Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

Particle numbers of lipoprotein subclasses and arterial stiffness among middle-aged men from the ERA JUMP study.

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 P<0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all P<0.0001) but not LDL cholesterol (LDL-C) (all P>0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all P>0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (P<0.01). 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.

Associations between accelerometer-derived physical activity and regional adiposity in young men and women.

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 (ß = -0.19; P = 0.02) as well as visceral AT (VAT) (ß = -0.30; P = 0.03). Among females sedentary time was positively associated with VAT (ß = 0.11; P = 0.04) and total active time was inversely associated with VAT (ß = -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.

Body mass index following natural menopause and hysterectomy with and without bilateral oophorectomy.

OBJECTIVE: 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 with natural menopause among middle-aged women. METHODS: 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, age and visit before the final menstrual period (FMP; for natural menopause) or surgery (for hysterectomy/oophorectomy). RESULTS: 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=0.19 kg m(-2) 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=0.21 kg m(-2) per year) as compared with following natural menopause (annual rate of change=0.08 kg m(-2) per year, P=0.03). CONCLUSION: 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.

Significant inverse association of marine n-3 fatty acids with plasma fibrinogen levels in Japanese in Japan but not in whites or Japanese Americans.

BACKGROUND/OBJECTIVES: 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. SUBJECTS/METHODS: In a population-based, cross-sectional study of 795 men aged 40-49 without CVD (262 whites in Allegheny County, Pennsylvania, USA, 302 Japanese in Kusatsu, Japan and 229 Japanese Americans in Honolulu, Hawaii, USA), 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. CONCLUSIONS: 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.

Menopausal bone changes and incident fractures in diabetic women: a cohort study.

SUMMARY: The purpose of this study was to evaluate the rate of bone loss and incident fractures in women with diabetes mellitus (DM) across menopause. During menopause, DM women experienced bone mineral density (BMD) loss that was faster at hip and slower at spine and had a higher risk of fractures, perhaps because of their earlier menopause. The increasing DM epidemic will contribute to higher fracture burden. INTRODUCTION: Women with DM have a higher risk of fractures independent of age, body mass index (BMI), and BMD. Our objective is to evaluate if women with DM experience greater bone loss and more fractures across menopause. METHODS: Two thousand one hundred seventy one women, aged 42 to 52 years at baseline (1996), enrolled in the Study of Women's Health Across the Nation (SWAN), a prospective study, with 8 years of annual follow up. One thousand three hundred forty six (62%) completed annual visit 7 (2004). Women with baseline fasting blood glucose level of ≥126 mg/dl and those being treated for diabetes were designated as DM. Annual assessment of menopausal stage, BMD, and urinary N-telopeptide (NTx) were carried out. Rate of change in BMD across menopause and annual self-report data for risk of incident fractures by DM status were determined. RESULTS: Despite higher baseline BMD at hip (p = <0.001), and lumbar spine (p = <0.001), rate of decline in BMD was faster at hip (ß = -0.45 vs. -0.11 gm/cm(2)/year, p = <0.001) for DM women, compared to non-DM. However, lumbar spine bone loss was slower in women with DM as compared to non-DM women (ß = 0.04 vs. -0.25 gm/cm(2)/year, p = 0.004). DM women experienced menopause 3 years earlier than non-DM women (p = 0.002), and age adjusted incident fractures were two fold higher in women with DM compared to non-DM (RR = 2.20, 95% CI: 1.26-3.85, p = <0.006). CONCLUSIONS: BMD loss is greater in hip and slower at spine in DM women during menopausal transition. Women with DM have a higher risk of fractures, perhaps because of their earlier menopause.

Executive function, memory, and gait speed decline in well-functioning older adults.

BACKGROUND: In community-dwelling older adults, global cognitive function predicts longitudinal gait speed decline. Few prospective studies have evaluated whether specific executive cognitive deficits in aging may account for gait slowing over time. METHODS: Multiple cognitive tasks were administered at baseline in 909 participants in the Health, Aging, and Body Composition Study Cognitive Vitality Substudy (mean age 75.2 ± 2.8 years, 50.6% women, 48.4% black). Usual gait speed (m/s) over 20 minutes was assessed at baseline and over a 5-year follow-up. RESULTS: Poorer performance in each cognitive task was cross-sectionally associated with slower gait independent of demographic and health characteristics. In longitudinal analyses, each 1 SD poorer performance in global function, verbal memory, and executive function was associated with 0.003-0.004 m/s greater gait speed decline per year (p =.03-.05) after adjustment for baseline gait speed, demographic, and health characteristics. CONCLUSIONS: In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging.

Admixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and has a higher prevalence in African Americans than Caucasians. Ankle-arm index (AAI) is the ratio of systolic blood pressure in the leg to that in the arm, and, when low, is a marker of PAD. METHODS: The authors used an admixture mapping approach to search for genetic loci associated with low AAI. Using data from 1040 African American participants in the observational, population based Health, Aging, and Body Composition Study who were genotyped at 1322 single nucleotide polymorphisms (SNPs) that are informative for African versus European ancestry and span the entire genome, we estimated genetic ancestry in each chromosomal region and then tested the association between AAI and genetic ancestry at each locus. RESULTS: The authors found a region of chromosome 11 that reaches its peak between 80 and 82 Mb associated with low AAI (p<0.001 for rs12289502 and rs9665943, both within this region). 753 African American participants in the observational, population based Cardiovascular Health Study were genotyped at rs9665943 to test the reproducibility of this association, and this association was also statistically significant (odds ratio (OR) for homozygous African genotype 1.59, 95% confidence interval (CI) 1.12 to 2.27). Another candidate SNP (rs1042602) in the same genomic region was tested in both populations, and was also found to be significantly associated with low AAI in both populations (OR for homozygous African genotype 1.89, 95% CI 1.29 to 2.76). CONCLUSION: This study identifies a novel region of chromosome 11 representing an area with a potential candidate gene associated with PAD in African Americans.

Education eclipses ethnicity in predicting the development of the metabolic syndrome in different ethnic groups in midlife: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: To determine the respective roles of socio-economic status (SES) and ethnicity in the risk of incident metabolic syndrome in middle-aged women. DESIGN AND PARTICIPANTS: A total of 3302 pre- and peri-menopausal women, not receiving hormone therapy at baseline, took part in the Study of Women's Health Across the Nation, a multi-site, community-based, longitudinal study of the menopausal transition. The main outcome measures were to ascertain the prevalence of the metabolic syndrome and the incidence of the metabolic syndrome over 5 years of follow-up. RESULTS: At baseline, the prevalence of the metabolic syndrome was 21% (n = 673). Among 2512 women without metabolic syndrome at baseline, 12.8% (n = 321) developed the metabolic syndrome during 5 years of follow-up. Both ethnicity and SES were significant univariate predictors of incident metabolic syndrome. In multivariate logistic regression models that included age at baseline, menopausal status and site, baseline smoking and alcohol consumption at follow-up visit 1, as well as baseline values of each of the components of the metabolic syndrome, only education was an independent predictor of incident metabolic syndrome. CONCLUSION: Approximately 13% of peri-menopausal women developed the metabolic syndrome during the 5-year follow-up period. Education, but not ethnicity, was an independent predictor of incident metabolic syndrome risk.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study.

The role of renin-angiotensin system (RAS) genes on the risk of lower extremity arterial disease (LEAD) in elderly people remains unclear. We assessed the relationship of genetic polymorphisms in RAS: G-6A, T174M and M235T of the angiotensinogen (AGT) gene, and the angiotensin-converting enzyme insertion/deletion (ACE_I/D) variant to the risk of LEAD in the Health, Aging and Body Composition (Health ABC) Study. This analysis included 1228 black and 1306 white men and women whose age ranged between 70 and 79 years at the study enrollment. LEAD was defined as ankle-arm index (AAI) <0.9. Genotype-phenotype associations were estimated by regression analyses with and without adjustment for established cardiovascular disease (CVD) risk factors. The proportion of LEAD was significantly higher in black (21.1%) than that in white elderly people (10.1%, P<0.0001). The distribution of AGT polymorphisms was also significantly different between black and white participants. There was no statistically significant association between the selected RAS genetic variants and LEAD after adjustment for age, antihypertensive medications, lipid-lowering medication, pack-year smoking, body mass index, low-density lipoprotein cholesterol, and prevalent diabetes and coronary heart disease. However, A-T haplotype of G-6A and M235T interacting with homozygous ACE_II (beta=-1.07, P=0.006) and with ACE inhibitors (beta=-1.03, P=0.01) significantly decreased the risk of LEAD in white but not in black participants after adjustment for the selected CVD risk factors. In conclusion, the study observed a gene-gene and gene-drug interaction for LEAD in the white elderly.

The association of bone mineral density measures with incident cardiovascular disease in older adults.

UNLABELLED: The associations of volumetric and areal bone mineral density (BMD) measures with incident cardiovascular disease (CVD) were studied in a biracial cohort of 2,310 older adults. BMD measures were inversely related to CVD in women and white men, independent of age and shared risk factors for osteoporosis and CVD. INTRODUCTION: We investigated the associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with incident cardiovascular disease (CVD) in older adults enrolled in the Health, Aging, and Body Composition study. METHODS: The incidence of CVD was ascertained in 2,310 well-functioning white and black participants (42% black; 55% women), aged 68-80 years. aBMD measures of the hip were assessed using DXA. Spine trabecular, integral, and cortical vBMD measures were obtained using QCT. RESULTS: During an average follow-up of 5.4 years, 23% of men and 14% of women had incident CVD. Spine vBMD measures were inversely associated with incident CVD in white men [HR(integral)=1.39, 95% CI 1.03-1.87; HR(cortical)=1.38, 95% CI 1.03-1.84], but not in black men. In women, aBMD measures of the total hip (HR = 1.36, 95% CI 1.03-1.78), femoral neck (HR = 1.44, 95% CI 1.10-1.90), and trochanter (HR = 1.34, 95% CI 1.04-1.72) exhibited significant associations with CVD in blacks, but not in whites. All associations were independent of age and shared risk factors between osteoporosis and CVD, and were not explained by inflammatory cytokines or oxidized LDL. CONCLUSION: Our results provide support for an inverse association between BMD and incident CVD. Further research should elucidate possible pathophysiological mechanisms linking osteoporosis and CVD.

Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the health, aging, and body composition study.

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index <0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [OR(integral)] = 1.34, 95% confidence interval [CI] 1.10-1.63; OR(trabecular )= 1.25, 95% CI 1.02-1.53; OR(cortical )= 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.

Japanese men have larger areas of visceral adipose tissue than Caucasian men in the same levels of waist circumference in a population-based study.

Visceral adipose tissue (VAT) is an independent risk factor for metabolic and cardiovascular disorders. There has been no study that demonstrated different abdominal fat distribution between Asian and Caucasian men. As the Japanese are less obese but more susceptible to metabolic disorders than Caucasians, they may have larger VAT than Caucasians at similar levels of obesity. We compared the abdominal fat distribution of the Japanese (n=239) and Caucasian-American (n=177) men aged 40-49 years in groups stratified by waist circumference in a population-based sample. We obtained computed tomography images and determined areas of VAT and subcutaneous adipose tissue (SAT). We calculated VAT to SAT ratio (VSR). The Japanese men had a larger VAT and VSR in each stratum, despite substantially less obesity overall. In multiethnic studies, difference in abdominal fat distribution should be considered in exploring factors related to obesity.

Reduced cerebral blood flow response and compensation among patients with untreated hypertension.

OBJECTIVE: To determine whether memory performance in hypertensive subjects induces diminished parietal and prefrontal blood flow activation relative to normotensive subjects but compensatory amygdala/hippocampal activation. METHODS: Thirty-seven untreated hypertensive subjects and 59 normotensive control subjects performed in two memory and one sensorimotor task while global and regional cerebral blood flow (rCBF) was assessed with [15O]water and PET. Neuropsychological, carotid artery ultrasound, and MRI assessments were obtained. RESULTS: When they were engaged in memory tasks, increases of CBF in hypertensive subjects were less than in normotensive subjects in the posterior parietal area, as expected; blunted responses were also shown within the middle posterior arterial watershed and thalamus. Relative to all other participants, hypertensive subjects that performed relatively well on verbal memory showed an enhanced rCBF response in the right amygdala/hippocampus. Furthermore, hypertensive, but not normotensive, subjects showed task-induced rCBF in the amygdala/hippocampal area that was significantly correlated with task-induced prefrontal rCBF. No confounding influences were identified from carotid artery or MRI measures. CONCLUSIONS: Memory performance in hypertensive individuals is related to a blunted regional cerebral blood flow (rCBF) response, particularly in parietal cortex. Potentially compensatory rCBF responses appear to occur in midbrain and correlate with prefrontal rCBF.

The relationship between C-reactive protein and carotid intima-media wall thickness in middle-aged women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with premature carotid atherosclerosis. C-Reactive protein (CRP) has been implicated as a vascular disease risk factor. The objective of this study was to determine whether elevated CRP is associated with increased carotid intima-media wall thickness (IMT) in PCOS women. Forty-seven PCOS patients and 59 similarly aged controls were screened for cardiovascular risk factors and concurrently underwent carotid ultrasonography (1996-1999). The main outcome measure was carotid IMT. CRP was significantly higher in PCOS patients than in controls (3.4 vs. 2.1 mg/dl; P = 0.002). In regression modeling, PCOS associated with IMT independently of CRP and age (P = 0.019). Body mass index reduced the association of PCOS and CRP with IMT and was also associated with IMT (P = 0.029). The CRP-IMT relationship was attenuated when either insulin or visceral fat was included in the PCOS-age-CRP model (P = 0.197 and P = 0.550, respectively). PCOS remained associated with IMT independent of insulin (P = 0.033) or visceral fat (P = 0.040). CRP does not appreciably mediate the effect of PCOS on IMT. Obesity partially explained the influence of PCOS and CRP on IMT. The effect of body mass index on the PCOS-IMT relationship was not completely determined by hyperinsulinemia or visceral fat, and might be mediated by other aspects of PCOS-related adiposity.

A "natural experiment" in cardiovascular epidemiology in the early 21st century.

Despite similar traditional risk factors, morbidity and mortality rates from coronary heart disease in western and non-western cohorts remain substantially different. Careful study of such cohorts may help identify novel risk factors for CHD, and contribute to the formulation of new preventive strategies

Educational attainment and coronary and aortic calcification in postmenopausal women.

OBJECTIVE: Low socioeconomic status is a risk factor for clinical coronary heart disease, a relatively crude outcome associated with important biases. By avoiding these biases, subclinical assessments could facilitate efforts to understand the association between socioeconomic status and coronary disease. The current study 1) evaluated the nature of the associations between educational attainment and subclinical atherosclerosis and 2) examined if biologic, behavioral, and psychosocial factors mediated these associations. METHODS: Participants were 308 women from the Healthy Women Study who underwent a clinic examination of risk factors either 5 (N = 32) or 8 (N = 276) years after the menopausal transition. Aortic and coronary calcification were measured using electron beam tomography. RESULTS: Logistic regression analysis with orthogonal polynomials revealed a marginally significant linear trend for coronary calcification, with the more educated groups showing lower calcification than the less educated groups. A significant linear trend was also observed for aortic calcification. In addition, a marginally significant quadratic trend was observed for aortic calcification so that the effect began to reverse at the highest level of education. Measured risk factors were associated with education and with the calcification outcomes, but they explained little of the associations between educational attainment and coronary or aortic calcification. None of the factors tested met the minimum criterion for mediation. CONCLUSIONS: The findings show that lower education is associated with greater early stage atherosclerosis. Subclinical assessments, such as electron beam tomography, represent useful alternatives for studies of socioeconomic status and coronary artery disease.

Coronary artery calcification in older adults to age 99: prevalence and risk factors.

BACKGROUND: Coronary artery calcification has been proposed as a noninvasive method to assess cardiovascular disease (CVD) risk. However, the prevalence and risk factors for coronary artery calcification in populations >65 years have not been well studied. METHODS AND RESULTS: Electron beam tomography was performed to assess coronary artery calcium (CAC) in 614 older adults aged, on average, 80 years (range, 67 to 99 years); 367 (60%) were women, and 143 (23%) were black. Calcium scores ranged from 0 to 5459. Median scores were 622 for men and 205 for women. Scores increased by age and were lower in blacks than in whites. Nine percent of subjects (n=57) had no CAC, and 31% (n=190) had a score lower than 100. A history of CVD was associated with calcium score. Age, male sex, white race, CVD, triglyceride level, pack-years of smoking, and asthma, emphysema, or bronchitis (chronic obstructive pulmonary disease) were independently associated with CAC score in the fourth quartile. CONCLUSIONS: A wide range of CAC scores was observed, suggesting adaptation with aging. CAC may have potential to predict CVD in older adults, but this remains to be determined.

Changes in cardiovascular risk factors during the perimenopause and postmenopause and carotid artery atherosclerosis in healthy women.

BACKGROUND AND PURPOSE: The objectives of this study were to describe the changes in cardiovascular risk factors during the perimenopausal and early postmenopausal years and correlate those changes in risk factors with carotid intimal-medial thickness (IMT) and plaque index measured 5 to 8 years after menopause. METHODS: Participants were women (n=372) from Allegheny County, Pennsylvania, enrolled in the Healthy Women Study who had been postmenopausal for at least 5 years. Risk factor changes were measured during the perimenopause, ie, between the premenopausal and first year postmenopausal examinations, and during the early postmenopause, ie, between the first and fifth year postmenopausal examinations. Carotid ultrasound scans measured IMT and plaque at examinations 5 to 8 years after menopause among 314 of the women. RESULTS: Increases in LDL cholesterol and triglycerides and declines in HDL cholesterol were greater during perimenopause than postmenopause, whereas increases in blood pressure and fasting glucose levels were greater during postmenopause. Premenopausal systolic and pulse pressure, LDL and HDL cholesterol, triglycerides, and body mass index predicted IMT and plaque. Only the change in pulse pressure between premenopausal and first year postmenopausal examinations was related to both IMT and plaque. CONCLUSIONS: Absolute risk for cardiovascular disease increases substantially in midlife, with a particularly adverse effect on lipid metabolism at the menopause. Premenopausal levels of risk factors are adequate to identify which women should be targeted for intervention.