Norepinephrine to increase blood pressure in endotoxaemic pigs is associated with improved hepatic mitochondrial respiration

ABSTRACT: INTRODUCTION: Low blood pressure, inadequate tissue oxygen delivery and mitochondrial dysfunction have all been implicated in the development of sepsis-induced organ failure. This study evaluated the effect on liver mitochondrial function of using norepinephrine to increase blood pressure in experimental sepsis. METHODS: Thirteen anaesthetized pigs received endotoxin (Escherichia coli lipopolysaccharide B0111:B4; 0.4 mug/kg per hour) and were subsequently randomly assigned to norepinephrine treatment or placebo for 10 hours. Norepinephrine dose was adjusted at 2-hour intervals to achieve 15 mmHg increases in mean arterial blood pressure up to 95 mmHg. Systemic (thermodilution) and hepatosplanchnic (ultrasound Doppler) blood flow were measured at each step. At the end of the experiment, hepatic mitochondrial oxygen consumption (high-resolution respirometry) and citrate synthase activity (spectrophotometry) were assessed. RESULTS: Mean arterial pressure (mmHg) increased only in norepinephrine-treated animals (from 73 [median; range 69 to 81] to 63 [60 to 68] in controls [P = 0.09] and from 83 [69 to 93] to 96 [86 to 108] in norepinephrine-treated animals [P = 0.019]). Cardiac index and systemic oxygen delivery (DO2) increased in both groups, but significantly more in the norepinephrine group (P < 0.03 for both). Cardiac index (ml/min per.kg) increased from 99 (range: 72 to 112) to 117 (110 to 232) in controls (P = 0.002), and from 107 (84 to 132) to 161 (147 to 340) in norepinephrine-treated animals (P = 0.001). DO2 (ml/min per.kg) increased from 13 (range: 11 to 15) to 16 (15 to 24) in controls (P = 0.028), and from 16 (12 to 19) to 29 (25 to 52) in norepinephrine-treated animals (P = 0.018). Systemic oxygen consumption (systemic VO2) increased in both groups (P < 0.05), whereas hepatosplanchnic flows, DO2 and VO2 remained stable. The hepatic lactate extraction ratio decreased in both groups (P = 0.05). Liver mitochondria complex I-dependent and II-dependent respiratory control ratios were increased in the norepinephrine group (complex I: 3.5 [range: 2.1 to 5.7] in controls versus 5.8 [4.8 to 6.4] in norepinephrine-treated animals [P = 0.015]; complex II: 3.1 [2.3 to 3.8] in controls versus 3.7 [3.3 to 4.6] in norepinephrine-treated animals [P = 0.09]). No differences were observed in citrate synthase activity. CONCLUSION: Norepinephrine treatment during endotoxaemia does not increase hepatosplanchnic flow, oxygen delivery or consumption, and does not improve the hepatic lactate extraction ratio. However, norepinephrine increases the liver mitochondria complex I-dependent and II-dependent respiratory control ratios. This effect was probably mediated by a direct effect of norepinephrine on liver cells.

Cardiomegaly in a premature neonate after venous umbilical catheterization

Umbilical venous catheters allow rapid central access in neonates, but may be associated with various complications. We present a case of a newborn with pericardial effusion following umbilical venous catheterization. An extremely low birth weight infant was intubated for respiratory distress syndrome and had umbilical venous and arterial lines in place. Massive cardiomegaly was noted on the subsequent chest X-ray. Echocardiography revealed a large pericardial effusion without signs of tamponade. After removing the catheter, the effusion gradually resolved. While pericardial effusion is a well-known complication of percutaneous long central lines, only a few case reports have documented sudden cardiovascular compromise associated with umbilical venous catheters. Pericardial effusion may be asymptomatic and should be suspected in infants with central catheters and progressive cardiomegaly. The prompt removal of catheters and, if signs of cardiac tamponade are present, emergency pericardiocentesis may prove to be life-saving.

Pulse contour analysis: a valid assessment of central arterial stiffness in children?

In adults the contour analysis of peripheral pressure waves in the upper limb reflects central aortic stiffness. Here, we wanted to demonstrate the appropriateness of pulse contour analysis to assess large artery stiffness in children. Digital volume pulse analysis, with the computation of the stiffness index and pulse wave velocity between carotid and femoral artery, were simultaneously determined in 79 healthy children between 8 years and 15 years (mean age 11.4 years, 32 girls). The stiffness index of 42 healthy adults (mean age 45.6 years, 26 women) served as control. Pulse wave velocity between carotid and femoral artery was directly correlated with systolic pressure and mean blood pressure, as well as with pulse pressure. The results from the stiffness index of children revealed the expected values extrapolated from the linear regression of adulthood stiffness index vs. age. Childhood stiffness index positively correlated with pulse wave velocity (r(2) = 0.07, P = 0.02) but not with blood pressure parameters. The exclusion of individuals with an increased vascular tone, as indicated by a reflexion index > 90%, improved the correlation between stiffness index and pulse wave velocity (r(2) = 0.13, P = 0.001). Our data indicate that digital volume pulse-based analysis has limitations if compared with pulse wave velocity to measure arterial stiffness, mostly in patients with a high vascular tone.

Crystalloids versus colloids for goal-directed fluid therapy in major surgery

INTRODUCTION: Perioperative hypovolemia arises frequently and contributes to intestinal hypoperfusion and subsequent postoperative complications. Goal-directed fluid therapy might reduce these complications. The aim of this study was to compare the effects of goal-directed administration of crystalloids and colloids on the distribution of systemic, hepatosplanchnic, and microcirculatory (small intestine) blood flow after major abdominal surgery in a clinically relevant pig model. METHODS: Twenty-seven pigs were anesthetized and mechanically ventilated and underwent open laparotomy. They were randomly assigned to one of three treatment groups: the restricted Ringer lactate (R-RL) group (n = 9) received 3 mL/kg per hour of RL, the goal-directed RL (GD-RL) group (n = 9) received 3 mL/kg per hour of RL and intermittent boluses of 250 mL of RL, and the goal-directed colloid (GD-C) group (n = 9) received 3 mL/kg per hour of RL and boluses of 250 mL of 6% hydroxyethyl starch (130/0.4). The latter two groups received a bolus infusion when mixed venous oxygen saturation was below 60% ('lockout' time of 30 minutes). Regional blood flow was measured in the superior mesenteric artery and the celiac trunk. In the small bowel, microcirculatory blood flow was measured using laser Doppler flowmetry. Intestinal tissue oxygen tension was measured with intramural Clark-type electrodes. RESULTS: After 4 hours of treatment, arterial blood pressure, cardiac output, mesenteric artery flow, and mixed oxygen saturation were significantly higher in the GD-C and GD-RL groups than in the R-RL group. Microcirculatory flow in the intestinal mucosa increased by 50% in the GD-C group but remained unchanged in the other two groups. Likewise, tissue oxygen tension in the intestine increased by 30% in the GD-C group but remained unchanged in the GD-RL group and decreased by 18% in the R-RL group. Mesenteric venous glucose concentrations were higher and lactate levels were lower in the GD-C group compared with the two crystalloid groups. CONCLUSIONS: Goal-directed colloid administration markedly increased microcirculatory blood flow in the small intestine and intestinal tissue oxygen tension after abdominal surgery. In contrast, goal-directed crystalloid and restricted crystalloid administrations had no such effects. Additionally, mesenteric venous glucose and lactate concentrations suggest that intestinal cellular substrate levels were higher in the colloid-treated than in the crystalloid-treated animals. These results support the notion that perioperative goal-directed therapy with colloids might be beneficial during major abdominal surgery.

Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury

INTRODUCTION: Maintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of detrimental blood glucose levels must be determined. METHODS: In 69 patients with severe traumatic brain injury (TBI), cerebral metabolism was monitored by assessing changes in arterial and jugular venous blood at normocarbia (partial arterial pressure of carbon dioxide (paCO2) 4.4 to 5.6 kPa), normoxia (partial arterial pressure of oxygen (paO2) 9 to 20 kPa), stable haematocrit (27 to 36%), brain temperature 35 to 38 degrees C, and cerebral perfusion pressure (CPP) 70 to 90 mmHg. This resulted in a total of 43,896 values for glucose uptake, lactate release, oxygen extraction ratio (OER), carbon dioxide (CO2) and bicarbonate (HCO3) production, jugular venous oxygen saturation (SjvO2), oxygen-glucose index (OGI), lactate-glucose index (LGI) and lactate-oxygen index (LOI). Arterial blood glucose concentration-dependent influence was determined retrospectively by assessing changes in these parameters within pre-defined blood glucose clusters, ranging from less than 4 to more than 9 mmol/l. RESULTS: Arterial blood glucose significantly influenced signs of cerebral metabolism reflected by increased cerebral glucose uptake, decreased cerebral lactate production, reduced oxygen consumption, negative LGI and decreased cerebral CO2/HCO3 production at arterial blood glucose levels above 6 to 7 mmol/l compared with lower arterial blood glucose concentrations. At blood glucose levels more than 8 mmol/l signs of increased anaerobic glycolysis (OGI less than 6) supervened. CONCLUSIONS: Maintaining arterial blood glucose levels between 6 and 8 mmol/l appears superior compared with lower and higher blood glucose concentrations in terms of stabilised cerebral metabolism. It appears that arterial blood glucose values below 6 and above 8 mmol/l should be avoided. Prospective analysis is required to determine the optimal arterial blood glucose target in patients suffering from severe TBI.

A standardized protocol for the prevention of clinically relevant venous air embolism during neurosurgical interventions in the semisitting position

OBJECTIVE: We report the results and complications associated with standardized intraoperative management designed for the prevention of hemodynamically relevant venous air embolism during surgery performed in the semisitting position. METHODS: A protocol for preoperative evaluation and intraoperative monitoring was developed and applied in 187 consecutive patients who underwent surgery in the semisitting position between 1999 and 2004. The protocol included preoperative transesophageal echocardiography examination (TEE), intraoperative TEE monitoring, catheterization of the right atrium and a combination of fluid input, positive end expiratory pressure, and standardized positioning aiming at a positive pressure in the transverse and sigmoid sinuses. Data were collected retrospectively from the charts and intraoperative anesthesiological protocols of the patients for the incidence of clinically relevant air embolism (i.e., TEE-diagnosed air embolism plus a decrease in end tidal CO2 or hemodynamic changes) and other complications related to the semisitting position. RESULTS: Three cases (1.6%) of relevant venous air embolism occurred in 187 patients. Only 1 case (0.5%) was hemodynamically relevant, with temporary arterial blood pressure decrease and heart rate increase. Pneumatocephalus leading to lethargy was a frequent postoperative finding, which resolved spontaneously in all except 1 patient with epileptic seizure and oculomotor nerve palsy attributable to space-occupying subdurally trapped air, which had to be treated surgically. There was no permanent morbidity or mortality related to the semisitting position. CONCLUSION: Fear of massive venous air embolism is one reason for dramatic decline in the use of the semisitting position in neurosurgical practice. We found that strict adherence to a standardized protocol using TEE monitoring before and during surgery; exclusion of patients with patent foramen ovale; and a combination of positive end expiratory pressure, fluid input, and a standardized position aiming a positive pressure in the transverse and sigmoid sinuses helped to greatly minimize this complication to a rate of 0.5% for hemodynamically relevant events.

In search of optimal compression therapy for venous leg ulcers: a meta-analysis of studies comparing diverse [corrected] bandages with specifically designed stockings

OBJECTIVE: In search of an optimal compression therapy for venous leg ulcers, a systematic review and meta-analysis was performed of randomized controlled trials (RCT) comparing compression systems based on stockings (MCS) with divers bandages. METHODS: RCT were retrieved from six sources and reviewed independently. The primary endpoint, completion of healing within a defined time frame, and the secondary endpoints, time to healing, and pain were entered into a meta-analysis using the tools of the Cochrane Collaboration. Additional subjective endpoints were summarized. RESULTS: Eight RCT (published 1985-2008) fulfilled the predefined criteria. Data presentation was adequate and showed moderate heterogeneity. The studies included 692 patients (21-178/study, mean age 61 years, 56% women). Analyzed were 688 ulcerated legs, present for 1 week to 9 years, sizing 1 to 210 cm(2). The observation period ranged from 12 to 78 weeks. Patient and ulcer characteristics were evenly distributed in three studies, favored the stocking groups in four, and the bandage group in one. Data on the pressure exerted by stockings and bandages were reported in seven and two studies, amounting to 31-56 and 27-49 mm Hg, respectively. The proportion of ulcers healed was greater with stockings than with bandages (62.7% vs 46.6%; P < .00001). The average time to healing (seven studies, 535 patients) was 3 weeks shorter with stockings (P = .0002). In no study performed bandages better than MCS. Pain was assessed in three studies (219 patients) revealing an important advantage of stockings (P < .0001). Other subjective parameters and issues of nursing revealed an advantage of MCS as well. CONCLUSIONS: Leg compression with stockings is clearly better than compression with bandages, has a positive impact on pain, and is easier to use.

Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial

INTRODUCTION: It is unclear to which level mean arterial blood pressure (MAP) should be increased during septic shock in order to improve outcome. In this study we investigated the association between MAP values of 70 mmHg or higher, vasopressor load, 28-day mortality and disease-related events in septic shock. METHODS: This is a post hoc analysis of data of the control group of a multicenter trial and includes 290 septic shock patients in whom a mean MAP > or = 70 mmHg could be maintained during shock. Demographic and clinical data, MAP, vasopressor requirements during the shock period, disease-related events and 28-day mortality were documented. Logistic regression models adjusted for the geographic region of the study center, age, presence of chronic arterial hypertension, simplified acute physiology score (SAPS) II and the mean vasopressor load during the shock period was calculated to investigate the association between MAP or MAP quartiles > or = 70 mmHg and mortality or the frequency and occurrence of disease-related events. RESULTS: There was no association between MAP or MAP quartiles and mortality or the occurrence of disease-related events. These associations were not influenced by age or pre-existent arterial hypertension (all P > 0.05). The mean vasopressor load was associated with mortality (relative risk (RR), 1.83; confidence interval (CI) 95%, 1.4-2.38; P < 0.001), the number of disease-related events (P < 0.001) and the occurrence of acute circulatory failure (RR, 1.64; CI 95%, 1.28-2.11; P < 0.001), metabolic acidosis (RR, 1.79; CI 95%, 1.38-2.32; P < 0.001), renal failure (RR, 1.49; CI 95%, 1.17-1.89; P = 0.001) and thrombocytopenia (RR, 1.33; CI 95%, 1.06-1.68; P = 0.01). CONCLUSIONS: MAP levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. Elevating MAP >70 mmHg by augmenting vasopressor dosages may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.

The prevalence of widespread central hypersensitivity in chronic pain patients

BACKGROUND Chronic pain is associated with generalized hypersensitivity and impaired endogenous pain modulation (conditioned pain modulation; CPM). Despite extensive research, their prevalence in chronic pain patients is unknown. This study investigated the prevalence and potential determinants of widespread central hypersensitivity and described the distribution of CPM in chronic pain patients. METHODS We examined 464 consecutive chronic pain patients for generalized hypersensitivity and CPM using pressure algometry at the second toe and cold pressor test. Potential determinants of generalized central hypersensitivity were studied using uni- and multivariate regression analyses. Prevalence of generalized central hypersensitivity was calculated for the 5th, 10th and 25th percentile of normative values for pressure algometry obtained by a previous large study on healthy volunteers. CPM was addressed on a descriptive basis, since normative values are not available. RESULTS Depending on the percentile of normative values considered, generalized central hypersensitivity affected 17.5-35.3% of patients. 23.7% of patients showed no increase in pressure pain threshold after cold pressor test. Generalized central hypersensitivity was more frequent and CPM less effective in women than in men. Unclearly classifiable pain syndromes showed higher frequencies of generalized central hypersensitivity than other pain syndromes. CONCLUSIONS Although prevalent in chronic pain, generalized central hypersensitivity is not present in every patient. An individual assessment is therefore required in order to detect altered pain processing. The broad basic knowledge about central hypersensitivity now needs to be translated into concrete clinical consequences, so that patients can be offered an individually tailored mechanism-based treatment.

Design and establishment of a biobank in a multicenter prospective cohort study of elderly patients with venous thromboembolism (SWITCO65+)

In the field of thrombosis and haemostasis, many preanalytical variables influence the results of coagulation assays and measures to limit potential results variations should be taken. To our knowledge, no paper describing the development and maintenance of a haemostasis biobank has been previously published. Our description of the biobank of the Swiss cohort of elderly patients with venous thromboembolism (SWITCO65+) is intended to facilitate the set-up of other biobanks in the field of thrombosis and haemostasis. SWITCO65+ is a multicentre cohort that prospectively enrolled consecutive patients aged ≥65 years with venous thromboembolism at nine Swiss hospitals from 09/2009 to 03/2012. Patients will be followed up until December 2013. The cohort includes a biobank with biological material from each participant taken at baseline and after 12 months of follow-up. Whole blood from all participants is assayed with a standard haematology panel, for which fresh samples are required. Two buffy coat vials, one PAXgene Blood RNA System tube and one EDTA-whole blood sample are also collected at baseline for RNA/DNA extraction. Blood samples are processed and vialed within 1 h of collection and transported in batches to a central laboratory where they are stored in ultra-low temperature archives. All analyses of the same type are performed in the same laboratory in batches. Using multiple core laboratories increased the speed of sample analyses and reduced storage time. After recruiting, processing and analyzing the blood of more than 1,000 patients, we determined that the adopted methods and technologies were fit-for-purpose and robust.

Identification of erosional mechanisms during past glaciations based on a bedrock surface model of the central European Alps

The bedrock topography beneath the Quaternary cover provides an important archive for the identification of erosional processes during past glaciations. Here, we combined stratigraphic investigations of more than 40,000 boreholes with published data to generate a bedrock topography model for the entire plateau north of the Swiss Alps including the valleys within the mountain belt. We compared the bedrock map with data about the pattern of the erosional resistance of Alpine rocks to identify the controls of the lithologic architecture on the location of overdeepenings. We additionally used the bedrock topography map as a basis to calculate the erosional potential of the Alpine glaciers, which was related to the thickness of the LGM ice. We used these calculations to interpret how glaciers, with support by subglacial meltwater under pressure, might have shaped the bedrock topography of the Alps. We found that the erosional resistance of the bedrock lithology mainly explains where overdeepenings in the Alpine valleys and the plateau occur. In particular, in the Alpine valleys, the locations of overdeepenings largely overlap with areas where the underlying bedrock has a low erosional resistance, or where it was shattered by faults. We also found that the assignment of two end-member scenarios of erosion, related to glacial abrasion/plucking in the Alpine valleys, and dissection by subglacial meltwater in the plateau, may be adequate to explain the pattern of overdeepenings in the Alpine realm. This most likely points to the topographic controls on glacial scouring. In the Alps, the flow of LGM and previous glaciers were constrained by valley flanks, while ice flow was mostly divergent on the plateau where valley borders are absent. We suggest that these differences in landscape conditioning might have contributed to the contrasts in the formation of overdeepenings in the Alpine valleys and the plateau.

Neotethys closure history of Anatolia: insights from 40Ar–39Ar geochronology and P–T estimation in high pressure metasedimentary rocks

The multiple high-pressure (HP), low-temperature (LT) metamorphic units of Western and Central Anatolia offer a great opportunity to investigate the subduction- and continental accretion-related evolution of the eastern limb of the long-lived Aegean subduction system. Recent reports of the HP–LT index mineral Fe-Mg-carpholite in three metasedimentary units of the Gondwana-derived Anatolide–Tauride continental block (namely the Afyon Zone, the Ören Unit and the southern Menderes Massif) suggest a more complicated scenario than the single-continental accretion model generally put forward in previous studies. This study presents the first isotopic dates (white mica 40Ar–39Ar geochronology), and where possible are combined with P–T estimates (chlorite thermometry, phengite barometry, multi-equilibrium thermobarometry), on carpholite-bearing rocks from these three HP–LT metasedimentary units. It is shown that, in the Afyon Zone, carpholite-bearing assemblages were retrogressed through greenschist-facies conditions at c. 67–62 Ma. Early retrograde stages in the Ören Unit are dated to 63–59 Ma. In the Kurudere–Nebiler Unit (HP Mesozoic cover of the southern Menderes Massif), HP retrograde stages are dated to c. 45 Ma, and post-collisional cooling to c. 26 Ma. These new results support that the Ören Unit represents the westernmost continuation of the Afyon Zone, whereas the Kurudere–Nebiler Unit correlates with the Cycladic Blueschist Unit of the Aegean Domain. In Western Anatolia, three successive HP–LT metamorphic belts thus formed: the northernmost Tavşanlı Zone (c. 88–82 Ma), the Ören–Afyon Zone (between 70 and 65 Ma), and the Kurudere–Nebiler Unit (c. 52–45 Ma). The southward younging trend of the HP–LT metamorphism from the upper and internal to the deeper and more external structural units, as in the Aegean Domain, points to the persistence of subduction in Western Anatolia between 93–90 and c. 35 Ma. After the accretion of the Menderes–Tauride terrane, in Eocene times, subduction stopped, leading to continental collision and associated Barrovian-type metamorphism. Because, by contrast, the Aegean subduction did remain active due to slab roll-back and trench migration, the eastern limb (below Southwestern Anatolia) of the Hellenic slab was dramatically curved and consequently teared. It therefore is suggested that the possibility for subduction to continue after the accretion of buoyant (e.g. continental) terranes probably depends much on palaeogeography.

Declining pine growth in Central Spain coincides with increasing diurnal temperature range since the 1970s

Growing evidence suggests environmental change to be most severe across the semi-arid subtropics, with past, present and projected drying of the Mediterranean Basin posing a key multidisciplinary challenge. Consideration of a single climatic factor, however, often fails to explain spatiotemporal growth dynamics of drought-prone ecosystems. Here, we present annually resolved and absolutely dated ring width measurements of 871 Scots pines (Pinus sylvestris) from 18 individual plot sites in the Central Spanish Pinar Grande forest reserve. Although comprising tree ages from 6 to 175 years, this network correlates surprisingly well with the inverse May–July diurnal temperature range (r = 0.84; p < 0.00011956–2011). Ring width extremes were triggered by pressure anomalies of the North Atlantic Oscillation, and the long-term growth decline coincided with Iberian-wide drying since the mid-1970s. Climate model simulations not only confirm this negative trend over the last decades but also project drought to continuously increase over the 21st century. Associated ecological effects and socio-economic consequences should be considered to improve adaptation strategies of agricultural and forest management, as well as biodiversity conservation and ecosystem service.

Evaluation of androgenicity, abdominal adiposity, blood pressure and types of ovulatory patterns in a sample of women with menstrual irregularities

Objective: To determine the prevalence of and the relationships between the degree and source of hyperandrogenemia, ovulatory patterns and cardiovascular disease risk indicators (blood pressure, indices or amount of obesity and fat distribution) in women with menstrual irregularities seen at endocrinologists' clinic. Design: A cross-sectional study design. Participants: A sample of 159 women with menstrual irregularities, aged 15-44, seen at endocrinologists' clinic. Main Outcome Measures: androgen levels, body mass index (BMI), waist-hip ratio (WHR), systolic and diastolic blood pressure (SBP & DBP), source of androgens, ovulatory activity. Results: The prevalence of hyperandrogenemia was 54.7% in this study sample. As expected, women with acne or hirsutism had an odds ratio 12.5 (95%CI = 5.2-25.5) times and 36 (95%CI = 12.9-99.5) times more likely to have hyperandrogenemia than those without acne or hirsutism. The main findings of this study were the following: Hyperandrogenemic women were more likely to have oligomenorrheic cycles (OR = 3.8, 95%CI = 1.5-9.9), anovulatory cycles (OR = 6.6, 95%CI = 2.8-15.4), general obesity (BMI $\ge$ 27) (OR = 6.8, 95%CI = 2.2-27.2) and central obesity (WHR $\ge$ 127) (OR = 14.5, 95%CI = 6.1-38.7) than euandrogenemic women. Hyperandrogenemic women with non-suppressible androgens had a higher mean BMI (29.3 $\pm$ 8.9) than those with suppressible androgens (27.9 $\pm$ 7.9); the converse was true for abdominal adiposity (WHR). Hyperandrogenemic women had a 2.4 odds ratio (95%CI = 1.0-6.2) for an elevated SBP and a 2.7 odds ratio (95%CI = 0.8-8.8) for elevated DBP. When age differences were accounted for, this relationship was strengthened and further strengthened when sources of androgens were controlled. When the differences in BMI were controlled, the odds ratio for elevated SBP in hyperandrogenemic women increased to 8.8 (95%CI = 1.1-69.9). When the age, the source of androgens, the amount of obesity and the type of obesity were controlled, hyperandrogenemic women had 13.5 (95%CI = 1.1-158.9) odds ratio for elevated SBP. Conclusions: In this study population, the presence of menstrual irregularities are highly predictive for the presence of elevated androgens. Women with elevated androgens have a high risk for obesity, more specifically for central obesity. The androgenemic status is an independent predictor of blood pressure elevation. It is probable that in the general population, the presence of menstrual irregularities are predictive of hyperandrogenemia. There is a great need for a population study of the prevalence of hyperandrogenemia and for longitudinal studies in hyperandrogenemic women (adrenarche to menopause) to investigate the evolution of these relationships. ^