Title: Patients with resistant or difficult to control hypertension were referred to a specialty hypertensi
1Evaluation and Treatment of Resistant or
Difficult to Control Hypertension
David Wojciechowski, Vasilios Papademetriou,
Charles Faselis and Ross Fletcher
Department of Medicine, Veterans Affairs Medical
Center and Georgetown University Hospital
Washington, DC
Figure 2 Change in eGFR (mL/min/1. 73m2) from
baseline to 6 months using the MDRD equation
Results
Abstract
Patients with resistant or difficult to control
hypertension were referred to a specialty
hypertension clinic. From July 1, 2006 to May
31, 2007 175 new patients were seen. Patients
were mostly male (94.86), African-American (84)
and averaged 64.02 years old. Co-morbidities
included diabetes (42.29), CKD 3 or greater
(28) with an average eGFR of 83.57
ml/min/1.73m2, hyperlipidemia (65.14), CAD
(15.43), CVA (11.43) and PVD (11.43). Ninety
patients underwent a baseline transthoracic
echocardiogram and of these 59 had pre-existing
LVH. At referral 93.71 of patients BP was
140/90 mm Hg. Average BP was 160/87 mm Hg.
Evaluation for secondary causes revealed
obstructive sleep apnea (8.57), non-compliance
(7.43), hyperaldosteronism (1.71) and renal
artery stenosis (0.57). The average number of
anti-hypertensive medications per patient at
baseline was 3.43. At 3 and 6 months it increased
to 4.06 and 4.18, respectively (p0.0008 and
137.62/74.03 mm Hg at 3 and 6 months,
respectively (p63.4 of patients achieved a blood pressure
140/90 mm Hg. At months 3 and 6, 100 of
patients were now on a diuretic with 8.4 and
8.5 of patients on two diuretics. The average
eGFR at month 6 was 79.36 ml/min/1.73m2 (p0.8018
compared to baseline). In conclusion, patients
referred for resistant or difficult to control
hypertension have a high prevalence of secondary
causes but can be controlled by making targeted
adjustments to their medical regimen. The average
number of medications needed is high and
ultimately all patients required a diuretic in
their regimen. By achieving a blood pressure
goal of less than 140/90 mmHg renal function
remained stable over the six month follow-up
period.
- A total of 175 new patients were seen in the HTN
clinic from July 1, 2006 to May 31, 2007 - At 3 and 6 months 154 and 153 patients had
follow-up data available, respectively - Patient baseline characteristics are shown in
Table 1 - Only 6.29 of patients had a BP 140/90 mm Hg at
the time of presentation - Changes in BP and anti-HTN medication use are
shown in Table 2 - As shown in Figrue 1 the average BP at 3 and 6
months fell to 135.55/74.55 and 137.62/74.03 mm
Hg, respectively - A total of 36 patients were found to have a
secondary cause of hypertension as shown in Table
3 - As shown in Figure 2 the 6 month follow-up eGFR
was 79.3633.95 ml/min/1.73m2
Table 1 Patient baseline characteristics
Table 2 Change in blood pressure and
anti-hypertension medication use at three and six
months compared to baseline
Characteristic N () Total Number of
Patients 175 Male 166 (94.86) Female 9
(5.42) Average Age 64.0211.67 years Average
Systolic Blood Pressure 160.0615.80 mmHg Average
Diastolic Blood Pressure 87.4513.86
mmHg Patients with BP 140/90 mmHg 11
(6.29) Patients with SBP 160 mmHg 85
(48.57) Ethnicity Caucasian 25
(14.28) African-American 147 (84) Other 3
(1.71) Average Duration of Hypertension 13.6611.
40 years Diabetes 74 (42.29) Dyslipidemia 114
(65.14) Coronary Artery Disease 27
(15.43) Cerebrovascular Disease 20
(11.43) Peripheral Vascular Disease 20
(11.43) Baseline Cardiac Echo 90 (51.43) Left
Ventricular Hypertrophy 59/90 (65.55) Left
Ventricular Mass Index 19973.5g/m2 Average
Ejection Fraction 55.58.07 Average
eGFR 83.5735.02 mL/min
Baseline Three Monthsa
Six Monthsa Systolic Blood Pressure
160.0615.80 mmHg 135.5517.40 mmHg
137.6215.96 mmHg
(p (p87.4513.86 mmHg 74.5513.10 mmHg
74.0311.70 mmHg
(p(p6.29 68.18
63.40 Patients with SBP 160
mmHg 48.57 6.49
7.19 Average
Number of Medications/Patient 3.43
4.06 (p0.0008)
4.18 (p 79.4
108.4b (p(p 68.6
76.6 (p0.1117) 82.4
(p0.0045) Patients on BB
62.9
67.5 (p0.3844) 66.7
(p0.4744) Patients on ACE-I
56.5
57.8 (p0.8270) 60.1
(p0.5227) Patients on ARB
27.4
32.5 (p0.3142) 32.0
(p0.3637) Patients on ACE-I and/or ARB
83.4 90.2
(p0.1646) 91.5 (p0.1099) Patients
on Spironolactone 0.6
3.2 (p0.0758)
4.6 (p0.0184) Patients on Hydralazine
6.8
9.2 (p0.4224) 11.8
(p0.1174) Patinets on Minoxidil
8.6
15.6 (p0.0493) 16.3 (p0.0329)
Introduction
p value compared to baseline 0.8018
Discussion
- Resistant hypertension (HTN) is defined as a
blood pressure (BP) 140/90 mmHg despite
compliance to a medical regimen that includes at
least 3 anti-hypertensive medications, one of
which must be a diuretic1 - Difficult to control HTN includes patients who
dont meet the strict criteria of resistant HTN
but nonetheless their BP is not controlled
despite aggressive intervention - The presence of resistant or difficult to control
HTN imparts significant target end-organ damage
and a higher long-term cardiovascular risk
compared to patients whose BP is controlled2 - In a general hypertensive patient population only
34-53 of patients have their BP controlled to a
target level of 140/90 mmHg3,4 - In a specialty HTN clinic only 59 of patients
with resistant HTN achieved a BP goal of 140/90
mmHg despite aggressive medication titration5 - In the Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial (ALLHAT)
after approximately 5 years of follow-up 34 of
patients HTN remained uncontrolled on an average
of 2 medications6 - Additionally, diuretics continue to be
underutilized 60 of patients with resistant or
difficult to control HTN will respond to the
addition of a diuretic7 - We conducted an observational study of all new
patients referred to a specialty HTN clinic at
the Washington Veterans Affairs Medical Center
over an 11 month time period to evaluate the
change in BP, trends in medication use and the
impact on renal function
- Our results are encouraging as we were able to
reach the target BP of 140/90 mm Hg in 63.4 of
patients by the end of the study period - At 3 and 6 month follow-up all patients were on
at least one diuretic with several patients on
two (a thiazide and a loop) diuretics this
proved to be the most beneficial intervention in
achieving BP control - This is consistent with data from ALLHAT in which
patients assigned to diuretic therapy achieved a
significantly lower SBP at all points over the 5
year study period - African-Americans have traditionally been thought
to be more difficult to get to BP goal compared
to Caucasians - Our data indicate that despite a predominantly
African-American resistant or difficult to treat
population adequate BP control can still be
achieved - Secondary causes of HTN were slightly more
prevalent in our patients compared to the rate of
5-10 that has previously been reported this
stresses the importance of including
non-compliance as a cause of treatment resistance
or failure - Adequate BP control is essential in preventing
the progression of CKD the BP reduction achieved
in our study yielded a stable eGFR at 6 months of
follow-up
a All p values are compared to baseline. b 8.4
of patients were on two diuretics. c 8.5 of
patients were on two diuretics.
Methods
Figure 1 Change in systolic and diastolic blood
pressure from baseline to 3 and 6 months
- An observational study was conducted of all new
patients referred to a specialty hypertension
clinic at the Washington DC VA Medical Center
from July 1, 2006 to May 31, 2007 for the
treatment of resistant or difficult to control
HTN - The primary outcomes assessed were the change in
BP and anti-hypertensive medication use at months
3 and 6 compared to baseline and the change in
eGFR at month 6 compared to baseline - All patients were evaluated by a senior physician
who is a certified HTN specialist - After the baseline visit patients were seen at
months 3 and 6 additional follow-up was
scheduled between study visits as needed at the
discretion of the attending physician for further
medication adjustment to reach the target BP of
140/90 - For the data analysis BP was recorded at
baseline, 3 and 6 months measurements were
performed in a seated position after 5 minutes of
rest - Anti-hypertension medication use was recorded at
baseline and at months 3 and 6 - The eGFR as determined by the 5-variable MDRD
equation was calculated at baseline and at month
6 - Work up for secondary causes of HTN was carried
out following clinical guidelines and as
clinically warranted - Screening tests for secondary HTN included serum
aldosterone level, plasma renin activity, Doppler
ultrasonography or MRA of the renal arteries,
overnight sleep study, TSH, and plasma free
metanephrines - BP data is presented as a mean SD a paired t
test was performed to compare the BP at months 3
and 6 to baseline - eGFR is presented as a mean SD a paired t test
was performed to compare the baseline eGFR to the
6 month eGFR - The total number of anti-hypertension medications
used is presented as the average number of
anti-hypertension medications used per patient - A paired t test was performed to compare the
average number of medications used per patient at
months 3 and 6 to baseline - Medication use is also presented as the
percentage of patients receiving each class of
medication - An unpaired t test was performed to compare
specific medication use at baseline to months 3
and 6
Conclusions
- Resistant or difficult to treat hypertensive
patients can achieve a BP goal of 140/90 mm Hg
with vigilant follow-up and aggressive medication
titration - On average these patients will require at least
four anti-hypertensive medications - In order to reach the goal BP a diuretic must be
added - By achieving a BP goal of 140/90 mm Hg renal
function remained stable over the six month
follow-up period
p value compared to baseline
References
Total Patients with a Secondary Cause (Average
Age 60.08 years)
36 (20.57) Single Cause Obstructive
Sleep Apnea
15 (8.57) Non-Compliance
13 (7.43) Hyperaldosteronism
3
(1.71) Renal Artery Stenosis
1 (0.57) Mixed
Cause Hyperaldosteronism and Obstructive Sleep
Apnea 2 (1.14) Renal Artery Stenosis and
Obstructive Sleep Apnea 1 (0.57) Non-Compliance
and Obstructive Sleep Apnea 1 (0.57)
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Table 3 Evaluation of secondary causes of
hypertension