The independent associations of anti-Müllerian hormone and estradiol levels over the menopause transition with lipids/lipoproteins: The Study of Women's health Across the Nation.

BACKGROUND: The menopause transition (MT) is linked to adverse changes in lipids/lipoproteins. However, the related contributions of anti-Müllerian hormone (AMH) and estradiol (E2) are not clear. OBJECTIVE: To evaluate the independent associations of premenopausal AMH and E2 levels and their changes with lipids/lipoproteins levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1)] over the MT. METHODS: SWAN participants who transitioned to menopause without exogenous hormone use, hysterectomy, or bilateral oophorectomy with data available on both exposure and outcomes when they were premenopausal until the 1st visit postmenopausal were studied. RESULTS: The study included 1,440 women (baseline-age:mean±SD=47.4±2.6) with data available from up to 9 visits (1997-2013). Lower premenopausal levels and greater declines in AMH were independently associated with greater TC and HDL-C, whereas lower premenopausal levels and greater declines in E2 were independently associated with greater TG and apo B and lower HDL-C. Greater declines in AMH were independently associated with greater apoA-1, and greater declines in E2 were independently associated with greater TC and LDL-C. CONCLUSIONS: AMH and E2 and their changes over the MT relate differently to lipids/lipoproteins profile in women during midlife. Lower premenopausal and/or greater declines in E2 over the MT were associated with an atherogenic lipid/lipoprotein profile. On the other hand, lower premenopausal AMH and/or greater declines in AMH over the MT were linked to higher apo A-1 and HDL-C; the later found previously to be related to a greater atherosclerotic risk after menopause.

Is race or ethnicity associated with under-utilization of statins among women in the United States: The study of women's health across the nation.

BACKGROUND: Rates of statin use among minority women are unclear. HYPOTHESIS: We hypothesized that statin use would vary by race/ethnicity with lower rates among minority women compared with Whites. METHODS: Data from the study of women's health across the nation, a multiethnic cohort of women collected between 2009 to 2011 were used to examine reported statin use by race/ethnicity and risk profile. Multivariable logistic modeling was performed to estimate the odds ratio (OR) of statin treatment. RESULTS: Of the 2399 women included, 234 had a diagnosis of atherosclerotic disease (ASCVD), 254 were diabetic (without ASCVD), 163 had an LDL ≥190 mg/dL, and 151 had a 10 year ASCVD pooled risk score ≥7.5%. Statins were used by 49.6% of women with CVD; 59.8% of women with diabetes without known ASCVD; 42.3% of women with an LDL ≥190 mg/dL; and 19.9% of women with an ASCVD risk ≥7.5%. Rates of statin use were 43.8% for women with ≥ two prior ASCVD events and 69.4% for women with ≥ one prior ASCVD event plus multiple high-risk conditions. Among women eligible for statins, Black women had a significantly reduced adjusted odds of being on a statin (OR 0.53, 95% confidence interval [CI] 0.36-0.78) compared with White women. CONCLUSIONS: In this cohort of multiethnic women, rates of statin use among women who would benefit were low, with Black women having lower odds of statin use than White women.

Menopausal Hormone Therapy and Risks of First Hospitalized Heart Failure and its Subtypes During the Intervention and Extended Postintervention Follow-up of the Women's Health Initiative Randomized Trials.

BACKGROUND: We assessed whether postmenopausal hormone therapy (HT) was associated with incident heart failure (HF) and its subtypes and examined whether there was a modifying effect of age on the associations. METHODS AND RESULTS: Postmenopausal women aged 50-79 enrolled in the Women's Health Initiative HT trials were analyzed. The 16,486 women with a uterus were randomized to receive conjugated equine estrogens (CEE 0.625 mg/day) plus medroxyprogesterone acetate (MPA 2.5 mg/day) or placebo, and 10,739 women with prior hysterectomy were randomized to receive CEE (0.625 mg/day) alone or placebo. Incident HF was defined as the first HF hospitalization. HF with reduced ejection fraction (HFrEF) or preserved EF (HFpEF) was defined as EF < 50% or ≥ 50%. During the intervention phase, median follow-up was 5.6 years in the CEE-plus-MPA trial and 7.2 years in the CEE-alone trial. During the cumulative follow-up of 18.9 years, women randomized to HT vs placebo in the 2 combined trials had incidence rates of 3.90 vs 3.89 per 1000 person-years for total HF; 1.25 vs 1.40 per 1000 person-years for HFrEF, and 1.88 vs 1.79 per 1000 person-years for HFpEF, respectively. There were no significant effects of HT on the risk of total incident HF or its subtypes in either trial, and age at randomization did not significantly modify the results. CONCLUSIONS: Postmenopausal HT did not alter the risk of hospitalization for HF or its subtypes during the intervention or cumulative 18.9 years of follow-up, and results did not vary significantly by age at randomization. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT0000611 https://clinicaltrials.gov/ct2/show/NCT00000611?cond=women%27s±health±initiative&rank=5.

Healthy Lifestyle During the Midlife Is Prospectively Associated With Less Subclinical Carotid Atherosclerosis: The Study of Women's Health Across the Nation.

Background Measures of subclinical atherosclerosis are predictors of future cardiovascular outcomes as well as of physical and cognitive functioning. The menopausal transition is associated with accelerated progression of atherosclerosis in women. The prospective association between a healthy lifestyle during the midlife and subclinical atherosclerosis is unclear. Methods and Results Self-reported data on smoking, diet, and physical activity from 1143 women in the Study of Women's Health Across the Nation were used to construct a 10-year average Healthy Lifestyle Score ( HLS ) during the midlife. Markers of subclinical atherosclerosis were measured 14 years after baseline and included common carotid artery intima-media thickness ( CCA - IMT ), adventitial diameter ( CCA - AD ), and carotid plaque. The associations of average HLS with CCA - IMT and CCA - AD were estimated using linear models; the association of average HLS with carotid plaque was estimated using cumulative logit models. Average HLS was associated with smaller CCA - IMT and CCA - AD in the fully adjusted models ( P=0.0031 and <0.001, respectively). Compared with participants in the lowest HLS level, those in the highest level had 0.024 mm smaller CCA - IMT (95% confidence interval: -0.048, 0.000), which equals 17% of the SD of CCA - IMT , and 0.16 mm smaller CCA - AD (95% confidence interval: -0.27, -0.04), which equals 24% of the SD of CCA - AD . Among the 3 components of the HLS , abstinence from smoking had the strongest association with subclinical atherosclerosis. Conclusions Healthy lifestyle during the menopausal transition is associated with less subclinical atherosclerosis, highlighting the growing recognition that the midlife is a critical window for cardiovascular prevention in women.

Modifiable Risk Factors for Incident Heart Failure in Atrial Fibrillation.

OBJECTIVES: This study sought to identify modifiable risk factors and estimate the impact of risk factor modification on heart failure (HF) risk in women with new-onset atrial fibrillation (AF). BACKGROUND: Incident HF is the most common nonfatal event in patients with AF, although strategies for HF prevention are lacking. METHODS: We assessed 34,736 participants in the Women's Health Study who were free of prevalent cardiovascular disease at baseline. Cox models with time-varying assessment of risk factors after AF diagnosis were used to identify significant modifiable risk factors for incident HF. RESULTS: Over a median follow-up of 20.6 years, 1,495 women developed AF without prevalent HF. In multivariable models, new-onset AF was associated with an increased risk of HF (hazard ratio [HR]: 9.03; 95% confidence interval [CI]: 7.52 to 10.85). Once women with AF developed HF, all-cause (HR: 1.83; 95% CI: 1.37 to 2.45) and cardiovascular mortality (HR: 2.87; 95% CI: 1.70 to 4.85) increased. In time-updated, multivariable models accounting for changes in risk factors after AF diagnosis, systolic blood pressure >120 mm Hg, body mass index ≥30 kg/m2, current tobacco use, and diabetes mellitus were each associated with incident HF. The combination of these 4 modifiable risk factors accounted for an estimated 62% (95% CI: 23% to 83%) of the population-attributable risk of HF. Compared with women with 3 or 4 risk factors, those who maintained or achieved optimal risk factor control had a progressive decreased risk of HF (HR for 2 risk factors: 0.60; 95% CI: 0.37 to 0.95; 1 risk factor: 0.40; 95% CI: 0.25 to 0.63; and 0 risk factors: 0.14; 95% CI: 0.07 to 0.29). CONCLUSIONS: In women with new-onset AF, modifiable risk factors including obesity, hypertension, smoking, and diabetes accounted for the majority of the population risk of HF. Optimal levels of modifiable risk factors were associated with decreased HF risk. Prospective assessment of risk factor modification at the time of AF diagnosis may warrant future investigation.

Vitamin E supplementation and the risk of heart failure in women.

BACKGROUND: Oxidative stress may contribute to the development of heart failure (HF); however, an increased risk of HF has been observed with antioxidant therapy in secondary prevention trials. No large clinical trials have addressed the role of antioxidant therapy in the primary prevention of HF. METHODS AND RESULTS: We examined the effect of vitamin E and HF risk in 39 815 initially healthy women, aged at least 45 years at baseline, who were enrolled in the Women's Health Study, a randomized, double-blind, placebo-controlled trial of vitamin E (600 IU every other day). Over a median follow-up of 10.2 years, there were 220 incident HF events. In proportional hazards models, adjusting for age and randomized aspirin and beta carotene treatment, vitamin E assignment did not significantly affect HF risk (hazards ratio [HR], 0.93; 95% CI, 0.71-1.21; P=0.59). These results did not change with multivariate adjustment for other risk factors, including interim myocardial infarction. In a prespecified subgroup analysis, vitamin E was inversely related to developing HF with normal ejection fraction (≥50%) with HR 0.59 (95% CI, 0.38-0.92; P=0.02), but there was no statistically significant effect on the risk of developing systolic HF (HR, 1.26; 95% CI, 0.84-1.89; P=0.26). CONCLUSIONS: In this population of apparently healthy women, vitamin E did not affect the overall risk of HF. The possible benefit on diastolic HF requires confirmation in larger populations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

The menopausal transition and cardiovascular risk.

The incidence of cardiovascular disease, which is the leading single cause of death among women, increases substantially after menopause. This may be related to adverse changes in cardiovascular risk factors that occur during the menopausal transition. Proatherogenic changes in lipid and apolipoprotein profiles seem to be specifically related to ovarian aging; unfavorable changes in other cardiovascular risk factors may be influenced more by chronologic aging. Whether these changes are due to aging or to menopause itself, increased attention to risk factor modification in the pre- and perimenopausal years will help reduce future cardiovascular disease risk among women.

Risk of death and cardiovascular events in initially healthy women with new-onset atrial fibrillation.

CONTEXT: The risks associated with new-onset atrial fibrillation (AF) among middle-aged women and populations with a low comorbidity burden are poorly defined. OBJECTIVES: To examine the association between incident AF and mortality in initially healthy women and to evaluate the influence of associated cardiovascular comorbidities on risk. DESIGN, SETTING, AND PARTICIPANTS: Between 1993 and March 16, 2010, 34,722 women participating in the Women's Health Study underwent prospective follow-up. Participants were 95% white, older than 45 years (median, 53 [interquartile range {IQR}, 49-59] years), and free of AF and cardiovascular disease at baseline. Cox proportional hazards models with time-varying covariates were used to determine the risk of events among women with incident AF. Secondary analyses were performed among women with paroxysmal AF. MAIN OUTCOME MEASURES: Primary outcomes included all-cause, cardiovascular, and noncardiovascular mortality. Secondary outcomes included stroke, congestive heart failure, and myocardial infarction. RESULTS: During a median follow-up of 15.4 (IQR, 14.7-15.8) years, 1011 women developed AF. Incidence rates per 1000 person-years among women with and without AF were 10.8 (95% confidence interval [CI], 8.1-13.5) and 3.1 (95% CI, 2.9-3.2) for all-cause mortality, 4.3 (95% CI, 2.6-6.0) and 0.57 (95% CI, 0.5-0.6) for cardiovascular mortality, and 6.5 (95% CI, 4.4-8.6) and 2.5 (95% CI, 2.4-2.6) for noncardiovascular mortality, respectively. In multivariable models, hazard ratios (HRs) of new-onset AF for all-cause, cardiovascular, and noncardiovascular mortality were 2.14 (95% CI, 1.64-2.77), 4.18 (95% CI, 2.69-6.51), and 1.66 (95% CI, 1.19-2.30), respectively. Adjustment for nonfatal cardiovascular events potentially on the causal pathway to death attenuated these risks, but incident AF remained associated with all mortality components (all-cause: HR, 1.70 [95% CI, 1.30-2.22]; cardiovascular: HR, 2.57 [95% CI, 1.63-4.07]; and noncardiovascular: HR, 1.42 [95% CI, 1.02-1.98]). Among women with paroxysmal AF (n = 656), the increase in mortality risk was limited to cardiovascular causes (HR, 2.94; 95% CI, 1.55-5.59). CONCLUSION: Among a group of healthy women, new-onset AF was independently associated with all-cause, cardiovascular, and noncardiovascular mortality, with some of the risk potentially explained by nonfatal cardiovascular events.

Incremental diagnostic value of regional left ventricular function over coronary assessment by cardiac computed tomography for the detection of acute coronary syndrome in patients with acute chest pain: from the ROMICAT trial.

BACKGROUND: The incremental value of regional left ventricular function (LVF) over coronary assessment to detect acute coronary syndrome (ACS) is uncertain. METHODS AND RESULTS: We analyzed 356 patients (mean age, 53+/-12 years; 62% men) with acute chest pain and inconclusive initial emergency department evaluation. Patients underwent 64-slice contrast-enhanced cardiac computed tomography before hospital admission. Caregivers and patients remained blinded to the results. Regional LVF and presence of coronary atherosclerotic plaque and significant stenosis (>50%) were separately assessed by 2 independent readers. Incremental value of regional LVF to predict ACS was determined in the entire cohort and in subgroups of patients with nonobstructive coronary artery disease, inconclusive assessment for stenosis (defined as inability to exclude significant stenosis due to calcium or motion), and significant stenosis. During their index hospitalization, 31 patients were ultimately diagnosed with ACS (8 myocardial infarction, 22 unstable angina), of which 74% (23 patients) had regional LV dysfunction. Adding regional LVF resulted in a 10% increase in sensitivity to detect ACS by cardiac computed tomography (87%; 95% confidence interval, 70% to 96%) and significantly improved the overall accuracy (c-statistic: 0.88 versus 0.94 and 0.79 versus 0.88, for extent of plaque and presence of stenosis, respectively; both P<0.03). The diagnostic accuracy of regional LVF for detection of ACS has 89% sensitivity and 86% specificity in patients with significant stenosis (n=33) and 60% sensitivity and 86% specificity in patients with inconclusive coronary computed tomographic angiography (n=33). CONCLUSIONS: Regional LVF assessment at rest improves diagnostic accuracy for ACS in patients with acute chest pain, especially in those with coronary artery disease and thus may be helpful to guide further management in patients at intermediate risk for ACS.

Influence of blood pressure and blood pressure change on the risk of congestive heart failure in the elderly.

BACKGROUND: While elevated blood pressure (BP) has been consistently associated with incident congestive heart failure (CHF), much less is known about the effect of BP change. We therefore assessed the association of BP change over time with subsequent risk of CHF. METHODS: 4655 participants >/=65 years old from the prospective Established Populations for Epidemiologic Studies of the Elderly program who were alive and free of CHF after six years of follow-up were included. Categories of sustained high BP, sustained low BP, BP progression and BP regression were defined according to BP differences between study entry and six years of follow-up. The primary endpoint was incident CHF subsequent to the six year examination. RESULTS: During 4.3 years of follow-up after the six year examination, 642 events occurred. The hazard ratio (HR) (95% confidence interval (CI)) for systolic BP > or =160 compared to <120 mm Hg at six years was 1.39 (1.04-1.86). Conversely, the lowest diastolic BP category at six years was associated with an increased risk of incident CHF (HR (95% CI) <70 mm Hg versus 70-79 mm Hg 1.42 (1.18-1.71)). Systolic and diastolic BP were better predictors than pulse pressure. The HRs (95% CI) for incident CHF associated with sustained high systolic BP > or =160 mm Hg and systolic BP progression were 1.35 (0.97-1.89) and 1.45 (1.14-1.85), respectively. Conversely, significant associations were found in those with sustained low diastolic BP or diastolic BP regression (HR (95% CI) 1.42 (1.11-1.83) and 1.45 (1.19-1.76), respectively). CONCLUSION: While persistently elevated systolic BP and systolic BP progression were strong predictors of CHF in the elderly, inverse associations were found with regard to diastolic BP. Systolic and diastolic BP were better predictors of CHF than pulse pressure.

Coronary computed tomography angiography for early triage of patients with acute chest pain: the ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial.

OBJECTIVES: This study was designed to determine the usefulness of coronary computed tomography angiography (CTA) in patients with acute chest pain. BACKGROUND: Triage of chest pain patients in the emergency department remains challenging. METHODS: We used an observational cohort study in chest pain patients with normal initial troponin and nonischemic electrocardiogram. A 64-slice coronary CTA was performed before admission to detect coronary plaque and stenosis (>50% luminal narrowing). Results were not disclosed. End points were acute coronary syndrome (ACS) during index hospitalization and major adverse cardiac events during 6-month follow-up. RESULTS: Among 368 patients (mean age 53 +/- 12 years, 61% men), 31 had ACS (8%). By coronary CTA, 50% of these patients were free of coronary artery disease (CAD), 31% had nonobstructive disease, and 19% had inconclusive or positive computed tomography for significant stenosis. Sensitivity and negative predictive value for ACS were 100% (n = 183 of 368; 95% confidence interval [CI]: 98% to 100%) and 100% (95% CI: 89% to 100%), respectively, with the absence of CAD and 77% (95% CI: 59% to 90%) and 98% (n = 300 of 368, 95% CI: 95% to 99%), respectively, with significant stenosis by coronary CTA. Specificity of presence of plaque and stenosis for ACS were 54% (95% CI: 49% to 60%) and 87% (95% CI: 83% to 90%), respectively. Only 1 ACS occurred in the absence of calcified plaque. Both the extent of coronary plaque and presence of stenosis predicted ACS independently and incrementally to Thrombolysis In Myocardial Infarction risk score (area under curve: 0.88, 0.82, vs. 0.63, respectively; all p < 0.0001). CONCLUSIONS: Fifty percent of patients with acute chest pain and low to intermediate likelihood of ACS were free of CAD by computed tomography and had no ACS. Given the large number of such patients, early coronary CTA may significantly improve patient management in the emergency department.

Waist-height ratio as a predictor of coronary heart disease among women.

BACKGROUND: It is not yet established what specific measures of obesity might be most strongly associated with risk of coronary artery disease. We compared the waist-height ratio to waist-hip ratio, waist circumference, and body mass index as predictors of subsequent coronary heart disease (CHD) in a group of predominantly postmenopausal women. METHODS: The data come from the prospective Nurses' Health Study cohort. We included 45,563 women in 1986 who were aged 40-65 years and were free of heart disease, stroke, and cancer. Waist circumference, hip circumference, height, weight, age, and other covariates were collected by questionnaire. Our primary end point was incident coronary heart disease reported up to June 2002. Areas under the receiver operating characteristic curves (AUCs) were estimated nonparametrically for each of the anthropometric measures. We estimated differences between the AUCs for weight-height ratio and the other measures, with corresponding 95% confidence intervals. We used Cox proportional hazard models to estimate the relationships with risk of CHD. RESULTS: Waist-height ratio, waist-hip ratio, and waist circumference were similar in predicting subsequent risk of CHD. All 3 waist-derived measures were superior to body-mass index (BMI) in predicting CHD. The unadjusted AUCs were 0.62 (95% confidence interval = 0.60-0.64) for waist-height ratio, 0.63 (0.61-0.65) for waist-hip ratio, 0.62 (0.60-0.64) for waist-circumference, and 0.57 (0.55-0.59) for BMI. CONCLUSION: Waist-height ratio is comparable with waist circumference and waist-hip ratio for prediction of coronary heart disease incidence among middle-aged and older women, but superior to BMI.

Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition?

OBJECTIVES: This prospective study examined whether changes in traditional and novel coronary heart disease (CHD) risk factors are greater within a year of the final menstrual period (FMP), relative to changes that occur before or after that interval, in a multiethnic cohort. BACKGROUND: Understanding the influence of menopause on CHD risk remains elusive and has been evaluated primarily in Caucasian samples. METHODS: SWAN (Study of Women's Health Across the Nation) is a prospective study of the menopausal transition in 3,302 minority (African American, Hispanic, Japanese, or Chinese) and Caucasian women. After 10 annual examinations, 1,054 women had achieved an FMP not due to surgery and without hormone therapy use before FMP. Measured CHD risk factors included lipids and lipoproteins, glucose, insulin, blood pressure, fibrinogen, and C-reactive protein. We assessed which of 2 models provided a better fit with the observed risk factor changes over time in relation to the FMP: a linear model, consistent with chronological aging, or a piecewise linear model, consistent with ovarian aging. RESULTS: Only total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B demonstrated substantial increases within the 1-year interval before and after the FMP, consistent with menopause-induced changes. This pattern was similar across ethnic groups. The other risk factors were consistent with a linear model, indicative of chronological aging. CONCLUSIONS: Women experience a unique increase in lipids at the time of the FMP. Monitoring lipids in perimenopausal women should enhance primary prevention of CHD.

Ethnic differences in C-reactive protein concentrations.

BACKGROUND: Limited data exist regarding the ethnic differences in C-reactive protein (CRP) concentrations, an inflammatory marker associated with risk of cardiovascular disease (CVD). We hypothesized that known CVD risk factors, including anthropometric characteristics, would explain much of the observed ethnic variation in CRP. METHODS: We performed a cross-sectional analysis of 3154 women, without known CVD and not receiving hormone therapy, enrolled in the Study of Women's Health Across the Nation (SWAN), a multiethnic prospective study of pre- and perimenopausal women. RESULTS: The study population was 47.4% white, 27.7% African-American, 8.5% Hispanic, 7.7% Chinese, and 8.6% Japanese; mean age was 46.2 years. African-American women had the highest median CRP concentrations (3.2 mg/L), followed by Hispanic (2.3 mg/L), white (1.5 mg/L), Chinese (0.7 mg/L), and Japanese (0.5 mg/L) women (all pairwise P < 0.001 compared with white women). Body mass index (BMI) markedly attenuated the association between ethnicity and CRP. After adjusting for age, socioeconomic status, BMI, and other risk factors, African-American ethnicity was associated with CRP concentrations >3 mg/L (odds ratio 1.37, 95% CI 1.07-1.75), whereas Chinese and Japanese ethnicities were inversely related (0.58, 0.35-0.95, and 0.43, 0.26-0.72, respectively). CONCLUSIONS: Modifiable risk factors, particularly BMI, account for much but not all of the ethnic differences in CRP concentrations. Further study is needed of these ethnic differences and their implications for the use of CRP in CVD risk prediction.

Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study.

OBJECTIVES: The aim of this study was to examine the value of measurement of the interleukin-1 receptor family member ST2 in patients with dyspnea. BACKGROUND: Concentrations of ST2 have been reported to be elevated in patients with heart failure (HF). METHODS: Five hundred ninety-three dyspneic patients with and without acute destabilized HF presenting to an urban emergency department were evaluated with measurements of ST2 concentrations. Independent predictors of death at 1 year were identified. RESULTS: Concentrations of ST2 were higher among those with acute HF compared with those without (0.50 vs. 0.15 ng/ml; p < 0.001), although amino-terminal pro-brain natriuretic peptide (NT-proBNP) was superior to ST2 for diagnosis of acute HF. Median concentrations of ST2 at presentation to the emergency department were higher among decedents than survivors at 1 year (1.08 vs. 0.18 ng/ml; p < 0.001), and in multivariable analyses, an ST2 concentration > or =0.20 ng/ml strongly predicted death at 1 year in dyspneic patients as a whole (HR = 5.6, 95% confidence interval [CI] 2.2 to 14.2; p < 0.001) as well as those with acute HF (hazard ratio [HR] = 9.3, 95% CI 1.3 to 17.8; p = 0.03). This risk associated with an elevated ST2 in dyspneic patients with and without HF appeared early and was sustained at 1 year after presentation (log-rank p value <0.001). A multi-marker approach with both ST2 and NT-proBNP levels identified subjects with the highest risk for death. CONCLUSIONS: Among dyspneic patients with and without acute HF, ST2 concentrations are strongly predictive of mortality at 1 year and might be useful for prognostication when used alone or together with NT-proBNP.

Dietary intakes of flavonols and flavones and coronary heart disease in US women.

Dietary flavonols and flavones are subgroups of flavonoids that have been suggested to decrease the risk of coronary heart disease (CHD). The authors prospectively evaluated intakes of flavonols and flavones in relation to risk of nonfatal myocardial infarction and fatal CHD in the Nurses' Health Study. They assessed dietary information from the study's 1990, 1994, and 1998 food frequency questionnaires and computed cumulative average intakes of flavonols and flavones. Cox proportional hazards regression with time-varying variables was used for analysis. During 12 years of follow-up (1990-2002), the authors documented 938 nonfatal myocardial infarctions and 324 CHD deaths among 66,360 women. They observed no association between flavonol or flavone intake and risk of nonfatal myocardial infarction or fatal CHD. However, a weak risk reduction for CHD death was found among women with a higher intake of kaempferol, an individual flavonol found primarily in broccoli and tea. Women in the highest quintile of kaempferol intake relative to those in the lowest had a multivariate relative risk of 0.66 (95% confidence interval: 0.48, 0.93; p for trend = 0.04). The lower risk associated with kaempferol intake was probably attributable to broccoli consumption. These prospective data do not support an inverse association between flavonol or flavone intake and CHD risk.

Association of atrial fibrillation and amino-terminal pro-brain natriuretic peptide concentrations in dyspneic subjects with and without acute heart failure: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study.

BACKGROUND: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnosis or exclusion of heart failure (HF) in dyspneic patients. Atrial fibrillation (AF) may cause dyspnea in the absence of acute HF and may also affect plasma levels of NT-proBNP. METHODS: We prospectively enrolled 599 patients presenting with dyspnea to the emergency department and obtained a blood sample for NT-proBNP measurement. The diagnosis of AF was identified via presentation electrocardiogram. A final diagnosis of HF was determined by blinded study physicians using all available hospital records for each subject through 60 days of follow-up. We assessed the association between the presence of AF and level of NT-proBNP in subsets of patients with and without HF. RESULTS: Of 599 dyspneic patients, 75 (13%) were in AF at presentation; these patients had significantly higher median NT-proBNP levels when compared with those without AF (2934 vs 294 pg/mL, P < .0001). Among patients with acute HF, AF was present in 28%; NT-proBNP levels were lower in those with AF versus those without (3488 vs 4492 pg/mL, P < .001), but AF was not independently associated with NT-proBNP after multivariable adjustment. In patients without acute HF, median NT-proBNP concentrations were significantly higher in those with AF than in those without (932 vs 121 pg/mL, P = .02); in these subjects, AF was the strongest predictor of an NT-proBNP concentration in a range consistent with acute HF (odds ratio 9.94, 95% CI 2.97-33.3, P < .001). CONCLUSION: Atrial fibrillation is associated with higher NT-proBNP concentrations in dyspneic patients, particularly in those without acute HF.

Coronary multidetector computed tomography in the assessment of patients with acute chest pain.

BACKGROUND: Noninvasive assessment of coronary atherosclerotic plaque and significant stenosis by coronary multidetector computed tomography (MDCT) may improve early and accurate triage of patients presenting with acute chest pain to the emergency department. METHODS AND RESULTS: We conducted a blinded, prospective study in patients presenting with acute chest pain to the emergency department between May and July 2005 who were admitted to the hospital to rule out acute coronary syndrome (ACS) with no ischemic ECG changes and negative initial biomarkers. Contrast-enhanced 64-slice MDCT coronary angiography was performed immediately before admission, and data sets were evaluated for the presence of coronary atherosclerotic plaque and significant coronary artery stenosis. All providers were blinded to MDCT results. An expert panel, blinded to the MDCT data, determined the presence or absence of ACS on the basis of all data accrued during the index hospitalization and 5-month follow-up. Among 103 consecutive patients (40% female; mean age, 54+/-12 years), 14 patients had ACS. Both the absence of significant coronary artery stenosis (73 of 103 patients) and nonsignificant coronary atherosclerotic plaque (41 of 103 patients) accurately predicted the absence of ACS (negative predictive values, 100%). Multivariate logistic regression analyses demonstrated that adding the extent of plaque significantly improved the initial models containing only traditional risk factors or clinical estimates of the probability of ACS (c statistic, 0.73 to 0.89 and 0.61 to 0.86, respectively). CONCLUSIONS: Noninvasive assessment of coronary artery disease by MDCT has good performance characteristics for ruling out ACS in subjects presenting with possible myocardial ischemia to the emergency department and may be useful for improving early triage.

MDCT in early triage of patients with acute chest pain.

OBJECTIVE: Current risk stratification of patients with acute chest pain but normal initial cardiac enzymes and nondiagnostic ECG is inefficient. We sought to determine whether contrast-enhanced MDCT-based detection of stenosis is feasible and improves early and accurate triage of patients with acute chest pain. SUBJECTS AND METHODS: We studied 40 patients (53% men; mean age, 57 +/- 13 years) with chest pain who were awaiting hospital admission to rule out an acute coronary syndrome (ACS) despite the absence of diagnostic ECG changes and normal cardiac enzymes on emergency department presentation. Patients underwent contrast-enhanced MDCT before hospital admission. Afterward, patients received standard clinical care. All physicians involved in the patients' care were blinded to the results of MDCT. An expert panel established the presence or absence of ACS based on American Heart Association (AHA) guidelines. The MDCT images were evaluated for the presence of significant coronary artery stenosis (diameter reduction > 50%) and were used to make a triage decision. RESULTS: All five patients (12.5%) with ACS (one with non-ST elevation myocardial infarction, four with unstable angina pectoris) had at least one significant coronary stenosis on MDCT (sensitivity, 100% [95% CI, 49-100%)]. ACS was ruled out in 35 patients (87.5%). Significant coronary stenosis was excluded in 26 of the 35 patients without ACS by MDCT (specificity, 74% [CI, 75-88%]), potentially saving 70% of unnecessary hospital admissions. CONCLUSION: MDCT-based detection of significant coronary stenoses has tremendous potential to decrease the number of unnecessary hospital admissions, without reducing appropriate admission rates, in patients with chest pain who have nondiagnostic ECG results and normal cardiac enzymes. These results are likely to further improve with advances in MDCT technology.