A feasibility study of microwave therapy for precancerous actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a common premalignant skin lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Microwave therapy is an established cancer treatment and has been used for plantar viral warts. OBJECTIVES: To evaluate the efficacy and feasibility of microwave as a treatment for AK. METHODS: Stage I was a dose-setting study, in which seven participants had the dielectric properties of 12 thick and 22 thin AKs assessed for optimization of the microwave dose used for treatment in Stage II. Stage II was a randomized, internally controlled trial evaluating 179 AKs in 11 patients (93 treated, 86 untreated controls) on the scalp/forehead or dorsal hand. Participants received one treatment initially and a repeat treatment to unresolved AKs at week 4. The response was assessed at six visits over 4 months. The primary outcome was partial or complete resolution of the treated AKs. RESULTS: A significantly higher proportion of treated AK areas responded than untreated (90% vs. 15%; P < 0·001). Thin AKs were more responsive than thick AKs. The site did not affect efficacy. Pain was severe, but brief (80% reported pain lasting 'a few seconds only'). Adverse effects were minimal (erythema, n = 6; flaking, n = 3; itch, n = 3). All participants who would chose microwave therapy over their current treatment cited the shorter discomfort period. CONCLUSIONS: Microwave therapy is a portable, safe and effective treatment for AK. An easy-to-deliver, acceptable therapy for AK is attractive as a prevention strategy. While these results are promising, a larger randomized controlled trial is needed against an effective comparator to confirm clinical efficacy and patient acceptability. What is already known about this topic? Actinic keratoses (AKs) are common precancerous skin lesions. Successful treatment of AK can prevent cutaneous squamous cell carcinoma (cSCC). Most topical therapies for AK require repeated application over weeks and drive local skin inflammation, leading to poor compliance. An easy-to-deliver and effective treatment for AK, suitable for use in primary care, could reduce cSCC. What does this study add? Microwave therapy is a feasible, effective treatment for AK. Ninety per cent of treated AKs showed full or partial resolution at 120 days post-treatment. Microwave therapy was painful, but the pain was short-lived (seconds) and this short discomfort period was cited as the main reason that microwave was preferred to their current treatment.

NSAID-exacerbated respiratory disease: a meta-analysis evaluating prevalence, mean provocative dose of aspirin and increased asthma morbidity.

BACKGROUND: The prevalence and mean provocative dose of oral aspirin (MPDA) triggering respiratory reactions in people with asthma have been inconsistently reported, and the relationship between NSAID-exacerbated respiratory disease (NERD) and asthma morbidity was less well quantified. METHODS: A systematic review was performed by identifying studies diagnosing NERD using blinded, placebo-controlled oral provocation challenge tests (OPCTs) or by self-reported history in people with asthma. Data were extracted, and effect estimates for changes in respiratory function, MPDA and asthma morbidity were pooled using random-effects meta-analysis. RESULTS: The prevalence of NERD in adults with asthma was 9.0% (95% CI 6-12%) using OPCTs and 9.9% (95% CI 9.4-10.5%) using self-reported history from questionnaires. The MPDA in adults with NERD was 85.8 mg (95% CI 73.9-97.6). In people with NERD, the risk of: uncontrolled asthma was increased twofold (RR 1.96 (95% CI 1.25-3.07)); severe asthma and asthma attacks was increased by 60% (RR 1.58 (95% CI 1.15-2.16) and RR 1.59 (95% CI 1.21-2.09), respectively); emergency room visits was increased by 80% (RR 1.79 (95% CI 1.29-2.49)); and asthma hospitalization was increased by 40% (RR 1.37 (95% CI 1.12-1.67)) compared to people with NSAID-tolerant asthma. CONCLUSIONS: Respiratory reactions triggered by oral aspirin in people with asthma are relatively common. At the population level, the prevalence of NERD was similar when measured using appropriately conducted OPCTs or by self-reported history. On average, respiratory reactions were triggered by clinically relevant doses of oral aspirin. Asthma morbidity was significantly increased in people with NERD who potentially require more intensive monitoring and follow-up.

Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality.

BACKGROUND: Adjuvant endocrine therapy is recommended for women with oestrogen receptor-positive breast cancer, but many women do not take the medication as directed and they stop treatment before completing the standard 5-year duration. METHODS: This retrospective cohort study conducted between 1993 and 2008 of all women with incident breast cancer, who are residing in the Tayside region of Scotland, examined adherence to prescribed adjuvant tamoxifen or aromatase inhibitors (AIs). Survival analysis examined the effect of adherence on all-cause mortality, breast cancer death and recurrence, using linked prescribing, cancer registry, clinical cancer audit, hospital discharge and death records. RESULTS: A total of 3361 women with breast cancer were followed for a median 4.47 years (interquartile range (IQR)=2.04-8.55). The median overall adherence was 90% (IQR=90-100%), but the annual adherence reduced after a longer period from diagnosis. Low adherence of <80% was associated with poorer survival (hazard ratios=1.20; 95% confidence interval=1.03-1.40, P=0.019). There was no significant difference for low adherence over the treatment period and recurrence, or breast cancer death, but patients with high annual adherence for 5 years had better outcomes than those with 3 or less. CONCLUSION: Low adherence to all adjuvant endocrine therapy for women with breast cancer, whether tamoxifen or AI, increases the risk of death.

Prevalence estimates of diagnosed viral hepatitis B, liver condition outcomes and hospitalization costs: a population record-linkage study in Tayside, Scotland.

We estimated prevalence and incidence of liver condition outcomes, and costs to the health service of diagnosed hepatitis B virus (HBV) in Tayside, UK. HBV patients were identified from electronic virology data between 1989 and 2003. The health resource costs of HBV for surface antigen-positive (HBsAg+) patients and HBV (HBsAg+ or immune, i.e. recovered) patients were calculated. A total of 633 patients had HBV (275 HBsAg+), and were more likely to be male (62% vs. 48%), older (mean age 42.6 vs. 39 . 2 years) and deprived than the general population. The prevalence of immune individuals increased steadily. Post-HBV diagnosis, 24% of immune and 13% of HBsAg+ patients were diagnosed with a liver condition. The median cost per immune patient (£3023) was greater than per HBsAg+ patient (£1498) (P=0.02). While increasing prevalence of immune HBV patients highlights an increase in screening and treatment, the costs associated with this group are high.

Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs.

AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. METHODS: Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008. RESULTS: There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p = 3 × 10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%). CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.

Integration of e-learning resources into a medical school curriculum.

BACKGROUND: E-learning has the potential to make important contributions to medical education, but there has been limited study of a blended approach in which the digital resources are introduced alongside traditional teaching methods such as lectures. METHODS: We describe the successful embedding of an e-learning resource into 3 of the 5 weeks of cardiovascular system teaching for 164 first-year medical students by providing scheduled slots in the timetables. A questionnaire completed by the students at the end of the 5 weeks had a response rate of 66%. Students varied in how they made use of the resource, some systematically working through it and others browsing and studying sections felt to be personally most relevant. RESULTS: Almost all (96%) rated the e-learning resources as probably or definitely of value: they particularly valued interactive activities, animations, video demonstrations, video clips of experts and self-assessment exercises. Graduate students had a significantly more favourable assessment of the e-learning resources than their undergraduate colleagues, while female students felt the value in supporting existing learning opportunities more strongly than male students. CONCLUSIONS: It should not be assumed that all students will choose to use an e-learning resource in the same way and instructional design should enable alternative approaches. The sequence in which the e-learning resource is used in relation to the other learning opportunities, such as lectures and PBL group discussions, may be important and merits further consideration. The experiences reported in this study provide encouragement and pointers for others engaged in the integration of e-learning in their curriculum.

Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer.

Increasing duration of tamoxifen therapy improves survival in women with breast cancer but the impact of adherence to tamoxifen on mortality is unclear. This study investigated whether women prescribed tamoxifen after surgery for breast cancer adhered to their prescription and whether adherence influenced survival. A retrospective cohort study of all women with incident breast cancer in the Tayside region of Scotland between 1993 and 2002 was linked to encashed prescription records to calculate adherence to tamoxifen. Survival analysis was used to determine the effect of adherence on all-cause mortality. In all 2080 patients formed the study cohort with 1633 (79%) prescribed tamoxifen. The median duration of use was 2.42 years (IQR=1.04-4.89 years). Longer duration was associated with better survival but this varied over time. The hazard ratio for mortality in relation to duration at 2.4 years was 0.85, 95% CI=0.83-0.87. Median adherence to tamoxifen was 93% (interquartile range=84-100%). Adherence <80% was associated with poorer survival, hazard ratio 1.10, 95% CI=1.001-1.21. Persistence with tamoxifen was modest with only 49% continuing therapy for 5 years of those followed up for 5 years or more. Increased duration of tamoxifen reduces the risk of death, although one in two women do not complete the recommended 5-year course of treatment. A significant proportion of women have low adherence to tamoxifen and are at increased risk of death.

Long-term adherence to statin treatment in diabetes.

AIMS: To determine the patterns and predictors of long-term adherence to statin therapy in all patients with diabetes in the community setting. METHODS: We retrospectively studied patients with diabetes who were resident in Tayside, Scotland from 1 January 1989 to 31 May 2003 and initiated statin treatment during that time. The main outcome measure was percentage of days covered (PDC) by a statin, calculated at regular intervals. Predictors of suboptimal adherence (PDC < 80%) were identified using generalized linear models for repeated measures. RESULTS: Six thousand four hundred and sixty-two patients were included in the study. In the first year, the mean PDC was 87, 61% in the first and second quarter, respectively, and 65% after 13 years. Less than 50% of patients maintained a PDC of > 80% after 13 years. Predictors of poor long-term adherence were younger age, higher HbA(1c), no history of smoking, no cardiovascular morbidity at baseline and occurrence of cardiovascular disease after statin commencement. CONCLUSIONS: This study suggests that barriers to long-term adherence to statins tend to arise early on in the therapeutic course. In general, long-term adherence is poor in patients with diabetes, especially among those with few other cardiovascular risk factors.

A study of the safety of current gastrointestinal endoscopy (EGD).

BACKGROUND AND STUDY AIMS: Previous attempts at assessing the safety of upper gastrointestinal endoscopy have been hampered by incomplete data collection. We aimed to assess the 30-day mortality associated with esophagogastroduodenoscopy (EGD) and assess the important risk factors. PATIENTS AND METHODS: A retrospective cohort study was conducted of patients who underwent endoscopy at Ninewells Hospital in Dundee between 1 June 2000 and 31 May 2003. A total of 11 501 EGDs were performed in 8926 patients. These patients were record-linked to the death registry and the database of hospital admissions in order to calculate the all-cause 30-day mortality. An expert panel judged whether EGD had caused or contributed to the deaths. Logistic regression analysis was performed on outcomes of all-cause and EGD-contributed mortality. RESULTS: The median age of the patients was 62 years (interquartile range 48 - 74 years), 54 % were women, and 94 % of procedures were diagnostic. A total of 395 patients died within 30 days (all-cause 30-day mortality rate 4.4 %). One patient death was caused directly by the EGD (procedure-caused mortality rate 1 in 9000). EGD was judged to have contributed to patient deaths at a rate of 1 in 182, based on majority agreement of experts: some factors associated with these deaths were percutaneous endoscopic gastrostomy insertion (odds ratio [OR] 18.39, 95 % confidence interval [CI] 5.71 - 59.22), melena or hematemesis indications (OR 9.01, 95 % CI 3.53 - 22.99), and esophageal varices (OR 6.28, 95 % CI 1.54 - 25.60). CONCLUSIONS: A causal death rate of 1 in 9000 suggests that EGD is very safe. However, certain patient groups have an increased mortality, and the risks and benefits of EGD should be carefully evaluated in each patient.

Agreement between community echocardiography and hospital echocardiography in patients suspected of having left ventricular systolic dysfunction.

BACKGROUND: Smaller echocardiography machines, when used in hospitals, are accurate for detecting left ventricular dysfunction and valvular disease. This paper assessed the detection of left ventricular dysfunction and of valvular disease in the community setting by a smaller machine. AIMS: To measure the agreement in patients with suspected heart failure between community echocardiography and traditional echocardiography in the hospital in detecting left ventricular dysfunction and significant valve disease. METHODS: Suspected heart failure patients were referred to one of the authors (SJ) for community echocardiography using a Siemens Cypress machine. The patients had a second echocardiogram in the hospital by another sonographer who was blinded to the results of the first echocardiogram. The reports of the two sonographers were assessed for agreement using kappa statistics. RESULTS: 458 patients had a community echocardiogram and 136 agreed to a second echocardiogram in the hospital. There was excellent agreement, kappa = 0.87 (0.06 SE), for the detection of left ventricular dysfunction between community echocardiography and the hospital machine. The detection of significant valvular disease was good, kappa = 0.75 (0.06) between the community echocardiogram and hospital machines. CONCLUSIONS: In suspected heart failure patients, community echocardiography gives comparable results to traditional hospital echocardiography for left ventricular dysfunction detection and for significant valvular disease detection.

Hospitalizations for people with type 1 and type 2 diabetes compared with the nondiabetic population of Tayside, Scotland: a retrospective cohort study of resource use.

OBJECTIVE: To compare the hospitalizations of people with type 1 and type 2 diabetes with those of the nondiabetic population of Tayside, Scotland. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study set in Tayside, Scotland. Study subjects were eligible for inclusion if they lived in Tayside from 1 January 1995 to 31 December 1995. The primary end point was hospitalization. Comparisons between people with and without diabetes were assessed using logistic regression modeling. RESULTS: The fixed population for the year 1995 included 366,849 people registered with a Tayside general practitioner; 7,735 (2.1%) of these had diabetes. Approximately 25% of all study subjects with diabetes had at least one hospital admission, compared with 12% of the nondiabetic population. The length of stay was highest for patients with type 2 diabetes (median of 7 days). People with diabetes accounted for 8.2% of the total bed days and had approximately double the risk of admission. Type 2 diabetic patients had increased risks of myocardial infarction and stroke; both type 1 and type 2 diabetic patients were at increased risk for an endocrine/metabolic admission or renal failure. The risk of ophthalmic admissions, especially for cataract, was much higher in patients with type 1 diabetes compared with the nondiabetic population. CONCLUSIONS: Type 2 diabetes was associated with more frequent and longer admissions compared with the nondiabetic population. This was due to a higher risk of neurological, cardiovascular, renal, and ophthalmic hospitalizations compared with people without diabetes.

Diet as a risk factor for peripheral arterial disease in the general population: the Edinburgh Artery Study.

The Edinburgh Artery Study included a cross-sectional survey of 1592 men and women (aged 55-74 y). One aim was to examine relationships between an indicator of peripheral arterial disease, the ankle brachial pressure index (ABPI), and dietary factors. Nutrient intake was derived from a food-frequency questionnaire. Higher frequency of consumption of fiber-containing foods was associated with greater mean ABPI in males and higher consumption of meat and meat products were significantly associated with low mean ABPI in males and females. In a multiple linear regression with ABPI as outcome and energy-adjusted nutrients as predictors, cereal fiber (P = 0.02) and alcohol (P = 0.04) were positively associated with the ABPI in males but not in females. Dietary vitamin E(alpha-tocopherol) intake was positively associated with ABPI (P = 0.04) independently of smoking and other nutrients. Dietary vitamin C intake was significantly related to ABPI (P = 0.006) only among those who had ever smoked.

Selegiline and mortality in subjects with Parkinson's disease: a longitudinal community study.

OBJECTIVE: To estimate mortality by drug use in a cohort of patients with PD relative to age- and sex-matched comparators. METHODS: two longitudinal cohorts of patients with 7 and 11 years' duration of PD were constructed with matched comparators in Tayside, Scotland. Subjects were eligible for inclusion if they received a first prescription for an anti-Parkinson's drug from July 1989 to December 1995, with no PD drug prescription in the previous 6 months. Those who had previously taken a neuroleptic drug or were younger than 40 years of age were excluded. RESULTS: Overall, subjects with PD in relation to comparators had higher mortality with a rate ratio (RR) of 1.76 (95% CI 1.11, 2.81) in the 7-year cohort. There was significantly greater mortality in patients with PD who received levodopa monotherapy (RR = 2.45, 95% CI 1.42, 4.23) relative to the comparators, adjusting for previous cardiovascular drug use and diabetes. However, there was no significant difference in mortality in those with PD receiving combination therapy of selegiline with levodopa and other drugs in relation to the comparators (RR = 0.92, 95% CI 0.37, 2.31). CONCLUSIONS: Subjects with PD had twice the rate of mortality relative to age- and sex-matched comparators. However, those subjects who received selegiline at any time in combination with co-careldopa or co-beneldopa showed no significant difference in mortality compared with the comparators. Monotherapy with levodopa was associated with the highest mortality.

Smoking, haemostatic factors and lipid peroxides in a population case control study of peripheral arterial disease.

The aim of this study was to determine differences between cases of peripheral arterial disease and healthy controls in levels of haemostatic factors and lipid peroxides and the influence of cigarette smoking. The study groups were selected from the Edinburgh Artery Study which is a random sample survey of men and women aged 55-74 years. Mean levels of plasma fibrinogen, von Willebrand factor, beta-thromboglobulin, plasminogen activator inhibitor (type I), cross-linked fibrin degradation products and lipid peroxides were markedly elevated in 121 study cases compared with 126 age- and sex-matched controls. For example, cross-linked fibrin degradation products had a geometric mean of 106.8 ng/ml (95% confidence interval (CI) 95.3, 119.8) in study cases and 74.7 ng/ml (95% CI 67.0, 83.4) in controls (P < 0.001). Inclusion of smoking in logistic regressions of each factor on peripheral arterial disease significantly reduced the odds of disease for von Willebrand factor and for cross-linked fibrin degradation products, but had little effect on the increased odds associated with fibrinogen, beta-thromboglobulin, plasminogen activator inhibitor and lipid peroxides. We conclude that, in men and women in Edinburgh, peripheral atherosclerosis is associated with lipid peroxidation, endothelial disturbance, platelet activation, elevated fibrinogen, fibrin formation and increased inhibition of fibrinolysis. The most important effects of cigarette smoking in promoting atherosclerosis may be endothelial disturbance and fibrin formation.

Physical activity level is an independent predictor of the diurnal variation in blood pressure.

OBJECTIVE: The aim of this study was to define the relationship between physical activity and the magnitude of the percentage fall in blood pressure at night (nocturnal dip). METHODS: We simultaneously monitored 24-h ambulatory blood pressure and measured physical activity by actigraphy in 434 patients. Blood pressure was measured every 20 min; the actigraph integrated an activity score every 10 s. Mean daytime and night-time activity were calculated from mean scores for the 15 min preceding each blood pressure measurement. Nocturnal dip in systolic and diastolic blood pressure (SBP and DBP) were regressed on mean (log-transformed) daytime activity. Mean night-time activity, age, gender, smoking status, body mass index (BMI) and clinic blood pressure were added into a multiple linear regression. RESULTS: The patient group was heterogeneous in age, gender and mean 24-h blood pressure. Mean daytime activity level was significantly and positively associated with the magnitude of the nocturnal dip in both SBP and DBP. Increased night-time activity was significantly associated with a smaller nocturnal dip. Older patients had a smaller nocturnal dip per log unit daytime activity. Nocturnal dip in SBP was greater in males, and smaller in those taking antihypertensive medications. Smoking, BMI and clinical blood pressure level were not associated with the extent of the nocturnal dip after adjustment for other factors. CONCLUSIONS: Daytime and night-time physical activity levels are independently and significantly predictive of the magnitude of the nocturnal dip in blood pressure. Variation in activity may confound interpretation of 24-h ambulatory blood pressure monitoring, and contribute to the poor reproducibility of dipper status.

The influence of physical activity on the variability of ambulatory blood pressure.

The aim of this study was to assess the contribution of physical activity levels to blood pressure (BP) variability, and to assess the effect age, gender, body mass index, and use of antihypertensive medications on this relationship. We simultaneously monitored 24-h ambulatory BP by automated recorder and activity by actigraphy in 431 patients. Mean activity scores for the 5, 10, 15, and 20 min preceding each BP measurement were calculated, and BP and heart rate were related to these variables using linear mixed model regression. Various patient characteristics were added to the mixed model as covariates. Patients were heterogeneous in age (48 +/- 13 years), sex (49% men), and average 24-h BP (132/81 +/- 15/10 mm Hg). Mean daytime activity level was 44 +/- 15 U. During the daytime, systolic BP (r = 0.33), diastolic BP (r = 0.29), and heart rate (r = 0.42) correlated best with the average activity for the 15 min preceding each measurement (P < .001). Variance was very high, with activity explaining from 0% to 62% of BP variability for different individuals. Men and the obese had a greater reactivity of systolic BP to activity; older patients and those on antihypertensive therapy had a lower reactivity of heart rate. Blood pressure level is significantly associated with physical activity, but the percentage of variance of BP explained by physical activity varies greatly between individuals. Correlation is strongest between BP and average activity integrated over the previous 15 min. Much of the variance in blood pressure remains unexplained.

Physical activity and risk of peripheral arterial disease in the general population: Edinburgh Artery Study.

STUDY OBJECTIVE: To determine associations between physical activity at age 35-45 years with peripheral arterial disease and cardiovascular risk factors at age 55-74 years. DESIGN: Cross sectional survey of the general population--Edinburgh Artery Study. The presence of peripheral arterial disease was determined using the WHO/Rose questionnaire on intermittent claudication, and the ankle brachial pressure index at rest and during reactive hyperaemia. Levels of physical activity undertaken at the time of the survey and at the times the subjects were aged 35-45 years were measured by self administered recall questionnaire. SETTING: City of Edinburgh, Scotland. PARTICIPANTS: Altogether 1592 men and women aged 55 to 74 years, selected from the age-sex registers of 10 general practices spread geographically and socioeconomically throughout the city. MAIN RESULTS: Participation in moderate or strenuous activity when aged 35-45 years was reported by 66% of men and 40% of women. In men, but not in women, less peripheral arterial disease (measured by an increasing trend in the ankle brachial pressure index) was found with increasing amounts of exercise at age 35-45 years (p < 0.001). Higher levels of exercise at age 35-45 years were associated with lower blood viscosity (p < 0.05) and plasma fibrinogen levels (p < 0.05) in men and women aged 55-74 years, and also with higher current alcohol intake (p < 0.001) and high density lipoprotein cholesterol concentrations (p < 0.01) in women aged 55-74 years. After adjustment for age, sex, life-time smoking, social class, body mass index, and alcohol intake, the association between leisure activity aged 35-45 years and the ankle brachial pressure index aged 55-74 years remained highly significant in men who had at some time smoked (p < 0.001) but not in men or women who had never smoked (p > 0.05). CONCLUSION: The risk of peripheral arterial disease, particularly among male smokers, is inversely related to previous physical activity in early middle age, suggesting a protective effect of exercise.

Does the Dundee Step Test predict outcome in treated hypertension? A sub-study protocol for the ASCOT trial. Anglo-Scandinavian Cardiac Outcome Trial.

Treated hypertensive subjects may remain five times more likely to die of cardiac and cerebrovascular diseases than normotensive subjects with equivalent resting blood pressure (BP) levels. Research evidence suggests that exercise BP is a better predictor of end-organ damage and mortality than resting BP, and data from our centre show that a significant proportion of treated hypertensives have uncontrolled BP during a 5-min Dundee Step Test. The prognostic usefulness of exercise BP has yet to be translated into clinical practice because of the lack of a suitable technique. The Dundee Step Test is being evaluated in the ASCOT (Anglo-Scandinavian Cardiac Outcome Trial) study, a 5-year follow-up multicentre, multinational trial comparing the effect of newer (amlodipine and perindopril) and older (bendroflumethiazide and atenolol) antihypertensive agents stratified according to cholesterol levels on cardiac outcome. If the value of the Dundee Step Test is proven, then it may be adopted into routine clinical practice for the assessment of exercise BP. This may result in the improved management of hypertension with a subsequent reduction in morbidity and mortality. The publication of this study protocol is meant to be a statement of on-going research which may stimulate interest among those with an interest in this area of research. Journal of Human Hypertension (2000) 14, 75-78.

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.

How well do office and exercise blood pressures predict sustained hypertension? A Dundee Step Test Study.

Exercise systolic blood pressure (BP) appears to be a better predictor of cardiac mortality than casual office BP. We tested whether this could be explained by exercise systolic BP being a better predictor of sustained hypertension than casual office BP. Exercise systolic BP was measured using the lightweight 3-min single stage, submaximal Dundee Step Test in 191 consecutive subjects (102 male, age 52 (s.d. 13) years) who were referred to a specialist hypertension clinic for assessment. Exercise systolic BP was compared with office BP and daytime ambulatory BP (ABP). Sustained hypertension was defined as a mean daytime systolic and/or diastolic ABP of >/=140/90 mm Hg. Receiver operating characteristic (ROC) curves of exercise systolic BP and office BP in predicting sustained hypertension were compared. The positive predictive value of office diastolic BP >/=90 mm Hg and office systolic BP >/=140 mm Hg for sustained hypertension were 64% and 67% respectively. However, exercise systolic BP >/=180 mm Hg had a positive predictive value of 76%. Twenty-two percent (42/191) of subjects had an exercise systolic BP rise to >/=210 mm Hg, and 93% of this group had sustained hypertension on ABP. Whilst exercise systolic BP was a better predictor of sustained hypertension using currently recommended office BP treatment thresholds, the ROC curves of these indices were not different. In a multiple regression analysis, exercise systolic BP was an independent predictor of sustained hypertension, accounting for 36% of the variance of daytime systolic ABP after adjusting for age, gender and antihypertensive drug treatment. In conclusion, exercise systolic BP was a marginally better predictor of sustained hypertension than office BP. This may partly explain why exercise systolic BP is a potent predictor of cardiac mortality.