Introduction. Several biomedical findings have established the effects of hypertension on haemostasis and roles of blood coagulation products in the clinical course of hypertension. Methods. This cross-sectional study aimed at determining effects of hypertension on prothrombin time (PT) and activated partial thromboplastin time (APTT) in hypertensive patients in comparison with normotensive subjects attending a tertiary hospital in Calabar. Forty-two (42) hypertensive patients and thirty-nine (39) normotensive control subjects were investigated for PT and APTT using Quick one-stage methods. Results. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) correlated positively with APTT  in hypertensive patients. DBP, SBP, PT, and APTT were significantly higher in hypertensive patients when compared to normotensive subjects (P < 0.05). DBP correlated negatively with duration of illness  in hypertensive patients and positively with age of normotensive subjects . Conclusion. The results obtained indicated that measurements of PT and APTT may serve as indices for evaluating hemostatic abnormalities in hypertensive patients and guide for antihypertensive therapy. However, to have better understanding of hemostatic activities in hypertension, it is recommended to conduct D-dimer, platelet factors, and protein assays. Cardiovascular diseases account for about one-third of premature deaths in men and one-quarter in women and arterial hypertension is one of the most significant risk factors for cardiovascular diseases . DespiteAccording to recent epidemiologic data, the overall prevalence of 28% of the general population is suffering from hypertension in Sub-Saharan Africa, the prevalence rate in Nigeria is put at 22% with steady annual increase .Hypertension is classified as either primary or secondary. It is primary when no medical cause can be found to explain the raised blood pressure. This type represents between 90 and 95% of hypertension cases . SecondaRisk factors associated with hypertension include age, race, family history, obesity, sedentary lifestyle, alcohol abuse, and stress among others. Hypertension increases hardening of the arteries and predisposes individuals to heart disease, peripheral vascular disease, and strokes –10.Hypertensive patients are at high risk for the development of cardiovascular diseases , whereasCoagulation abnormalities in pregnant women have been reported to be more serious in women with hypertension (preeclampsia) than in those without hypertension . In patiBesides platelet aggregability and coagulation activation, fibrinolysis, that is, plasma tissue-type plasminogen activator activity, appears to be a major factor related to the risk of cardiovascular disease –22.Prothrombin time (PT) and activated partial thromboplastin time (APTT) have been shown to be associated with elevated systolic and diastolic blood pressures in hypertensive and normotensive patients . In a stThe main aim of this study is to assess possible association between prothrombin time and activated partial thromboplastin time with effects of blood pressures in hypertensive and normotensive subjects and their significant utility for screening hemostatic dysfunction in hypertensive patients.2 and a population of 371,022 at the 2006 census.The study was conducted at the University of Calabar Teaching Hospital, Calabar, Cross River State. Calabar is the capital city of Cross River State which is divided into Calabar Municipal and Calabar South Local Governments and is located at the coastal southeastern area (4°57′N 8°19′E) of Nigeria. It has an area of 604 kmA total of eighty-onesubjects were enrolled into the study. Forty-two (42) hypertensive patients aged between 30 and 80 years and thirty-nine (39) normotensive control subjects were investigated for PT and APTT using Quick one-stage methods. The selection of patients was done with the support of the physician and nursing staff of the Medical Outpatient Department (MOPD) of University of Calabar Teaching Hospital (UCTH), Calabar. The procedures employed consisted of a questionnaire interview, taking of patient's history, and blood pressure measurement.the presence of the history of primary hypertension;elevated blood pressure (≥140/90 mmHg);no history of administration of anticoagulant therapy;no history of chronic viral infection and/or liver diseases ;having not been on long-term drug regimen;must be within normal range body mass index;being with no trace of underlying causes.The inclusion criteria are as follows:the absence of family history of primary hypertension;normal blood pressure (<140/90 mmHg);those on anticoagulant therapy;those with chronic viral infections and/or liver diseases such as HBV, HCV, HIV, and alcoholism;obese individuals.The exclusion criteria are as follows:the absence of family history of hypertension;normal blood pressure (<140/90 mmHg);no history of administration of anticoagulant therapy;no history of chronic viral infection and/or liver diseases ;having not been on long-term drug regimen;must be within normal body mass index;with no trace of underlying causes.The inclusion criteria are as follows:the presence of family history of hypertension;elevated blood pressure (≥140/90 mmHg);the absence of family history of primary hypertension;normal blood pressure (<140/90 mmHg);those on anticoagulant therapy;those with chronic viral infections and/or liver diseases such as HBV, HCV, HIV, and alcoholism;obese individuals.The exclusion criteria are as follows:The ethical clearance was obtained from the Ethical Committee of UCTH, Calabar, Cross River State, Nigeria. Informed consent was obtained from all participating subjects. This was done via an informed consent form duly completed by all the subjects.Semistructured administered questionnaires were used to obtain data such as age, marital status, clinical signs and symptoms, and provisional diagnosis.Four and a half-millilitres (4.5 mL) of blood sample was drawn from hypertensive and normotensive subjects and discharged into a 0.5 mL of 3.13% trisodium citrate sample bottle. The anticoagulated samples were centrifuged at 4000 rpm for 10 minutes and platelet poor plasma stored in a deep freezer at −20°C until assayed. Standard method of Quick one-stage analysis by  was usedt-test, Pearson's correlation analysis, and analysis of variance on Microsoft Excel and SPSS software version 18 . Results were presented as the mean ± standard deviation. A two-sided P < 0.05 was considered statistically significant for t-test (used to determine the differences between the groups) and Pearson's correlation analysis was used to determine the intervariable associations of the various groups.The generated data was systematically analysed as appropriate for means, standard deviation, Student's P < 0.05).Diastolic blood pressures, systolic blood pressures, Prothrombin Time Test and Activated Partial Thromboplastin Time Test were significantly higher in hypertensive patients when compared to normotensives ; their prothrombin time was 14.28 ± 1.80, 15.00 ± 2.67, and 14.50 ± 1.87 seconds, respectively, while their activated partial thromboplastin time was 34.89 ± 4.57, 37.37 ± 6.07, and 35.33 ± 6.05 seconds, respectively, as shown in r = 0.3072; P < 0.05)   in hypertensive patients  in normotensive subjects   (P < 0.05) (Systolic blood pressure correlated positively with PTTK ( < 0.05)  and with < 0.05)  in hyperpatients  and posisubjects . A posit < 0.05)  and in n < 0.05) . More so < 0.05)  but nega < 0.05) . There w < 0.05) . However < 0.05) .Haemostatic system is directly involved in the atherosclerotic process. Hypertension is an atherosclerotic risk factor causing endothelial dysfunction; therefore, endothelial damage, platelets hyperactivation, and drugs are involved in the coagulation and fibrinolytic system , 30. ProP < 0.05) [The findings of this study show significant increases in the prothrombin time and activated partial thromboplastin time of hypertensive patients when compared to those of the normotensives (control). This increase could be due to endothelial damage as a result of atherosclerosis caused by hypertension on these patients ( < 0.05) .The prothrombin time and activated partial thromboplastin time of hypertensive patients increase with increase in duration of hypertension which may be due to prolonged endothelial wall effect as this will lead to sustained release of vasoactive substances that interfere coagulation cascades, and these indices eventually decrease as the antihypertensive therapy continues, even lower than before they started treatment; this finding is in consonance with Lee's work and that of Mirsaiedi et al. , 33.There was a positive correlation between systolic pressure and activated partial thromboplastin time in hypertensive patients which could be due to the risk factors associated with hypertension, for example, atherosclerosis, endothelial dysfunction and antihypertensive drugs , 35.There was a negative correlation between diastolic pressure and duration of illness and a probable explanation to this could be that reduced exposure of the vascular walls to pressure in those with lower duration will give a higher pressure than those who have higher exposure to this tension because their blood vessels might be weaker and cannot exert resistance or pressure against blood flow when compared to those with lower duration –38.P < 0.05); this supports the findings of Akputuzor et al. and Mirsaiedi et al. [Positive correlation of systolic and diastolic blood pressure of normotensive subjects was observed across gender distribution, but negative correlation between systolic blood pressure in male hypertensive subjects; these findings are in conformity with previous studies –41. Theri et al. , 42. ProDue to the fact that there was significant increase in prothrombin time and activated partial thromboplastin time of hypertensive patients when compared with normotensive (control) subjects, assessment of these parameters may serve as prognostic indices for evaluating hypertensive patients in whom there was clinical evidence of hemostatic abnormality and guide for antihypertensive therapy. However, to have complete understanding of hemostatic activities in hypertension, it is recommended to conduct D-dimer, platelet factors, and protein assays.


The autonomous cardiovascular control can contribute to progression of migraine. However, current data on cardiovascular reactivity in migraine, especially severe forms, are essentially contradictory. The main aim of this study was to compare the autonomous regulation of circulation in patients with episodic and chronic migraine and healthy subjects.Seventy three migraine patients (mean age 35 ± 10) including episodic migraine  and chronic migraine  along with age-match control  were examined. The autonomic regulation of circulation was examined with the tilt-table test, a deep breathing and Valsalva Maneuver, handgrip test, cold-stress vasoconstriction, arterial baroreflex and blood pressure variability.p <0.001), the increase in diastolic blood pressure in handgrip test (p <0.001), mean blood pressure in the late stage of the second phase of Valsalva Maneuver (p <0.001) and blood pressure variability (p <0.005) were all higher in patients with migraine than in the control group.The changes in heart rate induced by deep breathing, Valsalva Maneuver, and blood pressure in tilt-table test in patients with migraine did not differ from the control group. In contrast, the values of cold-stress-vasoconstriction forearm blood-flow reactivity (Thus, both episodic and chronic migraine are associated with significant disturbances in autonomous control resulting in enhanced vascular reactivity whereas the cardiac regulation remains largely unchanged. The activation of the trigeminovascular system comprising somatic and autonomous nerves and meningeal vessels, plays a central role in the pathogenesis of migraine –3. DurinConclusions on the reduced sympathetic reactivity are often based on results of the orthostatic load and handgrip test, which, however, are not mediated by the sympathetic nerves exclusively as evidenced by results of microneurography . Cold stIn contrast to variable results with sympathetic control, many studies indicated reduced parasympathetic control in migraine –29. In pn = 51) and chronic migraine (n = 22). All migraine patients involved in this study were primary patients who consulted our medical center for the first time. They did not receive preventive treatment at least two months before the study. The treatment was prescribed after the study to exclude its influence on the research results. Only five patients of the group of episodic migraine and one of the group of chronic migraine were suffering from the migraine with aura. Chronic migraine patients had no triptan overuse. The diagnosis of migraine was made using the criteria of the International Classification of Headache Disorders, 3rd edition (beta version) [The study group involved 73 patients , aged 35.3 ± 10.1 years, and consisted of patients with frequent episodic (version) . Patientversion) .Patients had no clinically significant comorbidities. They did not take medicines affecting circulation or interfering with autonomous control in the day of investigation, and the day before. The control group included 71 age-matched (mean age 35.3 ± 12.1 years) healthy volunteers . All patients and volunteers were between 18 and 50 years old. The basic clinical characteristics of both groups are presented in the Table Tilt-test is capable to evaluate the activity of the sympathetic nervous system directed to maintain the hemodynamic parameters despite a decrease in diastolic refilling due to the reduction of venous return [s return , 36. TheThe deep breathing test allows estimation of mainly the parasympathetic regulation of the heart mediated by the vagus nerve [us nerve . It shouus nerve . The deeValsalva Maneuver designed to study the autonomic regulation of heart rate, as well as neurogenic vascular reactivity [The standard activity . To perfactivity . The heaactivity .Handgrip test measures changes in the level of diastolic blood pressure, which reflects the neurogenic vascular reactivity providing increased vascular resistance in response to mechanical stimulation of the muscle afferents [fferents . This tefferents . The diaСold-stress induced vasoconstriction reporting sympathetic cardiovascular responses independently from baroreflex function [function  was carrBoth the spontaneous arterial baroreflex, which reflects parasympathetic cardiovascular regulation , and beaResearch plan included the following sequence of tests:T-test for independent sample. To assess the relationship between indicators of vasomotor regulation, Pearson correlation coefficients were used. All data are presented as the mean value ± standard deviation (SD). Bonferroni correction was applied for comparative analysis of three groups with the significance level p < 0.017. Nevertheless, for comparison between two migraine groups and the control the difference was assumed to be significant when p < 0.025.Statistical analysis was performed using the software STATISTICA 10. The comparative analysis was carried out by using the parametric p < 0.017) of the heart rate in patients with chronic migraine compared to the episodic migraine.The general characteristics of the patients in both groups and the control group are shown in Table p > 0.017 for all parameters, Table The cardiac regulation in episodic and chronic migraine was addressed by performing the deep breathing test, calculating the Valsalva index, and by measuring the arterial baroreflex. However, we found that the heart rate changes induced by the deep breathing, the Valsalva index, or arterial baroreflex, as well as the initial heart rate, were not different between both migraine groups and control (nd stage), handgrip test, cold-stress vasoconstriction, and measured the blood pressure variability. Unlike the cardiac regulation, in vascular reactivity patients in both migraine groups (episodic and chronic migraine) were different from the control group. Thus, in four of these tests, we obtained significant differences between the control and migraine groups. The strongest effect (p < 0.001) was observed in the later stage of the second phase of the Valsalva Maneuver when the mean blood pressure had 3-fold increase in episodic and chronic migraine groups compared to the control . Cold-stress vasoconstriction demonstrated highly significant (p < 0.001) changes in the episodic and chronic migraine groups, as well , which shows vascular reactivity mediated by sympathetic efferent nerves. However, in the group of chronic migraine this parameter was not significantly different from the control group  to chronic migraine , 50. TheAlthough the data presented here are not robust, all our patients underwent the multiple testing, which is essentially time consuming. Despite the numerous tests used in this study, they reflect the vasomotor reactivity only indirectly. The direct approach for the study of the sympathetic response in migraine would be the recording of the activity of the sympathetic nerves, which however has a limited use in the clinical practice due to the invasive nature of this procedure. In addition, vascular regulation may change during acute attacks, which would represent, however, the aim and the target of the future separate studies.In conclusion, our study revealed that in patients with episodic or chronic migraine without hypertension the cardiac reactivity almost did not differ from the control group, whereas the vascular reactivity was largely enhanced. The most significant differences in the vascular reactivity in patients with migraine were presented as the more significant growth of the blood pressure at the later stage of the second phase of the Valsalva Maneuver and in the response of the blood flow to the cold stress. Unchanged orthostatic blood pressure response in patients with migraine may be associated with the limited specificity of this test.This study was conducted in accordance with ethical standards presented in the 1964 Declaration of Helsinki. The protocol of this study was approved by the Ethics Committee of the Pavlov First Saint-Petersburg State Medical University. All subjects provided a written consent for this study.


Introduction. Rennin-angiotensin system and salt diet play important roles in blood pressure control. We hypothesized that the high-salt intake during pregnancy influences the degree of angiotensin-dependent control of the blood pressure in adult offspring. Methods. Female Wistar rats in two groups (A and B) were subjected to drink tap and salt water, respectively, during pregnancy. The offspring were divided into four groups as male and female offspring from group A (groups 1 and 2) and from group B (groups 3 and 4). In anesthetized matured offspring mean arterial pressure (MAP), heart rate and urine output were measured in response to angiotensin II (AngII)  infusion.  Results. An increase in MAP was detected in mothers with salt drinking water (P < 0.05). The body weight increased and kidney weight decreased significantly in male offspring from group 3 in comparison to group 1 (P < 0.05). MAP and urine volume in response to AngII infusion increased in group 3 (P < 0.05). These findings were not observed in female rats.  Conclusion. Salt overloading during pregnancy had long-term effects on kidney weight and increased sex-dependent response to AngII infusion in offspring (adult) that may reveal the important role of diet during pregnancy in AngII receptors. Normal pregnancy is associated with large changes in function and anatomy of cardiovascular system. Occasionally, pregnancy is accompanied by a condition called preeclampsia, which is characterized by edema, increased intravascular coagulation, proteinuria, increased systemic vascular resistance, and hypertension. Pregnancy-induced hypertension is a major cause of maternal and fetal mortality –3. High-Higher blood pressure was observed in offspring from mothers subjected to high-sodium intake during pregnancy and lactation , 14, 15.β-estradiol [Renin angiotensin system plays an important role in blood pressure control, and its activity was reported to be gender-related –21. The stradiol –25.Accordingly, it is hypothesized that different salt diets may influence renin angiotensin system or renal function in offspring. To test this hypothesis, adult male and female offspring from the mothers that received high-salt drinking water during pregnancy were subjected to AngII infusion and the blood pressure response was determined. ad libitum standard rat diet in a 12-hour light/dark cycle. The rats were randomly divided into two groups. Rats were maintained on tap water (group A) and high-salt water (2%) (group B) before mating until delivery. High-salt water was prepared as 20 grams of salt in one liter of water. Pregnant female rats were carefully monitored at the end of pregnancy to determine the exact date of birth. On the day of weaning (30th day of life), mothers were prepared for surgery, and offspring were divided into four groups as described in the following. Groups 1 and 2 are male (group 1) and female (group 2) offspring from mothers who received tap water during pregnancy. Groups 3 and 4 are male (group 3) and female (group 4) offspring from mothers who received high-salt water during pregnancy.Eight female Wistar rats were individually housed in cages with temperature controlled at about 25°C and maintained withAll offspring in the aforementioned four groups were weighed in days 30, 45, and 60 after birth. Finally, these animals ) with the mean age of 70.2 ± 1.08 days were subjected to experimental procedures. All the animal experimental procedures described in this study were approved in advance by the Isfahan University of Medical Sciences Ethics Committee.The sodium chloride was purchased from Merck KGaA ; angiotensin II and Evans Blue were obtained from Sigma .Thirty days after delivery, mothers in groups A and B were anesthetized with ketamine , the trachea was cannulated to facilitate ventilation, and a catheter was implanted into the carotid artery. After basic stabilization for 30–60 min, blood pressure was measured and then blood sample was collected.+; then, after the equilibrium time (30–60 min), direct blood pressure was continuously monitored. Then, a series of intravenous infusions of AngII  via the jugular vein was commenced. Each dose was administered until arterial blood pressure equilibration was achieved (in about a 10 min period), and then the measurements were performed for 3–5 minutes. At the end of the study, Evans Blue [In experimental groups 1 to 4, the animals were weighed and anesthetized with urethane (1.5 g/kg). The trachea was isolated to insert an air ventilation tube. Then, the carotid artery was cannulated to record blood pressure and jugular vein was cannulated for AngII infusion. A catheter was implanted into the bladder to measure urine volume. Urine output was collected online during AngII infusion for period of one hour. After surgical procedures, basal blood sample (0.5 mL) was collected from the carotid artery and then centrifuged at 6000 g for 20 min to determine serum levels of nitrite (stable NO metabolite) and Naans Blue  solution+ was also measured by a flame photometer.The level of nitrite was measured using a colorimetric assay kit  that involved the Griess reaction. Briefly, after adding sulfanilamide solution and after incubation, N-(1-naphthyl)ethylenediamine solution was added. Next, the sample absorbance was measured by a microreader in the wavelength of 492 nm. The nitrite concentration of samples was determined by comparing with the nitrite standard reference curve. The serum level of Naμg) to aorta weight (gr) was determined as the endothelial permeability.Endothelial permeability of the aorta was measured by the EB method. Briefly, one hour after EB injection, a piece of thoracic aorta was obtained and immediately weighed. Then, 2 cc formamide  was added and placed in an oven (80°C) for 24 hours. After cooling, the absorbance was measured at 623 nm. The standard curve of EB concentration was plotted and the EB concentration (Serum volume was measured using EB . Sixty m−1 min−1 AngII) and their interactions. The P value <0.05 was considered statistically significant. The Student's t-test was used to compare other factors between the groups. Mothers in groups A and B were compared in the number of newborn via Mann-Whitney values.Data were expressed as mean ± SEM. Body weight and MAP and heart rate (HR) response to AngII were compared via repeated measures anova for different groups of factors and doses . In group B, higher MAP and serum Na+ levels, and lower serum nitrite level were obtained, indicating that the salt diet during pregnancy increased MAP 30 days after delivery.Maternal data are shown in P < 0.05). Such observation was not detected in female animals  and the two groups of female animals groups 2 and 4) . Results and 3 an and 4 . + and endothelial permeability of aorta as EB uptake  (P < 0.05). However, kidney weight (KW g/100 g body weight) in group 3 was significantly less than that in group 1 (P < 0.05). Such finding was not observed in female groups 2 and 4  . Also, s 2 and 4 .The major findings of this study indicated that high-salt intake during pregnancy decreased kidney weight and increased plasma volume and increased the vascular, heart, and urine output responses to graded AngII infusion in male but not in female adult offspring. It is well known that salt diet is accompanied with increased vascular resistance and arterial pressure –5, and iHigh-salt intake during pregnancy promotes MAP, heart rate, and urine output responses to AngII in male offspring. Increase in body weight and plasma volume and decrease in kidney weight were also observed in such male offspring. High-salt drinking water during pregnancy may not alter MAP, heart rate, and urine output response to AngII in female offspring. The results obtained suggest the effect of salt drinking water during pregnancy in development of RAS in male offspring.


Hypertension, defined as a systolic/diastolic blood pressure of 140/90 mmHg or greater, is estimated to carry a 3-fold increased risk of developing cardiovascular disease (CVD), while treating hypertension significantly reduces CVD events, and stroke in particular. Among the many risk factors involved, there is much recent interest in the role of genetic factors that might predispose to hypertension.in vivo in homozygous individuals. In recent years we showed that CVD patients with the relevant MTHFR 677TT genotype (compared to CC or CT genotypes) had significantly higher blood pressure, and that blood pressure was highly responsive to riboflavin intervention, specifically in the TT genotype group [Evidence from genome-wide association studies has identified an association between blood pressure and the gene encoding the folate-metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR), while recent meta-analyses of observational studies show an increased risk of hypertension in people homozygous for the 677C→T polymorphism in MTHFR. Riboflavin vitamin B2) in the form of FAD acts as a cofactor for MTHFR and we have been studying its modulating role in relation to this polymorphism. The variant enzyme is known from molecular studies to become inactive as a result of having an increased propensity to dissociate from FAD, but our earlier work suggested that supplementation with low-dose riboflavin could stabilise MTHFR activity pe group . Further in the fAlthough the precise mechanism linking this polymorphism to hypertension remains to be established, it would appear that the biological perturbation that leads to higher blood pressure in individuals with the MTHFR 677TT genotype is modifiable by correcting the variant MTHFR enzyme through enhancing riboflavin status. Thus riboflavin, targeted specifically at this genetically at-risk group, may offer a personalized non-drug approach to managing hypertension.


Affective temperaments  measure subclinical manifestations of major mood disorders. Furthermore, cumulating evidence suggests their involvement in somatic disorders as well. We aimed to assess associations between affective temperament scores and blood pressure and arterial stiffness parameters in hypertensive patients.In this cross-sectional study, 173 patients with well-controlled or grade 1 chronic hypertension, with no history of depression, completed the TEMPS-A, Beck Depression Inventory (BDI) and Hamilton Anxiety Scale (HAM-A) questionnaires in three GP practices. Arterial stiffness was measured with tonometry (PulsePen).β = 0.529, p = 0.042), while hyperthymic temperament score was negatively related to augmentation index independent of age, sex, smoking, heart rate, BDI, HAM-A and the use of alprazolam . A significant interaction was found between cyclothymic temperament score and sex in predicting brachial systolic blood pressure (p = 0.025), between irritable and anxious temperament scores and sex in predicting pulse wave velocity  and an interaction with borderline significance between hyperthymic temperament score and sex in predicting augmentation index (p = 0.052).According to multiple linear regression analysis, cyclothymic temperament score was positively associated with brachial systolic blood pressure independently of age, sex, total cholesterol, brachial diastolic blood pressure, BDI, HAM-A and the use of alprazolam (The present findings highlight elevated blood pressure among subjects with high cyclothymic temperament as well as an increased level of arterial stiffening in subjects with low hyperthymic scores suggesting that affective temperaments may play a role in the development of hypertension and arterial stiffening and may thus represent markers of cardiovascular risk. Sex differences were also present in these associations. Cardiovascular diseases are the leading cause of morbidity and mortality in most industrialized countries worldwide, despite highly effective preventive treatments. A continuous linear relationship between elevated blood pressure and incident cardiovascular events is well known at all ages and in all ethnic groups –5. In adDepression is also a common public health problem in the Western world and its strong connection with cardiovascular diseases is broadly recognized . The patTemperament is regarded as an inherited part of personality and represents the biologically stable core of emotional reactivity , 15; howWe hypothesized that individual affective temperament scores may be related to brachial blood pressure as well as arterial stiffness in chronic hypertensive patients. We speculated a positive association in instances of depressive, cyclothymic, irritable or anxious temperaments and an inverse association in instances of hyperthymic temperament. We also hypothesized the presence of sex differences in relation to these studied associations.In the present cross-sectional study, 173 Caucasian patients with well-controlled or grade 1 chronic (on medication for >3 months) hypertension were investigated in three primary care practices. Patients with atrial fibrillation and treated depression or with dementia potentially interfering with the completion of questionnaires were excluded. Patients on moderate doses of alprazolam (<0.5 mg/day) were not excluded. All of the 48 patients of our previous pilot study  were alsTemperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) was used to assess affective temperaments on depressive, cyclothymic, hyperthymic, irritable and anxious subscales, requiring ‘yes’ (score 1) or ‘no’ (score 0) answers [depressive temperament: questions 1 to 21 (21 points)cyclothymic temperament: questions 22 to 42 (21 points)hyperthymic temperament: questions 23 to 63 (21 points)irritable temperament: questions 64 to 84 anxious temperament: questions 85 to 110 (26 points).The  answers . TEMPS-ATEMPS-A has been extensively studied, translated into more than 25 languages and validated in several of the latter. Similarities and differences were also found in national samples which suggest that distribution of affective temperaments has both universal and cultural-specific characteristics .Beck Depression Inventory (BDI), created by Aaron T. Beck, is a 21-question multiple-choice self-report questionnaire and is one of the widely used instruments for measuring depression severity. Participants are asked to make ratings on a four point scale, where a higher score correlates with more severe depression [The pression .Hamilton Anxiety Scale (HAM-A) was used to study the severity of anxiety. The scale consists of 14 items, each item is scored on a scale of 0 (not present) to 4 (severe anxiety) [The anxiety) .Measurements were performed in a temperature-controlled room, between 7.00 and 8.00 a.m. prior to blood collection. Patients were required to fast overnight and refrain from smoking and drinking caffeine-containing beverages before the procedure, but to take their usual blood pressure medication. Upon arrival and after 5 min rest, two brachial blood pressure measurements were taken on each arm in the sitting position with a validated oscillometric blood pressure device (Omron M3). The mean value of the higher side of arms was further taken into calculation as brachial systolic (SBPbrach) and diastolic (DBPbrach) blood pressures and heart rate. Brachial pulse pressure (PPbrach) was also calculated from these data. The subjects were next fitted with arterial stiffness measurement device and were asked to rest in the supine position for approximately 15 min before being measured. Arterial stiffness parameters were evaluated with the gold-standard tonometric method  . This mep < 0.05 was considered to be significant. SPSS 13.0 for Windows was used for all calculations.Descriptive data are expressed as mean ± standard deviation or median with interquartile ranges or percentages. Normality of continuous parameters was tested with the Kolmogorov-Smirnov test. Pearson correlation coefficients were calculated to study the relationship between affective temperament scores and demographic, hemodynamic or arterial stiffness parameters. Multiple linear regression analysis was used to study the determinants of these hemodynamic or arterial stiffness parameters which were associated in univariate analysis with affective temperaments. Based on literature data, sex differences in the association between affective temperaments and the studied hemodynamic or arterial stiffness parameters  were expA total of 173 subjects were included. Baseline demographic and laboratory parameters, current medication, TEMPS-A, BDI and HAM-A scores, central blood pressure and arterial stiffness parameters are summarized in Table p = 0.056) and depressive temperament score of Aix (p = 0.595). Table Table p = 0.012) after adjustment for age, sex, brachial systolic blood pressure, GFR-EPI, blood glucose and duration of hypertension, although became non-significant after further adjustment for BDI and HAM-A scores and the use of alprazolam (p = 0.078). The same results were also found for anxious temperament score and PWV: the significant association (p = 0.043) that was present after adjustment for age, sex, brachial systolic blood pressure, GFR-EPI, blood glucose and duration of hypertension disappeared after further adjustment for BDI and HAM-A scores and the use of alprazolam (p = 0.475).With regard to the association between PWV and irritable temperament score, the correlation still remained significant  which was absent in women . After adjustment for age, brachial diastolic blood pressure, cholesterol and triglycerides, this interaction became non-significant .When studying the interaction between cyclothymic temperament score and sex in predicting brachial systolic blood pressure, a significant association was found (p = 0.021). There was a positive association between irritable temperament score and PWV in men  which was absent in women  , however the strength of the association remained similar . The interaction became non-significant (p = 0.168) after further adjustment for BDI and HAMA-A scores and the regular use of alprazolam .There was also a significant interaction between irritable temperament score and sex in predicting PWV (35) Fig. . After ap = 0.023). There was a positive association between anxious temperament score and PWV in men  which was absent in women  , however the strength of the association remained similar in men . The interaction became non-significant (p = 0.135) after further adjustment for BDI and HAMA-A scores and the regular use of alprazolam .Similarly to irritable temperament, there was also a significant interaction between the anxious temperament score and sex in predicting PWV (89) Fig. . After ap = 0.052) was found between sex and hyperthymic affective temperament in predicting Aix. An inverse association was found in women  which was absent in men   after further adjustment for age, smoking, heart rate and uric acid .An interaction with borderline significance (11) Fig. . This inTo the best of our knowledge, this is the first study to demonstrate that, in chronic hypertensive patients, cyclothymic temperament score is associated with brachial systolic blood pressure while hyperthymic temperament score is independently related to the augmentation index after adjustment for potential confounders including severity of depression and anxiety and the use of alprazolam. Sex differences were also found in relation with brachial systolic blood pressure and cyclothymic temperament score, pulse wave velocity and irritable and anxious temperament scores and augmentation index and hyperthymic temperament score.Previous findings support our present observations that affective temperaments are associated with cardiovascular pathology. For example, patients with cyclothymic, irritable and anxious temperaments were shown to have a tendency to obesity . DepressAn increasing cyclothymic temperament score was found herein to be associated with a higher brachial systolic blood pressure. This temperament shows a central dimension that includes rapid fluctuations in mood and emotional instability. Such alterations can span from lethargy to eutonia, from pessimistic brooding to optimistic, from hypersomnia to decreased need for sleep or from introverted self-absorption to uninhibited people-seeking . In contThere are existing data in the literature regarding the association between personality traits and arterial stiffening. In a study by Midei and Matthews, higher trait anxiety and hostility were associated with a higher PWV . In the Augmentation index is an accepted parameter of pulse wave analysis. Aix is associated with age, sex, body height, smoking and heart rate , 42, assSignificant interactions were also found in the present study between sex and cyclothymic temperament score in predicting brachial systolic blood pressure, between sex and irritable temperament as well as between sex and anxious temperament scores in predicting PWV, while the interaction between sex and hyperthymic temperament score in predicting Aix had borderline significance. These findings are consistent with the study of Williams et al., where trait anger was associated with elevated arterial stiffness in men, while in women the association was marginally significant . These rThe pathophysiological background of our findings is complex and remains to be clarified. Subjects in states of anger or hostility show elevated levels of inflammation , 48 and One of the limitations of the present analysis is the relatively low number of chronic hypertensive patients used to study the associations between affective temperaments and blood pressure or arterial stiffness parameters, which limits the generalizability of our results, as well as the number of entered confounders into regression analyses. Another main limitation stems from its cross-sectional design which precludes causal inference. Moreover, although our methodology used standardized questionnaires and excluded patients with dementia, a complete exclusion of misinterpretations or mistakes by patients is nevertheless impossible.In conclusion, the elevated blood pressure among subjects with high cyclothymic temperament and the increased level of arterial stiffening in subjects with low hyperthymic scores suggest that affective temperaments might play a role in the development of hypertension and arterial stiffening and thus could represent potential markers of cardiovascular risk. The discovered sex differences in numerous studied associations may be the consequence of the known differences in affective temperaments between men and women. Cumulating data suggest that the identification of affective temperaments in the future can improve both the psychopathological and cardiovascular risk stratification of patients leading to a more accurate, personalized patient management.AIx, augmentation index; ARB, angiotensin II receptor blocker; BDI, Beck depression inventory; BMI, body mass index; Cyclothymic temp. score, cyclothymic affective temperament score; DBPbrach, brachial diastolic blood pressure; GFR-EPI, glomerular filtration rate assessed by the chronic kidney disease epidemiology collaboration glomerular filtration rate equation; HAM-A, Hamilton anxiety scale; HR, heart rate; Hyperthymic temp. score, hyperthymic affective temperament score; PPAmp, pulse pressure amplification; PPB, brachial pulse pressure; PPbrach, brachial pulse pressure; PPcentr, central pulse pressure; PWV, pulse wave velocity; SBPbrach, brachial systolic blood pressure; SBPcentr, central systolic blood pressure; TEMPS-A, the temperament evaluation of Memphis Pisa, Paris and San Diego questionnaire


Chronic kidney disease (CKD) has emerged as a public health challenge in countries around the world. The cost of management of CKD is enormous and unaffordable to most patients in the developing world. There is a dearth of data on characteristics of Ghanaian CKD patients at presentation.This was a prospective cross sectional study of CKD patients during their first visit to the renal clinic of a tertiary hospital adult renal service. Following informed consent, a questionnaire was used to gather demographic, anthropometric and clinical details of patients. Laboratory data of patients were also collected and analysed.The majority (64.5%) of 203 participants were male. Most were less than 60 years old and about one third were unemployed. Across all age groups stage 5 disease was the commonest presentation; however only 4.3% could afford to initiate haemodialysis. The mean number of dialysis sessions was 12.4 (range 6-18). Chronic glomerulonephritis (33%), hypertension (21.2%) and diabetes mellitus (22.2%) were found to be the leading causes of CKD. Common complications of CKD at presentation included anaemia (86.7%), pulmonary oedema (31%), high blood pressure (55%), and infection.Early detection of CKD and institution of measures to slow disease progression are to be encouraged. There is the need to make renal replacement therapy increasingly accessible and affordable to patients. The kidneys play a central role in fluid, electrolyte and acid base homeostasis in humans. In chronic kidney disease (CKD), irreversible damage results in an inability of the kidneys to perform its vital homeostatic, excretory and synthetic functions. CKD is the presence of kidney damage, manifested by abnormal albumin excretion or decreased kidney function that lasts longer than three months as quantified by measured or estimated glomerular filtration rate (eGFR) . ProgresThis prospective cross sectional study was carried out over a 1-year period from June 2011 to May 2012 at the Komfo Anokye Teaching Hospital (KATH). KATH, the second largest hospital in Ghana is located in Kumasi and caters for patients in the middle and northern zones of the country. There are clinical services for both adult and paediatric renal patients. Haemodialysis is the main mode of Renal Replacement Therapy (RRT). The study population was all CKD patients accessing services at the KATH Renal Clinic. Consecutive consenting new CKD patients, 18 years or older were recruited into the study. Informed consent was obtained from all study participants or their legal representatives prior to inclusion in the study. A questionnaire was administered to each patient to obtain the demographic data, anthropometric data, and clinical history. Clinical examination and laboratory findings were also recorded. The height was measured with the patient standing barefooted on flat surface. Blood pressure was measured using IntellisenseTM M3 automatic Blood Pressure monitor . The pulse pressure was calculated as the difference between the systolic and diastolic blood pressures. A midstream urine sample was analysed for proteinuria using dipstick testing  and the degree of proteinuria classified as normal, mild or heavy. Abdominopelvic ultrasonography was done to assess the architecture of the kidneys. The haemoglobin (Hb) level and Hb indices were measured at KATH haematology laboratory with an auto analyser . Liver function tests (LFT), blood urea nitrogen (BUN) and serum creatinine levels (based on modified Jaffe method) were measured at the KATH biochemistry laboratory using an auto-analyser . Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD-4) equation and the stage of CKD noted.Ethical statement: Ethical approval for the study was received from the Committee on Human Research Publications and Ethics (CHRPE) of the School of Medical Sciences, Kwame Nkrumah University of Science and Technology and the Komfo Anokye Teaching Hospital.Definition of terms: CKD was defined as the presence of kidney damage, manifested by abnormal albumin excretion or decreased kidney function, quantified by measured or estimated glomerular filtration rate (GFR) that persists for more than three months. In the absence of previous data on eGFR or markers of kidney damage, chronicity was inferred from clinical presumption of kidney disease for >3 months. Proteinuria was defined as normal (urine dipstick negative), mild (urine dipstick reading trace or 1 + ), or heavy . Hypertension was defined as the presence of a persistently elevated systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg in patients aged 15 years and above, and/or the use of antihypertensive drugs and/or past medical history of hypertension. Diabetes mellitus (DM) was defined as a random blood glucose level of 11.1mmol/L or greater, and/or fasting blood glucose level of 7.0mmol/L or greater, and/or use of insulin or an oral hypoglycaemic agent. Anaemia was defined as haemoglobin (Hb) level < 11 g/dL. Primary cause of renal disease: The determination of the primary cause of renal disease was based on history, physical examination, and laboratory investigations such as ultrasonography, urinalysis, blood chemistry, and serology. Histological documentation of the primary renal disease was not done since renal biopsies were not a part of this study. The diagnosis of chronic glomerulonephritis (CGN) was largely clinical, based on classical symptoms of loin pain, haematuria, proteinuria, and reduced urine output. Reduced kidney size (<9cm) as well as loss of corticomedullary differentiation were utilised as sonographic evidence of chronic glomerulonephritis. HIV-associated nephropathy (HIVAN) was diagnosed if patient was confirmed HIV positive with low CD4 T cell count and had proteinuria, oedema, and normal-sized or enlarged kidneys on ultrasound. Hypertension was noted as the cause of renal disease in cases with documented medical record if hypertension predated kidney disease and also if there was absence of proteinuria, normal renal function indices, and preserved renal sizes in presence of hypertension early in the illness. Diabetic nephropathy (DN) was diagnosed if patient had a long history of DM, evidence of significant proteinuria with presence of other complications of diabetes mellitus and had normal or increased renal sizes on ultrasound.Data analysis: Data was entered into Microsoft Excel 2007 and analysed using Epi Info version 7.1.2.0. Charts were generated with Microsoft excel.A total of 203 participants were recruited for the study. The basic demographic characteristics of the participants are represented in There was a preponderance of males in this cohort (64.5% vs 35.5%) and this is comparable to similar studies done in Spain  and UnitSeveral factors may account for the younger age of patients with CKD in the developing world. There is a high prevalence of infections /infestations and these contribute to the development of chronic glomerulonephritis, which is the leading cause of CKD in developing countries . AdditioAs pertains in other developing countries , the majComplications of chronic kidney disease were common in this study. Anaemia was present in 86.7% of patients. The majority (58.6%) had microcytic hypochromic anaemia. The high prevalence of anaemia is consistent with findings from other African studies , 33 howeHigh mean systolic and diastolic blood pressures were recorded among study participants. This has implications for reducing the rate of cardiovascular disease as there is evidence that blood pressure control reduces the rate of cardiovascular disease in CKD patients . Blood pAdvanced stages of chronic kidney disease are common in patients seeking care at the Komfo Anokye Teaching Hospital. Although majority of affected persons are in the economically active age groups, more than a third of patients are unemployed. Chronic glomerulonephritis (33.0%), hypertension (21.2%) and diabetes mellitus (22.2%) are common causes of chronic kidney disease. Less common aetiologies include Autosomal Dominant Polycystic Kidney Disease, sickle cell nephropathy and obstructive uropathy. The majority of patients have an associated anaemia. Uncontrolled hypertension, pulmonary oedema, and anaemia were common complications during initial assessment of CKD patients. Only a limited proportion of patients are able to afford haemodialysis. It is important to implement appropriate screening programmes to aid early detection of CKD in at risk populations. Early detection and aggressive control of the risk factors for development of CKD are necessary to prevent and reduce the scourge of CKD in resource poor settings where services for renal replacement therapy are not widely available or are unaffordable for most patients requiring such services.


Progression from nonsevere sepsis—i.e., sepsis without organ failure or shock—to severe sepsis or shock among emergency department (ED) patients has been associated with significant mortality. Early recognition in the ED of those who progress to severe sepsis or shock during their hospital course may improve patient outcomes. We sought to identify clinical, demographic, and laboratory parameters that predict progression to severe sepsis, septic shock, or death within 96 h of ED triage among patients with initial presentation of nonsevere sepsis.This is a retrospective cohort of patients presenting to a single urban academic ED from November 2008 to October 2010. Patients aged 18 years or older who met criteria for sepsis and had a lactate level measured in the ED were included. Patients were excluded if they had any combination of the following: a systolic blood pressure <90 mmHg upon triage, an initial whole blood lactate level ≥4 mmol/L, or one or more of a set of predefined signs of organ dysfunction upon initial assessment. Disease progression was defined as the development of any combination of the aforementioned conditions, initiation of vasopressors, or death within 96 h of ED presentation. Data on predefined potential predictors of disease progression and outcome measures of disease progression were collected by a query of the electronic medical record and via chart review. Logistic regression was used to assess associations of potential predictor variables with a composite outcome measure of sepsis progression to organ failure, hypotension, or death.p < 0.01) and a diastolic blood pressure <52 mmHg at ED triage  were independently associated with disease progression to severe sepsis or shock within 96 h of ED presentation. There were no deaths within 96 h of ED presentation.In this cohort of 582 ED patients with nonsevere sepsis, 108 (18.6 %) experienced disease progression. Initial serum albumin <3.5 mg/dL (OR 4.82; 95 % CI 2.40–9.69; In our patient cohort, serum albumin <3.5 g/dL and an ED triage diastolic blood pressure <52 mmHg independently predict early progression to severe sepsis or shock among ED patients with presumed sepsis. Recent literature suggests that patients with sepsis who develop organ dysfunction represent approximately 25 % of those who initially present to the emergency department (ED) with sepsis , 2. MortWhile attention has been placed on early, appropriate treatment of severe sepsis and septic shock in the ED –10, no tPrognostication rules exist to predict mortality among septic patients in the ED , 11, 12;We hypothesized that there are clinical, demographic, and laboratory parameters that independently predict early sepsis progression. The goal of this study is to identify specific parameters that are associated with a composite outcome of progression to severe sepsis, shock, or death within 96 h of ED triage among ED patients who initially present with nonsevere sepsis.This was a retrospective single-center cohort study of adult ED patients with suspected sepsis. A computerized decision support system in the electronic medical record was used to screen for eligible patients from November 2008 to October 2010. The institutional review board of the study site approved the study with a waiver of informed consent.Patient records were reviewed for all patients presenting to the ED at the Jacobi Medical Center, an academic teaching hospital in the Bronx, NY, with an annual ED census of 75,000 patients. Patients were included in the study if they (1) were 18 years of age or older, (2) had sepsis (two out of four SIRS criteria and suspicion of infection based on an accepted consensus definition ), and  as performed by the Jacobi Medical Center information technology (IT) department using a preexisting electronic decision support system. The support system automatically combined triage vital signs with the white blood cell count then alerted the clinician that lactate testing was recommended for patients with suspected infection who meet two or more SIRS criteria. Clinicians were electronically queried about the presence or absence of infection upon completion of the ED electronic medical record once a clinical disposition was recorded.Patients were excluded from the study if they 1) had a systolic blood pressure less than 90 mmHg upon ED triage and (2) exhibited any signs of organ dysfunction upon initial evaluation. The organ systems assessed were respiratory, renal, coagulation, hematologic, hepatic. We used a slightly modified form of standard definitions provided in a prior paper  met with all research associates collectively and individually to provide a standardized orientation on how data should be extracted. The data abstractors were audited weekly. Four reviewers abstracted the data on potential predictor variables from the ED summaries, admission notes, and hospital discharge summaries. Three independent reviewers abstracted information about the presence of the outcome of interest—progression of patients in nonsevere sepsis to severe sepsis or death within 96 h of ED triage. Both groups were blinded to the information collected by the other group. The abstractors used REDCap , a secured internet data management computer program, to enter the data on both predictors and outcomes. REDCap utilizes online DCIs and allows automatic entry into a spreadsheet, which obviates the need for manual data entry to a spreadsheet and minimizes transcription error. DCIs were designed for both predictor and outcome variables. Ten percent of patients had all variables collected by a second unblinded abstractor (AH or NG) to confirm reliability of data.Information on underlying comorbidities was collected by chart review. Three reviewers  searched the electronic medical record in the ED summaries, admission notes, and discharge summaries looking for the following comorbidities: diabetes mellitus (DM), coronary artery disease (CAD), congestive heart failure (CHF), cirrhosis and/or diagnosis of hepatitis B and/or C, chronic kidney disease, chronic obstructive pulmonary disease (COPD), asthma, acquired immune deficiency syndrome (AIDS), alcohol dependence, and cancer. These secondary diagnoses were chosen based on previously reported associations with sepsis mortality –21.All relevant patient information collected via manual chart review of the electronic medical record was assessed for interrater reliability. All variables collected by the DCIs showed at least good agreement .The primary outcome is a composite measure of sepsis progression. Disease (sepsis) progression was defined as the development of one or more of the following within 96 h of ED presentation: 1) organ dysfunction .The relationship between each candidate predictor and the primary composite outcome of sepsis progression was assessed using univariate analyses. All continuous variables were converted to categorical variables in an effort to find clinically meaningful cutoffs. Pearson’s chi-squared or Fisher’s exact tests were used for categorical variables, as appropriate. All variables that were statistically significant at an alpha <0.25 in univariate analysis were included in a logistic regression model. . Wald statistics were used to assess each variable’s statistical significance in the model. An alpha of 0.05 decided whether a variable would be retained in the model. Regression diagnostics were assessed using the Hosmer and Lemeshow goodness-of-fit test. Influential datapoints and covariate patterns were checked using the delta chi-squared and delta deviance influence statistics. Tests for interaction were conducted between predefined groups of variables.All statistical analysis was conducted with STATA 10.1 .Nine hundred ninety-five patients met the inclusion criteria during the study period from November 2008 to October 2010. After applying the exclusion criteria and subsequently excluding three patients who signed out of the hospital against medical advice, there were 582 eligible patients found in our chart review who had nonsevere sepsis in the emergency department. One hundred eight (18.6 %) of the patients meeting the inclusion criteria went on to develop the composite outcome of severe sepsis or shock within 96 h of ED presentation. (No patients died within this time period). Table Table p = 0.08; not shown].Among patients initially presenting to the ED in nonsevere sepsis, an initial serum albumin <3.5 g/dL  and an ED triage diastolic blood pressure <52 mmHg  were both independently associated with the development of severe sepsis or shock within 96 h of ED presentation. There were no deaths within the first 96 h of ED presentation in our sample. History of AIDS had an OR 2.23 to predict disease progression when controlling for age, diastolic blood pressure, and serum albumin, but this relationship did not reach statistical significance [Table While there were no deaths within 96 h of presentation to the ED, our sample had five (5) deaths throughout the hospital course; 3 (0.63 %) of them did not have disease progression within 96 h of ED presentation, while the remaining 2 (1.85 %) did.In the present study, almost one in five patients presenting to the ED with sepsis experienced disease progression. This incidence is in keeping with prior reports in the literature, which range from 12 to 26 % , 24. SevThe two associations we found are biologically plausible. Serum albumin is commonly considered a marker of nutritional status, but the reasons for hypoalbuminemia among hospitalized patients are complex. In a metabolically stressed state, decreased enteral protein intake and increased intravascular catabolism are partly responsible, but the two primary reasons for low albumin levels in sepsis are (1) increased transcapillary loss and (2) impaired hepatic production. Under normal circumstances, the transcapillary escape rate (TER) of albumin—i.e., the amount of intravascular albumin that leaves the bloodstream in the capillary beds—is about 5 % per hour. That amount increases by about twofold in patients with sepsis , and up Cytokines also directly suppress albumin production by the liver. Albumin has anti-inflammatory effects, including decreased platelet aggregation , so its A diastolic blood pressure of 52 mmHg corresponds with a mean arterial pressure of 65 mmHg and a systolic blood pressure of 90 mmHg. The latter two values are defined as clinical hypotension. Though a patient may not be hypotensive by mean arterial pressure or by systolic blood pressure in the ED, a low diastolic blood pressure upon triage may be an early, subtle sign that a septic patient may go on to have disease progression. Diastolic blood pressure is one marker of vascular tone. One study demonstrated that levels of endogenous inflammatory mediators such as nitrous oxide and TNF-alpha are associated with progression to severe sepsis, shock, or death . These cThe shared pathophysiology of hypoalbuminemia and low diastolic blood pressure and what they represent in sepsis add credibility to our findings. The infectious pathogen and damaged host tissue create a cytokine and chemokine “storm” in the early phase of sepsis that activates the innate and adaptive host responses. Hypoalbuminemia and low diastolic blood pressure are markers of two microcirculatory abnormalities—loss of endothelial barrier function and low capillary perfusion pressure, respectively—caused by extensive cytokine-derived endothelial damage. Those microcirculatory derangements are major contributors to organ failure in sepsis .Early identification and prevention of organ dysfunction or hemodynamic compromise highlights a very important principle in the treatment of patients with sepsis. The early goal-directed therapy trial by Rivers et al.  showed aOur study adds useful information to the pool of available studies that seek to identify factors associated with disease progression in sepsis , 37–40. Though the factors we found to be associated with sepsis progression are plausible, several other variables failed to exhibit similar relationships. Glickman et al. found an association with age and disease progression , though Any continuous predictors were dichotomized before entry into our model. For instance, diastolic blood pressure was dichotomized at 52 mmHg. This value corresponds to the diastolic blood pressure if the systolic blood pressure is 90 mmHg and the mean arterial blood pressure is 65. Clinical hypotension is defined in the literature as a systolic blood pressure less than 90 mmHg and/or a mean arterial blood pressure less than 65 mmHg. Serum bicarbonate was dichotomized at 20 mmHg, which was the lower limit of normal at the study site. Serum albumin was dichotomized at 3.5 g/dL because any value below this is considered hypoalbuminemia. Serum sodium was dichotomized at 145 mEq/L because sepsis disease progression has been associated with an initial serum sodium above that value . The goaOur dataset had a high percentage of missing data for the components that made up our primary outcome. Our full composite outcome variable had eight components: pulmonary dysfunction, hematologic dysfunction, renal dysfunction, liver dysfunction, coagulopathy, hyperlactatemia, shock, and death, all within 96 h of ED presentation. Of these, liver dysfunction , coagulopathy (measured by INR and PTT), and hyperlactatemia could not be assessed on a large number of patients  because no repeat values were sent within 96 h of ED presentation. We took two actions in our analysis to address this issue: (1) we made assumptions about missing repeated measures of organ dysfunction; (2) we performed a sensitivity analysis using outcomes in which we had <5 % missing repeated measures. If any one of these values were missing, we assumed that patients who were discharged from the hospital did not have those specific organ dysfunctions in the full composite outcome variable for disease progression. We may have introduced misclassification bias by assuming the absence of organ dysfunction from missing datapoints. After testing associations with potential predictors to our primary composite outcome of disease progression, we ran a separate analysis of a reduced composite outcome—using only respiratory failure, renal dysfunction, thrombocytopenia, or development of shock. The aim was to see if bias related to missing data may account for an absence of expected associations. We performed a sensitivity analysis with a reduced disease progression outcome variable to address this problem. Albumin <3.5 g/dL became the only independent predictor of the reduced disease progression outcome. Diastolic blood pressure <52 mmHg no longer was statistically significant in the model with reduced disease progression outcome.Mortality within 96 h of ED presentation was included as an outcome, unlike some studies that assessed only sepsis progression , 37, 39.Our study suffers from some important limitations. This study was based on a chart review with some missing data. Repeat laboratory tests that would indicate disease progression were not available for all patients, presumably because they were not ordered. It is probable that these data were not missing randomly. Less sick patients would be less likely to receive repeat tests than those who were sicker. Given the probable non-random distribution of missing data, imputation was not performed. In the absence of any other information, we categorized these patients as not having disease progression, thus introducing potential for misclassification bias. We conducted a sensitivity analysis by excluding these patients and found a difference in our conclusions. However, we avoided other possible limitations of chart review methodology by following strict protocol that blinded the data collection of predictors and outcomes, used standardized chart review techniques and DCIs, and systematically monitored the data collection. Another limitation is the inherent selection bias in our sample. Only patients for whom a lactate level was sent by the treating physician could be included. It is possible that clinicians in our ED only sent a lactate on sicker patients, potentially biasing our sample and limiting the generalizability of our findings. However, our sample had a lower mortality rate and similar incidence of sepsis progression compared to previously published studies with comparable objectives , 24.Our study demonstrated that an initial serum albumin <3.5 g/dL and an ED triage diastolic blood pressure <52 mmHg had independent, statistically significant associations with early future progression to severe sepsis or shock among patients with nonsevere sepsis. Future studies should validate our findings in a larger multicenter cohort with a low percentage of missing data. The next step would be to derive and validate a prediction tool for ED identification of nonsevere sepsis patients at increased risk of disease progression. This could lay the groundwork for further studies of interventions aimed at reducing sepsis progression in this population.


Developing countries are disproportionately affected by hypertension, with Black women being at greater risk, possibly due to differences in body fat distribution. The objectives of this study were: (1) To examine how different measures of body composition are associated with blood pressure (BP) and incident hypertension; (2) to determine the association between baseline or change in body composition, and hypertension; and (3) to determine which body composition measure best predicts hypertension in Black South African women. The sample comprised 478 non-hypertensive women, aged 29–53 years. Body fat and BP were assessed at baseline and 8.3 years later. Body composition was assessed using dual-energy X-ray absorptiometry (DXA) (n = 273) and anthropometry. Hypertension was diagnosed based on a systolic/diastolic BP ≥140/90 mmHg, or medication use at follow-up. All body composition measures increased (p<0.0001) between baseline and follow-up. SBP and DBP increased by ≥20%, resulting in a 57.1% cumulative incidence of hypertension. Both DXA- and anthropometric-derived measures of body composition were significantly associated with BP, explaining 3–5% of the variance. Baseline BP was the most important predictor of hypertension (adjusted OR: 98–123%). Measures of central adiposity were associated with greater odds (50–65%) of hypertension than total adiposity (44–45%). Only change in anthropometric-derived central fat mass predicted hypertension (adjusted OR: 32–40%). This study highlights that body composition is not a major determinant of hypertension in the sample of black African women. DXA measures of body composition do not add to hypertension prediction beyond anthropometry, which is especially relevant for African populations globally, taking into account the severely resource limited setting found in these communities. Hypertension is a global problem, currently affecting more than 1 billion individuals worldwide ,3. The bObesity, which is a well-recognized risk factor for hypertension ,6, has bHistorically, body composition has been measured using basic anthropometry , however dual-energy X-ray absorptiometry (DXA) technology is now available in which total body composition and body fat distribution can be measured with a high degree of accuracy and objectivity ,23. IndeThis prospective study, consisting of two waves of data collection, took place at the Medical Research Council (MRC)/University of the Witwatersrand (WITS) Developmental Pathways for Health Research Unit (DPHRU) at the University of the Witwatersrand. The first wave of data collection (baseline data) took place between 2002 and 2003 and the follow-up period was between 2011 and 2014, with an average follow up period of 8.3±1.1 years . The curDuring baseline recruitment, questionnaires were used to assess possible confounders including age, socio-economic status (SES), tobacco use, physical activity, personal history of hypertension and treatment, and family history of hypertension. The SES was based on household amenities . ParticiDuring follow-up, the same anthropometric and DXA measures were recorded and a similar questionnaire was used to assess tobacco use, physical activity, personal history of hypertension and treatment, and family history of hypertension. Information regarding SES was not included in the follow-up questionnaire. Questions related to menopause status and contraceptive use were included in the follow-up questionnaire. The Stages of Reproductive Ageing Workshop + 10 (STRAW+10) criteria ,29 were The outcome variables of our study were absolute blood pressure at baseline and follow-up, the change in blood pressure over time, and incident hypertension in this population. Blood pressure measurements were taken in a seated position after 30 minutes of seated rest. The measurement conditions (e.g. time of day) and environment were similar for baseline and follow-up measures. The SBP and DBP were recorded twice on the right arm using a standard mercury sphygmomanometer and appropriately sized cuff. The average of the two measures was used to determine blood pressure levels. Pulse pressure (PP) was determined by subtracting the DBP from the SBP and the mean arterial pressure (MAP) was calculated based on the formula: [DBP + PP/3]. Participants were classified as being hypertensive if they had a SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg [From the total sample of 478 participants that underwent anthropometric measurements, only 273 underwent DXA analysis at both time points. The participants who had DXA measures were similar in age, BMI, WC and blood pressure to those who did not have DXA measures (data not shown).th-75th percentiles. Change in body composition and blood pressure between baseline and follow-up evaluations were assessed using paired-sample Student-t tests or Wilcoxon-rank test. Pearson’s correlation coefficients were used to assess the relationships between body composition measures and blood pressure variables. Based on the results of these associations, robust multiple linear regression models were used to assess the independent effects of body fat and fat distribution, as well the change in these variables, on blood pressure levels, while adjusting for age at baseline. Multivariable logistic regression models were used to determine potential anthropometric- and DXA-derived predictors of hypertension, while adjusting for baseline age and baseline systolic blood pressure. In separate linear and logistic regression analysis  and skewed variables as median and 25In the sub-group of participants with data available on all anthropometric- and DXA-derived measures (n = 273), anthropometric-derived measures of total body fat (BMI) and central body fat (WC and WHtR) were compared to DXA-derived measures of total body fat (fat mass) and central body fat (trunk fat mass) as predictors of hypertension. AUC was used to determine the discriminatory power of these models. Statistical significance was based on a p<0.05. All analyses were performed using STATA version 13 .th-75th percentiles) age of the sample population was 40 (36–45) years, and the mean (±SD) follow-up period was 8.3±1.1 years (range: 7–12 years). At baseline, 38.5% of the participants had access to running water and 47.5% had flushing toilets inside their homes. No SES data was available at follow-up. Few women smoked at baseline (4.1%), but this more than doubled at follow up . Information related to menopausal status and contraceptive use was not included in the questionnaire at baseline, however at follow-up, 31% of the women were pre-menopausal, 23.1% were peri-menopausal and 45.9% were post-menopausal. Fourteen percent of women were using hormonal contraceptives.All measures of body composition increased significantly from baseline to follow-up . Both SBP and DBP increased significantly over the follow-up period, with SBP increasing by 20.7% and DBP increasing by 20.5%  in predicting hypertension, no significant difference was found between the models . These results are important in the practical setting, since data on change in body composition is not always available and this study highlights the fact that baseline body composition is sufficient and is in fact a stronger predictor of hypertension.In this study we also compared anthropometric- to DXA-derived measures of body fat and fat distribution to determine whether DXA-derived measures offer additional advantage in predicting hypertension or blood pressure. When comparing the AUC of the anthropometric- with DXA-derived measures of total and central adiposity, the indices correlated similarly. Our findings therefore suggest that, compared to basic anthropometry, DXA-derived measures of body composition do not offer an additional advantage in predicting hypertension or blood pressure in this Black SA population, however additional studies need to be conducted with other cardiovascular outcomes. Similarly, Maximova  showed tA limitation of our study was that measurements were only taken at two time points, limiting the interpretation of changes during the intervening period. Other limitations include convenience sampling, small sample size for the measured covariates, and not measuring other covariates, such as sodium intake. Additionally, baseline menopausal status was not measured. To our knowledge, this is the first longitudinal study that has examined changes in body composition and body fat distribution, examining both anthropometric-derived and DXA-derived measures of body composition, in relation to hypertension risk in a female African population. The results obtained from this study are essential to understanding the role of body fat and fat distribution in relation to hypertension risk in the Black female population. Since the high incidence of hypertension is only partially explained by body fat and fat distribution, additional studies are important to determine which factors contribute most to the high incident hypertension.In conclusion, this study highlights the high incidence of hypertension in a black female population, which is significantly associated with baseline body fat, in particular central adiposity. This highlights the necessity to measure central adiposity when screening for hypertension risk. Our study highlights that we cannot generalize risk factors of hypertension to the same extent to all populations. Body fat and fat distribution differ between ethnic groups and this study highlights that body composition is not the major determinant of hypertension in the sample of black African women, but that more critical mechanistic work is needed to determine what is causing the significant increase in hypertension with age and menopausal transitions in the African population. Finally, DXA-derived measures of body composition do not add to hypertension prediction beyond anthropometry-derived measures. Since anthropometry is an affordable and easy measure to acquire, these findings are especially valuable taking into account the severely resource limited setting found in low and middle income countries.S1 DatasetLabels used in dataset, 03, baseline; swt, follow-up; ac, absolute change, rc, relative change; bmi, body mass index; wc, waist circumference; whr, waist-to-hip ratio; wheightr, waist-to-height ratio; msbp, mean systolic blood pressure; mdbp, mean diastolic blood pressure; pp, pulse pressure; map, mean arterial pressure; pc, percentage; hypertensive_03_bp; participants with high blood pressure at baseline; hypertensive_swt_bpmeduse; participants with high blood pressure and/or using medication to treat hypertension at follow-up; fhhypertension, family history of hypertension.(XLSX)Click here for additional data file.S1 Table2 for each model. ‘Baseline’ represents the baseline body fat and fat distribution variable and ‘Δ’ represents the change in body fat and fat distribution variable; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial blood pressure; PP, pulse pressure; BMI, body mass index; WC, waist-circumference; HC, hip-circumference, WHtR, waist-to-height-ratio; PA, physical activity; FHH, family history of hypertension.Data presented as β-coefficient, standard error (SE) and p-value. As well as R(PDF)Click here for additional data file.S2 Table2 for each model. ‘Baseline’ represents the baseline body fat and fat distribution variable and ‘Δ’ represents the change in body fat and fat distribution variable; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial blood pressure; PP, pulse pressure; FM, fat mass; PA, physical activity; FHH, family history of hypertension.Data presented as β-coefficient, standard error (SE) and p-value. As well as R(PDF)Click here for additional data file.S3 TableData presented as odds ratio, 95% confidence interval (CI), area under ROC curve (AUC). BP, blood pressure; BC, body composition; Δ BC, change in body composition; PA, physical activity; FHH, family history of hypertension.(PDF)Click here for additional data file.S4 TableData presented as odds ratio, 95% confidence interval (CI), area under ROC curve (AUC). BP, blood pressure; Δ, change in body composition; FM, fat mass; PA, physical activity; FHH, family history of hypertension.(PDF)Click here for additional data file.