67coat hypertension or nonadherence. The remaining 300 patients with true RH had a
mean age of 67 years with frequent comorbidities including obesity (body mass
index, 30 ± 6 kg/m^2 ), diabetes (38%), left ventricular hypertrophy (65%), and 24-h
urinary protein >1 g (23%). In the first 6 months, the prevalence of those achieving
controlled BP increased from 12% to 19% while incidence of true RH increased
from 26% to 38%, largely driven by intensified drug therapy. Predictors of persis-
tent RH included proteinuria and diabetes. A composite outcome of renal death was
defined as all-cause mortality or requiring dialysis or renal transplantation. After a
median follow-up of 3 years, 79 renal deaths occurred with significantly more
events in the group with RH at 6 months. Compared to the non-RH group, the
adjusted risk of renal death for true RH was approximately doubled (HR, 1.9; 95%
CI, 1.1–3.0). The authors speculated that the characteristics of RH in CKD might be
different with proteinuria rather than GFR being a better predictor. However, their
findings largely reflect non-CKD studies in that baseline evidence of cardiovascular
end-organ damage predicts RH. There are further difficulties when statistically
regarding the competing risks of renal transplantation, dialysis, and death as having
equally adverse outcomes when renal transplantation might well improve survival
compared to advanced CKD.
In a prospective cohort study, the same authors reported prognosis of 436 CKD
patients [ 17 ]. The diagnosis of aTRH was office BP ≥130/80 mmHg, despite adher-
ence to three full-dose antihypertensive drugs including a diuretic or use of ≥4 anti-
hypertensives irrespective of BP. Patients were asked the number of times they had
missed taking their prescribed medication in the last 2 weeks and were excluded
from analysis if the missing rate for medication was ≥ 20%. The cohort was pheno-
typed into controlled (ambulatory BP <125/75 mmHg without aTRH); pseudoresis-
tant (aTRH and ambulatory BP <125/75 mmHg); sustained hypertension (ambulatory
BP ≥125/75 mmHg without aTRH); and true RH (ambulatory BP ≥125/75 mmHg
with aTRH). Compared to the controlled BP group, those with true RH had greater
body mass index, more frequent diabetes, proteinuria, left ventricular hypertrophy,
prior cardiovascular disease, and lower eGFR. After a median of 4.8 years of fol-
low-up, there were 165 renal events (end-stage renal disease or death due to renal
failure) and 109 cardiovascular events (fatal and nonfatal myocardial infarction,
heart failure, stroke, peripheral or coronary revascularization, amputation for periph-
eral vascular disease). Patients with true RH showed worse renal and cardiovascular
event-free survival in unadjusted analyses (Fig. 5.2). In multivariable- adjusted event
analyses, true RH was associated with double the risk of renal events and 2.7-fold
increased risk of cardiovascular events (renal event HR, 2.0; 95% CI, 1.1–3.4; car-
diovascular event HR, 2.7; 95% CI, 1.6–4.4). Notably pseudoresistance was not
associated with increased cardiorenal risk and sustained hypertension had interme-
diate risk being predictive of renal but not cardiovascular events. This study exem-
plifies the incremental risk for phenotypes of RH in CKD that can only be parsed
using ABPM. Use of ABPM identified 43% of subjects with suboptimal BP for
whom office BP control was adequate. The risk for cardiorenal events was highest
in patients with “true” RH. Those with sustained and pseudoresistant hypertension
were not at increased cardiovascular risk compared to control subjects. Those with
5 Resistant Hypertension and Outcomes in Patients with and Without Chronic Kidney...