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Sleep, Stress, and Symptoms Among People With Heart Failure During the COVID-19 Pandemic.
O'Connell, M, Jeon, S, Conley, S, Linsky, S, Redeker, NS
The Journal of cardiovascular nursing. 202301;38(2):E55-E60
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COVID-19 pandemic raised concerns about the effects of stress on mental health and sleep deficiency. Cognitive behavioural therapy for insomnia (CBT-I) has been shown to improve sleep quality and insomnia severity, as well as anxiety and depression, and may be protective during times of stress, including the COVID-19 pandemic. The aim of this study was to examine changes in sleep, sleep-related cognitions, stress, anxiety, and depression among people with heart failure (HF). This study was a randomised controlled trial of the effects of CBT-I compared with HF self-management education (attention-control condition), the “HeartSleep Study.” Results showed that improvements in insomnia severity, sleep quality, latency, and efficiency, sleep-related cognitions and stress, anxiety, and depression after participation in CBT-I or an HF self-management class were sustained during the pandemic. Authors conclude that their findings confirm the clinical benefits of CBT-I for people with HF and comorbidities and also suggest the potential benefits of HF self-management education.
Abstract
BACKGROUND The COVID-19 pandemic raised concerns about the effects of stress on sleep and mental health, particularly among people with chronic conditions, including people with heart failure (HF). OBJECTIVE The aim of this study was to examine changes in sleep, sleep-related cognitions, stress, anxiety, and depression among people with HF who participated in a randomized controlled trial of cognitive behavioral therapy for insomnia before the COVID-19 pandemic. METHODS Participants self-reported sleep characteristics, symptoms, mood, and stress at baseline, 6 months after cognitive behavioral therapy for insomnia or HF self-management education (attention control), and during the pandemic. RESULTS The sample included 112 participants (mean age, 63 ± 12.9 years; 47% women; 13% Black; 68% New York Heart Association class II or III). Statistically significant improvements in sleep, stress, mood, and symptoms that occurred 6 months post treatment were sustained during the pandemic. CONCLUSIONS Improving sleep and symptoms among people with HF may improve coping during stressful events, and cognitive behavioral therapy for insomnia may be protective.
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Inflammation moderates the effects of lifestyle modification on neurocognition among individuals with resistant hypertension.
Avorgbedor, F, Blumenthal, JA, Hinderliter, A, Ingle, K, Lin, PH, Craighead, L, Tyson, C, Kraus, W, Sherwood, A, Smith, PJ
Journal of clinical hypertension (Greenwich, Conn.). 2023;25(1):106-110
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Hypertension is one of the primary causes of cardiovascular disease, stroke, Alzheimer’s Disease, and Alzheimer’s Disease and related dementias (AD/ADRD). Among individuals with hypertension, those with resistant hypertension (RH) appear to have the greatest risk of cerebrovascular disease and associated cognitive impairment. The aim of this study was to investigate the potential influence of individual differences in pre-treatment inflammatory profiles on changes in cognition following lifestyle modification among RH participants in the TRIUMPH clinical trial. This study is a report based on the TRIUMPH study which was a randomised clinical trial. One hundred forty patients with RH were randomised with 2:1 allocation to either a 4-month Centre-based Lifestyle intervention or Standardized Education and Physician Advice. Results show that basal levels of elevated peripheral inflammation may represent an intermediate phenotype of risk for cognitive decline. In fact, individuals with higher levels of c-reactive protein at baseline demonstrated greater improvements in Executive Function/Learning following participation in an intensive lifestyle intervention. Authors conclude that their findings may help inform targeted treatments to reduce ADRD among middle-aged and older adults with cardiovascular disease risk factors.
Abstract
Individuals with resistant hypertension (RH) have the greatest risk of cerebrovascular disease and cognitive impairment among individuals with hypertension. Elevated levels of pro-inflammatory cytokines may represent a critical yet unexamined factor influencing the impact of healthy lifestyle changes on cognitive function. We explored the influence of inflammation on changes in cognition following lifestyle modification among individuals with RH participating in the TRIUMPH clinical trial. One hundred forty participants with RH completed a battery of neurocognitive tests along with the inflammatory marker C-reactive protein (hsCRP) and were subsequently randomized to an intensive 4-month lifestyle modification intervention or to education and physician advice control. Results indicated that the effects of lifestyle modification on Executive Function and Learning were moderated by pre-intervention hsCRP levels (P = .049), with treatment efficacy increasing across levels of baseline inflammation levels (low: d = 0.12; mild: d = 0.43; moderate: d = 0.81). We conclude that inflammatory profiles may help identify individuals more likely to improve executive functioning resulting from lifestyle modification.
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Inflammatory and insulinemic dietary patterns and risk of endometrial cancer among US women.
Romanos-Nanclares, A, Tabung, FK, Sinnott, JA, Trabert, B, De Vivo, I, Playdon, MC, Eliassen, AH
Journal of the National Cancer Institute. 2023;115(3):311-321
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Expert Review
Conflicts of interest:
None
Take Home Message:
- Endometrial cancer is increasing in many populations, and evidence links this to rising obesity and increasing age.
- Dietary factors that increase systemic inflammation and raise blood insulin levels appear associated with the development of EC in the population of women studied.
- Women with obesity are at increased risk of developing EC, compared with women in the normal weight range, and the dietary inflammatory and insulinemic potential may contribute to this association
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This cohort study examined the incidence of endometrial cancer (EC) in women recruited to two large prospective studies in the USA. The Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHS-II) recruited female nurses from 1984 to 2016 and 1991 to 2017 respectively. These large studies have produced significant epidemiological data, reporting associations between lifestyle factors and health outcomes across many health conditions including cancer. The two studies had combined recruitment of 237950 women and a follow up rate of 90%. This analysis applied two novel dietary indices developed and validated using cohorts within the NHS and NHS-II studies and a parallel study in male health professionals, the Health Professionals Follow-Up Study (HPFS).
Methods
Data collection:
- Researchers collected medical histories and lifestyle information using self-administered questionnaires at intervals during the study.
- In this subset analysis, 133756 women with an intact uterus were studied, which represented 2823221 person years of follow up.
- Physical activity, smoking status, medication use including contraceptive use and hormone replacement therapy were recorded. Diabetes diagnosis and anthropometric data were collected.
- Dietary intakes were assessed using a semi-quantitative food frequency questionnaire (FFQ) of 116 foods items in NHS, increased to 130 food items NHS-II. The FFQ had previously been validated using 24-hour dietary recall and multi-week dietary records.
Analysis of dietary impact:
- The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory potential (EDIP) index were developed and validated using stepwise regression models (reported in detail elsewhere). Intakes of 39 predetermined food items within the FFQ were compared with biomarkers from three cohorts of matched cases, nested within the NHS and NHS-II studies and the HPFS, which studied male health professionals.
- Biomarkers for inflammation used to develop EDIP were plasma concentrations of IL-6, C-reactive protein (CRP), TNF-α receptor 2 (TNFαR2), and adiponectin. Validation of the EDIP identified eighteen foods of which 9 were considered anti-inflammatory and 9 proinflammatory.
- Plasma C-peptide was the biomarker for insulinemic impact for EDIH, validated to scores for intake of eighteen food groups; thirteen positively associated with C-peptide and five inversely associated.
- These indices therefore score dietary pattern, however, notably, there were some curious findings for individual foods identified as pro-inflammatory (tomatoes) and anti-inflammatory (pizza), which were noted in the publication reporting development of the EDIP.
Findings
- There were 1565 diagnoses of endometrial cancer, of which 1462 Type 1 EC were considered, discounting rare or uncertain EC subtypes.
- Associations between EDIH and EDIP scores by quintile and endometrial cancer were calculated and identified increased incidence of EC with more inflammatory and insulinemic dietary patterns. For dietary inflammatory potential assessed using EDIP, comparing highest to lowest quintile, HR = 1.46, (95% CI = 1.24 to 1.73; Ptrend < .001). For dietary insulinemic potential, comparing highest to lowest quintile, hazard ratio (HRQ5vsQ1) = 1.58, 95% CI = 1.34 to 1.87; Ptrend < .001).
- Multivariate analysis indicated a substantial effect of the combined scores on EC risk.
- However, adjusting these scores for BMI attenuated the effect, with HR close to 1 after adjustment (EDIP HR = 1.03, 95% CI = 0.87 to 1.22; EDIH HR = 1.01, 95% CI = 0.85 to 1.21). Body mass index was assessed to explain 60.4% of the association of endometrial cancer with dietary inflammatory potential as expressed as EDIP and 71.8% of inflammatory potential as expressed as EDIH. These data suggest therefore that adiposity and obesity are strongly influential in these effects.
Clinical practice applications:
- Endometrial cancer is increasing in incidence in industrialised countries, predicted to overtake colorectal cancer as the leading type of cancer in women in the USA by 2030.
- There is clear evidence for a link with obesity and with unopposed oestrogen. This study demonstrates the impact of dietary intake on EC risk and highlights a role for appropriate nutritional guidance to support women who may be at risk of developing EC.
- Since the association with inflammatory and insulinemic foods appears strongly influenced by obesity, measures to address body composition are important.
Considerations for future research:
- Apparent anomalies in the inflammatory potential scores reman unexplained, although overall dietary pattern is more important to consider than intakes of individual food items.
- This study did not report biomarkers of insulin resistance and BMI was the only anthropometric data reported. Analysis of risk associated with body composition and adiposity would be useful. For example, waist to height ratio is considered a useful anthropometric indicator
- Further exploration of the role of dietary insulinemic impact on insulin resistance could include measurement of HbA1c in this patient group.
- As exposure to excess unopposed oestrogen is also implicated in EC, assessment of oestrogen metabolism and adiposity would also add to the understanding of this condition.
Abstract
BACKGROUND Although unopposed estrogen exposure is considered a major driver of endometrial carcinogenesis, chronic inflammation and insulin resistance and hyperinsulinemia are also major endometrial cancer risk factors. However, it is unclear whether diets with inflammatory or insulinemic potential are associated with risk of endometrial cancer. METHODS We followed 48 330 women from the Nurses' Health Study (1984-2016) and 85 426 women from the Nurses' Health Study II (1989-2017). Using food frequency questionnaires, we calculated repeated measures of empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores, which characterize the potential of the whole diet to modulate circulating biomarkers of inflammation or C-peptide, respectively. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for type I endometrial cancer risk. RESULTS We documented 1462 type I endometrial cancer cases over 2 823 221 person-years of follow-up. In the pooled multivariable-adjusted analyses, women in the highest compared with lowest quintiles were at higher risk of type I endometrial cancer (EDIP HRQ5vsQ1 = 1.46, 95% CI = 1.24 to 1.73; Ptrend < .001; EDIH HRQ5vsQ1 = 1.58, 95% CI = 1.34 to 1.87; Ptrend < .001). Additional adjustment for body mass index attenuated the associations (EDIP HR = 1.03, 95% CI = 0.87 to 1.22; EDIH HR = 1.01, 95% CI = 0.85 to 1.21), and mediation analyses showed that body mass index may explain 60.4% (95% CI = 37.4% to 79.6%; P < .001) and 71.8% (95% CI = 41.0% to 90.4%; P < .001) of the association of endometrial cancer with EDIP and EDIH, respectively. CONCLUSIONS In this large cohort study, higher dietary inflammatory and insulinemic potential were each associated with increased endometrial cancer incidence, and this association may be almost entirely mediated by adiposity.
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Effects of the Dietary Approaches to Stop Hypertension Diet on Change in Cardiac Biomarkers Over Time: Results From the DASH-Sodium Trial.
Belanger, MJ, Kovell, LC, Turkson-Ocran, RA, Mukamal, KJ, Liu, X, Appel, LJ, Miller, ER, Sacks, FM, Christenson, RH, Rebuck, H, et al
Journal of the American Heart Association. 2023;12(2):e026684
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Most deaths from cardiovascular disease (CVD) can be attributed to specific modifiable risk factors. The Dietary Approaches to Stop Hypertension (DASH) diet, rich in fruits, vegetables, low-fat dairy and reduced in saturated fat and cholesterol, is associated with a lower risk of CVD events over time. The aim of this study was to examine the time course of change in biomarkers of cardiac injury, strain, and inflammation from consuming the DASH diet in comparison with a typical American diet. This study is a secondary analysis of the DASH-Sodium randomised clinical trial which recruited adult men and women, aged ≥22years. The participants were randomly assigned in a parallel-arm design to the DASH diet or a typical American diet (control) in a 1:1 ratio. Results show that in comparison with a typical American diet, the DASH diet reduced two of the investigated biomarkers progressively over a 12-week period. Authors conclude that their findings highlight the need for public health policies and interventions that support sustained adherence to a healthy eating pattern for cardiovascular health.
Abstract
Background The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to reduce biomarkers of cardiovascular disease. We aimed to characterize the time course of change in biomarkers of cardiac injury (high-sensitivity cardiac troponin I), cardiac strain (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and inflammation (hs-CRP [high-sensitivity C-reactive protein]) while consuming the DASH diet. Methods and Results The DASH-Sodium trial was a randomized controlled trial of 412 adults with elevated blood pressure or hypertension. Participants were randomly assigned to 12 weeks of the DASH diet or a typical American diet. Energy intake was adjusted to maintain body weight. Measurements of high-sensitivity cardiac troponin I, NT-proBNP, and hs-CRP were performed in stored serum specimens, collected at baseline and ≈4, 8, and 12 weeks after randomization. In both the control diet and DASH diet, levels of NT-proBNP decreased; however, there was no difference between diets (P-trend compared with control=0.22). On the DASH diet versus control, levels of high-sensitivity cardiac troponin I decreased progressively during follow-up (P-trend compared with control=0.025), but a statistically significant between-diet difference in change from baseline levels was not observed until week 12 (% difference, 17.78% [95% CI, -29.51% to -4.09%]). A similar pattern was evident for hs-CRP (P-trend compared with control=0.01; % difference at week 12, 19.97% [95% CI, -31.94% to -5.89%]). Conclusions In comparison with a typical American diet, the DASH diet reduced high-sensitivity cardiac troponin I and hs-CRP progressively over 12 weeks. These results suggest that the DASH diet has cumulative benefits over time on biomarkers of subclinical cardiac injury and inflammation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000608.
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The effects of prebiotics on gastrointestinal side effects of metformin in youth: A pilot randomized control trial in youth-onset type 2 diabetes.
Dixon, SA, Mishra, S, Dietsche, KB, Jain, S, Mabundo, L, Stagliano, M, Krenek, A, Courville, A, Yang, S, Turner, SA, et al
Frontiers in endocrinology. 2023;14:1125187
Abstract
DISCLOSURE SUMMARY Dr. Yadav is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. All other authors have no conflicts of interest to disclose. BACKGROUND Metformin is the only approved first-line oral glucose lowering agent for youth with type 2 diabetes mellitus (Y-T2DM) but often causes gastrointestinal (GI) side effects, which may contribute to reduced treatment adherence and efficacy. Prebiotic intake may reduce metformin's side effects by shifting microbiota composition and activity. OBJECTIVE The aims of this study were to determine the feasibility and tolerability of a prebiotic supplement to improve metformin-induced GI symptoms and explore the changes in glycemia and shifts in the microbiota diversity. METHODS In a two-phase pilot clinical trial, we compared, stool frequency and stool form every 1-2 days, and composite lower GI symptoms (weekly) at initiation of daily metformin combined with either a daily prebiotic or a placebo shake in a 1-week randomized double-blind crossover design (Phase 1), followed by a 1-month open-labeled extension (Phase 2). Plasma glycemic markers and stool samples were collected before and after each phase. RESULTS Six Y-T2DM (17.2 ± 1.7y (mean ± SD), 67% male, BMI (42 ± 9 kg/m2), HbA1c (6.4 ± 0.6%)) completed the intervention. Stool frequency, stool composition, and GI symptom scores did not differ by group or study phase. There were no serious or severe adverse events reported, and no differences in metabolic or glycemic markers. After one week Phase 1metformin/placebo Proteobacteria, Enterobacteriaceae, and Enterobacteriales were identified as candidate biomarkers of metformin effects. Principle coordinate analyses of beta diversity suggested that the metformin/prebiotic intervention was associated with distinct shifts in the microbiome signatures at one week and one month. CONCLUSION Administration of a prebiotic fiber supplement during short-term metformin therapy was well tolerated in Y-T2DM and associated with modest shifts in microbial composition. This study provides a proof-of-concept for feasibility exploring prebiotic-metformin-microbiome interactions as a basis for adjunctive metformin therapy. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/, identifier NCT04209075.
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Acute beetroot juice reduces blood pressure in young Black and White males but not females.
Grosicki, GJ, Flatt, AA, Cross, BL, Vondrasek, JD, Blumenburg, WT, Lincoln, ZR, Chall, A, Bryan, A, Patel, RP, Ricart, K, et al
Redox biology. 2023;63:102718
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Cardiovascular (CV) disease is the leading cause of death in the United States. Out of all ethnic groups, CV disease is particularly common in black Americans. High blood pressure (BP) is one of the main contributors to CV disease, and black Americans exhibit a disproportionally higher incident rate of high BP when compared to other ethnic groups. Partly this is due to genetic and physiological differences, yet is also influenced by social, socioeconomic, and environmental factors. One physiological difference that may contribute to higher BP in black adults appears to be a reduced availability of nitric oxide (NO). NO is a gas that is abundant in the human body. It regulates vascular tone and elasticity of the arteries, and therefore helps to manage blood pressure. Nitrates that occur in foods can be converted to NO and thus contribute to NO levels in the body. Beetroot juice (BRJ) is rich in nitrates. This study examined whether BRJ supplementation can reduce resting BP and cardiovascular reactivity in adults. The randomized, placebo-controlled, crossover-design study was completed by 18 black and 20 white young adults, male and female, with an average age of 21. The study monitored heart rate, BP and arterial stiffness in a variety of settings. The study also assessed socioeconomic status, perceived discrimination, sleep and dietary intake. The main findings from this investigation were that despite young black adults having higher resting BP, acute BRJ supplementation reduced the pressure to a similar extent in young black and white adults, but primarily in males. This reduction correlated with increased levels of circulating nitrites. However, acute BRJ supplementation did not influence resting arterial stiffness. The result also highlighted previously seen racial differences relating to social determinants of health and lifestyle, which may contribute to the elevated BP values seen in black participants. The study demonstrated that dietary nitrate from beetroot juice has the potential to be a cost-effective blood pressure-lowering strategy for young black and white males. Yet the findings also highlighted the complex interplay of social, lifestyle, and underlying physiological factors that influence racial differences when it comes to CV health
Abstract
A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.
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The impact of Dietary Weight loss, Aerobic Exercise, and Daylong Movement on Social Cognitive Mediators of Long-term Weight loss.
Fanning, J, Nicklas, B, Furlipa, J, Rejeski, WJ
Journal of behavioral medicine. 2023;46(3):499-508
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Obesity in older adults predisposes individuals to physical disability, a host of chronic diseases, and premature mortality. A strong body of evidence indicates that well-designed structured exercise interventions increase older adults’ self-efficacy and satisfaction with their physical functioning, and these are important social cognitive outcomes closely linked with quality of life and health behaviour change. The main aim of this study was to investigate changes in walking self-efficacy and satisfaction after the 6-month intensive phase of the intervention. This study was a secondary analysis of the Empowered with Movement to Prevent Obesity and Weight Regain (EMPOWER) study, which was an 18-month, three-group, single-blind randomised trial. A total of 183 participants were randomly assigned to one of the three treatment arms: weight loss + structured exercise (WL+EX), WL+ sitting less and moving more across the day (SL), or WL+EX+SL. Results showed that: - participants demonstrated improvements in self-efficacy and satisfaction following the 6-month intervention weight loss and physical activity intervention. - participants who received an exercise intervention focused on sustained walking demonstrated significantly better self-efficacy for walking relative to those who did not (WL+SL). - both WL+EX and WL+EX+SL regressed to baseline levels of self-efficacy for walking by month 18, only WL+SL did not significantly decrease self-efficacy scores, sustaining a significant increase over baseline. Authors conclude that programs focused on daylong movement may contribute to improved self-efficacy and satisfaction. Thus, health promotion professionals should demonstrate flexibility in the ways in which physical activity is prescribed for older adults since not everyone resonates with traditional structured exercise.
Abstract
This report contrasts the impact of a dietary weight loss intervention (WL) paired with aerobic exercise (EX) and/or sitting less and moving throughout the day (SL) on self-efficacy for walking (hereafter walking self-efficacy) and satisfaction with physical functioning (hereafter satisfaction). Additional analyses examined dose-response associations between change in weight and changes in these key outcomes. Older adults (N = 112; age = 70.21[Formula: see text]4.43) were randomized to 6 months of WL+EX, WL+SL, or WL+EX+SL followed by a 12-month maintenance period. All groups reported increases in walking self-efficacy at month 6 with greater improvements in WL+EX and WL + EX+SL. Only WL+SL demonstrated improved walking self-efficacy at month 18. All conditions demonstrated improved satisfaction scores at both time points. Changes in walking self-efficacy and satisfaction were negatively associated with change in weight over the 6-month intervention and after the maintenance period. These results support the utility of WL + SL for improving key social cognitive outcomes in aging.
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Metabolomic Profiles Associated With Blood Pressure Reduction in Response to the DASH and DASH-Sodium Dietary Interventions.
Kim, H, Appel, LJ, Lichtenstein, AH, Wong, KE, Chatterjee, N, Rhee, EP, Rebholz, CM
Hypertension (Dallas, Tex. : 1979). 2023;80(7):1494-1506
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DASH (Dietary Approaches to Stop Hypertension) diet is recommended for reducing blood pressure (BP) and the risk of cardiovascular disease (CVD). The DASH diet emphasises the intake of fruits, vegetables, and low-fat dairy, includes a variety of protein sources and it is low in red and processed meats and sugar-sweetened beverages. The aim of this study was to identify metabolites associated with differences in systolic blood pressure (SBP) or diastolic blood pressure (DBP) in response to the diet interventions. This study used data from 2 randomised controlled feeding trials (DASH trial and DASH-Sodium trial). Results show the identification of 42 unique metabolites (9 serum and 33 urine) which were significantly associated with changes in SBP or DBP DASH diet versus control diet interventions. Furthermore, pathway overrepresentation analysis revealed metabolite pathways that were relevant for the association between DASH diet and BP. Authors conclude that their findings provide insights on formulating intervention strategies to reduce BP.
Abstract
BACKGROUND The DASH (Dietary Approaches to Stop Hypertension) diets reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. We identified metabolites associated with systolic BP or diastolic BP (DBP) changes induced by dietary interventions (DASH versus control arms) in 2 randomized controlled feeding studies-the DASH and DASH-Sodium trials. METHODS Metabolomic profiling was conducted in serum and urine samples collected at the end of diet interventions: DASH (n=219) and DASH-Sodium (n=395). Using multivariable linear regression models, associations were examined between metabolites and change in systolic BP and DBP. Tested for interactions between diet interventions and metabolites were the following comparisons: (1) DASH versus control diets in the DASH trial (serum), (2) DASH high-sodium versus control high-sodium diets in the DASH-Sodium trial (urine), and (3) DASH low-sodium versus control high-sodium diets in the DASH-Sodium trial (urine). RESULTS Sixty-five significant interactions were identified (DASH trial [serum], 12; DASH high sodium [urine], 35; DASH low sodium [urine], 18) between metabolites and systolic BP or DBP. In the DASH trial, serum tryptophan betaine was associated with reductions in DBP in participants consuming the DASH diets but not control diets (P interaction, 0.023). In the DASH-Sodium trial, urine levels of N-methylglutamate and proline derivatives (eg, stachydrine, 3-hydroxystachydrine, N-methylproline, and N-methylhydroxyproline) were associated with reductions in systolic BP or DBP in participants consuming the DASH diets but not control diets (P interaction, <0.05 for all tests). CONCLUSIONS We identified metabolites that were associated with BP lowering in response to dietary interventions. REGISTRATION URL: https://www. CLINICALTRIALS gov/ct2/show/NCT03403166; Unique identifier: NCT03403166 (DASH trial). URL: https://www. CLINICALTRIALS gov/ct2/show/NCT00000608; Unique identifier: NCT00000608 (DASH-Sodium trial).
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Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.
Deng, N, Reyes-Uribe, L, Fahrmann, JF, Thoman, WS, Munsell, MF, Dennison, JB, Murage, E, Wu, R, Hawk, ET, Thirumurthi, S, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;29(21):4361-4372
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Lynch syndrome (LS) is a genetic disorder conferring a 60% lifetime risk of developing colorectal cancer (CRC). Exercise is associated with a reduction in CRC risk in the general population, potentially mediated via modulation of inflammation. The aim of this non-randomised, controlled trial was to test whether an intervention consisting of 3 x 45-minute cycling classes per week for 12 months affects inflammatory factors (prostaglandin E2, PGE2) in the colorectal mucosa and blood and whether this intervention is feasible in LS carriers. The control group received usual care with one session of exercise counselling. Of 60 patients invited to join the study, 21 (35%) agreed to take part. Of the 11 participants in the intervention group, 9 (81.2%) completed the study with an average adherence to the intervention of 51.3%, compared to 7/10 completing in the control group. VO2 peak (maximal aerobic capacity) increased significantly in the intervention group, compared to the control group over the 12 months. Patients in the intervention group also had a significant reduction in colonic and systemic PGE2 levels compared to controls following intervention. Changes in gene expression which may reflect an increased immune surveillance of the colon were also observed in the intervention group. The authors concluded that the study confirmed that exercise may modulate inflammation in the colonic mucosa in patients at high risk of CRC and that further randomised studies are necessary to confirm the potential benefits of exercise for patients with LS.
Abstract
PURPOSE Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study.
Yu Chen, H, Dina, C, Small, AM, Shaffer, CM, Levinson, RT, Helgadóttir, A, Capoulade, R, Munter, HM, Martinsson, A, Cairns, BJ, et al
European heart journal. 2023;44(21):1927-1939
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Aortic stenosis (AS) is a form of heart disease that is an abnormal narrowing of the aortic valve in the heart, which restricts blood flow. Although being over the age of 75 appears to increase the risk for development, it is unclear as to who else may be at risk. A better understanding of genetic factors, which may be involved in its development could better help to identify those at risk. This meta-analysis of 10 cohort studies aimed to determine genetic contributors to AS and possible mechanisms involved. The results showed that 15 different gene variations were strongly associated with AS including those in the CELSR2-SORT1, NLRP6, LPA and SMC2 genes. Interestingly some of these genes were also identified in individuals with African and Latin American ancestry. It was concluded that these genes, many of which are associated with hardening of the arteries, altered lipid metabolism, excess storage of fat, and inflammation may all contribute to AS. This study could be used by healthcare professionals to understand that there are specific genetic contributors to the development of AS and that in the future we may be able to target these to identify high-risk individuals and use them in therapeutic management.
Abstract
AIMS: Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. METHODS AND RESULTS A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. CONCLUSION Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.