The ACC/AHA and ESC/ESH Hypertension Guidelines: Contrasting Versions of Idiosyncratic Excellence

The American College of Cardiology/American Heart Association (ACC/AHA)1 and European Society of Cardiology/European Society of Hypertension (ESC/ESH)2 hypertension guidelines are evidence-based, highly detailed, but distinctly different approaches to the management of hypertension. Arguably though both can be described as voluminous idiosyncratic versions of excellence. And, yet, these guidelines have a few commonalities. Both guidelines emphasize the importance of accurate blood pressure (BP) measurement, obtaining out-of-office BP determinations, as well as the importance of diet and lifestyle modifications for preventing and adjunctively treating hypertension. Also, the majority of individuals who qualify for drug therapy in both guidelines do so at the 140/90 mm Hg threshold. Both guidelines detach the BP threshold for initiation of drug therapy from the ultimate on-treatment BP target. The drug classes recommended for initial therapy were similar being thiazide diuretics, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), and calcium antagonists; in the ESC/ESH guideline beta blockers were also a recommended initial therapy. The ESC/ESH guidelines are, however, more conservative in the areas of BP threshold for diagnosing hypertension, follow-up of non-hypertensive BP levels, and the timing of initiating antihypertensive drug therapy. However, their recommendation for initiating combination drug therapy is more expansive and nuanced than the ACC/AHA recommendation for prescribing two-drug therapy. In this commentary, we will compare of the ACC/AHA and ESC/ESH hypertension guidelines with focus on the following areas: (i) hypertension diagnosis, (ii) BP treatment thresholds and targets, (iii) defining high-risk status, (iv) patient evaluation, (v) initial drug therapy, (vi) combination drug therapy, and (vii) the impact of SPRINT BP measurement technique on their recommendations. Finally, consideration will be given to the factors that are likely responsible for the strikingly divergent recommendations produced by these hypertension guidelines. In the ACC/AHA guideline, hypertension is diagnosed at the ≥ 130/80 mm Hg threshold but not until BP ≥ 140/90 mm Hg in the ESC/ESH guidelines. Both guidelines recommend multiple BP readings be obtained, both in and outside of the office, to confirm the diagnosis of hypertension except in persons with extreme BP elevations (BP ≥ 180/110 mm Hg). In neither guideline does the diagnosis of hypertension equate to immediate pharmacological therapy for all diagnosed individuals. In the ACC/AHA guideline when BP is 130–139/80–89 (stage 1 hypertension), only 31% of those qualify for immediate drug therapy3; those qualifying are high-risk individuals (known cardiovascular disease or 10-year Atherosclerotic cardiovascular disease (ASCVD) risk ≥ 10%), age 65 years and older, diabetes, and/or chronic kidney disease (CKD). When BP is consistently ≥140/90 mm Hg, individuals qualify for immediate prescription of drug therapy. In the ESC/ESH guideline, low-risk hypertensive patients (those with grade 1 hypertension [BP 140–159/90–99 mm Hg]) without hypertension-mediated organ damage (HMOD) or high-risk status (cholesterol >310 mg/dl, grade 3 hypertension [BP ≥ 180/110 mm Hg], most persons with diabetes mellitus, estimated glomerular filtration rate [EGFR] 30–59 ml/minute/1.73 m2, left ventricular hypertrophy [LVH], or 10-year Systemic Coronary Risk Evaluation system [SCORE] 5%–10%) should be considered for drug therapy after 3–6 months of lifestyle modification if the BP remains hypertensive. Two commonalities between the guidelines are that lifestyle modification should be prescribed along with drug therapy and should also be prescribed for individuals, prior to initiation of drug therapy, with BP above the normal range. In the ACC/AHA guideline, the BP target is <130/80 mm Hg for most patients. Those 65 years and older have target BP <130 mm Hg systolic, however a diastolic blood pressure (DBP) target was not recommended due to the determination that the available evidence was insufficient to do so. The ESC/ESH BP target recommendations are significantly more nuanced than those in the ACC/AHA guideline. An initial BP target <140/90 mm Hg is recommended for all, if BP therapy is well tolerated. However, the ultimate BP target is <130/80 mm Hg for most patients. The influence of age on recommended BP targets is also much more evident in the ESC/ESH guidelines. A systolic blood pressure (SBP) target range of 120–129 mm Hg is specified for persons <65 years, 130–139 mm Hg systolic for those 65–79 years, 130–139 mm Hg systolic, if tolerated, for persons ≥ 80 years. The DBP target is <80 mm Hg in all individuals irrespective of age and co-morbidity. The ACC/AHA guideline considers high-risk CVD status as a compelling rationale for the initiation of drug therapy in persons with stage 1 hypertension (130–139/80–89 mm Hg). The ESC/ESH guidelines acknowledge data showing that drug-treated hypertensives with the highest pretreatment risk have the greatest absolute CVD risk reduction.4 Yet other data were cited showing only modest CVD risk reduction when high-risk patients are treated when baseline BP <140/90 mm Hg, except possibly in those with coronary artery disease (CAD). Accordingly, in the ESC/ESH guideline the only group with BP below the hypertensive range for which drug therapy was even considered was in very high-risk individuals with CVD, especially CAD, with high-normal BP (135–139/85–89 mm Hg).5 The ESC/ESH guideline recommends age-specific target BP ranges for SBP to ensure safety given the relatively low BP targets for many patients. The ACC/AHA guideline, however, did not specify lower BP bounds along with their recommended BP targets. The ACC/AHA guidelines define high risk (for CVD) as any one of the following: diabetes, CKD, prior CVD, ASCVD 10-year risk ≥ 10%, and ≥ 65 years of age. High-risk status is used to identify individuals with stage 1 hypertension who qualify for immediate drug therapy. Again, the ESC/ESH guideline is more detailed and nuanced as two elevated risk categories have been put forth—very high and high risk. Very high risk is defined as established cardiovascular or renal disease (including such conditions as myocardial revascularizations, atheromatous plaque on imaging, atrial fibrillation) as well as manifestations of HMOD; HOMD is defined as LVH, microalbuminuria, ankle brachial index (ABI) <0.9, and hemorrhages/exudates on fundoscopic examination. Consideration for drug therapy is given for this extreme risk group, although the guideline writers were more favorable for initiating drug therapy in persons with CVD, especially CAD, in individuals with high-normal BP. High risk in the ESC/ESH guidelines is defined as most persons with diabetes mellitus, CKD (EGFR 30–59 ml/minute/1.73 m2), LVH, 1-year SCORE risk 5%–10%, or very high single risk factor (cholesterol >310 mg/dl, grade 3 hypertension ≥180/110 mm Hg). Young persons with diabetes, but no other risk factors are not necessarily deemed high risk. The ESC/ESH guideline does not use high-risk status to determine who qualifies for treatment at sub-hypertensive levels (<140/90 mm Hg). Rather, in this guideline high-risk status determines who should receive immediate prescription of drug therapy in grade 1 hypertension (140–159/90–99 mm Hg). There is significant overlap in the recommended patient evaluation. Recommended testing common to both guidelines include fasting blood glucose, complete blood count, creatinine/EGFR, lipid panel, serum sodium and potassium, electrocardiogram, and a urinalysis. Unique to the ACC/AHA guidelines is Thyroid stimulating hormone and calcium. Included in the ESC/ESH panel of recommend tests, but considered optional in the ACC/AHA guideline, is urine albuminuria and uric acid. Echocardiography was also considered an optional test in the ACC/AHA guideline. Unique to the ESC/ESH guideline is liver function testing and hemoglobin A1C. The ESC/ESH guideline put forth a comprehensive panel of tests—echocardiography, carotid ultrasound, abdominal ultrasound and Doppler studies, pulse wave velocity, ABI, cognitive function testing and brain imaging—as more in-depth measures to establish the presence of HMOD. In addition, both guidelines recommend the assessment of all hypertensive individuals for orthostatic hypotension at their initial visit. This important because most patients with orthostatic hypotension do not have symptoms and patents with suggestive orthostatic symptoms infrequently have orthostatic hypotension. There is substantial though not complete agreement between these two guidelines regarding the recommended drug classes for initial therapy. The dually recommended drug classes include thiazide diuretics, calcium antagonists, ACEI and ARBs. In the ESC/ESH guidelines one additional drug class, beta blockers, has been included in initially recommended drug classes. Neither guideline recommends initiating antihypertensive drug therapy at any BP level with more than two drugs. However, the ESC/ESH recommendation is more expansive than the corollary ACC/AHA guidance regarding the initiation of two-drug therapy. The ESC/ESH guideline recommends starting treatment with two drugs, ideally a single-pill combination, in most hypertensives except frail older persons and those with low-risk grade 1 hypertension, particularly when baseline SBP is <150 mm Hg. Favored single-pill combination therapy is a thiazide diuretic or calcium antagonist plus either an ACEI or an ARB. Conversely, the ACC/AHA guideline recommends two-drug therapy when BP is >20/10 mm Hg above target. Single-pill combination therapy was not specifically recommended by the ACC/AHA guideline, however, it was acknowledged that most of the data supporting this recommendation came from single-pill combination comparisons to monotherapy. Both guidelines appear to have considered the strongly positive SPRINT study results6 when making their respective recommendations. And, both guidelines appear to have considered the method of BP measurement used in SPRINT and its impact on how SPRINT BP measurements relate to those obtained in usual clinical practice. The ACC/AHA guideline recommended a BP target <130/80 for most hypertensives despite the impressive SPRINT data clinical and mortality outcomes for the intensive (SBP target <120) compared to standard treatment (<140 mm Hg). The ESC/ESH guideline states explicitly that the SPRINT results did not clarify the optimal BP initiation threshold for drug therapy because of the use of unattended automated office BP measurement (along with a standard measurement protocol). This guideline further proffered that SPRINT SBP likely corresponded to 130–140 mm Hg (intensive group) and 140–150 mm Hg (standard group) in usual clinical practice. Avoidance of white coat hypertension was the primary reason put forth to explain the putative discrepancy between SPRINT BP readings and those obtained in routine clinical practice. The SPRINT protocol did specify a standard approach to BP measurement but actually did not provide guidance on whether measurements were to be attended or unattended. Fewer than one-half (4,087) of randomized SPRINT participants had unattended rest period and BP measurements whereas an even smaller number (2,247) had attended rest period and BP measurements.7 Despite other data suggesting substantive differences between attended and unattended BP measurements,8,9,10 in SPRINT there was essentially no difference in BP between the aforementioned groups either at baseline or during follow-up. Nor was there any difference between these two groups in the occurrence of serious adverse events or in the magnitude of reduction in the primary composite study end point. On the other hand, there is no question that BP measurements in research settings are systematically lower than those obtained in routine clinical practice.8 They always have been. Comparative research has shown that research BP measurements (attended) are ~ 9/6 mm Hg lower than BP measurements obtained in routine clinical practice.8 The difference between unattended and attended research BP measurements relative to those obtained in routine clinical practice appear to be of similar magnitude. Arguably, this suggests that the primary driver of systematically lower BP readings in research compared to clinical settings is the standard measurement protocol and BP measurement equipment, not whether the BP measurements are attended or unattended. The process of developing virtually every disease-based guideline can be characterized as a rigorous, evidence-based approach yielding distinct, voluminous, idiosyncratic recommendations for practitioners. The ACC/AHA and ESC/ESH guidelines are no exception as their writing committees produced exquisitely detailed evidence-based guidelines with distinctly different recommendations across many areas of hypertension diagnosis, evaluation, treatment, and follow-up. Given that both guidelines are evidence-based, how could their recommendations diverge as much as they do given that both writing groups had access to essentially the same body of data in the published literature? One reason perhaps is that one guideline group might consider some data not considered by other writing groups; in that regard, the ESC/ESH guideline appears to have relied more on meta-analyses than the ACC/AHA guideline. Even when identical data are considered and interpreted similarly, guideline committees will differentially weigh their importance. Data, per se, are the granular currency for developing interpretations, a necessary step when developing clinical recommendations. However, it is at this step where guideline committees most substantively differ. The differing interpretations of the target populations to which SPRINT data are relevant illustrate this point nicely. The ESC/ESH guideline explicitly stated that the overwhelming majority of patients in the SPRINT study were drug treated prior to randomization and therefore provided little information about the benefits and risks of treatment in drug naïve persons with new onset stage 1 hypertension despite endorsing a target BP <130/80 mm Hg for most hypertensives. The ACC/AHA guideline made no distinction between those with BP in the stage 1 hypertensive range as they extrapolated the positive SPRINT findings to individuals with new onset stage 1 hypertension. The ACC/AHA and ESC/ESH hypertension guidelines provide thoughtful though differing approaches to virtually every aspect of hypertension diagnosis, evaluation, treatment, and follow-up. These guidelines minimally overlap and both also differ substantively with other published guidelines. The respective guideline committees almost assuredly believe that the process they followed led to the best possible recommendations for practitioners. Yet, there is no empiric proof of this. Both guidelines offer practitioners an evidence-based, rational approach to hypertension management and treatment. Perhaps their greatest commonality is their length, complexity, and the logistical barriers to their full implementation in clinical practice.