Is exercise blood pressure a marker of vascular endothelial function?
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Blood Pressure↗
Biomedical subjects
T M MacDonald
Publications and source records attributed to T M MacDonald.
Epidemiology and economic burden of viral hepatitis: an observational population based study.
OBJECTIVE: To describe the epidemiology and estimate the health resource use of patients with viral hepatitis in Tayside, Scotland, using record linkage techniques. DESIGN: A retrospective observational study. SETTING: Liver disease database, Tayside, Scotland. PATIENTS: All subjects resident in Tayside in the study period 1989-1999 and registered on the Epidemiology of Liver Disease in Tayside (ELDIT) database. MAIN OUTCOME MEASURES: Incidence and prevalence of known viral hepatitis in Tayside, survival of subjects diagnosed with viral hepatitis, and the health resource use with respect to hospital admissions compared with the general population. RESULTS: There were 4992 patients identified with viral hepatitis in the study period 1989-1999; 86 were IgM positive anti-hepatitis A, 187 patients were hepatitis B surface antigen (HBsAg) positive, and 469 were anti-hepatitis C (HCV) positive. HCV and HBsAg seropositive patients were more likely to be hospitalised and stay in hospital longer, less likely to survive after six years, and used more drugs of potential abuse than the general population. There was an increase in cost per admission and per patient as a consequence of liver disease. CONCLUSIONS: A record linkage population based study of viral hepatitis allows outcomes to be identified and costed. Those at risk of viral hepatitis infection in the Tayside population should be informed about the future implication to their health and costs to society. The health service should investigate the cost effectiveness of vaccination and opportunity costs to the health service of viral hepatitis taking into consideration the increasing incidence and prevalence of disease.
Adult↗
Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study.
OBJECTIVE: To examine whether allopurinol is associated with any alteration in mortality and hospitalisations in patients with chronic heart failure (CHF). This hypothesis is based on previous data that a high urate concentration is independently associated with mortality with a risk ratio of 4.23 in CHF. DESIGN: Retrospective cohort study. SETTING: Medicines Monitoring Unit, Ninewells Hospital, Dundee, UK. PATIENTS: 1760 CHF patients divided into four groups: those on no allopurinol, those on long term low dose allopurinol, those on short term low dose allopurinol, and those on long term high dose allopurinol. MAIN OUTCOME MEASURES: Total mortality, cardiovascular mortality, cardiovascular hospitalisations, cardiovascular mortality or hospitalisations. RESULTS: Long term low dose allopurinol was associated with a significant worsening in mortality over those who never received allopurinol (relative risk 2.04, 95% confidence interval (CI) 1.48 to 2.81). This may be because low dose allopurinol is insufficient to negate the adverse effect of a high urate concentration. However, long term high dose (> or = 300 mg/day) allopurinol was associated with a significantly better mortality than longstanding low dose allopurinol (relative risk 0.59, 95% CI 0.37 to 0.95). This may mean that high dose allopurinol can fully negate the adverse effect of urate and return the mortality to normal. CONCLUSIONS: Long term high dose allopurinol may be associated with a better mortality than long term low dose allopurinol in patients with CHF because of a dose related beneficial effect of allopurinol against the well described adverse effect of urate. Further work is required to substantiate or refute this finding.
Aged↗
Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study.
OBJECTIVE: To investigate patients' adherence to statin treatment prescribed following their first myocardial infarction (MI) and to estimate the effect of adherence to statins on recurrence of MI and all cause mortality. DESIGN: Cohort study using a record linkage database. SETTING: Tayside, Scotland, UK. PATIENTS: Patients who experienced their first MI between January 1990 and November 1995. MAIN OUTCOME MEASURES: Percentage of statin use and adherence to statins by patients after an MI and the relative risk of hospitalisation for recurrent MI. The effect of adherence on all cause mortality was also examined. The covariates used were age, sex, socioeconomic deprivation, serum cholesterol concentration, diabetes mellitus, cardiovascular drug use, and other hospitalisations. RESULTS: Of 5590 patients who experienced an incident MI, 717 (12.8%) experienced at least one further MI. Only 7.7% of patients used statins after an MI during the study period. Compared with those not taking statins, those who had 80% or better adherence to statin treatment had an adjusted relative risk of recurrent MI of 0.19 (95% confidence interval (CI) 0.08 to 0.47) and all cause mortality of 0.47 (95% CI 0.22 to 0.99). There was no significant reduction in either end point for those who were less than 80% adherent to statins. CONCLUSIONS: Despite the infrequent use of statin during the study period, good adherence to statin treatment was associated with lower risk of recurrent MI.
Adult↗
Nebivolol reverses endothelial dysfunction in essential hypertension: a randomized, double-blind, crossover study.
BACKGROUND: Vascular endothelial dysfunction may predict future atherosclerosis. Hence, an antihypertensive agent that reverses endothelial dysfunction and lowers blood pressure might improve the prognosis of patients with hypertension. We hypothesized that nebivolol, a vasodilating beta-blocker, could improve endothelial dysfunction. We tested this hypothesis by comparing the effects of nebivolol and atenolol on endothelial function. METHODS AND RESULTS: Twelve hypertensive patients with a mean ambulatory blood pressure of 154+/-7/97+/-10 mm Hg were randomized after a 2-week placebo run-in period (baseline) in a double-blind, crossover fashion to 8-week treatment periods with either 5 mg of nebivolol with 2.5 mg of bendrofluazide or 50 mg of atenolol with 2.5 mg of bendrofluazide. Forearm venous occlusion plethysmography and intra-arterial infusions of acetylcholine and N(G)-monomethyl-L-arginine (L-NMMA) were used to assess stimulated and basal endothelium-dependent nitric oxide release, respectively. Sodium nitroprusside was used as an endothelium-independent control. Nebivolol/bendrofluazide and atenolol/bendrofluazide each lowered the clinic blood pressure to the same extent (132+/-7/82+/-6 and 132+/-9/83+/-8 mm Hg, respectively; P<0.001 from baseline). The vasodilatory response to acetylcholine was significantly increased with nebivolol/bendrofluazide (maximum percentage change in forearm blood flow [mean+/-SEM], 435+/-27%, P<0.001) but not with atenolol/bendrofluazide. Similarly, the endothelium-dependent vasoconstrictive response to L-NMMA was significantly improved only with nebivolol treatment (percentage change in forearm blood flow, -54+/-5%; P<0.001). The response to sodium nitroprusside was not different between treatments, suggesting that the endothelium-independent pathway was unaffected. CONCLUSIONS: Nebivolol/bendrofluazide increased both stimulated and basal endothelial nitric oxide release, whereas for the same degree of blood pressure control, atenolol/bendrofluazide had no effect on nitric oxide bioactivity. Thus, nebivolol may offer additional vascular protection in treating hypertension.
Acetylcholine↗
Severity of overdose after restriction of paracetamol availability. Study's results conflict with those of other papers.
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Acetaminophen↗
Pharmacoepidemiological research at the Medicines Monitoring Unit, Scotland: data protection and confidentiality.
The Medicines Monitoring Unit (MEMO) is a University-based organization that uses record-linkage techniques to construct an observational database for the population of Tayside, Scotland (approximately 400,000 people). This contains healthcare data indexed by a unique identifier, including data on all prescriptions dispensed, which facilitates pharmacoepidemiological (and other) research. It has hitherto been possible to carry out drug safety studies in the entire population, with access to original medical records of patients where necessary, that have satisfied ethical concerns and confidentiality legislation. However, the recent UK Data Protection Act 1998 (which enforces the 1995 European Directive on Data Protection) has important implications for MEMO's research. The Act has necessitated changes to the way in which research studies are carried out, with MEMO's objective being to ensure that research can continue while protecting the rights and privacy of individual patients. This involves anonymization of data, seeking specific ethical approval for research studies and obtaining relevant permissions from 'Caldicott Guardians', as described in this article.
Bioethics↗
Seasonal changes in temperature and light drive acclimation of photosynthetic physiology and macromolecular content in Lobaria pulmonaria.
Lobaria pulmonaria (L.) Hoffm. is an epiphytic lichen common to temperate deciduous forests where it copes with large changes in temperature and light levels through repeated annual cycles. Samples of L. pulmonaria were taken from a deciduous forest in southeastern Canada at 35-day intervals from February 1999 to February 2000 and also from a rare population in an evergreen forest in March and August 1999. At field-ambient temperatures and light levels, the realised photosystem II (PSII) electron transport was low both in the summer and winter, with transient peaks in the spring and autumn. In contrast, the seasonal pattern of potential electron transport measured at a fixed 20 degrees C peaked in winter, showing the importance of temperature in driving photosynthesis to low levels in the winter despite an acclimation of electron-transport potential to exploit the high ambient light. Realised gross CO2 uptake was correlated with PSII electron transport at mechanistically plausible rates at all sampling sites in the summer but not in the winter, indicating electron diversion away from CO2 fixation in the winter. Chlorophyll content was highest in the dark summer months. The amount of ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO) large subunit (LSU) was highest in spring. Changes in the level of this hyperabundant protein and in the activity of PSII maintained a relatively constant rate of maximum CO2 uptake per RuBisCO LSU from April through November, despite great changes in the seasonal light and temperature. L. pulmonaria acclimates between light and temperature stress in the winter months to light-limitation in the dark summer months. Transition intervals in the spring and autumn, with warm, bright and wet conditions, are likely the most amenable times for growth.
Acclimatization↗
Hypersensitivity reactions associated with exposure to naproxen and ibuprofen: a cohort study.
The aim of the study was to evaluate the risks of hospitalisation and death due to hypersensitivity reactions associated with the NSAIDs naproxen and ibuprofen, using a record-linkage database for Tayside, Scotland (population 400,000). Cohorts of patients exposed to naproxen (n=54,038) and ibuprofen (n=79,513) were assembled. There were no deaths due to hypersensitivity. There was an increased risk of unvalidated hypersensitivity reactions during periods on-drug versus off-drug in patients exposed to naproxen and ibuprofen. However, after checking medical records, none of the three valid cases of hypersensitivity in the naproxen cohort and neither of the two in the ibuprofen cohort were judged to be due to NSAID exposure. A "worst-case" scenario gave an adjusted rate-ratio of on-drug with naproxen versus on-drug with ibuprofen of 1.63 (0.50, 5.29). The study shows that hypersensitivity reactions associated with NSAID use are rare, and provides no evidence that the risks of hypersensitivity reactions differ between naproxen and ibuprofen.
Anti-Inflammatory Agents, Non-Steroidal↗
Isolated diastolic heart failure as a cause of breathlessness in the community: the Arbroath study.
The aim of this study was to examine the prevalence of exercise limitation due to diastolic heart failure among patients felt to have cardiac breathlessness by their general medical practitioner but not referred to hospital. We found that 18% of patients had a simple investigated profile compatible with isolated diastolic dysfunction as a cause of their symptoms. Symptoms appeared to pre-date major cardiac events (infarction; stroke; arrhythmia) that dominated the subsequent clinical course. The patients in this group have adverse cardiovascular risk profiles. Obesity was a common co-morbidity which may impair detailed 2-D echocardiographic assessment.
Adult↗
Aldosterone to renin ratio as a determinant of exercise blood pressure response in hypertensive patients.
Aldosterone to renin ratio (ARR) is a marker of inappropriate aldosterone activity in hypertension. Since aldosterone may adversely affect vascular compliance, we hypothesised that the ARR would relate to exercise blood pressure (BP) responses in hypertension. Blood sampling was done in untreated hypertensives for plasma renin activity (PRA, ng/mL/hr) and plasma aldosterone (PA, pmol/L). ARR was derived by dividing the PA value by the PRA value, and this index was normalised by natural logarithm (lnARR) for further analyses. Each patient underwent 24-h ambulatory BP (ABP), and a 3-min submaximal exercise test using the Dundee Step Test. The Spearman rank correlation coefficients between lnARR and office BP (OBP), ABP and exercise BPs and BP changes estimated during exercise were assessed. A total of 119 (66 males) hypertensive subjects aged 48 (s.d. 12) years were studied. The respective OBP, ABP, exercise BP and the change in exercise BP were 167(23)/105(11), 140(15)/87(10), 189(26)/107(12) and 25(15)/2(9) mmHg. lnARR was significantly correlated with exercise systolic BP (r = 0.24, P < 0.001), exercise diastolic bp (r = 0.23, P < 0.05), systolic abp (r = 0.22, P < 0.05) and systolic obp (r = 0.19, P < 0.05). in a multiple regressional analysis controlling for age and sex and all other bp measurements to assess the relative strengths of correlation between all the bp indices with lnarr, only exercise systolic bp (P = 0.012) and the change in systolic BP during exercise (negatively, P = 0.013) emerged as significant independent predictors of lnARR. In conclusion, there was an independent and significant correlation between ARR and exercise systolic BP.
Adult↗
Exercise blood pressure correlates with the maximum heart rate corrected QT interval in hypertension.
Submaximal exercise systolic blood pressure (ExSBP) is a recognised predictor of cardiac mortality. This study examined the possibility that this might be related to increased QT dispersion or prolonged maximum QT(c) interval (QTcmax). Twenty-nine untreated hypertensive subjects were assessed. Each subject underwent an echocardiographic examination and a 24-h ambulatory blood pressure (ABP). ExSBP was measured during a 3-min lightweight submaximal Dundee step test. In multiple regressional analyses, only left ventricular mass index significantly predicted QT dispersion (R2 = 22.4%, P = 0.018) and QT(c) dispersion (R(2) = 25.3%, P = 0.012). However, with respect to QTcmax, ExSBP (R2 = 21.6%, P = 0.02) emerged as the sole significant predictor of this index. Five (17.2%) out of the 29 subjects had prolonged QTcmax > or = 430 ms and these subjects were not differentiated by 24-h ABP (146 (s.d. 21)/83 (16) vs 140 (14)/88 (11) mm Hg, P = Ns) but by ExSBP (226 (15) vs 188 (24) mm Hg, P = 0.002). In conclusion, systolic blood pressure measured during exercise correlated with QT(c) max in hypertension. This finding may partly explain the prognostic value of exercise blood pressure.
Adult↗
Blood pressure determinants of left ventricular wall thickness and mass index in hypertension: comparing office, ambulatory and exercise blood pressures.
Left ventricular (LV) mass relates positively and continuously to cardiac mortality and thus its regression is a rational therapeutic aim. Whilst the office blood pressure (BP) relates poorly to LV mass, it was unclear whether the 24-h ambulatory BP or the exercise systolic BP (ExSBP) was the stronger correlate of LV structural indices. We studied 49 hypertensive patients with a mean age of 45 (s.d. 12) years with a mean body mass index of 27.1(3.9) kg/m(2). The mean (s.d.) of office BP, ambulatory BP and ExSBP measured at the end of the first three stages of Bruce protocol treadmill exercise I, II and III were 161(20)/99(10), 140(13)/89(10), 190(30), 198(30) and 201(33) mm Hg respectively. The LV indices measured echocardiographically were LV septal thickness (IVSd) (1.1(0.2) cm), LV posterior wall thickness (LVPWd) (1.0(0.1) cm) and LV mass indexed to body surface area (LVMI) (123(30) g/m(2)). Age and gender (male) had the highest correlations with the LV indices. Of the BP measures, the stage II ExSBP's correlation with the LV indices was consistently higher than all other ExSBP, office systolic BP and 24-h systolic ambulatory BP. In a stepwise multiple regression analysis on IVSd, after adjusting for age and gender, the stage II ExSBP was independently associated with IVSd (beta= 0.018 (s.e. 0.008), P = 0.024). When only BP measures were considered as explanatory variables only stage II ExSBP was a significant predictor (P = 0.0001) of IVSd as was the case with LVPWd (P = 0.006) and LVMI (P = 0.0008). Submaximal exercise BP measured at a workload comparable to physical activity encountered in daily life correlated more closely with the left ventricular wall thickness and mass. The exercise BP should perhaps be normalised in hypertension management to optimise regression of LV hypertrophy.
Adult↗
The prescribing of acid suppressants prior to the endoscopic diagnosis of Barrett's oesophagus and oesophagitis.
BACKGROUND: There has been a dramatic rise in incidences of Barrett's oesophagus and oesophageal adenocarcinoma. It has been suggested that the introduction and use of acid suppression therapy may be a factor in the rising incidences of Barrett's oesophagus and oesophageal adenocarcinoma. METHODS: This was a record linkage study, using a prescribing database and an endoscopy database. Patients who had undergone their first endoscopy during the period 1992-1995 and received the diagnosis of Barrett's oesophagus or oesophagitis were identified. The prescribing of acid suppressants was compared for the 3 years prior to endoscopy, between those with Barrett's oesophagus and those with oesophagitis. RESULTS: There was no significant difference between the Barrett's patients and the oesophagitis patients in the proportion that had been exposed to acid suppression therapy (53.4% vs. 51.7%, P=0.704). The mean number of days of prescribing among those who had been exposed to acid suppression therapy was higher in the Barrett's group (340.5 vs. 237.0 days, P=0.001). CONCLUSIONS: Patients with Barrett's oesophagus have received more acid suppressant therapy prior to diagnosis. The reasons for this are not clear. However, 46.6% of Barrett's patients have not been exposed to acid suppressant therapy.
Antacids↗
Record-linkage methodology for prescribing research.
Record-linkage refers to the linking together of data relating to the same individual from separate source files. In this paper, we discuss ways in which the technique can enhance observational prescribing research in large populations. We draw upon the work of the Medicines Monitoring Unit (MEMO), University of Dundee, to illustrate its contribution to prescribing research.
Data Collection↗
Prior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested case-control study with multivariate analysis for other risk factors.
Trimethoprim resistance is increasingly prevalent in community-acquired urinary infections. The objective of this study was to evaluate the association between exposure to community-prescribed trimethoprim and other risk factors in subjects and subsequent trimethoprim-resistant urinary tract infection. The design was a nested case-control study using a record-linkage database. Study subjects submitted a urine sample to the Ninewells Hospital Laboratory between July 1993 and December 1995. Antibiotic exposure in subjects with trimethoprim-resistant isolates (cases) was compared with antibiotic exposure in subjects with trimethoprim-susceptible isolates (controls). Study subjects were drawn from the catchment area of a large teaching hospital in Tayside, Scotland. There were 13765 males and females aged 1-106 years who submitted their first urine sample for culture during the study period. After adjustment for significant risk factors and confounding variables, logistic regression analysis showed exposure to trimethoprim [odds ratio (OR) 4.35] or any antibiotic other than trimethoprim (OR 1.32) to be predictive of resistance. The growth of Proteus spp. (OR 115.14) and bacterial growth other than Escherichia coli and Proteus spp. (OR 2.83) were also predictor variables. Hospitalization in the previous 6 months was not independently associated with trimethoprim resistance. In conclusion, trimethoprim resistance was independently associated with exposure to trimethoprim and to antibiotics other than trimethoprim. Reduction in trimethoprim prescribing alone may not reduce the prevalence of trimethoprim resistance.
Anti-Infective Agents, Urinary↗
A review of the medical treatment of primary aldosteronism.
PURPOSE: Use of the aldosterone-to-renin ratio (ARR) has suggested that at least one in 10 hypertensive subjects have primary aldosteronism (PA). There is thus a timely need to review the literature for effective drug therapies and to speculate on other therapeutic options by taking into account recent advances in understanding of the PA disease pathophysiological process. DATA SOURCE: A MEDLINE and EMBASE search of all articles published from the start of the databases until July 1999 and reviews of the bibliographies of textbooks. STUDY SELECTION: Primary research articles on the medical treatment of PA with emphasis on diagnosis, treatment option, drug dosage, therapeutic response and adverse drug effect. DATA EXTRACTION: Study design and quality were assessed. Relevant data on diagnostic methodology, drug usage and response were analysed and compared. DATA SYNTHESIS: A select number of subjects with aldosterone-producing adenoma (APA) can be expected to respond well to surgical treatment For the majority of PA cases especially subjects with idiopathic hyperaldosteronism (IHA), long-term medical treatment is now safe and feasible although no randomized controlled trials have been carried out to date. The best therapeutic response is obtained by directly antagonizing aldosterone at the receptor level using medium to low dose spironolactone and this response can be predicted by a raised ARR. The response to other potassium-sparing diuretics and calcium channel blockers are modest. IHA responds better than angiotensin II-unresponsive APA to angiotensin converting enzyme inhibitors and this may also be true with angiotensin II receptor blockers. The discovery of the aldosterone synthase gene opens up the possibility for gene therapy. CONCLUSION: The diagnosis of PA allows appropriate management with resultant blood pressure control in many hypertensive subjects who otherwise have resistant hypertension despite multiple drug therapy.
Aldosterone↗
Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data.
AIMS: The diabetogenic effect of diuretics, as well as the indication for prescribing them, may impact on fetal growth. We analysed whether the purchase of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth. METHODS: During 1991-98 all women who purchased prescription drugs for diuretics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database (MEMO), Scotland. Information on birth weight and gestational age was obtained from the Danish Birth Registry, the Danish Hospital Discharge Registry and the Scottish Tayside Neonatal Database. Information on diabetes, hypertension and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescription diuretics during pregnancy were used as a reference group in both cohorts. RESULTS: Danish women who purchased prescription loop diuretics during pregnancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescription loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during their pregnancy were at increased risk of preterm delivery (< 37 completed weeks); ORs: 1.8 (CI; 1.2, 2.7)NJDP, 1.9 (CI; 0.9, 4.3)MEMO. The proportion of hypertension among women who purchased prescription thiazides was 15.8%, and the risk of having an infant with a birth weight (BW) < 2500 g was increased; ORs: 2.6 (CI; 1.4, 5.0)NJDP, 2.4 (CI; 0.8, 7.8)MEMO. CONCLUSIONS: Prescribing diuretics during pregnancy was associated with differences in birth weight and incidence of preterm delivery. Confounding by indication may explain the findings.
Benzothiadiazines↗