65lent left ventricular hypertrophy (50% vs 13.5%), diabetes (13.8 versus 3.2%), and
higher serum creatinine (1.0 ± 0.4 vs 0.8 ± 0.2 mg/dl). The masked hypertensive
group had a greater prevalence of left ventricular hypertrophy (23% versus 13.5%).
After a mean of 5 years of follow-up, 63 cardiovascular events occurred (myocar-
dial infarction, coronary or peripheral revascularization, hospitalization for heart
failure, fatal and nonfatal strokes, and renal failure requiring dialysis). Multivariable
Cox regression showed age, smoking, LDL cholesterol, left ventricular hypertro-
phy, diabetes, masked hypertension, and true RH were independent predictors of
cardiovascular events. Compared to the normotensive responder group, pseudore-
sistance had equivalent prognosis for cardiovascular events (relative risk, 1.2; 95%
CI, 0.5–3.3). Masked hypertension doubled the relative risk of cardiovascular events
(2.3; 95% CI, 1.1–4.7). True RH nearly trebled the relative risk of cardiovascular
events (2.9; 95% CI, 1.0–8.4). This study emphasized the high cardiovascular risk
associated with masked hypertension and true RH and the relatively benign progno-
sis of pseudoresistance. This underlines the practical and prognostic importance of
ABPM in reclassifying patients to avoid overtreating those with white coat hyper-
tension and undertreating those with masked hypertension. To date, there are no
clinical outcome data describing clinical outcomes of masked hypertension relative
to RH in the setting of CKD.
Most observational studies of aTRH describe clinical outcomes based on base-
line prevalence in cross-sectional studies. Daugherty and coworkers used longitudi-
nal healthcare insurance registry data to report the first estimate of new-onset aTRH
from 205,750 patients with incident hypertension [ 12 ]. Definition of incident aTRH
was an increase from using 1 to 3 or more antihypertensive drugs with BP
140/90 mmHg or >130/80 mmHg for those with diabetes mellitus or chronic kid-
ney disease. Pseudoresistance was determined by nonadherence to therapy using
pharmacy data but could not exclude white coat or masked hypertension as only
office BP was available. Incident aTRH developed in 1.9% (n = 3960) of the entire
cohort during a median follow up of 1.5 years. Resistant patients were more often
older, male, with higher rates of diabetes mellitus, CKD, and other comorbidities.
After a median follow-up of 3.8 years and exclusion of 5876 (25%) patients with
prior cardiovascular events, a total of 18,036 patients remained. There were 344
(1.9%) deaths and 2206 (12.2%) incident cardiovascular events. Univariate analyses
showed more frequent cardiovascular events in the aTRH group compared to non-
resistant hypertension group (18% vs 13.5%, respectively). In unadjusted and
adjusted survival analyses, patients with aTRH were significantly more likely to
experience the combined outcomes of death, myocardial infarction, congestive
heart failure, stroke, or CKD, (unadjusted HR, 1.5; 95% CI, 1.4–1.7; adjusted HR,
1.5; 95% CI, 1.3–1.6). Sensitivity analyses excluding 269 patients with pseudoresis-
tance due to nonadherence did not alter the findings. This study showed that among
patients with incident hypertension newly starting treatment, 1 in 50 will go on to
develop resistant hypertension within 1.5 years. In addition, one in six patients tak-
ing three hypertension medications will continue to meet criteria for resistant hyper-
tension over follow-up. Adverse cardiovascular outcomes were 50% higher in those
with incident aTRH hypertension than in those without.
5 Resistant Hypertension and Outcomes in Patients with and Without Chronic Kidney...