Incidental Coronary Arterial Calcification for Cardiovascular Risk Assessment in Men With Prostate Cancer Undergoing PET/CT Imaging.

BACKGROUND: Cardiovascular (CV) disease is common among men with prostate cancer and the leading cause of death in this population. There is a need for CV risk assessment tools that can be easily implemented in the prostate cancer treatment setting. METHODS: Consecutive patients who underwent positron emission tomography/computed tomography (PET/CT) for recurrent prostate cancer at a single institution from 2012 to 2017 were identified retrospectively. Clinical data and coronary calcification on nongated CT imaging were obtained. The primary outcome was major adverse CV event (MACE; myocardial infarction, coronary or peripheral revascularization, stroke, heart failure hospitalization, or all-cause mortality) occurring within 5 years of PET/CT. RESULTS: Among 354 patients included in the study, there were 98 MACE events that occurred in 74 patients (21%). All-cause mortality was the most common MACE event (35%), followed by coronary revascularization/myocardial infarction (26%) and stroke (19%). Coronary calcification was predictive of MACE (HR = 1.9, 95% CI: 1.1-3.4, P = .03) using adjusted Kaplan-Meier analysis. As a comparator, the Framingham risk score was calculated for 198 patients (56%) with complete clinical and laboratory data available. In this subgroup, high baseline Framingham risk (corresponding to 10-year risk of CV disease > 20%) was not predictive of MACE. CONCLUSIONS: MACE was common (21%) in men with recurrent prostate cancer undergoing PET/CT over 5 years of follow-up. Incidental coronary calcification on PET/CT was associated with increased risk of MACE and may have utility as a CV risk predictor that is feasible to implement among all prostate cancer providers.

Intensive Versus Traditional Cardiac Rehabilitation: Mortality and Cardiovascular Outcomes in a 2016-2020 Retrospective Medicare Cohort.

BACKGROUND: Traditional cardiac rehabilitation (CR) improves cardiovascular outcomes and reduces mortality, but less is known about the relative benefit of intensive CR (ICR) which incorporates greater lifestyle education through 72 sessions (versus 36 in CR). Our objective was to determine whether ICR is associated with a mortality and cardiovascular benefit compared with CR. METHODS: Retrospective cohort study of Medicare Fee-For-Service beneficiaries in a 100% sample, claims data set. Qualifying events were captured from May 1, 2016 to December 31, 2019 and ICR/CR utilization captured from May 1, 2016 to December 31, 2020. Among patients attending at least 1 day of either CR or ICR, Cox proportional hazards models using a 1 to 5 propensity score match were used to compare utilization and the association of ICR versus CR participation with (1) all-cause mortality and (2) cardiovascular-related hospitalizations or nonfatal cardiac events. Dose-response was assessed by the number of days attended. RESULTS: From 2016 to 2019, 1 277 358 unique patients met at least one qualifying indication for ICR/CR from 2016 to 2019. Of these, 262 579 (20.6%) and 4452 (0.4%) attended at least one session of CR or ICR, respectively (mean [SD] age, 73.2 [7.8] years; 32.3% female). In the matched sample, including 26 659 total patients (median, 2.4-year follow-up), ICR was associated with 12% lower all-cause mortality (multivariable adjusted hazard ratio, 0.88 [95% CI, 0.78-0.99]; P=0.036) compared with CR but no significant difference for cardiovascular-related hospitalization or nonfatal cardiac events. The mortality benefit was seen for both ICR and CR per day strata, with each modality demonstrating a clear dose-response benefit. CONCLUSIONS: ICR is associated with lower mortality than traditional CR among Medicare beneficiaries but no difference in cardiovascular-related hospitalization or nonfatal cardiac events. Moreover, ICR and CR demonstrate a dose-response relationship for mortality. Additional studies are needed to confirm these observations and to better understand the mechanisms by which ICR may lead to a reduction in mortality.

Prospective Study of the Impact of Outpatient Intensive Cardiac Rehabilitation on Diet Quality, Health-related Quality of Life, and Cardiovascular Health Indices.

Intensive cardiac rehabilitation (ICR) programs are approved by the Centers for Medicare & Medicaid Services on the basis of their expected benefits for cardiovascular disease (CVD) risk factors and health outcomes. However, the impact of outpatient ICR on diet quality, quality of life (QOL), and CVD risk factors has not been prospectively assessed. The aim of this cohort study was to test the hypothesis that patients enrolled in a Pritikin outpatient ICR program would show improved diet quality, QOL, and CVD health indexes, and that the improvements would be greater than those of patients in traditional cardiac rehabilitation (CR). Patients enrolled in ICR (n = 230) or CR (n = 62) were assessed at baseline and at visit 24. Diet quality was assessed using the Rate Your Plate questionnaire, and QOL was assessed through the Dartmouth COOP Functional Health Assessment questionnaire. Secondary end points included anthropometrics, CVD biomarkers, hemodynamics, and fitness. Patients in ICR programs displayed significant improvements at visit 24 versus baseline in Rate Your Plate and Dartmouth COOP Functional Health Assessment scores, weight, body mass index (BMI), waist circumference, fat mass, total and low-density lipoprotein cholesterol, 6-minute walk distance, and grip strength. Patients in ICR had greater improvements in diet quality (p = 0.001), weight (p = 0.001), and BMI (p <0.001) than did those in CR. In summary, this prospective study of Pritikin outpatient ICR revealed significant improvements in diet quality, QOL, adiposity, and other CVD risk factors. The improvements in diet quality, body weight, and BMI were greater than those observed with traditional CR.

Benefits of the First Pritikin Outpatient Intensive Cardiac Rehabilitation Program.

PURPOSE: Intensive cardiac rehabilitation (ICR) is a comprehensive, medically supervised exercise treatment program covered by Medicare for patients with approved cardiac diagnoses. The aim of this study was to determine the benefits of the first Pritikin outpatient ICR program. METHODS: This retrospective analysis included patients referred to ICR or traditional cardiac rehabilitation (CR) during the first 7 yr (2013-2019) at the first facility to implement Pritikin ICR. Intensive cardiac rehabilitation is composed of 36 education sessions on nutrition, exercise, and a healthy mindset, in addition to 36 monitored exercise sessions that comprise traditional CR. Assessments included anthropometrics (weight, body mass index, and waist circumference), dietary patterns, physical function (6-min walk test, [6MWT] Short Physical Performance Battery [SPPB: balance, 4-m walk, chair rise], handgrip strength), and health-related quality of life (Dartmouth COOP, 36-item Short Form Survey). Baseline and follow-up measures were compared within and between groups. RESULTS: A total of 1963 patients enrolled (1507 ICR, 456 CR, 66.1 ± 11.4 yr, 68% male, 82% overweight or obese); 1141 completed the program (58%). The ICR patients completed 22 exercise and 18 education sessions in 9.6 wk; CR patients completed 19 exercise sessions in 10.3 wk. ICR resulted in improvements ( P < .001 pre vs post) in all anthropometric measures, dietary patterns, 6MWT distance, all SPPB components, grip strength, and health-related quality of life. The improvements in anthropometrics and dietary patterns were greater in ICR than in CR. CONCLUSIONS: The Pritikin outpatient ICR program promoted improvements in several cardiovascular health indices. Critical next steps are to assess long-term health outcomes after ICR, including cardiac events and mortality.

Intensive Cardiac Rehabilitation Is Markedly Underutilized by Medicare Beneficiaries: RESULTS FROM A 2012-2016 NATIONAL SAMPLE.

PURPOSE: Intensive cardiac rehabilitation (ICR) was developed to enhance traditional cardiac rehabilitation (CR) by adding sessions focused on nutrition, lifestyle behaviors, and stress management. Intensive CR has been Medicare-approved since 2010, yet little is known about national utilization rates of ICR in the Medicare population or characteristics associated with its use. METHODS: A 5% sample of Medicare claims data from 2012 to 2016 was used to identify beneficiaries with a qualifying indication for ICR/CR and to quantify utilization of ICR or CR within 1 yr of the qualifying diagnosis. RESULTS: From 2012 to 2015, there were 107 246 patients with a qualifying indication. Overall, only 0.1% of qualifying patients participated in ICR and 16.2% in CR from 2012 to 2016, though utilization rates of both ICR and CR increased during this period (ICR 0.06 to 0.17%, CR 14.3 to 18.2%). The number of ICR centers increased from 15 to 50 over the same period. There were no differences between ICR and CR enrollees with respect to age, sex, race, discharge location, median income, dual enrollment, or number of comorbidities. Compared with eligible beneficiaries who did not attend ICR or CR, those who attended either program were younger, more likely to be male and White, and had higher median income. CONCLUSIONS: Although ICR and CR have a class 1 indication for the treatment of cardiovascular disease and the number of ICR centers has increased, ICR is not widely available and remains markedly underutilized. Continued research is needed to understand the barriers to program development and patient participation.

Assessment of Nonfatal Myocardial Infarction as a Surrogate for All-Cause and Cardiovascular Mortality in Treatment or Prevention of Coronary Artery Disease: A Meta-analysis of Randomized Clinical Trials.

Importance: Although nonfatal myocardial infarction (MI) is associated with an increased risk of mortality, evidence validating nonfatal MI as a surrogate end point for all-cause or cardiovascular (CV) mortality is lacking. Objective: To examine whether nonfatal MI may be a surrogate for all-cause or CV mortality in patients with or at risk for coronary artery disease. Data Sources: In this meta-analysis, PubMed was searched from inception until December 31, 2020, for randomized clinical trials of interventions to treat or prevent coronary artery disease reporting mortality and nonfatal MI published in 3 leading journals. Study Selection: Randomized clinical trials including at least 1000 patients with 24 months of follow-up. Data Extraction and Synthesis: Trial-level correlations between nonfatal MI and all-cause or CV mortality were assessed for surrogacy using the coefficient of determination (R2). The criterion for surrogacy was set at 0.8. Subgroup analyses based on study subject (primary prevention, secondary prevention, mixed primary and secondary prevention, and revascularization), era of trial (before 2000, 2000-2009, and 2010 and after), and follow-up duration (2.0-3.9, 4.0-5.9, and ≥6.0 years) were performed. Main Outcomes and Measures: All-cause or CV mortality and nonfatal MI. Results: A total of 144 articles randomizing 1 211 897 patients met the criteria for inclusion. Nonfatal MI did not meet the threshold for surrogacy for all-cause (R2 = 0.02; 95% CI, 0.00-0.08) or CV (R2 = 0.11; 95% CI, 0.02-0.27) mortality. Nonfatal MI was not a surrogate for all-cause mortality in primary (R2 = 0.01; 95% CI, 0.001-0.26), secondary (R2 = 0.03; 95% CI, 0.00-0.20), mixed primary and secondary prevention (R2 = 0.001; 95% CI, 0.00-0.08), or revascularization trials (R2 = 0.21; 95% CI, 0.002-0.50). For trials enrolling patients before 2000 (R2 = 0.22; 95% CI, 0.08-0.36), between 2000 and 2009 (R2 = 0.02; 95% CI, 0.00-0.17), and from 2010 and after (R2 = 0.01; 95% CI, 0.00-0.09), nonfatal MI was not a surrogate for all-cause mortality. Nonfatal MI was not a surrogate for all-cause mortality in randomized clinical trials with 2.0 to 3.9 (R2 = 0.004; 95% CI, 0.00-0.08), 4.0 to 5.9 (R2 = 0.06; 95% CI, 0.001-0.16), or 6.0 or more years of follow-up (R2 = 0.30; 95% CI, 0.01-0.55). Conclusions and Relevance: The findings of this meta-analysis do not appear to establish nonfatal MI as a surrogate for all-cause or CV mortality in randomized clinical trials of interventions to treat or prevent coronary artery disease.

Racial Disparities in Modifiable Risk Factors and Statin Usage in Black Patients With Familial Hypercholesterolemia.

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively; P=0.15). However, Black versus EA patients had significantly greater prevalence of modifiable risk factors, including body mass index (mean, 32±7 kg/m2 versus 29±6 kg/m2; P<0.001), hypertension (82% versus 50%; P<0.001), diabetes (39% versus 15%; P<0.001), and current smoking (16% versus 8%; P=0.006). Black versus EA patients also had significantly lower usage of statins (61% versus 73%; P=0.004) and other lipid-lowering agents. In a fully adjusted multivariate model, race was not independently associated with ASCVD (odds ratio, 0.92; 95% CI, 0.60-1.49; P=0.72). Conclusions The strongest predictors of ASCVD in Black patients with familial hypercholesterolemia were hypertension and cigarette smoking. These data support wider usage of statins and other lipid-lowering therapies and greater attention to modifiable risk, specifically blood pressure management and smoking cessation.

Gibbs distribution for statistical analysis of graphical data with a sample application to fcMRI brain images.

This paper develops object-oriented data analysis (OODA) statistical methods that are novel and complementary to existing methods of analysis of human brain scan connectomes, defined as graphs representing brain anatomical or functional connectivity. OODA is an emerging field where classical statistical approaches (e.g., hypothesis testing, regression, estimation, and confidence intervals) are applied to data objects such as graphs or functions. By analyzing data objects directly we avoid loss of information that occurs when data objects are transformed into numerical summary statistics. By providing statistical tools that analyze sets of connectomes without loss of information, new insights into neurology and medicine may be achieved. In this paper we derive the formula for statistical model fitting, regression, and mixture models; test their performance in simulation experiments; and apply them to connectomes from fMRI brain scans collected during a serial reaction time task study. Software for fitting graphical object-oriented data analysis is provided.

Anemia: an independent predictor of death and hospitalizations among elderly patients with atrial fibrillation.

BACKGROUND: Anemia and atrial fibrillation (AF) are common among the elderly. Anemia is an independent predictor of mortality and morbidity for numerous cardiovascular and noncardiovascular diseases, but the association of anemia with mortality and hospitalizations in patients with AF requires clarification. METHODS: Subjects were 13,067 Medicare beneficiaries hospitalized with AF and included in the National Registry of Atrial Fibrillation II data set. Index hospitalization hematocrit (Hct) was obtained by structured chart abstraction. Cox proportional hazards models quantified the association of Hct with mortality and re-hospitalizations during a median follow-up period of 12 months. RESULTS: The mean age was 79.8 years, 58% were women, and the mean Hct was 39.2%. Hematocrit was significantly (P < .0001) associated with risk of death and of rehospitalization even after adjustment for demographic information, comorbid conditions, and use of cardiovascular medications. As compared to a Hct of 40% to 44.9%, the adjusted hazard ratios for mortality were 1.66 for Hct <25%, 1.50 for 25% to 29.9%, 1.28 for 30% to 34.9%, 1.07 for 35% to 39.9%, 1.03 for 45% to 49.9%, and 1.10 for > or = 50%. The association between anemia and mortality was significant in men and women but stronger in men (P = .006 for interaction). Compared to the category 40% to 44.9%, the risk of rehospitalization was increased to 28% (adjusted hazard ratio 1.28, 95% CI 1.15-1.43) in the Hct category 25% to 29.9%. CONCLUSION: Anemia is an independent predictor of mortality and of hospitalizations in elderly patients with AF. Studies are needed to assess the effect of treatment of anemia on clinical outcomes.

Use and effectiveness of warfarin in Medicare beneficiaries with atrial fibrillation.

BACKGROUND AND PURPOSE: More than 2 million Americans have atrial fibrillation, and without antithrombotic therapy, their stroke rate is increased 5-fold. In randomized controlled trials, warfarin prevented 65% of ischemic strokes (hazard ratio [HR], 0.35; 95% CI, 0.26 to 0.48) compared with no antithrombotic therapy. However, the effectiveness of warfarin therapy outside of clinical trials is unknown, especially in black and Hispanic populations. Our goal was to quantify use of warfarin therapy, frequency of International Normalized Ratio monitoring, and effectiveness for stroke prophylaxis in Medicare beneficiaries with atrial fibrillation. METHODS: This was a cohort study of Medicare beneficiaries with atrial fibrillation who were hospitalized between March 1998 and April 1999 in all 50 US states. The primary outcome was incident hospitalizations for ischemic stroke based on validated International Classification of Diseases, 9th Revision, Clinical Modification codes. RESULTS: Two thirds of ideal anticoagulation candidates were prescribed warfarin on hospital discharge. In unadjusted analyses, the stroke rates per 100 patient years of warfarin therapy were 5.2 in (non-Hispanic) white Medicare beneficiaries, 10.6 in black beneficiaries, and 12.2 in Hispanic beneficiaries. After adjusting for comorbid conditions, warfarin prescription was more frequent and monitoring more regular in white Medicare beneficiaries than in black or Hispanic beneficiaries (P<0.0001). Warfarin use was associated with 35% fewer ischemic strokes (HR, 0.65; 95% CI, 0.55 to 0.76) compared with no antithrombotic therapy but was less effective in black and Hispanic beneficiaries (P for interaction=0.048). CONCLUSIONS: The use, monitoring, and effectiveness of warfarin therapy are suboptimal in Medicare beneficiaries, especially in black and Hispanic beneficiaries.

Comorbidity indices to predict mortality from Medicare data: results from the national registry of atrial fibrillation.

BACKGROUND: By accounting for level of comorbidity, risk-adjustment models should quantify the risk of death. How accurately comorbidity indices predict risk of death in Medicare beneficiaries with atrial fibrillation is unclear. OBJECTIVES: We sought to quantify how well 3 administrative-data based comorbidity indices (Deyo, Romano, and Elixhauser) predict mortality compared with a chart-review index. DESIGN: We undertook a retrospective cohort study using Medicare claim data (1995-1999) and medical record review. SUBJECTS: We studied Medicare beneficiaries (n = 2728; mean age = 77) with a common cardiac dysrhythmia, atrial fibrillation. MEASURES: The outcome was time to death with the accuracy of the comorbidity indices measured by the c-statistic. RESULTS: Correlation between Deyo and Romano indices was strong, but weak between them and the other indices. Prevalence of many comorbidity conditions varied with different indices. Compared with demographic data alone (c = 0.64), all comorbidity indices predicted death significantly (P < 0.001) better: the c index was 0.76 for Deyo, 0.78 for Romano, 0.76 for Elixhauser, and 0.75 for medical record review. The 95% confidence intervals of the c-statistic for the 4 indices overlapped with one another. Key comorbidity conditions for death included metastatic cancer, neuropsychiatric disease, heart failure, and liver disease. CONCLUSION: The predictive accuracy of 3 administrative-data based indices was similar and comparable with chart-review.

Accuracy of ICD-9-CM codes for identifying cardiovascular and stroke risk factors.

OBJECTIVES: We sought to determine which ICD-9-CM codes in Medicare Part A data identify cardiovascular and stroke risk factors. DESIGN AND PARTICIPANTS: This was a cross-sectional study comparing ICD-9-CM data to structured medical record review from 23,657 Medicare beneficiaries aged 20 to 105 years who had atrial fibrillation. MEASUREMENTS: Quality improvement organizations used standardized abstraction instruments to determine the presence of 9 cardiovascular and stroke risk factors. Using the chart abstractions as the gold standard, we assessed the accuracy of ICD-9-CM codes to identify these risk factors. MAIN RESULTS: ICD-9-CM codes for all risk factors had high specificity (>0.95) and low sensitivity (< or =0.76). The positive predictive values were greater than 0.95 for 5 common, chronic risk factors-coronary artery disease, stroke/transient ischemic attack, heart failure, diabetes, and hypertension. The sixth common risk factor, valvular heart disease, had a positive predictive value of 0.93. For all 6 common risk factors, negative predictive values ranged from 0.52 to 0.91. The rare risk factors-arterial peripheral embolus, intracranial hemorrhage, and deep venous thrombosis-had high negative predictive value (> or =0.98) but moderate positive predictive values (range, 0.54-0.77) in this population. CONCLUSIONS: Using ICD-9-CM codes alone, heart failure, coronary artery disease, diabetes, hypertension, and stroke can be ruled in but not necessarily ruled out. Where feasible, review of additional data (eg, physician notes or imaging studies) should be used to confirm the diagnosis of valvular disease, arterial peripheral embolus, intracranial hemorrhage, and deep venous thrombosis.