Olson, Thomas P.

Introduction: Postural orthostatic tachycardia syndrome (POTS) is a chronic syndrome with symptoms of orthostatic intolerance, tachycardia, and exercise intolerance. POTS predominately affects young females, with notable variations in incidence and manifestations between females and males. Limited data exist on sex differences in the response to cardiopulmonary exercise test (CPET) in patients diagnosed with POTS. Methods: Retrospective analysis of 307 POTS patients who underwent CPET between 2000 and 2023 at Mayo Clinic. Diagnosis of POTS was confirmed by tilt-table testing with a sustained increase in heart rate (HR)≥ 30 bpm or HR>120 bpm 10-min post-tilt and without orthostatic hypotension. Patients were grouped by sex (male: n=48 and female: n=259). Predicted peak values were calculated and independent t-tests were used to compare between-group differences. Results: There were no significant differences between males and females for age (28±8 vs 27±7, years) or body mass index (24±5 vs 24±5, kg/m 2 ) (both p>0.05). The time between diagnosis and CPET was not significantly different between males and females (21±113 vs 44±280 days, p>0.05). Resting HR was lower in male patients (76±17 vs 85±18 bpm, p<0.05). At peak exercise, there was no difference in respiratory exchange ratio (1.18±.2 vs 1.17±0.1, p>0.05). Males had significantly lower peak HR (171±22 vs 176±19 bpm) and lower percent (%) predicted peak HR (88±12 vs 93±13 %) (both p<0.05) compared to females. Peak oxygen consumption (VO 2 peak) was significantly higher in males (29.2±8 vs 24.9±7 mL/kg/min), however; % predicted VO 2 peak was lower in males (65±17 vs 71±18 %) (both p<0.05). Peak oxygen (O 2 ) pulse was higher in males (14±4 vs 9±2 mL/beat, p<0.05) with no difference in % predicted peak O 2 pulse (73±17 vs 78±17 %, p>0.05). Conclusion: These data suggest male patients achieved a lower peak HR, % predicted peak HR, and % predicted VO 2 peak than female patients. Both male and female patients utilized a similar % predicted peak O 2 pulse. These findings suggest male POTS patients demonstrate more impaired exercise tolerance compared to female patients. Additional research is needed to fully elucidate the underpinning physiologic mechanisms responsible for impaired exercise tolerance in POTS and the apparent sex differences in exercise capacity.

Background: Cardiac rehabilitation (CR) patients demonstrate a high burden of chronic conditions (CC). Both multimorbidity (MM; ≥2 coexisting CC) and aging negatively impact functional capacity, whereas CR improves performance. Age-related difference in cardiorespiratory fitness (CRF, peak oxygen uptake (VO 2 )) in CR patients with MM has not been studied. Hypothesis: We hypothesized improvement in CRF will be attenuated by MM with increasing age in CR patients. Aims: We aimed to identify age-related differences in CRF improvement in CR patients with MM. Methods: Patients ≥18 yrs old who attended ≥1 CR sessions from 1999-2017 and completed cardiopulmonary exercise stress test before and after CR were included. The prevalence of CC was assessed using Rochester Epidemiology Project records-linkage system. Age categories included: Younger (18-49 yrs), Midlife (50-64 yrs) and Older (≥65 yrs). CRF categories included: <0%, 0-8% and >8%. Analysis included Kruskal-Wallis and Chi-squared. Results: Of 622 patients, 75.4% were male. Mean age: 62.9±11.2 yrs; Younger (n=70) age: 42.7±6.8 yrs, 67.1% male; Midlife (n=283) age: 58.3±4.3 yrs, 78.8% male; Older (n=269) age: 73.0±5.2 yrs, 74.0% male. BMI was 29.9±5.4 kg/m 2 (Younger: 30.0±6.7, Midlife: 30.4±5.6, Older: 29.3±4.7; p<.05). Median (Q1, Q3) no. of CR sessions attended was 33(22, 35), with lower attendance in the Younger group: 25(16,34) vs Midlife: 33(20,35) and Older: 34 (29,35), p<.05. Overall, percent change in peak VO 2 was 11.5±21.6% (Younger: 18.8±22.8%, Midlife: 11.6±19.5%, Older: 9.4±23.1%; p<.01). The median number of CC was 7(5,8) with significant differences across groups: Younger: 5(3,7), Midlife: 6(5,8), Older: 7(6,9), p<.01. Number of CC increased with age across all CRF categories (p<.01, Fig. 1). However, there was no difference in number of CC within age groups across categories of CRF, Table 1. Conclusions: Our results suggest that MM increases with age in patients attending CR; however, within a given age group, improvement in CRF does not appear dependent on MM. The impact of age appears to have a greater impact than MM on CRF improvement. Individualized treatment plans should focus on the impact of age-related disparities on CRF improvement among CR patients with MM.

Abstract Background Hemoglobin S (HbS) causes sickling disorders. In the laboratory, confirmation of HbS in patient samples with varying percentages is essential. Assessment is routinely performed using capillary electrophoresis (CE) and/or high-performance liquid chromatography. Sickle solubility (SS) exploits decreased solubility of HbS under reducing conditions and is a confirmatory test. SS is unreliable with low HbS, elevated HbF, severe anemia, erythrocytosis, hyperglobulinemia, extreme leukocytosis, hyperlipidemia, or increased serum proteins. Infant samples commonly have low percentages of HbS, high HbF, and limited sample volume. Intact globin chain Mass Spectrometry (MS) is used to identify abnormal hemoglobin variants by detecting the mass change (normal α/β/γ mass =15127/15867/15996 amu), respectively). MS has potential advantages in sensitivity and efficiency over SS and requires lower input sample volume. Herein we compare the utility of MS versus SS for confirmation of HbS. Methods Twenty-three EDTA-anticoagulated blood samples containing low percentages of HbS were identified. SS was performed on 30μL washed packed cells (requires 200μL whole blood) per standard methods. Intact Quadrupole Time-of-Flight MS (Accurate-Mass Q-TOF LC/MS 6520, Agilent Technologies, California) was performed using 10μL whole blood sample in acetonitrile solution reagent and results were compared. HbS and HbF levels were assayed by capillary electrophoresis (Sebia, France) per standard methods. Results Select results are summarized in Table 1. SS detected HbS percentages to 4.8% when HbF was low but not 6% HbS when Hb F is high. MS showed no HbF interference and identified HbS peaks (at 15837 amu) down to 3.1%. HbS percentages &lt;3.1 were undetected by both methods. Conclusions Overall, MS was superior to SS for confirming HbS, particularly in samples with low variant percentage and/or elevated HbF. MS is also optimal when sample volume is minimal, such as for infants. Percentages of HbS &lt;3% require methods such as IEF or DNA sequencing for confirmation.

ABSTRACT Background The optimal exercise regimen for alleviating sarcopenia remains uncertain. This study aimed to investigate the efficacy of high‐intensity interval training (HIIT) over moderate‐intensity continuous training (MICT) in ameliorating sarcopenia. Methods We conducted a randomized crossover trial to evaluate plasma proteomic reactions to acute HIIT (four 4‐min high‐intensity intervals at 70% maximal capacity alternating with 4 min at 30%) versus MICT (constant 50% maximal capacity) in inactive adults. We explored the relationship between a HIIT‐specific protein relative to MICT, identified via comparative proteomic analysis, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and sarcopenia in a paired case–control study of elderly individuals (aged over 65). Young (3 months old) and aged (20 months old) mice were randomized to sedentary, HIIT and MICT groups (five sessions/week for 4 weeks; n = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1 and differentiation markers MyoD, myogenin and MyHC‐II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D‐galactose‐induced myoblast senescence, measuring senescence‐associated β‐galactosidase and markers like p21 and p53. Results The crossover trial, including 10 sedentary adults (32 years old, IQR 31–32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case–control study of 84 older adults (84 years old, IQR 69–81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95%CI, 2.02–27.34] pg/mL, p = 0.03) and was associated with skeletal muscle index ( R 2 = 0.51, p < 0.001) and hand grip strength ( R 2 = 0.54, p < 0.001). In the preclinical study, aged mice exhibited higher EEF1E1 mRNA and protein levels in skeletal muscle compared to young mice, accompanied by a lower muscle mass and strength, increased cellular senescence and protein degradation markers and reduced muscle differentiation efficiency (all p < 0.05). HIIT reduced EEF1E1 expression and mitigated age‐related muscle decline and atrophy in aged mice more effectively than MICT. Notably, EEF1E1 downregulation via siRNA significantly counteracted D‐galactose‐induced myoblast senescence as evidenced by reduced markers of muscle protein degradation and improved muscle differentiation efficiency (all p < 0.05). Conversely, treatments that increased EEF1E1 levels accelerated the senescence process ( p < 0.05). Further exploration indicated that the decrease in EEF1E1 was associated with increased SIRT1 level and enhanced autophagy. Conclusions This study highlights the potential of HIIT as a promising approach to prevent and treat sarcopenia while also highlighting EEF1E1 as a potential intervention target.

Abstract Background The United States Department of Health and Human Services has defined 21 chronic conditions lasting one year or greater and which require ongoing medical treatment. The presence of multiple chronic conditions (multimorbidity) is closely linked to greater physical disability, increased health care utilization, reduced quality of life, and higher mortality rates. In the general population, studies have shown the prevalence of multimorbidity to be greater in females compared to males. Recently, data has suggested that patients enrolled in cardiac rehabilitation (CR) have a significantly greater number of chronic conditions compared to the general population. Whether these same sex differences in the prevalence of individual chronic conditions are present in the CR population has not been examined. Purpose The purpose of this study is to determine whether differences exist in the prevalence of individual chronic conditions between male and female CR patients. We hypothesize that female CR patients will demonstrate greater prevalence of individual chronic conditions compared to men. Methods Using the local Epidemiology Project records-linkage system, we identified patients who attended (≥1) CR sessions from 1995-2019. The prevalence of 21 chronic conditions was extracted from the patients’ medical records at the time of enrollment in CR (Table 1). We conducted chi-squared analysis to identify differences in the prevalence of each individual chronic condition between the sexes. Statistical significance was defined by p≤0.05. Results Of the 13,056 CR patients identified (age: 65.7±12.8 yrs old), 4,107 (31.5%) were female. Male CR patients were significantly younger compared to female counterparts (64.8±12.1 yrs old vs. 67.6±13.6 yrs old; p≤0.001). Females demonstrated a greater number of total chronic conditions compared to males (median (IQR): 7.0 (5.0, 9.0) vs 6.0 (5.0, 8.0); p≤0.001). Females demonstrated a greater prevalence of the following 12 individual chronic conditions compared to males: HTN, CHF, ARR, STR, ART, CAN, CPD, HEP, OST, ANX, DEM, and DEP (p≤0.05, for all). There was a trend for greater prevalence of ARR in females compared to males (p=0.07). In contrast, males experienced a greater prevalence of the following four chronic conditions compared to females: CAD, LIP, AST, and SUB (p≤0.001, for all). There were no differences between sexes for CKD (p=0.87), SZO (p=0.70), or AUT (p=0.31). Conclusion Our data suggest the trend for greater prevalence of chronic conditions in females in the general population is consistent within the CR population. Specifically, 12 of 21 (57%) individual chronic conditions were significantly more prevalent in female CR patients whereas only 4 (19%) conditions were more prevalent in males. These data emphasize the need to better understand the relationship between sex and risk for individual chronic conditions, particularly in patients enrolled in CR.

Abstract Background Patients enrolled in cardiac rehabilitation (CR) demonstrate a greater burden of co-occurring chronic conditions (CC) compared to the general population. Studies have shown that the prevalence of multimorbidity among noninstitutionalized, civilian US adults is higher among women compared to men. These CC are often grouped and categorized as Cardiometabolic, Somatic, and Mental Health based on the origin and organ system the condition affects. Importantly, sex differences between categorizations of CC in patients undergoing CR has not been examined. Purpose Because patients enrolled in CR are known to have multiple Cardiometabolic conditions, the aim of this study is to examine sex differences in the prevalence of non-cardiometabolic conditions in the CR population. Methods We extracted data on all 21 CC defined by the US Department of Health and Human Services using the local Epidemiology Project records-linkage system. Our study population included participants who attended (≥1) CR sessions from 1995 to 2019. The CC were categorized into cardiometabolic (CMC), Somatic, and Mental health groups (Table 1), and as CMC only, CMC + Somatic only, CMC + Mental health only, and CMC + Somatic + Mental health groups (Table 2). The sex differences in the number of CC within these groups were analyzed by Kruskal-Wallis test and prevalence were analyzed by Pearson’s Chi-squared test, where p&lt;0.05 was significant. Results We identified 13,056 CR patients (68.5% males) who were ≥18 years old with a mean age of 65.7±12.7 yrs (67.6±13.6 yrs in females and 64.8±12.1 yrs in males). Median [Q1, Q3] number of CC was 7 [5,9], with females having a greater number (7 [5, 9]) than males (6 [5,8]), p&lt;0.001. Both sexes had at least 1 CMC with a median of 5 [3,5] CMC and no differences between sexes (p&gt;0.05); however, females demonstrated more somatic and mental health conditions compared to males (p&lt;0.001, for both, Table 1). When grouping categories of CC, females demonstrated a higher number of CC in CMC + Somatic + Mental health as well as CMC + Somatic only groups (p&lt;0.001, for both, Table 2), with a higher prevalence in the former group only. While the number of CC in CMC + Mental health group was similar between sexes, the prevalence was lower in females. In contrast, the CMC only grouping demonstrated a higher number of CC and prevalence among males (p&lt;0.05). Conclusion Our data suggest that females enrolled in CR demonstrate a significantly higher number of CC compared to males. Although males have a higher prevalence of CMC, the prevalence of Somatic ± Mental health conditions in addition to CMC is significantly greater in females. These data demonstrate the importance of considering sex differences in the prevalence of non-CMC when formulating individualized treatment plans for CR patients.