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ObjectiveTo investigate the occurrence of and risk factors for progression of carotid intima media thickness (IMT) and plaque in women with and without SLE.MethodsA cohort of 149 women with SLE and 126 controls participated in SOLVABLE (Study of Lupus Vascular and Bone Long-term Endpoints). Demographics, cardiovascular and SLE factors, and laboratory assessments were collected at baseline. Carotid IMT and plaque were measured using B-mode ultrasound at baseline and at 5-year follow-up. Regression models were used to identify predictors of progression in carotid IMT and plaque; multivariate models were adjusted for age, hypertension and total cholesterol to high-density lipoprotein ratio.ResultsThe mean±SD follow-up time was 5.35±0.60 years in cases and 5.62±0.66 years in controls. The mean IMT change per year was 0.008±0.015 mm in cases and 0.005±0.019 mm in controls (p=0.24). At follow-up, 31.5% of cases and 15% of controls had plaque progression, with a relative risk for plaque progression of 2.09 (95% CI 1.30 to 3.37). In SLE cases, higher fasting glucose and lower fibrinogen were associated with IMT progression after adjustment. Larger waist circumference and non-use of hydroxychloroquine were associated with plaque progression after adjustment.ConclusionPotential modifiable risk factors for carotid IMT and plaque progression in women with SLE were identified, suggesting that monitoring of glucose and waist circumference and use of hydroxychloroquine may be beneficial.

Background The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. Objectives This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Methods Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. Results A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p Conclusions Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

Background and Purpose— Emerging work has linked menopausal vasomotor symptoms (VMS) to subclinical cardiovascular disease (CVD) among women. However, VMS are dynamic over time. No studies have considered how temporal patterns of VMS may relate to subclinical CVD. We tested how temporal patterns of VMS assessed over 13 years were related to carotid intima media thickness (IMT) among midlife women. Methods— The Study of Women’s Health Across the Nation is a longitudinal cohort study of midlife women. Eight hundred and eleven white, black, Hispanic, and Chinese participants with a well-characterized final menstrual period completed measures of VMS, a blood draw, and physical measures approximately annually for 13 years. Women underwent a carotid artery ultrasound at study visit 12. Results— Four trajectories of VMS were identified by trajectory analysis (consistently high, early-onset, late-onset, persistently low VMS) and tested in relation to carotid indices in linear regression models. Results indicated that women with early-onset VMS had both greater mean IMT (beta, b [standard error, SE]=0.03 [0.01], P =0.03) and greater maximal IMT (b [SE]=0.04 [0.01], P =0.008) than women with consistently low VMS, adjusting for demographics and CVD risk factors. Conclusions— This is the first study to test trajectories of VMS in relation to subclinical CVD. Women with VMS early in the menopause transition had higher mean IMT and maximal IMT than those with consistently low VMS across the transition. Associations were not accounted for by demographic factors nor by CVD risk factors. Results can signal to women in need of early CVD risk reduction.

Objective Higher parity is associated with increased subclinical cardiovascular disease (CVD) in mid-life and older women and with increased CVD risk overall. The relationship between parity, subclinical CVD, and infertility in young women with overweight and obesity has been infrequently evaluated. Methods Reproductive histories were obtained in 191 (66%) young women with overweight and obesity (BMI 25-39.9 kg/m2) participating in a weight loss trial. Baseline carotid intima-media thickness (IMT) and inter-adventitial diameter (IAD) were assessed via B-mode ultrasound. Linear regression was used to estimate the relationship between parity and carotid measures, adjusted for demographic, cardiovascular, and reproductive risk factors. Results Nulliparous women (n = 70, age 34.9 ± 7.1) had increased common carotid IAD (0.230 mm, SE 0.08, P = 0.003) and mean common carotid artery (CCA) IMT (0.031 mm, SE 0.01, P = 0.007) compared with parous women (n = 102, age 39.5 ± 4.9), persisting after adjustment for age, race, and CVD risk factors. No other reproductive factors were statistically significantly associated. Conclusions Nulliparity is associated with markers of less healthy carotid arteries in a sample of disease-free 25- to 45-year-old women with overweight or obesity. This may represent a beneficial effect of pregnancy or indicate overall better health in women with overweight/obesity who are capable of childbearing.

Prior studies evaluating metabolic syndrome (MetS) and incident peripheral artery disease (PAD) have been limited by use of modified MetS criteria and restriction to clinical PAD end points. We investigated MetS and risk of developing a low ankle-brachial index (ABI) and clinical PAD in the Cardiovascular Health Study, a population-based cohort of adults aged ≥65 years. Participants with MetS met at least 3 of 5 Adult Treatment Panel III criteria. Baseline C-reactive protein-MetS or fibrinogen-MetS were defined as presence of 3 of 6 components, with elevated C-reactive protein (>3 mg/L) or fibrinogen (>341 mg/dL) as a sixth component. Incident low ABI, defined as ABI

To determine whether serum concentrations of long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in the incidence rate of coronary artery calcification (CAC) between Japanese men in Japan and white men in the USA.In a population based, prospective cohort study, 214 Japanese men and 152 white men aged 40-49 years at baseline (2002-2006) with coronary calcium score (CCS)=0 were re-examined for CAC in 2007-2010. Among these, 175 Japanese men and 113 white men participated in the follow-up exam. Incident cases were defined as participants with CCS≥10 at follow-up. A relative risk regression analysis was used to model the incidence rate ratio between the Japanese and white men. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline.Mean (SD) serum percentage of LCn3PUFA was100% higher in Japanese men than in white men (9.08 (2.49) vs 3.84 (1.79), respectively, p0.01). Japanese men had a significantly lower incidence rate of CAC compared to white men (0.9 vs 2.9/100 person-years, respectively, p0.01). The incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% CI 0.150 to 0.690; p0.01). After adjusting for age, systolic blood pressure, low density lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant (0.262, 95% CI 0.094 to 0.731; p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376, 95% CI 0.090 to 1.572; p=0.18).LCn3PUFAs significantly contributed to the difference in the incidence of CAC between Japanese and white men.

Mortality from coronary heart disease (CHD) in women in Japan is one of the lowest in developed countries. In an attempt to shed some light on possible reasons of lower CHD in women in Japan compared with the United States, we extensively reviewed and analyzed existing national data and recent literature.We searched recent epidemiological studies that reported incidence of acute myocardial infarction (AMI) and examined risk factors for CHD in women in Japan. Then, we compared trends in risk factors between women currently aged 50-69 years in Japan and the United States, using national statistics and other available resources.Recent epidemiological studies have clearly shown that AMI incidence in women in Japan is lower than that reported from other countries, and that lipids, blood pressure (BP), diabetes, smoking, and early menopause are independent risk factors. Comparing trends in risk factors between women in Japan and the United States, current levels of serum total cholesterol are higher in women in Japan and levels have been similar at least since 1990. Levels of BP have been higher in in Japan for the past 3 decades. Prevalence of type 2 diabetes has been similar in Japanese and white women currently aged 60-69 for the past 2 decades. In contrast, rates of cigarette smoking, although low in women in both countries, have been lower in women in Japan.Differences in risk factors and their trends are unlikely to explain the difference in CHD rates in women in Japan and the United States. Determining the currently unknown factors responsible for low CHD mortality in women in Japan may lead to new strategy for CHD prevention.

Women with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD). Traditional CVD and SLE-disease related risk factors do not fully account for this increased risk. Perivascular adipose tissue (PVAT) is a visceral adipose depot in close proximity to blood vessels possibly influencing CVD. We hypothesized that women with SLE have an increased volume of descending thoracic aortic PVAT (aPVAT) associated with increased vascular calcification.Using electron beam computed tomography, we quantified the aPVAT in clinically CVD-free SLE women (n = 135) and age-/race-matched healthy controls (HC, n = 152). Coronary artery calcification (CAC) and aortic calcification (AC) were quantified using Agatston scores and the aPVAT was quantified using standard Hounsfield Units (HU) for adipose tissue.Women with SLE had greater median aPVAT (32.2 cm(3) vs HC aPVAT 28.6 cm(3), p = 0.0071) and greater median AC (26.0 vs HC AC 6.0, p = 0.0013) than the healthy control women. Total aPVAT (per 25 cm(3)) remained significantly associated with SLE after adjusting for CVD risk factors (Odds Ratio 1.74 [95% Confidence Interval: 1.04-2.9], p = 0.034), but was attenuated when adjusting for circulating inflammatory markers (p = 0.34). In a logistic regression analysis, SLE aPVAT (per 25 cm(3)) was associated with AC (6.78 [2.0-23], p = 0.0019), which remained significant after adjusting for circulating inflammatory markers (p = 0.0074), and CAC (2.66 [1.4-5.0], p = 0.0028).Total aPVAT is greater in clinically CVD-free SLE women than in age-/race-matched controls and is associated with calcification in different vascular beds.

We considered that women with prior preterm birth (PTB) would have evidence of subclinical atherosclerosis, endothelial dysfunction, and arterial stiffness.Four to 12 years after pregnancy, blood pressure and fasting lipids were analyzed, and women underwent evaluation, following standardized protocols, of carotid intima-media thickness (IMT), brachial flow-mediated dilation (FMD), and pulse wave velocity (PWV). Women with prior preterm (37 weeks, n=181) or term births (= 37 weeks, n=306) were compared. Those with preeclampsia or term small-for-gestational-age (SGA) births were excluded.Women with a prior preterm vs. term birth had higher blood pressure, on average, and a more atherogenic lipid profile. They also had marginally higher IMT (0.579 standard error [SE] 0.005-vs. 0.567 [0.004] mm, p=0.06), adjusted for body size, demographics, and smoking. IMT differences were greater among those with non-preeclamptic-indicated PTB (0.034 mm, p=0.05) and PTB34 weeks (0.024 mm, p=0.04) compared to those with term births. These differences appeared to be explained in part by the atherogenic lipid elevations in women with preterm birth. Women with prior PTB34 weeks tended to have lower FMD, but results were not statistically significant. PWV did not differ according to PTB.In the decade following pregnancy, women with non-preeclamptic-indicated PTB or PTB delivered before 34 weeks had higher blood pressure, atherogenic lipids, and IMT compared to women with term births. There may be subgroups of women with a prior PTB with excess cardiovascular risk that is detectable before overt clinical disease.

OBJECTIVE The aim of this manuscript was to report the risk of incident peripheral arterial disease (PAD) in a large randomized clinical trial that enrolled participants with stable coronary artery disease and type 2 diabetes and compare the risk between assigned treatment arms. RESEARCH DESIGN AND METHODS The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomly assigned participants to insulin sensitization (IS) therapy versus insulin-providing (IP) therapy for glycemic control. Results showed similar 5-year mortality in the two glycemic treatment arms. In secondary analyses reported here, we examine the effects of treatment assignment on the incidence of PAD. A total of 1,479 BARI 2D participants with normal ankle-brachial index (ABI) (0.91–1.30) were eligible for analysis. The following PAD-related outcomes are evaluated in this article: new low ABI ≤0.9, a lower-extremity revascularization, lower-extremity amputation, and a composite of the three outcomes. RESULTS During an average 4.6 years of follow-up, 303 participants experienced one or more of the outcomes listed above. Incidence of the composite outcome was significantly lower among participants assigned to IS therapy than those assigned to IP therapy (16.9 vs. 24.1%; P < 0.001). The difference was significant in time-to-event analysis (hazard ratio 0.66 [95% CI 0.51–0.83], P < 0.001) and remained significant after adjustment for in-trial HbA1c (0.76 [0.59–0.96], P = 0.02). CONCLUSIONS In participants with type 2 diabetes who are free from PAD, a glycemic control strategy of insulin sensitization may be the preferred therapeutic strategy to reduce the incidence of PAD and subsequent outcomes.

Bone mineral density (BMD) has been inversely associated with subclinical and clinical cardiovascular disease (CVD) in population studies, but the potential mechanisms underlying this relationship are unclear. To test if there is a genetic basis underlying this association, we determined the phenotypic and genetic correlations between BMD and carotid artery ultrasound measures in families. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were used to measure BMD in 461 individuals with African ancestry belonging to seven large, multigenerational families (mean family size 66; 3414 total relative pairs). Carotid artery ultrasound was used to measure adventitial diameter (AD) and intima-media thickness (IMT). Phenotypic and genetic correlations between BMD and carotid measures were determined using pedigree-based maximum likelihood methods. We adjusted for potential confounding factors, including age, sex, body weight, height, menopausal status, smoking, alcohol intake, walking for exercise, diabetes, hypertension, serum lipid and lipoprotein levels, inflammation markers, and kidney function. We found statistically significant phenotypic (ρ = −0.19) and genetic (ρG = −0.70) correlations (p

Aortic stiffness is being recognized as a predictor of cardiovascular disease (CVD) and all-cause mortality independent of blood pressure (BP), age, and other CVD risk factors.1 Aortic stiffness can be measured noninvasively by carotid–femoral pulse wave velocity (cfPWV), which is considered the gold standard method. In fact, the European Society of Hypertension/European Society of Cardiology added cfPWV as a factor to assess future CVD risk in recently published guidelines for the management of arterial hypertension.2 A recent meta-analysis reported that supplementation of marine n-3 fatty acids (FAs) improved aortic stiffness.3 The randomized clinical trials (RCTs) in the meta-analysis4–12 and 1 more recent RCT13 have several characteristics. First, subjects in these RCTs were individuals with type 2 diabetes,5,9 metabolic syndrome,10 hyperlipidemia,11,12 or individuals who were obese or overweight.4,6–8 Thus, the result may not be extrapolated to the general population. Second, although the differential effect of 2 major marine n-3 FAs: eicosapentaenoic (EPA; 20:5 n-3) and docosahexaenoic acids (DHA; 22:6 n-3), on CVD risk factors is a current research topic,14 only 1 RCT11 reported the effect of each of DHA and EPA on aortic stiffness separately. Third, although cfPWV is regarded as the gold standard to evaluate aortic stiffness, these RCTs, except for one study,13 used other methods. Finally, most of these RCTs examined the effect of >1 gram of fish oil on aortic stiffness,4–7,9–11,15 as compared with

The prevalence of coronary artery calcification (CAC) in Japanese men is lower than in white and Japanese-American men. It is unclear if aortic calcification (AC) strongly linked to smoking is also lower in Japanese men who have many times higher smoking prevalence compared to US men.We conducted a population-based study of 903 randomly-selected men aged 40-49 years: 310 Japanese men in Kusatsu, Japan, 301 white men in Allegheny County, US, and 292 Japanese men in Hawaii, US (2002-2006). The presence of AC was assessed by electron-beam tomography. AC was defined as Agatston aortic calcium scores (AoCaS)0 and ≥ 100.Japanese (35.8%) had significantly less AoCaS0 compared to both white (68.8%, p0.001) and Japanese-American (62.3%, p0.001) but similar AoCaS ≥ 100 (19.4%, 18.3%, 22.6%, respectively, p=0.392). The pack-years of smoking, which was highest in Japanese, was the most important single associate of AC in all populations. Additionally age, low-density-lipoprotein cholesterol (LDL-C), and triglycerides in Japanese; body-mass index (BMI) in white; and BMI, LDL-C, hypertension, diabetes, and lipid medications in Japanese-American were independent associates of AC. The risk of AC using either cut points adjusted for pack-years of smoking and additional risk factors was lower in Japanese compared to both white and Japanese-American. AC and CAC had moderately positive and significant correlations in Japanese (r=0.26), white (r=0.39), and Japanese-American (r=0.45).The prevalence of AC defined both0 and ≥ 100 was significantly lower in Japanese than in white and Japanese-American men after adjusting for cigarette smoking and additional risk factors.

We examined the association between serum lipoprotein subclasses and the three measures of arterial stiffness, that is, (i) carotid-femoral pulse wave velocity (cfPWV), which is a gold standard measure of central arterial stiffness, (ii) brachial-ankle PWV (baPWV), which is emerging as a combined measure of central and peripheral arterial stiffness and (iii) femoral-ankle PWV (faPWV), which is a measure of peripheral arterial stiffness. Among a population-based sample of 701 apparently healthy Caucasian, Japanese American and Korean men aged 40-49 years, concentrations of lipoprotein particles were assessed by nuclear magnetic resonance (NMR) spectroscopy, and the PWV was assessed with an automated waveform analyzer (VP2000, Omron, Japan). Multiple linear regressions were performed to analyse the association between each NMR lipoprotein subclasses and PWV measures, after adjusting for cardiovascular risk factors and other confounders. A cutoff of P0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all P0.0001) but not LDL cholesterol (LDL-C) (all P0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all P0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (P0.01). In this study of healthy middle-aged men, as compared with cfPWV, both baPWV and faPWV had stronger associations with particle numbers of lipoprotein subclasses. Our results may suggest that both baPWV and faPWV are related to arterial stiffness and atherosclerosis, whereas cfPWV may represent arterial stiffness alone.

Objective Empirical evidence supports an inverse relationship between physical activity (PA) and adiposity, but studies using detailed measures of both are scarce. The relationship between regional adiposity and accelerometer-derived PA in men and women are described. Design and Methods Cross-sectional analysis included 253 participants from a weight loss study limited to ages 20-45 years and BMI 25-39.9 kg m−2. PA data were collected with accelerometers and expressed as total accelerometer counts and average amount of time per day accumulated in different intensity levels [sedentary, light-, and moderate-to-vigorous intensity PA (MVPA)]. Accumulation of time spent above 100 counts was expressed as total active time. Computed tomography (CT) was used to measure abdominal and adipose tissue (AT). Multivariate linear regression analyses were used to assess the relationship between regional adiposity (dependent variable) and the various PA levels (independent variable), and were executed separately for men and women, adjusting for wear time, age, race, education, and BMI. Results Among males, light activity was inversely associated with total AT (β = −0.19; P = 0.02) as well as visceral AT (VAT) (β = −0.30; P = 0.03). Among females sedentary time was positively associated with VAT (β = 0.11; P = 0.04) and total active time was inversely associated with VAT (β = −0.12; P = 0.04). Conclusions Findings from this study suggest that PA intensity level may influence regional adiposity differently in men and women. Additional research is needed in larger samples to clarify the difference in these associations by sex, create recommendations for the frequency, duration and intensity of PA needed to target fat deposits, and determine if these recommendations should differ by sex.

Recent data suggest excess circulating aldosterone promotes cardiometabolic decline. Weight loss may lower aldosterone levels, but little longitudinal data is available in normotensive adults. We aimed to determine whether, independent of changes in sodium excretion, reductions in serum aldosterone are associated with favorable changes in obesity-related factors in normotensive overweight/obese young adults. We studied 285 overweight/obese young adult participants (body mass index ≥ 25 and

The liver is an insulin-responsive organ that contributes significantly to both whole body insulin sensitivity and availability of sex steroids through the production of sex hormone binding globulin (SHBG). Our objective was to explore whether lower SHBG was associated with ectopic liver fat and mediated its effect on insulin resistance in The Study of Women's Health Across the Nation (SWAN).A subset of midlife African American and Caucasian women from SWAN (n = 208; 50.9 ± 0.18 yrs; 71% Caucasian) had computed tomography scans to quantify visceral, subcutaneous and liver fat. Blood samples were collected and assayed for hormonal and metabolic markers.The cohort, while overweight, was generally healthy, and both liver fat and SHBG were unaffected by menopausal stage or race. Both higher liver fat and lower SHBG levels were significantly associated with higher insulin concentrations after adjustment for adiposity (r = -0.25, P0.001 and r = -0.18, P = 0.01). SHBG and liver fat had additive effects on insulin concentrations such that women with the lowest SHBG and the highest fat levels had the highest values (interaction P = 0.09). The association between SHBG and insulin was more apparent among women with fattier livers. SHBG and liver fat appear to have independent effects on insulin levels as adjustment for each other did not diminish the strength of either association (P = 0.023 and 0.001 respectively).These results confirmed the strong independent associations between increased liver fat and decreased SHBG with increased metabolic risk in midlife women. Further these data underscore the need for additional research into the role of liver fat in modifying SHBG's influence on insulin levels.

OBJECTIVE: Recently, it was demonstrated that information on carotid intima-media thickness (CIMT) and plaque may improve coronary heart disease (CHD) risk prediction through reclassification of some individuals to the correct risk category using the Framingham risk score. Our objective was to assess the currently unknown cost-effectiveness of CIMT measurements in primary prevention. METHODS: A hypothetical cohort of men and women aged 50-59 years and at intermediate or high CHD risk based on data from the Atherosclerosis Risk in Communities Study was simulated using a Markov model. Myocardial infarction (MI) events were used as a proxy for CHD. The effectiveness of pharmaceutical treatment was varied in the analysis. Sensitivity analysis was performed to obtain robust results. RESULTS: CIMT-based reclassification induced a 1% lower absolute risk of MI and 0.01-0.02 increase in quality-adjusted life years (QALYs) for men, and a 1-3% lower risk, and 0.03-0.05 increase in QALYs for women, over a period of 20-30 years. Corresponding costs were an additional $100 per man, and a cost-saving of $200-300 per woman. Over a 10-year period CIMT measurements were cost-effective with a probability of 66% (men), and 94% (women). Over a 30-year period, CIMT measurements had acceptable cost-effectiveness for men and women. CONCLUSION: Performing CIMT measurements in asymptomatic men and women aged 50-59 years results in additional, but small, health benefits. It takes time for these health benefits to outweigh the initial CIMT measurement costs. Our results support CIMT measurements for cardiovascular risk stratification, in particular for women, when focusing on long-term health.

A low ankle–brachial index (ABI) is associated with increased risk for cardiovascular events and mortality. Physical inactivity in individuals with a low ABI may further increase their risk for cardiovascular events. The purpose of this paper is to examine the relationship between the intensity of free-living physical activity and cardiovascular disease (CVD) risk by ABI status. During 2003–2004, the National Health and Nutrition Examination Survey included an accelerometer module and collected ABI data. Individuals were classified as having a normal (1–1.4) or low (< 1) ABI. The Framingham risk score (FRS) was used to determine CVD risk. Multiple linear regression was used to determine the association of total accelerometer counts and time spent at various physical activity intensity levels with FRS by ABI groups. Individuals with a low ABI spent less time engaging in moderate-to-vigorous intensity physical activity (MVPA) (9.1 min/day vs 13.2 min/day; p = 0.06) when compared to those with a normal ABI. There were no differences in light intensity physical activity (LPA) or sedentary behavior between ABI groups. Total accelerometer counts were inversely related to FRS. MVPA, but not LPA, was inversely related to FRS in both normal and low ABI groups ( p < 0.001 and p = 0.001, respectively). In conclusion, these findings suggest that even modestly higher levels of physical activity may be beneficial for secondary risk prevention in this high-risk group.

The aim of this study is to assess whether the levels and progression rates of carotid intima-media thickness (IMT) and adventitial diameter (AD) vary by menopausal stage.Two hundred forty-nine women (aged 42-57 y; 49% premenopausal and 46% early perimenopausal) from the Study of Women's Health Across the Nation were included in the current analysis. Participants were followed up for up to 9 years (median, 3.7 y) and underwent up to five carotid scans. Linear mixed-effect models were used for the analysis.The overall rate of change in IMT was 0.007 mm/year. Independent of age and race, the progression rate of IMT increased substantially in the late perimenopausal stage (0.017 mm/y) compared with both the premenopausal stage (0.007 mm/y) and the early perimenopausal stage (0.005 mm/y; P ≤ 0.05). For AD, although the overall rate of change was negative (-0.009 mm/y), significant positive increases in the rate of change were observed in the late perimenopausal stage (0.024 mm/y) and the postmenopausal stage (0.018 mm/y) compared with the premenopausal stage (-0.032 mm/y; P0.05). In the final models, the postmenopausal stage was independently associated with higher levels of IMT and AD (P0.05) compared with the premenopausal stage.During the menopausal transition, the carotid artery undergoes adaptation that is reflected in adverse changes in IMT and AD. These changes may have an impact on the vulnerability of the vessel to disease in older women.

Although the cross-sectional relationship of arterial stiffness with cerebral small vessel disease is consistently shown in middle-aged and young-old adults, it is less clear whether these associations remain significant over time in very old adults. We hypothesize that arterial stiffness is longitudinally associated with white matter characteristics, and associations are stronger within watershed areas. Neuroimaging was obtained in 2006–2008 from 303 elderly (mean age 82.9 years, 59% women, 41% black) with pulse wave velocity (PWV) measures in 1997–1998. Multivariable regression models estimated the coefficients for PWV (cm/sec) in relationship to presence, severity, and spatial distribution of white matter hyperintensities (WMH), gray matter volume, and fractional anisotropy from diffusion tensor, adjusting for demographic, cardiovascular risk factors, and diseases from 1997–1998 to 2006–2008. Higher PWV in 1997–1998 was associated with greater WMH volume in 2006–2008 within the left superior longitudinal fasciculus (age and total brain WMH adjusted, P =0.023), but not with WMH in other tracts or with fractional anisotropy or gray matter volume from total brain ( P >0.2). Associations were stronger in blacks than in whites, remaining significant in fully adjusted models. Elderly with WMH in tracts related to processing speed and memory are more likely to have had higher PWV values 10 years prior, before neuroimaging data being available. Future studies should address whether arterial stiffness can serve as an early biomarker of covert brain structural abnormalities and whether early arterial stiffness control can promote successful brain aging, especially in black elderly.

OBJECTIVES The present cross-sectional study aimed to a) examine associations between measures of psychological well-being, specifically life satisfaction and life engagement, and intima media thickness, a subclinical marker of atherosclerosis; b) investigate if the interaction of psychological well-being and life events correlated with intima media thickness; and c) explore these relationships across race. METHODS A sample of 485 women (38% African American and 62% white; mean [standard deviation] age = 50.2 [2.9] years) underwent ultrasonography to assess carotid artery intima media thickness (IMT). The women completed self-report measures of life satisfaction, life engagement, and life events. RESULTS Average (standard deviation) IMT was 0.666 (0.10) mm. Life satisfaction showed a significant, independent, inverse relationship with IMT, after controlling for demographic, behavioral, psychological, and cardiovascular covariates (β = -0.105, p = .039), such that each 1-point higher life satisfaction score was correlated with a significant 0.008-mm lower level of mean IMT. No significant association was seen between life events and IMT (r = 0.05, p = .32), and life satisfaction did not interact with life events on IMT (β = -0.036, p = .46). No significant interaction between life satisfaction and race on IMT was observed (β = 0.068, p = .37). In contrast to life satisfaction, life engagement was not a significant correlate of IMT (r = -0.07, p = .12). CONCLUSIONS Life satisfaction, a measure of psychological well-being, is an important independent correlate of subclinical atherosclerosis in middle-aged women.

Obesity increases cardiovascular disease risk and adversely affects vascular structure and function. Few studies have evaluated the vascular effects of non-surgical weight reduction in the severely obese. We hypothesized that weight loss and improvements in cardiometabolic factors would reduce common carotid artery intima-media thickness (CIMT) and inter-adventitial diameter (AD) in severely obese adults.We performed carotid ultrasound and measured cardiometabolic factors in 90 severely obese participants (body mass index (BMI)≥35 kg/m(2), age 30-55) at baseline and 6 months in a randomized clinical trial of dietary intervention with (n=45) or without (n=45) physical activity.The achieved weight loss (mean=8%) did not differ significantly by intervention group (P=0.10) and resulted in a 0.07 mm mean decrease in AD (P=0.001). AD change was positively correlated with changes in BMI, waist circumference, abdominal visceral and subcutaneous fat, and body fat mass, and AD decreased more in men (P0.05 for all). After multivariable adjustment, changes in BMI (P=0.03) and abdominal subcutaneous fat (P=0.04) were significant determinants of AD change. Although CIMT did not decrease significantly overall (-0.008 mm, P=0.16), individuals who lost at least 5% of their body weight experienced a significant mean reduction in CIMT of 0.02 mm (P=0.002). CIMT change was positively correlated with changes in BMI, waist circumference, fat-free mass, leptin, and insulin (P0.05 for all). After multivariable adjustment, insulin reduction remained a significant determinant of CIMT decrease (P=0.03).A 6 month intensive behavioral intervention can significantly reverse metabolic and vascular abnormalities in severely obese adults.

Objective To determine whether endogenous sex hormones (estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), and follicle stimulating hormone (FSH)) are longitudinally associated with progression of atherosclerosis among women at midlife. Methods 249 Pre- or early peri-menopausal women (42–57 years) from the Study of Women's Health Across the Nation (SWAN) were followed for up to 9 years (median = 3.7 years) and had up to 5 repeated measures of common carotid intima-media thickness (IMT) and adventitial diameter (AD). Linear mixed models were used for statistical analysis. Final models included age at baseline, time since baseline, cycle day of blood draw, race, income, SBP, BMI, insulin resistance index, lipids, C-reactive protein and co-morbidity. Results In final models for IMT, each one log unit decrease in SHBG was associated with a 0.005 mm/year increase in IMT progression ( P = 0.003). E2, T, and FSH were not associated with level or progression of IMT. For AD, each one log unit decrease in E2 was associated with a 0.012 mm/year increase in AD progression ( P = 0.04) and each one log unit increase in FSH was associated with a 0.016 mm/year increase in AD progression ( P = 0.003). T and SHBG were not associated with progression or level of AD. Conclusions Independent of SBP, BMI, lipids and other covariates, lower E2 and SHBG, and higher FSH were associated with increased subclinical atherosclerosis progression in women at midlife.

The aim of this study was to determine whether postmenopause status is associated with self-reported limitations in physical function.The Study of Women's Health Across the Nation is a multisite, multiethnic, longitudinal study of midlife women. Women aged 45 to 57 years (N = 2,566) completed the physical function scale of the Medical Outcomes Study Short-Form 36 on visit 4 (2000-2001). Scores created a three-category variable of physical function limitations: none (86-100), moderate (51-85), and substantial (0-50). In the Study of Women's Health Across the Nation, menopause status is a five-category list variable based on menstrual bleeding patterns and gynecological surgery. Premenopausal and perimenopausal women using hormones (n = 284) or missing physical function scores (n = 46) were excluded. Multinomial logistic regression was used to relate physical function and menopause status after adjustment for age, ethnicity, site, education, body mass index (BMI), and self-reported diabetes, hypertension, arthritis, depressive symptoms, smoking, and hormone use among postmenopausal women.Of 2,236 women, 8% were premenopausal, 51% were early perimenopausal, 12% were late perimenopausal, 24% were naturally postmenopausal, and 5% were surgically postmenopausal. In the full model, substantial limitations in physical function were higher in postmenopausal women, whether naturally postmenopausal (odds ratio, 3.82; 95% CI, 1.46-10.0) or surgically postmenopausal (odds ratio, 3.54; 95% CI, 1.15-10.84), than in premenopausal women. These associations were attenuated by higher BMI and depressive symptoms but remained significant. Moderate limitations in physical function were not significantly related to menopause status.Women experiencing surgical or naturally occurring postmenopause report greater limitations in physical function compared with premenopausal women, independent of age and only partly explained by higher BMI and depressive symptoms. This suggests that physiological changes in menopause could contribute directly to limitations in physical function.

Arterial stiffness decreases with weight loss in overweight/obese young adults. We aimed to determine the mechanisms by which this occurs.We evaluated carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) in 344 young adults (23% male, BMI 25-40 kg/m(2)) at baseline, 6, and 12 months in a behavioral weight loss intervention. Linear mixed models were used to evaluate associations between weight loss and arterial stiffness and to examine whether improvements in obesity-related factors explained these associations.At 6 months (7% mean weight loss), there was a significant median decrease of 47.5 cm/s in cfPWV (p 0.0001) and a mean decrease of 11.7 cm/s in baPWV (p = 0.049). At 12 months (6% mean weight loss), only cfPWV remained reduced. In models adjusting for changes in mean arterial pressure and obesity-related factors, changes in BMI (p = 0.01) and common carotid artery diameter (p = 0.003) were positively associated with change in cfPWV. Reductions in heart rate (p 0.0001) and C-reactive protein (p = 0.02) were associated with reduced baPWV and accounted for the association between weight loss and reduced baPWV.Weight loss is associated with reduced cfPWV independently of changes in established hemodynamic and cardiometabolic risk factors, but its association with reduced baPWV is explained by concurrent reductions in heart rate and inflammation.

Cigarette smoking is a risk factor of coronary heart disease. Vascular calcification such as coronary artery calcium (CAC) and aortic calcium (AC) is associated with coronary heart disease. The authors hypothesised that cigarette smoking is associated with coronary artery and aortic calcifications in Japanese and Koreans with high smoking prevalence.Random samples from populations of 313 Japanese and 302 Korean men aged 40-49 years were examined for calcification of the coronary artery and aorta using electron beam CT. CAC and AC were quantified using the Agatston score. The authors examined the associations of cigarette smoking with CAC and AC after adjusting for conventional risk factors and alcohol consumption. Current and past smokers were combined and categorised into two groups using median pack-years as a cut-off point in each of Japanese and Koreans. The never-smoker group was used as a reference for the multiple logistic regression analyses.The ORs of CAC (score ≥10) for smokers with higher pack-years were 2.9 in Japanese (p0.05) and 1.3 in Koreans (non-significant) compared with never-smokers. The ORs of AC (score ≥100) for smokers with higher pack-years were 10.4 in Japanese (p0.05) and 3.6 in Koreans (p0.05).Cigarette smoking with higher pack-years is significantly associated with CAC and AC in Japanese men, while cigarette smoking with higher pack-years is significantly associated with AC but not significantly with CAC in Korean men.

Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men.We examined the association in 906 men aged 40-49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography.Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1-100 (n=411), 101-300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/s) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), P for trend0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group.The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40s.

Cholesterol metabolism is believed to play a role in the development of Alzheimer's disease (AD). Oxysterol metabolites of cholesterol, 24S-hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have been associated with AD. We investigated whether oxysterols were associated with markers of cerebrovascular disease prior to the onset of cognitive impairment. Oxysterols were quantified in 105 participants (average age: 80 ± 4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study who remained cognitively normal at blood draw in 2002, had MRI in 1992 and 1998, and annual cognitive assessment for incident AD and mild cognitive impairment made by consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were associated with age, gender, the presence of high grade white matter hyperintensities, and brain infarcts on prior MRI. Participants with higher plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to develop incident cognitive impairment over 8 years of follow-up. Higher levels of 24-OHC suggest increased cholesterol metabolism occurring in the brains of participants with cerebrovascular disease prior to the onset of cognitive impairment. Measurement of oxysterols may provide information about cholesterol metabolism and brain disease over the cognitive impairment process.

Background— Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events. Methods and Results— We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3′- BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, β=−0.075±0.012 SD/allele, P =2.8×10 −10 ; replication β=−0.086±0.020 SD/allele, P =1.4×10 −6 ). Combined results for rs7152623 from 11 cohorts gave β=−0.076±0.010 SD/allele, P =3.1×10 −15 . The association persisted when adjusted for mean arterial pressure (β=−0.060±0.009 SD/allele, P =1.0×10 −11 ). Results were consistent in younger (P =2.3×10 −9 ) and older (9 cohorts, n=12 026, β=−0.061±0.014 SD/allele, P =9.4×10 −6 ) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02–1.08; P =0.0013) and heart failure (hazard ratio=1.10, CI=1.03–1.16, P =0.004). Conclusions— Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.

Carotid atherosclerosis is a marker for atherosclerotic disease in other vascular beds; however, racial differences in this association have not been fully examined. The purpose of this report was to evaluate racial differences in the relationship between carotid plaque and calcification in the aorta and coronary arteries among women transitioning through menopause.A total of 540 African American and white women with a median age of 50 years were evaluated from the Study of Women's Health Across the Nation. Carotid plaque (none vs. any) was assessed with B-mode ultrasound, and aortic calcification (AC; 0,0-100, and100) and coronary artery calcification (CAC; 0,0-10, and10) were assessed with CT.For the total cohort, higher prevalence of plaque was significantly associated with higher levels of AC but not CAC. The interaction of race and carotid plaque was significant in models with AC and CAC as dependent variables (P = 0.03 and 0.002, respectively). Among African Americans, there was an inverse relationship, although not significant, between carotid plaque and high AC (100; odds ratio [OR], 0.75; 95% CI, 0.10-5.48) and between plaque and high CAC (10; OR, 0.20; 95% CI, 0.03-1.52) in fully adjusted models. In contrast, for whites, significant positive associations existed between carotid plaque and high AC (OR, 4.12; 95% CI, 1.29-13.13) and borderline associations for high CAC (OR, 1.83; 95% CI, 0.66-5.19).This study demonstrates that the presence of carotid plaque seemed to be a marker for AC and potentially CAC in white women, but not African American middle-aged women, during the menopausal transition.

OBJECTIVE Unrealistic optimism-typically conceptualized as underestimation of comparative risk-has been previously associated with poorer health behaviors and outcomes, but no research to date has examined the association between unrealistic optimism and subclinical or clinical disease endpoints. Here, cross-sectional data from one time point in the Pittsburgh Healthy Heart study are used to examine whether unrealistic optimism about risk of heart disease is associated with carotid artery intima-media thickness (IMT), a subclinical marker of atherosclerosis. METHODS Participants were 148 adults aged 57-77. Objective risk score was calculated using the Framingham calculator, and IMT was regressed on risk score and perceived risk. Controlling for the Framingham risk score effectively equated risk across the sample, meaning that lower risk perceptions represented unrealistic optimism. RESULTS When controlling for the risk score, risk perceptions were negatively associated with IMT (β = -.21, p < .01, t = -2.79, d = .46), a finding that was not moderated by gender. The risk score was also associated with IMT (β = .42, p < .001, t = 5.55, d = .91). CONCLUSIONS Unrealistic optimism was associated with subclinical atherosclerosis. Future longitudinal research is necessary to evaluate the temporal sequence as well as to examine putative explanatory mechanisms.

Introduction Nursing personnel injury related to patient transfer is epidemic, and reduction of injury rates is a national priority. Hierarchical task analysis (HTA) was chosen to address this issue. Method HTA methods were used to create an optimum task set and protocol which consisted of Internet-based education, simulation practice, and debriefing. Participants (N = 71) were randomly assigned to teams to perform simulated transfers. Pre- to postintervention transfer success was evaluated by ergonomic experts. Results Each team improved significantly from pre- to postintervention (N = 19), with every protocol step demonstrating improvement (N = 10). Interrater reliability of the evaluation instrument was calculated (.43–.83). Conclusion Simulation was used successfully to improve transfer success. This approach shows promise in reduction of transfer-related nursing injury.

Depressive disorders have been associated with cardiovascular disease (CVD), but the impact of depression on early atherogenesis has not been well described, particularly in women and minorities. The relation between repeated episodes of high depressive symptoms and coronary calcium (CAC) is unknown in women at midlife when depression is common. Participants in the Study of Women's Health Across the Nation Heart study were assessed annually for depressive symptoms (Center for Epidemiological Studies Depression Scale [CES-D scale]) over 5 years before CAC assessment and classified as high (CES-D ≥16) or not. CAC, measured by computed tomography, was analyzed as a categorical variable using cumulative logit partial proportional odds models. In these middle-aged women free of CVD and diabetes (194 black, 334 white), high depressive symptoms over 5 years were common; 19% had 1, 9% had 2, and 11% experienced ≥3 episodes. CAC was low; 54% had no CAC, 25% had scores from 0 to 10, and 21% had CAC ≥10 Agatston score. After adjusting for CVD risk factors, women with ≥3 episodes were twice as likely to have significant CAC (≥10 Agatston units) than women with no depressive episodes (odds ratio 2.20, 95% confidence interval 1.13 to 4.28, p = 0.020) with no difference by race. Women with 1 or 2 episodes did not differ from women with no episodes. In conclusion, in healthy women aged 46 to 59 years without clinical CVD or diabetes, persistent depressive symptoms were significantly associated with elevated CAC scores, suggesting that they are more likely to have pathophysiological and behavioral effects on the development of subclinical CVD than does a single episode of elevated depressive symptoms.

Arterial stiffness is a marker of cardiovascular health. Arterial stiffness and C-reactive protein (CRP) are linked to cardiovascular outcomes. Increases in both inflammation and arterial stiffness are known to occur with menopause. The association between CRP and arterial stiffness is well accepted; however, no study has determined whether there are differences in this association by menopause status and race, independent of age.The cross-sectional association between CRP and aortic pulse wave velocity (PWV), a validated measure of central arterial stiffening, was evaluated in 307 African American and white women enrolled in an ancillary study to the Study of Women's Health Across the Nation. Women were categorized into premenopausal or early perimenopausal (n = 185) and late perimenopausal or postmenopausal (n = 122).Natural log-transformed CRP was not associated with PWV in a linear regression model adjusted for age and cardiovascular risk factors (β = 15.9, P = 0.11). Moreover, models stratified by menopause status showed a linear relationship between CRP and PWV among late perimenopausal or postmenopausal women (β = 36.2, P = 0.049) but not for premenopausal or early perimenopausal women (β = 5.9, P = 0.61). The menopause status × log-transformed CRP and menopause status × race interactions were significant in their respective models adjusted for age and risk factors (P = 0.03 for both); however, when combined into one model, the two interactions were slightly attenuated (P = 0.063 and 0.052, respectively).Menopause is strengthening the association between CRP and PWV, independent of age, and this effect seems to be stronger among African American women. This study provides a potential mechanism for the increased risk of cardiovascular disease among postmenopausal women.

Vasomotor symptoms (VMS; hot flashes and/or night sweats), are experienced by most women transitioning through the menopause.1 VMS are associated with sleep disturbance,2 depressed mood,3 and overall decrements in physical, social, and emotional quality.4 Most women with menopausal symptoms, principally VMS, seek treatment for them.5 Despite their prevalence and impact on women’s lives, the physiology of VMS is not well understood. Leading etiologic models cite VMS as thermoregulatory heat dissipation events occurring in the context of the menopausal withdrawal of gonadal hormones.6 However, many other central and peripheral systems have been implicated in VMS, and the need for better understanding of the physiology of VMS has been recognized.7 In addition to the quality of life implications of VMS, emerging evidence is linking VMS to cardiovascular risk. In the Women’s Health Initiative (WHI)8 and the Heart and Estrogen/Progestin Replacement Study (HERS),9 older postmenopausal women with moderate-severe VMS at the study baseline were at greatest cardiovascular risk with hormone use. Our findings from the Study of Women’s Health Across the Nation Heart Study (SWAN Heart) further showed that midlife women with hot flashes had indices of greater subclinical cardiovascular disease, including poorer endothelial function,10 greater aortic calcification,10 and greater intima media thickness11 than women without hot flashes. Others have found similar findings for endothelial function.12 Associations generally persist with adjustment for standard cardiovascular risk factors. The reason(s) for links between VMS and cardiovascular risk is not fully understood. One study has suggested that hot flash severity may be associated with alterations in inflammatory processes.13 Altered inflammation and hemostasis, two inter-related systems,14 play key roles in the pathogenesis of CVD. These alterations have been related, in many cases prospectively, to CVD risk.15 In fact, the endothelium, dysfunction of which has been linked to VMS, plays a central role in regulating blood coagulation and inflammation.16 The primary study aim was to examine the associations between VMS and inflammatory and hemostatic markers in SWAN, a large, longitudinal study of women transitioning through the menopause. We assessed the longitudinal relations of VMS to hs-CRP (high sensitivity C-reactive protein), an acute phase reactant prospectively associated with CVD risk,17 the procoagulant/anti-fibrinolytic hemostatic markers, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA-ag), and Factor VIIc (FVIIc), and the acute-phase reactant protein, fibrinogen,18 all of which have been linked to CVD risk.15, 18–19 We hypothesized that VMS would be associated with adverse alterations in inflammation and hemostasis after adjusting for potential confounding/explanatory factors (e.g., smoking, obesity, educational attainment) as well as serum estradiol (E2), a gonadal hormone associated with both VMS 20–21 and inflammation/hemostasis.22 We also evaluated any modification of these associations by menopausal stage as well as race/ethnicity, given the importance of these factors to VMS and cardiovascular risk.

Background Numerous studies reported beneficial effects of marine n-3 fatty acids (n-3 FAs) on cardiovascular disease (CVD) and its risk factors. However, the association of marine n-3 FAs with plasma fibrinogen, a risk factor for CVD, remains uncertain. Methods In a population-based, cross-sectional study of 795 men aged 40-49 without CVD (262 whites in Allegheny County, Pennsylvania, US, 302 Japanese in Kusatsu, Japan, and 229 Japanese Americans in Honolulu, Hawaii, US), we examined the association of marine n-3 FAs with plasma fibrinogen. Serum FAs were measured by capillary gas-liquid chromatography. Marine n-3 FAs were defined as the sum of docosahexaenoic, eicosapentaenoic, and docosapentaenoic acids. Plasma fibrinogen was measured by an automated clot-rate assay. Multiple linear regression analyses were performed to assess the association. Results White, Japanese, and Japanese American men had mean marine n-3 FAs levels of 3.47%, 8.78%, and 4.46%, respectively. Japanese men had a significant inverse association of marine n-3 FAs with fibrinogen (standardized regression coefficient of -0.11, p=0.049), after adjusting for age, body-mass index, and current smoking. The significant inverse association remained after further adjusting for diabetes, C-reactive protein, triglycerides and other variables. White or Japanese American men did not show a significant association. Conclusion We observed the significant inverse association of marine n-3 FAs with fibrinogen in Japanese, but not in whites or Japanese Americans. The observation suggests that marine n-3 FAs at very high levels, as seen in the Japanese, may decrease plasma fibrinogen levels.

OBJECTIVE The aim of this study was to examine whether obesity modifies the effects of endogenous steroid sex hormones on arterial calcification in women at midlife. METHODS Associations between estradiol, testosterone, sex hormone-binding globulin, and free androgen index and the presence and extent of coronary and aortic calcification were evaluated in 187 obese (body mass index, ≥30 kg/m) and 281 nonobese (body mass index

Stiffness of the central arteries in aging may contribute to cerebral microvascular disease independent of hypertension and other vascular risk factors. Few studies of older adults have evaluated the association of central arterial stiffness with longitudinal cognitive decline.We evaluated associations of aortic pulse wave velocity (centimeters per second), a measure of central arterial stiffness, with cognitive function and decline in 552 participants in the Health, Aging, and Body Composition (Health ABC) study Cognitive Vitality Substudy (mean age ± SD = 73.1 ± 2.7 years, 48% men and 42% black). Aortic pulse wave velocity was assessed at baseline via Doppler-recorded carotid and femoral pulse waveforms. Global cognitive function, verbal memory, psychomotor, and perceptual speed were evaluated over 6 years.After adjustment for demographics, vascular risk factors, and chronic conditions, each 1 SD higher aortic pulse wave velocity (389 cm/s) was associated with poorer cognitive function: -0.11 SD for global function (SE = 0.04, p.01), -0.09 SD for psychomotor speed (SE = 0.04, p = .03), and -0.12 SD for perceptual speed (SE = 0.04, p.01). Higher aortic pulse wave velocity was also associated with greater decline in psychomotor speed, defined as greater than 1 SD more than the mean change (odds ratio = 1.42 [95% confidence interval = 1.06, 1.90]) but not with verbal memory or longitudinal decline in global function, verbal memory, or perceptual speed. Results were consistent with mixed models of decline in each cognitive test.In well-functioning older adults, central arterial stiffness may contribute to cognitive decline independent of hypertension and other vascular risk factors.

Disorders of mineral metabolism are associated with a greater risk for cardiovascular (CVD) events in patients with kidney failure.1–3 Recent studies demonstrate that this link may exist in the general population as well,4–6 even in individuals with ostensibly normal kidney function. Specifically, higher serum intact parathyroid hormone (iPTH) and phosphorus levels and lower 25-hydroxyvitamin D levels are associated with incidence4–7 and recurrence8 of CVD events, CVD mortality,5,6,9 and peripheral arterial disease10 in community-living populations, independent of kidney function and traditional CVD risk factors. Although the mechanisms responsible are unknown, it is possible that disordered mineral metabolism may contribute to arterial calcium deposition and associated arterial stiffening. Therefore arterial stiffening may be in the causal pathway between altered mineral metabolism and CVD events. Several studies have shown that abnormalities in mineral metabolism are associated with arterial calcification in community-living populations,7,10–12 but the relationship with arterial stiffening remains largely untested. There are no studies to our knowledge that evaluate the relationships between serum mineral metabolism markers and arterial pulse wave velocity (aPWV) in community-living populations. Increasingly, aPWV has been used as a clinical gold-standard measure of large-artery stiffness. This measure is associated with CVD risk factors and independently associated with incidence rates of CVD events and CVD mortality in community-living elderly persons.13 In order to investigate the potential mechanisms linking abnormalities in mineral metabolism with CVD events, we evaluated the associations between mineral metabolism markers (serum 25-hydroxyvitamin D, iPTH, phosphorus, and calcium) and aPWV in a community-living population of well-functioning elderly persons who were part of the Health Aging and Body Composition (Health ABC) study. We hypothesized that higher serum phosphorus and iPTH and lower 25-hydroxyvitamin D would be associated with greater aPWV, independent of kidney function and traditional CVD risk factors.

OBJECTIVES: To examine the association between cardiovascular disease (CVD) and its risk factors and age-associated hearing loss in a cohort of older black and white adults. DESIGN: Cross-sectional cohort study. SETTING: The Health, Aging, and Body Composition (Health ABC) Study, a community-based cohort study of older adults from Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Two thousand forty-nine well-functioning adults (mean age 77.5; 37% black). MEASUREMENTS: Pure-tone audiometry measurement and history of clinical CVD were obtained at the fourth annual follow-up visit. Pure-tone averages in decibels reflecting low (250, 500, and 1,000 Hz), middle (500, 1,000, and 2,000 Hz), and high (2,000, 4,000, and 8,000 Hz) frequencies were calculated for each ear. CVD risk factors, aortic pulse-wave velocity (PWV), and ankle\u2013arm index (AAI) were obtained at study baseline. RESULTS: In sex-stratified models, after adjustment for age, race, study site, and occupational noise exposure, risk factors associated with poorer hearing sensitivity in men included high triglyceride levels, high resting heart rate, and history of smoking. In women, poor hearing sensitivity was associated with high body mass index, high resting heart rate, fast PWV, and low AAI. CONCLUSION: Modifiable risk factors for CVD may play a role in the development of age-related hearing loss.

Adolescents with polycystic ovary syndrome (PCOS) have insulin resistance and higher rates of the metabolic syndrome.Our objective was to compare the effects of 6 months treatment with drospirenone/ethinyl estradiol (EE) (3 mg/30 μg) vs. rosiglitazone (4 mg) daily on the hormonal and cardiometabolic profiles of overweight/obese adolescents with PCOS.We conducted a randomized, double-blinded, parallel clinical trial in an academic hospital, with n = 46 patients.The primary outcome measure was insulin sensitivity, hepatic with [6,6-(2)H(2)]glucose and peripheral with a 3-h hyperinsulinemic-euglycemic clamp. Other outcome measures included plasma androgen profile and response to ACTH stimulation, glucose and insulin response to oral glucose tolerance test, insulin secretion with a 2-h hyperglycemic clamp, fasting lipid profile, inflammatory markers, intima media thickness, aortic pulse wave velocity, body composition by dual-energy x-ray absorptiometry, and abdominal adiposity by computed tomography scan.Drospirenone/EE resulted in greater reductions in androgenemia. Neither treatment led to change in weight or body mass index, but rosiglitazone led to a significant decrease in visceral adiposity. Compared with drospirenone/EE, treatment with rosiglitazone improved hepatic and peripheral insulin sensitivity and lowered fasting and stimulated insulin levels during the oral glucose tolerance test. Treatment with drospirenone/EE was associated with elevations in total cholesterol, high-sensitivity C-reactive protein and leptin concentrations, whereas treatment with rosiglitazone led to lower triglycerides and higher adiponectin concentrations. Neither treatment affected intima media thickness or pulse wave velocity.In overweight/obese adolescents with PCOS, 6 months treatment with rosiglitazone was superior to drospirenone/EE in improving the cardiometabolic risk profile, and effective but inferior in attenuating hyperandrogenemia. Additional studies are needed to test insulin sensitizers in the treatment of the reproductive and cardiometabolic aspects of PCOS.

Age-related mechanisms that lead to sarcopenia are not entirely understood. Basal leg blood flow declines with aging by augmented sympathetic vasoconstriction and arterial stiffening, thus a dysfunction in blood vessel dynamics may have an independent role on sarcopenia. We determined whether pulse wave velocity (PWV), marker of arterial stiffness, was associated with skeletal muscle decline. Observational cohort study of older adults(70–79 years) living in Pittsburgh, PA, USA or Memphis, TN, USA. Analyses included 2,405 participants. Correlations among muscle parameters including skeletal muscle density and intermuscular adipose tissue using mid-thigh CT scans were assessed. Linear mixed models tested the association between the change in the sarcopenic index (SI) (assessed by dual energy X-ray absorptiometry) over time and baseline PWV independently of multiple confounders. SI was defined: appendicular lean mass/squared height and calculated at every follow-up (n = 6). Baseline PWV was significantly higher in black women compared to white women (930 ± 431 vs. 843 ± 366; p = 0.0001), while there were no significant differences between black and white men (943 ± 402 vs. 911 ± 375; p = 0.1786). Baseline analyses showed an independent negative association between PWV and muscle parameters after adjusting for confounders in both genders. The PWV-by-race interaction was significant in women and analyses are reported separately by race. Prospective mixed models showed that PWV was an independent determinant of the SI in all men (β = −0.1043; p = 0.0065) and in white women (β = −0.1091; p = 0.0192). In analyses examining the effect of arterial stiffness on limb lean mass over time, PWV correlated with lower leg (β = −0.2196; p = 0.0002)and arm mass (β = −0.0985; p = 0.0011) in all men and lower leg mass(β = −0.1608; p = 0.0027)in white women. In older persons, arterial stiffening is associated with skeletal muscle mass decline differently for race and gender.

Musculoskeletal injury in the workplace is the primary work-related factor in loss of nursing personnel from the workforce. Moving or transferring patients is the dominant contributing event. A simulation educational approach has not been closely studied in this area but may have advantages over traditional approaches. Specific aims were to (1) evaluate the effect of a simulation intervention on success of patient transfers in a clinical setting and (2) measure change in participants' knowledge and attitude as a result of the intervention.A prospective, observational, longitudinal design was used. Baseline patient transfer observations were conducted on control and intervention units. An optimum task set was developed using hierarchical task analysis methods. Subjects (N = 71) completed pre- and postintervention knowledge and attitude assessments. The intervention consisted of simulated patient transfers using a mannequin, education, and training, followed by repeated simulated transfers using a mannequin with debriefing. Observations of patient transfers in patient care areas were repeated at 4 and 12 weeks.Patient transfer success improved from 66% at baseline to 88% at the 4-week measurement point (t = 7.447, P ≤ 0.0004). At 12 weeks, transfer success had decreased to 71%, with addition of new employees between weeks 4 and 12 confounding the 12-week measurement. Knowledge improved from a baseline of 65% to 95% postsimulation intervention (z = -6.634, P ≤ 0.0004). Attitude change was also evaluated with significance seen with 12 of 15 items (P ≤ 0.05).A simulation intervention was successful in significantly improving knowledge and changing subject perceptions with regard to this task. Skills acquired through simulation successfully transferred to the clinical setting. Improvement in success for patient moves not trained in the simulation laboratory suggests that acquired skills were generalizable and supports application to different settings.

Objective: The risk of cardiovascular disease increases after menopause. Recent evidence suggests that it is possible for high-density lipoprotein (HDL) to become proatherogenic or dysfunctional in certain situations. Our objective was to evaluate whether the relationship of HDL cholesterol (HDL-C) to subclinical cardiovascular disease differed across the menopausal transition, which would provide insight for this increased risk. Methods: Aortic calcification (AC), coronary artery calcification (CAC), carotid plaque, and intima media thickness (IMT) were measured in an ancillary study of the Study of Women’s Health Across the Nation. Women not using hormone therapy were stratified into premenopausal or early perimenopausal (Pre/EP, n = 316) and late perimenopausal or postmenopausal (LP/Post, n = 224). Results: The inverse relationship of HDL-C to subclinical atherosclerosis measures among Pre/EP women was weaker or reversed among LP/Post women, adjusted for age, site, race, systolic blood pressure, glucose, body mass index, smoking, menopause status, and low-density lipoprotein cholesterol. Specifically, multivariable modeling demonstrated an inverse association between HDL-C level and AC and IMT among Pre/EP women; however, the protective effect of HDL-C for AC, left main CAC, carotid plaque, and IMT was not seen in LP/Post women. In a small subset (n = 53), LP/Post women had more total and small HDL particles, higher triglyceride levels, and more total low-density lipoprotein particles compared with Pre/EP women (P G 0.05). Conclusions: These results suggest that the protective effect of HDL may be diminished as women transition in menopause. Future studies should examine whether this may be due to changes in HDL size, functionality, or related changes in other lipids or lipoproteins.

OBJECTIVE Emerging evidence suggests associations between menopausal hot flashes and cardiovascular risk. However, whether hot flashes are associated with intima media thickness (IMT) or IMT changes over time is unknown. We hypothesized that reported hot flashes would be associated with greater IMT cross-sectionally and with greater IMT progression over 2 years. METHODS Participants were 432 women aged 45 to 58 years at baseline participating in the Study of Women's Health Across the Nation (SWAN) Heart, an ancillary study to the SWAN. Measures at the SWAN Heart baseline and follow-up visit 2 years later included a carotid artery ultrasound, reported hot flashes (past 2 weeks: none, 1-5 d, ≥6 d), and a blood sample for measurement of estradiol. RESULTS Women reporting hot flashes for 6 days or more in the prior 2 weeks had significantly higher IMT than did women without hot flashes at the baseline (mean [SE] difference, 0.02 [0.01] mm; P=0.03) and follow-up (mean [SE] difference, 0.02 [0.01] mm; P=0.04) visits, controlling for demographic factors and cardiovascular risk factors. Reporting hot flashes at both study visits was associated with higher follow-up IMT relative to reporting hot flashes at neither visit (mean [SE] difference, 0.03 [0.01] mm; P=0.03). Associations between hot flashes and IMT largely remained after adjusting for estradiol. An interaction between hot flashes and obesity status was observed (P=0.05) such that relations between hot flashes and IMT were observed principally among overweight/obese women. Hot flashes were not associated with IMT progression. CONCLUSIONS These findings provide some indication that women reporting hot flashes for 6 days or more in the prior 2 weeks may have higher IMT than do women without hot flashes, particularly for women who are overweight or obese. Further work should determine whether hot flashes mark adverse underlying vascular changes.

Background: Limited data suggest that the effects of abdominal subcutaneous adipose tissue (SAT) on cardiovascular disease risk may depend on accompanying amounts of abdominal visceral adipose tissue (VAT). Objective: The objective was to examine whether abdominal VAT area modifies the effects of abdominal SAT area on subclinical atherosclerosis and cardiometabolic risk factors in both whites and African Americans. Design: Computed tomographic measures of abdominal SAT and VAT were examined in relation to carotid intima-media thickness (cIMT) and cardiometabolic risk factor levels in 500 African American and white women in midlife. A VAT · SAT interaction term was evaluated. Results: The mean (6SD) age of the sample was 51.0 6 2.9 y, and 37% were African American. Higher amounts of SAT and VAT were associated with higher cIMT, blood pressure, homeostasis model assessment insulin resistance index (HOMA-IR), and concentrations of glucose, triglycerides, and insulin and with lower concentrations of HDL cholesterol. However, in African Americans, but not in whites, higher amounts of VAT significantly attenuated associations between higher amounts of SAT and higher insulin concentrations (P for interaction = 0.032) and HOMA-IR (P for interaction = 0.011) and reversed associations with cIMT (P for interaction = 0.005) and glucose (P for interaction = 0.044). Conclusions: These results suggest that in midlife African American but not white women, adverse associations between abdominal SAT and cardiometabolic risk factors are attenuated and, in the case of subclinical atherosclerosis, are reversed as VAT amounts increase. Given that African American women suffer disproportionately from obesity and cardiovascular disease, further research into the role of this effect modification on obesity-associated vascular disease in African American women is warranted. Am J Clin Nutr 2011;93:719‐26.