Chronic Cardiometabolic Diseases Research Articles

Non-alcoholic fatty liver disease: a multi-system disease influenced by ageing and sex, and affected by adipose tissue and intestinal function.

In recent years, a wealth of factors are associated with increased risk of developing non-alcoholic fatty liver disease (NAFLD) and NAFLD is now thought to increase the risk of multiple extra-hepatic diseases. The aim of this review is first to focus on the role of ageing and sex as key, poorly understood risk factors in the development and progression of NAFLD. Secondly, we aim to discuss the roles of white adipose tissue (WAT) and intestinal dysfunction, as producers of extra-hepatic factors known to further contribute to the pathogenesis of NAFLD. Finally, we aim to summarise the role of NAFLD as a multi-system disease affecting other organ systems beyond the liver. Both increased age and male sex increase the risk of NAFLD and this may be partly driven by alterations in the distribution and function of WAT. Similarly, changes in gut microbiota composition and intestinal function with ageing and chronic overnutrition are likely to contribute to the development of NAFLD both directly (i.e. by affecting hepatic function) and indirectly via exacerbating WAT dysfunction. Consequently, the presence of NAFLD significantly increases the risk of various extra-hepatic diseases including CVD, type 2 diabetes mellitus, chronic kidney disease and certain extra-hepatic cancers. Thus changes in WAT and intestinal function with ageing and chronic overnutrition contribute to the development of NAFLD - a multi-system disease that subsequently contributes to the development of other chronic cardiometabolic diseases.

Network Support and Negative Life Events Associated With Chronic Cardiometabolic Disease Outcomes

Stress from negative life events may be an important risk factor for chronic cardiometabolic conditions, which are increasingly prevalent among young adults. Support from personal networks is known to buffer stress from negative life events. Yet, evidence for these relationships among both young and older adults remains unclear. Longitudinal data came from the University of California, Berkeley Social Networks Study (2015-2018), which followed young (aged 21-30 years) and late middle-aged (aged 50-70 years) adults over 4 years. Weighted hybrid fixed and random effects models (completed in 2020) were used to examine the causal relationships among 4 negative life events, distinct forms of network support (e.g., social companionship, emergency help), and self-reported chronic cardiometabolic disease outcomes (i.e., hypertension, diabetes, or a heart condition). Among young adults, both the death of a close tie (average marginal effect=0.10, p<0.001) and financial difficulties (average marginal effect=0.07, p<0.05) were associated with a higher probability of chronic cardiometabolic outcomes. Higher numbers of confidants (average marginal effect= -0.03, p<0.01) and practical helpers (average marginal effect= -0.02, p<0.01) were associated with a lower probability of chronic cardiometabolic outcomes, whereas higher numbers of social companions were associated with a higher probability of having chronic cardiometabolic outcomes among young adults (average marginal effect=0.02, p<0.01). Negative life events may be important risk factors for chronic cardiometabolic disease outcomes, particularly among young adults. Although there is no evidence of network support mediating the effects of negative life events, increases in network support were directly associated with chronic cardiometabolic outcomes.

Subjective social isolation or loneliness in older adults residing in social housing in Ontario: a cross-sectional study.

Background:Older adults face greater risk of social isolation, but the extent of social isolation among low-income older adults living in social housing is unknown. This study aims to explore the rate of, and risk factors contributing to, subjective social isolation or loneliness among older adults in social housing.Methods:We conducted a cross-sectional study of data collected from a community program held in the common rooms of 55 social housing buildings in 14 communities across Ontario, Canada, from May 2018 to April 2019. Participants were program attendees aged 55 years and older who resided in the buildings. Program implementers assessed social isolation using the 3-Item Loneliness Scale from the University of California, Los Angeles and risk factors using common primary care screening tools. We extracted data for this study from the program database. We compared the rate of social isolation to Canadian Community Health Survey data using a 1-sample χ2 test, and evaluated associations between risk factors and social isolation using univariate and multivariate logistic regressions.Results:We included 806 residents in 30 buildings for older adults and 25 mixed-tenant buildings. Based on the 3-Item UCLA Loneliness Scale, 161 (20.0%) of the 806 participants were socially isolated. For those aged 65 and older, the rate of social isolation was nearly twice that observed in the same age group of the general population (36.1% v. 19.6%; p < 0.001). Risk factors were age (65–84 yr v. 55–64 yr adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01–3.93), alcohol consumption (adjusted OR 2.45, 95% CI 1.09–5.54), anxiety or depression (adjusted OR 6.05, 95% CI 3.65–10.03) and income insecurity (adjusted OR 2.10, 95% CI 1.24–3.53). Protective factors were having at least 1 chronic cardiometabolic disease (adjusted OR 0.44, 95% CI 0.24–0.80), being physically active (adjusted OR 0.47, 95% CI 0.30–0.73) and having good to excellent general health (adjusted OR 0.60, 95% CI 0.39–0.90).Interpretation:The high rate of social isolation in low-income older adults living in social housing compared with the general population is concerning. Structural barriers could prevent engagement in social activities or maintenance of social support, especially for older adults with income insecurity and anxiety or depression; interventions are needed to reduce subjective social isolation in this population.

Body mass index and severity/fatality from coronavirus disease 2019: A nationwide epidemiological study in Korea.

Obesity has been reported as a risk factor for severe coronavirus disease 2019 (COVID-19) in recent studies. However, the relationship between body mass index (BMI) and COVID-19 severity and fatality are unclear. This study included 4,141 COVID-19 patients who were released from isolation or had died as of April 30, 2020. This nationwide data was provided by the Korean Centers for Disease Control and Prevention Agency. BMI was categorized as follows; < 18.5 kg/m2, 18.5-22.9 kg/m2, 23.0-24.9 kg/m2, 25.0-29.9 kg/m2, and ≥ 30 kg/m2. We defined a fatal illness if the patient had died. Among participants, those with a BMI of 18.5-22.9 kg/m2 were the most common (42.0%), followed by 25.0-29.9 kg/m2 (24.4%), 23.0-24.9 kg/m2 (24.3%), ≥ 30 kg/m2 (4.7%), and < 18.5 kg/m2 (4.6%). In addition, 1,654 (41.2%) were men and 3.04% were fatalities. Multivariable analysis showed that age, male sex, BMI < 18.5 kg/m2, BMI ≥ 25 kg/m2, diabetes mellitus, chronic kidney disease, cancer, and dementia were independent risk factors for fatal illness. In particular, BMI < 18.5 kg/m2 (odds ratio [OR] 3.97, 95% CI 1.77-8.92), 25.0-29.9 kg/m2 (2.43, 1.32-4.47), and ≥ 30 kg/m2 (4.32, 1.37-13.61) were found to have higher ORs than the BMI of 23.0-24.9 kg/m2 (reference). There was no significant difference between those with a BMI of 18.5-22.9 kg/m2 (1.59, 0.88-2.89) and 23.0-24.9 kg/m2. This study demonstrated a non-linear (U-shaped) relationship between BMI and fatal illness. Subjects with a BMI of < 18.5 kg/m2 and those with a BMI ≥ 25 kg/m2 had a high risk of fatal illness. Maintaining a healthy weight is important not only to prevent chronic cardiometabolic diseases, but also to improve the outcome of COVID-19.

Neighbourhood characteristics as a predictor of adherence to dietary recommendations: A population-based cohort study of Finnish adults.

Aims: To investigate the association of six-year cumulative level of socioeconomic neighbourhood disadvantage and population density with subsequent adherence to dietary recommendations, controlling for preceding dietary adherence, in adults in Finland. Methods: Population-based Health and Social Support (HeSSup) study participants from four age groups (20–24, 30–34, 40–44 and 50–54 years at baseline in 1998). Data on diet and alcohol consumption were obtained from the 2003 and 2012 surveys and information on neighbourhoods from Statistics Finland Grid database (n = 10,414 men and women). Participants diet was measured as adherence to Nordic Nutrition recommendation (score range 0–100). Neighbourhood disadvantage was measured by median household income, proportion of those with primary education only and unemployment rate, and population density by the number of adult population between years 2007 and 2012. Linear models were used to assess the associations of neighbourhood characteristics with the score for adherence to dietary recommendations in 2012. Results: Cumulative neighbourhood socioeconomic disadvantage was associated with slightly weaker (1.49 (95% confidence interval (CI) −1.89 to −1.09) point decrease in dietary score) adherence while higher population density was associated with better (0.70 (95% CI 0.38−1.01) point increase in dietary score) adherence to dietary recommendations. These associations remained after controlling for prior dietary habits, sociodemographic, chronic cardio-metabolic diseases, and severe life events. Conclusions: These longitudinal findings support the hypothesis that neighbourhood characteristics affect dietary habits.

Abstract 14607: Randomized Controlled Trial of Once-Per-Week Intermittent Fasting for the Reduction of Low-Density Lipoprotein Cholesterol

Introduction: High-frequency intermittent fasting (IF) diets reduce weight similarly to continuous calorie restriction (CR). In patients with type 2 diabetes, twice-weekly IF and CR equivalently reduced HbA1c. IF may improve chronic disease risk factors, but no controlled trial has evaluated whether IF reduces low-density lipoprotein cholesterol (LDL-C), regardless of weight loss, in patients with elevated LDL-C. Hypothesis: The Weekly ONe-Day watER-only Fasting interventionaL (WONDERFUL) randomized (1:1) controlled trial (NCT02770313) tested whether IF reduced LDL-C compared to ad libitum control over 6 months. Methods: Subjects (N=103) were ages 21-70 years, not taking a statin, had elevated baseline LDL-C (90-189 mg/dL for ages 21-39, 90-159 mg/dL for ages 40-70, ≥90 mg/dL for statin intolerant/contraindicated), and had diet-controlled type 2 diabetes or ≥1 metabolic syndrome feature but no anti-diabetes medication. The water-only IF regimen was 4 weeks of 2/week 24-hour IF followed by 22 weeks of 1/week 24-hour IF. Exclusions included pregnant, lactating, or chronic disease (e.g., CAD, MI, stroke/TIA, CKD, COPD, cancer, PE, PAD, DVT, dementia, type 1 diabetes). Results: At baseline, IF (n=50) and control (n=53) were, respectively, 49.3±12.0 and 47.0±9.8 years of age, 66.0% and 67.9% females, weight 103±24 and 100±21 kg, and LDL-C 124±19 and 128±20 mg/dL. Lost to follow-up (n=5 IF, n=4 control) and withdrawals (n=7 IF, n=16 control) gave a final sample of n=71 (n=38 IF, n=33 control). LDL-C change from baseline to 6 months was not different between IF and control (Table). HOMA-IR, one of 4 pre-specified secondary endpoints, was improved (-0.75 vs. -0.10) at p≤0.01 vs. control (Table). Conclusions: A once-per-week IF regimen did not reduce LDL-C compared to control, but HOMA-IR was significantly reduced. This more sustainable IF regimen may reduce some chronic cardiometabolic disease risks (e.g., HOMA-IR) with minimal effects on cholesterol and weight.

Association between relative hand-grip strength and chronic cardiometabolic and musculoskeletal diseases in Koreans: A cross-sectional study

ObjectivesThis study evaluated clinical and cardiometabolic markers associated with relative hand-grip strength (HGS), and investigated odds ratios (ORs) for chronic cardiometabolic and musculoskeletal diseases according to relative HGS. MethodsThis cross-sectional observational study enrolled subjects from the Korea National Health and Nutrition Examination Survey who were 50 years and older (N = 2451). Information on chronic diseases was taken by individual surveys and other proper criteria were applied for undiagnosed subjects. Absolute HGS was calculated from the maximal bilateral HGS (kg) as measured by a dynamometer and relative HGS was calculated by dividing absolute HGS by body mass index (BMI). Associated clinical and cardiometabolic markers to relative HGS were investigated and ORs for chronic diseases according to relative HGS tertiles were estimated from multivariate linear or logistic regression analyses. ResultsThe mean relative HGS (kg/BMI) was 3.1 ± 0.6 for men and 1.9 ± 0.5 for women. Insulin-resistance parameters and high-sensitivity C-reactive protein were negatively and high-density lipoprotein cholesterol was positively related with relative HGS in both sexes adjusting for age and lifestyle factors, while systolic blood pressure showed negative relationship in women. High ORs for various chronic diseases were observed in the lowest relative HGS tertile of both sexes, but high OR for hyperlipidemia was observed only in women. ConclusionsRelative HGS is a convenient measure for overall muscle strength according to body size and may have an influence on chronic disease development or aggravation. Thus, relative HGS might be a cost-effective and useful tool to screen for prevalent chronic diseases in elderly population.

Improving Engagement Among Patients With Chronic Cardiometabolic Conditions Using mHealth: Critical Review of Reviews.

BackgroundThe burden imposed by cardiometabolic diseases remains a principal health care system concern. Integration of mobile health (mHealth) interventions is helpful for telemonitoring of these patients, which enables patients to be more active and take part in their treatment, while being more conscious and gaining more control over the outcomes. However, little is known about the degree to which users engage, and the extent to which this interaction matches the usage pattern for which mHealth interventions were designed.ObjectiveThe aim of this study was to describe the characteristics and results of studies on mHealth solutions that measured the effects of interventions with patient engagement in the context of chronic cardiometabolic diseases.MethodsA critical review of systematic reviews was conducted to recover data on interventions focused on the engagement of patients with chronic cardiometabolic diseases using mHealth technologies. Articles (from January 1, 2010) were searched in the Medlars Online International Literature Medline (Medline/Pubmed), Embase, Cochrane Library, PsycINFO, and Scielo databases. Only studies that quantified a measure of engagement by patients with cardiometabolic disease were included for analysis. The Critical Appraisal Skills Programme (CASP) was used to determine included studies considering the quality of the data provided. The Scottish Intercollegiate Guidelines Network (SIGN) checklist was used to assess the quality of the evidence according to the methodology used in the studies reviewed. Engagement was defined as the level of patient implication or participation in self-care interventions. Engagement measures included number of logs to the website or platform, frequency of usage, number of messages exchanged, and number of tasks completed.ResultsInitially, 638 papers were retrieved after applying the inclusion and exclusion criteria. Finally, only three systematic reviews measuring engagement were included in the analysis. No reviews applying a meta-analysis approach were found. The three review articles described the results of 10 clinical trials and feasibility studies that quantified engagement and met the inclusion criteria assessed through CASP. The sample size varied between 6 and 270 individuals, who were predominantly men. Cardiac disease was the principal target in the comparison of traditional and mHealth interventions for engagement improvement. The level of patient engagement with mHealth technologies varied between 50% and 97%, and technologies incorporating smartphones with a reminder function resulted in the highest level of engagement.ConclusionsmHealth interventions are an effective solution for improving engagement of patients with chronic cardiometabolic diseases. However, there is a need for advanced analysis and higher-quality studies focused on long-term engagement with specific interventions. The use of smartphones with a single app that includes a reminder function appears to result in better improvement in active participation, leading to higher engagement among patients with cardiometabolic diseases.

Cardiometabolic Diseases: Biochemistry, Pathophysiology and Medical Innovations

It gives us great pleasure, to write this invited overview on, Biochemistry, pathophysiology and Medical Innovations, to the Journal of Biochemistry and Modern Applications. In an earlier article on a similar topic, we described a biochemistry course, that is offered at the Cambridge University UK, called The Molecules in Medical Science, which focuses on diseases, that are familiar by name and of high relevance like diabetes and cancer. Harvard Medical School, on the other hand, says, preparation of medical school in the 21st century, should reflect contemporary developments in medical knowledge, the pace of discovery and the permeation of biochemistry, cell biology, and genetics into most areas of medicine. Oxford Royale Academy looks at biomedicine the following way; -Biochemistry, as the name suggests, is where Biology meets Chemistry: it is the study of the living things, at a molecular level- or, to put it another way, the study of the very foundations of life. On the other hand, pathophysiology deals with a variety of altered metabolism, which drives the normal physiology out of gear, and promotes the development of risks, for various metabolic diseases. The Cardiometabolic Syndrome represents a constellation of metabolic abnormalities that are risk factors for the development of metabolic diseases, which in turn promote vascular diseases. Major metabolic diseases include hypertension, excess weight, obesity, and type-2 diabetes. Vascular diseases remain the number one killer worldwide and have retained this status for over a century. There is considerable debate, about whether the treatment of the disease itself is superior, or just the management of observed risks is enough? In view of such debates, there is a great need for the development of technologies that will facilitate early diagnosis and better management of progression, or regression of diseases. Furthermore, advances in research in the fields of genetics, cellular biology, molecular biology, and emerging diagnostic tools, will improve our ability to manage chronic cardiometabolic diseases. In this overview, we have discussed advances in the various fields, the disconnect that exists between the researchers and clinicians, as well as between technologists and the end-users.

Adolescent Obesity: Diet Quality, Psychosocial Health, and Cardiometabolic Risk Factors.

Obesity is a multifaceted chronic condition with several contributing causes, including biological risk factors, socioeconomic status, health literacy, and numerous environmental influences. Of particular concern are the increasing rates of obesity in children and adolescents, as rates of obesity in youth in the United States have tripled within the last three decades. Youth from historically disadvantaged backgrounds tend to have higher rates of obesity compared to other groups. Adolescents often do not meet intake recommendations for certain food groups and nutrients, which may contribute to a heightened risk of obesity. With obesity disproportionately affecting adolescents (ages 12–19 years), negative effects of excess adiposity may be particularly salient during this critical period of development. The presentation of chronic cardiometabolic disease symptoms typically observed in adults, such as hypertension, hyperglycemia, dyslipidemia, and inflammation, are becoming increasingly common in adolescents with obesity. Additionally, there is dynamic interplay between obesity and psychosocial health, as adolescents with obesity may have increased levels of stress, depressive symptoms, and reduced resilience. To reduce and prevent adolescent obesity, the implementation of theory-driven multicomponent school- and community-based interventions have been suggested. These interventions promote knowledge and self-efficacy for healthful practices that have the potential to progress to sustained behavior change.

Wearable Technology and Physical Activity Behavior Change in Adults With Chronic Cardiometabolic Disease: A Systematic Review and Meta-Analysis.

To evaluate the effectiveness of wearable device interventions (eg, Fitbit) to improve physical activity (PA) outcomes (eg, steps/day, moderate to vigorous physical activity [MVPA]) in populations diagnosed with cardiometabolic chronic disease. Based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses, an electronic search of 5 databases (Medline, PsychINFO, Scopus, Web of Science, and PubMed) was conducted. Randomized controlled trials (RCTs) published between January 2000 and May 2018 that used a wearable device for the full intervention in adults (18+) diagnosed with a cardiometabolic chronic disease were included. Excluded trials included studies that used devices at pre-post only, devices that administered medication, and interventions with no prospective control group comparison. Thirty-five studies examining 4528 participants met the inclusion criteria. Study quality and RCT risk of bias were assessed using the Cochrane Collaboration Tool. Meta-analyses to compute PA (eg, steps/day) and selected physical dispersion and summary effects were conducted using the raw unstandardized pooled mean difference (MD). Sensitivity analyses were examined. Statistically significant increases in PA steps/day (MD = 2592 steps/day; 95% confidence interval [CI]: 1689-3496) and MVPA min/wk (MD = 36.31 min/wk; 95% CI: 18.33-54.29) were found for the intervention condition. Wearable devices positively impact physical health in clinical populations with cardiometabolic diseases. Future research using the most current technologies (eg, Fitbit) will serve to amplify these findings.

The Complex Interplay between Lipids, Immune System and Interleukins in Cardio-Metabolic Diseases.

Lipids and inflammation regulate each other. Early studies on this topic focused on the systemic effects that the acute inflammatory response—and interleukins—had on lipid metabolism. Today, in the era of the obesity epidemic, whose primary complications are cardio-metabolic diseases, attention has moved to the effects that the nutritional environment and lipid derangements have on peripheral tissues, where lipotoxicity leads to organ damage through an imbalance of chronic inflammatory responses. After an overview of the effects that acute inflammation has on the systemic lipid metabolism, this review will describe the lipid-induced immune responses that take place in peripheral tissues and lead to chronic cardio-metabolic diseases. Moreover, the anti-inflammatory effects of lipid lowering drugs, as well as the possibility of using anti-inflammatory agents against cardio-metabolic diseases, will be discussed.

Health status of children conceived by assisted reproductive technologies: endocrinologist’s position

Assisted reproductive technologies (ART) are currently widely used around the world because of the increased prevalence of infertility (presently, about 15% of married couples suffer from infertility), as well as the increased access to treatment and public funding for this method. Hence, the number of children conceived by ART is steadily increasing every year.&#x0D; This review focuses on the pressing problem of the health status of children conceived by assisted reproductive technologies (ART) by analyzing modern publications on the state of physical, gonadal and psychosomatic development, features of the endocrine system and cardiometabolic diseases, the risk of imprinting changes, congenital malformations and oncological disorders.&#x0D; The data presented that there is no increased risk of childhood cancer or deterioration in quality of life. However, it is expected that the cardiovascular and metabolic risk factors found in childhood can worsen in later life and may ultimately be responsible for chronic cardiometabolic disease. Furthermore, the issue of fertility, especially in the male population conceived by ART, remains open, thus requiring additional longer-term research.

Let thy food be thy medicine….when possible

There is no evidence that Hippocrates, although being credited for it, ever literally stated ‘let thy food be thy medicine and thy medicine be thy food’. However, yet in line with Hippocrates’ philosophy, we are currently witnessing a reappraisal of the complementarity of nutrition and pharmacology. Recent studies not only underline the therapeutic potential of lifestyle interventions, but are also generating valuable insights in the complex and dynamic transition from health to disease. Next to this, nutritional biology can significantly contribute to the discovery of new molecular targets. It is clear that most of the current top-selling drugs used in chronic cardio-metabolic diseases modulate relatively late-stage complications, which generally indicate already longer existing homeostatic imbalances. Pharmacologists are increasingly aware that typical multifactorial disorders require subtle, multiple target pharmacological approaches, instead of the still often dominating ‘one disease - one target - one drug’ paradigm. This review discusses the recent developments in the pharma-nutrition interface and shows some relevant mechanisms, including receptors and other targets, and examples from clinical practice. The latter includes inflammatory diseases and progressive loss of muscle function. The examples also illustrate the potential of targeted combinations of medicines with nutrition and (or) other life-style interventions, to increase treatment efficacy and (or) reduce adverse effects. More attention to a potentially negative outcome of drug-food combinations is also required, as shown by the example of food-drug interactions. Together, the developments at the food-pharma interface underline the demand for intensified collaboration between the disciplines, in the clinic and in science.

External Validation of a Tool Predicting 7-Year Risk of Developing Cardiovascular Disease, Type 2 Diabetes or Chronic Kidney Disease

BackgroundChronic cardiometabolic diseases, including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD), share many modifiable risk factors and can be prevented using combined prevention programs. Valid risk prediction tools are needed to accurately identify individuals at risk.ObjectiveWe aimed to validate a previously developed non-invasive risk prediction tool for predicting the combined 7-year-risk for chronic cardiometabolic diseases.DesignThe previously developed tool is stratified for sex and contains the predictors age, BMI, waist circumference, use of antihypertensives, smoking, family history of myocardial infarction/stroke, and family history of diabetes. This tool was externally validated, evaluating model performance using area under the receiver operating characteristic curve (AUC)—assessing discrimination—and Hosmer–Lemeshow goodness-of-fit (HL) statistics—assessing calibration. The intercept was recalibrated to improve calibration performance.ParticipantsThe risk prediction tool was validated in 3544 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab).Key ResultsDiscrimination was acceptable, with an AUC of 0.78 (95% CI 0.75–0.81) in men and 0.78 (95% CI 0.74–0.81) in women. Calibration was poor (HL statistic: p < 0.001), but improved considerably after intercept recalibration. Examination of individual outcomes showed that in men, AUC was highest for CKD (0.85 [95% CI 0.78–0.91]) and lowest for T2D (0.69 [95% CI 0.65–0.74]). In women, AUC was highest for CVD (0.88 [95% CI 0.83–0.94)]) and lowest for T2D (0.71 [95% CI 0.66–0.75]).ConclusionsValidation of our previously developed tool showed robust discriminative performance across populations. Model recalibration is recommended to account for different disease rates. Our risk prediction tool can be useful in large-scale prevention programs for identifying those in need of further risk profiling because of their increased risk for chronic cardiometabolic diseases.

Assessing Microvascular Function in Humans from a Chronic Disease Perspective

Microvascular dysfunction (MVD) is considered a crucial pathway in the development and progression of cardiometabolic and renal disease and is associated with increased cardiovascular mortality. MVD often coexists with or even precedes macrovascular disease, possibly due to shared mechanisms of vascular damage, such as inflammatory processes and oxidative stress. One of the first events in MVD is endothelial dysfunction. With the use of different physiologic or pharmacologic stimuli, endothelium-dependent (micro)vascular reactivity can be studied. This reactivity depends on the balance between various mediators, including nitric oxide, endothelin, and prostanoids, among others. The measurement of microvascular (endothelial) function is important to understand the pathophysiologic mechanisms that contribute to MVD and the role of MVD in the development and progression of cardiometabolic/renal disease. Here, we review a selection of direct, noninvasive techniques for measuring human microcirculation, with a focus on methods, interpretation, and limitations from the perspective of chronic cardiometabolic and renal disease.

The role of osteoprotegerin in the crosstalk between vessels and bone: Its potential utility as a marker of cardiometabolic diseases.

Among the numerous molecules that are being studied for their potential utility as biomarkers of cardiovascular diseases, much interest has been shown in the superfamily of tumor necrosis factor (TNF) receptors. Members of this family include osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor κB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). These signals may be expressed and regulated, and their functions could be involved in several physiological and pathological processes. The relationship between bone regulatory proteins and vascular biology has attracted attention, and it has been suggested that OPG may mediate vascular calcification and cardiometabolic diseases. OPG is steadily released from vascular endothelial cells in response to inflammatory stimuli, suggesting that it plays a modulatory role in vascular injury, inflammation, and atherosclerosis. Vascular calcification, a hallmark of atherosclerosis, is similar to bone remodeling. It is an actively regulated mechanism that includes both inductive and inhibitory processes. There is a temporal link between the development of osteoporosis and vascular calcification, which is particularly marked in post-menopausal women and the elderly. The precise nature of the link between bone metabolism, vascular calcification and cardiovascular disease is largely unknown but increasing evidence suggests that the triad of RANK/RANKL/OPG may be important in the initiation of various diseases. An increased release of OPG is associated with increased cardiovascular risk and it is suggested that increased OPG levels resulting from vascular damage correspond to a protective mechanism. Circulating OPG levels could be used as independent biomarkers of cardiovascular disease in patients with acute or chronic cardiometabolic disease and thus an improved prognosis.

Abstract P113: Lipid-related Genetic Variants and Lipid Outcomes in a Cohort of Chilean Children

Dyslipidemia is an important risk factor for chronic cardiometabolic diseases. Lipid traits are highly heritable and there are currently &gt;185 established loci influencing lipid levels in adults. Recent studies have confirmed that variants associated with lipids influence lipid levels across the lifecourse, and in ancestrally diverse populations. Given that Hispanic/Latinos (HL) shoulder much of the cardiometabolic burden in the United States, it is important to identify genetic variants that contribute the greatest risk for elevated lipid levels across life stages. Thus, our primary aim is to examine the association of known lipid variants with lipid traits identified in large study of adult participants from a Chilean infancy cohort of primarily European-descent. The sample assessed from 2008 to 2013 (n=546) had genotyping and well-measured lipid phenotypes (median age: 16.8 years, interquartile range: 16.6, 16.9). We assessed single variant associations using linear regression for high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG), assuming an additive genetic model, adjusted for sex. Additionally, we regressed phenotypes onto weighted trait-specific polygenic risk scores (PRS). Only six variants from the Chilean sample met the a priori threshold of power &gt; 0.8. We found statistically significant effect sizes (mmol/l (se)) for four of the six variants: rs3764261 (0.16 (0.04)) and rs1532085 (0.05 (0.04)) for HDL and rs1260326 (0.34 (0.15)) and rs964184 (0.33 (0.15)) for TG. For each significant variant, direction of effect matched the multiethnic adult GWAS from which SNPs were selected. We compared our findings to a previous study in Finnish children at age 18 years (n=1,216) and found an opposite direction of effect for our significant HDL variants. Likewise, when comparing coefficients for the PRS between the Chilean and Finnish youth sample we found the association to be stronger in the Chilean sample for every trait and gender group with the exception of LDL for males. The lipid loci explained the least amount of total variance for LDL (males=4% and females=5%) and the most amount of variance for HDL (males=20% and females=14%). In conclusion, there is evidence that lipid loci from a HL sample of adolescents contain similar associations as those from European children and adults. Despite the small sample size and possibility for bias with different ancestral groups we found meaningful and statistically significant associations relating lipid loci in a HL cohort of Chilean adolescents with those found in European ancestral groups. These associations emphasize the importance of adolescence as a time for disease prevention given studies demonstrating both the persistence of associations between PRS and lipids over the life course and the increasing role PRS plays in predicting disease.

For Super-Utilizers, Integrated Care Offers A New Path.

Many health systems continue to experiment with the best way to care for those patients who end up in the hospital most frequently.

Addressing unmet basic resource needs as part of chronic cardiometabolic disease management

Addressing unmet basic resource needs as part of chronic cardiometabolic disease management