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J Clin Hypertens (Greenwich). 2011;13:582–587. ©2011 Wiley Periodicals, Inc.
Cerebral microangiopathy is a cause of cognitive impairment and indicates high risk for clinically overt cerebrovascular disease. It develops in patients with or without hypertension, and different pathologies may play a supporting role. In this pilot study, the authors aimed to elucidate risk factors contributing to the deleterious action of hypertension on cerebral small vessels. A cross-sectional study in 42 patients with treatment-resistant hypertension was performed. Microangiopathy was investigated by cerebral magnetic resonance imaging (MRI). Determinants were identified by clinical investigation, computed tomography, intima-media thickness and pulse wave velocity measurement, and urinary albumin excretion. Nineteen of 42 patients had cerebral microangiopathy (23 controls). Patients were different with respect to heart rate (60.5±10.2 vs 69.7±15.1 beats per minute; P=.029) and systolic blood pressure during nighttime (138±13 mm Hg vs 126±18 mm Hg; P=.019). In addition, there were significant differences in pulse wave velocity (10.7±2.0 m/s vs 9.4±1.4 m/s; P=.034), peripheral pulse pressure (70.8±16.3 mm Hg vs 59.2±13.6 mm Hg; P=.016), central pulse pressure (62.9±15.8 mm Hg vs 50.3±14.2 mm Hg; P=.012), and aortic augmentation pressure (15.9±6.0 vs 11.8±6.6; P=.040). Systolic blood pressure and signs of hypertensive vasculopathy such as peripheral and central pulse pressure and pulse wave velocity were associated with cerebral microangiopathy in patients with long-standing treatment-resistant hypertension.
Cerebral microangiopathy is commonly detected on magnetic resonance imaging (MRI) in elderly hypertensive patients and includes the very early stage of microvascular disease (white matter hyperintensities [WMHs] and lacunar infarctions). Smooth muscle hypertrophy, replacement by extracellular, matrix and enhanced small-vessel permeability are generally considered key pathogenetic features, with mural deposition of serum protein detectable specifically in areas of blood–brain barrier breakdown (hyaline arteriolosclerosis, lipohyalinosis). Cerebral microangiopathy identifies a group of individuals at high risk for clinically overt cerebrovascular disease.1 It also has been discussed to be a frequent cause of cognitive impairment and dementia in the elderly; however, the association between the extent of the disease as assessed by cross-sectional MRI studies and cognitive impairment has repeatedly been shown to be weak or even absent.2–4
Established risk factors are advancing age,5–7 cardiac disease,7 diabetes mellitus,8 and hypercholesterolemia.9 Hypertension is a further risk factor,5–7,10 which has been shown to be of particular importance because not only the initiation but also the progression of cerebral microangiopathy appears to depend on actual blood pressure (BP) readings. This was confirmed in the Austrian Stroke Prevention Study, in which the progression of WMHs in 273 clinically healthy patients was studied. A total of 45.1% patients in the group had hypertension with WMHs and 28.1% patients had hypertension without WMHs (P=.006). At 3-year follow-up WMHs were increased in 18% of patients, and the baseline degree of WMH and diastolic BP were the strongest determinants of progression.11 On the other hand, the data illustrate that hypertension is not a prerequisite for the development or progression of cerebral microangiopathy.11 This was also shown in a prior autopsy study in which cerebral small-vessel disease (usually manifested as concentric hyaline wall thickening but not lipohyalinosis and fibrinoid necrosis) was also present in patients who were nonelderly, nondiabetic, and nonhypertensive.12
Taken together, there appears to be a complex interrelationship between BP and a number of other risk factors contributing to cerebral microangiopathy. There is further possibility that different pathologies in patients with or without hypertension may play a supporting role. This is further complicated by the unknown threshold below which an impact of BP can certainly be ruled out and above which there is a definite impact. Because of these considerations, we focused on patients with long-standing uncontrolled hypertension (treatment-resistant hypertension) in this pilot study to gain an in-depth understanding of risk factors that contribute to the deleterious action of long-standing uncontrolled hypertension on cerebral small vessels.