Author + information
- Paolo Verdecchia, MDa,∗ (, )@ospedaleperugia@UniperugiaNews,
- Fabio Angeli, MDb and
- Gianpaolo Reboldi, MD, PhD, MScc
- aFondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital Santa Maria della Misericordia, Perugia, Italy
- bDivision of Cardiology and Cardiovascular Pathophysiology, Hospital Santa Maria della Misericordia, Perugia, Italy
- cDepartment of Medicine, University of Perugia, Perugia, Italy
- ↵∗Address for correspondence:
Dr. Paolo Verdecchia, Fondazione Umbra Cuore e Ipertensione-ONLUS, Division of Cardiology, Hospital Santa Maria della Misericordia, Piazzale G. Menghini 1, Perugia 06156, Italy.
In untreated hypertensive patients with systolic blood pressure (BP) ≥160 mm Hg or diastolic BP ≥100 mm Hg, guidelines concur in recommending prompt initiation of antihypertensive drug treatment in addition to lifestyle measures (1–3). If BP is lower, in the range of 140 to 159 mm Hg systolic or 90 to 99 mm Hg diastolic, the 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines recommended pharmacological treatment only in the presence of target organ damage or established cardiovascular (CV) disease (2). The 2018 ESH/ESC guidelines, anticipated at the 2018 ESH meeting in Barcelona (4) and to be published in concomitance with the 2018 ESC meeting in Munich, adopted a more liberal position in recommending antihypertensive drug treatment in addition to lifestyle measures in all individuals with systolic BP (SBP) 140 to 159 mm Hg or diastolic BP (DBP) 90 to 99 mm Hg, even in those at low or moderate CV risk. Such position coincides with that of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines, approved also by another 9 scientific societies in the United States, which recommend antihypertensive drug treatment in all subjects with SBP 140 to 159 mm Hg or DBP 90 to 99 mm Hg, regardless of their absolute CV risk (3).
Hence, it is without question that there is agreement among the societies that subjects with SBP/DBP ≥140/90 mm Hg should be treated at any level of total CV risk. However, recommendations are not univocal in subjects with SBP/DBP between 130/80 and 139/89 mm Hg (5). Two preliminary considerations should be made. First, these subjects represent a non-negligible proportion of the general population. The 2011 to 2014 NHANES (National Health and Nutrition Examination Survey) showed that these subjects are 13.7% (95% confidence interval: 12.7% to 14.9%) of all U.S. adults not taking antihypertensive medications (6). Second, it is a fairly heterogeneous cohort in terms of absolute CV risk (6). About 4.2% of the individuals have a history of established CV disease, 9.1% have diabetes, 3.4% have chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m2), and 15.6% have a 10-year predicted cardiovascular disease risk (pooled cohort risk equations) ≥10% (6).
Unfortunately, guidelines use different expressions to categorize these subjects. For instance, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure included these subjects in the category of “pre-hypertension” (120 to 139/80 to 89 mm Hg), a definition aimed to identify subjects “at high risk of developing hypertension” (7). Conversely, the 2013 (2) and 2018 ESH/ESC guidelines (4) and the Canadian guidelines (8) adopted the term “high-normal BP” instead of “pre-hypertension” to emphasize the concept that BP values in the range of 130 to 139/85 to 89 mm Hg are in no way synonymous with hypertension. A completely different approach has been adopted by the 2017 ACC/AHA hypertension guidelines, which included the subjects with SBP/DBP 130 to 139/80 to 89 mm Hg in the category of Stage I hypertension (3). This decision was based on evidence from individual studies and meta-analyses that the hazard ratios for coronary artery disease and stroke are significantly increased in these subjects with Stage I hypertension versus those with BP <120/80 mm Hg (3).
Regardless of the different definitions, the key question is whether pharmacological treatment must be initiated when BP is 130 to 139/80 to 89 mm Hg. Regrettably, there are no event-based placebo-controlled studies in this group of subjects, and therefore, guidelines must rely on observational studies and meta-analyses. The 2017 ACC/AHA hypertension guidelines clearly recommended drug treatment, in addition to lifestyle measures, in these subjects in the presence of at least 1 of the following conditions: 1) diabetes; 2) chronic kidney disease; 3) a history of cardiovascular disease (including heart failure, stable ischemic heart disease, and peripheral artery disease); 4) a predicted 10-year CV risk ≥10%; 5) age ≥65 years (3). The position of the 2018 ESH/ESC guidelines is more complex (4). Subjects with SBP/DBP 130 to 139/85 to 89 mm Hg “may be considered” for drug treatment only in the presence of established CV disease (especially coronary artery disease), or whether their BP approaches 140/90 mm Hg even if their absolute CV risk is low or moderate (4). The list of conditions denoting established CV disease is very long, encompassing transient ischemic attack, angina pectoris, stroke, cerebral hemorrhage, myocardial infarction, coronary revascularization, atherosclerotic plaques, heart failure, peripheral artery disease, chronic kidney disease, and atrial fibrillation. Intriguingly, initiation of antihypertensive treatment in hypertensive patients with diabetes is recommended by the 2018 ESH/ESC guidelines only if untreated BP is >140/90 mm Hg, with a target SBP ≤130 mm Hg (but not <120 mm Hg). For unclear reasons, such a BP goal is recommended only in diabetic patients with pre-treatment SBP >140 mm Hg, not in diabetic patients with “high-normal” BP.
For the considerations outlined in the preceding text, it appears timely and important to conduct outcome-based studies to stratify the risk of CV disease and mortality in subjects with SBP/DBP 130 to 139/80 to 89 mm Hg in relation to the existence of clinical conditions that would dictate the initiation of antihypertensive treatment.
In this issue of the Journal, Colantonio et al. (9) present an analysis of the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, a prospective population-based study. Subjects entered the study in years 2003 to 2007 and were followed up to year 2014. Overall, 4,094 major CV events occurred. As expected, there was a rise in the rate of CV events across the 3 BP categories defined by the 2017 ACC/AHA hypertension guidelines (<130/80, 130 to 139/80 to 89, and ≥140/90 mm Hg). The authors categorized subjects by absence or presence of antihypertensive drug treatment at study entry. Subsequently, each of the 2 groups was subdivided by presence or absence of clinical conditions dictating initiation (in untreated subjects) or intensification (in treated subjects) of drug treatment according to the 2017 ACC/AHA guidelines. An interesting part of the study was the analysis of untreated subjects with baseline SBP/DBP 130 to 139/80 to 89 mm Hg. In this group, the rate of CV disease and all-cause mortality (per 1,000 person-years) was 6-fold higher among participants with 2017 AHA/ACC indication to initiate drug treatment (20.5 and 29.6, respectively) than in those without such indication (3.4 and 4.8, respectively). When restricting the analysis to treated subjects with SBP/DBP 130 to 139/80 to 89 mm Hg, the rate of CV disease and all-cause mortality was considerably higher among those with 2017 ACC/AHA indication to intensify drug treatment (22.4 and 29.9, respectively) than in those without such indication (3.8 and 5.6, respectively).
The study by Colantonio et al. (9) is timely and important because it supports the position of the 2017 ACC/AHA indications to initiate or intensify drug treatment in subjects with SBP/DBP 130 to 139/80 to 89 mm Hg in the presence of well-defined clinical markers of increased CV risk. A major limitation of the study is the lack of information on initiation, intensification, or tolerance of pharmacological treatment during follow-up. As acknowledged by the authors, some of the subjects may have initiated drug treatment at different times of follow-up, with expected prognostic benefit. CV risk in those with an indication for initiation or intensification of drug treatment could thus be actually higher than that estimated at entry.
Lastly, the study by Colantonio et al. (9) also lends some support to the 2018 ESC/ESH guidelines recommendation to initiate antihypertensive drug treatment at least in some individuals with “high-normal BP” (SBP/DBP 130 to 139/85 to 89 mm Hg) and increased CV risk. Future studies should clarify the cost-effectiveness of treating, or intensifying treatment, in this large proportion of subjects so frequently encountered in everyday clinical practice.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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