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Blood pressure should be evaluated and treated in the context of overall cardiovascular risk
Atherothrombotic cardiovascular disease is now the leading cause of morbidity and mortality worldwide, with mortality exceeding that for the traditional scourges of infectious diseases, trauma, and malnutrition.1 Evidence suggests that most of the burden of disease is caused by unfavourable levels of several easily identified risk factors: arterial blood pressure, blood lipids, glucose concentrations, body mass index, tobacco use, and physical activity.2
Outcomes can be improved by selective interventions that drive risk factors towards optimum levels, but important questions remain about which risk factors should be treated, in which patients, to what levels, and by what means. The study in this week's BMJ by Conen and colleagues3 helps to answer some of these questions. It compares cardiovascular risk over two years in women with high normal blood pressure (130-139/85-89 mm Hg) to those with normal blood pressure (120-129/75-84 mm Hg) and those with baseline hypertension. It found that women with normal blood pressure had a lower risk of a major cardiovascular event (hazard ratio 0.61, 95% confidence interval 0.48 to 0.76) and of incident hypertension (0.42, 0.40 to 0.44) than women with high normal blood pressure.
While some risk factors, such as tobacco use, are categorical, others—blood pressure and blood lipids in particular—are continuous over a wide range. The association of increased cardiovascular disease with the highest levels of these continuous risk factors led to a strategy of identifying thresholds for individual risk factors above which treatment was recommended. It is clear now, however, that such a strategy is flawed for two reasons.
Firstly, the notion that risk factors have a threshold value below which they do not confer risk, and above which they do, is biologically implausible and empirically false. The relation between blood pressure or serum cholesterol and ischaemic heart disease is “log linear,” implying that a given change in the risk factor (such as a drop in systolic blood pressure of 10 mm Hg or a reduction in low density lipoprotein cholesterol of 1 mmol/l) reduces the incidence of heart disease by an equal proportion. This occurs regardless of its baseline value across a very broad range, and down to values rarely encountered in Western populations.4 Thus, relative risk reduction is constant, but absolute risk reduction is greater in patients with a higher baseline risk, regardless of why their baseline risk is high.
Observational data pooled from 61 prospective studies of over a million adults found proportional reductions in the incidence of mortality from stroke, ischaemic heart disease, and other vascular causes for a given reduction in systolic or diastolic blood pressure within each decade of life between 50 and 90 years.5 Risk of adverse outcomes declined down to a systolic blood pressure of 115 mm Hg, and a diastolic blood pressure of 75 mm Hg, beyond which insufficient data were available. No significant difference was seen in the relation between blood pressure and all cause mortality in men and women. The incremental risk associated with mildly raised blood pressure has been confirmed.6
The second reason why focusing on treatment thresholds of individual risk factors is a flawed strategy is that patients' overall risk of atherothrombotic disease depends on the interplay between all their risk factors. Applying a threshold for treatment for one particular risk factor ignores this and leads to recommendations to overtreat some low risk people and undertreat some high risk ones. For example, a young person who does not smoke and does not have diabetes, and who has a total cholesterol of 5.0 mmol/l and high density lipoprotein cholesterol of 1.4 mmol/l, would have a relatively low absolute risk of cardiovascular disease, even if his or her systolic blood pressure were 160 mm Hg.7 None the less, current guidelines would identify such a patient as needing antihypertensive treatment.8 9 Conversely, the same guidelines would not recommend antihypertensive treatment for an older person who smoked and who had a systolic blood pressure of 135 mm Hg, lower high density lipoprotein cholesterol, and higher total cholesterol, even though a reduction of systolic blood pressure of 10 mm Hg would reduce absolute risk more in the second patient than the first because of the higher baseline risk.7
The study by Conen and colleagues should be interpreted in this context. Because of its large number of participants and careful methodology, the findings of increased risk associated with high normal blood pressure in women are probably valid. This finding is consistent with the graduated risk of blood pressure over a broad range and has been seen in other studies. That said, it would be an oversimplification to say that the study defines a new threshold for “hypertension” that should force guidelines to be revised. Rather, it should remind practitioners that their goal should not be to treat blood pressure to achieve an arbitrary value, but to treat patients with a combination of interventions with known efficacy to lower their risk of atherothrombotic disease. This approach has been advocated for years,7 10 11 but it is not widely embraced. Such an approach requires blood pressure (even at values below 130/90 mm Hg) to be interpreted as just one factor that contributes to overall risk.
Competing interests: ISN has received payment for speaking on behalf of Merck regarding its cholesterol lowering drugs but not for several years. ISN has no current ties to Merck.
Provenance and peer review: Commissioned; not externally peer reviewed.