Mid to Late Life Hypertension Trends and Cerebral Small Vessel Disease in the Framingham Heart Study

Abstract

The duration and lifetime pattern of hypertension is related to risk of stroke and dementia. In turn, cerebral small vessel disease (CSVD) is the most frequent form of cerebrovascular disease underlying dementia and stroke. Thus, study of the relation of mid to late life hypertension trends with CSVD late in life will help understand hypertension’s role and inform preventive efforts of CSVD consequences. We studied 1686 Framingham Heart Study Offspring cohort participants free of stroke and dementia, who were examined in mid and late life, and had available brain magnetic resonance imaging during late life. We related hypertension trends between mid and late life (normotension–normotension N-N, normotension-hypertension N-H, hypertension-hypertension H-H) to cerebral microbleeds and covert brain infarcts (CBI), overall and stratified by brain topography. We used multivariable logistic regression analyses to calculate odds ratio and 95% CIs for CSVD measures. The prevalence of CSVD in late life was 8% for cerebral microbleeds and 13% for covert brain infarcts and increased with longer hypertension exposure across all brain regions. Compared with the trend pattern of N-N, both N-H and H-H trends had higher odds of mixed cerebral microbleeds (2.71 [1.08–6.80], and 3.44 [1.39–8.60], respectively); H-H also had higher odds of any cerebral microbleeds or covert brain infarcts (1.54 [1.12–2.20]), and any covert brain infarcts (1.55 [1.08–2.20]). The burden of CSVD also increased with longer hypertension exposure. Our results highlight hypertension having a major role in subclinical CSVD, across subtypes and brain regions, and call attention to improve recognition and treatment of hypertension early in life.

Hypertension-induced cognitive impairment: from pathophysiology to public health

“…Hypertension associated with advanced age, cerebral amyloid angiopathy or AD 114 are the major risk factors for cerebral microhaemorrhages 113 . The prevalence of cerebral microhaemorrhages correlates with the duration of hypertension exposure 115 and is >50% among individuals older than 65 years 113 . CKD is also associated with an increased prevalence of cerebral microhaemorrhages, and experimental studies suggest that this effect might be at least partly due to elevated levels of urea that alter the cytoskeleton of endothelial cells and tight junction proteins 116 .…”

Associations Between Brain Volumes and Cognitive Tests with Hypertensive Burden in UK Biobank

“…Additionally, the role of duration of hypertension on brain structures and cognition is less extensively studied, however examples in the literature imply increased duration of hypertension (particularly starting in midlife) is related to poorer cognition or brain health with few studies focussing on both in the same population or using extensive measures of global and sub brain structures [19][20][21].…”

Cerebral Small Vessel Disease in Sporadic and Familial Alzheimer Disease

“…Blood pressure is one of the most widely evaluated risk factors for dementia and AD in particular. Hypertension is a risk for white matter (WM) damage as well as clinically covert lesions such as arteriolosclerosis, microbleeds, microinfarcts, infarcts, endothelial damage and vascular inflammation 13,[16][17][18][19] . Although non-demented normally ageing individuals have histories of hypertension, large cohort studies suggest an association between systolic hypertension (>160 mm Hg) in midlife and late onset AD by a risk of 18-25% 20 or decreased risk of AD in the short term, possibly due to reverse causation 21 .…”

“…Findings from other longitudinal studies such as Atherosclerosis Risk in Communities (ARIC) 26 and SPRINT MIND 27 suggest intensive blood pressure control would be beneficial for the risk of dementia and AD. Long-term hypertension may have a major role in subclinical cerebral SVD across subtypes and brain regions highlighting the need to recognise and treat hypertension early in life 18 . It is not unlikely that long-standing increase or variability in blood pressure may disrupt vasoregulatory functions, promote blood-brain barrier (BBB) damage and cause neurodegeneration 28 .…”

“…Hypertension is a risk for WM damage as well as clinically covert lesions such as arteriolosclerosis, microbleeds, microinfarcts, infarcts, endothelial damage, and vascular inflammation. 13 , 16 , 17 , 18 , 19 Although nondemented, normally aging individuals have histories of hypertension, large cohort studies suggest an association between systolic hypertension (>160 mm Hg) in midlife and late-onset AD by a risk of 18% to 25% 20 or decreased risk of AD in the short term, possibly due to reverse causation. 21 Blood pressure variability, albeit visit-to-visit or day-to-day, is also associated with progression of AD, 22 and optimal blood pressure management appears to be important for prevention of dementia.…”