The directional and temporal nature of relationships between overweight and obesity and hysterectomy with or without oophorectomy is not well understood. Overweight and obesity may be both a risk factor for the indications for these surgeries and a possible consequence of the procedure. We used prospective data to examine whether body mass index (BMI) increased more following hysterectomy with and without bilateral oophorectomy compared to natural menopause among middle-aged women.
BMI was assessed annually for up to 10 years in the Study of Women’s Health Across the Nation (SWAN (n=1962). Piecewise linear mixed growth models were used to examine changes in BMI before and after natural menopause, hysterectomy with ovarian conservation, and hysterectomy with bilateral oophorectomy. Covariates included education, race/ethnicity, menopausal status, physical activity, self-rated health, hormone therapy use, antidepressant use, and age the visit prior to the final menstrual period (FMP; for natural menopause) or surgery (for hysterectomy/oophorectomy).
By visit 10, 1780 (90.6%) women reached natural menopause, 106 (5.5%) reported hysterectomy with bilateral oophorectomy, and 76 (3.9%) reported hysterectomy with ovarian conservation. In fully adjusted models, BMI increased for all women from baseline to FMP or surgery (annual rate of change=.19 kg/m2 per year), with no significant differences in BMI change between groups. BMI also increased for all women following FMP, but increased more rapidly in women following hysterectomy with bilateral oophorectomy (annual rate of change=.21 kg/m2 per year) as compared to following natural menopause (annual rate of change=.08 kg/m2 per year, p=.03).
In this prospective examination, hysterectomy with bilateral oophorectomy was associated with greater increases in BMI in the years following surgery than following hysterectomy with ovarian conservation or natural menopause. This suggests that accelerated weight gain follows bilateral oophorectomy among women in midlife, which may increase risk for obesity-related chronic diseases.
menopause; oophorectomy; BMI; women’s health
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/m2, 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 (P<0.05 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 (P<0.05 for all). After multivariable adjustment, insulin reduction remained a significant determinant of CIMT decrease (P=0.03).
A6 month intensive behavioral intervention can significantly reverse metabolic and vascular abnormalities in severely obese adults.
Severe obesity; Carotid intima-media thickness; Carotid diameter; Lifestyle modification
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.
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.
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.
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.
subclinical atherosclerosis; sex hormones; women
To determine if post-menopausal status is associated with self-reported limitations in physical function.
SWAN is a multi-site, multi-ethnic, longitudinal study of midlife women. Women aged 45–57 years (N=2,566) completed the Medical Outcomes Study Short-Form Physical Function Scale at visit 4 (2000–2001); scores created a 3-category variable of physical function limitations: none (86–100), moderate (51–85) and substantial (0–50). Menopausal status in SWAN is a 5-category list variable based on menstrual bleeding patterns and gynecological surgery. Pre-and peri-menopausal women using hormones (n=284) or missing physical function scores (n=46) were excluded. Multinomial logistic regression was used to relate physical function and menopausal status adjusting for age, ethnicity, site, education, body mass index (BMI), self-reported diabetes, hypertension, arthritis, depressive symptoms, smoking and hormone use among postmenopausal women.
Of 2,236 women, 8% were pre-, 51% early peri-, 12% late peri-, 24% natural post-, and 5% surgical post-menopausal status. In the full model, substantial limitations in physical function were higher in post-menopausal compared to pre-menopausal women whether it occurred naturally (OR 3.82; 95% CI: 1.46–10.0) or surgically (OR 3.54; 95% CI: 1.15–10.84). These associations were attenuated by higher BMI and depressive symptoms, but remained significant. Moderate limitations in physical function were not significantly related to menopausal status.
Women with surgical or naturally occurring post-menopause reported greater limitations in physical function than pre-menopausal women, independent of age, only partly explained by higher BMI and depressive symptoms. This suggests that physiologic changes of menopause could contribute directly to limitations in physical function.
Physical functioning; Functional limitations; Menopause; Menopausal status; SF-36
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, p<0.001 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.
liver fat; sex hormone binding globulin; perimenopause; ectopic fat; insulin resistance
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/m2) 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.
arterial stiffness; obesity; lifestyle modification
We recently reported that Japanese had higher liver fat at a lower level of BMI compared with non-Hispanic whites (NHW).
We hypothesize that ethnic difference in fat storage capacity contributes to this ethnic difference in liver fat.
To examine this, we assessed liver fat among 244 Japanese-American aged 40-49, using regional computed-tomography images, along with metabolic variables.
Despite the similar BMI between Japanese-Americans and NHW men, Japanese-Americans had more liver fat (liver to spleen attenuation ratio: 1.03 ± 0.22 for Japanese-Americans, and 1.07 ± 0.15 for NHW men; p<0.05) and tended to have a greater disposition for fatty liver with an increase in BMI than NHW, indicating a clear difference between the two groups. In addition, liver fat is less in Japanese-Americans compared with Japanese men (1.03 ± 0.22 vs. 1.01 ± 0.16; p<0.05), despite of a much higher BMI. These ethnic differences support the hypothesis that higher fat storage capacity indeed seems to be associated with less liver fat. In all the groups, liver fat content strongly correlated with triglycerides, homeostasis model assessment-insulin resistance, and C-reactive protein (CRP). Nevertheless, these metabolic variables were worse in Japanese-Americans, despite of less liver fat, compared with Japanese. Moreover, CRP levels were least among Japanese with highest liver fat, and highest among NHW men with least liver fat, despite of a strong positive association between CRP and fatty liver within each population.
Fat content in the liver is intermediate for Japanese-Americans compared with Japanese and NHW men, which supports the hypothesis of less fat storage capacity among Japanese, closely linked to ethnic difference in predisposition to fatty liver.
Ethnicity; Fatty liver; Genetic; Environmental; CRP
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/second) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), p for trend <0.001). 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 40’s.
aortic stiffness; aortic calcification; international multi-ethnic study
Coronary heart disease (CHD) incidence and mortality remain very low in Japan despite major dietary changes and increases in CHD risk factors that should have resulted in substantial increase in CHD rates (Japanese paradox). Primary genetic effects are unlikely, given the substantial increase in CHD in migrant Japanese to the U.S. For men aged 40–49, levels of total cholesterol and blood pressure have been similar in Japan and the U.S. throughout their lifetime. The authors tested the hypothesis that levels of subclinical atherosclerosis, coronary artery calcification and intima-media thickness of the carotid artery (IMT), in men aged 40–49 are similar in Japan and the U.S. The authors conducted a population-based study of 493 randomly-selected men: 250 men in Kusatsu, Shiga, Japan, and 243 white men in Allegheny County, Pennsylvania, U.S. in 2002–2005. The Japanese had a less favorable profile of many risk factors than the whites. Prevalence ratio for the presence of coronary calcium score ≥10 in the Japanese compared to the whites was 0.52 (95% CI, 0.35, 0.76). Mean (SE) IMT was significantly lower in the Japanese (0.616 (0.005) versus 0.672 (0.005) mm, p<0.01). Both associations remained significant after adjusting for risk factors. The findings warrant further investigations.
Atherosclerosis; epidemiology; men; risk factors
Since World War II (WWII), exposures to westernized lifestyle have occurred in many non-Western countries, including Japan. National surveys showed that risk factor profiles for atherosclerosis around 1990 were similar in men in the post WWII birth cohorts in the United States (US) and Japan. We compared the degree of coronary calcium and other factors in men in the post WWII birth cohort: men aged 40-49 between the US and Japan.
We conducted a cross sectional study examining randomly selected 100 men from Kusatsu, Japan, and 100 men from Allegheny County, US. Coronary calcium was assessed using electron-beam computed tomography.
Systolic blood pressure, total cholesterol, LDL-cholesterol and smoking rates were higher among the Japanese (122.6 ± 14.1 versus 113.7 ± 9.6 mmHg, p<0.01; 5.72 ± 0.90 versus 4.99 ± 0.81 mmol/l (220.9 ± 34.6 versus 192.8 ± 31.3 mg/dl), p<0.01; 3.52 ± 1.01 versus 3.10 ± 0.78 mmol/l (136.0 ± 39.0 versus 119.7 ± 30.0 mg/dl), p<0.01; and 48 versus 15%, p<0.01, respectively). Triglycerides and fibrinogen were similar. HDL-cholesterol was higher among the Japanese. Body mass index, fasting insulin, and C-reactive protein were higher among the Americans. Prevalence of coronary artery calcium score > 0 was strikingly lower among the Japanese than the Americans (13 % versus 47 %, p <0.01).
Much lower prevalence of coronary calcium despite a less favorable profile of many major independent risk factors in the Japanese might imply that there are strong protective factors against atherosclerosis in the Japanese. Further investigation is of critical importance.
Subclinical atherosclerosis; electron-beam computed tomography; US; Japan; epidemiology; risk factors; post Word War II birth cohort; coronary calcium
The exact form of the association between systolic blood pressure (SBP) and heart failure (HF) risk in the elderly remains incompletely defined, especially in individuals not receiving antihypertensive medications. Our aim was to examine the association between SBP and HF risk in the elderly.
Competing-risks proportional hazards modeling of incident HF risk, utilizing 10-year follow-up data from two NIH-sponsored cohort studies; the Cardiovascular Health Study (inception: 1989-90 and 1992-93) and the Health ABC Study (inception: 1997-98).
4408 participants (age, 72.8 [4.9] years; 53.1% women, 81.7% white; 18.3% black) without prevalent HF and not receiving antihypertensive medications at baseline.
Main outcome measures
Incident HF, defined as first adjudicated hospitalisation for HF.
Over 10 years, 493 (11.1%) participants developed HF. Prehypertension (120-139 mmHg), stage 1 (140-159 mmHg), and stage 2 (≥160 mmHg) hypertension were associated with escalating HF risk; hazard ratios vs. optimal SBP (<120 mmHg) in competing-risks models controlling for clinical characteristics were 1.63 (95% CI, 1.23-2.16; P=0.001), 2.21 (95% CI, 1.65-2.96; P<0.001), and 2.60 (95% CI, 1.85-364; P<0.001), respectively. Overall 255 of 493 (51.7%) HF events occurred in participants with SBP <140 mm Hg at baseline. Increasing SBP was associated with higher HF risk in women than men; no race-SBP interaction was observed. In analyses with continuous SBP, HF risk had a continuous positive association with SBP to levels as low as 113 mmHg in men and 112 mmHg in women.
There is a continuous positive association between SBP and HF risk in the elderly for levels of SBP as low as <115 mmHg; over half of incident HF events occur in individuals with SBP <140 mmHg.
epidemiology; hypertension; heart failure; risk stratification
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with increased prevalence of cardiovascular disease (CVD) and depression. Although depression may contribute to CVD risk in population-based studies, its influence on cardiovascular morbidity in SLE has not been evaluated. We evaluated the association between depression and vascular disease in SLE.
A cross-sectional study was conducted from 2002–2005 in 161 women with SLE and without CVD. The primary outcome measure was a composite vascular disease marker consisting of the presence of coronary artery calcium and/or carotid artery plaque.
In total, 101 women met criteria for vascular disease. In unadjusted analyses, several traditional cardiovascular risk factors, inflammatory markers, adiposity, SLE disease-related factors, and depression were associated with vascular disease. In the final multivariable model, the psychological variable depression was associated with nearly 4-fold higher odds for vascular disease (OR 3.85, 95% CI 1.37, 10.87) when adjusted for other risk factors of age, lower education level, hypertensive status, waist-hip ratio, and C-reactive protein.
In SLE, depression is independently associated with vascular disease, along with physical factors.
SYSTEMIC LUPUS ERYTHEMATOSUS; CARDIOVASCULAR DISEASE; DEPRESSION CALCIFICATION; CAROTID PLAQUE; PSYCHOSOCIAL FACTORS
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.
Aging; Sarcopenia; Pulse wave velocity; Vascular stiffness
To examine associations between vasomotor symptoms and lipids over 8 years, controlling for other cardiovascular risk factors, estradiol (E2) and follicle-stimulating hormone (FSH).
Study of Women’s Health Across the Nation participants (N=3201), aged 42–52 at entry, completed interviews on frequency of hot flushes and night sweats (none, 1–5 days, 6 days or more, in the past 2 weeks) physical measures (blood pressure, height, weight), and blood draws (low-density lipoprotein [LDL], high-density lipoprotein [HDL], apolipoproteinA-1, apolipoprotein B [apoB], lipoprotein(a), trigycerides, serum E2, FSH) yearly for 8 years. Relations between symptoms and lipids were examined in linear mixed models adjusting for cardiovascular risk factors, medications, and hormones.
Compared to no flushes, experiencing hot flushes was associated with significantly higher LDL [1–5 days: beta (β) (standard error (SE)) =1.48(.47), p<0.01; 6 days or more: β(SE)=2.13(.62), p<.001], HDL [1–5 days: β(SE)=.30(.18),; 6 days or more: β(SE)=.77(.24), p<.01], apolipoproteinA-1 [1–5 days: β(SE)=.92(.47), p<.10; 6 days or more: β(SE)=1.97(.62), p<.01], apolipoproteinB [1–5 days: β(SE)=1.41(.41), p<.001; 6 days or more: β(SE)=2.51(.54), p<.001], and triglycerides [1–5 days: percent change(95%CI)=2.91(1.41–4.43), p<.001; 6 days or more: percent change(95%CI)=5.90(3.86–7.97), p<.001] in multivariable models. Findings largely persisted adjusting for hormones. Estimated mean differences between hot flashes 6 days or more compared with no days ranged from less than 1 (HDL) to 10 mg/dL (triglycerides). Night sweats were similar. Associations were strongest for lean women.
Vasomotor symptoms were associated with higher LDL, HDL, apolipoproteinA-1, apolipoproteinB, and triglycerides. Lipids should be considered in links between hot flushes and cardiovascular risk.
Women gain visceral fat during pregnancy. Studies examining the impact of breastfeeding on maternal body composition are inconclusive. We examined the extent to which breastfeeding was associated with visceral adiposity in a sample of US women. This was a cross-sectional analysis of 351 women aged 45–58 years, who were free of clinical cardiovascular disease and had not used oral contraceptives or hormone replacement therapy in the 3 months prior to enrollment in the Study of Women’s Health Across the Nation (SWAN)-Heart Study (2001–2003). History of breastfeeding was self-reported. Computed tomography was used to assess abdominal adiposity. Among premenopausal/early-peri-menopausal mothers, those who never breastfed had 28% greater visceral adiposity (95% confidence interval (CI): 11–49, P = 0.001), 4.7% greater waist-hip ratio (95% CI: 1.9–7.4, P < 0.001), and 6.49 cm greater waist circumference (95% CI: 3.71–9.26, P < 0.001) than mothers who breastfed all of their children for ≥3 months in models adjusting for study site; age; parity; years since last birth; socioeconomic, lifestyle, and family history variables; early adult BMI; and current BMI. In comparison to women who were nulliparous, mothers who breastfed all of their children for ≥3 months had similar amounts of visceral fat (P > 0.05). In contrast, premenopausal/early-peri-menopausal mothers who had never breastfed had significantly greater visceral adiposity (42% (95% CI: 17–70), P < 0.001), waist circumference (6.15 cm (95% CI: 2.75–9.56), P < 0.001), and waist-hip ratio (3.7% (95% CI: 0.69–6.8), P = 0.02) than nulliparous women. No significant relationships were observed among late peri-menopausal/postmenopausal women. In conclusion, until menopause, mothers who did not breastfeed all of their children for ≥3 months exhibit significantly greater amounts of metabolically active visceral fat than mothers who had breastfed all of their children for ≥3 months.
Black women experience higher rates of cardiovascular disease (CVD) than white women, though evidence for racial differences in subclinical CVD is mixed. Few studies have examined multiple roles (number, perceived stress, and/or reward) in relation to subclinical CVD, or whether those effects differ by race.
To investigate the effects of multiple roles on 2-year progression of coronary artery calcification (CAC).
Subjects were 104 black and 232 white women (mean age 50.8 years). Stress and reward from four roles (spouse, parent, employee, caregiver) were assessed on 5-point scales. CAC progression was defined as an increase of ≥10 Agatston units.
White women reported higher rewards from their multiple roles than black women, yet black women showed cardiovascular benefits from role rewards. Among black women only, higher role rewards were related significantly to lower CAC progression, adjusting for BMI, blood pressure, and other known CVD risk factors. Blacks reported fewer roles but similar role stress as whites; role number and stress were unrelated to CAC progression.
Rewarding roles may be a novel protective psychosocial factor for progression of coronary calcium among black women.
multiple roles; role stress; role reward; women; middle-aged; coronary artery calcium
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 is to evaluate racial differences in the relationship between carotid plaque and calcification in the aorta and coronary arteries among women transitioning the menopause.
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 versus any) was assessed with B-mode ultrasound and aortic (AC; 0, >0–100, >100) and coronary artery calcification (CAC; 0, >0–10, >10) with computed tomography.
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, 0.002, respectively). Among African Americans, there was an inverse relationship, although not significant, between carotid plaque and high AC (>100) (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 for high CAC (OR 1.83, 95%CI: 0.66–5.19).
This study demonstrated the presence of carotid plaque appeared to be a marker for AC and potentially CAC in White women during the menopause transition, but not African American middle-aged women.
Atherosclerosis; Plaque; Carotid Arteries; Coronary Disease; African Americans and Calcium
Cigarette smoking is a risk factor of coronary heart disease (CHD). Vascular calcification such as coronary artery calcium (CAC) and aortic calcium (AC) is associated with CHD. We hypothesized 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 to 49 were examined for calcification of the coronary artery and aorta using electron beam computed tomography. Coronary artery calcium (CAC) and aortic calcium (AC) were quantified using the Agatston score. We 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 categorized into two groups using median pack-years as a cutoff point in each of Japanese and Koreans. The never smoker group was used as a reference for the multiple logistic regression analyses.
The odds ratios of CAC (score ≥10) for smokers with higher pack-years were 2.9 in Japanese (P<0.05) and 1.3 in Koreans (non-significant) compared to never smokers. The odds ratios of AC (score ≥100) for smokers with higher pack-years were 10.4 in Japanese (P<0.05) and 3.6 in Koreans (P<0.05).
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.
atherosclerosis; cigarette smoking; coronary calcium; aortic calcium; Japanese; Koreans
Circulating aldosterone is increased in obesity and is associated with arterial stiffening in hypertensives and older adults. We aimed to determine whether serum aldosterone is associated with pulse wave velocity (PWV), a measure of arterial stiffness, in normotensive overweight and obese adults aged 20–45 years (n=344). We measured heart-femoral, femoral-ankle and brachial-ankle PWV. The sample was 77% female with mean BMI 32.9 kg/m2 (SD 3.9), median serum aldosterone 106.5 pg/mL (IQR 79.9, 155.5), and mean 24-hour urinary sodium excretion 185.9 mEq/day (SD 69.6). Higher serum aldosterone was not significantly correlated with any PWV measure in bivariate analysis. However, in multiple linear regression, adjusting for age, sex, race, height, heart rate, mean arterial pressure, and waist circumference, higher log aldosterone was associated with greater log heart-femoral PWV (β(se)=0.042(0.021), p=0.049). After adjusting for C-reactive protein, this association was no longer significant (β(se)=0.035(0.021), p=0.10). Circulating aldosterone may play an important role in vascular inflammation and aortic stiffening in normotensive overweight and obese adults.
aldosterone; arterial stiffness; inflammation; obesity; RAAS
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 Alzheimer’s disease (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 was 80±4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study (CHS-CS) 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 (MCI) 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 (WMH) 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.
oxysterols; 24S-hydroxycholesterol; cerebrovascular disease; dementia and Alzheimer’s disease
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.
Aging; Arterial stiffness; Cognitive decline
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 (Pre/EP, n=185) and late perimenopausal or postmenopausal (LP/Post, 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 menopausal status showed a linear relationship between CRP and PWV among LP/Post women (β=36.2, p=0.049), but not for Pre/EP women (β=5.9, p=0.61). The menopausal status*logCRP and menopausal 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.
Arterial Stiffness; C-Reactive Protein; Menopause; Cardiovascular Disease; African American
We examined several risk factors as possible independent predictors of aortic stiffness progression among a population based sample of US men.
Methods and Results
A total of 240 men aged 40–49 from the Allegheny County site of the ERA JUMP Study, who were free of CVD at baseline were evaluated. Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) at baseline and after 4.6±0.21(mean±SD) years of follow-up. Progression of cfPWV was evaluated as relative annual change in cfPWV (% change/year). Using linear regression, both baseline potential risk factors and their annual changes were evaluated as possible risk factors for cfPWV progression. Baseline age, follow-up time, race, heart rate, and medications use were forced in all models. During follow-up, relative to baseline level, cfPWV increased 0.3%±5.3% per year. In final models the independent predictors of degree of cfPWV progression were lower levels of adiponectin (β(SE): −1.8(0.8), P=0.03), higher levels of systolic blood pressure (SBP) (β(SE): 0.07(0.03), P=0.02), greater annual change in SBP (β(SE): 0.3(0.2), P=0.04), and alcohol consumption ≥ 2 times/week (β(SE): 1.6(0.7), P=0.02).
Lower levels of adiponectin, higher levels and annual changes of SBP, and alcohol consumption ≥2 times/week are associated with greater progression in aortic stiffness among relatively healthy middle-aged US men.
arteriosclerosis; hypertension; risk factors; pulse wave velocity; stiffness
Reduced gait speed is associated with falls, late-life disability, hospitalization/institutionalization and cardiovascular morbidity and mortality. Aging is also accompanied by a widening of pulse pressure (PP) that contributes to ventricular-vascular uncoupling. The purpose of this study was to test the hypothesis that PP is associated with long-distance gait speed in community-dwelling older adults in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study.
Brachial blood pressure and 400-meter gait speed (average speed maintained over a 400-meter walk at “usual” pace) were assessed in 424 older adults between the ages of 70–89 yrs at risk for mobility disability (mean age = 77 yrs; 31% male). PP was calculated as systolic blood pressure (BP) – diastolic BP.
Patients with a history of heart failure and stroke (n = 42) were excluded leaving 382 participants for final analysis. When categorized into tertiles of PP, participants within the highest PP tertile had significantly slower gait speed than those within the lowest PP tertile (p<0.05). Following stepwise multiple regression, PP was significantly and inversely associated with 400-meter gait speed (p<0.05). Other significant predictors of gait speed included: handgrip strength, body weight, age and history of diabetes mellitus (p<0.05). Mean arterial pressure, systolic BP and diastolic BP were not predictors of gait speed.
Pulse pressure is associated long-distance gait speed in community-dwelling older adults. Vascular senescence and altered ventricular-vascular coupling may be associated with the deterioration of mobility and physical function in older adults.
Emerging research suggests links between menopausal hot flashes and cardiovascular risk. The mechanisms underlying these associations are unclear, due in part to the incomplete understanding of the physiology of hot flashes. We aimed to examine the longitudinal associations between hot flashes/night sweats and both inflammatory and hemostatic markers, controlling for cardiovascular risk factors and estradiol concentrations.
Participants in the Study of Women’s Health Across the Nation (SWAN) (N=3199), a longitudinal cohort study, were ages 42–52 years at cohort entry. Women completed interviews (hot flashes, night sweats: none, 1–5, 6 days in past 2 weeks), physical measures (blood pressure; height; weight), and a blood draw (C-reactive protein, high sensitivity; plasminogen activator inhibitor-1; Factor VIIc, tissue plasminogen activator antigen (tPA-ag); fibrinogen; glucose; serum estradiol) yearly for 8 years. Hot flashes/night sweats were examined in relation to each inflammatory/hemostatic marker in linear mixed models adjusting for demographic factors, cardiovascular risk factors, and medication use, and additionally serum estradiol.
Compared to experiencing no flashes, reporting hot flashes was associated with higher tPA-aglog (hot flashes 1–5 days: % change (95%CI): 3.88(2.22–5.58), p<0.0001; ≥6 days: % change (95%CI): 4.11(1.95–6.32), p<0.001) and higher Factor VIIclog (hot flashes ≥6 days: % change (95%CI): 2.13(0.80–3.47), p<0.01) in multivariable models. Findings persisted after adjusting for estradiol. Findings for night sweats were similar but attenuated with adjustment.
Frequent hot flashes were associated with higher Factor VIIc and tPA-ag. Hemostatic pathways may be relevant to understanding hot flashes physiology and links between hot flashes and cardiovascular risk.
Menopause; vasomotor symptoms; hot flashes; inflammation; coagulation; hemostasis