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Background: Loss of renal function is accompanied by a progressive increase in markers of inflammation; it is unknown whether they share common genetic pathways. Study Design: We evaluated the shared heritability of estimated glomerular filtration rate (eGFR) and markers of inflammation and endothelial activation in 524 twin males from the Vietnam Era Twin Registry; 9 twins were excluded due to incomplete or incorrect data. Models were adjusted for age, race, body mass index, smoking, hypertension, diabetes mellitus, prior coronary artery disease and intercurrent medications. Results: The mean eGFR was 89 ± 13 ml/min/1.73 m2 (range 35–146); eGFR, intracellular adhesion molecule (ICAM) and TNF-α receptor (TNF-αR) were moderately heritable (all ∼50%), while IL-6 receptor (IL-6R) and P-selectin were highly heritable (68 and 76%, respectively). IL-6R and TNF-αR showed a significant inverse association with eGFR (p = 0.04 and p < 0.0001) while the association with ICAM and P-selectin was direct (p = 0.001 and p = 0.06). Bivariate structural equation models showed that the association between eGFR and biomarkers was due to unique environmental factors and there were no shared genetic pathways. Conclusion: We found no shared genetic pathways between renal function and inflammation. Thus, increased inflammation represents a response to declining renal function rather than being a mechanism contributing to renal deterioration.

Objectives: We sought to identify baseline clinical, angiographic, and hemodynamic variables associated with optimal bare-metal stent (BMS) deployment, allowing selection of patients for treatment with BMS. Background: Patients with fractional flow reserve (FFR) >0.90 after BMS have low (0.90 and MACE after BMS. Methods: In 586 patients from the multicenter post-BMS FFR registry, we developed multivariable logistic regression models to identify clinical, angiographic, and hemodynamic variables associated with post-stent FFR ≥0.90 and 6-month MACE. Results: After adjusting for potential confounders, baseline FFR (odds ratio [OR]: 5.0) and stent diameter (OR: 2.5 per millimeter) were predictive of post-stent FFR >0.90. Lower FFR (OR: 7.8); smaller stent diameter (OR: 3.7 per millimeter); longer stent length (OR: 1.0 per millimeter); and larger minimal luminal diameter (OR: 2.2 per millimeter) were predictors of MACE. In patients receiving 3-mm diameter stents, baseline FFR >0.70 yielded significantly higher likelihood of achieving post-stent FFR >0.90 than baseline FFR ≤0.70 (77% vs. 63%, p < 0.05); and in patients receiving 0.70 (40% vs. 15% vs. 13%, p < 0.05). Conclusions: In patients receiving BMS, baseline FFR and stent diameter are predictors of post-stent FFR >0.90; and baseline FFR, stent diameter, stent length, and minimal luminal diameter are predictors of MACE. These variables may allow selection of patients who will have excellent results with BMS.

Elevated levels of postprandial triacylglycerol-rich lipoproteins (ppTRLs) are atherogenic. Patients with type 2 diabetes mellitus (T2DM) have exaggerated postprandial lipemia associated with elevation or prolonged residence of ppTRL remnants. We examined whether dietary fatty acid compositions (DFACs) decrease atherogenic lipid profiles in ppTRL subfractions in T2DM Chinese patients. A single-blind randomized controlled trial was conducted among 28 T2DM patients. Patients consumed 1 of 3 standardized DFAC-specific fat meals: equidominant (1:1:1), polyunsaturated fatty acid (PUFA)-dominant (PUFA-D, 1:1.7:2.3), or monounsaturated fatty acid (MUFA)-dominant (MUFA-D, 1:1.7:1.2) meals. Numbers in parenthesis, respectively, represent the ratio of saturated fatty acids, MUFA, and PUFA to saturated fatty acids. The MUFA-D meal was the control. Triacylglycerol and cholesterol levels were measured in Svedberg flotation rate (S(f)) greater than 400, S(f) 60 to 400, S(f) 20 to 60, and S(f) 12 to 20 ppTRL subfractions at fasting (0 hour) and 2, 4, and 6 hours after the consumption of the fat meals. Effects of DFACs on mean concentrations of triacylglycerols and cholesterol averaged over 0, 2, 4, and 6 hours in ppTRL subfractions were assessed using linear mixed models. Stability and robustness were validated with 1000 bootstrap replicates. Contrasted to the control, equidominant meal reduced 6-hour average triacylglycerol levels in S(f) greater than 400 (P = .002, bootstrap P < .05) and S(f) 20 to 60 (P = .02, bootstrap P < .05) subfractions, and decreased average S(f) 20 to 60 cholesterol (P = .04, bootstrap P < .05); PUFA-D decreased S(f) greater than 400 average triacylglycerol levels (P = .09, bootstrap P < .05). Bootstrap samples suggested that PUFA-D decreased average S(f) 20 to 60 cholesterol levels (bootstrap P < .05). Therefore, modifying DFACs attenuates the atherogenic lipid profile of ppTRLs in T2DM patients; but increasing PUFA ratio may be more feasible.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited progressive disorder associated with significant pain and discomfort affecting quality of life. This study determined the impact of pain medication use and other clinical, biochemical and genetic characteristics on the physical and mental well being of predialysis ADPKD patients using the Short Form 36 (SF-36) questionnaire.The authors prospectively evaluated ADPKD patients in the Cohort Study, funded by the Polycystic Kidney Disease Foundation. Data on clinical, biochemical, and radiologic variables were collected in patients who were given the Short Form-36 questionnaire. Variables independently associated with the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores were identified.One hundred fifty-two patients had a mean PCS and MCS of 46.9 +/- 11.3 and 51.0 +/- 9.0, similar to the general population and better than the ESRD population. Eleven (7%) reported pain medication intake within 1 mo of evaluation and demonstrated lower PCS than those not taking pain medications. Patients with GFRor= 80 ml/min/1.73 m(2) had greater PCS than those with GFR80 ml/min/1.73 m(2). Age, BMI, pulse pressure, pain medication use, and education level independently associate with PCS and account for 32% of the variability of the measurement. Pulse pressure correlated with MCS.Predialysis ADPKD patients assess their quality of life similar to the general population. Age, BMI, pulse pressure, pain medication intake, and education level link to their physical well-being.

Objectives We sought to study the potential role of balloon aortic valvuloplasty (BAV) in sizing the aortic annulus in patients before transcatheter heart valve (THV) implantation. Background Despite clinicians9 growing experience with THV procedures, the best method of annulus sizing remains unclear. Methods Twenty-three patients with aortic stenosis (l1.0 cm2) who were undergoing surgical valve replacement were enrolled. Pre-operative echocardiographic measurements of the annulus and computed tomography measurements of valve calcium were made. Intraoperatively, a valvuloplasty balloon of known size and inflatable pressure was inserted into the aortic valve and inflated. The development of intraballoon pressure in addition to the nominal inflation pressure (AIBP) reflected the apposition of balloon and valve. Surgical annulus was measured by cylindrical sizers. Results In patients with tricuspid valves, AIBP was generated in 11 of 12 patients when the balloon diameter was greater than the surgically measured annulus, regardless of leaflet calcification (2 of 10 patients when balloon ≤ surgical annulus). In bicuspid valves, high AIBP (∼1 atm) was encountered with balloons that were within 1 mm of annulus size, and leaflet dehiscence occurred with larger balloons (n = 2 patients). Annulus size was underestimated by transthoracic echocardiogram and transesophageal echocardiogram compared with surgery (p l 0.001): transthoracic echocardiogram = 21.5 ± 1.8 mm, transesophageal echocardiogram = 22.0 ± 1.6 mm and surgical = 23.2 ± 1.9 mm (range 20 to 27 mm, mode 22 mm). Conclusions These data suggest that measuring AIBP during balloon aortic valvuloplasty in tricuspid valves is an important adjunctive measurement of the aortic annulus and may help in determining the appropriate THV size.

It has not been clearly established whether percutaneous coronary intervention (PCI) can provide an incremental benefit in quality of life over that provided by optimal medical therapy among patients with chronic coronary artery disease.We randomly assigned 2287 patients with stable coronary disease to PCI plus optimal medical therapy or to optimal medical therapy alone. We assessed angina-specific health status (with the use of the Seattle Angina Questionnaire) and overall physical and mental function (with the use of the RAND 36-item health survey [RAND-36]).At baseline, 22% of the patients were free of angina. At 3 months, 53% of the patients in the PCI group and 42% in the medical-therapy group were angina-free (P0.001). Baseline mean (+/-SD) Seattle Angina Questionnaire scores (which range from 0 to 100, with higher scores indicating better health status) were 66+/-25 for physical limitations, 54+/-32 for angina stability, 69+/-26 for angina frequency, 87+/-16 for treatment satisfaction, and 51+/-25 for quality of life. By 3 months, these scores had increased in the PCI group, as compared with the medical-therapy group, to 76+/-24 versus 72+/-23 for physical limitation (P=0.004), 77+/-28 versus 73+/-27 for angina stability (P=0.002), 85+/-22 versus 80+/-23 for angina frequency (P0.001), 92+/-12 versus 90+/-14 for treatment satisfaction (P0.001), and 73+/-22 versus 68+/-23 for quality of life (P0.001). In general, patients had an incremental benefit from PCI for 6 to 24 months; patients with more severe angina had a greater benefit from PCI. Similar incremental benefits from PCI were seen in some but not all RAND-36 domains. By 36 months, there was no significant difference in health status between the treatment groups.Among patients with stable angina, both those treated with PCI and those treated with optimal medical therapy alone had marked improvements in health status during follow-up. The PCI group had small, but significant, incremental benefits that disappeared by 36 months. (ClinicalTrials.gov number, NCT00007657.)

Background— The Mediterranean diet is protective against cardiovascular disease; a proposed mechanism is through a reduction in systemic inflammation. It is unknown to what extent the association between the Mediterranean diet and inflammation is due to genetic or other familial factors. Methods and Results— We administered the Willett food frequency questionnaire to 345 middle-aged male twins and assessed adherence to the Mediterranean diet using a published adherence score. Fasting plasma levels of interleukin-6, C-reactive protein, and known cardiovascular risk factors were measured. Mixed-effect regression analyses were used to examine the relationship between diet score and inflammatory biomarkers after accounting for known cardiovascular risk factors. Adherence to the Mediterranean diet was associated with reduced levels of interleukin-6 ( P P =0.10) after adjustment for total energy intake, other nutritional factors, known cardiovascular risk factors, and use of supplements and medications. When the overall association of adherence to the diet with interleukin-6 levels was partitioned into between- and within-pair effects, the between-pair effect was not significant ( P =0.9) and the within-pair effect was highly significant ( P Conclusions— Shared environmental and genetic factors are unlikely to play a major role in the association between adherence to the Mediterranean diet and systemic inflammation. These results support the hypothesis that reduced inflammation is an important mechanism linking Mediterranean diet to reduced cardiovascular risk.

Diabetes is a stronger risk factor for coronary heart disease in women than in men. Whether diabetes also poses greater risks to women after percutaneous coronary intervention (PCI) has not been examined.We examined 20586 PCI procedures at Emory University Hospitals (Atlanta, GA) between 1990 and 2003. Hazard ratios (HRs) for 1-year major adverse cardiac events were calculated comparing diabetic with nondiabetic patients by sex and study year. Data were adjusted for demographic and clinical factors using Cox proportional hazards models.Despite increasing patient age and comorbidity burden, diabetic and nondiabetic men had a significant improvement in PCI outcomes between 1990 and 2003 (P.001). Diabetic women also tended to have improved PCI outcomes over time (P = .073), but not nondiabetic women (P = .206). Overall, diabetes had a stronger association with adverse outcomes in women (HR 1.93, 95% CI 1.55-2.40) than in men (HR 1.26, 95% CI 1.09-1.47) (P = .002 for the interaction between sex and diabetes). The excess risk associated with diabetes in women, however, was largely driven by early study years (1990-1993). This excess risk associated with diabetes in women declined over time, and diabetes had a similar effect on outcomes in both women and men in more recent years (P = .010 for the interaction between sex, diabetes, and time).Percutaneous coronary intervention outcomes of diabetic and nondiabetic men have improved in recent years. However, among women, diabetic patients had greater improvements in outcomes after PCI compared with nondiabetic patients. As a result, diabetes is no longer a stronger risk factor for adverse outcomes after PCI in women than in men.

Patients with thick (Breslow4 mm) primary melanoma and/or regional nodal metastasis have a high risk of tumor recurrence. High-dose adjuvant interferon (IFN) alfa-2b offersor=10% improvement in relapse-free survival and overall survival with significant toxicity.The objective was to determine which prognostic factors and patient characteristics are significant in the decision to undergo IFN therapy.Of 781 patients who underwent sentinel lymph node (SLN) biopsy, 135 of 781 (17.3%) had positive SLN or thick melanomas and were informed of a/=50% risk of recurrence/disease-related mortality and offered IFN. Telephone surveys delineated reasons behind patients' decisions to accept IFN.Acceptors, 60 of 135 (45%), decided to take IFN alfa-2b whereas 75 of 135 (55%) declined. Being female (OR, 2.4; 95% CI, 1.17-5.03; p=.017) and positive SLN status (OR, 2.2; 95% CI, 1.01-4.97; p=.048) were strongly associated with patients who chose IFN. Acceptors of IFN were younger, more influenced by physicians, and less affected by depression and side effect profile (p.05 for all). Decliners were more concerned by strained relationships with family and social life (p.05).Gender and positive SLN were predictive of high-risk melanoma patients' acceptance of IFN treatment. Physician insight into melanoma patients' therapeutic decision-making process can guide patients through this difficult disease.

During Mohs micrographic surgery of nonmelanoma skin cancer (NMSC), inflammation in histologic frozen sections has been found to occasionally presage the detection of tumors in frozen sections of adjacent excision specimens.To quantify the correlation between the location of inflammation without visible tumor in histologic frozen sections and the location of subsequently detected NMSC.A retrospective cohort study of 3148 cases pertaining to frozen sections associated with the staged excision of NMSC was performed from September 8, 2008, to September 18, 2009, at an urban academic medical center, with the collected data analyzed on May 9, 2013.Consecutive cases of Mohs micrographic surgery performed at an academic medical center.For each wedge-shaped tissue segment corresponding with 1 hour of time on a clock face, the proportion of patients with inflammation at the source location of the segment who subsequently had a tumor at this same location; the proportion of patients who had neither inflammation nor subsequent tumor at the source location of the segment; the probability of subsequent tumor at this location given the prior finding of inflammation at the same location; and the probability that a location was without tumor in the absence of preexisting inflammation at that location.Of the medical records of 3148 cases of NMSC that were reviewed, 60 showed inflammation in histologic frozen sections from an excision specimen that was followed by tumor in the subsequent excision specimen. Of these 60, 39 (65%) were b asal cel carcinoma and 21 (35%) were squamous cell carcinomas; 53 (88%) were Mohs stage 1. In 7 of 12 segments, a significant positive correlation was found between the presence of inflammation and the presence of nearby tumor with correlation coefficients ranging from 0.196 to 0.384 (P .05) . The probability that tumor was absent when inflammation was not seen at a particular location (ie, clock-face segment) in preceding sections from that location was 91%, with segment-specific probability values ranging from 82% to 96%.During Mohs micrographic surgery of NMSC with the examination of frozen sections, histologic inflammation is modestly predictive of adjacent tumor whereas lack of inflammation strongly predicts that no additional tumor will be found.

Background: Healthcare disparities are a major public health concern. It is known that ethnicity and educational status independently predict health outcomes. Higher numbers of the American Heart Association's (AHA) ideal Life’s Simple 7 metrics (LS7) are associated with better cardiovascular health. In this study, we investigated the interplay of ethnicity and education on the attainment of ideal cardiovascular health (ICH) among employees of Baptist Health South Florida (BHSF), a large nonprofit health care organization. Methods: The data collected during BHSF annual voluntary wellness examination included age, gender, race, ethnicity and education. We assessed cardiovascular health using the LS7 metrics. Components of the LS7 metrics (smoking, physical activity, body mass index, diet, total cholesterol, blood pressure, and blood glucose) were categorized into ideal, intermediate and poor, according to AHA criteria. Study participants who met 6-7 ideal metrics were considered to have attained ICH. Results: The study population consisted of 9056 individuals (Mean age 43 ± 12 years, 74% women). Among employees with postgraduate education, 12% of white employees met the ideal for 6-7 LS7 metrics, 15% for Hispanic and 4% for Black employees. For employees with college degrees, the prevalence of 6-7 ideal LS7 metrics was 14%, 16% and 8% for white, Hispanic and black employees respectively (Figure). Overall, the odds of meeting 6-7 ideal LS7 metrics was lower for Hispanic and black employees compared to white employees of similar education (Table). These differences were especially large in those with high school education or less. Conclusion: Minorities are at an increased risk of poor cardiovascular health particularly those with the lowest educational achievement. Comprehensive workplace wellness programs that target these groups will improve cardiovascular health and employee productivity, in addition to saving health care costs.

Introduction: We aim to evaluate cost-effectiveness of recent FDA advisory committee recommended PCSK9 inhibitors for reducing cardiovascular disease (CVD) risk from societal & U.S. third-party payer perspective. Methods: A Markov model was used to evaluate costs and effects associated with addition of PCSK9 inhibitor to standard of care (SOC) based on a) estimated 53% 1-year relative risk reduction (SOC 1 year CVD event rate: 2.18%, PCSK9 inhibitor+SOC: 0.95%), b) indirect annual CVD reduction probability (using Framingham risk) via mean 61% LDL lowering among at CV risk patients. The model considers cycles of 1 year. Post CVD events last 5 years, after that time individuals go back to treatment state if no subsequent CVD observed. Health state costs were derived from published evidence. Survival probabilities >1 year were transformed to annual probabilities assumed on survival models. From societal perspective, cost per Quality-Adjusted Life Years (QALYs) gained are presented. We estimated payer’s perspective on net benefit balancing treatment vs. avoided cost and premium revenues over patient lifespan. Results: The table highlights societal gains and payer’s net benefit across range of estimated annual drug cost. At willingness-to-pay threshold of $100,000/QALY, PCSK9 inhibitors appear cost-effective if priced annually at $2500. At annual cost of $10,000, cost/QALY gained with PCSK9 inhibitor is nearly $400,000. From payer’s perspective, approximate net benefit was -$11,000 to -$51,000 per patient treated across annual drug cost range. Net benefits were only positive if treatment priced around $500/year. Conclusion: This study provides insights to facilitate discussion among healthcare stakeholders for considering future PCSK9 inhibitor’s utility balancing estimated benefits while accounting need for additional financial resources. Gaps between social & private benefits need to be aligned for appropriate PCSK9 inhibitors adoption in U.S.

Introduction: There has been increased focus on the relationship between sleep duration and cardiovascular disease, however, there is limited understanding of the association of sleep duration with cardiovascular health (CVH). In this study we examine the relationship between sleep duration and the American Heart Association’s ideal CVH in a large employee population. Methods: Data for this study was collected from participants at the 2014 health risk assessment in which they reported their average hours of sleep, their dietary patterns. In person, participants were weighed and their heights were measured. They also had blood pressure, blood glucose, total cholesterol measurements as well as breath carbon monoxide tests for smoking. The ideal for each CVH metric was estimated for each of the 7 metrics. Sleep duration was grouped into less than 6 hours, 6 to 7.9 hours and 8 or more hours. Ideal CVH was classified as presence of 6-7 ideal metrics. Results: A total of 9700 participants (mean age 43yrs, 74% female) completed the 2014 health risk assessment and had complete data on the variables of interest. Overall, more females and persons without college degrees slept for less than 6 hours. Compared to those with less than 6 hours of sleep, those with 8 or more hours of sleep had 1.6 times the odds of ideal diet (95% CI: 1.1-2.6), 1.7 times the odds of having ideal BMI (95% CI: 1.4-2.1), 1.3 times the odds of having ideal BP (95% CI: 1.1-1.5) and 2.4 times the odds of achieving ideal physical activity (95% CI: 2.4 - 2.9) after controlling for age, sex and educational levels. Comparing to those with less than 6 hours of sleep and with a reference of 0-2 ideal metrics, participants with 8 or more hours of sleep were 2.7 times as likely to have ideal CVH (see figure). Conclusions: Our study findings underscore the importance of promoting sleep health for optimizing ideal CVH. Further studies are needed to determine generalizability of our results.

Early childhood trauma has been associated with increased risk for subsequent coronary heart disease (CHD), but little is known regarding what role genetic and shared familial factors play in this relationship. Early trauma was measured retrospectively in 562 male middle-aged twins with the Early Trauma Inventory. CHD was assessed by history and by myocardial perfusion imaging with positron emission tomography [(13)N] ammonia. Coronary flow reserve, a measure of coronary microcirculatory function, was defined as the ratio of myocardial blood flow at rest to flow during stress. Early trauma was associated with a higher prevalence of CHD by clinical history, OR = 1.48 per early trauma inventory quartile increase, 95% CI [1.18, 1.86]. When within- and between-pair effects were estimated, only the between-pair association was significant, OR = 1.76, 95% CI [1.30, 2.40], showing that the odds of CHD in the twin pair increased as the average early trauma exposure in the pair increased. A marginal between-pair (but not within-pair) relationship was also found between early trauma and coronary flow reserve (n = 416, unstandardized B = -0.04, SE B = 0.02, p = .036). In conclusion, early trauma was associated with CHD and familial factors played a key role.

Endothelial dysfunction is more prevalent in African Americans (AAs) compared with whites. The authors hypothesized that nebivolol, a selective β1 -antagonist that stimulates nitric oxide (NO), will improve endothelial function in AAs with hypertension when compared with metoprolol. In a double-blind, randomized, crossover study, 19 AA hypertensive patients were randomized to a 12-week treatment period with either nebivolol 10 mg or metoprolol succinate 100 mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-N(G) -monomethylarginine (L-NMMA) and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared with metoprolol treatment (21% vs 12% reduction in FBF, P=.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (P

Background: Because of its high prevalence and direct contribution to cardiovascular diseases (CVD), hypertension is among the most expensive components of CVD, representing nearly 50% of the total direct medical cost of CVD in the U.S. Yet, little is known about the per-patient cost of CVD episodes among hypertensives. Methods: This study used insurance claims data from over 16,000 individuals diagnosed with hypertension and enrolled in a private health insurance plan between 2008 and 2010. About one million medical and pharmacy insurance claims generated by these hypertensive patients were extracted for the analysis. Six CVD were included in the study: Myocardial infarction (MI), unstable angina (UA), stable angina (SA), transient ischemic attack (TIA), stroke, and congestive heart failure (CHF). Direct medical costs (ambulatory, emergency, hospital visits and medications) for each CVD were obtained on a weekly basis over 26 weeks before and after a recorded CVD episode. Per-patient direct medical costs were estimated by taking a before-after difference in cost, corrected by censoring due to deaths and insurance plan exits. Average costs were segmented by age groups (40-64 and 65 or over). Costs were adjusted to 2010 U.S. dollars. Results: The most expensive CVD episode among hypertensives was UA ($17,704; 95%CI $11,632-22,644), followed by MI ($13,480; 95%CI $8,328-18,752), stroke ($13,223; 95%CI $8,080-17,556), CHF ($12,462; 95%CI $9,734-15,335), SA ($6,991; 95%CI $4,178-9,947), and TIA ($5,787; 95%CI $2,671-9,670). CVD costs converged to pre-event cost levels within the next 4 to 14 months after the recorded CVD episode. Some CVD costs (CHF, UA, MI) rose 1 to 3 weeks before the recorded event, while others (stroke, TIA, SA) clearly started during the week of the recorded event (see Figure 1 comparing CHF and stroke). For the former, pre-event costs explained up to 30% of total costs. Conclusions: Cost estimates of CVD episodes among hypertensive patients are consistent with results from the scarce literature in this area. Moreover, our study finds evidence of increased medical resource utilization weeks before the recording of the CVD episode. Omitting these pre-event costs leads to an underestimate of the true costs of CVD.

Introduction: There is limited evidence relating lipoprotein subfractions or their composite measures to subclinical markers of atherosclerosis. In this study, we tested whether combinations of lipoprotein subfractions independently predict the presence of Coronary Artery Calcification (CAC) among presumably healthy people with high cardiovascular disease (CVD) risk. Methods: Cardio IQ™ Ion Mobility lipoprotein fractionation was measured at baseline in 172 high CVD risk participants of the Baptist Employee Healthy Heart Study (BEHHS). Principal component analysis was used to check for eventual components of CVD risk. Using bootstrap techniques, we created 1000 data sets of size 5000 and analyzed results of logistic regression. Results: Three principal components (PC) accounted for 88% variability. PC1 represented an increase in all lipoprotein measures; PC2 a decrease in HDL, large and medium LDL with an increase in VLDL and small and very small LDL; PC3 an increase in HDL, and a decrease in LDL subfractions and large IDL particles. The adjusted odds ratios for the presence of CAC were: 1.01(0.98 - 1.03) for PC1, 1.22(1.17-1.27) for PC2 and 0.90 (0.85 - 0.97) for PC3. PC2 and PC3 were associated with p-values smaller than 0.05 in 100% and 88% of all models. Conclusion: PCA of lipoprotein subfractions identified 3 independent components of CVD risk. PC2, proxy for the “atherogenic lipoprotein phenotype”, was consistently associated with the presence of underlying coronary artery calcification. There is potential to explore how lipoprotein subfractions as determined by a safe, inexpensive blood test can be used to stratify CVD risk in younger but high risk individuals.

Background: Self reporting of health information by participants in employer sponsored programs may result in under reporting of this data. Since policies are formulated on the basis of analysis of available data, underreported data may adversely inform healthcare policy decisions in workplace and other relevant settings. In this study, we examine the disparity in measured versus self reported body mass index (BMI) in a large, diverse working population participating in a work-based Health Risk Assessment (HRA). Methods: Baptist Health South Florida, a large not-for-profit health care organization, conducts a HRA annually for its employees. The HRA consists of an online health questionnaire and an in-person assessment of biometric measures. Participants report their height and weight in the online questionnaire, and height and weight is measured during collection of biometric information, from which BMI is calculated. BMI was categorized as: not obese (2 ), obese (30 - 34.9kg/m 2 ) and morbidly obese (≥35kg/m 2 ). Results: A total of 9536 persons self reported their BMI and subsequently had BMI measured. Mean age of the participants was 43.1 years (± 12.1). Mean BMI was 28.6 (± 6.2) and 27.8 (± 5.9) respectively for measured and self reported BMI respectively. Among all participants, 90% self reported accurately in their respective weight categories, while 9% underreported their weight. However, among obese participants (n=3168), 72% correctly self-reported their BMI. Approximately 29% of obese class I participants reported BMIs in the non-obese category, while about 22% of those with BMI ≥35 kg/m 2 reported as being in Obese class I (2 ). There was a high degree of agreement overall observed between measured and self reported BMI (κ = 0.84; Intra Class Coefficient = 0.89). Conclusion: Despite of a high degree of overall agreement between measured and self reported BMI, obese participants considerably underreport BMI. Thus, underreporting of self-reported data should be taken into account during program planning and formulation of healthcare policy decisions in the workplace.

Introduction: To date multiple ongoing clinical trials are testing impact of human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) in high risk patients with established CVD already on statins. It is of interest to explore the added value of these therapies in individuals free of established CVD. The aim of this study is to assess the implications of population baseline risk considered for clinical trials, in evaluating impact of PCSK9 inhibitors in primary prevention settings. Methods: We simulated scenarios among primary prevention cohorts recruited with 5 year CVD event rates ranging from 5-25%. In the control group, 30% relative risk reduction (RRR) with highest tolerated statin dose was considered. The NNT and drug cost with additional PSCK9 inhibitor therapy to prevent one cardiac event were calculated across varying (20-40%) RRR thresholds. The annual cost of PCSK9 inhibitors was estimated in range of $3000-$7,000. We considered ≤ $0.5 million as upper limit for willingness to pay to prevent 1 event in 5 years. Results: The table highlights: a) absolute event rates anticipated in the controls as well with additional PCSK9 inhibition; b) the calculated NNT; and c) costs to prevent one cardiac event across the spectrum of baseline CVD risk levels. Among those with estimated 5 year absolute risk of 10%, the threshold for willingness to pay was achieved provided PCSK9 inhibition achieved 40% RRR with annual cost of $3000. Among individuals with >20% absolute 5 year baseline risk, the threshold for willingness to pay was realized even with 20% RRR in all scenarios if annual cost was limited to $3000. Conclusion: Future discussion for clinical trials assessing efficacy of PCSK9 inhibitors in reducing CVD events in primary prevention settings must focus on enrichment strategies for recruiting a ‘high risk’ population. These strategies will likely facilitate acceptable NNT and public willingness to pay for these emerging novel therapies.

Introduction: To date multiple ongoing clinical trials are testing impact of human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) with established CVD already receiving optimal statin treatment. There is considerable interest in exploring added value of these therapies among high risk groups free of established CVD such as those with diabetes mellitus (DM). Coronary artery calcium (CAC) testing has shown to accurately identify those at high and low risk for cardiac event in short-intermediate term. The aim of the current study is to assess potential implications of enrichment strategies via CAC testing for future clinical trials evaluating impact of PCSK-9 inhibitors in DM free of established CVD Methods: In our analysis, 5-year CVD rates among DM individuals were estimated from published literature. In the placebo (control) group, 30% relative risk reduction (RRR) with highest tolerated statin dose was considered. The NNT and drug cost with additional PSCK-9 inhibitor therapy to prevent one cardiac event were calculated across varying (20-40%) RRR thresholds. The annual cost of PCSK-9 inhibitors was estimated in range of $3000-$7,000. We considered ≤ $0.5 million as upper limit for willingness to pay to prevent 1 CVD event in 5 years. Results: The table highlights a) absolute event rates with additional PCSK-9 inhibition, b) the calculated NNT, and c) costs to prevent one cardiac event across the entire DM cohort as well among CAC subgroups. Among all diabetics, the NNT to prevent one event ranged from 48-95 with estimated additional 20-40% RRR with PCSK-9 inhibitors; the threshold for willingness to pay in all scenarios was >$ 0.5 million. The respective NNT among 38% of diabetics with CAC=0 were 89-179 and unacceptable high cost to prevent 1 event. Among individuals with at least moderate CAC burden (>100 & >400), the threshold for willingness to pay was realized in most scenarios Conclusion: It is imperative that future discussion designing clinical trials assessing efficacy of PCSK-9 inhibitors such as DM focus on enrichment strategies such as CAC testing for recruiting an appropriately ‘high risk’ cohort as well as excluding those who are least likely to benefit. These strategies will likely facilitate acceptable NNT and public willingness to pay for these emerging novel therapies

Background: A major shortcoming of lifestyle improvement programs has been the difficulty in understanding the recruitment and follow-up strategies that yield the best results in terms of targeted health outcomes and retention rates. In this study, we compare the retention rates, short and long-term outcomes of a tailored workplace lifestyle intervention program targeted at high CVD risk working populations before and after implementation of changes made to the program based on a behavioral assessment (BA) analysis. Methods: The My Unlimited Potential (MyUP) is a year long lifestyle intervention program conducted among high-CVD risk employees of Baptist Health South Florida. The program was initially designed to have a 9-week intensive phase, with a year long follow-up period. During the intensive phase, participants had supervised structured physical fitness training as well as nutritional counseling. Due to concerns about sub-optimal retention rates and outcomes, the program was modified based on the results of a behavioral assessment of the initial participants (see figure). An additional level of participant screening was introduced with the aim of recruiting those who were least likely to drop-out and most likely to succeed in the program. The program was also modified to have a 12-week intensive phase. Results: At all follow-up periods, the retention rate was higher among those in the post BA group (see table). Although persons in the post-BA group achieved significantly greater reduction in weight, BMI and body fat the absolute differences between groups was minimal. The measured reduction in systolic (SBP) and diastolic blood pressures (DBP) were greater in the pre-BA group at the end of the intensive phase but this was reversed by 1 year in which only those who received the revised intervention had sustained reduction in DBP. There was no significant between-group difference in the laboratory parameter changes, including HbA1c and hsCRP. Conclusion: Using a behavioral assessment modification module improves retention rates with minimal improvement in outcomes. BA modification should be used in programs with low retention rates but may be of minimal impact on long term outcomes.

Introduction: A recent meta-analysis showed that erectile dysfunction (ED) was associated with elevated cardiovascular disease (CVD) mortality. However, findings from studies examining the relationship between ED and sub-clinical CVD have been conflicting. This study summarizes the current evidence related to the association of ED and vascular disease as measured by flow mediated dilation (FMD) of the endothelium and carotid intima media thickness (CIMT). Methods: We searched multiple internet databases for published literature on studies assessing the association of ED and FMD, and CIMT between 1964 and 2014. A total of 11 studies met the inclusion criteria for examining the association between ED and FMD, while 7 studies met criteria for assessing the association with CIMT. Fixed-effect and random-effect models were used to assess and compare the standardized mean difference (SMD) of FMD and CIMT between persons with and without ED. Results: From a total of 795 individual participant data (590 with and 205 without ED), persons with ED had a 0.66mm (0.49, 0.83) increase in CIMT by fixed effects model or 0.67mm (0.44, 0.90) by random effects model compared to those without ED. Similarly, from 1055 individual participant data (536 with and 419 without ED), ED was associated with a significant reduction in FMD by both fixed effect (-1.10% (95% CI: -2.10, -0.95)) and random effect models (-1.53% (95% CI: -2.10, -0.95)). There was significant heterogeneity among studies assessing the relationship between ED and FMD (I2 = 93.2%, p Conclusion: This study confirms that ED is associated with both worsening endothelial function and increased CIMT. Thus, worsening vascular function may be a pathogenic mechanism for increased CVD morbidity and mortality in persons with ED. A diagnosis of ED should prompt a thorough CV work-up and aggressive preventive management.

Background: The Life’s simple 7 (LS7) health metrics were introduced by the American Heart Association (AHA) to assess cardiovascular health. Studies have linked higher numbers of ideal LS7 health metrics to lower incidence of both cardiovascular and non-cardiovascular diseases. In the workplace, employees typically complete a health risk assessment (HRA) to assess their health status. In this study, we examined the association between an individual’s perception of overall health using an HRA and the LS7 health metrics. Methods: Data for the LS7 health metrics and the perception of overall health were collected during the annual voluntary wellness fairs and HRAs for employees of a large nonprofit health care organization in South Florida. Each LS7 health metric (smoking, physical activity, body mass index, blood pressure, total cholesterol and blood glucose) was classified as ideal, intermediate or poor according to AHA criteria. On the HRA questionnaire, participants rated their overall health as poor to fair, good to very good or excellent. Intraclass correlation coefficient (ICC) and kappa statistics (k) were computed to determine the agreement between the LS7 classification and perception of overall health status taken from the HRA. Results: 9364 employees had complete wellness fair and HRA data in 2014. Mean age (SD) was 43 years (12), 75% were women. The table below shows the categories of overall health by LS7 and HRA classification. Approximately 43% of study participants differed in the assessment of their health status using the HRA when compared to the LS7 categories with nearly one-third of study participants overestimating and 11% underestimating their overall health. ICC was 0.13. K and weighted k were 0.06 and 0.01 respectively (P Conclusion: In this study, we noted significant variation between the perception of overall health and the classification of health status based upon LS7 health metrics with only 57% of employees classifying their health status in agreement with their achievement of LS7 metrics. Further public health efforts should be directed towards increasing the awareness and use of the LS7 in the workplace as a measure of overall health.

Background: Diabetes mellitus is one of the leading conditions resulting in high health costs and lost productivity. In recent year there is a growing interest for managing these chronic conditions through engagement of workplace wellness programs. In this study we examined the short and long term effects of an ongoing multicomponent lifestyle intervention improvement program (My Unlimited Potential (MyUP), among employees of Baptist Health South Florida (BHSF), a large not-for-profit health care system. Method: The present analysis focuses on the efficacy of an intensive lifestyle workplace intervention among individuals presenting with diabetes mellitus. The intervention provided tools to improve physical activity, stress and dietary habits. A multi-disciplinary team made up of an advanced nurse practitioner (ARNP), registered dietician (RD), exercise physiologist (EP), certified diabetic educator (CDE), and registered nurse (RN) met with participants to provide one-on-one counseling and training. Results: The current study assessed 33 (58 years +/- 8.8, 67% female) employees with diabetes mellitus enrolled in the MyUp wellness program who completed baseline, 12-weeks, 6 months and 1 year assessments. Significant short and long term improvements in cardio-metabolic risk factors were observed (Table1). Positive change in distribution of cardiovascular risk factors was noticed at 3, 6 and 12 months (Fig1). Conclusion: These results suggest that a multi component workplace lifestyle modification program results in both short and long term improvement in cardiovascular disease risk among employees with diabetes mellitus. Further large studies are needed to confirm our study findings.

Introduction: Arterial stiffness is an independent predictor of cardiovascular disease (CVD) morbidity and mortality, and has been shown to be of prognostic value in CVD. A risk factor independent association between arterial stiffness and traditional lipids has been described extensively but it is unclear whether an independent relationship exists with lipoprotein subclasses. Methods: The Baptist Employee Healthy Heart Study (BEHHS) is a lifestyle intervention study examining the effects of web-based programs on reducing CVD risk in high-risk persons. Participants had their brachial arterial augmentation index (AIx, a measure arterial stiffness) assessed using the EndoPAT 2000 device. The AIx is standardized to gender-matched non-selective populations. Cardio IQ™ Ion Mobility lipoprotein fractionation was utilized for advanced lipid subclass measurement. Results: The population consisted of 182 participants, (74% women, 49% Hispanic) with a mean age of 52 ± 9 years. There was a significant trend association between quartiles of AIx and total LDL, small LDL, small and large IDL, small, large and total HDL, and small VLDL. In multivariate analysis, only small and large IDL, total LDL and small VLDL showed independent significant association with AIx. Conclusions: Several lipoprotein subclasses demonstrate independent significant associations with arterial stiffness. Thus, a safe and relatively inexpensive blood test may be useful in identifying probable vascular disease in a relatively young high traditional CVD risk population. Longitudinal studies are required to fully understand the temporal relationship between the lipoprotein subclasses and arterial stiffness.

In 2010, the American Heart Association set 2020 national goals for promoting cardiovascular health (CVH), emphasizing measurement of reproducible health behaviors and health factors and attaining ideal CVH status [(1)][1]. In this letter, we describe the frequency of ideal status for individual

WATERPIPE SMOKING is popular among adolescents in the Eastern Mediterranean Region.1,2 Evidence from many countries in the region suggests that the waterpipe is the most common form of tobacco use among youth.1–3 The last Global Youth Tobacco Survey (GYTS 2009) found that 11.5% of adolescents in Jordan were current cigarette smokers compared to 20.7% current waterpipe smokers.4 Both sexes, 27.1% of boys and 15.6% of girls, reported waterpipe smoking in Jordan.4 Waterpipe smoking is widely believed to be less harmful, less addictive and generally safer than cigarette smoking.5 Given the recent spread of waterpipe smoking, evidence of long-term major health effects of waterpipe smoking, such as cancer and cardiovascular disease, is still scarce.6 Available evidence, however, shows that waterpipe smoking exposes smokers to the main carcinogenic and cardiovascular toxic substances present in cigarettes.7 For example, our team has recently reported that waterpipe smokers are exposed to tobacco-specific nitrosamines in comparable amounts to cigarette smokers.8 Moreover, there is strong evidence to suggest that waterpipe smoking is associated with nicotine dependence, including abstinence-induced withdrawal and craving symptoms, which are relieved by subsequent waterpipe smoking.9 Several researchers have recently suggested that waterpipe smoking can lead to cigarette use.10–13 This has major implications for tobacco control, especially in societies with high levels of waterpipe smoking among youth. As evidence for waterpipe use patterns and delivery of the addictive substance, nicotine, has accumulated, the waterpipe-to-cigarette gateway concept was developed further to suggest a possible pathway for this transition.14–16 Compared to cigarettes, waterpipe smoking is a stationary, time-consuming practice, and is not readily accessible. These features led one of our group (WM) to suggest that adolescents who become addicted to nicotine through waterpipe use are likely to resort to the more accessible cigarettes to satisfy their smoking urge.15 The relation between dependence and access is therefore likely to be a major predictor of the transition from waterpipe to cigarette smoking.15,16 On the other hand, the move from ‘less harmful’ tobacco products, such as waterpipes or ecigarettes, to harmful cigarettes represents a unique transition, characterized by the ‘gateway’ hypothesis, beyond the commonalities underlying youthful experimentation with different addictive substances.17,18 The present study examines the potential role played by waterpipe smoking as a gateway to cigarette smoking using a longitudinal study design based on a theoretical framework of behavioral change (attitudes, social influences and self-efficacy),19 as well as evidence of the patterns and determinants of waterpipe use.20,21 We also compared the risk of initiation to cigarette smoking between waterpipe-only smokers and never smokers among schoolchildren (mean age 12.6 years at baseline) in Irbid, Jordan, and examined the dose-related gradient of this risk based on the frequency of waterpipe use as a proxy measure for nicotine dependence.22

BACKGROUND: Obesity is strongly related to chronic health problems and concomitant increased healthcare costs for employers. The aim of the study is to explore the distribution of obesity categories and estimate associated health costs among self-insured employees of Baptist Health South Florida (BHSF), a large not-for-profit health care organization. METHODS: Distribution of BMI categories was determined among individuals participating in a voluntary health risk assessment (HRA) available to employees eligible for health benefits. The potential estimates of obesity related costs to BHSF were imputed using CDC's Obesity Cost Calculator based on data from NHIS and MEPS (http://www.cdc.gov/leanworks/costcalculator/disclaimer.html). RESULTS: Overall 9996 (aged 43.1±12.1 years, 75% females, 75% Hispanic, 35% hypertensive, 4% diabetic) employees participated in 2013 annual HRA and wellness fair. The age-adjusted mean BMI was 29.3 (95% CI, 29.1-29.5) for men and 28.3 (95% CI, 28.15-28.45) kg/m2 for women. The table describes distribution of BMI categories according to gender and age groups. The age-adjusted prevalence of obesity (BMI>30 kg/m2) was 36% (95% CI, 34%-37%) among men and 32% (95% CI, 31%-33 %) among women. In BHSF employee population, 6% (n=581) were classified as morbidly obese (BMI>=40) and 7% (n=748) individuals met criteria for bariatric surgery. Total annual estimated cost attributable to high BMI (>25) were $8.05 million (74% medical and 26% work lost) of which 41% were contributed by 14% employees with BMI>35. The average attributable cost per high BMI employee ranged from $598 among those with BMI 25-29.9 to $2695 with BMI>=40. CONCLUSIONS: One third of employees (predominantly female and Hispanic) in a large health care organization (BHSF) were obese. Given the significant financial burden imposed by obesity large self-insured organizations like BHSF have a lot to gain by introducing evidence-driven weight reduction programs, and tracking the success of these programs in the workforce.

Introduction: With the development of new health metrics to define ideal cardiovascular health (CVH), several studies have examined the distribution of the American Heart Association (AHA) 2020 ideal CVH metrics both within and outside the United States (US). In this meta-analysis of proportions, we synthesized available data on ideal CVH metrics distribution in US cohorts and compared them with non-US populations. Methods: A MEDLINE database search was conducted using relevant free text terms such as “life’s simple 7”, “AHA 2020”, “American Heart Association 2020” and “ideal cardiovascular health” between January 2000 and October 2014. Studies were included in the meta-analysis if the proportions achieving ideal for 0, 1, 2, 3, 4, 5 or ≥6 ideal CVH metrics were known or could be estimated. A meta-analysis of proportions was conducted for US and non-US studies using a random effect model (REM). REM models were chosen because of the significant heterogeneity among studies. Results: Overall the pooled data consisted of 10 US cohorts with a total population of 94,761 participants and 6 non-US cohorts with a total of 130,242 participants. The table shows the pooled prevalence of ideal CVH factors in this population. Overall the pooled estimates of US cohorts showed 15% had 0-1 ideal CVH metrics (inter-study range: 7-22%), while 3% (inter-study range: 1-10%) had 6-7 ideal CVH metrics. This is comparable to 12% (inter-study range 1-17%) and 2% (inter-study range: 1-12%) for 0-1 and 6-7 ideal CVH metrics in the non-US studies. Conclusion: The proportion of persons achieving 6 or more ideal CVH metrics in both US and non-US cohorts is very low and the distribution of CVH metrics is similar in both US and non-US populations. Considering the strong association with worse outcomes, a coordinated global effort at improving CVH should be considered a priority.

Introduction: Fibroblast Growth Factor 23 (FGF23) is bone-derived hormone regulating phosphate homeostasis as part of a newly described bone-kidney axis. Several studies have demonstrated that elevated circulating FGF23 levels are independently associated with cardiovascular mortality. Methods: A systematic review was conducted according to Meta-analysis of Observational Studies in Epidemiology Group guidelines. Six databases (PubMed-Central, Ovid-MEDLINE, EMBASE, Web of Science, BIOSIS and Cochrane Database of Systematic Reviews) were searched for articles published between 2000 and 2014 examining the longitudinal association between FGF23 and CVD mortality among populations without prior CVD, Chronic Kidney Disease, or Diabetes. The review yielded 1,961 articles, of which 982 met the inclusion criteria. About 893 abstracts were excluded during the title and abstract screen, and an additional 92 after full text review. Only three articles met the review criteria and were included in the meta-analysis. Data from selected articles were abstracted and independently assessed for quality by two reviewers. Summary estimates and associated 95% confidence intervals were included in fixed and random-effects models. The presence of heterogeneity was evaluated using a Q-statistic with a conservative p-value of 0.10. All analyses were performed using R library meta. Results: Data for 15,379 participants were included in the meta-analysis. The hazard ratio for quartiles two and four when compared with quartile one,the reference category, were 1.29 (1.06- 1.58; p=0.01) and 1.31 (1.077-1.59; p=0.0068) respectively. There was no significant difference in CVD mortality between the third and first quartile. There was also no evidence of heterogeneity observed (I2 = 0%, p = 0.611). Conclusions: This study found a U-shaped association between FGF23 and CVD mortality suggesting that either low or high serum levels increase risk for CVD mortality. Current strategies focus on lowering high levels of circulating FGF23, but little attention has been given to understanding optimal levels necessary to prevent CVD mortality. If this U-shaped relationship between FGF23 and CVD mortality is real, the possible links, causes, and mechanisms require additional research.

OBJECTIVES To determine the relationship between clinically relevant blood pressure (BP) groups and nonalcoholic fatty liver disease (NAFLD) presence and severity especially in the milieu of other metabolic risk factors. PATIENTS AND METHODS From a Brazilian cohort of 5362 healthy middle-aged men and women who presented for yearly physical examination and testing, the cross-sectional relationship between BP categories and NAFLD was assessed. BP groups were categorized as normal, prehypertension (PHT), and hypertension (HTN) according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification. NAFLD was ultrasound diagnosed, excluding persons with alcohol consumption more than 20 g/day. NAFLD severity was estimated using the Fibrosis-4 (FIB-4) risk score. RESULTS The prevalence of NAFLD was 36.2%. Participants with NAFLD were older (mean 46 vs. 42 years, P

This study details 6- and 12-month cardio-metabolic outcomes of an intense 12-week workplace lifestyle intervention program, the My Unlimited Potential (MyUP), conducted in a large healthcare organization.This study was conducted among 230 employees of Baptist Health South Florida with high cardiovascular disease (CVD) risk. Employees were considered at high risk and eligible for the study if they had two or more of the following cardio-metabolic risk factors: total cholesterol ≥ 200 mg/dl, systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg, hemoglobin A1C (HbA1c) ≥ 6.5%, body mass index (BMI) ≥ 30 kg/m(2) .At the end of 12 weeks, there was significant reduction in the mean BMI, SBP and DBP, serum lipids, and HbA1c among persons with diabetes. At 1 year, there was significant decline in the mean BMI, SBP and DBP, HbA1c, and high-sensitivity C-reactive protein, and in the prevalence of poor BP control, BMI ≥ 35 kg/m(2) , and abnormal HbA1c among all persons and those with diabetes.This intensive 12-week lifestyle change program was successful at improving cardio-metabolic risk factors at 1 year. This study provides a template for other workplace programs aimed at improving CVD risk in high-risk employees.

Elevated blood pressure (BP) is associated with greater risk of cardiovascular disease (CVD), and evidence suggests that prior BP levels may be at least as important as current BP in prediction models. We analyzed the determinants of CVD risk in Offspring Framingham Heart Study participants (n = 3344). The baseline Cox model included the traditional risk factors and current systolic BP to predict 20-year risk of CVD (643 events). Current systolic BP was significant, and the associated hazard ratio was 1.09 for 10 mm Hg (confidence interval [CI] 95%: 1.04-1.15). A second model used the traditional risk factors plus antecedent BP (hazard ratio [HR] = 1.19; CI 95%: 1.10-1.24). In a third model that included traditional risk factors and both current and antecedent BP, the antecedent BP was significant (HR = 1.18; CI 95%: 1.08-1.23), but the current BP was not statistically significant (HR = 1.01; CI 95%: 0.97-1.09). Antecedent BP showed a significantly stronger effect on risk of CVD than current BP.

Introduction Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown. Methods and Results We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C‐reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD ( P P P P P P =0.008) with the addition of suPAR. Conclusion Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.

Background Coronary heart disease (CHD) and diabetes may have synergistic effects on symptoms, self-management, and general and cardiac-specific health status. Purpose We compared symptom distress, self-management difficulties, and general and cardiac-specific health status in patients with CHD by the presence and severity of diabetes. Methods We performed a cross-sectional study of 1013 patients enrolled in the COURAGE trial, with the use of clinical data, the Symptom Distress Scale, the Self-Management Difficulties Scale, the Short-Form 36, and the Seattle Angina Questionnaire. Results Patients with diabetes and greater severity of diabetes had worse findings in symptom distress, self-management difficulties, and general and cardiac-specific health status than patients without diabetes. Conclusions A robust effect of diabetes on symptom distress and self-management difficulties was found in patients with CHD. The results from the Seattle Angina Questionnaire illustrate difficulty in attributing physical limitations to specific symptoms or conditions, and show the experience of comorbid conditions to be synergistic. Clinicians’ understanding of this synergy and integration of condition-specific care with general treatment and self-management practices are needed.

Background Staphylococcus aureus is a common cause of endocarditis. Previous studies have shown that the mortality rate associated with S aureus endocarditis remains high, and methicillin resistance is becoming more prevalent. Methods Over the past 4 years, 283 patients with suspected endocarditis were referred to the cardiology department of Grady Memorial Hospital for echocardiography. Their clinical course and demographic information was entered into a database. Among these patients, 87 (30.6%) were confirmed to have endocarditis, with 41 (47.1%) of them culture positive for either methicillin-resistant (MRSA) or methicillin-sensitive S aureus (MSSA). Of these patients, 14 were MRSA culture positive, and 27 were MSSA culture positive. These two groups were compared with respect to demographic information and morbidity and mortality outcomes. Results The MRSA and MSSA groups were found to be similar upon analysis in all baseline characteristics. There was a nonstatistical trend among the two groups in origin of infection, as the MRSA group tended toward nosocomial infection more often. Outcomes, including surgery, death, and complications were also found to be similar between the two groups. Conclusions There does not seem to be difference in the outcome of MRSA versus MSSA endocarditis. Nosocomial infection may predispose patients to MRSA endocarditis, but a larger study with a greater sample size is necessary to evaluate these questions more accurately.

Psychological trauma is a major public-health problem, and trauma victims frequently turn to the Internet for medical information related to trauma. The Internet has many advantages for trauma victims, including low cost, privacy, use of access, and reduced direct social interactions. However, there are no regulations on what is posted on the Internet, or by whom, and little is known about the quality of information currently available related to the topic of psychological trauma. The purpose of this study was to evaluate the quality of Internet sites related to the topic of psychological trauma. The top 20 hits for searches on Google, AllTheWeb, and Yahoo were tabulated, using search words of 'psychological trauma', 'stress', 'PTSD', and 'trauma'. From these searches, a list of 94 unique unsponsored hits that represented accessible websites was generated. Fourteen sites were unrelated or only peripherally related, and eight were related but were not comprehensively evaluated because they represented brochures, online book sales, etc. Seventy-two websites underwent evaluation of the content, design, disclosure, ease of use, and other factors based on published guidelines for medical information sites. Forty-two per cent of sites had inaccurate information, 82% did not provide a source of their information, and 41% did not use a mental-health professional in the development of the content. Ratings of content (e.g. accuracy, reliability, etc.) were 4 (2 SD) on a scale of 1 - 10, with 10 being the best. There were similar ratings for the other variables assessed. These findings suggest that although abundant, websites providing information about psychological trauma are often not useful, and can sometimes provide inaccurate and potentially harmful information to consumers of medical information.

Objectives This study sought to evaluate the long-term cost effectiveness of a clopidogrel loading strategy before percutaneous coronary intervention (PCI) followed by continued treatment for one year. Background The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized trial of 2,116 patients, showed the effectiveness of antiplatelet therapy with clopidogrel 300 mg before PCI and 75 mg daily for one year afterward compared with placebo load and placebo days 29 to 365 in reducing the combined risk of death, myocardial infarction, and stroke. All patients received clopidogrel on days 1 to 28 and aspirin on days 1 to 365. Methods All hospitalizations were assigned a diagnosis-related group. Associated costs were estimated three ways (including professional costs): 1) Medicare costs, 2) MEDSTAT costs, and 3) blend with Medicare for those age ≥65 years and MEDSTAT for those age Results The primary composite end point occurred in 89 (8.45%) clopidogrel patients and in 122 (11.48%) placebo patients (relative risk reduction [RRR] 26.9%; 95% confidence interval [CI] 3.9% to 44.4%). The number of life-years gained (LYG) with clopidogrel was 0.1526 (95% CI 0.0263 to 0.2838) using Framingham data and 0.1920 (95% CI 0.054 to 0.337) using Saskatchewan data. Average total costs were $664 higher for the clopidogrel arm (95% CI −$461 to $1,784). The incremental cost-effectiveness ratios (ICERs) based on Framingham data ranged from $3,685/LYG to $4,353/LYG, with over 97% of bootstrap-derived ICER estimates below $50,000/LYG. The ICERs based on Saskatchewan data were $2,929/LYG to $3,460/LYG, with over 98% of estimates below $50,000/LYG. Conclusions Platelet inhibition with clopidogrel loading before PCI followed by therapy for one year is highly cost effective.

Outcomes of percutaneous coronary intervention (PCI) of the ostia of the major epicardial coronary arteries in the modern era of stenting have not been clearly defined. We evaluated data from all PCIs performed from 1998 to 2001 in the proximal segments of the major epicardial coronary arteries entered into a large cardiac database and compared ostial with nonostial PCI outcomes. Of 2,484 patients who underwent PCI of a proximal coronary artery (left anterior descending, left circumflex, or right coronary), 223 patients had ostial narrowing and 2,261 patients had proximal, nonostial narrowing. Baseline characteristics were similar between the 2 groups, except that patients with ostial narrowing tended to be older and have shorter narrowings than did patients with nonostial narrowings. Stenting occurred in 89% of all patients and was similar in patients with ostial or nonostial narrowings. Procedural success was the same for ostial and nonostial PCI (96% vs 95%, p = 0.95). One-year event-free survival rate was lower in patients who underwent ostial PCI (69% vs 80%, p = 0.0019), largely due to a greater need for repeat PCI (19% vs 10%, p

Staphylococcus aureus has become the leading cause of endocarditis in most published series, and nosocomial acquisition is becoming more frequent. Previous studies involved community acquired methicillin-sensitive S aureus (MSSA), but recently, methicillin-resistant S aureus(MRSA) infection has increased. This may reflect the growing presence of this microorganism in clinical practice. Few data exist comparing the relative rates of endocarditis with MSSA and MRSA bacteremia. The purpose of this study was to compare these rates in a bacteremic population referred for diagnostic echocardiography.Since July 1999, the demographic and clinical information of 104 consecutive patients with at least 2 blood cultures with positive results for S aureus who were referred for echocardiography to be evaluated for endocarditis at Grady Memorial Hospital (Atlanta, Ga) have been entered into a database. This database has further been restricted to patients who have undergone either a transesophageal echocardiogram or a transthoracic echocardiogram.Of the 104 patients with S aureus bacteremia, 53 had an infection of MSSA and 51 had an infection of MRSA. There were 33 patients (31.7%) with echocardiographically confirmed endocarditis, 23 patients (43.4%) in the MSSA group versus 10 patients (19.6%) in the MRSA group (P.009). Community-acquired MSSA bacteremia was the cause of most of the community-acquired S aureus endocarditis (20 patients [87%] vs 3 patients [30%], P =.004), and the nosocomial-acquired MRSA bacteremia was the cause of most of the nosocomial-acquired S aureus endocarditis (3 patients [13%] vs 7 patients [70%], P =.0001).Our study confirms that S aureus bacteremia is associated with high rates of endocarditis. MSSA bacteremia is associated with higher rates of endocarditis than MRSA. Community MSSA is the cause of most of the community endocarditis, whereas nosocomial MRSA is the cause of most of the MRSA endocarditis. Patients with S aureus bacteremia should be aggressively evaluated for endocarditis.

The introduction of Proprotein covertase subtilisin/kexin type 9 (PCSK9) inhibitors has been heralded as a major advancement in reducing low-density lipoprotein cholesterol levels by nearly 50%. However, concerns have been raised on the added value to the health care system in terms of their costs and benefits. We assess the cost-effectiveness of PCSK9 inhibitors based on a decision-analytic model with existing clinical evidence. The model compares a lipid-lowering therapy based on statin plus PCSK9 inhibitor treatment with statin treatment only (standard therapy). From health system perspective, incremental cost per quality adjusted life years (QALYs) gained are presented. From a private payer perspective, return-on-investment and net present values over patient lifespan are presented. At the current annual cost of $14,000 to $15,000, PCSK9 inhibitors are not cost-effective at an incremental cost of about $350,000 per QALY. Moreover, for every dollar invested in PCSK9 inhibitors, the private payer loses $1.98. Our study suggests that the annual treatment price should be set at $4,250 at a societal willingness-to-pay of $100,000 per QALY. However, we estimate the breakeven price for private payer is only $600 per annual treatment. At current prices, our study suggests that PCSK9 inhibitors do not add value to the U.S. health system and their provision is not profitable for private payers. To be the breakthrough drug in the fight against cardiovascular disease, the current price of PCSK9 inhibitors must be reduced by more than 70%.

Introduction: A family history (FH) of premature coronary artery disease (CAD) is an important prognostic risk factor. Emerging evidence suggests that CAD location as well as severity may be heritable. We sought to investigate the association between a FH of premature CAD with the location and severity of angiographically phenotyped CAD. Methods: 2854 patients undergoing coronary angiography were enrolled from the Emory Cardiovascular Biobank. A FH of CAD was defined as having any male or female relative with history of CAD at age ≤55 or ≤65 year old respectively. Coronary angiograms were phenotyped using a 17 segment AHA model. Proximal disease was defined as having ≥70% lesion in the left main or proximal portion of any of the three major epicardial arteries, while CAD severity was assessed by counting the number of vessels with ≥70% stenosis. Results: Among this population (mean age 63±12, male 67%, diabetes 33%), 21% reported a positive FH of premature CAD. After adjustment for age, gender, and traditional cardiovascular risk factors, those with a positive FH were more likely to have significant CAD than those without a positive FH (OR 1.3 (1.1-1.7)). They were 40% more likely to have single vessel (OR 1.4(1.1-1.7)) and up to 80% more likely to have multi-vessel disease (OR 1.8 (1.4-2.4)). In addition, they were also much more likely to have left main (OR 1.9 (1.3-2.8)) and proximal vessel involvement (OR 1.5 (1.2 - 1.9)), but not distal vessel stenosis (OR 1.1 (0.9-1.4)). Conclusions: A FH of CAD is associated with a greater likelihood of multi-vessel and proximal anatomical disease. Whether site specific disease is genetically mediated remains to be explored.

Introduction: Metabolic syndrome, the clustering of multiple cardiovascular risk factors, is established as a risk factor for CVD. Shorter or longer sleep duration has been reported to be associated with increased risk of metabolic syndrome (MS) and diabetes mellitus (DM) through increased insulin resistance (IR). However, it is not known if impaired sleep alters IR in a high-risk population with known MS/DM. Methods: The Baptist Employee Healthy Heart Study is an ongoing lifestyle intervention study examining the effects of web-based interventions on reducing CVD risk in individuals with MS/DM. Sleep duration was self reported by the participants. Daily sleep duration was categorized into sleep 8 hours (long). Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting insulin and fasting glucose level. Results: The population consisted of 182 participants (74% women, 49% Hispanic, mean age 52 ± 9 years). In this study the mean sleep duration was 7±5 hours and mean HOMA-IR was 5.2 ± 5.6 units. Systolic and diastolic blood pressure, BMI, waist circumference, total cholesterol level and LDL cholesterol level did not apparently differ across the groups. Both short and long sleepers tended to have lower HDL cholesterol level and higher triglyceride level (p8hrs (9.52±10.7), p Conclusions: In this study of high metabolic risk individuals, sleep duration was associated with increased insulin resistance and highlights the importance of improving sleep hygiene in the clinical management of high risk individuals with MS and DM.