with controlled hypertension whose absolute risk exceeds their age/sex absolute risk standard and the .... will never reach an absolute risk reduction goal of.
Journal of Human Hypertension (1998) 12, 391–395 1998 Stockton Press. All rights reserved 0950-9240/98 $12.00 http://www.stockton-press.co.uk/jhh
ORIGINAL ARTICLE
Reconciling different measures of risk in the treatment of hypertension: a community-based study T Fahey1 and TJ Peters2 1
Division of Primary Health Care and 2Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK
Background: There is disagreement as to how cardiovascular risk in hypertensive patients should be measured. In particular, whether absolute risk measurement alone is a realistic index on which to base treatment goals. Method: A cross-sectional study on 895 treated hypertensive patients in 18 general practices in the UK. Reporting on the distribution and magnitude of agespecific absolute risk. The percentage of individuals with controlled hypertension whose absolute risk exceeds their age/sex absolute risk standard and the percentage of individuals with uncontrolled hypertension whose risk is less than their age/sex absolute risk standard. Results: Overall, 62.8% (95% CI 59.6–66%) individuals had an absolute risk that exceeded 20% over 10 years. The magnitude of absolute risk was considerable (range
3.5–87.8%) and increasing absolute risk was significantly associated with age. Of those individuals with controlled hypertension 50.5% (95% CI 45.1–55.8%) had an absolute risk which exceeded their age/sex absolute risk standard. Conversely, 30.4% (95% CI 26.6–34.2%) of those with uncontrolled hypertension had an absolute risk that was less than their age/sex absolute risk standard. Conclusions: The distribution and magnitude of absolute risk is significantly associated with age. Appreciation of such a relationship is needed when setting realistic treatment goals according to an absolute risk standard, particularly in the elderly. In addition, the use an age/sex absolute risk standard is likely to further modify treatment goals in individuals at high and low absolute risk of cardiovascular disease.
Keywords: hypertension; cardiovascular risk; treatment goal
Introduction Guidelines and commentaries concerning individual and population control of raised blood pressure (BP) have recently emphasised the need to account for demographic and co-morbid factors as well as BP reading alone.1–3 By taking into account these factors, explicit calculation of absolute risk of a cardiovascular event and benefit from therapy can be made.1,4 The main consequence of this approach is that elderly individuals at higher risk of cardiovascular disease become candidates for treatment at the expense of the middle-aged, in whom the absolute likelihood of cardiovascular disease is lower.5 There are, however, misgivings about adopting an uncritical approach based on absolute risk when managing high BP.6,7 Firstly, there is concern that absolute benefits are calculated from short term randomised controlled trials. Such an approach may over emphasise absolute benefits in the elderly at the expense of lifetime/actuarial benefit in the Correspondence: Dr T Fahey, Division of Primary Health Care, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK Received 27 August 1997; revised 8 January 1998; accepted 10 January 1998
middle-aged.8 Secondly, when basing treatment decisions on absolute risk alone, no account is taken of the fact that absolute risk increases with age. A method has been proposed to account for this fact by estimating the difference between an individual’s absolute risk and the standard absolute risk for a person of the same age and sex. The resulting index of risk being known as the marginal risk.6,9 The consequence of taking a risk-based approach is that the number and category of individuals eligible for treatment will change, depending of what approach to risk is taken.9 Until now, discussion about using a reference age/sex absolute risk standard and the calculation of marginal risk has been focused on newly diagnosed hypertensive patients.9 However, in the context of achieving treatment goals amongst treated hypertensive patients, knowledge of and adjustment for the age/sex absolute risk for individuals patients has not been explored. This study aims to present data from a representative UK population of treated hypertensive patients and re-examine the magnitude of absolute risk and the use of an age/sex absolute risk standard in the context of achieving treatment goals. The objectives of this present study was two-fold. Firstly, to quantify the magnitude and distribution of age-specific absolute risk in a UK community-
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based population of hypertensive subjects. Secondly, to quantify marginal absolute risk in the context of an age/sex specific absolute risk standard amongst treated hypertensive patients. We then calculated subsequent attainment of control of hypertension according to absolute risk when compared to this marginal reference.9 Thus we were interested in the characteristics of two groups: firstly, individuals classified as having controlled hypertension by an absolute risk measurement but who had a higher marginal risk (compared to their age/sex specific absolute risk standard), and secondly those who were classified as having uncontrolled hypertension by absolute risk measurement but who had a lower marginal risk (compared to their age/sex specific absolute risk standard).
Subjects and methods Details of the methodology has been described elsewhere.10 Briefly, individual patient-based morbidity data were collected from October 1994 to February 1995 in 18 out of the 20 Oxfordshire practices who subscribe to the VAMP (Value Added Medical Products) computer system. A systematic sample of 50 patients was obtained by taking every 10th person from the practice hypertension register. To be defined as hypertensive for the purposes of this study a patient had to: (1) have the diagnosis of hypertension clearly marked in their record in the computer database; and (2) be taking BP-lowering medication at the time of the study. Calculation of individual absolute risk Morbidity data were collected so that the absolute risk of a cardiovascular event could be calculated according to the Framingham risk profile.11,12 The information required was: age, sex, systolic BP (averaged over the three most recent readings, when present), HDL cholesterol, total cholesterol, history of cigarette smoking, diabetes, left ventricular hypertrophy, atrial fibrillation and previous cardiovascular disease.11,12 Absent data were treated as missing for the purposes of absolute risk calculation. An absolute risk ⭓20% over a 10-year period was taken as ‘uncontrolled’ and ⬍20% as ‘controlled’ hypertension for the purposes of this study, consistent with hypertension guidelines that have used Framingham equations to calculate absolute risk.1
ent formats. Firstly, absolute risk is presented as a descriptive statistic (median, interquartile range, minimum and maximum) in age-specific categories. Secondly, marginal risk is presented for individuals who are deemed to have controlled (absolute risk ⭐20% over 10 years) or uncontrolled hypertension (absolute risk ⭓20% over 10 years) on an absolute risk scale according to age-specific categories. Finally, the characteristics of individuals in three categories are described: individuals with uncontrolled hypertension according to an absolute risk score alone, individuals with uncontrolled hypertension according to an absolute risk score but who have a marginal risk less than their age/sex specific absolute risk standard, and thirdly, individuals with controlled hypertension according to an absolute risk score but who have a marginal risk greater than their age/sex specific absolute risk standard.
Results Individual absolute risk Overall 562 (62.8%, 95% CI 59.6–66.0%) individuals had an absolute risk that exceeded 20% over a 10-year period. Age was significantly associated with increasing absolute risk, the percentage of individuals with an absolute risk that exceeded 20% increased from 5.2% (95% CI 1.7–11.6%) for those aged 40– 49 to 95.4% (95% CI 92.4 –97.5%) for those aged 70 to 79 (2 = test for trend, 359.5, P ⬍ 0.001). In addition, as age increases, so does the spread and magnitude of absolute risk in individuals (Figure 1). Marginal risk and relationship with absolute risk in terms of control of hypertension When individual absolute risk was subtracted from the age/sex specific absolute risk standard, 168 (50.5%, 95% CI 45.1–55.8%) individuals who were deemed to have controlled hypertension had an absolute risk that exceeded their absolute risk for age and sex, that is their marginal risk was higher than expected when compared to the age/sex specific absolute risk standard. Conversely, 171 (30.4%,
Obtaining of an age/sex specific absolute risk standard and subsequent calculation of marginal risk The age-specific absolute risk of a cardiovascular event was extracted from published Framingham data.11,12 Marginal risk was then calculated by subtracting individual absolute risk score from an age/sex specific absolute risk standard.11,12 The resulting marginal risk score obtained was an estimate of how much more or less each individual’s absolute cardiovascular risk was compared to their age/sex specific absolute risk standard. Consequently results are presented in two differ-
Figure 1 Box and whisker plot of absolute risk of a cardiovascular event (10-year period) in age-specific categories.
Risk and hypertension T Fahey and TJ Peters
95% CI 26/6–34/2%) who were deemed to have uncontrolled hypertension had an absolute risk that was less than their absolute risk for age and sex, making their marginal risk less than the age/sex specific absolute risk standard. The proportion of individuals with controlled hypertension whose marginal risk exceeded the age and sex reference standard was highest in the 40 to 49-year-old age group and diminished significantly with increasing age (2 test for trend = 66.5, P ⬍ 0.001). For individuals with uncontrolled hypertension, there were significant differences between the observed proportions of individuals with a lower absolute risk than the age/sex specific absolute risk standard, though the pattern was not a simple linear trend (2 = 20.2, degrees of freedom = 3, P ⬍ 0.001; Table 1). When the magnitude of absolute risk was examined in those with controlled hypertension (absolute risk ⭐20% over 10 years), seven individuals (7.6%, 95% CI 2.2–13.0%) aged between 40 to 49 had an absolute risk of between 10 and 20% higher than their age/sex specific absolute risk standard. Conversely, in those subjects with uncontrolled hypertension (absolute risk ⭓20% over 10 years), 36 (7.1%, 95% CI 5.0–9.6%) had an absolute risk that was between 10 and 27% below their age/sex specific absolute risk standard. Lastly, the characteristics of individuals in three categories of risk— uncontrolled according to absolute risk standard, uncontrolled according to absolute risk but with a smaller marginal risk compared to age/sex specific absolute risk standard, and controlled according to absolute risk but with a larger marginal risk compared to age/sex specific absolute risk standard—are presented in Table 2.
Discussion This study confirms that age is an important determinant of absolute risk and that poor control, defined as an absolute risk in excess of 20% over 10 years, increases with age.13 Furthermore, aging was associated with an increase in the distribution and magnitude of absolute risk in this study. In the oldest age group in this study the highest individual
Table 1 Age specific risk compared to the age/sex specific risk standard of a cardiovascular event of 10 years, for those with controlled (⬍20% absolute risk) and uncontrolled hypertension (⭓20% absolute risk) Age group (years)
40– 49 50–59 60–69 70–79
Percentage (95% CI) of individuals whose risk Marginal risk ⭓age/sex standard, even though they are controlled hypertensives
Marginal risk ⭐age/sex standard, even though they are uncontrolled hypertensives
85.9 (77.0–92.3) 44.1 (35.1–53.0) 33.9 (25.1– 42.8) 0
0 17.0 (7.7–30.8) 40.8 (34.3– 47.4) 25.3 (20.4 –30.3)
absolute risk exceeded conventional levels for controlled hypertension by a factor of two. The implication of these findings is that hypertension guidelines based on a cut-off absolute risk of 20% over 10 years fail to take into account the magnitude of absolute risk in the elderly population. As absolute risk is determined by several unalterable risk factors—age, sex, previous cardiovascular event and the presence of diabetes—most elderly individuals will never reach an absolute risk reduction goal of 20%. Hypertension guidelines need to account for this heterogeneity in absolute risk, particularly in the elderly population. A consequence of this would be that individual attainment could be set in the context of a more realistic treatment goal—an individual with an initial absolute risk of 45% reducing their risk to 30% represents highly tangible benefits in terms of reduced morbidity and mortality, which goes unrecognised when a 20% absolute risk standard is applied. The introduction of an age/sex specific absolute risk standard highlights the fact that mean absolute risk is determined by a group of individuals with a heterogeneous risk profile.4 Of those individuals with controlled hypertension, a significantly larger proportion of younger individuals had an absolute risk that exceeded the mean risk for a person of that age and sex (Table 2). Using this age/sex reference to guide individual treatment may mean more aggressive treatment of the middle-aged, compensating for over-reliance on using an absolute risk index in isolation.6 Conversely, in those with uncontrolled hypertension, although there were significant differences between the age groups, there was no linear relationship between increasing age and the proportion of individuals with a reduced risk when compared to their age/sex standard. Introduction of an age/sex reference when discussing treatment options in individual patients provides the background against which individual treatment goals can be discussed. By placing prevention of cardiovascular disease in an absolute (predicted absolute cardiovascular risk) and relative (predicted cardiovascular risk when compared to individuals of the same age and sex) context, additional information is conveyed to both patient and doctor. Thus, use of an age/sex specific absolute risk standard may help in resolving the dilemma of conveying risk to patients as either an absolute or relative risk.5,14 Using an absolute risk as the criterion to detect and control high BP is a relatively recent development.3 However, as with other cardiovascular risk factors (eg, hypercholesterolaemia and non-rheumatic atrial fibrillation)15,16 measurement of absolute risk gives a realistic index of the likely benefits and risks of treatment. Prevention of cardiovascular disease is likely to require a multi-factorial approach, both in lifestyle advice and prescription of drugs.17 In this context, age/sex reference standards should enable the realistic setting of goals in the prevention of cardiovascular disease, whether this is by means of treatment with anti-hypertensive treatment, smoking cessation, cholesterol lowering drugs or anti-thrombotic treatment.
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Table 2 Characteristics of three groups, uncontrolled, uncontrolled but with reduced age/sex marginal risk and controlled but with excess age/sex marginal risk* Uncontrolled (⭓20% in 10 yrs)
Number (%) patients Number (%) males Age (standard deviation) Mean systolic BP (standard deviation) Mean diastolic BP (standard deviation) Number (%) smokers Mean total cholesterol (standard deviation)
562 304 69 158 88 114 6.3
(63%) (54%) (7) (18) (9) (23%) (1.1)
Uncontrolled (⭓20% in 10 yrs), Controlled (⭐20% in 10 yrs), marginal risk ⬍age/sex marginal risk ⬎age/sex standard standard 171 131 68 146 86 6 6.2
(19%) (77%) (6) (14) (8) (4%) (1.2)
168 60 67 149 90 16 6.0
(19%) (36%) (8) (14) (8) (10) (1.2)
*Percentages change in each row because denominators differ because of missing data.
There are several limitations to this study. Firstly, the Framingham model may not necessarily predict cardiovascular risk in a UK population because associations between risk factors and disease may have altered over the last 30 years.4 Secondly, the population in which data from observational studies and randomised controlled trials were collected may not be representative when applied to other populations, limiting their subsequent generalisability.2 For these reasons, the probabilities of absolute cardiovascular risk may engender a false sense of precision in an individual clinical context.2 In addition, the direction of bias when making an absolute risk assessment in individuals may be difficult to predict. Observational studies on which risk calculations are based are likely to be under-estimates of risk due to imprecision of single once-off measurement.4 Conversely, patients recruited to randomised trials in the elderly were generally fitter with fewer co-morbid factors, therefore making treatment benefits potentially more substantial when applied to sicker populations.18 When making an individual choice concerning the management of hypertension, calculating the probability of a cardiovascular event is only part of the overall equation. Individual utilities-explicit, quantified choices about health states-concerning acceptance of death, disability, side effects of therapy and the consequences of labelling need to be elicited from patients before rational treatment choices are made.19,20 Recent evidence from patients with angina has shown that individual utilities differ considerably in patients with the same severity of disease when a clinical scoring system is used.21 More work is needed in hypertensive subjects to assess individual utilities and to see how they relate to absolute cardiovascular risk. Ultimately hypertension guidelines will need to acknowledge and encourage quantification of patient preferences as well as the probability of cardiovascular risk.22
Acknowledgements We would like to thank all 18 general practices for allowing us access to their computer records and clinical notes and to colleagues in the Department of Social Medicine, University of Bristol for helpful comments on earlier drafts of this paper.
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