Research in Context
Evidence before this study We searched PubMed for reports on associations between blood pressure (BP) and grey matter volumes (GMV) in young adults by use of the MeSH terms [hypertension OR blood pressure] AND [atrophy OR grey matter OR gray matter OR brain volume] and no language or date restrictions. We found a systematic review and meta-analysis from 2013 which identified 28 studies that investigated associations of higher BP with GMV across ages. In the majority of studies, higher BP or hypertension was associated with lower total or regional GMV. Qualitatively, these reductions were predominant in frontal and (medial) temporal lobes. The meta-analysis revealed consistent reductions in hippocampal volumes with high BP/hypertension across studies. However, none of the reports investigated BP-GMV associations in young adults, i.e. younger than 40 years of age.
Added value of this study In this image-based meta-analysis of four previously unpublished cross-sectional studies that included 423 healthy young adults in total, resting BP ≥120/80 mmHg was associated with lower grey matter volume in several brain regions, including frontal, parietal and subcortical structures (including hippocampus). Our study suggests that subtle pressure-related brain alterations can be observed before 40 years of age and in ranges where BP is still considered “normal” by current guidelines for the management of hypertension.
Implications of all the available evidence Our study is the first to show that BP-associated grey matter alterations emerge continuously across the range of BP and earlier in adulthood than previously assumed. Elevated BP is globally highly prevalent and an important risk factor for cerebrovascular disease and overall health loss. Our results suggest that treating hypertension or maintaining a lower BP in early adulthood might be essential for preventing the pathophysiological cascade of asymptomatic cerebrovascular disease to symptomatic end-organ damage, such as stroke and dementia.
In light of our results, large-scale prospective brain imaging studies should include young adults to investigate whether brain changes related to sub-hypertensive BP in early adulthood could serve as early biomarkers for subsequent development of cerebrovascular disease later in life. Such data would provide evidence for future recommendation guidelines for the management of elevated BP in young adults and for the prevention of cerebrovascular disease at older ages. Our results also speak in favor of considering individual BP levels as continuous measures – in addition to a categorical cut-off – which could facilitate the initiation of early preventive actions.
Background Arterial hypertension (HTN) dramatically increases the risk for stroke and neurodegenerative disease, but signatures of macro- and microangiopathic brain damage are already visible in magnetic resonance imaging (MRI) of asymptomatic HTN patients. Blood pressure (BP) levels that initiate detrimental effects on brain tissue are still undefined. Their identification may be important for successful BP-management and prevention of subsequent cerebrovascular disease. Our objective was to test whether elevated BP relates to lower grey matter volume (GMV) in young adults who had not been diagnosed as hypertensive (≥140/90 mmHg) previously.
Methods We related BP and GMV from structural 3 Tesla T1-weighted MRI of 423 healthy adults between 19-40 years (age=27.7±5.3 years, 177 women, systolic BP (SBP)=123.2±12.2 mmHg, diastolic BP (DBP)=73.4±8.5 mmHg). Data originated from four previously unpublished cross-sectional studies conducted in Leipzig, Germany. We performed voxel-based morphometry on each study separately and combined results in image-based meta-analyses (IBMA) to assess cumulative effects across studies. Resting BP was assigned to one of four categories: (1) SBP<120 mmHg and DBP<80 mmHg, (2) SBP 120-129 mmHg or DBP 80-84 mmHg, (3) SBP 130-139 mmHg or DBP 85-89 mmHg, (4) SBP≥140 mmHg or DBP≥90 mmHg.
Findings IBMA yielded: (a) regional GMV decreased linearly as peripheral BP increased; (b) significantly decreased GMV with higher peripheral BP when comparing individuals in sub-hypertensive categories 3 and 2, respectively, to those in category 1; (c) lower BP-related GMV was found in regions including hippocampus, amygdala, thalamus, frontal and parietal structures (e.g. precuneus).
Interpretation In young adults without previously diagnosed HTN, BP≥120/80 mmHg was associated with lower GMV in regions that have previously been related to GM decline in older individuals with manifest HTN. This suggests that subtle pressure-related brain alterations might occur earlier in adulthood than previously assumed and already at subhypertensive BP levels.