Adjustment For Standard Risk Factors Research Articles

The LDL-C/Apo B predicts coronary atherosclerotic heart disease in non-diabetic patients without high LDL-C

The apolipoprotein B (Apo B), Apo B/A1 ratio, lipoprotein (a), and low-density lipoprotein cholesterol (LDL-C)/Apo B ratio are associated with coronary artery disease (CAD). However, the association between these parameters and CAD in non-diabetic patients without high LDL-C levels is unclear. Our goal was to assess which parameter was most strongly associated with CAD in non-diabetic patients without high LDL-C levels. This study included 487 non-diabetic patients with LDL-C < 130.0 mg/dL. All the patients underwent coronary computed tomographic angiography. We assessed the significance of each continuous atherogenic biomarker for CAD (incidence of coronary plaque and revascularization) without and after adjustment for standard risk factors. The LDL-C/Apo B ratio and lipoprotein (a) were significant risk factors for the incidence of coronary plaque on multivariate analysis after adjustment for standard risk factors. The LDL-C/Apo B ratio was significant for the incidence of revascularization in multivariate analysis after adjustment for standard risk factors. The degree of coronary calcification and plaque burden according to the tertile of LDL-C/Apo B showed significant differences between the groups. Our data indicate that LDL-C/Apo B ratio is the most predictive parameter for coronary atherosclerosis in non-diabetic patients without high LDL-C levels.

CD34+ progenitors are predictive of mortality and are associated with physical activity in cardiovascular disease patients

Background and aimsCirculating progenitor cells (CPCs) play an important role in vascular repair and can influence cardiovascular (CV) health and longevity. Exercise is known to modulate these cells via mobilization from the bone marrow. The primary aims of this study were to evaluate the association of CPCs with mortality and explore the association between physical activity (PA) and CPCs. Methods1751 individuals from the Framingham Offspring cohort (66 ± 9 years [40–92 years], 54% female) were included in the study. CPCs (CD34+, CD34+CD133+, CD34+CD133+KDR+) were measured by flow cytometry. Multivariable Cox regression analyses were performed to investigate relationship of CPCs with future CV event and mortality. Multivariate regression analyses were performed to determine the relationship between self-reported PA and CPC counts. ResultsFollowing adjustment for standard risk factors, there was an inverse association between CD34+ CPCs and all-cause mortality (hazard ratio (HR) per unit increase in CD34+, 0.79; 95% CI 0.64–0.98, p = 0.036). CD34+CD133+ CPCs were inversely associated with CV mortality (HR 0.63, 95% CI 0.44–0.91, p = 0.013). Associations of CD34+ and CD34+CD133+ with mortality were strongest in participants with pre-existing CVD. PA was associated with CD34+ CPCs only in CVD participants (PA Index: β = 0.176, p = 0.003; moderate-to-vigorous [MVPA]: β = 0.159, p = 0.007). This relationship was maintained after adjustment for confounding variables. ConclusionsA higher number of CD34+ and CD34+ CD133+ CPCs was inversely associated with all-cause and CV mortality. These associations were strongest in participants with CVD. PA is independently associated with CD34+ CPCs in individuals with CVD only, suggestive of greater benefit for this population group.

Moderate and vigorous physical activity levels are associated with circulating CD34+ progenitor cells which are predictive of all-cause and cardiovascular mortality

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Edinburgh Napier University Research Excellence Grant Background Circulating progenitor cells (CPCs) play an important role in vascular repair and may influence cardiovascular (CV) health and longevity. Physical activity is known to promote vascular health and may do so by modulating CPC counts. Purpose The primary aims of this study were to evaluate the association of CPCs with mortality and explore the association between physical activity (PA) and CPCs. Methods We studied 1,751 individuals from the Framingham Offspring cohort (66 ± 9 years, 54% female). CPCs (CD34+, CD34 + CD133+, CD34 + CD133 + KDR+) were measured from blood samples by flow cytometry. Multivariable cox regression analyses were performed to investigate the relationship of CPCs with future CV event, mortality, and all-cause mortality. Multivariate regression analyses were performed to determine the relationship between self-reported PA and CPC counts. Results Following adjustment for standard risk factors, there was an inverse association between CD34+ CPCs and all-cause mortality (hazard ratio (HR) per unit increase in CD34+, 0.79; 95% CI 0.64 – 0.98). CD34 + CD133+ CPCs were inversely associated with CV mortality (HR 0.63, 95% CI 0.44 – 0.91, P = 0.013). Associations of CD34+ and CD34 + CD133+ with mortality were strongest in participants with pre-existing CVD. PA was associated with CD34+ CPCs only in CVD participants. This relationship was maintained after adjustment for confounding variables. Conclusions Higher number of CD34+ and CD34+ CD133+ CPCs were inversely associated with all-cause and CV mortality. These associations were strongest in participants already diagnosed with CVD. PA is independently associated with CD34+ CPCs in individuals with CVD only, suggestive of greater benefit for this population group.

Small Dense Low-Density Lipoprotein Cholesterol Is the Most Atherogenic Lipoprotein Parameter in the Prospective Framingham Offspring Study.

BackgroundElevated plasma levels of direct low‐density lipoprotein cholesterol (LDL‐C), small dense LDL‐C (sdLDL‐C), low‐density lipoprotein (LDL) triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and lipoprotein(a) have all been associated with incident atherosclerotic cardiovascular disease (ASCVD). Our goal was to assess which parameters were most strongly associated with ASCVD risk.Methods and ResultsPlasma total cholesterol, triglycerides, high‐density lipoprotein cholesterol, direct LDL‐C, sdLDL‐C, LDL triglycerides, remnant lipoprotein particle cholesterol, triglyceride‐rich lipoprotein cholesterol, and lipoprotein(a) were measured using standardized automated analysis (coefficients of variation, <5.0%) in samples from 3094 fasting subjects free of ASCVD. Of these subjects, 20.2% developed ASCVD over 16 years. On univariate analysis, all ASCVD risk factors were significantly associated with incident ASCVD, as well as the following specialized lipoprotein parameters: sdLDL‐C, LDL triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and direct LDL‐C. Only sdLDL‐C, direct LDL‐C, and lipoprotein(a) were significant on multivariate analysis and net reclassification after adjustment for standard risk factors (age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, and high‐density lipoprotein cholesterol). Using the pooled cohort equation, many specialized lipoprotein parameters individually added significant information, but no parameter added significant information once sdLDL‐C (hazard ratio, 1.42; P<0.0001) was in the model. These results for sdLDL‐C were confirmed by adjusted discordance analysis versus calculated non–high‐density lipoprotein cholesterol, in contrast to LDL triglycerides.ConclusionssdLDL‐C, direct LDL‐C, and lipoprotein(a) all contributed significantly to ASCVD risk on multivariate analysis, but no parameter added significant risk information to the pooled cohort equation once sdLDL‐C was in the model. Our data indicate that small dense LDL is the most atherogenic lipoprotein parameter.

Fatty Acid Binding Protein-4 and Risk of Cardiovascular Disease: The Cardiovascular Health Study.

BackgroundFABP‐4 (fatty acid binding protein‐4) is a lipid chaperone in adipocytes and has been associated with prognosis in selected clinical populations. We investigated the associations between circulating FABP‐4, risk of incident cardiovascular disease (CVD), and risk of CVD mortality among older adults with and without established CVD.Methods and ResultsIn the Cardiovascular Health Study, we measured FABP4 levels in stored specimens from the 1992–993 visit and followed participants for incident CVD if they were free of prevalent CVD at baseline and for CVD mortality through June 2015. We used Cox regression to estimate hazard ratios for incident CVD and CVD mortality per doubling in serum FABP‐4 adjusted for age, sex, race, field center, waist circumference, blood pressure, lipids, fasting glucose, and C‐reactive protein. Among 4026 participants free of CVD and 681 with prevalent CVD, we documented 1878 cases of incident CVD and 331 CVD deaths, respectively. In adjusted analyses, FABP‐4 was modestly associated with risk of incident CVD (mean, 34.24; SD, 18.90; HR, 1.10 per doubling in FABP‐4, 95% CI, 1.00–1.21). In contrast, FABP‐4 was more clearly associated with risk of CVD mortality among participants without (HR hazard ratio 1.24, 95% CI, 1.10–1.40) or with prevalent CVD (HR hazard ratio 1.57, 95% CI, 1.24–1.98). These associations were not significantly modified by sex, age, and waist circumference.ConclusionsSerum FABP‐4 is modestly associated with risk of incident CVD even after adjustment for standard risk factors, but more strongly associated with CVD mortality among older adults with and without established CVD.

Killer immunoglobulin-like receptor genotypes and chronic myeloid leukemia outcomes after imatinib cessation for treatment-free remission.

Background Natural Killer (NK) cells are innate lymphoid cells that can be cytotoxic toward a large panel of solid tumors and hematological malignancies including chronic myeloid leukemia (CML). Such a cytotoxicity depends on various receptors. Killer immunoglobulin‐like receptors (KIR) belong to these receptors and are involved in maturation process, then in the activation abilities of NK cells. Methods: We investigated the prognostic impact of the KIR2DL5B genotype in 240 CML patients included in two clinical trials investigating tyrosine kinase inhibitors (TKI) discontinuation: STIM and STIM2. Results: After adjustment for standard risk factors in CML, we found that the inhibitory receptor KIR2DL5B‐positive genotype was independently related to a delayed second deep molecular remission (HR 0.54, 95% CI [0.32‐0.91], P = 0.02) after TKI rechallenge but not to time to first deep molecular remission or treatment‐free remission rates. Conclusion: These results suggest that KIR2DL5B could carry a role in lymphocyte‐mediated control of leukemic residual disease control in patient with CML relapse.

FATTY ACID BINDING PROTEIN-4 AND RISK OF CARDIOVASCULAR DISEASE: THE CARDIOVASCULAR HEALTH STUDY

Background FABP-4 (fatty acid binding protein-4) is a lipid chaperone in adipocytes and has been associated with prognosis in selected clinical populations. We investigated the associations between circulating FABP-4, risk of incident cardiovascular disease (CVD), and risk of CVD mortality among older adults with and without established CVD. Methods and Results In the Cardiovascular Health Study, we measured FABP4 levels in stored specimens from the 1992-993 visit and followed participants for incident CVD if they were free of prevalent CVD at baseline and for CVD mortality through June 2015. We used Cox regression to estimate hazard ratios for incident CVD and CVD mortality per doubling in serum FABP-4 adjusted for age, sex, race, field center, waist circumference, blood pressure, lipids, fasting glucose, and C-reactive protein. Among 4026 participants free of CVD and 681 with prevalent CVD, we documented 1878 cases of incident CVD and 331 CVD deaths, respectively. In adjusted analyses, FABP-4 was modestly associated with risk of incident CVD (mean, 34.24; SD, 18.90; HR, 1.10 per doubling in FABP-4, 95% CI, 1.00-1.21). In contrast, FABP-4 was more clearly associated with risk of CVD mortality among participants without (HR hazard ratio 1.24, 95% CI, 1.10-1.40) or with prevalent CVD (HR hazard ratio 1.57, 95% CI, 1.24-1.98). These associations were not significantly modified by sex, age, and waist circumference. Conclusions Serum FABP-4 is modestly associated with risk of incident CVD even after adjustment for standard risk factors, but more strongly associated with CVD mortality among older adults with and without established CVD.

Rheumatoid factors do not predict cardiovascular disease and mortality in the general population in the Busselton Health Survey

BackgroundRheumatoid Factors (RF) are antibodies directed against the Fc portion of IgG and are involved in clearance of immune complexes. While RF can develop in a wide range of conditions, higher RF levels indicate a greater risk for a severe disease course in Rheumatoid Arthritis (RA) patients including cardiovascular complications and premature death. We investigated whether RF also constitute a risk factor for these outcomes in the general population.MethodsWe included 2,323 participants (46% male, mean age 50 years) free of CVD at baseline in 1972. RF positivity was defined as a score of ≥2 by latex agglutination (scale 0–5). All outcomes during 42-year follow-up were obtained from state-wide registries. The predictive value of RF for coronary heart disease, all cardiovascular disease and all-cause mortality was estimated by adjusted hazard ratios (HR) from Cox regression models.ResultsAfter adjustment for standard risk factors, RF positivity was not predictive of future CHD (HR 1.05, p = 0.61), CVD (HR 1,04, p = 0.63) or mortality (HR 1.03, p = 0.70) in the full CVD-free cohort. In an interaction model, RF in 41 out of 355 participants with an RA history was not predictive of CHD (HR 0.92, p = 0.77) or CVD events (HR 1.15, p = 0.51), but there was a borderline significant association with overall mortality (HR 1.41, CI 0.97–2.04, p = 0.07).ConclusionsRF detected by Latex agglutination do not independently predict future CHD, CVD or death in the general population. However, the presence of RF in the context of a history of RA is associated with a moderate, borderline significant increase in the long term adjusted risk for all-cause mortality.

Abstract 18337: Comparison of the Distribution and Predictive Value of Framingham Risk Factors and Coronary Artery Calcium for Major Coronary Events Between Asian (South Korean) and Framingham Cohorts

Background: Coronary artery calcium (CAC) predicts major adverse cardiovascular events (MACE) beyond Framingham risk factors (RF) across multiple ethnic groups within the United States. However, its value in other, non-US populations is unknown. Methods: We prospectively obtained data on RF and MACE in asymptomatic adults from the registry-based ESCORT Study (4502 Koreans) and the population-based Framingham Heart Study (FHS, 3141 Whites), who underwent computed tomography to assess CAC. The primary composite endpoint of MACE included CV death, acute myocardial infarction and unstable angina with revascularization. We compared association of traditional RF and CAC with MACE in the two cohorts using multivariate Cox proportional hazard regression analysis, examining CAC both as a categorical variable using established cut-points and as a continuous variable using log 2 [CAC + 1]. We tested for interaction between ethnicity and CAC categories. Results: Over median 55 (ESCORT) or 60 (FHS) month follow-up, there were 95 MACE (ESCORT=45, FHS=50). ESCORT participants had greater prevalence of smoking, diabetes and hypertension (p&lt;0.001 all) and greater 10-year Framingham risk score (11.4% vs 8.2%). In contrast, mean CAC prevalence and score were significantly lower in ESCORT (21.9%, 25.3 Agatston units, AU) vs FHS (41.5%, 99.9 AU). In ESCORT, more RF (age, male sex, systolic BP, HDL_C, diabetes) were predictive of MACE vs FHS (age only.) After adjustment for standard RF, doubling of CAC score (1-unit increase in log 2 [CAC + 1]) resulted in a 40% increase in risk of MACE in each cohort. Low CAC (1-100) was a significant predictor of MACE only in ESCORT but not in FHS (interaction p-value = 0.099.) Conclusion: There were significant differences in the burden and distribution of RF and CAC between Asian (South Korean) and white US (FHS) cohorts . CAC is a strong predictor of MACE in both cohorts, however lower CAC scores have greater predictive value in the Korean cohort.

Body Fat Distribution, Incident Cardiovascular Disease, Cancer, and All-Cause Mortality

The aim of this study was to determine whether ectopic fat depots are prospectively associated with cardiovascular disease, cancer, and all-cause mortality. The morbidity associated with excess body weight varies among individuals of similar body mass index. Ectopic fat depots may underlie this risk differential. However, prospective studies of directly measured fat are limited. Participants from the Framingham Heart Study (n= 3,086; 49% women; mean age of 50.2 years) underwent assessment of fat depots (visceral adipose tissue, pericardial adipose tissue, and periaortic adipose tissue) using multidetector computed tomography and were followed up longitudinally for a median of 5.0 years. Cox proportional hazards regression models were used to examine the association of each fat depot (per 1 SD increment) with the risk of incident cardiovascular disease, cancer, and all-cause mortality after adjustment for standard risk factors, including body mass index. Overall, there were 90 cardiovascular events, 141 cancer events, and 71 deaths. After multivariable adjustment, visceral adipose tissue was associated with cardiovascular disease (hazard ratio: 1.44; 95% confidence interval: 1.08 to 1.92; p= 0.01) and cancer (hazard ratio: 1.43; 95% confidence interval: 1.12 to 1.84; p= 0.005). Addition of visceral adipose tissue to a multivariable model that included body mass index modestly improved cardiovascular risk prediction (net reclassification improvement of 16.3%). None of the fat depots were associated with all-cause mortality. Visceral adiposity is associated with incident cardiovascular disease and cancer after adjustment for clinical risk factors and generalized adiposity. These findings support the growing appreciation of a pathogenic role of ectopic fat.

Incremental Value of Biochemical and Echocardiographic Measures in Prediction of Ischemic Stroke

American Indians have high rates of stroke. Improved risk stratification could enhance prevention, but the ability of biochemical and echocardiographic markers of preclinical disease to improve stroke prediction is not well-defined. We evaluated such markers as predictors of ischemic stroke in a community-based cohort of American Indians without prevalent cardiovascular or renal disease. Laboratory markers included C-reactive protein, fibrinogen, urine albumin-to-creatinine ratio, and glycohemoglobin (HbA1c), whereas echocardiographic parameters comprised left atrial diameter, left ventricular mass, mitral annular calcification, and the ratio of early to late mitral diastolic velocities. Predictive performance was judged by indices of discrimination, reclassification, and calibration. After adjustment for standard risk factors, only HbA1c, albuminuria, and left atrial diameter were significantly associated with first ischemic stroke. Addition of HbA1c, although not urine albumin-to-creatinine ratio, to a basic clinical model significantly improved the C-statistic (0.714 versus 0.695; P=0.044), whereas left atrial diameter modestly enhanced integrated discrimination improvement (0.90%; P=0.004), but not the C-statistic (0.701; P=0.528). When combined with HbA1c, left atrial diameter further increased integrated discrimination improvement (1.81%; P<0.001) but not the C-statistic (0.716). No marker achieved significant net reclassification improvement. In this cohort at high cardiometabolic risk, HbA1c emerged as the foremost predictor of ischemic stroke when added to traditional risk factors, affording substantially improved discrimination, with a more modest contribution for left atrial diameter. These findings bolster the role of HbA1c in cardiovascular risk assessment among persons with glycometabolic disorders and provide impetus for further study of the incremental value of echocardiography in high-risk populations.

Triglycerides and Cardiovascular Disease

A long-standing association exists between elevated triglyceride levels and cardiovascular disease* (CVD).1,2 However, the extent to which triglycerides directly promote CVD or represent a biomarker of risk has been debated for 3 decades.3 To this end, 2 National Institutes of Health consensus conferences evaluated the evidentiary role of triglycerides in cardiovascular risk assessment and provided therapeutic recommendations for hypertriglyceridemic states.4,5 Since 1993, additional insights have been made vis-a-vis the atherogenicity of triglyceride-rich lipoproteins (TRLs; ie, chylomicrons and very low-density lipoproteins), genetic and metabolic regulators of triglyceride metabolism, and classification and treatment of hypertriglyceridemia. It is especially disconcerting that in the United States, mean triglyceride levels have risen since 1976, in concert with the growing epidemic of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM).6,7 In contrast, mean low-density lipoprotein cholesterol (LDL-C) levels have receded.7 Therefore, the purpose of this scientific statement is to update clinicians on the increasingly crucial role of triglycerides in the evaluation and management of CVD risk and highlight approaches aimed at minimizing the adverse public health–related consequences associated with hypertriglyceridemic states. This statement will complement recent American Heart Association scientific statements on childhood and adolescent obesity8 and dietary sugar intake9 by emphasizing effective lifestyle strategies designed to lower triglyceride levels and improve overall cardiometabolic health. It is not intended to serve as a specific guideline but will be of value to the Adult Treatment Panel IV (ATP IV) of the National Cholesterol Education Program, from which evidence-based guidelines will ensue. Topics to be addressed include epidemiology and CVD risk, ethnic and racial differences, metabolic determinants, genetic and family determinants, risk factor correlates, and effects related to nutrition, physical activity, and lipid medications. In the United States, the National Health and …

Tumor volume and patient weight as predictors of outcome in children with intermediate risk rhabdomyosarcoma

AbstractBACKGROUND:The objectives of this study were to compare tumor volume and patient weight versus traditional factors of tumor size (greatest dimension) and patient age and to determine which parameters best discriminated outcome among pediatric patients with intermediate‐risk rhabdomyosarcoma (RMS).METHODS:Complete information was available for 370 patients with nonmetastatic RMS who were enrolled in the Children's Oncology Group (COG) intermediate‐risk study D9803 (1999‐2005). The Kaplan‐Meier method was used to estimate survival distributions. A recursive partitioning model was used to identify prognostic factors that were associated with event‐free survival (EFS). Cox proportional hazards regression models were used to estimate the association between patient characteristics and the risk of failure or death.RESULTS:For all patients with intermediate‐risk RMS, a recursive partitioning algorithm for EFS suggested that prognostic groups should be defined optimally by tumor volume (with a transition point at 20 cm3), patient weight (with a transition point at 50 kg), and embryonal histology. Tumor volume and patient weight added significant outcome information to the standard prognostic factors, including greatest tumor dimension and patient age (P = .02). The ability to resect the tumor completely was not associated significantly with the size of the patient, and patient weight did not significantly modify the association between tumor volume and EFS after adjustment for standard risk factors (P = .2).CONCLUSIONS:The factors that had the strongest association with EFS were tumor volume, patient weight, and histology. On the basis of regression modeling, tumor volume and patient weight were superior predictors of outcome compared with greatest tumor dimension and patient age in children with intermediate‐risk RMS. The current results indicated that the prognostic performance of tumor volume and patient weight should be assessed in an independent prospective study. Cancer 2011. © 2010 American Cancer Society.

Confounding by Dietary Patterns of the Inverse Association Between Alcohol Consumption and Type 2 Diabetes Risk

The ability to interpret epidemiologic observations is limited because of potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as standard risk factors and selected nutrients, the authors modeled the longitudinal association between alcohol consumption and 7-year risk of type 2 diabetes mellitus in 2,879 healthy adults enrolled in the Framingham Offspring Study (1991-2001) by Cox proportional hazard models. After adjustment for standard risk factors, consumers of > or =9.0 drinks/week had a significantly lower risk of type 2 diabetes mellitus compared with abstainers (hazard ratio = 0.47, 95% confidence interval (CI): 0.27, 0.81). Adjustment for selected nutrients had little effect on the hazard ratio, whereas adjustment for dietary pattern variables by factor analysis significantly shifted the hazard ratio away from null (hazard ratio = 0.33, 95% CI: 0.17, 0.64) by 40.0% (95% CI: 16.8, 57.0; P = 0.002). Dietary pattern variables by partial least squares showed similar results. Therefore, the observed inverse association, consistent with past studies, was confounded by dietary patterns, and this confounding was not captured by individual nutrient adjustment. The data suggest that alcohol intake, not dietary patterns associated with alcohol intake, is responsible for the observed inverse association with type 2 diabetes mellitus risk.

Heart Disease and Stroke Statistics—2009 Update

Heart Disease and Stroke Statistics—2009 Update

Heart Disease and Stroke Statistics—2009 Update

We thank Drs Sean Coady, Eric L. Ding, Brian Eigel, Gregg C. Fonarow, Linda Geiss, Cherie James, Michael Mussolino, and Michael Wolz for their valuable comments and contributions. We acknowledge Tim Anderson and Tom Schneider for their editorial contributions, and Karen Modesitt for her administrative assistance. Disclosures ⇓⇓⇓⇓ View this table: Writing Group Disclosures View this table: Writing Group Disclosures, Continued View this table: Writing Group Disclosures, Continued View this table: Writing Group Disclosures, Continued # Summary {#article-title-2} Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay …

Uric Acid and Insulin Sensitivity and Risk of Incident Hypertension

Uric acid, insulin sensitivity, and endothelial dysfunction may be important in the development of hypertension. Corresponding circulating biomarkers are associated with risk of hypertension, but because these factors may be interrelated, whether they independently affect risk is unknown. In 1496 women aged 32 to 52 years without hypertension at baseline, we prospectively analyzed the associations between fasting plasma levels of uric acid, insulin, triglycerides, the insulin sensitivity index, and 2 biomarkers associated with endothelial dysfunction (homocysteine and soluble intercellular adhesion molecule-1) and the odds of incident hypertension. Odds ratios were adjusted for standard risk factors and then for all biomarkers plus estimated glomerular filtration rate and total cholesterol level. Population-attributable risk was estimated for biomarkers significantly associated with hypertension. All the biomarkers were associated with incident hypertension after adjustment for standard hypertension risk factors. However, after simultaneously controlling for all the biomarkers, estimated glomerular filtration rate, and total cholesterol level, only uric acid and insulin levels were independently associated with incident hypertension. Comparing the highest and lowest quartiles of uric acid levels, the odds ratio was 1.89 (95% confidence interval, 1.26-2.82). A similar comparison yielded an odds ratio of 2.03 (95% confidence interval, 1.35-3.05) for insulin levels. Using an estimated basal incidence rate of 14.6 per 1000 annually, 30.8% of all hypertension occurring in young women annually is associated with uric acid levels of 3.4 mg/dL or greater (to convert to micromoles per liter, multiply by 59.485). For insulin levels of 2.9 microIU/mL or greater (to convert to picomoles per liter, multiply by 6.945), this proportion is 24.2%. Differences in uric acid and insulin levels robustly and substantially affect the risk of hypertension in young women. Measuring these biomarkers in clinical practice may identify higher-risk individuals.

Anxiety predicted premature all-cause and cardiovascular death in a 10-year follow-up of middle-aged women

Objective Research on emotional distress and mortality has largely focused on depression in men and in elderly populations. We examined the relation between anxiety and mortality in women at midlife, adjusting for depression. Study Design and Setting At baseline, 5,073 healthy Dutch women aged 46–54 years (mean = 50.4 ± 2.1) and living in Eindhoven, completed a three-item anxiety scale (“being anxious/worried,” “feeling scared/panicky,” “ruminating about things that went wrong;” Cronbach's α = 0.77). The primary outcome was all-cause mortality at 10-year follow-up; secondary outcomes were cardiovascular and lung/breast cancer death. Results At follow-up, 114 (2.2%) women had died at the mean age of 56.4 ± 3.1 years. Lung cancer (23%), cardiovascular disease (18%), and breast cancer (15%) were the major causes of death. Smoking, living alone, and lower education were related to mortality, but depression was not. Adjusting for these variables, anxiety was associated with a 77% increase in mortality risk (hazard ratio [HR] = 1.77, 95% confidence interval [CI]: 1.14–2.74, P = 0.011). Anxiety was related to cardiovascular death (HR = 2.77, 95% CI: 1.17–6.58, P = 0.021); there was also a trend for lung cancer death (HR = 1.91, 95% CI: 0.90–4.06, P = 0.095) but not for breast cancer death. Conclusion Anxiety predicted premature all-cause and cardiovascular death in middle-aged women, after adjustment for standard risk factors and depression.

Abstract 3605: Lipoprotein-Associated Phospholipase A 2 and Myocardial Infarction in Women

Lipoprotein-Associated Phospholipase A 2 (Lp-PLA 2 ) is an enzyme that hydrolyzes oxidized phospholipids in low-density lipoprotein, creating pro-inflammatory molecules that are hypothesized to play a role in the development of coronary heart disease. Many of the previous studies that have shown Lp-PLA 2 activity to be associated with a moderate increase in risk for CHD have been conducted mostly among men. The one previous study among women was small and reported a modest nonsignificant increase in risk. Thus, the association of Lp-PLA 2 with CHD risk in women warrants exploration. We conducted a nested case-control study among participants in the Nurses’ Health Study who provided a blood sample in 1989 –1990. With approximately 15 years of follow-up through 2004 we identified 438 incident cases of fatal and non-fatal MI and used incidence density sampling to match controls to cases (2:1) based on age, smoking status, date of blood draw, and fasting status at the time of blood draw. Lp-PLA 2 activity was measured using a colorimetric activity assay. We used conditional logistic regression in multivariate models. Compared to women in the lowest tertile, the relative risk of CHD for women in the second and third tertiles of Lp-PLA 2 activity were 1.75 (95% CI 1.26 –2.44) and 2.67 (1.94 – 3.69), respectively (p for trend = 0.002). After further adjustment for LDL cholesterol, c-reactive protein,body mass index, alcohol intake, aspirin use, physical activity, and post-menopausal hormone use, and histories of hypercholesterolemia, diabetes, and hypertension, the relative risks were similar: 1.81 (1.26 – 2.60) comparing the second to the first tertile, and 2.26 (1.54 – 3.30) comparing the third to the first tertile (p trend &lt; 0.001). Further adjustment for HDL cholesterol modestly attenuated the relative risks to 1.62 (1.13 – 2.35) and 1.81 (1.20 – 2.71) (p trend = 0.007). The significantly elevated relative risks were not appreciably modified by HDL or LDL. In conclusion, we found that Lp-PLA 2 activity was associated with increased risk for MI among women. Adjustment for standard risk factors modestly attenuated this relationship, but Lp-PLA 2 remained a strong independent predictor of MI in this population of women healthy at baseline.

The Association of Differing Measures of Overweight and Obesity With Prevalent Atherosclerosis: The Dallas Heart Study

This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort. Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden. Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score >10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging. In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend <0.001 for each). After multivariable adjustment for standard risk factors, prevalent CAC was more frequent in the fifth versus first quintile of WHR (odds ratio 1.91, 95% confidence interval 1.30 to 2.80), whereas no independent positive association was observed for BMI or WC. Similar results were observed for aortic plaque in both univariable and multivariable-adjusted analyses. The c-statistic for discrimination of prevalent CAC was greater for WHR compared with BMI and WC in women and men (p < 0.001 vs. BMI; p < 0.01 vs. WC). We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden.