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population-based prospective cohort that included 9294 non-institutionalized indi-
viduals aged 65 years or older randomly selected from electoral rolls of three French
cities from March 1999 to March 2001. Both office BP and kidney function were
measured in a standardized manner at baseline in 8695 participants of which 4265
were had treated hypertension. Hypertension groups were defined as controlled if
office BP was <140/90 mmHg with ≤3 antihypertensive drug classes, and as uncon-
trolled nonresistant, if it was ≥140/90 mmHg with ≤2 drugs; aTRH was defined as
uncontrolled BP ≥140/90 mmHg in patients receiving ≥3 antihypertensive drug
classes or ≥4, regardless of BP. Baseline prevalence of aTRH, controlled nonresis-
tant hypertension and uncontrolled nonresistant hypertension was 6.5%, 62.3%, and
31.2%, respectively. The overall mean MDRD-eGFR was 74 ± 17.0 mL/min/1.73 m^2.
Participants with aTRH were significantly older with greater prevalence of obesity,
diabetes, and history of cardiovascular disease. Prevalence of CKD as defined by
eGFR <60 mL/min/1.73 m^2 was 35% in the aTRH group compared to 19% and 17%
in the controlled and uncontrolled hypertension groups, respectively. Around 75%
of the participants with aTRH reported taking diuretics and renin-angiotensin sys-
tem inhibitors, while less than 66% reported calcium channel blockers and beta-
blockers. At the 4-year follow-up, 1629 of 3865 participants with treated
hypertension had a second creatinine measurement; 739 also had urine protein or
albumin creatinine ratio. Progression of CKD was determined by a calculated slope
using the difference between the baseline and 4-year eGFR divided by the follow-up
time. Multinomial regression was used to estimate odds ratios for the association of
aTRH at the 4-year follow-up with an eGFR decline rate ≥3 mL/min/1.73 m^2 per
year adjusted for age, gender, smoking, obesity, diabetes, history of cardiovascular
disease, and study site. This cutoff was selected due to being roughly three times
greater than the annual physiological kidney function decline due to aging. At base-
line, lower MDRD-eGFR values were independently associated with higher odds of
aTRH, compared to both reference groups (odds ratio for eGFR decline of 15 mL/
min/1.73 m^2 of 1.29 [95% CI, 1.16–1.48] relative to controlled hypertension or 1.33
[95% CI, 1.19–1.48] relative to uncontrolled nonresistant hypertension. At 4 years,
6.4% were classified with aTRH, 50% with controlled hypertension, and 43.5%
with uncontrolled nonresistant hypertension. Among those without aTRH at base-
line, 149 participants developed new-onset aTRH with a calculated incidence of
3.5% over 4 years (0.5 per 100 person-years). Baseline MDRD-eGFR level was not
related to new-onset aTRH. In contrast, a rapid MDRD-eGFR decline ≥3 mL/
min/1.73 m^2 per year was significantly associated with greater risk of new-onset
aTRH, regardless of the reference group and independent of mean MDRD-eGFR
over the period and other covariates (Table 5.3). International guidelines define pro-
gression of CKD as an eGFR decline rate ≥5 mL/min/1.73 m^2 per year. Use of this
eGFR cutoff tended to higher odds ratios. Use of the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equation for eGFR did not change these
associations. This study provides a rare estimate of incidence of aTRH reporting
7 in 50 hypertensive participants on ≤2 drugs developed aTRH over 4 years. The
standardized incidence of 0.7 new cases per 100 person-years compares to the only
previous estimate of 0.5 per 100 person-years [ 12 ]. The low prevalence of aTRH in
A. Odudu et al.