As the case detection rates of hypertension increase in adult Nigerians, achieving target blood pressure (BP) control has become an important management challenge.To describe medication adherence and BP control amongst adult Nigerians with primary hypertension attending a primary care clinic of a tertiary hospital in a resource-poor environment in Eastern Nigeria.A cross-sectional study was carried out in 140 adult patients with primary hypertension who have been on treatment for at least 6 months at the primary care clinic of Federal Medical Centre, Umuahia. A patient was said to have achieved goal BP control if the BP was < 140 per 90 mmHg. Adherence was assessed in the previous 30 days using a pretested researcher-administered questionnaire on 30 days of self-reported therapy. Adherence was graded using an ordinal scoring system of 0–4; an adherent patient was one who scored 4 points in the previous 30 days. Reasons for non-adherence were documented.p = 0.03), antihypertensive medication duration ≥3 years (p = 0.042), and taking ≥ one form of antihypertensive medication (p = 0.04). BP at the recruitment visit was significantly higher than at the end of the study (p = 0.036). The most common reason for non-adherence was forgetfulness (p = 0.046).Adherence to medication and BP control rates were 42.9% and 35.0% respectively. BP control was significantly associated with medication adherence (The rate of BP control amongst the study population was low, which may be connected with low medication adherence. This study urges consideration of factors relating to adherence alongside other factors driving goal BP control. Hypertension is therefore one of the most common causes of disability and death amongst the adult Nigerian population, and plays an important role in the causation of hypertensive heart failure, heart attack, arteriosclerosis, renal failure and stroke.4 Adequate control of BP was reported to reduce the incidence of stroke by an average of 35% – 40%, myocardial infarction by 20% – 25% and heart failure by more than 50%.5 For individuals of 40–70 years of age each increment of 20 mmHg in systolic BP or 10 mmHg in diastolic BP doubles the risk of cardiovascular disease across the entire BP range from 115 per 75 mmHg to 185 per 115 mmHg.6Hypertension is the most common cardiovascular disorder, posing a major clinical and public health challenge to populations in socio-economic and demographic transition.8 The primary focus of antihypertensive therapy is to achieve a goal BP of < 140 per 90 mmHg for the general population and < 130 per 80 mmHg for special high-risk populations such as patients with diabetes mellitus, renal disease and adverse cardiovascular events such as myocardial infarction and stroke.3 The magnitude of BP control differs between the developing11 and developed countries.12 In Nigeria, BP control rates in adult patients range from 24.2% to 35.8% according to published studies.14 These disparities are probably due to a milieu of limited healthcare facilities, widespread personal and family poverty, ignorance, poverty of knowledge and other diverse factors.16Achieved BP is not synonymous with target or goal BP control, and the benefits of goal BP control have been elucidated in previous studies.18 some of which are related to the patients, the health professionals and government. Amongst the patient-related factors is adherence to antihypertensive medication. Adherence is one of the challenges of antihypertensive medication and is defined conceptually as the degree to which the patient conforms with treatment as prescribed.19 Several methods of measuring adherence to medication have been described.22 There is no ‘gold standard’ for precise measurement of adherence.20 Clinical measures include the use of questionnaires for 30 days of self-reported (self-administered) therapy. Pharmacological measures involve determination of serum and urinary concentrations of drugs or using biological markers integrated into the tablets.21 Although having higher sensitivity and specificity, pharmacological methods are not routinely used in clinical practice.21 Recently the medication event monitoring system (MEMS) was introduced.22 Assessment of adherence using the MEMS device involves microprocessor-based monitoring. Unfortunately the MEMS device is not readily available in the study area.Blood pressure control is influenced by multiple factors,In order to provide necessary health services for management of hypertension in health facilities in Nigeria, clinicians should identify and determine the prevailing level of BP control and factors responsible for poor BP control. This study therefore provides additional evidence on the contribution of adherence factors to the growing problem of goal BP control in Nigeria. It is against this background that the researchers were motivated to study medication adherence and BP control amongst adults with primary hypertension attending a primary care clinic of a tertiary medical centre in a resource-poor environment in Eastern Nigeria.The Ethics Committee of the Federal Medical Centre (FMC), Umuahia, Abia State, Eastern Nigeria, granted approval for the study. Informed written consent was obtained from the respondents before recruitment into the study.This was a clinic-based descriptive cross-sectional study carried out on 140 patients from April 2011 to November 2011 at the Department of Family Medicine of the FMC, Umuahia, which is a tertiary hospital in Abia State, Eastern Nigeria.Umuahia is the capital of Abia State in south-east Nigeria. The State is endowed with abundant mineral and agricultural resources, with a supply of professional, skilled, semi-skilled and unskilled manpower. Economic and social activities here are low compared to industrial and commercial cities such as Onitsha, Port Harcourt and Lagos. Until recently the capital city of Lagos and its environs have witnessed an upsurge in the number of banks, hotels, schools, markets, industries and fast food restaurants in addition to changing dietary and social lifestyles.The FMC is located in the metropolitan city of Umuahia. This is a tertiary hospital established with the tripartite mandate of service delivery, training and research, and serves as a referral centre for primary and secondary public health institutions as well as missionary and private hospitals in Abia and the neighbouring states of Imo, Ebonyi, Rivers and Akwa Ibom. The Department of Family Medicine serves as a primary care clinic within the tertiary hospital setting of the medical centre. All adult patients, excluding those who need emergency healthcare services, paediatric patients and antenatal women, are first seen at the Department of Family Medicine, where diagnoses are made. Patients who need primary care are managed and followed up in the clinic, whilst those who need specialist care are referred to the respective core specialist clinics for further management. The clinic is run by consultant family physicians and postgraduate resident doctors in Family Medicine.3 goal BP is < 130 per 80 mmHg, and special high-risk populations such as hypertensive patients with diabetes mellitus, renal disease and previous adverse cardiovascular events such as myocardial infarction and stroke. The eligible patients were consecutively recruited for the study.The inclusion criteria were adult hypertensive patients aged ≥ 18 years who gave informed verbal consent, had been on outpatient treatment for hypertension in the clinic for at least 6 months, and who recorded at least three clinic visits . Exclusion criteria included critically ill patients, those with an established cause of hypertension, patients whose recommended23 for estimating minimum sample size for descriptive studies when studying proportions with an entire population size < 10 000 using an estimated population size of 200 adult hypertensive patients, based on the previous annual hypertensive patients’ attendance records at the clinic. These 200 adult hypertensives excluded other hypertensive patients referred to and being followed up in other medical outpatients’ clinics in the medical centre. The diabetic hypertensives were also excluded from this recorded number. The authors assumed that 50% of the adult hypertensives would have a good BP control rate and adhere to treatment, at a 95% confidence level with a 5% margin of error. This gave a sample estimate of 132 patients. A sample size of 140 adult hypertensive patients was selected to allow for attrition.Sample size estimation was determined using the formula14 as follows: all the time = 4 points, most times = 3 points, sometimes = 2 points, rarely = 1 point, never = 0. Four points indicated adherence, whilst 0–3 points meant non-adherence. Reasons for non-adherence were documented for those who scored 0–3 points.Adherence was assessed by use of a pretested, interviewer-administered questionnaire on 30 days of self-administered and reported therapy. Patients were seen at the recruitment visit, penultimate visit before the end of the study and then at the end of the study visit. At the end of study visit the adherence section of the data collection tool was administered. Information collected at the end of study visit included, (1) how many times per day do you take your BP medication?, (2) how many tablets do you take specific to your hypertensive condition?, (3) how often do you take your BP medication , (4) how many dose(s) of your antihypertensive drugs have you missed in the previous one month? and (5) how much of your previous BP medication is remaining after the previous one-month visit? Adherence was graded using an ordinal scoring system of 0–4 points developed by the authors from a review of the literaturePretesting of the adherence section of the data collection tool was done internally at the Family Medicine clinic of the FMC and externally at the Family Medicine clinic of the FMC in Owerri, Eastern Nigeria. Five diabetic hypertensive patients of the FMC in Umuahia were randomly used for pre-testing of the questionnaire, which lasted for one day, and five hypertensive patients were used in the FMC in Owerri. The pretesting was done to assess the applicability of the questionnaire tool internally and externally. All of the patients used for pretesting of the questionnaire instrument gave valid and reliable responses, confirming the clarity and applicability of the questionnaire tool, and questions were interpreted with the same meaning as intended. The questionnaire was administered by three resident doctors who were recruited and trained for the study, once to each eligible respondent at the end of study visit.2 The baseline BP was recorded at the time of recruitment (recruitment visit), subsequent BP was measured at the penultimate visit before the end of study visit, and then at the end of study visit. The duration of hypertension, class and number of antihypertensive drugs and reasons for non-adherence to antihypertensive medication were documented. Fasting blood sugar, urinalysis, urea and creatinine were done. Diagnosis of diabetes mellitus was based on a venous plasma glucose level of ≥ 126 mg/dL after an overnight fast, which was confirmed by a repeat test at the second clinic visit.24 The basic demographic variables of age, sex, marital status, education and occupation were also documented.BP readings were based on the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification and guidelines.2 A patient was defined as having goal BP control if his or her BP at the end of study visit was < 140 per 90 mmHg.3 An adherent patient was defined as one who had a score of 4 points  for the previous 30 days by the end of the study visit.The authors defined hypertension as a systolic and/or diastolic BP ≥ 140 per 90 mmHg or documented use of antihypertensive medications in a person previously diagnosed with hypertension.t-test served to compare means. The level of statistical significance was set at p < 0.05.The results generated were analysed using Statistical Package for Social Sciences (SPSS) software version 13.0  for calculation of percentages for categorical variables and means for continuous data. Means with standard deviations of continuous variables were generated where appropriate. Percentages and frequencies were compared by Chi-square analysis and the Student's The age of the hypertensive patients ranged from 32 to 83, years with mean age of 52 ± 7.4 years. There were 56 (40.0%) males and 84 (60.0%) females, with a male to female ratio of 1: 1.5 .χ2 = 3.18; df = 1; p - value = 0.042) (Ninety-eight (70.0%) patients had been hypertensive for less than 3 years, whilst 42 (30.0%) had been hypertensive for 3 years or more. Of the 49 patients that had good BP control, 29 (59.2%) had been hypertensive for 3 years or more whilst 20 (40.8%) had been hypertensive for less than 3 years. The difference between the two groups was statistically significant (= 0.042) .t = 4.26; p-value = 0.036).The mean BP at the recruitment visit (170.6 ± 10.4 per100.8 mmHg ± 12.3 mmHg) was higher than the mean BP at the end of study visit (130.6 ± 4.4 per 80.3 mmHg ± 8.6 mmHg). This difference was statistically significant  (Sixty (42.9%) out of 140 patients were adherent, whilst 80 (57.1%) were not adherent. Of the 49 patients who had good BP control, 45 (91.8%) were adherent whilst 4 (8.2%) were not adherent. BP control was significantly higher in those that adhered to antihypertensive medication compared with non-adhering patients ( = 0.03) .χ2 = 5.11; df = 2; p-value = 0.04) (Blood pressure control by number of antihypertensive medications . The dif = 0.04) .χ2 = 6.03; df = 4; p-value = 0.046) (The most common reason proffered for non-adherence to medications by the hypertensive patients was forgetfulness (32.4%). Other reasons included feeling of well-being (25.6%), lack of funds (25.6%), advice by spiritual leaders (8.7%) and herbal remedies (7.7%). This marginal difference was statistically significant (= 0.046) .10 31.4% reported in Osogbo, south-west Nigeria,11 and 33% reported in Kano, Northern Nigeria.14 However, the BP control rate in this study is lower than the 35.8% reported in Ilorin, North Central Nigeria13 and 40.0% reported in South Africa.25 The findings of this study corroborate previous reports that adequate BP control rates are low in Nigeria and occur only in a fraction of treated hypertensives.14 These disparities are probably due to a milieu of limited healthcare facilities, misconceptions and health beliefs about hypertensive disorder.26The BP control rate in this study of 35.0% is higher than the 24.2% reported in Port Harcourt, Rivers State, south-south Nigeria,3 Although low BP control rates are due to multiple factors, in this study this may not be unconnected from patient factors of adherence (forgetfulness) to medication amongst others. Clinicians attending to adult Nigerians with primary hypertension should therefore ask specific questions in order to uncover medication problems. in the early stages, since hypertension is a silent killer that usually shows no specific symptoms. This will enable adult Nigerians with primary hypertension to benefit from the life-saving benefits of antihypertensive medications. This study has shown that BP control was significantly higher amongst patients that adhered to their medication. The adherence rate of 42.9% in this study is lower than that of 45.0% reported in Kano, Northern Nigeria14 and of 43.0% reported in Lake City in the USA.27 The findings of this study have demonstrated the contribution of adherence in BP control amongst the study population. Although there may be other inter-patient variability amongst the study population that may contribute to poor BP control despite adherence to medications, efforts should therefore be made by clinicians to ensure that their adult hypertensive patients adhere to their antihypertensive medications. Clinicians inquiring about medication adherence during their encounters with adult hypertensive patients remains imperative in the drive to lower BP to goal levels. Without regular feedback on medication adherence between clinicians and hypertensive patients, a patient with poor BP control may never achieve their BP target.Although adequate BP control does not completely obviate the risk of developing complications of hypertension, experience from developed countries has left no doubt that there is no magic bullet for adequate BP control amongst hypertensives.28 on critical evaluation of literature on medication compliance that adherence to medication tends to increase over time for patients on chronic medication such as hypertensive patients.Blood pressure control was significantly associated with duration of hypertension. The finding of a higher BP control rate amongst patients who had had their hypertensive condition for three or more years could be attributed to their increasing contact with the hospital and other health facilities where the importance of consistent antihypertensive medication is emphasised. These patients with longer duration of hypertensive medication, by virtue of their frequent contact with health facilities, are also more likely to be aware of the fatal and non-fatal complications of uncontrolled BP. In addition, it could be a reflection of wider social interaction with other hypertensive patients who are adherent to antihypertensive medication. This result supports the observation by Nichol Venturin and Sung29 and is consistent with a rational approach for treatment of hypertension in adult Black hypertensives.2 This could be a reflection of the pathophysiological mechanisms involved in Black hypertensive patients,2 and provides additional evidence on the growing need for combination therapy amongst the study population. This therefore calls for wider application of evidence-based hypertensive management guidelines in addition to diverse actions against hypertension, because adequate control of BP is associated with more health benefits and less risk of adverse cardiovascular events.15This study has also shown that BP control is related to the number of antihypertensive medications. This finding is similar to reports from other parts of Nigeria,30 Non-adherence resulting from forgetfulness, amongst other reasons, could lead to poor BP control and higher costs in physicians’ visits. This has also shown that forgetting to take antihypertensive medication is not a problem that adult patients outgrow. Awareness of this by clinicians is crucial for optimal care of adult Nigerian hypertensive patients in the study area. Clinicians should therefore be aware of these subtleties, because they can influence the quality and quantity of care delivered to these patients.Although low BP control rates are polyfactorials, this study observed that the most common reason proffered for by non-adhering hypertensive patients was forgetfulness. This could be attributed to life-competing psychosocial demands amongst the study population, who were mainly traders. This finding has buttressed the report that psychosocial variables are additional barriers to adherence to antihypertensive medication.Despite the publication of major clinical trials on the benefits of attaining target BP amongst hypertensives, the actual BP control rates in adult hypertensive Nigerians remains a management challenge. Suffice it to say that substantial risk of cardiovascular events still exists, despite treatment of hypertension, depending on the difference between achieved BP and target BP. However, the bulk of mortality associated with cardiovascular disease is principally attributed to unsatisfactory BP control resulting in target organ damage. Hence there is a need to determine the magnitude of BP control amongst adult hypertensives in the study centre as part of the search for an effective intervention to prevent complications of hypertension amongst the study population. This study therefore provides additional evidence on the growing problem of BP control rates in Nigeria, and calls for improved management of hypertension through adherence counselling as well as strengthening the quality of care. This will enable adult hypertensive Nigerians to benefit from the life-saving advantages of goal BP control.The limitations imposed by the self-reported and qualitative measure of adherence for the study are recognised by the authors. Also, the sample size for the study was relatively small, but was more than the minimum estimated sample size for the study and was the number of patients seen within the proposed duration of the study.The questionnaire was administered by three resident postgraduate medical doctors. This could have introduced interviewers’ influence and bias, since some patients couldn't clinically give true responses to questions related to adherence in the presence of their physicians. However, pre-testing of the questionnaire internally and externally using the same resident medical doctors did not reveal this limitation. In addition, the respondents were assured of confidentiality prior to the interview.The BP control rate amongst the study population was low. This may not be unconnected with low adherence amidst other factors determining target BP control. The most common reason for non-adherence was forgetfulness. This study urges consideration of adherence factors alongside the milieu of other factors driving goal BP control. The use of reminders such as an alarm system or beepers amongst other interventions to overcome forgetfulness is advocated.


Acute kidney injury (AKI) is associated with extended hospital stay, a high risk of progressive chronic kidney diseases, and increased mortality. Patients undergoing radical prostatectomy are at increased risk of AKI because of intraoperative bleeding, obstructive uropathy, older age, and preexisting chronic kidney disease. In particular, robot-assisted laparoscopic radical prostatectomy (RALP), which is in increasing demand as an alternative surgical option for retropubic radical prostatectomy (RRP), is associated with postoperative renal dysfunction because pneumoperitoneum during RALP can decrease cardiac output and renal perfusion. The objective of this study was to compare the incidence of postoperative AKI between RRP and RALP.We included 1340 patients who underwent RRP (n = 370) or RALP (n = 970) between 2013 and 2014. Demographics, cancer-related data, and perioperative laboratory data were evaluated. Postoperative AKI was determined according to the Kidney Disease: Improving Global Outcomes criteria. Operation and anesthesia time, estimated blood loss, amounts of administered fluids and transfused packed red blood cells, and the lengths of the postoperative intensive care unit and hospital stays were evaluated. Propensity score matching analysis was performed to reduce the influence of possible confounding variables and adjust for intergroup differences between the RRP and RALP groups.P < 0.001). However, the estimated blood loss and amount of administered fluids in RALP were significantly lower than in RRP (both P < 0.001). Also, RALP demonstrated a significantly lower incidence of transfusion and smaller amount of transfused packed red blood cells than RRP (both P < 0.001). Importantly, the incidence of AKI in RALP was significantly lower than in RRP . Furthermore, the length of hospital stay in RALP was also significantly shorter (P < 0.001).After performing 1:1 propensity score matching, the RRP and RALP groups included 307 patients, respectively. The operation time and anesthesia time in RALP were significantly longer than in the RRP group (both The incidence of AKI after RALP is significantly lower than after RRP. RALP can therefore be a better surgical option than RRP in terms of decreasing the frequency of postoperative AKI. RALP has been known to be related to lower blood loss and blood transfusion rates and shorter hospital stays in comparison with RRP.10 However, RALP requires a longer operation time and results in worse physiological changes due to pneumoperitoneum and the steep Trendelenburg position in comparison with RRP.12 The glomerular filtration rate, renal blood flow, and urine output can thereby decrease with intraperitoneal carbon dioxide insufflation during RALP.15Radical prostatectomy is a standard surgical treatment for clinically localized prostate cancer.17 However, there have been no comparable studies to date on the evaluation of AKI between RRP and RALP. Therefore, we aimed in our current study to compare the incidence of postoperative AKI based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria between RRP and RALP using propensity score matching analysis.Acute kidney injury (AKI) is increasingly recognized as a serious postoperative complication and is linked to increased health costs and adverse outcomes including progression to chronic kidney disease and death.Following approval by the institutional review board of Asan Medical Center, the records of all patients who underwent RRP or RALP at Asan Medical Center, Seoul, Republic of Korea between January 2013 and December 2014 were searched. Of the 1376 searched patients, we excluded those who underwent additional procedures (n = 8) or had any history of chronic kidney disease (n = 28). A final cohort of 1340 patients was included in the present study  and colloid (Volulyte). Systolic arterial blood pressure was maintained at 90 mm Hg or more during surgery. If systolic arterial blood pressure was less than 80 mm Hg, vasoactive drugs  were administered. The hemoglobin concentration was maintained at 7 g/dL or more; if the hemoglobin concentration was less than 7 g/dL, a packed red blood cell transfusion was planned.18 For RRP, a lower midline abdominal incision was made and the endopelvic fascia was opened from the base of the prostate to the apex. For RALP, pneumoperitoneum was established using a Veress needle, and 6 trocars were inserted. For RALP, the prostate was dissected using the antegrade approach. In both surgeries, bilateral pelvic lymph node dissection was performed, and the neurovascular bundles were spared for all potent patients. After the surgical specimen was removed, vesicourethral anastomosis was performed using a 20-Fr urethral catheter.The key procedures for RRP and RALP were performed according to the standard protocols of our institution.−1.154 × age−0.203 × [0.742 if female] × [1.210 if African-American].19We collected information regarding the baseline characteristics and laboratory, intraoperative, and postoperative data from the computerized patient record system at our institution . The baseline characteristics included age, height, weight, body mass index, comorbidities , and the use of prescribed medications . Cardiac disease included ischemic heart disease and heart failure. Heart failure was defined as a history of any type of heart failure that was diagnosed by a cardiologist regardless of medication or decreased ejection fraction . Cerebrovascular disease was defined as a history of carotid artery stent or angioplasty, transient ischemic attack, stroke, or cerebral hemorrhagic event. Data on the status of patient's cancer including prostate-specific antigen (PSA) level and Gleason score were collected. The estimated glomerular filtration rate (eGFR), hematocrit, albumin, uric acid, and C-reactive protein levels were collected as preoperative laboratory data. eGFR was calculated using the 4-variable  Modification of Diet in Renal Disease Study equation: eGFR = 186 × serum creatinine20Intraoperative data included operation time, anesthesia time, estimated blood loss, volume of administered fluids, volume of transfused packed red blood cells, and the use of vasoactive drugs. The operation time was defined as the time between first incision and the end of the operation. Anesthesia time was defined as the time from anesthesia induction to tracheal extubation. Estimated blood loss was evaluated by the amount of lost red cell mass, which was calculated using the perioperative change in the hematocrit and transfused red cell mass using the following equation: lost red cell mass (mL) = patient's estimated blood volume (mL) × (preoperative hematocrit in % − postoperative hematocrit in %) + (transfused packed red blood cell in units × 250 (mL) × 0.6).21 However, in the present study, the urine output criterion was not included due to the inconsistency in urine output measurement. The secondary endpoints included the lengths of postoperative intensive care unit and hospital stay.The primary endpoint of this study was the comparison of the incidences of AKI based on the KDIGO criteria between RRP and RALP. According to KDIGO criteria, AKI is defined as an increase in serum creatinine by 0.3 mg/dL or more within 48 hours or an increase in the serum creatinine by 1.5 times or more within the prior 7 days.t test or Mann–Whitney U test for continuous variables, as appropriate. Data are presented as the mean ± standard deviation, or number (percentage), as appropriate. We performed 1:1 propensity score matching analysis to reduce the influence of possible confounding variables and adjust intergroup differences between RRP and RALP groups. To determine the propensity score, a multiple logistic regression model was run using the following 17 variables: age, height, weight, body mass index, hypertension, diabetes mellitus, cardiac disease, cerebrovascular disease, taking beta-blockers or nonsteroidal anti-inflammatory drugs, PSA level, Gleason score, preoperative eGFR, hematocrit, albumin, uric acid, and C-reactive protein .Before propensity score matching, we compared data between the RRP and RALP groups using the Chi-square test or Fisher exact test for categorical variables and the student P < 0.001) (Table P < 0.001) (Table P < 0.001) (Table P = 0.044) . However, there were no significant differences in the lengths of stay in the intensive care unit between the groups.A total of 1340 patients who underwent RRP (n = 370) or RALP (n = 970) were included in the current analyses. Age, height, weight, presence of cardiac disease, PSA, preoperative hematocrit, and albumin level demonstrated statistically significant differences between RRP and RALP groups (Table 1) Table . However1) Table . Also, t1) Table . Importa) Figure . FurtherIn the present study, we found that the incidence of AKI after RALP was significantly lower than after RRP. The amounts of intraoperative blood loss and transfused packed red blood cells in RALP were also significantly lower, and the duration of hospital stay was significantly shorter in comparison with RRP.22 Nevertheless, the exact incidence of AKI after radical prostatectomy using validated criteria have never been determined. Our present study provides the first information on the incidence of AKI after radical prostatectomy according to the KDIGO criteria, which can detect even acute subclinical increases in serum creatinine or decreases in eGFR after surgery.Postoperative AKI is associated with increased costs, morbidity, and mortality and can increase the risk of progressive chronic kidney disease. Patients undergoing radical prostatectomy are at increased risk for AKI because of the common occurrences such as obstructive uropathy, older age, and preexistent chronic kidney disease, as well as intraoperative bleeding.15 These physiologic changes consequently stimulate the renin-angiotensin system and further decreases renal blood flow.24 All of these can contribute to the impairment of renal function. However, previous studies on this issue have reported that postoperative renal function is unaltered after RALP, even under using a pressure of 20 mm Hg for pneumoperitoneum.26 However, these earlier reports analyzed the change in the creatinine clearance or the value of eGFR to measure the differences between preoperative and postoperative renal function, instead of using validated criteria. Also, those studies analyzed only patients that underwent RALP, so the outcomes were not comparable to patients who underwent RRP. In our present study, we used the KDIGO criteria to define AKI, and its incidence between RRP and RALP groups were compared using propensity score matching analysis to reduce the influence of confounding variables and adjust intergroup differences between groups. Therefore, we believe that our present results are highly reliable for the evaluation of AKI after radical prostatectomy.The results of our current analyses showed a postoperative AKI incidence of 5.5% after RALP and 10.4% after RRP. RALP often requires pneumoperitoneum with an intra-abdominal pressure of more than 15 mm Hg for better visualization of the surgical field and continues for more than 3 hours. Direct compression of the intra-abdominal vessels and renal parenchyma by pneumoperitoneum can decrease cardiac output, renal blood flow, the glomerular filtration rate, and urine output.10 RALP demonstrated lower blood loss and blood transfusion rate in comparison with RRP. The steep Trendelenburg position for RALP under pneumoperitoneum improves visualization, and thus bleeding from the dorsal vein complex during surgery can be more easily controlled.25 Furthermore, the tamponade effect by pneumoperitoneum also contributes to reduced blood loss.27 Generally, anemia and blood transfusion are well-known important risk factors of renal injury after cardiac surgery.31 The pathogenesis is unclear, but several mechanisms have been suggested: high vulnerability to hypoxic injury to the kidney and iron-mediated oxidative kidney injury.35 A previous study of 8799 patients who underwent lower-extremity revascularization to investigate the effects of blood transfusion demonstrated that intraoperative blood transfusion was associated with renal failure, as well as morbidity and mortality.36 Another study of 1034 cardiac surgery patients reported that the patients who received a nonleukoreduced red blood cell transfusion were at a higher risk of acute kidney injury and in-hospital mortality than the patients who received leukoreduced red blood cell transfusion.37 Another retrospective study of trauma patients demonstrated that the transfusion of red blood cell stored for more than 14 days was associated with increased renal dysfunction and mortality.38 In our current study, the higher incidence of AKI after RRP may result from the decreases in cardiac output and renal perfusion, diminished oxygen delivery, and increased oxidative stress to the kidney that are associated with a larger amount of blood loss during RRP. Furthermore, the higher incidence of red blood cell transfusion during RRP may also be responsible for the higher incidence of AKI.There are several comparative studies between RRP and RALP in terms of surgical, oncological, and functional outcomes. In line with a previous report,39 In our current study, none of the patients with postoperative AKI previously had rhabdomyolysis or urinary tract obstruction after RRP or RALP.Rhabdomyolysis and urinary tract obstruction can occur after robotic or nonrobotic radical prostatectomy and may be associated with development of AKI. Rhabdomyolysis can lead to glomerular filtration rate impairment. However, prostatectomy-related rhabdomyolysis is a very rare complication, and its incidence is reported to be 0.08%.41 Thus, we performed propensity score matching analysis for 17 confounding variables to minimize these biases. In addition, there are many difficulties in performing a randomized controlled trial to compare RALP and RRP because most patients are unwilling to accept the idea of randomization to a particular surgical treatment. Thus, propensity score matching analysis can be a reliable second-best strategy for comparing RALP and RRP.The inevitable limitation of our current study comes from its retrospective design. Many confounders such as age, body mass index, comorbidities, and preoperative anemia may affect the accurate evaluation of the incidence of postoperative AKI. Also, previous studies show that cancer characteristics  might predict the risk of complications.In conclusion, postoperative AKI occurs at a lower incidence after RALP than RRP. This result provides valuable information on the additional benefit of RALP, which has many well-known advantages in comparison with RRP. Accordingly, RALP can be a better surgical option in terms of decreasing postoperative AKI than RRP.


ΔSUA) and change in eGFR (ΔeGFR) during the same period. Multivariate regression analysis of ΔeGFR indicated that the increase in SUA over time were a negative predictor of the change in eGFR. Our result indicates that the decline of eGFR over years is larger in subjects with an increased SUA level, which helps to underline the importance of SUA level management in the context of kidney function preservation.Serum uric acid (SUA) level has been proposed to have important connections with chronic kidney disease (CKD), while the impact of SUA level on the natural history of glomerular filtration rate (GFR) decline remains unknown. The present study aims to study the association of the SUA level with the GFR decline in a general population. Two thousand, seven hundred and eighty-nine subjects who visited the Health Checkup Clinic both at 2008 and 2013 were identified. A significant inverse correlation was observed between change in SUA from 2008–2013 ( Uric acid (UA) is a poorly soluble end product of purine nucleotides degradation, and hyperuricemia is defined as serum uric acid (SUA) level >420 umol/L (7 mg/dl) in males and >360 umol/L (>6 mg/dl) in females . Recent 2)  has attracted a lot of nephrologists and there are many studies published. It has been established that in patients with gout and acute UA nephropathy, the treatment of hyperuricemia is of clinical benefits. For patients without gout and acute nephropathy, the first aspect is the relationship between hyperuricemia and CKD progression. Whether SUA is an independent risk factor or only a marker of the progression of CKD is still a matter of debate. In the past, hyperuricemia was thought to be simply a reflection of kidney damage because it was assumed that a decrease in kidney blood flow causes the decrease in UA clearance. However, high uric acid levels was reported to be associated with increased rates of glomerular filtration rate (GFR) decline in multiple cross sectional studies in CKD patients . On the 2) .While the conclusion is still uncertain, most studies were done study the relationship of hyperuricemia and CKD incidence/progression, it also remains unknown whether the SUA level is associated with the natural decline of GFR with aging. It is important to study the strategies that could prevent the incidence of CKD and preserve the GFR in general population. The present study aims to study the association of the SUA level with the GFR decline in a general population who visited the Health Checkup Clinic regularly, and our results suggested a role of SUA level in the GFR decline.The protocol of this study was approved by the Clinical Investigation Ethics Committee of Shandong Provincial Hospital Affiliated Shandong Provincial Hospital (Reference No. 2015-040) and was conducted in strict adherence with the principles of the Declaration of Helsinki.This is a retrospective study. Computer-based data of Health Checkup Clinic, Shandong Provincial Hospital Affiliated to Shandong University  were available from Jan 1st, 2008–Dec 31st, 2013. Subjects who visited the Heath Checkup at 2008 and 2013 were identified using ID numbers, birthdates and other identifiers. All subjects are >18 years old. This study excludes outpatient or clinical patients. Patients with acute kidney injury, amputation, heart failure, severe liver disease, infection disease, malignant disease and pregnancy were excluded. To confirm the accuracy, all the matches were visually inspected. Thus, we identified 2,789 adults, of which 205 subjects were excluded for incomplete records. This left 2,584 subjects  for analysis. All subjects gave the oral consent that the Health Checkup Clinic of Shandong Provincial Hospital could use the anonymous data for research purpose only when they visited at the first time.In 2008 and 2013, all subjects completed a detailed questionnaire administered by trained interviewers on life style factors such as smoking, consumption of alcohol and physical activity. Weight and height were measured with light indoor clothes and without shoes. An automated sphygmomanometer was used to measure systolic and diastolic blood pressures (SBP/DBP) with subjects in the seated position in triplicate. A blood sample was taken after an overnight fast. Biomedical parameters including serum uric acid, serum creatinine (Scr), fasting plasma glucose (FPG) and lipids were measured using a biochemical auto-analyzer in the Clinical Laboratory of the Shandong Provincial Hospital affiliated to Shandong University using standardized procedures.ΔeGFR) were calculated as the eGFR at 2013 minus the eGFR at 2008 (eGFR13 − eGFR08). Hyperuricemia is defined as serum uric acid level >420 umol/L (7 mg/dl) in males and >360 umol/L (>6 mg/dl) females  divided by the square of the height (m). Estimated Glomerular Filtration Rate (eGFR) was calculated using Modification of Diet in Renal Disease (MDRD) formula for Chinese . Accordi females .p < 0.05 were considered to be statistically significant. Kolmogorov-Smirnov test was used for normality distribution. Descriptive statistics are presented as means with standard deviations for normally distributed data, median with interquartile range  for non-normally distributed data, and frequencies with percentage for categorical data. Paired t-test were used for normally distributed continuous variables, while Wilcoxon Signed-Rank test were used for non-normally distributed data in comparison between data in year of 2008 and that in 2013. Univariate and multivariate linear regression analysis was employed to estimate the relationship between SUA level and eGFR change over 5 years.Statistical analysis was conducted by using SAS, version 9.4 (SAS Institute Inc). The graph was drafted using SPSS, version 22. Values of p < 0.01). While the decline of eGFR across the 5-year period was statistically significant –101.19  mL/min/1.73 m2, p = 0.08) but in a very small manner. There were no differences in the BMI, systolic blood pressure (BP). Fasting plasma glucose (FPG), serum total cholesterol (TC) and serum triglycerides (TG) were slightly increased in 2013 compared to 2008, and the diastolic BP was marginally decreased. The ratio of subjects with dipstick-positive proteinuria at 2008 and 2013 was 3.4% and 2.8% respectively.ΔeGFR) . In contrast, a significant inverse correlation was observed between change in SUA from 2008–2013 (ΔSUV) and ΔeGFR during the same period as shown in r = −0.37, p < 0.01).Univariate linear regression analysis did not indicate a significant correlation between baseline SUA at 2008 and the change in eGFR from 2008–2013 . Drinking alcohol (p = 0.95) or smoking (p = 0.98), BMI (p = 0.42), systolic blood pressure (SBP) (p = 0.87), and diastolic blood pressure (DBP) (p = 0.52) were not associated with ΔeGFR.As listed in p-value >0.05). The baseline SUA is lower in the Increased SUA group. Together with SUA level, BMI, DBP, FPG and TG, were lower in the Increased SUA group compared with the other two groups. eGFR of the Increased SUA group was the highest. This indicates that the Increased SUA was at a “healthier” state at 2008. However, after 5 years, the eGFR of the Increased SUA group declined by 5.26  mL/min/1.73 m2, and the eGFR of the Decreased SUA group incremented by 3.23  mL/min/1.73 m2 with a p-value <0.01.Secondary analyses included a trichotomized variable defined by subject’s SUA increase versus decline from year 2008–2013. For a changed SUA level <10 umol/L, either increased or decreased, it is not clinically meaningful since it could be the experiment error. Therefore, we divided the subjects into three groups: subjects with increased SUA (ΔSUA >10 umol/L), those with unchanged SUA (−10 umol/L < ΔSUA < 10 umol/L), and those with decreased SUA (ΔSUA < −10 umol/L). The demographic characteristics of threes groups were shown in p of univariate linear regression analysis <0.1, and second, there were differences among three groups. Together with the trichotomized variable defined by subject’s SUA change, baseline SUA, FPG, TC, TG, and baseline eGFR were fitted in the multiple linear regression model. The collinearity diagnostics show that vif was close to 0, and condition index was >10, indicating that multicollinearity exists. However, there were no closely related variables detected. Using forward stepwise selection with inclusion criteria of p < 0.05 and exclusion criteria of p > 0.10, we get the multivariate regression analysis results as shown in 2 of 0.17.Based on the result of univariate linear regression analysis and the comparison between the three groups, we identified the independent variables that were put into multivariate linear regression model. They meet both criteria, first, The present study demonstrates that the change in SUA during a 5-year period is inversely associated with the decline of eGFR during the same period.Chronic kidney disease (CKD) has become a global public health problem because of the high prevalence and the accompanying increase in the risk of end-stage renal disease (ESRD), cardiovascular disease and premature death . There a2, allopurinol or control was randomly assigned. Those patients with lower serum uric acid levels by the use of allopurinol had an increase in eGFR of 3.3 ± 1.2 mL/min/1.73 m2 per year, whereas eGFR decreased 1.3 ± 0.6 mL/min/1.73 m2 in the control group during a 12-month follow-up (p < 0.04) (2 at 6 months. Placebo group showed a significant decrease of eGFR from 32.6 ± 11.6–28.2 ± 11.5 mL/min/1.73 m2 (p < 0.003)  . In anot< 0.003) . Thus, lIn contrast with studies that were done in patients who already have chronic kidney disease, our results show that in health check-up individuals, the increase in SUA level is associated with a greater decline in GFR in a 5-year period. This is in consistent with previous studies that show lowering uric acid level also could preserve GFR in individuals with normal kidney function. Serum uric acid level >480 umol/L (8 mg/dL) or <300 umol/L (5 mg/dL) was found to be linked with a subsequent increased risk for kidney failure within 2 years (2.9-fold in men and 10.0-fold in women) in a study of 6,400 individuals with normal kidney function . AnotherIn our study, we focused on the relationship between SUA level changes and eGFR changes, while the predictive value of hyperuricemia on the incidence of CKD or Cardiovascular Disease (CVD) was not explored. SUA as a risk factor for the incidence of CVD was clearly shown by two recent meta analysis . In one The mechanisms that uric acid leads to CKD progression are not fully understood. Uric acid crystals are able to adhere to the renal epithelial cells, which could induce an acute inflammatory response . Besides2 from 2008–2013 (There are limitations in our study. The major limitation of the present study is that our study subjects were not randomly sampled. Thus, some selection bias cannot be excluded in the cohort. This might explain that some continuous variables in our study are not normally distributed. Second, there are no information on medications used, such as uricosuric drugs, xanthine oxidase, and anti-hypertension drugs. So there are maybe some other confounding factors that could not be detected by our analysis. Third, some subjects showed increased or decreased eGFR that is greater than 50 mL/min/1.73 m008–2013 , which mIn conclusion, in this retrospective study, we observed that larger decline of eGFR over years is associated with the increased SUA level in general population. Together with more causal mechanisms to be discovered, our findings help to underline the importance of SUA level management in the context of kidney function preservation.10.7717/peerj.1859/supp-1Supplemental Information 1Click here for additional data file.


Central sites are good at capturing short-term temporal trends in pollution associated with meteorological changes over regional areas. Linear mixed-effect models that accounted for repeated measures within one person were used to examine the associations between blood pressure variables and daily average of ambient PNC, PM2.5, or BC, controlling for demographic characteristics and major confounders including temperature. Our PNC model predicted that a higher PNC of 10,000 particles/cm3 was associated with higher DBP of 2.40 mmHg (p = 0.03), independent of other factors in the model. There were no significant associations for PM2.5 or BC. Post hoc subgroup analyses by obesity status showed that positive associations of DBP with PNC were more pronounced among obese individuals than non-obese individuals. These results suggested that PNC levels are associated with increased blood pressure, which may contribute to cardiovascular disease risk. More research is needed to assess the relationship between PNC and blood pressure and to address possible residual confounding.Elevated blood pressure is an indicator of cardiovascular stress and increased risk of cardiovascular-related morbidity and mortality. There is emerging evidence suggesting air pollutants, including particulate matter (PM), could promote hypertension, thereby increasing cardiovascular disease risk. Repeated measurement analyses were conducted to examine the associations of three types of PM with systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) in 220 participants, (mean age = 58.5 years) from the Community Assessment of Freeway Exposure and Health study (CAFEH), most of whom live near a major highway. Ambient levels of air pollutants including particle number concentration  concentration), fine PM (PM Exposur2.5 is capable of producing pro-inflammatory vasoconstrictive events that can elevate BP [Blood pressure (BP) elevation serves as an indicator of CV stress and increased risk of CV-related morbidity and mortality, as it suggests disruption of normative vascular homeostasis via complex pathophysiologic mechanisms . There ievate BP . This poet al. (2012) found positive correlations between both PM2.5 and BC concentration (averaged from 1–5 days before examination) and BP in a cohort of subjects with type 2 diabetes mellitus [More recently, Hoffman mellitus . Positivmellitus ,5,6,7. Aet al. (2010), for example, utilized ambulatory BP monitoring, whereas Hoffman et al. (2012) measured the brachial artery BP of the dominant arm [Protocols for BP measurements, however, are study-specific and variable. Delfino nant arm ,4. It isnant arm ,6.2.5, and BC with SBP, DBP and pulse pressure (PP). The study population was a subset of individuals participating in the Community Assessment of Freeway Exposure and Health study (CAFEH) [We examined the association of central site PNC, PM (CAFEH) . PNC has (CAFEH) ,4,5. To The study methods for CAFEH have been reported previously in detail . Data frEnrolled participants completed a survey at their residence that included demographic information and smoking status, categorized as current, former, or never. Upon completing the in-home survey, participants were invited to attend two field clinics  after fasting through the night. Clinics were held in the morning in the study areas near the highway. We assumed 9 a.m. for blood pressure measurement for the purposes of analysis because we did not have records of the exact time of each blood draw. We know that actual times varied between 7 a.m. and noon, with most between 8:00 a.m. and 10:30 a.m.BP was taken with the participants seated using an automatic blood pressure machine, which minimizes influence of technique . DBP and SBP were measured by a nurse in the right and then left arms (R-L). An additional BP measurement on the right arm was taken (measurement R-L-R) during second clinic visits in both study areas. Out of 204 participants in Somerville, 111 (54.4%) participants had three BP measurements (R-L-R); and in Dorchester, 93 out of 251 (37.0%). The average of R-L BP measures (termed average-arm SBP or DBP) was used as the dependent variable for our main analysis; and left-arm or right-arm BP measures were used for sensitivity analysis . PP, the numeric difference between SBP and DBP, was calculated using the average R-L BP measures. A total of 270 participants attended a first clinic visit and 220 attended a second clinic, with BP measures at each clinic visit. Therefore, 50 participants had a BP measure at only clinic visit 1, while 220 participants had second BP measures. Two hundred and nineteen participants’ repeated blood pressure measurements were used for the models. Use of antihypertensive medications was recorded from medications at each home and coded by a physician. Height and weight were recorded using a standard scale  and stadiometer .r = 0.78 and 0.79, respectively, at the first clinic visit; and r = 0.80 and 0.65, respectively, at the second clinic visit). However, Bland–Altman limits-of-agreement plots [As expected, left and right arm SBP and DBP measurements were strongly correlated with each other  of the Countway Library of Medicine at Harvard Medical School (HMS). The site is located on Huntington Avenue in Boston, fewer than 7 km from participant residences. Given the spatial variability of PNC, this distance likely introduced a degree of exposure misclassification. A Beta-Attenuation Mass Monitor  was used to measure hourly PM2.5 concentrations. The hourly concentrations were calibrated with the 24-h PM2.5 mass concentrations collected by the Harvard Impactor (HI). PNC was monitored continuously using a condensation particle counter . During the study period, the CPC malfunctioned from 1 March 2011 to 8 August 2011, which resulted in about seven months of missing PNC data. Our PNC analysis excludes blood pressure measurements during this time period. Black carbon (BC) was measured continuously using an Aethalometer  based on optical transmittance at a wavelength of 880 nm. We obtained temperature data from the weather station at Boston Logan airport.Ambient PNC, PMThe daily average of each pollutant and temperature were calculated using 24-h moving averages of the hourly data prior to 9 a.m. on each clinic visit date for each participant. Any missing hourly data within the 24 h resulted in missing daily averages.2.5, or BC. Our models accounted for the correlations between the repeated measures within one person. Mixed models included a random intercept for each person and an unstructured (assumption free) covariate matrix structure.The analysis presented here was for temporal variability only, consistent with similar studies in the literature that assess short-term variation in biological measures relative to central site air monitoring data. We used maximal likelihood mixed-effects, repeated-measures models to evaluate the associations between SBP or DBP and daily average of ambient PNC, PM3), PM2.5 (μg/m3), or BC (μg/m3) was the main independent variable. Both dependent and independent variables were time-varying. Daily average temperature (°C) was included in all models as a time-varying covariate. The quadratic term of the centering temperature measure was used in the PNC model because the untransformed temperature measure was highly collinear with PNC (r = −0.75). The correlation matrix of pollutants, temperature, and quadratic-centering transformed temperature measure is shown in For each model, the dependent variable was PP or the average of SBP or DBP in both arms. Sensitivity analyses using first right-arm, left-arm, and the repeated right-arm (second clinic only) SBP or DBP were conducted for all statistical models. Daily average (the 24 h prior to 9 a.m. on the clinic date) of PNC  were chosen a priori and left in all models without considering their statistical significance. Other covariates were chosen based on prior knowledge of potential confounders for their associations with both blood pressure and traffic-related air pollution [The same set of time-constant covariates, measured only at baseline, was adjusted in all models including: age (year), gender , race , income level , education level , smoking status , obesity status (obese or non-obese), use of hypertension medications (yes or no), sampling method (random or convenience sample), and distance to highway I-93 (≤400 or ≥1000 m). Demographic covariates . Robust standard errors were calculated using the Huber-White Sandwich Estimator. All During the study period from August 2009 to June 2011, 270 participants attended a first clinic visit and 220 attended a second clinic . The twoForty-two percent (42%) of the participants at first clinic visits and 36% at the second clinic had a SBP difference greater than 10 mmHg between right and left arms. The DBP difference between arms was less, with a 14% difference in first clinic and 20% in second clinic also see .2.5 and BC were closely correlated to each other (r = 0.79). PNC, on the other hand, was poorly correlated with the other two pollutants  (p = 0.001) and obesity (p = 0.001).The average-arm DBP model, but not the SBP or PP model, was found to have a significant association with PNC after controlling for demographics, temperature, seasonal variation, and other major confounders ( = 0.05) . Other iPost hoc subgroup analyses by obesity status showed that the positive association between average-arm DBP and PNC was more pronounced among obese individuals (p = 0.043) than non-obese individuals (p = 0.53). The subgroup analysis among non-obese individuals did not reach statistical significance but showed a similar trend . The models using the repeated right-arm BP measures (at visit 2 only) found significant associations with PNC higher by 10,000 particles/cm3 associated with a 4.05 mmHg higher SBP (p = 0.05) and a 2.33 mmHg higher DBP (p = 0.08). Using the left arm, the association between PNC and DBP was p = 0.06, or just outside statistical significance.The same models for each pollutant were repeated using first right-arm, left-arm, and the repeated right-arm BP measures as the dependent variables to see whether choice of BP measures would affect our findings. The sensitivity analyses resulted in similar associations compared with our main analyses using average-arm BP measures. Specifically, the sensitivity analysis models for the first right-arm BP measures (at both visits) predicted that if PNC was higher by 10,000 particles/cm2.5 and BC, although the association just missed statistical significance (p = 0.06) for repeated right arm PP with BC  were related to BC or PM2.5 if the PNC measures were a better exposure estimate for BC and PM2.5 at the participant’s home. We found that temperature was a significant confounder in BC and PM2.5 models, but not in the PNC models after adjustment for other potential confounders including seasonal variations. Thus, the associations between PNC levels and BP that we observed wereunlikely to be confounded by temperature or seasonal variation in blood pressure.We found that central site PNC levels in the preceding day were significantly associated with higher levels of DBP. We did not find a statistically significant association between either BC or PMterature ,4. It al2.5 may be associated with elevation of SBP and DBP, there are also a small number of studies with null findings similar to ours [2.5 elevation is capable of disrupting vascular hemodynamics to induce hypertension [While there is evidence suggesting that exposure to PM to ours ,4,5,6. Brtension . The litrtension ,4, whichOur finding that PNC in the preceding day was significantly associated with DBP elevation is consistent with two studies ,5 and inOur findings are biologically plausible as there is mounting evidence in the literature that PM inhalation leads to a cascade of systemic inflammatory and oxidative stress responses, as well as stimulation of the autonomic nervous system, which is associated with increased cardiovascular risks ,18,19. AStudies have reported that PM-exposed lungs release pro-inflammatory cytokines such as Interleukin-6 (IL-6) and C-reactive protein (CRP) into the blood stream . As a re2.5, predicted short-term higher blood pressure after adjusting for temperature and individual-level confounding factors such as age, BMI, gender, smoking, and hypertension. Our data are consistent with an upregulating effect of PNC on the blood pressure of near-highway residing adults. PNC has been successfully used as a proxy for UFPs which are potentially more toxic than other PM size classes  [We observed that PNC, but not BC or PM, PM2.5) .2.5, which is a regional pollutant. But for PNC, in particular, ambient levels vary considerably across small geographic areas [Our analysis has numerous limitations. The air pollution was monitored at a central site, consistent with most studies of this sort; however, this study design likely leads to a degree of exposure misclassification. This is less of a problem for PMic areas . Thus, iOur findings contribute to a modest, but growing literature assessing the association of PNC with BP. More research is needed to assess the potential for PNC to contribute to cardiovascular risk.


Recent guidelines for the diagnosis and management of hypertension reversed the historical trend to recommend lower blood pressure (BP) thresholds to diagnose hypertension in high-risk individuals, such as patients with diabetes and elderly patients. The decision to raise the BP thresholds for diagnosis of hypertension in patients with diabetes was mostly based on the findings of the ACCORD trial. Nonetheless, the results of the ACCORD trial are within the predicted benefit to prevent coronary artery disease and stroke by meta-analysis of randomized controlled trials (RCT), particularly in regard to the prevention of stroke. The Eighth Joint National Committee (JNC 8) did not address prehypertension. There are many RCT done in individuals with prehypertension and concomitant cardiovascular disease showing the benefit of treatment of these patients. Trials exploring the efficacy of interventions to prevent cardiovascular disease in individuals with prehypertension free of cardiovascular disease would be hardly feasible in face of the low absolute risk of these individuals. Considering the risks of prehypertension for cardiovascular disease and the fast progression to hypertension of a large proportion of individuals with prehypertension, it is worth to consider drug treatment for individuals with prehypertension. RCT showed that the progression to hypertension can be partially halted by BP-lowering agents. These and ongoing clinical trials are herein revised. Prehypertension may be a window of opportunity to prevent hypertension and its cardiovascular consequences. The concept of prehypertension was proposed by the Seventh Joint National Committee (JNC 7)  report aInternational guidelines for the diagnosis and management of hypertension were recently released •, 3. A hEuropean guidelines established 140/85 mmHg as the new target to diagnose hypertension in patients with diabetes , insteadThe authors of the US and the European guidelines based their new target recommendations for BP treatment on the results of randomized clinical trials (RCT). They should be complimented by the initiative, which recognizes the primacy of the results of RCT to justify medical decisions. Nonetheless, the results of the ACCORD trial could have another interpretation •. MoreovThe ACCORD study tested the hypothesis that lowering blood pressure beyond guideline recommendations would confer higher cardiovascular protection •. The trRelative risk reduction for cardiovascular events in the ACCORD trial was within the predicted by the meta-analysis of risk  and confThere is a proof of the concept that high blood pressure is the major risk for cardiovascular disease •. The siRandomized controlled trials done in patients with subclinical or clinical cardiovascular disease  demonstrated significant reduction of cardiovascular events with the use of blood pressure-lowering agents independently of baseline blood pressure . Table 1The meta-analysis by Law and associates  demonstrBesides the risks of prehypertension for cardiovascular disease, it is a precursor of hypertension in high proportion of individuals. Many studies have identified the cardiovascular risks of prehypertension and the incidence of hypertension –24. In PTaken together, these evidences support the view that most guidelines moved to the wrong direction. Evidences still do not show the whole picture and should be completed by indirect evidences and analogous models to build the theory. If someone wants to live more than 100 years, he or she should keep blood pressure below 120 by 80 mmHg, which are the usual BP values of worldwide centenarians.Two large clinical trials showed that the prevention of hypertension by drug treatment is feasible and well tolerated. In the TROPHY study , 772 indThe results of the TROPHY study originated an intense debate, mostly because of the criteria employed to diagnose hypertension. In the total, 70 % of the diagnoses were based on the detection of hypertensive levels at three different visits, not necessarily consecutive, which could have resulted from random transgressions of the prespecified thresholds on three occasions, rather than a change in the usual blood pressure of the patients . AccordiIn the study PHARAO , 1008 inThere is no further study published looking at the effect of blood pressure-lowering drugs on the incidence of hypertension. Studies evaluated the effect of drug and nondrug interventions over BP in patients with prehypertension. The most interesting one compared the effect of aspirin 100 mg administered on awakening and at bedtime and with a group submitted to lifestyle change recommendations on 48-h BP measured by ambulatory blood pressure (ABP) monitoring . There wNebivolol apparently reduced central BP compared to placebo in a randomized controlled trial. However, the authors did not test for the between-group differences and did not adjust for the higher baseline values of measurements of central hemodynamics in patients allocated to the active treatment . A placeAn anti-stress therapy (mindfulness-based stress reduction) was compared with muscle relaxation training in a randomized controlled trial. There was a small reduction of office BP in the anti-stress therapy, but it was not confirmed by ABP monitoring . In a smStudies examining the benefit of drug treatment of patients with prehypertension free of cardiovascular disease are warranted . There ahttp://www.chictr.org/en/proj/show.aspx?proj=554) aims to investigate whether low-dose antihypertensive treatment of with either indapamide, an angiotensin receptor blocker (ARB), reserpine compound, or placebo reduces the risk of cardiovascular events and development of hypertension and diabetes in high-normal blood pressure individuals with cardiovascular risk factors in China. In total, 10,806 subjects aged 45–79 years were randomized between 2008 and 2012. The primary endpoint is the combination of nonfatal stroke, nonfatal myocardial infarction, and fatal cardiovascular events. The secondary endpoints include the development of hypertension and diabetes. Details about the duration of the study were not reported.The CHINON study (We are conducting the PREVER study, a nationwide double-blind, placebo-controlled, randomized clinical trial in Brazil , which aGuidelines, regulatory authorities, and researchers have been reluctant to recommend drug interventions for individuals with prehypertension. It is unlikely that in a foreseen future there will be definite evidences that drug intervention in individuals with prehypertension is the key to control the burden of hypertension. In the mean time, partial and indirect evidences may be used to support the idea that it is worth to interfere at this point of the natural history of hypertension. The results of the ongoing clinical trials may contribute to strengthen this interpretation.


High blood pressure levels have been associated with elevated atherogenic blood lipid fraction, but epidemiological surveys often give inconsistent results across population sub-groups. To determine the extent to which there are differences in lipid profile based on blood pressure levels, we assessed lipid profile of subjects with high-normal blood pressure and compared with those of hypertensives and optimally normal blood pressure.The study was a cross–sectional comparative study conducted at Aminu Kano Teaching Hospital, Kano, Nigeria. Fasting lipid levels were examined among randomly selected patients with optimally normal blood pressure (group 1), high – normal blood pressure (group 2) and those with hypertension (group 3). Optimal blood pressure was defined as systolic blood pressure (SBP) of < 120 mmHg/or diastolic blood pressure (DBP) of < 80 mmHg; and high- normal blood pressure as SBP of 130 – 139 mmHg and/or DBP of 85 – 89 mmHg.A total of 300 subjects were studied, 100 in each group. The mean age of subjects in group 1 was 27.32 ± 8.20 years and 60% were female, while that of group 2 was 34.04 ± 6.25 years, and 53% were female, and that for group 3 was 52.81 ± 13.3 years and 56% were female. The mean total cholesterol (TC) for subjects in group1 (3.96 ± 0.40 mmol/L) was significantly lower than levels in group2 (4.55 ± 1.01 mmol/L); P = <0.001. Subjects in group 3 (5.20 ± 1.88 mmol/L), however had statistically significant higher mean TC when compared with group 2; (P = 0.03). The difference between the groups for low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) followed the same pattern as that of TC, with statistically significant increasing trend across the blood pressure categories. Levels of high density lipoprotein cholesterol (HDL-C) were however similar across the three groups . Increased TC (>5.2 mmol/L) was absent in group1, but found among 11% of group2 subjects and 40% of those in group 3 . Mean fasting plasma glucose (FPG) was 3.8 ± 0.4 mmol/L, 4.7 ± 1.1 mmol/L, 5.1 ± 1.9 mmol/L and for subjects in groups 1, 2 and 3 respectively (p > 0.05 for groups 2 Vs 1 and p <0.001 for groups 2 Vs 3). The differences in mean body mass index (BMI) between the groups followed a similar trend as that of FPG. Multivariate logistic regression analysis showed that FPG, TG and BMI were the strongest predictors of prehypertension .The study has shown a significant increase in plasma TC, LDL-C and TG values as blood pressure levels increased from optimally normal, across high-normal to hypertensive levels. There was a similar trend for FPG and BMI, demonstrating the central role that blood pressure plays in these metabolic disorders in Nigerians. These findings are relevant in terms of both prevention and treatment of cardiovascular morbidities and mortality. High – normal blood pressure (BP) levels have been found to be associated more frequently than normal BP with other cardiovascular disease (CVD) risk factors such as dyslipidaemia, dysglycaemia, overweight/obesity, micro-albuminuria and increased circulating levels of various inflammatory markers such as C-reactive protein, and homocysteine .The clustering of these CVD risk factors significantly increases cardiovascular disease, a leading cause of morbidity and mortality . HoweverPlasma cholesterol levels vary significantly in various population groups due to differences in geographical locations, cultural, economical and social conditions, dietary habits and genetic make up , 3.The relationship between high-normal BP and other CVD risk factors including plasma lipids has not been well described in Sub–Sahararan Africans including Nigerians. In the present study therefore, we studied plasma lipid levels in patients with high-normal BP compared with hypertensives and those with optimally normal BP. The results of this study will guide judicious utilization of the scarce resources available for health care and other competing needs given that the assay for plasma lipids is expensive and the subjects with high-normal BP are not “CVD patients”.The study was cross sectional and comparative, carried out in Aminu Kano Teaching Hospital (AKTH), a tertiary healthcare institution in Kano State, North- western Nigeria. The study protocol was approved by the research ethics committee of AKTH, before the commencement of the study. The study conformed to the Declaration of Helsinki on investigations involving human subjects  .The stuThe study population comprised of patients at least 18 years of age, attending the Cardiology and General Outpatient (GOP) clinics of the Hospital. There were 3 patient groups.Group 1 – Subjects with optimally normal blood pressure who presented to GOP with minor ailments;Group 2 – Subjects with high - normal blood pressure who also presented to the GOP with minor ailments; andGroup 3 – Hypertensive subjects on treatment and attending the cardiology clinic (first comparative group); andOne hundred patients were selected and evaluated in each group as described below. This sample size was calculated based on the prevalence of high-normal BP of 16.9% in a community-based study in Edo State, Nigeria, using a validated formula , 6. On ePatients already selected previously were excluded if they visited any of the clinics again for another consultation. Also excluded were subjects less than 18 years of age, pregnant women and those on drugs known to increase blood pressure like steroids and contraceptive pills, or to modify the lipids such as statins.Blood pressure was measured using mercury sphygmomanometer based on standardized techniques .All participants were fasted overnight for 10 – 12 hours after which venous samples were obtained for plasma concentrations of total cholesterol (TC) and fasting plasma glucose (FPG). Samples for total cholesterol were placed in labeled plain universal bottles while those samples for fasting plasma glucose were placed in fluoride oxalate bottles. They were analyzed in the hospital Chemical Pathology laboratory using the auto-analyzer machine . Body mass index (BMI) was calculated from the weight in kilograms taken with minimal clothing using a standardized weight scale and divided by the square height in meters. Height was taken using stadiometer without shoes or head gear.2  [Optimal blood pressure was defined as systolic blood pressure (SBP) of < 120 mmHg and/or diastolic blood pressure (DBP) of < 80 mmHg; high- normal blood pressure as SBP of 130 – 190 mmHg and/or DBP of 85 – 89 mmHg; while hypertension was defined as SBP of ≥ 140 mmHg and/or DBP of ≥ 90 mmHg, using 2003 World Health Organization/ International Society of Hypertension (WHO/ISH) guidelines [0 Kg/m2) .Data analysis was done using SPSS version 19.0. Quantitative variables were expressed as means and standard deviations. Qualitative variables were expressed as percentages. The chi-square test or Fisher’s exact test where applicable were used in comparing proportions, while Student’s t-test was used to compare means. Logistic regression analysis was used to assess the association of age, anthropometric and serum parameters to blood pressure . A p-value of ≤0.05 was considered significant.There were 100 patients in each of the three groups. The mean age of the subjects in group 1 was 27.32 ± 8.2 years, for group 2, 34.04 ± 6.25 years and 52.18 ± 13.3 years for group 3. The subjects in group 2 were significantly older than those in group 1 (P = < 0.001) while subjects for group 3 were significantly older than those in group 2 (P = < 0.001). There was however no significant statistical differences in gender distribution between the three groups. (P = 0.3) for each comparison. The other baseline characteristics are shown in Table Plasma lipids for the three groups are presented in Table Comparing the proportion of increased TC, high LDL-C, low HDL-C and high TG, there were statistically significant differences between both groups 1 and 2; and groups 2 and 3 except for HDL-C and TG between groups 2 and 3 (P = 0.24 and 0.6) . The pattern of dyslipidaemia among the three groups is shown in Figure The results of multivariable analysis showed that age, BMI, FPG and TG were predictors of high-normal BP  than subjects with high-normal BP, while subjects with high-normal BP had significantly higher mean TC than those with optimal BP. This finding differs from that of Isezuo tensives . It was tensives . The higet al. [Low HDL-C was the most common dyslipidaemia among the groups. Hypertensives had highest mean HDL-C level, followed by subjects with optimally normal BP and then subjects with high-normal BP, a trend similar to what was reported by Lee et al. . The finet al. , 14. TheThe pattern of distribution of mean LDL-C and TG among the groups was however similar to what was reported by previous authors, in which hypertensives had significantly higher mean LDL-C and TG than than subjects with high-normal BP, while subjects with high-normal BP had significantly higher mean LDL-C and TG than those with optimal BP , 12, 15.et al. in Singapore, the present study showed age, BMI , FBG and TG as significant predictors for high-normal BP [et al., reported DM, impaired glucose tolerance and cigarette smoking as significant predictors of both pre-hypertension and hypertension [The present study also shows increases in plasma cholesterol, FPG, and BMI levels as the blood pressure increased, demonstrating the central role that blood pressure plays in these metabolic disorders in Nigerians. Similar to what was obtained by Lee ormal BP . In addirtension .These findings are relevant in terms of both prevention and treatment of cardiovascular morbidities and mortality. In principle, many of the patients we studied could benefit from the polypill. The use of the “polypill” particularly in low income countries like ours might lower cost and increase efficiency and adherence by delivering multiple intervention in a single pill, than same medications prescribed and taken separately. Most polypill contain one to three antihypertensive agents, a statin and some in addition contain aspirin. This idea has still not been widely studied and implemented. There are several challenges to make a successful polypill. Technically, the agents must be stable when combined, and there must be no adverse reactions when the medications are taken together and at same time of the day. Furthermore, it needs to be produced, marketed and distributed, and it must be economically viable.Although the sample size in the present study was above the estimated minimum, a larger sample size could have demonstrated statistically significant differences between the groups in the BMI and FPG, as was the case in cholesterol levels. Still, the observed trend for the FPG and BMI is relevant in generating hypotheses.The present study has shown that dyslipidaemia is common among subjects with high-normal BP. There was a clear gradient of plasma lipids concentrations rising from subjects with optimally normal BP, across those with high-normal BP, to the group with hypertension. There was a similar trend for FPG and BMI.This study forms a basis for larger population based studies to determine plasma lipid profile among subjects with high- normal BP in this environment. We also recommend that individuals with high-normal BP should be screened for other CVD risk factors and have them corrected through initiation of lifestyle measures in order to prevent them developing hypertension and other complications.


Objective To systematically review studies quantifying the associations of long term (clinic), mid-term (home), and short term (ambulatory) variability in blood pressure, independent of mean blood pressure, with cardiovascular disease events and mortality.Data sources Medline, Embase, Cinahl, and Web of Science, searched to 15 February 2016 for full text articles in English.Eligibility criteria for study selection Prospective cohort studies or clinical trials in adults, except those in patients receiving haemodialysis, where the condition may directly impact blood pressure variability. Standardised hazard ratios were extracted and, if there was little risk of confounding, combined using random effects meta-analysis in main analyses. Outcomes included all cause and cardiovascular disease mortality and cardiovascular disease events. Measures of variability included standard deviation, coefficient of variation, variation independent of mean, and average real variability, but not night dipping or day-night variation.Results 41 papers representing 19 observational cohort studies and 17 clinical trial cohorts, comprising 46 separate analyses were identified. Long term variability in blood pressure was studied in 24 papers, mid-term in four, and short-term in 15 (two studied both long term and short term variability). Results from 23 analyses were excluded from main analyses owing to high risks of confounding. Increased long term variability in systolic blood pressure was associated with risk of all cause mortality , cardiovascular disease mortality , cardiovascular disease events , coronary heart disease , and stroke . Increased mid-term and short term variability in daytime systolic blood pressure were also associated with all cause mortality .Conclusions Long term variability in blood pressure is associated with cardiovascular and mortality outcomes, over and above the effect of mean blood pressure. Associations are similar in magnitude to those of cholesterol measures with cardiovascular disease. Limited data for mid-term and short term variability showed similar associations. Future work should focus on the clinical implications of assessment of variability in blood pressure and avoid the common confounding pitfalls observed to date.Systematic review registration PROSPERO CRD42014015695. Blood pressure is a leading risk factor for cardiovascular disease.10However, understanding this variability has been hampered by statistical and clinical methodological problems. Some analyses of variability have not adjusted for mean blood pressure, potentially confounding high variability with high mean blood pressure,Other studies failed to use consistent blood pressure monitoring equipment over time, to define a consistent measurement protocol, or to account for change in drugs, leaving doubt as to the source of any observed variability.We searched Medline, Embase, Cinahl, and Web of Science to 15 February 2016 for full text articles in English describing trials and prospective cohort studies in adults that assessed the association of periods of variability in blood pressure with cardiovascular outcomes (see supplementary table e1). Long term variability was measured through clinic blood pressure monitoring, mid-term through home monitoring, and short term through ambulatory monitoring. Studies included in recent systematic reviewsStudies had to consider at least one of the following outcomes: all cause mortality, cardiovascular events , or cardiovascular mortality (including sudden death). We excluded studies only assessing intermediate outcomes  or concerning nocturnal dipping or day-night variation, as these have been considered previously.28Studies in disease specific populations  were included, except those in patients receiving haemodialysis where changes in blood pressure , mid-term (at home), or short term (through ambulatory monitoring). Studies of clinic monitoring had to measure visit-to-visit variability over at least five clinic visits. Studies of home monitoring had to consider day-by-day variability over at least 12 measurements on at least three days.33Using prespecified forms, two reviewers (SS/SW and KL/RM) independently extracted data on study and patient characteristics and two (SS and KC/RS) on statistical results (see supplementary table e2). Hazard ratios were extracted for every variability measure and outcome. The hazard ratio from the analysis with the greatest adjustment for confounders but containing only a single variability measure was extracted. Where required data were not available, we emailed the study authors.2 test and I2 statistic.Hazard ratios were converted to standardised hazard ratios, using a general method for regression models (see supplementary table e3).Where studies used multiple measures of variability, we included hazard ratios in analysis according to the following hierarchy (preferred to least preferred): standard deviation, coefficient of variation, variation independent of mean, average real variability, standardised residual, root successive variance, and other. Where hazard ratios were calculated using data from the same primary study but reported in different papers, we included the most recently published hazard ratio. We combined the hazard ratios for study subgroups before inclusion.Two reviewers (SS and RS) independently assessed the risk of bias using the QUIPS tool,Publication bias was assessed by Egger’s test.37Two lay representatives contributed to the design and content of the National Institute for Health Research programme grant from which this work arose. Results from this work have been presented as part of the wider programme at regular steering group meetings.54Searches identified 5861 references. Removal of duplicates and screening by two reviewers yielded 41 full text articles for inclusion  in all of the 36 included studies (see supplementary table e5). Similarly, the potential for confounding was introduced because of the analysis (or this was unclear) in all 46 separate analyses. Results from 23 analyses were excluded from our main analyses on the basis of the three prespecified criteria: eight analyses failed to correctly adjust for mean blood pressure, 15 did not account for major drug change during the measurement period, and 20 did not separate the measurement and follow-up periods. Results from four analyses (three studies) were not reported in sufficient detail to allow data extraction.Using QUIPS, most of the 46 analyses were rated at moderate risk of bias for study participation, often because of inclusion criteria based on blood pressure readings and a potential for regression to the mean effects (see supplementary table e6). Eighteen analyses were at high risk of bias because the measurement period for blood pressure variability was confounded by follow-up (n=17), and one analysisTwenty four papers reported results from 27 studies that measured blood pressure variability in clinics (long term). Results from three studies2=70.7%, P=0.02) was reduced after removal of a study in patients with previous stroke or vascular disease2=34.9%, P=0.21).Eight studies examined long term variability in systolic blood pressure and all cause mortality, of which four had sufficiently low risk of bias to be included in the main analysis  but only a single study examining cardiovascular disease events was suitable for inclusion .2=82.1%, P<0.001). Results were similar after omission of the hazard ratio from the UK-TIA trial,2=0.0%, P=0.62).Fourteen studies reported results for stroke events, of which six were included in the main analysis . Across all outcomes, secondary analysis including results from all studies regardless of risk of bias did not alter results.Four papers reported results from two studies that measured mid-term variability in home blood pressure monitoring. All four papers were of sufficient quality to be included in main analyses, but a lack of data from distinct studies meant it was only possible to perform formal meta-analysis for the all cause mortality outcome. Variability in systolic blood pressure was a significant predictor of death when blood pressure was measured in the morning or evening, or both , which combined results across cohorts.Fifteen papers examined short term variability in ambulatory blood pressure in 11 distinct studies. We were unable to include results from many studies,Three studies examined daytime variability in systolic blood pressure and all cause mortality, of which two were included in the main analysis (fig 5No associations were found between variability in blood pressure and cardiovascular disease (see supplementary figure e7) or coronary heart disease events (see supplementary figure e8), although results became significant in secondary analyses. The supplementary file details the results for night-time and 24 hour systolic ambulatory blood pressure (see figures e9 to e18).There was no evidence of publication bias for any outcome in relation to long term, mid-term, or short term variability in systolic blood pressure as judged by Egger’s test. Significant findings for clinic monitoring would remain unchanged for all outcomes even if at least 20 null effect studies were included in meta-analyses, except for myocardial infarction where only a single null effect study would be required. Results for home monitoring would become non-significant after the addition of a single null effect study and those for variability in ambulatory blood pressure would become non-significant by the addition of between one and six null effect studies, depending on outcome and period of measurement.This review has systematically assessed the literature for the association of long term (clinic monitoring), mid-term (home monitoring), and short term (ambulatory) variability in blood pressure with cardiovascular outcomes and mortality. Long term variability in measurements is significantly associated with all cause and cardiovascular disease mortality, cardiovascular disease events, stroke, and myocardial infarction, independent of mean blood pressure. Mid-term and short term variability are also associated with mortality, and limited data for other outcomes also broadly support an association with cardiovascular outcomes. Across all analyses , the hazard ratios for coronary heart disease events were smaller than those for stroke, suggesting that the effect observed for cardiovascular disease events—as with mean blood pressure—may be driven primarily by cerebrovascular events.This review includes over one million person years of data and combines the results from long, mid-term, and short-term blood pressure measurement, allowing comparison. We have addressed the methodological issues that are particular to research on variability in blood pressure and have shown that although there is now considerable evidence on this topic, most studies are of poor quality or poorly reported. By limiting our main analysis to studies that avoid potential sources of confounding, this review confirms that the apparent prognostic value of blood pressure variability is a true prospective association and can be demonstrated even in studies with low risk of bias.In this review we used standardised hazard ratios to overcome the diversity of measures for variability used in primary studies, and hence combined more data. For example, our meta-analysis for long term variability and stroke events includes 14 studies, more than double the number in previous analyses.28Finally, we demonstrated the robustness of results to possible unpublished null effect studies across long term, mid-term, and short term variability in blood pressure. Although results for long term variability may be considered conclusive, results for mid-term and short term variability are more susceptible to publication bias and may warrant further investigation.Included studies were primarily in older adults (mean age 48.5 to 77 years) and those at increased risk of cardiovascular disease  and conducted in European or East Asian populations. Hence the applicability of our findings to younger or healthier people and other ethnic groups is unknown. Studies in patients with a history of cerebrovascular events reported the largest hazard ratios, but significant associations remained after removal of these studies from analyses, and so findings remain applicable to people free from cerebrovascular disease. In studies in hypertensive patients,Lack of data from distinct cohorts prevented formal meta-analyses for many outcomes for to mid-term variability in blood pressure. A previous review was similarly limited by paucity of data,In several analyses, there was significant heterogeneity between studies, potentially due to outlying studies in specific populations  or to approximations necessary during data extraction, such as conversion from categorical , it was not feasible to do this for all factors. Further adjustment for confounders might be possible using individual patient data but was beyond the scope of this review. The importance of consideration and reporting of such confounding factors in future work on blood pressure variability  should be emphasised. Although our results indicate that these may be less important in the assessment of blood pressure variability, they may prove instrumental in other clinical areas.The mechanism linking blood pressure variability to cardiovascular events is not well understood. Short term variability in blood pressure is affected by behavioural, emotional, and postural influences on cardiovascular physiology and cardiac rhythm.79The estimated standardised hazard ratio for the effect of long term variability in blood pressure on cardiovascular disease mortality was 1.18. For comparison, the effect of mean blood pressure on cardiovascular disease mortality reported in a previous meta-analysisHow does blood pressure variability compare with other risk factors for cardiovascular disease? A recent reviewVariability in blood pressure is not easily assessed clinically, and it is unclear if certain measures of variability should be preferred. Some measures could be calculated by hand , whereas others could be automatically calculated by electronic health records. This would enable doctors to account for both mean and variability in blood pressure concurrently when assessing cardiovascular risk. For example, assuming a standard deviation for variability (standard deviation) in systolic blood pressure of 5 mm Hg, an individual with variable blood pressure readings  could be considered at 18% greater risk of cardiovascular disease events than a similar person with stable blood pressure . This may be particularly important for patients with a highly variable but comparatively low mean blood pressure or for whom traditional cardiovascular risk estimates lie close to treatment thresholds. Further work is needed to determine the feasibility of obtaining such additional information, and the clinical impact on subsequent risk management.Long term variability in blood pressure measured in adults at clinic visits is associated with cardiovascular and mortality outcomes, over and above the effect of mean blood pressure. Mid-term (home monitoring) and short term (ambulatory monitoring) variability in blood pressure is also associated with all cause mortality, but the association with cardiovascular disease outcomes requires further investigation in novel cohorts.It is well established that patients with high blood pressure are at higher risk of future cardiovascular diseaseSome studies have also suggested that patients with higher variability in blood pressure over time are at higher risk compared with patients with the same mean blood pressure levelIt is not clear whether this risk depends on the method of measurement of variability, and few have correctly accounted for mean blood pressure or changes in treatmentMethodological errors are present in approximately half of prospective studies of blood pressure variability, but the association of long term (clinic) variability in blood pressure with future cardiovascular disease is found even in studies that avoid errorsMid-term and short term variability in blood pressure measured at home or by ambulatory monitoring, respectively, has been little studied comparatively, but shows similar associations with outcomes