Mid to Late Life Hypertension Trends and Cerebral Small Vessel Disease in the Framingham Heart Study.
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ABSTRACT:
SUBMITTER: Petrea RE
PROVIDER: S-EPMC7577565 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveWe investigated the association between circulating biomarkers of inflammation and MRI markers of small vessel disease.MethodsWe performed a cross-sectional study relating a panel of 15 biomarkers, representing systemic inflammation (high-sensitivity C-reactive protein, interleukin-6, monocyte chemotactic protein-1, tumor necrosis factor α, tumor necrosis factor receptor 2, osteoprotegerin, and fibrinogen), vascular inflammation (intercellular adhesion molecule 1, CD40 ligand, P-selectin, lipoprotein-associated phospholipase A2 mass and activity, total homocysteine, and vascular endothelial growth factor), and oxidative stress (myeloperoxidase) to ischemic (white matter hyperintensities/silent cerebral infarcts) and hemorrhagic (cerebral microbleeds) markers of cerebral small vessel disease (CSVD) on MRI in 1,763 stroke-free Framingham offspring (mean age 60.2 ± 9.1 years, 53.7% women).ResultsWe observed higher levels of circulating tumor necrosis factor receptor 2 and myeloperoxidase in the presence of cerebral microbleed (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1-4.1 and OR 1.5, 95% CI 1.1-2.0, respectively), higher levels of osteoprotegerin (OR 1.1, 95% CI 1.0-1.2), intercellular adhesion molecule 1 (OR 1.7, 95% CI 1.1-2.5), and lipoprotein-associated phospholipase A2 mass (OR 1.5, 95% CI 1.1-2.1), and lower myeloperoxidase (OR 0.8, 95% CI 0.7-1.0) in participants with greater white matter hyperintensity volumes and silent cerebral infarcts.ConclusionsOur study supports a possible role for inflammation in the pathogenesis of CSVD, but suggests that differing inflammatory pathways may underlie ischemic and hemorrhagic subtypes. If validated in other samples, these biomarkers may improve stroke risk prognostication and point to novel therapeutic targets to combat CSVD.
| S-EPMC4345647 | biostudies-literature
Project description:Development of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socio-economic status or of vascular risk factor exposures. We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socio-economic status), adult small vessel disease, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n = 1080; mean age = 59 years); the Dutch Famine Birth Cohort (n = 118; mean age = 68 years); the Lothian Birth Cohort 1936 (LBC1936; n = 617; mean age = 73 years), and the Simpson's cohort (n = 110; mean age = 78 years). We analysed each small vessel disease feature individually and summed to give a total small vessel disease score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult socio-economic status. Higher birth weight was associated with fewer lacunes [odds ratio (OR) per 100 g = 0.93, 95% confidence interval (CI) = 0.88 to 0.99], fewer infarcts (OR = 0.94, 95% CI = 0.89 to 0.99), and fewer perivascular spaces (OR = 0.95, 95% CI = 0.91 to 0.99). Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point = 0.99, 95% CI 0.98 to 0.998), fewer infarcts (OR = 0.98, 95% CI = 0.97 to 0.998), fewer lacunes (OR = 0.98, 95% CI = 0.97 to 0.999), and lower total small vessel disease burden (OR = 0.98, 95% CI = 0.96 to 0.999). Low education was associated with more microbleeds (OR = 1.90, 95% CI = 1.33 to 2.72) and lower total brain volume (mean difference = -178.86 cm3, 95% CI = -325.07 to -32.66). Low childhood socio-economic status was associated with fewer lacunes (OR = 0.62, 95% CI = 0.40 to 0.95). Early life factors are associated with worse small vessel disease in later life, independent of each other, vascular risk factors and adult socio-economic status. Risk for small vessel disease may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may improve lifelong brain health and contribute to the prevention of dementia and stroke in older age.
| S-EPMC8719837 | biostudies-literature
Project description:It is unknown whether relations between early-life factors and overall health in later life apply to burden of cerebral small vessel disease (cSVD), a major cause of stroke and dementia. We explored relations between early-life factors and cSVD in the Lothian Birth Cohort, a healthy aging cohort. Participants were recruited at age 70 (N = 1091); most had completed a test of cognitive ability at age 11 as part of the Scottish Mental Survey of 1947. Of those, 700 participants had brain MRI that could be rated for cSVD conducted at age 73. Presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0-4 representing all MRI cSVD features. We tested associations with early-life factors using multivariate logistic regression. Greater SVD score was significantly associated with lower age-11 IQ (OR higher SVD score per SD age-11 IQ = .78, 95%CI 0.65-.95, p=.01). The associations between SVD score and own job class (OR higher job class, .64 95%CI .43-.95, p=.03), age-11 deprivation index (OR per point deprivation score, 1.08, 95%CI 1.00-1.17, p=.04), and education (OR some qualifying education, .60 95%CI .37-.98, p=.04) trended towards significance (p<.05 for all) but did not meet thresholds for multiple testing. No early-life factor was significantly associated with any one individual score component. Early-life factors may contribute to age-73 burden of cSVD. These relations, and the potential for early social interventions to improve brain health, deserve further study.
| S-EPMC5076451 | biostudies-literature
Project description:AbstractHypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease, the most common cerebrovascular disease. However, the causal relationship between hypertension and cerebral small vessel disease remains unclear. Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease. Chronic hypertension and lifestyle factors are associated with risks for stroke and dementia, and cerebral small vessel disease can cause dementia and stroke. Hypertension is the main driver of cerebral small vessel disease, which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction, leukoaraiosis, white matter lesions, and intracerebral hemorrhage, ultimately resulting in cognitive decline and demonstrating that the brain is the target organ of hypertension. This review updates our understanding of the pathogenesis of hypertension-induced cerebral small vessel disease and the resulting changes in brain structure and function and declines in cognitive ability. We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.
| S-EPMC10883517 | biostudies-literature
Project description:Mid-life hypertension is a major risk factor for developing dementia later in life. While anti-hypertensive drugs restore normotension, dementia risk remains above baseline suggesting that brain damage sustained during transient hypertension is irreversible. The current study characterized a rat model of transient hypertension with an extended period of normotensive recovery: F344 rats were treated with L-NG-Nitroarginine methyl ester (L-NAME) for 1 month to induce hypertension then allowed up to 4 months of recovery. With respect to cognitive deficits, comparison between 1 month and 4 months of recovery identified initial deficits in spatial memory that resolved by 4 months post-hypertension; contrastingly, loss of cognitive flexibility did not. The specific cells and brain regions underlying these cognitive deficits were investigated. Irreversible structural damage to the brain was observed in both the prefrontal cortex and the hippocampus, with decreased blood vessel density, myelin and neuronal loss. We then measured theta-gamma phase amplitude coupling as a readout for network function, a potential link between the observed cognitive and pathological deficits. Four months after hypertension, we detected decreased theta-gamma phase amplitude coupling within each brain region and a concurrent increase in baseline connectivity between the two regions reflecting an attempt to maintain function that may account for the improvement in spatial memory. Our results demonstrate that connectivity between prefrontal cortex and hippocampus is a vulnerable network affected by transient hypertension which is not rescued over time; thus demonstrating for the first time a mechanistic link between the long-term effects of transient hypertension and dementia risk.
| S-EPMC9260147 | biostudies-literature
Project description:Background and purposeIt is currently unclear whether midlife systemic inflammation promotes the development of white matter (WM) abnormalities and small vessel disease in the elderly. We examined the association of midlife systemic inflammation with late-life WM hyperintensity volume, deep and periventricular WM microstructural integrity (fractional anisotropy and mean diffusivity [MD]), cerebral infarcts, and microbleeds in a biracial prospective cohort study.MethodsLinear and logistic regression examined the relation between midlife high-sensitivity C-reactive protein (CRP)-a nonspecific marker of inflammation-and brain magnetic resonance imaging markers assessed 21 years later in the Atherosclerosis Risk in Communities Study.ResultsWe included 1485 participants (baseline age, 56[5]; 28% black). After adjusting for demographic factors and cardiovascular disease, each SD increase in midlife CRP was associated with lower fractional anisotropy (-0.09 SD; 95% confidence interval, -0.15 to -0.02) and greater MD (0.08 SD; 95% confidence interval, 0.03-0.15) in deep WM and lower fractional anisotropy (-0.07 SD; 95% confidence interval, -0.13 to 0.00) in periventricular WM. We found stronger associations between CRP and periventricular WM microstructural integrity among black participants (P interaction=0.011). Although an association between higher CRP levels and greater WM hyperintensity volume was found only among APOE ε4-positive participants in our primary analysis (0.14 SD; 95% confidence interval, 0.01-0.26; P interaction=0.028), this relationship extended to the entire sample after accounting for differential attrition. Midlife CRP was not associated with the presence of cerebral infarcts or microbleeds in late life.ConclusionsOur findings support the hypothesis that midlife systemic inflammation may promote the development of chronic microangiopathic structural WM abnormalities in the elderly.
| S-EPMC5705320 | biostudies-literature
Project description:Hypertension (HT) and its cerebral complications are extremely vexing medical and social problems. Despite the obvious association between hypertension and the clinical and neuroimaging features of cerebral microangiopathy (CMA) (also known as cerebral small vessel disease), the causal links between them remain ambiguous. Besides, antihypertensive therapy as the only way to manage these patients does not always prevent brain damage. Knowledge about the key factors and mechanisms involved in HT and CMA development is important for predicting the risk of cerebral complications and developing new approaches to their prevention and treatment. At present, genome-wide association studies and other approaches are used to investigate the common hereditary mechanisms of HT and CMA development, which will explain a large number of CMA cases not associated with hypertension, lack of a correlation between HT severity and the degree of cerebral injury, and failure of antihypertensive therapy to prevent CMA progression. Epigenetic markers likely play a modulating role in the development of these diseases.
| S-EPMC6087821 | biostudies-literature
Project description:Limited data exist regarding systolic blood pressure (SBP) through mid- to late-life and late-life cardiac function and heart failure (HF) risk. Among 4578 HF-free participants in the ARIC study (Atherosclerosis Risk in Communities) attending the fifth visit (2011-2013; age 75±5 years), time-averaged cumulative SBP was calculated as the sum of averaged SBPs from adjacent consecutive visits (visits 1-5) indexed to total observation time (24±1 years). Calculations were performed using measured SBPs and also incorporating antihypertensive medication specific effect constants (underlying SBP). Outcomes included comprehensive echocardiography at visit 5 and post-visit 5 incident HF, HF with preserved ejection fraction, and reduced ejection fraction. Higher cumulative SBP was associated with greater left ventricular mass and worse diastolic measures (all P<0.001), associations that were stronger with underlying compared with cumulative SBP (all P<0.05). At 5.6±1.2 years follow-up post-visit 5, higher cumulative measured and underlying SBP were associated with incident HF (hazard ratio per 10 mm Hg for measured: 1.12 [1.01-1.24]; underlying: 1.19 [95% CI, 1.10-1.30]) and HF with preserved ejection fraction (measured: 1.15 [1.00-1.33]; underlying: 1.28 [1.14-1.45]), but not HF with reduced ejection fraction (measured: 1.11 [0.94-1.32]; underlying: 1.11 [0.96-1.24]). Associations with HF and HF with preserved ejection fraction were more robust with cumulative underlying compared with measured SBP (all P<0.05). Time-averaged cumulative SBP in mid to late life is associated with worse cardiac function and risk of incident HF, especially HF with preserved ejection fraction, in late life. These associations were stronger considering underlying as opposed to measured SBP, highlighting the importance of prevention and effective treatment of hypertension to prevent late-life cardiac dysfunction and HF.
| S-EPMC8262121 | biostudies-literature
Project description:ImportanceHuman brain development and maintenance is under both genetic and environmental influences that likely affect later-life dementia risk.ObjectiveTo examine environmental influences by testing whether time-dependent secular differences occurred in cranial and brain volumes and cortical thickness over birth decades spanning 1930 to 1970.Design, setting, and participantsThis cross-sectional study used data from the community-based Framingham Heart Study cohort for participants born in the decades 1930 to 1970. Participants did not have dementia or history of stroke and had magnetic resonance imaging (MRI) obtained from March 18, 1999, to November 15, 2019. The final analysis dataset was created in October 2023.ExposureYears of birth ranging from 1925 to 1968.Main measuresCross-sectional analysis of intracranial, cortical gray matter, white matter, and hippocampal volumes as well as cortical surface area and cortical thickness. The secular measure was the decade in which the participant was born. Covariates included age at MRI and sex.ResultsThe main study cohort consisted of 3226 participants with a mean (SD) age of 57.7 (7.8) years at the time of their MRI. A total of 1706 participants were female (53%) and 1520 (47%) were male. The birth decades ranged from the 1930s to 1970s. Significant trends for larger intracranial, hippocampal, and white matter volumes and cortical surface area were associated with progressive birth decades. Comparing the 1930s birth decade to the 1970s accounted for a 6.6% greater volume (1234 mL; 95% CI, 1220-1248, vs 1321 mL; 95% CI, 1301-1341) for ICV, 7.7% greater volume (441.9 mL; 95% CI, 435.2-448.5, vs 476.3 mL; 95% CI, 467.0-485.7) for white matter, 5.7% greater value (6.51 mL; 95% CI, 6.42-6.60, vs 6.89 mL; 95% CI, 6.77-7.02) for hippocampal volume, and a 14.9% greater value (1933 cm2; 95% CI, 1908-1959, vs 2222 cm2; 95% CI, 2186-2259) for cortical surface area. Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean [SD] age, 60.0 [2.8] years) and 1950s (mean [SD] age, 59.0 [2.8] years) resulted in similar findings.Conclusion and relevanceIn this study, secular trends for larger brain volumes suggested improved brain development among individuals born between 1930 and 1970. Early life environmental influences may explain these results and contribute to the declining dementia incidence previously reported in the Framingham Heart Study cohort.
| S-EPMC10964161 | biostudies-literature
Project description:ObjectiveOur aim was to investigate the relationship of carotid structure and function with MRI markers of cerebral ischemic small-vessel disease.MethodsThe study comprised 1,800 participants (aged 72.5 ± 4.1 years, 59.4% women) from the 3C-Dijon Study, a population-based, prospective cohort study, who had undergone quantitative brain MRI and carotid ultrasound. We used multivariable logistic and linear regression adjusted for age, sex, and vascular risk factors.ResultsPresence of carotid plaque and increasing carotid lumen diameter (but not common carotid artery intima-media thickness) were associated with higher prevalence of lacunar infarcts: odds ratio (OR) = 1.60 (95% confidence interval [CI]: 1.09-2.35), p = 0.02 and OR = 1.24 (95% CI: 1.02-1.50), p = 0.03 (by SD increase). Carotid plaque was also associated with large white matter hyperintensity volume (WMHV) (age-specific top quartile of WMHV distribution): OR = 1.32 (95% CI: 1.04-1.67), p = 0.02, independently of vascular risk factors. Increasing Young elastic modulus and higher circumferential wall stress, reflecting augmented carotid stiffness, were associated with increasing WMHV (effect estimate [β] ± standard error: 0.0003 ± 0.0001, p = 0.024; β ± standard error: 0.005 ± 0.002, p = 0.008). Large WMHV was also associated with increasing Young elastic modulus (OR = 1.22 [95% CI: 1.04-1.42], p = 0.01) and with decreasing distensibility coefficient (OR = 0.83 [95% CI: 0.69-0.99], p = 0.04), independently of vascular risk factors. Associations of carotid lumen diameter with lacunar infarcts and of carotid stiffness markers with WMHV were independent of carotid plaque.ConclusionsIn addition to and independently of carotid plaque, increasing carotid lumen diameter and markers of carotid stiffness were associated with increasing prevalence of lacunar infarcts and increasing WMHV, respectively.
| S-EPMC3590057 | biostudies-literature