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).
From Booth, J et al. Proceedings
of the Royal Society of Medicine. 1977.
Guest Post by
Hillel Sternlicht, MD
Author, Concepts in Hypertension Newsletter
Author, Concepts in Hypertension Newsletter
