Risk Score Components Research Articles

Circulating MicroRNA-19 and cardiovascular risk reduction in response to weight-loss diets

MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (β[SE]=0.33 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.3 [0.12], P=0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction=0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction=0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity. In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. ClinicalTrials.gov NCT00072995.

Blood pressure measurements during treadmill exercise testing and the risk for the future development of atrial fibrillation.

Hypertension is a well-established risk factor for the onset and progression of atrial fibrillation (AF). Blood pressure (BP) measurements during routine exercise stress testing (EST) may identify subjects at increased risk for developing AF. We performed a retrospective analysis of treadmill EST carried out using the Bruce protocol in patients aged ≥40 years without a history of AF (n = 17,617; 42% women). BP was measured at rest, peak exercise, and 2-min recovery and analyzed for its association with the risk for developing AF. During a mean follow-up of 7 years, AF was documented in 4.5% of the patients. The incidence rate of AF per 1000 person-years increased with the rise in CHA2DS2VASc scores (3.26 for a Score=0 to 19.78 for scores ≥6). In a multivariate analysis, adjusting for risk score components and exercise capacity, systolic BP measurements taken at rest (≥130 vs. ≤110 mmHg), peak exercise (>170 vs. ≤150 mmHg), and recovery (>150 vs. ≤130 mmHg) were associated with an increased risk for AF: the hazard ratios (HRs) were 1.56 (95% CI, 1.30-1.87), 1.21 (1.01-1.45), and 1.33 (1.10-1.62), respectively. Similarly, diastolic BP measurements taken at rest (≥90 vs. <80 mmHg), peak exercise (≥100 vs. <90 mmHg), and recovery (>90 vs. ≤80 mmHg) were associated with an increased risk for AF: the HRs were 1.80 (1.36-2.38), 2.08 (1.28-3.37), and 1.56 (0.81-3.02), respectively. The association of exercise BP with AF was further observed when the BPs were analyzed as continuous variables and in subjects without a baseline diagnosis of hypertension. In conclusion, systolic and diastolic BP taken at the rest, peak exercise and recovery phases of EST may provide independent predictive information regarding future risk for developing AF.

Clinical Frailty Scale classes are independently associated with 6-month mortality for patients after acute myocardial infarction.

AimsData on the prognostic value of frailty to guide clinical decision-making for patients with myocardial infarction (MI) are scarce. To analyse the association between frailty classification, treatment patterns, in-hospital outcomes, and 6-month mortality in a large population of patients with MI.Methods and resultsAn observational, multicentre study with a retrospective analysis of prospectively collected data using the SWEDEHEART registry. In total, 3381 MI patients with a level of frailty assessed using the Clinical Frailty Scale (CFS-9) were included. Of these patients, 2509 (74.2%) were classified as non-vulnerable non-frail (CFS 1–3), 446 (13.2%) were vulnerable non-frail (CFS 4), and 426 (12.6%) were frail (CFS 5–9). Frailty and non-frail vulnerability were associated with worse in-hospital outcomes compared with non-frailty, i.e. higher rates of mortality (13.4% vs. 4.0% vs. 1.8%), cardiogenic shock (4.7% vs. 2.5% vs. 1.9%), and major bleeding (4.5% vs. 2.7% vs. 1.1%) (all P < 0.001), and less frequent use of evidence-based therapies. In Cox regression analyses, frailty was strongly and independently associated with 6-month mortality compared with non-frailty, after adjustment for age, sex, the GRACE risk score components, and other potential risk factors [hazard ratio (HR) 3.32, 95% confidence interval (CI) 2.30–4.79]. A similar pattern was seen for vulnerable non-frail patients (fully adjusted HR 2.07, 95% CI 1.41–3.02).ConclusionFrailty assessed with the CFS was independently and strongly associated with all-cause 6-month mortality, also after comprehensive adjustment for baseline differences in other risk factors. Similarly, non-frail vulnerability was independently associated with higher mortality compared with those with preserved functional ability.

A Retrospective Exploratory Analysis on Cardiovascular Risk and Cognitive Dysfunction in Multiple Sclerosis.

Background. Cardiovascular comorbidities have been associated with cognitive decline in the general population. Objectives. To evaluate the associations between cardiovascular risk and neuropsychological performances in MS. Methods. This is a retrospective study, including 69 MS patients. For all patients, we calculated the Framingham risk score, which provides the 10-year probability of developing macrovascular disease, using age, sex, diabetes, smoking, systolic blood pressure, and cholesterol levels as input variables. Cognitive function was examined with the Brief International Cognitive Assessment for MS (BICAMS), including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). Results. Each point increase of the Framingham risk score corresponded to 0.21 lower CVLT-II score. Looking at Framingham risk score components, male sex and higher total cholesterol levels corresponded to lower CVLT scores (Coeff = −8.54; 95%CI = −15.51, −1.57; and Coeff = −0.11; 95%CI = −0.20, −0.02, respectively). No associations were found between cardiovascular risk and SDMT or BVMT-R. Conclusions. In our exploratory analyses, cardiovascular risk was associated with verbal learning dysfunction in MS. Lifestyle and pharmacological interventions on cardiovascular risk factors should be considered carefully in the management of MS, given the possible effects on cognitive function.

Evaluating the Validity of Risk Scoring in Predicting Pacemaker Rates following Transcatheter Aortic Valve Replacement.

Introduction Requirement of permanent pacemaker (PPM) implantation is a known and common postoperative consequence of transcatheter aortic valve replacement (TAVR). The Emory risk score has been recently developed to help risk stratify the need for PPM insertion in patients undergoing TAVR with SAPIEN 3 valves. Our aim was to assess the validity of this risk score in our patient population, as well as its applicability to patients receiving self-expanding valves. Methods We conducted a retrospective review of 479 TAVR patients without preoperative pacemakers from November 2016 through December 2018. Preoperative risk factors included in the Emory risk score were collected for each patient: preoperative QRS, preoperative right bundle branch block (RBBB), preoperative syncope, and degree of valve oversizing. Multivariable analysis of the individual variables within the scoring system to identify predictors of PPM placement was performed. The predictive discrimination of the risk score for the risk of PPM placement after TAVR was assessed with the area under the receiver operating characteristic curve (AUC). Results Our results demonstrated that, of the 479 patients analyzed, 236 (49.3%) received balloon-expandable valves and 243 (50.7%) received self-expanding valves. Pacemaker rates were higher in patients receiving self-expanding valves than those receiving balloon-expandable valves (25.1% versus 16.1%, p=0.018). The Emory risk score showed a moderate correlation with pacemaker requirement in patients receiving each valve type, with AUC for balloon-expandable and self-expanding valves of 0.657 and 0.645, respectively. Of the four risk score components, preoperative RBBB was the only predictor of pacemaker requirement with an AUC of 0.615 for both balloon-expandable and self-expanding valves. Conclusion. In our cohort, the Emory risk score had modest predictive utility for PPM insertion after balloon-expandable and self-expanding TAVR. The risk score did not offer better discriminatory utility than that of preoperative RBBB alone. Understanding the determinants of PPM insertion after TAVR can better guide patient education and postoperative management.

A comparison between body mass index and waist circumference for identifying continuous metabolic syndrome risk score components in Iranian school-aged children using a structural equation modeling approach: the CASPIAN-V study.

The purpose of this study was to investigate the association of anthropometric indices with continuous metabolic syndrome (cMetS) risk score components in a large population-based sample of children and adolescents. This multi-centric study was performed on 3843 students aged 7-18years who were selected by multistage, stratified cluster sampling method from 30 provinces of Iran. Demographic, anthropometric and biochemical factors were obtained and standardized residuals (z-scores) were calculated for MetS components. A structural equation modeling approach was applied to evaluate the relationships among the study variables and to implement the subsequent structural modeling. The mean age of the participants (52.3% boys) was 12.4 ± 3.05years. Standardized scores of body mass index (ZBMI) and waist circumference (ZWC) had a direct effect on standardized scores of mean arterial pressure (ZMAP) (0.23 and 0.24 in boys and 0.22 and 0.23 in girls, respectively) and triglyceride (ZTG) (0.07 and 0.04 in boys and 0.02 and 0.06 in girls, respectively), but the effect of ZWC was stronger than ZBMI on these variables. Age, socioeconomic status and sedentary behaviors showed a positive direct effect on ZWC (0.01, 0.05 and 0.07 in boys and 0.05, 0.08 and 0.002 in girls, respectively). These variables induced indirect effects on cMets risk score components through ZWC. The magnitude of association between WC and continuous metabolic syndrome risk score components was higher compared to BMI in school-aged children, emphasizing on paying more attention to central obesity in childhood. Level V, cross-sectional descriptive study.

Incremental prognostic value of renal function for stroke prediction in atrial fibrillation

BackgroundRenal function has been associated with an increased stroke risk in patients with atrial fibrillation (AF). However, whether renal function incrementally adds to risk prediction in both anticoagulated and non-anticoagulated patients with AF is unclear. MethodsWe used data from the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF)—a national, prospective, outpatient AF registry in patients aged >18 years (2010−2011). The association between baseline renal function and risk of stroke/systemic embolism (SSE) was evaluated in proportional hazards models adjusting for stroke risk score components. We compared discrimination of 2-year outcomes using C-indices and evaluated calibration by comparing event rates in ORBIT-AF to published rates from an external clinical trial population (ROCKET AF) and an observational cohort (ATRIA). ResultsAmong 9743 patients included in the analysis, the median age was 75 years (interquartile range [IQR] 67–82), 89.5% were white, 43% were female, and 76% were taking oral anticoagulation (OAC). Over a median follow-up of 2.3 years, 214 SSE events occurred (1.00 per 100 patient-years). Continuous creatinine clearance (CrCl) was not associated with SSE risk after adjusting for other clinical factors (components of CHADS2 or CHA2DS2-VASc). Discrimination for predicting stroke (C-index; 95% CI) was similar for R2CHADS2 (0.65; 0.61–0.69), CHADS2 (0.65; 0.61–0.69), and CHA2DS2-VASc (0.66; 0.62–0.70). Conclusions and relevanceIn a community patient population with AF, renal dysfunction was not independently associated with embolic risk beyond other established risk factors in either OAC-treated or untreated patients. Additional study is needed to identify clinical factors that incrementally add to stroke risk prediction.

Significant relationships between a simple marker of redox balance and lifestyle behaviours; Relevance to the Framingham risk score.

Oxidative stress has been closely linked to the progressive cell damage associated with emerging non-communicable disease (NCDs). Early detection of these biochemical abnormalities before irreversible cell damage occurs may therefore be useful in identifying disease risk at an individual level. In order to test this hypothesis, this study assessed the relationship between a simple measure of redox status and lifestyle risk factors for NCDs, and the population-based risk score of Framingham. In a cross-sectional study design, 100 apparently healthy middle-aged males (n = 48) and females (n = 52) were asked to complete a comprehensive lifestyle assessment questionnaire, followed by body fat percentage and blood pressure measurements, and blood collection. The ratio of plasma total antioxidant capacity to hydroperoxide (TAC/HPX) was used as an index of redox balance. One-way ANOVA and multiple linear regression analysis were performed to analyse the association between TAC/HPX, lifestyle components and other plasma biomarkers. The TAC/HPX ratio was higher in males compared to females (t96 = 2.34, P = 0.021). TAC/HPX was also lower in participants with poor sleep quality (t93 = 2.39, P = 0.019), with high sleep apnoea risk (t62.2 = 3.32, P = 0.002), with high caffeine (F(2, 93) = 3.97, P = 0.022) and red meat intake (F(2, 93) = 5.55, P = 0.005). These associations were independent of gender. Furthermore, the TAC/HPX ratio decreased with increasing body fat percentage (F(2, 95) = 4.74, P = 0.011) and depression score (t94 = 2.38, P = 0.019), though these associations were dependent on gender. Importantly, a negative association was observed between TAC/HPX levels and the Framingham risk score in both males (r(45) = -0.39, P = 0.008) and females (r(50) = -0.33, P = 0.019) that was independent of other Framingham risk score components. Findings from this study suggests that a relatively simple measure of redox balance such as the TAC/HPX ratio may be a sensitive indicator of redox stress, and may therefore serve as a useful biomarker for assessing an individual’s specific NCD risk linked to unhealthy lifestyle practices.

Comparing SF-36® scores versus biomarkers to predict mortality in primary cardiac prevention patients

BackgroundRisk stratification plays an important role in evaluating patients with no known cardiovascular disease (CVD). Few studies have investigated health-related quality of life questionnaires such as the Medical Outcomes Study Short Form-36 (SF-36®) as predictive tools for mortality, particularly in direct comparison with biomarkers. Our objective is to measure the relative effectiveness of SF-36® scores in predicting mortality when compared to traditional and novel biomarkers in a primary prevention population. Methods7056 patients evaluated for primary cardiac prevention between January 1996 and April 2011 were included in this study. Patient characteristics included medical history, SF-36® questionnaire and a laboratory panel (total cholesterol, triglycerides, HDL, LDL, ApoA, ApoB, ApoA1/ApoB ratio, homocysteine, lipoprotein (a), fibrinogen, hsCRP, uric acid and urine ACR). The primary outcome was all-cause mortality. ResultsA low SF-36® physical score independently predicted a 6-fold increase in death at 8years (above vs. below median Hazard Ratio [95% confidence interval] 5.99 [3.86–9.35], p<0.001). In a univariate analysis, SF-36® physical score had a c-index of 0.75, which was superior to that of all the biomarkers. It also carried incremental predictive ability when added to non-laboratory risk factors (Net Reclassification Index=59.9%), as well as Framingham risk score components (Net Reclassification Index=61.1%). Biomarkers added no incremental predictive value to a non-laboratory risk factor model when combined to SF-36 physical score. ConclusionThe SF-36® physical score is a reliable predictor of mortality in patients without CVD, and outperformed most studied traditional and novel biomarkers. In an era of rising healthcare costs, the SF-36® questionnaire could be used as an adjunct simple and cost-effective predictor of mortality to current predictors.

GRACE risk score: Sex-based validity of in-hospital mortality prediction in Canadian patients with acute coronary syndrome

BackgroundAlthough there are sex differences in management and outcome of acute coronary syndromes (ACS), sex is not a component of Global Registry of Acute Coronary Events (GRACE) risk score (RS) for in-hospital mortality prediction. We sought to determine the prognostic utility of GRACE RS in men and women, and whether its predictive accuracy would be augmented through sex-based modification of its components. MethodsCanadian men and women enrolled in GRACE and Canadian Registry of Acute Coronary Events were stratified as ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation ACS (NSTE-ACS). GRACE RS was calculated as per original model. Discrimination and calibration were evaluated using the c-statistic and Hosmer-Lemeshow goodness-of-fit test, respectively. Multivariable logistic regression was undertaken to assess potential interactions of sex with GRACE RS components. ResultsFor the overall cohort (n=14,422), unadjusted in-hospital mortality rate was higher in women than men (4.5% vs. 3.0%, p<0.001). Overall, GRACE RS c-statistic and goodness-of-fit test p-value were 0.85 (95% CI 0.83–0.87) and 0.11, respectively. While the RS had excellent discrimination for all subgroups (c-statistics >0.80), discrimination was lower for women compared to men with STEMI [0.80 (0.75–0.84) vs. 0.86 (0.82–0.89), respectively, p<0.05]. The goodness-of-fit test showed good calibration for women (p=0.86), but suboptimal for men (p=0.031). No significant interaction was evident between sex and RS components (all p>0.25). ConclusionsThe GRACE RS is a valid predictor of in-hospital mortality for both men and women with ACS. The lack of interaction between sex and RS components suggests that sex-based modification is not required.

Abstract P054: Translation of Diabetes Interventions Into Community Settings: 12-month Results of the Lifestyle Intervention for the Treatment of Diabetes Trial

Objective: Professionally delivered intensive lifestyle weight loss interventions (LWLs) have been shown to improve weight status and CVD risk factors among adults with diabetes in rigorously conducted trials. We report the 12-month results of a trial in which a LWL was delivered by community health workers (CHWs), among predominantly minority and/or lower socioeconomic status participants. Research Design and Methods: We recruited overweight or obese adults with diabetes and without CVD primarily via review of electronic medical records and physician referrals. The study featured two 12-month interventions: (1) LWL delivered by trained CHWs in community settings which involved weekly group sessions and 3 individual sessions with an interventionist, or (2) diabetes self-management education (DSM) comprised of 12 monthly group sessions delivered at a primary care clinic. The main outcome was change in United Kingdom Prospective Diabetes Study (UKPDS) estimated 5-year CVD risk at 12 months; secondary outcomes included weight loss, UKPDS risk score components (hemoglobin A1c, blood pressure, lipids) and use of medications affecting these components. Results: We screened 1102 and randomized 260 adults (age range 23-83, mean 55.9, 67% female, 48% black, 52% &lt; college degree, mean A1c 7.6%, 37.3% A1c&lt;7%, mean BMI 37.7 kg/m 2 ). Baseline demographic and CVD risk factors were equally distributed between the 2 groups of 130 participants each. At 12 months, 92.3% of LWL and 98% of DSM participants were retained. There was not a significant difference in 5-year UKPDS estimated CVD risk by arm (increased from 5.1% to 5.9% in LWL, and 5.5% to 6.1% in DSM, group comparison p=0.61). There was no evidence of effect modification by the pre-specified parameters of gender, race/ethnicity or baseline BMI. Follow-up A1c, SBP, and total cholesterol did not significantly differ by arm. Weight loss was greater in LWL compared to DSM participants (mean of 3.2% vs 1.1% of total body weight, p=0.02). At least 5% weight loss was achieved by 30.8% of LWL and 18.1% of DSM participants (p=0.02). Among LWL participants, 11.7% discontinued their diabetes medication compared to only 1.6% of DSM participants (p=0.005); 87.5% of those who discontinued medication had achieved an A1c&lt;7% at follow-up, compared to 36.8% who continued using diabetes medication. Hypertension and lipid lowering medication use did not differ by arm. Conclusions: In a diverse sample of adults with diabetes, a CHW-delivered LWL intervention produced greater weight loss compared to a monthly DSM education, but did not appreciably alter 5-year UKPDS-estimated CVD risk, A1c, or CVD risk factors. The average weight loss achieved (3.2%) may not have been sufficient to produce meaningful changes in metabolic functioning and CVD risk factors, however, some participants in both interventions achieved improved glycemic control without use of medications.

Aptamer-Based Proteomic Profiling Reveals Novel Candidate Biomarkers and Pathways in Cardiovascular Disease.

Single-stranded DNA aptamers are oligonucleotides of ≈50 base pairs in length selected for their ability to bind proteins with high specificity and affinity. Emerging DNA aptamer-based technologies may address limitations of existing proteomic techniques, including low sample throughput, which have hindered proteomic analyses of large cohorts. To identify early biomarkers of myocardial injury, we applied an aptamer-based proteomic platform that measures 1129 proteins to a clinically relevant perturbational model of planned myocardial infarction (PMI), patients undergoing septal ablation for hypertrophic cardiomyopathy. Blood samples were obtained before and at 10 and 60 minutes after PMI, and protein changes were assessed by repeated-measures analysis of variance. The generalizability of our PMI findings was evaluated in a spontaneous myocardial infarction cohort (Wilcoxon rank-sum). We then tested the platform's ability to detect associations between proteins and Framingham Risk Score components in the Framingham Heart Study, performing regression analyses for each protein versus each clinical trait. We found 217 proteins that significantly changed in the peripheral vein blood after PMI in a derivation cohort (n=15; P<5.70E-5). Seventy-nine of these proteins were validated in an independent PMI cohort (n=15; P<2.30E-4); >85% were directionally consistent and reached nominal significance. We detected many protein changes that are novel in the context of myocardial injury, including Dickkopf-related protein 4, a WNT pathway inhibitor (peak increase 124%, P=1.29E-15) and cripto, a growth factor important in cardiac development (peak increase 64%, P=1.74E-4). Among the 40 validated proteins that increased within 1 hour after PMI, 23 were also elevated in patients with spontaneous myocardial infarction (n=46; P<0.05). Framingham Heart Study analyses revealed 156 significant protein associations with the Framingham Risk Score (n=899), including aminoacylase 1 (β=0.3386, P=2.54E-22) and trigger factor 2 (β=0.2846, P=5.71E-17). Furthermore, we developed a novel workflow integrating DNA-based immunoaffinity with mass spectrometry to analytically validate aptamer specificity. Our results highlight an emerging proteomics tool capable of profiling >1000 low-abundance analytes with high sensitivity and high precision, applicable both to well-phenotyped perturbational studies and large human cohorts, as well.

Abstract 17261: Comparing SF-36 Scores versus Traditional and Novel Biomarkers to Predict Mortality in Primary Cardiac Prevention Patients

Background: Risk stratification plays an important role in evaluating patients with no known cardiovascular disease (CVD). Few studies have investigated health-related quality of life questionnaires such as the Medical Outcomes Study Short Form-36 (SF-36 ® ) as predictive tools for mortality, particularly in direct comparison with biomarkers. Our objective is to measure the relative effectiveness of SF-36 ® scores in predicting mortality when compared to traditional and novel biomarkers in a primary prevention population. Methods: The study analyzed patient characteristics and all-cause mortality among 7056 consecutive patients evaluated for primary cardiac prevention in a cardiology clinic at Cleveland Clinic between January 1996 and April 2011. Patient characteristics included history and physical examination, SF-36 ® questionnaire and a laboratory panel consisting of total cholesterol, triglycerides, HDL, LDL, apolipoprotein A, apolipoprotein B, fasting glucose, hemoglobin A1c, creatinine, homocysteine, lipoprotein(a), fibrinogen, high-sensitivity C-reactive protein, uric acid and urine albumin:creatinine ratio. The primary outcome was all-cause mortality. Results: A low SF-36 ® physical score independently predicted a 6-fold increase in death at 8 years (above vs. below median Hazard Ratio [95% confidence interval] 5.99 [3.86-9.35], p&lt;0.001). In a univariate analysis, SF-36 ® physical score had a c-index of 0.75, which was superior to that of all the biomarkers. It also carried incremental predictive ability when added to non-laboratory risk factors (Net Reclassification Index = 45.4%), as well as Framingham risk score components (Net Reclassification Index = 59.4%). Biomarkers added no incremental predictive value to a non-laboratory risk factor model when combined to SF-36 physical score. Conclusions: The SF-36 ® physical score is a reliable predictor of mortality in patients without CVD, and outperformed most studied traditional and novel biomarkers. In an era of rising healthcare costs, the SF-36 ® questionnaire could be used as a simple and cost-effective predictor of mortality.

Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score in Young Adults Predicts Coronary Artery and Abdominal Aorta Calcium in Middle Age: The CARDIA Study.

We explored whether, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary and abdominal risk scores measured at 18 to 30 years of age and changes in these scores would more strongly predict coronary artery calcium (CAC) and abdominal aortic calcium (AAC) assessed 25 years later, than scores measured 25 years later. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3008 participants had measurements of risk score components at 5-year intervals beginning at 18 to 30 years of age. CAC and AAC were assessed at 43 to 55 years of age. Odds ratios (ORs) for the presence and extent of CAC/AAC per/point higher score and c-statistics for predicting CAC/AAC were calculated. The prevalence of CAC was 28% and AAC was 53%. For each 1 point higher PDAY score, the odds of CAC were higher using baseline scores than year 25 scores (OR, 1.29; 95% confidence interval [CI], 1.25-1.33 versus OR, 1.12; 95% CI, 1.11-1.14). For AAC, ORs at years 0 and 25 were similar (OR, 1.29; 95% CI, 1.24-1.34 versus OR, 1.22; 95% CI, 1.19-1.26). C-statistic for CAC prediction was higher at year 0 than year 25 (0.731 versus 0.705) but similar at years 0 and 25 for AAC (0.665 versus 0.670). ORs for CAC were highest at baseline, and, for AAC, ORs were highest at year 10. Including change in PDAY scores with baseline scores improved prediction. Atherosclerosis risk and change in risk assessed in young adulthood years before subclinical atherosclerosis imaging provide strong prediction of future subclinical atherosclerosis. CAC and AAC reflect chronic risk exposure in addition to risk measured at the time of study.

Abstract 12640: Urine Albumin-to-Creatinine Ratio Outperforms Other Biomarkers in Predicting Death

Background: Risk stratification plays an important role in evaluating patients with no known cardiovascular disease (CVD). Few studies have investigated the role of high-normal urine albumin-to-creatinine ratio as a predictive tool for mortality (normal range defined as &lt;30 mg/g). Our study aims to measure the relative effectiveness of a high-normal urine albumin-to-creatinine ratio in predicting mortality when compared to traditional biomarkers in a primary prevention population. Methods: 8123 consecutive primary prevention patients evaluated at the Cleveland Clinic Preventive Cardiology Clinic between January 1996 and September 2012 were included in the analysis. Of this patient cohort, 12% had diabetes while 43% had hypertension. The primary outcome was all-cause mortality. Results: A urine albumin-to-creatinine ratio above the median (&gt;6 mg/g) independently predicts a 4.4-fold increase in death at 8 years (Hazard Ratio [95% confidence interval] 4.45 [2.56-7.73], p&lt;0.001). When compared to traditional biomarkers such as hsCRP, homocysteine, fibrinogen and lipids, urine albumin-to-creatinine ratio was a better predictor of mortality with a C-index of 0.72. The urine albumin-to-creatinine ratio also improved the predictive ability of the Framingham risk score components, with an increase in C-index from 0.77 to 0.84, and a Net Reclassification Index (NRI) of 64%. Conclusions: The urine albumin-to-creatinine ratio is a reliable predictor of mortality in a primary cardiac prevention population. In an era of rising medical costs, the urine albumin-to-creatinine could be used as a relatively non-costly predictor of mortality in this population.

Comparative prognostic utility of conventional and novel lipid parameters for cardiovascular disease risk prediction: Do novel lipid parameters offer an advantage?

Comparative data on the prognostic utility of novel lipid parameters vs. conventional lipid parameters in predicting coronary events are scant. We sought to compare the predictive value of various lipid measures for coronary events and to further examine the incremental value of novel lipid parameters over traditional cardiovascular risk factors in estimating cardiac risk. We performed a post-hoc analysis of the National Heart Lung and Blood Institute limited access dataset of Multi-Ethnic Study of Atherosclerosis subjects (n = 6693). The lipid measures considered in the estimation of coronary risk were conventional and novel lipid parameters, the latter included total low-density lipoprotein (LDL), high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL)-particle concentrations (LDL-p, HDL-p and VLDL-p), LDL-p/HDL-p ratio, and LDL-p subfractions. The outcome measured was occurrence of any coronary event (CE) that included myocardial infarction, resuscitated cardiac arrest, cardiac death, and angina. During an average follow up of 4.5 years, 228 patients developed coronary events. In the multivariate Cox proportional hazards model, TC/HDL-c (HR: 3.27; 95% CI: 1.95 to 5.47, P < .0001) was a stronger predictor of CE. Among the novel lipid parameters, LDL-p/HDL-p (hazard ratio 2.84; 95% confidence interval 1.89 to 4.26; P < .0001) was a powerful independent predictor of CE. The c-statistics were similar for both LDL-p/HDL-p and TC/HDL-c ratios (0.60). The addition of LDL-p/HDL-p ratio to the Framingham risk score components resulted in a very small increase in the overall C statistic. In our large study cohort, a predictive model for future coronary events incorporating the best-available novel lipid parameter (LDL-p/HDL-p ratio) was comparable with the same model that incorporated conventional lipid ratios such as the TC/HDL-c ratio . The use of LDL-p/HDL-p ratio did not appear to offer incremental value over more traditional risk prediction models.

S13 The primary results of the MOSAIC trial: does CPAP for minimally symptomatic OSA reduce daytime sleepiness or calculated vascular risk?

IntroductionCPAP treatment for symptomatic OSA improves sleepiness, and reduces vascular risk by reducing blood pressure (BP) and cholesterol. Minimally symptomatic OSA is far more prevalent than symptomatic disease, and treatment...

Prospective analysis of personality and behavioral vulnerabilities and gender influences in the later development of disordered eating.

This article presents the 2-year findings of a prospective investigation of the precursors to the later development of an eating disorder in adolescents. The sample consisted of 852 girls and 815 boys who began to study in Grades 7-10 and participated for 3 consecutive years. For both genders, the strongest predictors of Year 3 risk status were Years 1 and 2 risk scores. When the effects of Year 1 and Year 2 risk were controlled, race (Caucasian) and poor interoceptive awareness at Year 2 were significant predictors of disordered eating at Year 3 for girls. Previous risk status was the only significant predictor of Year 3 risk for boys. Gender difference evaluations in the risk score components indicated that a significantly greater proportion of girls than boys endorsed behaviors that were similar to eating disorder diagnostic criteria. Poor interoceptive awareness may provide a vulnerability for eating disorders; possible pathways were discussed.