We hypothesized that increased BPV in sick preterm infants, by exceeding the cerebral autoregulatory capacity, is associated with cerebral oxygenation changes which closely follow the blood pressure fluctuations. We assessed the autoregulatory capacity in the early postnatal period, by determining the correlation between BPV  weeks were studied on the first 3 postnatal days. Spectral analysis  was used to calculate coherence of MABP and TOI; BPV was quantified using power spectral density of MABP.Overall, maximum Coherence showed a trend for positive correlation with BPV . Infants identified as clinically unstable with documented brain injury (n = 7) had high Coherence values at low BPV. Separate analysis of stable infants  revealed a significant association between maximum Coherence and BPV .Fluctuation in cerebral oxygenation is closely associated with increased BPV in preterm infants undergoing intensive care. Moreover, in the critically sick preterm infant, blood pressure-dependent variations in cerebral oxygenation occur even with relatively lower BPV, suggesting they have severely impaired autoregulation, and placing them at greater vulnerability to cerebral injury arising from blood pressure fluctuations. In support of the potential adverse effect of high BPV on preterm brain injury, high BPV in hypertensive adults has been reported to be an important determinant of end organ injury Cerebral periventricular haemorrhage and white matter injury are most likely responsible for the majority of neurological deficits in survivors of preterm birth Cerebral oxygenation and autoregulation in sick preterm infants have been assessed using Spatially resolved spectroscopy (SRS) In this study, we aimed to determine the relationship between cerebral autoregulatory capacity and BPV in extremely preterm infants. To assess the implications for injury we focused on the first 3 postnatal days when most intraventricular haemorrhages (IVH) occur in preterm infants This project had approval from Monash Medical Centre Human Research Ethics Committee and written parental informed consent was obtained prior to each study.Preterm infants were eligible if they were born at ≤29 weeks gestational age, with a birth weight ≤1000 gm, and an intra-arterial catheter. Infants with major congenital abnormalities were excluded.Thirty-two extremely low birthweight infants  were stuSeven infants were clinically extremely unwell during the study, and subsequently had documented brain injury or died. These infants included one who died on day 3 due to systemic embolism secondary to pulmonary interstitial emphysema, and five who sustained severe cerebral injury . One additional infant had severe pulmonary hemorrhage with resultant profound hypoxemia and severe metabolic acidosis during the study; the MRI at term-corrected age showed loss of white matter in the periventricular region. The cranial ultrasound findings in the other 25 infants ranged from normal (n = 16), to grade I (n = 7) or grade II (n = 2) IVH.Spatially resolved spectroscopy  was employed for continuous TOI recording. Two aligned photodetectors are housed inside the detection probe, fixed at 4 cm from the emission probe. The probes were placed over the temporo-parietal region of the infants. The SRS algorithm 2) were displayed on a cotside monitor. Arterial oxygen saturation (SaO2) was obtained via an oximeter  from an oximetry probe secured to the right upper limb.Continuous measurements of MABP were obtained from an indwelling intra-arterial catheter connected to a transducer monitoring system . The blood pressure waveforms and values, along with the continuously monitored transcutaneous partial pressure of carbon dioxide (PaCO2 (less than 8 mmHg fluctuation) and SaO2 (less than 5% fluctuation), were divided into 20-minute segments for subsequent analysis. TOI recordings were excluded from analysis if movement artifacts caused a baseline shift of ≥10%. In practice this excluded recordings during spontaneous head movements, physical examinations, radiographs, clinical procedures, and other events requiring handling of the infant. Segments were also excluded if arterial pressure recordings were interrupted by blood gas sampling or limb movements when the intra-arterial line was in a peripheral limb site/placement.Analogue signals of the cotside physiologic data were collected and digitised at 400 Hz , and were then down- sampled to 6 Hz to allow for offline spectral analysis with TOI which was collected simultaneously. Uninterrupted simultaneous recordings of TOI and MABP, with stable PaCOTOI(f) and PMABP(f)], and their cross PSD  were used to generate the coherence function for the two signals |PTOI,MABP(f)|2/[|PTOI(f)| |PMABP(f)|], and their transfer function, PTOI,MABP(f)/PMABP(f).Correlation between continuous measurements of MABP and TOI were quantified in a frequency-specific manner by established spectral analysis techniques MABP(f)] of MABP.The coherence function characterizes the frequency dependent correlation of MABP with TOI. The numeric value of the coherence function (Coh) at a given frequency ranges between zero and 1.0; Coh values of ≥0.5 are considered to represent significant frequency-specific concordance between the 2 waveforms The transfer function gain  represents the magnitude of change in the output (TOI) arising from a unity change in the input (MABP) at a given frequency. Impaired autoregulation, signified by a large magnitude change of TOI for a nominal change of MABP, gives rise to a high magnitude for G. G values were used for analysis only if the corresponding Coh of the 20-minute segment was ≥0.5, since at Coh <0.5, the fundamental assumption for linear transfer function gain may be violated Coh, BPV and G values were averaged for frequencies between 0.003 and 0.02 Hz. The upper limit was chosen to be 0.02 Hz as autonomic vascular control of cerebral autoregulatory processes occur at frequencies below this level The correlation between Coh and BPV was analysed by selecting the highest Coh value on each of the 3 postnatal days, and also the overall maximum Coh value over the entire 3 postnatal days. We selected these peak values of Coh as representative of periods of greatest autoregulatory impairment which may place the infant at greatest clinical risk of cerebral injury For infants with maximum Coh ≥0.5, the corresponding G values were compared between infants of different degree of clinical sickness.t test was used to determine the difference between BPV for infants receiving inotropic support and those who were not, and also to determine the difference in TOI values between the 7 critically sick infants and the rest of the infants. The Mann-Whitney Rank Sum test was used to determine the difference in the median values of G between the 7 critically sick infants and the rest of the infants, as the data did not show a normal distribution. One Way Repeated Measures ANOVA was used to determine change in MABP and TOI over the 3 days. A P-value of less than 0.05 was considered statistically significant.Sequential data analysis was performed  to evaluate the relationship between Coh and BPV. Firstly, Analysis of Covariance (ANCOVA) 2 values averaged for each postnatal day in all infants showed a positive correlation , while the TOI and SaO2 values averaged for each postnatal day showed a trend for positive correlation .The mean (± SD) numbers of 20-minute segments free of movement artefacts per infant used for analysis, were 5(±1.6), 5.1(±1.6) and 5(±1.8) on postnatal days 1–3 respectively. The averaged MABP and TOI for the infants on postnatal days 1–3 are shown in The correlation between Coh and BPV within infants ANCOVA,  was sign2 = 0.08, P = 0.06, 2 = 0.24, P = 0.006, The single maximum Coh of each infant over the entire 3 days showed a trend towards positive association with the corresponding BPV (R2 (P = 0.14) respectively. Of the 10 infants who received inotropic support, 2 developed Grade III-IV IVH; in these infants there was no evident relationship between their level of hypotension, the institution of inotropic support and the development of moderate to severe IVH.Median (IQR) G associated with maximum Coh was higher in 7 critically unwell infants compared with the rest of the infants in the study . BPV for 20-minute segments associated with ongoing inotropic support was not significantly different from those without support, with values of 3.31(±4.17) and 3.97(±4.49) mmHgTo our knowledge this is the first study in extremely preterm infants to employ spectral analysis to examine the relationship between fluctuations in cerebral oxygenation and BPV that takes account of the specific clinical status of the infants. Overall, our results revealed a significant positive association between the degree of coherence of cerebral TOI with MABP (Coh), and the extent of blood pressure variability (BPV) on the first and third postnatal days. In clinically stable infants, a significant correlation between the maximum Coh and BPV emerged after exclusion of those infants with cerebral injury or who were clinically very unwell, suggesting that the form of relationship between Coh and BPV may be altered in infants who are critically ill with low TOI values. As increased Coh indicates cerebral autoregulatory impairment 2 and PaCO2, the Coh values and the relationships between Coh and BPV do not reflect these associations, as all coherence analyses for MABP and TOI were conducted within infants using data segments with stable PaCO2 and SaO2. Technically, increased Coh could be evident at higher BPV due to the improved ‘signal-to-noise’ ratio at higher BPV Though overall physiological relationships were evident between TOI, SaOLimited or impaired cerebral autoregulation in sick preterm infants has been shown in previous studies The association between Coh and BPV in relation to the clinical stability of the very preterm infant is summarized schematically in The factors underlying different degrees of BPV in preterm infants have not been studied. Normal BPV arises from the interaction between external stimuli and the regulatory mechanisms involved with behavioural variations, respiration and cardiovascular control. High frequency oscillations in BP are related to the effect of respiration on cardiac output and also by sympathetic control of vasomotor tone In adult hypertension, high BPV is associated with end organ damage independent of absolute blood pressure values An advantage of our application of frequency domain analysis is that it allows analysis of Coh and BPV in the very low frequency range. Since the amplitude of spontaneous MABP variations increase as their frequency decreases, significant disturbance in cerebral perfusion are more likely at these very low frequencies. A potential limitation of the coherence and transfer function analysis is the assumption that the MABP-TOI relationship can be modeled as a linear and stationary system Our study has demonstrated that in very preterm infants high blood pressure variability may easily exceed cerebral autoregulatory capacity, thereby generating significant fluctuations in cerebral oxygenation. The most critically sick infants exhibit blood pressure-dependent variations in cerebral oxygenation even with relatively low blood pressure variability, placing them at greater vulnerability to cerebral injury arising from blood pressure fluctuations.Our study suggests potential value of continuous monitoring of TOI and BPV, combined with spectral analysis, in clinical evaluation of sick preterm infants. This evaluation may identify those preterm infants who are at greatest risk of cerebral injury, guide clinical decision-making in relation to blood pressure management, and help develop strategies to minimize fluctuations in cerebral perfusion.


In other cells, activation of GCH-I leads to the formation of 5,6,7,8-tetrahydrobiopterin (BH4), the necessary cofactor of amino acid hydroxylases like phenylalanine 4-hydroxylase (PAH). Serum concentrations of phenylalanine, tyrosine, neopterin, and high sensitivity C-reactive protein (hsCRP) were measured in 1196 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography. The phenylalanine to tyrosine ratio (Phe/Tyr) served as an estimate of phenylalanine hydroxylase (PAH) enzyme activity. Serum concentrations of phenylalanine and tyrosine and of Phe/Tyr did not differ between individuals with or without CAD (Welch's t-test: P = n.s.). Higher neopterin and hsCRP concentrations were observed in CAD patients compared to controls (P < 0.0001) and they correlated with Phe/Tyr  concentrations. In conclusion, immune activation is associated with higher Phe/Tyr in CAD patients. Data indicates subnormal PAH activity which might be involved in the precipitation of neuropsychiatric symptoms in patients.Higher serum neopterin is associated with increased mortality in patients with coronary artery disease (CAD). Preferentially Th1-type cytokine interferon- Serum neopterin concentrations were determined by a commercially available radioimmunoassay  with a sensitivity of 1 nmol/L neopterin and an interassay coefficient of variation ranging from 3.9% to 8.2% . GFR wasribed in ).t-test, which does not assume equal variances. Correlation between variables was assessed by the nonparametric Spearman's rank correlation test, which was done with the program GraphPad Prism . For these calculations, the following assumptions concerning CAD were made: no CAD (0–10% stenosis) = 0, 11–49% stenosis = 1, one vessel disease = 2, and two- or three-vessel disease = 3. Acute coronary syndrome (ACS) was classified as: no ACS = 0, unstable angina pectoris = 1, non-ST-elevation myocardial infarction (NSTEMI) = 2, and ST-elevation myocardial infarction (STEMI) = 3.Patients were stratified according to the presence or absence of CAD. Frequencies between subgroups were compared by Fisher's exact test. Differences of mean laboratory variables among patient groups with and without CAD were tested for significance by Welch's P-to-enter” set at 0.05, and the “P-to-remove” at 0.10.We examined the relationship between Phe/Tyr, neopterin, hsCRP, calculated GFRs, systolic and diastolic blood pressure, ACS scores, sex, body mass index (BMI) and age by linear regression analysis using a stepwise version of a linear regression model as implemented in the program SPSS 11.0 for Windows . This technique identifies the subset of variables that predict the dependent variable in the best way. We used forward variable selection with “t test: P = n.s.). Patients with CAD had higher neopterin and hsCRP concentrations and higher systolic blood pressures but lower calculated GFRs and total, HDL- and LDL cholesterol concentrations than the control group.Among the 1196 study subjects, 20.8% had no CAD (control group), whereas 79.2% presented with CAD; 87% of the studied cohort reported on antihypertensive drug medication. As seen from rs = −0.264), neopterin (rs = 0.216), hsCRP (rs = 0.122), and BMI (rs = −0.135) had the strongest relationship. Phe/Tyr increased with age and was positively correlated with serum neopterin, hsCRP, and ACS score, but inversely correlated with calculated GFRs, body mass index, diastolic and systolic blood pressure, and the number of daily smoked cigarettes . There wn = 1196, r = 0.405, r2 = 0.164, P < 0.001). As calculated from a t-statistics, all the variables, neopterin , and hsCRP concentrations , GFR , BMI , age , and the number of daily smoked cigarettes , significantly contributed to Phe/Tyr which indicates an independent influence of these variables.To examine the relationship between Phe/Tyr, neopterin, hsCRP, calculated GFRs, systolic and diastolic blood pressure, ACS score, sex, BMI, and age, linear regression analysis was done. When a stepwise regression was performed, including all univariately significant variables as candidates, all variables with the exception of ACS score, sex, and diastolic and systolic blood pressure were included in the model. Thereby, the following equation resulted: Phe/Tyr = 1.338 + 0.0029 × [Neopterin] + 0.002 × [CRP] − 0.0022 × GFR − 0.0016 × Age − 0.0057 × BMI − 0.0008 × Cigarettes per day. By this equation about 16% of the variation of the Phe/Tyr could be explained  which is produced by macrophages upon stimulation by IFN-oduction . Consequoduction , 28. Recoduction .Candida albicans and against anaerobic, Gram-positive commensals of Bifidobacterium and Lactobacillus species [In general, oxidative stress may interfere with the tertiary structure of proteins by oxidation of sulfhydryl groups. Such structural changes may downregulate catalytic activity as was demonstrated recently for the reduction of disulphide-bridges in human ß-defensin 1 (hBD-1) which becomes a potent antimicrobial peptide against the opportunistic pathogenic fungus  species . Thereby4 deficiency. As a consequence of the very limited possibilities to determine BH4 concentrations directly in clinical settings, the monitoring of Phe/Tyr was proposed as an indirect marker of BH4 functional activity [γ, GTP-cyclohydrolase I is induced and primarily leads to the formation of BH4. In humans and primates only a significant production of neopterin is detected in cells of the monocytes-macrophages lineage, whereas in other cells and in other species only the biosynthesis of BH4 is of relevance [4, the necessary cofactor of several monooxygenases of amino acids including PAH [4 to 7,8-dihydrobiopterin (BH2) is associated with NOS uncoupling that results in the production of vasoconstrictory superoxide anion  at the expense of vasodilatory NO [The increase of Phe/Tyr in CAD patients may be due to impaired function of PAH resulting from BHactivity . During elevance . BH4, thding PAH , nitric ding PAH , and of ding PAH , is releatory NO . As a coα was reported to be associated with low dopamine concentrations in the cerebrospinal fluid and correlated with fatigue scores [According to the literature, alterations of phenylalanine and of Phe/Tyr could be involved in a wide spectrum of neuropsychiatric abnormalities , 12, 35.e scores . UnfortuIn conclusion, our study provides data that patients with CAD and higher serum neopterin or CRP levels may exhibit higher Phe/Tyr, an abnormality which is most probably due to impaired PAH activity. However, results need to be confirmed by further investigation. Still, our data indicate disturbed phenylalanine metabolism in patients which could possibly be associated with neuropsychiatric disturbances, because phenylalanine metabolism is closely related to neurotransmitter biosynthesis.


To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and diastolic blood pressure (DBP) with decline in renal function and time until the start of renal replacement therapy (RRT) in patients with CKD stages IV-V on pre-dialysis care.st 2008). Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT.In the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up  and 0.05  ml/min/1.73 m2/month respectively) and an earlier start of RRT  and 1.16  respectively). Furthermore, patients with SBP and DBP above the BP target goal of < 130/80 mmHg experienced a faster decline in renal function  ml/min/1.73 m2/month) and an earlier start of RRT ), compared to patients who achieved the target goal (11%). Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg) and patients with both SBP and DBP below the target (< 130/80 mmHg), showed that the results were almost similar as compared to patients with both SBP and DBP above the target  ml/min/1.73 m2/month and adjusted HR 2.24 ). Therefore, it seems that especially having SBP above the target is harmful.A total of 508 patients, 57% men and median (IQR) age of 63 (50-73) years, were available for analyses. Mean (SD) decline in renal function was 0.35 (0.75) ml/min/1.73 mIn pre-dialysis patients with CKD stages IV-V, having blood pressure  above the target goal for CKD patients (< 130/80 mmHg) was associated with a faster decline in renal function and a later start of RRT. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are major public health problems worldwide, because of rapidly increasing numbers of prevalent and incident cases -3. The dHigh blood pressure is an important independent predictor of decline in renal function in the general population  and in sTherefore, it is important to study the association of blood pressure with progression of CKD in patients with CKD stages IV-V on pre-dialysis care. Guidelines from the Kidney Disease Outcomes Quality Initiative (K/DOQI), Seventh Report of the Joint National Committee (JNC 7), and the American Heart Association (AHA) propose a blood pressure treatment target goal of < 130/80 mmHg through all stages of CKD -22. Becast 2008, whichever was earliest. Predefined data on demography, anthropometry, and clinical symptoms were extracted from medical charts at inclusion. All available data concerning laboratory measurements during pre-dialysis care were extracted from the Hospital Information Systems. The study was approved by the Institutional Review Boards of the participating hospitals and conducted in concordance with Good Clinical Practice Guidelines.The PREdialysis PAtient REcord-1 (PREPARE-1) study is a follow-up study in which consecutive incident adult patients with CKD stages IV-V were included from outpatient clinics of eight Dutch hospitals when referred for pre-dialysis care between 1999 and 2001. Patients had been referred to these outpatient clinics if creatinine clearance was below 20 ml/min. Furthermore, in these patients the need for RRT was expected within one year. Patients who spent less than one month on pre-dialysis care and patients with prior RRT were excluded. The clinical course of pre-dialysis patients was followed through the medical charts until the start of dialysis, transplantation, death, or January 1Blood pressure and variables used for adjustment in multivariable analyses were assessed at the first pre-dialysis visit (baseline) and measured according to the standard care applied in each individual hospital. The standard procedure for measuring blood pressure is using a device dependent on cuff occlusion of the arm, with the patient in sitting or lying position. The blood pressure treatment target goal was defined as SBP < 130 mmHg and DBP < 80 mmHg according to the K/DOQI, JNC 7, and AHA guidelines -22. EstiFor the present analyses, the first year of pre-dialysis care was used as follow-up time, because blood pressure was only assessed at baseline and blood pressure levels can change during pre-dialysis care. Therefore, we expect that the effect of baseline blood pressure on progression of CKD weakens after several years of follow-up. Outcomes were decline in renal function and time until the start of RRT. The rate of decline in renal function was estimated by fitting a regression line through the available eGFR measurements for each individual patient. This resulted in slopes expressing the monthly loss of eGFR. eGFR measurements between one month prior to inclusion and one year after inclusion were used and at least two measurements had to be available to estimate the rate of decline. Patients with eGFR measurements only available between one month prior to inclusion and one month thereafter were excluded from the analyses for decline in renal function (n = 20). The start of RRT was defined as starting dialysis or being transplanted within the first year of pre-dialysis care.Continuous data were expressed as mean  and skewed data as median . Baseline characteristics were presented for the total study population and stratified for patients below or above the blood pressure treatment target goal. SBP and DBP were both analyzed in steps of 10 mmHg increase and in categories. We used clinically relevant categories for SBP (< 130 (reference group), 130-149, 150-169, 170-189, and ≥ 190 mmHg) and for DBP (< 80 (reference group), 80-89, 90-99, and ≥ 100 mmHg). The reference categories chosen were based on the treatment target goal of < 130/80 mmHg. Furthermore, the range of the SBP and DBP categories (steps of 10 and 20 mmHg respectively) were selected by using the distribution of these variables, to end up with enough power in each category. Additionally, SBP and DBP were combined based on the treatment target goal of < 130/80 mmHg. The additional effect of having DBP above 80 mmHg on top of having SBP above 130 mmHg, compared to the single effect of SBP ≥ 130 mmHg or DBP ≥ 80 mmHg, was investigated. For this analysis, patients were stratified into four categories based on the combination of SBP and DBP (< 130/< 80 (reference group), ≥ 130/< 80, < 130/≥ 80, and ≥ 130/≥ 80 mmHg).A linear regression analysis was used to assess the association of blood pressure with decline in renal function during the first year of follow-up. Multivariable analyses were used to adjust for the possible confounders age, sex, race, smoking, primary kidney disease, presence of cardiovascular disease , and presence of diabetes mellitus (DM).The Kaplan-Meier method was used to estimate the crude risk and a Cox proportional hazard regression analysis was used to estimate the adjusted risk of starting RRT during the first year of pre-dialysis care. The risk of starting RRT was adjusted for the same confounders used in the multivariable linear regression analyses. The time from the first pre-dialysis visit until the start of RRT or end of the first year of follow-up was used in the Cox proportional hazard regression as follow-up time. Mortality and lost to follow-up were censored events. All p-values are two-tailed and p < 0.05 was considered statistically significant. Data were analyzed with PASW/SPSS version 17.st 2008) instead of the first year of follow-up, to investigate whether differences in follow-up time lead to different results. Second, a sensitivity analysis was performed with SBP and DBP stratified in quartiles and quintiles to make sure that the associations found are robust and not dependent on the choice of categories. Third, it can be argued that our analyses should be additionally adjusted for proteinuria, hemoglobin, and baseline eGFR. However, data regarding proteinuria, hemoglobin, and baseline eGFR were not available for all patients included in the analyses . Therefore, adjusting for these variables was only performed as a sensitivity analysis, in order to maintain power.Multiple sensitivity analyses were performed. First, sensitivity analyses were performed with only the first six months or with complete follow-up . Most of the patients on pre-dialysis care were referred by nephrologists (76%). This percentage was the same in patients below and patients above the target -inhibitors and/or diuretics whereas patients above the target were prescribed calcium-antagonists and beta-blockers just as often (Table 2/month. Mean (SD) decline in renal function was not dependent on the number of eGFR measurements and was 0.37 (0.89), 0.38 (0.62), 0.41 (0.72), and 0.26 (0.71) ml/min/1.73 m2/month for patients with 2-6, 7-9, 10-13 and ≥ 14 eGFR measurements (quartiles) respectively. The analysis of SBP in steps of 10 mmHg showed a linear association, every 10 mmHg increase in SBP resulted in an accelerated decline in renal function  ml/min/1.73 m2/month, Table 2/month) resulted in an accelerated decline in renal function (Table The median (IQR) number of available eGFR measurements during the first year of follow-up was 9 6-13) and 98.6% of the patients had three or more eGFR measurements. In the total group of 436 patients, mean (SD) decline in renal function was 0.35 (0.75) ml/min/1.73 m and 98.62/month, Table 2/month) resulted in an accelerated decline in renal function. However, the most pronounced decline in renal function was present in patients with DBP ≥ 100 mmHg.Every 10 mmHg increase in DBP also resulted in an accelerated decline in renal function  ml/min/1.73 m2/month). Adjustment for confounders did not change these results essentially  showed that patients with SBP and/or DBP above the target had an accelerated decline in renal function compared to patients with SBP and DBP below the target (mean (SD) decline 0.13 (0.85) ml/min/1.73 m2 at the start of RRT respectively. The crude association of SBP and DBP categories with time until the start of RRT is shown in Figure During the first year of follow-up, of all patients 23% started hemodialysis and 22% peritoneal dialysis, 1% was transplanted, 5% died, 1% was lost to follow-up while 48% were still on pre-dialysis care. Median (IQR) follow-up time was 351 (144-365) days, while follow-up time in patients starting RRT was 145 (87-234) days. In patients below and above the blood pressure treatment target goal at baseline, mean eGFR was 6.7 and 8.2 ml/min/1.73 mUsing the blood pressure treatment target goal (SBP < 130 mmHg and DBP < 80 mmHg) showed that patients with SBP above the target and DBP below the target started RRT earlier ) compared to patients with both SBP and DBP below the target Table . Patient2/month respectively) and an earlier start of RRT  and 1.10  respectively). Second, other choices of blood pressure categories showed the same results as found in the primary analyses. Third, when including the covariates proteinuria, hemoglobin, and baseline eGFR in the model (sample size of 404 patients), the point estimates for decline in renal function and time until the start of RRT remained similar. With every 10 mmHg increase in SBP or DBP, decline in renal function accelerates  and 0.07  ml/min/1.73 m2/month respectively) and the start of RRT is earlier  and 1.17  respectively).To test the robustness of our findings, several sensitivity analyses were performed. First, in a sensitivity analysis with only six months of follow-up, results of the primary analyses were confirmed and point estimates were similar. Analyses with complete follow-up showed the same trend as in the primary analyses, however the associations were somewhat diluted. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function  and 0.05  ml/min/1.73 mThe results of this study show that 89% of the patients with CKD stages IV-V starting pre-dialysis care did not reach the blood pressure treatment target goal of SBP < 130 mmHg and DBP < 80 mmHg, even though the majority of these patients (92%) were treated with antihypertensive drugs. Both higher SBP and DBP were associated with a faster progression of CKD. More specific, patients with SBP ≥ 130 mmHg or DBP ≥ 100 mmHg had an accelerated decline in renal function (eGFR) during pre-dialysis care which was accompanied by an earlier start of RRT, compared to patients with SBP < 130 mmHg or DBP < 100 mmHg. Further analysis showed that in patients with SBP above the target goal (≥ 130 mmHg), additionally having DBP above the target goal (≥ 80 mmHg) did not result in an accelerated decline in renal function or an earlier start of RRT.2/month respectively). Our data are in line with the findings of several observational studies such as the MDRD study [2. However, CKD patients with an eGFR below 13 ml/min/1.73 m2 were excluded from the MDRD study because they were likely to start dialysis before the effect of diet and blood pressure control could be evaluated [et al [Our study is the first European study to report on the association of both SBP and DBP with the progression of CKD, as assessed by decline in renal function and time until the start of RRT, in a well-defined population of pre-dialysis patients with CKD stages IV-V. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function  and 0.05  ml/min/1.73 mRD study , which svaluated . Furtherd [et al , who fouet al [Our data are not in line with some previous published interventional trials on the effect of lowering blood pressure in CKD patients -29. Theset al . Finally2 are not treated by a nephrologist [2, but only to those receiving pre-dialysis care. However, for clinical practice our cohort is a very representative and relevant population. Second, for estimating the rate of decline in renal function, we assumed that the decline in renal function is linear in advanced CKD stages. It has been shown previously that linearity of the course in eGFR is a plausible assumption, although on theoretical grounds over a longer period of time an exponential decline could be present [The PREPARE-1 study has potential strengths and limitations. First, in our cohort an equal number of patients started HD and PD and therefore the results cannot be generalized to the United States pre-dialysis population. Furthermore, it has been estimated that in the general population 36-65% of the patients with an eGFR below 15 ml/min/1.73 mrologist . Therefo present . Third, What could be an explanation for the found association of hypertension with an accelerated decline in renal function and an earlier start of RRT? Endothelial dysfunction is a pathological consequence of hypertension  leading The proposed blood pressure treatment target goal for patients with CKD is < 130/80 mmHg, according to the K/DOQI, JNC 7, and AHA treatment guidelines for hypertension in CKD patients -22. The The PREPARE-1 study is an independent academic study designed and carried out by the Department of Clinical Epidemiology from the Leiden University Medical Center in collaboration with the Hans Mak Institute (Naarden) and the participating hospitals. This study was funded by an unrestricted grant from Amgen (the Netherlands and Switzerland). The sponsor of the study was not involved in study design, collection of data, statistical analyses, interpretation of data, writing of the manuscript, or in the decision to submit the paper for publication. None of the authors have declared a conflict of interest.MCMdG performed the statistical analyses and drafted the manuscript. NV collected data and revised the manuscript critically. NH, DJdJ, EWB, YWJS, FWD, and DCG contributed to the conception and the design and revised the manuscript critically. All authors have given final approval for this version to be submitted.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/12/38/prepub


Hypertension is a common cardiovascular disease, affecting adults worldwide and it accounts for up to 30% of all deaths. The need for better control of arterial hypertension justifies observational studies designed to better understand the real-life management of hypertensive patients. The ASTRAL study was primarily designed to evaluate the percentage of hypertensive patients achieving blood pressure goals after eight weeks of treatment with a fixed-dose combination of ramipril/hydrochlorothiazide (HCTZ).The study was a multi-centre, non-comparative, open-label, observational study conducted in 36 centres in five sub-Saharan African countries, namely Cameroon, Congo Brazzaville, Democratic Republic of Congo (DRC), Madagascar and Nigeria. Four hundred and forty-nine men and women 18 years of age or older with hypertension not controlled by an ACE inhibitor, a diuretic or any other monotherapy or anti-hypertensive combination not containing a diuretic in a fixed dose were considered eligible for inclusion in this eight-week study. The study consisted of three visits, visit one (V1) at baseline, visit two (V2) after four weeks and visit three (V3) after eight weeks.p < 0.001) and –31.7/–17.9 mmHg (p < 0.001), respectively. There were 60.2% of the non-diabetics on prior monotherapy who, at eight weeks, fulfilled the primary blood pressure goal for SBP and DBP, versus 26.5% of the diabetic patients, also on monotherapy. Few adverse events were reported, with facial oedema and dry cough recurring twice in two patients.The mean age of the patients was 54.7 ± 11.7 years (20–90 years) and most were categorised by the WHO criteria as either overweight or obese (71.6%). After four and eight weeks of treatment with the study drug, systolic and diastolic blood pressures significantly changed from baseline: –24.7/–14.2 mmHg (Fixed-dose combination of ramipril/HCTZ is therefore effective, tolerable and has a good safety profile for blood pressure control in black Africans. Hypertension is the most prevalent cardiovascular (CV) disease in adults worldwide and is a major risk factor for both cardiovascular and cerebrovascular morbidity and mortality.3Age, ethnicity, obesity, smoking, excessive consumption of alcohol and physical inactivity are among the risk factors identified to be associated with hypertension. The JNC-7 and recent European guidelinesThe primary outcome of the ASTRAL study was to evaluate the percentage of hypertensive patients achieving BP goals after eight weeks of treatment with a fixed-dose combination of ramipril/HCTZ, hence to generate data on the effectiveness of the fixed-dose combination.Ethics committee approval to undertake the survey was obtained from hospitals in each country in accordance with national and local regulations. Written, signed consent was obtained from each of the patients included. The study was conducted in accordance with the Helsinki II Declaration.The study was a multi-centre, non-comparative, open-label, observational study conducted across 36 centres in five sub-Saharan African countries . Men and women 18 years of age or older with arterial hypertension uncontrolled by an ACE inhibitor, a diuretic, or any other monotherapy or anti-hypertensive combination not containing a diuretic in a fixed dose were considered eligible for inclusion in the study. Exclusion criteria were: known hypersensitivity to any component of the study drug (Tritazide®), history of angio-oedema, patients with severe renal or hepatic dysfunction, severe gout, secondary hypertension, and all pregnant or breastfeeding women. Although the study was initially planned to include 460 consecutive hypertensive patients from the 36 participating centres, only 449 patients could be recruited and included to receive the study drug; 408 (90.9%) of these patients completed the study. The reasons for non-completion of the study are summarised in 2 and obese if ≥ 30 kg/m2, according to the WHO guidelines.13Three visits were scheduled during the study. At visit one (week 0), demographic data, history of co-morbidities, duration of hypertension, blood pressures at first diagnosis of hypertension and previous anti-hypertensive treatment given, concomitant medications, and CV risk factors were recorded. SBP and DBP were measured and recorded in the seated position after five minutes of rest in the medical office, using a validated and calibrated electronic sphygmomanometer  with an appropriate cuff size. A blood pressure target was established, recommended lifestyle modifications were given to the patient and the ramipril/HCTZ daily dose was prescribed, based exclusively on the decision of the treating physician and in accordance with the prescribing information in the summary of the product characteristics or package insert. Body weight was recorded in kilograms and height was measured in metres to determine the body mass index (BMI) which was recorded as overweight if ≥ 25 kg/mAt the follow-up visits at weeks four and eight , BP was measured, adverse events were assessed and treatment compliance rating was evaluated by taking into account the unused number of tablets returned by the patient on the follow-up visit and expressed as good (< four of 28 tablets returned), average (five to nine of 28 tablets returned) or poor (≥ 10 of 28 tablets returned). The necessity for titration to a higher dose of the study drug was evaluated in response to BP goal.The primary outcome of the ASTRAL study was to evaluate the percentage of hypertensive patients achieving BP goals after eight weeks of treatment with a fixed-dose combination of ramipril/HCTZ. Blood pressure control was defined as SBP < 140 mmHg and/or DBP < 90 mmHg in non-diabetics and SBP < 130 mmHg and/or DBP < 80 mmHg in diabetic patients. The secondary objectives included the assessment of variations in SBP and DBP values between visits, compliance with treatment, tolerance of the treatment and the factors influencing BP control.t-test.The statistical analysis was performed by ClinStat CC, Pretoria, South Africa. All analyses were carried out on SAS (release 9.1.3). Descriptive statistical analyses were performed. Qualitative variables were expressed as frequency counts and percentages. Quantitative variables were summarised by mean values, standard deviations, minimum and maximum values. Within-subject comparisons (changes in blood pressures at weeks four and eight relative to baseline) were tested for significance by the paired p-value < 0.05 was considered as significant.A logistic regression analysis was performed with goal achievement as a dependent variable and the following predictor variables: age, gender, history of diabetes, alcohol consumption, renal dysfunction, diabetic nephropathy, microalbuminuria, cerebrovascular accident and heart failure, BMI, concomitant treatment with NSAIDs, daily dose of study drug and BP at inclusion. In the logistic regression analysis, the following predictor variables were numeric: age, systolic blood pressure, diastolic blood pressure and daily doses of study drugs. All the other predictor variables were categorical. Adverse events were listed, indicating intensity, relationship with the study drug, discontinuation in the study, corrective treatment, outcome and seriousness. A 2 and most of the patients were categorised as either overweight or obese (72%).The baseline demographic and clinical features, co-morbidities and associated CV risk factors of all the patients and for patients from the five participating countries are shown in Tables Patients with a history of diabetes made up 19.6% of the study population and 2.4% were unaware of their diabetes status. There was a high number of patients with associated hypertension-related end-organ damage or co-morbidities (35.6%), such as previous cerebrovascular accidents, coronary artery disease and heart failure, accounting for 6.9, 1.3 and 6.5%, respectively. At the start of the study, only 17.1% of the patients had no known CV risk factor. No statistically significant differences were observed between the different countries in the baseline characteristics of the patients.At baseline, the mean SBP and DBP were 168.9 ± 19.2 and 102.6 ± 12.3 mmHg, respectively and most of the patients (70.8%) had been on only one or no anti-hypertensive agent before the study. Also, most of the patients  started and remained on a standard dose (5/25 mg) or half-standard dose (2.5/12.5 mg) of the fixeddose combination ramipril/HCTZ for the duration of the study p < 0.001) and –14.2/–17.9 mmHg (p < 0.001) for DBP The patterns of BP changes observed in this study were similar across the five participating countries. At V2 and V3, BP significantly changed from baseline: –24.7/–31.7 for SBP mmHg (Compliance with the fixed-dose combination of ramipril/HCTZ was 89.2% at week four and 92.6% at week eight of the study p < 0.05). Other factors associated with the attainment of BP goal were age , DBP  and SBP . However, with the logistic regression performed separately for diabetics and non-diabetics, no statistically significant predictors were found for goal achievement for diabetic patients. SBP at visit one was the only significant predictor of goal achievement in non-diabetic patients .The multivariate logistic regression analysis showed that in the ASTRAL study, diabetes was the most significant factor independently associated with BP goal attainment. The likelihood of achieving BP control in diabetic patients was 4.94 times less than in non-diabetic patients ,During the ASTRAL study period, there were eight episodes of reported adverse events by six patients who were on either half-standard or standard therapy, suggesting that the adverse events may not have been dose related. It is nonetheless not surprising that facial oedema and dry cough were the two most common, given that these two, together with hyperkalaemia, hypotension and renal dysfunction, are known and commonly reported adverse effects of ACE inhibitor use.In the HOPE study,19One limitation of the ASTRAL study has been the inability to measure or document changes in serum electrolytes and certain metabolic parameters, such as sodium, potassium, uric acid and glucose, which are known to be affected by thiazide diuretics. The modern tendency is for low-dose HCTZ (12.5 mg) to be recommended to avoid these metabolic complications and this has been incorporated into recent guidelines.There are also concerns, particularly regarding the increased incidence of new-onset diabetes with the higher dose. This is a controversial topic but it has never been shown in a large outcome study that new-onset diabetes worsens outcomes.A few patients were titrated upwards to ramipril 10 mg/HCTZ 50 mg for better BP control and although no significant adverse effects were reported, this raises some concerns about evaluating drug efficacy against its potential adverse effects, particularly electrolyte imbalances. Although this high dose of HCTZ has been used in major outcome studies, we would rather recommend the addition of alternative anti-hypertensive agents to achieve BP control until further safety information is available. In this study, the majority of patients did not require more than 25 mg HCTZ in the fixed-dose combination to achieve BP control.Fixed-dose combination of ramipril/HCTZ is an effective, tolerable anti-hypertensive agent with a good safety profile, which can be used to control BP in black Africans. This combination may be more effective in non-diabetics than patients with diabetes mellitus. Extended study with this combination is still needed to assess its long-term efficacy and safety.


Background. Since the treatment of hypertension is beneficial for the elderly, we have undertaken this study that aims to evaluate the management of hypertension in elderly patient in Côte d'Ivoire. Methods. A retrospective study was conducted among 854 hypertensive elderly patients of Abidjan Cardiology Institute who were followed for a minimum of one year, between January 2000 and December 2009. Results. The patients mean age was 73.1 ± 5.3 years, and 59% were women. At the first presentation, it was mostly systolic-diastolic hypertension (51.8%) and isolated systolic hypertension (38.5%). Mean blood pressure was 169.4 ± 28.4 mmHg for systolic, 95.3 ± 15.7 mmHg for diastolic, and 74.1 ± 22.8 mmHg for pulse pressure. Pulse pressure was ≥60 mmHg in 80.4%. According to the European Guidelines stratification of the cardiovascular risk-excess attributable to high blood pressure, 82.1% of the sample had a very high added risk. The pharmacological therapy was prescribed in 93.5%. More than 66% of patients were receiving ≥2 antihypertensive drugs including fixed-dose combination drugs. The most common agents used were diuretics (63.5%) followed by angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in 61.3%. The most common agents used for monotherapy were calcium antagonists. When ≥2 drugs were used, diuretics and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were the most common. Blood pressure control was achieved in 42.6%. Conclusion. The control of elderly hypertension can be effective in Sub-Saharan Africa. He required at least two antihypertensive drugs to meet the recommended blood pressure target.  Hypertension is an important worldwide public-health challenge because it is one of the most common chronic conditions , 2. The Hypertension is a major risk factor for cardiovascular (CV) disease –7. It reAge is the most powerful risk factor for hypertension, death, and cardiovascular death . The worRecently, numerous large clinical trials have provided evidence of the benefits of reducing BP in the elderly. Meta-analysis of clinical trials showed that treatment of hypertension in older adults is as beneficial as that in younger adults , 12. It There are few Sub-Saharan African data about management of hypertension in elderly. It was in this context that we undertook the present study at Institute of Cardiology of Abidjan, the single university hospital managing cardiovascular diseases in Côte d'Ivoire. This study aims to describe characteristics, risk factors, treatment and control of blood pressure of elderly hypertensive patients.We undertook a retrospective descriptive study involving patients seen at the outpatient clinics of the Institute of Cardiology of Abidjan. The study period spans 10 years, between January 2000 and December 2009. The study population was hypertensive elders (aged at least 65 years) with a regular followup at the Institute of Cardiology of Abidjan within one year. This series includes patients who had been on an initial treatment upon referral to our center. Data were collected from the information contained in medical records. 2. Waist circumference was recorded when available. Dyslipidaemia was defined according to our biochemistry laboratory standard when the level of total cholesterol was >2 g/dL, LDL-cholesterol >1.4 g/dL, or HDL-cholesterol <0.4 g/L. Diabetic patients were informed and treated for diabetes as per standard clinical practice. New diabetic patients detected at Institute of Cardiology of Abidjan were diagnosed based on the standard value in our laboratory, fasting plasma glucose >1.26 g/dL on repeated measurement. The overall management of diabetes was coordinated by the individual patient's physician and not by the Cardiology staff of Institute of Cardiology of Abidjan. The assessment of the impact of hypertension has systematically included electrocardiogram and plasma creatinine. All strokes were documented by a brain computerized tomography scan imaging. Echocardiogram was frequently performed, and the results were included in the data collection. Finally, when other tests were seldom performed , they were not used for analysis. We used the definition and classification hypertension standards of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) . We haveThe ESH and ESC categorization of total risk as low, moderate, high, and very high added risk has the merit of simplicity and was, therefore, chosen for risk stratification . In addiP value of ≤ 0.05 was considered for statistical significance. Data analysis was conducted using IBM SPSS Statistics 17 software. Univariate analysis was performed for significant associations. A During the study period, 2575 hypertensive Black Africans patients have had a regular follow-up of at least one year. Among these patients, 849 were elderly subjects. The mean age was 73.1 ± 5.3 years (range 65–98 years), 59% were female. At first presentation blood pressure was inappropriately controlled in 90.8% patients. It was mostly systolic-diastolic hypertension (51.8%) and isolated systolic hypertension (38.5%). Diastolic hypertension was observed in 0.5% . Mean blDiabetes was found in 18.6% of patients. It was type 2 in 61.4%. At least one target organ damage was observed in 50%. Isolated cardiac complications were the most frequent (37.9%). The cardiovascular risk factors other than hypertension and the results of target organ damage are reported in Echocardiography was performed in 50.2%. The recorded anomalies were a left ventricular diastolic dysfunction (39.2%), hypertensive cardiomyopathy (32.1%) and minor lesions  (19.6%). Application of the cardiovascular risk stratification according to the European Guideline for the management of arterial hypertension identified a very high added risk in 82.1%, a high added risk in 4.8%, a moderate add risk in 7.5% and a low add risk in 5.7%. β-blockers (19%), and centrally acting sympatholytics (4.5%). Antihypertensive drugs were used in monotherapy or combination . Diabetic patients as well as those with kidney failure have received significantly more RAS-blockers for the treatment of hypertension than other patients , age (P = 0.48), duration of treatment of hypertension (P = 0.13), the number of consultation (P = 0.13), and the duration of hypertension (P = 0.27) did not influence the control of blood pressure. Hypertension was best controlled with multiple drugs therapy . Pulse pressure was significantly lowered in females (P = 0.03) ( = 0.03) .This study found that a significant proportion of patients (33%) who visit the ICA are elderly. In the elderly a significant part of hypertension is represented by systolic hypertension. Increased arterial stiffness may increase cardiovascular morbidity and mortality because of an elevation of systolic blood pressure (SBP), which raises left ventricular afterload, and because of a decrease in diastolic blood pressure (DBP), which alters coronary perfusion . These eAccording to Skurnick et al. , the PP Cardiovascular risk of our patients was very high in most cases. As has been previously described, it is suggested that Black Africans present more severe forms of arterial hypertension and a greater risk of target organ damage –23. Overβ-blockers, calcium antagonists, and RAS blockers can adequately lower blood pressure, significantly improving cardiovascular outcome [The main benefits of antihypertensive treatment are blood pressure lowering per se, largely independent of the drugs employed. Diuretics,  outcome . Several outcome . There i outcome  recommenIn monotherapy, calcium antagonists were the most prescribed. Calcium antagonists have shown effectiveness in lowering BP in the older hypertensive patient. Significant reductions in stroke risk in older hypertensive patients were demonstrated in the Systolic Hypertension Europe and China Trials , 28. FurIn most cases, combination therapy was required for our patients. According to Aronow  if bloodThere is no information on treatment tolerance, particularly on orthostatic hypotension occurrence in the elderly often polymedicated patients. This limit is due to the retrospective nature of our study. Also in these elderly patients with high cardiovascular risk, it would be interesting to describe cardiovascular events occurred during the year-long or more followup. Furthermore, the control rate of hypertension obtained does not reflect the reality of the management of hypertension in Côte d'Ivoire. There is certainly a bias due to the method of recruitment of our population. Patients who were regularly monitored for at least one year showed probably best treatment adherence.Despite the classical reduced life expectancy in Sub-Saharan African population because of various illnesses, numerous elderly people exist. One must deal with the specific health needs of the elderly. Their blood pressure is characterized by the frequency of isolated systolic hypertension. Elderly hypertensive patients have a very high cardiovascular risk. Diuretics as recommended were the drugs most prescribed. The control rate of hypertension was significant, mostly at the cost of combination therapy.


Patients with sickle cell anemia (SCA) have usually lower diastolic, systolic and mean blood pressure (BP) than the general population. However, BP values ≥120/70 mmHg considerably increase the risk for acute and chronic complications in SCA. The aim of this study was to identify biological factors associated with relative hypertension in adults with SCA. We compared the hematological, lipid and hemolytic profiles, as well as blood viscosity, between SCA patients with normal BP  and those with relative hypertension . Our results demonstrated that male gender , triglycerides , blood viscosity  and body mass index  were independent risks factors for relative hypertension in SCA. No association was found between the BP status and the positive history of painful vaso-occlusive crisis or acute chest syndrome. An association between triglycerides level and the occurrence of these two major acute complications was detected. Our study suggests that male gender, increased triglycerides level, BMI and blood viscosity could increase the risk for developing relative hypertension in SCA. In addition, our results support a role of moderately elevated triglycerides in the pathophysiology of vaso-occlusive events. Patients with sickle cell anemia (SCA) have lower systolic, diastolic and mean blood pressure (BP) compared with age- and sex-matched controls According to the Poiseuille law, blood viscosity is a key component of vascular resistance and mean BP. Several studies, in non-SCA population, reported an association between increased blood viscosity and HTN Moreover, a recent growing interest has been devoted to the study of lipid levels in SCA because they might be involved in the pathophysiology of several complications. The lipid profile differs significantly between SCA patients and the general population The aim of the present study was to identify biological factors associated with systemic rHTN or HTN  regularly followed by the Sickle Cell Center at the Academic Hospital of Pointe-à-Pitre . All patients were in steady-state condition at the time of the study: no blood transfusions in the previous three months and absence of acute episodes , acute chest syndrome (ACS), stroke, priapism) at least two months before inclusion into the study. SCA patients under treatment modifying blood rheology were also excluded, except for those on hydroxyurea (HU).All patients were informed about the purpose and procedures of the study, and gave their written consent. The study was conducted in accordance with the guidelines set by the Declaration of Helsinki and was approved by the Regional Ethics Committee .2 (Kg/m2). Systolic and diastolic BPs were measured as recommended Height (cm) and weight (kg) were measured for all patients. Body mass index was calculated , citrate agar electrophoresis, and cation-exchange high performance liquid chromatography , and was confirmed by DNA studies Blood samples were drawn after a 12-hrs overnight fasting, between 8∶00 a.m. and 10∶00 a.m., and were immediately used for analyses. Measurements of serum lipids levels ) and hemolytic markers  were performed using standard biochemistry, and AIP was calculated. TG level below 1.69 mM is currently considered as normal. A value of AIP greater than 0.21 suggests increased cardiovascular risk Hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), reticulocytes (RET), red blood cell (RBC), platelet (PLT) and white blood cell (WBC) counts were determined using hematology analyzer .−1 using a cone/plate viscometer  Blood viscosity was measured after complete oxygenation of the blood, at native Hct, at 25°C and at a shear rate of 225 s± SD. Unpaired Student’s t-test and chi-square test were used for continuous covariates and for categorical covariates, respectively, to compare biological parameters between the different groups. Pearson test was used for correlations. Principal component analysis was used to derive the hemolytic component.Results are presented as means <0.05. Analyses were conducted using SPSS .To identify risk factors associated with HTN in SCA patients, we used a binary  multivariate logistic model. Variables of interest at p<0.10 by univariate analysis were included as covariates in the multivariate regression models. Significance level was defined as pTotal cholesterol, HDL-C and LDL-C did not differ between the two groups . In contAt that time, no large study has identified lipids cut-off values above which SCA patients might be at risk for cardiovascular events. The American Heart Association defined cut-off values in the general population with TG level below 1.69 mM being normal. Accordingly to this classification, eighty-five patients had normal TG level, eleven patients had TG level between 1.70 and 2.25 mM (i.e. borderline-high concentration) and one had TG level above 2.25 mM (i.e. high concentration). The proportion of patients with a positive history of VOC or ACS within the previous year was compared between patients with normal TG and those with borderline/high TG. Compared to the group with normal TG level, the group with borderline/high TG level exhibited a greater proportion of patients with a positive history of VOC  and ACS , respectively.A binary multivariate logistic model was used to identify factors associated with HTN in SCA patients and included gender, BMI, TG and blood viscosity. Hb, Hct, hemolytic component or RBC counts were not included in the model to avoid co-linearity effects with blood viscosity. BMI and TG levels were not significantly correlated. PP was not included in the model because it contains some information on the absolute BP level The present study demonstrates for the first time that 1) male gender, BMI, TG level and blood viscosity are independently associated with relative HTN in SCA; 2) relative HTN is not associated with greater VOC or ACS occurrence; 3) borderline/high TG level is associated with greater VOC or ACS occurrence.The impact of atherogenic indices and lipoproteins in arterial wall thickness and stiffness has been previously evaluated in children and adolescents not affected by SCA and it has been shown that elevated total cholesterol, TG, LDL-C and low HDL-C levels predict subclinical atherosclerosis in adulthood Recently, associations were reported between increased TG level or AIP and endothelial dysfunction in SCA patients Because of the low Hct and Hb levels, blood viscosity in SCA patients is usually lower than in the general population 2) than the limit defining overweight. Nevertheless, we reported an independent association between increased BMI and relative HTN, which confirms previous findings in SCA 2) and showed a 32.6% fat composition, indicating high levels of adiposity. Since fat accumulation and adipocytes secretion are responsible for many hormonal changes playing a role in the development of vascular dysfunction and HTN in the general population As a consequence of the increased resting energy expenditure caused by the increased erythropoietic and cardiac activities Rodgers et al Our report clearly suggests that male gender, increased TG level, BMI and blood viscosity could increase the risk for developing relative HTN or HTN. In addition, for the first time, our results support a potential role of moderately elevated TG in the pathophysiology of vaso-occlusive events, thus providing further evidence of a role of lipids in the SCA pathophysiology. Further studies are needed to evaluate the longitudinal associations between HTN, lipid profile and the occurrence of acute and chronic complications in SCA patients. In addition, nutritional aspects have not been investigated in our study, and vitamin D deficiency has been recently reported to participate in the development of hypertension


There are few studies to be found in the literature on ankle–brachial index in sickle cell disease. The aim of this study was to compare ankle–brachial index of steady-state adult sickle cell anaemia patients with that of normal controls.A descriptive cross-sectional study of 62 sickle cell anaemia patients and 62 age- and gender-matched normal controls was carried out in the adult outpatient sickle cell clinics and the cardiac centre of the University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria from February to August 2007. The supine brachial and ankle blood pressures were measured separately with the cuff of the mercury sphygmomanometer applied to the right arm and right calf, respectively.p < 0.001). The mean indices for ankle–brachial index were 0.88 ± 0.09 and 1.03 ± 0.06, respectively for patients and controls. This difference was statistically significant (p < 0.001). Seventy three per cent of the patients had ankle–brachial index less than 0.9 compared with controls (5%). This was also significant (p < 0.001).The ankle systolic blood pressure was lower in patients with sickle cell anaemia than in the controls ( Ankle–brachial blood pressure index is defined as the ratio of the brachial systolic blood pressure and the ankle systolic blood pressure. A lower ankle–brachial index (< 0.09) was associated with a 4.2-fold increase in relative risk of cardiovascular mortality in a study on asymptomatic male subjects when compared to those with a normal ankle–brachial index.2An ankle–brachial blood pressure index greater than 1.3 indicates poor compressibility of the arteries and signifies the presence of arterial calcification, which is common in diabetes mellitus. This makes the diagnosis of peripheral vascular disease less reliable and is the main limitation of the ankle–brachial blood pressure index. The other limitation of note is where patients with a high-grade aorto–iliac stenosis or occlusion present with a normal ankle–brachial blood pressure index at rest due to the presence of a rich collateral network.3When compared to the gold standard of angiography, hospital studies have shown an ankle–brachial blood pressure index less than 0.9 to be 95% sensitive in detecting healthy subjects.5A Chinese population-based comparison of ankle–brachial blood pressure index determined from consecutive auscultatory or Doppler measurements at the posterior tibia and brachial arteries showed that the mean ankle–brachial blood pressure index values were significantly higher on Doppler than on auscultatory measurements, with intermediate levels on oscillometric determination. The differences between the three measurements were not homogenously distributed across the range of ankle–brachial blood pressure index values.6Few studies on this subject are to be found in the literature. This study was aimed at comparing the ankle–brachial index of steady-state adult sickle cell anaemia patients with that of normal controls.A descriptive cross-sectional study of 62 sickle cell anaemia patients and 62 age- and gender-matched normal controls was carried out in the adult outpatient sickle cell clinics and the cardiac centre of the University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria from February to August 2007. The study subjects were drawn from adult patients (age ≥ 18 years)The weight and height of each subject were recorded and the surface area was determined from a standard formula.Data were presented as means ± standard deviation. In order to examine the effect of anaemia on the variables, the subjects were classified, based on the haematocrit values, into four classes in accordance with the World Health Organisation classification of anaemia, as follows: class 1, normal (haematocrit ≥ 36%); class 2, mild anaemia (haematocrit 30–35.9%); class 3, moderate anaemia (haematocrit 21–29.9%); class 4, severe anaemia (haematocrit 18–20.9%).9post hoc multiple comparison of means using the Tukey’s honestly significant difference test. Intra-class differences in parameters between patients and controls in the same haematocrit class were analysed using the independent Student’s t-test. All statistical analyses were carried out using the Statistical Packages for Social Sciences  software version 11.0. Statistical tests with probability values less than 0.05 were considered statistically significant.Inter-class differences in blood pressures in the patients were compared by one-way analysis of variance and p < 0.001) The age and gender distribution of the subjects are shown in p < 0.001) p < 0.001). Seventy three per cent (73.33%) of the patients had ankle–brachial index less than 0.9, compared with controls (5%). This was also significant (p < 0.001).The ankle systolic blood pressure was lower in sickle cell anaemia patients than in the controls , ankle systolic blood pressure , ankle diastolic blood pressure  and ankle–brachial index , as well as pulse pressure .post hoc multiple comparisons of means using the Tukey’s honestly significant difference test showed that the observed difference in systolic blood pressure was accounted for by the difference in haematocrit between the moderate and severe anaemia groups . For the ankle systolic blood pressure, differences were significant in the mild versus severe anaemia group  and in the moderate versus severe anaemia group . The mean pulse pressure for patients with mild anaemia was significantly different from patients with moderate anaemia .Pair-wise The finding in this study of a significant reduction in ankle–brachial index in sickle cell anaemia is intriguing. Ankle–brachial index was found to be significantly lower in patients with severe anaemia (haematocrit 18–20.9%) than in patients with mild anaemia (haematocrit 30–35.9%). A comparison of ankle–brachial index in patients and controls with comparable haematocrit (30–35.9%) demonstrated no difference in values. This suggests the significant role of chronic anaemia in the reduction of ankle–brachial index in sickle cell anaemia, although the mechanism of this effect is difficult to explain. It is also possible that the subset of patients with severe anaemia may have represented patients with more severe disease and therefore more severe cardiovascular complications. Ankle–brachial index in this study did not significantly correlate with the age of the patients (duration of chronic anaemia) Autopsy studies on sickle cell anaemia patients have reported fibromuscular dysplastic narrowing involving multiple small arteries, as well as intravascular plugs of sickled erythrocytes.A reduced ankle–brachial blood pressure index has been associated with significantly increased risk of cardiovascular disease and stroke that is independent of other risk factors.14A low ankle-to-brachial blood pressure ratio (< 0.9) could be a relatively easy-to-obtain marker of increased cardiovascular risk in patients with sickle cell anaemia. Further studies are recommended to evaluate the prognostic implications of reduced ankle–brachial index in patients with sickle cell anaemia.


This retrospective cohort study examined the sex- and age-specific impact of hypertension on medical expenditures.In 2006, we analyzed the medical expenditure records of 42 426 Japanese National Health Insurance beneficiaries  who lived in Ibaraki, Japan, were aged 40 to 69 years, and underwent health checkups in 2002. Blood pressure was classified into 4 categories according to the criteria outlined in the seventh report of the Joint National Committee.The difference in median total expenditure between the hypertension categories and the normotension category was 119 585 yen (140 360 yen vs 20 775 yen) for men aged 40 to 54 years, 126 160 yen (204 070 yen vs 77 910 yen) for men aged 55 to 69 years, 125 495 yen (158 025 yen vs 32 530 yen) for women aged 40 to 54 years, and 122 370 yen (208 700 yen vs 86 330 yen) for women aged 55 to 69 years. The median total and outpatient medical expenditures markedly differed between patients with stage 1 hypertension and stage 2 hypertension (which included people on antihypertensive medication) in both sexes and all age subgroups. The median total and outpatient medical expenditures were higher among women than among men in all blood pressure categories.The impact of hypertension on medical expenditures was similar in all age groups. Therefore, from the perspective of medical economics, prevention of the onset of hypertension seems equally important for all age subgroups. However, this remains to be studied.The associations of systolic blood pressure with all-cause mortality and the incidence of and mortality from cardiovascular disease have been reported to be age-dependent among whites,A better understanding of the effects of age on the relationship between blood pressure and medical expenditures among the Japanese population is extremely important for public health planning and the targeting of prevention programs. Therefore, we examined sex- and age-specific relationships between blood pressure levels and medical expenditures in a large, retrospective, cohort study.To examine the age-specific association between hypertension and medical expenditures, a large, retrospective, cohort study was carried out. The subjects were selected from Japanese beneficiaries of the National Health Insurance system in Ibaraki, Japan. A total of 46 014 beneficiaries were enrolled. They were aged 40 to 69 years in 2002 (17 763 men and 28 251 women), were beneficiaries from April 2002 through March 2007, and underwent health checkups conducted by the Ibaraki Health Service Association from April 2002 through March 2003. Beneficiaries who were no longer covered by the insurance system, such as those who died or changed their address, were not included. The health checkups were conducted in accordance with local government regulations. The data were collected by the Ibaraki Prefectural Government from local governments and the Ibaraki National Health Insurance Organization, after linkage to medical expenditure records in 2006; all data were depersonalized to ensure anonymity. The protocol of this study was approved by the institutional review board of Dokkyo Medical University School of Medicine.The data collected included blood pressure measurements, anthropometric measurements, and information from blood samples and from interview questionnaires dealing with smoking status, daily alcohol intake, and history of diabetes. A total of 3588 subjects (1594 men and 1994 women) with incomplete data or a history of heart disease or stroke at baseline were excluded; thus, the study included 42 426 subjects (16 169 men and 26 257 women). The medical expenditure records of the subjects were analyzed in 2006.The health checkups were conducted from April 2002 through March 2003. At the health checkups, each subject’s blood pressure in the right arm was measured in the seated position after at least 5 minutes rest by trained observers using standard mercury sphygmomanometers. Height in stockinged feet and weight in light clothing were also measured. The body mass index (BMI) was calculated as weight in kilograms divided by the square of their height in meters.12 The laboratory has also participated in external standardization and satisfied the criteria for precision and accuracy for the measurement of blood samples by the Japan Medical Association, the Japanese Association of Medical Technologists, and the Japan Society of Health Evaluation and Promotion.Non-fasting blood samples were drawn from seated participants into 2 polyethylene terephthalate tubes: one with an accelerator, and the other with sodium fluoride and ethylenediaminetetraacetic acid. Serum total cholesterol and serum triglyceride levels were measured using an enzyme method with an H7350 device . High-density lipoprotein cholesterol levels were measured in the same laboratory using a direct assay with an H7350 device. The plasma glucose level was measured using the hexokinase/glucose-6-phosphate dehydrogenase method with an H7170 device . The measurements of serum total cholesterol and high-density lipoprotein cholesterol levels were standardized by the Osaka Medical Center for Health Science and Promotion under the US National Cholesterol Reference Method Laboratory Network (CRMLN). The laboratory in the Osaka Medical Center for Health Science and Promotion has been standardized since 1975 by the CDC-NHLBI Lipid Standardization Program administered by the Centers for Disease Control and Prevention ; the laboratory has satisfied the criteria for both precision and accuracy of lipid measurements.An interview was conducted to determine hypertension medication (yes or no), diabetes mellitus medication (yes or no), smoking status , and alcohol intake .The subjects were linked to monthly medical expenditure records with bill dates from May 2006 through April 2007. Most of the records were for visits or hospitalizations in April 2006 through March 2007. The medical expenditure records for pharmacies were included, while the records for dental consultations and treatments were excluded. The medical expenditures were expressed in Japanese yen .13 the subjects were classified with regard to their blood pressure into 4 categories: systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg (normotension), systolic blood pressure 120 to 139 mm Hg or diastolic blood pressure 80 to 89 mm Hg (pre-hypertension), systolic blood pressure 140 to 159 mm Hg or diastolic blood pressure 90 to 99 mm Hg (stage 1 hypertension), and systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg (stage 2 hypertension). Subjects on hypertension medication were included in the stage 2 hypertension group. Diabetes mellitus was defined as a fasting plasma glucose level of ≥7.0 mmol/L (126 mg/dL), a non-fasting plasma glucose level of ≥11.1 mmol/L (200 mg/dl), or use of antidiabetic medication.Using the criteria outlined in the seventh report of the Joint National Committee,Adjusted geometric means for the total sample, outpatients, and inpatients by blood pressure category for each sex and age subgroup  were calculated using the least-square method. For the participants with 0 yen expenditures, logarithmic transformations were performed by replacing 0 yen with 1 yen. Covariates included age (years), BMI, serum total cholesterol level (mmol/L), high-density lipoprotein cholesterol level (mmol/L), log-transformed triglyceride level (mmol/L), fasting status (yes or no), diabetes mellitus (yes or no), smoking status , and alcohol intake . An analysis of covariance was conducted to test the association between blood pressure and medical expenditures. The analysis was repeated with the interaction term of (age group) × (blood pressure category).All statistical analyses were conducted using SAS, version 9.1 .The subjects’ baseline characteristics by blood pressure category are shown in Table Sex- and age-specific medical expenditures in 2006 by blood pressure category in 2002 are shown in Table The multivariate -adjusted geometric means for total and outpatient medical expenditures were significantly associated with blood pressure category in both sexes and all age subgroups (data not shown).11The results of this large retrospective cohort study showed that the impact of hypertension on medical expenditure was similar across age groups among beneficiaries of the National Health Insurance system in Japan. The differences in the median total and outpatient medical expenditures between hypertensive and normotensive people were both approximately 100 000 yen. The median total and outpatient medical expenditures were markedly different between subjects with stage 1 hypertension and stage 2 hypertension (which included subjects on antihypertensive medication) among both sexes and all age subgroups. The results show that the use of antihypertensive medication results in high medical expenditure. Therefore, lifestyle modification to avoid both the onset of hypertension and the need for antihypertensive medication can be effective in reducing medical expenditures. In addition, median total and outpatient medical expenditures were higher among women than among men in each blood pressure category. Moreover, to the best of our knowledge, this is the first study to show that hypertension has a similar impact on medical expenditure across age subgroups, even though age has been reported to affect the relationship between hypertension and cardiovascular mortality.2–4 The Health Promotion Research Committee of the Shiga National Health Insurance Organizations4 has shown an association between hypertension and medical expenditures. That study, which involved 4191 National Health Insurance beneficiaries who were aged 40 to 69 years, residents of Shiga, Japan, and followed for 10 years, showed that the crude arithmetic mean total medical expenditure per person per month was 45 947 yen for men with stage 2 hypertension. In contrast, the mean expenditure was 15 009 yen for men with normal blood pressure. The arithmetic mean expenditure was 23 332 yen for women with stage 2 hypertension and 14 222 yen for women with normal blood pressure. The medical expenditures in that study were higher than those in the present study, which may be due to the low medical expenditures of the present study area, as compared with Japan as a whole (http://www.mhlw.go.jp/topics/bukyoku/hoken/iryomap/05/01.html). Kitazawa et al3 showed an association between blood pressure and medical expenditures among 2165 Japanese employees with a mean age of 44.8 years who were beneficiaries of government health insurance. The sex- and age-adjusted geometric mean total medical expenditure per person per year was 12 950 yen for subjects with hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg), while the geometric mean expenditure was 6315 yen for subjects with normal blood pressure (systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg). The Baltimore Worksite Hypertension Control Project,2 a study of 3601 employees of the state of Maryland, also showed a positive association between hypertension and medical expenditure. The results of the present study are consistent with these previous studies with regard to the positive association between hypertension and medical expenditure.Several studies have reported a positive association between hypertension and medical expenditures.2–4 a strength of the present study is the use of a large sample size in which sex- and age-stratified analysis is possible. In addition, all blood samples were measured using the same device, the same reagent, and the same quality control program.Compared to previous studies,http://www.mhlw.go.jp/topics/bukyoku/hoken/iryomap/05/01.html), and (2) the participants were limited to people who underwent health checkups. However, the findings may be applicable to persons who underwent health checkups in other regions. A second limitation of the present study is that there was a short interval between the health checkups and the recording of medical expenditures. Furthermore, beneficiaries who were no longer covered, such as those who had died or changed address, were not included. Thus, medical expenditures, especially for inpatients, may be underestimated. Third, medical expenditures were not classified by disease. Further investigation is therefore warranted to completely elucidate the long-term and disease-specific impact of age on the relationship between hypertension and medical expenditures.The present study also had several limitations. The possibility of selection bias cannot be ruled out, and the generalizability of the present study is uncertain because (1) the medical expenditure per person was lower in the present study areas than in Japan as a whole (see In conclusion, the impact of hypertension on medical expenditures was similar in all age groups. Therefore, from the perspective of medical economics, the prevention of the onset of hypertension seems equally important for all age subgroups.


High-pulse pressure has previously been found to be inversely related to the prevalence of migraine and tension-type headache in an adult population. This inverse relationship has now been demonstrated to be present among adolescents also, supporting the results from a previous study in adults, that blood pressure regulation may be linked to the pathophysiology of headache.The relationship between blood pressure and headache in youth has not been explored and the objective of the present study was to provide data on this association in an adolescent population. Cross-sectional data from a large population-based survey, the Young-HUNT study, on 5,847 adolescents were used to evaluate the association between blood pressure  and recurrent headache, including migraine and tension-type headache. Increasing pulse pressure was inversely related to recurrent headache prevalence, and both tension-type headache and migraine. For systolic blood pressure such an inverse relationship was present for recurrent headache and tension-type headache prevalence. For migraine, the results were not significant, although there was a tendency in the same direction ( A relationship between migraine and blood pressure (BP) has long been suspected, but the direction of the association has been controversial . For manThe Nord-Trøndelag Health Study (HUNT) is one of the largest epidemiologic studies ever performed. Nord-Trøndelag County is located in the middle of Norway and is fairly representative of the population as a whole and the study is aimed at several large public health issues.n = 382). The few 12-year-old students in the first year of junior high were also excluded (n = 126). Questionnaires, where the headache question had not been answered (n = 221) were excluded, leaving a total study population of 8,255 (81%). Within a month after completing the questionnaire, a clinical examination was performed in schools during school hours and included spirometry, weight, height and BP measurements. The intention was to let the whole population undergo a headache interview performed by trained nurses in connection with the clinical examination [n = 8,255) and the questionnaire-based population that also were interviewed  [In 1995–1997, all students in junior high schools aged 13–15 years) and high schools (aged 16–19 years), of the county of Nord-Trøndelag, were invited to participate in the youth part of the Nord-Trøndelag Health Study, the Young-HUNT study. A total of 8,984 students (88%) out of 10,202 invited individuals completed a comprehensive self-administered questionnaire with different health-related items during one school hour. The study followed the school year instead of the calendar year. As adolescents usually graduate from high school, in the calendar year they become 19, about half of the 19-year olds had left school and were not invited. Accordingly, the 19-year-old students in the study population were excluded   with theBlood pressure is a measure of the force applied to the wall of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries, and is usually represented by two values. The systolic arterial pressure is defined as the peak pressure in the arteries, which occurs at the beginning of the cardiac cycle. The diastolic arterial pressure is the lowest pressure which is present in the resting phase of the cardiac cycle. BP is also characterized by its pulsatile and steady components. The pulsatile component, estimated by PP (SBP−DBP), represents BP variation during the cardiac cycle and is affected by left ventricular ejection fraction, arterial stiffness, early pulse wave reduction and heart rate. The steady component, estimated by MAP, is a function of left ventricular contractility, heart rate and vascular resistance and elasticity averaged over time .BP was measured with the adolescent sitting . First, A written consent from the parents was required for students younger than 16 years of age. The Young-HUNT study was approved by the Regional committee for ethics in medical research, and by the Norwegian data inspectorate.p < 0.001. A two-sided trend test was performed to evaluate the probability of a linear relationship between BP categories and headache prevalence. To further assess deviation from the linearity assumption, a trend test for BP as a continuous variable was performed for the different headache categories, in which, the trend test for BP as a categorical variable had shown significance. As a continuous variable the p value ranged from p = 0.002 to p < 0.0001. Spearman’s correlation coefficient (rs) was used to investigate the relationship between headache frequency and BP categories. Statistical analyses were performed using SPSS version 14.0 for Windows .The prevalence odds ratio (OR) for the association between recurrent headache (including subgroups migraine and TTH) and different BP groups was estimated using multiple logistic regression. In order to establish uniform groups, subjects with two or more recurring headaches  were omitted from the analyses. The term “recurrent headache” in this paper refers to the headache variable obtained during the interview and includes subjects with migraine, TTH and non-classifiable headache, while “headache” is used as a more general and unspecific term. SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP) and PP were each divided into six categories using the 10, 25, 50, 75 and 90% in the cross-sectional data. Potential confounding was evaluated by adjusting for age and weight. As the results were not affected when weight was added as covariates to the model, this variable was omitted. Due to several statistical calculations, the level of significance was set at p trend value <0.001) with increasing SBP values analyzing boys and girls together. For migrainous headache the same tendency was observed, but the finding was not significant (p = 0.05).There was a linear trend of decreasing prevalence of overall recurrent headache Fig.  and TTH p trend value is 0.36), migraine  or TTH .For DBP, there was no association with the prevalence of overall recurrent headache .p trend value <0.001) and TTH . Stratifying for sex and diagnostic group, this inverse relationship was not significant (data not shown).In boys and girls, combined analyses revealed a highly significant inverse relationship between increasing PP and recurrent headache Fig. , and forPP increases with age in the general population. To evaluate the influence of age on the relationship between PP and headache prevalence, we split the data in two, using the median PP value as cut-off, and plotted the prevalence of migraine and TTH versus age Fig. . In bothp trend value is 0.37), migraine  or TTH  in the combined analyses or the analyses stratified by gender and diagnostic group (data not shown).Mean arterial pressure was not associated with the prevalence of recurrent headache . For SBP, DBP and MAP, no significant association with recurrent headache frequency was observed.Recurrent headache frequency for both genders combined was categorized into four different groups; less than one day per month (less than monthly), 1–3 days per month (monthly), 1–5 days per week (weekly), more than 5 days per week (daily). There was a weak negative correlation between recurrent headache frequency and PP . For SBP, DBP and MAP, no significant association with use of migraine-specific medication was found. Use of common analgesics showed a weak negative association with PP  and SBP . For DBP and MAP, no significant association was observed.To determine whether the level of BP influenced use of pain-relieving medication, use of common analgesics and migraine-specific medication for both genders combined were subclassified into three categories each; never used, periodic use and almost daily use. A weak negative association was present between the use of migraine-specific medication and PP  may be excited by pharmacologically induced changes in BP , 32.Further research into the relationship between headache and BP may give valuable information on pathophysiological mechanisms involved in headache/migraine, general pain-modulating mechanisms and mode of action of antihypertensive drugs used for migraine prophylaxis.