Electronic search programs are effective in identifying patients with minimal trauma fractures.

We assessed two electronic search tools that screen medical records for documented fractures. Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. A hybrid tool combining the methodology of both tools is likely to improve the identification of those with osteoporosis. PURPOSE: Most patients who suffer a minimal trauma fracture remain undiagnosed, placing them at high risk of refracture. Case finding can be improved by electronic search tools that screen medical records for documented fractures. Here, we assessed the efficacy of two new programs, AES and XRAIT, in identifying patients with minimal trauma fracture. METHODS: Each tool was applied to search the electronic medical record and/or radiology reports at two tertiary hospitals in Sydney, Australia, from 1 July to 31 December 2018. Samples of the extracted reports were then manually reviewed to determine the sensitivity of each program in detecting minimal trauma fractures. RESULTS: At the two centers, AES detected 872 and 1364 cases, whereas XRAIT identified 1414 and 2180 patients with fractures, respectively. The true positive rate for "any fracture" was similar for both instruments (77-88%). However, the ability to detect "minimal trauma fractures" differed between programs and centers (53-75% accuracy), with each tool identifying separate subsets of patients. Concordance between both tools was less than half of the combined total number of minimal trauma fractures (43-45%). Considering the total number of minimal trauma fractures detected by both tools combined, AES correctly identified 52-55% of cases while XRAIT identified 88-93% of cases. CONCLUSION: Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. Hybrid tools combining the methodology of XRAIT and AES are likely to improve the identification of patients who require investigation and treatment for osteoporosis.

The humanistic burden associated with caring for patients with advanced non-small cell lung cancer (NSCLC) in three European countries-a real-world survey of caregivers.

PURPOSE: This study evaluated the humanistic burden on caregivers of patients with advanced non-small cell lung cancer (aNSCLC) as the disease progresses. METHODS: Data were drawn from a cross-sectional study of patients with aNSCLC and their caregivers conducted in France, Germany, and Italy between 2015 and 2016. Data were collected by medical chart review and patient and caregiver questionnaires. The EuroQol five-dimension three-level (EQ-5D-3L) was used to evaluate patient and caregiver health status. Caregivers also completed the Work Productivity and Activity Impairment (WPAI) questionnaire and Zarit Burden Interview (ZBI). RESULTS: The population for the analysis consisted of 427 caregivers (mean age 53.5 years; 72.6% female; 54.9% spouse; 36.2% in full-time employment) and 427 matched patients (mean age 66.2 years; 68.6% male). Most (69.5%) patients were receiving first-line therapy for advanced disease. Patients' caregivers provided a mean of 29.5 h of support per week. Significant differences in EQ-5D-3L scores were observed between caregivers of patients receiving first and later lines of therapy in France (0.87 vs. 0.78; p = 0.0055). Among employed caregivers, overall work impairment was considerable and ranged from 21.1% in Germany to 30.4% in France and 29.7% in Italy. Caregivers of patients receiving later lines of therapy in France rated their own health status as significantly worse than did those caring for patients receiving first-line therapy (82.7 vs. 72.9; p = 0.0039). CONCLUSIONS: Informal caregivers provided the majority of support for patients with advanced NSCLC and their caregiving activities impose a significant humanistic burden.

Role of extrapulmonary conversion in mediating the systemic pressor activity of angiotensin I.

The effect of antibodies against angiotensin II (AII) on systemic pressor responses to intravenously injected AII and angiotensin I (AI) was studied in a group of bioassay rats. AII antibody was only 29% as effective in neutralizing AI given intravenously as it was in neutralizing AII injected by the same route. Control plasma caused no change in the relative potencies of AI and AII. In a further series of experiments, AII antibody was significantly less effective in blocking intra-arterial AI than in blocking intravenous AI. The potency of intra-arterial AI, initially less than that of intravenous AI, became nearly twice that of intravenous AI after antibody administration, a result which could not occur if AI were inactive before lung transit. Thus, AI can elicit systemic pressor activity independently of pulmonary conversion to AII. However, since the intra-arterial AI responses were abolished by an inhibitor of angiotensin-converting enzyme, the activity would appear to be mediated by peripheral conversion to AII rather than by an intrinsic action of the decapeptide. Both series of experiments suggest that the efficacy of AII antibody in abolishing the systemic pressor activity of AI is highly dependent on the site of conversion of the AI to AII. The occurrence of localized intramural conversion of AI to AII near arteriolar receptors in vivo may so minimize exposure of the liberated AII to circulating antibody as to render AII immunization an inefficient means of blocking endogenous pressor activity of the renin-angiotensin system.

Renal hypertension in rats immunized against angiotensin I and angiotensin II.

Rats, actively immunized against angiotensin I (AI) and angiotensin II (AII), were subjected to unilateral renal artery constriction to determine whether the resulting hypertension, which may still ensue in the animal immunized against AII, could be prevented by such combined immunity. Sustained immunity to both AI and AII neither changed preoperative blood pressures of the rats from those of control mock-immunized rats nor altered the incidence or severity of renal dip hypertension. Vascular hyperresponsiveness to small quantities of free angiotensin could not be invoked to explain the hypertension, for there was no significant difference between mock-immunized hypertensive animals, and those remaining normotensive, regarding pressor sensitivity to intravenous AI, AII, renin, and norepinephrine. (AI + AII)-immunized hypertensive rats required AI doses averaging 260 times greater than nonimmune hypertensives to elicit equipressor responses, and were refractory to renin, but not to norepinephrine. Thus, while previous studies have not excluded direct participation of endogenous AI in renal clip hypertension in rats, evidence from our experiments makes it extremely difficult to sustain any pressor function therein for circulating AI or AII. Our results also preclude involvement of AII produced from circulating AI by conversion within arteriolar walls, close to receptor sites, since AI immunity would block this mechanism of action.

Comparison of the effects on renin release of beta adrenergic antagonists with differing properties.

Continuous 6-h infusions of the beta adrenergic blockers d,l-propranolol or oxprenolol significantly reduced plasma renin activity (PRA) and mean blood pressure in the resting rabbit and prevented the stimulatory effects of isoproterenol on renin release and heart rate. These actions were due to blockade of beta receptors, for the inactive isomer, d-propranolol, had no effect. Despite sustained high plasma concentrations of d,l-propranolol (0.2 mug/ml) in the unstimulated animal, PRA did not fall below 36% of control values, suggesting that basal renin secretion is maintained partly by factors other than beta adrenergic mechanisms.Prindolol, another beta blocker, also abolished the effects of isoproterenol on renin and on the heart, and reduced blood pressure in the resting animal. However, prindolol increased resting PRA and heart rate, and in animals already receiving d,l-propranolol, it raised PRA and heart rate without further altering blood pressure. This suggests that the effect on PRA of prindolol was due to its intrinsic sympathomimetic activity and not hypotension-mediated mechanisms. The observation that the blood pressure-lowering effect of prindolol was associated with a rise in PRA, while another beta antagonist, H 35/25, lowered PRA but had no effect on blood pressure, indicates that the hypotensive action of beta blockers is unrelated to their effects on renin release. In both unstimulated and isoproterenol-challenged animals, only blockers possessing beta-1 receptor affinity (d,l-propranolol, oxprenolol, prindolol, practolol, and metoprolol) affected heart rate, while effects on PRA were more prominent with agents possessing beta-2 activity (d,l-propranolol, oxprenolol, prindolol, and H 35/25). Thus, the changes in PRA caused by the beta adrenergic blockers appear to be dependent upon the summation of their direct effects, antagonistic or sympathomimetic, on beta-2 adrenergic receptors regulating renin release.

Distribution of fatty acids incorporated into triacylglycerols by microsome/cytosol preparations from adipose tissue.

Microsome/cytosol preparations from adipose tissue of the mouse, pig, rat and chicken and from pig liver synthesize triacylglycerols containing a fatty acid distribution consistent with that in their respective fats. Since the incorporation of fatty acids depends on the presence of glycerol phospahte and no loss of tritium occurs during the incorporation of sn-[2-3 H]glycerol 3-phosphate into triacylglycerols, it would appear that the specific distribution is a property of the transacylases of the glycerophosphate pathway. The apparent Michaelis constant for sn-glycerol 3-phosphate, measured either by sn-glycerol 3-phosphate or palmitate incorporation, averaged 1.4-10-4 M both the mouse and pig adipose tissue enzyme systems.

Self-association of insulin. Its pH dependence and effect of plasma.

We investigated some self-association properties of monocomponent porcine insulin with a simple and novel procedure that for the first time permits the association properties of insulin to be studied in mixed protein solutions. With this semiquantitative procedure, the monomer form of insulin was separated from aggregates during centrifuge desalting on Sephadex G-25. The proportion of monomer in solutions of insulin was estimated by monitoring [125I]monoiodoinsulin recovery off the gel. The self-association properties of insulin were studied in plasma with this procedure over the concentration range of physiologically circulating levels to storage concentrations of the hormone. We estimated the equilibrium constant for the formation of dimers to be 1.5 X 10(4)/M in pooled human plasma at pH 7.4 and 37 degrees C. This estimate was indistinguishable from that obtained for insulin in a defined phosphate-albumin buffer under similar conditions. This result provides direct confirmation that insulin is not associated with a circulating serum binding protein(s) and that insulin is present predominantly as a monomer in plasma. We also used the method to investigate the self-association properties of insulin over a wide pH range. The equilibrium constant for the formation of dimers decreased only 6-fold over a 9.2 pH unit increase from pH 2 to 11.2 but almost 200-fold for the additional 1.5 pH unit increase from pH 11.2 to 12.7. We conclude that a residue of pK 12 is critical to the maintenance of the quaternary structure of insulin. We assign this role to the single B22-arginyl residue in insulin.

Effects of sodium depletion on plasma renin activity and on the urinary excretion of cyclic AMP and aldosterone in hypoparathyroid patients.

The effect of sodium depletion on plasma renin activity (PRA), urinary cyclic AMP and urinary aldosterone excretion was studied in hypoparathyroid patients whose basal urinary cylic AMP excretion (urinary cAMP) was less than 50% of that observed in normal subjects. During 7 days of sodium depletion, PRA, urinary aldosterone and urinary cAMP each rose significantly. Administration of the beta-blocker propranolol, 160 mg/day, during 5 further days of sodium depletion produced a fall in PRA and urinary cAMP, but no change in urinary aldosterone excretion. The dissociation in these effects suggests that the increase in aldosterone secretion during sodium depletion may be mediated by pathways other than the renin-angiotensin and adenyl cyclase systems. There was a high degree of correlation between PRA and urinary cAMP (P less than 0.001) during the period of sodium depletion, but not significant relationship between these parameters was found during control and propranolol phases, or in control studies in normal subjects. These findings suggest that beta-adrenergic receptors have a role in mediating the effects of sodium depletion upon renin secretion and adenyl cyclase activity.

Ketanserin and prazosin: a comparison of antihypertensive and biochemical effects.

A randomized crossover trial was conducted in 15 patients with essential hypertension to compare the actions of prazosin, a specific alpha 1-adrenoceptor blocker, and ketanserin, an antagonist at alpha 1-adrenergic and serotonin receptors. After placebo dosing for 2 weeks, active drug was given double-blind in two 4-week phases. Satisfactory control of supine blood pressure was obtained in nine of the 12 subjects who completed the prazosin phase and 11 of the 15 subjects who completed the ketanserin phase. Whether comparison was based on supine, erect, postexercise, or ambulatory values, the blood pressure responses to prazosin (2 or 4 mg/day) and ketanserin (40 or 80 mg/day) were closely similar. Neither of the drugs significantly altered supine or erect pulse rates, body weight, serum triglyceride concentrations, plasma renin activity, or urinary aldosterone excretion, and their side effect profiles were similar. The serum cholesterol concentration was lowered by prazosin but was not affected by ketanserin. However, no other features were observed that distinguished the clinical effects of ketanserin from those of prazosin.

On the combination of alpha- and beta-adrenoceptor blockade in hypertension.

A randomized double-blind crossover trial was conducted in 20 patients with moderate to severe hypertension to compare the efficacy of labetalol, which combines alpha- and beta-adrenoceptor blocking properties, with that of metoprolol alone or in combination with prazosin. After placebo for 1 wk, active medication was given in two 6-wk phases. During one phase, metoprolol (100 to 400 mg/day) was given with prazosin (2 to 4 mg/day) as an option in the last 3 wk, whereas during the other phase, labetalol (200 to 1000 mg/day) was given alone. Satisfactory control of supine blood pressure was obtained in 10 patients with metoprolol and in another four patients after the addition of prazosin. During the labetalol phase, blood pressure control was achieved in 11 of 19 patients tested. Gastrointestinal disturbances, nasal congestion, impotence, failure to ejaculate, scalp tingling, and headache were more prevalent in the labetalol phase than in the other. In four cases these occurred in patients who did not require prazosin. Supine, erect, and exercise pulse rates were reduced by both metoprolol with or without prazosin and by labetalol; the effects were less in the labetalol phase. These differences could arise from an action of labetalol on cardiac presynaptic alpha-adrenoceptors. Adjunctive use of prazosin in nonresponders to metoprolol increases the response rate and avoids unnecessary deployment of alpha-adrenoceptor blockade in patients whose blood pressure can be controlled by beta-blockade alone.

A study of the interaction between the hypotensive actions of doxazosin and enalaprilat in anaesthetized rats.

OBJECTIVE AND DESIGN: This study was designed to test whether previous work, which showed that the angiotensin converting enzyme (ACE) inhibitor enalaprilat potentiated the alpha 1-adrenoceptor antagonist activity of doxazosin in isolated rat tail arteries, could be extended to demonstrate a synergistic hypotensive effect of these two drugs. METHODS: Groups of untreated or chronically deoxycorticosterone acetate (DOCA)-salt-treated female Sprague-Dawley rats were used. Rats were anaesthetized with Inactin (barbiturate); drugs were administered via a jugular venous catheter; blood pressure was monitored via a carotid arterial catheter. RESULTS: In previously untreated rats, pretreatment with enalaprilat shifted the dose-response curve for the hypotensive effect of doxazosin to the left, indicating synergism. In rats dosed with DOCA-salt (which suppresses renin and angiotensin II production): (1) there was no synergism between the hypotensive actions of enalaprilat and doxazosin; (2) doxazosin was more potent than in untreated rats; and (3) enalaprilat lowered blood pressure, suggesting a hypotensive mechanism separate from ACE inhibition. CONCLUSION: In the absence of angiotensin II (resulting from enalaprilat administration or from chronic DOCA-salt), doxazosin had a greater hypotensive action than in the presence of angiotensin II. This is consistent with the concept that angiotensin II modulates alpha 1-adrenoceptor activity.

Effects of carbidopa and of intravenous saline infusion into normal and hypertensive subjects on urinary free and conjugated dopamine.

OBJECTIVE: To investigate the possible role played by endogenous dopamine as a modulator of renal sodium (Na+) reabsorption after a combined Na+ and volume load. DESIGN: A randomized placebo-controlled study. METHODS: Ten healthy volunteers and four hypertensive patients were subjected to intravenous infusions of 21 0.9% saline (308 mmol Na+) administered from 1000 to 1300 h after oral administration of placebo or of carbidopa, a dopamine decarboxylase inhibitor. RESULTS: Studies on control subjects after placebo showed that natriuresis occurred during the 6 h after commencement of the saline infusion, with falls in plasma albumin concentration, plasma renin activity and plasma aldosterone concentration; in comparison with results of mock infusion (6 mmol Na+) there was no change in the urinary excretion of dopamine and noradrenaline (In their free or conjugated forms). There was, however, a marked surge in excretion of urinary conjugated dopamine and in the dopamine: noradrenaline ratio from 1300 to 1600 h, after either type of infusion. Administration of carbidopa before the saline infusion resulted in a marked decrease in excretion of urinary free dopamine, but had no effect on the surge in excretion of urinary conjugated dopamine. Saline infusion decreased proximal fractional Na+ reabsorption. Administration of carbidopa delayed but did not prevent this decrease. The effects of saline infusion and of carbidopa on the urinary excretion of dopamine and noradrenaline from hypertensive patients were similar to those observed with the healthy volunteers. CONCLUSIONS: These findings indicate that volume expansion by intravenous saline infusion has no appreciable effect on the urinary free dopamine excretion from normal or hypertensive humans; with any apparent increase, it is important to exclude the possibility of conversion of conjugates to free dopamine in vitro. Furthermore, that carbidopa administration did not inhibit the afternoon surge of conjugated dopamine suggests that administration of carbidopa is deficient as a tool to investigate the functional role of the renal dopamine system.

Efficacy of an angiotensin II receptor antagonist in managing hyperaldosteronism.

OBJECTIVE: To determine whether an angiotensin II receptor antagonist decreases blood pressure in patients with hyperaldosteronism and hypertension who are taking other antihypertensive agents. DESIGN: A double-blind randomized placebo-controlled crossover study. PATIENTS AND METHODS: Blood pressure and hormonal responses to 2-week courses of placebo/irbesartan (150 mg/day given by mouth at 08.05 h) were assessed in 10 patients with hyperaldosteronism. Clinic blood pressure was measured by sphygmomanometer, and plasma concentrations of aldosterone, cortisol, angiotensin II, electrolytes and renin activity (PRA) were determined weekly. Automated 24 h ambulatory blood pressure recordings were made at the end of the active and placebo phases. RESULTS: Irbesartan caused a post-dose decrease in ambulatory blood pressure (systolic, P = 0.02; diastolic, P = 0.05) in the period from 10.00 h to 20.00 h. Clinic blood pressure, measured at trough, was not significantly decreased. Plasma aldosterone decreased (P < 0.03) and PRA increased (P < 0.04) in the first week of active treatment with irbesartan, but differences between the placebo and active-treatment groups were not significant in the second week. There were no significant changes in plasma concentrations of angiotensin II, cortisol or potassium in either week. In the second week of irbesartan treatment, there were associations between change in plasma aldosterone and maximal change in ambulatory blood pressure (systolic and diastolic). CONCLUSION: Irbesartan has a role in combination antihypertensive treatment of patients with hyperaldosteronism.

A controlled study of the effects of isosorbide mononitrate on arterial blood pressure and pulse wave form in systolic hypertension.

OBJECTIVE: To determine the effect of an extended-release nitrate preparation on the arterial pulse wave and blood pressure of patients in whom systolic blood pressure was elevated in part by exaggerated pulse-wave reflectance. DESIGN: A double-blind randomized placebo-controlled crossover study was carried out. PATIENTS AND METHODS: The subjects were ten elderly patients with systolic hypertension resistant to conventional anti-hypertensive therapy. Pharmacodynamic responses to 2-week courses of placebo/isosorbide mononitrate (ISMN) were assessed in seven subjects by an ambulatory blood pressure monitor, and in all ten subjects by standard sphygmomanometry, arterial pulse-wave analysis and measurement of plasma nitrate concentration during peak and trough. RESULTS: Ambulatory systolic blood pressure was decreased by ISMN (P < 0.02) between 1000 and 2200 h. Ambulatory diastolic blood pressure fell with ISMN (P < 0.01) during the last 4 h of this period. At peak plasma nitrate levels, ISMN decreased the aortic systolic blood pressure (P < 0.01), ejection peak (P < 0.02) and augmentation component (P < 0.001) of the pulse wave; heart rate increased slightly (P < 0.03). CONCLUSION: ISMN has a role as an adjunct in the anti-hypertensive therapy of patients with refractory systolic hypertension due to exaggerated pulse-wave reflectance.

Erythrocyte cation fluxes in the normotensive and hypertensive clients of a health screening clinic.

Erythrocyte cation transport was measured in vitro using 22Na+ and 86Rb+ uptake techniques in Caucasian men with newly-detected hypertension and in male control groups. The Na+, K+ cotransport [determined by ouabain-resistant frusemide-sensitive (ORFS) components of Na+ or Rb+ influx], sodium pump activity (determined by ouabain-sensitive Rb+ influx) and erythrocyte Na+ and K+ concentrations were not significantly altered in hypertensive men. The total Na+ influx in hypertensives (n = 59) was significantly greater (P less than 0.001) than in controls. The difference was mainly attributable to an increase in the ouabain-resistant frusemide-resistant component of this flux. The total Rb+ influx in hypertensives (n = 39) was also greater (P less than 0.005) than in controls. Overall, both total Na+ influx and total Rb+ influx were positively correlated (P less than 0.01) with diastolic blood pressure and with habitual dietary intake of alcohol. Multivariate analyses after controlling for the effect of blood pressure showed that mean corpuscular volume (MCV) and alcohol intake were statistically significant predictor variables for total Rb+ influx, although not for total Na+ influx. The results are compatible with increased diffusion of cations across the erythrocyte membrane in hypertension, but raise the question of a possible role of alcohol intake in mediating this effect.

Effects of dietary sodium deprivation on erythrocyte sodium concentration and cation transport in normotensive and untreated hypertensive subjects.

There is controversy about the effects of dietary sodium deprivation on cellular cation transport. Using washed erythrocytes for in vitro 22Na and 86Rb uptake studies, we studied the effects of a strict low-salt diet (20 mmol/day) for 4 days in 14 normotensive and 13 hypertensive subjects. Urinary sodium excretion fell from 147 +/- 13 to 18 +/- 3 mmol/24 h in the normotensive group and from 155 +/- 16 to 20 +/- 2 mmol/24 h in the hypertensive group. In both groups, there was a fall in plasma sodium concentration and activation of the renin-aldosterone axis. Both systolic and diastolic blood pressures fell in the hypertensive, but not the normotensive group. There were small but significant (P less than 0.025) decreases in cell cation concentrations and passive cation transport in the normotensive, but not the hypertensive group. No significant change in sodium pump activity or in Na+K+ cotransport was seen in either group. These observations provide no support for the concept that a decrease in dietary sodium intake can induce changes in cell cation transport, detectable in vitro, to which reduction in blood pressure may be attributed.

Drug-induced hypertension: pathogenesis and management.

PIP: Estrogenic compounds are the most important group of drugs that can induce hypertension. Studies have shown an incidence of significant hypertension amounting to less than 1% after 1 year of taking oral contraceptives and about 2% after 5 years. The ratio of the incidence of hypertension among ''takers'' to that of ''nontakers'' has been assessed at 1.8 by 1 study and 2.6 by another. Small but significant increments in systolic and diastolic pressures can be discerned during the first 2 years of treatment. Cessation of treatment has resulted in pressures returing to pretreatment levels within 3 months. In those previously normal the highest readings during oral contraceptive use were only 155/90 mm of Hg. Severe hypertension is more likely to occur in the predisposed, and malignant hypertension has been reported. Previous hypertension, toxemia of pregnancy, obesity, and nephropathy are predisposing conditions. Although progestagens, used alone, do not cause clinical hypertension the incidence of hypertension associated with an estrogen-progestogen combination was directly related to the dose of progestagen used. Weight gain is often observed in oral contraceptive users and is occasionally accompanied by edema and hypertension. There is a marked increase in the circulating level of renin substrate (angiotensinogen) which is caused by the estrogen component of the pill. The increase in renin substrate is associated with increase in plasma levels of renin activity, angiotensin 2, and aldosterone, together with a fall in plasma renin concentration. The suppression of plasma renin concentration can persist for weeks after stopping the pill. The factors responsible for hypertension are probably intrinsic and may be either neural, vascular, or renal. Patients taking oral contraceptives should have blood pressure checks at 6-month intervals, and more frequently in high risk cases. In the management of those with only mild blood pressure elevation, such patients should change to a preparation with the lowest available estrogen dosage, 30 mcg of ethinyl estradiol, or reserve the method for use during crucial periods of family planning. With moderate hypertension the oral contraceptive should be suspended for 3-6 months. If the blood pressure falls, oral contraceptives should not be resumed but another method recommended. Continuing hypertension requires further study and possibly elective sterilization. Severe hypertension requires withdrawal of the pill, urgent investigation, and treatment. Other drugs may cause hypertension. Management of these patients is outlined. Structural formulae of progesterone, norethisterone acetate, medroxyprogesterone acetate, and norgestrel are shown.^ieng

The role of renin in the antihypertensive action of beta-adrenoreceptor blocking agents.

Since the original reports suggesting that the antihypertensive action of beta-adrenoreceptor blocking drugs is related to their inhibitory action on renin release, much evidence has been put forward both to refute and support this hypothesis. Our studies of the acute and chronic effects of treatment with propranolol in hypertensive patients showed that the antihypertensive action of the drug was of later onset than the initial cardio-depressant and renin-suppressive effects and had little relationship to the pre-treatment levels of treatment-induced changes in plasma renin activity (PRA). When pindolol was substituted for propranolol in these studies PRA rose, but blood pressure control was undisturbed. Again, in animal experiments, although a range of different beta-adrenoreceptor blocking agents induced decreases in both blood pressure and PRA, the hypotensive effects of pindolol was associated with a rise in PRA. Further, PRA proved to be a poor guide to therapeutic effectiveness in the treatment of an unselected population of hypertensive patients with propranolol. It is concluded that the antihypertensive action of beta-adrenoreceptor blocking agents, as a class, is not dependent upon suppression of PRA.

Caffeine consumption and blood pressure: an epidemiological study.

A cross-sectional survey of 5147 Australians attending a health screening clinic was conducted to determine if there was an association between habitual consumption of caffeine, or particular caffeine-containing beverages, and blood pressure. The average caffeine consumption of the study population was 240 mg/day. Caffeine consumption within the last three hours was found to be associated with significantly higher mean systolic and diastolic blood pressure in both sexes after controlling for age, adiposity, first degree relatives with hypertension, serum cholesterol level, alcohol consumption and tobacco smoking. Mean systolic and diastolic blood pressures differed significantly by 4 mmHg and 2 mmHg respectively for both males and females between those who had consumed caffeine within the last three hours and those who had not consumed it within the last nine hours (p less than 0.01). Average caffeine consumption per day was not associated with blood pressure in either sex after controlling for time since caffeine consumption. Logistic regression analysis was used to estimate the relative risk of high blood pressure (treated and untreated) for the groups consuming and not consuming caffeine in the last three hours. This relative risk was significantly greater than unity in females only (p less than 0.05). After controlling for time since caffeine consumption, caffeine consumption per day was not associated with significantly increased risk of high blood pressure.