Wednesday, October 10, 2018

The curse of wisdom—making sense of the ever-changing blood pressure targets Part 1

The curse of wisdom—making sense of the ever-changing blood pressure targets
Part 1

“All things will be ambiguous, for this is the curse of wisdom.” -Greg Bear (1951-present)

            Our initial understanding of hypertension, like others disease states, evolved fitfully.  While the circulatory system was first identified by Harvey in the early 1600s, a full century would pass before Stephen Hales cannulated the carotid artery of a horse (Circa 1730) and observed the bobbing of its blood in a glass tube. Incremental advances over the subsequent 125 years allowed for measurement of blood pressure in the 1860s through radial artery pulsation analysis both invasively (Etienne Marey) and ultimately non-invasively (Samuel Siegfried Karl Ritter von Basch). These efforts culminated in Nikolai Korotkov’s description (1905) of the sounds generated by the turbulent blood flow created upon relief of an upstream arterial occlusion. Of course, the ability to externally compress a vessel would not have been possible without the introduction of a brachial artery cuff by Scipione Riva-Rocci’s (1900).         

            In the decades that followed, an approximate sense of readings consistent with “normal” and elevated blood pressures emerged. Perhaps even before the 1930’s, “hypertension” was an accepted medical term. However, at that time, it was purely descriptive (i.e. blood pressure higher than the normal) and did not connote a pathologic process. Eminent physicians of that era such as Paul Dudley White felt elevated blood pressure was an adaptive response necessary to ensure satisfactory perfusion; therefore, hypertension was not only benign but also essential. 
Concerned with offering policies to only the healthiest of individuals, it was life insurance actuaries that unequivocally noted the pathologic significance of elevations in blood pressure. As noted by the New York Life statistician Louis Dublin in 1949, “It is clear from the table that mortality rises steadily and markedly with increasing elevation of both the systolic and diastolic pressure.” (Dublin Length of Life 1949). So it began, the journey of blood pressure control as defined by the actuarial scientist. 


 From Dublin, L et al. Length of Life: A study of the life table. 1949.

             In light of this multi-century journey from discovering and measuring blood pressure to identifying harmful elevations in the same, the number and scope of therapeutic trials in the last 50 years is dizzying. From the first randomized controlled trial (VACoop1 in 1967)
seeking to establish whether diastolic blood pressures between 115-129mm Hg merit treatment, double-blind randomized trials, each with thousands and often tens of thousands of patients have been realized. For example, as early as 1979, the Hypertension Detection and Follow up trial enrolled 11,000 individuals and in 1985 the Medical Research Council study recruited 17,000.  Research has not only focused on the effects of an achieved blood pressure on broad outcomes such as all-cause mortality, but whose primary outcome is geared towards a specific disease state such as preeclampsia (CHIPS NEJM 2015), secondary stroke prevention (SPS3 Lancet 2013), kidney and disease progression (MDRD NEJM 1994).  Other trials have focused on optimal agents for various clinical scenarios such as resistant hypertension (PATHWAY-2 Lancet 2015), the elderly (SystEur Lancet 1997), or establishing the preferred second agent when monotherapy is insufficient (ACCOMPLISH NEJM 2008). Moreover, there are dozens of trials comparing anti-hypertensive classes through the application of similar achieved blood pressures in each arm. These range from the very broad to specialized populations such as AA with CKD (AASK JAMA 2001) or normotensives with coronary artery disease (CAMELOT JAMA 2004).