Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism: An Individual Participant Data Meta-Analysis of Prospective Studies.

BACKGROUND: Much controversy surrounds the association of traditional cardiovascular disease risk factors with venous thromboembolism (VTE). METHODS: We performed an individual level random-effect meta-analysis including 9 prospective studies with measured baseline cardiovascular disease risk factors and validated VTE events. Definitions were harmonized across studies. Traditional cardiovascular disease risk factors were modeled categorically and continuously using restricted cubic splines. Estimates were obtained for overall VTE, provoked VTE (ie, VTE occurring in the presence of 1 or more established VTE risk factors), and unprovoked VTE, pulmonary embolism, and deep-vein thrombosis. RESULTS: The studies included 244 865 participants with 4910 VTE events occurring during a mean follow-up of 4.7 to 19.7 years per study. Age, sex, and body mass index-adjusted hazard ratios for overall VTE were 0.98 (95% confidence interval [CI]: 0.89-1.07) for hypertension, 0.97 (95% CI: 0.88-1.08) for hyperlipidemia, 1.01 (95% CI: 0.89-1.15) for diabetes mellitus, and 1.19 (95% CI: 1.08-1.32) for current smoking. After full adjustment, these estimates were numerically similar. When modeled continuously, an inverse association was observed for systolic blood pressure (hazard ratio=0.79 [95% CI: 0.68-0.92] at systolic blood pressure 160 vs 110 mm Hg) but not for diastolic blood pressure or lipid measures with VTE. An important finding from VTE subtype analyses was that cigarette smoking was associated with provoked but not unprovoked VTE. Fully adjusted hazard ratios for the associations of current smoking with provoked and unprovoked VTE were 1.36 (95% CI: 1.22-1.52) and 1.08 (95% CI: 0.90-1.29), respectively. CONCLUSIONS: Except for the association between cigarette smoking and provoked VTE, which is potentially mediated through comorbid conditions such as cancer, the modifiable traditional cardiovascular disease risk factors are not associated with increased VTE risk. Higher systolic blood pressure showed an inverse association with VTE.

A prospective study of dietary patterns and cancer mortality among Blacks and Whites in the REGARDS cohort.

Marked racial differences exist in dietary patterns and obesity, as well as cancer mortality. This study aims to assess whether dietary patterns are associated with cancer mortality overall and by race. We identified 22,041 participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Dietary patterns were categorized into: Convenience (Chinese and Mexican foods, pasta, pizza), Plant-based (fruits, vegetables), Southern (added fats, fried foods, sugar-sweetened beverages), Sweets/Fats (sugary foods) and Alcohol/Salads (alcohol, green-leafy vegetables, salad dressing). Using Cox regression, we examined the association between quartiles of dietary patterns and cancer mortality, adjusted for potential confounders, overall among all participants and stratified by race. A total of 873 cancer deaths were observed over the 10-year observation period: 582 (66.7%) in Whites and 291 (33.3%) in Blacks. Greater adherence to the Southern dietary pattern was associated with an increased risk of cancer mortality (4th vs. 1st quartile HR: 1.67; 95% CI: 1.32-2.10) overall, especially among Whites (4th vs. 1st quartile HR: 1.59; 95% CI: 1.22-2.08). The convenience (HR: 0.73; 95% CI: 0.56-0.94) and Plant-based (HR: 0.72; 95% CI: 0.55-0.93) dietary patterns were associated with up to a 28% reduced risk of cancer mortality, but only among Whites. Greater adherence to the Southern dietary pattern increased the risk of cancer mortality, while greater adherence to the convenience and Plant-based diets reduced the risk of cancer mortality among Whites. Racial differences were observed in the association between dietary patterns and cancer mortality, but warrant further study.

Low-Density Lipoprotein Cholesterol Concentrations and Association of High-Sensitivity C-Reactive Protein Concentrations With Incident Coronary Heart Disease in the Multi-Ethnic Study of Atherosclerosis.

High-sensitivity C-reactive protein (hs-CRP) has been associated with coronary heart disease (CHD) in numerous but not all observational studies, and whether low levels of low-density lipoprotein cholesterol (LDL-C) alter this association is unknown. In the Multi-Ethnic Study of Atherosclerosis (2000-2012), we prospectively assessed the association of hs-CRP concentrations with incident CHD in participants who did not receive lipid-lowering therapy, as well as in those with LDL-C concentrations less than 130 mg/dL (n = 3,106) and those with LDL-C concentrations of 130 mg/dL or greater (n = 1,716) at baseline (2000-2002). Cox proportional hazard analyses were used to assess the associations after adjustment for socioeconomic status, traditional risk factors, body mass index, diabetes, aspirin use, kidney function, and coronary artery calcium score. Loge hs-CRP was associated with incident CHD in participants with LDL-C concentrations of 130 mg/dL or higher (hazard ratio (HR) = 1.29, 95% confidence interval (CI): 1.05, 1.60) but not in those with LDL-C concentrations less than 130 mg/dL (HR = 0.88, 95% CI: 0.74, 1.05; P for interaction = 0.003). As a whole, loge hs-CRP was not associated with incident CHD in participants who had not received lipid-lowering therapy at baseline (HR = 1.05, 95% CI: 0.92, 1.20) and who had mean LDL-C concentrations less than 130 mg/dL. These findings suggest that LDL-C concentrations might be a moderator of the contribution of hs-CRP to CHD.

Autonomic dysfunction in early breast cancer: Incidence, clinical importance, and underlying mechanisms.

Autonomic dysfunction represents a loss of normal autonomic control of the cardiovascular system associated with both sympathetic nervous system overdrive and reduced efficacy of the parasympathetic nervous system. Autonomic dysfunction is a strong predictor of future coronary heart disease, vascular disease, and sudden cardiac death. In the current review, we will discuss the clinical importance of autonomic dysfunction as a cardiovascular risk marker among breast cancer patients. We will review the effects of antineoplastic therapy on autonomic function, as well as discuss secondary exposures, such as psychological stress, sleep disturbances, weight gain/metabolic derangements, and loss of cardiorespiratory fitness, which may negatively impact autonomic function in breast cancer patients. Lastly, we review potential strategies to improve autonomic function in this population. The perspective can help guide new therapeutic interventions to promote longevity and cardiovascular health among breast cancer survivors.

Cardiorespiratory fitness in survivors of cervical, endometrial, and ovarian cancers: The Cooper Center Longitudinal Study.

BACKGROUND: Cardiorespiratory fitness (CRF), a strong predictor of mortality, is impaired among cancer patients. There is limited data, however, regarding CRF levels in women diagnosed with gynecologic cancers. METHODS: We compared CRF among ovarian, endometrial, and cervical cancer cases (n=89) to age-matched controls (n=89) in the Cooper Center Longitudinal Study (CCLS). CRF was evaluated by a maximal treadmill exercise tolerance test using a modified-Balke protocol. Conditional logistic regression was used to test for case-control differences in cardiorespiratory fitness, after controlling for age and body mass index, and adhering to the matched pairs design. RESULTS: The mean ages of cancer cases and controls were 50.9 years and 51.1 years, respectively (p=0.81). Peak METs (1 MET=3.5 mL kg(-1)min(-1)) were 9.2 ± 2.0 in cancer cases compared to 10.0 ± 2.2 in controls (p=0.03). When stratifying by type of cancer, peak METs were 8.9 ± 2.2, 8.4 ± 1.9, 9.5 ± 2.0 for patients with ovarian, endometrial, and cervical cancer, respectively. A gynecological cancer diagnosis was associated with greater odds of having 1-MET lower CRF compared to controls (OR 1.31, 95% CI: 1.05-1.64, p=0.018), after controlling for age and BMI. CONCLUSION: Gynecologic cancer survivors were more likely to have a 1-MET lower CRF than controls. Given a 1-MET change in CRF is associated with a significant, we advocate for more robust research regarding CRF in gynecologic cancer patients.

A Prospective Analysis of Plasma Adiponectin and Risk of Incident Cancer: The Dallas Heart Study.

BACKGROUND: Adiponectin dysregulation is postulated to affect cancer risk via modulation of insulin resistance and inflammation. Epidemiologic studies evaluating this relationship have conflicting results and data from non-white cohorts are lacking. We examined the association between adiponectin and risk of cancer incidence in the multiethnic Dallas Heart Study (DHS). METHODS: Participants enrolled in the DHS and known adiponectin values were included. Incident cancer cases were identified through a systematic linkage of the DHS and the Texas Cancer Registry. Univariate/multivariate analysis were performed to test the association between adiponectin and incident cancer after adjusting for age, diabetes status, gender, ethnicity, C-reactive protein level, smoking status, and body mass index. Adiponectin level was evaluated both as a continuous variable and in race/ethnicity specific quartiles. RESULTS: Of 3444 individuals, there were 152 incident cancers. The study population was comprised of 44.4% men, and 51.05% were black. Baseline median adiponectin levels were 6.43 mcg/mL (interquartile range [IQR], 4.37-9.45 mcg/mL) in the incident cancer group versus 6.33 mcg/mL (IQR, 4.57-9.97 mcg/mL) in those without cancer. In multivariable analysis, adiponectin level was not associated with cancer incidence after adjusting for covariates. In analyses stratified by race/ethnic group, no association was observed in white, Hispanic, or African American subgroups. CONCLUSIONS: In this study of a predominant ethnic minority population, no association between adiponectin and cancer incidence was demonstrated. Despite preclinical rationale and confirmatory findings in other studies, this association may not replicate across all ethnic populations. Additional studies with strong minority representation are warranted to further examine this association.

Health behavior change following a diagnosis of ductal carcinoma in situ: An opportunity to improve health outcomes.

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that comprises approximately 20% of new breast cancer diagnoses. DCIS is predominantly detected by screening mammography prior to the development of any clinical symptoms. Prognosis following a DCIS diagnosis is excellent, due to both the availability of effective treatments and the frequently benign nature of the disease. However, a DCIS diagnosis and its treatment have psychological and physical impacts that often lead to adverse changes in health-related behaviors, including changes in physical activity, body weight, alcohol intake, and smoking, which may represent a greater threat to the woman's overall health than the DCIS itself. Depending on age at diagnosis, women diagnosed with DCIS are 3-13 times more likely to die from non-breast cancer related causes, such as cardiovascular disease, than from breast cancer. Thus, the maintenance and improvement of healthy behaviors that influence a variety of outcomes after diagnosis may warrant increased attention during DCIS management. This may also represent an important opportunity to promote the adoption of healthy behaviors, given that DCIS carries the psychological impact of a cancer diagnosis but also a favorable prognosis. Particular focus is needed to address these issues in vulnerable patient subgroups with pre-existing higher rates of unhealthy behaviors and demonstrated health disparities.

Racial differences in breast cancer, cardiovascular disease, and all-cause mortality among women with ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) of the breast represents 15-20% of new breast cancer diagnoses in the US annually. However, long-term competing risks of mortality, as well as racial differences in outcomes among US women with DCIS, are unknown. Case data from the years 1978-2010 were obtained using SEER*Stat software available through the National Cancer Institute from the 2010 SEER registries. Included were all women aged 40 and over with newly diagnosed DCIS. There were 67,514 women in the analysis, including 54,518 white women and 6,113 black women. A total of 12,173 deaths were observed over 607,287 person-years of follow-up. The 20-year cumulative incidence of all-cause death among women with DCIS was 39.6% (CI 38.9-40.3). The corresponding 20-year rates for breast cancer death and CVD death were 3.2% (CI 3.0-3.4) and 13.2% (CI 12.8-13.7), respectively. Black women with DCIS had a higher risk of death compared to white women, with these hazard ratios elevated throughout the entire study period. For example, between 1990 and 2010, black women had a higher risk of all-cause death (HR 3.06, CI 2.39-3.91), breast cancer death (HR 5.78, CI 3.16-10.57), and CVD death (HR 6.43, CI 3.61-11.45) compared to white women diagnosed between 50 and 59 years of age. The risk of all-cause and CVD death was greater than breast cancer death among women diagnosed with DCIS over 20 years. Black women had higher risks of dying from all-causes compared to white women. These differences persisted into the modern treatment era.

The influence of adjuvant therapy on cardiorespiratory fitness in early-stage breast cancer seven years after diagnosis: the Cooper Center Longitudinal Study.

We examined cardiorespiratory fitness (CRF) levels in early stage breast cancer patients and determined whether CRF differs as a function of adjuvant therapy regimen. A total of 180 early breast cancer patients representing three treatment groups (surgery only, single-, and multi-modality adjuvant therapy) in the Cooper Center Longitudinal Study (CCLS) were studied. A non-cancer control group (n = 180) matched by sex, age, and date of the CCLS visit was included. All subjects underwent an incremental exercise tolerance test to symptom limitation to assess CRF (i.e., peak metabolic equivalents [METs] and time to exhaustion). The mean time from breast cancer diagnosis to exercise tolerance testing was 7.4 ± 6.2 years. In adjusted analyses, time to exhaustion and peak METs were incrementally impaired with the addition of surgery, single-, and multi-modality adjuvant therapy compared to those of matched controls (p = 0.006 and 0.028, respectively). CRF was lowest in the multi-modality group compared to all other groups (all p's < 0.05). Despite being 7 years post-diagnosis, asymptomatic early breast cancer survivors have marked reductions in CRF. Patients treated with multi-modal adjuvant therapy have the greatest impairment in CRF.

Physical activity participation, health perceptions, and cardiovascular disease mortality in a multiethnic population: the Dallas Heart Study.

BACKGROUND: Physical activity (PA) participation differs by ethnicity, but contributing factors and cardiovascular (CV) outcomes related to these disparities are not well understood. We determined whether health beliefs regarding the benefit of PA contribute to ethnic differences in participation and assessed how these differences impact CV mortality. METHODS: The Dallas Heart Study is a longitudinal study of CV health. We assessed PA participation and health perceptions by questionnaire among 3,018 African American, Hispanic, and white men and women at baseline visit (2000-2002). Participant mortality was obtained through 2008 using the National Death Index. RESULTS: African Americans (odds ratio 0.65, 95% CI 0.53-0.80) and Hispanics (odds ratio 0.34, 95% CI 0.26-0.45) were less likely to be physically active compared with whites even after accounting for income, educational status, age, sex, body mass index, diabetes, hypertension, and hyperlipidemia. Beliefs regarding the benefits of PA did not contribute to this disparity, as >94% of individuals felt PA was effective in preventing a heart attack across ethnicity. Physical activity participation was associated with a lower risk of all-cause mortality (hazard ratio [HR] 0.66, 95% CI 0.46-0.93) and CV disease death (HR 0.56, 95% CI 0.32-0.97) in multivariable adjusted models. Similar results were seen when restricting to African Americans (CV disease death, HR 0.57, 95% CI 0.31-1.05). CONCLUSIONS: Ethnic minorities reported less PA participation, and lack of PA was associated with higher CV mortality overall and among African Americans. Health perception regarding the benefits of PA did not contribute to this difference, indicating there are other ethnic-specific factors contributing to physical inactivity that require future study.

ACCF/SCAI/AATS/AHA/ASE/ASNC/HFSA/HRS/SCCM/SCCT/SCMR/STS 2012 appropriate use criteria for diagnostic catheterization: American College of Cardiology Foundation Appropriate Use Criteria Task Force Society for Cardiovascular Angiography and Interventions American Association for Thoracic Surgery American Heart Association, American Society of Echocardiography American Society of Nuclear Cardiology Heart Failure Society of America Heart Rhythm Society, Society of Critical Care Medicine Society of Cardiovascular Computed Tomography Society for Cardiovascular Magnetic Resonance Society of Thoracic Surgeons.

The American College of Cardiology Foundation, in collaboration with the Society for Cardiovascular Angiography and Interventions and key specialty and subspecialty societies, conducted a review of common clinical scenarios where diagnostic catheterization is frequently considered. The indications (clinical scenarios) were derived from common applications or anticipated uses, as well as from current clinical practice guidelines and results of studies examining the implementation of noninvasive imaging appropriate use criteria. The 166 indications in this document were developed by a diverse writing group and scored by a separate independent technical panel on a scale of 1 to 9, to designate appropriate use (median 7 to 9), uncertain use (median 4 to 6), and inappropriate use (median 1 to 3). Diagnostic catheterization may include several different procedure components. The indications developed focused primarily on 2 aspects of diagnostic catheterization. Many indications focused on the performance of coronary angiography for the detection of coronary artery disease with other procedure components (e.g., hemodynamic measurements, ventriculography) at the discretion of the operator. The majority of the remaining indications focused on hemodynamic measurements to evaluate valvular heart disease, pulmonary hypertension, cardiomyopathy, and other conditions, with the use of coronary angiography at the discretion of the operator. Seventy-five indications were rated as appropriate, 49 were rated as uncertain, and 42 were rated as inappropriate. The appropriate use criteria for diagnostic catheterization have the potential to impact physician decision making, healthcare delivery, and reimbursement policy. Furthermore, recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research. © 2012 Wiley Periodicals, Inc.

Interactions between smoking, pulmonary surfactant protein B, and atherosclerosis in the general population: the Dallas Heart Study.

OBJECTIVE: Pulmonary surfactant protein B (SP-B), an alveolar protein normally detectable at only very low concentrations in blood, circulates at higher levels among smokers and those with alveolar injury and inflammation. We hypothesized that SP-B may serve as a marker of the vascular effects of smoking and would thus be associated with subclinical measures of atherosclerosis. METHODS AND RESULTS: Plasma levels of SP-B were measured in 3294 subjects, ages 30 to 65, enrolled in the Dallas Heart Study, a probability-based population sample of Dallas County adults. Coronary artery calcium (CAC) was measured by computed tomography and abdominal aortic plaque (AP) by magnetic resonance imaging. The cohort comprised 29% current and 17% former smokers. The overall prevalence of CAC was 22%, and that of AP was 39%. Median SP-B levels were 5-fold higher among current versus never smokers (P<0.0001) and were significantly correlated with estimated pack-years smoked (Spearman ρ=0.35, P<0.0001). Increasing levels of SP-B also associated with other traditional cardiac risk factors and higher levels of inflammatory biomarkers. In univariable analyses, increasing SP-B quartiles associated with higher prevalence of both CAC and AP (P(trend)<0.0001 for each). In multivariable analyses adjusting for traditional cardiovascular risk factors, SP-B remained associated with AP (OR 1.87 for the 4th versus 1st quartiles, 95% confidence interval 1.39 to 2.51; P<0.0001) but not CAC. An interaction was observed between SP-B, smoking status, and AP (P(interaction)=0.01), such that SP-B associated with AP in current smokers (adjusted OR 2.15 for the 4th versus 1st quartile, 95% confidence interval 1.26 to 3.67; P=0.005) but not in former or never smokers. CONCLUSIONS: Circulating levels of SP-B increase with greater smoking burden and independently associate with abdominal AP among current smokers. Our findings support further investigation of the role of SP-B as a marker of the vascular effects of smoking.

Fitness, fatness, and systolic blood pressure: data from the Cooper Center Longitudinal Study.

BACKGROUND: Modifying risk factors to delay or prevent hypertension is critical for subsequent cardiovascular risk reduction. Therefore, understanding the independent and joint associations between cardiorespiratory fitness, obesity, and systolic blood pressure (SBP) is of major significance. In this study, we assessed the relative contribution of body mass index (BMI) and cardiorespiratory fitness to SBP in a large, healthy population. METHODS: Blood pressure, BMI, and cardiorespiratory fitness were measured in 35,061 patients seen for a preventive health examination (1990 to present). BMI was treated as a continuous variable and categorized into sex-specific quartiles. Cardiorespiratory fitness was defined as time achieved during maximal exercise testing and categorized into age- and sex-adjusted quintiles. Generalized linear models were used to determine the independent contribution of fitness and BMI on systolic blood pressure estimates. RESULTS: The study group was predominately white men (69%) with an average age of 46 years. Normal-weight subjects had a mean SBP 12 mm Hg lower than in the obese (115 vs 127 mm Hg, P < .001), while being high- fit was associated 6 mm Hg difference in mean SBP comparing the highest and lowest fitness quintile (119 vs 125 mm Hg, P < .001). Normal-weight individuals with a cardiorespiratory fitness level greater than the first quintile (Q1) had the lowest mean SBP (P < .001). Both BMI and cardiorespiratory fitness were associated with SBP (P < .001 for both); however, when assessed simultaneously, BMI had a greater impact on SBP estimates than fitness. CONCLUSION: When comparing lifestyle risk factors BMI and cardiorespiratory fitness, BMI was a more important factor in predicting SBP. Importantly, only modest fitness levels among normal-weight individuals were associated with the lowest systolic blood pressure estimates.

Implications of increased C-reactive protein for cardiovascular risk stratification in black and white men and women in the US.

BACKGROUND: We evaluated prevalence and correlates of increased high-sensitivity C-reactive protein (hsCRP) in a large population of blacks and whites, and the impact of hsCRP measurement on coronary heart disease risk reclassification. METHODS: We studied 19 080 participants of the REGARDS (REasons for Geographic And Racial Differences in Stroke) study (age >45 years, without vascular diagnoses, and living dispersed across the US). A total of 8309 nondiabetic participants not using lipid-lowering medications were classified into 4 risk categories based on the Framingham vascular disease risk score. Participants with hsCRP <1 mg/L were reclassified to the next lower risk group, and those with hsCRP >3 mg/L to the next higher risk group. We also assessed reclassification of risk based on the Reynolds vascular risk score, incorporating hsCRP and family history. RESULTS: Overall, 40% of participants had hsCRP >3 mg/L. Blacks, women, and obese people were at highest risk for increased hsCRP. Among nondiabetic women at 5%-20% Framingham vascular predicted risk, hsCRP data led to reclassification of 48% to a higher risk group and 19% to a lower risk group. For men, these percentages were 24% and 40%. Blacks were more often reclassified to a higher risk group than whites. Reynolds vascular risk score data led to reclassification of 85% of women and 67% of men, almost exclusively to a lower risk group than the Framingham vascular score. CONCLUSIONS: In this national study, a majority of participants, especially blacks and women, were reclassified to a different 10-year vascular risk category on the basis of hsCRP testing after risk assessment. With the inclusion of hsCRP testing data, the Reynolds risk score classified the population differently than the new Framingham vascular score. .

Coronary artery calcium scores and risk for cardiovascular events in women classified as "low risk" based on Framingham risk score: the multi-ethnic study of atherosclerosis (MESA).

OBJECTIVE: To assess coronary artery calcium (CAC) score and subsequent risk for coronary heart disease (CHD) and cardiovascular (CVD) events among asymptomatic women judged to be at low risk by the Framingham risk score (FRS), a common approach for determining 10-year absolute risk for CHD. Based on population survey data, 95% of American women are considered at low risk based on FRS. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) included 3601 women aged 45 to 84 years at baseline. The CAC score was measured by coronary computed tomography. Cox proportional hazard models were used to examine the CHD and CVD risk associated with CAC score among women classified as "low risk" based on FRS. RESULTS: Excluding women with diabetes and those older than 79 years, 90% of women in MESA (mean +/- SD age, 60 +/- 9 years) were classified as "low risk" based on FRS. The prevalence of CAC (CAC score > 0) in this low-risk subset was 32% (n = 870). Compared with women with no detectable CAC, low-risk women with a CAC score greater than 0 were at increased risk for CHD (hazard ratio, 6.5; 95% confidence interval, 2.6-16.4) and CVD events (hazard ratio, 5.2; 95% confidence interval, 2.5-10.8). In addition, advanced CAC (CAC score > or = 300) was highly predictive of future CHD and CVD events compared with women with nondetectable CAC and identified a group of low-risk women with a 6.7% and 8.6% absolute CHD and CVD risk, respectively, over a 3.75-year period. CONCLUSIONS: The presence of CAC in women considered to be at low risk based on FRS was predictive of future CHD and CVD events. Advanced CAC identified a subset of low-risk women at higher risk based on current risk stratification strategies.

Implications of C-reactive protein or coronary artery calcium score as an adjunct to global risk assessment for primary prevention of CHD.

BACKGROUND: C-reactive protein (CRP) or coronary artery calcium (CAC) score have been suggested to identify a higher risk subset of intermediate-risk individuals, who potentially could be considered for more aggressive therapy. In the Multi-Ethnic Study of Atherosclerosis (MESA), we estimated the proportion of intermediate-risk participants whose risk status might change based on additional testing using CRP and/or CAC score. METHODS: Framingham 10-year CHD risk scores (FRS) were calculated and cross tabulations were used to determine the percent of individuals at intermediate-risk by FRS with a CRP >3mg/L and/or CAC score >100 AU. Similar analyses were performed using the gender-specific 75th percentile for CRP and CAC. RESULTS: Of the 30% of participants (N=1450) classified as intermediate-risk by FRS, 30% had a CRP >3mg/L and 33% had a CAC score >100 AU. Among intermediate-risk women, 49% had a CRP >3mg/L compared to 27% of intermediate-risk men (p<0.0001) while the same percent of intermediate-risk women and men (33%) had a CAC score >100 AU. Eleven percent or less of men or women had both a high CRP and CAC score whether conventional or gender-specific cut points were used. When the percent of intermediate-risk individuals with an elevated CRP and/or CAC score in MESA were applied to NHANES III data, over a million intermediate-risk individuals would move to high risk status if CRP or CAC screening directed treatment strategies were uniformly adopted in the U.S. CONCLUSION: There were differences in the number of intermediate-risk individuals reclassified as high risk depending on the screening test used, the cut points selected, and the demographics of the individuals being screened. These data highlight current limitations of broadly using risk markers such as CRP and CAC score in an intermediate-risk population.

C-reactive protein concentration and incident hypertension in young adults: the CARDIA study.

BACKGROUND: There is increasing evidence that C-reactive protein (CRP) concentration, a measure of inflammation, is an independent risk factor for the development of hypertension in older adults. However, it is unknown whether a similar relationship exists in younger individuals. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study was initiated in 1985-1986 to determine the factors that are associated with coronary risk development in young adults. C-reactive protein concentrations were measured in 3919 African American and white men and women enrolled in CARDIA using blood specimens from the year 7 examination (1992-1993), when the age of the cohort was 25 to 37 years, and the year 15 examination (2000-2001). RESULTS: In unadjusted analyses, CRP concentrations greater than 3 mg/L, compared with those less than 1 mg/L, was associated with a 79% greater risk of incident hypertension (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.40-2.28). However, CRP concentration did not predict risk of incident hypertension after adjusting for year 7 body mass index (BMI) (OR, 1.14; 95% CI, 0.86-1.53) or year 7 BMI and other potential confounders (OR, 1.13; 95% CI, 0.83-1.52). In addition, year 7 CRP concentration was not associated with change in systolic or diastolic blood pressure after adjusting for BMI (P = .10 and P = .70, respectively). These findings were similar within each of the race- and sex-specific groups. CONCLUSION: C-reactive protein is associated with hypertension in young adults, but in contrast to the finding in older populations, the association is no longer present after adjusting for BMI.

Physical Activity and Adiposity-related Inflammation: The MESA.

PURPOSE: Physical activity is associated with decreased adiposity-related inflammation in adults. Whether this association is independent of central obesity is unknown but important for understanding the mechanisms associated with reducing cardiometabolic disease risk through physical activity. This study examined whether associations of physical activity and obesity-related inflammatory markers were independent of central adiposity. METHODS: Between 2002 and 2005, 1970 participants from the Multi-Ethnic Study of Atherosclerosis completed detailed health history and physical activity questionnaires, underwent physical measurements including computed tomography to quantify abdominal visceral and subcutaneous fat, and measurements of adiponectin, leptin, interleukin-6, tumor necrosis factor-alpha, and resistin. Statistical analyses included analysis of covariance and multivariable-adjusted regression. RESULTS: The mean (range) age of participants was 64.7 (55-84) yr and 50% were women. After adjustment for age and sex, and compared with the lowest quartile, inflammatory markers in the highest quartile of moderate-to-vigorous physical activity were 16% higher for adiponectin and 30%, 26%, and 9% lower for leptin, interleukin-6, and resistin, respectively (P < 0.05 for all). In linear regression adjusted for demographics, dyslipidemia, hypertension, diabetes, smoking, glomerular filtration rate, renin, and aldosterone, each standard deviation increment of moderate-to-vigorous physical activity was associated with significantly higher levels of adiponectin (ß = 0.04) and lower levels of leptin (ß = -0.06), interleukin-6 (ß = -0.08), and resistin (ß = -0.05, P < 0.05 for all). The associations with leptin, interleukin-6, and resistin were independent of total and central adiposity (P < 0.05), whereas the association between moderate-to-vigorous physical activity and adiponectin was attenuated by central adiposity (P > 0.05). There were no significant interactions by race/ethnicity or sex. CONCLUSIONS: Moderate-to-vigorous physical activity was associated with a more favorable profile of inflammatory markers, independent of relevant cardiometabolic disease risk factors including central obesity.

Health-related behaviors and mortality outcomes in women diagnosed with ductal carcinoma in situ.

PURPOSE: Women diagnosed with ductal carcinoma in situ (DCIS) of the breast are at greater risk of dying from cardiovascular disease and other causes than from breast cancer, yet associations between health-related behaviors and mortality outcomes after DCIS have not been well studied. METHODS: We examined the association of body mass index, physical activity, alcohol consumption, and smoking with mortality among 1925 women with DCIS in the Wisconsin In Situ Cohort study. Behaviors were self-reported through baseline interviews and up to three follow-up questionnaires. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality after DCIS, with adjustment for patient sociodemographic, comorbidity, and treatment factors. RESULTS: Over a mean of 6.7 years of follow-up, 196 deaths occurred. All-cause mortality was elevated among women who were current smokers 1 year prior to diagnosis (HR = 2.17 [95% CI 1.48, 3.18] vs. never smokers) and reduced among women with greater physical activity levels prior to diagnosis (HR = 0.55 [95% CI: 0.35, 0.87] for ≥5 h per week vs. no activity). Moderate levels of post-diagnosis physical activity were associated with reduced all-cause mortality (HR = 0.31 [95% CI 0.14, 0.68] for 2-5 h per week vs. no activity). Cancer-specific mortality was elevated among smokers and cardiovascular disease mortality decreased with increasing physical activity levels. CONCLUSIONS: There are numerous associations between health-related behaviors and mortality outcomes after a DCIS diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Women diagnosed with DCIS should be aware that their health-related behaviors are associated with mortality outcomes.

An Analysis of Individual Body Fat Depots and Risk of Developing Cancer: Insights From the Dallas Heart Study.

OBJECTIVE: To examine the association between specific adipose tissue depots and the risk of incident cancer in the Dallas Heart Study. PATIENTS AND METHODS: Individuals without prevalent cancer in the Dallas Heart Study underwent quantification of adipose depots: visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, and liver fat by magnetic resonance imaging, and subcutaneous lower-body fat (LBF) by dual-energy X-ray absorptiometry from January 1, 2000, through December 31, 2002, and were observed for the development of cancer for up to 12 years. Multivariable Cox proportional hazards modeling was performed to examine the association between fat depots and cancer. RESULTS: Of 2627 participants (median age, 43 years; 69% nonwhite race), 167 (6.4%) developed cancer. The most common primary sites of cancer were the breast (in women) and the prostate (in men). In multivariable models adjusted for age, sex, race, smoking, alcohol use, family history of malignancy, and body mass index, a 1-SD increase in VAT was not associated with increased risk of cancer (hazard ratio [HR], 0.94; 95% CI, 0.77-1.14). In contrast, each 1-SD increase in LBF was associated with a reduced incidence of cancer (HR, 0.69; 95% CI, 0.52-0.92) in the fully adjusted model. CONCLUSIONS: In this study, adiposity-associated cancer risk was heterogeneous and varied by fat depot: VAT was not independently associated with incident cancer, and LBF seemed to protect against cancer development. Further studies of the adiposity-cancer relationship, including serial assessments, are needed to better elucidate this relationship.