Epidemiology of blood pressure guidelines: out with the old, in with the new?

This editorial refers to ‘Cardiovascular risk across blood pressure categories defined by the 2024 ESC and 2023 ESH hypertension guidelines: insights from a Korean Nationwide Cohort Study’, by D.Y. Cheon et al., https://doi.org/10.1093/eurjpc/zwaf573. Blood pressure (BP) guidelines have been available for decades and are a cornerstone in the modern management of hypertension. The first American guidelines were published in the 1970s and the first joint European one in 2003.1,2 Many other BP guidelines are available from continental and national professional societies. Furthermore, BP guidelines are regularly updated as new evidence accrues, with the latest European guideline published in 2024 and the latest American one in 2025.3,4 According to the European Society of Cardiology (ESC), their guidelines are designed to ‘evaluate and summarize available evidence with the aim of assisting health professionals in proposing the best diagnostic or therapeutic approach for an individual patient with a given condition’.3 Similarly, the American College of Cardiology (ACC)/American Heart Association (AHA) state that their guidelines, ‘are based on systematic methods to evaluate and classify evidence’ and are designed to ‘improve quality of care’.4 Therefore, the core purpose of these BP guidelines is unquestionably clinical. Neither the ESC nor the ACC/AHA explicitly state that their BP guidelines have a core research purpose. Nonetheless, BP guidelines are also of major interest to academic researchers. As a case in point, the 2024 ESC BP guidelines have been cited over 1300 times in the first year since publication.3 Research related to guidelines is justified and necessary. First, by summarizing and evaluating the most recent evidence, guidelines are well positioned to identify gaps in clinical knowledge that need to be filled by future research. Second, it is necessary that researchers model the implications of guideline recommendations (particularly new or updated recommendations) on future clinical care. Impactful research in the wake of BP guidelines has been published on the prevalence of adults fitting the particular BP classifications provided by the guidelines and on the numbers of adults in the population who are eligible for the main treatment recommendations.5 Third, after the guidelines have been released and disseminated, it is important that research efforts track the actual implementation of recommendations into routine clinical care. To take just one example, the 2024 INTERASPIRE study showed that only 38.6% of coronary heart disease patients in 14 countries from all 6 World Health Organization regions are treated to the appropriate guideline-recommended secondary prevention BP target of <130/80 mmHg.6 However, sometimes guidelines generate research that could be argued to be circular in logic. This can happen when a guideline uses previously reported research to make a specific recommendation but then that specific recommendation is subjected to new but repetitive forms of the same type of research in order to confirm its validity. Should we really be surprised when a recommendation based on robust but ‘old’ research is confirmed, simply based on repeating the same type of research but in a ‘new’ form? Epidemiologic research is particularly susceptible to this type of recursive circularity. For example, to simplify communication and clinical decision-making, BP guidelines provide recommendations for the categorization of BP. These BP categories can differ across various guidelines and change over time with new evidence. This is especially true when categorizing the BP level considered to be abnormal. Indeed, there is no universally agreed criteria to define abnormality in medicine [i.e. one can theoretically define abnormality of BP based on a cut-point in the population distribution of BP (e.g. 99th percentile), or based on the BP level above which risk for cardiovascular disease (CVD) is increased, or based on other considerations]. Complicating matters, the true relationship between BP and CVD risk is continuous and log-linear in nature, rather than categorical. Based on a large body of previously published (i.e. old) evidence, the 2024 ESC guidelines proposed three simplified BP categories: (i) non-elevated (office BP <120/70 mmHg), (ii) elevated (office BP 120–139/70–89 mmHg), and (iii) hypertension (office BP ≥140/90 mmHg).3 The BP range for the elevated category was chosen by the ESC in large part because numerous randomized clinical trials have shown that treatment with BP-lowering medication down to an average achieved systolic BP of 120 mmHg can reduce subclinical and clinical CVD among adults with both hypertensive and non-hypertensive BP levels, though for the latter only in the concomitant setting of high CVD risk.3,7 Non-elevated was then chosen by the ESC as the categorical term to use for those with BP <120/70 mmHg because a wealth of epidemiologic studies from all regions of the world have consistently demonstrated that relative risk for CVD is beginning to increase at BP levels starting from at least 115/70 mmHg and perhaps even from systolic BP levels as low as 90 mmHg.3,8 Therefore, at least from a prognostic point of view, labelling persons with BPs <120/70 mmHg as ‘normal’ might be misleading (we simply do not know what a normal BP is) and might demotivate primordial CVD prevention via healthy lifestyle choices. In this issue of the European Journal of Preventive Cardiology, Cheon and colleagues report new research on the prognostic significance of the three BP categories recommended by the 2024 ESC guidelines.9 The authors study a composite outcome of CVD and death and include a ‘real-world’ registry sample of 2 604 340 Korean adults without prior CVD and who had a mean of 12 years follow-up starting from 2009. They found that, relative to the non-elevated BP category, both the elevated BP and hypertension categories had significantly higher risks for the composite outcome [adjusted hazard ratio (aHR) 1.07 (95% CI: 1.06–1.08) and 1.20 (95% CI: 1.19–1.22), respectively]. Risks for the individual outcomes of ischaemic stroke and myocardial infarction were also higher in both the elevated BP and hypertension categories. These findings from Korea are not surprising given that the ‘old’ epidemiologic research mentioned above has already shown beyond doubt that CVD risk beginnings to increase at BP levels starting from at least 115/70 mmHg.3,8 Furthermore, this excess CVD risk from BP is known to be present in all races and ethnicities. The seminal report by Lewington and colleagues on this topic even included prognostic BP data from ∼100 000 Asian participants.8 Besides confirming prior epidemiologic research in a real-world sample of Korean adults, what else can we learn from the well-conducted report by Cheon and colleagues? While the increases in relative risk for each BP category in their study were of statistical significance, they were arguably quite modest clinically (7% relative risk increase for elevated BP and 20% relative risk increase for hypertension). In contrast, in one of the first descriptions of hypertension as a risk factor for CVD from a 1957 report of the Framingham Heart Study, the relative risk increase of CVD events among hypertensive persons was four-fold (400%).10 Similarly, an approximately two-fold (200%) increased relative risk for CVD associated with BPs in the elevated range (office BP 120–139/70–89 mmHg) was reported decades ago.10 We hypothesize that the lower than anticipated relative risks in the present report by Cheon et al.9 may be explained in part by the fact that all included participants were eligible for BP-lowering treatment as deemed clinically necessary (either prior to baseline or during follow-up). Therefore, this is not a natural history study of the effects of untreated BP. In fact, over one quarter of participants in this Korean study were already on BP-lowering medications at baseline. Treatment of hypertension during follow-up would be expected to attenuate the true epidemiologic risk for CVD for BP levels in the elevated and hypertension categories. Another possible explanation for the lower than anticipated relative risks reported by Cheon et al.9 is the fact that the authors excluded events during the first year after baseline BP was measured. While this approach is reasonable to reduce bias from reverse causation, it is also likely to significantly reduce the magnitude of true risk for the various BP categories endorsed by the 2024 ESC guideline. In conclusion, the current study takes a new and fresh look at an old research question and, thankfully, confirms the prior studies used by the 2024 ESC guideline to generate their BP categories. In reporting lower than anticipated magnitudes of CVD risk for these BP categories, this study also reminds us that sometimes, like good wine, old natural history epidemiology research can actually be better than new epidemiology research, especially when the latter studies are conducted in the setting of widespread use of contemporary prevention treatments. Sarah Carolan [Writing—original draft (lead)], and John William McEvoy (Conceptualization [lead]; Supervision [lead]; Writing—review & editing [lead]) None. No new data were generated or analysed in support of this editorial, besides data reported in the manuscript by Cheon et al.