Acetaminophen increases blood pressure in patients with coronary artery disease.

BACKGROUND: Because traditional nonsteroidal antiinflammatory drugs are associated with increased risk for acute cardiovascular events, current guidelines recommend acetaminophen as the first-line analgesic of choice on the assumption of its greater cardiovascular safety. Data from randomized clinical trials prospectively addressing cardiovascular safety of acetaminophen, however, are still lacking, particularly in patients at increased cardiovascular risk. Hence, the aim of this study was to evaluate the safety of acetaminophen in patients with coronary artery disease. METHODS AND RESULTS: The 33 patients with coronary artery disease included in this randomized, double-blind, placebo-controlled, crossover study received acetaminophen (1 g TID) on top of standard cardiovascular therapy for 2 weeks. Ambulatory blood pressure, heart rate, endothelium-dependent and -independent vasodilatation, platelet function, endothelial progenitor cells, markers of the renin-angiotensin system, inflammation, and oxidative stress were determined at baseline and after each treatment period. Treatment with acetaminophen resulted in a significant increase in mean systolic (from 122.4±11.9 to 125.3±12.0 mm Hg P=0.02 versus placebo) and diastolic (from 73.2±6.9 to 75.4±7.9 mm Hg P=0.02 versus placebo) ambulatory blood pressures. On the other hand, heart rate, endothelial function, early endothelial progenitor cells, and platelet function did not change. CONCLUSIONS: This study demonstrates for the first time that acetaminophen induces a significant increase in ambulatory blood pressure in patients with coronary artery disease. Thus, the use of acetaminophen should be evaluated as rigorously as traditional nonsteroidal antiinflammatory drugs and cyclooxygenase-2 inhibitors, particularly in patients at increased cardiovascular risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00534651.

Risk of cardiovascular events and blood pressure control in hypertensive HIV-infected patients: Swiss HIV Cohort Study (SHCS).

BACKGROUND: Prevalence of hypertension in HIV infection is high, and information on blood pressure control in HIV-infected individuals is insufficient. We modeled blood pressure over time and the risk of cardiovascular events in hypertensive HIV-infected individuals. METHODS: All patients from the Swiss HIV Cohort Study with confirmed hypertension (systolic or diastolic blood pressure above 139 or 89 mm Hg on 2 consecutive visits and presence of at least 1 additional cardiovascular risk factor) between April 1, 2000 and March 31, 2011 were included. Patients with previous cardiovascular events, already on antihypertensive drugs, and pregnant women were excluded. Change in blood pressure over time was modeled using linear mixed models with repeated measurement. RESULTS: Hypertension was diagnosed in 2595 of 10,361 eligible patients. Of those, 869 initiated antihypertensive treatment. For patients treated for hypertension, we found a mean (95% confidence interval) decrease in systolic and diastolic blood pressure of -0.82 (-1.06 to -0.58) mm Hg and -0.89 (-1.05 to -0.73) mm Hg/yr, respectively. Factors associated with a decline in systolic blood pressure were baseline blood pressure, presence of chronic kidney disease, cardiovascular events, and the typical risk factors for cardiovascular disease. In patients with hypertension, increase in systolic blood pressure [(hazard ratio 1.18 (1.06 to 1.32) per 10 mm Hg increase], total cholesterol, smoking, age, and cumulative exposure to protease inhibitor-based and triple nucleoside regimens were associated with cardiovascular events. CONCLUSIONS: Insufficient control of hypertension was associated with increased risk of cardiovascular events indicating the need for improved management of hypertension in HIV-infected individuals.

Evaluation of arterial compliance-pressure curves. Effect of antihypertensive drugs.

A new high-precision ultrasonic device was developed to determine noninvasively arterial compliance as a function of blood pressure. Because of the nonlinear elastic properties of arterial walls, measurements of compliance can be appropriately compared only if obtained over a range of pressures. This apparatus was used to evaluate in a double-blind, parallel fashion the effect of three different antihypertensive drugs and of a placebo on radial artery compliance. Thirty-two normotensive volunteers were randomly allocated to an 8-day, once-a-day oral treatment with either a placebo, 100 mg atenolol, 20 mg nitrendipine, or 20 mg lisinopril. Blood pressure, heart rate, radial artery diameter, and arterial compliance were measured immediately before as well as 6 hours after dosing on the first and last days of the study. On the eighth day of administration, within 6 hours after dosing, lisinopril induced an acute increase in radial artery diameter, from 2.99 +/- 0.06 to 3.28 +/- 0.09 mm (mean +/- SEM, p less than 0.01). The compliance-pressure curve was shifted upward on day 1 (p less than 0.01) as well as on day 8 (p less than 0.05). None of the other drugs induced any significant modification of these parameters. Arterial compliance has a strong nonlinear dependency on intra-arterial pressure and therefore has to be defined as a function of pressure. Antihypertensive drugs acting by different mechanisms may have different effects on the mechanical properties of large arteries.

Discordant prevalence of hypertension using two different automated blood pressure measurement devices: a population-based study in Dar es Salaam (Tanzania).

OBJECTIVE: The estimation of blood pressure is dependent on the accuracy of the measurement devices. We compared blood pressure readings obtained with an automated oscillometric arm-cuff device and with an automated oscillometric wrist-cuff device and then assessed the prevalence of defined blood pressure categories. METHODS: Within a population-based survey in Dar es Salaam (Tanzania), we selected all participants with a blood pressure >/= 160/95 mmHg (n=653) and a random sample of participants with blood pressure <160/95 mmHg (n=662), based on the first blood pressure reading. Blood pressure was reassessed 2 years later for 464 and 410 of the participants, respectively. In these 874 subjects, we compared the prevalence of blood pressure categories as estimated with each device. RESULTS: Overall, the wrist device gave higher blood pressure readings than the arm device (difference in systolic/diastolic blood pressure: 6.3 +/- 17.3/3.7 +/- 11.8 mmHg, P<0.001). However, the arm device tended to give lower readings than the wrist device for high blood pressure values. The prevalence of blood pressure categories differed substantially depending on which device was used, 29% and 14% for blood pressure <120/80 mmHg (arm device versus wrist device, respectively), 30% and 33% for blood pressure 120-139/80-89 mmHg, 17% and 26% for blood pressure 140-159/90-99 mmHg, 12% and 13% for blood pressure 160-179/100-109 mmHg and 13% and 14% for blood pressure >/= 180/110 mmHg. CONCLUSIONS: A large discrepancy in the estimated prevalence of blood pressure categories was observed using two different automatic measurement devices. This emphasizes that prevalence estimates based on automatic devices should be considered with caution.

Pulmonary-artery pressure and exhaled nitric oxide in Bolivian and Caucasian high altitude dwellers.

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Association between white-coat effect and blunted dipping of nocturnal blood pressure.

In this study, we assessed whether the white-coat effect (difference between office and daytime blood pressure (BP)) is associated with nondipping (absence of BP decrease at night). Data were available in 371 individuals of African descent from 74 families selected from a population-based hypertension register in the Seychelles Islands and in 295 Caucasian individuals randomly selected from a population-based study in Switzerland. We used standard multiple linear regression in the Swiss data and generalized estimating equations to account for familial correlations in the Seychelles data. The prevalence of systolic and diastolic nondipping (<10% nocturnal BP decrease) and white-coat hypertension (WCH) was respectively 51, 46, and 4% in blacks and 33, 37, and 7% in whites. When white coat effect and nocturnal dipping were taken as continuous variables (mm Hg), systolic (SBP) and diastolic BP (DBP) dipping were associated inversely and independently with white-coat effect (P < 0.05) in both populations. Analogously, the difference between office and daytime heart rate was inversely associated with the difference between daytime and night-time heart rate in the two populations. These results did not change after adjustment for potential confounders. The white-coat effect is associated with BP nondipping. The similar associations between office-daytime values and daytime-night-time values for both BP and heart rate suggest that the sympathetic nervous system might play a role. Our findings also further stress the interest, for clinicians, of assessing the presence of a white-coat effect as a means to further identify patients at increased cardiovascular risk and guide treatment accordingly.

Brachial or wrist blood pressure in obese patients: which is the best?

OBJECTIVE: Blood pressure (BP) measured in obese patients with a large arm circumference using a cuff of standard width may be overestimated. METHODS: We compared in this study the BP readings obtained with oscillometric devices at the left arm (OMRON HEM 705-CP) and the left wrist (OMRON R6) (Omron Medizintechnik, Mannheim, Germany) in lean (n=15) and obese (n=11) patients. RESULTS: No difference was found in diastolic BP between the two groups, nor between the arm and the wrist. Systolic BP measured at the arm was, however, significantly lower in obese (99+/-9 mmHg, mean+/-SD) than in lean (107+/-14 mmHg; P<0.001) patients, whereas systolic BP determined at the wrist averaged 106 mmHg in both groups. CONCLUSION: The use of validated wrist BP measuring devices appears therefore particularly appealing in obese individuals with a large arm circumference

Pore size distribution in soils irrigated with sodic water and wastewater

Soil porosity, especially pore size distribution, is an important controlling factor for soil infiltration, hydraulic conductivity, and water retention. This study aimed to verify the effect of secondary-treated domestic wastewater (STW) on the porosity of a sandy loam Oxisol in the city of Lins, state of São Paulo, Brazil. The two-year experiment was divided into three plots: soil cultivated with corn and sunflower and irrigated with STW, soil cultivated and irrigated with sodic groundwater, and non-irrigated and non-cultivated soil (control). At the end of the experiment, undisturbed core samples were sampled from 0 to 2.0 m (8 depths). The water retention curves were obtained by tension plates and Richard's pressure plate apparatus, and the pore size distribution inferred from the retention curves. It was found that irrigation with treated wastewater and treated groundwater led to a decrease in microporosity (V MI), defined as the pore class ranging from 0.2 to 50 μm diameter. On the other hand, a significant increase in cryptoporosity (V CRI) (< 0.2 μm) was identified throughout the soil profile. The presence of Na+ in both waters confirmed the role of this ion on pore size distribution and soil moisture (higher water retention).

Respiratory nitric oxide and pulmonary artery pressure in children of aymara and European ancestry at high altitude.

Invasive studies suggest that healthy children living at high altitude display pulmonary hypertension, but the data to support this assumption are sparse. Nitric oxide (NO) synthesized by the respiratory epithelium regulates pulmonary artery pressure, and its synthesis was reported to be increased in Aymara high-altitude dwellers. We hypothesized that pulmonary artery pressure will be lower in Aymara children than in children of European ancestry at high altitude, and that this will be related to increased respiratory NO. We therefore compared pulmonary artery pressure and exhaled NO (a marker of respiratory epithelial NO synthesis) between large groups of healthy children of Aymara (n = 200; mean +/- SD age, 9.5 +/- 3.6 years) and European ancestry (n = 77) living at high altitude (3,600 to 4,000 m). We also studied a group of European children (n = 29) living at low altitude. The systolic right ventricular to right atrial pressure gradient in the Aymara children was normal, even though significantly higher than the gradient measured in European children at low altitude (22.5 +/- 6.1 mm Hg vs 17.7 +/- 3.1 mm Hg, p < 0.001). In children of European ancestry studied at high altitude, the pressure gradient was 33% higher than in the Aymara children (30.0 +/- 5.3 mm Hg vs 22.5 +/- 6.1 mm Hg, p < 0.0001). In contrast to what was expected, exhaled NO tended to be lower in Aymara children than in European children living at the same altitude (12.4 +/- 8.8 parts per billion [ppb] vs 16.1 +/- 11.1 ppb, p = 0.06) and was not related to pulmonary artery pressure in either group. Aymara children are protected from hypoxic pulmonary hypertension at high altitude. This protection does not appear to be related to increased respiratory NO synthesis.

Nutrient relations during an eucalyptus cycle at different population densities

To synchronize nutrient availability with the requirements of eucalyptus during a cultivation cycle, the nutrient flow of this system must be well understood. Essential, for example, is information about nutrient dynamics in eucalyptus plantations throughout a cultivation cycle, as well as impacts on soil nutrient reserves caused by the accumulation and subsequent export of nutrients via biomass. It is also important to quantify the effect of some management practices, such as tree population density (PD) on these fluxes. Some nutrient relations in an experiment with Eucalyptus grandis, grown at different PDs in Santa Barbara, state of Minas Gerais, Brazil, were evaluated for one cultivation cycle. At forest ages of 0.25, 2.5, 4.5, and 6.75 years, evaluations were carried out in the stands at seven different PDs (between 500 and 5,000 trees ha-1) which consisted in chemical analyses of plant tissue sampled from components of the aboveground parts of the tree, from the forest floor and the litterfall. Nutrient contents and allocations of the different biomass components were estimated. In general, there were only small and statistically insignificant effects of PD on the nutrient concentration in trees. With increasing forest age, P, K, Ca and Mg concentrations were reduced in the aboveground components and the forest floor. The magnitud of biochemical nutrient cycling followed the sequence: P > K > N > Mg. At the end of the cycle, the quantities of N, P, Ca and Mg immobilized in the forest floor were higher than in the other components.

Pulmonary-artery pressure and exhaled nitric oxide in bolivian and caucasian high altitude dwellers

Rapport de synthèse : Plusieurs études suggèrent que les populations vivant en haute altitude sont mieux protégées contre l'hypertension pulmonaire hypoxique que celles originaires de la plaine. Cependant, les mécanismes sous jacents ne sont pas bien compris. Chez les Tibétains, la synthèse augmentée par le système respiratoire de monoxyde d'azote (NO) atténue l'hypertension pulmonaire hypoxique. Il a été spéculé que ce mécanisme pourrait représenter un mode généralisé d'adaptation à la haute altitude, mais il n'existe pas de preuve directe qui consume cette hypothèse. Nous avons donc mesuré la pression artérielle pulmonaire (par échocardiographie Doppler) ainsi que la concentration du NO dans l'air exhalé chez 34 Boliviens en bonne santé, nés et ayant toujours vécus en haute altitude (3600 m) et chez 34 Caucasiens apparentés pour l'âge et le sexe, nés en basse altitude mais vivant depuis de nombreuses années à cette même haute altitude (3600 mètres). La pression artérielle pulmonaire (24.3±5.9 vs. 24.7±4.9 mm Hg) et le NO exhalé (19.2±7.2 vs. 22.5±9.5 ppb) étaient similaires chez les Boliviens et les Caucasiens. Il n'y avait aucune corrélation entre la pression artérielle pulmonaire et le NO respiratoire dans les deux groupes. Ces résultats ne fournissent donc aucune évidence que les Boliviens nés en haute altitude sont mieux protégés contre l'hypertension pulmonaire hypoxique que les Caucasiens nés à basse altitude. Cela suggère que l'atténuation de l'hypertension pulmonaire par une synthèse accrue de NO respiratoire ne représente pas un mode universel d'adaptation des populations à la haute altitude. Abstract : There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler echocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean ± SD systolic right ventricular to right arterial pressure gradient (24.3 ± 5.9 vs. 24.7 ± 4.9 mmHg) and exhaled NO (19.2 ± 7.2 vs. 22.5 ± 9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between ,pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Cardiorenal end points in a trial of aliskiren for type 2 diabetes.

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).

Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults.

Serum uric acid (SUA) concentration is independently associated with blood pressure (BP) in adults. We examined this association in young adults at an age where anti-hypertension treatment, other potential confounding factors and co-morbidity are unlikely to occur. We assessed BP, anthropometric variables including weight, height, waist circumference (WC), body fat percent (using bioimpedance), lifestyle behaviors, SUA and blood lipids in 549 participants aged 19-20 years from a population-based cohort study (Seychelles Child Development Study). Mean (s.d.) SUA was higher in males than females, 0.33 (0.08) and 0.24 (0.07) mmol l(-1), respectively. Body mass index (BMI) was higher in females than males but BP was markedly higher in males than in females. SUA was associated with both systolic and diastolic BP. However, the magnitude of the linear regression coefficients relating BP and SUA decreased by up to 50% upon adjustment for BMI, WC or body fat percent. The association between SUA and BP was not altered upon further adjustment for alcohol intake, smoking, triglycerides or renal function. In fully adjusted models, SUA remained associated with BP (P<0.05) in females. In conclusion, adiposity substantially decreased the association between SUA and BP in young adults, and BP was independently associated with SUA in females. These findings suggest a role of adiposity in the link between hyperuricemia and hypertension.

The effect of continuous positive airway pressure on total cerebral blood flow in healthy awake volunteers.

PURPOSE: Continuous positive airway pressure (CPAP) is the gold standard treatment for obstructive sleep apnea. However, the physiologic impact of CPAP on cerebral blood flow (CBF) is not well established. Ultrasound can be used to estimate CBF, but there is no widespread accepted protocol. We studied the physiologic influence of CPAP on CBF using a method integrating arterial diameter and flow velocity (FV) measurements obtained for each vessel supplying blood to the brain. METHODS: FV and lumen diameter of the left and right internal carotid, vertebral, and middle cerebral arteries were measured using duplex Doppler ultrasound with and without CPAP at 15 cm H(2)O, applied in a random order. Transcutaneous carbon dioxide (PtcCO(2)), heart rate (HR), blood pressure (BP), and oxygen saturation were monitored. Results were compared with a theoretical prediction of CBF change based on the effect of partial pressure of carbon dioxide on CBF. RESULTS: Data were obtained from 23 healthy volunteers (mean ± SD; 12 male, age 25.1 ± 2.6 years, body mass index 21.8 ± 2.0 kg/m(2)). The mean experimental and theoretical CBF decrease under CPAP was 12.5 % (p < 0.001) and 11.9 % (p < 0.001), respectively. The difference between experimental and theoretical CBF reduction was not statistically significant (3.84 ± 79 ml/min, p = 0.40). There was a significant reduction in PtcCO(2) with CPAP (p = <0.001) and a significant increase in mean BP (p = 0.0017). No significant change was observed in SaO(2) (p = 0.21) and HR (p = 0.62). CONCLUSION: Duplex Doppler ultrasound measurements of arterial diameter and FV allow for a noninvasive bedside estimation of CBF. CPAP at 15 cm H(2)O significantly decreased CBF in healthy awake volunteers. This effect appeared to be mediated predominately through the hypocapnic vasoconstriction coinciding with PCO(2) level reduction. The results suggest that CPAP should be used cautiously in patients with unstable cerebral hemodynamics.

A Mendelian randomization approach to assess the causal relationship of gamma-glutamyl transferase with blood pressure and insulin

Background: Elevated levels of g-glutamyl transferase (GGT) have been associated with subsequent risk of elevated blood pressure (BP), hypertension and diabetes. However, the causality of these relationships has not been addressed. Mendelian randomization refers to the random allocation of alleles at the time of gamete formation. Such allocation is expected to be independent of any behavioural and environmental factors (known or unknown), allowing the analysis of largely unconfounded risk associations that are not due to reverse causation. Methods: We performed a cross-sectional analysis among 4361 participants to the population based CoLaus study. Associations of sex-specific GGT quartiles with systolic BP, diastolic BP and insulin levels were assessed using multivariable linear regression analyses. The rs2017869 GGT1 variant, which explained 1.6% of the variance in GGT levels, was used as an instrument to perform a Mendelian randomization analysis. Results: Median age of the study population was 53 years. After age and sex adjustment, GGT quartiles were strongly associated with systolic and diastolic BP (all p for linear trend <0.0001). After multivariable adjustment, these relationships were significantly attenuated, but remained significant for systolic (b(95%CI)¼1.30 (0.32;2.03), p¼0.007) and diastolic BP (b (95%CI)¼0.57 (0.02;1.13), p¼0.04). Using Mendelian randomization, we observed no positive association of GGT with either systolic BP (b (95%CI)¼-5.68 (-11.51-0.16), p¼0.06) or diastolic BP (b (95%CI)¼ -2.24 (-5.98;1.49) p¼0.24). The association of GGT with insulin was also attenuated after multivariable adjustment. Nevertheless, a strong linear trend persisted in the fully adjusted model (b (95%CI)¼0.07 (0.04;0.09), p<0.0001). Using Mendelian randomization, we observed a similar positive association of GGT with insulin (b (95%CI)¼0.19 (0.01-0.37), p¼0.04). Conclusion: In this study, we found evidence for a direct causal relationship between GGT and insulin, suggesting that oxidative stress may be causally implicated in the pathogenesis of type 2 diabetes mellitus.