Risk Of Future Disease Research Articles

(205) Erectile Dysfunction is an Independent Risk Factor for Major Adverse Cardiovascular Events

Abstract Introduction Erectile dysfunction (ED) and cardiovascular disease share similar risk profiles which include: aging, hypertension, diabetes, smoking, obesity, and dyslipidemia. Previous literature has suggested ED as a potential harbinger of future cardiovascular disease. Objective As such, we sought to investigate the association between ED and major adverse cardiovascular events (MACE) using a large population based database. As a secondary objective, we sought to investigate the relationship of place of residence (rural or urban) in regards to the incidence of MACE. Methods A propensity-weighted, retrospective cohort study was conducted by accessing provincial health administrative databases. Eligibility criteria included men 18 years and older, with no prior ED or MACE, who had at least 1 year of provincial health coverage from their index date between June 1st 1996 to March 31st 2018. ED was defined as having at least two ED prescriptions filled within one year (including oral, intraurethral, and/or injection therapies). MACE was defined as myocardial infarction, coronary revascularization procedures, ischemic stroke, or hospitalizations for heart failure. We then classified study groups into ED Urban, ED Rural, No ED Urban and No ED Rural. Multiple logistic regression model that included age categories, socioeconomic status, index year, diabetes, hypertension, dyslipidemia and renal disease was used to determine the propensity score. Stabilized inverse propensity treatment weighting was then applied to the propensity score. A cox proportional hazard model was used to examine our primary outcome of time to a MACE. Results The median time to a MACE was 2721, 2620, 2520, and 2438 days in the ED Urban (N=32,138), ED Rural (N=17,821), No ED Rural (N=145,209) and No ED Urban (N=233,073) study groups, respectfully. The ED Rural, ED Urban and No ED Rural study groups had a 54% (Hazard Ratio [HR] 1.54, 95% CI [1.45 – 1.63]), 26% (HR 1.26, 95% CI[1.20 – 1.32]) and 14% (HR 1.14, 95% CI[1.11 – 1.18]) higher risk of a MACE event as compared to the No ED Urban group, in weighted analyses, respectfully. Among individuals with ED, men from a rural setting had a 22% (HR 1.22, 95% CI[1.14 – 1.32]) higher risk of a MACE event, as compared from an urban setting. Conclusions Our study demonstrates that men diagnosed with ED had a higher risk of MACE as compared to controls. ED is demonstrated to be an independent risk factor for MACE when controlling for comorbidities. In addition, men residing in rural communities had a higher risk of MACE as compared to other urban counterparts. It is imperative for health care professionals who manage patients with ED to discuss the risk of future cardiovascular disease and identify comorbid conditions to mitigate risk. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific.

The Association between Adverse Pregnancy Outcomes and Laboratory Measures as Risk for Cardiovascular Disorders

Background; Due to the complicated etiology of cardiovascular illnesses, a thorough risk assessment is necessary for screening reasons. Many published studies relate the pregnancy complications and future cardiovascular disease (CVD) risk. Objective; Investigate the association between risk factors of the laboratory measures and adverse pregnancy outcomes (APOs) with level of cardiovascular disorders risk. Methods; Adult women were enrolled in a cross-sectional study, and they were divided into 2 groups according to whether they had a history of adverse pregnancy outcomes or not. Laboratory and clinical measurements were carried out, and The CVD risk was calculated according to Framingham risk score. Results; All women enrolled were over 40 years age, mostly obese, had predominantly A+ve and O+ve blood group phenotypes. As compared to the low risk category, women with a positive history of pregnancy-induced hypertension and preeclampsia were 7.5 times more likely to be in the intermediate group while those with a positive history of stillbirth were 17.2 times more likely to be in the high-risk group. Conclusion; With reference to the low risk category, a positive history of pregnancy-induced hypertension and preeclampsia was predictor for intermediate CVD risk, while a positive history of stillbirth was predictor for high CVD risk.

The ME-BYO index: A development and validation project of a novel comprehensive health index.

Quantifying health status and identifying modifiable factors are essential for effective and individualized prevention of age-related conditions and for promoting health during aging. The ME-BYO concept from Kanagawa Prefecture, one of Japan's largest prefectures, can be used to establish a healthy aging society. In disease etiology, ME-BYO considers the status of an individual's body and mind as changing continuously from healthy to sick instead of being a dichotomy between the two. ME-BYO conceptualizes the entire process of this change. The ME-BYO index was developed in 2019 to comprehensively and numerically measure and visualize an individual's current health status and future disease risk by quantifying data on the four domains of metabolic function, locomotor function, cognitive function, and mental resilience. The ME-BYO index has been implemented in the personal health management application "My ME-BYO." However, scientific validation of this index and the development of a practical application using healthcare data remain to be completed. In 2020, our research team started a project to refine the ME-BYO index using data from the Kanagawa ME-BYO prospective cohort study, which is a large population-based genomic cohort study. This project will scientifically evaluate the ME-BYO index and develop a practical application for promoting healthy aging.

Preeclampsia: Prevalence, Risk Factors, and Impact on Mother and Fetus

Objectives: Preeclampsia is one of the most common hypertensive disorders in pregnancy accounting for >50,000 maternal deaths, and over 500,000 fetal deaths worldwide. The incidence of preeclampsia is estimated to be 7 times higher in developing countries like India. Women with preeclampsia are several folds more likely to contract cardiovascular diseases such as ischemic heart disease, stroke, and thromboembolism later in life. This study aims to record the prevalence of preeclampsia, examine the incidence of various associated risk factors and document, and analyze the effects preeclampsia has on the mother and fetus. Materials and Methods: A cross-sectional study was conducted. Five hundred pregnant women were randomly selected based on availability of medical records. Prevalence of preeclampsia was identified in them and the preeclamptic population was further studied for various risk factors and epidemiological factors. The impact on mother and fetus was also studied. The data obtained from the medical records were entered into MS excel and variables were expressed as frequency and proportions. Analysis was done on SPSS 26.0 and major data were subjected to Chi-square test for determining significance. Results: Out of a total of 500 pregnant women, 31 developed preeclampsia; hence, the prevalence of preeclampsia was found to be 6.2%. Of the 31 preeclamptic women, majority belonged to the 20–29 age group (51.6%), 19 (61.2%) had a pre-pregnancy body mass index >23, thus being classified as overweight or obese. Thirteen of these 19 (41.9%) were obese class 1, while 5 (16.1%) were obese class 2. Only two patients were multiparous, while nulliparous and primiparous women accounted for 48.38 and 45.16% of preeclamptic women. Twenty of the 31 women had preeclampsia with severe features and this was found to be significantly associated with delivering a baby having lower birth weight (P < 0.05). A significant 45.1% (14 of the 31 women) had to undergo preterm delivery and 48.38% of the preeclamptic women terminated pregnancy by a lower segment cesarean section. Two of the women were also diagnosed with elevated liver enzymes and low platelets syndrome. With respect to the fetal outcomes, 48.4% of infants had low birth weight. Intrauterine fetal death, fetal growth restriction, and cleft lip and palate were also documented in few neonates. Conclusion: Preeclampsia has a high morbidity and mortality rate as well as an increased risk for future cardiovascular diseases. Hence, risk factors which are in an individual’s self-control such as weight must be modified to prevent unfavorable complications. Pregnant women at risk of preeclampsia should be identified and high-quality antenatal care should be given to minimize the complications of preeclampsia both for the mother and the fetus. More research avenues must be explored on this subject so that enhanced treatment and management options can emerge.

The SGLT2 inhibitor, empagliflozin reduces early progressive proteinuria in obese SS rats

Childhood/prepubertal obesity (PPO) is a world-wide epidemic and is considered a risk factor for renal injury. Therefore, there is a need to control this trend to decrease the future risk of chronic kidney disease. Recently, we reported that the SS LepR mutant rat is a novel model to study the mechanisms of renal injury associated with PPO. The SS LepR mutant rat develops progressive renal injury in the absence of hyperglycemia before puberty. SGLT2 inhibitors have been demonstrated to exert renoprotective effects independent of lowering blood glucose. Therefore, the objective of this study was to determine the effects of SGLT2 blockade with empagliflozin on the early progression of proteinuria in SS LepR mutant rats, during PPO. Four-week-old SS and SS LepR mutant rats (n = 5/group) were either treated with vehicle (diet) or empagliflozin (30 mg/kg/day, orally) for four weeks. While the SS LepR mutant rats had significantly higher body weights vs SS rats, there were no detectable differences in body weight or blood glucose levels in response to empagliflozin treatment in SS LepR mutant rats. We observed a significant increase in plasma insulin in control SS LepR mutant rats vs SS rats (7±1 vs 1±0.3 ng/mL, respectively, p<0.05), and treatment with empagliflozin did not have any effect on plasma insulin in SS LepR mutant rats (8±2 ng/mL). At baseline, we did not observe any significant difference in urine flow rate between control SS LepR mutant vs SS rats. After two weeks of treatment, while there was no observed difference in urine flow rate between SS LepR mutant and SS rats (17±3 ml/day vs 18±2 ml/day, respectively), empagliflozin significantly increased urine flow rate in SS LepR mutant rats (29±4 ml/day, p<0.05), but not in SS rats (17±3 ml/day). At baseline, we observed a difference in proteinuria between control SS LepR mutant vs SS rats (68±11 vs 6±3 mg/day, respectively, p<0.05), which remained elevated over the course of the study (471±75 vs 32±5 mg/day, respectively, p<0.05). Treatment with empagliflozin significantly decreased proteinuria in SS LepR mutant rats (223±52 mg/day, p<0.05) without affecting SS rats (27±8 mg/day). At the end of the study, we observed a significant increase in GFR in control SS LepR mutant rats vs SS rats (2.4±0.6 vs 0.5 mL/min/gkwt, respectively, p<0.05). Treatment with empagliflozin only significantly reduced GFR in SS LepR mutant rats (0.9±0.2 mL/min/gkwt, p<0.05). In conclusion, these data suggest that empagliflozin attenuates renal hyperfiltration and confers renoprotective effects during the early progression of renal disease associated with PPO. DK109133 and HL151407 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Influence of Hydration Status and Plasma Copeptin on Ambulatory Blood Pressure in Healthy Young Adults

BACKGROUND: Adequate hydration is essential for regulating various physiological systems and may influence blood pressure (BP). Hypohydration is linked with elevated copeptin (surrogate of arginine vasopressin), which is associated with elevated cardiovascular disease risk. However, there is limited information on the influence of hydration and copeptin on ambulatory BP measures in young adults. Therefore, we sought to investigate associations between hydration, copeptin, and ambulatory BP. METHODS: We studied 41 participants (19 M/22 F, 24 White/17 Black, age 21±1 years, body mass index 26±5 kg/m 2 , screening BP 111± 10/67±8 mmHg; Mean ± SD) who provided a 24-hour urine sample. We measured urine specific gravity (USG), urine osmolality (OSM), and plasma copeptin as biomarkers of hydration. We used ambulatory BP monitoring (Suntech Oscar2) to assess BP during daytime (1000-2000) and nighttime (0000-0600). Our primary outcomes were plasma copeptin (pmol/L) and night-to-day BP dip ratio (nighttime/daytime BP) in dehydrated (USG >1.020 or OSM >800 mOsm/kg) vs euhydrated participants. Statistical procedures included Student’s t-tests and Mann-Whitney U tests. We also used Spearman’s rho correlation (controlling for BMI, sex, and race). We set α at ≤0.05. RESULTS: Copeptin concentration was elevated in dehydrated compared with euhydrated participants (USG: 6.6±2.9 vs 4.3±2.0 pmol/L, p<0.005; OSM: 6.6±2.7 vs 4.1±2.0 pmol/L, p<0.001). After controlling for BMI, sex, and race, copeptin was associated with USG (rho=0.44, p=0.005) and OSM (rho=0.51, p=0.001). Systolic and diastolic BP dip ratios did not differ by hydration status for either USG or OSM ( ps>0.179). Additionally, adjusted BP dip ratios were not correlated with OSM or USG ( ps>0.149). Plasma copeptin was not associated with BP dip ratios ( ps>0.155) but was associated with absolute nocturnal systolic (rho=-0.34, p=0.036) and diastolic BP dip (rho=-0.33, p=0.041). When we split participants by low and high copeptin concentration (median split), higher copeptin was associated with a lower (i.e., worse) systolic BP dip ratio (0.87±0.06 vs 0.90±0.06, p=0.048) and lower absolute nocturnal systolic and diastolic BP dip ( ps<0.01). CONCLUSIONS: Hydration biomarkers were correlated with plasma copeptin, but not ambulatory BP. The significance of our findings are that higher copeptin was associated with blunted nocturnal BP dipping in younger adults, which could predispose them to increased future cardiovascular disease risk. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exposure of wild Caspian seals (Pusa caspica) to parasites, bacterial and viral pathogens, evaluated via molecular and serological assays

Disease surveillance of marine mammal populations is essential to understand the causes of strandings, identify potential threats to animal health, and to support development of conservation strategies. Here we report the first large multi-pathogen screening of prevalence for viruses, bacteria and parasites in a sample of 177 live, healthy, wild Caspian seals (Pusa caspica), captured and released during satellite telemetry studies 2007-2017. Employing molecular and serological assays we assess prevalence of pathogens known to be of significance for marine mammal health worldwide, and evaluate the results in relation to Caspian seal health and conservation. RT-PCR, and PCR assays find evidence for infection by Canine Distemper Virus (CDV), Phocine herpes virus, phocine adenovirus and Influenza A at prevalences of 5%, 6.4%, 21.7%, and 4% respectively. The genomes of CDV isolates collected in 2008 showed 99.59% identity with the 2000 Caspian seal CDV epizootic strain. A partial coding sequence for the Us2 gene from the Caspian seal herpes virus was identical to PhHV-1 isolate PB84, previously reported from a harbor seal (Phoca vitulina), while amplicon sequences for the adenovirus polymerase gene indicated a novel strain. ELISA assays detected exposure to Influenza A (55% of tested samples), adenovirus (25%), coronavirus (6%), CDV (8%), herpes virus (94%), Toxoplasma gondii (2.6%) and heartworm (1%). Hemagglutination inhibition (HI) tests detected exposure to Influenza B at a prevalence of 20%, and Leptospira microscopic agglutination tests detected suspected exposure to Leptospira serovars in 9% of tested samples. Overall, the risks, profile and prevalence of pathogens in Caspian seals appear comparable to other wild phocid seal populations. Our results suggest Caspian seals have exposure pathways to pathogens with epizootic potential or ability to cause significant morbidity, and that disease impacts could reduce the resilience of the population to other conservation threats. Caspian seals are listed as Endangered by the International Union for Conservation of Nature (IUCN), and we recommend that resources are invested to support further surveillance programs and to understand how anthropogenic pressures may influence future disease risks. A translated version of this abstract is available in Russian and Kazakh in the Supplementary Material (Presentation 1 and Presentation 2)

Circulating progranulin in human infants: relation to prenatal growth and early postnatal nutrition.

Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases. We longitudinally assessed PGRN concentrations in infants born appropriate (AGA) or small for gestational age (SGA), the latter being at risk for obesity and type 2 diabetes, especially if they experience an excessive postnatal catch-up in weight and are formula-fed (FF). The study population consisted of 183 infants who were exclusively breast-fed [(BF), AGA, n = 66; SGA, n = 40], or FF (AGA, n = 31; SGA, n = 46) over the first 4 months. Assessments included auxology, fasting glucose, insulin, IGF-1, high-molecular-weight adiponectin, PGRN and body composition (by DXA), at birth, and at age 4 and 12 months. PGRN levels were low at birth and unaffected by prenatal growth. PGRN increased at 4 and 12 months, although to a lesser extent in SGA infants, and was unrelated to the mode of feeding. PGRN correlated with markers of adiposity, inflammation and insulin resistance in both AGA and SGA infants, especially in those FF. The attenuated increase of PGRN levels in SGA infants over the first year of life, along with the association to markers of unhealthy metabolic profile, might point to a role of PGRN in future disease risks. Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases. In healthy infants, PGRN concentrations are low at birth and experience a significant and progressive increase up to age 12 months, which is less marked in infants born small for gestational age (SGA) and is unrelated to the mode of feeding. Circulating PGRN is related to markers of adiposity, inflammation, and insulin sensitivity, especially in formula-fed SGA infants. PGRN may play a role in the metabolic adaptations of SGA infants during early life, potentially contributing to the risk for obesity and type 2 diabetes in this population.

Insulin resistance is more frequent in type 1 diabetes patients with long disease duration.

To investigate the clinical status of insulin resistance (IR) and its correlation with disease duration in patients with type 1 diabetes (T1D). Cross-sectional data from a T1D cohort were obtained (n=923). IR-related metabolic disorders including hypertension, obesity, and dyslipidemia were used as outcome variables to explore the cut-off point for estimated glucose disposal rate (eGDR) by restricted cubic spline (RCS) curve. Regression models were used for multivariate analysis of the clinical factors associated with IR. The correlation between the status of IR and diabetes duration was depicted with the RCS curve. IR-related metabolic disorders were observed in 39.4% of patients, with 9.1% meeting the criteria for metabolic syndrome. Specifically, patients with ≥10years of T1D were more likely to have IR-related metabolic disorders (54.7% vs. 36.9%, p<0.05). The presence of IR, defined as an eGDR ≤9.0mg/kg/min, was observed in 42.2% of patients. Patients with IR had a longer diabetes duration (3.5 vs. 2.7, years, p=0.003) and higher insulin dose (0.5 vs. 0.4, units per kg per day, p<0.001). Moreover, the presence of IR showed a gradual increase during 10years' disease duration and further analysis showed that diabetes duration ≥10years was a key element behind the development of IR and IR-related metabolic disorders. The status of IR is common in T1D patients, especially in those with ≥10years of disease duration. Therapies targeting balancing glycaemic control and IR are needed to decrease the future risk of cardiovascular diseases in T1D. ClinicalTrials.gov NCT03610984 (cohort study of patients with type 1 diabetes).

Major clinical approaches to proper nutrition and lifestyle change during pregnancy: a systematic review

Having a healthy pregnancy with the birth of a healthy child is the goal of the entire process that involves this phase. Nutrology is important in this context to reduce the risk of future chronic diseases in the child and unfavorable outcomes for the pregnant woman and the fetus. Lifestyle change generates a positive impact on every phase of life in which it is carried out. But it is known that changes in parents at least 3 months before conception, during pregnancy, and breastfeeding are related to the improvement in the quality of gametes and the expression of healthy genes. Food consumption is increasingly far from ideal. There was an increase in the consumption of ultraprocessed foods and a decrease in natural foods. Thus, the recommended dietary intake is not achieved by a large part of the Brazilian population. Therefore, it is necessary to supplement mainly during pregnancy due to increased needs. Therefore, the present study carried out a concise systematic review to list the main clinical approaches to the effects of adequate nutrition and lifestyle changes in human pregnancy.

Polygenic score: An anchor holding the whole life course.

Polygenic score: An anchor holding the whole life course.

Preventing Adverse Cardiovascular Outcomes in Pregnancy Complicated by Obesity.

Obesity is a chronic disease that is becoming increasingly prevalent, and more individuals of reproductive age have obesity prior to becoming pregnant. Obesity in pregnancy is associated with short- and long-term adverse consequences for both the birthing person and their offspring which have been associated with increased long-term cardiovascular morbidity and mortality. The goal of this review is to discuss what is currently understood about the relationship between maternal obesity and adverse pregnancy outcomes (APOs), the association between APOs and future cardiovascular disease (CVD) risk, and what evidence-based interventions can be implemented to prevent adverse outcomes in this population. Maternal obesity has been associated with an increased risk of APOs such as gestational diabetes, hypertensive disorders of pregnancy, and preterm birth as well as an increased risk of future CVD, such as metabolic syndrome, chronic hypertension, coronary heart disease, and stroke. The impact of maternal obesity also extends beyond the pregnant individual to the offspring, increasing the risk of fetal, neonatal, and infant mortality, as well as of congenital malformations, prematurity, and long-term health problems such as insulin resistance and childhood obesity. Prevention guidelines are incorporating the increased risk of adverse outcomes from maternal obesity into formalized risk assessments to guide both prenatal and postpartum care. It is becoming evident that a multidisciplinary cardio-obstetrics team is an important part of providing comprehensive care for pregnant individuals with obesity and other cardiovascular risk factors, including preexisting CVD and a history of prior APOs. There remains a need for further studies to better understand the mechanisms underlying the relationship between maternal obesity and APOs, as well as the racial and ethnic disparities that have been noted in the prevalence of APOs and associated CVD risk and mortality. There is increasing awareness that obesity in pregnancy is associated with various short- and long-term adverse maternal and offspring outcomes. There are multiple screening and prevention strategies that may be implemented before, during, and after pregnancy to prevent these adverse outcomes.

Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

The prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated. To determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population. This cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti-beta-2 glycoprotein I [aβ2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023. Associations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons. Among the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aβ2GPI IgM (63 [2.6%]), and aβ2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aβ2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aβ2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aβ2GPI IgA negatively correlated with cholesterol efflux capacity (r = -0.055; P = .009) and positively correlated with circulating oxidized LDL (r = 0.055; P = .007). aβ2GPI IgA-positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. In this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aβ2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.

Proteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction.

Given the limited accuracy of clinically used risk scores such as the Systematic COronary Risk Evaluation 2 system and the Second Manifestations of ARTerial disease 2 risk scores, novel risk algorithms determining an individual's susceptibility of future incident or recurrent atherosclerotic cardiovascular disease (ASCVD) risk are urgently needed. Due to major improvements in assay techniques, multimarker proteomic and lipidomic panels hold the promise to be reliably assessed in a high-throughput routine. Novel machine learning-based approaches have facilitated the use of this high-dimensional data resulting from these analyses for ASCVD risk prediction. More than a dozen of large-scale retrospective studies using different sets of biomarkers and different statistical methods have consistently demonstrated the additive prognostic value of these panels over traditionally used clinical risk scores. Prospective studies are needed to determine the clinical utility of a biomarker panel in clinical ASCVD risk stratification. When combined with the genetic predisposition captured with polygenic risk scores and the actual ASCVD phenotype observed with coronary artery imaging, proteomics and lipidomics can advance understanding of the complex multifactorial causes underlying an individual's ASCVD risk.

Low carbohydrate high fat ketogenic diets on the exercise crossover point and glucose homeostasis.

In exercise science, the crossover effect denotes that fat oxidation is the primary fuel at rest and during low-intensity exercise with a shift towards an increased reliance on carbohydrate oxidation at moderate to high exercise intensities. This model makes four predictions: First, >50% of energy comes from carbohydrate oxidation at ≥60% of maximum oxygen consumption (VO2max), termed the crossover point. Second, each individual has a maximum fat oxidation capacity (FATMAX) at an exercise intensity lower than the crossover point. FATMAX values are typically 0.3-0.6g/min. Third, fat oxidation is minimized during exercise ≥85%VO2max, making carbohydrates the predominant energetic substrate during high-intensity exercise, especially at >85%VO2max. Fourth, high-carbohydrate low-fat (HCLF) diets will produce superior exercise performances via maximizing pre-exercise storage of this predominant exercise substrate. In a series of recent publications evaluating the metabolic and performance effects of low-carbohydrate high-fat (LCHF/ketogenic) diet adaptations during exercise of different intensities, we provide findings that challenge this model and these four predictions. First, we show that adaptation to the LCHF diet shifts the crossover point to a higher %VO2max (>80%VO2max) than previously reported. Second, substantially higher FATMAX values (>1.5g/min) can be measured in athletes adapted to the LCHF diet. Third, endurance athletes exercising at >85%VO2max, whilst performing 6 × 800m running intervals, measured the highest rates of fat oxidation yet reported in humans. Peak fat oxidation rates measured at 86.4 ± 6.2%VO2max were 1.58 ± 0.33g/min with 30% of subjects achieving >1.85g/min. These studies challenge the prevailing doctrine that carbohydrates are the predominant oxidized fuel during high-intensity exercise. We recently found that 30% of middle-aged competitive athletes presented with pre-diabetic glycemic values while on an HCLF diet, which was reversed on LCHF. We speculate that these rapid changes between diet, insulin, glucose homeostasis, and fat oxidation might be linked by diet-induced changes in mitochondrial function and insulin action. Together, we demonstrate evidence that challenges the current crossover concept and demonstrate evidence that a LCHF diet may also reverse features of pre-diabetes and future metabolic disease risk, demonstrating the impact of dietary choice has extended beyond physical performance even in athletic populations.

Snacktivity™ to promote physical activity and reduce future risk of disease in the population: protocol for a feasibility randomised controlled trial and nested qualitative study

BackgroundMany people do not regularly participate in physical activity, which may negatively impact their health. Current physical activity guidelines are focused on promoting weekly accumulation of at least 150 min of moderate to vigorous intensity physical activity (MVPA). Whilst revised guidance now recognises the importance of making small changes to physical activity behaviour, guidance still focuses on adults needing to achieve at least 150 min of MVPA per week. An alternative ‘whole day’ approach that could motivate the public to be more physically active, is a concept called Snacktivity™. Instead of focusing on achieving 150 min per week of physical activity, for example 30 min of MVPA over 5 days, Snacktivity™ encourages the public to achieve this through small, but frequent, 2–5 min ‘snacks’ of MVPA throughout the whole day.MethodsThe primary aim is to undertake a feasibility trial with nested qualitative interviews to assess the feasibility and acceptability of the Snacktivity™ intervention to inform the design of a subsequent phase III randomised trial. A two-arm randomised controlled feasibility trial aiming to recruit 80 inactive adults will be conducted. Recruitment will be from health and community settings and social media. Participants will be individually randomised (1:1 ratio) to receive either the Snacktivity™ intervention or usual care. The intervention will last 12 weeks with assessment of outcomes completed before and after the intervention in all participants. We are interested in whether the Snacktivity™ trial is appealing to participants (assessed by the recruitment rate) and if the Snacktivity™ intervention and trial methods are acceptable to participants (assessed by Snacktivity™/physical activity adherence and retention rates). The intervention will be delivered by health care providers within health care consultations or by researchers. Participants’ experiences of the trial and intervention, and health care providers’ views of delivering the intervention within health consultations will be explored.DiscussionThe development of physical activity interventions that can be delivered at scale are needed. The findings from this study will inform the viability and design of a phase III trial to assess the effectiveness and cost-effectiveness of Snacktivity™ to increase physical activity.Trial registrationISRCTN: 64851242.

Comparison of anthropometric parameters and laboratory test results before and after the COVID-19 outbreak among Chinese children aged 3-18 years.

To compare the physiological health of Chinese children around the COVID-19 lockdown. We extracted data on children's anthropometric and laboratory parameters from May to November in both 2019 and 2020 from the Health Checkup Center, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Overall, 2162 children aged 3~18 years without comorbidities in 2019 and 2646 in 2020 were assessed. Mann Whitney U tests were used to compare differences between the above health indicators before and after COVID-19 outbreak. Quantile regression analyses adjusted for age, sex and body mass index (BMI) were also used in analysis. Chi-square tests and Fisher's exact tests were used for comparing differences of categorical variables. Compared with children examined in 2019 before the outbreak, children in 2020 had a higher median z score of BMI for age (-0.16 vs. -0.31), total cholesterol (TC, 4.34 vs. 4.16 mmol/L), low density lipoprotein cholesterol (LDL-C, 2.48 vs. 2.15 mmol/L), high density lipoprotein cholesterol (HDL-C, 1.45 vs. 1.43 mmol/L) and serum uric acid (290 vs. 282 μmol/L), and a lower hemoglobin (Hb, 134 vs. 133 g/L), triglycerides (TG, 0.70 vs. 0.78 mmol/L) and 25(OH)D (45.8 vs. 52.2 nmol/L), all P < 0.05. No differences were identified for waist height ratio, blood pressure and fasting glucose (both P > 0.05). However, in regression models after adjusting, BMI, TC, LDL-C, blood glucose and sUA were positively correlated with year; while Hb, TG and 25(OH)D were negatively correlated with year (all P < 0.05). Accordingly, children in 2020 had a higher prevalence of overweight/obesity (20.6 vs. 16.7%, P < 0.001), hypercholesterol (16.2%vs. 10.2%, P < 0.001), high LDL-C (10 vs. 2.9%, P < 0.001), hyperuricemia (18.9 vs.15.1%, P = 0.002), vitamin D deficiency (22.6 vs. 8.1%, P < 0.001) and a lower prevalence of high TG (4.3 vs. 2.8%, P = 0.018) compared with children in 2019. In this real-world study, we found that long-term lockdown due to COVID-19 outbreak might cause adverse impact on children's metabolic health, which might increase their future risk of cardiovascular diseases. Thus, parents, health professionals, educationists, and caregivers should pay more attention to children's dietary pattern and lifestyle, especially in this new normal against COVID-19.

Patient Perspectives on a Pilot Virtual Follow-up Program After Hypertensive Disorders of Pregnancy: A Qualitative Study

BackgroundHypertensive disorders of pregnancy (HDPs) are a risk factor for future cardiovascular disease; therefore, follow-up and implementation of early interventions is recommended. We performed a qualitative study to assess the feasibility and user response to a mobile-health tool and virtual consultation aimed at educating people with an HDP on future cardiovascular risk, and at better understanding patients’ priorities for postpartum care. MethodsParticipants with a history of an HDP in the past 5 years had access to an online educational tool and participated in a virtual consultation to discuss their cardiovascular risks after experiencing an HDP. Participants were invited to a focus group to obtain feedback on their postpartum experience and the Her-HEART program. ResultsA total of 20 female participants were enrolled in the study between January 2020 and February 2021. Of these, 16 participants took part in 1 of 5 focus groups. Participants reported a lack of awareness of future cardiovascular disease risks prior to participating in the program, and identified barriers to counselling, including traumatic birth experiences, inappropriate timing, and competing priorities. Participants reported that the virtual Her-HEART program was an effective avenue to provide counselling on long-term cardiovascular risks. They highlighted the importance of coordinated care pathways and mental health support in postpartum follow-up programs. ConclusionWe have shown the feasibility of providing an educational website and virtual consultation to facilitate counselling in people affected by HDPs. Our results shed light on patient-reported priorities related to the content and delivery of postpartum counselling after an HDP.

Temporal relationship between hyperuricemia and hypertension and its impact on future risk of cardiovascular disease

BackgroundAlthough hyperuricemia and hypertension are significantly correlated, their temporal relationship and whether this relationship is associated with risk of cardiovascular disease (CVD) are largely unknown. This study aimed to examine temporal relationship between hyperuricemia and hypertension, and its association with future risk of CVD. MethodsThis study included 60,285 participants from the Kailuan study. Measurement of serum uric acid (SUA), systolic and diastolic blood pressure (SBP and DBP) were obtained twice at 2006 (baseline) and 2010. Cross-lagged and mediation analysis were used to examine the temporal relationship between hyperuricemia and hypertension, and the association of this temporal relationship with CVD events risk after 2010. ResultsAfter adjusting for covariates, the cross-lagged path coefficients (β1) from baseline SUA to follow-up SBP and DBP were significantly greatly than path coefficients (β2) from baseline SBP and DBP to follow-up SUA (β1=0.041 versus β2=0.003; Pdifference<0.0001 for SBP; β1=0.040 versus β2=0.000; Pdifference<0.0001 for DBP). The path coefficients from baseline SUA to follow-up SBP and DBP in group with incident CVD were significantly greatly than that in group without incident CVD (Pdifference of β1 in the two groups was 0.0018 for SBP and 0.0340 for DBP). Furthermore, SBP and DBP partially mediated the effect of SUA on incident CVD, the mediation effect was 57.64% for SBP and 46.27% for DBP. Similar mediated results were observed for stroke and myocardial infarction. ConclusionIncreased SUA levels probably precede elevated BP, and BP partially mediates the pathway from SUA to incident CVD.

Perimenopause and/or menopause help-seeking among women from ethnic minorities: a qualitative study of primary care practitioners' experiences.

Each woman's experience of the perimenopause and/or menopause is individual and unique. Research shows women from ethnic minorities often have different experiences from their White peers, and these are not being considered in conversations about the menopause. Women from ethnic minorities already face barriers to help-seeking in primary care, and clinicians have expressed challenges in cross cultural communication including the risk that women from ethnic minorities' perimenopause and/or menopause health needs are not being met. To explore primary care practitioners' experiences of perimenopause and/or menopause help-seeking among women from ethnic minorities. A qualitative study of 46 primary care practitioners from 35 practices across 5 regions of England, with patient and public involvement (PPI) consultations with 14 women from three ethnic minority groups. Primary care practitioners were surveyed using an exploratory approach. Online and telephone interviews were conducted and the data were analysed thematically. The findings were presented to three groups of women from ethnic minorities to inform interpretation of the data. Practitioners described a lack of awareness of perimenopause and/or menopause among many women from ethnic minorities, which they felt impacted their help-seeking and communication of symptoms. Cultural expressions of embodied experiences could offer challenges to practitioners to 'join the dots' and interpret experiences through a holistic menopause care lens. Feedback from the women from ethnic minorities provided context to practitioner findings through examples from their individual experiences. There is a need for increased awareness and trustworthy information resources to help women from ethnic minorities prepare for the menopause, and clinicians to recognise their experiences and offer support. This could improve women's immediate quality of life and potentially reduce future disease risk.