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Importance: The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.Objective: To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial.Design, Setting, and Participants: Analysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (Intervention: Vericiguat titrated to 10 mg daily vs placebo.Main Outcomes and Measures: The primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH.Results: Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.Conclusions and Relevance: Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.Trial Registration: ClinicalTrials.gov Identifier: NCT02861534.

Aim: To assess feasibility and patient satisfaction with a pharmacist-delivered medication therapy management (MTM) plus pharmacogenetic (PGx) testing service. Methods: Thirty patients from a cardiology outpatient clinic were enrolled to attend two MTM sessions, undergo PGx testing and complete pre- and post-intervention surveys. Outcome measures included duration of MTM sessions, clinical application of test results, self-reported medication adherence, patient recall of results and perceived value of testing and MTM. Results: Overall, patients were very satisfied with the MTM plus PGx testing service. About half of participants (47%) were able to accurately recall their PGx test results. Comparable to MTM without PGx testing, the first MTM session averaged 40 min and the follow-up MTM session averaged 15 min. Conclusion: PGx testing incorporated into a clinical MTM service offered by pharmacists may be a feasible delivery model and is satisfactory to patients.

The development and implementation of worksite health and wellness programs (WHWPs) in the United States (US) hold promise as a means to improve population health and reverse current trends in non-communicable disease incidence and prevalence. However, WHWPs face organizational, economic, systematic, legal, and logistical challenges which have combined to impact program availability and expansion. Even so, there is a burgeoning body of evidence indicating WHWPs can significantly improve the health profile of participating employees in a cost effective manner. This foundation of scientific knowledge justifies further research inquiry to elucidate optimal WHWP models. It is clear that the development, implementation and operation of WHWPs require a strong commitment from organizational leadership, a pervasive culture of health and availability of necessary resources and infrastructure. Since organizations vary significantly, there is a need to have flexibility in creating a customized, effective health and wellness program. Furthermore, several key legal issues must be addressed to facilitate employer and employee needs and responsibilities; the US Affordable Care Act will play a major role moving forward. The purposes of this review are to: 1) examine currently available health and wellness program models and considerations for the future; 2) highlight key legal issues associated with WHWP development and implementation; and 3) identify challenges and solutions for the development and implementation of as well as adherence to WHWPs.

Aim: To describe the rationale and design of a pilot study evaluating the integration of pharmacogenetic (PGx) testing into pharmacist-delivered medication therapy management (MTM). Study rationale: Clinical delivery approaches of PGx testing involving pharmacists may overcome barriers of limited physician knowledge about and experience with testing. Study design: We will assess the addition of PGx testing to MTM services for cardiology patients taking three or more medications including simvastatin or clopidogrel. We will measure the impact of MTM plus PGx testing on drug/dose adjustment and clinical outcomes. Factors associated with delivery, such as time to prepare and conduct MTM and consult with physicians will be recorded. Additionally, patient interest and satisfaction will be measured. Anticipated results: We anticipate that PGx testing can be practically integrated into standard a MTM service, providing a viable delivery model for testing. Conclusion: Given the lack of evidence of an effective PGx delivery models, this study will provide preliminary evidence regarding a pharmacist-delivered approach.

In overweight/obese individuals, cardiometabolic risk factors differ by race and sex categories. Small-molecule metabolites and metabolic hormone levels might also differ across these categories and contribute to risk factor heterogeneity. To explore this possibility, we performed a cross-sectional analysis of fasting plasma levels of 69 small-molecule metabolites and 13 metabolic hormones in 500 overweight/obese adults who participated in the Weight Loss Maintenance trial. Principal-components analysis (PCA) was used for reduction of metabolite data. Race and sex-stratified comparisons of metabolite factors and metabolic hormones were performed. African Americans represented 37.4% of the study participants, and females 63.0%. Of thirteen metabolite factors identified, three differed by race and sex: levels of factor 3 (branched-chain amino acids and related metabolites, p

Advances in the mechanistic understanding of atheroma initiation, repair, progression, and rupture have solidified the pivotal role played by the immune system in the pathophysiology of atherosclerotic vascular disease. These mechanistic findings have been extended into humans, with a strong evidence basis for the independent association between elevated blood markers of inflammation and future cardiovascular (CV) events. Investigations with statins as well as more conventional anti-inflammatory medications provide indirect evidence to support the concept that modifying immune responses can improve CV outcomes; however, robust evidence to support the use of anti-inflammatory treatment strategies to manage atherosclerotic vascular disease is still lacking. Such evidence may emerge from a new wave of clinical trials directly exploring the effects of targeted immune modulation on CV risk. These trials will provide key additional insights into atherosclerosis and will help determine the fate of immune modulation as a new treatment strategy in atherosclerotic vascular disease.

Background— Patients with diabetes mellitus (DM) are at high risk for mortality after myocardial infarction (MI). Despite an overall trend of reduced mortality after MI, the mortality gap between MI patients with and without DM did not decrease over time in previous analyses. We assessed recent trends in hospital mortality for patients with MI according to DM status. Methods and Results— We analyzed data from the National Registry of Myocardial Infarction, a contemporary registry of MI patients treated in 1964 hospitals, representing approximately one fourth of all US acute care hospitals. The study comprised 1734431 MI patients enrolled from 1994 to 2006, including 502315 (29%) with DM. Crude hospital mortality decreased in all patients between 1994 and 2006 but remained higher in patients with DM compared with those without DM throughout the study. The absolute difference in mortality between patients with and without DM significantly narrowed over time, from 15.6% versus 11.5% in 1994 to 8.0% versus 6.8% in 2006 ( P P P Conclusions— The hospital mortality gap between MI patients with and without DM narrowed significantly from 1994 to 2006, with the greatest improvement observed in women with DM.

Randomized clinical trials of exercise training regimens in sedentary individuals have provided a mechanistic understanding of the long-term health benefits and consequences of physical activity and inactivity. The sedentary control periods from these trials have provided evidence of the progressive metabolic deterioration that results from as little as 4–6 mo of continuing a physically inactive lifestyle. These clinical trials have also demonstrated that only a modest amount of physical activity is required to prevent this metabolic deterioration, and this amount of physical activity is consistent with current physical activity recommendations (150 min/wk of moderate intensity physical activity). These recommendations have been issued to the general population for a vast array of health benefits. While greater adherence to these recommendations should result in substantial improvements in the health of the population, these recommendations still remain inadequate for many individuals. An individual's physical activity requirements are influenced by such factors as an individual's diet, nonexercise physical activity patterns, genetic profile, and medications. Improving the understanding of how these factors influence an individual's physical activity requirements will help advance the field and help move the field toward the development of more personalized physical activity recommendations.

Objectives This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort. Background Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden. Methods Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score >10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging. Results In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend Conclusions We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden.

Results from recent clinical trials have advanced our understanding of the role of HMG-CoA reductase inhibitors (statins) in the management of patients following acute coronary syndrome (ACS) episodes. In aggregate, these trials have demonstrated the safety and efficacy associated with initiation of intensive statin therapy prior to hospital discharge following an ACS episode, independent of baseline low-density lipoprotein (LDL) cholesterol concentrations. Based on the results of these trials, there is now compelling evidence to support intensive lipid lowering with high-dose statins initiated prior to hospital discharge for all patients suffering ACS episodes with a target for LDL cholesterol of 70 mg/dL or lower, recommendations that have been incorporated into clinical practice guideline recommendations in the most recent position statement from the National Cholesterol Education Panel.

Elevated troponin is increasingly recognized as a marker of cardiac injury and poor outcomes in diverse disease states. It was hypothesized that patients with infective endocarditis (IE) and elevated cardiac troponin would have more extensive IE and worse clinical outcomes. Patients were enrolled as part of the International Collaboration on Endocarditis (ICE) prospective cohort study; analysis of these patients was done retrospectively. Data from 83 consecutively enrolled patients from a single center were evaluated. Cardiac troponin I (cTnI) was drawn for clinical indications and before any cardiac surgery in 51 of the 83 patients. Outcomes evaluated were hospital mortality, annular or myocardial abscess on the basis of echocardiography or surgery, and central nervous system events. Of 51 patients with cTnI drawn, 33 (65%) had elevated cTnI > or =0.1 mg/dl. There were no differences in age, gender, prosthetic valve IE, Staphylococcus aureus IE, or history of coronary artery disease, congestive heart failure, or diabetes mellitus between patients with and without cTnI elevations. Patients with elevated cTnI were less likely to have isolated right-sided IE and more likely to have left ventricular systolic dysfunction or renal dysfunction (p

The Screening for Heart Attack Prevention and Education (SHAPE) Task Force recommends noninvasive atherosclerosis imaging of all asymptomatic men (aged 45-75 years) and women (aged 55-75 years), except those at very low risk, to augment conventional cardiovascular risk assessment algorithms.Among 2611 participants in the Dallas Heart Study aged 30 to 65 years who underwent computed tomography to measure coronary artery calcification, low-density lipoprotein cholesterol (LDL-C) therapeutic targets were calculated using both National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and SHAPE algorithms. The proportion of subjects reclassified as being "at goal" for LDL-C vs "not at goal" after implementation of the SHAPE recommendations was determined.More subjects were identified with LDL-C levels greater than or equal to goal based on SHAPE than on NCEP-ATP III (27.4% vs 21.6%), with 7.0% of individuals reclassified as having unmet LDL-C goals and 1.1% of individuals reclassified as at goal. When more aggressive optional LDL-C goals were implemented, 31.7% had LDL-C levels greater than or equal to goal using SHAPE recommendations vs 28.1% using NCEP-ATP III recommendations, with 6.3% of subjects reclassified as being not at goal and 2.7% as being at goal.The SHAPE recommendations resulted in bidirectional reclassification of eligibility for lipid-lowering therapy in subjects aged 30 to 65 years. While broad implementation of these recommendations would modestly increase cholesterol-lowering drug use in this age range, the magnitude of the increase depends on whether standard or optional LDL-C goals are targeted.

This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort.Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden.Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging.In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend0.001 for each). After multivariable adjustment for standard risk factors, prevalent CAC was more frequent in the fifth versus first quintile of WHR (odds ratio 1.91, 95% confidence interval 1.30 to 2.80), whereas no independent positive association was observed for BMI or WC. Similar results were observed for aortic plaque in both univariable and multivariable-adjusted analyses. The c-statistic for discrimination of prevalent CAC was greater for WHR compared with BMI and WC in women and men (p0.001 vs. BMI; p0.01 vs. WC).We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden.

Can biomarkers improve prediction of future cardiovascular events in patients with cardiovascular disease?

High performance preparative chromatographic systems are described which facilitate the isolation and purification of some naturally occurring, novel mycinamicins. Facile separation and excellent recovery of these macrolide antibiotics was obtained with a C-18 radially compressed Prep 500 cartridge using methanol/trifluoroacetic acid mobile phases. Semi-preparative chromatography on a C-8 reversed-phase sorbent incorporating a volatile ammonium acetate buffer was utilized in the final purification of an enriched mixture of intermediate components. Monitoring of isolated fractions with analytical HPLC provided direct support for the effectiveness of the preparative isolation.