High Blood Pressure in Coronary Artery Disease: When to Start Treating and What to Target?

Michael Böhm; Felix Mahfoud

Disclosures

Eur Heart J. 2018;39(43):3864-3866. 

Arterial hypertension is the most significant global risk factor for cardiovascular morbidity and mortality, exhibiting the highest prevalence worldwide, though being approachable by different antihypertensive treatments. During the last decades, controversial discussions were held around optimal blood pressure (BP) values, providing the largest benefit of preventing cardiovascular events in patients with different levels of risk while also being safe.[1] Previous guidelines for hypertension management recommended BP targets of <140/90 mmHg for most patients.[2] The recent guidelines of the American College of Cardiology and the American Heart Association revised the definition of hypertension and, in particular, changed the BP targets in high-risk patients to even lower values (<130/<80 mmHg),[3] which will also be proposed by the 2018 European Society of Cardiology/European Society of Hypertension guidelines.[4] Evidence for lower BP goals was provided by the Systolic Blood Pressure Intervention Trial (SPRINT),[5] which indeed had an impact on the recommendations provided by the new guidelines.[3,4] SPRINT was an NIH-funded study, randomizing patients to an intensive BP control arm (<120 mmHg) compared with a more lenient BP-lowering strategy (<140 mmHg). Numerous discussions, even viewpoints from different individuals and geographies, have critically discussed SPRINT, mainly addressing the unique technique of unattended BP measurements, patient selection, patients' risk profiles, and applied antihypertensive drugs.[6–8]Further supported by large meta-analysis,[9,10] the new guidelines introduced a BP target of 120–129 mmHg systolic (SBP) and 70–79 mmHg diastolic (DBP). The critical point in this context is the fact that these recommendations in clinical practice will be applied to high-risk patients, including those with coronary artery disease, although only very few patients in SPRINT had evident disease of the coronary arteries. In addition, a minority of patients were considered normotensive according to the 2013 guidelines, and left untreated. Therefore, the question arises of whether in individuals with coronary artery disease being normotensive according to previous guidelines (BP goal of <140 mmHg), BP-lowering treatment should be initiated early to achieve an SBP of <130 mmHg and <80 mmHg, respectively. Finally, SPRINT used unattended automated BP measurements, a unique technique, which has not made its way into daily practice. BP obtained by this measurement modality has been shown to be ~7 mmHg lower than average daytime ambulatory and ~15 mmHg lower than standard office BP readings.[9,10]

Investigators of the CLARIFY registry around Emmanuelle Vidal-Petiot should be congratulated for adding an important piece of evidence to the extensive speculations in the field of optimal BP thresholds, generated in previously normotensive individuals from a large real-world patient cohort with coronary artery disease (a total of 31 303 individuals, of which 5956 were normotensive). They separated non-hypertensive individuals according to previous guidelines into groups with on-treatment BP levels of 130–139 mmHg, 120–129 mmHg, and <120 mmHg for SBP and 80–89 mmHg, 70–79 mmHg, and <70 mmHg for DBP, respectively.[10] They documented similar risk between patients with SBP values of 120–129 mmHg and 130–139 mmHg. Risk was lower in those patients at an achieved DBP of <79 mmHg compared with 80–89 mmHg, where risk increased. Interestingly, neither for SBP nor for DBP was risk amplified at low levels (SBP <120 mmHg or DBP of <70 mmHg), suggesting the absence of a J-curve in this particular population.

These findings shed a critical light on the BP risk association in high-risk patients with coronary artery disease, because this population was under-represented in previous trials, including SPRINT. A recent meta-analysis of SPRINT showed that intensive BP control resulted in similar risk reductions in patients with and without cardiovascular disease.[11] Interestingly, the J-curve observed in SPRINT was analogous in those with and without cardiovascular disease.[11] In the study of Vidal-Petiot et al. published in this issue of the European Heart Journal,[10] increased risk at particularly low SBP (<120 mmHg) and DBP (<70 mmHg) was not observed. This is in contrast to the total population of CLARIFY[12] and an analysis from ONTARGET, a population with high risk mainly after a cardiovascular event such as stroke or myocardial infarction.[13] Although there is a discrepancy between CLARIFY,[12]ONTARGET,[13] and SPRINT[11] in this regard, one might speculate that risk in patients with hypertensive-mediated organ damage or previous hypertension could follow a J-curve, while this was not observed in the non-hypertensive subgroup of CLARIFY.[10]Remarkably, in this report[10] the risk significantly increased in patients with DBP >80 mmHg, which was also in line with previously published studies.[11–13] Therefore, the guideline-recommended target in patients with coronary artery disease of DBP >70 to <80 mmHg is supported by this analysis, while it is less significant for the SBP target of <130 mmHg. It is important to reiterate that in high-risk patients with reasonably controlled SBP (120–140 mmHg) and in patients with a SBP control according to the new guidelines (120–129 mmHg), the J-shape curve for DBP persisted.[14] As DBP typically follows SBP, it might be clinically important that very low levels of DBP may occur particularly when lower SBP targets are recommended by guidelines and targeted. Thus, in patients with co-morbid cardiovascular disease and hypertension, this might be relevant,[11–14] but probably not in non-hypertensives. Therefore, the 2018 ESC/ESH guidelines for hypertension management[4] introduced a target BP window with a lower boundary for SBP and DBP, because the J-curve phenomenon was shown in several studies, including SPRINT,[11] CLARIFY,[12] and ONTARGET.[13] Another problem arises from the fact that controlling SBP to targets might inevitably be accompanied by a drop in DBP <70 mmHg. It indeed remains unclear whether in the latter case SBP control provides enough benefits to over-ride the risks associated with too low DBP values. From a scientific standpoint, targeting SBP levels in the high 120–129 mmHg but avoiding those low DBP levels might render patients at lower risk. The open question is whether such a granular and precise BP adjustment is clinically achievable at all. The report by Vidal-Petiot et al.[10] precisely addresses the question of when to initiate antihypertensive treatment in patients with high risk due to coronary artery disease and high BP (>130–139 mmHg). However, it is of equal importance whether in treated patients with hypertension, medical treatment should be further intensified at BP levels of 130–139 mmHg to achieve targets of 120–129 mmHg at a DBP of 70–79 mmHg. It should indeed encourage investigators to conduct an analysis from this and other databases in response to this unanswered question. In conclusion, the analysis from CLARIFY[10] provides another piece in the puzzle from observational and post-hoc analyses, which are of extreme importance to gain further insight into optimal BP management strategies, in particular when strict BP control is mandated in high cardiovascular risk patients, where data are still sparse.

Take Home Figure.

(A) Achieved blood pressure, SBP (upper part, red) and DBP (lower part, blue), and hazard ratio for the composite of cardiovascular death, myocardial infarction, and stroke in normotensive individuals with coronary artery disease.10 There was no significant difference in adjusted hazard ratios for SBP but a significant increased risk for DBP >80–89 mmHg but not below that. These data were derived in non-hypertensive individuals showing that only an increased DBP >80 mmHg is associated with increased risk. (B) In non-hypertensives with coronary artery disease, there is no association of risk with achieved SBP between <120 mmHg and 139 mmHg (upper part, left) and an increased risk at DBP 80–89 mmHg (lower part, left). In hypertensives, no data are available with this specific approach. According to the CLARIFY12 and the ONTARGET13 databases, at particularly low SBP and DBP as well as BPs >130 mmHg >80 mmHg, risk is increased.

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