Summary
Arterial stiffness and excessive pressure pulsatility have emerged as important risk factors for cardiovascular disease. Arterial stiffness increases with age and in the presence of ...traditional cardiovascular disease risk factors, such as hypertension, diabetes and lipid disorders. Pathologic stiffening of large arteries with advancing age and risk factor exposure predominantly involves the elastic aorta and carotid arteries, whereas stiffness changes are relatively limited in muscular arteries. Aortic stiffening is associated with increased pulse wave velocity and pulse pressure, which are related but distinct measures of the pulsatile energy content of the pressure waveform. A dramatic increase in pulsatile energy content of pressure and flow waves in the arterial system places considerable pulsatile stress on the heart, large arteries and distal circulation. Large artery stiffening is associated with abnormalities in microvascular structure and function that may contribute to tissue damage, particularly in susceptible high flow organs such as the brain and kidneys. This brief review summarizes results of recent research on risk factors for and adverse effects of large artery stiffening.
To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging.
Stroke- and dementia-free ...Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume TCBV, white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively).
Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05).
Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.
Digital pulse amplitude augmentation in response to hyperemia is a novel measure of peripheral vasodilator function that depends partially on endothelium-derived nitric oxide. Baseline digital pulse ...amplitude reflects local peripheral arterial tone. The relation of digital pulse amplitude and digital hyperemic response to cardiovascular risk factors in the community is unknown.
Using a fingertip peripheral arterial tonometry (PAT) device, we measured digital pulse amplitude in Framingham Third Generation Cohort participants (n=1957; mean age, 40+/-9 years; 49% women) at baseline and in 30-second intervals for 4 minutes during reactive hyperemia induced by 5-minute forearm cuff occlusion. To evaluate the vascular response in relation to baseline, adjusting for systemic effects and skewed data, we expressed the hyperemic response (called the PAT ratio) as the natural logarithm of the ratio of postdeflation to baseline pulse amplitude in the hyperemic finger divided by the same ratio in the contralateral finger that served as control. The relation of the PAT ratio to cardiovascular risk factors was strongest in the 90- to 120-second postdeflation interval (overall model R(2)=0.159). In stepwise multivariable linear regression models, male sex, body mass index, ratio of total to high-density lipoprotein cholesterol, diabetes mellitus, smoking, and lipid-lowering treatment were inversely related to PAT ratio, whereas increasing age was positively related to PAT ratio (all P<0.01).
Reactive hyperemia produced a time-dependent increase in fingertip pulse amplitude. Digital vasodilator function is related to multiple traditional and metabolic cardiovascular risk factors. Our findings support further investigations to define the clinical utility and predictive value of digital pulse amplitude.
Abstract
Background
Frailty is a risk factor for cardiovascular disease (CVD). Underlying mechanisms to explain the connection between frailty and CVD are unclear. We sought to examine the ...association between frailty and arterial stiffness, a precursor of hypertension and CVD.
Methods
We conducted a cross-sectional analysis of community-dwelling Framingham Heart Study Offspring and Omni participants ≥60 years of age examined in 2005–2008. Frailty was defined primarily according to the Fried physical phenotype definition, which identifies nonfrail, prefrail, and frail individuals. Arterial stiffness was assessed using carotid–femoral pulse wave velocity (CFPWV). Generalized linear regression was used to examine the association between frailty level and CFPWV (modeled as −1000/CFPWV in msec/m, then transformed back to the original scale, m/s), adjusted for age, sex, cohort, mean arterial pressure, heart rate, height, and smoking.
Results
Of 2,171 participants (55% women, 91% white), 45% were prefrail and 7% were frail. Mean ages were 67, 70, and 73 years, and adjusted CFPWV least squares means were 10.0 (95% CI, 9.9–10.1), 10.3 (10.2–10.5), and 10.5 m/s (10.1–11.0); p = .0002 for nonfrail, prefrail, and frail groups, respectively. Results were similar using the Rockwood cumulative deficit model of frailty, and in a sensitivity analysis adjusting for prevalent coronary heart disease and diabetes.
Conclusions
Prefrailty and frailty were associated with higher arterial stiffness in a cohort of community-dwelling older adults. Arterial stiffness may help explain the relationship between frailty and CVD.
Previous work from the Framingham Heart Study suggests that brain changes because of arterial aging may begin in young adulthood and that such changes precede cognitive deficits. The objective of ...this study was to determine the association of arterial stiffness with measures of white matter and gray matter (GM) integrity in young adults.
One thousand nine hundred three participants from the Framingham Heart Study Third Generation (mean age, 46±8.7 years) had complete tonometry measurements and brain magnetic resonance imaging (T1-weighted and diffusion tensor imaging). Tonometry measures included carotid-femoral pulse wave velocity, augmentation index, carotid-brachial pressure amplification, and central pulse pressure. Fractional anisotropy and GM density images were computed from diffusion tensor imaging and T1 images. Registration to a common anatomic template enabled voxel-based linear regressions relating measures of fractional anisotropy and GM to tonometry measures, adjusting for relevant covariables.
Higher carotid-femoral pulse wave velocity was associated with lower regional fractional anisotropy, including the corpus callosum and the corona radiata (8.7 and 8.6 cc, respectively, P<0.001), as well as lower GM density in the thalamus region (0.9 cc, P<0.001). Analyses did not reveal significant associations between other tonometry measures and fractional anisotropy or GM.
Among young healthy adults, higher aortic stiffness was associated with measures of reduced white matter and GM integrity in areas implicated in cognitive decline and Alzheimer's disease. Greater aortic stiffness may result in subclinical vascular brain injury at ages much younger than previously described.
Background Excess transmission of pressure pulsatility caused by increased arterial stiffness may incur microcirculatory damage in end organs (target organ damage TOD ) and, in turn, elevate risk for ...cardiovascular disease ( CVD ) events. Methods and Results We related arterial stiffness measures (carotid-femoral pulse wave velocity, mean arterial pressure, central pulse pressure) to the prevalence and incidence of TOD (defined as albuminuria and/or echocardiographic left ventricular hypertrophy) in up to 6203 Framingham Study participants (mean age 50±15 years, 54% women). We then related presence of TOD to incident CVD in multivariable Cox regression models without and with adjustment for arterial stiffness measures. Cross-sectionally, greater arterial stiffness was associated with a higher prevalence of TOD (adjusted odds ratios ranging from 1.23 to 1.54 per SD increment in arterial stiffness measure, P<0.01). Prospectively, increased carotid-femoral pulse wave velocity was associated with incident albuminuria (odds ratio per SD 1.28, 95% CI, 1.02-1.61; P<0.05), whereas higher mean arterial pressure and central pulse pressure were associated with incident left ventricular hypertrophy (odds ratio per SD 1.37 and 1.45, respectively; P<0.01). On follow-up, 297 of 5803 participants experienced a first CVD event. Presence of TOD was associated with a 33% greater hazard of incident CVD (95% CI , 0-77%; P<0.05), which was attenuated upon adjustment for baseline arterial stiffness measures by 5-21%. Conclusions Elevated arterial stiffness is associated with presence of TOD and may partially mediate the relations of TOD with incident CVD . Our observations in a large community-based sample suggest that mitigating arterial stiffness may lower the burden of TOD and, in turn, clinical CVD .
Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report ...results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10(-7). The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P < 5 × 10(-8)) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.
Aortic stiffness is associated with cognitive decline and cerebrovascular disease late in life, although these associations have not been examined in young adults. Understanding the effects of aortic ...stiffness on the brain at a young age is important both from a pathophysiological and public health perspective. The aim of this study was to examine the cross-sectional associations of aortic stiffness with cognitive function and brain aging in the Framingham Heart Study Third Generation cohort (47% men; mean age, 46 years). Participants completed the assessment of aortic stiffness (carotid-femoral pulse wave velocity), a neuropsychological test battery assessing multiple domains of cognitive performance and magnetic resonance imaging to examine subclinical markers of brain injury. In adjusted regression models, higher aortic stiffness was associated with poorer processing speed and executive function (Trail Making B-A; β±SE, -0.08±0.03; P<0.01), larger lateral ventricular volumes (β±SE, 0.09±0.03; P<0.01) and a greater burden of white-matter hyperintensities (β±SE, 0.09±0.03; P<0.001). When stratifying by age, aortic stiffness was associated with lateral ventricular volume in young adults (30-45 years), whereas aortic stiffness was associated with white-matter injury and cognition in midlife (45-65 years). In conclusion, aortic stiffness was associated with cognitive function and markers of subclinical brain injury in young to middle-aged adults. Prospective studies are needed to examine whether aortic stiffening in young adulthood is associated with vascular cognitive impairment later in life.
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