systolic/diastolic blood pressure that persistently exceeds 140/90 mmHg in the
clinical setting, although the most recent guidelines for hypertension management
suggest that for individuals over 60, this cut point should be 150/90 (James et al.
2013 ). An estimated 78 million adults in the USA (33% of the population) are
reported to have hypertension (Go et al. 2013 ). Over the past five decades,
numerous clinical trials and epidemiological studies that have longitudinally eval-
uated the risks associated with varying levels of blood pressure show that hyper-
tension is a significant risk factor for cardiovascular disease and stroke (e.g., James
1991 ; Wong et al. 2012 ; James et al. 2013 ). Because of this association, the
pharmaceutical industry has produced a cornucopia of drugs designed to either
lower circulatingfluid volume, lessen arterial vasoconstriction, or promote arterial
vasodilation as a means of lowering blood pressure, so that people with hyper-
tension can presumptively decrease their risk of cardiovascular morbidity and
mortality to that of people with“normal”blood pressure levels (Wong et al. 2012 ;
James et al. 2013 ).
While the level of ausculted blood pressure measured in the physician’soffice
has been a standard of cardiovascular health determination, the circadian variation
of blood pressure, until relatively recently, has been of minimal interest. The
increasing use of automated ambulatory blood pressure monitors in cardiovascular
medicine over the past three decades has confirmed that there is enormous intraday
variability in blood pressure (James2007a; Flores 2013 ). Health conditions such as
white coat hypertension (Pickering et al. 1988 ; Ohkubo et al. 2005 ) and masked
hypertension (Ohkubo et al. 2005 ; Pickering et al. 2007 ; Angeli et al. 2010 ) have
been defined from the difference in blood pressures measured in the clinic and over
24h during daily life, and recent studies suggest that there is a significant difference
in cardiovascular morbidity risk associated with these designations (e.g.,
Konstantopoulou et al. 2010 ; Pierdomenico and Cuccurullo 2011 ; Hermida et al.
2012 ). Other aspects of the circadian variation in blood pressure, such as the
waking–sleep difference in blood pressure (dipping) (Fagard et al. 2009 ; Cuspidi
et al. 2010 ; Hansen et al. 2011 ) and the surge in pressure upon awakening (Kario
2010 ; Yano and Kario 2012 ) have also been shown to predict cardiovascular
morbidity and mortality (James 2013 ). In a recent study that pooled data from 11
international databases, the prognostic value of 24-h blood pressure variability was
evaluated in 8938 patients (Hansen et al. 2010 ). There was a median of 11.3 years
follow-up, with 1242 deaths and 1049 fatal or non-fatal cardiovascular events
across the databases (Hansen et al. 2010 ). The study evaluated the following: (1) the
standard deviation of the 24-h mean pressure weighted for the interval between
consecutive readings; (2) the average of the daytime and nighttime standard devi-
ations, weighted for the duration of the daytime and nighttime interval; and (3) the
“average real variability”(ARV24) which has been defined as the mean of the
absolute differences of consecutive measurements as risk factors for all cause and
cardiovascular morbidity and mortality (Flores 2013 ). The analysis found modest
independent relationships between diastolic ARV24 and cardiovascular mortality,
and systolic ARV24 and cardiovascular mortality. In models excluding the average
24-h blood pressure, the 24-h systolic and diastolic standard deviation predicted
148 G.D. James