69the American Heart Association definition of uncontrolled hypertension
(>140/90 mmHg) on three or more antihypertensive medication classes (uncon-
trolled aTRH) or controlled hypertension (<140/90 mmHg) on four or more
antihypertensive medications (controlled aTRH) [ 5 ]. Absence of aTRH was defined
as controlled hypertension on three or less antihypertensive medications or uncon-
trolled hypertension on one or two classes of antihypertensive medication.
Sensitivity analyses explored the subgroup who were intolerant of diuretics. The
Morisky Medication Adherence Scale was used [ 27 ]. Compared to those without
aTRH, the aTRH group had a higher prevalence of diabetes (46% vs 29%), coronary
artery disease (35% vs 21%), and prior stroke (14% vs 9%). The aTRH group also
had predominantly black ethnicity (60%) with higher waist circumference, greater
baseline prevalence of CKD (28% vs 15%), and greater baseline albuminuria (34%
vs 18%). Over around 5 years of follow-up, the multivariable-adjusted hazard ratio
associated with aTRH versus no aTRH was 1.7 (95% CI, 1.3–2.2) for coronary
heart disease and 1.3 (95% CI, 1.1–1.5) for all-cause mortality. The hazard ratio for
stroke was not statistically significant (1.3; 95% CI, 0.9–1.7). Comparing uncon-
trolled aTRH to controlled aTRH showed a hazard ratio of 2.3 (95% CI, 1.2–4.5) for
coronary heart disease that was not seen for stroke or all-cause mortality. This study
shows the association of aTRH with an increased risk of coronary heart disease and
all-cause mortality but not stroke. Within the aTRH group uncontrolled aTRH had
greater risks of coronary heart disease compared with controlled aTRH. The study
emphasizes the stepwise increase in cardiovascular risk from nonresistant hyperten-
sion, to controlled aTRH and uncontrolled aTRH among a group defined only by
office BP.
Cross-sectional studies consistently show a strong incremental association
between stage of CKD and prevalence of aTRH, but little is known about the longi-
tudinal effect of aTRH on CKD progression in terms of the rate of decline in eGFR,
particularly in the elderly. Recent insights were provided by a population-based
study in a community-dwelling elderly population [ 21 ]. The Three-City study is a
Fig. 5.3 (a) Cumulative incidence of composite cardiovascular outcomes (composite of myocar-
dial infarction [MI], stroke, peripheral arterial disease [PA D], and congestive heart failure [CHF])
between patients with and without apparent treatment resistant hypertension (ATRH). (b)
Cumulative incidence of renal outcomes between patients with and without ATRH. (a, b), Top line,
No ATRH; bottom line, ATRH (Reused with permission from Thomas et al. [ 11 ])
5 Resistant Hypertension and Outcomes in Patients with and Without Chronic Kidney...