Sarah Wilson

Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension

Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication. We evaluated the effect among 1411 participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment. Among those who received spironolactone, the mean age was 63 years (SD: ±8 years), 77% were men, and 40% had diabetes. Spironolactone was initiated a median of 3.2 years (interquartile range: 2.0 to 4.4 years) after randomization and added to a mean of 2.9 (SD: ±0.9) other antihypertensive drugs. The median duration of spironolactone treatment was 1.3 years (interquartile range: 0.6 to 2.6 years). The median dose of spironolactone was 25 mg (interquartile range: 25 to 50 mg) at both the start and end of the observation period. During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: ±18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. Spironolactone was generally well tolerated; 6% of participants discontinued the drug because of adverse effects. The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities (principally hyperkaliemia), which were recorded as adverse events in 6% and 2% of participants, respectively. In conclusion, spironolactone effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of ≈3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension.

Comparison of methods to identify individuals at increased risk of coronary disease from the general population

Abstract Objectives To evaluate the guidelines on measurement of cholesterol in the national service framework for coronary heart disease and to compare alternative strategies for identifying people at high risk of coronary disease in the general population. Design Comparison of methods (national service framework criteria, Sheffield tables, age threshold of 50 years, estimated risk assessment using fixed cholesterol values) for identifying people with a 10 year coronary event risk of 15% or greater. Setting Health survey for England 1998. Subjects 6307 people aged between 30 and 74 years with no history of myocardial infarction, stroke, or angina. Main outcome measures Proportion of the total population selected for measurement of cholesterol and proportion of people at 15% or greater risk identified. Results The national service framework guidelines selected 43.4% (95% confidence interval 42.2% to 44.6%) of the study population for cholesterol measurement and identified 81.2% (80.2% to 82.2%) of those at 15% or greater risk. The Sheffield tables selected 73.1% (72.0% to 74.2%) for cholesterol measurement and identified 99.91% (99.83% to 99.99%) of those at 15% or greater risk. An age threshold of 50 years selected 46.3% (45.1% to 47.5%) for cholesterol measurement and identified 92.8% (92.1% to 93.4%) of those at 15% or greater risk. Estimated risk assessments using fixed cholesterol values selected 17.8% (16.8% to 18.7%) for cholesterol measurement and identified 75.9% (74.8% to 76.9%) of those at 15% or greater risk. Conclusion Measuring the cholesterol concentration of everyone aged 50 years and over is a simple and efficient method of identifying people at high risk of coronary disease in the general population.

Predicting coronary risk in the general population - is it necessary to measure high density lipoprotein cholesterol?

Background The Joint British Societies Coronary Risk Prediction Charts recommend the use of a high-density lipoprotein cholesterol value of 1 mmol/l where actual values have not been measured. It is important to quantify the impact of this advice if risk assessments are to be sufficiently accurate to guide treatment decisions. Design The risks of 5005 individuals from the Health Survey for England 1998 were calculated using the Joint British Societies charts. Each individuals risk was recalculated assuming a high-density lipoprotein cholesterol value of 1 mmol/l. These risk estimates were compared with those derived from the Framingham equation. Methods Using the Framingham equation as the gold standard, the positive and negative predictive values, sensitivity and specificity with 95% confidence intervals of the Joint British charts with actual and estimated high-density lipoprotein cholesterol values were calculated. Results At the 30% 10-year coronary heart disease risk threshold using measured high-density lipoprotein cholesterol values, the charts had a sensitivity of 83% and specificity of 99%. Using an estimated high-density lipoprotein cholesterol value of 1 mmol/l reduced the sensitivity to 58% with a specificity of 98%. Conclusions In the presence of measured high-density lipoprotein cholesterol values there was good agreement between the Framingham equation and the Joint British Societies charts. The use of a fixed high-density lipoprotein cholesterol value of 1 mmol/l introduced important and significant errors into the risk assessment. This study reinforces the need to measure both total and high-density lipoprotein cholesterol when assessing coronary risk.

Methods to identify increased risk of coronary disease in the general population. Authors' reply

Editor—Assmann et al have misunderstood the pragmatic question our study answered. In the United Kingdom treatment decisions for the primary prevention of cardiovascular disease are based on the Framingham 10 year coronary risk equation.1 Measuring the cholesterol of the entire population is not currently recommended.1 Given that the NHS has a finite budget we asked how general practitioners can target cholesterol measurement, and hence accurate risk assessment, to those people most likely to benefit from drug treatment to reduce their chance of a stroke or heart attack. We chose to combine the results of our analyses for men and women because, despite sex differences in risk, the optimum age cut-off point to maximise both sensitivity and specificity is similar for both sexes. Our strategy of screening everyone over the age of 50 identified 91% of men and 98% of women at 15% or more 10 year coronary risk. Finally, Assmann et al are concerned about people under 50 being neglected because they are not offered a cholesterol test. Although a clinician may not measure cholesterol routinely, this does not imply that they ignore other important risk factors, such as smoking, obesity, and raised blood pressure. Our study has shown that routine cholesterol measurement, and hence accurate risk assessment, in everyone aged 50 and over is a simple and efficient method of identifying people at high risk of coronary disease in the general population.

Evaluation of cardiovascular risk equations using the ASCOT cohort.

S Wilson, D Collier, A Johnston, N Poulter, G Feder, J Robson and M Caulfield Department of Clinical Pharmacology and Department General Practice and Primary Care, St. Bartholomew’s and The Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK; Cardiovascular Studies Unit, Dept. Clinical Pharmacology and Therapeutics, Imperial College School of Medicine at St Mary’s, Paddington, London W2 1PG, UK; Department of General Practice and Primary Care, St Bartholomew’s and The Royal London School of Medicine and Dentistry, Mile End Road, London E1 4NS, UK