Erica J Wallis

Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials

OBJECTIVE To determine the cardiovascular and coronary risk thresholds at which aspirin for primary prevention of coronary heart disease is safe and worthwhile. DESIGN Meta-analysis of four randomised controlled trials of aspirin for primary prevention. The benefit and harm from aspirin treatment were examined to determine: (1) the cardiovascular and coronary risk threshold at which benefit in prevention of myocardial infarction exceeds harm from significant bleeding; and (2) the absolute benefit expressed as number needed to treat (NNT) for aspirin net of cerebral haemorrhage and other bleeding complications at different levels of coronary risk. MAIN OUTCOME MEASURES Benefit from aspirin, expressed as reduction in cardiovascular events, myocardial infarctions, strokes, and total mortality; harm caused by aspirin in relation to significant bleeds and major haemorrhages. RESULTS Aspirin for primary prevention significantly reduced all cardiovascular events by 15% (95% confidence interval (CI) 6% to 22%) and myocardial infarctions by 30% (95% CI 21% to 38%), and non-significantly reduced all deaths by 6% (95% CI −4% to 15%). Aspirin non-significantly increased strokes by 6% (95% CI −24% to 9%) and significantly increased bleeding complications by 69% (95% CI 38% to 107%). The risk of major bleeding balanced the reduction in cardiovascular events when cardiovascular event risk was 0.22%/year. The upper 95% CI for this estimate suggests that harm from aspirin is unlikely to outweigh benefit provided the cardiovascular event risk is 0.8%/year, equivalent to a coronary risk of 0.6%/year. At coronary event risk 1.5%/year, the five year NNT was 44 to prevent a myocardial infarction, and 77 to prevent a myocardial infarction net of any important bleeding complication. At coronary event risk 1%/year the NNT was 67 to prevent a myocardial infarction, and 182 to prevent a myocardial infarction net of important bleeding. CONCLUSIONS Aspirin treatment for primary prevention is safe and worthwhile at coronary event risk ⩾ 1.5%/year; safe but of limited value at coronary risk 1%/year; and unsafe at coronary event risk 0.5%/year. Advice on aspirin for primary prevention requires formal accurate estimation of absolute coronary event risk.

Is the Framingham risk function valid for northern European populations? A comparison of methods for estimating absolute coronary risk in high risk men

Objective To examine the validity of estimates of coronary heart disease (CHD) risk by the Framingham risk function, for European populations. Design Comparison of CHD risk estimates for individuals derived from the Framingham, prospective cardiovascular Münster (PROCAM), Dundee, and British regional heart (BRHS) risk functions. Setting Sheffield Hypertension Clinic. Patients—206 consecutive hypertensive men aged 35–75 years without preexisting vascular disease. Results There was close agreement among the Framingham, PROCAM, and Dundee risk functions for average CHD risk. For individuals the best correlation was between Framingham and PROCAM, both of which use high density lipoprotein (HDL) cholesterol. When Framingham was used to target a CHD event rate > 3% per year, it identified men with mean CHD risk by PROCAM of 4.6% per year and all had CHD event risks > 1.5% per year. Men at lower risk by Framingham had a mean CHD risk by PROCAM of 1.5% per year, with 16% having a CHD event risk > 3.0% per year. BRHS risk function estimates of CHD risk were fourfold lower than those for the other three risk functions, but with moderate correlations, suggesting an important systematic error. Conclusion There is close agreement between the Framingham, PROCAM, and Dundee risk functions as regards average CHD risk, and moderate agreement for estimates within individuals. Taking PROCAM as the external standard, the Framingham function separates high and low CHD risk groups and is acceptably accurate for northern European populations, at least in men.

Coronary and cardiovascular risk estimation for primary prevention: validation of a new Sheffield table in the 1995 Scottish health survey population.

Abstract Objective: To examine the accuracy of a new version of the Sheffield table designed to aid decisions on lipids screening and detect thresholds for risk of coronary heart disease needed to implement current guidelines for primary prevention of cardiovascular disease. Design: Comparison of decisions made on the basis of the table with absolute risk of coronary heart disease or cardiovascular disease calculated by the Framingham risk function. The decisions related to statin treatment when coronary risk is ≥years; aspirin treatment when the risk is ≥ 15% over 10 years; and the treatment of mild hypertension when the cardiovascular risk is≥0% over 10 years. Setting: The table is designed for use in general practice. Subjects: Random sample of 1000 people aged 35–64 years from the 1995 Scottish health survey. Main outcome measures: Sensitivity, specificity, and positive and negative predictive values of the table. Results: 13% of people had a coronary risk of ≥15%, and 2.2% a risk of ≥30%, over 10 years. 22% had mild hypertension (systolic blood pressure 140–159 mm Hg). The table indicated lipids screening for everyone with a coronary risk of ≥15% over 10 years, for 95% of people with a ratio of total cholesterol to high density lipoprotein cholesterol of ≥8.0, but for <50% with a coronary risk of <5% over 10 years. Sensitivity and specificity were 97% and 95% respectively for a coronary risk of ≥15% over 10 years; 82% and 99% for a coronary risk of ≥30% over 10 years; and 88% and 90% for a cardiovascular risk of ≥20% over 10 years in mild hypertension. Conclusion: The table identifies all high risk people for lipids screening, reduces screening of low risk people by more than half, and ensures that treatments are prescribed appropriately to those at high risk, while avoiding inappropriate treatment of people at low risk.

The rationale for differing National recommendations for the treatment of hypertension

This article examines the rationale for the differences in the guidelines for hypertension management of four national or international bodies: the Joint National Committee (JNC-V), The World Health Organization/International Society of Hypertension (WHO-ISH), the British Hypertension Society (BHS), and the New Zealand guidelines. These guidelines agree on many aspects of management, but differ on two very important points-the drugs of first choice for hypertension, and the indications for drug treatment of uncomplicated mild hypertension. JNC-V recommends treatment routinely of all people with a sustained blood pressure of 140/90 mm Hg, whereas the BHS guidelines advise treatment routinely at 160/100 mm Hg. Such differences in the threshold for treatment have a major impact on the proportion of the adult population to be treated, and on the benefit from treatment. JNC-V was heavily influenced by the Hypertension Detection and Follow-up Program (HDFP), which appeared to show a large benefit from the treatment of uncomplicated mild hypertension, whereas the BHS guidelines were influenced by the Medical Research Council (MRC) Trial, which showed a very small benefit. However, the apparent differences in absolute benefit between these, and other, randomized controlled trials is related entirely to differences in the absolute cardiovascular risk of the populations studied. In populations and in individual patients the benefit from antihypertensive treatment is determined by the absolute cardiovascular risk. Blood pressure by itself is a very weak predictor of risk or benefit from treatment. In uncomplicated mild hypertension the need for drug therapy should be based on the absolute risk of cardiovascular complications, estimated by considering age, sex, serum cholesterol level, diabetes mellitus status, and smoking habits, in addition to blood pressure. Doctors cannot estimate absolute risk accurately informally or intuitively, and the next generation of guidelines should incorporate a simple but accurate method for estimating cardiovascular risk, similar to that in the New Zealand guidelines. The decision to treat, or not treat, uncomplicated mild hypertension should be based on a formal estimate of absolute cardiovascular risk and not on an arbitrary blood pressure threshold. As regards drugs of first choice, the available evidence supports strongly the stance of JNC-V and JNC VI that diuretics and beta-blockers should be preferred unless they are contraindicated, or unless there are positive indications for other drug classes.

Coronary and cardiovascular risk estimation in uncomplicated mild hypertension. A comparison of risk assessment methods.

Objective To compare the accuracy of five risk assessment methods in identifying patients with uncomplicated mild hypertension at high coronary heart disease (CHD) and cardiovascular disease (CVD) risk. Design Comparison of risk estimates using each risk assessment method with CHD risk ⩾ 15% and CVD risk ⩾ 20% over 10 years calculated using the Framingham risk functions. Setting British population. Subjects People aged 35–64 years with uncomplicated mild systolic hypertension (systolic blood pressure (SBP) 140–159 mmHg, n = 202) from the 1995 Scottish Health Survey. Main outcome measures Sensitivity, specificity, positive and negative predictive values. Results Compared with CHD risk ⩾ 15% over 10 years, the Sheffield table and Joint British Societies (JBS) Chart had good sensitivity and specificity (> 90%). The New Zealand (NZ) Chart had sensitivity 83% and specificity 89%. Compared with CVD risk ⩾ 20% over 10 years the Sheffield table had sensitivity 81%, the JBS Chart had sensitivity 63%, and the NZ Chart had sensitivity 75%. All had good specificity (> 90%). For CHD risk and CVD risk the World Health Organization/International Society of Hypertension (WHO–ISH) and United States Joint National Committee VI (JNC-VI) methods had high sensitivity at the cost of very poor specificity (< 50%). Conclusion In patients with uncomplicated mild hypertension, the Sheffield table and JBS Chart both identified CHD risk ⩾ 15% over 10 years with acceptable accuracy, while the NZ Chart was less accurate. Compared with CVD risk ⩾ 20% over 10 years, these three risk assessment methods were all less accurate, but the Sheffield table retained the highest sensitivity (P < 0.05 versus JBS Chart, P = NS versus NZ Chart). The WHO–ISH and JNC-VI methods had unacceptably low specificities compared with both measures of risk and failed to differentiate between those at high and low risk.

CARDIOVASCULAR AND CORONARY RISK ESTIMATION IN HYPERTENSION MANAGEMENT

For many years decisions to treat or not treat hypertension with drugs were made considering the level of blood pressure alone. There was vigorous debate over whether patients should be treated at diastolic pressures of 110, 100, 90 mm Hg or some other threshold. However, epidemiological studies show that the risk of cardiovascular complications such as stroke or myocardial infarction is not determined by blood pressure alone, but is strongly influenced by other major risk factors such as age, sex, smoking habit, lipid concentrations, diabetes, target organ damage such as left ventricular hypertrophy (LVH), and established vascular disease such as angina or myocardial infarction.1 Furthermore clinical trials have shown that the absolute risk of cardiovascular disease (CVD) determines the chance of benefit from antihypertensive treatment.2 In 1995 a New Zealand guideline development group turned this knowledge into practice and recommended that treatment of hypertension should be determined by absolute cardiovascular disease risk and not blood pressure thresholds alone.3 Since then most international and national guidelines have embraced the principle of targeting antihypertensive drug treatment at absolute CVD risk, although the details and methods of estimating CVD risk differ greatly between guidelines. In the UK the British Hypertension Society and Joint British Societies (which include cardiology, lipid, hypertension, and diabetes specialist groups) have developed guidelines for the management of uncomplicated mild hypertension according to estimated absolute coronary heart disease (CHD) risk.4,5 This means that hypertension guidelines and guidelines for statins and aspirin in primary prevention cannot be implemented without a working knowledge of the estimation of absolute CHD or CVD risk. This article discusses the principle and practice of using absolute CVD or CHD risk for decisions on antihypertensive treatment. Hypertension is consistently associated with an increased risk of cardiovascular complications, including stroke, myocardial infarction, heart …

Is coronary risk an accurate surrogate for cardiovascular risk for treatment decisions in mild hypertension? A population validation.

Objective To examine the relationship between coronary (CHD) and cardiovascular (CVD) risk in patients with uncomplicated mild hypertension and to determine the accuracy of using CHD risk ⩾ 15% over 10 years to identify for antihypertensive treatment those patients with CVD risk ⩾ 20% over 10 years as advised in recent British guidelines. Design Comparison of decisions made using CHD risk ⩾ 15% over 10 years calculated by the Framingham risk function and estimated using a simple table with CVD risk ⩾ 20% over 10 years. Setting British population. Subjects People aged 35–64 years with uncomplicated mild systolic hypertension (SBP 140–159 mmHg, n = 624) from the 1995 Scottish Health Survey. Main outcome measures Relationship between CHD and CVD risk. Sensitivity, specificity, positive and negative predictive values (PPV and NPV). Results CHD risk 15% over 10 years was equivalent to CVD risk 21% over 10 years. Exact CHD risk ⩾ 15% over 10 years had sensitivity 79%, specificity 98%, PPV 94% and NPV 93% in detecting CVD risk ⩾ 20% over 10 years. Use of the table to estimate CHD risk ⩾ 15% over 10 years gave sensitivity 88%, specificity 90%, PPV 76% and NPV 95%. Conclusion CHD risk appears acceptably accurate for targeting treatment in mild hypertension. The risk assessment table, which slightly overestimates CHD risk, was more sensitive in identifying patients with CVD risk ⩾ 20% over 10 years and may be preferable to using exact CHD risk. European guidelines which suggest targeting treatment for mild hypertension at CHD risk ⩾ 20% over 10 years are over-conservative compared with British guidelines.

Population implications of lipid lowering for prevention of coronary heart disease: data from the 1995 Scottish health survey

OBJECTIVE To determine the proportion of the population, firstly, with cholesterol ⩾ 5.0 mmol/l and, secondly, with any cholesterol concentration, who might benefit from statin treatment for the following: secondary prevention of coronary heart disease (CHD); primary prevention at CHD risk 30%, 20%, 15%, and 6% over 10 years; and primary prevention at projected CHD risk 20% over 10 years (CHD risk at age 60 years if actual age < 60 years). SUBJECTS Random stratified sample of 3963 subjects aged 35–64 years from the Scottish health survey 1995. RESULTS For secondary prevention 7.8% (95% confidence interval (CI) 6.9% to 8.6%) of the population with cholesterol ⩾ 5.0 mmol/l would benefit from statins. For primary prevention, the prevalence of people at CHD risk 30%, 20%, 15%, and 6% over 10 years is 1.5% (95% CI 1.2% to 1.9%), 5.4% (95% CI 4.7% to 6.1%), 9.7% (95% CI 8.8% to 10.6%), and 32.9% (95% CI 31.5% to 34.4%), respectively. At projected CHD risk 20% over 10 years, 12.4% (95% CI 11.4% to 13.5%) would be treated with statins. Removing the 5.0 mmol/l cholesterol threshold makes little difference to population prevalence at high CHD risk. CONCLUSIONS Statin treatment would be required for 7.8% of the population for secondary prevention. For primary prevention, among other factors, guidelines should take into account the number of patients needing treatment at different levels of CHD risk when choosing the CHD risk to target. The analysis supports a policy of targeting treatment at CHD risk 30% over 10 years as a minimum, as recommended in current British guidelines, with a move to treating at CHD risk 15% over 10 years as resources permit.

Implication of recent trials with b-hydroxy-b-methylglutaryl coenzyme A reductase inhibitors for hypertension management

BACKGROUND There is broad agreement that statin treatment should be targeted at absolute coronary heart disease (CHD) risk but no consensus on the level of risk to target. We have examined the implications of adopting three different treatment policies for the management of hypertensive patients in the UK using data from treated hypertensives aged 35-69 years included in the Health Survey for England (1993). METHODS We calculated the proportion of hypertensive patients with existing atherosclerotic cardiovascular disease requiring statin treatment for secondary prevention of CHD. For those without atherosclerotic cardiovascular disease (primary prevention), we estimated CHD risk from the Framingham equation and examined the proportion with CHD risk exceeding thresholds of 4.5, 3 and 1.5% per year. RESULTS Twenty-one percent of treated hypertensives would require statin treatment for secondary prevention of CHD. When the CHD event threshold for statin treatment was set at > or =4.5% per year [equivalent to a number needed to treat (NNT) in 5 years of 13] a further 0.6% of hypertensive patients were identified for treatment; at a threshold of 3.0% per year (NNT = 20) 5.5% of patients were identified for primary prevention; and at a threshold of 1.5% per year (NNT = 40) 28.5% of patients were identified for primary prevention. CONCLUSIONS Those needing secondary prevention are first priority for statins and 21% of hypertensive patients will require treatment Formulation of guidelines for primary prevention should take into account the NNT; the proportion of patients targeted for treatment; the cost-effectiveness and the total cost of treatment. Current British guidance will entail treating an additional 5.5% of hypertensive patients for primary prevention and therefore 27% of hypertensive patients.

Dietary Supplements and their Role in the Prevention and Treatment of Coronary Heart Disease

Despite all the strategies to prevent coronary heart disease (CHD) and the advances in the treatment of existing disease it remains one of the major causes of morbidity and mortality in the Western world. The lifetime risk of coronary events is such that most adult men will suffer a coronary event and the proportion of women similarly affected, although smaller, is still sizeable. Prevention of CHD is one of the UK Government’s key targets set out in ‘Saving lives: our healthier nation’ and whilst rates of CHD have begun to fall, the UKremains one of the world’s black spots for coronary disease [1]. Although much public concern is about death from HIV and cancer, heart disease remains numerically a much greater threat to health. Even in the developing world CHD, once infrequent compared with deaths due to infectious diseases, is now an important disease.