Bilateral thoracoscopic splanchnicectomy (BTS) is a well-known technique to alleviate intractable pain in patients with chronic pancreatitis. BTS not only disrupts afferent fibers from the pancreas that mediate pain but also postganglionic sympathetic fibers, which originate in segments T5–T12 and which innervate the vasculature of the liver, pancreas, and the adrenal gland. The purpose of this study was to assess whether and how BTS affects sympathetic noradrenergic and adrenomedullary function in patients with chronic pancreatitis.Sixteen patients with chronic pancreatitis for at least 1 year underwent autonomic function testing before and 6 weeks after BTS for intractable pain. Testing was performed during supine rest and during sympathetic stimulation when standing.P = 0.001). One patient showed orthostatic hypotension after BTS. Baseline plasma norepinephrine levels and plasma norepinephrine responses to sympathetic activation during standing were not reduced by BTS. In contrast, supine plasma epinephrine levels and responses during standing were significantly reduced (P < 0.001). Parasympathetic activity was unaffected by BTS as shown by unaltered Valsalva ratio, I-E difference, and ΔHRmax.Supine and standing systolic and diastolic blood pressure were significantly lower post-BTS compared with pre-BTS (BTS for pain relief in patients with chronic pancreatitis reduced adrenomedullary function, due to disruption of the efferent sympathetic fibers to the adrenal gland. BTS did not affect noradrenergic sympathetic activity, although blood pressure was lower after the sympathectomy. Chronic pancreatitis is a fibroinflammatory disease of the pancreas. Pain is the main reason for these patients to seek medical help. The goal of surgical therapy is to alleviate pain, preferably without morbidity or mortality and with preservation of pancreatic function. In the absence of an anatomical substrate or when previous surgery has not been successful, nerve interruption, such as celiac blockade or splanchnicectomy, are recommended . BilaterThe splanchnic nerves predominantly consist of sympathetic fibers and the contribution of visceral pain afferents, which accompany the sympathetic nerves is relatively small . SympathSixteen patients (10 men and 6 women), with chronic pancreatitis for at least 1 year, who underwent bilateral thoracoscopic splanchnicectomy (BTS) for disabling pain were studied for the effects of sympathectomy on sympathetic activity. Median age was 49 (range 32–68) years. All patients had chronic pancreatitis, diagnosed by means of endoscopic retrograde cholangiopancreaticography, computed tomography, and/or magnetic resonance cholangiopancreaticography, according to standard criteria [®, Johnson & Johnson Medicals, Amersfoort, The Netherlands). At the end of the procedure, the lungs are reexpanded and the trocar sites closed without routine use of chest drains.We used a technique for BTS that was slightly modified from that described by Cuschieri et al. . In summSedative medication, which remained unaltered after the operation, was stopped the day before testing, while analgesic treatment was continued. All patients underwent noninvasive measurement of blood pressure and heart rate by the Finapres device  before and 6 weeks after BTS . Blood pStanding up maneuver. Patients were asked to stand up within 5 s and to remain in the upright position for 2 min. The systolic (SBP) and diastolic blood pressure (DBP) responses to the upright position were calculated from the blood pressure values 50–80 s after standing up compared with those of the supine rest position. Orthostatic hypotension was defined as a decrease of systolic blood pressure of more than 20 mmHg after standing. The difference between the maximal heart rate at standing (15–20 s after standing up) and the supine heart rate was calculated and expressed as ∆HRmax. The quotient between maximal heart rate and minimal heart rate after standing up was calculated as T/B ratio (tachycardia/bradycardia ratio) [a ratio) .Forced breathing. Each patient performed six maximal respirations in 1 minute in the supine position, and both inspiration and expiration were synchronized with the program clock on the computer. Heart rate was computed from the RR-interval and the difference between maximal and minimal heart rate during each cycle of 10 seconds was measured and averaged for the six respiratory cycles (I-E difference) [ference) .Valsalva maneuver. All patients were instructed to maintain an expiratory pressure of 40 mmHg for 15 s by means of forced expiration into a mouthpiece connected to a manometer. The maneuver was performed in triplicate. The maximum heart rate during the maneuver was divided by the minimum heart rate after the manoeuvre  [a ratio) .After voiding, a cannula was inserted in an antecubital vein and a blood sample was drawn after 20 min of supine rest. To assess the effects of mild sympathetic stimulation, a second blood sample was drawn after 5 min of standing. Blood samples were collected into chilled tubes containing heparin and were immediately placed on ice. All samples were centrifuged (at 4°C) within 1 hour after blood sampling and plasma samples were stored at −80°C until assayed for concentrations of norepinephrine (NE) and epinephrine (EPI), using high-performance liquid chromatography . All sam® for Windows . Demographic data are presented as median and range, and all other data are presented as medians and interquartiles (IQR). Differences were considered statistically significant if P < 0.05.For all variables, nonparametric tests were used. Preoperative and postoperative data of the entire group were compared using the paired Wilcoxon signed rank-sum test. Relative and absolute differences between baseline and standing NE and E levels (Δ) were calculated. We performed statistical analysis using SPSSIn all 16 patients, BTS was technically successful, meaning that all potentially nerve-bearing tissue on each side had successfully been transected.P < 0.01; Table P = 0.012, and 3 mmHg , whereas SBP did not. One patient demonstrated orthostatic hypotension before BTS, which persisted after the procedure. One patient who had no orthostatic hypotension before BTS demonstrated asymptomatic orthostatic hypotension after BTS. Heart rate showed a similar increase with standing both before and after BTS.After BTS, supine as well as standing, both median systolic and diastolic blood pressures were significantly lower than before BTS . The median relative increment in plasma NE was 89% , ranging from 3.06–7.68 nmol/L. During standing, the plasma NE levels of the entire group increased significantly from a median 2.0 nmol/L IQR 1.37–3.49) to a median 3.53 nmol/L . In the upright position, plasma NE rose to 4.52 nmol/L , and the median relative increment was slightly but significantly higher than before BTS , which was not significantly different from the pre-BTS plasma NE level (P < 0.001). The relative increment of plasma EPI was 37%  nmol/L). During standing plasma EPI levels rose to median 0.12 nmol/L . After BTS, plasma EPI levels did not increase after standing. In each individual patient, both the supine and the standing plasma EPI levels were lower after BTS. Consequently, both the relative and the absolute increments in plasma EPI were significantly reduced after BTS  and significantly lower than before BTS (–0.04 andInterruption of sympathetic nerves by BTS for pain relief in patients with chronic pancreatitis reduces baseline and stimulated EPI plasma levels. In contrast, there is no effect on sympathetic noradrenergic and parasympathetic function. Furthermore, the blood pressure was significantly reduced after BTS.Because the sympathetic nerves to the adrenal gland are interrupted by BTS and because the adrenal medulla is almost the sole source of circulating EPI, it is not surprising that adrenomedullary function is impaired, which is reflected by the decrease in plasma EPI levels. This effect has been shown before in animal studies and for the first time now in human subjects . The preNoradrenergic sympathetic nerves supplying the splanchnic vascular bed also are disrupted by BTS, but plasma NE levels were unaltered, suggesting that overall sympathetic nervous function is unimpaired. Although the splanchnic vascular bed is richly innervated by sympathetic nerves and the hepatic-mesenteric spillover amounts to approximately 40%, a relatively low fraction of circulating plasma NE is coming from the mesenteric organs, such as pancreas and liver . In addiVariable effects on blood pressure have been reported after thoracic sympathectomy. In contrast to Noppen et al. , who fouIncreased renal sympathetic activity causes hypertension and sympathectomy is applied for the treatment of hypertension –25. BecaOnly one patient demonstrated orthostatic hypotension after BTS but was asymptomatic. Clinical significant orthostatic hypotension has only been reported in a minority of patients after both bilateral and unilateral thoracoscopic splanchnicectomy for pain in chronic pancreatitis , 27.Reduction of pain may be held responsible for lowering blood pressure. Stress caused by pain causes an increase in blood pressure, by increasing the muscle sympathetic nerve activity . HoweverBilateral thoracoscopic splanchnicectomy is a surgical procedure in which the splanchnic nerves are dissected by a thoracoscopic approach. After 6 months follow-up 60–75% of the patients have pain relief . BecauseBilateral splanchnicectomy does not seem to have significant clinical side-effects. However, some caution is warranted regarding the hypotensive effect, especially in younger patients with a normal to low preoperative blood pressure. In patients with hypertension, BTS may necessitate adjustments in the antihypertensive treatment.


Vascular calcification (VC) contributes to high mortality rates in chronic kidney disease (CKD). High serum phosphate and FGF23 levels and impaired phosphaturic response to FGF23 may affect VC. Therefore, their relative contribution to abdominal aortic calcification (AAC) was examined in patients CKD stages 3–4.Potential risk factors for AAC, measured by the Kauppila Index (KI), were studied in 178 patients.In multivariate linear analysis, AAC associated positively with age, male gender, CKD-stage, presence of carotid plaques (CP) and also with FGF23, but negatively with fractional excretion of phosphate (FEP). Intriguingly, FEP increased with similar slopes with elevations in PTH, with reductions in GFR, and also with elevations in FGF23 but the latter only in patients with none (KI = 0) or mild (KI = 1-5) AAC. Lack of a FEP-FGF23 correlation in patients with severe AAC (KI > 5) suggested a role for an impaired phosphaturic response to FGF23 but not to PTH in AAC. Logistic and zero-inflated analysis confirmed the independent association of age, CKD stage, male gender and CP with AAC, and also identified a threshold FEP/FGF23 ratio of 1/3.9, below which the chances for a patient of presenting severe AAC increased by 3-fold. Accordingly, KI remained unchanged as FEP/FGF23 ratios decreased from 1/1 to 1/3.9 but markedly increased in parallel with further reductions in FEP/FGF23 < 1/3.9.In CKD 3–4, an impaired phosphaturic response to FGF23 with FEP/FGF23 < 1/3.9 associates with severe AAC independently of age, gender or CP. Cardiovascular disease is the main cause of mortality in chronic kidney disease (CKD) patients -4 and vaHigh serum FGF23 also induces cardiovascular disease through mechanisms unrelated to abnormal phosphate homeostasis . BecauseCross-sectional study that enrolled 205 patients CKD stages 3 and 4, according to K/DOQI guidelines , from thData collected include: age, gender, CKD etiology, presence of diabetes, hypertension, pulse pressure, smoking status and prior history of cardiovascular disease. Estimated glomerular filtration rates (eGFR) were calculated using the Modification of Diet in Renal Disease (MDRD) equation . At the Fasting venous blood samples and a 24 hour urine collection were obtained between 8–9 AM, to minimize daily circadian variations in serum phosphate levels. Routine tests included lipid profile, serum levels of glucose, albumin, C reactive protein (CRP), creatinine, phosphate, calcium, CaxP product, bone-specific alkaline phosphatase.Selected parameters of mineral metabolism included: Serum levels of intact PTH , 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin  by radioimmunoassay (Biosource®) and radioreceptor assay Gamma-B dihydroxyvitamin D, IDS Hybritec®, respectively. Vitamin D supplementation (400 IU/day) in vitamin D deficient patients eliminated seasonal differences in serum 25(OH)D in patients recruited during the winter (68.8%). Urinary calcium, sodium, and phosphate excretion in 24 h and their respective fractional excretions (FE) were measured. FEP = [Urinary P (mg/dl) × Serum Creatinine (mg/dl)] / [Serum P (mg/dl) × Urinary creatinine (mg/dl)] × 100. Protein intake was estimated using a standard formula, as previously described .Serum FGF23 and soluble α-Klotho were measured with Elisa kits for human C-Term FGF23  and for soluble α-Klotho , following manufacturer’s protocols with intra- and inter-assay coefficient of variation of 5%.AAC measured by the Kauppila index (KI)  was obtaCarotid ultrasound  measured the presence of carotid plaques (CP) and carotid intima-media thickness , as previously described .Data are presented as mean ± SD for quantitative variables, and as percentage of patients for descriptive, qualitative variables. A logarithmic transformation of serum FGF23 allowed achieving a distribution close to normal. KI tertiles defined patients as: Non-calcified (KI = 0), moderately calcified: KI values ≥1 up to 5; and severely calcified: KI higher than 5. The statistical significance of the differences among the 3 KI-based subgroups was measured with Kruskal-Wallis for quantitative variables and chi-square tests for qualitative variables (or Fisher test for expected frequencies below 5). Differences in KI, FEP and FGF23 among CKD 3 and 4 were assessed using the Kruskal-Wallis test. The Pearson correlation coefficient measured the linear correlation between KI values as the dependent variable with each of every other quantitative variable in bivariate analysis.A scatterplot, with linear and nonparametric regression lines assessed the relationship between FEP/FGF23 in logarithmic scale (base 2) with the Kauppila index. The non parametric regression to delineate mean fitting was implemented as a local polynomial surface regression with a smoothing degree of 0.96. For dispersion from the mean fit, we used an estimate of the square root of the variance function, with separate smoothing of the squares of the positive and negative residuals from the mean fit. This analysis identified the ratio FEP/FGF23 = 1/3.9 as a critical cutoff point further used in multivariate analysis. Multivariate linear regression and logistic regression analyses identified the variables that contributed significantly to either explain the variability in KI as a continuous variable, or to discriminate patients without AAC (KI = 0) or with severe AAC (KI > 5), respectively. The significance of interaction effects of KI tertiles on the relationship of FGF23, PTH or eGFR with FEP was assessed using Likelihood Ratio (LR) tests. The area under the ROC curve (AUC) assessed the discrimination capability of the logistic model and the Hosmer-Lemeshow goodness-of-fit tests measured model calibration. A zero-inflated regression model was used to simultaneously fit the high frequency of KI = 0 in our patient population with actual KI scores. Due to overdispersion, the Negative Binomial distribution was chosen over the Poisson distribution to fit KI scores. The explanatory variables chosen minimized residual deviance when comparing hierarchical models according to LR tests. Data were analyzed using the software: “Statistics for the Social Sciences” SPSS 11.0, and/or the free software R. For all tests, a p < 0.05 was considered statistically significant.Table In bivariate analysis, KI associated positively with age , pulse pressure ; IMT  and log FGF23 . Also, KI was higher at later stages of CKD (3 vs. 4: mean (SD) of 2.8 (3.29) vs. 4.5 (4.63); Mann–Whitney p = 0.023), in patients with carotid plaques (4.9 (4.47) vs. 1.3 (2.25); p < 0.001; smokers (4.8 (4.05) vs. 3.4 (4.37); p =0.004), history of cardiovascular disease (5.3 (4.53) vs. 3.0 (3.90); p < 0.001) or receiving diuretics (4.5 (4.33) vs. 2.8 (4.03); p = 0.005). Interestingly, serum PTH, 25(OH)D, or calcitriol levels did not associate with KI.Multivariate regression analyses, using KI as a quantitative variable Table , identifBecause serum FGF23 and FEP increase in parallel with the progressive reductions in renal function in the course of CKD, the observed inverse association between FEP and KI suggested a role for resistance to FGF23 phosphaturic actions in the severity of AAC. Indeed, linear regression analyses between serum FGF23 and FEP as the dependent variable Figure A, discri2(FEP/FGF23) normalized the distribution of FEP/FGF23 ratios. Figure 2(FEP/FGF23) < log2(1/3.9). Indeed, the odd ratios in these highly sensitive logistic models  transformation logRenal resistance to the phosphaturic actions of FGF23 develops with the progressive reductions in renal klotho in the course of CKD . However2 (FEP/FGF23) < log2 (1/3.9) was associated directly and significantly with higher KI scores in both models. Instead, age, CKD stage, male gender and carotid plaques, but not log2 (FEP/FGF23) < log2 (1/3.9) associated negatively with KI = 0. These results suggest that the progressive deterioration of the capacity of the kidney to respond to FGF23 increasing FEP may only associate with the severity of already ongoing AAC.For further validation of the independent association of a FEP/FGF23 ratio below 1/3.9 with severe AAC we used a zero-inflated model, as 32% of our patients showed a KI = 0. Table The results of this cross-sectional study enhance our current understanding on the key issue of the impact of renal resistance to FGF23 on critical outcomes in CKD, specifically, on the severity of AAC. To our knowledge, this is the first study to present evidence of the association between renal resistance to the phosphaturic actions of FGF23, but not to PTH-driven phosphaturia, and the degree of AAC in patients CKD-stages 3 and 4. Indeed, analysis of the relationship between KI scores and FEP/FGF23 ratios in these patients identified a FEP/FGF23 ratio, which marks a critical point for the impairment in the renal response to FGF23 phosphaturic actions that associates with a 3-fold enhancement of the risk of severe AAC.Our analysis of the relationship of abnormalities in the phosphate/FGF23 axis with VC in CKD stages 3 and 4 supports a prior report  showing To evaluate VC, we measured abdominal aortic calcification (AAC) with the semiquantitative but cost/effective Kauppila Index (KI). KI strongly correlates with coronary calcium scores from computer beam tomography  and reflThe accuracy of FEP measurements can also be questioned, as urinary phosphate excretion depends upon several factors, including not only the integrity of glomerular and tubular renal function, but also dietary phosphate intake (mainly in proteins), serum levels of the phosphaturic hormones FGF23 and PTH, and renal content of Klotho, the co-receptor required for FGF23 actions . HoweverThe multivariate analysis also has limitations: Its determination coefficients indicate that these models explain only 28% of the variability in KI. Also, KI values were 0 in a third of patients. However, highly sensitive logistic regression analysis confirmed the key role of impaired phosphaturic response to FGF23 in AAC, as in patients with FEP/FGF23 ratios below 1/3.9 the chances to develop severe AAC increased by 3 to 4-fold. Importantly, zero- inflated and binomial models have corroborated the accuracy of our logistic model in identifying variables associated with severe AAC in CKD patients, including the new threshold of FEP/FGF23 ratios below 1/3.9, which strongly associated to a higher risk for severe AAC. Indeed, KI scores did not change with progressive reductions in the renal response to FGF23 phosphaturic actions before reaching an almost 4-fold elevation in FGF23 without changes in FEP, but markedly increased in parallel with further reductions in the phosphaturic response to FGF23 as measured by FEP/FGF23 ratios below 1/3.9.Our results are in agreement with a very recent report by Dominguez et al., demonstrating that the association between FGF23 levels and adverse cardiovascular outcomes was modified by FEP values. In models adjusted for CVD risk factors, kidney function, and PTH, those patients who had FGF23 above the median but FEP below the median had the highest risks of both all-cause mortality and CVD events . In summAlso, as proven for hemodialysis patients , atheromA FEP/FGF23 > 1/3.9 may help protect CKD patients from severe AAC independently of age, gender, CKD stage and the presence of clinical atheromatosis in the carotid arteries. Undoubtedly, these findings need to be validated in prospective, well powered clinical trials.The authors declare that they have no competing interests.LC obtained all the patient’s data and designed the study. AD helped in the analysis of the data and in the writing of the manuscript. FS helped in the analysis of the data. MMA performed the statistical analysis. JMV and EF designed the study, analyzed the data, wrote the manuscript and obtained funding. All authors read and approved the final manuscript.LC and AD share first authorship.JMV and EF share senior authorship.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/14/221/prepub


Behavioral medicine is an interdisciplinary field concerned with the development and integration of behavioral and biomedical science, knowledge, and techniques relevant to health and illness and the application of this knowledge and these techniques to prevention, diagnosis, treatment, and rehabilitation. From a behavioral medicine standpoint, hypertension is a lifestyle disorder, aggravated by unhealthy diet, adiposity, excessive alcohol intake, and stress. The World Health Organization has identified hypertension as the number one risk factor for mortality worldwide . AlthougThe main focus of this special issue is to highlight the role of behavioral and psychological factors in the etiology, prevention, and treatment of hypertension. Two papers review mechanisms through which biobehavioral factors influence and are affected by increases in blood pressure. J. R. Jennings and A. F. Heim argue that findings from human neuroimaging suggest the brain is an early target for hypertension. W. Gerin and colleagues propose a model to explain the effects of cumulative exposure to stress (including ruminative stress) that leads, over time, to an upward resetting of the resting blood pressure, resulting in an increased risk of hypertension.Another five papers in the issue examine the impact of sleep, anxiety, anger, depressed mood, and various health behaviors on blood pressure, blood pressure regulation, and endothelial function. These papers provide an excellent sense of current investigations into the impact of various candidate psychological/behavioral factors on hypertension, as well as some of the intricacies and challenges involved in deriving clinically meaningful conclusions from this work.The issue shifts focus to consider the impact of psychological interventions on blood pressure, with a review of a stress management intervention, meditation. While meditation techniques appear to produce small yet meaningful reductions in blood pressure, the review also points to serious methodological shortcoming and the need to attain a higher standard of quality, with more randomized controlled trial studies. Another paper suggests stress-activated gene × environment interactions may contribute to individual variability in blood pressure reductions from behavioral interventions.A series of papers consider the uptake of behavioral medicine interventions, including self-monitoring of blood pressure in hypertension, a relatively simple and easily adopted activity that is associated with small but meaningful clinical improvements. The special issue ends with a provocative review of behavioral versus public health efforts to curb an obvious target for health behavior change, sodium consumption.In highlighting some of the key areas of endeavor in the field of behavioral medicine, we hope to encourage readers to incorporate psychological and behavioral variables into their research on hypertension. Given the web of underlying causality, we believe that such an approach has considerable potential to inform efforts aimed at better understanding the causes, consequences, and treatment of hypertension.Tavis CampbellTavis CampbellSimon L. BaconSimon L. BaconJoel E. DimsdaleJoel E. DimsdaleDouglas CarrollDouglas Carroll


The Visceral Adiposity Index (VAI) is a sex-specific mathematical index, based on Waist Circumference (WC), Body Mass Index (BMI), triglycerides (TG) and HDL cholesterol (HDL) levels, indirectly expressing visceral adipose function and insulin sensitivity. Our aim was to find the optimal cut-off points of VAI identifying a visceral adipose dysfunction (VAD) associated with cardiometabolic risk in a Caucasian Sicilian population.Medical check-up data of 1,764 Primary Care patients (PC patients) were retrospectively and cross-sectionally examined using a receiver-operating characteristic (ROC) curve to determine appropriate stratified-for-age cut-off of VAI, for the identification of PC patients with Metabolic Syndrome (MetS) according to the NCEP-ATP III criteria. The PC patients with higher VAI scores were subdivided into three groups according to VAI tertiles . Finally, VAD classes were compared to classical cardio- and cerebrovascular risk factors as independent predictors of coronary heart disease and/or myocardial infarction, transient ischemic attack and/or ischemic stroke.Moderate and severe VADs proved to be independently associated with cardiovascular events [ and  respectively]. Mild, moderate and severe VADs were found to be independently associated with cerebrovascular events .Our study suggests that among Caucasian Sicilian subjects there are clear cut-off points of VAI able to identify a VAD strongly associated with cardiometabolic risk. The term 'cardiometabolic risk' was coined by the American Diabetes Association  and the Furthermore, in order to predict VAT-associated cardiometabolic risk, it would be highly desirable to perform routine evaluation of "visceral adipose dysfunction" (VAD) by adipocytokine assessment. This approach, however, is also unfeasible because of the complexity of the 'adipose endocrine organ' function , and agaRecently our research group developed the Visceral Adiposity Index (VAI), a mathematical model that uses both anthropometric (body mass index [BMI] and WC) and functional (triglycerides [TG] and high-density lipoprotein [HDL] cholesterol) simple parameters . This inMoreover, this index has been studied in specific populations of patients: in a specific cohort of patients with genotype 1 chronic hepatitis C, VAD identified by a higher VAI score proved to be independently associated with both steatosis and necroinflammatory activity and directly correlated with viral load ; in a spThis cross-sectional retrospective study therefore had a 2-fold objective:1) to identify in a Caucasian Sicilian population, stratified for age, VAI cut-off points strongly associated with Metabolic Syndrome (MetS) using the receiver operating characteristic (ROC) curve analysis;2) to examine the relationship between this surrogate and indirect VAD measure and cardio- and cerebrovascular events.This retrospective cross-sectional study was performed in collaboration with 10 National Health Service Primary Care Physicians (PCPs) on 13,195 individuals from the town of Alcamo, in Western Sicily (The AlkaMesy Study) as previously described [Data have been recorded by PCPs since 1996 using the Millewin computed medical chart .2), age of first heart and/or cerebrovascular event, diagnosis of diabetes mellitus according to the American Diabetes Association [For 1,764 of the 13,195 PC patients, complete information was available on the following aspects: age, sex, smoking habits, WC (cm), BMI  were excluded because data were not available at the time of the event.WC was measured at the midpoint between the lower rib and the iliac crest. Blood chemistry analyses were performed in accredited laboratories of the National Health Service in Alcamo.2 [LDL cholesterol was calculated using the Friedwald equation. Glomerular Filtration Rate (GFR) was estimated from serum creatinine using the MDRD formula and was expressed as ml/min/1.73 m2 .TG is Triglycerides levels expressed in mmol/l and HDL is HDL-Cholesterol levels expressed in mmol/l:VAI score was calculated as described  using tht test for continuous variables and by the χ2-test and Fisher's exact test (when appropriate) for categorical variables. The Anova trend analysis and the χ2-test for trend were used to assess means and proportions of the population characteristics across the four PC patient groups . Multiple logistic regression models were performed to explore possible determinants of cardio- and cerebrovascular events using two predictive models for dichotomic variables: "coronary heart disease (CHD) or myocardial infarction (MI)" and "transient ischemic attack (TIA) or ischemic stroke (IS)".The Statistical Packages for Social Sciences SPSS version 17 and MedCalc version 11.3 were used for data analysis. Baseline characteristics were presented as mean ± Standard Deviation (SD) for continuous variables; rates and proportions were calculated for categorical data. Normality of distribution for quantitative data was assessed by the Kolmogorov-Smirnov test. Because HbA1c did not present normal distribution, it was therefore log-transformed. Receiver-operating characteristic (ROC) curve analyses were performed to determine appropriate cut-off points of VAI in identifying PC patients with MetS. Differences between groups in univariate analysis were detected by the unpaired Student's Variables associated with the dependent variable on univariate analysis  were included in two multivariate regression models.P value of <0.05 was considered statistically significant.In the first model the following independent variables were included: Age and Total Cholesterol as continuous variables; gender , smoking , VAD categories , MetS , diabetes mellitus/FPG > 5.6 mmol/l , high blood pressure  as categorical  variables. In the second model the following independent variables were included: age and GFR as continuous variables; gender , VAD categories , MetS , diabetes mellitus/FPG > 5.6 mmol/l , high blood pressure  as categorical  variables. To avoid effects of multicollinearity with VAD categories the variables High Tryglicerides, Low Hdl Cholesterol, Increased WC and BMI were not included in either regression model. A with VAD absent"; in the remaining 402 subjects, the first VAI tertile of PC patients was defined "with mild VAD", the second tertile "with moderate VAD" and the third tertile "with severe VAD"  were subdivided into age quintiles in order to identify optimal age-stratified cut-off points of VAI identifying the presence of MetS. Optimal VAI cut-off points were: 2.52 (age < 30 years), 2.23 (age ≥ 30 and < 42 years), 1.92 (age ≥ 42 and < 52 years), 1.93 (age ≥ 52 and < 66 years) and 2.00 (age ≥ 66 years) , severe VAD , age at the time of event , smoking  and male gender  were independently correlated with cardiovascular events (CHD and/or MI). With regard to cerebrovascular events (TIA and/or IS), mild VAD , moderate VAD , severe VAD , age at time of event , male gender  showed an independent association; a weak inverse independent association was found with GFR   was observed for age (p < 0.001), BMI (p < 0.001), WC (p < 0.001), fasting glucose (p < 0.001), ALT p = 0.002), total cholesterol (p < 0.001) and LDL cholesterol (p < 0.001). The prevalence of patients with MetS, diabetes, high blood pressure, low HDL cholesterol, high triglycerides, CHD and/or MI, TIA and/or IS, increased significantly across the four groups . A significant reducing trend was seen for GFR (p < 0.001) .PC patients with VAI scores greater than these cut-off points were arbitrarily defined as having mild, moderate or severe Since visceral fat is universally claimed to be more strongly associated with cardiometabolic risk than subcutaneous fat, we believe that emphasis should be given to the new model represented by VAD, since it is widely reported that visceral fat is more strongly associated with cardiometabolic risk compared with subcutaneous fat ,19 and tPC patients with VAD ranging from mild to severe, showed a significant trend of increased prevalence of all components of the MetS and of cardio- and cerebrovascular events. A significant increased trend for age, fasting glucose, ALT, total cholesterol, TG and HDL was also observed.Moderate and severe VAD proved to be independently associated with cardiovascular (CHD and/or MI) events, together with smoking, male gender and age at the time of events, when compared with other conventional dichotomic risk factors, such as diabetes mellitus/FPG > 5.6 mmol/l, high blood pressure, total cholesterol and MetS. Furthermore, only mild, moderate and severe VAD together with male gender and age at the time of events proved to be independently associated with cerebrovascular (TIA and/or IS) events.Surprisingly, VAD was independently associated with cardio- and cerebrovascular events, but not with MetS diagnosed according to the ATP III criteria. A possible explanation might lie in the fact that the 5 variables proposed in the ATP III criteria are not used as quantitative continuous variables, but rather as dichotomous variables. Thus, such screening tools might prove to be less efficient for the optimal assignment of a patient with cardiometabolic risk related to his/her visceral obesity. Indeed, the 'presence' or the 'absence' of an abnormality may be too crude to identify the individual risk profile. Lastly, with current Mets diagnosis criteria, tools are considered as a homogeneous entity, which is very unlikely, especially as regards diabetes and high blood pressure ,25.For VAI, which represents a global calculator of non-glycemic and non-hemodynamic components of the MetS, while on one hand the variables are treated as continuous variables, on the other two important aspects are taken into consideration, i.e. BMI and gender. In fact, women have, on average, more subcutaneous fat and less visceral fat than men .per se as a diagnostic tool for cardiovascular and cerebrovascular events, since it includes physical (BMI and WC) and metabolic (TG and HDL) parameters, it may, however, indirectly reflect other non-classical risk factors, i.e. altered production of adipocytokines, increased lipolytic activity and plasma-free fatty acids. In fact, visceral obesity and "High-Triglyceride/Low-HDL-Cholesterol Dyslipidemia" were proposed by Unger et al. [visceral fat dysfunction, when associated with physiological age-linked leptin resistance, leads to pancreatic lipotoxicity with subsequent beta-cell apoptosis and diabetes onset, muscle insulin resistance, liver insulin resistance and NAFLD, lipotoxic cardiomyopathy and generalized endothelial dysfunction [Although VAI cannot be claimed r et al. , who sugfunction .In conclusion, given the simplicity of WC and BMI measurement and TG and HDL assessment, and the identification of reference cut-off points in a Caucasian population, we suggest that VAI would be an easy tool for the assessment of VAD, and might be useful in daily clinical practice and in population studies for the assessment of cardiometabolic risk associated with visceral obesity.The authors declare that they have no competing interests.All authors contributed to the intellectual development of this work, and approved the final manuscript. MCA designed the study, performed the statistical analysis of data, searched the literature and wrote the draft paper; MP searched the literature; CG and AG coordinated the study, searched the literature and provided critical corrections to the manuscript.


CKD-Epi significantly overestimated and aMDRD underestimated baseline GFRs. Less than half estimates deviated by <10% from measured values. One-year estimated GFR changes did not detect measured changes. Both formulas underestimated GFR changes by 50%. Less than 9% of estimates deviated <10% from measured changes. Extent of deviations even exceeded that of measured one-year GFR changes. In ADPKD, prediction formulas unreliably estimate actual GFR values and fail to detect their changes over time. Direct kidney function measurements by appropriate techniques are needed to adequately evaluate treatment effects in clinics and research.Trials failed to demonstrate protective effects of investigational treatments on glomerular filtration rate (GFR) reduction in Autosomal Dominant Polycystic Kidney Disease (ADPKD). To assess whether above findings were explained by unreliable GFR estimates, in this academic study we compared GFR values centrally measured by iohexol plasma clearance with corresponding values estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas in ADPKD patients retrieved from four clinical trials run by a Clinical Research Center and five Nephrology Units in Italy. Measured baseline GFRs and one-year GFR changes averaged 78.6±26.7 and 8.4±10.3 mL/min/1.73 m All considered trials conformed to the Declaration of Helsinki guidelines and were approved by the “Comitato di Bioetica della Azienda Ospedaliera Ospedali Riuniti di Bergamo”. In addition, for the ALADIN Study Ethics Committees of Lecce, Milan, Naples, and Treviso approved the trial. All included patients provided written consent to trial participation. Data were handled in respect of patient anonymity and confidentiality.2 (by aMDRD equation) who had been included in four studies designed, conducted, and monitored by the Investigators of the Clinical Research Center for Rare Diseases “Aldo e Cele Daccò” of the Mario Negri Institute . The “Safety and Efficacy of Long-acting Somatostatin Treatment in Autosomal Dominant Polycystic Kidney Disease” study We used measured and estimated GFR data obtained from homogeneous cohorts of adult ADPKD subjects with baseline eGFR >30 mL/min/1.73 mAll studies excluded ADPKD patients with evidence of concomitant systemic, renal parenchymal (proteinuria ≥1 gr/24 hours) or urinary tract disease, diabetes, cancer, psychiatric disorders, as well as pregnant or lactating women or fertile women without effective contraception. Considered variables were recorded according to similar timetables in case record forms and databases which had a similar frame. Thus, the homogeneity in patient characteristics, study design and organization, monitored variables, and data handling procedures allowed the merging of data in a common meta-database and all considered outcomes could be analyzed with a minimized risk of reasonably predictable biases.1) by the formula: CL1 = Dose/AUC, where AUC is the area under the plasma concentration-time curve. According to Bröchner-Mortensen 1)−(0.001218×CL12). GFR values were then normalized to 1.73 m2 of body surface area (BSA).GFR was centrally determined at the laboratory of the Clinical Research Center at patient inclusion and one year apart by using the iohexol plasma clearance technique. GFR was determined by the plasma clearance of iohexol. Briefly, on the morning of renal function evaluation, 5 ml of iohexol solution  was injected intravenously over 2 minutes. Blood samples were then taken at 120, 180, 240, 300, 360, 420, and 480 min for patients with expected mGFR≤40 mL/min, and at 120, 150, 180, 210, and 240 min for those with expected mGFR>40 mL/min. Blood iohexol plasma levels were measured by high-performance-liquid chromatography. The clearance of iohexol was calculated according to a one-compartment model  and demographic and anthropometric data considered in CKD-Epi and aMDRD equations  2 considered separately.Data were expressed as mean ± standard deviation (SD) or median. The relationships between measured and estimated GFR values at baseline, as well as between one-year changes in measured and estimated GFRs, were studied by regression analyses considering Pearson correlation coefficient and Lin concordance correlation coefficient as an index to evaluate the degree to which pairs of observations fall on the 45° line through the origin Bias, mean percent error (MPE) and mean percent absolute error (MAPE) were determined as previously described 2 or exceeding 30 kg/m2, respectively). Serum creatinine exceeded the upper limit of the normal range (1.30 mg/dL) in 39 cases. The GFR was less than the lower limit of the normal range (80–120 mL/min/1.73 m2) in 62 cases. Only six patients were hyperfiltering (mGFR>120 mL/min/1.73 m2). No patient was on concomitant treatment with drugs known to interfere with creatinine tubular handling.Baseline data were available from 111 patients. They were relatively young and predominantly male subjects . Thirty-2. On the basis of the results of Bland-Altman analyses, the performance of the two equations was similarly poor at any degree of renal function, with a trend to greater errors for higher levels of mGFR  for increasing levels of baseline mGFR (2 (The GFRs estimated by CKD-Epi and aMDRD formulas were significantly correlated (p<0.001) with measured GFRs . Mean pe of mGFR . The difine mGFR . Analyse mGFR  for increasing levels of baseline mGFR  and ≥70 (n = 46) mL/min/1.73 m(DOC)Click here for additional data file.


Recent guidelines on cardiovascular disease prevention advocate the importance of psychological risk factors, as they contribute to the risk of developing cardiovascular disease. However, most previous research on psychological distress and cardiovascular factors has focused on selected populations with cardiovascular disease.The primary aim was to determine the prevalence of depression, anxiety, and Type D personality in elderly primary care patients with hypertension. Secondary aim was to examine the relation between elevated systolic blood pressure and depression, anxiety, and Type D personality.A cross-sectional study in primary care practices located in the south of the Netherlands.N = 605), between 60 and 85 years , were recruited for this study. All patients underwent a structured interview including validated self-report questionnaires to assess depression (PHQ-9), anxiety (GAD-7), and Type D personality (DS14) as well as blood pressure assessment.Primary care hypertension patients . This study showed no relation between psychological distress and elevated systolic blood pressure in elderly primary care patients with hypertension.Depression was prevalent in 5 %, anxiety in 5 %, and Type D personality in 8 %. None of the distress measures were associated with elevated systolic blood pressure of >160 mmHg (all  Hypertension is an important risk factor for cardiovascular disease, such as coronary artery disease (CAD), heart failure and stroke  with theOne of the key messages in the 2012 European guidelines on cardiovascular disease prevention in clinical practice is that assessment of psychosocial factors such as depression, anxiety, and Type D personality (the tendency to experience negative emotions combined with the tendency to inhibit expression of emotions ) in patiIn patients with hypertension, psychological distress may serve as a barrier against adequate medication adherence . Prior fThe objectives of the current study were to examine (1) the prevalence of symptoms of depression and anxiety and Type D personality in elderly primary care patients with hypertension, and (2) the relation between elevated symptoms of depression, anxiety, Type D personality, and systolic blood pressure.Between June 2010 and January 2012, primary care patients aged between 60 and 85 years, with diagnosed hypertension according to their medical records, were recruited for this cross-sectional study from five general practices affiliated with the primary care organisation PoZoB. Exclusion criteria were: Previous diagnosis of heart failure; current treatment by a cardiologist; history of severe psychiatric illness other than mood or anxiety disorders; cognitive impairments; terminal cancer; insufficient knowledge of the Dutch language; illiteracy or inability to read due to visual impairments. The study protocol was approved by the medical ethics committee of the Elisabeth Hospital, Tilburg, the Netherlands. All participants provided informed consent.Demographic variables assessed during a structured interview at the local GP office included age, gender, education level, and marital status. Clinical variables assessed during the structured interview included height, weight, blood pressure (after 20 and 40 min of resting), current smoking, alcohol consumption, current or past depression, and current or past anxiety. Information on clinical variables obtained via chart extraction and using ICPC codes were previous myocardial infarction, peripheral arterial disease, cerebrovascular accident or transient ischaemic attack (CVA/TIA), chronic obstructive pulmonary disease (COPD), type 2 diabetes, and years since diagnosis of hypertension.Psychological distress was assessed with patient-report questionnaires which were filled out during the structured interview. The 14-item Type D Scale (DS14) was used to assess Type D personality with 7 items tapping into negative affectivity (NA) and 7 items into social inhibition (SI). Items are rated on a 5-point Likert scale. The SI and NA scales can be used as continuous scales (range 0–28), and also to classify patients as ‘Type D’ versus ‘non-Type D’, using a cut-off of 10 on both NA and SI that was found to be optimal according to item response theory . The DS1Both the PHQ-9 and the GAD-7 are derived from the Primary Care Evaluation of Mental Disorders (PRIME-MD), which was originally designed for the diagnosis of five mental disorders  in the primary care setting by using DSM IV criteria .Statistical analyses were performed using IBM Statistical Package for the Social Sciences version 18.0. Because previous research has shown differences in prevalence of depression and anxiety between men and women, the different psychological indices are reported for the total group and for men and women separately [n = 2), missing all PHQ-9, GAD-7, and DS14 scores (n = 1), and insufficient knowledge of the Dutch language (n = 11). This resulted in 605 patients (66 %) who could be included in the analyses. The baseline characteristics for the total sample and stratified by systolic blood pressure ≤160 mmHg and >160 mmHg, are shown in Table n = 174). A systolic blood pressure of >160 mmHg was associated with higher age (p = 0.006), regular alcohol consumption (p = 0.006), and an elevated diastolic blood pressure of >90 mmHg (p < 0.001). Using the age categories 60–70 years, 70–80 years, and 80–85 years, prevalence of elevated systolic blood pressure increased significantly with age (p = 0.018) .Of the 913 patients with hypertension approached, 619 (68 %) agreed to participate. Fourteen patients were excluded post-hoc as they met the exclusion criterion of being treated by a cardiologist  hypertension patients represent a large proportion of primary care patients where cardiovascular risk management is recommended .A limitation of the study is the cross-sectional design, which does not allow to draw conclusions about causation or to evaluate symptoms over time. Furthermore, there were only limited data available on patients who refused participation. It is possible that patients who refused participation were more likely to be depressed and anxious, and more likely to have a Type D personality . FurtherIn conclusion, a low prevalence of symptoms of anxiety, symptoms of depression, and Type D personality was found in the current study. Furthermore, this study shows no relation between depression, anxiety, and Type D personality and an elevated systolic blood pressure. Therefore, prospective research in primary care populations with hypertension is needed to evaluate the evolvement of psychological distress in association with hypertension over time, and to study the association between psychological distress, hypertension, and long-term cardiovascular outcomes.


The present study was designed to evaluate the relationship between high-sensitivity C-reactive protein (hs-CRP) and arterial stiffness according to sex in patients with arterial hypertension.A case-series study was carried out in 258 hypertensive patients without antecedents of cardiovascular disease or diabetes mellitus. Nephelometry was used to determine hs-CRP. Office or clinical and home blood pressures were measured with a validated OMRON model M10 sphygmomanometer. Ambulatory blood pressure monitoring was performed with the SpaceLabs 90207 system. Pulse wave velocity (PWV) and central and peripheral augmentation index (AIx) were measured with the SphygmoCor system, and a Sonosite Micromax ultrasound unit was used for automatic measurements of carotid intima-media thickness (IMT). Ambulatory arterial stiffness index and home arterial stiffness index were calculated as “1-slope” from the within-person regression analysis of diastolic-on-systolic ambulatory blood pressure.Central and peripheral AIx were greater in women than in men: 35.31 ± 9.95 vs 26.59 ± 11.45 and 102.06 ± 20.47 vs 85.97 ± 19.13, respectively. IMT was greater in men (0.73 ± 0.13 vs 0.69 ± 0.10). hs-CRP was positively correlated to IMT (r = 0.261), maximum (r = 0.290) and to peripheral AIx (r = 0.166) in men, and to PWV in both men (r = 0.280) and women (r = 0.250). In women, hs-CRP was negatively correlated to central AIx (r = −0.222). For each unit increase in hs-CRP, carotid IMT would increase 0.05 mm in men, and PWV would increase 0.07 m/sec in men and 0.08 m/sec in women, while central AIx would decrease 2.5 units in women. In the multiple linear regression analysis, hs-CRP explained 10.2% and 6.7% of PWV variability in women and men, respectively, 8.4% of carotid IMT variability in men, and 4.9% of central AIx variability in women.After adjusting for age, other cardiovascular risk factors and the use of antihypertensive and lipid-lowering drugs, hs-CRP was seen to be positively correlated to carotid IMT in men, and negatively correlated to central AIx in women. The association of hs-CRP to arterial stiffness parameters differs between men and women. The association of high-sensitivity CRP (hs-CRP) to cardiovascular morbidity-mortality has not been sufficiently clarified. Some studies have identified hs-CRP as an independent predictor of cardiovascular events, hypertension and diabetes-3. It ofThe studies that analyze the relationship between hs-CRP and arterial stiffness, as well as behavior according to sex, are inconclusive-11. A prA cross-sectional study was carried out in a primary care setting. We consecutively included all hypertensive subjects visiting primary care clinics between January 2008 and January 2011, and referred to the research unit for the assessment of cardiovascular risk. Hypertension was diagnosed when the mean of three recordings in the clinic under basal conditions and separated in time revealed systolic blood pressure (SBP) ≥140 and/or diastolic blood pressure (DBP) ≥ 90 mmHg. On each visit at least two recordings were made, spaced more than one minute apart. The included 258 hypertensive patients were aged 30–80 years without history of cardiovascular disease (ischemic heart disease or stroke) or diabetes mellitus. Sample size calculation indicated that the 258 patients included in the study were sufficient to detect a minimum correlation coefficient between hs-CRP and arterial stiffness parameters of 0.20 in a two-sided test, with a significance level of 0.05 and a power of 0.90. The study was approved by an independent ethics committee of Salamanca University Hospital (Spain), and all participants gave written informed consent according to the general recommendations of the Declaration of Helsinki.The clinical, anthropometric and analytical data collected are shown in TableMeasurement was obtained by performing three measurements of systolic (SBP) and diastolic blood pressure (DBP), using the average of the last two, with a validated OMRON model M10 sphygmomanometer , and following the recommendations of the European Society of Hypertension. The meaThree measurements were made in the morning (between 6:00 and 9:00 a.m.), and three in the afternoon/evening (between 6:00 and 9:00 p.m.), over a period of 7 days, with a minimum interval of one minute between measurements, and excluding the first measurement and the values corresponding to the first day of measurement. The samABPM was performed on a day of standard activity, with an adequate cuff for the size of the patient’s arm. A control system , validated according to the protocol of the British Hypertension Society, was used − diastolic blood pressure [DBP])/(first peak SBP-DBP) × 100 (%). Using the SphygmoCor System (Vx pulse wave velocity), and with the patient in the supine position, the pulse wave of the carotid and femoral arteries was analyzed, estimating the delay with respect to the ECG wave and calculating the PWV. Distance measurements were taken with a measuring tape from the sternal notch to the carotid and femoral arteries at the sensor location.For AASI and HASI estimation, the regression slope of diastolic on systolic blood pressure was computed for each individual on the basis of 24-hour ABPM (AASI) and also HBP readings (HASI) over 6 days. AASI as well as HASI were defined as one minus the respective regression slope of DBP on SBP. AASI was also computed from waking or sleeping blood pressure. Blood pressure variability ratio (BPVR) was defined as SD (SBP)/SD(DBP), AASI (BPVR) as 1-[1/SD (SBP)/SD (DBP)] in 24-hour blood pressure-24, and The individuals performing the different tests were blinded to the clinical data of the patient. All organ damage assessment measures were made within a period of 10 days.t-test for independent samples and Ji Square for qualitative variables. Pearson’s correlation coefficient was used to estimate the relationship between quantitative variables. We performed linear regression analysis using high-sensitive C-reactive protein as independent variables and using IMT, PWV and CAIx as dependent variables. We have performed multiple linear regression analysis with interaction effects (between gender and hs-CRP) using IMT, PWV and CAIx as dependent variables and high-sensitive C-reactive protein as independent variables, establishing 7 models: model 1, without adjusted; model 2, adjusting for gender and interaction gender x hs-CRP, model 3, adding age; model 4, adding the waist circumference; model 5, adding 24 hours SBP and 24 hours heart rate; model 6, adding Atherogenic Index ; model 7, adding Antihypertensive and Lipid-lowering Drugs. We performed multiple linear regression analysis using IMT, PWV and CAIx as dependent variables and high-sensitive C-reactive protein as independent variables, establishing 6 models: model 1, without adjusted; model 2, adjusting for age; model 3, adding the waist circumference; model 4, adding SBP, ABPM 24 hours and heart rate 24 hours; model 5, adding Atherogenic Index; model 6, adding Antihypertensive and Lipid-lowering Drugs. All analyzes were performed by gender and variables not normally distributed we used the neperian logarithm (LN). The data were analyzed using the SPSS version 18.0 statistical package .Continuous variables were expressed as the mean ± standard deviation (SD), while frequency distributions were used for qualitative variables. The difference in means between two-category quantitative variables has been analyzed using the Student The clinical characteristics, cardiovascular risk factors, blood pressure values, IMT, PWV, CAIx, PAIx, AASI, HASI and antihypertensive and lipid-lowering drugs considered globally and by sexes are reported in TableTableFigureThe interaction analysis, showed that the effect of hs-CRP toward IMT maximum and CAIx depends of the gender (P < 0.05) Table.2 = 0.545, beta 0.026 and p = 0.016). In men, 6.7% of the variability of PWV could be explained by hs-CRP (beta =0.066), versus 10.2% in women (beta = 0.078). Statistical significance was maintained after adjusting for age in men , but was lost in the next model with waist circumference. In contrast, in women statistical significance was maintained to adjustment of the fourth model  . In women, 4.9% of the variability of CAIx could be explained by hs-CRP, statistical significance being maintained after adjusting of the different models . The association of hs-CRP to the rest of the parameters used to assess arterial stiffness disappeared after adjusting for age  of the variability of IMT could be explained by hs-CRP – statistical significance being maintained after the adjustments made in the different models , though Janner et al., in the general population, only observed a relationship in young males. These dOn the other hand, the disparity of results relating hs-CRP to PWV and CAIx in males reinforces the idea that the findings are not inter-exchangeable and differ according to patient sex.The present study has some limitations, including its cross-sectional design, which does not allow us to establish cause-effect relationships between hs-CRP and the arterial stiffness parameters. In turn, the study population was recruited through consecutive sampling, which precludes generalization of the results. Nevertheless, the distribution of the population analyzed is similar to that of the real-life population of hypertensive subjects with cardiovascular risk factors and no previous cardiovascular disease. Lastly, estimation of the central PWV based on the radial PWV, using the transference function, has been questioned-38.In conclusion, this study shows that after adjusting for age, cardiovascular risk factors and the use of antihypertensive and lipid-lowering drugs, hs-CRP exhibits a positive correlation to IMT in men, a negative correlation to CAIx in women, and a positive correlation to PWV in both sexes. Therefore, in order to clarify the role of hs-CRP in relation to the parameters commonly used to assess arterials stiffness in both males and females, prospective studies must be carried out to clarify this association and to define the differences between sexes.hs-CRP: High-sensitive CRP; PWV: Pulse wave velocity; AIx: Augmentation index; IMT: Intima-media thickness; AASI: Ambulatory arterial stiffness index; HASI: Home arterial stiffness index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HBP: Home blood pressure; ABPM: Ambulatory blood pressure monitoring; CAI: Central augmentation index; PAI: Peripherical augmentation index; BPVR: Blood pressure variability ratio.The authors declare that they have no competing interests associated with this paper.MAGM devised the study, designed the protocol, participated in fund raising, interpretation of results, prepared the manuscript draft and corrected the final version of the manuscript. JIRR and CAC participated in the study design, data collection and manuscript review. MCPA and VMV performed all analytical methods, interpretation of results, and manuscript review. ERS, LGS and MGS participated in the study design, interpretation of results, and manuscript review. LGO participated in the protocol design, fund raising, analysis of results, and final review of the manuscript. Finally, all authors reviewed and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/12/37/prepub


Hydatidiform mole cases are usually uncomplicated. However, few cases can be associated with perioperative complications of a critical nature, which can lead to substantial mortality and morbidity. Here is a report of one such case, which, in spite of extensive perioperative management, led to mortality. Molar pregnancy is common in Oriental countries — Philippines, China, Indonesia, Japan and India, as also in Africa and Central and Latin America. The incidence in India is one in 400; 80% of tA moderately built 25-year-old female, with a 24-week molar pregnancy was brought to the operation theatre in the wee hours of the morning for emergency suction-evacuation. Her medical and surgical histories were unremarkable. She was highly irritable, afebrile and moderately pale. She had a pulse rate of 156 beats / minute, blood pressure of 110/80 mm Hg, respiratory rate of 32 breaths / minute and mild pedal oedema. The other general and systemic examinations were unremarkable. Her haemoglobin level was 8 g%. Her thyroid function tests were markedly deranged showing severe biochemical hyperthyroidism . The serum βhCG levels were markedly raised. An ultrasonogram showed signs of a complete molar pregnancy.2) at 99%. The surgical procedure lasted for 15 minutes. The total intraoperative blood loss was approximately 300 mL. Ringers Lactate of 500 ml was infused intraoperatively. One unit of blood was started. She was extubated after reversal. On the table, she appeared slightly restless and mildly tachypnoeic with SpO2 98% on room air. She was awake. Her chest was clear. She was shifted to the postoperative ward. Within half an hour, fine crepitations developed in her chest. She was given Inj. Furosemide 60 mg and was shifted to the Intensive Care Unit. A central venous pressure (CVP) line was inserted. The CVP was 10 cm of water. Slowly, over the next six hours, she became a lot more tachypnoeic. The crepitationsincreased. Blood pressure was stable. She was intubated and put on mechanical ventilation with positive end-expiratory pressure (PEEP). She was nursed in a propped-up position. As per the physician’s advice, she was put on Inj. Metaprolol 5 mg OD, Tab Carbimazole 20 mg bd and Inj. Furosemide 40 mg bd. The next day, her condition remained the same. Urine output was maintained. She was tachypnoeic. Haemoglobin was 7.6 g%. A chest X-ray revealed bilateral fluffy opacities with normal cardiac size, suggestive of pulmonary oedema. An electrocardiogram revealed tachycardia. Arterial blood gas analysis revealed a low pO2. She was unable to maintain SpO2even on an fraction of inspired oxygen (Fio2) of 100% and PEEP. Thyroid function tests done 24 hours postoperatively showed improvement, but they were still deranged . The tachycardia persisted. Her blood pressure fell. Except for tachycardia, there were no other signs of high cardiac output. Dopamine and dobutamine infusions were started. Her condition worsened. In spite of extensive resuscitation efforts tried by us according to the advanced cardiac life support (ACLS) guidelines, she died 36 hours after evacuation of the mole.Pre-induction, the patient was given intravenous (IV) dexamethasone 2 mg, IV Fentanyl 100 μg and IV Metaprolol 0.5 mg. The pulse rate came down to 100 beats / minute. Rapid sequence induction was done with Inj. Thiopentone 250 mg and IV Succinyl choline 80 mg. A cuffed oral endotracheal tube No. 7 was passed. She was maintained on oxygen and nitrous oxide on intermittent positive pressure ventilation, with Vecuronium as a muscle relaxant. Intraoperatively, the pulse rate was maintained at around 100 beats/ minute, blood pressure at 110 / 60 mm Hg and oxygen saturation  and spinal anaesthesia (SA) are the various anaesthesia techniques that can be adopted for a case of evacuation of molar pregnancy.46 GA was4234Every anaesthesiologist should be well aware of the critical nature of perioperative complications that can be associated with a molar pregnancy. A detailed pre-anaesthesia work-up, pre-operative optimisation of the patient’s thyroid and volume status, planning and conducting anaesthesia carefully and being prepared for advanced perioperative anaesthetic management are a must for any case of molar pregnancy.


Diabetic macular edema (DME) with neurosensory retinal detachment (NSD) remains an important cause of visual loss in patients with diabetes. The aim of the study was to elucidate the association of systemic and ocular risk factors with NSD in DME.In a retrospective case–control study, we reviewed clinical records of all the subjects with DME seen between January 2010 and December 2010. Cases and controls were selected based on optical coherence tomography and stereoscopic biomicroscopy review. NSD was defined as subfoveal fluid accumulation under detached retina with or without overlying foveal thickening. The association between the presence of NSD, blood pressure, lipid status and various other biochemical parameters was evaluated.Group I (cases) included 37 eyes of 33 patients having DME with NSD and Group II (controls) included 30 eyes of 21 patients having DME without NSD. Patients ranged in age (mean ± SD) from 50 to 62 years (56.6 +/-6.78) for cases and from 51 to 65 years (58.4+/-7.84) for controls. The duration of diabetes ranged from 4 to 15 year (mean 9.45+/-6.08) among cases and 4 to 14 years (9.7+/-5.12) among controls. Significant risk factors for NSD were high values of systolic and diastolic blood pressure (p = 0.039 and 0.043 respectively).High systolic and diastolic blood pressures are independent and significant risk factors for NSD in DME. Diabetic macular edema (DME) remains a major cause of visual loss in patients with diabetes . OpticalThe prognosis of DME is decided by many factors, such as the presence of NSD, inner segment/outer segment (IS/OS) conjunction and integrity of the external limiting membrane (ELM) line -13. IS/OThe presence of NSD is found to adversely affect the prognosis of DME. NSD can significantly limit effective laser treatment of the macula . The preThis study was a retrospective chart review of patients with diagnosed DME seen between Jan 2010 to Dec 2010. Cases and controls were selected based on SD-OCT review. Group I (cases) included 37 eyes of 33 patients who were diagnosed as DME with NSD on OCT and Group II (controls) included 30 eyes of 21 patients who had DME without NSD. The macular edema was diagnosed by biomicroscopy according to the criteria reported by ETDRS. NSD type DME was defined as subfoveal fluid accumulation with distinct outer border of detached retina with or without overlying foveal thickening . Two readings were taken with a five minutes interval and their mean indication was taken as the blood pressure. In most of the subjects, the blood pressure measurement was taken on the day of complete ophthalmic examination which included OCT. In the remaining subjects, blood pressure was measured on the day of OCT review which was 1 or 2 days later. The biochemical parameters noted were fasting and post-prandial blood sugar levels, hemoglobin, glycosylated hemoglobin, blood pressure and renal function tests (serum urea and serum creatinine). All biochemical parameters were done at same laboratory using standard techniques. The grading of diabetic retinopathy was done based on modified klein classification as mild, moderate and severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy . The modt-test was used to compare proportions among neurosensory detachment status with the independent measured (continuous) variables in Univariate analyses. P value less than 0.05 was considered significant. Multivariate analyses could not be done because of small sample size in both the groups.A computerized database was created for all the records. Statistical analyses were performed using SPSS Windows version 14.0 . All the data were expressed as mean ± S.D or as percentage. The normality of distribution was checked for all factors by Kolmogorov–Smirnov analysis. The data in the study followed normal distribution, hence we used the parametric tests to determine significance. Chi-square test was used to compare proportions among neurosensory detachment status with the independent categorical variables and the Student’s A total of 37 eyes of 33 patients who had NSD with DME  and 30 eyes of 21 patients who had DME without NSD  were included in our study. All patients included were of type 2 diabetes mellitus. The patients ranged in age from 50 to 62 years among the cases (mean 56.6 +/-6.7) and 51 to 65 among the controls (mean 58.4+/7.84). The duration of diabetes ranged from 4 to 15 years (mean 9.45+/-6.08) among cases and 4 to 14 years (9.7+/-5.12) among controls. Group 1 included 28 males (84.8%) and 5 females (15.2%) and Group 2 included 14 males (67.7%) and 7 females (33.3%).Table Table DME remains the leading cause of visual loss among patients with diabetes mellitus. Among the various patterns of DME, NSD under the fovea has been reported in 3–31% of patients. The pathogenesis of NSD is linked not only to the limitations of the draining vascular system, but also to impairment in the function of the RPE. Kang et al. reported that in diabetic eyes, the incidence of CME and NSD increasd with the existence of retinal vascular hyperpermeability and the pathology of these two phenomena might share a common pathogenesis in this regard .Various systemic factors have been associated with increased incidence of DME like severity of diabetic retinopathy, poor glycemic control and duration of diabetes. Hypertension, proteinuria, dyslipidemia, uncontrolled renal parameters, and PRP for PDR , have also been associated with increased risk of DME. Although all these factors are known to correlate with increased incidence of DME, very few studies have correlated the presence of uncontrolled systemic disease and biochemical parameters with increased incidence of NSD in DME. Poor control of systemic factors could be related to increased leakage from the capillaries with loss of vascular integrity as well to an impaired function of RPE. One study demonstrated the presence of high HbA1c levels in the patients with diabetic CME and NSD, compared to those with diabetic CME and no associated NSD . In our Increased blood pressure has been implicated, through the effects of increased blood flow, to cause damage to the retinal capillary endothelial cells in eyes of diabetic patients . ElevateChoroidal vascular damage causes ischemic damage to the RPE and leads to breakdown of the blood-retinal barrier with transudation of fluid into subretinal space. Hayreh observed that the presence of NSD was correlated to the degree of choroidal circulation disruption. Fluid overload has also been implicated as a cause of NSD .Anemia is another known risk factor for DME. Low hemoglobin levels can occur in diabetic patients secondary to renal disease or can occur independently. However, the renal disease as measured by serum urea and creatinine was not found to be associated with NSD in this study. Futhermore, anemia was not found as an independent risk factor for formation of NSD. Low hemoglobin has been described as an independent baseline risk factor in the EDTRS for the development of DME and severe visual loss . Other sIn conclusion, we found high systolic and diastolic blood pressures to be independent and significant risk factors for NSD in DME. The present study suggests that the treating ophthalmologists should get a complete systemic workup done for the presence of co-morbidities especially high blood pressure in subjects with NSD in DME. Achieving adequate metabolic control of associated conditions should be aimed in such subjects. Prospective studies are warranted to see whether decreasing the blood pressure of the patient will help in the resolution of NSD in DME.The authors declare that they have no competing interests.AG carried out the data collection, data analysis, and drafted the manuscript. RR conceived the study, and participated in its design and coordination and helped to draft the manuscript. VK helped in data collection, data analysis and performed the statistical analysis. TS helped to conceive the study, supervised the entire study and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2415/14/47/prepub


Induction of anesthesia and endotracheal intubation often creates a period of hemodynamic instability in hypertensive patients. Endotracheal intubation of the trachea stimulates laryngeal and tracheal sensory receptors, resulting in a marked increase in the elaboration of sympathetic amines.This trial aimed to evaluate and compare the efficacy of fentanyl and fentanyl plus lidocaine in attenuating the hemodynamic responses to laryngoscopy and endotracheal intubation in hypertensive patients.We conducted a prospective, randomized, double-blind trial in 37 patients with hypertension in the Rasoul-Akram Hospital, Tehran, Iran, from March to December 2011. The patients were randomly divided into two groups (fentanyl group and fentanyl plus lidocaine group). The fentanyl group received 2 mcg/kg and the fentanyl plus lidocaine group received 1.5mg lidocaine and 2mcg/kg fentanyl. Hemodynamic variables were recorded at baseline, after giving inductive anesthetic agents, and 1, 3 and 5 minutes after performing endotracheal intubation.We evaluated 37 patients including 15 males (40.54%) and 22 females (59.46%), with a mean age of 56.08 ± 10.85 years. There were no significant differences between the two groups regarding; heart rate, systolic blood pressure and diastolic blood pressure before induction, 3 minutes before intubation and 1, 3 and 5 minutes after intubation.Fentanyl and fentanyl plus lidocaine effectively decreased the hemodynamic response to tracheal intubation, however, neither fentanyl nor fentanyl plus lidocaine, could inhibit all hemodynamic responses, moreover fentanyl plus lidocaine was not more effective than fentanyl alone. Tracheal intubation may induce; hypertension, tachycardia, and/or arrhythmia. These tracheal responses are mediated by sympathetic responses and are normally well tolerated by normotensive patients. However, induction of anesthesia and endotracheal intubation often produces a period of hemodynamic instability for hypertensive patients and regardless of the level of preoperative blood pressure control, many patients with hypertension display an accentuated hypotensive response to induction of anesthesia, followed by an exaggerated hypertensive response to endotracheal intubation. Endotracheal intubation of the trachea stimulates laryngeal and tracheal sensory receptors, resulting in a marked increase in the elaboration of sympathetic amines , this sympathetic stimulation results in tachycardia and elevation of blood pressure -7. Thus This trial aimed to evaluate and to compare the efficacy of fentanyl and fentanyl plus lidocaine in attenuating hemodynamic responses to laryngoscopy and endotracheal intubation in ASA class ІІ patients (hypertensive patients).P values ≤ 0.05 were considered significant.We conducted a prospective, randomized, double-blind trial in 37 patients with hypertension in the Rasoul-Akram Hospital, Tehran, Iran, from March to December 2011. The study protocol was confirmed by the Ethical Committee of the Tehran University of Medical Sciences, furthermore, written informed consent was obtained from all patients. Including criteria comprised; elective surgery with general anesthesia, 65 > age > 20, ASA class ІІ patients (hypertensive patients). Excluding criteria; patients undergoing heart surgery, ASA III or above, CHF . The fentanyl group received 2 mcg/kg and the fentanyl plus lidocaine group received 1.5mg lidocaine and 2mcg/kg fentanyl. Patients received their morning dose of anti-hypertensive medication before surgery. A routine pre-operative check-up was done in all patients and baseline vitals were noted, next patients received normal saline or ringer 5ml/kg in the admission operation room, and then they were oxygenation for three minutes. In the operating room, an intravenous line was started. Patients were attached to the following monitors; ECG, noninvasive blood pressure monitor, pulse oximetery. The baseline values (pre-anesthetic reading) for; mean arterial pressure (MAP) {MAP = DBP + 1/3 (SBP-DBP)}, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded. Anesthesia was induced by thiopental given in a 3-5 mg/kg dose with fentanyl, or lidocaine plus fentanyl, next succinylcholine was given in a dose of 1-1.5 mg/kg succinylcholine given approximately 30-60 seconds before endotracheal intubation and induction was confirmed by loss of eyelash reflexes. Fentanyl or lidocaine plus fentanyl was administered three minutes prior to intubation. The hemodynamic variables; MAP), SBP, DBP, and HR were recorded after giving inductive anesthetic agents and trial drugs . Then a laryngoscopy was performed by a professional anesthetist with a standard Macintosh laryngoscope blade and the trachea was intubated with an appropriate size cuffed endotracheal tube and the patient was ventilated with oxygen. Hemodynamic variables; MAP, SBP, DBP, and HR were recorded 3 and 5 minutes after performing endotracheal intubation. We also recorded any possible complications such as; bradycardia (HR < 50), hypotension (SBP < 90), bronchospasm, seizure and rigidity. All results were expressed as mean ± SD. Hemodynamic variables in the present study were analyzed statistically by using a t-test. We evaluated 37 patients including 15 males (40.54%) and 22 females (59.46%) with a mean age of 56.08 ± 10.85 years. There was no significant difference between the two groups regarding HR, SBP and DBP in the patients before induction, three minutes before intubation and 1, 3 and 5 minutes after intubation. We found that fentanyl and fentanyl plus lidocaine are effective medications on hemodynamic responses  decreasing before induction, three minutes before intubation and 1, 3 and 5 minutes after intubation. However, we did not discern any significant difference between the efficacy of the two kinds of medication (fentanyl and fentanyl plus lidocaine). Endotracheal intubation is a stressful noxious force stimuli, it stimulates laryngeal and tracheal sensory receptors, resulting in a marked increase in the expansion of sympathetic amines , and this increase in the sympathetic amines leads to complications especially in patient with cardiovascular diseases. Responses to endotracheal intubation arise essentially due to sympathetic stimulation causing increases in blood pressure, increases in heart rate and tachyarrhythmia. In normal patients, these responses are significantly high, but they are generally well tolerated, whereas in patients with cardiovascular diseases, many complications may occur like; increases in systolic and diastolic blood pressure, increases in heart rate, tachyarrhythmia, cerebral hemorrhage, left ventricular failure, and in rare conditions, myocardial ischemia -25. Thes


Medical societies have developed guidelines for the detection, treatment and control of hypertension (HTN). Our analysis assessed the extent to which such guidelines were implemented in Germany in 2003 and 2001.doc) was defined as coding hypertension in the clinical appraisal questionnaire. Alternative definitions used were physician’s diagnosis or the patient’s self-reported diagnosis of hypertension , physician’s or patient’s self-reported diagnosis or a BP measurement with a systolic BP≥140 mmHg and/or a diastolic BP≥90  and diagnosis according to the National Health and Nutrition Examination Survey (HTNNHANES). The results were compared with the similar German HYDRA study to examine whether changes had occurred in diagnosis, treatment and adequate blood pressure control (BP below 140/90 mmHg) since 2001. Factors associated with pharmacotherapy and control were determined.Using standardized clinical diagnostic and treatment appraisal forms, blood pressure levels and patient questionnaires for 55,518 participants from the cross-sectional Targets and Essential Data for Commitment of Treatment (DETECT) study (2003) were analyzed. Physician’s diagnosis of hypertension , hyperlipidemia and diabetes mellitus (DM). Significant positive predictors of adequate blood pressure control were CHD and antihypertensive medication. Inadequate control was associated with increasing age, male sex and obesity.The overall prevalence rate for hypertension was 35.5% according to HTNRates of treated and controlled hypertension according to NHANES criteria in DETECT remained low between 2001 and 2003, although there was some minor improvement. Hypertension (HTN) is a common cause for patient contacts with primary physicians, and there is evidence of suboptimal treatment and inadequate blood pressure control Patients with hypertension alone have an increased risk for cardiovascular morbidity and mortality Our analysis compares the results of the DETECT study with 55,518 participants in 2003 for the estimated prevalence rates using different definitions for diagnosis of hypertension and compares treatment and control rates with the results of the Hypertension and Diabetes Risk Screening and Awareness Study (HYDRA) study Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment) was initiated to estimate the prevalence and comorbidity patterns of primary care patients and to evaluate new strategies for the prevention and early detection of chronic diseases http://www.detect-studie.de and about the HYDRA study on http://www.hydra-studie.de. HYDRA was a precursor study of DETECT with identical methods of sampling, design and also assessment of hypertension th or 18th September 2003 were included in the DETECT study. The sampling was based on 1060 regional segments in Germany , 7053 primary care physicians being randomly selected as a sample from all 64707 physicians who had been working as primary care physicians in Germany in 2003 DETECT (The DETECT study was approved by the ethics committee of the Dresden University of Technology (TU Dresden). Written informed consent was received from all participants.doc); b) physician’s diagnosis or the patient’s self-reported diagnosis of hypertension ; c) physician’s or patient’s self-reported diagnosis or a BP measurement with a systolic BP≥140 mmHg and/or a diastolic BP≥90 ; d) diagnosis according to the National Health and Nutrition Examination Survey (HTNNHANES) or treatment with antihypertensive drugs, irrespective of the doctor’s or patient’s self-reported diagnosis. For the estimation of the proportion of diagnosed patients (<140/90 mmHg) we used the HTNNHANES criterion for defining hypertension In order to allow a comparison of the DETECT study specifically with the previous HYDRA study and further related studies in Germany, this paper applies the methods used and described in a previous study for the measurement of prevalence of hypertension The physicians’ questionnaire explicitly asked for the existence of 28 specified medical diagnoses and also allowed for adding further diagnoses. CHD, DM and hyperlipidemia were exclusively defined as physicians’ based diagnoses (newly diagnosed or previously known) 2 , 25 to <30 kg/m2 (overweight) and ≥30 kg/m2 (obesity). Waist circumference (WC) was categorized into the following groups: ≤94 cm for males and ≤80 cm for females as not overweight, >94 cm and ≤102 cm for males and >80 cm and ≤88 cm for females as pre-obese, >102 cm for males and 88 cm for females as obese.The patients’ questionnaire contained information about physical activity and smoking status as cardiovascular risk factors. Physical activity was classified as either more than or equal to 2 hours per week versus physical activity with less than 2 hours per week on average . Smoking status of the participants was defined as use of any tobacco product in the past 4 weeks and categorized as yes/no. BMI was categorized into three groups: <25 kg/mDETECT study participants were analyzed with respect to socio-demographic, comorbidities and cardiovascular lifestyle risk factors. Gender and age-group specific estimates of prevalence rates of hypertension were determined applying alternative definitions of hypertension in unselected primary care patients. Also the prevalence of hypertension according to JNC 7 categories was analyzed. Determinants associated with pharmacotherapy and adequate BP control of hypertension such as socio-demographic comorbidities and cardiovascular lifestyle risk factors were evaluated using multiple logistic regression. Education in years was included in the models as potentially explanatory factor. The patients were clustered by primary care units and to account for the clustered structure of the data, robust standard errors were estimated by the Huber-White Matrix. Data were weighted for non-response and attrition during the recruitment phase. Categorical data were presented as absolute frequencies (n) and weighted percentages (%w), metric variables by weighted mean and standard deviation. A two-sided alpha-level of 0.05 was chosen as criterion for statistical significance. All statistical analyses were conducted using STATA 11.2 .doc) was present in 35.5% of all participants  showed slightly higher prevalence rates: 41.8% in all participants, 6.4% in the youngest age group and 69.5% in the oldest age group. Physician’s or patient’s self-reported diagnosis or a BP measurement with a systolic BP≥140 mmHg and/or a diastolic BP≥90  prevalence rates increased to 55.2% in all participants and were 15.4% and 82.1% in the youngest and oldest age group, respectively. Prevalence rates for hypertension diagnosis according to the National Health and Nutrition Examination Survey (HTNNHANES) were in a similar range as for HTNdoc,pat,bp: 56.0% in all participants, 13.3% in the youngest and 86.8% in the oldest age group. Comparing the estimated prevalence rates for HTNdoc, HTNdoc,pat, HTNdoc,pat,bp and HTNNHANES, the largest differences measured as ratio of 2 estimated prevalence rates were seen in the youngest age group comparing HTNdoc and HTNNHANES. The biggest percent difference in absolute number was present in the oldest age group comparing HTNdoc to HTNNHANES. Limitations of the DETECT study exist, because there was only single measurement of blood pressure in a primary care setting done. Some patients have been excluded from the study, because of time restrictions of the physician or no clinical assessment was possible ants see . The preThe categories of the measured BP values according to the JNC 7 classification are shown in NHANES cases were diagnosed  by the physicians. In the youngest there was the smallest proportion of diagnosed HTNNHANES cases (17.4% only). In the age group 75+ the fraction of physician diagnosed cases was highest (71.0%). The rates of HTNNHANES cases, which were diagnosed and also treated by physicians increased with higher age: 12.1% in the youngest age group and 65.7% in the oldest age group. Among HTNNHANES cases the proportion of patients with adequate blood pressure control was 21.4% across all groups; it was 5.8% in the youngest and 23.3% in the oldest age group.Across all age groups 61.5% of HTNThe comparison presented in 2 , a history of CHD , a physician based diagnosis of hyperlipidemia , DM  or previous myocardial infarction . An alternative specification with waist circumference (reference category: not overweight) instead of BMI as a measure of cardiovascular risk gave very similar results. Smoking was negatively associated with receiving antihypertensive medication .doc cases, the factors associated with adequate blood pressure control (less than 140/90 mmHg) were female sex , the presence of CHD , previous myocardial infarction  and antihypertensive medication  . An alternative specification with waist circumference (reference category: not overweight) instead of BMI as a measure of cardiovascular risk gave also very similar results in this regression. Comorbidities  such as physical activity and smoking status) had no effect on blood pressure control.In HTN23–1.61) . With indoc and highest for HTNNHANES. Comparison of diagnosis and treatment rates and of the proportion with adequate control among patients in the DETECT and HYDRA studies showed only a small improvement in treatment and control rates between 2001 and 2003 and a slight decline in diagnosis rates. The comorbidities of CHD and previous myocardial infarction were associated with pharmacotherapy and adequate blood pressure control, whereas for patients with other comorbidities such as DM and hyperlipidemia control was less likely.Prevalence of hypertension was dependent on the definition used, and was lowest for HTNdoc and HTNdoc,pat and highest for HTNNHANES and HTNdoc,pat,bp . This shows that a considerable fraction of people with hypertension had not been diagnosed by physicians. As a consequence treatment and control rates of HTNNHANES based cases are lower in comparison with treatment and control rates based on physician based diagnoses.Different definitions of hypertension revealed remarkable differences in prevalence rates. The prevalence rates were lowest for HTNdoc with 38.8% and slightly lower for HTNNHANES with 50.4%. HTNdoc,pat with 39.5% and HTNdoc,pat,bp with 52.4% were almost in the same range as in the DETECT study. The total prevalence of hypertension based only on physician’s assigned diagnosis should be considered with caution and these results were found in both studies. The degree of underestimation is more pronounced for the younger patients, but is still notable in the older age groups. Our results for the prevalence rate of hypertension are in accordance with a population-based study for Germany  with prevalence rates only slightly lower if applying NHANES definition criteria in this study (53.5% for men and 43.6% for women) Only one study (HYDRA) which is similar to the current one uses the same definitions for hypertension and for the calculation of the prevalence, diagnosis, treatment and control of hypertension doc definition. Between these six countries there was a range of prevalence rates of hypertension between 78% in UK and 90% in Italy, the prevalence in Germany being 86%. The surprisingly high prevalence rates of hypertension in comparison to the DETECT and HYDRA study can be explained partly by the fact, that these surveys were visit-based and not population-based. Physician sampling was based on a quota criterion – each physician had a minimum of 15 patients per week with a cardiovascular disease to be included in the respective countries. Sicker patients were oversampled and as a consequence a selection problem with a high proportion of patients with comorbidities existed. The high prevalence rates for hyperlipidemia with 49% and for DM with 29% in the German CardioMonitor survey are in accordance with this interpretation. The prevalence rates in the DETECT study were much lower for hyperlipidemia with 29.5% and for DM with 12.1%.In a cohort study with original and offspring cohort members of the Framingham Heart Study, the prevalence rate of hypertension according to the NHANES criteria was 27.3% in participants younger than 60 years of age, 63.0% in participants between 60 and 79 years of age and 74.0% in participants above 80 years of age On the one hand, there is a decrease in the proportion of patients diagnosed by physicians in the DETECT study in comparison to the HYDRA study. On the other hand, age-specific treatment and control rates were slightly higher. This means that, despite continuous efforts to improve management of hypertension which have included the publication of the HYDRA results, intense continuous medical education (CME) and intensive training programs, there is only a slight improvement of treatment and control and even a decline in the diagnosis rate.The WHO-Monica-Augsburg study, conducted in 1994/95, has also reported diagnosis, treatment and control rates which have been in a lower range Higher control rates of hypertension were reported in the USA compared to those in Germany DETECT also allowed for the evaluation of the impact of patient characteristics as determinants of pharmacotherapy. Patients with higher age and BMI and comorbidities such as CHD, DM, myocardial infarction, hyperlipidemia showed a higher probability of receiving pharmacotherapy, in agreement with guidelines. These results are partially different from those of the ESTHER study, which is a cohort study conducted in a primary care setting in the German Federal State of Saarland In the DETECT study female sex, a lower BMI, CHD, previous myocardial infarction and antihypertensive medication were associated with adequate blood pressure control. This is in accordance with guideline recommendations that in patients with comorbidities such as CHD or previous myocardial infarction blood pressure control is of high importance. These results are in contrast to the results of the ESTHER study. In this study the only significant negative predictor of an adequate blood pressure in patients with both DM and hypertension was higher age. The difference between DETECT and ESTHER could be explained first by the fact that hypertensive patients with DM are a special subpopulation of hypertensive patients, and second, by choosing a different cut-off point for adequate blood pressure control with a systolic BP of 130 mmHg and a diastolic BP of 85 mmHg in the ESTHER study.Results for the prediction of adequate blood pressure control in the DETECT study are also in part in agreement with data for hypertensive patients with DM treated in primary care clinics in the USA NHANES definition, because the phenomenon of white coat hypertension could subsequently lead to an underestimation of treatment rates and blood pressure control. In the original study which defined the HTNNHANES criteria for measuring prevalence in the US, two sets of measurements during two different visits had been taken As a first limitation of the DETECT study it should be mentioned that blood pressure measurement was only done once, and not repeatedly, under primary care conditions. For a high degree of certainty about diagnosis of hypertension different methods and using the average of several measurements are recommended Differing definitions of hypertension exist and as a consequence the prevalence rates of hypertension vary accordingly in the DETECT and HYDRA studies. A comparison of the rates of treated and controlled hypertension in the DETECT study with the HYDRA study show indications of small improvements in proportions of patients adequately controlled, although levels of control remain low. With respect to proportions of people diagnosed, there is even a decline. Hypertensive patients with risk factors such as obesity and associated comorbidities such as CHD, hyperlipidemia and DM were more likely to receive antihypertensive drugs in accordance with guidelines. A higher rate of adequate blood pressure control was achieved in patients with obesity and CHD, but not those with DM or hyperlipidemia.