Casual blood pressure measurements have been extensively questioned over the lastfive decades. A significant percentage of patients have different blood pressurereadings when examined in the office or outside it. For this reason, a change inthe paradigm of the best manner to assess blood pressure has been observed. Themethod that has been most widely used is the Ambulatory Blood PressureMonitoring - ABPM. The method allows recording blood pressure measures in 24hours and evaluating various parameters such as mean BP, pressure loads, areasunder the curve, variations between daytime and nighttime, pulse pressurevariability etc. Blood pressure measurements obtained by ABPM are bettercorrelated, for example, with the risks of hypertension. The main indicationsfor ABPM are: suspected white coat hypertension and masked hypertension,evaluation of the efficacy of the antihypertensive therapy in 24 hours, andevaluation of symptoms. There is increasing evidence that the use of ABPM hascontributed to the assessment of blood pressure behaviors, establishment ofdiagnoses, prognosis and the efficacy of antihypertensive therapy. There is nodoubt that the study of 24-hour blood pressure behavior and its variations byABPM has brought more light and less darkness to the field, which justifies thetitle of this review. However, the value of casual blood pressure has beenquestioned in all these contexts in the last five decades.Since Riva-Roc ci2 it has been known that a significantpercentage of patients have higher blood pressure measures when they are taken inthe clinic setting than at home. In addition, blood pressure measures taken bydifferent observers - the patient, the physician, or the nurse - are also different,particularly when taken by the physician, who obtains the highestmeasures.4 This may lead to erroneous blood pressure readings,incorrect diagnosis and inappropriate management of the disease.6Since the study published by Ai man & Goldshi ne in 1940,11These aspects have changed the paradigm of the best method to assess blood pressurebehavior. The ambulatory blood pressure monitoring - ABPM is the method of choicefor 24 hour-blood pressure monitoring considering its advantages established inprevious reviews and guidelines.12This is especially due to advances in the techniques for 24-blood pressure monitoringand use of state-of-the-art equipment, which have been more appropriate, easier touse, relatively low cost, validated by strict international protocols, automatic,and electronically sophisticated, offering reliable performance.15Another reason for the increasing use of ABPM is the evidence that blood pressurereadings obtained by this method are more correlated with the effects ofhypertension, as compared with others.16 demonstrated the benefits of ABPM, and theattractive possibility of measuring blood pressure during patients' dailyactivities.In the 60's decade (i.e. five decades ago), Kain et al.17According to a search performed on MEDLINE database on May 11, 2015, since 2001,more than 2000 articles have been published every five years, showing theimportance of this revolutionary method in the establishment of diagnosis andprognosis of patients with altered blood pressure, and in the assessment of theantihypertensive therapy. The first study, published in 1962, was crucial fordemonstrating the assessment of 24-hour blood pressure without an observer,using a semi-automatic method.The use of ABPM has been consolidated in Brazil, similarly to what has occurredin the world. In 1982, Prof. Mauricio Wajngarten and colleagues presented, forthe first time, a 24-hour blood pressure recording in the Brazilian Congress ofCardiology .Programa Nacionalde Atualização em MAPA e Hipertensão , an on-site course, run by the authorsin more than 150 editions from 1996. The program has been run by the CorporateUniversity of the Brazilian Society of Cardiology since 2011, as one of thestrategies of distance education in cardiology.The use of ABPM has spread in our community by means of courses offeredthroughout the country. One example was the PRONAM - MAPA -Monitorização Ambulatorial da PressãoArterial (ABPM - Ambulatory Blood Pressure Monitoring) werepublished in 1995, 1998, 2004, 2007 and 2014. One of them was translated toSpanish and offered in Spanish-speaking countries in 2001.Besides, under our supervision and with the contribution of specialists in thefield, five editions of the book 22The Brazilian Societies of Cardiology, Hypertension and Nephrology have publishedguidelines on ABPM since 1993.25 including in children and adolescents26, have contributed to a broad,consistent use of the method.Additionally, international guidelines that regulated the  use of ABPM,27Nowadays, it is possible to monitor blood pressure measures during 24-hourperiods or longer, with assessment of hemodynamic parameters that reflect bloodpressure fluctuations: mean systolic and diastolic blood pressures, pressureoverload, areas under the curve, blood pressure changes between sleep andwakefulness, blood pressure variability, pulse pressure, among others. Thesedata may be represented in an analytical summary or graphics showing thevariability of blood pressure by time.Therefore, the use of ABPM has considerably increased. This is explained by thefact that the measures obtained by ABPM better reflect blood pressure behavior.Also, the development of more comfortable, reliable, safer devices significantlydecreased the limitations for the routine use of the method. The increasing use of ABPM in clinical practice may increase, since healthinsurance plans from all over the world, probably motivated by these data, haveadded ABPM to the list of exams considered as 'useful' and acceptable to beperformed.22 are described in The indications, advantages and limitations of ABPM, according to the V Brazilianguidelines for the use of ABPM28 In 2011,the National Institute for Health and Care Excellence (NICE) recommended the useof ABPM for all individuals with blood pressure ≥ 140/ 90 mm Hg, measuredat the physician's office, for considering it a cost-effectiveprocedure29. Thisrecommendation allows the diagnosis of white coat hypertension, with costsavings, according to a study that used a cost-effectiveness analysis, based onthe probabilistic Markov model.30 However, patients with marked hypertension are not includedin NICE recommendation, since they are normotensive in the physician's office.This situation tends to be solved as the costs of the ABPM decreases, and theexam may be indicated for hypertensive and normotensive patients.31With respect to the indication of ABPM, it is worth mentioning that in 2001,i.e., more than one decade ago, the Centers for Medicare and Medcaid Servicesrecommended the reimbursement of the exam cost for patients with suspected whitecoat hypertension.22 and international27 guidelines. In general, themain objective of using ABPM is based on the decision whether or not to treatthe patient on the basis of his/her blood pressure measures. Considering thatthe beginning of the antihypertensive therapy will be based on blood pressuremeasures, two types of error, undesirable and potentially harmful to the patientmay occur in case the values do not represent the real behavior of bloodpressure. First, if casual blood pressure, i.e. taken in the physician's office,overestimates the real value, therapy may be unnecessarily started; on the otherhand, if it underestimates the real value, the patient may be deprived of abeneficial therapy. Therefore, it is crucial to obtain reliable values, trulyrepresentative of blood pressure behavior.The use of ABPM in the assessment of blood pressure behaviors has spread and beencorroborated by national22Thanks to the use of ABPM, today we know that blood pressure values obtained inthe office setting may be higher, similar or lower than those obtained by themethod. From these differences, four diagnosis may be identified: normotension,hypertension, white coat hypertension (detected in the physician's office only),and masked hypertension (white coat normotension).22Normotension is characterized by normal blood pressure values in the office (<140/90 mmHg) and in 24-hour ABPM (≤ 125/75 mmHg), while hypertension ischaracterized by abnormal blood pressure values in the office (≥ 140/90mmHg) and in ABPM (≥ 130/85 mmHg).8 It occurs when abnormal blood pressure values are obtainedin the office (≥ 140/90 mm Hg) and normal values are obtained during theABPM (≤ 135/85 mm Hg).32Interestingly, in this case, there is a change from the diagnosis ofnormotension detected out of the office setting to the diagnosis of hypertensiondetected in the office. Since there are no pathognomonic signs of white coathypertension, the most common characteristics that help in the diagnosis are:elderly patients, women, pregnant women, non-smokers, patients with diagnosis ofstage 1 hypertension after blood pressure readings in the office, andindividuals without target-organ lesions.33 The attributable risk of white coat hypertension hasbeen extensively discussed.32Some studies have indicated that white coat hypertension has an intermediatecardiovascular risk, between normotension and hypertension, closer tonormotension though  bloodpressure, without changing the diagnosis from normotension to hypertension. Whenthe differences are higher than 20 and 10 mm Hg for systolic and diastolicpressure, respectively, the white coat effect is considered significant. Itoccurs in almost all individuals, at higher or lower degrees,38 It is definedby the presence of normal blood pressure values obtained in the office (<140/90 mmHg) and abnormal ABPM values (> 130/85 mm Hg).22 There is a change of diagnosisfrom hypertension during daily living to normotension in the office setting.Multivariate analysis studies have identified as associated risk factors: maskedhypertension, male sex, smoking, and body mass index.39 Masked hypertension is associated withincreased risk of cardiovascular morbidity and mortality. However, since officemeasures are normal, this risk may be underestimated.40 A meta-analysis of 12 studies, involving 4,884untreated subjects - 2,467 normotensive, 1,641 hypertensive subjects, and 776with masked hypertension - showed an association between masked hypertension andincreased risk of structural changes in left ventricle. The risk observed insubjects with masked hypertension is nearly twice as high as that amongnormotensive subjects  x 100 ÷ mean daytime pressure. Thus,according to this calculation of pressure reduction between daytime andnighttime, individuals may be classified as: dippers (≥ 10%), nondippers(< 10%), reverse dippers (≤ 0%) or extreme dippers (≥20%).49 Ben-Dov et al.50 followed 3957 for a mean of 6.5 years, andobserved that the mortality rate was higher in nondippers compared with dippers.Extreme dippers and dippers had similar risk. In another study,51 nondippers and reverse dippershad higher mortality risk. However, these individuals were older, and had ahigher prevalence of non-white subjects, smokers, diabetes, hypertension,coronary disease, congestive heart failure and renal failure. Therefore,although nondipping and reverse dipping pose a higher mortality risk, this isassociated with other cardiovascular risk factors.There are evidences that 24-hour blood pressure behavior, considering these bothperiods of the day, is important for the prognosis.53 increasedactivity during the night, sleep apnea, insulin resistance, endothelialdysfunction, or all of these factors may be involved.In an international database including 8,711 individuals from 10 popuIations,isolated nighttime hypertension, i.e., subjects with increased blood pressureduring sleep and normal awake blood pressure, was associated with increasedtotal mortality risk and cardiovascular events. The mechanisms of nighttimehypertension and its correlation with poor prognostic have not been elucidated.Increased sympathetic activity, reduced baroreceptor sensitivity or autonomicdysfunction, a decrease in sodium excretion during daytime, nocturnal sodiumexcretion,54 407 underwent ABPM duringsiesta (118 ± 58 minutes). Siesta had an effect on cardiac structuralparameters, and on systolic and diastolic pressure during daytime. Patients witha 0-5% reduction in arterial pressure had thicker interventricular septum andposterior wall as compared with those with a reduction greater than 5%.With respect to siesta, in the study by Gomes, Pierin and Mion,Then, the use of ABPM to assess the decrease in blood pressure and the meanvalues during sleep may provide important prognostic information for theclinical practice.55The 24-hour ABPM offers an adequate short-term variability evaluation ofbetween-measurement intervals not longer than 15 minutes. However, the methoddoes not assess more complex parameters of blood pressure variability, includingspectral index and analysis of baroreflex sensitivity, since it does not providea beat-by-beat recording of arterial pressure.57Longitudinal studies have shown that short-term variability may contribute tocardiovascular risk. Patients with increased arterial pressure variability havea higher risk for developing white coat hypertension of maskedhypertension.59More recently, a new index for short-term blood pressure variability has beenproposed - the average real variability (ARV) - which is a more reliablerepresentation of time series variability than standard deviation, and may beless sensitive to the relative low sampling frequency of the ABPM devices. Theresults suggest that the ARV adds prognostic value to the ABPM and may be usedin therapeutic approaches to control blood pressure variability. It has beenshown that 48 blood pressure readings in 24 hours were appropriate to calculatethe ARV without loss or prognostic information.60 and Boggia et al.61 highlight that blood pressurevariability on ABPM does not enhance the prediction of cardiovascular riskcompared to the mean blood pressure, particularly in low-risk individuals.Blood pressure variability is not routinely assessed in ABPM, since its normalvalues have not been established. It is still unknown whether a reduction inshort-term variability induced by the therapy is associated with a decrease inmortality and morbidity. Also, whether the antihypertensive therapy is indicatednot only to reduce mean 24-hour blood pressure, but also to stabilize bloodpressure and optimize cardiovascular protection. Dolan & O'Brien50 It should be mentioned, however, that this measure isstrongly influenced by an alerting reaction during measuring by the physician inthe office, especially concerning systolic arterial pressure. Thus, measurementsof pulse pressure in the office setting may be overestimated. Verdecchia etal.63 studied 2010patients using ABPM and, according to the tertile distribution of pulse pressuredistribution, the rate of total cardiovascular events was 1.19; 1.81 and 4.92,and that of fatal events was 0.11, 0.17 and 1.23. In these studies, patientswith pulse pressure by ABPM higher than 53 mmHg were considered of high risk.Prospective, well-designed studies using ABPM are needed to establish the realprospective meaning of pulse pressure in the general population.Pulse pressure has been considered an important prognostic marker, especially inpatients aged greater than 55 years.64 who showed a directrelationship between the areas and left ventricle mass. Thus, these areas may beused as a parameter in the assessment of blood pressure behavior andtarget-organ lesions.Areas under the pressure curve have been studied by Nobre and Mion,53The need of an adequate control of blood pressure in 24 hours iswell-established. The assessment and follow-up of hypertensive patients undertreatment, using ABPM, seems to be more efficient than officemeasurements.Nonetheless, two issues need to be considered. First, will the cost of ABPM forhypertension control in treated patients be higher compared with officemeasurements? Second, is there any evidence that treated patients withcontrolled hypertension based on ABPM information will have a better prognosis,expressed by lower morbidity and mortality rates?66 showed, in an elegant study published in 1997,involving 419 hypertensive patients receiving antihypertensive drug treatment(213 based on ABPM compared with 206 based on office measurements), that thecost of the use of ABPM was not higher than office measurements during the studyperiod. This was explained by the fact that individuals with white coathypertension were excluded from the group receiving antihypertensive therapy,the number of antihypertensive drugs was lower in the group monitored by ABPM,and the number of physician visits was lower in the ABPM group as compared withthe group monitored by office measurements. Cost analysis in both groupsrevealed that the costs of ABPM were outweighed by less intensive drug treatmentand fewer physician visits.Regarding the first issue, Staes sen et al.67 demonstrated in a prospective, randomizedstudy on 851 patients, that morbidity and mortality were lower in patients thatunderwent ABPM for the evaluation of antihypertensive treatment. A total of 1298patients were included in the study, and 851 of them concluded the 5-yearfollow-up period. Blood pressure control was assessed by office measurements in439 patients, and by ABPM in 412 patients. In the ABPM group, 20 primary events were registered,whereas in the other group, 35 primary events have occurred (p = 0.037). Inaddition, 22% of patients had white coat hypertension and were excluded from theantihypertensive drug treatment.With respect to the second issue, Schrader et al.68 showedthat ambulatory systolic pressure higher than 135 mmHg had a strong correlationwith the prognosis of patients treated with antihypertensive therapy,independently of blood pressure measured at the physician's office.Also, Cle ment et al In relation to the role of ABPM in the guidance of the antihypertensivetreatment, further studies to confirm and extend the information that the use ofthis method will lead to lower morbidity and mortality from arterialhypertension are needed.One practical issue that remains unsolved is: despite the above considerationsabout the method to assess blood pressure for 24 hours, how can ABPM bereasonably applied in the clinical practice?69 for the use of ABPM to identify blood pressurebehaviors , such asthe area under the pressure curve, possibility of evolution of the devices, anduse of the ABPM in specific populations should be incorporated to the clinicalpractice soon.Cheaper, more reliable and more comfortable monitors, in addition to studiesshowing the reduction in cardiovascular morbidity and mortality by the ABPM,used in the diagnosis and antihypertensive treatment, should be the near futureof 24-hour ABPM.Therefore, after these considerations, it can be stated that the ABPM isdefinitely indicated for suspected white coat hypertension, white coatnormotension or masked hypertension, and for establishing blood pressurebehavior as in hypertension during sleep. In addition, it is the best prognosticmarker in different types of blood pressure behavior, with relevant role in theassessment of the antihypertensive treatment.The studies on blood pressure behavior and its variations during people's dailyactivity have undoubtedly become less obscure, enlightened by the advent ofABPM, which completes five decades of clinical application and progression.Therefore, it is fair to say, in light of these data, that the title of thisreview: "Ambulatory blood pressure monitoring: five decades of moreenlightenment and less darkness" is clearly justified.We believe that, in consonance with the title of this review, the ABPM has shedlight to the understanding of blood pressure behaviors in the last five decades,drastically reducing the darkness of the diagnosis of hypertension and bloodpressure variations. The ABPM allowed the establishment of the prognosis ofpatients with altered blood pressure and the assessment of antihypertensive drugtreatment in use.


Hypertension is a major health issue, particularly in medically underserved populations that may suffer from poor health literacy, poverty, and limited access to healthcare resources. Management of the disease reduces the risk of adverse outcomes, such as cardiovascular or cerebrovascular events, vision impairment due to retinal damage, and renal failure. In addition to pharmacological therapy, lifestyle modifications such as diet and exercise are effective in managing hypertension. Current diet guidelines include the DASH diet, a low-fat and low-sodium diet that encourages high consumption of fruits and vegetables. While the diet is effective in controlling hypertension, adherence to the diet is poor and there are few applicable dietary alternatives, which is an issue that can arise from poor health literacy in at-risk populations. The purpose of this review is to outline the effect of specific dietary components, both positive and negative, when formulating a dietary approach to hypertension management that ultimately aims to improve patient adherence to the treatment, and achieve better control of hypertension. Hypertension is estimated by the Centers for Disease Control and Prevention to affect approximately 30% of adults in the United States . It is aHypertension to an extent correlates to the prevailing socioeconomic and geographical characteristics of a region, as well as to individual behavioral factors, and can pose a significant public health concern in populations defined by economic hardship, poverty, reduced health care access, low health literacy, and lack of resources due to geographic isolation –7. For eTreatment of hypertension centers on managing blood pressure within a target range while trying to minimize drug-associated side effects. Treatment protocol for hypertension is evolving, with guidelines set forth by the JNC 7 in 2004, and again modified in the JNC 8 in 2014. The JNC 7 defined blood pressure control as <140/90 mmHg, or <130/80 mmHg in those with kidney disease or diabetes, whereas the JNC 8 suggested new standards in patients ≥ 60 years of age without kidney disease or diabetes to <150/90 mmHg . To achiAmong the lifestyle and diet modifications that are recommended, one that is recommended to all persons with hypertension, regardless of pharmacological intervention, is the DASH (Dietary Approaches to Stop Hypertension) diet, a diet that advocates the consumption of fiber and potassium via fruits and vegetables, reduction in total and saturated fat via a reduction in meat and animal products, and intake of adequate protein via lean meat and low-fat dairy products instead of high fat or processed meat . This diCertain diets rich in fruits and vegetables, such as the vegetarian diet and the Mediterranean Diet, have demonstrated efficacy in controlling blood pressure . The mecPomegranate juice is rich in phytochemicals and polyphenols, which have antioxidant and anti-inflammatory functions that have been reported to promote cardiovascular health ,21. PomeCitrus fruits, such as oranges and grapefruits, have also demonstrated antihypertensive properties. A single-blind randomized crossover study of 22 healthy patients aged 18–59 showed that after drinking 500 ml/day of commercial citrus sinensis juice, both DBP and SBP decreased , while natural orange juice did not show significant effects . Citrus Garlic is a vegetable that has been investigated for its cardiovascular benefits. In addition to its antioxidant properties, the antihypertensive effects of garlic have been linked to its allicin content, a sulfur compound that can inhibit angiotensin II and promote vasodilation . A meta-Dairy products are major sources of protein and nutrition within vegetarian diets and the Mediterranean Diet, both of which have been shown to be effective in controlling blood pressure . The mecIn a study by Drouin-Chartier et al., 76 weight-stable adults with mild-to-moderate hypertension consumed three daily servings of dairy products or a control that was equivalent in macronutrient and sodium content during four-week treatment periods. The study demonstrated an association between dairy consumption and a significant decrease in ambulatory SBP in men , though no significant change in ambulatory DBP was observed . The observed effect on SBP was not significant in women. However, endothelial function, as measured by the reactive hyperemia index (RHI) significantly improved in both men and women consuming dairy compared to controls when adjusted for energy intake  . In the Spices, including chili peppers, cinnamon, black pepper, and turmeric, can also have antihypertensive effects. In addition to their flavor-enhancing qualities, these spices have been used for centuries worldwide as herbal medicines within the practice of traditional medicine, and have become the subjects of increased focus within the Western medical paradigm as possible adjunct therapies due to their wide therapeutic indices and minimal side effect profiles.Capsicum genus, and is a natural irritant to humans. The effects of capsaicin on blood pressure have been shown to vary depending on the amount ingested. Studies have indicated that ingestion of large quantities of capsaicin-rich peppers can induce a hypertensive crisis. The proposed explanation for this reaction is via a decreased release of calcitonin gene-related peptide (CGRP) from myocardial C fibers that are sensitive to capsaicin [Capsicum genus, including bell peppers and paprika, exert a strong inhibitory effect on Angiotensin Converting Enzyme (ACE). This research suggests that peppers of the Capsicum genus may be useful as dietary cofactors in hypertension management, and especially in ACE-dependent hypertension. A study performed by Ranilla et al. demonstrated that the ACE inhibitory activity significantly correlates with the total phenolic contents  but not with the antioxidant activity, with paprika and red peppers showing the highest ACE inhibition (92% and 84% respectively) [Capsaicin is the active component in red peppers, yellow peppers, paprika peppers, and other plants in the apsaicin ,32. Whilctively) . A similctively) .Cinnamon has been reported to reduce blood sugar in patients with diabetes, and studies have shown that agents that enhance insulin sensitivity or reduce circulating insulin levels also lower blood pressure. Cinnamon extracts have been shown in several studies to have antihypertensive and vasorelaxant effects in rats. In a study by Nyadjeu et al. acute intravenous administration of the MECZ  showed long-lasting decrease in blood pressure  in L-NAME-induced hypertensive rats . In anotBlack pepper is one of the most ubiquitous spices used in cuisine worldwide. The essential oils within black pepper have known antioxidant activity as well as the ability to inhibit ACE . Black pCurcumin, the active ingredient in turmeric, has many potential beneficial effects on blood pressure. It has been shown to inhibit hypertension-induced increase in myocardial cell diameter as well as significant inhibition in perivascular fibrosis in rat models, and could therefore be a therapeutic agent for heart failure, which can arise from chronic uncontrolled hypertension . CurcumiIn summary, when formulating an antihypertensive diet, certain spices can be helpful in the reduction and maintenance of blood pressure. Like garlic, these spices enhance flavor for greater palatability, and may help in lowering salt intake.Green tea is a commonly consumed beverage known for its widespread health benefits. Of particular interest is a group of polyphenols within green tea known as catechins, of which the key one is epigallocatechin gallate (EGCG). EGCG stimulates nitric oxide synthesis in endothelial cells to promote vasodilation and reduces synthesis of endothelin-1, a vasoconstrictor, to improve overall vascular function ,45. AddiIn a longitudinal population study by Tong et al. conducted on 1109 Chinese adults, green tea consumption was demonstrated to inversely correlate with changes in blood pressure over a five-year period in a dose-dependent manner . Among tOmega-3 fatty acids (n−3FAs) have been extensively studied for their cardiovascular health benefits. The major types of omega-3 fatty acids include eicosapentaenoic acid (EPA) and docosohexaenoic acid (DHA) found primarily in seafood and fish oil, and alpha-linolenic acid (ALA) found primarily in plant sources such as flaxseed and walnuts . Omega-3In the INTERMAP study, a population study of 4680 adults aged 40–59 from China, Japan, the United Kingdom, and the United States, the dietary n−3FA intake was studied to determine its effect on blood pressure. Participants were observed on two consecutive days at baseline, then two consecutive days three weeks later. The results showed an inverse correlation among all participants between dietary n−3FA intake and both SBP and DBP after three weeks (>1.9 g/day n−3FA: −0.55 mmHg SBP and −0.57 mmHg DBP), with ALA, DHA, and EPA all demonstrating antihypertensive effects . In a loSeveral trace elements, such as copper and zinc, play an important role in maintaining blood pressure. The exact method is not clear but abnormal copper and zinc metabolism have been implicated as risk factors for development of hypertension and vascular disease –55.Serum calcium levels have been shown to be associated with cardiovascular disease (CVD) , but theMagnesium affects blood pressure by modulating vascular tone and reactivity. Hypomagnesemia is associated with diabetes and metabolic syndrome, with magnesium playing a major role is regulation of blood pressure . MagnesiFructose is a sugar monomer that can exist in its free monomer form, bound to glucose as a component of the sucrose dimer, and in high levels in sweeteners such as high-fructose corn syrup (HFCS). Common dietary sources of fructose include fruits and sugar-sweetened beverages, as well as sources of sucrose, which is commonly processed into table sugar from sugarcane. It has been a source of dietary controversy, with excess consumption being linked to metabolic disorders . In the Demonstrating this link between fructose consumption and hypertension within human populations, however, has been controversial. Some studies have been able to demonstrate a link. In a cross-sectional study by Jalal et al. of 4528 adults, 1754 of whom were prehypertensive or had Stage 1 or Stage 2 hypertension, fructose consumption was determined by dietary survey and its relation to blood pressure was assessed. The median fructose consumption in this study was 74 g/day, with consumption of at least 74 g/day demonstrating an increased risk of elevated blood pressure  . In an IIn contrast, other studies have not demonstrated a link between fructose consumption and hypertension. In one study of 267 adults, subjects were fed sugar-sweetened milk containing fructose, glucose, sucrose, or HFCS, for 10 weeks. This study found no significant changes in blood pressure or uric acid levels between groups. However, this study administered fructose in levels associated with the 50th percentile population consumption level , and did not test the extremes of fructose consumption that could be occurring within the standard American diet ,72. AnotSodium has long been implicated in the development and progression of hypertension. However, the mechanisms by which it may contribute to hypertension are not fully clear. Sodium does play a major role in fluid balance, and dysregulation in this process can contribute to excess fluid retention, resulting in hypertension. Additionally, sodium can also induce the production of vasoconstrictive prostaglandins. This is a result of the action of sodium on renal medullary interstitial cells, promoting NFκB signaling and COX-2 expression and leading to increased levels of PGE2 .Dietary sodium restriction is one of the foundations of antihypertensive diets. In a study of 412 adults that were prehypertensive or mildly hypertensive, reductions in dietary sodium were associated with decreases in SBP, with the greatest decreases associated with the lowest sodium intakes. Compared to a high-sodium control diet, a low-sodium (≤65 mmol/day) DASH diet was associated with a decrease in SBP of 11.5 mmHg in patients with hypertension, and a decrease in SBP of 7.1 mmHg in patients without hypertension . In a meThe DASH diet is a safe and powerful tool in the management of hypertension, and patient education by the physician and other health professionals can play a major role in encouraging adherence to the diet ,15. In c


Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross-sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital. Sociodemographic details, blood pressure, urine albumin : creatinine ratio, and adherence using the MMAS-8 questionnaire were noted. Independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. Results. 85 subjects were evaluated. Mean age was 42.4 (SD ± 12.2) years, with a male : female ratio of 1.9 : 1. Fifty-five patients (64.7%) had uncontrolled hypertension (BP ≥ 130/80 mmHg). On univariate analysis, male sex , higher levels of proteinuria (p = 0.042), and nonadherence to antihypertensives  were associated with uncontrolled hypertension. On logistic regression analysis, male sex  and nonadherence  were independently associated with uncontrolled hypertension. Conclusion. Factors associated with poor blood pressure control in this cohort were male sex and nonadherence to antihypertensives. Emphasis on adherence to antihypertensive therapy must be pursued within this population. Renal transplantation is the preferred therapy for patients with end stage renal disease, with improved quality of life and survival compared to dialysis. The prevalence of hypertension remains high at 80–90% , despiteTreatment goals of hypertension among renal transplant recipients are more stringent than in the general hypertensive population. KDIGO  guidelines recommend target blood pressure levels of <130/80 mmHg . In KenyThe consequences of uncontrolled hypertension in this population include increased cardiovascular mortality and morbidity. Cardiovascular disease is the leading cause of mortality among renal transplant recipients, more than mortality from infection and malignancy combined . In addiNonadherence to antihypertensive treatment is an important and often unrecognized risk factor that contributes to reduced control of blood pressure. The WHO estimates that up to 50% of patients with chronic illnesses are nonadherent to long-term therapy .p = 0.028) [Indeed, nonadherence to antihypertensive medications as determined by the 8-item Morisky Medication Adherence scale (MMAS-8) was found to be predictive of elevated systolic and diastolic pressures among patients in Portugal [= 0.028) . Other p= 0.028) –13.Uncontrolled hypertension among our renal transplant recipients is common. We thus sought to determine demographic, social, and clinical factors associated with poor blood pressure control. We also sought to determine adherence rates to antihypertensive therapy, and its relation to blood pressure control.It is cross-sectional.Kenyatta National Hospital (KNH) Renal Unit, Nairobi, Kenya, is a national referral and teaching hospital with a rapidly growing renal transplant program.The entire cohort of renal transplant recipients were hypertensive, more than 2 months posttransplant, 18 years of age and above, and not on dialysis due to nonfunctional grafts and gave informed written consent.To determine factors associated with poor blood pressure control among renal transplant recipients. or systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. Controlled blood pressure was defined as BP < 130/80 mmHg as per KDIGO guidelines [Hypertension was defined as either the use of antihypertensive therapyLevel of adherence to antihypertensive medications was categorized as high score 8), medium (score 6-7), or low (score < 6). Medium and low adherence levels were both considered nonadherent [, medium Informed written consent was obtained prior to patient enrolment into the study. Participants' sociodemographic history and clinical history were then recorded in a predesigned questionnaire. Blood pressure measurement  and anthSerum creatinine was determined using the Mindray Clinical Chemistry Analyzer. Urine albumin : creatinine ratio measurement was done using the Clinitek Microalbumin Analyzer.Daily internal quality control was carried out before sample analysis to validate the results obtained. External quality assessment was provided by Huqas company, a local proficiency testing provider.Statistical analysis was carried out using Statistical Package for Social Sciences (SPSS) version 17.0, .t-test was used to compare means of continuous variables .Association between uncontrolled hypertension and categorical variables  was done using the Chi-square test of association or Fischer's exact test for small numbers, as appropriate. Student's Estimates of the risks of uncontrolled hypertension were presented as odds ratios. The independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. All the statistical tests were performed at 5% level of significance.Ethical approval was given by the KNH/UoN Ethics and Research Committee, and all procedures were in accordance with the institutional ethical standards. Patients gave informed written consent. Confidentiality of patient records was maintained at all times.μmol/L. Microalbuminuria was noted in 42.4% of patients, and 10.5% had macroalbuminuria. Mean BMI was 24.8 (±4.4) kg/m2. 55 patients  had uncontrolled hypertension. Mean systolic blood pressure was 132.5 (±17.3) mmHg and mean diastolic blood pressure was 82.8 (±13.1) mmHg. Mean number of antihypertensive medications taken was 2.1 (±0.9).All 85 eligible renal transplant recipients who gave consent were enrolled. Baseline characteristics are described in Two-thirds of the patients (67.1%) were nonadherent to antihypertensive medication. The mean MMAS-8 score was 6.8. Of the nonadherent patients, about a quarter (23.5%) forgot to take their medications.p = 0.006), higher levels of proteinuria (p = 0.042), and nonadherence to antihypertensive medication  were associated with uncontrolled hypertension. Association between uncontrolled hypertension and other variables including number of antihypertensive medications, recipient and donor age, GFR, and cyclosporine use did not reach statistical significance (p = 0.034) and nonadherence to antihypertensives   .We found a high prevalence of uncontrolled hypertension among our renal transplant recipients. This is significant because cardiovascular disease remains the leading cause of mortality among renal transplant recipients . Our purThe study population was relatively young, mean age of 42.4 (±12.2) years. This is about a decade younger than that noted in studies carried out in developed countries. Mason et al. found a mean age of 50.2 years among renal transplant recipients in UK . ChronicMale : female ratio was 1.9 : 1. The male predominance is a reflection of the gender distribution of patients with chronic kidney disease attending nephrology clinics locally. Males may be more economically advantaged compared to their female counterparts, enabling them to access the relatively expensive renal transplantation services.64.7% of our study participants did not achieve target blood pressure levels. This figure is higher than that found among renal transplant recipients in Jordan  and in UOnly a third of our study population was found to be fully adherent to their antihypertensive medications. Our adherence level was comparable to that found by Achieng' et al. in a study done among patients with hypertension attending medical outpatient clinics at the Kenyatta National Hospital . 31.8% oMale sex was independently associated with uncontrolled hypertension in our study. In an analysis of data from the third National Health and Nutrition Survey, Hyman and Pavlik found male sex to be independently associated with uncontrolled blood pressure among 16,095 adults in the US . This seNonadherence to antihypertensive medications was independently associated with poor blood pressure control among our study participants. Oliveira-Filho et al. in Portugal also demonstrated that nonadherence as measured by the same tool, the MMAS-8, was predictive of elevated systolic and diastolic pressures among patients with hypertension [a = 0.83 versus 0.63) [Our study had several strengths. It is, to our knowledge, the first study in Sub-Saharan Africa to explore the factors linked with uncontrolled hypertension among renal transplant recipients. Secondly, the tool used for assessment of adherence was the MMAS-8 questionnaire, validated for use in different cultural settings and with a higher reliability than its predecessor, the MMAS-4 (us 0.63) .On the other hand, we faced several limitations. As the renal transplant population is still growing, we were limited in terms of participant numbers, as this is a limited sized cohort of patients. However, all eligible patients were included. In addition, this was a cross-sectional study, and hence causality cannot be inferred. Finally, consequences of the poor blood pressure control were not studied.Nevertheless, our study was able to explore the possible factors that may be associated with uncontrolled hypertension in this unique population of patients. We were further able to determine the level of adherence to antihypertensive medications and possible reasons for nonadherence.There is a high rate of uncontrolled hypertension among local renal transplant recipients. It was noted that adherence to antihypertensive medications was low. Predictors of poor blood pressure control were male sex and nonadherence to antihypertensive therapy.We thus recommend intensification of blood pressure control among local renal transplant recipients. Studies to look into the patient-perceived reasons for nonadherence would be prudent. Strategies to improve levels of adherence to antihypertensive medications among renal transplant recipients should also be put in place.Finally, we recommend follow-up analytical studies as the renal transplant recipient population grows, to look further into the associations alluded to in this cross-sectional study.


The number of centenarians is projected to rise rapidly. However, knowledge of evidence-based health care in this group is still poor. Hypertension is the most common condition that leads to multiple organ complications, disability, and premature death. No guidelines for the management of high blood pressure (BP) in centenarians are available. We have performed a cross-sectional study to characterize clinical and functional state of Polish centenarians, with a special focus on BP. The study comprised 86 consecutive 100.9 ± 1.2 years old (mean ± SD) subjects (70 women and 16 men). The assessment included structured interview, physical examination, geriatric functional assessment, resting electrocardiography, and blood and urine sampling. The subjects were followed-up on the phone. Subjects who survived 180 days (83 %) as compared to non-survivors had higher systolic BP (SBP), diastolic BP (DPB), mean arterial pressure (MAP), pulse pressure (PP), higher mini-mental state examination, Barthel Index of Activities of Daily Living and Lawton Instrumental Activities of Daily Living Scale scores, higher serum albumin and calcium levels, and total iron-binding capacity, while lower serum creatinine, cystatin C, folate, and C-reactive protein levels. SBP ≥140 mm Hg, DBP ≥90 mm Hg, MAP ≥100 mm Hg, and PP ≥40 mm Hg were associated with higher 180-day survival probability. Results suggest that mildly elevated blood pressure is a marker for better health status in Polish centenarians. The number of oldest-old people, including centenarians, is projected to rise rapidly over the next decades  subjects (70 women and 16 men).The assessment included structured interview, physical examination, geriatric functional assessment, resting electrocardiography, and blood and urine sampling. Resting BP was measured at both arms according to the standard protocol. If there was a difference between the arms, the higher value was taken for further analysis. Mean arterial pressure (MAP) was calculated as a sum of diastolic BP (DBP) and 1/3 of the difference between systolic BP (SBP) and DBP. Pulse pressure (PP) was calculated as a difference between SBP and DBP. Ankle-brachial index (ABI) was calculated according to the recommendations of the American Heart Association, with ABI <0.9 indicating lower extremity peripheral arterial disease , iron, and total iron-binding capacity were measured only in 49 subjects. CKD-EPI creatinine-cystatin C equation  formula , serum levels of albumin, glucose, insulin, bilirubin, creatinine, folate, vitamin BThe study subjects were followed up on the phone for at least 180 days after the examination.Two subjects refused their consent for blood sampling.U test was used to compare the data between 180-day survivors and non-survivors. P < 0.05 was considered statistically significant.The obtained data were analyzed using STATISTICA software version 10 . Linear and nonlinear regression models were used to assess relationships between selected variables. The Kaplan-Meier method was used to estimate survival probability in subgroups of centenarians distinguished on the basis of different values of the analyzed variables, while differences between these subgroups were assessed with the Wilcoxon-Gehan statistic. The nonparametric Spearman’s rank correlation coefficient was used to assess relationships between functional measures and variables analyzed in the study. Nonparametric Mann-Whitney The study protocol was approved by the Bioethical Committee of the Medical University of Silesia. Written informed consent was obtained from each subject and/or their carer after the aim of the study; protocol and risks were explained.12, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, thyrotropin, sodium, potassium, phosphorus (inorganic) and iron, as well as in serum alanine aminotransferase activity, eGFR, ABI or Romhilt-Estes ECG scores were found. Individuals with SBP ≥140 mm Hg had higher 180-day survival probability (p = 0.007), similar to those with DBP ≥90 mm Hg (p = 0.046), MAP ≥100 mm Hg (p = 0.011), and PP ≥40 mm Hg (p < 0.001) , while SBP ≥150 mm Hg was not associated with significantly higher 180-day survival probability (p = 0.068). Inverted-U-shaped relationships, according to the second-degree polynomial pattern between MMSE score and SBP, Barthel Index and SBP, MMSE score and MAP, as well as Barthel Index and MAP were revealed , pain (78 %), and falls (77 %). The most frequent reported diseases were as follows: dementia 73 %), heart failure (65 %), and osteoarthritis (64 %). The majority of subjects (89 %) never smoked. Sixty-three percent of subjects used at least one antihypertensive drug. Characteristics of the group are presented in Table  %, heartHypertension is one of the most common medical conditions leading to multiple cardiovascular complications, disability, and premature death  (Briasoulis et al. Limitations of the presented study encompass low inclusion rate of candidates, causing the observation to be extended in time, a relatively small study group, single BP measurement, and incomplete number of laboratory tests. Telephone-documented 180-day survival defined the life span, whereas the progression of mental and functional disability associated with BP measurements in the surviving centenarians could not be determined due to the lack of the control assessment. Most of the difficulties resulted from the nature of this centenarian cohort. Nevertheless, the observation demonstrated that functional status has higher prognostic value for 180-day survival than any clinical measures, and BP at the level considered as mild hypertension is associated both with better functional status and higher short-term survival probability in Polish centenarians. As it was discussed in our previous paper (Szewieczek et al. Mildly elevated blood pressure is a marker for better health status in Polish centenarians.


Obstructive sleep apnea (OSA) is suggested as a potential risk factor of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism is still far from clear. The aim of this observational study was to investigate the influence of OSA-related hypoxia on severity of liver injury in patients with NAFLD.Consecutive patients with ultrasound-diagnosed NAFLD who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for biological profile measurements, and demographic data were collected. Subjects were divided into control, moderate, and severe groups.2). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, gamma glutamyltransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose, and high-sensitivity C-reactive protein significantly increased with the aggravation of OSA. In multivariate analysis, oxygen desaturation index was the major contributing factor for elevated ALT , average O2 saturation was the major independent predictor of elevated AST .A total of 85 subjects with 73 males and 12 females were included (mean age, 44.67 ± 1.28 years; mean body mass index, 27.28 ± 0.33 kg/mOSA-related hypoxia was independently associated with the biochemical evidence of liver injury in the presence of NAFLD. Obstructive sleep apnea (OSA) is characterized by repetitive episodes of partial or complete obstruction of the upper airway during sleep, resulting in sleep fragmentation and hypoxemia. The prevalence of OSA among the adult population is high, being 2 to 4 % in the general population and 35 to 45 % in obese individuals , 2. TherNAFLD represents a wide spectrum of liver disorders from isolated steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is a common cause of chronic liver disease, affecting 30 % of the general adult population and up to 60 to 70 % of diabetic and obese patients . Liver bIn C57BL/6 J mice with diet-induced obesity (DIO), intermittent hypoxia for 6 months caused significant increase in serum transaminases, inflammation, and fibrosis. However, the DIO mice without hypoxia showed only hepatic steatosis but no histological evidence of steatohepatitis . Given tAll consecutive patients who presented to our sleep laboratory because of symptoms of sleep apnea between December 2012 and October 2013 were included in the study. We selected subjects with ultrasound-diagnosed NAFLD. All patients completed an Epworth sleepiness scale (ESS) and a detailed questionnaire on sleep symptoms, history of alcohol consumption and smoking, medical history, and medications. Individuals with hepatitis virus B and/or C were excluded by systematic history taking and blood tests. Other exclusion criteria included known diagnosis of OSA and use of CPAP within the prior 3 months, excess alcohol intake , current use of hepatotoxic drugs and other causes of chronic liver disease, severe cardiopulmonary chronic disease, or acute inflammatory disease. Figure 2). Waist circumference was measured at a level midway between the lower costal margin and the iliac crest. Blood pressure was gauged by a standard mercury sphygmomanometer on the right arm with the participants in a sitting position after 5 min of rest—the average of two measurements, with 1-min interval, was considered. Fasting blood was taken in the morning for the measurement of serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (Alk Phos), total bilirubin (T. bilirubin), gamma glutamyltransferase (GGT), and lipid profile comprising total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG). All blood samples were analyzed using the Modular P800 autoanalyzer . High-sensitivity C-reactive protein (hs-CRP) was measured with a BNII nephelometer . The value of mean arterial pressure (MAP) was calculated by the following equation: diastolic blood pressure + 1/3 (systolic blood pressure − diastolic blood pressure).Body weight and height were measured in bare feet and light clothing in the morning with the same equipments. Body mass index (BMI) was calculated by dividing body weight to height square (kg/m2) ≥4 % per hour of total sleep time. Polysomnographical parameters including lowest O2 saturation (LaSO2), mean nocturnal oxygen saturation (average SpO2), and the percentage of sleep time with SpO2 < 90 % (T90 %) were also recorded. OSA was defined as absent when AHI was <10 events/h, moderate when it was 10–50 events/h, and severe when it was ≥50 events/h [Overnight polysomnography  was performed with recording of the following parameters: electroencephalography, electrooculography, electromyography, airflow using nasal and oral thermistors, respiratory effort using thoracic and abdominal impedance belts, arterial oxyhemoglobin saturation using pulse oximetry, snoring using tracheal microphone, and body position using a sensor. The polysomnography started, on average, at 22:00 hours (lights off) and finished around 06:00 hours (lights on). Sleep staging was scored according to the criteria of American Academy of Sleep Medicine (AASM) published in 2007 . Apnea wevents/h .Abdominal ultrasound was performed using a 3.5 MHz transducer  by an experienced radiologist who was unaware of the aim of the study and blinded to the laboratory values. Both subcostal and intercostal scanning was done. Images were captured in a standard fashion with the subject in the supine position and with the right arm raised above the head. Normal liver parenchyma was seen as solid homogenous echo texture, which was midway between the renal cortex and pancreatic echogenicity Fig. . Fatty lp value was <0.05.Statistical analyses were performed using SPSS v 17.0 . All variables were tested for normal distribution before analysis. Data were expressed as mean ± SD, median (interquartile range), and number (percentage) for normally distributed, skewed, and categorical data, respectively. Normally distributed continuous variables were compared by using one-way ANOVA for multiple-group comparison. Non-normally distributed continuous variables were compared by using Kruskal–Wallis H (K) for multiple-group comparison. Chi-square test or Fisher’s exact test was performed for categorical variables. Correlations between variables were explored using the Spearman rank test. All descriptive data not in normal distribution were ln-transformed before multivariate analysis. Multiple linear regression analysis was performed to determine the independent predictors of ALT and AST. A stepwise selection method was used in the multivariate analysis. Differences were considered significant if the 2  and mean age was 44.67 ± 1.28 years . OSA (AHI ≥10 events/h) found in 71 (83.5 %) patients, was moderate in 36 patients, and severe (AHI ≥50 events/h) in 35 patients.Eighty-five subjects with ultrasound-diagnosed NAFLD, including 73 males and 12 females, were finally included . There were no significant differences among the three groups for age, current smoking, sex ratio, medications, or ESS score.The anthropometric and polysomnographic characteristics of the patients are presented in Table p = 0.001, p = 0.005, p = 0.000, p = 0.000, and p = 0.001, respectively). In addition, a statistically significant positive association with the fasting glucose as well as negative association with HDL-C was seen. ALT increased from 19.00 to 54.00 U/L with OSA severity (p = 0.000). AST increased from 21.50 to 36.00 U/L with OSA severity (p = 0.001). A statistically significant increase in the prevalence of elevated serum aminotransferases was observed from controls to severe OSA group.The metabolic and liver function parameters are reported in Table 2 . Hs-CRP, as an expression of inflammation, was also correlated with ALT and AST . Stepwise multiple linear regression analyses were used to determine predictors of ALT and AST. These analyses identified ln ODI , ln TG  and age  as independent explanatory variables for ln ALT , ln TG  and ln AHI  for ln AST . Nocturnal hypoxia was associated with the elevation of liver enzymes, independent of a variety of relevant factors such as age, gender, obesity, inflammation, blood pressure, serum glucose, and lipid profile, which suggested that nocturnal hypoxia might be a risk factor in the progression of NAFLD.2, lower average SpO2, higher AHI, and higher ALT/AST compared with non-NASH controls. Multivariate analysis showed that the LaSO2 was independently associated with histological NASH. Polotsky et al. [Several studies evaluating the relationship between OSA and NAFLD have been conducted, and the results were conflicting. A study including 109 OSA patients showed that ALT and AST levels significantly correlated with the severity of nocturnal hypoxia, but not with the AHI or metabolic syndrome features. On regression analysis, T90 % remained a stronger predictor of the variance in ALT . It shouy et al. . Howevery et al.  found thy et al.  evaluatey et al. . Factors2 were the determinant factors predicted serum liver enzyme levels after controlling for confounders. At the same time, our results showed that liver injury was better predicted by markers of oxygen desaturation than by AHI, which was consistent with previous reports [We focused on patients with ultrasound-diagnosed NAFLD and demonstrated that ODI and average SpO reports , 7, 9. T reports . This hy reports . In anot reports .Conflicting results were also observed in the effect of CPAP treatment on NAFLD. Chin et al.  observedα1-anti-trypsin deficiency, and auto-immune hepatitis by medical history rather than blood test. Furthermore, confounding factors such as BMI and waist circumference were not matched for each group, and multivariate analysis was performed to overcome the limitation. Another potential limitation is the use of serum aminotransferases as a surrogate marker of liver injury. Various other noninvasive methods to assess NAFLD have been used, including Steato Test for hepatic steatosis, Nash Test for NASH, and Fibro Test for liver fibrosis. Although liver biopsy is the best way to confirm the diagnosis of NAFLD and to determine the severity of this disease, it could not be widely performed for ethical reasons. However, previous studies have reported less than 10 % of nonalcoholic fatty liver and as many as 100 % of NASH patients with elevated serum aminotransferases [There are several limitations of our study that will require further evaluation. Its cross-sectional design allowed us to support a correlation but not a causative relationship between OSA and the severity of NAFLD. Second, the sample size of the present study was relatively small, and it could not be analyzed separately by sex since female subjects were few. In addition, we excluded other rare forms of chronic liver disease such as Wilson disease, sferases , 30, andsferases , 19, 27.In conclusion, our study showed that nocturnal hypoxia in patients with OSA was a risk factor of liver injury in the presence of NAFLD. For a better understanding of this complex relationship, further randomized controlled studies including patients with histologically proven NAFLD and PSG defined OSA are needed to establish whether there is an independent association between them.


Intentional lowering of blood pressure helps to produce a desirably clean surgical field. Many drugs can be used to induce a hypotensive state, but due to their high potency and rapid effect, drugs that more easily and safely control the induction of hypotension are desirable.To investigate the effects of premedication with oral clonidine on intraoperative bleeding and hemodynamic variables in patients undergoing cesarean sections.A total of 110 patients classified as American Society of Anesthesiologists (ASA) physical status I and II and who were scheduled for elective cesarean section under general anesthesia were enrolled. The patients were randomized to receive either oral clonidine (0.2 mg) or identical-looking placebo tablets 90 minutes before arriving at the operating room. Induction of anesthesia was performed by the same standard protocol in all patients. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were recorded before and after induction; immediately after intubation; 5, 10, and 15 minutes thereafter; at the time of extubation; and one hour after the operation. The surgeons were asked to rate the quality of the operative field on a four-point scale that ranged from mild (1) to abundant bleeding (2).Intraoperative SBP was lower in the clonidine group. After both intubation and extubation, the increases in SBP, DBP, and HR in clonidine-treated subjects were significantly less than the changes in the control patients. The amount of fentanyl given to control blood pressure and HR was significantly less in the clonidine group . The responses to the four-point scale indicated that intraoperative bleeding in the clonidine group was less than in the placebo group .Premedication with oral clonidine can improve the hemodynamic management of cesarean cases. Intentionally lowering blood pressure is used to produce a desirably clean surgical field. Anesthesiologists have suggested many drugs, including volatiles, propofol, and remifentanil, for inducing a hypotensive state. In resistant cases, labetalol, nitroglycerin, and other peripherally acting vasodilators have been used to supplement the hypotensive action of first-line agents . HoweverWe conducted a randomized, double-blind, placebo-controlled study to investigate the effects of oral clonidine premedication on intraoperative bleeding and hemodynamic variables in patients undergoing cesarean section.At the time of this study, in the maternity wing of Sadi Hospital, 147 patients were classified as physical status I and II under the American Society of Anesthesiologists system and were scheduled for elective cesarean section under general anaesthesia. Of these patients, 110 patients responded that they were interested in participating in the study and were enrolled. After informed consent was obtained, the patients were randomized to receive either oral clonidine (0.2 mg) or identical-looking placebo tablets 90 minutes before arrival to the operating room. The randomization was performed by the hospital pharmacy by using a table of random numbers, and the patients, investigators, surgeons, and nurses involved in the patients’ care were blind to the assignment groups. Exclusion criteria were significant heart disease that contraindicated the use of controlled hypotension, medically important liver or kidney dysfunction, known allergies to clonidine, SBP > 160 mmHg, DBP > 90 mmHg, or pulse rate < 50 beats/min at the time of the preanesthetic visit. The institutional research ethics committee approved the study protocol.Patients were pretreated with dextrose-free crystalloids (500–700 mL) prior to induction. Induction of anesthesia was performed with thiopental 4 to 5 mg/kg and succinylcholine (1 to 1.5 mg/kg). Following tracheal intubation, anesthesia was maintained with 0.5% halothane delivered in a gas mixture of N2O (50%) and O2 (50%). After returning to spontaneous breathing, 0.5 mg/kg of atracurium was administered. Controlled mechanical ventilation with an initial tidal volume of 10 mL/kg and respiratory frequency of 10 breaths /min was adjusted to maintain normocapnia. After delivery, we continued to apply the volatile agent  and administered 2 mg of morphine and 2 mg of midazolam, as well as increasing N2O concentration to 70%. Muscle relaxation was reversed with neostigmine (0.05 mg/kg) and atropine (0.02 mg/kg). Lactated Ringer’s solution was administered at a constant rate of 2 to 4 mL/kg/h using an infusion pump throughout the operation. The lowest MAP accepted was 60 mmHg. The desired control of MAP was attained with inspired concentration increments of halothane up to a maximum of 1 vol% as required. When it was unsuccessful, intravenous bolus of fentanyl (1 μg/kg) was administered. When hypotension occurred (MAP < 60 mmHg), fluid challenge (Ringer’s solution 10 mL/kg) and intravenous ephedrine (10 mg increments) were administered. During the operation, ECG monitoring, pulse oximetry, and capnometry were performed continuously.SBP and DBP as well as HR were recorded before and after induction; immediately after intubation and 5, 10, and 15 minutes thereafter; at the time of extubation; and also one hour postoperatively. After the operation, the surgeons were asked to rate the quality of the operative field on a four-point scale:1 = bleeding, so mild it was not even a surgical nuisance;2 = mild bleeding, a nuisance but without interference with accurate dissection;3 = moderate bleeding that moderately compromised surgical dissection;4 = massive bleeding that significantly interfered with dissection.All the procedures were performed by the same team of surgeons.Data were expressed as Mean ± standard deviation. Quantitative variables were compared with two-sample independent t tests, and nominal data were analyzed with χ2 tests. Within-group comparisons of hemodynamic parameters were performed with paired-sample t tests. P < 0.05 were considered statistically significant. Statistical analyses were performed using the Statistical Package for Social Sciences software, version 11.0 .Patients’ characteristics  and hemoAlthough clonidine has been used successfully as an adjunct for hypotensive techniques -5, anoth


Heart failure has become one of the major causes of hospitalization worldwide. Hypertension, diabetes mellitus and hyperlipidemia are the major causes of heart failure. In order to effectively prevent heart failure, blood pressure, blood glucose and cholesterol levels shall be closely monitored and controlled as well as medication adherence. This study aimed to investigate the role of pharmacist intervention in prevention of heart failure in high risk elderly patients in the community of Hong Kong.This study aimed to investigate the role of pharmacist intervention in prevention of heart failure in highrisk elderly patients in the community of Hong Kong.This prospective uncontrolled study was conducted between July 2012 and April 2013 with two revisits every 3 to 4 months to review elderly patients’ medication profiles as well as assess their blood pressure (BP), random capillary blood glucose (RCBG) level, cholesterol levels, signs and symptoms of heart failure and the compliance level. The results collected at the baseline data were analyzed and compared with those collected at the last follow-up visit.p < 0.001) was found. For chronic disease management, significant reduction in LDL-cholesterol level  and triglyceride level  was observed in overall participants. Yet, no significant reduction in BP level or RCBG level was observed in overall subjects. Significant reduction in mean Morisky Medication Adherence Score  indicated improvement in medication compliance in participants.A significant increase in number of subjects free of symptoms of heart failure  contains supplementary material, which is available to authorized users. Heart Failure (HF) is a serious condition worldwide, with around 5.7 million people in United States of America being the victims. Also, the disease was found to be a contributing cause in more than 280,000 deaths 1 in 9) in 2008  in 9 in . These fIt has been investigated that hypertension , 5, 7, dHigh blood pressure as defined in Joint National Committee (JNC) 7 : ≥ 130/8High blood glucose as defined in Standard of Medical Care in Diabetes 2012 : RCBG ≥ Dyslipidemia as defined in ATP III : LDL levThis was a prospective uncontrolled study of which subjects were recruited from seven elderly centers in Hong Kong during the Pharmacy Outreach Service in July and August 2012. Patients with recent symptoms of HF were included in this study. These symptoms were evaluated by a questionnaire designed to correspond to the New York Heart Association (NYHA) functional classification of HF. High-risk subjects would also be selected, defined as two out of three of the following criteria were met:Patients who were younger than 65 years old or diagnosed with the following medical conditions, namely malignancies, dementia, psychiatric disorders, Alzheimer’s diseases, Parkinson’s diseases or epilepsy, were excluded in the study. Patients without the need of pharmacological management of their hypertension, diabetes, or dyslipidemia were also excluded. Other exclusion criteria include previous participations in the Chinese University of Hong Kong (CUHK) Outreach Service, current involvement in other clinical trials and the presence of communication barriers. The current project was approved by the Joint Chinese University of Hong Kong-New Territories East Cluster (CUHK-NTEC) Clinical Research Ethics Committee (Reference number: 2014.012). All recruited subjects had been consented prior to joining the current project.Subjects were revisited twice every 3 to 4 months from October 2012 to November 2012 and from February 2013 to April 2013. At each visit, subjects’ BP, RCBG level and cholesterol level were measured, and their demographic data and medication profiles were reviewed and recorded. The Omron HEM-7011 electronic blood pressure monitor  was used for measuring the blood pressure. This electronic device had achieved an “A/A” performance classification under the British Hypertension Society criteria and passed the Association for the Advancement of medical instrumentation requirements . The ranThe workflow of each visit is summarized in Fig. The baseline data were compared to those obtained in the last follow-up visit in order to analyze the impacts of POS on community elders’ management of risk factors associated with HF. McNemar’s test was used for the assessment of HF symptoms while paired t-test was utilized to detect changes in BP, RCBG, cholesterol levels and Morisky Medication Adherence Scale. According to previous POS studies –21, meanThe number of subject needed was calculated using the equation below :\documenAt least 40 subjects would be required to identify a 10mmHg change of the systolic blood pressure and at least 26 subjects would be needed to identify a change in 10mmHg of diastolic blood pressure with a power of 80%, a significance level of 0.05 and with an assumption of 40% drop-out rate. Therefore, at least 66 subjects would be required.p value of <0.05 was defined as statistically significant.All statistical analysis were performed using SPSS 16.0 and a p < 0.001) were found to be free of symptoms of HF, spanning the period between baseline and the last visit. A significant reduction of mean number of HF symptoms experienced by each subject was observed (p < 0.001). In addition, there were fifteen less elderly patients  based on the questionnaire. The other HF symptoms that were found to be sensitive to pharmacist intervention included, shortness of breath , fatigue easily , edema  and physical activity limitation when climbing stairs in particular   was achieved in subjects with Stage II hypertension. The reduction of RCBG level  was also significant in not well-controlled subjects (Table p = 0.038), and in triglyceride level .For the impact of POS on the risk factors management of heart failure, namely hypertension, diabetic mellitus and hyperlipidemia, no significant improvement was observed in BP and glycemic control in overall participants. However, significant reduction in SBP level  (Table p = 0.607). In addition, results showed a significant increase by 23.19% (p = 0.001) in the number of subjects with high compliance level. Forgetfulness (30.4%) was found to be the most common reason for non-compliance, followed by improper administration time (20.3%) and fear of adverse drug reaction (18.8%).Non-compliance to medications is also a contributing factor of HF, 66.99% of the elderly patients were identified to be medication non-compliant. The Morisky score results showed a significant reduction in mean score by 0.54 ± 1.50 (It has been suggested by HFSA that patients at risk of cardiovascular disease are also at high risk for developing HF, and early identification and treatment of risk factors are recognized of utmost importance in limiting the public health impact of HF . HyperteIn addition, the role of pharmacist in managing risk factors of HF was also investigated in the study. According to the US NHANES I Epidemiologic Follow-up Study, not well-controlled hypertension was found to be positively and significantly associated to increased risk of HF . This stIt was clearly established in prior studies that diabetes is a risk factor for HF -29. In tHFSA has suggested that hyperlipidemia is a risk factor for the development of HF . MeanwhiSeveral studies have suggested that non-compliance can be a precipitating factor of HF exacerbation , 33 as wThe current study has several limitations. There was selection bias during sampling since this was not a randomized trial, which was also reflected in the unequal distribution in gender in the sample. There were more female subjects involved in the POS probably due to their better health-seeking behavior but this was consistent with the previous POS . A randoPharmacy outreach service has significantly improved HF symptoms management and medication compliance in the high-risk community elderly patients. It has also improved cholesterol management in overall subjects. Further investigation with improved study design shall be conducted in order to evaluate and provide sound evidence on pharmacist role in preventing HF in community elderly patients.The study was approved by the Ethics Committee, CUHK-New Territories East Cluster, Hospital Authority, Hong Kong.


Renal sinus fat (RSF) has been recognized as a risk factor for arterial hypertension. This study was addressed to examine whether also para- and perirenal fat accumulation is associated to higher 24-h mean systolic (SBP) and/or diastolic blood pressure (DBP) levels in overweight and obese subjects.IR]), and 24-h aldosterone urine levels were measured. Ambulatory blood pressure monitoring (ABPM) was measured with 15 min intervals from 7.0 a.m. to 11.0 a.m. and with 30 min intervals from 23.0 to 7.0 for consecutive 24 h, starting from 8:30 AM. Measurement of para- and perirenal fat thickness was performed by ultrasounds by a duplex Doppler apparatus.A cohort of 42 overweight and obese patients, 29 women and 13 men, aged 25–55 years, not treated with any kind of drug, was examined. Body mass index (BMI), waist circumference (WC), fasting insulin and glucose serum levels, insulin resistance (assessed by using the homeostasis model assessment [HOMAp < 0.01), insulin (p < 0.01), HOMAIR (p < 0.01), and 24-h mean DBP levels (p < 0.05). 24-h mean DBP was also significantly and positively correlated with 24-h aldosterone urine concentrations (p < 0.001). A multivariate analysis by multiple linear regression was performed; the final model showed that the association of 24-h mean DBP as dependent variable with PUFT  and daily aldosterone production  was independent of other anthropometric, hormone and metabolic parameters.Para- and perirenal ultrasonographic fat thickness (PUFT) was significantly and positively correlated with WC (This study shows a positive independent association between PUFT and mean 24-h diastolic blood pressure levels in overweight and obese subjects, suggesting a possible direct role of PUFT in increasing daily diastolic blood pressure. Obesity, and visceral obesity in particular, is associated with higher cardiovascular morbidity and mortality and is recognized as a major public health problem , 2. The Central fat accumulation provides an explanation for the higher risk of coronary heart disease, that persists after accounting for BMI and common risk factors . Waist cThere are several potential mechanisms that might explain the tendency to deposit adipose tissue in ectopic versus nonectopic depots. One hypothesis suggests that, in states of positive energy balance, excess free fatty acids are initially stored subcutaneously, but once the capacity of subcutaneous adipose tissue is reached, storage shifts to ectopic sites,  . The faiPara- and perirenal fat is that enclosed from the inner side of the abdominal musculature to the surface of the kidney . RSF is As far as we are aware, no study has examined the possibility of a relationship between para- and perirenal fat thickness and daily blood pressure levels in humans and, in particular, in overweight and obese subjects having any pharmacological interference.We hypothesized that PUFT was associated with higher 24-h mean systolic (SBP) and/or diastolic blood pressure (DBP) in overweight and obese subjects. To address this hypothesis, we measured the association between PUFT and daily blood pressure levels, measured by ambulatory blood pressure measurement (ABPM) in overweight and obese patients without stable hypertension.The present study was performed in a population of 42 seemingly healthy men and women, either overweight or obese, aged 25–55 years, not using any kind of drug at the moment of enrollment. Anthropometric , 24-h urine aldosterone levels, fasting glucose and insulin serum levels, and insulin resistance were also measured in the subjects under study.The study subjects were consecutively enrolled at the Outpatient Clinic of Clinical Nutrition, Medical Oncology, Department of Biomedical Sciences and Human Oncology, Section of Clinical Oncology, University of Bari, School of Medicine. They had come to the Outpatient Clinic with the idea of losing weight and receiving advice on diet and lifestyle.As regards the criteria for inclusion, subjects enrolled had to have a BMI over 25.0, to be older than 18 years and to not be using any kind of drug .Exclusion criteria were endocrinological diseases, chronic inflammatory diseases, diabetes mellitus, stable hypertension, angina pectoris, stroke, transient ischemic attack, heart infarction and congenital heart disease.On this basis, respecting the inclusion and exclusion criteria, the study enrolled 42 consecutive patients, represented by 29 women and 13 men, aged 25–55 years.Informed consent was given verbal by all subjects for the study, and the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation  and with the Helsinki Declaration of 1975, as revised in 2000. The study was approved by the local ethics committee , according to a general statement of adherence to standards.Based on routine blood tests, urinalysis, electrocardiogram, physical examination and medical history, all subjects were judged in good health. None of them had fasting blood glucose levels higher than 126 mg/dl. All subjects had apparent normal function, since all of them showed eGFR > 90 ml/min and none of them showed proteinuria. No participant was on a limited calorie diet nor had been taking part in intense physical activity before enrollment. During the period of testing, all participants agreed to not undertake any sporting activity and to maintain their normal diet. The day prior to measuring, the subjects were requested to abstain from alcohol and caffeine.th rib (minimum waist).BMI was calculated as the weight (kg rounded to the nearest kg) divided by the square of height (m rounded to the nearest centimetre). Waist circumference was measured at the anatomic waistline, that should be the narrowest part of the abdomen, which is at the natural indentation between the iliac crest and the 10Blood samples were taken between 8 and 9 am after fasting overnight. Serum insulin concentrations were determined by radioimmunoassay . 24-h urinary collection for measurement of aldosterone levels was collected at home the day before the 24-h blood pressure measurement. 24-h urinary aldosterone concentrations were measured by chemiluminescent immunoassay , Italy).IR) [Plasma glucose levels were determined by the glucose-oxidase method . Insulin resistance was assessed by using the homeostasis model assessment (HOMAIR) .Ambulatory blood pressure was measured with 15 min intervals from 7.0 a.m to 11.0 a.m. and with 30 min intervals from 23.0 to 7.0 for consecutive 24 h, starting from 8:30 AM . Heart rate was measured over 24 h by the same instrument.P < 0.0001). PUFT was measured three times. The intraoperator coefficient of variation was 4.5 %. Sonographer (N.C.) was blinded to any other aspect of the study. An ultrasound image of PUFT is shown in Fig. Measurement of PUFT was performed as previously described by our group , and ultP ≤ 0.20. Significant independent variables were identified by a stepwise approach. By this approach, we constructed a final model of adequate statistical power (at least 15 subjects for each variable). Data are expressed as unstandardized (B) and standardized (β) regression coefficient. All analyses were performed using SPSS for Windows, release 17.0 ; P < 0.05 was considered statistically significant.Results are expressed as mean ± standard deviation. To test the significant independent relationship between PUFT or 24-h mean diastolic blood pressure and anthropometric, hormone and metabolic parameters we determined Pearson correlation coefficient, since all the data were normally distributed. Furthermore, to test the independent relationship between 24-h mean DBP and the other examined parameters we constructed multivariate models by multiple linear regression analysis based on 24-h mean diastolic blood pressure (dependent variable) and significant variables by univariate analysis; clinically significant variables were forced in the models if −2) was 25.0 ± 8.1 cm. The 24-h mean DBP was 82.4 ± 8.5 mmHg.The general, anthropometric, metabolic and hormone parameters from the study population are shown in Table r = 0.39; p = 0,01), insulin , HOMAIR , and 24-h mean DBP levels  , diurnal SBP , diurnal DBP , nocturnal SBP  and nocturnal DBP . Furthermore, 24-h mean SBP directly correlated with 24-h urine aldosterone levels , but not with RSF .No correlation was found between 24-h mean SBP and anthropometric, hormone and metabolic parameters in subjects under study, except for 24-h mean DBP  , diurnal mean SBP  and DBP , and nocturnal mean SBP  and DBP . No correlation was found between mean DBP and office SBP or DBP.Table 01) Fig. , 24-h meR = 0.34; p = 0.026) and 24-h urine aldosterone levels  was independent of other variables added to the models ; obviously, we did not add any other measure of blood pressure. Indeed, in the final model, PUFT ranked as the second correlate 1 (β = 0.17) of 24-h mean DBP, while the strong independent correlate was daily aldosterone production (β = 0.51).As shown in Table This study, performed in overweight and obese otherwise healthy subjects, shows a direct independent relationship between 24-h diastolic blood pressure (as measured by ambulatory blood pressure measurement) and both para- and perirenal fat thickness (measured by ultrasounds) and daily aldosterone production.To the best of our knowledge, this is the first evidence demonstrating that PUFT is a powerful independent predictor of higher 24-h mean DBP levels.It has been shown that compression of renal artery and vein, and lymphatic vessels, increases renal hydrostatic pressure  and activates RAAS, with higher 24-h urine aldosterone levels . Even thThe direct independent relationship between 24-h mean DBP levels and daily aldosterone urine concentrations is in line with previous studies showing that BMI predicts aldosterone concentrations in overweight-obese primary hypertensive patients .IR) did not show a significant relationship 24-h mean SBP or DBP levels. These results are in line with our previous study performed in overweight and obese patients, normotensive or with recently developed hypertension, never treated with antihypertensive drugs, showing that insulin and HOMAIR were not significantly different between normotensive and hypertensive subjects and were not associated to hypertension or to 24-h mean SBP or DBP levels [Fasting insulin and glucose levels and insulin resistance , but not BMI, showed a significant correlation with PUFT, strongly suggesting that PUFT progressively increases with abdominal fat accumulation.per se is more important that BMI or central fat accumulation for diastolic blood pressure. Moreover, these results are again in line with our previous study, showing that BMI and waist circumference were not significantly different between normotensive and hypertensive subjects [On the other hand, both BMI and waist circumference did not show a significant association with 24-h mean SBP or DBP levels in this study. These findings suggest that PUFT subjects .Office systolic and diastolic blood pressure did not show a significant association with PUFT and 24-h mean SBP or DBP levels, suggesting that office blood pressure measurements are a weak way to evaluate risk factors for hypertension or to perform the diagnosis of hypertension.IR, suggesting that para- and perirenal fat accumulation is paralleled by a progressive increase in insulin resistance and insulin levels.PUFT was significantly and positively correlated with insulin and HOMAConcerning the possible interest of the present study, the relationship between RSF and blood pressure was already known , but theIn conclusion, this study, performed in overweight or obese otherwise healthy subjects, shows a positive association between PUFT and mean daily diastolic blood pressure, independently of anthropometric, hormone and metabolic parameters. Our findings suggest that measurement of PUFT may represent a helpful parameter to evaluate the risk of developing hypertension in overweight and obese subjects.


Ineffective esophageal motility (IEM), or frequent failed peristalsis in the Chicago Classification, is a common motility abnormality describing a non-specific manometric pattern of peristaltic failure. With the addition of multichannel intraluminal impedance technology to high resolution esophageal manometry (HRM), evaluation of bolus transit simultaneously with esophageal contraction is possible. However, manometric predictors of incomplete bolus transit (IBT) in the setting of IEM have not been fully characterized.REB-approved retrospective chart review of patients diagnosed with IEM at a regional gut motility centre. All subjects were clinically assessed prior to HRM with a detailed history containing the patient's primary complaints, other pertinent symptoms and demographic information. HRM with impedance studies  were performed by standard protocol. Summary (averaged) data from each patient was compared. To examine which manometric variables best predicted the percentage of swallows with incomplete bolus transit for any given patient, a multiple linear regression was performed using selected variables, and adjusted for age and gender (SPSS 21). All tests were two-sided and significance was set at the 95% level.230 patients  with a manometric diagnosis of IEM were included. The primary complaints of patients included dysphagia (33.9%), heartburn/reflux (33.0%), chest pain (11.7%), other (10.9%), and cough (8.7%). Many patients had more than one symptom; however there were no significant differences in baseline characteristics across primary symptom groups (data not shown). The multiple regression model fit was highly significant  with an adjusted r square of 0.373. In the model, decreasing proportions of peristaltic contractions correlated significantly with decreased bolus transit (ie higher percentage of incomplete bolus transit). Similarly, higher intrabolus pressure correlated significantly with higher percentages of incomplete bolus transit. The remainder of the manometric variables were not significantly associated with IBT. Gender was not significant but increasing age was associated with less IBT.As expected, peristaltic contractions predict adequate bolus transit in aggregate data, while increased intrabolus pressure predicted incomplete bolus transit. Further questions being evaluated in this study sample include effects of medications and connective tissue disorders on HRM and bolus transit variables in the setting of IEM.


The experiments were conducted in adult offspring. Antenatal hypoxia caused intrauterine growth restriction, and resulted in a gender-dependent increase Angiotensin II (Ang II)-induced BP response in male offspring, but significant decrease in BP response in female offspring. The baroreflex sensitivity was not significantly altered. Consistent with the reduced blood pressure response, antenatal hypoxia significantly decreased Ang II-induced arterial vasoconstriction in female offspring. Ovariectomy had no significant effect in control animals, but significantly increased Ang II-induced maximal BP response in prenatally hypoxic animals and eliminated the difference of BP response between the two groups. Estrogen replacement in ovariectomized animals significantly decreased the BP response to angiotensin II I only in control, but not in hypoxic animals. The result suggests complex programming mechanisms of antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary dysfunction results in the phenotype of reduced vascular contractility and BP response in female adult offspring.In utero exposure to adverse environmental factors increases the risk of cardiovascular disease in adulthood. The present study tested the hypothesis that antenatal hypoxia causes a gender-dependent programming of altered arterial blood pressure response (BP) in adult offspring. Time-dated pregnant rats were divided into normoxic and hypoxic (10.5% O In addition, a number of studies have shown that adverse environment-induced low birth weight is associated with low blood pressure in offspring Adverse in utero environment Hypoxia during gestation is one of the most common intrauterine stresses that may alter fetal growth and development. Previous studies have suggested a possible link between maternal hypoxia and increased risk of cardiovascular dysfunction in offspring 2 from days 15 to 21 of gestation, as reported previously All procedures and protocols were approved by the Institutional Animal Care and Use Committee of Loma Linda University (IACUC#8110036) and followed the guidelines by the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Time-dated pregnant Sprague-Dawley rats which were non previous breeders were purchased from Charles River Laboratories . The rats were randomly divided into 2 groups: (1) normoxic control (n = 20) and (2) hypoxic (n = 18) treatment of 10.5% OPrevious studies have suggested that the puberty age of female Sprague Dawley rat is about 55 days-old 2 levels were determined with a commercially available estradiol ELISA kit (BioQuant BQ180S).Plasma EOffspring at 3-month-old was implanted with a catheter in the femoral artery to record arterial blood pressure and heart rate, and a catheter in the femoral vein for drug administration, as described previously 2 and 5% CO2. Isometric tensions were measured at 37°C, as described previously Aortas were isolated from animals, cut into 4-mm rings and mounted in 10-ml tissue baths containing modified Krebs solution equilibrated with a mixture of 95% O2 (-log EC50) and the maximum response (Emax). Results were expressed as mean ± SEM. Statistical significance (P<0.05) was determined by analysis of variance (ANOVA) followed by Neuman-Keuls post hoc testing or Student's t test, where appropriate.Concentration-response curves were analyzed by computer-assisted nonlinear regression to fit the data using GraphPad Prism  to obtain pDAs shown in vs. 1.98±0.11 g; P>0.05) (data not shown), suggesting the lack of effect of antenatal hypoxia on electromechanic coupling and vascular contractility. As shown in 2 (–log EC50) values of angiotensin II-induced contractions, as compared with the control . However, angiotensin II-induced maximal contractions were significantly decreased in antenatal hypoxia-treated female offspring, as compared with the control group .Ang II produced a time-dependent increase in arterial blood pressure in both control and hypoxia-treated adult offspring. As shown in Since our functional data indicated a gender difference in response to antenatal hypoxia, we hypothesized that alteration of estrogen level may play a key role in hypoxia-mediated changes of blood pressure response. We determined the plasma estrogen levels in different groups of female offspring. As shown in To determine whether ovarian function plays a key role in the antenatal hypoxia-induced effect in female offspring, Ang II-induced blood pressure response was determined in OVX animals. Unlike the findings in the sham animals, in OVX animals there was no significant difference in Ang II-induced blood pressure response between the control and hypoxic groups  antenatal hypoxia resulted in a decrease in arterial blood pressure response to angiotensin II, which was not mediated by a change in the baroreflex sensitivity; (2) OVX had no significant effect on angiotensin II-induced blood pressure response in normoxic control animals, but significantly increased it in hypoxic animals and eliminated the difference between the control and antenatal hypoxic female offspring seen in the sham animals; (3) estrogen replacement caused a significant decrease in angiotensin II-mediated response in normoxic control animals, but not in antenatal hypoxic animals resulting in a reversal of blood pressure responses seen in the sham animals.2 groups. However, 3 months after OVX treatment, the OVX rats had significantly higher body weights than the sham groups, suggesting that ovaries play an important role in regulation of female body weight. Similar findings have been reported in previous studies In present studies, we did not monitor the maternal food and water consumption, but previous studies in a similar hypoxic animal model have demonstrated that hypoxia reduces maternal food consumption The finding that antenatal hypoxia had no significant effect on blood pressure under resting condition in adult offspring is in agreement with findings in several different animal models in utero adverse environment may lead to reprogramming of ovarian function and alter ovarian steroid hormones release in adulthood The gender differences of fetal programming of cardiovascular dysfunction in offspring have been reported in many different animal models The present study demonstrated further that estrogen replacement in OVX animals decreased blood pressure response in normoxic control females. This supports the notion that estrogen plays an important role in regulating arterial blood pressure and in the protection of females from development of hypertensive reactivity. The finding that estrogen replacement in OVX animals had no significant effect on angiotensin II-mediated blood pressure response in antenatal hypoxic animals is very intriguing, and suggests a complexity of mechanisms in hypoxia-induced programming of ovarian steroid hormone function in female offspring. As shown in the diagram of in utero adverse stimuli during gestation and an increased risk of cardiovascular disease later in life. Gestational hypoxia is one of the most important and clinically relevant stresses to the fetal development. The present investigation shows a gender-dependent programming of blood pressure response in adult offspring and provides novel evidence of a complex mechanism in antenatal hypoxia-mediated programming of ovarian steroid hormone function in regulating vascular and blood pressure response in female offspring. Although the findings of the present study may not support the hypothesis that all models of fetal stress and intrauterine growth restriction lead to programming of hypertension later in life, whether the phenotype of reduced blood pressure response in female offspring really represents a “good” adaptation is certainly debatable given that it is a perturbation from the normal physiology. The complexity of mechanisms in fetal stress-mediated developmental programming of ovarian steroid function and vascular response warrants further investigation of its pathophysiological significance in the understanding of cardiovascular disease evolvement in females.Large epidemiological and animal studies indicate a link between