Medication induced blood pressure reduction; assessment of cerebral perfusion and cognition in hypertensive elderly

Hypertension affects as much as 77% of the elderly population, over age 70. The
majority (approximately 60%) of these hypertensive patients have isolated
systolic hypertension. Hypertension is an important risk factor for
cardiovascular disease. Study shows that the benefits of antihypertensive
treatment clearly extend to elderly subjects age over 70. Despite the benefits
of treatment, blood pressure control is inadequate in the majority of patients.
Contributing to these low treatment rates is the widespread concern about the
negative effects of blood pressure lowering on morbidity and quality of life.
Specifically it is feared that lowering of blood pressure to the targets
proposed by recent guidelines (ESH/ESC 2007, JNC-7) may cause cerebral
hypoperfusion, resulting in ischemia, cognitive decline and/or falls. At
present, no data are available to deal adequately with the concerns that many
clinicians have when deciding if and how to treat elderly subjects with
hypertension. This study will demonstrate whether older patients maintain a
stable cerebral perfusion when their blood pressure is adequately reduced to
meet blood pressure targets set by current guidelines

To demonstrate that after a reduction in systolic blood pressure between 20 and
80mmHg within 3 months to reach a target of 140 mmHg, cerebral blood flow is
not lower than prior to the start of treatment.

Prospective, open-label design with blinded end-points. Anti-hypertensive
treatment will be open-label as this therapy is aimed at reaching a specific
target BP. During analysis of the endpoints, the researcher will be blinded for
patient identity and if the data concerns baseline or end measurement.

Methods:
Run-in phase
To obtain an actual BP status, eligible patients will receive standardized
blood pressure measurements during two home visits. If BP-level is according to
inclusion criteria (systolic pressure 160mmHg), patients will visit the GP*s
office once for diagnostic evaluation which is essentially identical to what is
considered *guideline care* in the evaluation and treatment of hypertension in
general practice. Specifically, patients will receive a thorough work-up of
hypertension, including assessment of cardiovascular risk factors, exclusion of
secondary causes, and evaluation of targetorgan damage and cardiovascular
disease.

Treatment phase
Subjects will receive hypertensive treatment to lower blood pressure
(<=140mmHg). The researcher, supervised by project group members, will be
responsible for titration of treatment and will perform BP measurements and
clinical evaluation during two-weekly house calls. In order to reach target BP
of systolic BP <=140mmHg within 8-12 weeks, medication will be uptitrated if the
decline in BP is less than 20mmHg per 2 weeks and clinical evaluation does not
contraindicate an increase of medication.

Measurements
There are 3 measurement sessions: 1 after the run-in phase and 2 sessions after
the treatment phase. Each measurement session consist of 2 parts on different
days. Part 1 during a house call, consists of neuropsychological testing and
fitting of the 24h-ABPM device. For part 2 subjects will visit the RUNMC.
Effects of blood pressure lowering on cerebral hemodynamics will be measured
here using state-of-the-art techniques in this field: MRI, transcranial Doppler
sonography, Near-Infrared-Spectroscopy and Finapres.

The patients will be subjected to diagnostic evaluation and treatment which is
essentially identical to what is considered *routine care* in the evaluation
and treatment of hypertension in general practice. Hypertensive treatment will
lower blood pressure to the level set by current guidelines (ESH/ESC 2007,
JNC-7). The selected hypertensive agents proposed by these guidelines have
proven their effectiveness and safety in extensive clinical use. A gradual
blood pressure reduction will be accomplished, starting with a low dose
combination therapy and gradual uptitration, based on blood pressure level and
clinical evaluation.
The tests performed for research purposes: MRI, TCD, NIRS and Finapres are
non-invasive and save. However, these tests and the repeated visits are
time-consuming and therefore place a considerable burden on participating
patients and their caregivers. The requirement to lie still for a period of one
hour during MRI scanning can be seen as a burden for elderly patients. The
principal investigator has had previous experience with elderly patients,
including Alzheimer patients undergoing the proposed non-invasive methods.
These patients tolerated these investigations very well.