OBJECTIVE:To determine arterial stiffness and β-amyloid (Aβ) deposition in the brain of dementia-free older adults.
METHODS:We studied a cohort of 91 dementia-free participants aged 83–96 years. In ...2009, participants completed brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid plaques in human brain). In 2011, we measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed (e.g., brachial ankle PWV baPWV) vascular beds, using a noninvasive and automated waveform analyzer.
RESULTS:A total of 44/91 subjects were Aβ-positive on PET scan. Aβ deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in baPWV resulted in a 2-fold increase in the odds of being Aβ-positive (p = 0.007). High white matter hyperintensity (WMH) burden was associated with increased central PWV, systolic BP, and MAP. Compared to Aβ-negative individuals with low WMH burden, each SD increase in PWV was associated with a 2-fold to 4-fold increase in the odds of being Aβ-positive and having high WMH.
CONCLUSIONS:Arterial stiffness was associated with Aβ plaque deposition in the brain, independent of BP and APOE ε4 allele. The associations differed by type of brain abnormality and vascular bed measured (e.g., WMH with central stiffness and Aβ deposition and mixed stiffness). Arterial stiffness was highest in individuals with both high Aβ deposition and WMH, which has been suggested to be a “double hit” contributing to the development of symptomatic dementia.
IMPORTANCE Recent studies show that cerebral β-amyloid (Aβ) deposition is associated with blood pressure and measures of arterial stiffness in nondemented individuals. OBJECTIVE To examine the ...association between measures of arterial stiffness and change in Aβ deposition over time. DESIGN, SETTING, AND PARTICIPANTS Deposition of Aβ was determined in a longitudinal observational study of aging by positron emission tomography using the Pittsburgh compound B twice 2 years apart in 81 nondemented individuals 83 years and older. Arterial stiffness was measured with a noninvasive and automated waveform analyzer at the time closest to the second positron emission tomography scan. All measures were performed under standardized conditions. Pulse wave velocity (PWV) was measured in the central (carotid-femoral and heart-femoral PWV), peripheral (femoral-ankle PWV), and mixed (brachial-ankle PWV) vascular beds. MAIN OUTCOMES AND MEASURES The change in Aβ deposition over 2 years was calculated from the 81 individuals with repeat Aβ–positron emission tomography. RESULTS The proportion of Aβ-positive individuals increased from 48% at baseline to 75% at follow-up. Brachial-ankle PWV was significantly higher among Aβ-positive participants at baseline and follow-up. Femoral-ankle PWV was only higher among Aβ-positive participants at follow-up. Measures of central stiffness and blood pressure were not associated with Aβ status at baseline or follow-up, but central stiffness was associated with a change in Aβ deposition over time. Each standard deviation increase in central stiffness (carotid-femoral PWV, P = .001; heart-femoral PWV, P = .004) was linked with increases in Aβ deposition over 2 years. CONCLUSIONS AND RELEVANCE This study showed that Aβ deposition increases with age in nondemented individuals and that arterial stiffness is strongly associated with the progressive deposition of Aβ in the brain, especially in this age group. The association between Aβ deposition changes over time and generalized arterial stiffness indicated a relationship between the severity of subclinical vascular disease and progressive cerebral Aβ deposition.
BACKGROUND AND PURPOSE—Atherogenic changes in lipids occur among women around the time of the natural menopause, that is, within 1 year of the final menstrual period (FMP). We investigated whether ...lipid changes around the FMP are related to carotid intima-media thickness, interadventitial diameter, and plaque in postmenopausal women.
METHODS—A total of 863 natural postmenopausal women with no history of heart attack or stroke underwent carotid ultrasound scans at follow-up year 12 or 13 of the Study of Women’s Health Across the Nation. Estimates of their annual change in lipids were segmented into the year before and after the FMP, before the year before FMP, and 1 year after FMP. Multivariate analyses were adjusted for sociodemographic characteristics, time from FMP to scan, baseline body mass index and systolic blood pressure, and use of medications for hypertension and diabetes mellitus at the scan.
RESULTS—Smaller increases in high-density lipoprotein cholesterol and apolipoprotein A1 within 1 year of the FMP were related to greater interadventitial diameter, β (SE)=−0.036 (0.015), P=0.02, and β (SE)=−0.035 (0.013), P=0.006, respectively. Greater increases in low-density lipoprotein cholesterol within 1 year of FMP were related to greater likelihood of plaque scores ≥2, odds ratio, 1.071; 95% confidence interval, 1.018–1.127; P=0.009. Magnitude of associations was reduced but remained significant with further adjustment for premenopausal lipid levels. The difference in probability of elevated plaque scores was 50% between those in the highest and lowest low-density lipoprotein cholesterol change tertiles.
CONCLUSIONS—Changes in lipids as women approach the FMP provide useful clinical information for understanding postmenopausal carotid indices.
Objective: Self-compassion is a positive psychological construct characterized by extending compassion toward oneself, often during periods of suffering. Whereas self-compassion has been associated ...with psychological outcomes, research linking self-compassion to physical health is limited. We tested the hypothesis that greater self-compassion would be associated with less subclinical cardiovascular disease (CVD) as assessed by carotid intima-media thickness (IMT). We adjusted for demographics, CVD risk factors and additionally depressive symptoms in these associations. Method: Women (N = 195; M age = 59 years) without CVD were recruited. Women completed questionnaires (Neff Self-Compassion Scale, Center for Epidemiology Studies of Depression Scale); physical measures (body mass index BMI, blood pressure BP); phlebotomy (lipids, insulin resistance); and ultrasound assessments of the carotid artery (mean, maximal IMT). Cross-sectional associations between self-compassion and IMT were assessed in linear regression models covarying for age, race/ethnicity, education, and CVD risk factors (BMI, BP, insulin resistance, lipids, medications), and additionally depressive symptoms. Results: Higher self-compassion was associated with lower mean IMT B(SE)=−.03 (.01), p = .02, adjusting for demographic factors and CVD risk factors. Associations persisted adjusting for depressive symptoms. When considering self-compassion subscale bifactors, the positive self-compassion bifactor (self-compassion), but not negative self-compassion bifactor (self-coldness), was related to lower IMT. Conclusions: Self-compassion is associated with lower subclinical CVD. Associations were not explained by standard CVD risk factors nor by depressive symptoms. Future research should consider whether enhancing self-compassion improves women's vascular health.
Aims/hypothesis
At the same level of BMI, white people have less visceral adipose tissue (VAT) and are less susceptible to developing type 2 diabetes than Japanese people. No previous ...population-based studies have compared insulin resistance and insulin secretion between these two races in a standardised manner that accounts for VAT. We compared HOMA-IR, HOMA of beta cell function (HOMA-β%) and disposition index (DI) in US white men and Japanese men in Japan.
Methods
We conducted a population-based, cross-sectional study, comprising 298 white men and 294 Japanese men aged 40–49 years without diabetes. Insulin, glucose, VAT and other measurements were performed at the University of Pittsburgh. We used ANCOVA to compare geometric means of HOMA-IR, HOMA-β% and DI, adjusting for VAT and other covariates.
Results
White men had higher HOMA-IR, HOMA-β% and DI than Japanese men, and the difference remained significant (
p
< 0.01) after adjusting for VAT (geometric mean 95% CI): 3.1 (2.9, 3.2) vs 2.5 (2.4, 2.6), 130.8 (124.6, 137.3) vs 86.7 (82.5, 91.0), and 42.4 (41.0, 44.0) vs 34.8 (33.6, 36.0), respectively. Moreover, HOMA-IR, HOMA-β% and DI were significantly higher in white men even after further adjustment for BMI, impaired fasting glucose and other risk factors.
Conclusions/interpretation
The higher VAT-adjusted DI in white men than Japanese men may partly explain lower susceptibility of white people than Japanese people to developing type 2 diabetes. The results, however, should be interpreted with caution because the assessment of insulin indices was made using fasting samples and adjustment was not made for baseline glucose tolerance. Further studies using formal methods to evaluate insulin indices are warranted.
It is unknown whether inflammatory/hemostatic biomarkers are associated with coronary artery calcium (CAC) progression. Our purpose was to evaluate the associations of baseline levels of C-reactive ...protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen, and circulating factor VII with CAC progression in healthy midlife women. Inflammatory/hemostatic biomarkers were measured at baseline. CAC was quantified by computed tomography scans at baseline and after 2.3 ± 0.5 years of follow-up. Significant CAC progression was defined as present if (1) follow-up CAC Agatston score was >0 if baseline CAC score = 0; (2) annualized change in CAC score was ≥10 if baseline CAC score >0 to <100; and (3) annualized percent change in CAC score was ≥10% if baseline CAC score ≥100. Extent of CAC progression was defined as log(CAC(follow-up) +25) − log(CAC(baseline) +25)/year. Logistic and linear regression models were used as appropriate, and the final models were adjusted for baseline CAC score, age, study site, race/ethnicity, menopausal status, sociodemographics, traditional cardiovascular disease (CVD) risk factors, family history of CVD, and CVD medication use. The study included 252 women (baseline age 51.2 ± 2.6 years; 67.5% white; 56.4% premenopausal or early perimenopausal). In final models, only log(PAI-1) was associated with presence of CAC progression (odds ratio 1.91, 95% CI 1.24 to 2.93; per 1 log unit increase in PAI-1; p = 0.003). In addition, higher log(PAI-1) was marginally associated with greater extent of CAC progression (p = 0.06). In conclusion, PAI-1 is associated with the presence of CAC progression in middle-aged women. Targeting PAI-1 may decrease atherogenesis beyond conventional CVD risk factors.
The menopause transition is increasingly recognized as a time of importance for women's brain health. A growing body of work indicates that the classic menopausal symptom, vasomotor symptom (VMS), ...may be associated with poorer cardiovascular health. Other work links VMS to poorer cognition. We investigate whether VMS, when rigorously assessed using physiologic measures, are associated with greater white matter hyperintensity volume (WMHV) among midlife women. We consider a range of potential explanatory factors in these associations and explore whether VMS are associated with the spatial distribution of WMHV.
Women aged 45-67 years and free of hormone therapy underwent 24 hours of physiologic VMS monitoring (sternal skin conductance), actigraphy assessment of sleep, physical measures, phlebotomy, and 3 Tesla neuroimaging. Associations between VMS (24-hour, wake, and sleep VMS, with wake and sleep intervals defined by actigraphy) and whole brain WMHV were considered in linear regression models adjusted for age, race, education, smoking, body mass index, blood pressure, insulin resistance, and lipids. Secondary models considered WMHV in specific brain regions (deep, periventricular, frontal, temporal, parietal, and occipital) and additional covariates including sleep.
The study sample included 226 women. Physiologically assessed VMS were associated with greater whole brain WMHV in multivariable models, with the strongest associations observed for sleep VMS (24-hour VMS, BSE = 0.095 0.045,
= 0.032; Wake VMS, BSE = 0.078 0.046,
= 0.089, Sleep VMS, BSE = 0.173 0.060,
= 0.004). Associations were not accounted for by additional covariates including actigraphy-assessed sleep (wake after sleep onset). When considering the spatial distribution of WMHV, sleep VMS were associated with both deep WMHV, periventricular WMHV, and frontal lobe WMHV.
VMS, particularly VMS occurring during sleep, were associated with greater WMHV. Identification of female-specific midlife markers of poor brain health later in life is critical to identify women who warrant early intervention and prevention. VMS have the potential to serve as female-specific midlife markers of brain health in women.
Background The menopausal transition is characterized by increased cardiovascular risk, weight gain, and increased adiposity for many women. The adipose-derived secretory proteins adiponectin and ...leptin are associated with insulin resistance, metabolic syndrome, and cardiovascular disease but their role in subclinical atherosclerotic disease is unclear. This cross-sectional study evaluated the associations of adiponectin and leptin with carotid artery intima-media thickness, adventitial diameter, presence of carotid plaques, and brachial-ankle pulse wave velocity (baPWV) in women aged 54 to 65 years. Methods and Results Participants were 1399 women from SWAN (Study of Women's Health Across the Nation), a community-based study of women transitioning through menopause. Carotid ultrasound and baPWV measures were obtained at SWAN follow-up visits 12 or 13, when 97% of participants were post-menopausal. Adipokines were assayed from serum specimens obtained concurrently at these visits. Linear and logistic regression models were used to evaluate adiponectin or leptin, both log-transformed attributable to skewness, in relationship to carotid artery intima-media thickness, adventitial diameter, baPWV, and presence of carotid plaque. Covariates included age, race, study site, smoking, alcohol use, obesity, cardiovascular disease risk factors, and menopausal status. Lower levels of adiponectin were related to greater carotid artery intima-media thickness, wider adventitial diameter, and faster baPWV; associations were attenuated after adjusting for cardiovascular disease risk factors. Higher levels of leptin were associated with greater carotid artery intima-media thickness and wider adventitial diameter in minimally and fully adjusted models, and contrary to expectation, with slower baPWV, particularly among women with diabetes mellitus or obesity. Conclusions Adiponectin and leptin are 2 important inflammatory pathways that may contribute to adverse subclinical cardiovascular disease risk profiles in women at midlife.
OBJECTIVE:A few studies have examined the longitudinal association of blood pressure (BP) with arterial stiffness progression, and the results were inconsistent. The objective of this study was to ...investigate the roles of initial BP and its longitudinal change on the progression of arterial stiffness measured using brachial–ankle pulse wave velocity (baPWV).
METHOD:Study participants (n = 656) were from population-based samples of healthy men aged 40–49 years at baseline (213 White Americans, 47 African-Americans, 152 Japanese Americans and 244 Japanese in Japan). BP measures, baPWV and other factors were examined at baseline and 4–7 years later. General linear regression was applied for statistical analyses.
RESULT:Annual change in SBP (standardized coefficient0.33, P < 0.001), but not its baseline level (standardized coefficient0.03, P = 0.495), had a positive significant association with the progression of baPWV after adjusting for a wide range of standard cardiovascular risk factors. Similarly, annual changes in DBP (standardized coefficient0.35, P < 0.001), pulse pressure (standardized coefficient0.15, P = 0.001) and mean arterial pressure (standardized coefficient0.37, P < 0.001) were positively associated with the progression of baPWV. None of the baseline measures were related to the progression of baPWV.
CONCLUSION:Our findings imply that, regardless of initial BP, effective monitoring and controlling of BP is important to slow down arterial wall stiffening and hence reduce cardiovascular risk.
Abstract
Context
Reproductive hormones are important to the pathophysiology of cardiovascular disease (CVD) in women. However, standard estradiol (E2) and testosterone (T) assays lack sensitivity at ...the levels of postmenopausal women.
Objective
Investigate relations of mass spectrometry–assessed estrone (E1), E2, and T and SHBG and subclinical CVD in women.
Design, Setting, and Participants
Three hundred and four perimenopausal and postmenopausal women aged 40 to 60 years underwent subclinical CVD measurements. E1, E2, and T were assayed using liquid chromatography–tandem mass spectrometry; free T (FT) was estimated using ensemble allostery models. Regression models were adjusted for CVD risk factors.
Main Outcome Measures
Carotid artery intima media thickness, interadventitial diameter (IAD), and plaque; brachial flow mediated dilation (FMD).
Results
Higher E1 was related to higher FMD β(SE) = 0.77 (0.37), P = 0.04, indicating better endothelial function. Higher E2 was related to lower IAD β(SE) = −0.07 (0.02), P = 0.004, indicating less carotid remodeling. Higher SHBG was related to higher FMD β(SE) = 1.31 (0.40), P = 0.001, yet higher IAD β(SE) = 0.15 (0.06), P = 0.02 and plaque OR (95% CI) = 1.84 (1.16 to 2.91), P = 0.009; FT showed a similar yet inverse pattern of relations as SHBG. Thus, higher SHBG and lower FT were associated with better endothelial function, yet greater carotid remodeling and plaque.
Conclusions
Endogenous E1 levels were related to endothelial function and E2 to vascular remodeling, suggesting distinct roles of these estrogens. SHBG and FT have complex roles depending on the vessel under study.
In midlife women, mass spectrometry–assessed estrone was related to endothelial function and estradiol to vascular remodeling. SHBG and free testosterone findings varied by vascular system.
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