Hypertension in the Elderly May Be Associated with Progressive Brain Atrophy
Abstract & Commentary
By Michael T. Lin, MD
Assistant Professor of Neurology and Neurosciences, Weill Cornell Medical College
Dr. Lin reports no financial relationships relevant to this field of study. This article originally appeared in the October 2013 issue of Neurology Alert.
Synopsis: Mid-life hypertension may be a risk factor for late-life brain atrophy and may exacerbate neurodegeneration. However, lowering blood pressure too aggressively in those with advanced atherosclerotic vascular disease may also result in late-life brain atrophy.
Source: Jochemsen HM, et al. Blood pressure and progression of brain atrophy: The SMART-MR study. JAMA Neurol 2013;70:1046-1053.
Hypertension is well established as a risk factor
for vascular brain lesions. There is also emerging evidence that abnormal blood pressure may be a risk factor for neurodegeneration. Several cross-sectional studies have shown that high blood pressure in midlife is associated with more brain atrophy later in life, whereas in late life, low blood pressure is associated with more brain atrophy. However, there is little prospective evidence relating blood pressure and brain atrophy.
The SMART-MR (Secondary Manifestations of ARTerial disease-Magnetic Resonance) study in the Netherlands is a prospective, cohort study of MRI brain changes in patients with arterial disease — coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysm. Of 1309 patients enrolled from 2001-2005, 663 had MRIs at baseline and during follow-up from 2006-2009. Average follow-up time was 3.9 years, average age was 57, and 81% were men. The ventricular fraction was used as a measure of subcortical brain atrophy, and the ventricular fraction increased with time in all blood pressure groups.
The key findings were 1) that in those with low diastolic blood pressure (DBP) at baseline, the increase in ventricular fraction was greater than in those with high DBP at baseline (this finding was driven primarily by patients with coronary artery disease); and 2) in those with normal or high DBP at baseline, the increase in ventricular fraction was less if DBP decreased over time than if it increased. Findings were adjusted for demographic factors, other vascular risk factors, alcohol consumption, baseline brain volume, and baseline burden of strokes and white matter lesions.
Of note, previous studies found that low blood pressure was associated with increased brain atrophy in late life, whereas this study observed low DBP to be associated with increased brain atrophy in mid-life in patients with arterial disease. The authors hypothesized that patients with arterial disease have early vascular aging with increased arterial stiffness, impaired endothelial function, and impaired cerebral autoregulation, making them more vulnerable to low blood pressure. Because this association of low blood pressure and increased brain atrophy occurred primarily in patients with coronary artery disease, baseline low DBP might represent poor cardiac output and insufficient brain perfusion. On the other hand, in those with higher DBP at baseline, the association of decline in blood pressure over time with less brain atrophy suggests that treating abnormally high blood pressure will be beneficial.
Strengths of this study include its prospective design and large numbers of patients. The poor follow-up rate is a weakness, and it is not clear whether these findings will generalize to patients without arterial disease. Nonetheless, many patients do have arterial disease, and this study further emphasizes the emerging understanding of how vascular risk factors are related to neurodegeneration as well as stroke. Practically, the study suggests that blood pressure should be treated in patients with hypertension, but should not be lowered further in patients who already have normal or low blood pressure, particularly in the setting of an acute intercurrent illness.