Exercise Cardio-Oncology: Exercise as a Potential Therapeutic Modality in the Management of Anthracycline-Induced Cardiotoxicity

Anthracyclines are one of the most effective chemotherapy agents and have revolutionized cancer therapy. However, anthracyclines can induce cardiac injuries through ‘multiple-hits', a series of cardiovascular insults coupled with lifestyle risk factors, which increase the risk of developing short- and long-term cardiac dysfunction and cardiovascular disease that potentially lead to premature mortality following cancer remission. Therefore, the management of anthracycline-induced cardiotoxicity is a serious unmet clinical need. Exercise therapy, as a non-pharmacological intervention, stimulates numerous biochemical and physiologic adaptations, including cardioprotective effects, through the cardiovascular system and cardiac muscles, where exercise has been proposed to be an effective clinical approach that can protect or reverse the cardiotoxicity from anthracyclines. Many preclinical and clinical trials demonstrate the potential impacts of exercise on cardiotoxicity; however, the underlying mechanisms as well as how to implement exercise in clinical settings to improve or protect against long-term cardiovascular disease outcomes are not clearly defined. In this review, we summarize the current evidence in the field of “exercise cardio-oncology” and emphasize the utilization of exercise to prevent and manage anthracycline-induced cardiotoxicities across high-risk and vulnerable populations diagnosed with cancer.

Interaction of obesity polygenic score with lifestyle risk factors in an electronic health record biobank

Background Genetic and lifestyle factors have considerable effects on obesity and related diseases, yet their effects in a clinical cohort are unknown. This study in a patient biobank examined associations of a BMI polygenic risk score (PRS), and its interactions with lifestyle risk factors, with clinically measured BMI and clinical phenotypes. Methods The Mass General Brigham (MGB) Biobank is a hospital-based cohort with electronic health record, genetic, and lifestyle data. A PRS for obesity was generated using 97 genetic variants for BMI. An obesity lifestyle risk index using survey responses to obesogenic lifestyle risk factors (alcohol, education, exercise, sleep, smoking, and shift work) was used to dichotomize the cohort into high and low obesogenic index based on the population median. Height and weight were measured at a clinical visit. Multivariable linear cross-sectional associations of the PRS with BMI and interactions with the obesity lifestyle risk index were conducted. In phenome-wide association analyses (PheWAS), similar logistic models were conducted for 675 disease outcomes derived from billing codes. Results Thirty-three thousand five hundred eleven patients were analyzed (53.1% female; age 60.0 years; BMI 28.3 kg/m2), of which 17,040 completed the lifestyle survey (57.5% female; age: 60.2; BMI: 28.1 (6.2) kg/m2). Each standard deviation increment in the PRS was associated with 0.83 kg/m2 unit increase in BMI (95% confidence interval (CI) =0.76, 0.90). There was an interaction between the obesity PRS and obesity lifestyle risk index on BMI. The difference in BMI between those with a high and low obesogenic index was 3.18 kg/m2 in patients in the highest decile of PRS, whereas that difference was only 1.55 kg/m2 in patients in the lowest decile of PRS. In PheWAS, the obesity PRS was associated with 40 diseases spanning endocrine/metabolic, circulatory, and 8 other disease groups. No interactions were evident between the PRS and the index on disease outcomes. Conclusions In this hospital-based clinical biobank, obesity risk conferred by common genetic variants was associated with elevated BMI and this risk was attenuated by a healthier patient lifestyle. Continued consideration of the role of lifestyle in the context of genetic predisposition in healthcare settings is necessary to quantify the extent to which modifiable lifestyle risk factors may moderate genetic predisposition and inform clinical action to achieve personalized medicine.

The Role of Fructose as a Cardiovascular Risk Factor: An Update

There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their prevention should be assessed and managed comprehensively and not by the evaluation of individual risk factor components. Lifestyle risk factors for CVD include low degree of physical activity, high body mass index, alcohol consumption, smoking, and nutritional factors. Indeed, nutritional risk factors for CVD include unhealthy dietary behaviors, such as high intake of refined foods, unhealthy fats, added sugars, and sodium and a low intake of fruits, vegetables, whole grains, fiber, fish, and nuts. Even though there is no definitive association between CVD incidence and high consumption of total sugar, such as sucrose and fructose, there is, however, evidence that total sugars, added sugars, and fructose are harmfully associated with CVD mortality. Since high fructose intake is associated with elevated plasma triglyceride levels, as well as insulin resistance, diabetes hyperuricemia, and non-alcoholic fatty liver disease, further longitudinal studies should be conducted to fully elucidate the potential association between certain sugars and CVD.

Impact of Behavioral Risk Factors on Mortality Risk in Older Korean Women

Background: To investigate the impact of lifestyle risk factors on all-cause and cardiovascular disease (CVD) mortality in Korean women aged 60 yr and older. Methods: Data (n = 3,034) obtained from the Korean longitudinal study of aging were analyzed. Exposures included lifestyle risk factors, such as smoking, alcohol abuse, underweight/obesity, physical inactivity, and unintentional weight loss. Primary outcomes were premature deaths from specific and all-causes. Results: During 9.6±2.0 yr of follow-up, there were 628 cases (20.7%) of death from all causes, of which 137 cases (4.5%) were from CVD. Compared to zero risk factor (hazard ratio, HR=1), crude HR of all-cause mortality was 2.277 (95% confidence interval, CI, 1.712 ~ 3.030, P < 0.001) for one risk factor, 2.977 (95% CI, 2.124 ~ 4.003, P < 0.001) for two risk factors, and 5.154 (95% CI, 3.515 ~ 7.557, P < 0.001) for three or more risk factors. Compared to zero risk factor (HR=1), crude HR of CVD mortality was 2.035 (95% CI, 1.422 ~ 2.913, P < 0.001) for one risk factor, 2.468 (95% CI, 1.708 ~ 3.567, P < 0.001) for two risk factor, and 4.484 (95% CI, 2.830 ~ 7.102, P < 0.001) for three or more risk factors. Adjusted HRs of all-cause (P = 0.016) and CVD (P = 0.050) for three or more risk factors only remained significant for three or more risk factors. Conclusion: The current findings showed that individual and combined lifestyle risk factors were significantly associated with increased risks of all-cause and CVD mortality in older Korean women.

The relationship between lifestyle risk factors and depression in Korean older adults: a moderating effect of gender

Background Little is known regarding the role of gender as a possible modulator in determining the associations between lifestyle risk factors and depression in older adults. Objectives This study examined whether gender modulates the relationship between depression and lifestyle risk factors in Korean adults aged 65 years and older (n = 3700). Methods Data were obtained from the 2016 and 2018 Korea National Health and Examination Survey. The primary outcome was depression, assessed with the patient health questionnaire-9. As exposures, smoking habits, at-risk alcohol consumption, and physical inactivity were assessed with a standardized questionnaire. In addition, mean adequacy ratio (MAR) as an indicator of overall nutritional inadequacy was assessed with dietary intakes of macro- and micronutrients. Results In men only, either two or three and more risk factors were significantly associated with higher depression risk (OR (95% confidence interval, CI) = 2.886 (1.003–8.299) and OR (95% CI) = 3.109 (1.064–9.097), respectively). In women only, either two or three and more risk factors were also significantly associated with higher depression risk (OR (95% CI) = 1.505 (1.067–2.124) and OR (95% CI) = 2.828 (1.527–5.239), respectively). In particular, the presence of smoking habits and MAR were the major determinants of depression (OR (95% CI) = 1.835 (1.09–3.10) and OR (95% CI) = 1.585 (1.125–2.233), respectively) in women only. Finally, a moderation analysis with the Hayes PROCESS Macro showed a significant moderating effect of gender (β (95% CI) = 0.633 (0.206 ~ 1.060)) on the relationship between risk factors and depression. In addition, the slope of the relationship was much steeper in women than in men. Conclusion Current findings suggest that lifestyle risk factors are more closely associated with depression risk in women than in men.

The Neurochemistry of Alzheimer’s Disease: One of the Most Common Causes of Reduced Capability in the Adult Population

Alzheimer’s disease (AD) is the most common form of dementia and is characterised by the triad of amyloid plaques, tau pathology and neurodegeneration. Except for a strong association with the susceptibility gene, specifically the apolipoprotein E (APOE) ε4 allele, the pathogenesis of the most common age-related sporadic form of AD is largely unknown. However, several genetic and environmental risk factors have been proposed. A potential problem is that most population-based studies on AD risk-profiling have not used biomarkers reflecting amyloid and tau pathology to classify patients and controls. Given the complex pathophysiology of late-onset AD and the difficulties in correctly diagnosing AD on purely clinical grounds, this introduces a risk of misclassification of both control subjects and clinically diagnosed AD cases. Importantly, in recent years, there has been a very successful development of blood biomarkers for AD pathophysiologies, including brain amyloidosis (amyloid β ratio), tau pathology (phosphorylated tau) and neurodegeneration (neurofilament light). Numerous studies have shown these biomarkers to correlate with amyloid and tau pathology load evaluated by PET and with MRI measures of neurodegeneration, and to predict future cognitive decline. The employment of blood biomarkers in epidemiological studies may foster an understanding of which and how specifically lifestyle risk factors are linked to AD, and repeated blood sampling in intervention trials may provide evidence as to whether controlling lifestyle factors may affect specific AD pathophysiologies.

Dietary Patterns among Adolescents Are Associated with Growth, Socioeconomic Features, and Health-Related Behaviors

Dietary patterns (DPs), usually established in adolescents, are important modifiable risk factors in the etiology of malnutrition and chronic diseases. This study aimed to identify DPs of adolescents and examine their associations with growth, sociodemographic, and lifestyle characteristics. A nationally representative, school-based, cross-sectional study was conducted in Israeli adolescents aged 11–18 years during 2015–2016. A self-administered survey queried sociodemographics, health behaviors, and diet. Weight and height were measured, and WHO height z-scores and BMI cutoffs were calculated. Food frequency questionnaire data were analyzed using principal components analysis (PCA) to identify DPs. Associations between growth, lifestyle, and sociodemographic characteristics and DPs were modeled using multivariable logistic regressions. A total of 3902 adolescents (46% males, mean age 15.2 ± 1.6 years) completed the survey. PCA identified five DPs, accounting for 38.3% of the total variance. The first two prominent DPs were the ‘plant-based food’ DP, which was associated with the female sex, higher socioeconomic status, overweight/obesity, and healthy lifestyle and the ‘junk food’ DP, which was associated with lower SES, unhealthy lifestyle, and lower height z-scores. Our results elucidate major DPs that strongly correlate with lifestyle risk behaviors and suboptimal growth among adolescents. Implementing screening for DPs should be further examined to identify higher risk health factors among youth.

Influence of Risk Factors for Male Infertility on Sperm Protein Composition

Male infertility is a common health problem that can be influenced by a host of lifestyle risk factors such as environment, nutrition, smoking, stress, and endocrine disruptors. These effects have been largely demonstrated on sperm parameters (e.g., motility, numeration, vitality, DNA integrity). In addition, several studies showed the deregulation of sperm proteins in relation to some of these factors. This review inventories the literature related to the identification of sperm proteins showing abundance variations in response to the four risk factors for male infertility that are the most investigated in this context: obesity, diabetes, tobacco smoking, and exposure to bisphenol-A (BPA). First, we provide an overview of the techniques used to identify deregulated proteins. Then, we summarise the main results obtained in the different studies and provide a compiled list of deregulated proteins in relation to each risk factor. Gene ontology analysis of these deregulated proteins shows that oxidative stress and immune and inflammatory responses are common mechanisms involved in sperm alterations encountered in relation to the risk factors.

Memory Problems During COVID in Low-Income Older Adults

Prevention, with widespread lifestyle risk reduction at the community-level, is considered an effective method to decrease Alzheimer’s disease (AD). Diverse low-income older adults in Virginia managing either diabetes/cardiovascular symptoms, were offered weekly lifestyle telephone-health coaching for 12-weeks, providing education, motivations, self-efficacy, and referral services for AD lifestyle risk. Participants provided positive anecdotal feedback and the need for continued health coaching during COVID-19. Thirty participants (predominantly African American/Black female) consented for continued health coaching during the pandemic with 47% reporting memory problems. Findings indicated poorer health status associated with reporting memory problems for poor physical health days, poor mental health days, total mental/physical health poor days, sad days, worried days, tired days, feelings of emptiness, feelings of rejection, feelings of failure, little interest/pleasure, and feeling down. This preliminary work creates the impetus for future large-scale AD prevention investigations to improve the lives of AD-risk, low-income, diverse older adults reporting memory problems.