Medina‐Inojosa, José R.

Introduction: Multimorbidity is associated with physical disability, increased health care utilization, reduced quality of life, and mortality. Whereas most literature has focused on the co-occurrence of somatic conditions, we aim to (i) establish the prevalence of combined somatic and mental health multimorbidity (SMM) in cardiac rehabilitation (CR) patients, and (ii) determine the most prevalent co-occurrence of cardio-metabolic conditions (CMC) with other somatic or mental health conditions in CR patients. Methods: Using the Rochester Epidemiology Project records-linkage system, we identified residents of Southern MN and Western WI who attended (≥1) CR sessions from 1995 to 2019. The prevalence of 18 chronic conditions defined by the US Department of Health and Human Services was electronically extracted. Heat maps were created to assess the pairwise prevalence of cardio-metabolic (CMC; n=6) with mental (n=5) and other somatic (n=7) chronic conditions (Table 1) . Results: We included 13,056 patients; 68.5% were male. Patients were 65.5±12.5 years old with 44.7% ≤65 years old. Median number of conditions was 7 (Range 0-18) with 52.6% of patients having ≥7 conditions. Hyperlipidemia (89.3%), hypertension (79.5%), and arrhythmias (72.4%) were the most prevalent CMC. The prevalence of combined SMM (≥2 conditions) was 44.9% and was higher in those <65 years ( p <.0001). Depression (26.8%) and anxiety (24.7%) were the most common mental conditions involved in SMM and frequently co-occurred with CMC. Among other prevalent somatic conditions, arthritis (51.7%), chronic obstructive pulmonary disease (33.5%), and cancer (29.3%) co-occurred with CMC (Figure 1). Conclusions: Half of patients in CR have ≥7 chronic conditions. Somatic and mental health multimorbidity (SMM) is highly prevalent and is more frequent in those younger than 65 years old. Our results highlight the critical need to better understand the clinical burden of SMM in patients undergoing CR.

Background: Artificial intelligence (AI)-based analysis of the electrocardiogram (ECG) can estimate the probability of having atrial fibrillation (AF) while in sinus rhythm. We evaluated the association between the probability of AF using AI-ECG and incident ischemic stroke (I-Stroke) and cardiovascular (CV) mortality. Methods: We evaluated a community-based cohort of consecutive patients that sought primary care in Olmsted County, MN, from the years 1998 to 2000 followed-up through March 2016. Inclusion criteria were ages 40-79, an electrocardiogram within 2 years and complete CHA2DS2-VASc data. We excluded those with known atherosclerotic CV disease or AF. The AI network was developed in 180,000 patients (649,931 ECG). The primary endpoint was incident I-Stroke; secondary endpoint was I-Stroke or CV mortality; validated in duplicate. Multivariate cox models adjusted for age, sex, history of hypertension, diabetes, heart failure, and in CHA2DS2-VASc Score subgroups (categorized as low=0, moderate=1, and high risk ≥2). Results: We included 14,601 patients, mean age 53.2±13.08 (51% women, 95% whites), CHA2DS2-VASc score 1.3±1.2, median follow-up of 16.3 years, IQR 14.5-17.5, 727 (4.9%) had an I-Stroke and 1309 (8.9%) had I-Stroke or died from CV causes. When comparing the 5 th vs the 1 st quintile, those with high AI-ECG AF probability had increased risk for I-Stroke (HR 3.25, 95%CI 2.55-4.14, P-for trend <.0001 Figure-A ) and ischemic stroke or CV mortality (HR 5.73, 95%CI 4.69-6.99, P-for trend <.0001 Figure-B ). This remained significant after adjustments. Furthermore, AI-ECG AF probability was associated with I-Stroke across CHA2DS2-VASc risk levels (HR 2.43 for high, 2.33 for moderate, 1.98 for low CHA2DS2-VASc risk, all P<0.01). Conclusion: The AI-ECG AF algorithm predicts long-term I-Stroke and CV mortality and may refine CHA2DS2-VASc. These results highlight the utility of the AI enabled ECG when estimating I-Stroke or CV mortality risk.

Introduction: The presence of chronic somatic and mental health conditions is complex and challenging for patients and the health care system due to the health deficit accumulation, worsening outcomes, and increased health care utilization. While previous studies on multimorbidity have focused on somatic chronic conditions, we aim to assess the relation between somatic, mental, and combined somatic-mental multimorbidity (SMM) and impact on Major Adverse Cardiac Events (MACE) in patients enrolled in phase II outpatient cardiac rehabilitation (CR). Methods: Using the Rochester Epidemiology Project records-linkage system, we identified patients from Olmsted County, Minnesota who were 18 years old and attended (≥1) CR sessions at Mayo Clinic Rochester. The prevalence of 18 (somatic=13; mental=5) chronic conditions defined by the US Department of Health and Human Services was ascertained electronically. Results: We included 618 patients; 24.4% were female. Patients were 61.5±11.0 years old with 38.0% ≥65 years old. Overall median number of chronic conditions was 6 (Range 0-13) with 98.8% of patients having ≥2 conditions. The prevalence of combined SMM was 44.6%. Mean follow-up was 7.3± 4.5 years, 147 (23.7%) patients had MACE (number): acute coronary syndrome (46), percutaneous coronary intervention (33), heart failure (16), stroke (8), coronary artery bypass grafting (4), ventricular arrhythmias (4), or death (65). Risk of MACE in patients with SMM was significantly higher compared to patients with only somatic conditions (HR: 1.62, 95% CI: 1.14-2.30, p=0.01 ), Figure 1. The association remained significant after adjustment for age and sex ( p=0.006 ). Conclusions: Our results show that somatic-mental multimorbidity (SMM) in CR patients is highly prevalent and imposes a higher risk of MACE compared with patients who have only somatic conditions highlighting the importance of individualized assessment and care plans to reduce adverse events and mortality.

Introduction: Coronary artery disease (CAD) has been associated with cognitive decline. Cardiac rehabilitation (CR) is a class 1A recommendation for patients with CAD as it reduces future cardiac events and mortality. However, the impact of CR on incidence of mild cognitive impairment (MCI) and dementia has not been extensively studied. We investigated the association of CAD on incidence of MCI and dementia; and whether CR attendance reduces incidence of MCI and dementia in patients with CAD Methods: The Mayo Clinic Study of Aging (MCSA), a prospective, population-based cohort was probed for this study. At baseline and every 15-months thereafter, subjects were evaluated for MCI and dementia using a standardized protocol. Data on CR participation were collected via record linkage to the Rochester Epidemiology Project. To evaluate association with incident MCI or dementia, cox proportional hazard models were used and adjusted for age, sex, and clinical predictors of cognitive decline. Participants with MCI at baseline were excluded for MCI analysis and adjusted for in dementia analysis. Results: We included 5960 MCSA participants (female: 50%; age: 70±13). Of those, 1934 participants (32%) had CAD and 702 (12%) had MCI at baseline. Mean follow-up was 3.9±3.7yrs, with 760 incident cases of MCI (13%) and 290 cases of dementia (5%). CAD was a significant predictor of MCI and dementia, although after adjustment for other clinical predictors, CAD was only associated with MCI incidence ( Table 1, Figure ). Incidence of dementia was reduced in CAD patients who had a greater attendance at CR when adjusted for other predictors of cognitive decline ( Table 2 ). Attendance at CR did not reduce incidence of MCI ( Table 2 ). Conclusions: CAD was a significant predictor of MCI and dementia. In patients with CAD, a higher attendance of CR was associated with reduced incidence of dementia but not MCI. Specific CR programming and outcome targets may be needed to prevent MCI in patients with CAD.

Introduction: Cardiac rehabilitation (CR) is associated with improvements in exercise capacity (peak oxygen uptake (VO 2 peak)); however, 23% of CR patients do not improve VO 2 peak following CR. CR adherence (i.e. number of CR sessions attended) has been proposed to play an important role in VO 2 peak improvement following CR, but has not been investigated. Identifying clinical predictors of VO 2 peak improvement are critical as the degree of VO 2 peak improvement is associated with improved long-term outcomes in these patients. Purpose: To determine if clinical characteristics and number of CR sessions attended were predictive of patients who exhibited improvement in VO 2 peak following CR. Methods: Using the Rochester Epidemiology Project records-linkage system, we identified all consecutive patients >18 years old from Olmsted County, Minnesota who underwent cardiopulmonary exercise testing prior to and following CR from 1999 to 2017. Regression models were created to assess clinical predictors of VO 2 peak improvement (>0% baseline) following CR. Results: The analysis included 804 patients (75% men) with a mean age of 60.7±12.4 years. Of the 804 patients, 609 (76%) patients exhibited VO 2 peak improvement following CR. Significant univariate predictors of VO 2 peak improvement included younger age (OR: 0.99, 95% CI: 0.97-1.00), lower pre-CR VO 2 peak (OR: 0.97, 95% CI: 0.94-0.99), history of peripheral artery disease (OR: 0.48, 95% CI: 0.32-0.73), and smoking (OR: 0.63, 95% CI: 0.45-0.90). Significant independent predictors of VO 2 peak improvement from a multivariate analysis included younger age (OR: 0.98, 95% CI: 0.96-1.00), number of CR sessions (OR: 1.02, 95% CI: 1.01-1.03), lower pre-CR VO 2 peak (OR: 0.94, 95% CI: 0.91-0.96), history of peripheral artery disease (OR: 0.42, 95% CI: 0.27-0.66), and smoking (OR: 0.56, 95% CI: 0.39-0.82). Conclusions: These findings demonstrate the importance of CR adherence and individual clinical characteristics in influencing VO 2 peak improvement following CR in patients with CVD. These findings may influence the clinical practice by providing specific clinical characteristics to account for when personalizing the CR treatment plan to maximize positive outcomes.

Introduction: Plasma ceramides (CER) are sphingolipids associated with adverse events and mortality in patients with established coronary artery disease (CAD) and/or risk factors for CAD. The ability of these same specific ratios of CER to predict major adverse cardiovascular events (MACE) in subjects without CAD in the community is less certain. We tested the hypothesis that CER are associated with MACE in a community-based cohort free of CAD at enrollment. Methods: In a prospective community-based cohort we performed passive follow-up using a record linkage system to ascertain the composite outcome of MACE, defined as acute myocardial infarction, coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention), stroke or death. CER were analyzed as continuous variables, ratios and quintiles adjusting for potential confounders. Results: We included 1221 subjects, 49% males, mean age ± (SD) 61.1±9.6 years. After a median follow-up of 16 years (IQR 1.7), 297 patients had a MACE: Myocardial infarction (105), coronary artery bypass surgery (53), percutaneous coronary intervention (92), stroke (137) and all-cause death (120). Some had more than one event. Ratios of CER were significantly associated with MACE in unadjusted and adjusted models, see Figure 1-A. This association was independent of LDL-C, total cholesterol, Apo-B and traditional CAD risk factors. Those in the highest quintile of (24:1/24:0) CER ratio had more than two-fold risk of MACE, HR 2.32 (95% CI, 1.59-3.46). There was a dose-response association across quintiles of CER ratios and MACE, Figure 1-B.: Conclusions: Elevated CER plasma ratios are associated with MACE in patients with no CAD in the community. The risk conferred by plasma CER is independent of traditional risk factors, including lipids, and has a dose-response.

Introduction: Cardiac rehabilitation (CR) is recommended for secondary prevention following a coronary artery disease (CAD) event. The association between CR attendance and long-term major cardiovascular events (MACE)in the community has not been previously reported . Hypothesis: We tested the hypothesis that higher CR participation would be related to a lower risk of MACE,in residents of Olmsted county, Minnesota. Methods: We performed a community-based retrospective longitudinal study on patients referred to CR for CAD events or procedures between the years 2002 and 2012. Follow-up was performed using a record linkage system from the Rochester Epidemiology Project. CR participation was assessed as the number of CR sessions attended, and was analyzed as a continuous variable, as quintiles and also as a binomial variable using 12 sessions as the cutoff. The composite outcome MACE was defined as having an acute coronary syndrome (myocardial infarction (MI) or unstable angina), revascularization (CABG or PCI), ventricular arrhythmias requiring hospitalization, stroke or death from any cause. Multivariate models were adjusted for age and gender and also for factors associated with MACE in the univariate analysis. Results: Our cohort included 2273 patients, 69% males, mean age (SEM) 64 (0.26) years. After a mean follow-up of 6 (0.07) years, 827 patients had an event: MI (73), unstable angina (113), CABG(53), PCI (260), ventricular arrhythmia (13), stroke (72) and death (243). Participation in 12 or more sessions (vs <12 sessions) had a lower rate of MACE (HR 0.81, 95% CI 0.70-0.93, p=0.003, see Figure1 . After adjusting for smoking, hypertension, diabetes and history of MI the association remained significant HR 0.85, 95% CI 0.74-0.98, p=0.03. Conclusions: A higher participation in CR was associated with a lower risk of MACE. These results provide additional evidence of important CR health advantages and expand on previous evidence of a dose-response benefit of CR.

The aim of the present study was to evaluate the association between television viewing/physical activity (TVV/PA) interactions and cardiometabolic risk in an adult European population. A total of 2155 subjects (25–64 years) (45.2% males), a random population-based sample were evaluated in Brno, Czechia. TVV was classified as low (<2 h/day), moderate (2–4), and high (≥4). PA was classified as insufficient, moderate, and high. To assess the independent association of TVV/PA categories with cardiometabolic variables, multiple linear regression was used. After adjustments, significant associations were: High TVV/insufficient PA with body mass index (BMI) (β = 2.61, SE = 0.63), waist circumference (WC) (β = 7.52, SE = 1.58), body fat percent (%BF) (β = 6.24, SE = 1.02), glucose (β = 0.25, SE = 0.12), triglycerides (β = 0.18, SE = 0.05), and high density lipoprotein (HDL-c) (β = −0.10, SE = 0.04); high TVV/moderate PA with BMI (β = 1.98, SE = 0.45), WC (β = 5.43, SE = 1.12), %BF (β = 5.15, SE = 0.72), triglycerides (β = 0.08, SE = 0.04), total cholesterol (β = 0.21, SE = 0.10), low density protein (LDL-c) (β = 0.19, SE = 0.08), and HDL-c (β = −0.07, SE = 0.03); and moderate TVV/insufficient PA with WC (β = 2.68, SE = 1.25), %BF (β = 3.80, SE = 0.81), LDL-c (β = 0.18, SE = 0.09), and HDL-c (β = −0.07, SE = 0.03). Independent of PA levels, a higher TVV was associated with higher amounts of adipose tissue. Higher blood glucose and triglycerides were present in subjects with high TVV and insufficient PA, but not in those with high PA alone. These results affirm the independent cardiometabolic risk of sedentary routines even in subjects with high-levels of PA.

Abstract We here posit that measurements of midlife cognition can be instructive in understanding cognitive disorders. Even though molecular events signal possible onset of cognitive disorders decades prior to their clinical diagnoses, cognition and its possible early changes in midlife remain poorly understood. We characterize midlife cognition in a cognitively healthy population‐based sample using the Cogstate Brief Battery and test for associations with cardiovascular, adiposity‐related, lifestyle‐associated, and psychosocial variables. Learning and working memory showed significant variability and vulnerability to psychosocial influences in midlife. Furthermore, midlife aging significantly and progressively increased prevalence of suboptimal cognitive performance. Our findings suggest that physiological changes in cognition, measured with simple tests suitable for use in everyday clinical setting, may signal already in midlife the first clinical manifestations of the presymptomatic biologically defined cognitive disorders. This pilot study calls for longitudinal studies investigating midlife cognition to identify clinical correlates of biologically defined cognitive disorders.

Ideal cardiovascular health (CVH) is defined for the presence of ideal behavioral and health metrics known to prevent cardiovascular disease (CVD). The association of circulatory phospho- and sphingo-lipids to primary reduction in cardiovascular risk is unclear. Our aim was to determine the association of CVH metrics with the circulating lipid profile of a population-based cohort. Serum sphingolipid and phospholipid species were extracted from 461 patients of the randomly selected prospective Kardiovize study based on Brno, Czech Republic. Lipids species were measured by a hyphenated mass spectrometry technique, and were associated with poor CVH scores, as defined by the American Heart Association. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE) species were significantly lower in ideal and intermediate scores of health dietary metric, blood pressure, total cholesterol and blood fasting glucose compared to poor scores. Current smokers presented higher levels of PC, PE and LPE individual species compared to non-smokers. Ceramide (Cer) d18:1/14:0 was altered in poor blood pressure, total cholesterol and fasting blood glucose metrics. Poor cardiovascular health metric is associated with a specific phospho- and sphingolipid pattern. Circulatory lipid profiling is a potential biomarker to refine cardiovascular health status in primary prevention strategies.