, in patients with ESUS associated with non-stenosing extracranial/intracranial carotid atherosclerotic plaques, in order to define a more complete cardiovascular risk profile in this subgroup of patients.The data that support the findings of this study are available from the corresponding author upon reasonable request. We enrolled 100 patients, admitted consecutively to our Stroke Unit  for ESUS, defined according to criteria proposed by the Cryptogenic Stroke/ESUS International Working Group (All the patients underwent carotid ultrasonography procedure by means of iE33 ultrasound system (probe 1.8–3.6 MHz) : in all patients ICA stenosis degree (ECST method)  and plaqPlaques were classified according to the five type classification : Type 1 BP monitoring was performed using validated oscillometric devices , in the first 24 h from the admission in the Hospital. BP was recorded for 24 h every 30 min, between 06:00 h to midnight, and hourly, from midnight to 06:00 h. For inclusion in the study, at least 80% of valid BP and heart rate measurements for each subject were needed.The following parameters were evaluated: SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure; PP, pulse pressure; and HR, heart rate.The 24-h ABPM data were divided into daytime (06:00–22:00 h) and night-time (22:00–06:00 h) values. Dipping pattern was defined as follows: dippers had a ≥10% but <20% fall in SBP; non-dippers had an SBP fall <10% but >0%; extreme dippers had an SBP fall ≥20%; and reverse dippers had an SBP increase .By plotting the individual values of SBP and DBP measurements, obtained through 24-h non-invasive monitoring, the linear regression slope of DBP on SBP was obtained and assumed as a global measure of arterial compliance, and its complement (1 minus the slope), named ASI, has been taken as a measure of arterial stiffness . Normal post-hoc test were performed: Dunn's test for Kruskal-Wallis, multiple unpaired t-test with false discovery rate correction for ANOVA and multiple Fisher exact test with false discovery rate correction for approximation of Fisher exact test. Multivariate logistic regression was evaluated, and the stepwise procedure based on Akaike's criterion was performed. Odds Ratio (OR) and their confidence intervals (CI) were calculated. A p-value below 0.05 was considered statistically significant.Statistical analysis was performed using the GraphPad Instat computer software  and R version 3.6.2. All results were presented as mean ± SD values. Normal distribution of quantitative variables was preliminary tested using the Kolmogorov–Smirnov test, instead, the homoscedasticity with Bartlett's test. Kruskal-Wallis or ANOVA tests, according to the normality distribution and the homoscedasticity, where used to compare mean differences of NSA groups with ATS confirmatory group; for qualitative variables, an approximation of Fisher exact test was used. When these tests were statistically significant In our study, we enrolled 100 patients with ESUS. As a confirmatory group we also evaluated a group of 48 patients with stroke due to atherosclerosis, comparable with NSA-ESUS in terms of age and sex see .NSA-ESUS patients and atherosclerotic stroke patients were older than non-NSA patients. The neurological deficit was more severe in patients with atherosclerotic stroke than in non-NSA patients. In both NSA-ESUS and atherosclerotic strokes, we found a substantially greater proportion of subjects with hypertension; furthermore, the laboratory parameters showed increased levels of HbA1c in NSA-ESUS in comparison with non-NSA group and increased levels of C-reactive protein (CRP) in strokes due to atherosclerosis in comparison with non-NSA group .Considering the hemodynamic parameters, in NSA-ESUS, SBP, ASI, and PP were significantly higher than in non-NSA patients . In compOR = 2.92 for ASI > 0.70, 95% CI 1.18–7.56), diabetes , age .Multivariate logistic regression model was constructed to determine the factors associated with NSA-ESUS. The following variables were initially evaluated: age (>65 years), clinical severity of ischemic stroke (NIHSS score ≥8), presence of hypertension, presence of diabetes mellitus, C reactive protein levels, presence of arterial stiffness (ASI > 0.70). Akaike's information criterion showed that the best subset of associated variables for NSA-ESUS were the following: ASI > 0.70 (The novel findings of our study are the following: (1) ESUS patients with NSA have a specific cardiovascular profile risk, similar to patients with stroke due to atherosclerosis, (2) NSA-ESUS patients have higher ASI values in comparison with non-NSA ESUS.Indeed, our results demonstrated that in ESUS patients arterial stiffness  is significantly associated with the presence of non-stenosant carotid plaques, independent of other risk factors.Arterial stiffness is a well-known risk factor for cardiovascular events , associaThe association between this subtype of ESUS and arterial stiffness is particularly important in order to explain some possible collateral effects of anticoagulant therapy in these patients. Indeed, in NSA-ESUS, a recent study showed that aspirin was safer than rivaroxaban, determining lower rates of major bleeding . Since pOur cohort of patients presented higher NIHSS values in comparison with other previous studies , 22, eveLastly, our cohort of patients with non-NSA-ESUS had lower levels of CRP in comparison with strokes due to atherosclerosis; instead NSA-ESUS seem to have intermediate values, but not significantly different in comparison with both non-NSA ESUS and atherosclerotic strokes. It is well-known the pathogenic link among inflammation, atherosclerosis, and arterial stiffness , thus thThis study has the following limitations: the recruitment was mono-centric, the sample size is small, there are no data about the link between arterial stiffness and possible long-term complications . In this view our study represents a hypothesis-generating research, thus further studies are needed in order to confirm our findings.Our findings shed light on specific cardiovascular risk profiles underlying different subtypes of ESUS, suggesting the presence of increased arterial stiffness in NSA-ESUS patients with a risk factors profile similar to strokes due to atherosclerosis.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the University Hospital of Siena, Italy. The patients/participants provided their written informed consent to participate in this study.MA: conception and design of the work. MA, PL, CM, FG, RT, CD, and GM: substantial contributions to the acquisition of data for the work. MA, PL, CM, CD, and AC: substantial contributions to the analysis of data for the work. MA, PL, GM, and AC: substantial contributions to the interpretation of data for the work and revising the draft of the work critically for important intellectual content. MA, PL, and AC: drafting the work. MA, PL, CM, FG, RT, CD, GM, and AC: final approval of the version to be published and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors contributed to the article and approved the submitted version.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.


Leptin levels  were higher in PMR than in MCVRF subjects . Serum levels of adiponectin (ng/mL) were higher in PMR patients , while no difference in serum levels of resistin (ng/mL) was found between PMR and MCVRF subjects (0.37/0.16–0.66 vs 0.26/0.14–1.24). Our study shows an increased subclinical vascular damage in PMR patients compared to those with MCVRF, paving the way for further studies aimed at planning primary cardiovascular prevention in this population.The aim of the study was to investigate the presence of subclinical vascular damage in polymyalgia rheumatica (PMR). We enrolled PMR patients having major cardiovascular risk factors (MCVRF) and, as controls, patients with MCVRF. All underwent: color Doppler ultrasound to evaluate the common carotid intima-media thickness (IMT), the anterior–posterior abdominal aortic diameter (APAD), and the prevalence of carotid artery stenosis; the cardio-ankle vascular index (CAVI) to measure arterial stiffness together with the ankle-brachial index (ABI) to investigate the presence of lower-extremity peripheral arterial disease. Finally, we measured the serum levels of adipocytokines implicated in vascular dysfunction. As a result, 48 PMR and 56 MCVRF patients were included. An increase of IMT , CAVI  and APAD values  was found in PMR patients with respect to controls. No differences were reported in the prevalence of carotid artery stenosis or ABI values between the two groups. A significant correlation between IMT and CAVI in PMR and MCVRF subjects (r Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder occurring in individuals at the age of 50 years or older, characterized by aching and stiffness in the proximal regions of the extremities as well as elevated markers of inflammation9. Incidence increases with age, peaks between 70 and 80 years, and is greater in women that are affected 2–3 times more frequently than men9. PMR has been associated, both in men and women, with a 2.6 increased risk for vascular events, including cardiovascular, cerebrovascular, and peripheral vascular events10. While in patients with RA and SLE the greatest cardiovascular risk occurs in established disease, in PMR the excess risk was seen both early in the disease and throughout the follow-up period11. The relevance of this issue is further supported by the observation that cardiovascular comorbidities in patients with PMR were mainly responsible for an increase in direct medical costs compared to age- and sex-matched controls from the same community in a Minnesota County12. However, a systematic review found inconsistent results, with some studies reporting a positive association and others no association between PMR and vascular disease13.The association of chronic inflammatory rheumatic disorders such as rheumatoid arthritis (RA), spondyloarthritis, gout, systemic lupus erythematosus (SLE), and scleroderma with an increased risk of vascular disease, especially cardiovascular and cerebrovascular disease, is a consolidated matter14 and the cardio-ankle vascular index (CAVI), a method for estimating arterial stiffness and predicting cardiovascular risk developed by measuring pulse wave velocity (PWV) and blood pressure15.The aim of our study was to investigate the presence of subclinical vascular damage in patients with PMR through a validated and non-invasive approach, including the common carotid intima-media thickness (IMT) assessment16 also having major cardiovascular risk factors (MCVRF), including hypertension, diabetes, hypercholesterolemia, cigarette smoking, and obesity, were recruited from the Rheumatology Unit at Sapienza University of Rome, Rome, Italy. As controls, consecutive Caucasian patients with MCVRF were enrolled at the Angiology Unit at Sapienza University of Rome, Rome, Italy, as long as a PMR diagnosis had been excluded.Between May 2017 and May 2018, consecutive Caucasian patients with PMR according to the EULAR classification criteria17. Diabetes was defined on the basis of fasting plasma glucose levels ≥ 126 mg/dL on 2 separate occasions18 or the use of anti-diabetic drugs. In accordance with the 2013 American College of Cardiology/American Heart Association Guidelines (ACC/AHA), hypercholesterolemia was defined as total cholesterol ≥ 220 mg/dL or the use of lipid-lowering drugs19. Finally, obesity was defined as a body mass index (BMI) of 30 kg/m2 or above20. All patients had a color Doppler ultrasound assessment and a CAVI measurement. We also analyzed the serum levels of adipocytokines known to be implicated in vascular dysfunction21.At recruitment, data on demographics, disease duration, treatments (with particular focus on glucocorticoids for PMR patients) were obtained by direct questioning and collected in a computerized form. Hypertension was defined as values ≥ 140 mmHg systolic blood pressure (SBP) and/or ≥ 90 mmHg diastolic blood pressure (DBP) according to the criteria published in 2013 by the European Society of Hypertension (ESH) and European Society of Cardiology (ESC)This study was conducted in accordance with the Declaration of Helsinki, and informed consent was obtained from all the patients. The study design was approved by the Ethical Committee of Sapienza University of Rome, Rome, Italy .22. Mannheim Carotid IMT Consensus (2004–2006) established guidelines for IMT assessment and distinction between IMT and atherosclerotic plaque by ultrasound based on localization, natural history, risk factors and predictive value for vascular events14.The measurement of common carotid artery IMT is a well-established cardiovascular risk marker, being both a measure of early atherosclerosis and of smooth muscle hypertrophy/hyperplasia23. Furthermore, we carried out ultrasound imaging of anterior–posterior abdominal aortic diameter (APAD) to screen for abdominal aortic aneurysm occurrence. Abdominal aorta was assessed by a 3.5 MHz convex transducer in longitudinal and transverse planes from the level of the diaphragm to the bifurcation. Aneurysm was defined as infrarenal arterial enlargement with a maximum diameter ≥ 30 mm associated to loss of arterial wall parallelism24.In all patients we performed a two-dimensional echo color Doppler ultrasound of the common carotid arteries, adopting a high definition vascular echograph (Esaote MyLab 50 X-Vision) in order to detect the IMT and the prevalence of carotid stenosis. Carotid artery color Doppler ultrasound was performed by a 7.5 MHz linear transducer, using an overhead technique, with the examiner seated behind the patient’s head. The patient was positioned supine, with its head slightly extended backwards and turned opposite to the side of interrogation. The degree of carotid artery stenosis, where present, was measured according to the European Carotid Surgery Trial (ECST) criteria15:a and β are constants. Scale conversion constants are determined so as to match CAVI with PWV using Hasegawa’s method. All measurements and calculations are made together and automatically in VaSera . This equation was derived from Bramwell-Hill’s formula and the stiffness parameter β. CAVI uses blood pressure cuffs with sensors on all four limbs to generate plethysmographs. The cuffs are placed on bilateral upper and lower extremities while the patient is in supine position with the limbs at the same level as the heart, in a comfortable position in a warm room. Measurement of ankle-brachial index (ABI), a tool to assess the presence of lower-extremity peripheral arterial disease17, was performed during CAVI measurement. Report from the instrument used for CAVI measurement included ABI index value as an output data. ABI was calculated directly by the instrument by using superior and inferior limb systolic pressure measurement. The mean bilateral (right/left side) CAVI and ABI values were used in our analysis.Since arterial stiffness has been associated with atherosclerosis, we also studied patients by CAVI, a blood pressure-independent index that measures the stiffness of the aorta, femoral artery and tibial artery. CAVI is calculated using the formula below enriched with measurements from an electrocardiogram, phonocardiogram, brachial artery waveform, and ankle artery waveformThe serum levels of leptin, adiponectin, and resistin were measured in PMR patients and controls. Venous blood samples were taken after 12 h of nocturnal fasting, then centrifuged and the serum stored at − 35 °C until analysis was performed by using a commercial ELISA according to the manufacturer’s instructions .2 test for quantitative and categorical variables, respectively. Bivariate analysis was conducted using the Pearson rho coefficient and Spearman correlation coefficient for quantitative variables. The statistical analysis was carried out using SPSS, release 23.0 . The statistical significance was set at p < 0.05. A sample size of at least 18 patients per group was estimated for 80% power by assuming a 5% significance level and considering a 2.6 relative risk for vascular events associated with PMR10 and a 50% prevalence of cardiovascular disease in the general population.Descriptive statistics  were used to present quantitative variables, whereas percentages and frequencies were generated for qualitative variables. Differences between patients with PMR and MCVRF controls were tested using Student’s t test or Mann–Whitney test when appropriate and χForty-eight patients with PMR and 56 with MCVRF were included in the study. The main demographic and clinical data are shown in Table A significant increase of IMT values (median/25th–75th percentile) was found in PMR compared to MCVRF controls   in patients with PMR compared to MCVRF controls , in the absence of aortic aneurysm  were higher in patients with PMR than in MCVRF subjects . Likewise, serum levels of adiponectin (ng/mL) were higher in patients with PMR   and carotid IMT or CAVI values nor between the mean cumulative dosage of glucocorticoids and carotid IMT or CAVI values.Glucocorticoids are the recommended first-line treatment in PMR, but their role in promoting an increased cardiovascular risk is controversial. Potential side effects of glucocorticoids, including hypertension, hyperlipidemia, and diabetes mellitus may indeed participate in this adverse outcome39. Leptin and resistin showed pro-atherogenic effects under experimental conditions, whereas adiponectin seems to have both anti- and pro-inflammatory activity, probably explained by its different isoform40. In RA patients, adiponectin showed critical pro-inflammatory properties, being elevated in serum and synovial fluid, strongly expressed at the synovium level, and directly correlating with disease activity and radiologic progression41. Similarly, in our PMR patients we observed significantly higher serum levels of leptin and adiponectin compared to MCVRF controls, which parallels the increased cardiovascular risk demonstrated by ultrasound and CAVI, although no correlation was found with clinical and laboratory features of the patients. Serum levels of leptin and adiponectin had been previously investigated in two studies including a small number of PMR patients, where a significant increase was observed after treatment with glucocorticoids43. Conversely, glucocorticoids are able to reduce serum levels of resistin, as shown in a small number of patients with systemic autoimmune diseases44. Indeed, unlike leptin and adiponectin, resistin is mainly produced by bone marrow-derived mononuclear cells with some contribution from adipocytes45. It is conceivable that we did not observe any difference in serum levels of resistin between PMR and MCVRF probably due to the effect of glucocorticoid therapy in patients with PMR.Finally, we measured serum levels of adipocytokines, which are considered biomarkers of cardiovascular risk since their levels are increased in patients with metabolic syndrome, insulin resistance, and obesityThe main limitation of our study is represented by the cross-sectional design, which does not help to establish a cause-effect ratio between inflammation and vascular lesions. In such a design, the timing of the snapshot does not assure to be representative and a longitudinal follow-up should be prompted to support the data.In conclusion, we evaluated for the first time the presence of subclinical vascular damage in patients with PMR. Our results show an increase in subclinical cardiovascular lesions with respect to patients with MCVRF, paving the way for further studies aimed at planning primary cardiovascular prevention in PMR patients. If our data will be confirmed in longitudinal studies, the cardiovascular risk profile should be considered as part of the overall management of PMR patients by using validated algorithms which may suggest lifestyle changes and additional treatments.


CMR adenosine first pass perfusion yields excellent results for the detection of significant coronary artery disease. As in patients after coronary artery bypass grafts (CABG) myocardial perfusion is more complex and additionally the kinetic of a first pass bolus may by altered due to different distances through the bypasses and/or native vessels, this patient group has been excluded from most published studies. Parameters like speed of contrast wash-in  and peak enhancement are indirectly used for visual analysis and may be altered post CABG imitating perfusion defects without significant stenosis. In this case, adenosine perfusion would be an inadequate diagnostic test.Aim of the study was to evaluate semiquantitative perfusion parameters in patients after CABG in order to evaluate contrast kinetics in areas supplied by native coronaries and different bypass grafts.32 patients post CABG were included into the study consisting of adenosine first pass (0.05 mmol/kg Gd-DTPA) perfusion (3 short axis views/heart beat) and late Gadolinium enhancement before undergoing invasive coronary angiography. In invasive angiography, areas perfused by native coronaries and the different bypasses were identified. In these areas upslope, time to 50% peak enhancement, time to peak enhancement and relative peak enhancement were calculated using the ViewForum . Only segments without vessel stenosis and without LGE were used for final analysis.Results are displayed in Table Semiquantitaive parameters of first pass adenosine perfusion are similar in areas supplied by native vessels or by different bypass grafts. These parameters are indirectly used for visual analysis . Therefore the possible different contrast kinetic through grafts and native vessel does not seem to be a limiting factor for the accuracy of first pass adenosine perfusion in patients post CABG.


O padrão pressórico não-dipper é definido por uma redução inferior a 10% na pressão arterial noturna e está associado a doenças cardiovasculares. Acredita-se que a inflamação desempenhe um papel na patogênese da doença pulmonar obstrutiva crônica (DPOC) e no padrão pressórico não-dipper e ambas as doenças estão associadas a uma qualidade de vida mais baixa. O objetivo deste estudo foi o de investigar os efeitos do padrão pressórico não-dipper em pacientes com DPOC. Foi realizado um estudo transversal incluindo 142 pacientes com DPOC. O Questionário Respiratório de Saint George e a Escala de Qualidade de Vida Euro foram utilizados para a coleta de dados. Para entender a rigidez arterial, o índice de aumento e a velocidade da onda de pulso foram medidos; subsequentemente, foi realizada a monitorização ambulatorial da pressão arterial de 24 horas. Foi aplicado um modelo de regressão logística multivariável para entender a relação entre as diferentes variáveis independentes e o padrão pressórico. Foram considerados estatisticamente significativos valores de p inferiores a 0,05. Como resultado, 76,1% (n = 108) dos pacientes apresentaram o padrão pressórico não-dipper. Os pacientes com padrão não-dipper apresentaram valores mais altos de proteína C reativa , índice de aumento  e pontuação total no Questionário Respiratório de Saint George , em comparação com os pacientes com padrão dipper. Adicionalmente, com o aumento do número de pessoas que habitavam o domicílio, verificou-se que o padrão pressórico não-dipper era mais frequente . O padrão pressórico não-dipper pode aumentar o risco cardiovascular ao desencadear a inflamação e pode afetar adversamente o prognóstico da DPOC diminuindo a qualidade de vida relacionada à doença.  Quando a redução da pressão arterial noturna é inferior a 10%, isto é chamado de padrão pressórico não-dipper, que é conhecido por estar associado a doenças cardiovasculares e lesões em órgãos-alvo.2 O índice de aumento (Aix) e a velocidade da onda de pulso (VOP) são indicadores de rigidez arterial que podem prever eventos cardiovasculares futuros, e os valores de Aix e VOP são mais elevados no padrão pressórico não-dipper.4 É controverso como o padrão pressórico não-dipper causa esses efeitos, mas acredita-se que esse padrão induz a expressão de citocinas do endotélio e desencadeia um processo inflamatório.5 Os marcadores de inflamação, como a proteína C reativa (PCR), a relação neutrófilos/linfócitos (NLR) e a relação plaquetas/linfócitos (PLR), são mais altos entre os indivíduos com pressão arterial não-dipper em comparação com seus pares.5Uma redução de mais de 10% da pressão arterial noturna é um processo fisiológico7 A presença de um processo inflamatório na patogênese tanto da DPOC quanto da pressão arterial não-dipper sugere que a incidência de padrão pressórico não-dipper possa ser alta em pacientes DPOC.8 Seus efeitos negativos na qualidade de vida constituem outro ponto comum de ambas as doenças.10 A qualidade de vida é a percepção de saúde do indivíduo e tem um impacto direto na sua saúde física e mental; também está relacionado ao número de exacerbações e hospitalizações agudas na DPOC.9A inflamação sistêmica desempenha um papel importante na patogênese da DPOC, e acredita-se que a PCR e a NLR podem ser usados como marcadores diagnósticos e prognósticos da DPOC.Estudos que investigaram os efeitos dos padrões de pressão arterial na DPOC são bastante limitados e a elucidação deste assunto pode ser um guia para o manejo da DPOC. O objetivo deste estudo é investigar o efeito do padrão pressórico não-dipper nos valores laboratoriais e na qualidade de vida na DPOC.O diagnóstico da DPOC deve ser confirmado por espirometria em pacientes com dispneia, tosse crônica, produção crônica de expectoração e exposição a fatores de risco de DPOC. Em nosso estudo, pacientes com diagnóstico de DPOC por especialistas em doença torácica e, portanto, em uso de medicação, foram aceitos como DPOC. Além disso, os exames espirométricos dos pacientes foram verificados pelo sistema de computador.Este estudo transversal foi realizado em pacientes com DPOC, com idades entre 18 e 80 anos, que foram admitidos à clínica de internamento ou ambulatória para doenças pulmonares do Hospital de Treinamento e Pesquisa Atatürk da Universidade Izmir Katip Celebi. O estudo excluiu pacientes que, além da DPOC, apresentavam infecção ativa conhecida, malignidade, insuficiência cardíaca congestiva, diabetes mellitus ou insuficiência renal. O estudo foi realizado entre janeiro e junho de 2018.11O tamanho da amostra foi calculado por meio do programa GPOWER 3.1. Usando o achado de uma pesquisa anterior, presumimos que os níveis médios de PCR seriam de 4,9 ± 1,7 mg/lt no grupo não-dipper e de 3,8 ± 1,5 mg/lt no grupo dipper. Para mostrar as diferenças entre os dois grupos, o tamanho da amostra necessário foi calculado em 128, com poder de 95% e uma taxa de erro tipo 1 bilateral de 5%. Aumentamos o tamanho da amostra em 10% e visamos chegar a 140 pacientes.2], sobrepeso  e obeso [≥ 30 kg/m2]). O estado civil foi dividido em dois grupos (solteiro e casado). O consumo de álcool também foi dividido em dois grupos (sim e não). Os locais onde os pacientes foram incluídos no estudo foram divididos em dois grupos (serviço de internação e ambulatório) e o histórico familiar de DPOC foi categorizado em dois grupos (sim e não). Os pacientes com diagnóstico de hipertensão por um médico e em uso de medicamentos prescritos foram considerados hipertensos. Pacientes que fumavam regularmente, pelo menos uma vez ao dia, foram considerados fumantes ativos. Em relação às variáveis contínuas, os pacientes foram solicitados a responder a perguntas como idade, número de pessoas que moravam em seus domicílios, anos de tabagismo e número de maços, número de admissões na unidade de emergência devido à DPOC durante o último ano e número de internações hospitalares por DPOC.Para examinar os dados sociodemográficos, o nível de escolaridade foi categorizado em dois grupos . A faixa de renda foi categorizado em três grupos (≥ 1.500 liras turcas (TL), 1.501 a 3.499 TL e ≤ 3.500 TL). Os valores do índice de massa corporal foram divididos em três categorias  é uma escala de qualidade de vida desenvolvida especialmente para o sistema respiratório que pode ser utilizada em pacientes com asma e DPOC, bem como em pacientes com bronquiectasia e sarcoidose.13 A escala é composta por 5 dimensões, incluindo mobilidade, autocuidado, atividades diárias, dor e humor. As pontuações mais altas indicam maior qualidade de vida.13 A utilidade da pontuação EQ-5D foi calculada usando o algoritmo MVH-A1 por Dolan.14 Este algoritmo fornece uma faixa de −0,594 a +1, onde valores mais altos indicam melhor qualidade de vida. A validade e a confiabilidade da escala foram confirmadas para o contexto turco.13A Escala de Qualidade de Vida Euro (EQ-5D) é uma escala de qualidade de vida geral de 5 questões, cada uma consistindo de 3 níveis.Após a aplicação do questionário e da coleta de sangue, os pacientes foram examinados quanto ao Aix e à VOP. Um aparelho Mobil-O-Graph®  calculou o Aix e a VOP registrando a pressão arterial braquial oscilométrica; o manguito subsequentemente reinsuflou na fase diastólica durante aproximadamente 10 segundos, registrando as ondas de pulso braquial com um sensor de pressão de alta fidelidade.Para medição da pressão arterial de 24 horas, os pacientes foram monitorados com um dispositivo Mobil-O-Graph NG® . O dispositivo foi ajustado para realizar medição de 24 horas, uma vez a cada 15 minutos durante o dia e uma vez a cada 30 minutos à noite. No dia seguinte, no mesmo horário, os pacientes devolveram os dispositivos. O braço não dominante foi usado para a medição, e as medidas diurnas e noturnas foram ajustadas de acordo com as horas de sono e vigília dos pacientes. Os pacientes foram orientados a continuar suas atividades habituais e a evitar exercícios exaustivos. Os exames de sangue foram obtidos dos pacientes antes da administração do tratamento. Entre os pacientes hospitalizados no serviço de doenças pulmonares, o questionário foi aplicado no mesmo dia. O dispositivo de monitorização ambulatorial da pressão arterial de 24 horas (MAPA 24h) foi aplicado em condições semelhantes para os pacientes ambulatoriais.2 Quando o descenso da pressão arterial foi inferior a 10%, foi considerada como padrão pressórico não dipper2. Os exames de sangue de PCR foram realizados no analisador automático Architect C16000  e o hemograma foi analisado no dispositivo de sangue total Mindray BC-6800 .Os resultados da medição da MAPA 24h foram examinados e, quando os valores médios noturnos das pressões arteriais sistólica e diastólica apresentavam um descenso de 10% ou mais em relação aos valores médios diurnos, considerava-se como pressão arterial dipper.A aprovação ética deste estudo foi obtida do Comitê de Ética em Pesquisa Clínica Intervencionista da Universidade Izmir Katip Celebi sob parecer número 164 (data de aprovação: 22 de dezembro de 2016). Todos os procedimentos deste estudo estavam de acordo com a Declaração de Helsinque de 1975, atualizada em 2013. Foi obtido o consentimento informado de todos os participantes incluídos no estudo.A análise estatística foi realizada no SPSS versão 16. Neste estudo, a distribuição das variáveis contínuas foi avaliada pelo teste de Kolmogorov-Smirnov e os dados não foram distribuídos normalmente. As variáveis contínuas foram apresentadas como medianas e intervalos interquartis (IIQ). A comparação estatística dos dois grupos independentes foi realizada usando o teste U de Mann Whitney. As comparações entre grupos de variáveis categóricas foram realizadas por meio do teste do qui-quadrado. A força de associação entre duas variáveis contínuas foi avaliada por meio de testes de correlação de Spearman.Os efeitos independentes com respeito à presença de pressão arterial não-dipper dos diferentes fatores de identificação foram examinados usando modelos de regressão logística. O teste de Hosmer-Lemeshow foi usado para avaliar o ajuste do modelo. As variáveis independentes com p ≤ 0,10 na análise bivariada foram incluídas no modelo de regressão logística multivariada com método de eliminação para trás. Devido à alta correlação entre a pressão sanguínea sistólica noturna e a pressão arterial média noturna, apenas a pressão arterial média noturna foi adicionada ao modelo. Os coeficientes ajustados são apresentados com seus intervalos de confiança de 95%. Todos os valores de p foram bicaudais e os valores de p inferiores a 0,05 foram considerados estatisticamente significativos.Foram convidados para o estudo 167 pacientes; destes, 12 não quiseram usar o aparelho MAPA 24h ou não quiseram participar no estudo devido a falta de tempo. Foram excluídos 13 pacientes devido a medidas inadequadas de MAPA 24h, e o estudo foi concluído com 142 pacientes. No total, 23,9% (n = 34) dos pacientes tinham padrão pressórico dipper e 76,1% (n = 108) tinham padrão não dipper. Desses pacientes, 43% (n = 61) foram incluídos da clínica de internação e 57% (n = 81) eram pacientes ambulatoriais.De acordo com a análise univariada, as variáveis sociodemográficas como idade, sexo e estado civil não afetaram significativamente o padrão pressórico. Por outro lado, o número mediano de pessoas que habitavam o domicílio foi mais alto nos pacientes que tinham padrão pressórico não-dipper em comparação com aqueles com padrão pressórico dipper. A relação entre as variáveis sociodemográficas e o padrão pressórico é apresentada naOs valores médios da pressão sanguínea sistólica noturna, pressão arterial média noturna, Aix e PCR foram significativamente maiores entre os participantes com padrão pressórico não-dipper em comparação com seus pares. A associação entre a pressão arterial de 24 horas e os resultados laboratoriais é mostrada naDe acordo com a análise de regressão logística multivariada, a PCR , o Aix  e a pontuação total do SGRQ  eram mais altos nos pacientes com padrão pressórico não-dipper do que naqueles com o padrão dipper. Além disso, os indivíduos com padrão pressórico não-dipper viviam em domicílios mais lotados, em comparação com os indivíduos com padrão pressórico dipper  .Neste estudo, nós investigamos os efeitos dos padrões pressóricos dipper e não-dipper nos resultados laboratoriais e na qualidade de vida de pacientes com DPOC. De acordo com os achados do nosso estudo, os pacientes com DPOC e padrão pressórico não-dipper apresentaram valores mais altos de PCR e Aix, bem como menor qualidade de vida devido à DPOC. O aumento na prevalência do padrões pressórico não-dipper com o número de pessoas habitando o domicílio foi outro achado do estudo.2 Em nosso estudo, 76,1% dos pacientes com DPOC apresentaram o padrão pressórico não-dipper. Nersesyan et al. verificaram que a taxa do padrão pressórico não-dipper em pacientes com DPOC foi de 72,7%.15 No estudo realizado por Aidar et al.,8 o descenso na pressão noturna foi superior a 10%, em relação à pressão diurna, no grupo controle saudável, enquanto o valor médio da pressão noturna em pacientes com DPOC foi inferior a 10%, em relação à pressão diurna.8 Embora os dados de frequência não tenham sido compartilhados no estudo de Aidar et al.,8 entende-se que a queda da pressão arterial noturna era insuficiente em pacientes com DPOC. A presença de processos inflamatórios com base em ambas as condições pode explicar a associação entre a pressão não-dipper e a DPOC. No entanto, os efeitos de cada fator um sobre o outro ainda não são claros.8 Neste estudo, os níveis de PCR foram mais altos entre os indivíduos com padrão pressórico não-dipper. Um estudo anterior conduzido por Kaya et al.11 apresentou o mesmo achado, onde os valores de PCR foram mais altos em pacientes com padrão não-dipper, em comparação com pacientes com o padrão dipper.11 Estudos prévios têm demonstrado que a pressão não-dipper diminui o número de células progenitoras endoteliais, interrompe os mecanismos de reparo vascular e a homeostase endotelial e conseqüentemente induz a inflamação, aumentando a expressão de citocinas endoteliais.5 Em nosso estudo, sugerimos que os níveis mais elevados de PCR em indivíduos com padrão pressórico não-dipper foram causados por mecanismos semelhantes.A MAPA 24h usada para diagnóstico e acompanhamento da hipertensão fornece informações sobre a presença de pressão dipper e não-dipper.5 Golpe et al. investigaram a relação entre o padrão pressórico e marcadores inflamatórios em pacientes com DPOC, concluindo que o padrão pressórico não afeta os níveis de neutrófilos e linfócitos.16 Visto que a amostra do nosso estudo consistia apenas de pacientes com DPOC e que as vias inflamatórias desempenham um papel importante na DPOC, os valores de NLR e PLR podem não ter sido afetados pelo padrão pressórico.Em nosso estudo, não houve diferença significativa entre os valores de NLR e PLR com respeito aos padrões pressóricos. Estudos anteriores mostraram que os valores de NLR e PLR são mais elevados em pacientes com pressão arterial não-dipper.4 O Aix é considerado um dos melhores indicadores de rigidez arterial e condições relacionadas à aterosclerose e acredita-se que ele preveja eventos cardiovasculares próximos.3 A pressão arterial não-dipper desencadeia o processo inflamatório e causa aterosclerose e arteriosclerose, e acredita-se que esteja associada ao aumento do risco de mortalidade cardiovascular e danos aos órgãos-alvo.3 Considerando o risco aumentado de inflamação e aterosclerose causado pela pressão arterial não-dipper, pode-se esperar que o Aix seja mais alto em indivíduos com padrão pressóricos não-dipper. Como resultado desse achado corroborado por nosso estudo, pode ser útil monitorar de perto os pacientes com DPOC e o padrão pressórico não-dipper, a fim de melhorar o manejo de doenças cardiovasculares.Como resultado de nosso estudo, encontramos valores de Aix mais altos entre os pacientes com pressão arterial não-dipper; este achado está de acordo com os resultados de estudos anteriores na literatura.17 O estudo de Wacker et al. relatou que, em associação com a carga da doença, a pontuação do SGRQ prediz exacerbações agudas da DPOC, hospitalizações devido a exacerbações e mortalidade devido a todas as causas.9 Em indivíduos com o padrão pressórico não-dipper, a nossa pontuação média no SGRQ foi mais alto; isto pode indicar a importância do controle da pressão arterial durante o manejo da DPOC.Em nosso estudo, a qualidade de vida geral medida pela EQ-5D foi menor em pacientes com padrões pressórico não-dipper de acordo com as análises univariadas; no entanto, essa relação perdeu sua importância nas análises multivariadas. As pontuações da escala de qualidade de vida do SGRQ, que são específicas para a DPOC, foram mais altas em pacientes com padrão pressórico não-dipper e essa relação permaneceu significativa nas análises multivariadas. Um dos motivos para isso pode ser o fato de que a EQ-5D mede a qualidade de vida geral, enquanto o SGRQ é específico para a DPOC. Considerando que a qualidade de vida geral de indivíduos com DPOC é inferior à de indivíduos saudáveis, o padrão pressórico não-dipper em pacientes com DPOC pode diminuir a qualidade de vida ainda mais.18 Visto que o estresse fisiologicamente desencadeia a liberação da epinefrina e da norepinefrina, pode-se esperar que o padrão pressórico não-dipper seja mais frequente em pessoas com fatores de alto estresse.19 Além disso, a taxa de superlotação descreve a proporção de pessoas que vivem em moradias superlotadas, conforme definido pelo número de cômodos disponíveis para a família, o tamanho da família, a idade de seus membros e a sua situação familiar; 40% da população da Turquia vive em moradias superlotadas.20 Esta realidade pode constituir um alto risco para o a população turca em relação ao desenvolvimento do padrão pressórico não-dipper.Em nosso estudo, verificamos que o aumento no número de pessoas habitando o domicílio aumentou a prevalência do padrão pressórico não-dipper. Maior número de pessoas morando no mesmo domicílio e o número de filhos são fatores que aumentam a responsabilidade e, consequentemente, levam ao estresse em indivíduos.22 A nossa taxa de participação foi menor do que a esperada; no entanto, determinamos diferenças nos principais indicadores, como PCR e as pontuações de qualidade de vida EQ5D e SGRQ, que estavam relacionados às hipóteses primárias e alcançamos mais de 90% nos cálculos de poder post hoc para esses parâmetros.É necessário mencionar que existem algumas limitações em nosso estudo. Primeiro, considerando que o nosso estudo é transversal, há um problema de temporalidade em que não podemos ter certeza se o fator precedeu ou não a ocorrência do desfecho. Em nosso caso, não sabemos se a inflamação causou o padrão pressórico não-dipper ou vice-versa; portanto, estudos prospectivos são necessários para avaliar a causalidade. A não inclusão de um grupo de controle saudável pode ser uma limitação. Comparar indivíduos saudáveis com pacientes com DPOC pode fornecer melhores informações sobre os efeitos dos padrões pressóricos. Além disso, em nosso estudo, não foi investigada a presença de síndrome da apneia do sono. Tem sido verificado que o padrão pressórico não-dipper é alto em pacientes com síndrome da apnéia do sono e a síndrome da apnéia do sono é comum em pacientes com DPOC.O padrão pressórico não-dipper foi mais comum em pacientes com DPOC e os pacientes com DPOC e pressão arterial não-dipper apresentaram níveis de PCR e valores Aix mais elevados. Isto representa um risco aumentado de doenças cardiovasculares e lesões em órgãos-alvo. Ao mesmo tempo, o padrão não-dipper de pressão arterial afeta adversamente a qualidade de vida dos pacientes com DPOC e isso parece afetar negativamente as exacerbações da doença, hospitalizações e mortalidade. Por estes motivos, o monitoramento rigoroso da pressão arterial em pacientes com DPOC pode contribuir para o aumento da qualidade de vida individual e a redução dos níveis de mortalidade relacionados às doenças cardiovasculares. 1Chronic obstructive pulmonary disease (COPD) is highly prevalent worldwide; it is characterized by the limitation of airway flow and, according to the World Health Organization, it will be the third leading cause of death in 2030.2. If the reduction in blood pressure at night is less than 10%, it is called the non-dipper blood pressure pattern, which is known to be associated with cardiovascular disease and end-organ damage.2The augmentation index (Aix) and pulse wave velocity (PWV) are indicators of arterial stiffness that can predict future cardiovascular events, and Aix and PWV values are higher in the non-dipper blood pressure pattern.4It is controversial how non-dipper blood pressure pattern causes these effects, but it is thought that this pattern induces cytokine expression from the endothelium and triggers an inflammatory process.5Inflammation markers such as C-reactive protein (CRP), the neutrophil-lymphocyte ratio (NLR), and the platelet-lymphocyte ratio (PLR) are higher among individuals with non-dipper blood pressure compared to their counterparts.5A reduction in blood pressure by more than 10% at night is a physiological process7The presence of an inflammatory process in the pathogenesis of both COPD and non-dipper blood pressure suggests that the incidence of non-dipper blood pressure pattern may be high in patients with COPD.8Another common point of both diseases is their negative effects on quality of life.10Quality of life is the health perception of the individual, and it has a direct impact on physical and mental health; it is also related to the number of acute exacerbations and hospitalizations in COPD.9Systemic inflammation plays a major role in the pathogenesis of COPD, and it is believed that CRP and NLR can be used as markers for diagnosis and prognosis of COPD.Studies that have investigated the effects of blood pressure patterns on COPD are quite limited, and elucidation of this subject might be a guide for COPD management. The aim of this study is to investigate the effect of non-dipper blood pressure pattern on laboratory values and quality of life in COPD.The diagnosis of COPD should be confirmed via spirometry in patients with dyspnea, chronic cough, chronic sputum production, and exposure to risk factors of COPD. In our study, patients diagnosed with COPD by chest disease specialists, who were therefore taking medication, were accepted as COPD. In addition, spirometry examinations of patients were checked by the computer system.This cross-sectional study was conducted with patients with COPD, between the ages of 18 and 80 years, who were admitted to Izmir Katip Celebi University Atatürk Training and Research Hospital’s inpatient or outpatient clinic for pulmonary diseases. The study excluded patients who, in addition to COPD, had known active infection, malignancy, congestive heart failure, diabetes mellitus, or renal failure. The study was conducted between January and June 2018.11The sample size was calculated using the GPOWER 3.1 program. By using a previous research finding, we assumed the mean CRP levels would be 4.9 ± 1.7 mg/lt in the non-dipper group and 3.8 ± 1.5 mg/lt in the dipper group. In order to show the differences between the two groups, the required sample size was calculated at 128, with 95% power and a two-sided type-1 error rate of 5%. We increased the sample size by 10% and aimed to reach 140 patients.2], overweight [25 to 29.99 kg/m2], and obese [≥ 30 kg/m2]). Marital status was divided into two groups (single and married). Alcohol intake was also divided into two groups (yes and no). Places where patients were included in the study were divided into two groups (inpatient service and outpatient clinic), and COPD history in their families was categorized into two groups (yes and no). Patients diagnosed with hypertension by a physician and receiving prescription medication were considered as having hypertension. Patients who smoked regularly, at least once a day, were considered as active smokers. Regarding continuous variables, patients were asked to respond to questions such as age, number of people living at home, years of smoking and package numbers, number of admissions to the emergency unit due to COPD during the last year, and number of hospital admissions for COPD.In order to examine sociodemographic data, education level was categorized into two groups (middle school or lower and high school or higher). Income level was categorized into three groups (≥ 1500 Turkish Liras (TL), 1501 to 3499 TL, and ≤ 3500 TL). Body mass index values were divided into three categories  is a quality of life scale especially developed for the respiratory system that can be used in patients with asthma and COPD, as well as in patients with bronchiectasis and sarcoidosis.13The scale is composed of 5 dimensions, including mobility, self-care, daily activities, pain, and mood. Higher scores indicate higher quality of life.13The utility of the EQ-5D score was computed using the MVH-A1 algorithm by Dolan.14This algorithm provides a range from −0.594 to +1, where higher values indicate better quality of life. The scale’s validity and reliability have been confirmed in Turkish settings.13The Euro Quality of Life Scale (EQ-5D) is a 5-question overall quality of life scale, each consisting of 3 levels.After the administration of the questionnaire and blood sampling, patients were examined in terms of Aix and PWV. A Mobil-O-Graph®  device calculated the Aix and PWV by recording oscillometric brachial blood pressure; the cuff subsequently reinflated at the diastolic phase for approximately 10 seconds, recording brachial pulse waves with a high-fidelity pressure sensor.For 24-hour blood pressure measurement, patients were monitored with a Mobil-O-Graph NG®  device. The device was adjusted to perform a 24-hour measurement, once every 15 minutes during the day and once every 30 minutes at night. The next day, at the same time, patient returned the devices. The non-dominant arm was used for measurement, and day and night measurements were adjusted according to the patients’ sleeping and waking hours. Patients were instructed to continue their usual activities and to avoid exhausting exercise. Blood tests were obtained from patients before treatment was administered. Among patients who were hospitalized in the pulmonary diseases service, the questionnaire was applied on the same day. The 24-hour ambulatory blood pressure monitoring (24-h ABPM) measuring device was applied in similar conditions for outpatients.2. When the decrease in blood pressure was less than 10%, it was considered as non-dipper blood pressure pattern.2CRP blood tests were carried out in a Architect C16000 autoanalyzer , and the hemogram was analysed in a Mindray BC-6800 whole blood device .The results of 24-h ABPM measurement were examined, and, if nighttime average values of systolic and diastolic blood pressures were decreased by 10% or more with respect to day-time average values, this was considered as dipper blood pressureThe ethical approval for the study was obtained from the Izmir Katip Celebi University Interventional Clinical Research Ethics Committee under decision number 164 . All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.Statistical analysis was performed using SPSS version 16. In this study, the distribution of the continuous variables were assessed with Kolmogorov-Smirnov test, and the data were not distributed normally. Continuous variables were presented as medians and inter quartile ranges (IQR). Statistical comparison of two independent groups was performed using the Mann Whitney U test. The between-group comparisons of categorical variables were performed using the chi-square test. The strength of association between two continuous variables was assessed using Spearman correlation tests.Independent effects with respect to the presence of non-dipper blood pressure of the different identifying factors were examined using logistic regression models. The Hosmer-Lemeshow test was used for assesing the model fit. Independent variables with p ≤ 0.10 on bivariate analysis were included in the multivariate logistic regression model with a “backward” elimination method. Due to high correlation between nighttime systolic blood pressure and nighttime mean arterial pressure, only nighttime mean arterial pressure was added to the model. Adjusted coefficients are presented with their 95% confidence intervals. All p values were two-tailed, and p values lower than 0.05 were considered statistically significant.One hundred and sixty-seven patients were invited to the study. Twelve patients did not want to wear the 24-h ABPM device or did not want to participate in the study due to lack of time. Thirteen patients were excluded from the study due to inappropriate 24-h ABPM measurements, and the study was completed with 142 patients. In total, 23.9% (n = 34) of the patients had dipper and 76.1% (n = 108) had non-dipper blood pressure pattern. Among these patients, 43% (n = 61) participated from the inpatient clinic, and 57% (n = 81) were outpatients.According to univariate analysis, sociodemographic variables such as age, sex, and marital status did not significantly affect the blood pressure pattern. On the other hand, the median number of people living in the household were higher in those who had non-dipper blood pressure pattern compared to those with dipper blood pressure pattern. The relationship between sociodemographic variables and blood pressure pattern is presented inMean nighttime systolic blood pressure, mean nighttime arterial pressure, Aix, and CRP values were significantly higher among participants with non-dipper blood pressure pattern compared to thier counterparts. The association between 24-hour blood pressure and laboratory results are shown inAccording to multivariate logistic regression analysis, CRP , Aix , and SGRQ total score  were higher in patients with non-dipper blood pressure pattern than in those with dipper blood pressure. In addition, individuals with non-dipper blood pressure pattern were living in more crowded houses, compared to individuals with dipper blood pressure pattern  .In this study, we investigated the effects of the dipper and non-dipper blood pressure patterns on laboratory results and quality of life of patients with COPD. According to our study findings, patients with COPD and non-dipper blood pressure pattern had higher CRP and Aix values and lower quality of life due to COPD. The increase in the prevalence of the non-dipper blood pressure pattern with the number of people living at home is another finding of the study.2In our study, 76.1% of patients with COPD had a non-dipper blood pressure pattern. Nersesyan et al. found that the rate of non-dipper blood pressure pattern in patients with COPD was 72.7%.15In the study performed by Aidar et al.,8the decrease in nighttime blood pressure was higher than 10%, with respect to daytime blood pressure, in the healthy control group, while the mean value of nighttime blood pressure in patients with COPD was below 10%, with respect to daytime blood pressure.8Although the frequency data were not shared in the study by Aidar et al.,8it was understood that the decrease in nighttime blood pressure of patients with COPD was insufficient. The presence of inflammatory processes based on both conditions might explain the association between non-dipper blood pressure and COPD. However, the effects of each factor on one another are still unclear.8In this study, CRP levels were higher among individuals with non-dipper blood pressure pattern. A previous study conducted by Kaya et al.11presented the same finding, where CRP values were higher in patients with non-dipper pattern, compared to patients with dipper blood pressure.11Previous studies have shown that non-dipper blood pressure decreases the number of endothelial progenitor cells, disrupts vascular repair mechanisms and endothelial homeostasis, and consequently induces inflammation by increasing the expression of endothelial cytokines.5In our study, we suggest that the higher CRP levels in individuals with the non-dipper blood pressure pattern were caused by similar mechanisms.The 24-h ABPM used for diagnosis and follow-up of hypertension provides information about the presence of dipper and non-dipper blood pressure.5Golpe et al. investigated the relationship between blood pressure pattern and inflammatory markers in patients with COPD, and they concluded that blood pressure pattern does not affect neutrophil and lymphocyte levels.16Given that the sample of our study only consisted of patients with COPD and that inflammatory pathways play a major role in COPD, the NLR and PLR values may not have been affected by the blood pressure pattern.In our study, there was no significant difference between NLR and PLR values based on blood pressure patterns. Previous studies have shown that NLR and PLR values are higher in patients with non-dipper blood pressure.4Aix is considered as one of the best indicators of arterial stiffness and atherosclerosis-related conditions, and it is thought to predict oncoming cardiovascular events.3Non-dipper blood pressure triggers the inflammatory process and causes atherosclerosis and arteriosclerosis, and it is thought to be associated with increased risk for both cardiovascular mortality and end-organ damage.3Considering the increased risk of inflammation and atherosclerosis caused by non-dipper blood pressure, Aix might be expected to be higher in individuals with non-dipper blood pressure pattern. As a result of this finding supported by our study, it might be useful to closely monitor patients with COPD and non-dipper blood pressure pattern, in order to improve management of cardiovascular diseases.As a result of our study, we found higher Aix values among patients with non-dipper blood pressure; this finding is in concordance with the results of previous studies in the literature.17The study of Wacker et al. reported that, in association with disease burden, SGRQ score predicts acute COPD exacerbations, hospitalizations due to exacerbations, and deaths due to all causes.9In individuals with a non-dipper blood pressure pattern, our mean SGRQ score was higher, which may indicate the importance of blood pressure control during COPD management.In our study, the general quality of life measured by EQ-5D was lower in patients with non-dipper blood pressure pattern according to univariate analyses; however, this relationship lost its significance in multivariate analyses. SGRQ quality of life scale scores, which were specific for COPD, were higher in patients with non-dipper blood pressure pattern, and this relationship remained significant in multivariate analyses. One reason for this could be due to the fact that the EQ-5D measures the overall quality of life, while the SGRQ is specific for COPD. Considering that the overall quality of life of individuals with COPD is lower than that of healthy individuals, the non-dipper blood pressure pattern in patients with COPD may further decrease the quality of life.18As stress physiologically triggers the release of epinephrine and norepinephrine, the non-dipper blood pressure pattern can be expected to be more frequent in people with high stress factors.19Moreover, the overcrowding rate describes the proportion of people living in overcrowded dwellings, as defined by the number of rooms available to the household, the household’s size, its members’ ages, and their family situation; 40% of the population of Turkey lives in overcrowded families.20This case may constitute a high risk for people of Turkey for the development of non-dipper blood pressure pattern.In our study, we found that the increase in the number of people living at home increased the prevalence of the non-dipper blood pressure pattern. Increased number of people living in the same house and the number of children are factors that increase the responsibility and hence lead to stress on individuals.22Our participation rate was lower than expected; however, we determined differences in major indicators such as CRP and EQ-5D and SGRQ quality of life scores, which were related to the primary hypotheses, and we achieved more than 90% power in post hoc power calculations for these parameters.It is necessary to mention that there are some limitations to our study. First, as our study is cross-sectional, there is a temporality problem where we cannot be sure whether the factor preceded the occurrence of the outcome or not. In our case, we do not know whether inflammation caused non-dipper blood pressure pattern or vice verse; hence, prospective studies are needed in order to assess causality. Failure to include a healthy control group may be a limitation. Comparisons of healthy individuals and patients with COPD might provide better information regarding the effects of blood pressure patterns. Also, in our study, the presence of sleep apnea syndrome was not investigated. Non-dipper blood pressure pattern was found to be high in patients with sleep apnea syndrome, and sleep apnea syndrome is common in patients with COPD.The non-dipper blood pressure pattern was more common in patients with COPD, and patients with COPD and non-dipper blood pressure had higher CRP levels and Aix values. This poses an increased risk of cardiovascular disease and end-organ damage. At the same time, the non-dipper blood pressure pattern adversely affects quality of life of patients with COPD, and this is thought to negatively affect exacerbations of the disease, hospitalizations, and mortality. For these reasons, close monitoring of blood pressure in patients with COPD may contribute to increased individual quality of life and decreased levels of mortality related to cardiovascular diseases.


BackgroundSickle cell disease (SCD), a chronic hemolytic disorder, results in cumulative end-organ damage affecting major organs such as the cardiovascular, renal, and central nervous systems. Effects of modifiable risk factors, such as blood pressure (BP), on the development of end-organ complications in SCD have not been well studied, particularly among the pediatric population. Relative hypertension in patients with SCD increases their risks of stroke, cardiovascular complications, and death. The primary hypothesis of this study was that abnormal BP patterns are common among patients with SCD and they impact end-organ complications.MethodsPatients with SCD  were enrolled from the Children’s Hospital at Montefiore (N = 100). For each patient, demographic data were collected, biochemical variables in urine and blood samples were analyzed, BP was determined with ambulatory blood pressure monitoring (ABPM), and an echocardiogram was performed. The prevalence of abnormalities in BP parameters was defined, and their relationships with measures of SCD severity and end-organ damage were assessed.ResultsSufficient ABPM data were available for 67 patients. Enrolled children were 13 ± 4 years . Assessment of diurnal variation demonstrated that 81% of patients had abnormal systolic nocturnal dipping and 61% had abnormal diastolic nocturnal dipping. Abnormalities in the diurnal pattern were associated with reticulocytosis and hyperfiltration. Microalbuminuria was present in 19% (n = 13) of patients, of which 77% (n = 10) were females (p = 0.014). Diastolic load and abnormal nocturnal dipping were associated with hyperfiltration but not with microalbuminuria.ConclusionsBP abnormalities detected with ABPM in SCD patients are prevalent and perhaps are a risk factor for end-organ complications. Further studies are required to identify the mechanisms underlying these relationships and their longitudinal changes. Sickle cell disease (SCD) is the most common inherited disorder of red blood cells in the United States . MortaliIn general, hypertension is the most important modifiable risk factor for cardiovascular and renal disease . PatientStudy participants and study designClinically stable children  with SCD from a pediatric sickle cell clinic at Children’s Hospital at Montefiore, Albert Einstein College of Medicine, were enrolled from November 2015 until October 2017. The study was approved by the Institutional Review Board of Children’s Hospital at Montefiore. Inclusion criteria were a diagnosis of SCD , confirmed with hemoglobin electrophoresis. Exclusion criteria were recent hospitalization, pain crisis within the prior 14 days, ongoing treatment with an antihypertensive agent, and known chronic kidney or congenital heart disease. Patients or guardians provided written informed assent/consents. Patients ≥ 18 years were allowed to consent, those 13-18 years were allowed to assent with legal guardian consent, and parents provided consent for children under the age of 13 years.Baseline characteristics of each participant, including age, gender, weight, height, and BP, and co-morbidities such as sleep apnea, were recorded. Patients underwent 24-hour ABPM with a Spacelabs 90207 model monitor, which is compact and lightweight and has five cuff sizes available for accuracy. A trained nurse or trained pediatric nephrology fellow placed and programed ABPMs. An appropriate-sized cuff was attached to the patient’s non-dominant arm, and the device was programmed to record BP every 20 minutes during the daytime and every 30 minutes during nighttime. A study was considered interpretable when at least one BP reading per hour was valid and >25 readings in a 24-hour period were valid. The same day that an ambulatory BP monitor was placed, blood and urine samples were collected and analyzed for complete blood count, creatinine, lactate dehydrogenase (LDH), reticulocyte count, fetal hemoglobin, urine microalbumin, and urine creatinine. Estimated glomerular filtration rate (eGFR) was measured with the modified Schwartz formula for patients < 18 years old .BP load, pre-hypertension, hypertension, and masked hypertension were defined according to the most recent ABPM statement issued by the American Heart Association . BPs in Adequate nocturnal dipping was defined as at least a 10% decrease, relative to diurnal BP, in nocturnal systolic and diastolic BP. Blunted dipping was defined as <10% drop in nocturnal systolic or diastolic BP, extreme dipping as >20% drop in nocturnal systolic or diastolic BP, and reverse dipping as sleep systolic or diastolic BP higher than awake systolic or diastolic BP.2 for patients <10 years old and as >140 mL/min/1.73 m2 for patients ≥10 years old [The systolic BP index was calculated as the measured mean BP divided by the 95th percentile for sex and height . Hyperfiears old .EchocardiogramEchocardiograms were obtained at the scheduled time annually. If echocardiogram results were more than one year old at the time of enrollment, then a repeated study was requested. All echocardiograms were performed according to the institutional protocol and in accordance with the American Society of Echocardiography published guidelines on performing and quantifying pediatric echocardiograms .Data analysisDescriptive statistics (mean ± standard deviation) were generated for all demographic characteristics. All values were checked for normality. Means, confidence intervals, standard deviations, standard errors, ranges, p-values, and equality of variances were calculated for all variables. Demographic information, anthropomorphic data, and all echocardiographic measurements and calculations were compared between patients with and without hypertension.Pearson and Spearman correlation and multivariate regression analyses were performed. All tests were two-sided. Statistical significance was defined as p < 0.05. Statistical analyses were performed with SPSS Version 22 .Of 100 patients who were enrolled, 67  were included in the analysis; the mean age was 13 ± 4 years old. Thirty-three patients were excluded due to the lack of sufficient data on ABPM (n = 29) or because a pain crisis occurred after enrollment (n = 4). Patients with no echocardiogram within one year of ABPM or insufficient echocardiogram were excluded from the cardiac analyses (n = 21)  were hypertensive , and 9% (n = 6) were pre-hypertensive Figure .Abnormal systolic nocturnal dipping was present in 81% n = 53); of these, 10% (n = 7) had reverse systolic dipping ; 9% had reverse dipping and 9% had extreme diastolic nocturnal dipping. Abnormal nocturnal dipping and hypertension were noted across all age groups. BP parameters were not associated with low hematocrit (hct), markers of inflammation , or Echocardiograms demonstrated that 61% of patients (30/49) had left ventricle (LV) dilation, but all had a normal systolic function, assessed by ejection fraction, and there was no evidence of significant pulmonary hypertension. Correlations between echocardiographic findings and laboratory hematologic findings are shown in Table As expected, results showed that left ventricular mass volume index (LVMI) and end-diastolic volume (EDV) were significantly related to hct, hemolysis (LDH), and inflammation . Correlations between ambulatory BP variables and echocardiographic markers of size and systolic function were not significant except for diastolic load, diastolic nocturnal dipping, and 24-hour diastolic BP variability .Correlations between markers of renal function and laboratory hematologic findings are shown in Table Hyperfiltration was related to hct, hemolysis (LDH), and inflammation (WBC). In addition, protein in urine was significantly related to hemolysis (LDH) and inflammation (WBC). Correlations between markers of renal function and ambulatory BP variables are shown in Table Hyperfiltration was related to higher diastolic load, worse nocturnal dipping, and higher average heart rate. Relationships between markers of renal function and echocardiographic findings are shown in Table Hyperfiltration was significantly related to higher left ventricular mass and lower mass-to-volume ratio. Renal function was positively correlated with left ventricular systolic function.2 for all but one of the patients; the patient was not hypertensive, did not have microalbuminuria, and had normal echocardiograms. There was no significant difference in microalbuminuria or eGFR in patients who were on hydroxyuria versus those who were not.Microalbuminuria was present in 19% of patients (n = 13), of whom 77% (n = 10) were female (p = 0.014). Of the 28 patients who had a sleep study, eight (28.5%) were found to have sleep apnea. All but one of the patients with sleep apnea had either blunted or reverse systolic nocturnal dipping . eGFR was >90 mL/min/1.73 mAbnormal nocturnal dipping was seen in 81% of patients; of those, 10% had reverse dipping. BP follows a circadian rhythm; levels rise during daytime or with activity and fall during nighttime or with sleep. Abnormal circadian patterns are associated with renal and cardiovascular complications in patients with chronic kidney disease or diabetes, and even within the healthy population -20. Our The overall rate of ambulatory hypertension of 7.42% 5/67) observed in this study population is comparable to reported prevalence in the general population of pediatric patients -22. In a7 observePrevious studies have proposed adding ABPM as a standard of care for all patients with SCD . Togethe2 (measured with 99mTc-DTPA) in children with SCD who were <16 years of age; it was shown to decline during the second decade of life, with a mean eGFR of around 133 ± 31 mL/min/1.73 m2 in children >16 years of age [2) was lower than in the previous studies [2, as determined by serum creatinine measurements. Low eGFR was not associated with high WBC, high LDH, low hemoglobin, or nocturnal hypertension, as was demonstrated in the past [2) were on hydroxyurea. The etiology of lower mean eGFR observed in this study, as compared to published studies, is unclear but may be related to the differences in measured 99mTc-DTPA versus calculated eGFR. Further studies are needed to establish the causal relationship and potential benefit of treating diastolic nocturnal dipping and diastolic load to slow the progression of sickle cell nephropathy.Consistent with other studies, 19% (n = 13) of patients in our study had microalbuminuria, most of whom were females (11/13). Abnormal dipping in patients with microalbuminuria did not differ from that in patients without microalbuminuria, which is inconsistent with the results of previous studies. In concordance with previous studies, most (49%) of our study population had hyperfiltration . Previous of age . In the  studies -25. Of nthe past . HyperfiMany studies of adults showed that SCD is associated with elevated cardiac output, cardiomegaly, cardiac dysfunction/diastolic dysfunction, and pulmonary hypertension -28. In oLimitationsConclusions drawn from the results of this study are limited by the study’s small size and cross-sectional design. All enrolled patients could not be included in the analysis because some did not have valid ABPM results or interpretable echocardiograms. Patients were included if they had at least 25 ABPM readings, which is fewer than the recommended number of measurements in the research. General limitations of ABPM that may affect measurements and detection of nocturnal abnormalities include differences between bedtime and actual sleep time, as well as discomfort due to the monitor; however, these limitations are likely to impact our study to the same extent that they impact others that have used ABPM. Data were not reproduced. Microalbuminuria was determined from a single random sample. Also, the use of creatinine to calculate eGFR may affect results. Finally, 23% of patients were on chronic transfusion, and some received ABPM on the last day of transfusion or one day after the completion of transfusion, which may affect hemoglobin and markers of hemolysis.Abnormal BP patterns were noted for patients with SCD, and accurate diagnosis of most of these abnormalities requires ABPM. Thus, the use of ABPM in this at-risk population may be warranted. SCD patients have other risk factors, such as hemolysis, vaso-occlusion, and chronic inflammation, that could contribute to end-organ complications. However, patients who are at high risk of sustained hypertension  need to be assessed and treated carefully to lessen end-organ damage. Long-term follow-up studies are needed to assess the role of abnormal nocturnal dipping in stroke, cardiovascular, or renal complications.