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Biomedical subjects

Eoin O'Brien

Publications and source records attributed to Eoin O'Brien.

At least 19 recordsLinked to original sources
PubMed2006

Aliskiren reduces blood pressure and suppresses plasma renin activity in combination with a thiazide diuretic, an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker.

Thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all cause reactive rises in plasma renin activity. We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering. In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (n=23), ramipril (n=21), or irbesartan (n=23). In the diuretic combination study, the addition of 25 mg of hydrochlorothiazide to 150 mg of aliskiren daily for 3 weeks significantly lowered daytime pressure, compared with aliskiren monotherapy (systolic/diastolic mean change from baseline [SEM]: daytime: -18.4 [2.1]/ -10.6 [1.7] versus -10.4 [1.8]/-5.8 [1.4]; nighttime: -15.6 [2.7]/-8.1 [1.8] versus -8.8 [2.9]/-5.0 [2.2]). In the angiotensin-converting enzyme inhibitor combination study, the addition of 75 or 150 mg of aliskiren to 5 mg of ramipril alone for 3 weeks further lowered both daytime and nighttime pressures compared with ramipril monotherapy (daytime: -10.5 [2.9]/-8.1 [2.1] and -14 [3.7]/-8.7 [2.3] versus -6.1 [2.4]/-5.9 [1.5]; nighttime: -8.1 [2.6]/-5.3 [2.4] and -9.6 [3.4]/-5.3 [2.4] versus -2 [2.3]/-0.7 [2.2]). In the angiotensin receptor blocker combination study, the addition of 75 or 150 mg of aliskiren to 150 mg of irbesartan alone, for 3 weeks, resulted in significantly lower nighttime pressures compared with irbesartan monotherapy (daytime: -14.8 [2]/-8.2 [1.3] and -13.3 [1.6]/-6.8 [0.9] versus -11.4 [1.6]/-6.5 [1.1]; nighttime: -16.1 [2.4]/-8.6 [1.7] and -13.2 [2.7]/-7.2 [1.9] versus -9.0 [2.5]/-4.7 [1.9]). Aliskiren (150 mg) alone significantly inhibited plasma renin activity by 65% (P<0.0001). Ramipril and irbesartan monotherapy caused 90% and 175% increases in plasma renin activity, respectively. By contrast, when aliskiren was coadministered with hydrochlorothiazide, ramipril, or irbesartan, plasma renin activity did not increase but remained similar to baseline levels or was decreased (combination therapy versus untreated; median [interquartile range]; aliskiren and hydrochlorothiazide: 0.4 [0.2 to 1.1] versus 0.7 [0.5 to 1.3]; ramipril and aliskiren: 0.5 [0.3 to 0.9] versus 0.6 [0.5 to 0.8]; irbesartan and aliskiren: 0.4 [0.2 to 0.9] versus 0.6 [0.4 to 0.9]). These results suggest that renin inhibition with aliskiren in these combinations increases renin-angiotensin system suppression, improves 24-hour blood pressure control, and may ultimately provide better end-organ protection in patients with hypertension.

Adult↗
PubMed2006

Potential synergy between lipid-lowering and blood-pressure-lowering in the Anglo-Scandinavian Cardiac Outcomes Trial.

AIMS: A prespecified objective of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was to assess whether any synergistic effects were apparent between the lipid-lowering and blood-pressure-lowering regimens in preventing cardiovascular events. METHODS AND RESULTS: A total of 19 257 hypertensive subjects were randomized to an amlodipine-based regimen or an atenolol-based regimen. Of these, 10 305 subjects with total cholesterol < or =6.5 mmol/L were further randomized to atorvastatin 10 mg daily or placebo. In this analysis, the effects of atorvastatin were compared with placebo on coronary heart disease (CHD), cardiovascular and stroke events in those assigned amlodipine-based and atenolol-based regimens. In the ASCOT lipid-lowering arm (LLA), overall, atorvastatin reduced the relative risk of the primary endpoint of non-fatal myocardial infarction and fatal CHD events by 36% (HR 0.64, CI 0.50-0.83, P=0.0005), total cardiovascular events by 21% (HR 0.79, CI 0.69-0.90, P=0.0005), and stroke by 27% (HR 0.73, CI 0.56-0.96, P=0.024). However, atorvastatin reduced the relative risk of CHD events by 53% (HR 0.47, CI 0.32-0.69, P<0.0001) among those allocated the amlodipine-based regimen, and by 16% (HR 0.84, CI 0.60-1.17, p: n.s.) among those allocated the atenolol-based regimen (P=0.025 for heterogeneity). There were no significant differences between the effects of atorvastatin on total cardiovascular events or strokes among those assigned amlodipine (HR 0.73, CI 0.60-0.88, P<0.005 and HR 0.69, CI 0.45-1.06, P: n.s., respectively) or atenolol (HR 0.85, CI 0.71-1.02, P: n.s and HR 0.76, CI 0.53-1.08, P: n.s, respectively). Differences in blood pressure and lipid parameters (placebo corrected) between the two antihypertensive treatment limbs could not account for the differences observed in CHD outcome. CONCLUSION: These findings of an apparent interaction between atorvastatin and an amlodipine-based regimen in the prevention of CHD events are of borderline significance, and hence generate an hypothesis that merits independent evaluation in other trials.

Adult↗
PubMed2006

Ambulatory arterial stiffness index derived from 24-hour ambulatory blood pressure monitoring.

We hypothesized that 1 minus the slope of diastolic on systolic pressure during 24-hour ambulatory monitoring (ambulatory arterial stiffness index [AASI]) might reflect arterial stiffness. We compared AASI with established measures of arterial stiffness and studied its distribution in Chinese and European populations. We used 90207 SpaceLabs monitors and the SphygmoCor device to measure AASI, central and peripheral pulse pressures, the central (CAIx) and peripheral (PAIx) systolic augmentation indexes, and aortic pulse wave velocity. In 166 volunteers, the correlation coefficient between AASI and pulse wave velocity was 0.51 (P<0.0001). In 348 randomly recruited Chinese subjects, AASI correlated (P<0.0001) with CAIx (r=0.48), PAIx (r=0.50), and central pulse pressure (r=0.50). AASI increased with age and mean arterial pressure but decreased with body height. Both before and after adjustment for arterial wave reflections by considering height and heart rate as covariates, AASI correlated more (P<0.0001) closely with CAIx and PAIx than 24-hour pulse pressure. Among normotensive subjects, the 95th percentile of AASI was 0.55 in Chinese and 0.57 in 1617 Europeans enrolled in the International Database on Ambulatory Blood Pressure Monitoring. The upper boundary of the 95% prediction interval of AASI in relation to age ranged from 0.53 at 20 years to 0.72 at 80 years. In conclusion, AASI is a new index of arterial stiffness that can be easily measured under ambulatory conditions. Pending additional validation in outcome studies, normal values of AASI are probably <0.50 and 0.70 in young and older subjects, respectively.

Adolescent↗
PubMed2006

Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in the Dublin Outcome Study.

We hypothesized that the dynamic relation between diastolic and systolic blood pressure over 24 hours provides a measure of arterial stiffness and might, therefore, predict cardiovascular mortality over and above pulse pressure. At baseline, while not on antihypertensive medication, 11 291 patients (mean age, 54.6 years; 5965 women) underwent ambulatory blood pressure monitoring. Using all of the blood pressure readings, we plotted diastolic against systolic blood pressure from each individual and calculated the regression slope. The ambulatory arterial stiffness index (AASI) was defined as 1 minus this regression slope. Over a median follow-up of 5.3 years, 566 cardiovascular deaths occurred, including 151 from stroke and 358 from cardiac disorders. Before and after adjustment for other cardiovascular risk factors, AASI and pulse pressure significantly predicted total cardiovascular mortality. AASI was a stronger predictor than pulse pressure for stroke (mutually adjusted relative hazard ratios for 1 SD increase, 1.21 versus 1.04; P=0.02 versus 0.66) with the opposite trend for cardiac mortality (relative hazard ratios, 1.03 versus 1.21; P=0.63 versus 0.002). In subjects with normal daytime ambulatory blood pressure (<135/<85 mm Hg), AASI was more predictive than pulse pressure of cardiovascular mortality (1.26 versus 0.96; P=0.04 versus 0.70) and of stroke mortality (1.81 versus 1.12; P=0.007 versus 0.58), whereas neither independently predicted cardiac mortality (1.11 versus 0.89; P=0.47 versus 0.40). AASI is a novel measure of arterial stiffness, which can be readily determined from ambulatory blood pressure recordings and which independently predicts cardiovascular mortality, even in normotensive subjects.

Adult↗
PubMed2006

Ambulatory arterial stiffness index predicts stroke in a general population.

OBJECTIVE: The ambulatory arterial stiffness index (AASI) can be computed from individual 24-h blood pressure recordings. METHODS: We investigated the prognostic value of AASI and 24-h pulse pressure in a random sample of 1829 Danes, aged 40-70 years. We adjusted for sex, age, body mass index, mean arterial pressure, smoking, diabetes, ratio of total to high-density lipoprotein cholesterol, and history of cardiovascular disease with Cox regression. RESULTS: Over a median follow-up of 9.4 years, incidences of fatal and nonfatal endpoints were 40 for stroke, 150 for coronary heart disease, and 212 for cardiovascular events. In fully adjusted models, the hazard ratios associated with 1 SD increase (0.14 U) in the AASI were 1.62 (95% confidence interval, 1.14-2.28; P = 0.007) for stroke, 0.96 (0.80-1.14; P = 0.62) for coronary heart disease, and 1.06 (0.91-1.23; P = 0.49) for cardiovascular events. None of these ratios reached significance for pulse pressure (P > 0.47). The AASI still predicted stroke after excluding individuals with previous cardiovascular disease or after adjustment for systolic and/or diastolic blood pressure instead of mean arterial pressure. CONCLUSIONS: In a randomly recruited European population, the AASI was a strong predictor of stroke, beyond traditional cardiovascular risk factors, including the mean arterial pressure and pulse pressure.

Adult↗
PubMed2006

Ambulatory arterial stiffness index: determinants and outcome.

OBJECTIVES: We hypothesized that one minus the slope of diastolic on systolic blood pressure in individual 24-h ambulatory blood pressure recordings (ambulatory arterial stiffness index) might reflect arterial stiffness and predict cardiovascular mortality. METHODS: In volunteers and a population recruited in China, we studied concordance between ambulatory arterial stiffness index and established indexes of arterial stiffness. We assessed the predictive value of ambulatory arterial stiffness index in relation to cardiovascular outcome in Irish hypertensive patients. RESULTS: In 166 healthy volunteers, aged 22-83 years, the correlation coefficient between ambulatory arterial stiffness index and pulse wave velocity was 0.51 (P<0.001). In 348 randomly recruited Chinese, the correlations between ambulatory arterial stiffness index and both the central and peripheral systolic augmentation indexes were significantly stronger than those for 24-h ambulatory pulse pressure, particularly in study participants younger than 40 years. Among normotensive participants, the 95th percentile of the ambulatory arterial stiffness index was 0.55 in 234 Chinese and 0.57 in 1617 Europeans enrolled in the International Database on Ambulatory Blood Pressure Monitoring. The upper boundary of the 95% prediction interval of the ambulatory arterial stiffness index in relation to age ranged from 0.53 at 20 years to 0.72 at 80 years. In 11 291 patients enrolled in the Dublin Outcome Study, both ambulatory arterial stiffness index and 24-h ambulatory pulse pressure significantly predicted cardiovascular mortality. Ambulatory arterial stiffness index was a strong predictor of fatal stroke in normotensive participants, whereas pulse pressure better predicted heart attack in hypertensive patients. CONCLUSION: Ambulatory arterial stiffness index is a novel measure of arterial stiffness, which can be readily determined from ambulatory blood pressure recordings and which independently predicts cardiovascular mortality.

Adult↗
PubMed2006

Ambulatory arterial stiffness index: rationale and methodology.

OBJECTIVES: Increased arterial stiffness is associated with the development of cardiovascular disease and may even predict its development at an early stage. Increased pulse pressure is seen as a marker of increased arterial stiffness and can be readily measured by ambulatory blood pressure monitoring. We propose another surrogate measure of arterial stiffness derived from ambulatory blood pressure monitoring that may predict cardiovascular mortality over and above pulse pressure, namely, the dynamic relationship between diastolic and systolic blood pressure over 24 h--the ambulatory arterial stiffness index. METHODS: Using all blood pressure readings over the 24-h period from 11 291 (5965 women; mean age 54.6 years) patients referred for ambulatory blood pressure monitoring to a blood pressure clinic, diastolic blood pressure was plotted against systolic blood pressure, and the regression slope was calculated; ambulatory arterial stiffness index was defined as one minus this regression slope. RESULTS: Both ambulatory arterial stiffness index and pulse pressure were higher in women (0.42 vs. 0.40 and 57.0 vs. 55.3 mmHg, respectively). For the entire group, the correlation between ambulatory arterial stiffness index and pulse pressure was 0.5. CONCLUSIONS: Ambulatory arterial stiffness index is a new measure that is readily available from ambulatory blood pressure monitoring and may provide added prognostic information for cardiovascular outcome.

Adult↗
PubMed2006

Aliskiren: a renin inhibitor offering a new approach for the treatment of hypertension.

In recent years, the renin-angiotensin-aldosterone system has been shown to be crucial not only in blood pressure haemostasis but also in the evolution of atherosclerosis, which ultimately determines morbidity and mortality. The angiotensin-converting enzyme inhibitors and, recently, the angiotensin receptor blockers (with their low adverse-effect profile) have added a new dimension to the drug treatment of hypertension. Just a decade after the introduction of angiotensin receptor blockers, physicians treating hypertension are now offered another exciting approach to achieving blockade of the renin-angiotensin-aldosterone system through the inhibition of renin. This review outlines the background evidence for aliskiren, the first orally active renin inhibitor.

Amides↗
PubMed2005

Polymorphisms of the Flavin containing monooxygenase 3 (FMO3) gene do not predispose to essential hypertension in Caucasians.

BACKGROUND: The recessive disorder trimethylaminuria is caused by defects in the FMO3 gene, and may be associated with hypertension. We investigated whether common polymorphisms of the FMO3 gene confer an increased risk for elevated blood pressure and/or essential hypertension. METHODS: FMO3 genotypes (E158K, V257M, E308G) were determined in 387 healthy subjects with ambulatory systolic and diastolic blood pressure measurements, and in a cardiovascular disease population of 1649 individuals, 691(41.9%) of whom had a history of hypertension requiring drug treatment. Haplotypes were determined and their distribution noted. RESULTS: There was no statistically significant association found between any of the 4 common haplotypes and daytime systolic blood pressure in the healthy population (p = 0.65). Neither was a statistically significant association found between the 4 common haplotypes and hypertension status among the cardiovascular disease patients (p = 0.80). CONCLUSION: These results suggest that the variants in the FMO3 gene do not predispose to essential hypertension in this population.

Adult↗
PubMed2005

Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study.

The purpose of this study was to determine if ambulatory blood pressure measurement predicted total and cardiovascular mortality over and beyond clinic blood pressure measurement and other cardiovascular risk factors; 5292 untreated hypertensive patients referred to a single blood pressure clinic who had clinic and ambulatory blood pressure measurement at baseline were followed up in a prospective study of mortality outcome. Multiple Cox regression was used to model time to total and cause-specific mortality for ambulatory blood pressure measurement while adjusting for clinic blood pressure measurement and other risk factors at baseline. There were 646 deaths (of which 389 were cardiovascular) during a median follow-up period of 8.4 years. With adjustment for gender, age, risk indices, and clinic blood pressure, higher mean values of ambulatory blood pressure were independent predictors for cardiovascular mortality. The relative hazard ratio for each 10-mm Hg increase in systolic blood pressure was 1.12 (1.06 to 1.18; P<0.001) for daytime and 1.21 (1.15 to 1.27; P<0.001) for nighttime systolic blood pressure. The hazard ratios for each 5-mm Hg increase in diastolic blood pressure were 1.02 (0.99 to 1.07; P=NS) for daytime and 1.09 (1.04 to 1.13; P<0.01) for nighttime diastolic pressures. The hazard ratios for nighttime ambulatory blood pressure remained significant after adjustment for daytime ambulatory blood pressure. These results have 2 important clinical messages: ambulatory measurement of blood pressure is superior to clinic measurement in predicting cardiovascular mortality, and nighttime blood pressure is the most potent predictor of outcome.

Adult↗
PubMed2005

Recommendations for blood pressure measuring devices for office/clinic use in low resource settings.

This paper, which summarizes the conclusions of a WHO Expert meeting, is aimed at proposing indications to develop technical specifications for an accurate and affordable blood pressure measuring device for office/clinic use in low resource settings. Blood pressure measuring devices to be used in low resource settings should be accurate, affordable, and easily available worldwide. Given the serious inherent inaccuracy of the auscultatory technique, validated and affordable electronic devices, that have the option to select manual readings, seem to be a suitable solution for low resource settings. The agreement on the technical specifications for automated blood pressure measuring devices for office/clinic use in low resource settings included the following features: high accuracy, adoption of electronic transducers and solar batteries for power supply, standard rates of cuff inflation and deflation, adequate cuff size, digital display powered by solar batteries, facilities for adequate calibration, environmental requirements, no need of memory function, resistance to shock and temperature changes, and low cost. Availability of a device with these features should be accompanied by adequate training of health care personnel, who should guarantee implementation of the procedures recommended in recent European and American Guidelines for accurate blood pressure measurement.

Blood Pressure Determination↗
PubMed2005

Unmasking hypertension.

Explore the source record for details and available documents.

Blood Pressure Monitoring, Ambulatory↗
PubMed2005

Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial--lipid-lowering arm (ASCOT-LLA).

OBJECTIVE: This study aims to establish the benefits of lowering cholesterol in diabetic patients with well-controlled hypertension and average/below-average cholesterol concentrations, but without established coronary disease. RESEARCH DESIGN AND METHODS: In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA), 10,305 hypertensive patients with no history of coronary heart disease (CHD) but at least three cardiovascular risk factors were randomly assigned to receive 10 mg atorvastatin or placebo. Effects on total cardiovascular outcomes in 2,532 patients who had type 2 diabetes at randomization were compared. RESULTS: During a median follow-up of 3.3 years, concentrations of total and LDL cholesterol among diabetic participants included in ASCOT-LLA were approximately 1 mmol/l lower in those allocated atorvastatin compared with placebo. There were 116 (9.2%) major cardiovascular events or procedures in the atorvastatin group and 151 (11.9%) events in the placebo group (hazard ratio 0.77, 95% CI 0.61-0.98; P = 0.036). For the individual components of this composite end point, the number of events occurring in the diabetes subgroup was small. Therefore, although fewer coronary events (0.84, 0.55-1.29; P = 0.14) and strokes (0.67, 0.41-1.09; P = 0.66) were observed among the patients allocated atorvastatin, these reductions were not statistically significant. CONCLUSIONS: Atorvastatin significantly reduced the risk of major cardiovascular events and procedures among diabetic patients with well-controlled hypertension and without a history of CHD or markedly elevated cholesterol concentrations. The proportional reduction in risk was similar to that among participants who did not have diagnosed diabetes. Allocation to atorvastatin prevented approximately 9 diabetic participants from suffering a first major cardiovascular event or procedure for every 1,000 treated for 1 year.

Adult↗