Central Blood Pressure for Guiding Hypertension Management
Hypertension is a common clinical problem. There is a continuous graded association of cardiovascular risk with brachial blood pressure (BP), and the clinical benefit of lowering BP with antihypertensive therapy is well accepted. Although there is no critical threshold to denote normal from abnormal brachial BP, an office brachial BP of <140/90 mm Hg is considered the optimal level to decrease risk from cardiovascular disease. Accordingly, these values represent the treatment goal in patients with hypertension who do not have associated conditions (ie, left ventricular [LV] hypertrophy) or high cardiovascular risk (ie, established coronary artery disease). More aggressive BP control is advocated in patients with compelling indications such as diabetes or proteinuria (at least <130/80 mm Hg). This approach has been questioned on the grounds that intensive therapy to lower BP does not necessarily equate to favorable clinical outcomes. Data from 3 major clinical trials in patients with type 2 diabetes and high cardiovascular risk showed no benefit, or possible harm, from intensively lowering BP. Similar observations have been reported in antihypertensive trials of patients with acute coronary syndrome, ischemic stroke, cardiovascular disease, or diabetes with end-organ damage. Furthermore, a Cochrane review concluded that antihypertensive therapy in elderly people (≥80 years) was of no benefit with respect to reducing all-cause mortality. Notwithstanding the large body of evidence showing the clinical benefits of antihypertensive therapy in people with high BP, the above findings support a rationale to explore approaches beyond aggressive antihypertensive therapy in the care of patients with hypertension.
In studies used to inform hypertension management guidelines, office BP has been measured by conventional upper arm (brachial artery) cuff methods. This technique is commonly used in clinical practice, and physicians rely on this information when making diagnostic and therapeutic decisions. There are several shortcomings with reliance on office brachial BP for these purposes. One major deficiency is that out-of-office BP values (eg, home or 24-hour ambulatory BP [24-ABPM]) are stronger determinants of cardiovascular morbidity and mortality compared with in-office BPs. Thus, reliance on office brachial BP alone may provide an inaccurate assessment of BP control, which could lead to either inadequate therapy (as in the case of masked hypertension) or possible unnecessary therapy (as in the case of white-coat hypertension with no other risk factors). Another shortfall of office brachial BP is that there is distortion of the arterial pressure pulse within the large arteries such that brachial systolic BP (SBP) may be significantly higher than central (ascending aortic) SBP. Indeed, although diastolic BP remains similar between the aorta and brachial artery (eg, 1–3 mm Hg), among individuals with similar brachial SBP, central SBP may be highly variable (ranging from 2 to >30 mm Hg lower) regardless of age, gender, or disease status. Thus, upper-arm SBP and pulse pressure are only estimations of pressure load experienced by the organs and a proxy of true risk related to BP.
Central BP can now be estimated rapidly and noninvasively by radial tonometry using commercially available equipment. The clinical significance of central BP indices, above and beyond brachial BP, has been consistently demonstrated in longitudinal observational studies, and these data were recently examined by meta-analysis wherein central hemodynamics were shown to independently predict future cardiovascular events and all-cause mortality. A more recent study reported that office estimates of central BP were more valuable in terms of predicting future mortality compared with the current reference standard of 24-ABPM. Most importantly, different antihypertensive agents can have significantly greater BP lowering effects on central aortic SBP compared with brachial SBP, but these effects cannot be ascertained by conventional upper-arm BP. Taken altogether, there may be a risk of overtreatment where titration decisions are based on brachial BP alone, whereas reducing therapy in lower risk patients may be possible when central BP is taken into consideration. Despite the apparent clinical superiority of central compared with brachial BP, to our knowledge, there are no reported studies that have sought to determine if knowledge of central BP values could help physicians with their therapeutic decisions. Moreover, we are unaware of evidence to suggest that treatment decisions based on central versus brachial BP may change or improve clinical outcomes. The Blood Pressure for GUIDing managEment (BP GUIDE) study aims to address these issues.
Background and Rationale
Hypertension is a common clinical problem. There is a continuous graded association of cardiovascular risk with brachial blood pressure (BP), and the clinical benefit of lowering BP with antihypertensive therapy is well accepted. Although there is no critical threshold to denote normal from abnormal brachial BP, an office brachial BP of <140/90 mm Hg is considered the optimal level to decrease risk from cardiovascular disease. Accordingly, these values represent the treatment goal in patients with hypertension who do not have associated conditions (ie, left ventricular [LV] hypertrophy) or high cardiovascular risk (ie, established coronary artery disease). More aggressive BP control is advocated in patients with compelling indications such as diabetes or proteinuria (at least <130/80 mm Hg). This approach has been questioned on the grounds that intensive therapy to lower BP does not necessarily equate to favorable clinical outcomes. Data from 3 major clinical trials in patients with type 2 diabetes and high cardiovascular risk showed no benefit, or possible harm, from intensively lowering BP. Similar observations have been reported in antihypertensive trials of patients with acute coronary syndrome, ischemic stroke, cardiovascular disease, or diabetes with end-organ damage. Furthermore, a Cochrane review concluded that antihypertensive therapy in elderly people (≥80 years) was of no benefit with respect to reducing all-cause mortality. Notwithstanding the large body of evidence showing the clinical benefits of antihypertensive therapy in people with high BP, the above findings support a rationale to explore approaches beyond aggressive antihypertensive therapy in the care of patients with hypertension.
In studies used to inform hypertension management guidelines, office BP has been measured by conventional upper arm (brachial artery) cuff methods. This technique is commonly used in clinical practice, and physicians rely on this information when making diagnostic and therapeutic decisions. There are several shortcomings with reliance on office brachial BP for these purposes. One major deficiency is that out-of-office BP values (eg, home or 24-hour ambulatory BP [24-ABPM]) are stronger determinants of cardiovascular morbidity and mortality compared with in-office BPs. Thus, reliance on office brachial BP alone may provide an inaccurate assessment of BP control, which could lead to either inadequate therapy (as in the case of masked hypertension) or possible unnecessary therapy (as in the case of white-coat hypertension with no other risk factors). Another shortfall of office brachial BP is that there is distortion of the arterial pressure pulse within the large arteries such that brachial systolic BP (SBP) may be significantly higher than central (ascending aortic) SBP. Indeed, although diastolic BP remains similar between the aorta and brachial artery (eg, 1–3 mm Hg), among individuals with similar brachial SBP, central SBP may be highly variable (ranging from 2 to >30 mm Hg lower) regardless of age, gender, or disease status. Thus, upper-arm SBP and pulse pressure are only estimations of pressure load experienced by the organs and a proxy of true risk related to BP.
Central BP can now be estimated rapidly and noninvasively by radial tonometry using commercially available equipment. The clinical significance of central BP indices, above and beyond brachial BP, has been consistently demonstrated in longitudinal observational studies, and these data were recently examined by meta-analysis wherein central hemodynamics were shown to independently predict future cardiovascular events and all-cause mortality. A more recent study reported that office estimates of central BP were more valuable in terms of predicting future mortality compared with the current reference standard of 24-ABPM. Most importantly, different antihypertensive agents can have significantly greater BP lowering effects on central aortic SBP compared with brachial SBP, but these effects cannot be ascertained by conventional upper-arm BP. Taken altogether, there may be a risk of overtreatment where titration decisions are based on brachial BP alone, whereas reducing therapy in lower risk patients may be possible when central BP is taken into consideration. Despite the apparent clinical superiority of central compared with brachial BP, to our knowledge, there are no reported studies that have sought to determine if knowledge of central BP values could help physicians with their therapeutic decisions. Moreover, we are unaware of evidence to suggest that treatment decisions based on central versus brachial BP may change or improve clinical outcomes. The Blood Pressure for GUIDing managEment (BP GUIDE) study aims to address these issues.