Traditional Framingham Risk Factors Research Articles

Supplementation of Antioxidants in Chronic Kidney Disease: Clinical Necessity or Wishful Thinking? A Bench to Bedside Translational Research.

Chronic Kidney Disease (CKD) patients are at increased risk for atherosclerosis, cardiovascular disease (CVD) and progression to end stage kidney disease (ESKD). This heavy CVD risk cannot be solely at-tributed to traditional Framingham risk factors. Oxidative stress (OS), defined as the disruption of balance between prooxidants and antioxidants in favor of the former, has emerged as a novel risk factor for CVD and CKD progression. Specifically, lipid peroxidation has been identified as a trigger for endothelial dys-function, the first step towards atherogenesis and protein oxidation has been associated with CKD progres-sion. The oxidation of proteins and lipids starts early in CKD, increases gradually with disease progression and is further exacerbated in ESKD, due to dialysis related factors. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease and progression of CKD, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from ex-perimental and clinical studies that test antioxidants for their possible beneficial effects against CVD and CKD progression such as vitamins E and C, statins, omega-3 fatty acids, trace elements, polyphenols and N-acetylcysteine. </p>.

The Controversies of Coronary Artery Disease in End-Stage Kidney Disease Patients: A Narrative Review.

Cardiovascular disease (CVD) accounts for more than 50% of deaths among patients with end-stage kidney disease (ESKD). Approximately 40-50% of ESKD patients have clinically significant coronary artery disease (CAD) due to atherosclerosis which accounts for a significant proportion of CVD risk. However, other CVD pathologies including myocardial fibrosis, vascular calcification and arterial stiffening play important contributory roles. The pathophysiology of CAD in ESKD is distinct from the general population. ESKD patients is typically have diffuse multi-vessel involvement with increased calcification that involves both intimal and medial layers of the arterial wall. There is a complex interplay between an increased burden of traditional Framingham risk factors and exposure to non-traditional risk factors including chronic inflammation and dialysis per se. Established treatments for CAD risk factors including cholesterol lowering with statin therapy have attenuated effects and ESKD patients also have worse outcomes after revascularisation. Recent trials such as the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) have established that direct modulation of inflammation improves CVD outcomes in the general population, which may prove to be a potential attractive therapeutic target in ESKD patients. Multiple retrospective observational studies comparing mortality outcomes between haemodialysis (HD) and peritoneal dialysis (PD) patients have been inconclusive. Randomised trials on this issue of clinical equipoise are clearly warranted but are unlikely to be feasible. Screening for stable CAD in asymptomatic ESKD patients remains a clinical dilemma which is unique to chronic dialysis patients being assessed for kidney transplantation. This has become particularly relevant in light of the recent ISCHEMIA-CKD trial which demonstrated no difference between optimal medical therapy and revascularisation upon CVD outcomes or mortality. The optimal strategy for screening is currently being investigated in the ongoing large international multi-centre CARSK trial. Here we discuss the pathophysiology, risk modification, treatment, screening and future directions of CAD in ESKD.

PREDICTION OF ATHEROSCLEROSIS DEVELOPMENT AND MODIFICATION OF ITS RISK FACTORS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Objective: Early-onset atherosclerosis with cardiovascular (CV) sequelae is the major cause of death in systemic lupus erythematosus (SLE); that cannot be explained only by traditional Framingham risk factors as SLE-related factors may also have an impact. The present study aimed to analyze the determinants of atherosclerosis development and risk factors modification by statin therapy in SLE patients. Design and method: This prospective randomized study included 100 SLE patients aged 40.9±1.4 years (90 females, 10 males) and 32 age-, sex-matched healthy controls. Brachial artery flow-mediated dilation (FMD), ultrasound of extracranial and peripheral arteries, and cardiac calcium scoring were used for the identification of atherosclerosis. 52 SLE patients with dyslipidemia were randomized to receive simvastatin 40 mg/day (n = 27) or placebo (n = 25). Lipid panel, FMD, and inflammatory markers were assessed at baseline and after 6 months. Results: The mean duration of SLE was 9.9±0.88 years. The disease activity index (SLEDAI) and SLE damage score (SLICC) were 11.8±0.6 and 1.85±0.13 points, respectively. In 66% of SLE patients, atherosclerosis was present in at least one vascular area which was 3.5 times more frequently compared with controls. Atherosclerosis of carotid arteries was detected in 41% of SLE patients, lower limb arteries, and coronary arteries in 58% and 39% of patients, respectively. FMD was significantly decreased in SLE patients compared to controls (7.95±0.49% vs 11.6±0.3%, p&lt;0.001). In multiple linear regression, age (p&lt;0.001), nephritis (p = 0.001), polyarthritis (p = 0.019), and Raynaud's syndrome (p = 0.045) were associated with low FMD. In binary logistic regression, independent determinants of the atherosclerosis development in SLE were age (p&lt;0.001), body mass index (BMI) (p = 0.001), anti-dsDNA (p = 0.023), FMD (p = 0.017) and malar rash (p = 0.02). After simvastatin treatment, the level of LDL-Cholesterol reduced by 42%, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 decreased by 34.7%, 51.1%, and 47.7% respectively, while FMD increased by 26.0% (p&lt;0.05); in the placebo group, there were no significant changes. Conclusions: The independent determinants of atherosclerosis in SLE patients were both traditional CV risk factors (age, BMI) and SLE-specific factors (anti-dsDNA, malar rash, FMD). In SLE patients with dyslipidemia, simvastatin may have not only lipid-lowering but also potentially anti-inflammatory benefits.

Iliac Artery Calcification Burden is Associated With Adverse Cardiovascular Outcomes and Mortality After Infrainguinal Revascularization for Chronic Limb-threatening Ischemia

Coronary artery calcification has been shown to increase cardiovascular risk beyond that predicted by traditional Framingham risk factors. The purpose of this study was to determine whether the burden of iliac artery calcification is associated with adverse cardiovascular events and mortality following infrainguinal interventions for chronic limb-threatening ischemia (CLTI).

CT Simulation is Useful for Quantifying Pre-Treatment Coronary Artery Calcification in Breast Cancer Patients

Women diagnosed with breast cancer often receive oncologic treatments like chemotherapy and radiation that increase their risk of having a significant cardiac event. If high-cardiovascular-risk women can be identified before treatment, measures could be taken to reduce cardiac toxicity resulting in a large impact on cardiac- and all-cause mortality. In addition to traditional Framingham risk factors, coronary artery calcium (CAC) score gives important prognostic information for risk of cardiac event. While a cardiac-cycle gated CT scan is the standard imaging modality for CAC quantification, non-gated scans have shown good concordance with gated scans and other CV risk factors. Herein, we undertake a survey of breast cancer patients to determine the distribution of cardiovascular risk using CAC score, and quantify the reproducibility of CAC score calculated using CT simulation scans for breast cancer patients. The 100 most recent patients carrying a diagnosis of breast cancer and having CT simulation scans (one primary and a subsequent scan for boost plan) within 2 weeks and 2 months apart were included. Patients’ CT simulation scans were screened for CAC in a treatment planning system. CT window was set between 100-120 Hounsfield units. For patients’ whose CT simulation scans were negative for calcium during screening, a CAC score of 0 was recorded. For any patient with CAC in any of his/her scans, were exported as DICOM files and imported into InTuition for manual CAC score calculation using the Agatston method. Briefly, the density (in Hounsfield units) of a lesion in a coronary artery is converted to a score. That score is then weighted by the area of the lesion in square millimeters. CAC score risk stratification was performed using previously defined Agatston score ranges, and concordance assessed between scans for each patient. There were 47 left breast, 48 right breast, and 5 bilateral breast cancer cases. 73% of patients had a CAC score of zero on both scans. The agreement of the absolute CAC score between CT sim scans of the same individual was high (Rˆ2 = 0.98). The CAC risk group concordance was 90%. Calculating a CAC from a CT simulation scan is feasible and has good replicability on multiple scans. Future directions for this research include improved treatment decision-making by leveraging this radiographic data to personalize treatments with more conformal therapies to avoid heart dose for women at higher baseline risk of CVD.

Coronary artery disease (CAD) risk factor analysis in an age-stratified hospital population with systemic lupus erythematosus (SLE)

ObjectivesPatients with systemic lupus erythematosus (SLE) are at higher risk for coronary artery disease (CAD) particularly at a younger age. We sought to determine the effect of risk factors on the prevalence of CAD in age stratified hospitalized patients with SLE. MethodsThe National Inpatient Sample (NIS) was queried for hospitalized patients with SLE during the years 2010–2015, and a control group without SLE. The study sample was stratified by age, 18–35 years, 36–55 years, and adults >55 years. The effect of SLE and traditional Framingham risk factors on the prevalence of CAD were assessed. Dominance analysis allowed for ranking of CAD risk factors in each age group. ResultsA total 167,466 patients were matched to an equal number of controls. 88.8% were women, 48.5% Caucasian and 29% African-American. In lupus patients 18–35 years prevalent risk factors included hyperlipidemia, hypertension, hypercoagulability and CKD. Diabetes and depression ranked least important. In middle and older patients, traditional risk factors were dominant. In adults >55 years the prevalence of CAD appears higher in Caucasians whereas in young patients 18–35 years, African Americans are dominant. ConclusionCAD in the young adult patient with SLE is represented predominately by an African-American population and it is dominated by a hypercoagulable state and a less significant role for diabetes. In the lupus cohort over 55 years, which is predominantly Caucasian, SLE specific factors are less significant.

Prognostic significance and dynamic change of plasma macrophage migration inhibitory factor in patients with acute ST-elevation myocardial infarction.

Macrophage migration inhibitory factor (MIF) has been reported as an inflammatory cytokine in many inflammatory diseases, including rheumatoid arthritis and ischemic diseases. However, dynamic changes of MIF within the first 24 hours on admission and potential prognostic significance following ST-elevation myocardial infarction (STEMI) have been little known. In this study, we examined the dynamic change of MIF level and its potential diagnostic and prognostic value after the onset of STEMI. Plasma MIF levels were evaluated in symptomatic subjects who received coronary angiogram with a median 27 months follow-up for the development of major adverse cardiovascular events (MACEs).Of all 993 subjects, patients with STEMI showed a significantly higher MIF levels than in patients with non-ST elevation acute coronary syndrome, stable angina, and normal coronary artery, respectively (P < .01). Plasma MIF levels elevated as early as 12 hours post-onset of STEMI and peaked rapidly within 24 hours, and remained elevated from about day 5 till day 9 during hospitalization. In multivariate analysis, MIF was associated with a decreased risk of MACEs occurrence in STEMI patients after adjustment for traditional cardiovascular risk factors [hazard ratio 0.81, (0.72-0.90), P < .001]. The ROC curve for MACEs was 0.72 (95% CI 0.62-0.80, P < .001) and 0.85 (95% CI 0.80-0.90, P < .001) using Framingham risk factors only and combined with MIF, individually.Measurement of MIF adds potential information for the early diagnosis of acute STEMI and significantly improves risk prediction of MACEs when added to a prognostic model with traditional Framingham risk factors.

Association between Type I interferon and depletion and dysfunction of endothelial progenitor cells in C57BL/6 mice deficient in both apolipoprotein E and Fas ligand

Patients with systemic lupus erythematosus (SLE) have a tremendously increased risk for cardiovascular disease (CVD), which could not be accounted in entirety by traditional Framingham risk factors. To study whether the accelerated atherosclerosis in SLE patients is mediated by type I interferon (IFN-I) through the regulation of endothelial progenitor cells (EPCs), we created a line of C57BL/6 mice with deficiency in both apolipoprotein E (ApoE−/−) and fas ligand (FasL−/−, gld.). As expected, the resultant gld. ApoE−/− mice exhibited both aggravated lupus-like disease and atherosclerosis under normal diet. Increased expression of IFN-I-stimulated genes (ISGs) was closely associated with depletion and dysfunction of EPCs, as well as with accelerated atherosclerotic lesion in gld. ApoE−/− mice. While only IFN-α instead of other interventions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IRS423 and IRS661, impaired EPC function in vitro. Mechanistically, activation or inhibition of the TLR7/9 signaling could modulate EPC number and function in vivo. Decreased proliferation rate and increased apoptotic rate of EPCs induced by IFN-α might contribute to the results to a certain extent. Thus, our data suggest that excessive expression of IFN-I through the activation of TLR7/9 signaling may induce accelerated atherosclerosis in lupus through the depletion or dysfunction of EPCs, suggesting that targeting IFN-I might have potential therapeutic effects on both lupus disease and premature atherosclerosis in SLE patients.

Serum Sortilin Associates With Aortic Calcification and Cardiovascular Risk in Men.

Genome-wide association studies and preclinical studies demonstrated a role of sortilin in lipid metabolism, inflammation, and vascular calcification-all cardiovascular risk factors. We evaluated the association of serum sortilin levels with the risk of major adverse cerebrovascular and cardiovascular events (MACCE) and the severity of abdominal aortic calcification (AAC). A cohort of community-dwelling men aged ≥50 years (n=830) was assessed. At baseline, sortilin levels were measured by ELISA, and AAC was assessed on lateral spine scans obtained by dual-energy X-ray absorptiometry. Men aged ≥60 years (n=745) were followed up prospectively for the incidence of MACCE. During the median follow-up of 7.9 years, 76 MACCE occurred. The unadjusted incidence of MACCE across increasing sortilin quartiles was 8.0, 7.4, 19.8, and 20.3 per 1000 person-years. In multivariate-adjusted analysis, sortilin associated with increased risk of MACCE (hazard ratio, 1.70 per SD; 95% confidence interval, 1.30-2.20; P<0.001). The third and fourth quartiles associated with 3.42-fold (95% confidence interval, 1.61-7.25; P<0.005) and 3.82-fold (95% confidence interval, 1.77-8.26; P<0.001) higher risk of MACCE compared with the first quartile. High sortilin also predicted MACCE independent of traditional Framingham risk factors. Higher sortilin associated with higher odds of severe AAC (score>5) after adjustment for confounders (odds ratio, 1.43 per SD; 95% confidence interval, 1.10-1.85; P<0.01). The highest sortilin quartile associated with 2-fold higher odds of severe AAC (versus 3 lower quartiles combined). After adjustment for low-density lipoprotein cholesterol, the odds of severe AAC remained significant. In older men, higher serum sortilin levels associated with higher MACCE risk and severe AAC independently of relevant confounders, including C-reactive protein and low-density lipoprotein cholesterol. This finding, however, needs to be validated in other cohorts.

Predictive value of galectin-3 for incident cardiovascular disease and heart failure in the population-based FINRISK 1997 cohort

ObjectivesGalectin-3 is an emerging biomarker playing an important, complex role in intracellular pathways of cardiovascular diseases and heart failure. We aimed therefore to investigate the predictive value of galectin-3 for incident cardiovascular disease and heart failure. MethodsGalectin-3 levels were measured in 8444 participants of the general population-based FINRISK 1997 cohort. Cox proportional hazards regression analyses, adjusting for traditional Framingham risk factors, prevalent valvular heart disease, eGFR (estimated glomerular filtration rate) as well as NT-proBNP, were used to examine the predictive power of galectin-3. Measurements of discrimination and reclassification using 10-fold cross-validation were performed to control for over-optimism. Cardiovascular death (CD), all-cause mortality, myocardial infarction (MI), ischemic stroke (hemorrhagic strokes were excluded) and heart failure (HF) were used as endpoints. ResultsDuring the follow-up of up to 15years there were in total 1136 deaths from any cause, 383 cardiac deaths, 359 myocardial infarctions, 401 ischemic strokes and 641 cases of incident heart failure. Hazard ratios (HR) were statistically significant for all-cause mortality (1.12, p<0.001), cardiac death (1.15, p=0.033) and heart failure (1.10, p=0.049). Statistical significance was lost when analyzing by gender except for all-cause mortality. No significant improvements were observed in model discrimination or overall reclassification upon inclusion of galectin-3. Compared to NT-proBNP, the predictive power of galectin-3 was weaker but both remained significant, independently of each other. ConclusionGalectin-3 levels were predictive for future cardiovascular events but improvements in discrimination and reclassifications were modest.

Calcification Propensity and Survival among Renal Transplant Recipients.

Calciprotein particle maturation time (T50) in serum is a novel measure of individual blood calcification propensity. To determine the clinical relevance of T50 in renal transplantation, baseline serum T50 was measured in a longitudinal cohort of 699 stable renal transplant recipients and the associations of T50 with mortality and graft failure were analyzed over a median follow-up of 3.1 years. Predictive value of T50 was assessed for patient survival with reference to traditional (Framingham) risk factors and the calcium-phosphate product. Serum magnesium, bicarbonate, albumin, and phosphate levels were the main determinants of T50, which was independent of renal function and dialysis vintage before transplant. During follow-up, 81 (12%) patients died, of which 38 (47%) died from cardiovascular causes. Furthermore, 45 (6%) patients developed graft failure. In fully adjusted models, lower T50 values were independently associated with increased all-cause mortality (hazard ratio, 1.43; 95% confidence interval, 1.11 to 1.85; P=0.006 per SD decrease) and increased cardiovascular mortality (hazard ratio, 1.55; 95% confidence interval, 1.04 to 2.29; P=0.03 per SD decrease). In addition to age, sex, and eGFR, T50 improved prognostication for all-cause mortality, whereas traditional risk factors or calcium-phosphate product did not. Lower T50 was also associated with increased graft failure risk. The associations of T50 with mortality and graft failure were confirmed in an independent replication cohort. In conclusion, reduced serum T50 was associated with increased risk of all-cause mortality, cardiovascular mortality, and graft failure and, of all tested parameters, displayed the strongest association with all-cause mortality in these transplant recipients.

Left ventricular global longitudinal strain is associated with novel uraemic toxins, obesity and arterial stiffness in chronic kidney disease

Background: Traditional Framingham risk factors are highly prevalent in patients with chronic kidney disease (CKD); however, they do not completely account for the accelerated cardiovascular (CV) risk in CKD. Recently global longitudinal strain (GLS) has emerged as a superior method for detecting, often subclinical, left ventricular(LV) systolic dysfunction as compared to ejection fraction(EF). This study aimed to determine the relationship between GLS, traditional risk factors and novel CKD-related risk factors in patients with CKD. Methods: This was a cross sectional study of patients with moderate CKD stages 3 and 4 (n=136). Clinical characteristics, anthropometric, biochemical data including markers of inflammation [C-reactive protein (CRP)], novel uraemic toxins [indoxyl sulphate(IS), p-cresyl sulphate(PCS)], and arterial stiffness [pulse wave velocity (PWV)] were measured. Inducible ischaemia was detected using exercise stress echo. Associations between GLS, traditional risk factors and CKD-related risk factors were explored using multivariate models. Results: The study population parameters included: mean age 59.4±9.8 years, 58% male, estimated glomerular filtration rate (eGFR) 44.4±10 ml/min/1.73m2, GLS -18.3±3.6% and EF 65.8%±7.8%. We demonstrated that GLS correlated with diabetes (r=0.21, p=0.01), history of heart failure (HF) (r=0.20, p=0.01), free IS (r=0.24, p=0.005) free PCS (r=0.23, p=0.007), body mass index (BMI) (r=0.28, p<0.001), and PWV (r=0.24, p=0.009). Following adjustment for demographic, baseline co-morbidities and laboratory parameters, GLS was independently associated with free IS, BMI and arterial stiffness (R2 for model = 0.30, p<0.0001). Conclusion: In the CKD cohort, LV systolic function, assessed using GLS, was associated with novel uraemic toxins, obesity and arterial stiffness.

Metabolic syndrome definitions and components in predicting major adverse cardiovascular events after kidney transplantation.

Metabolic syndrome (MetS) associates with cardiovascular risk post-kidney transplantation, but its ambiguity impairs understanding of its diagnostic utility relative to components. We compared five MetS definitions and the predictive value of constituent components of significant definitions for major adverse cardiovascular events (MACE) in a cohort of 1182 kidney transplant recipients. MetS definitions were adjusted for noncomponent traditional Framingham risk factors and relevant transplant-related variables. Kaplan-Meier, logistic regression, and Cox proportional hazards analysis were utilized. There were 143 MACE over 7447 patient-years of follow-up. Only the World Health Organization (WHO) 1998 definition predicted MACE (25.3 vs 15.5 events/1000 patient-years, P=0.019). Time-to-MACE was 5.5±3.5years with MetS and 6.8±3.9years without MetS (P<0.0001). MetS was independent of pertinent MACE risk factors except age and previous cardiac disease. Among MetS components, dysglycemia provided greatest hazard ratio (HR) for MACE (1.814 [95% confidence interval 1.26-2.60]), increased successively by microalbuminuria (HR 1.946 [1.37-2.75]), dyslipidemia (3.284 [1.72-6.26]), hypertension (4.127 [2.16-7.86]), and central obesity (4.282 [2.09-8.76]). MetS did not affect graft survival. In summary, although the WHO 1998 definition provides greatest predictive value for post-transplant MACE, most of this is conferred by dysglycemia and is overshadowed by age and previous cardiac disease.

Soluble vascular adhesion protein-1 predicts incident major adverse cardiovascular events and improves reclassification in a finnish prospective cohort study.

Vascular adhesion protein-1 (VAP-1) associates to subclinical atherosclerotic manifestations in young people, but its association to incident major adverse cardiovascular events (MACEs) and cardiovascular mortality in a general population is not known. We used a newly developed ELISA to measure soluble VAP-1 (sVAP-1) levels in 2775 participants (mean age, 60 years) from a prospective cohort study (the FINRISK 2002). During a mean follow-up of 9 years, 265 participants underwent a MACE, and these participants had higher levels of sVAP-1 than those without MACE (868 ng/mL and 824 ng/mL, respectively, P<0.001). In multivariate-adjusted Cox proportional hazard model including traditional Framingham risk factors (age, sex, systolic blood pressure, cholesterol, high-density lipoprotein cholesterol, smoking, prevalent diabetes mellitus, and antihypertensive treatment), sVAP-1 independently predicted incident MACE (P=0.0046) and MACE mortality (P=0.026). The impact of sVAP-1 in predicting the 9-year absolute risk of MACE was analyzed using integrated discrimination improvement and net reclassification improvement with 10-fold cross-validation. Inclusion of sVAP-1 in the Framingham model improved integrated discrimination improvement (P=0.042), and the clinical net reclassification improvement by correctly reclassifying 9% (P=0.0019) of people in the intermediate risk (5%-20%) group. sVAP-1 associated with increased risk of MACE and MACE mortality in people aged >50 years without prior MACE, and inclusion of sVAP-1 in the risk prediction model improved the clinical net reclassification improvement of incident MACE. Thus, sVAP-1 may be a potential new biomarker for cardiovascular diseases.

Effect of smoking and other traditional risk factors on the onset of coronary artery calcification: Results of the Heinz Nixdorf recall study

BackgroundCoronary artery calcium (CAC) indicates coronary atherosclerosis and can be present in very early stages of the disease. The conversion from no CAC to any CAC reflects an important step of the disease process as cardiovascular risk is increased in persons even with mildly elevated CAC. We sought to identify risk factors that determined incident CAC>0 in men and women from an unselected general population with a special focus on the role of smoking. MethodsAll 4814 persons that were initially studied in the Heinz Nixdorf Recall Study were invited to participate in the follow-up examination after 5.1 ± 0.3 years. All traditional Framingham risk factors were quantified using standard techniques. Smokers were categorized in never, former and present smokers. The CAC scores were measured from EBCT using the Agatston method. ResultsOverall, out of 342 men and 919 women with zero CAC at baseline, 107 (31.3%) men and 210 (22.9%) women had CAC>0 at second examination. In multivariable analysis, age (OR estimate per 5 years: 1.34 (95%CI: 1.21–1.47)), LDL cholesterol (per 10 mg/dL: 1.05 (95%CI: 1.01–1.10)), systolic blood pressure (per 10 mmHg: 1.19 (95%CI: 1.11–1.28)) and current smoking (1.49 (95%CI: 1.04–2.15)) were independent predictors of CAC onset. The probability of CAC onset steadily increased with age from 23.3% (men) and 15.3% (women) at age 45–49 years to 66.7% (men) and 42.9% (women) at age 70–74 years. The difference in age-dependent conversion rates was quantified by years between reaching a given level of CAC onset probability. We found a consistent pattern with respect to smoking status: presently (formerly) smoking middle-aged men convert to positive CAC 10 (5) years earlier than never smokers, for women (middle-aged to elderly) this time span is 8 (5) years. ConclusionSeveral traditional CVD risk factors are associated with CAC onset during 5 years follow-up. CAC onset is accelerated by approximately 10 (5) years for present (former) compared to never smokers.

Atherosclerosis in systemic lupus erythematosus.

Accelerated atherosclerosis and its long-term sequelae are a major cause of late mortality among patients with systemic lupus erythematosus (SLE). Traditional Framingham risk factors such as hypertension, hypercholesterolemia, diabetes, and smoking do not account in entirety for this risk. SLE specific factors like disease activity and duration, use of corticosteroids, presence of antiphospholipid antibodies, and others are important risk factors. SLE is considered a coronary heart disease; equivalent and aggressive management of all traditional risk factors is recommended. Despite their role in primary and secondary prevention in the general population, statins seem to have no effect on cardiovascular outcomes in adult or pediatric SLE populations. The use of hydroxychloroquine has a cardioprotective effect, and mycophenolate mofetil may reduce cardiovascular events based on basic science data and data from the transplant population. The role of vitamin D supplementation and treatment of hyperhomocysteinemia remain controversial, but due to the safety of therapy and the potential benefit, they remain as optional therapies.

GW24-e1860 Association between Lipoprotein-Associated Phospholipase A2 Activity and the Progression of Subclinical Atherosclerosis: Results from the CMCS-Beijing Study

ObjectivesLipoprotein-associated phospholipase A2 (Lp-PLA2) has been shown to be associated with an increased risk of clinical cardiovascular events. We aimed to investigate whether Lp-PLA2 is also associated with the progression...

381 Burden of Non-Alcoholic Fatty Liver Disease in the Veterans Administration

calculated, after adjustment for LDL, diabetes, metabolic syndrome, and BMI. RESULTS: When hepatic steatosis was added to the traditional Framinghammodel, it was independently associated with greater risk of CCS.100 {Odds ratio 2.85, 95% CI (1.26-6.44) p=0.012}. Compared to the Framingham model, the addition of hepatic steatosis non-significantly increased the c-statistic (0.776 vs 0.789, p=0.31). However, there was a significant value of IDI (Absolute IDI=0.17, Relative IDI=13.6%, p=0.045). This indicated that the spread in predicted probabilities between events and non-events separated by an additional 14%, after inclusion of hepatic steatosis . In addition, CCS .100 was independently associated with an increased risk of development of hepatic steatosis {0dds ratio 2.4, 95% CI (1.08-5.54) p= 0.03} CONCLUSION: Hepatic steatosis is an independent and a strong predictor of CCS.100 Agatston units in asymptomatic patients. It is associated with an increased risk of CAD beyond that expected from traditional Framingham risk factors or metabolic syndrome. The converse that significant CAD is an independent risk factor for hepatic steatosis was also demonstrated. Additional studies may determine the value of hepatic steatosis in models for comprehensive cardiac risk assessment.

Pulse Pressure and Subclinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis

Brachial pulse pressure (PP) has been found to be associated with markers of subclinical cardiovascular disease, including carotid intima-media thickness and left-ventricular mass index (LVMI), but it is unclear whether these associations are independent of traditional cardiovascular risk factors and of the steady, nonpulsatile component of blood pressure (BP). Moreover, it is unknown whether these associations are modified by gender, age, or race/ethnicity. We used multivariate linear regression models to assess the relationship between brachial PP and three markers of subclinical cardiovascular disease (CVD) (common carotid intima-media thickness (CC-IMT), internal carotid intima-media thickness (IC-IMT), and LVMI) in four race/ethnic groups in the Multi-Ethnic Study of Atherosclerosis. The models were adjusted for traditional Framingham risk factors (age, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, diabetes, smoking status), use of lipid-lowering medication, use of antihypertensive medication, study site, and mean arterial pressure (MAP). The assessment was done on 6,776 participants (2,612 non-Hispanic white, 1,870 African-American, 1,494 Hispanic, and 800 Chinese persons). The associations between brachial PP and CC-IMT, IC-IMT, and LVMI were significant in fully adjusted models. The three subclinical markers also showed significant interactions with gender (P < 0.0001), with stronger interactions in men. There was an interaction with age for LVMI (P = 0.004) and IC-IMT (P = 0.008). Race/ethnicity modified the association of PP with CC-IMT. Brachial PP was independently associated with subclinical CVD after adjustment for cardiovascular risk factors and mean arterial pressure (MAP). The strength of the association differed significantly for strata of gender, age, and race/ethnicity.

Relationship between obesity and unrecognized myocardial infarction: a EuroCMR multi-center study

Background Obesity is a major public health issue given its high cardiovascular morbidity and mortality. However, whether obesity predicts cardiovascular disease independent from traditional Framingham risk factors is controversial [1]. Delayed-enhancement CMR (DE-CMR) allows for sensitive and specific detection of unrecognized MI, which appears associated with adverse prognosis similar to clinically recognized MI. We examined the relationship between obesity and the prevalence of unrecognized myocardial scar (UScar) and/ or unrecognized MI (UMI) as determined by DE-CMR.