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In the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial, vericiguat reduced the risk of mortality due to cardiovascular problems and of hospitalization due to heart failure (HF) among patients with HF with reduced ejection fraction (HFrEF) and recent worsening HF events (WHFEs). The representativeness of the VICTORIA population of patients with WHFE in clinical practice is unknown.Patients with HF and ejection fraction45% were identified in the Practice Innovation And Clinical Excellence (PINNACLE) registry and were stratified by the occurrence of WHFEs. Characteristics and outcomes of patients in the PINNACLE registry with and without WHFEs were compared to the VICTORIA population. Of the 14,180 PINNACLE patients identified with HFrEF, 26.5% had had a WHFE. The VICTORIA population was similar to PINNACLE patients with WHFEs in mean age (67.3 vs 66.7), ejection fraction (28.9% vs 28.3%), body mass index (26.8 vs 27.6), and comorbidity burden. The rate of hospitalization because of HF at 1 year was 29.6% in the placebo group of VICTORIA, compared to 35.8% in PINNACLE patients with WHFEs and 13.3% in patients without WHFEs.The PINNACLE patients with WHFEs meeting the VICTORIA definition resembled the VICTORIA population in characteristics and outcomes, suggesting that VICTORIA's population may be generalizable to patients with WHFEs in clinical practice.

Background Although safety and tolerability of vericiguat were established in the VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial in patients with heart failure with reduced ejection fraction, some subgroups may be more susceptible to symptomatic hypotension, such as older patients, those with lower baseline systolic blood pressure (SBP), or those concurrently taking angiotensin receptor neprilysin inhibitors. We described the SBP trajectories over time and compared the occurrence of symptomatic hypotension or syncope by treatment arm in potentially vulnerable subgroups in VICTORIA. We also evaluated the relation between the efficacy of vericiguat and baseline SBP. Methods and Results Among patients receiving at least 1 dose of the study drug (n=5034), potentially vulnerable subgroups were those >75 years old (n=1395), those with baseline SBP 100–110 mm Hg (n=1344), and those taking angiotensin receptor neprilysin inhibitors (n=730). SBP trajectory was plotted as mean change from baseline over time. The treatment effect on time to symptomatic hypotension or syncope was evaluated overall and by subgroup, and the primary efficacy composite outcome (heart failure hospitalization or cardiovascular death) across baseline SBP was examined using Cox proportional hazards models. SBP trajectories showed a small initial decline in SBP with vericiguat in those >75 years old (versus younger patients), as well as those receiving angiotensin receptor neprilysin inhibitors (versus none), with SBP returning to baseline thereafter. Patients with SBP P =0.059). No difference existed between treatment arms in landmark analysis beginning after the titration phase (ie, post 4 weeks) (adjusted HR, 1.14; 95% CI, 0.93–1.38; P =0.20). The benefit of vericiguat compared with placebo on the primary composite efficacy outcome was similar across the spectrum of baseline SBP ( P for interaction=0.32). Conclusions These data demonstrate the safety of vericiguat in a broad population of patients with worsening heart failure with reduced ejection fraction, even among those predisposed to hypotension. Vericiguat’s efficacy persisted regardless of baseline SBP. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02861534.

Aims We evaluated the relation between baseline and new-onset atrial fibrillation (AF) and outcomes, and assessed whether vericiguat modified the likelihood of new-onset AF in patients with worsening heart failure (HF) with reduced ejection fraction in VICTORIA. Methods and results Of 5050 patients randomized, 5010 with recorded AF status at baseline were analysed. Patients were classified into three groups: no known AF (n = 2661, 53%), history of AF alone (n = 992, 20%), and AF on randomization electrocardiogram (n = 1357, 27%). Compared with those with no AF, those with history of AF alone had a higher risk of cardiovascular death [adjusted hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.01-1.47] without excess myocardial infarction or stroke; neither type of AF was associated with a higher risk of the primary composite outcome (time to cardiovascular death or first HF hospitalization), HF hospitalizations, or all cause-death. The beneficial effect of vericiguat on the primary composite outcome and its components was evident irrespective of AF status at baseline. Over a median follow-up of 10.8 months, new-onset AF occurred in 6.1% of those with no AF and 18.3% with history of AF alone (P < 0.0001). These events were not influenced by vericiguat treatment (adjusted HR 0.93, 95% CI 0.75-1.16; P = 0.51), but were associated with an increase in the hazard of both primary and secondary outcomes. Conclusions Atrial fibrillation was present in nearly half of this high-risk population with worsening HF. A history of AF alone at baseline portends an increased risk of cardiovascular death. Neither type of AF affected the beneficial effect of vericiguat. Development of AF post-randomization was associated with an increase in both cardiovascular death and HF hospitalization which was not influenced by vericiguat.

Objective To identify temporal trends in the use of exercise treadmill testing (ETT) and cardiorespiratory fitness (CRF) estimated by ETT in metabolic equivalents (METs). Patients and methods We compiled an ETT database of all available treadmill tests—including those with concomitant stress echocardiography and nuclear perfusion imaging studies—performed at Duke University Hospital from January 1, 1970- December 31, 2012. Six different ramp protocols were used in these combined modalities. CRF at maximal exertion was estimated using established metrics. Eligible patients were required to have no missing data on maximal treadmill speed, grade, and protocol. Results The most commonly used ETT protocol was the Bruce (n = 28,877), followed by manual test (n = 7390). Since the 1980’s, the use of ETT for clinical purposes declined substantially; there was a decreased trend in utilization of 9.4% over the decades 1990–1999 and 2000–2009. When standard protocol (Bruce) was assessed in isolation, trends in CRF decreased progressively from 1970 to 2012 (mean METs (standard deviation): 11.7 (4.3) to 10.5 (3.5)). After adjusting for baseline comorbidities, the trend was reduced to a lesser degree. Conclusions The use of ETT at our institution has declined over time, perhaps due to changes in clinical practice. In patients undergoing ETT using the standard Bruce protocol, CRF decreased progressively over the last five decades. Future studies are needed to clarify the etiology of the decrease in use of such a powerful predictor of clinical outcomes in our medical care environment.

Background Epidemiology of patients with worsening heart failure and reduced ejection fraction (HFrEF) in the real-world setting is not well described. Objectives The purpose of this study was to describe incidence, clinical characteristics, treatment, and outcomes of patients with HFrEF who develop worsening heart failure (HF) in the real-world setting. Methods Data on patients with incident HFrEF from the National Cardiovascular Data Registry PINNACLE were linked to pharmacy, private practitioner, and hospital claims databases. Incidence, clinical characteristics, treatment (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist) and outcomes of patients with worsening HF, defined as ≥90 days of stable HF with subsequent worsening requiring intravenous diuretic agents, were assessed. Results Of 11,064 HFrEF patients, 1,851 (17%) developed worsening HF on average 1.5 years following initial HF diagnosis. Patients who developed worsening HF were more likely to be African American, be octogenarians, and have higher comorbidity burden (p 50% target dose for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist, respectively. The 2-year mortality rate was 22.5%, and 56% of patients were rehospitalized within 30 days of the worsening HF event. Conclusions In the real-world setting, 1 in 6 patients with HFrEF develop worsening HF within 18 months of HF diagnosis. These patients have a high risk for 2-year mortality and recurrent HF hospitalizations. The use of standard-of-care therapies both before and after the onset of worsening HF is low. With high unmet medical need, patients with worsening HF require novel treatment strategies as well as greater optimization of existing guideline-directed therapy.

Introduction: The VICTORIA (Vericiguat Global Study in Subjects with HF with Reduced EF) trial included 5050 patients in 3 discrete subgroups reflecting their index worsening heart failure (HF) event: Methods: We compared primary composite (CV death and HFH) and secondary (all-cause death and HFH) outcomes across index event subgroups, both before and after adjusting for clinical covariates (HF duration, NYHA class, medical history, heart rate, HF medications and laboratory values including baseline NT-proBNP), as well as their response to vericiguat. Results: Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow up of 10.8 months, the absolute primary event rates were high in all subgroups (20.5 - 42.5 per 100 patient-years, Figure). Compared to the IV diuretic group highest relative risk was in HFH Conclusions: Among patients with worsening chronic HF, those within a 3 month window of HFH had almost a 1.5 times risk of CV death or HFH compared to those requiring IV diuretics but not HFH , irrespective of age or clinical risk factors. Vericiguat added to standard therapy was associated with similar benefit across the spectrum of risk in worsening HF.

Objectives The purpose of this study was to examine the treatment effect of vericiguat in relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at randomization. Background Vericiguat compared with placebo reduced the primary outcome of cardiovascular death (CVD) or heart failure hospitalization (HFH) in patients with HF with reduced ejection fraction (HFrEF) in the VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial. Because an interaction existed between treatment and the primary outcome according to pre-specified quartiles of NT-proBNP at randomization, we examined this further. Methods This study evaluated the NT-proBNP relationship with the primary outcome in 4,805 of 5,050 patients as a risk-adjusted, log-transformed continuous variable. Hazard ratios (HRs) and 95% confidence intervals (CIs) are presented. Results Median NT-proBNP was 2,816 pg/ml (25th to 75th percentile: 1,556 to 5,314 pg/ml). The study treatment effect varied across the spectrum of NT-proBNP at randomization (with log2 transformation, p for interaction = 0.002). A significant association between treatment effects existed in patients with levels 8,000 pg/ml (n = 672), the HR was 1.16 (95% CI: 0.94 to 1.41) for the primary outcome. Conclusions A reduction in the primary composite endpoint and its CVD and HFH components was observed in patients on vericiguat compared with subjects on placebo with NT-proBNP levels up to 8,000 pg/ml. This provided new insight into the benefit observed in high-risk patients with worsening HFrEF. (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF] [MK-1242-001] [VICTORIA]; NCT02861534)

The purpose of this study was to examine the treatment effect of vericiguat in relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at randomization.Vericiguat compared with placebo reduced the primary outcome of cardiovascular death (CVD) or heart failure hospitalization (HFH) in patients with HF with reduced ejection fraction (HFrEF) in the VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial. Because an interaction existed between treatment and the primary outcome according to pre-specified quartiles of NT-proBNP at randomization, we examined this further.This study evaluated the NT-proBNP relationship with the primary outcome in 4,805 of 5,050 patients as a risk-adjusted, log-transformed continuous variable. Hazard ratios (HRs) and 95% confidence intervals (CIs) are presented.Median NT-proBNP was 2,816 pg/ml (25th to 75th percentile: 1,556 to 5,314 pg/ml). The study treatment effect varied across the spectrum of NT-proBNP at randomization (with logA reduction in the primary composite endpoint and its CVD and HFH components was observed in patients on vericiguat compared with subjects on placebo with NT-proBNP levels up to 8,000 pg/ml. This provided new insight into the benefit observed in high-risk patients with worsening HFrEF. (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF] [MK-1242-001] [VICTORIA]; NCT02861534).

This trial sought to evaluate whether vericiguat, a novel oral soluble guanylate cyclase (sGC) stimulator, was superior to placebo, on a background of standard of care, in increasing the time to the first occurrence of the composite endpoints of cardiovascular (CV) death and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction (HFrEF). Deficiency in sGC-derived cyclic guanosine monophosphate (cGMP) causes both myocardial dysfunction and impaired endothelium-dependent vasomotor regulation that includes the myocardial microcirculation. Experimental studies have suggested multiple potential benefits of sGC stimulators including prevention, or even reversal, of left ventricular hypertrophy and fibrosis, as well as reduction of ventricular afterload through both systemic and pulmonary vasodilation. Hence, restoration of sufficient nitric oxide (NO)-sGC–cGMP signaling has been proposed as an important treatment target in HF. Vericiguat has been shown to directly stimulate sGC and enhance sGC sensitivity to endogenous NO. Available phase IIb data in HFrEF patients indicate vericiguat is safe and well-tolerated, and exploratory analyses indicate that it results in a dose-dependent, clinically significant reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP) at the highest tested dose. VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) is a randomized, placebo-controlled, parallel group, multicenter, double-blind, event-driven phase 3 trial of vericiguat in subjects with HFrEF. Approximately 4,872 subjects will be randomized to evaluate the efficacy and safety of vericiguat compared with placebo on a background of standard of care. After a screening phase of up to 30 days, eligible subjects will be treated until the required number of cardiovascular deaths is observed. The estimated median follow-up duration is approximately 18 months. All subjects will be followed until study completion to assess for the occurrence of endpoint events. VICTORIA will establish the efficacy and safety of vericiguat on cardiovascular death and HF hospitalization in patients with HFrEF. (A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III Clinical Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat in Subjects With Heart Failure With Reduced Ejection Fraction [HFrEF]—VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534)

Objectives This study sought to assess a novel physical rehabilitation intervention in older patients hospitalized for acute decompensated heart failure (ADHF). Background After ADHF, older patients, who are frequently frail with multiple comorbidities, have prolonged and incomplete recovery of physical function and remain at high risk for poor outcomes. Methods The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) pilot study was a 3-site, randomized, attention-controlled pilot study of a tailored, progressive, multidomain physical rehabilitation intervention beginning in the hospital and continuing for 12 weeks post-discharge in patients ≥60 years hospitalized with ADHF. The primary purpose was to assess the feasibility and reasonableness of the hypothesis that the novel rehabilitation intervention would improve physical function (Short Physical Performance Battery [SPPB]) over 3 months and reduce all-cause rehospitalizations over 6 months. Results The study enrolled 27 patients with ADHF (ages 60 to 98 years; 59% women; 56% African American; 41% with preserved ejection fraction [≥45%]). At baseline, participants had marked impairments in physical function, multiple comorbidities, and frailty. Study retention (89%) and intervention adherence (93%) were excellent. At 3 months, an intervention effect size was measured for the SPPB score of +1.1 U (7.4 ± 0.5 U vs. 6.3 ± 0.5 U), and at 6 months an effect size was observed for an all-cause rehospitalization rate of −0.48 (1.16 ± 0.35 vs. 1.64 ± 0.39). The change in SPPB score was strongly related to all-cause rehospitalizations, explaining 91% of change. Conclusions These findings support the feasibility and rationale for a recently launched, National Institutes of Health–funded trial to test the safety and efficacy of this novel multidomain physical rehabilitation intervention to improve physical function and reduce rehospitalizations in older, frail patients with ADHF with multiple comorbidities. (Rehabilitation and Exercise Training After Hospitalization [REHAB-HF]; NCT01508650; A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038)

International audience; Aim: Describe the distinguishing features of heart failure (HF) patients with reduced ejection fraction (HFrEF) in the VICTORIA (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction) trial.Methods and results: Key background characteristics were evaluated in 5050 patients randomized in VICTORIA and categorized into three cohorts reflecting their index worsening HF event. Differences within the VICTORIA population were assessed and compared with PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure). VICTORIA patients had increased risk of mortality and rehospitalization: New York Heart Association class (40% class III), atrial fibrillation (45%), diabetes (47%), hypertension (79%) and mean estimated glomerular filtration rate of 61.5 mL/min/1.73 m2 . Baseline standard of HF care was very good: 60% received triple therapy. Their N-terminal pro-B-type natriuretic peptide was 3377 pg/mL [interquartile range (IQR) 1992-6380]. Natriuretic peptides were 30% higher level in the 67% patients with HF hospitalization

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.

Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients with heart failure with reduced ejection fraction (HFrEF). An estimated 24 million people in the United States are affected by COPD, and its prevalence in patients with HFrEF ranges from 11% to 39% [(1,2)][1]. The high

This trial sought to evaluate whether vericiguat, a novel oral soluble guanylate cyclase (sGC) stimulator, was superior to placebo, on a background of standard of care, in increasing the time to the first occurrence of the composite endpoints of cardiovascular (CV) death and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction (HFrEF). Deficiency in sGC-derived cyclic guanosine monophosphate (cGMP) causes both myocardial dysfunction and impaired endothelium-dependent vasomotor regulation that includes the myocardial microcirculation. Experimental studies have suggested multiple potential benefits of sGC stimulators including prevention, or even reversal, of left ventricular hypertrophy and fibrosis, as well as reduction of ventricular afterload through both systemic and pulmonary vasodilation. Hence, restoration of sufficient nitric oxide (NO)-sGC-cGMP signaling has been proposed as an important treatment target in HF. Vericiguat has been shown to directly stimulate sGC and enhance sGC sensitivity to endogenous NO. Available phase IIb data in HFrEF patients indicate vericiguat is safe and well-tolerated, and exploratory analyses indicate that it results in a dose-dependent, clinically significant reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at the highest tested dose. VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) is a randomized, placebo-controlled, parallel group, multicenter, double-blind, event-driven phase 3 trial of vericiguat in subjects with HFrEF. Approximately 4,872 subjects will be randomized to evaluate the efficacy and safety of vericiguat compared with placebo on a background of standard of care. After a screening phase of up to 30 days, eligible subjects will be treated until the required number of cardiovascular deaths is observed. The estimated median follow-up duration is approximately 18 months. All subjects will be followed until study completion to assess for the occurrence of endpoint events. VICTORIA will establish the efficacy and safety of vericiguat on cardiovascular death and HF hospitalization in patients with HFrEF. (A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III Clinical Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat in Subjects With Heart Failure With Reduced Ejection Fraction [HFrEF]-VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534).

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.

Background Although epidemiologic studies have shown associations between sedentary behavior and mortality, few have focused on older women with adequate minority representation and few have controlled for both physical activity and functional status. Purpose The objective of this study was to determine the relationship between sedentary time and total; cardiovascular disease (CVD); coronary heart disease (CHD); and cancer mortality in a prospective, multiethnic cohort of postmenopausal women. Methods The study population included 92,234 women aged 50–79 years at baseline (1993–1998) who participated in the Women's Health Initiative Observational Study through September 2010. Self-reported sedentary time was assessed by questionnaire and examined in 4 categories (≤4, >4–8, ≥8–11, >11 hours). Mortality risks were examined using Cox proportional hazard models adjusting for confounders. Models were also stratified by age, race/ethnicity, body mass index, physical activity, physical function, and chronic disease to examine possible effect modification. Analyses were conducted in 2012–2013. Results The mean follow-up period was 12 years. Compared with women who reported the least sedentary time, women reporting the highest sedentary time had increased risk of all-cause mortality in the multivariate model (HR=1.12, 95% CI=1.05, 1.21). Results comparing the highest versus lowest categories for CVD, CHD, and cancer mortality were as follows: HR=1.13, 95% CI=0.99, 1.29; HR=1.27, 95% CI=1.04, 1.55; and HR=1.21, 95% CI=1.07, 1.37, respectively. For all mortality outcomes, there were significant linear tests for trend. Conclusions There was a linear relationship between greater amounts of sedentary time and mortality risk after controlling for multiple potential confounders.

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.

The epidemiological, clinical, and societal implications of the heart failure (HF) epidemic cannot be overemphasized. Approximately half of all HF patients have HF with preserved ejection fraction (HFpEF). HFpEF is largely a syndrome of the elderly, and with aging of the population, the proportion of patients with HFpEF is expected to grow. Currently, there is no drug known to improve mortality or hospitalization risk for these patients. Besides mortality and hospitalization, it is imperative to realize that patients with HFpEF have significant impairment in their functional capacity and their quality of life on a daily basis, underscoring the need for these parameters to ideally be incorporated within a regulatory pathway for drug approval. Although attempts should continue to explore therapies to reduce the risk of mortality or hospitalization for these patients, efforts should also be directed to improve other patient-centric concerns, such as functional capacity and quality of life. To initiate a dialogue about the compelling need for and the challenges in developing such alternative endpoints for patients with HFpEF, the US Food and Drug Administration on November 12, 2015, facilitated a meeting represented by clinicians, academia, industry, and regulatory agencies. This document summarizes the discussion from this meeting.

Background: Poor lifestyle behaviors are leading causes of preventable diseases globally. Added sugars contribute to a diet that is energy dense but nutrient poor and increase risk of developing obesity, cardiovascular disease, hypertension, obesity-related cancers, and dental caries. Methods and Results: For this American Heart Association scientific statement, the writing group reviewed and graded the current scientific evidence for studies examining the cardiovascular health effects of added sugars on children. The available literature was subdivided into 5 broad subareas: effects on blood pressure, lipids, insulin resistance and diabetes mellitus, nonalcoholic fatty liver disease, and obesity. Conclusions: Associations between added sugars and increased cardiovascular disease risk factors among US children are present at levels far below current consumption levels. Strong evidence supports the association of added sugars with increased cardiovascular disease risk in children through increased energy intake, increased adiposity, and dyslipidemia. The committee found that it is reasonable to recommend that children consume ≤25 g (100 cal or ≈6 teaspoons) of added sugars per day and to avoid added sugars for children

This study sought to assess a novel physical rehabilitation intervention in older patients hospitalized for acute decompensated heart failure (ADHF).After ADHF, older patients, who are frequently frail with multiple comorbidities, have prolonged and incomplete recovery of physical function and remain at high risk for poor outcomes.The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) pilot study was a 3-site, randomized, attention-controlled pilot study of a tailored, progressive, multidomain physical rehabilitation intervention beginning in the hospital and continuing for 12 weeks post-discharge in patients ≥60 years hospitalized with ADHF. The primary purpose was to assess the feasibility and reasonableness of the hypothesis that the novel rehabilitation intervention would improve physical function (Short Physical Performance Battery [SPPB]) over 3 months and reduce all-cause rehospitalizations over 6 months.The study enrolled 27 patients with ADHF (ages 60 to 98 years; 59% women; 56% African American; 41% with preserved ejection fraction [≥45%]). At baseline, participants had marked impairments in physical function, multiple comorbidities, and frailty. Study retention (89%) and intervention adherence (93%) were excellent. At 3 months, an intervention effect size was measured for the SPPB score of +1.1 U (7.4 ± 0.5 U vs. 6.3 ± 0.5 U), and at 6 months an effect size was observed for an all-cause rehospitalization rate of -0.48 (1.16 ± 0.35 vs. 1.64 ± 0.39). The change in SPPB score was strongly related to all-cause rehospitalizations, explaining 91% of change.These findings support the feasibility and rationale for a recently launched, National Institutes of Health-funded trial to test the safety and efficacy of this novel multidomain physical rehabilitation intervention to improve physical function and reduce rehospitalizations in older, frail patients with ADHF with multiple comorbidities. (Rehabilitation and Exercise Training After Hospitalization [REHAB-HF]; NCT01508650; A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038).

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.

A strategy using coronary artery calcium (CAC) screening to refine coronary heart disease risk assessment in moderately high risk (MHR) subjects (10-year risk 10%-20%) has been suggested. The potential impact of this strategy is unknown.Coronary artery calcium screening strategies focused on MHR subjects were modeled in 2,610 subjects aged 30 to 65 years undergoing Framingham risk scoring and CAC assessment in the Dallas Heart Study. The proportions of subjects eligible for imaging and reclassified from MHR to high risk (HR) (10-year risk20%) based upon CAC scores were determined.Only 1.0% of women and 15.4% of men were at MHR by Framingham risk scoring and thus eligible for imaging, and0.1% and 1.1% respectively, changed from MHR to HR using a CAC thresholdor = 400. Coronary artery calcium imaging targeting MHR subjects was also relatively inefficient (100 women, 14.3 men scanned per subject reclassified). Restricting to an older age range (45-65 years) or expanding the MHR group to 6% to 20% risk had virtually no impact on risk assessment in women. In a secondary analysis, a proposed imaging strategy targeting promotion of subjects from lower risk to MHR was more efficient and had greater yield than current recommendations targeting promotion from MHR to HR.Coronary artery calcium screening strategies focused on MHR subjects will have a negligible impact on risk assessment in women and a modest impact in men. Further studies are needed to optimize the use of CAC screening as an adjunct to coronary heart disease risk assessment, especially for women and those at seemingly lower risk.

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.

Older patients with acute decompensated heart failure (ADHF) have persistently poor outcomes including frequent rehospitalization despite guidelines-based therapy. We hypothesized that such patients have multiple, severe impairments in physical function, cognition, and mood that are not addressed by current care pathways. We prospectively examined frailty, physical function, cognition, mood, and quality of life in 27 consecutive older patients with ADHF at 3 medical centers and compared these with 197 participants in 3 age-matched cohorts: stable heart failure (HF) with preserved ejection fraction (n = 80), stable HF with reduced ejection fraction (n = 56), and healthy older adults (n = 61). Based on Fried criteria, frailty was present in 56% of patients with ADHF versus 0 for the age-matched chronic HF and health cohorts. Patients with ADHF had markedly reduced Short Physical Performance Battery score (5.3 ± 2.8) and 6-minute walk distance (178 ± 102 m) (p

BackgroundData from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables.ObjectivesThe study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER).MethodsAmong patients (n= 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [Vo2], exercise duration, percent predicted peak Vo2 [%ppVo2], ventilatory efficiency) were examined.ResultsOver a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p< 0.0001). Both %ppVo2 and exercise duration were equally able to predict (Wald chi-square: ∼141) and discriminate (c-index: 0.69) mortality. Peak Vo2 (ml·kg(-1)·min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppVo2, exercise duration, and peak Vo2 (ml·kg(-1)·min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak Vo2 of 10.9 ml·kg(-1)·min(-1) versus 5.3ml·kg(-1)·min(-1) in women.ConclusionsPeak Vo2, exercise duration, and % ppVo2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak Vo2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437).

Background—Despite evidence supporting the use of aspirin, β-blockers, angiotensin-converting enzyme inhibitors, and lipid-lowering therapies in eligible patients, adoption of these secondary prevention measures after coronary artery bypass grafting has been inconsistent. We sought to rigorously test on a national scale whether low-intensity continuous quality improvement interventions can be used to speed secondary prevention adherence after coronary artery bypass grafting. Methods and Results—A total of 458 hospitals participating in the Society of Thoracic Surgeons National Cardiac Database and treating 361 328 patients undergoing isolated coronary artery bypass grafting were randomized to either a control or an intervention group. The intervention group received continuous quality improvement materials designed to influence the prescription of the secondary prevention medications at discharge. The primary outcome measure was discharge prescription rates of the targeted secondary prevention medications...

Two novel chemokine receptor CCR-5 inhibitors, Sch 210971 (1) and Sch 210972 (2), were isolated from the fungal fermentation broth of Chaetomium globosum by normal- and reversed-phase HPLC purifications. The structure determination of 1 and 2 was accomplished on the basis of UV, MS, and NMR spectral data analyses including COSY, NOESY, HMQC, and HMBC experiments. The structure and relative configuration of 2 were determined unequivocally by X-ray crystallographic analysis. The major component 2 demonstrated a potent inhibitory activity of IC(50) = 79 nM in the CCR-5 receptor in vitro binding assay.

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.

Introduction: Exercise training improves outcomes in patients with chronic, stable heart failure (HF). However, little is known regarding patients with acute decompensated HF (ADHF) who are typically elderly, frail, with multiple co-morbidities and frequent rehospitalizations. Hypothesis: A novel rehabilitation intervention in older patients hospitalized for ADHF will be feasible and safe, improve physical function and reduce rehospitalizations. Methods: This was a 3-site, randomized, attention-controlled pilot study of a tailored, progressive, multi-domain (strength, balance, mobility and endurance) rehabilitation intervention beginning in the hospital and continuing for 12 weeks post-discharge. The primary outcome was the Short Physical Performance Battery (SPPB) score, a standardized measure of physical function in frail elderly, assessed by a blinded observer; the secondary outcome was rehospitalizations. Results: We enrolled 27 patients aged 60-98 years: 59% women, 56% African-American, 41% preserved EF. Patients had ~ 5 co-morbidities and markedly impaired physical function; > 50% were frail. Characteristics were similar between groups. Study retention (89%) and intervention adherence (93%) were excellent. Figure 1 shows change in SPPB score and 6-minute walk distance. All-cause rehospitalizations were reduced by 29% (1.16±0.35 vs. 1.64±0.39) and all-cause rehospitalization days were reduced by 47% (6.0± 2.5 vs. 11.4±2.8) at 6 month follow-up. The change in SPPB score explained 90% of the reduction in all-cause rehospitalizations. There were no adverse events related to the intervention. Conclusions: These findings support the feasibility, safety and potential efficacy of a novel multi-domain rehabilitation intervention to improve physical function and reduce rehospitalizations in older, frail ADHF patients with multiple comorbidities. An NIH-funded multi-center trial is being launched to confirm these findings.

Many people affected by cardiovascular disease (CVD) are working age. Employers bear a large percentage of the costs associated with CVD. Employers pay 80 times more in diagnosis and treatment than in prevention, although there is evidence that 50% to 70% of all diseases are associated with preventable health risks. As a result, the worksite is an appealing location to deliver health care.Cardiac rehabilitation has developed a track record of delivering improved outcomes for patients with CVD. Partnerships between cardiac rehabilitation providers and worksite health programs have the potential to improve referral and participation rates of employees with CVD. The current era of health reform in the United States that has been stimulated by the Affordable Care Act provides an ideal opportunity to reconsider worksite health programs as an essential partner in the health care team.

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

Although epidemiologic studies have shown associations between sedentary behavior and mortality, few have focused on older women with adequate minority representation and few have controlled for both physical activity and functional status.The objective of this study was to determine the relationship between sedentary time and total; cardiovascular disease (CVD); coronary heart disease (CHD); and cancer mortality in a prospective, multiethnic cohort of postmenopausal women.The study population included 92,234 women aged 50-79 years at baseline (1993-1998) who participated in the Women's Health Initiative Observational Study through September 2010. Self-reported sedentary time was assessed by questionnaire and examined in 4 categories (≤4,4-8, ≥8-11,11 hours). Mortality risks were examined using Cox proportional hazard models adjusting for confounders. Models were also stratified by age, race/ethnicity, body mass index, physical activity, physical function, and chronic disease to examine possible effect modification. Analyses were conducted in 2012-2013.The mean follow-up period was 12 years. Compared with women who reported the least sedentary time, women reporting the highest sedentary time had increased risk of all-cause mortality in the multivariate model (HR=1.12, 95% CI=1.05, 1.21). Results comparing the highest versus lowest categories for CVD, CHD, and cancer mortality were as follows: HR=1.13, 95% CI=0.99, 1.29; HR=1.27, 95% CI=1.04, 1.55; and HR=1.21, 95% CI=1.07, 1.37, respectively. For all mortality outcomes, there were significant linear tests for trend.There was a linear relationship between greater amounts of sedentary time and mortality risk after controlling for multiple potential confounders.

To identify novel biomarkers through metabolomic profiles that distinguish metabolically well (MW) from metabolically unwell (MUW) individuals, independent of body mass index (BMI).This study was conducted as part of the Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) project. Individuals from 3 cohorts were classified as lean (BMI25kg/m²), overweight (BMI≥25kg/m², BMI30kg/m²) or obese (BMI≥30kg/m²). Cardiometabolic abnormalities were defined as: (1) impaired fasting glucose (≥100mg/dL and ≤126mg/dL); (2) hypertension; (3) triglycerides ≥150mg/dL; (4) HDL-C40mg/dL in men,50mg/dL in women; and (5) insulin resistance (calculated Homeostatic Model Assessment (HOMA-IR) index of5.13). MW individuals were defined as having2 cardiometabolic abnormalities and MUW individuals had≥two cardiometabolic abnormalities. Targeted profiling of 55 metabolites used mass-spectroscopy-based methods. Principal components analysis (PCA) was used to reduce the large number of correlated metabolites into clusters of fewer uncorrelated factors.Of 1872 individuals, 410 were lean, 610 were overweight, and 852 were obese. Of lean individuals, 67% were categorized as MUW, whereas 80% of overweight and 87% of obese individuals were MUW. PCA-derived factors with levels that differed the most between MW and MUW groups were factors 4 (branched chain amino acids [BCAA]) [p.0001], 8 (various metabolites) [p.0001], 9 (C4/Ci4, C3, C5 acylcarnitines) [p.0001] and 10 (amino acids) [p.0002]. Further, Factor 4, distinguishes MW from MUW individuals independent of BMI.BCAA and related metabolites are promising biomarkers that may aid in understanding cardiometabolic health independent of BMI category.

The recent 2012 update of the Heart Disease and Stroke Statistics from the American Heart Association (AHA) emphasizes the continuing burden of cardiovascular disease (CVD) in the United States, with a prevalence of CVD nearing 40% in those approaching 60 years of age and exceeding 70% in older ages.1 Direct and indirect costs of CVD in the United States exceeded $300 billion in 2008, and the projected total costs of CVD in 2015 and 2030 are more than $500 billion and nearly $1200 billion, respectively.2 Recently, the AHA developed year 2020 impact goals to achieve ideal cardiovascular health, which is influenced greatly by key health behaviors of being physically active, maintaining appropriate dietary habits, and not smoking.3 The obesity epidemic in the United States has been a substantial contributor to the CVD burden, with current estimates of obesity prevalence being ≈20% in US children and adolescents and >33% in adults 20 to 74 years of age. It is well accepted that for most people, obesity is a direct outcome of an energy-rich diet, lack of sufficient physical activity (PA), or both. Another consequence of both obesity and insufficient PA is a reduction in cardiorespiratory (or aerobic) fitness (CRF) levels. Collectively, this evidence emphasizes that an individual’s health behaviors have a major role in the prevention of CVD, which is of critical importance in the United States and worldwide from a medical and economic perspective. Increasing attention is being given to the importance of PA and physical fitness (PF), both muscular fitness and especially CRF, for decreasing chronic diseases, promoting overall cardiovascular and general health, improving quality of life, and delaying CVD and mortality in the US population.4,5 Clearly, PF and CRF in particular are an underpinning for academic achievement, job productivity, and overall maintenance …

Much of the immense burden of cardiovascular disease is ultimately a consequence of unhealthy lifestyle choices, such as physical inactivity, caloric over-consumption, and tobacco use. Unfortunately, clinicians rarely have sufficient time or resources to meaningfully address these issues. Cardiac rehabilitation is a comprehensive program for the secondary prevention of cardiovascular events for a wide spectrum of patients and is designed to address the lifestyle factors related to cardiovascular disease. While cardiac rehabilitation initially focused on exercise training, it has expanded over time to include cardiovascular education, nutritional counseling, behavioral interventions, and pharmacologic therapy. A large body of literature on cardiac rehabilitation has accrued demonstrating its robust health benefits, 1,2 including a survival benefit among patients with coronary artery disease, 2 and now it is advocated by professional clinical organizations for several cardiovascular conditions. 1 Despite its clinical need, cardiac rehabilitation remains vastly underutilized in the US, with 30% of eligible patients enrolling nationwide. 2 While several reasons exist for this poor utilization, the most critical and potentially most correctable reason is widely acknowledged to be the referral process, as only 1 in 2 patients eligible for cardiac rehabilitation are currently being referred. 3 Opportunities for referral often present themselves during the chaotic hospital discharge process or the first outpatient clinic visit after hospitalization, when busy practitioners are in the midst of dealing with symptoms, further testing, medication titration, and other clinical issues. As a result, cardiac rehabilitation generally lies at the bottom of practitioners’ priority lists for ongoing therapy. Also, it is oftentimes unclear which provider should take responsibility for the referral. Further complicating the referral process, many insurance companies require preauthorization. Finally, even if a referral is eventually made, they are often ineffective, being delayed weeks to months after a cardiovascular event, well past the point when patients may be motivated, willing, or able to attend cardiac rehabilitation.

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.

Family history of premature myocardial infarction (FHMI) may be a useful marker of cardiovascular disease (CVD) risk in young subjects, but comparisons of its implications for CVD risk factor burden, prevalent atherosclerosis, and risk awareness between young men and women have not been reported.We analyzed data from 2404 young subjects with ages 30 to 50 in the Dallas Heart Study, which is a population-based study. Family history of premature MI was defined as a first-degree relative with myocardial infarction (MI) before age 50 (men) or 55 (women). Coronary artery calcification was measured by computed tomography scan, and perceived lifetime risk of MI was assessed by questionnaire. Analyses were sex-stratified.Women with versus without FHMI had an increased composite risk factor burden (or = 2 CVD risk factors, 49.1% vs 39.1%; P.001), an association not seen in men (P = .6). Family history of premature MI was independently associated with coronary artery calcification among women (adjusted odds ratio, 2.0; 95% confidence interval, 1.0-4.1) but not among men (adjusted odds ratio, 1.7; 95% confidence interval, 0.9-3.2). A higher proportion of subjects with FHMI versus no FHMI perceived their lifetime risk of MI to be ator = average in women (59.7% vs 47.4%; P.001) and men (75.0% vs 48.3%; P = .004), with the increment greatest among men (P interaction = .02).Despite a stronger association with CVD risk factors and atherosclerosis prevalence with FHMI among young women compared with men, young women with FHMI demonstrated less CVD risk awareness and worse lifestyle choices. Family history of premature MI may be an especially useful risk assessment tool in young women, and greater efforts are needed to promote CVD risk awareness among young women with FHMI.

Family history of myocardial infarction (FHMI) is an independent risk factor for cardiovascular (CV) events but may be more informative in certain subgroups. The association between FHMI and the presence of coronary artery calcium (CAC) was examined in various age and risk factor groups in the Dallas Heart Study (DHS), a population-based probability sample of subjects aged 30 to 65 years. Analyses were stratified by age (with the young group composed of men aged45 years and women aged55 years) and by the presence of 0, 1, 2, or2 CV risk factors. In the overall cohort of 2,743 subjects, FHMI was an independent predictor of CAC (adjusted odds ratio 1.3, 95% confidence interval 1.1 to 1.7), attributable to an independent association between FHMI and CAC in the young group (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1) that was not evident in the older subset (adjusted odds ratio 1.2, 95% confidence interval 0.91 to 1.6, interaction p = 0.02). In the young cohort, the association between FHMI and CAC was particularly robust in those withor = 2 risk factors (FHMI-by-risk factor interaction p = 0.04). In older subjects, FHMI was not associated with CAC for any risk factor category (p0.05 for each). In conclusion, this study suggests that FHMI is a more important predictor of atherosclerosis in young compared with older adults and, among the young, in those with multiple CV risk factors.