Hypertension continues to be a major contributor to global morbidity and mortality, fuelled by an abundance of patients with uncontrolled blood pressure despite the multitude of pharmacological options available. This may occur as a consequence of true resistant hypertension, through an inability to tolerate current pharmacological therapies, or non-adherence to antihypertensive medication. In recent years, there has been a rapid expansion of device-based therapies proposed as novel non-pharmacological approaches to treating resistant hypertension. In this review, we discuss seven novel devices—renal nerve denervation, baroreflex activation therapy, carotid body ablation, central iliac arteriovenous anastomosis, deep brain stimulation, median nerve stimulation, and vagal nerve stimulation. We highlight how the devices differ, the varying degrees of evidence available to date and upcoming trials. This review also considers the possible factors that may enable appropriate device selection for different hypertension phenotypes. Resistant hypertension (RHTN) continues to significantly contribute to the overall population’s cardiovascular morbidity and mortality . DependiWhilst many patients seem to express a preference for non-drug approaches to managing long-term conditions, historically the options for interventional treatments have been limited. However, the recent past has seen the introduction of a burgeoning array of device-based therapies for hypertension offering a more targeted approach to blood pressure (BP) lowering. In this review, we discuss seven novel device therapies, all at different stages of development and with varying degrees of evidence available to date. We highlight how they differ and consider potential factors that may enable appropriate device selection for different hypertension phenotypes.Of the novel device-based therapies for hypertension, renal denervation (RDN) has accumulated the largest body of evidence thus far. Current endovascular catheter systems typically access the renal arteries via the femoral artery and deliver radiofrequency (RF) or ultrasound (US) energy resulting in focal frictional heating of the arterial wall . Other dThe first proof-of-concept open-label study, SYMPLICITY HTN-1, demonstrated that unipolar RF RDN was associated with a mean reduction in office BP of 22/10 mmHg •. SubseqUp to 2014, studies of RDN have all been open-label, and thus criticised over the fact that a substantial placebo effect of device therapy may have arisen, particularly due to the invasive nature of the therapy which is associated with patient discomfort . In earlThe importance of specialist centres involved in both selecting patients for RDN and delivering the therapy itself may be highlighted in the DENERHTN trial. This open-label randomised controlled trial recruited from 15 French specialist tertiary hypertension care centres, demonstrated that in a well-selected cohort, RDN in addition to a standardised stepped-care antihypertensive treatment (SSAHT) resulted in a SBP that was 5.9 mmHg lower than that in the control SSAHT group .Although the sham-controlled clinical trial data has not been the most encouraging, registry data has been more heartening. The prospective Global SYMPLICITY Registry showed that in 998 patients, RDN resulted in a reduction in office and ambulatory systolic BP of 11.6 and 6.6 mmHg, respectively, at 6 months . The sinThe clinical trials to date demonstrate that RDN is a relatively safe procedure with a major adverse event rate of about 1.4 % ••. HowevAlthough there are more studies in RDN compared to the other device-based hypertension therapies, most studies of RDN were limited by insufficient sample sizes, unregulated in-trial changes in medications, infrequent use of sham control, lack of appropriate blinding, unknown procedural success and limited involvement of hypertension specialists . These iIt is worth recalling that the technical approaches to RDN are constantly in evolution. It is likely that different iterations of the technology will be associated with different technical success and complication rates. There is an increasing utilisation of multi-electrode catheters for RF ablation and irrigated balloon catheters for US ablation . AlternaBaroreflex activation therapy (BAT) is predicated upon the role of arterial baroreceptors in detecting carotid sinus and aortic arch distension in response to rises in arterial BP during systole, which then reflexively sends afferent nerve impulses into the nucleus tractus solitarius in the central nervous system. This in turn decreases the efferent sympathetic nervous system (SNS) discharge to the heart, peripheral vasculature and kidneys, resulting in negative inotropy, vasodilatation and reduced renin secretion, respectively. This also results in increased parasympathetic outflow with associated reduction in heart rate , 30. AltThe first-generation Rheos™ device  was initially evaluated in a feasibility study. In the non-randomised DEBuT-HT open-label trial with no comparator arm, implantation of the device in 45 patients with RHTN resulted in an average BP reduction of 21/12 mmHg at 3 months and 33/22 mmHg at 2 years . In a seThe next-generation update of this technology, Barostim neo™ system, utilises a smaller longer lasting generator and single lead carotid sinus stimulation . A preli2 or proteinuria). After 6 months, 23 patients managed with the Barostim neo™ system demonstrated a 17/9 mmHg fall in BP as compared to the 1/1 mmHg fall in the 21 patients in the control group , and a lower heart rate (−5 beats/min) [BAT also appeared to be effective in the setting of chronic kidney disease (eGFR <90 mL/min/1.73 mats/min) .The Barostim Hypertension Pivotal Trial  is currently in progress and aims to enrol 310 patients with RHTN randomised to receiving optimal medical management alone or in combination with the baroreflex activation therapy. BAT may also have a role outside of BP management and is currently being evaluated as an adjunctive therapy in heart failure .Carotid bodies are peripheral chemoreceptors that regulate sympathetic tone and respiratory minute ventilation in response to stimuli such as hypoxia, hypercapnia, hypoglycaemia, and acidosis. The ablation of carotid body (CB) function has been proposed as a target for circulatory regulation as increased efferent signalling from CBs is associated with hypertension that is reversible when the signalling is downregulated .In COPD patients undergoing bilateral CB resection, systolic BP was reduced by 40 mmHg at 6 months post-operatively in a hypertensive sub-group, despite no long-term improvement in ventilatory parameters . A recenAn ongoing uncontrolled observational study will assess the feasibility of unilateral endovascular CB ablation in a larger cohort of patients with RHTN. The targeted trial enrolment is set at 50 patients and is expected to report its findings in early 2017 . A separate trial in patients with RHTN aims to assess the effect of CB de-afferentation achieved by local US-guided infiltration of lidocaine followed by electrical stimulation . No prospective sham-controlled clinical trials have been registered to date.In contrast to the above devices that aim to be sympathomodulatory, a central iliac arterio-venous (AV) anastomosis intends to reduce effective arterial volume, systemic vascular resistance (SVR) and cardiac afterload, thus lowering BP. This is achieved by creating a 4-mm fixed calibre conduit between the proximal arterial and low resistance venous circulation, typically the external iliac artery and vein, using a nitinol stent-like device (ROX AV coupler) placed under fluoroscopic guidance . This diFormation of a central iliac AV anastomosis was initially studied in patients with COPD with the intention of improving exercise capacity . SubsequThe first investigation into central AV anastomoses in hypertension was the randomised controlled, open-label, ROX CONTROL HTN trial ••, in whThe main complication reported in the coupler group was a 29 % incidence of ipsilateral venous stenosis which was successfully managed by venoplasty and/or stenting. In a small subset of patients who had failed to respond to prior RDN, central AV anastomosis resulted in significant reduction in both the office BP (34/22 mmHg) and ambulatory BP (12/15 mmHg). This may suggest that AV coupler therapy may be beneficial in cases where sympathomodulation has failed .Early clinical experience with the coupler suggest that this novel approach which addresses mechanical aspects of the circulation has promise, but more long-term safety and efficacy data are clearly required. Requirement for an appropriate sham-controlled study may be confounded by spontaneous patient reporting of a palpable thrill at the site of the AV anastomosis. Presently, ongoing evaluation of the therapy is taking place within a global registry study  and a US pivotal study is in the pipeline.The role of specific sub-structures within the brain in modulating autonomic activity for cardiovascular reflexes has previously been indicated in animal studies. The stimulation of the periaqueductal gray region of cats and rats has been shown to be linked to changes in blood pressure, heart rate and vasodilatation , 51.To date, there is minimal data regarding the use of deep brain stimulation (DBS) as a treatment for hypertension. An initial description of DBS demonstrating benefit in refractory hypertension was based on targeted stimulation of the venterolateral periaquductal grey/periventricular grey for analgesia in stroke-associated hemibody central pain syndrome. The observed reduction in blood pressure of up to 33/13 mmHg appears to be independent of any analgesic effects, as it persisted even when pain levels returned to pre-surgical levels after several months . The sugThus far, there are no registered trials of DBS as a device-based therapy for hypertension, although BP responses to DBS are being evaluated in an on-going study wherein the primary indication is for relief of chronic neuropathic pain in patients with spinal cord injury .A novel implantable non-constant neurostimulator has been designed by Valencia Technologies (eCoin) to be small enough, approximately 2 cm in diameter, to be placed subcutaneously overlying the median nerve as a potential therapy for RHTN. Median nerve stimulation, albeit by a different electroacupuncture system, is already supported by limited data. In anaesthetised male rats, delivery of electroacupuncture at points overlying the median nerve reduced the sympathoexcitatory BP response to gastric distension . This BPhttp://valenciatechnologies.com/first-application).Although there are yet to be any peer-reviewed data for median nerve stimulation as a device-based therapy for RHTN, Valencia Technologies has indicated that their unpublished interim results showed the treatment group having a net change in systolic BP of 16.7 mmHg lower than that of the sham (implanted device but not activated) group .Whilst there have been significant efforts in creating devices that modulate the SNS at various points, the parasympathetic nervous system has been largely neglected. The vagus nerve, together with the thoracic ganglia, is the principle source of parasympathetic innervation of the heart with resultant negative inotropic and chronotropic effects.Vagal nerve stimulation (VNS) in Dahl salt-sensitive rats attenuated salt-induced hypertension and arrhythmias as compared to rats that had sham surgery . On its Limited experience of the impact of VNS on blood pressure comes from a report of two patients undergoing carotid endarterectomy and coronary bypass surgery. Stimulating the vagus nerve resulted in a current- and frequency-dependent lowering of systolic BP and heart rate. It is important to recognise that episodes of atrio-ventricular block and ventricular asystole were observed at higher current and frequency, but were reversible upon termination of VNS .A study of selective VNS in patients undergoing carotid endarterectomy and coronary artery bypass grafting, with four patients enrolled, has been completed, but the results have not yet been published .Variations in responses to antihypertensive drug therapy across the population have been well described. It would be reasonable to hypothesise that the device-based therapies discussed here, each targeting unique pathophysiological pathways, would have their respective determinants of responders and non-responders. It has been long established that renal norepinephrine spillover is negatively correlated with age , suggestThe heterogeneity of BP responses to RDN suggests that it might be effective in a select group of patients, as subgroup analyses suggest a better response in non-African Americans as well as in younger patients and those with preserved renal function •. This sHere, we have discussed seven different device-based therapies for hypertension (summarised in Table


Up to date, most of previous studies about Chinese prehypertension were conducted based on a small sample or in only one province, which could not represent the general population in China. Furthermore, no information on the ethnic difference in prevalence of prehypertension has been reported in China. The aim of this study is to examine the sex-specific, age-specific and ethnic-specific prevalence of prehypertension and associated risk factors in a large-scale multi-ethnic Chinese adult population.The subjects came from a large-scale population survey about Chinese physiological constants and health conditions conducted in six provinces. 47, 495 adults completed blood pressure measurement. Prehypertension was defined as not being on antihypertensive medications and having SBP of 120–139 mmHg and/or DBP of 80–89 mmHg. Odds ratio (OR) and its 95 % confidence interval (CI) from logistic models were used to reflect the prevalence of prehypertension.P < 0.001. The mean age of the subjects was 54.8 ± 14.0 years for hypertensive, 44.0 ± 16.0 years for prehypertensive and 35.3 ± 14.5 years for normotensive. With aging, subjects had more odds of getting prehypertension. Multivariate logistic model indicated that males , laborers with mental work , Yi  and Hui subjects , alcohol drinkers , the generally obese , the overweight , the abdominally obese  and subjects with family history of cardiovascular diseases  had higher prevalence of prehypertension. Subjects with higher educational level  and Miao , Tibetan , Tujia  subjects had lower prevalence.The mean age of all subjects was 43.9 ± 16.8 years. The prevalence of hypertension and prehypertension for all them was 29.5 and 36.4 %, respectively. The prevalence of hypertension and prehypertension for males  was higher than that for females , and High prevalence rate of prehypertension was general in Chinese adults. Many sociodemographic characteristics were significantly associated with prehypertension. There were important clinical significance and public health significance about age-specific, gender-specific and ethnic-specific Chinese prehypertension conditions studies. Cardiovascular diseases (CVD) and cerebrovascular diseases have gradually become the leading cause of mortality in both developed and developing countries over the last several decades. CVD has become the No. 1 cause of death 10 years ago in China , 3. In gThe Eighth Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure JNC-8) continued to recommend and emphasize lifestyle changing in prevention of hypertension , 7. In 2 continueHowever, little is known about the current situation of the prevalence of prehypertension in China. Most of previous estimates on the prevalence of prehypertension in china were only based on only one province of China or a small sample size, which could not represent the general Chinese population –16. FurtThis study is based on data from a large-scale population survey in a representative sample of general Chinese population from 2007 to 2011. The main purpose of that survey is to examine Chinese physiological constants and health conditions. It was supported by the basic performance key project by the ministry of science and technology of the People’s Republic of China, and has been approved by the review board of Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences annually. In brief, this survey was carried out in six provinces of China, which was selected according to the population size of the minorities, including Sichuan province, Heilongjiang province, Hunan province, Inner Mongolia autonomous region, Yunnan province and Ningxia Hui autonomous region. Three-stage cluster sampling method was used to select eligible subjects in each province. First, two or three cities were sampled according to their economical status and ethnic inhabitations of minorities. Then five or six communities and villages were randomly selected in each city. Among eligible people, we excluded participants suffering from severe chronic diseases and those with a high fever in the past 15 days. All included participants gave their informed consent to participant in the study. The procedure of this study involves physical examination including blood pressure measurement and face-to-face questionnaire interviews. Finally, out of 52, 265 included subjects, 47, 495 (90.9 %) subjects have complete data on all survey scales and blood pressure measure.Blood pressure was measured by trained physicians following standard guidelines, which involved American national high blood pressure education program and Chinese guidelines for hypertension prevention and treatment , 18. SubAverage values of two readings separated by 5 min were used in the analysis. The classification of normotensive (NT), prehypertensive (PRT) and hypertensive (HT) was based on the criteria from JNC-8 , 7. Subj2). Weight and height were measured to the nearest 0.1 kg or 0.1 cm with the subjects wearing light undergarments and no shoes according to standard procedure [2; overweight was defined as BMI less than 28 kg/m2 and equal to or greater than 24 kg/m2. Waist circumference (WC) was measured to the nearest 0.1 cm while subjects were in the standing position. According to the Chinese criteria by Working Group on Obesity in China [Sociocharacteristics included age, gender, marital status, educational level, occupation, ethnicity, smoking, alcohol drinking, high-salt diet condition, body mass index (BMI), abdominal obesity and family history of cardiovascular diseases. Age was categorized into 6 groups: 18–29, 30–39, 40–49, 50–59, 60–69 and 70–79 years old. Marital status included married, single, divorced and widowed. Educational level was categorized into three groups: illiterate or primary school, high school and university. Occupation referred to physical laborer or laborer with mental work. With broad range of ethnicity, subjects were grouped as Han, Yi, Miao, Mongolia, Tibetan, Hui, Tujia, Korean, Manchu, Yao, Dai, Qiang and all others. Smoking was categorized into never smokers, current smokers and former smokers. Alcohol drinking was categorized into regular drinkers and non-drinkers. Subjects were also categorized as liking high-salt diet or not. BMI was defined as weight (kg) divided by squared height . Two sided P < 0.05 was considered statistically significant.Database was constructed with EPI3.02 software by two data managers respectively and was corrected to guarantee the accuracy and integration of the data. Continuous variables were described with mean and standard deviation (SD). Categorical variables were described with number and percentage. The mean age was compared with analysis of variance. Blood pressure conditions were compared with Wilcoxon rank sum test. Univariate and multivariate logistic regression model was used to estimate odds ratio (OR) and its 95 % confidence interval (CI) for prehypertension. Variables with P < 0.001.Of all subjects, 16,211 individuals had normal blood pressure, 17,281 individuals were prehypertensive and 14,003 were hypertensive. The prevalence rates of HT and PRT were 29.5 and 36.4 % respectively. The mean age for NT subjects was 35.3 ± 14.5 years old, which seems younger than those with HT (54.8 ± 14.0) or PRT (44.0 ± 16.0), P < 0.001), male (P < 0.001), not single (P < 0.001), physical laborer (P < 0.001), lower educational level (P < 0.001), Yi and Korean (P < 0.001), smokers (P < 0.001), drinkers (P < 0.001), liking high-salt diet (P = 0.003), general obese or overweight (P < 0.001), abdominal obese (P < 0.001) and with family history of cardiovascular diseases (P < 0.001) have higher prevalence of HRT. The prevalence rates of HT and PRT were 33.2 and 41.1 % for males, 27.0 and 33.2 % for females respectively. 40.8 % of subjects in 18–29 years old were HT or PRT, but 89.7 % of subjects in seventies were HT or PRT. With aging, the proportion of NT subjects declined gradually. The prevalences of HT and PRT across demographic variables were shown in Table The basic characteristics were tabulated according to three blood pressure categories in Table Table In developed counties and developing counties, prevalence of hypertension and prehypertension was different from others. In general, the prevalence of hypertension has been highest in industrial countries. For example, Wang Y mentioned that approximately 60 % of American adults have prehypertension or hypertension . In ChinMultivariate logistic regression model analysis found that gender, age, educational level, occupation, ethnicity, smoking, alcohol drinking, BMI, abdominal obesity and family history of cardiovascular diseases were associated with prehypertension. Male subjects had twice risk of prehypertenion and then males should pay more attention to blood pressure control. Higher educational level was a protective factor of prehypertension, which was similar as the findings from industrialized countries, in which high educational level was found to be associated with lower risk of hypertension –24. PeopLife style factors were found closely associated with prehypertension. Contrary to the results in univariate analysis, current smokers had lower prevalence for prehypertension. Although association of smoking and prehypertension needs to be explored further, other studies reported similar results as this paper , 18, 29.Several limitations have to be mentioned. First, due to the nature of cross-sectional study design, we could not make causation between potential risk factors and prehypertension. Second, criteria of defining prehypertension and hypertension only based on one time measure of blood pressure without follow-up information might not truly represent the prehypertension and hypertension status. Hypertension could of course be defined in different ways, one way is self-reported, and another way is that it is based on diagnosis in patient records or administrative databases. The different definitions of prehypertension and hypertension limit the comparison of prevalence figures from different studies. Finally, recall bias might exist in the current study due to self-report high-salt diet conditions.Appropriately two-third of subjects was hypertensive or prehypertensive and high prevalence rate of prehypertension was general in Chinese adults. Many sociodemographic characteristics were significantly associated with hypertension and prehypertension conditions. There were important clinical significance and public health significance about age-specific, gender-specific and ethnic-specific hypertension and prehypertension studies in China. More health education should be provided for hypertensive people to treat their hypertension regularly. In addition, regular medical check-up and measuring blood pressure are necessary to improve awareness, treatment and control of hypertension.BMI, body mass index; CI, confidence interval; DBP, diastolic blood pressure; HT, hypertensive; JNC-8, the Eighth Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure; NT, normotensive; OR, Odds ratio; PRT, prehypertensive; SBP, systolic blood pressure; SD, standard deviation; WC, Waist circumference; WGOC, Working Group on Obesity in China


Purpose: To describe the diurnal variation of the ocular perfusion pressure (OPP) in normal, suspects and glaucoma patients.Materials and methods: Seventy-nine subjects were enrolled in a prospective study. The diurnal curve of intraocular pressure (IOP) was performed and blood pressure measurements were obtained. Each participant was grouped into one of the following based upon the clinical evaluation of the optic disk, IOP and standard achromatic perimetry (SAP): 18 eyes were classified as normal , 30 eyes as glaucoma suspect (GS) , C/D ration > 0.5 or asymmetry > 0.2 and/or ocular hypertension), 31 eyes as early glaucoma ] and glaucoma (18.77 ± 4.30 mm Hg) patients as compared to normal subjects (16.11 ± 2.27 mm Hg). In studying the diurnal variation of the OPP, we found lower values at 3 pm in normals (34.21 ± 2.07 mm Hg), at 9 am in suspects (54.35 ± 3.32 mm Hg) and at 12 pm in glaucoma patients (34.84 ± 1.44 mm Hg).Conclusion: Each group has a specific OPP variation during the day with the most homogeneous group being the suspect one. It is important to keep studying the IOP and OPP variation for increased comprehension of the pathophysiology of glaucomatous optic neuropathy.How to cite this article: Kanadani FN, Moreira TCA, Bezerra BSP, Vianello MP, Corradi J, Dorairaj SK, Prata TS. Diurnal Curve of the Ocular Perfusion Pressure. J Curr Glaucoma Pract 2016;10(1):4-6. Both have been defended by research groups on the last 150 years. In congenital, acute angle close and secondary glaucoma, clearly the increase in intraocular pressure (IOP) is enough to cause GON. However, innumerable findings of normal tension glaucoma (NTG) cannot satisfactorily be explained only by this theory. The fact is that the reduction of the ocular blood flow (OBF) frequently precedes the structural damage. It also occurs in other parts of the body of these glaucomatous patients, indicating that hemodynamic adjustments can at least partially be primary. The biggest cause of this reduction is not atherosclerosis, but a vascular disequilibrium that leads to the reduction of the ocular perfusion pressure (OPP) and insufficient autoregulation.2 Using the angiofluoresceinography Hayreh et al3 demonstrated a zone of the short posterior ciliary’s arterioles that supply the posterior portion of the optic nerve. This area can be vulnerable to the ischemia when the OPP is reduced. The OPP is defined as 2/3 of median arterial pressure (MAP) less IOP (OPP = 2/3 MAP-IOP).4511The reduced OBF can have a decisive implication in the pathophysiology of many ocular illnesses like diabetic retinopathy, age-related retinopathy, pigmentary retinosis, myopia and glaucoma. Abnormalities of the blood flow in glaucoma have been evaluated with diverse techniques, including angiofluoresceinography, colored Doppler, Doppler laser fluxometry and pulsatile ocular blood flow (POBF) tonograph.5 Leske MC 5 studying the relationship between blood pressure and glaucoma reported increased prevalence of glaucoma when the diastolic perfusion pressure fell below 55 mm Hg. A reduction in MAP or an increase in IOP can diminish the ocular perfusion, but the accurate mechanism of the regulation of the IOP is unknown. If the autoregulation mechanisms are continuous, the sanguineous flow will remain steady with a substantial fall of the ocular perfusion.4In agreement with the vascular theory, low systemic arterial pressure relative to IOP can lead to a low OPP, consequently, decreasing the perfusion of the optic nerve and leading to a glaucomatous loss of the visual field. On the contrary, systemic hypertension can increase the risk of damage to the small vessels of the optic disk.The aim of this study was to determine the OPP variation during the day in normal, suspects and glaucoma patients.Prospective and comparative study in which 79 eyes were enrolled. All patients were recruited in the Santa Casa’s Eye Clinic of Belo Horizonte. The normal individuals were volunteered friend or parents of the suspects and glaucoma patients. Informed consent was obtained from all participants following the Tenets of the Helsinki’s declaration.The diurnal curve of IOP was performed and blood pressure measurements were obtained. Each participant was grouped into one of the following based upon the clinical evaluation of the optic disk, IOP and standard achromatic perimetry (SAP): 18 eyes were classified as normal , 30 eyes as glaucoma suspect (GS) , C/D ration > 0.5 or asymmetry > 0.2 and/or ocular hypertension), 31 eyes as early glaucoma  10.1 . Results were expressed as mean ± standard deviation and paired Student’s t-test was used to evaluate the level of significance. A p value of 0.05 or less was considered significant.The mean IOP values in all groups did not follow any regular pattern. The peak IOP was found to be greater in suspect [18.70 ± 3.31 (mm Hg ± SD)] and glaucoma (18.77 ± 4.30 mm Hg) patients as compared to normal subjects (16.11 ± 2.27 mm Hg). In studying the diurnal variation of the OPP, we found lower values at 12 pm in normals (58.77 ± 10.45 mm Hg),  at 9 am All the OPP values were higher in the control group in all times in comparison to suspects and glaucoma patients. The same was found in suspects in comparison to glaucoma patients.5 investigating the relationship between OPP and incidence of open angle glaucoma (OAG) found a relative risk of 3.1 for patients with OPP < 41.0 mm Hg. Fuchsjäger-Mayrl et al11 reported that the hemodynamics of ocular parameters are lower in patients with OAG in comparison with normal patients. The diurnal changes of the IOP were similar in normal and POAG patients; however, the OPP was significantly different between these groups with significant reduction after lunch and presenting lesser value at 7 am of the morning. Our results had demonstrated an OPP of 60.45 mm Hg (SD 10.9) in normal patients, of 53.18 (SD 11.56) in suspects and of 51.96 mm Hg (SD 9.59) in glaucomatous patients.Leske et al67 In our normal group, the IOP fluctuation was 1.67 mm Hg. The same stability was found in our suspects (0.50 mm Hg) and in our glaucoma group (1.71 mm Hg).In patients with untreated glaucoma, the diurnal change in IOP has been reported to be between 4.8 and 18.4 mm Hg, whereas, in the normal eyes, it has been reported to be between 2.8 and 6.5 mm Hg.8 This renders ocular perfusion directly dependent on perfusion pressure. Interestingly, a very similar behavior is observed in patients with progression despite normal or normalized IOP,9 indicating that damage may occur if low perfusion pressure is combined with abnormal or insufficient autoregulation. All these observations indicate that vascular regulation or dysregulation, respectively, might be key factors in the pathogenesis of GON.Under physiological conditions, low perfusion pressure is compensated by low resistivity to flow (autoregulation). There are indications that this behavior might be altered in some subjects. It has been demonstrated that otherwise healthy subjects with vasospastic syndrome, do have altered blood flow regulation in their central retinal artery, as measured by color Doppler imaging (CDI).10 Despite this, we cannot quantify with any current diagnostic method, the real amount of blood in the anterior portion of the optic nerve, neither the level of existing gaseous exchange in this place. We also do not have a reliable technique to measure the blood flow in the anterior portion of the optic nerve. It is important to point out that although were not found any statistically significant difference on the OPP during the day, the absolute OPP value was lower in the glaucoma group in comparison to suspects and normals.There is evidence of an abnormal association between ocular perfusion parameters and systemic blood pressure in patients with glaucoma. However, these data refer to long-term adaptations of perfusion to the eye with blood pressure rather than a short-term increase in blood pressure.


Identifying White Coat Hypertension (WCH) may avoid inappropriate commitment of individuals to lifelong and costly blood pressure (BP) lowering medications’. We assessed the prevalence and determinants of WCH in urban clinical settings in Cameroon.Participants were a consecutive sample of adults, who underwent ambulatory BP measurements (ABPM) for the diagnosis of hypertension and evaluation of treatmentin three referral cardiac clinics in the cities of Yaounde and Douala, between January 2006 and July 2011. WCH was defined as an office-based systolic (or diastolic) BP ≥ 140(90) mmHg together with an average day time ambulatory systolic (and diastolic) BP < 135(85) mmHg.Of the 500 participants included, 188 (37.6%) were women, 230 (46%) were nonsmokers and 53 (10.6%) had diabetes mellitus. The mean age was 51.6±10.2years. The ABPM readings were higher in men than in women (p<0.05).The prevalence of WCH was 26.4% overall, 39.3% in women and22.4% in men (p=0.01).In multivariable analysis, body mass index was the only significant determinant of WCH , p<0.05).The prevalence of WCH was high in our study population and was correlated only with BMI. Accurate measurement of BP and appropriate diagnosis of hypertension using ABPM in this setting may help limiting the consequences of over estimating hypertension severity on individuals, families and health systems. Hypertension has been established as the commonest single risk factor for the occurrence of major cardiovascular events and deaths. It is a growing public health problem worldwide with a rapidly increasing prevalence in developing countries such as those in sub-Saharan Africa. The number of people affected is increasing so rapidly that some published data suggest that the prevalence of hypertension in developing countries is already matching that in developed countries –3. Such The use of automated blood pressure measuring techniques has facilitated the accurate diagnosis of white coat hypertension. However, there are still very little information on the prevalence and correlates of WCH in Africa. This study was carried out to determine the prevalence of masked hypertension and WCH, and determinants of WCH in major urban clinical settings in Cameroon.This was a cross sectional hospital-based study carried out in three specialized cardiovascular clinics  of the two major cities  of Cameroon. These towns were chosen because they represent the areas where most of internal medicine and cardiovascular specialists were located and were likely to request and interpret ABPM during the study period. The study was approved by the administrative authorities of the three health facilities, and ethical clearance was obtained from the Buea Faculty of Health Sciences Ethic Committee.st January 2009 to 31st December 2011. In the second recruitment phase (from 1st January 2012 to 31st July 2012), two hundred patients aged 18 years or above were referred to the recruiting centres for diagnosis of hypertension and/or evaluation of their antihypertensive medication. In the prospective phase, informed consent was obtained from the patients and those who accepted to undergo an ABPM and was included in the study.The study had two recruitment phases. First we retrospectively reviewed three hundred files of patients who had undergone ABPM from 1For both recruitment phases the following variables were collected: sex, age, educational level, medical history hypertension, diabetes, and smoking with quantification of pack/years in smokers, height and weight for calculation of body mass index (BMI), office systolic and diastolic BP, drug history, mean day time systolic (diastolic) ambulatory BP, mean night time systolic (diastolic) ambulatory BP. Participants were stratified for alcohol consumptioninto occasional alcohol consumers, low, moderate and excessive alcohol consumers. Excessive alcohol consumption was based on intake of either more than 3 (2 for women) standard glasses of wine per day or more than 10 (5 for women) local beers  per week. Moderate alcohol consumption was based on intake of 25-30 g per day. Those who smoked at least one cigarette per day at the time of consultation were classified as active smokers, and those who have smoked for at least 3 years in the past, but had stopped by the time of consultation, were classified as ex-smokers. The drug history included the number, name and class of the antihypertensive medications, and the time of the day the drug was taken.The office BP measurement was taken by a trained nurse after 10 minutes of rest, using automated electronic sphygmomanometers (OMRON M3 HEM-7200-E Omron Matsusaka Co Ltd Kyoto Japan) with the patient in a seated position. BP was taken in both arms. Three consecutive BP measurements were taken and the average of the 3 values (using the higher pressure arm) was considered as the office BP. The 24h-ABPM was done using a commercially available system (Space Labs 90207 system). A typical weekday was chosen for different patients and normal daily activities were allowed. BP was recorded during the day for every 15minutes (from 07:00 to 21:00) and every 30minutes during the night (from 21:00 to 07:00). The mean systolic and diastolic BP was calculated for daytime and night time within 24hrs of recording. ABPM records were considered valid only if the number of BP recordings were at least 70% of the expected readings assessedas valid by the software analysis; otherwise patients underwent a second recording. Patients showing no valid readings for greater than two hours also underwent a second recording. Patients were classified as having WCH if their office systolic (diastolic) BP was ≥ 140 (90) mmHg and their mean daytime ambulatory systolic BP was < 135 mmHg and ambulatory diastolic BP was < 85 mmHg. Patients were classified as having masked hypertension if their systolic (diastolic) BP was ≤ 140 (90) mmHg and their mean daytime ambulatory systolic BP was > 135 mmHg and ambulatory diastolic BP was > 85 mmHg [Data were analysed using the Statistical Package for Social Sciences  version 17.0 software. Results are summarized as counts and percentages for qualitative variables and as mean and standard deviation (SD) for quantitative variables. Groups comparison used the Student t-test for quantitative variables and the chi-square test for qualitative variables. To assess the determinants of WCH, multivariate logistic regression models were used. A p-value2 (A flow chart of adoption of ABPM data is shown in 2 . As expe2 . The cli2 .The distribution of various sub forms of hypertension was: masked hypertension (MHT):9%, normotension (NT):18%, WCH: 25% and sustained hypertension (SHT): 49%. Of the 125 patients presenting with WCH, 79 (23.7%) were on BP lowering medication .In both univariable and multivariable adjusted logistic regression models, the main driver of white coat hypertension was BMI . The preIn this cross sectional study of hypertensive groups of patients from Douala and Yaounde,Cameroon,we found a high prevalence of WCH. This high prevalence was largely influenced by adiposity. To our knowledge, this is the largest study of ABPM in a sub-Saharan African setting and the used methodology provides findings that are comparable to other studies onWCH. Our findings provide some suggestions on the segment of the population to be targetted by further investigations via ABPM for the purpose of diagnosing and treating hypertension in our resources-limited settings.The level of ABPM systolic BP(SBP) and diastolic BP(DBP) were high compared to other studies such as the PAMELA study and Australian data. The mean clinic BP in our study was 27/11 mmHg and 13/11 mmHg higher than in the PAMELA and Australian study respectively. Furthermore,the mean 24 H ABP readings in our study was 21/13 mmHg and 7/5 mmHg higher than in the PAMELA and Australian studies respectively , 11. ThiThe overall prevalence of WCH in our study population was 25.0%. This was higher than the 15.4% reported by Dolanand associates  in EuropStudies of the association between BMI and ABPM variables have shown conflictingfindings. In a large retrospective study of 3928 patients referred for ABPM, Ben-Dov et al  found noThe strengths of our study include the multicentre nature. It was carried in key centres highly engaged in performing ABPM, the rigorous data collection; the sample size was good and comparable to many other large database studies elsewhere. However, participating centres were based only in urban areas, and whether findings from this study apply to people in rural settings is unknown. Furthermore, the non-random selection of participants in the study suggests that our estimates of WCH could possibly carry some bias. Such a bias however, if any, is unlikely to affect the association of WCH with adiposity and may therefore not alter the main conclusion from this study.Despite theses hort comings, we do believe the present study has relevance both for clinical and public health reasons. Given the high prevalence of hypertension in the Cameroon population as largely reported in previous studies, the findings of our study are indicative of the important role of an accurate measurement of BP and diagnosis of hypertension using either ABPM or HBPM so as to reduce unnecessary commitment to a lifelong treatment with BP lowering medications. That up to a quarter of individuals labelled as hypertensive in this setting actually has WCH suggest by the way of simple arithmetic that over a quarter of resources dedicated to hypertension care in this setting are resources inappropriately used. Interestingly however, our study also suggest that this waste of resources could potentially be reduced just by considering for further investigation via ABPM, those in the upper tail of the BMI distribution who are diagnosed with hypertension based on office measurements.In conclusion, our study has provided findings showing a high prevalence of white coat hypertension in Cameroon which appear to be driven essentially by adiposity. A policy in this setting favouring the consideration of people with elevated BMI diagnosed with hypertension using office measurements, for further investigation via ABPM has a potential to limit the number of those who may unnecessarily be committed to chronic medications to control the BP levels.


Primary care physicians (PCPs) typically manage early chronic kidney disease (CKD), but recent guidelines recommend nephrology co-management for some patients with stage 3 CKD and all patients with stage 4 CKD. We sought to compare quality of care for co-managed patients to solo managed patients.2 separated by 90 days. We assessed process measures  and intermediate clinical outcomes (mean blood pressure and blood pressure control) and performed subgroup analyses by CKD stage.We conducted a retrospective cross-sectional analysis. Patients included in the study were adults who visited a PCP during 2009 with laboratory evidence of CKD in the preceding two years, defined as two estimated glomerular filtration rates (eGFR) between 15–59 mL/min/1.73 mp < 0.001 for all comparisons). After adjustment, co-management was associated with serum eGFR test , urine protein/albumin test , and ACE/ARB prescription . Co-management was associated with monitoring for anemia and metabolic bone disease, but was not associated with lipid monitoring, differences in mean blood pressure  or blood pressure control. A subgroup analysis of Stage 4 CKD patients did not show a significant association between co-management and ACE/ARB prescription .Of 3118 patients, 11 % were co-managed by a nephrologist. Co-management was associated with younger age (69 vs. 74 years), male gender (46 % vs. 34 %), minority race/ethnicity , hypertension (75 % vs. 66 %), diabetes (42 % vs. 26 %), and more PCP visits (5.0 vs. 3.9; For stage 3 and 4 CKD patients, nephrology co-management was associated with increased stage-appropriate monitoring and ACE/ARB prescribing, but not improved blood pressure control. Twenty-six million Americans have chronic kidney disease (CKD). Approximately 90 % of CKD patients are in an early stage of the disease and are typically cared for by primary care physicians (PCPs). U.S. and international guidelines recommend that physicians monitor for progression, monitor for complications, prescribe medications to delay progression, and focus on cardiovascular risk modification, all of which are within a PCP’s scope of practice . Recent 2, separated by 90 days and collected during routine clinical care between January 1, 2007 to December 31, 2008 . On average, patients saw nephrology twice during the year , tests monitoring for complications , both before and after adjustment for potential confounders (Table p = 0.04). Co-management was associated with mean diastolic blood pressure after adjustment only (p = 0.0007). Nephrology co-management was not associated with ACE/ARB prescription, mean systolic blood pressure, or blood pressure control.In stage 4 patients, nephrology co-management was associated with a higher rate of one test monitoring for progression , and tests monitoring for complications , both before and after adjustment for potential confounders  of stage 3 CKD patients and half of stage 4 CKD patients were co-managed by nephrology. Co-management was associated with socio-demographic differences, particularly in stage 3 CKD patients for whom co-management was associated with younger age, male gender and minority race/ethnicity. Co-management was associated with diabetes, hypertension, and more frequent PCP visits. After controlling for these potential confounders, co-management was associated with monitoring tests, both for progression and for complications. Co-management was associated with higher rates of ACE/ARB prescription in stage 3 CKD, but not in stage 4 CKD. Co-management was not associated with higher rates of cardiovascular risk modification through lipid monitoring or blood pressure control.Our finding of a difference between the two groups for ACE/ARB prescription in stage 3, though not in stage 4, is in concert with another recently published study from the Chronic Renal Insuffiency Cohort (CRIC) . One expCo-management was associated with age, gender, and race/ethnicity. These associations align with patients who have higher muscle mass. This may indicate PCPs are still using serum creatinine levels rather than eGFR to judge severity of CKD in early disease. The only socio-demographic characteristic associated with nephrology referral in stage 4 CKD was younger age. PCPs were more likely to refer patients with diabetes in the stage 3 subgroup, which may reflect a higher rate of urine albumin screening and appropriate subsequent referral of albuminuric patients . Patient2). They found a significant difference in serum hemoglobin testing, serum phosphorus testing, and serum PTH testing, but neither urine protein testing  nor ACE/ARB prescribing  [Other primary care CKD studies have revealed suboptimal urine protein testing, serum phosphorus testing, serum parathyroid hormone testing, prescription of ACE/ARB, and blood pressure control , 20–22. overall) . Ours isThere are several limitations to this study. There is a potential for type II error when we conclude that there is no difference in BP control between groups because co-managed patients may be sicker than solo managed patients. An analysis of anti-hypertensive regimens would help to elucidate any difference in management. There may be other patient level confounders for which we were unable to adjust. ACE/ARB prescriptions were assessed in all CKD patients, though these are only recommended for patients with either hypertension, diabetic kidney disease, or proteinuria. Our laboratory uses the MDRD equation to calculate eGFR without accounting for race. Generalizability is limited by the fact that the population is limited to one primary care network. We were unable to measure clinical outcomes such as progression to ESRD and mortality.Our findings have implications for the following: 1) PCP solo management, 2)  nephrology co-management, and developing a systematic approach to  referral to nephrology.First, PCPs should improve solo management in stage 3 CKD through monitoring for complications, monitoring for progression of disease, and intervening to delay progression. One successful approach is through point-of-care EHR alerts that remind the physician of the diagnosis and recommended management of stage 3 CKD. Such reminders have improved urine protein testing . A seconSecond, quality of care for co-managed patients could improve as well. Co-management did not increase the likelihood of cardiovascular risk modification in stage 3 or stage 4 CKD. PCPs and nephrologists working together should be able to control patients’ blood pressure, yet we saw no difference in this measure between solo managed and co-managed patients. Both EHR alerts and population management are likely to be part of the answer , 28, butThird, and just as critical as the first (i.e. improving PCP solo management) and the second (i.e. improving co-management), is developing a systematic approach to referral. The current approach relies on  creatinine-based estimates of kidney function that do not accurately predict whether and when patients might progress , 39; manThat being said, two studies showed a slowing of progression in stage 3 CKD when nephrologists monitored patients electronically and gave advice to PCPs , 41. At In conclusion, early CKD is commonly managed in primary care, but patients who are co-managed by nephrology receive better monitoring for progression and complications. Improving the quality of PCP solo management will help to close this gap. In addition, about one-quarter of early CKD patients have uncontrolled blood pressure whether they have been referred to a nephrologist or not. We should study interventions to improve co-management of blood pressure and to decrease cardiovascular events. These interventions should include population management, EHR tools, and patient-centered interventions. Finally, we have sophisticated tools to risk-stratify patients with CKD and we must learn how best to employ these tools in primary care practices to systematize referral of high-risk patients.


Previous studies of HIV-infected patients have shown significant associations between highly active antiretroviral therapy (HAART) and increased blood pressure; however, the mechanisms involved are less clear. Therefore, we sought to investigate the potential impact of body fat changes in mediating the effects of HAART on blood pressure changes among people living with HIV.CI) to determine the mediating effects of body mass index and waist circumference (mediators) on the total effects of HAART exposure (primary predictor) on blood pressure (outcome), while controlling for age, sex and other potential confounders.Four hundred six consenting patients (≥18 years of age) attending a tertiary HIV clinic in semi-urban Nigeria were recruited between August and November 2014 as part of a cross-sectional study. We performed bias-corrected bootstrap tests of mediation using 95 % confidence intervals  and diastolic blood pressure  after adjusting for age, sex, smoking status, CD4 count and duration of HIV infection. No significant mediating effect was observed with body mass index alone or in combination with waist circumference after adjusting for all potential confounders.Waist circumference remained a significant partial mediator of the total effects of HAART exposure on increasing systolic blood pressure  contains supplementary material, which is available to authorized users. Please see Additional file Antiretroviral drugs increase blood pressure by damaging the endothelial linings of blood vessels, which in turn interferes with the production of biological markers known to regulate blood pressure –3. NonetStudies evaluating the impact of antiretroviral therapy on blood pressure changes have usually controlled for measures of relative weight (such as body mass index) and body fat distribution (such as waist circumference) using multiple regression models: blood pressure is linearly regressed on antiretroviral status while adjusting for body mass index or waist circumference –11. HoweConsenting HIV-infected patients attending the HIV clinic at the Benue State University Teaching Hospital (BSUTH) in Nigeria were recruited between August and November 2014 as part of a cross-sectional study. The HIV clinic at BSUTH is one of two tertiary HIV clinics in Benue state, with approximately 30 patients in weekly attendance. Until two years ago, Benue had consistently recorded the highest prevalence of HIV across all states in Nigeria, accounting for more than 10 % of its resident population throughout the preceding decade . The curHIV-infected patients who were no less than 18 years old, naïve or exposed to HAART and able to communicate in English or Nigerian pidgin were included in the study. We sampled consecutive patients until we had recruited 406 participants, comprising 306 patients exposed to HAART and 100 HAART-naïve patients. HIV-infected patients who were less than 18 years old, pregnant and lactating mothers, persons in the advanced clinical stages of HIV infection (patients diagnosed with opportunistic infections or AIDS-defining illnesses), patients diagnosed with antiretroviral treatment failure and those with CD4 cell counts that had been assessed more than three months prior to the commencement of the study were considered ineligible for inclusion in the study.Figure For descriptive purposes, we summarized the distribution of the variables according to HAART status. The values were expressed as mean ± standard deviation for continuous variables and absolute numbers (percentages) for categorical variables. We stratified the association between body mass index/waist circumference and systolic/diastolic blood pressure by HAART status to rule out HAART status as an effect modifier. To investigate the potential impact of body mass index in mediating the effects of HAART on systolic and diastolic blood pressure, we estimated the mediation coefficients by fitting linear regression models following the steps outlined by Baron and Kenny:  in the fThe sample size calculation to evaluate mediation analysis for a linear model was given by the following equation: \documentn denotes the sample size; L is equal to 7.85, which is the linear statistic corresponding to ordinary least squares (OLS) regression for one predictor with a type I error of 0.05 and power of 0.8; k is equal to 1, which is the number of predictors in the OLS regression; and f is the coefficient of the regression equation corresponding to the indirect effect (Path AB) of the predictor variable on the outcome variable, through the mediator.where Assuming that the coefficients for Path A (0.14) and Path B (0.14) are small according to Cohen’s criteria for small effect sizes , 21, theTherefore, using these default values, we aimed for a sample size of 403.Patients in advanced clinical stages of HIV infection, such as those with opportunistic infections or other AIDS-defining illnesses, were considered particularly vulnerable and excluded from the study. Ethical approval was obtained from the BSUTH Health Research Ethics Committee in Nigeria (NHREC/08/11/2013B), and the University of Warwick Biomedical Science Research Ethics Committee, United Kingdom (REGO-2014-711). All patients provided written informed consent prior to participation.P < 0.05) and waist circumference (P < 0.0001) were significantly higher among HAART-exposed patients compared with HAART-naïve patients. Systolic and diastolic blood pressure levels were also significantly higher among HAART-exposed patients (P < 0.0001 for each). As shown in Table P < 0.0001 for each), in HAART-exposed (P < 0.0001 for each), and HAART-naïve patients (P < 0.0001 for each).Table CI: 0.37 to 2.70) and diastolic blood pressure , mediating 14 % and 10 % respectively of the total effects of HAART on systolic and diastolic blood pressure. Waist circumference mediated 15 %  and 12 %  of the total effects of HAART on systolic and diastolic blood pressure respectively. Combined body mass index/waist circumference accounted for 16 %  and 12 %  of the total effects of HAART on systolic and diastolic blood pressure levels, respectively.Table CI: 0.21 to 2.69, 13 % mediated) and diastolic blood pressure . Waist circumference also remained a significant partial mediator of the total effects of HAART on systolic blood pressure  and diastolic blood pressure  after adjusting for age, sex and smoking status. Similarly, the combination of body mass index with waist circumference mediated 15 %  and 11 %  of the total effects of HAART on systolic blood pressure and diastolic blood pressure respectively, after adjusting for age, sex and smoking status. However, while the mediating effects of body mass index and combined body mass index/waist circumference were attenuated by additional confounders, including CD4 cell count and duration of HIV infection, we observed that the mediating effects of waist circumference remained statistically significant, accounting for 11 %  and 9 %  of the total effects of HAART on systolic blood pressure and diastolic blood pressure, respectively.Table The main finding of this study of a sample of HIV-infected adults emphasizes the stronger impact of central fat distribution (measured by waist circumference), compared with relative weight (measured by body mass index), in mediating the associations of HAART with increased systolic and diastolic blood pressure, independent of factors that could attenuate these associations, such as age, sex, smoking status, CD4 cell count and duration of HIV infection. This finding is consistent with a large body of scientific evidence on the predominant role of central adiposity, as opposed to relative weight, in the aetiology of cardio-metabolic disorders –25. We aWe observed that slightly higher proportions of the total effects of HAART on systolic and diastolic blood pressure were mediated by the combined effects of body mass index/waist circumference, as opposed to either body mass index or waist circumference alone, after adjusting for traditional risk factors individually . Previous evidence asserting that the combined measure of body mass index and waist circumference better predicts hypertension, compared with either body mass index or waist circumference, broadly corroborate this finding , 29.The results of our study may have important clinical and public health implications. For instance, interventions aimed at weight management may be effective for blood pressure control among HIV-infected patients. Although lifestyle factors may be limited in predicting hypertension and other cardio-metabolic disorders in people living with HIV on HAART , lifestyWhile the mediating effects of body fat measures on the association between HAART and increased blood pressure may indicate a return to health, as opposed to a pathological process, we speculate that this phenomenon would only occur in HIV-infected patients in the advanced clinical stages of HIV infection . Such paOur findings must be interpreted with caution, given the observational nature of our study which precluded any causal inferences. In addition, the potential for residual confounding and bias is high in cross-sectional studies. The present study was set in semi-urban Nigeria, which may limit the generalizability of our findings to HIV-infected populations from rural settings or outside of the sub-Saharan African region. For instance, while reverse transcriptase inhibitors are the mainstay of antiretroviral therapy in sub-Saharan African countries –34, protDespite these limitations, our study presents important strengths. For instance, we present the first evidence of an alternative causal pathway to explain the effects of HAART exposure on blood pressure: the independent mediating role of waist circumference on the effects of HAART on systolic and diastolic blood pressure is a novel finding of the present study. Although blood pressure was not prospectively measured upon the initiation of HAART, we affirm that the mediation models presented in this study account for the direction of association, which favours the hypothesis that HAART influences changes in body fat measures, which in turn influence changes in blood pressure. It would seem biologically less plausible if the reverse (or any other kind of interaction) was the case. Secondly, the exclusion of patients in the advanced stages of HIV-infection from the study does not allow for an alternative interpretation of the findings, for instance, the impact of body mass index and waist circumference in mediating the effects of HAART on systolic and diastolic blood pressure are more likely to be pathological than indicative of a physiological return to health. Thirdly, the inclusion of important covariates as potential confounders in the mediation analyses ensures that estimates of the mediation effects are less likely to be exaggerated. Lastly, bootstrapping with bias-corrected 95 % confidence intervals was the preferred alternative to the Sobel-Goodman mediation test in ascertaining the statistical significance of the mediating effects. Unlike the latter, bootstrapping is not affected by sample size; hence, our relatively small-sized study is unlikely to produce inaccurate estimates of indirect effects , 41. In In conclusion, waist circumference partially mediates the effects of HAART on systolic and diastolic blood pressure, independent of covariates that could potentially attenuate these associations. Whether or not these associations are consistent in prospective analyses should be investigated by future studies.CI, confidence interval; DBP, diastolic blood pressure; DEXA, dual energy x-ray absorptiometry; HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus; SBP, systolic blood pressure; WC, waist circumferenceBMI, body mass index;


Patients may have lower (white coat hypertension) or higher (masked hypertension) blood pressure (BP) at home compared to the clinic, resulting in misdiagnosis and suboptimal management of hypertension. This study aimed to systematically review the literature and establish the most important predictors of the home-clinic BP difference.A systematic review was conducted using a MEDLINE search strategy, adapted for use in 6 literature databases. Studies examining factors that predict the home-clinic BP difference were included in the review. Odds ratios (ORs) describing the association between patient characteristics and white coat or masked hypertension were extracted and entered into a random-effects meta-analysis.2 increase, OR 1.07, 95% CI 1.01–1.14), current smoking status , and systolic clinic BP . Female sex was the only significant predictor of white coat hypertension .The search strategy identified 3,743 articles of which 70 were eligible for this review. Studies examined a total of 86,167 patients  and reported a total of 60 significant predictors of the home-clinic BP difference. Masked hypertension was associated with male sex  1.18–1.75), body mass index (BMI, per kg/mThere are a number of common patient characteristics that predict the home-clinic BP difference, in particular for people with masked hypertension. There is scope to incorporate such predictors into a clinical prediction tool which could be used to identify those patients displaying a significant masked or white coat effect in routine clinical practice. Ambulatory blood pressure monitoring (ABPM) is considered to be the “gold standard” measure of blood pressure, because multiple readings are taken and because it is associated with a range of cardiovascular outcomes and end organ damage.3–7 Ambulatory blood pressure is usually lower than clinic blood pressure8–11 due to the white coat effect  blood pressure targets are 5mm Hg lower than the corresponding clinic values.14 However, this “home-clinic blood pressure difference” is not always consistent. In some patients, blood pressures measured at home or with ABPM are higher than would be expected for the corresponding clinic blood pressure, the so-called masked effect  was then designed for use with MEDLINE and then adapted to run across the following databases: CINAHL (EBSCO), The Cochrane (Wiley) CENTRAL Register of Controlled Trials, EMBASE (Ovid), MEDLINE (Ovid) and MEDLINE In Process (Ovid), Science Citation Index – Expanded & Conference Proceedings Citation Index – Science, and The ZETOC (Mimas) database. Searches were carried out up to and including March 2014. In order to capture as broad a range of studies as possible, no language or date limits were applied, although animal studies, letters, comments, and review articles were excluded. In addition to searches of electronic databases, reference lists of studies included in the review were checked to identify any further relevant papers.A scoping search was carried out to identify background literature and provide an estimate of the volume of literature on the topic. A search strategy (see Two authors (J.P.S. and B.F.) reviewed the titles (10% independently) and abstracts (100% independently) of potentially relevant articles for inclusion. Studies were selected for full document screening and data extraction based on the following criteria:- Included a measure out-of-office blood pressure (home or ambulatory blood pressure).- Included a measure of clinic blood pressure.- A cross-sectional study examining data from a single time point.- Examined independent variables routinely available or measurable in a primary care clinic setting.- Examined the association between these variables and the home-clinic blood pressure difference, white coat or masked hypertension (outcome variable).- Included primary data.The review aimed to identify factors that could be utilized by clinicians in the routine diagnosis and management of hypertension in a Primary Care setting. Thus, studies were excluded from the review if they:- Examined patients in hospital for surgery or treatment for a specialist condition - Examined measurements taken in a nonclinical or pharmacy setting.- Studied patients aged below 18 years.Supplementary Appendix.Data were extracted from all relevant articles identified in the search strategy by J.P.S. and B.F. This included the study setting and population, basic patient demographics, clinic blood pressure, out-of-office blood pressure, and the outcome of interest . Where a logistic regression analysis was performed examining the association between specific variables and the home-clinic blood pressure difference, relevant odds ratios (ORs) for each predictor of this difference were extracted. The form used for data extraction is available in the 23 and CASP24 checklists for the assessment of cohort studies.During data extraction, the methodological quality and risk of bias of individual studies were assessed. This quality assessment covered domains of selection bias, detection bias, accuracy of measurement, analysis, and adjustment for confounding using a combination of questions from the QUADAS-225 This method allows for between-study heterogeneity in the true ORs and produces a pooled estimate and 95% CIs to summarize the association between independent predictors and white coat or masked hypertension. Where 95% CIs were not presented in an included article, they were estimated from the corresponding P values using the methods described by Altman and Bland.26The primary outcome of this review was to identify the most important factors that predict a significant home-clinic blood pressure difference. This was defined by (a) the number of studies citing specific risk factors for the home-clinic blood pressure difference, white coat or masked hypertension and (b) a pooled OR for the most commonly cited predictors of white coat or masked hypertension. This pooled estimate was based on log OR estimates and their confidence intervals (CIs) synthesized in a random-effects meta-analysis using the method of DerSimonian and Laird.27Sensitivity analyses were conducted focusing on those high quality studies that identified and corrected their analysis for confounding variables including age and sex. Where sufficient data were available, further sensitivity analyses explored the association between independent predictors and white coat or masked hypertension defined according to ambulatory blood pressure (daytime or 24 hour) or home monitoring and in subgroup populations: unselected patients and those with diagnosed hypertension .All analyses were conducted using STATA version 13.1 . Data are presented as proportions of the total study population, means with SD or ORs with 95% CIs unless otherwise stated.The search strategy identified 3,743 unique articles of which 70 were eligible for this review after title, abstract, and full text screening . StudiesSupplementary Table 2). Most studies (55/57) defined the threshold for white coat or masked hypertension (where appropriate) and examined the home-clinic blood pressure difference as the primary focus of the study (68/70). Forty-six studies identified important confounding variables and 44 of these corrected for this confounding in their analysis. Full details of the multivariate analysis conducted in each study are given in Supplementary Table 3).Included studies varied in methodological quality with sampling strategies and the representativeness of the study population described in only 21/70 studies (Supplementary Table 4). These factors were also commonly cited as predictors of both white coat and masked hypertension with the addition of diabetes and smoking status , current smoking status , and systolic clinic blood pressure  were all found to be significant predictors of masked hypertension (I2 = 70.4% (masked hypertension); I2 = 75.7% (white coat hypertension)), BMI (I2 = 62.0%), and systolic blood pressure (I2 = 81.4%) predictors of white coat and masked hypertension was significant (P < 0.05).Included studies reported a total of 60 significant predictors of the home-clinic blood pressure difference, white coat or masked hypertension. The most commonly cited predictors of the home-clinic blood pressure difference were sex 14 studies), age (11 studies), body mass index , and systolic (12 studies) and diastolic blood pressure (5 studies)  but BMI and systolic blood pressure no longer being predictive. When only studies that used home blood pressure to define masked hypertension were included, only sex remained a significant predictor, although there were insufficient studies to examine the relationship between BMI and masked hypertension. Using ambulatory blood pressure or home blood pressure to define white coat hypertension had no impact on the findings of the primary analysis although there were no longer sufficient data to examine the association with diabetes, smoking status and diastolic blood pressure (studies using ambulatory blood pressure), or age, BMI, and systolic and diastolic blood pressure (studies using home blood pressure). Similar findings were observed in the sensitivity analysis excluding low quality studies that did not account for confounding variables.In an unselected population, male sex and diabetes were predictive of masked hypertension ; OR 1.48, 95% CI 1.22–1.70 (diabetes)), while in hypertensive patients, only male sex remained significant  for masked uncontrolled hypertension, although there were no longer sufficient data to examine the association with systolic and diastolic blood pressure. Examining only patients from an unselected population, male sex was predictive of not having white coat hypertension  and systolic blood pressure was predictive of having white coat hypertension . In hypertensive patients, male sex remained predictive of not having white coat hypertension , although again, insufficient data were available to examine associations with BMI and systolic or diastolic blood pressure. The observed heterogeneity was not reduced in any sensitivity analyses examining studies by outcome measurement, sample populations, or methodological quality.This study has systematically reviewed all existing literature evaluating the association between patient characteristics and the home-clinic blood pressure difference. A large number of studies were identified examining a number of common factors which predict the home-clinic blood pressure difference or white coat or masked hypertension. Meta-analyses of the most commonly cited predictors revealed that sex, BMI, smoking status, and systolic blood pressure level were the most important predictors, although these associations were mediated by the method of out-of-office blood pressure monitoring and the population studied. There is scope to incorporate such predictors into a clinical prediction tool which could be used to identify those patients more likely to display a significant masked or white coat effect and therefore better target the use of out-of-office blood pressure monitoring in routine clinical practice.28 Although an attempt was made to extract details of the person taking clinic blood pressure from each included study, many did not report this or used both doctors and nurses to take readings without distinguishing between the 2, meaning a subgroup analysis by the type of person taking the clinic measurement was not possible.This is the largest systematic review to date of studies examining the association between patient factors and the home-clinic blood pressure difference. An extensive search strategy was used in multiple research literature databases to comprehensively capture all published articles relating to the study research question. Not all of the identified studies were directly comparable due to a lack of relevant data or the use of different statistical methods in the original study analyses. Thus, only 31/70 studies could be included in the meta-analysis. While sufficient data were available to analyze the primary outcome of this review, the lower number of studies eligible for meta-analysis meant some sensitivity and subgroup analyses were not possible. For instance, previous studies have suggested that the degree of white coat or masked effect may be affected by attributes of the person taking the clinic blood pressure measurement.The methodological quality of studies and the population of study varied widely between included studies and this may have contributed to the observed statistical heterogeneity. Indeed, the significant predictors of masked hypertension changed in sensitivity analyses excluding low quality studies that did not correct for confounding variables, although the statistical heterogeneity between studies remained significant. Only sex remained a significant predictor of both white coat and masked hypertension across patient populations and study quality.20–22 and clinical guidelines14 have discussed possible predictors of white coat and masked hypertension. Indeed, the present review demonstrates that the literature is becoming saturated with studies describing predictors of white coat or masked hypertension. Despite the large volume of articles studying this topic, little insight has been gained over the last 20 years and the patient factors commonly cited as significant predictors of the home-clinic blood pressure difference remain the same: age, sex, BMI, smoking status, and clinic blood pressure level.A number of previous reviewset al.,29 studied 770 individuals of White British, South Asian, or African-Caribbean ethnicity and found that when clinic blood pressure was defined using a single reading, non-hypertensive South Asian or African-Caribbean patients displayed less of a home-clinic blood pressure difference compared to White British patients. In contrast, hypertensive patients of South Asian or African-Caribbean origin had a greater home-clinic difference. The present review found only 2 studies examining ethnicity as a predictor of the home-clinic blood pressure difference31 and neither could be included in the meta-analysis. However, the recent Jackson Heart study32 (published after the searches in the present study were conducted) examined a population of 972 African-Americans and found male sex, current smoking status, diabetes, prescribed medication, and clinic blood pressure were significant predictors of masked hypertension. These findings are similar to those of the present review and suggest that our findings may be applicable to some ethnic minority groups.Recent studies have examined the influence of patient ethnicity on the home-clinic blood pressure difference. Martin 19 was more common in patients with characteristics associated with increased cardiovascular risk such as male sex, current smoking status, increasing BMI, and increasing blood pressure.34 White coat hypertension (associated with lower cardiovascular disease risk)19 was associated with female sex, which is also associated with lower cardiovascular disease risk .34This is the first systematic review to summarize all available evidence and present pooled estimates describing the most important predictors of white coat and masked hypertension. Seventy studies fulfilled our strict inclusion criteria and 60 different predictors of the home-clinic blood pressure difference were identified. It is unclear from the data included in this review as to why certain factors predict a white coat or masked effect to a greater degree than others. However, it is of interest that, in our analysis, significant predictors appeared to be related to the underlying cardiovascular disease risk associated with each condition: masked hypertension (associated with high cardiovascular disease risk)35 Those with white coat hypertension may be prescribed therapy when they do not need it while patients with masked hypertension are likely to be denied potentially beneficial treatment.15 Despite the large number of studies citing predictors of white coat and masked hypertension identified in this review, few have proposed a practical method for screening patients in routine clinical practice.21 Indeed, screening for white coat or masked hypertension is only useful if it reduces the number of patients potentially eligible for out-of-office monitoring. The number of predictive factors identified in this review makes their use to guide targeting of out-of-office monitoring impractical because a significant proportion of patients attending routine clinical practice are likely to present with at least one of these characteristics.It is important to identify patients with white coat and masked hypertension because failure to do so can result in significant misdiagnosis and mismanagement of hypertension.37 Viera et al.38 examined optimal clinic blood pressure levels for referral for ambulatory monitoring in patients with normal clinic pressure for detection of masked hypertension. They identified a threshold of greater than 120/82mm Hg as optimal but concluded that using clinic blood pressure alone was not an effective method of triaging for out-of-office monitoring because of high referral rates and moderate specificity. They suggested that a combination of factors, perhaps such as those identified in the present review, might be more effective at targeting ABPM efficiently.Some previous studies have suggested methods for targeted use of ABPM, mostly suggesting specific clinic blood pressure thresholds to target monitoring.14 suggests that practicing physicians consider screening for masked hypertension in high risk patients with normal clinic blood pressure, or screening for white coat hypertension in low risk patients with raised clinic blood pressure. This is still likely to result in a large number of patients being indicated for out-of-office blood pressure monitoring and future work should therefore focus on developing a single, practical, decision aid for targeted screening of white coat or masked hypertension, incorporating all of the significant predictors identified in this review.The European Society of HypertensionThere are a number of common patient characteristics that predict the home-clinic blood pressure difference including sex, current smoking status, increasing BMI, and increasing systolic blood pressure. There is scope to incorporate such predictors into a clinical prediction tool which could be used to identify those patients displaying a significant masked or white coat effect in routine clinical practice. Identification of such patients could help to better target antihypertensive treatment at those people with the most to gain.Omron and Lloyds Pharmacies in terms of blood pressure monitoring equipment. All other authors declared no conflict of interest.R.J.M. has received research funding from


Despite the positive outcomes reported with cardiac rehabilitation (CR), its impacts have been reported to be different from a region or country to another, which may be due to the different contents of rehabilitation programs.To investigate the effect of CR on cardiovascular risk factors.This is a retrospective cohort study on the data from Imam Ali Cardiac Rehabilitation Center in Kermanshah province, Iran from 2001 to 2008. We used paired t-test to evaluate the effect of CR on cardiovascular risk factors. Logistic regression or t-test  were used to assess the factors influencing re-admission (due to cardiac problems). The relationship between different variables and death was studied using univariate cox proportional hazard. P values < 0.05 were considered significant for all analyses.Out of 504 patients who completed rehabilitation, a total of 499 were analyzed. These 499 patients consisted of 383 men and 116 women. All anthropometric measurements, blood lipids (except HDL cholesterol), systolic and diastolic blood pressure, depression, anxiety and exercise capacity improved after rehabilitation . The improvement was observed in both sexes. A total of 39 patients were re-admitted to hospital after rehabilitation. Being female  and history of diabetes  increased the risk of re-admission significantly. Patients who were readmitted had higher anthropometric measurements at the beginning and the end of the program. Moreover, the initial exercise capacity of readmitted patients was lower than those who were not readmitted. After a maximal follow-up period of 6.3 years (median = 2.99 years), only eight patients expired . None of the variables in our study was significantly related to the survival rate.The comprehensive CR program in Imam Ali Center efficiently reduces cardiovascular risk factors and improves exercise capacity. Cardiovascular diseases constitute the number one cause of death worldwide. Cerebral and cardiac ischemic diseases are the two most common causes of death in all countries (whether high- or low-income) and thus it has been estimated that they will continue to top the list of mortality causes until 2030 . In IranCardiac rehabilitation (CR) includes all the activities aimed at helping patients with cardiovascular disease to achieve their optimal physical, mental and social conditions, so that they may pursue their normal roles in the society and maintain an active life. Thus, the objective of CR is to reduce recurrence of disease and its mortality, improve clinical improvement through controlled exercises, modify lifestyle and educate about health. Exercise, lifestyle changes such as quitting smoking, blood lipid control, blood pressure control, weight control and treating diabetes, as well as psychological instructions are among interventions which efficiently influence patient’s relative recovery. Studies indicate that as a result of these interventions, CR reduces recurrence and disability, and improves quality of life and reduces mortality considerably as well -6.Despite the positive outcomes reported with CR, it has been different from one region or country to another, and even different hospitals of one country have observed different results. These differences may be due to the content of CR program. On the other hand, CR programs with identical content may differ in terms of frequency and duration, and these differences will undoubtedly account for the observed discrepancies in terms of effect on cholesterol, High-density lipoprotein (HDL), Low-density lipoprotein (LDL) and blood pressure -12.Since no study has been conducted so far to evaluate the rehabilitation programs conducted at this center with their impacts on different health factors, as well as the fact that the programs are conducted relatively differently and the majority of patients are post-operative cardiac patients, we designed and conducted the present study.The Imam Ali CR Center is located in Kermanshah in western Iran. It has initiated its activity since 2001 and is currently the exclusive CR center in western Iran, covering patients even from neighboring provinces. This is a retrospective cohort study on the data from Imam Ali Cardiac Rehabilitation Center. The participants included all patients who were referred to this CR center from 2001 to 2008 and completed its programs.The CR program consists of medical and pharmaceutical evaluation, supervised exercise, and education and consultation for cardiovascular risk factors modification. The educational sessions address nutrition, medical, exercise  and psychological issues. The program is presented as a comprehensive course  or a short course .At the beginning of each course, the patients are evaluated for serum lipids, body mass index, waist circumference, blood pressure, depression, anxiety, smoking, diabetes, and exercise capacity in metabolic equivalents (METs) through maximal symptom limit exercise test. For the calculation of METs, we used modified Bruce protocol. Their information was recorded in their medical files. Once the CR program was completed, these evaluations were repeated and the changes were recorded again. All laboratory tests for blood lipids were performed in the laboratory of Imam Ali Hospital. In this study, data were extracted from patients’ medical files. Moreover, cases of readmission for cardiac problem and mortality  were identified through telephone calls made to patients or their families. All patients who had been readmitted were invited to refer to Imam Ali CR Center with their medical records. If the patients had moved from their previous address, we tried to locate them via friends or the telephone directory. Finally, those patients who could not be traced were searched for in the death registry of Kermanshah Province so that if expired, their date of death was recorded.In the present study, we classified patients as hypertensive when they declared being hypertensive and received treatment for hypertension, or those with diastolic and systolic blood pressures (at the beginning of the program) of equal to or more than 90 and 140 mmHg, respectively. Regarding diabetes, patients were labeled diabetic if they declared to be diabetic and received insulin or oral medicine, or those with fasting blood sugar levels of equal to or more than 126 mg/dL at the beginning of the program.We used Beck’s scale for diagnosis of depression. The patients were categorized in four groups in terms of severity of depression: no depression (0-9), mild depression (10-15), moderate depression (16-23), and severe depression (24-63). Spielberg’s scale was used for anxiety, categorizing patients as having no stress or mild stress (20-32), moderate stress (33-52), or severe stress (53-80). While Spielberg’s questionnaire can evaluate both the state and the trait of anxiety, in order to evaluate the effect of 2-3 months of the CR program we only used the “state” part.In the present study, changes in anthropometric characteristics and cardiovascular risk factors, which constituted a continuous quantitative measurement, were assessed using paired t-test on STATA software. The relationship between variables and readmission (due to cardiac diseases) was evaluated using logistic regression for nominal or ranked variables. For the continuous quantitative variables, the mean values in two groups (with and without readmission) were compared using t-test . In order to evaluate mortality, first the survival rate curve was plotted for all patients. Considering the small number of expired patients during the study period, it was impossible to study the relationship between different variables and patient mortality using a multivariate model and therefore we used univariate cox proportional hazard method to determine the relationship between major variables and death. P values < 0.05 were considered significant for all analyses.The present study was approved by ethics committee of Kermanshah University of Medical Sciences in 2009. After complete follow-up of patients till next event  we deleted all identifiers such as name, family name and father’s name.A total of 581 patients were referred to Imam Ali Center for CR from 2001 to 2008. Out of these patients, 504 completed the program; however, five patients were excluded from the study because of missing demographic data. Thus, a total of 499 patients were analyzed, consisting of 383 men and 116 women.The men and women were not significantly different in terms of mean age; however, the number of non-smokers, the illiterate, and patients with hypertension and diabetes were significantly higher among women . The majA comparison of risk factors and exercise capacity before and after rehabilitation indicated that all anthropometric measurements, systolic and diastolic blood pressure, blood lipids (except HDL), depression, anxiety, and exercise capacity improved after rehabilitation program  . This imOut of 499 patients referred for rehabilitation, 40 patients were readmitted to hospital for cardiac reasons; one patient was readmitted prior to initiation of rehab program, and was therefore excluded from the analysis. In the present study, factors of hypertension, smoking, education level, age, depression, stress, and marital status were not related to readmission . On the After a maximal follow-up period of 6.3 years , only eight patients expired , consisting of seven men and one woman. Among these, six patients were referred to the CR center following CABG/PCA. None of the variables in our study were significantly related to survival rate in the univariate analysis.The present study indicated that CR in combination with other interventions can efficiently improve the modifiable cardiovascular risk factors, except HDL. Furthermore, it was indicated that history of diabetes and female sex are two risk factors for readmission in patients referred for CR.Previous studies have indicated different results for the effect of comprehensive CR on mean blood lipids values. While some clinical trials have suggested that rehabilitation reduces total cholesterol effectively -10, otheSeveral points must be made about the anthropometric changes. In the present study, all anthropometric measurements  improved. Although relatively small (about 2%), the changes were statistically significant. As a matter of fact, many CR programs integrate weight control and thus it is expected that patients lose 10% weight (1-2 pounds per week) over a six-month period . HoweverOur study showed that CR has an impressive blood pressure–lowering effect: 11.3 mmHg for systolic and 6.0 mmHg for diastolic blood pressure. This study confirms the findings of previous studies that CR reduces both systolic and diastolic blood pressure , 22. A mAn important finding of the present study is the improved exercise capacity by 25%. After cardiac events, the METs level has been a shown to be a significant predictor of final prognosis of patients . ImproveThe present study shows an improvement in depression and anxiety following CR program which is in line with findings of previous studies , 31, 32.We also studied the factors related to readmission of patients after completion of CR program. Numerous studies have dealt with the effect of CR on readmission -36. It sThe survival rate was 97.5% in the present study. As a matter of fact, although previous studies have yielded controversial results regarding the effect of CR on survival rate in patients with cardiac events, most recent studies suggest a positive role for CR in terms of reducing mortality , 41. SinThe present study is the largest study conducted in western Iran, where the only CR center covers Kermanshah and its neighboring provinces, thus its findings are of immense value. Nonetheless, due to the short duration of follow-up and the low incidence of outcomes, it cannot identify the influential factors, which require further studies with longer durations of follow-up. On the other hand, we were unable to control the treatments that patients received during rehabilitation (which were often changed by physicians) and include them in our analysis. We are not able to determine the exact contribution of changes in medication in the observed improvements. In addition, because of no control group one may discuss that the observed improvement in risk factors might be the effect of factors other rather than CR. Prospective studies with inclusion of control group may circumvent this problem to a large extent. In addition, due to the small number of cases for some variables (e.g. active smokers among women), some of the statistical tests did not have sufficient power.In spite of the low popularity of CR programs among cardiologists in countries like Iran, such programs can efficiently reduce cardiovascular risk factors and improve exercise capacity in patients with heart disease. The outcomes of these programs in Imam Ali CR center in Kermanshah are comparable to CR programs in other centers. Such findings are in line with other studies to show that cardiologists’ fears are not rational. Though not certainly, we can believe that CR plays an important role in reducing the risk factors of CVD. History of diabetes as well as being female both increased the risk of readmission for cardiac reasons.