Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study.

BACKGROUND: The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. METHODS: Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). RESULTS: The mean age of women was 52.9 (± 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) µg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P = 0.10). CONCLUSIONS: In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00154180.

Projected impact of polypill use among US adults: Medication use, cardiovascular risk reduction, and side effects.

BACKGROUND: Polypills, which include multiple medications for reducing cardiovascular disease (CVD) risk in a single pill, have been proposed for population-wide use. The number of US adults eligible for polypills and potential benefits are unknown. METHODS: The National Health and Nutrition Examination Survey 2003-2004 and 2007-2008 were analyzed to estimate treatment rates for medications proposed for inclusion in polypills (aspirin, statin, an angiotensin-converting enzyme [ACE] inhibitor, and a thiazide-type diuretic for those without and a ß-blocker for those with a history of myocardial infarction) among US adults. The number of coronary heart disease (CHD) and stroke events potentially prevented through polypill use was projected by published meta-analyses and 3 large population-based cohort studies. Two polypill eligibility criteria were analyzed: (1) US adults ≥55 years and (2) US adults with a history of CVD. RESULTS: There are 67.6 million US adults ≥55 years and 15.4 million US adults with a history of CVD and, thus, eligible for polypills using the 2 outlined criteria. In 2007 to 2008, 37.3% of US adults ≥55 years and 57.0% of those with a history of CVD were taking statins. Use of other polypill medications was also low. Polypill use by US adults aged ≥55 years is projected to potentially prevent 3.2 million CHD events and 1.7 million strokes over 10 years. Among those with a history of CVD, the potential to prevent of 0.9 million CHD events and 0.5 million strokes is projected. CONCLUSIONS: Polypills have the potential to lower CVD incidence substantially among US adults.

High-molecular-weight adiponectin and incident ischemic stroke in postmenopausal women: a Women's Health Initiative Study.

BACKGROUND AND PURPOSE: Although low levels of adiponectin are associated with coronary heart disease and cardiovascular disease risk factors, it is unclear whether adiponectin levels are related to the risk of developing ischemic stroke. METHODS: We examined the relationship between baseline high-molecular-weight (HMW) adiponectin levels and incident ischemic stroke in postmenopausal women using data and specimens from the Hormones and Biomarkers Predicting Stroke Study, a case-control study nested within the Women's Health Initiative Observational Study. Included were 855 incident ischemic stroke cases and 855 control subjects matched for age, race-ethnicity, date of entry into the cohort, and follow-up time. ORs of incident ischemic stroke associated with baseline HMW adiponectin levels were calculated using conditional logistic regression modeling adjusting for body mass index, type 2 diabetes, hypertension, smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, physical activity, C-reactive protein, and aspirin use. RESULTS: Lower levels of HMW adiponectin were significantly associated with type 2 diabetes, hypertension, higher body mass index, waist circumference, glucose, and insulin levels and lower high-density lipoprotein cholesterol levels. The distribution of incident stroke cases by HMW adiponectin quartiles was 49.9%, 50.5%, 50.7%, and 48.9%, respectively (P=0.96). Multivariable-adjusted ORs of stroke associated with the top 3 quartiles of HMW adiponectin versus the first quartile were 0.99 (95% CI, 0.71 to 1.37), 1.37 (0.99 to 1.91), and 1.25 (0.88 to 1.79), respectively (P trend=0.14). CONCLUSIONS: Despite moderate associations between HMW adiponectin and cardiovascular disease risk factors, we found no evidence of an association between HMW adiponectin levels and incident ischemic stroke in these postmenopausal women.

Hepatocyte growth factor and the risk of ischemic stroke developing among postmenopausal women: results from the Women's Health Initiative.

BACKGROUND AND PURPOSE: Hepatocyte growth factor (HGF) is a potent angiogenic factor and may play a role in the development and progression of atherosclerotic lesions, the underlying mechanism of cardiovascular disease. However, there have been no prospective studies examining the relationship between HGF levels and risk of stroke. METHODS: We conducted a nested case-control study (972 incident stroke cases and 1:1 age-matched and race-matched controls) to prospectively evaluate the association between plasma HGF and risk of ischemic stroke within the Women's Health Initiative Observational Study, a cohort of postmenopausal women aged 50 to 79 years. RESULTS: Baseline HGF levels were correlated positively with body mass index, systolic blood pressure, low-density lipoprotein cholesterol, insulin resistance, and inflammatory markers, such as C-reactive protein, and inversely with high-density lipoprotein cholesterol (all P<0.05). Baseline HGF levels were higher among cases than controls (geometric means, 601.8 vs 523.2 pg/mL; P=0.003). Furthermore, the risk of incident ischemic stroke was significantly greater among women in the highest vs lowest quartile of plasma HGF levels (OR, 1.46; 95% CI, 1.12-1.91; P(trend)=0.003) in a conditional logistic regression model that adjusted for body mass index. These results were only slightly attenuated after further adjustment for additional stroke risk factors (OR, 1.39; 95% CI, 1.04-1.85; P(trend)=0.023). CONCLUSIONS: Circulating levels of HGF are associated with an increased risk of incident ischemic stroke, independent of obesity and other risk factors for cardiovascular disease, among postmenopausal women aged 50 to 79 years.

Alcohol consumption and the risk of coronary heart disease in postmenopausal women with diabetes: Women's Health Initiative Observational Study.

BACKGROUND: Although several observational studies have consistently reported an inverse association between moderate alcohol consumption and risk of coronary heart disease (CHD), it is yet not well established if this association also exists among people with type 2 diabetes. The aim of this study is to evaluate the association between the frequency and quantity of alcohol intake and the risk of developing CHD among postmenopausal women with diabetes. METHODS: We conducted a prospective cohort study, which included 3,198 women with self-reported diabetes and without any history of cardiovascular disease at baseline, in the Women's Health Initiative Observational Study. Alcohol intake was assessed by a semiquantitative food frequency questionnaire. The primary outcome of this study was CHD, which was validated by medical record review. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for the association of alcohol intake and risk of incident CHD while adjusting for several potential confounders. RESULTS: During the 22,546 person-years of follow-up, there were 336 incident cases of CHD. Both frequency and quantity of alcohol intake were inversely associated with the risk of developing CHD. Compared to nondrinkers, the multivariable HRs across categories of frequency of alcohol consumption (or=2 drinks/week) were 0.89 (95% confidence intervals [CI]: 0.63, 1.26), 0.84 (95% CI: 0.56, 1.25) and 0.65 (95% CI: 0.43, 0.99), respectively (p for trend: 0.04). This association did not appear to differ based on the type of the alcoholic beverage consumed. CONCLUSIONS: Moderate alcohol consumption of postmenopausal women with type 2 diabetes may have a benefit on CHD similar to that seen in postmenopausal nondiabetic women. The potential risks of alcohol on noncardiac outcomes may need consideration when recommending alcohol to women with diabetes.

Disordered eating in adulthood is associated with reported weight loss attempts in childhood.

OBJECTIVE: To determine whether history of attempted weight loss in childhood (age ≤ 12 years) is associated with binge eating disorder (BED) and unhealthy weight loss behaviors in adults. METHOD: Cross-sectional analysis from baseline visit data of 588 participants of a clinical trial. Data were collected from survey answers on health status, nutritional status, weight loss history, and weight loss behaviors. RESULTS: History of childhood weight loss attempts was associated with high odds of BED in adults (odds ratio [OR] 3.4; 95% confidence interval [CI] 2.8-6.3) and high odds of unhealthy weight loss behaviors (OR 2.3; 95% CI 1.2, 2.6). A linear trend was observed in which young age at first attempted weight loss was associated with increased odds of both BED and unhealthy weight loss behaviors. DISCUSSION: Weight loss attempts in childhood may be a risk factor for the development of unhealthy eating behaviors and BED in adults.

Cardiovascular risk factor variation within a Hispanic cohort: SWAN, the Study of Women's Health Across the Nation.

OBJECTIVES: Hispanics have less favorable cardiovascular risk profiles relative to other groups, although little is known regarding variability in risk profiles according to country of origin. Our goal was to examine the association of cardiovascular risk factors with country of origin and acculturation in a cohort of middle-aged Hispanic women. SETTING: Baseline data for participants at the New Jersey Site of the Study of Women's Health Across the Nation (SWAN). PARTICIPANTS: 419 women, aged 42-52 years, comprising 142 non-Hispanic Whites and 277 Hispanic: Central American (n = 29), South American (n = 106), Puerto Rican (n = 56), Dominican (n = 42) and Cuban (n = 44). MAIN OUTCOME MEASURES: BMI, smoking, blood pressure, lipid profiles, and presence of hypertension, hyperlipidemia, diabetes and metabolic syndrome were compared using univariate and multivariable models. RESULTS: LDL and HDL varied significantly across Hispanic subgroups (overall P < or = .05). Prevalence of metabolic syndrome was greatest in Puerto Rican women (48.2% vs 40.0%, 35.0%, 13.9% and 29.3% in Central American, South American, Dominican and Cuban women, respectively, P = .016). Central American women were least likely to smoke (P < .05 vs Puerto Rican, Cuban and South American). Prevalence of hypertension and diabetes were similar across groups. Differences in lipids and metabolic syndrome were not explained by acculturation, financial strain, education, physical activity, smoking or dietary fat intake. CONCLUSIONS: There is significant heterogeneity in cardiovascular risk status among middle-aged Puerto Rican, Cuban, Dominican, Central American and South American women, not explained by acculturation or socioeconomic indicators. These differences may be important for targeting screening and preventive interventions.

Elevated risk of type 2 diabetes and metabolic syndrome among Asians and south Asians: results from the 2004 New York City HANES.

OBJECTIVE: Although numerous studies have identified an elevated risk of diabetes or impaired fasting glucose among Asians, there are limited data examining variability in risk among Asian subpopulations. We estimated prevalence of diabetes (DM), metabolic syndrome (MS) and impaired fasting glucose (IFG), by race/ethnicity and by Asian subgroup. DESIGN, SETTINGS AND PARTICIPANTS: This study was conducted using the fasting subsample of the 2004 New York City Health and Nutrition Examination Survey (NYC HANES; n = 1,324), a local version of the NHANES. Using country of origin information, we constructed South Asian and other Asian categories. MAIN OUTCOME MEASURES: DM, MS and IFG. RESULTS: Age-standardized prevalence estimates of DM, MS and IFG were 10.8%, 13.3% and 21.4% among Whites, 16.1%, 12.0% and 32.4% among all Asians, and 35.4%, 17.7% and 15.9% among foreign-born South Asians, respectively. After adjusting for potential confounders, Asians had significantly higher odds of prevalent IFG (Adjusted odds ratio [AOR]:2.64; 95% confidence interval [CI]: 1.60-4.38) and MS (AOR:2.09; 95%CI: 1.19-3.68), compared to Whites. South Asians were more likely to have DM (AOR:4.88; 95%CI: 1.52-15.66) and MS (AOR:5.59; 95%CI: 1.69-18.50) compared to Whites, while other Asians were at increased prevalence of IFG (AOR:2.89; 95%CI: 1.65-5.07). CONCLUSION: Our findings suggest that the observed White/Asian disparity in DM risk may be primarily attributable to elevated risk among South Asians.

Healthy obesity.

PURPOSE OF REVIEW: To introduce the healthy obese phenotype, characterized by favorable cardiometabolic risk factors despite excess adipose tissue. The epidemiology of the healthy obese phenotype is presented, including associated risk of cardiovascular disease (CVD), and potential biologic mechanisms which may give rise to the phenotype are discussed. RECENT FINDINGS: Although it appears that approximately 30% of obese individuals maintain healthy cardiometabolic profiles, little published data exist examining the healthy obese phenotype. The healthy obese do not appear to be at increased risk of incident CVD events compared with at-risk obese, and the location of adipose tissue and the metabolic characteristics of the fat in a given location, including the presence of ectopic fat and associated adipocytokine response, may give rise to the phenotype. Recent data also suggest that weight loss among healthy obese may adversely impact their favorable cardiometabolic profile. SUMMARY: A high prevalence of the healthy obese phenotype has been reported, and these individuals appear to be at no increased risk of CVD. Further research is needed into the mechanisms that allow these individuals to maintain low risk of CVD despite excess adiposity and appropriate weight loss recommendations for this group.

Update on the metabolic syndrome: hypertension.

The presence of the metabolic syndrome identifies an individual at increased risk for diabetes, cardiovascular disease, and early mortality. However, the increased risk may vary by the absence or presence of hypertension. Current guidelines for the management of high blood pressure in the metabolic syndrome emphasize lifestyle modification as a first-line strategy. Pharmacologic treatment of elevated blood pressure in the metabolic syndrome may be necessary in the presence of other cardiovascular risk factors or to achieve adequate blood pressure control. Currently, there is no consensus as to which antihypertensive therapy should be used to treat hypertension in patients with the metabolic syndrome; it remains unclear whether achieving tight blood pressure control should outweigh the potential for development of glucose intolerance. Future research must focus on this issue given the high prevalence of the syndrome among hypertensive patients and high rates of progression to diabetes among those with the metabolic syndrome.

Major causes of death among men and women in China.

BACKGROUND: With China's rapid economic development, the disease burden may have changed in the country. We studied the major causes of death and modifiable risk factors in a nationally representative cohort of 169,871 men and women 40 years of age and older in China. METHODS: Baseline data on the participants' demographic characteristics, medical history, lifestyle-related risk factors, blood pressure, and body weight were obtained in 1991 with the use of a standard protocol. The follow-up evaluation was conducted in 1999 and 2000, with a follow-up rate of 93.4 percent. RESULTS: We documented 20,033 deaths in 1,239,191 person-years of follow-up. The mortality from all causes was 1480.1 per 100,000 person-years among men and 1190.2 per 100,000 person-years among women. The five leading causes of death were malignant neoplasms (mortality, 374.1 per 100,000 person-years), diseases of the heart (319.1), cerebrovascular disease (310.5), accidents (54.0), and infectious diseases (50.5) among men and diseases of the heart (268.5), cerebrovascular disease (242.3), malignant neoplasms (214.1), pneumonia and influenza (45.9), and infectious diseases (35.3) among women. The multivariate-adjusted relative risk of death and the population attributable risk for preventable risk factors were as follows: hypertension, 1.48 (95 percent confidence interval, 1.44 to 1.53) and 11.7 percent, respectively; cigarette smoking, 1.23 (95 percent confidence interval, 1.18 to 1.27) and 7.9 percent; physical inactivity, 1.20 (95 percent confidence interval, 1.16 to 1.24) and 6.8 percent; and underweight (body-mass index [the weight in kilograms divided by the square of the height in meters] below 18.5), 1.47 (95 percent confidence interval, 1.42 to 1.53) and 5.2 percent. CONCLUSIONS: Vascular disease and cancer have become the leading causes of death among Chinese adults. Our findings suggest that control of hypertension, smoking cessation, increased physical activity, and improved nutrition should be important strategies for reducing the burden of premature death among adults in China.

Alcohol consumption and risk for stroke among Chinese men.

OBJECTIVE: Stroke is a leading cause of death and long-term disability in China. The objective of this study was to examine the relation between alcohol consumption and risk for stroke among Chinese men. METHODS: We conducted a prospective cohort study among 64,338 Chinese men aged > or = 40 years who were free of stroke at baseline. Data on frequency and type of alcohol consumed were collected at the baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999 to 2000, which included determining vital status, interviewing participants or proxies, and obtaining hospital and medical records for incident and fatal strokes. RESULTS: Over the course of 493,351 person-years of follow-up, we documented 3,434 incident strokes (1,848 stroke deaths). After adjustment for age, body mass index, physical activity, urbanization (urban vs rural), geographic variation (north vs south), cigarette smoking, history of diabetes, and education, compared with nondrinkers, relative risk (95% confidence interval) of incident stroke was 0.92 (0.80-1.06) for participants consuming 1 to 6 drinks/week, 1.02 (0.93-1.13) for those consuming 7 to 20 drinks/week, 1.22 (1.07-1.38) for those consuming 21 to 34 drinks/week, and 1.22 (1.08-1.37) for those consuming 35 or more drinks per week (p for linear trend < 0.0001). The corresponding relative risks for stroke mortality were 0.93 (0.76-1.14), 0.98 (0.85-1.13), 1.15 (0.95-1.38), and 1.30 (1.11-1.52), respectively (p for linear trend = 0.0004; p for quadratic trend = 0.03). INTERPRETATION: These results suggest that heavy alcohol drinking may increase the risk for stroke in Chinese men and should be the target of strategies for prevention.

Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI: a meta-analysis.

OBJECTIVE: To determine which simple index of overweight and obesity is the best discriminator of cardiovascular risk factors. STUDY DESIGN AND SETTING: This is a meta-analysis of published literature. MEDLINE was searched. Studies that used receiver-operating characteristics (ROC) curve analysis and published area under the ROC curves (AUC) for overweight and obesity indices with hypertension, type-2 diabetes, and/or dyslipidemia were included. The AUC for each of the four indices, with each risk factor, was pooled using a random-effects model; male and female data were analyzed separately. RESULTS: Ten studies met the inclusion criteria. Body mass index (BMI) was the poorest discriminator for cardiovascular risk factors. Waist-to-height ratio (WHtR) was the best discriminator for hypertension, diabetes, and dyslipidemia in both sexes; its pooled AUC (95% confidence intervals) ranged from 0.67 (0.64, 0.69) to 0.73 (0.70, 0.75) and from 0.68 (0.63, 0.72) to 0.76 (0.70, 0.81) in males and females, respectively. CONCLUSION: Statistical evidence supports the superiority of measures of centralized obesity, especially WHtR, over BMI, for detecting cardiovascular risk factors in both men and women.

Associations of endogenous sex hormones with the vasculature in menopausal women: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: As associations between endogenous sex hormones and the vasculature are not well characterized, the objective was to examine the cross-sectional associations of menopausal status and endogenous sex hormones with vascular characteristics. DESIGN: Common carotid artery adventitial diameter and intima-media thickness were determined using B-mode ultrasonography among 483 middle-aged women enrolled in the Pittsburgh and Chicago sites of the Study of Women's Health Across the Nation. RESULTS: Sixty-two percent of women were pre- or early perimenopausal (<3 mo amenorrhea), 12% were late perimenopausal (3-12 mo amenorrhea), and 27% were postmenopausal (>or=12 mo amenorrhea). After adjustment for age, compared with pre-/early perimenopause, late perimenopause was associated with a 0.28-mm larger adventitial diameter (P=0.001), whereas postmenopause was associated with a 0.15-mm larger adventitial diameter (P=0.040). Adjustment for traditional cardiovascular risk factors slightly attenuated these associations, but the association with late perimenopause remained statistically significant (P=0.001). Each SD lower log estradiol value was associated with a 0.07-mm larger adventitial diameter after adjustment for traditional cardiovascular risk factors (P=0.023), whereas other endogenous hormones showed no associations. Intima-media thickness values were not significantly associated with menopausal status or endogenous sex hormones after adjustment for age. CONCLUSIONS: The menopausal transition and declining estrogen levels are associated with alterations of the peripheral vasculature, which may help to explain the increased risk of cardiovascular disease with postmenopause.

Change in adipocytokines and ghrelin with menopause.

OBJECTIVES: To determine if ghrelin and adipocytokine (leptin, adiponectin, resistin) levels vary with menopause stage or with estradiol (E2), testosterone (T), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) concentrations measured in three stages of the menopause transition. METHODS: A study of adipocytokines and menopause was nested in a population-based, longitudinal study of Caucasian women [Michigan Bone Health and Metabolism Study (MBHMS)]. Annual serum and urine samples, available from the MBHMS repository, were selected to correspond to the pre-, peri-, and postmenopause stages of the menopause transition. Participants included forty women, stratified into obese versus non-obese groups based upon their baseline body mass index, who had specimens corresponding to the three menopause stages. RESULTS: Mean resistin levels were approximately two times higher during premenopause compared to peri- or postmenopause. There were significantly lower adiponectin and higher ghrelin levels in the perimenopause stage, compared to either the pre- or postmenopause stage. Increases in FSH concentrations were significantly and positively associated with higher leptin in non-obese women (P<0.01) but not in obese women (P<0.23). Increases in FSH concentrations were also significantly (P<0.005) and positively associated with higher adiponectin concentrations but were negatively associated with ghrelin concentrations (P<0.005). Associations remained following adjustment for waist circumference, waist circumference change, chronological age, and time between measures. CONCLUSIONS: Menopause stages and underlying FSH changes are associated with notable changes in levels of the metabolically active adipocytokines and ghrelin and these changes may be related to selected health outcomes observed in women at mid-life.

Incidence and predictors of hypertension over 8 years among Chinese men and women.

OBJECTIVE: To determine the 8-year incidence of hypertension and its risk factors among Chinese adults. METHODS: A population-based sample of 10,525 Chinese adults aged > or = 40 years and free from hypertension at baseline was followed up from 1991 to 1999-2000. Incident hypertension was defined as systolic pressure > or = 140 mmHg, diastolic pressure > or = 90 mmHg, or current use of antihypertensive medication. RESULTS: Over a mean of 8.2 years of follow-up, 28.9% of men and 26.9% of women developed hypertension. Among men, independent predictors of incident hypertension were baseline age [relative risk (RR) per 5 years: 1.10; 95% confidence interval (CI): 1.07, 1.13], living in urban regions versus rural regions (RR: 0.74; 95% CI: 0.64, 0.85), alcohol drinking versus non-drinking (RR: 1.13; 95% CI: 1.02, 1.24), prehypertension versus normotension (RR: 1.70; 95% CI: 1.53, 1.88), heart rate (RR of third versus first tertile: 1.27; 95% CI: 1.13, 1.44), body mass index (RR of third versus first tertile: 1.28; 95% CI: 1.12, 1.46) and low versus high physical activity (RR: 1.27; 95% CI: 1.10, 1.47). Results were similar for women, with current smoking in place of alcohol drinking and opposite results for region. The population-attributable risk of modifiable risk factors was between 25 and 50%. CONCLUSIONS: These data indicate that the incidence of hypertension is high among these Chinese adults, and suggest that 25-50% of new hypertension cases could be prevented with risk factor modification. Given the excess cardiovascular mortality associated with hypertension, these data call for urgent improvements in hypertension prevention and control programs in China.

Relation between depressive symptoms and common carotid artery atherosclerosis in American persons > or =65 years of age.

Few epidemiologic studies have examined the association between depressive symptoms and atherosclerosis in subjects aged > or =65 years. Most of these studies were cross sectional and could not determine the temporality between depressive symptoms and the development of abnormal common carotid artery (CCA) intima-media thickness (CCA-IMT). To investigate the association between depressive symptoms and CCA atherosclerosis in subjects aged > or =65 years, data from 3,781 participants aged > or =65 years from the Cardiovascular Health Study were analyzed. The presence of depressive symptoms was measured by the Center for Epidemiologic Studies Depression Scale, while CCA-IMT as an indicator of CCA atherosclerosis was measured by B-mode carotid ultrasonography. Multivariate generalized estimation equations adjusted for age, gender, race, alcohol intake, blood glucose status, body mass index, and time showed that subjects aged > or =65 years with depressive symptoms had larger CCA-IMTs than those who did not have such symptoms (beta = 18.26 microm, SE 8.06, p = 0.03). Using 1,000 and 1,140 microm as cut-off points to exclude participants who had abnormal CCA-IMTs at baseline, the adjusted relative risks and the corresponding 95% confidence intervals of developing abnormal CCA-IMT over 3 years were 1.30 (95% confidence interval 1.10 to 1.44) and 1.21 (95% confidence interval 1.00 to 1.46), respectively. Similar results were obtained after excluding participants with prevalent cardiovascular disease at baseline. In conclusion, these data indicate that depressive symptoms are associated with the development of atherosclerosis in subjects aged > or =65 years.

Sex-hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN).

BACKGROUND: Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone-binding globulin (SHBG) as potential mediators of increasing cardiovascular (CV) risk in women at midlife. METHODS AND RESULTS: The correlation between reproductive hormones and CV risk factors was evaluated in a multiethnic (white, black, Hispanic, Chinese, and Japanese) sample of 3297 premenopausal and perimenopausal women. Testosterone and estradiol (E2) were evaluated along with SHBG and the free androgen index (FAI), the amount of testosterone not bound by SHBG. Low SHBG and high FAI were strongly and consistently related to elevated CV risk factors (higher insulin, glucose, and hemostatic and inflammatory markers and adverse lipids) even after controlling for body mass index (P<0.001 for all). Low levels of E2 were associated with elevated CV risk factors to a lesser degree. These observations were consistent across the 5 ethnic groups. Compared with whites, blacks had higher levels of SHBG and lower levels of FAI, and Chinese had lower levels of SHBG and higher levels of FAI. CONCLUSIONS: Low SHBG and high FAI are strongly associated with CV risk factors in racially diverse women, and thus, androgens likely play a role in the CV risk profile of perimenopausal women.

Relation of borderline peripheral arterial disease to cardiovascular disease risk.

Peripheral arterial disease (PAD) is a well-established risk factor for clinical cardiovascular disease (CVD). The impact of a low ankle-brachial index (ABI), higher than the generally recognized 0.9 cutpoint for PAD, on CVD risk is not well characterized. We analyzed data from the 1999 to 2002 National Health and Nutrition Examination Survey (n = 4,895), a nationally representative sample of United States adults, to determine the prevalence of PAD (ABI <0.90), borderline PAD (ABI 0.90 to 0.99), a low-normal ABI (1.00 to 1.09), and a normal ABI (1.10 to 1.29), and the association of these ABI levels with CVD. The prevalence of PAD, borderline PAD, a low-normal ABI, and a normal ABI was 5.0%, 8.7%, 27.8%, and 54.8%, respectively. After age, race/ethnicity, and gender adjustment, the odds ratios of a 10-year coronary heart disease (CHD) risk of >or=20%, CHD, stroke, and CVD were higher at lower ABI levels (each p trend <0.01). After additional adjustment for potential confounders, the odds ratios associated with a low-normal ABI, borderline PAD, and PAD, compared with those with a normal ABI, were 1.24 (95% confidence interval [CI] 0.91 to 1.70), 1.34 (95% CI 0.99 to 1.83), and 1.87 (95% CI 1.29 to 2.73), respectively (p trend <0.001) for CVD and 1.20 (95% CI 0.82 to 1.77), 1.45 (95% CI 0.80 to 2.63), and 2.02 (95% CI 1.20 to 3.39), respectively (p trend = 0.015) for a 10-year risk of CHD of >or=20%. In contrast, a trend was not present for CHD and stroke after multivariate adjustment. In conclusion, subjects with a low-normal ABI or with borderline PAD need screening for CVD risk factors, and interventions may be appropriate to prevent cardiovascular events.

Relationship between HbA1c level and peripheral arterial disease.

OBJECTIVE: Homeostatic glucose control may play an important role in the development of peripheral arterial disease among individuals without diabetes. We sought to evaluate the association of HbA(1c) (A1C) with peripheral arterial disease in a representative sample of the U.S. population with and without diabetes. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted among 4,526 National Health and Nutrition Examination Survey 1999-2002 participants > or = 40 years of age. Peripheral arterial disease was defined as an ankle-brachial index <0.9 (n = 327). RESULTS: Among nondiabetic subjects, the age-standardized prevalence of peripheral arterial disease was 3.1, 4.8, 4.7, and 6.4% for participants with an A1C <5.3, 5.3-5.4, 5.5-5.6, and 5.7-6.0%, respectively (P trend <0.001). The prevalence of peripheral arterial disease was 7.5 and 8.8% for diabetic participants with A1C <7 and > or = 7%, respectively. After multivariable adjustment and compared with nondiabetic participants with A1C <5.3%, the odds ratio (95% CI) of peripheral arterial disease for nondiabetic participants with an A1C of 5.3-5.4, 5.5-5.6, and 5.7-6.0% was 1.41 (0.85-2.32), 1.39 (0.70-2.75), and 1.57 (1.02-2.47), respectively, and it was 2.33 (1.15-4.70) and 2.74 (1.25-6.02) for diabetic participants with A1C <7 and > or = 7%, respectively. CONCLUSIONS: An association exists between higher levels of A1C and peripheral arterial disease, even among patients without diabetes. Individuals with A1C levels > or = 5.3% should be targeted for aggressive risk factor reduction, which may reduce the burden of subclinical cardiovascular disease even among those without diabetes.