Adjustment For Established Risk Factors Research Articles

The impact of plasma Epstein-Barr virus DNA and fibrinogen on nasopharyngeal carcinoma prognosis: an observational study.

Background:The impact of combining plasma fibrinogen levels with Epstein–Barr Virus DNA (EBV DNA) levels on the prognosis for patients with nasopharyngeal carcinoma (NPC) was evaluated.Methods:In this observational study, 2563 patients with non-metastatic NPC were evaluated for the effects of circulating plasma fibrinogen and EBV DNA levels on disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS).Results:Compared with the bottom biomarker tertiles, TNM stage-adjusted hazard ratios (HR, 95% confidence intervals (CIs)) for predicting DFS in fibrinogen tertiles 2 to 3 were 1.26 (1.00 to 1.60) and 1.81 (1.45 to 2.26), respectively; HR for EBV DNA tertiles 2 to 3 were 1.49 (1.12 to 1.98) and 4.24 (3.27 to 5.49), respectively. After additional adjustment for established risk factors, both biomarkers were still associated (P for trend <0.001) with reduced DFS (HR: 1.79, 95% CI, 1.43 to 2.25 for top fibrinogen tertiles; HR: 4.04, 95% CI: 3.10 to 5.27 for top EBV DNA tertiles compared with the bottom tertiles). For patients with advanced-stage disease, those with high fibrinogen levels (⩾3.34 g l−1) presented with worse DFS, regardless of EBV DNA ⩾4000 or <4000 copies ml−1 subgroup. Similar findings were observed for DMFS and OS.Conclusions:Circulating fibrinogen and EBV DNA significantly correlate with NPC patients survival. Combined fibrinogen and EBV DNA data lead to improved prognostic prediction in advanced-stage disease.

Symmetric Dimethylarginine as Predictor of Graft Loss and All-Cause Mortality in Renal Transplant Recipients.

Elevated symmetric dimethylarginine (SDMA) has been shown to predict cardiovascular events and all cause mortality in diverse populations. The potential role of SDMA as a risk marker in renal transplant recipients (RTR) has not been investigated. We analysed SDMA in the placebo arm of the ALERT study, a randomized controlled trial of fluvastatin in RTR. Mean follow up of was 5.1 years. Patients were grouped into quartiles based on SDMA-levels at study inclusion. Relationships between SDMA and traditional risk factors for graft function and all-cause mortality were analysed in 925 RTR using uni- and multivariable survival analysis. In univariate analysis SDMA was significantly associated with renal graft loss, all-cause death and major cardiovascular events. After adjustment for established risk factors including estimated glomerular filtration rate, an elevated SDMA level (4th quartile, >1.38 μmol/L) was associated with renal graft loss; hazard ratio (HR) 5.51 (95% CI 1.95-15.57, p=0.001) compared to the 1st quartile. Similarly,SDMA in the 4th quartile was independently associated with all-cause mortality (HR 4.56 95% CI 2.15-9.71, p<0.001), and there was a strong borderline significant trend for an association with cardiovascular mortality (HR 2.86, 95% CI 0.99-8.21, p=0.051). In stable RTR an elevated SDMA-level is independently associated with increased risk of all-cause mortality and renal graft loss.

Pain interference is associated with psychological concerns related to falls in community-dwelling older adults: multisite observational study.

Pain interference and psychological concerns related to falls (PCRF) are pervasive phenomena among community-dwelling older adults, yet their association remains elusive. The purpose of this study was to establish whether pain interference is associated with PCRF in community-dwelling older adults. This was a multisite cross-sectional study. Two hundred ninety-five community-dwelling older adults (mean age=77.5 years, SD=8.1; 66.4% female) participated in the study. All participants completed the Brief Pain Inventory (BPI) interference subscale, Short Falls Efficacy Scale-International (FES-I), Activities-specific Balance Confidence Scale (ABC), modified version of the Survey of Activities and Fear of Falling in Elderly Scale (mSAFFE), and Consequences of Falling Scale (CoF). Hierarchical multiple regression analysis were conducted. In the first step of the study, sociodemographic and known risk factors for psychological concerns related to falls were inserted into the model, followed by the BPI interference subscale score in the second step. One hundred sixty-nine participants (57.3%) reported some pain interference. The BPI interference subscale was highly correlated with all PCRF (r>.5, P<.0001). After the adjustment for established risk factors, the BPI interference subscale significantly increased the variance in the Short FES-I (R2 change=13.2%), ABC (R2 change=4.7%), mSAFFE (R2 change=5.0%), and CoF (R2 change=10.0%). Pain interference was a significant and independent predictor in the final model for the Short FES-1 (β=0.455, P<.001), ABC (β=-0.265, P<.001), mSAFFE (β=0.276, P<.001), and CoF (β=0.390, P<.001). The study was cross-sectional. Pain interference is an important contributing factor in each of the psychological concerns related to falls. Pain interference had the strongest impact on reducing falls efficacy and increasing older adults' concerns about the consequences of falling.

Atrial fibrillation in hypertrophic cardiomyopathy: prevalence, clinical correlations, and mortality in a large high-risk population.

BackgroundAtrial fibrillation (AF) is a common sequela of hypertrophic cardiomyopathy (HCM), but evidence on its prevalence, risk factors, and effect on mortality is sparse. We sought to evaluate the prevalence of AF, identify clinical and echocardiographic correlates, and assess its effect on mortality in a large high‐risk HCM population.Methods and ResultsWe identified HCM patients who underwent evaluation at our institution from 1975 to 2012. AF was defined by known history (either chronic or paroxysmal), electrocardiogram, or Holter monitoring at index visit. We examined clinical and echocardiographic variables in association with AF. The effect of AF on overall and cause‐specific mortality was evaluated with multivariate Cox proportional hazards models. Of 3673 patients with HCM, 650 (18%) had AF. Patients with AF were older and more symptomatic (P<0.001). AF was less common among patients with obstructive HCM phenotype and was associated with larger left atria, higher E/e’ ratios, and worse cardiopulmonary exercise tolerance (all P values<0.001). During median (interquartile range) follow‐up of 4.1 (0.2 to 10) years, 1069 (29%) patients died. Patients with AF had worse survival compared to those without AF (P<0.001). In multivariate analysis adjusted for established risk factors of mortality in HCM, the hazard ratio (95% confidence interval) for the effect of AF on overall mortality was 1.48 (1.27 to 1.71). AF did not have an effect on sudden or nonsudden cardiac death.ConclusionsIn this large referral HCM population, approximately 1 in 5 patients had AF. AF was a strong predictor of mortality, even after adjustment for established risk factors.

Plasma levels of active Von Willebrand factor are increased in patients with first ST-segment elevation myocardial infarction: a multicenter and multiethnic study.

Von Willebrand factor (VWF), a key player in hemostasis and thrombosis, is released from endothelial cells during inflammation. Upon release, VWF is processed by ADAMTS13 into an inactive conformation. The aim of our study was to investigate whether plasma levels of active VWF, total VWF, ADAMTS13, osteoprotegerin (OPG) and the ratios between VWF and ADAMTS13 are risk factors for first ST-segment elevation myocardial infarction (STEMI). We assessed 1026 patients with confirmed first STEMI and 652 control subjects from China, Italy and Scotland, within six hours after their cardiovascular event. Median plasma levels of total VWF, active VWF, OPG and ratios VWF/ADAMTS13 were increased, while plasma levels of ADAMTS13 were decreased in patients compared to controls. The odds ratio (OR) of STEMI in patients with high plasma levels of active VWF was 2.3 (interquartile range (IQR): 1.8-2.9), total VWF was 1.8 (1.4-2.3), ADAMTS13 was 0.6 (05-0.8), OPG was 1.6 (1.2-2.0) and high VWF/ADAMTS13 ratios was 1.5 (1.2-2.0). The OR for total VWF, active VWF and ratios VWF/ADAMTS13 remained significant after adjustment for established risk factors, medical treatment, C-reactive protein, total VWF, ADAMTS13 and OPG. When we adjusted for levels of active VWF, the significance of the OR for VWF and ratios VWF/ADAMTS13 disappeared while the OR for active VWF remained significant. We found evidence that plasma levels of active VWF are an independent risk factor for first STEMI in patients from three different ethnic groups. Our findings confirm the presence of VWF abnormalities in patients with STEMI and may be used to develop new therapeutic approaches.

Prediction of cardiovascular disease by abdominal obesity measures is dependent on body weight and sex – Results from two community based cohort studies

AimTo study waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), and waist-hip-height ratio (WHHR) as predictors of CVD, in men and women stratified by BMI (cut-off ≥25). Methods and resultsA cohort of n = 3741 (53% women) 60-year old individuals without CVD was followed for 11-years (375 CVD cases). To replicate the results, we also assessed another large independent cohort; The Malmö Diet and Cancer study – cardiovascular cohort (MDCC, (n = 5180, 60% women, 602 CVD cases during 16-years). After adjustment for established risk factors in normal-weight women, the hazard ratio (HR) per one standard deviation (SD) were; WHR; 1.91 (95% confidence interval (CI) 1.35–2.70), WC; 1.81 (95% CI 1.02–3.20), SAD; 1.25 (95% CI 0.74–2.11), and WHHR; 1.97 (95% CI 1.40–2.78). In men the association with WHR, WHHR and WC were not significant, whereas SAD was the only measure that significantly predicted CVD in men (HR 1.19 (95% CI 1.04–1.35). After adjustments for established risk factors in overweight/obese women, none of the measures were significantly associated with CVD risk. In men, however, all measures were significant predictors; WHR; 1.24 (955 CI 1.04–1.47), WC 1.19 (95% CI 1.00–1.42), SAD 1.21 (95% CI 1.00–1.46), and WHHR; 1.23 (95% CI 1.05–1.44). Only the findings in men with BMI ≥ 25 were verified in MDCC. ConclusionIn normal weight individuals, WHHR and WHR were the best predictors in women, whereas SAD was the only independent predictor in men. Among overweight/obese individuals all measures failed to predict CVD in women, whereas WHHR was the strongest predictor after adjustments for CVD risk factors in men.

Pro-Inflammatory Interleukin-1 Genotypes Potentiate the Risk of Coronary Artery Disease and Cardiovascular Events Mediated by Oxidized Phospholipids and Lipoprotein(a)

The aim of this study was to assess the influence of pro-inflammatory interleukin (IL)-1 genotype status on the risk for coronary artery disease (CAD), defined as >50% diameter stenosis, and cardiovascular events mediated by oxidized phospholipids (OxPLs) and lipoprotein (Lp) (a). OxPLs are pro-inflammatory, circulate on Lp(a), and mediate CAD. Genetic variations in the IL-1 region are associated with increased inflammatory mediators. IL-1 genotypes, OxPL on apolipoprotein B-100 (OxPL/apoB), and Lp(a) levels were measured in 499 patients undergoing coronary angiography. The composite genotype termed IL-1(+) was defined by 3 single-nucleotide polymorphisms in the IL-1 gene cluster associated with higher levels of pro-inflammatory cytokines. All other IL-1 genotypes were termed IL-1(-). Among IL-1(+) patients, the highest quartile of OxPL/apoB was significantly associated with a higher risk for CAD compared with the lowest quartile (odds ratio [OR]: 2.84; p = 0.001). This effect was accentuated in patients age ≤60 years (OR: 7.03; p < 0.001). In IL-1(-) patients, OxPL/apoB levels showed no association with CAD. The interaction was significant for OxPL/apoB (OR: 1.99; p = 0.004) and Lp(a) (OR: 1.96; p < 0.001) in the IL-1(+) group versus the IL-1(-) group in patients age ≤60 years but not in those age >60 years. In IL-1(+) patients age ≤60 years, after adjustment for established risk factors, high-sensitivity C-reactive protein, and Lp(a), OxPL/apoB remained an independent predictor of CAD. IL-1(+) patients above the median OxPL/apoB presented to the cardiac catheterization laboratory a mean of 3.9 years earlier (p = 0.002) and had worse 4-year event-free survival (death, myocardial infarction, stroke, and need for revascularization) compared with other groups (p = 0.006). Our study suggests that IL-1 genotype status can stratify population risk for CAD and cardiovascular events mediated by OxPL. These data suggest a clinically relevant biological link between pro-inflammatory IL-1 genotype, oxidation of phospholipids, Lp(a), and genetic predisposition to CAD and cardiovascular events.

Triglyceride–to–High-Density-Lipoprotein-Cholesterol Ratio Is an Index of Heart Disease Mortality and of Incidence of Type 2 Diabetes Mellitus in Men

BackgroundHigh triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) impart risk for heart disease. This study examines the relationships of TG/HDL-C ratio to mortality from all causes, coronary heart disease...

Psychological Resources are Associated with Reduced Incidence of Coronary Heart Disease. An 8-Year Follow-up of a Community-Based Swedish Sample

BackgroundA large number of studies have provided clear evidence for a link between the risk of coronary heart disease and psychological risk factors. Much less attention has been given to the potential protective effect of psychological resources.PurposeThe major aim of this study was to investigate the independent association between psychological resources and incidence of coronary heart disease (CHD) in an 8-year follow-up study of a Swedish community-based cohort.MethodsThe cohort consisted of 484 men and 497 women, aged 45–69 years at baseline. The incidence of first-time major event of CHD was analysed in relation to baseline levels of psychological resources, including mastery, self-esteem, and sense of coherence as well as psychological risk factors including cynicism and hostile affect, vital exhaustion, hopelessness, and depressive symptoms. In Cox proportional hazard models, adjustments were made for age, sex, eight traditional cardiovascular risk factors, and depressive symptoms.ResultsA total of 56 CHD events had occurred after the 8-year follow-up. After adjustment for age, sex, and eight traditional risk factors, a significantly decreased risk of CHD was found for mastery (HR 0.62 per SD, p = 0.003), self-esteem (HR 0.64, p = 0.004), and sense of coherence (HR 0.70, p = 0.031). An increased risk of CHD was found for vital exhaustion (HR 1.46, p = 0.014), hopelessness (HR 1.59, p = 0.003), and depressive symptoms (HR 1.45, p = 0.009). After further adjustment for depressive symptoms, significant associations remained for mastery (HR 0.67, p = 0.034), self-esteem (HR 0.69, p = 0.048), and hopelessness (HR 1.48, p = 0.023).ConclusionsThe psychological resources, mastery and self-esteem, showed robust protective effects on CHD, also after adjustment for established risk factors as well as depressive symptoms. In parallel, hopelessness was an independent risk factor for CHD. The results may have implications for novel approaches in preventive efforts.

White Blood Cell Count in Elderly Is Clinically Useful in Predicting Long-Term Survival

Introduction. White blood cell (WBC) count is often included in routine clinical checkups. We determined the prognostic impact of WBC count on all-cause, cardiovascular, and noncardiovascular mortality during an 11-year followup in a general population of 75-year-olds. Study Population. The study included 207 men and 220 women comprising 69% of the invited 75-year-olds in a defined geographical area. Main Results. The median WBC count (in 109/L) was 6.3 (interquartile range 5.4–7.2) for men and 5.7 (4.9–6.8) for women, P < 0.001 for sex difference. The hazard ratio (HR) for all-cause mortality per 109/L increase in WBCs was 1.16 (95% confidence interval, 1.03–1.32; P = 0.016) in men and 1.28 (1.10–1.50; P = 0.002) in women. These HRs were essentially unchanged by adjustment for established risk factors (current smoking, known hypertension, prior myocardial infarction, known diabetes, total cholesterol, high-density lipoprotein cholesterol, and body mass index). Furthermore, increased WBC count was significantly associated with cardiovascular mortality in both sexes and with noncardiovascular mortality in women. Conclusions. The WBC count deserves attention as a potentially clinical useful predictor of survival in the 75-year-olds, especially among women.

Presence of gallstones and the risk of cardiovascular diseases: The EPIC-Germany cohort study

Gallstones are common disorders associated with several cardiovascular risk factors. Gallstone formation and atherosclerosis may share key pathways, but studies on putative associations between gallstones and the risk of cardiovascular disease are sparse and non-conclusive. We studied the relationship between gallstones and the risk of subsequent cardiovascular diseases in the German arm of the European Prospective Investigation into Cancer and Nutrition (EPIC). The study comprises 46,468 participants from EPIC-Potsdam and EPIC-Heidelberg aged 35-65 years, free of cardiovascular diseases and diabetes at baseline. Information about the gallstone status at baseline was ascertained via questionnaires. For all incident cases of myocardial infarction and stroke confirmation was obtained from the treating physician. Relative risks were estimated using Cox proportional hazards regression. During eight years of follow-up, 919 participants suffered a stroke or myocardial infarction. After multivariable adjustment for established risk factors, subjects with reported gallstones (n = 4828) had an increased risk of cardiovascular diseases (hazard rate ratio (HR) = 1.24, 95% confidence interval (CI): 1.02, 1.50). In individuals, who underwent a cholecystectomy before baseline a 1.32-fold increase in risk was observed (95%CI: 1.05, 1.65). HRs differed depending on the presence of selected established risk factors (e.g. HR for cardiovascular diseases regarding gallstones in smokers = 1.66, 95%CI: 1.20, 2.30, and non-smokers = 1.09, 95%CI: 0.86, 1.38). Our results indicate an increased cardiovascular risk for gallstone formers, which cannot be counteracted by gallbladder removal and opens up perspectives for individualized prevention strategies.

Outcomes of coronary artery interventions: Comparing coronary artery bypass surgery and percutaneous coronary intervention in patients with unprotected left main stenosis

The purpose of this integrative review is to examine the existing literature comparing short- and long-term outcomes of both coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with unprotected left main coronary artery (ULMCA) stenosis. CABG has long been considered the standard of treatment for ULMCA stenosis; however, advancements in the use of PCI have made it a viable alternative treatment option. Sixteen articles were selected from a literature search using the PubMed database, with at least 1 year of follow-up and adjustment for established risk factors. The majority of studies found CABG and PCI with stenting to be comparable and equally safe treatment strategies for patients with ULMCA stenosis. Some studies found that PCI had a significantly lower risk for adverse events and mortality compared to CABG. However, a large number of studies found that PCI had a higher rate of target vessel restenosis. Advanced practice nurses have become a prominent and influential part of the healthcare delivery system. As such, advanced practice nurses should be educated on the current research about coronary artery interventions so that they may better screen, treat, and manage this patient population.

Low triiodothyronine: a pathway to coronary calcification in patients maintained on peritoneal dialysis

Low triiodothyronine: a pathway to coronary calcification in patients maintained on peritoneal dialysis

Adult Stature and Risk of Cancer at Different Anatomic Sites in a Cohort of Postmenopausal Women

Prospective studies in Western and Asian populations suggest that height is a risk factor for various cancers. However, few studies have explored potential confounding or effect modification of the association by other factors. We examined the association between height measured at enrollment in 144,701 women participating in the Women's Health Initiative and risk of all cancers combined and cancer at 19 specific sites. Over a median follow-up of 12.0 years, 20,928 incident cancers were identified. We used Cox proportional hazards models to estimate HR and 95% confidence intervals (CI) per 10 cm increase in height, with adjustment for established risk factors. We also examined potential effect modification of the association with all cancer and specific cancers. Height was significantly positively associated with risk of all cancers (HR = 1.13; 95% CI, 1.11-1.16), as well as with cancers of the thyroid, rectum, kidney, endometrium, colorectum, colon, ovary, and breast, and with multiple myeloma and melanoma (range of HRs: 1.13 for breast cancer to 1.29 for multiple myeloma and thyroid cancer). These associations were generally insensitive to adjustment for confounders, and there was little evidence of effect modification. This study confirms the positive association of height with risk of all cancers and a substantial number of cancer sites. Identification of single-nucleotide polymorphisms associated both with height and with increased cancer risk may help elucidate the association.

Associations Between Metabolomic Compounds and Incident Heart Failure Among African Americans: The ARIC Study

Heart failure is more prevalent among African Americans than in the general population. Metabolomic studies among African Americans may efficiently identify novel biomarkers of heart failure. We used untargeted methods to measure 204 stable serum metabolites and evaluated their associations with incident heart failure hospitalization (n = 276) after a median follow-up of 20 years (1987-2008) by using Cox regression in data from 1,744 African Americans aged 45-64 years without heart failure at baseline from the Jackson, Mississippi, field center of the Atherosclerosis Risk in Communities (ARIC) Study. After adjustment for established risk factors, we found that 16 metabolites (6 named with known structural identities and 10 unnamed with unknown structural identities, the latter denoted by using the format X-12345) were associated with incident heart failure (P < 0.0004 based on a modified Bonferroni procedure). Of the 6 named metabolites, 4 are involved in amino acid metabolism, 1 (prolylhydroxyproline) is a dipeptide, and 1 (erythritol) is a sugar alcohol. After additional adjustment for kidney function, 2 metabolites remained associated with incident heart failure (for metabolite X-11308, hazard ratio = 0.75, 95% confidence interval: 0.65, 0.86; for metabolite X-11787, hazard ratio = 1.23, 95% confidence interval: 1.10, 1.37). Further structural analysis revealed X-11308 to be a dihydroxy docosatrienoic acid and X-11787 to be an isoform of either hydroxyleucine or hydroxyisoleucine. Our metabolomic analysis revealed novel biomarkers associated with incident heart failure independent of traditional risk factors.

Clinical utility and prognostic value of left atrial volume assessment by cardiovascular magnetic resonance in non‐ischaemic dilated cardiomyopathy

Echocardiographic studies have shown that left atrial volume (LAV) predicts adverse outcome in small heart failure (HF) cohorts of mixed aetiology. However, the prognostic value of LAV in non-ischaemic dilated cardiomyopathy (DCM) is unknown. Cardiovascular magnetic resonance (CMR) allows accurate and reproducible measurement of LAV. We sought to determine the long-term prognostic significance of LAV assessed by CMR in DCM. We measured LAV indexed to body surface area (LAVi) in 483 consecutive DCM patients referred for CMR. Patients were prospectively followed up for a primary endpoint of all-cause mortality or cardiac transplantation. During a median follow-up of 5.3 years, 75 patients died and 9 underwent cardiac transplantation. After adjustment for established risk factors, LAVi was an independent predictor of the primary endpoint [hazard ratio (HR) per 10 mL/m(2) 1.08; 95% confidence interval (CI) 1.01-1.15; P = 0.022]. LAVi was also independently associated with the secondary composite endpoints of cardiovascular mortality or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.19; P = 0.003), and HF death, HF hospitalization, or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.18; P = 0.001). The optimal LAVi cut-off value for predicting the primary endpoint was 72 mL/m(2). Patients with LAVi >72 mL/m(2) had a three-fold elevated risk of death or transplantation (HR 3.00; 95% CI 1.92-4.70; P < 0.001). LAVi provided incremental prognostic value for the prediction of transplant-free survival (net reclassification improvement 0.17; 95% CI 0.05-0.29; P = 0.002). LAVi is a powerful independent predictor of transplant-free survival and HF outcomes in DCM. Assessment of LAV improves risk stratification in DCM and should be incorporated into routine CMR examination.

Insulin Sensitivity and Carotid Intima-Media Thickness

Objective— Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. Approach and Results— We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions known to affect carotid wall (diabetes mellitus, hypertension, and dyslipidemia). All subjects received an oral glucose tolerance test, a euglycemic hyperinsulinemic clamp (M/I as a measure of insulin sensitivity), and B-mode carotid ultrasound. In 833 participants (380 men), the carotid ultrasound was repeated after 3 years. In men, baseline intima-media thickness in the common carotid artery (CCA-IMT) was significantly higher ( P &lt;0.05) in the lowest M/I tertile, whereas in women CCA-IMT was higher ( P &lt;0.0005) in the highest fasting plasma glucose tertile (after adjustment for established risk factors). In multiple regression models, with CCA-IMT as the dependent variable and with risk factors and univariate metabolic correlates as independent variables, circulating free fatty acids and the leptin:adiponectin ratio replaced M/I as independent metabolic determinants of CCA-IMT in men. The strongest metabolic determinant of CCA-IMT in women was fasting plasma glucose. Three-year CCA-IMT changes were not associated with any cardio-metabolic risk factor. Conclusions— In young-to-middle aged apparently healthy people, the association of CCA-IMT with insulin sensitivity and its metabolic correlates differs between men and women. Lower insulin sensitivity is associated with higher IMT only in men; this association seems to be mediated by circulating free fatty acids and adipocytokines. In women, CCA-IMT is independently associated with fasting plasma glucose.

QRS Duration on Electrocardiography and Cardiovascular Mortality (from the National Health and Nutrition Examination Survey—III)

The relation of bundle branch block (BBB) with adverse outcome is controversial. We hypothesized that increased QRS duration is an independent predictor of cardiovascular (CV) mortality in a cross-sectional US population. This is a retrospective cohort study on prospectively collected data to assess the relationship between QRS duration on routine ECG and CV mortality. Participants included 8,527 patients with ECG data available from the National Health and Nutrition Examination Survey data set, representing 74,062,796 individuals in the United States. Mean age was 60.5 ± 13.6 years. Most subjects were white (87%) and women (53%). During the follow-up period of 106,244.6 person-years, 1,433 CV deaths occurred. Multivariate analysis revealed that the highest quartile of QRS duration was associated with higher CV mortality than lowest quartile (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.01 to 1.7, p = 0.04) after adjustment for established risk factors. Both left BBB (HR 2.4, 95% CI 1.3 to 4.7, p = 0.009) and right BBB (HR 1.90, 95% CI 1.2 to 3.0, p = 0.008) were significantly associated with increased CV mortality. The addition of the QRS duration in 10-millisecond increments to the Framingham Risk Score model resulted in 4.4% overall net reclassification improvement (95% CI 0.02 to 0.04; p = 0.00006). In conclusion, increased QRS duration was found to be an independent predictor of CV mortality in this cross-sectional US population. A model including QRS duration in addition to traditional risk factors was associated with improved CV risk prediction.

Red cell distribution width is associated with physical inactivity and heart failure, independent of established risk factors, inflammation or iron metabolism; the EPIC—Norfolk study

Red cell distribution width (RDW) is associated with increased risk of heart failure (HF). We examined in a healthy population (1) whether this association is independent of cardiovascular risk factors and iron metabolism and (2) whether RDW associates with physical activity. Hazard ratios (HRs, highest quartile versus lowest quartile of RDW) for the risk of HF were calculated in 17,533 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. During a follow-up of 11.2±2.2 years 640 participants developed a HF event. The HR for HF events was 1.44 (95%CI 1.15-1.80, p<0.001). There was a non-linear increase in HF risk across RDW quartiles. Adjustment for established risk factors (sex, age, diabetes, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol) attenuated the HR for HF to 1.40 (95%CI 1.11-1.77, p=0.001). Adjustment for CRP, iron and ferritin levels did not affect the HR for HF. RDW levels are inversely associated with physical activity (per category β=-0.37, 95%CI -0.053 to -0.021, p<0.0001), independent of iron metabolism. However, the association between HF and RDW levels was not changed by physical activity. This study confirms that RDW is associated with HF events in an apparently healthy middle-aged population. More importantly, we show that the underlying pathophysiology linking HF with anisocytosis is not reflected by conventional risk factors, nor it is explained by iron metabolism or inflammation. Furthermore, RDW levels were associated with physical inactivity, but this did not influence the RDW-associated-risk of heart failure.

Left Ventricular Global Function Index by Magnetic Resonance Imaging—A Novel Marker for Assessment of Cardiac Performance for the Prediction of Cardiovascular Events

Left ventricular (LV) function is generally assessed independent of structural remodeling and vice versa. The purpose of this study was to evaluate a novel LV global function index (LVGFI) that integrates LV structure with global function and to assess its predictive value for cardiovascular (CV) events throughout adult life in a multiethnic population of men and women without history of CV diseases at baseline. A total of 5004 participants in the Multi-Ethnic Study of Atherosclerosis underwent a cardiac magnetic resonance study and were followed up for a median of 7.2 years. The LVGFI by cardiac magnetic resonance was defined by the ratio of stroke volume divided by LV total volume defined as the sum of mean LV cavity and myocardial volumes. Cox proportional hazard models were constructed to predict the end points of heart failure, hard CV events, and a combined end point of all CV events after adjustment for established risk factors, calcium score, and biomarkers. A total of 579 (11.6%) CV events were observed during the follow-up period. In adjusted models, the end points of heart failure, hard CV events, and all events were all significantly associated with LVGFI (heart failure, hazard ratio=0.64, P &lt;0.0001; hard CV events, hazard ratio=0.79, P =0.007; all events, hazard ratio=0.79, P &lt;0.0001). LVGFI had a significant independent predictive value in the multivariable models for all CV event categories. The LVGFI was a powerful predictor of incident HF, hard CV events, and a composite end point, including all events in this multiethnic cohort.