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.

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.

Periodontitis as a risk for oral cancer: a case–control study

Background The aetiology of oral cancer is multifactorial, as various risk factors (genetics, socioeconomic and lifestyle factors) contribute to its development. Data in the literature suggest that people with periodontal disease have an increased risk of developing oral cancer, and the severity of periodontitis correlates with the appearance of oral squamous cell carcinoma. The aim of this study was to revise the non-genetic risk factors that may influence the development of OC, while focusing on the dental and periodontal status and OH. Methods Two hundred patients (hundred diagnosed with oral cancer and hundred without oral cancer) were enrolled in our case–control study, to evaluate the association between oral cancer and the presence and severity of periodontitis, while examining several risk factors that might be responsible for oral cancer formation. A questionnaire customised for oral cancer patients was used to obtain the socioeconomic and lifestyle risk factors that may influence the development of oral squamous cell carcinoma. The dental and periodontal status along with the level of oral hygiene was recorded quantitatively. The chi-square and Mann–Whitney tests and logistic regression were used for the statistical analysis. Results By considering both the case and the control groups, a significant correlation was found between the incidence of oral cancer and some socioeconomic factors and lifestyle habits, such as the sex, age, education and alcohol consumption of an individual. The mean value of the Silness-Löe plaque index was significantly higher in the case population. The number of completely edentulous patients was higher among the oral cancer population. The incidence of oral cancer was 57.1% in patients with periodontal disease. In comparison, the incidence of oral squamous cell carcinoma was only 28.6% among the patients without periodontitis. Most of the oral cancer patients (72.1%) had stage 4 periodontitis. On the other hand, the vast majority of the control group (51.6%) had stage 2 periodontitis. Conclusion Periodontitis can be an individual risk factor for oral cancer development. Periodontally compromised individuals should be strictly monitored, especially those with severe periodontitis and coexisting lifestyle risk factors. Maintaining their periodontal health in at-risk patients can minimize cancer risks.

Caregiver Engagement in Stroke Care: Opportunities and Challenges in Australia and Denmark

Globally, there is a rise in incident cases of stroke, particularly in low- and middle-income countries, due to obesity-related and lifestyle risk factors, including health issues such as high cholesterol, diabetes and hypertension. Since the early 20th century, stroke mortality has declined due to proper management of the risk factors and improved treatment practices. However, despite the decline in mortality, there is an increase in the levels of disability that requires long-term support. In countries such as Australia and Denmark, where most care is provided within the community; family members, generally spouses, assume the role of caregiver, with little to no preparation that affects the quality of care provided to the person living with stroke. While past research has highlighted aspects to improve caregiver preparedness of stroke and its impact on care; health planning, recovery, and public health policies rarely consider these factors, reducing engagement and increasing uncertainty. Hence, there is a need to focus on improving strategies during recovery to promote caregiver engagement. In this study, we, therefore, try to understand the needs of the caregiver in stroke that limit engagement, and processes employed in countries such as Australia and Denmark to provide care for the person with stroke. Based on our understanding of these factors, we highlight the potential opportunities and challenges to promote caregiving engagement in these countries.

Interaction of Alcohol Consumption and ABCG2 rs2231142 Variant Contributes to Hyperuricemia in a Taiwanese Population

Background: ABCG2 rs2231142 is an important genetic factor that contributes to the development of gout and hyperuricemia (HUA). Epidemiologic studies have demonstrated that lifestyle risk factors of HUA (e.g., alcohol consumption) and genetic predisposition (e.g., ABCG2 gene) together, contribute to enhanced serum uric acid levels. However, the interaction between ABCG2 rs2231142, alcohol consumption, and HUA in the Taiwanese population is still unclear. Therefore, this study investigated whether the risk of HUA is associated with ABCG2 rs2231142 variants and how this is affected by alcohol consumption. Method: study subjects were selected from the participants of the Taiwan Biobank database. Overall, 114,540 participants aged 30 to 70 years were enrolled in this study. The interaction between ABCG2 rs2231142, alcohol consumption, and serum uric acid (sUA) levels was analyzed by multiple logistic regression models. Results: the prevalence of HUA was 32.7% and 4.4 % in the male and female populations, respectively. In the whole study population, the minor T allele of ABCG2 rs2231142 was significantly associated with HUA risk, and the occurrence of HUA was high in TT genotype and TG genotype. The risk of HUA was significantly increased by the combined association of ABCG2 rs2231142 and alcohol consumption for TG/TT genotype compared to the GG genotype (wild-type genotype), especially among women. Conclusion: the ABCG2 rs2231142 is a crucial genetic locus for sUA levels in the Taiwanese population and our findings revealed that alcohol consumption combined with the ABCG2 rs2231142 risk allele contributes to increased HUA risk.