Prevention Of Cardiometabolic Diseases Research Articles

Gestational Diabetes Mellitus and Subsequent Risks of Diabetes and Cardiovascular Diseases: the Life Course Perspective and Implications of Racial Disparities.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications worldwide and the prevalence is continuously rising globally. Importantly, GDM is not an isolated complication of pregnancy. Growing evidence suggests that individuals with GDM, compared to those without GDM, have an increased risk of subsequent type 2 diabetes (T2D) and cardiovascular diseases (CVD). Substantial racial and ethnic disparities exist in the risk of GDM. However, the role of race and ethnicity in the progression from GDM to T2D and CVD remains unclear. The purpose of the current review is to summarize recent research about GDM and its life-course impacts on cardiometabolic health, including 1) the peak time of developing T2D and CVD risks after GDM, 2) the racial and ethnic disparities in the risk cardiometabolic diseases after GDM, 3) the biological plausibility and underlying mechanisms, and 4) recommendations for screening and prevention of cardiometabolic diseases among individuals with GDM, collectively to provide an updated review to guide future research. Growing evidence has indicated that individuals with GDM had greater risks of T2D (7.4 to 9.6 times), hypertension (78% higher), and CDV events (74% higher) after GDM than their non-GDM counterparts. More recently, a few studies also suggested that GDM could slightly increase the risk of mortality. Available evidence suggests that key CVD risk factors such as blood pressure, plasma glucose, and lipids levels are all elevated as early as < 1year postpartum in individuals with GDM. The risk of T2D and hypertension is likely to reach a peak between 3-6years after the index pregnancy with GDM compared to normal glycemia pregnancy. Cumulative evidence also suggests that the risk of cardiometabolic diseases including T2D, hypertension, and CVD events after GDM varies by race and ethnicity. However, whether the risk is higher in certain racial and ethnic groups and whether the pattern may vary by the postpartum cardiometabolic outcome of interest remain unclear. The underlying mechanisms linking GDM and subsequent T2D and CVD are complex, often involving multiple pathways and their interactions, with the specific mechanisms varying by individuals of different racial and ethnic backgrounds. Diabetes and CVD risk screening among individuals with GDM should be initiated early during postpartum and continue, if possible, frequently. Unfortunately, adherence to postpartum glucose testing with either obstetrician or primary care providers remained poor among individuals with GDM. A life-course perspective may provide critical information to address clinical and public health gaps in postpartum screening and interventions for preventing T2D and CVD risks in individuals with GDM. Future research investigating the racial- and ethnic-specific risk of progression from GDM to cardiometabolic diseases and the role of multi-domain factors including lifestyle, biological, and socio-contextual factors are warranted to inform tailored and culture-appropriate interventions for high-risk subpopulations. Further, examining the barriers to postpartum glucose testing among individuals with GDM is crucial for the effective prevention of cardiometabolic diseases and for enhancing life-long health.

Subclassification of obesity for precision prediction of cardiometabolic diseases.

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000). We detected five discordant profiles consisting of individuals with cardiometabolic biomarkers higher or lower than expected given their BMI, which generally increases disease risk, in total representing ~20% of the total population. Persons with discordant profiles differed from concordant individuals in prevalence and future risk of major adverse cardiovascular events (MACE) and type 2 diabetes. Subtle BMI-discordances in biomarkers affected disease risk. For instance, a 10% higher probability of having a discordant lipid profile was associated with a 5% higher risk of MACE (hazard ratio in women 1.05, 95% confidence interval 1.03, 1.06, P = 4.19 × 10-10; hazard ratio in men 1.05, 95% confidence interval 1.04, 1.06, P = 9.33 × 10-14). Multivariate prediction models for MACE and type 2 diabetes performed better when incorporating discordant profile information (likelihood ratio test P < 0.001). This enhancement represents an additional net benefit of 4-15 additional correct interventions and 37-135 additional unnecessary interventions correctly avoided for every 10,000 individuals tested.

Screening of the most common cardiometabolic diseases based on risk factor assessment among military personnel

Objective — to assess the prevalence of major cardiometabolic diseases by identifying their risk factors and comparing them with metabolic disorders and stress indicators in military personnel. Materials and methods. The study included 74 male military personnel with an average age of 43.4 [31.4; 50.6] years. Among all the participants, the proportion of individuals with hypertension (HTN) was 51.4%, with dyslipidemia (DLP) — 75.7%, with metabolic­associated steatotic liver disease (MASLD) — 48.6%, and with overweight or obesity — 51.4%. The participants were divided into groups based on the number of cardiometabolic diseases: group 1 (comparison) consisted of military personnel without HTN, DLP, or MASLD (n=14, 18.9%), group 2 — personnel with 1—2 of the above­mentioned cardiometabolic diseases (n=32, 43.2%), and group 3 — military personnel with comorbid pathology, including HTN, DLP, and MASLD (n=28, 37.8%). All participants were assessed for anthropometric profile, traditional clinical and biochemical indicators. Stress indicators included dehydroepiandrosterone sulfate (DHEA­S), cortisol, and oxidative stress marker 8­OH­deoxyguanosine (8­OH­DG), which were measured in the blood using immunoassay methods. Results. Among military personnel with HTN, overweight/obesity was twice as common (p=0.003, χ2=9.110), MASLD was 3.3 times more frequent (p=0.0001, χ2=19.598), and DLP was 1.7 times more frequent (p=0.0001, χ2=15.418). Among military personnel with MASLD, overweight/obesity was observed three times more frequently (p=0.0001, χ2=19.598), and dyslipidemia was 1.6 times more common (p=0.0001, χ2=13.416). Personnel with more cardiometabolic diseases were significantly older (p=0.003). In group 3, 21.4% had a normal BMI, while in group 1, 28.6% were overweight or had obesity (p=0.001). The increase in the number of cardiometabolic diseases between groups was accompanied by a significant reduction in skeletal muscle percentage (p=0.039 for group 1 vs group 2; p=0.001 for group 1 vs group 3; p=0.001 for group 2 vs group 3). Military personnel in group 3 had significantly higher BMI, waist circumference (WC), total fat percentage, and lower skeletal muscle percentage compared to groups 1 and 2 (p=0.001 for all comparisons). The highest levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid (UA), and the lowest AST/ALT ratio were observed in group 3 compared to group 1 (p=0.002; p=0.0001; p=0.001; p=0.0001) and group 2 (p=0.0001; p=0.0001; p=0.0001; p=0.0001), respectively. Alkaline phosphatase levels were significantly lower in group 3 compared to group 1 (p=0.048). Lipid profile deterioration was observed with an increase in the number of cardiometabolic diseases: total cholesterol (TC), triglycerides (TG), very low­density lipoprotein cholesterol (VLDL­C), and low­density lipoprotein cholesterol (LDL­C) levels were significantly higher in group 3 compared to group 1 (p=0.0001; p=0.0001; p=0.0001; p=0.007) and group 2 (p=0.0001; p=0.024; p=0.002; p=0.005), respectively. In group 2, only TG (p=0.0001) and VLDL­C (p=0.0001) levels were higher compared to group 1. DHEA­S levels were significantly lower in group 3 compared to group 1 (p=0.019), but no differences in cortisol levels were found. 8­OH­DG levels were significantly lower in groups 2 (p=0.003) and 3 (p=0.019) compared to group 1. Correlation analysis revealed that stress hormone levels were inversely associated with WC (p=0.016), AST (p=0.004), ALT (p=0.021), total bilirubin (p=0.033), UA (p=0.002), glycated haemoglobin (HbA1с) (p=0.024), TC (p=0.002), TG (p=0.001), and VLDL­C (p=0.001). Conclusions. Cardiometabolic diseases are highly prevalent among military personnel, and comorbidity is a frequent phenomenon that contributes to a significant increase in cardiovascular risk and highlights the need for optimized preventive and therapeutic strategies. The increase in the number of cardiometabolic diseases is associated with older age, worsened anthropometric status, liver function tests, increased uric acid levels, and deteriorating lipid profile. DHEA­S can be considered a marker of chronic stress in individuals with cardiometabolic comorbidity. Monitoring and timely correction of WC, AST, ALT, total bilirubin, UA, HbA1с, TC, TG, and VLDL­C levels among military personnel are necessary, as these indicators are related to stress and can improve cardiometabolic disease prevention.

Association of a composite trait for anthropometrics, adiposity and energy expenditure with cardiometabolic diseases: An age-stratified cohort and genetic risk score analysis.

Various anthropometric measures capture distinct as well as overlapping characteristics of an individual's body composition. To characterize independent body composition measures, we aimed to reduce easily-obtainable individual measures reflecting adiposity, anthropometrics and energy expenditure into fewer independent constructs, and to assess their potential sex- and age-specific relation with cardiometabolic diseases. Analyses were performed within European ancestry participants from UK Biobank (N = 418,963, mean age 58.0 years, 56% women). Principal components (PC) analyses were used for the dimension reduction of 11 measures of adiposity, anthropometrics and energy expenditure. PCs were studied in relation to incident type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). Multivariable-adjusted Cox regression analyses, adjusted for confounding factors, were performed in all and stratified by age. Genome-wide association studies were performed in half of the cohort (N = 156,295) to identify genetic variants as instrumental variables. Genetic risk score analyses were performed in the other half of the cohort stratified by age of disease onset (N = 156,295). We identified two PCs, of which PC1 reflected lower overall adiposity (negatively correlated with all adiposity aspects) and PC2 reflected more central adiposity (mainly correlated with higher waist-hip ratio, but with lower total body fat) and increased height, collectively capturing 87.8% of the total variance. Similar to that observed in the multivariable-adjusted regression analyses, we found associations between the PC1 genetic risk score and lower risks of CAD and T2D [CAD cases <50 years, odds ratio: 0.91 (95% confidence interval 0.87, 0.94) per SD; T2D cases <50 years, odds ratio: 0.76 (0.72, 0.81)], which attenuated with higher age (p-values 8.13E-4 and 2.41E-6, respectively). No associations were found for PC2. The consistently observed weaker associations of the composite traits with cardiometabolic disease suggests the need for age-specific cardiometabolic disease prevention strategies.

Beyond T-Trials, T4DM and TRAVERSE: the next large testosterone randomized controlled trial.

Lower testosterone concentrations have been associated with poorer health outcomes in ageing men, but proving causality and demonstrating potential for therapeutic benefit requires randomized clinical trials (RCTs). This review discusses recent observational findings and results of major testosterone RCTs, to explore the need for another, larger trial. Evidence of Leydig cell impairment emerges in men above the age of 70 years. Lower testosterone is associated with diabetes risk, and also risk of incident dementia. An individual participant data meta-analysis found that below thresholds of testosterone of 7.4 nmol/L and 5.3 nmol/l respectively, risks of all-cause mortality and cardiovascular deaths in men increased. Testosterone for the Prevention of Type 2 Diabetes Mellitus (T4DM), a multicentre RCT, showed that testosterone treatment prevented or reverted type 2 diabetes in men at high risk. Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE), a cardiovascular safety trial, demonstrated cardiovascular and prostate safety of testosterone treatment in men with or at risk of cardiovascular disease. T4DM confirmed findings from the Testosterone Trials (T-Trials) that testosterone improved sexual function, and bone microarchitecture and density. However, in TRAVERSE, testosterone-treated men had a higher risk of clinical bone fractures, but not major osteoporotic fractures. Men with disorders of the hypothalamic-pituitary-testicular (HPT) axis causing androgen deficiency warrant consideration for testosterone therapy. In men with an intact HPT axis, testosterone treatment is a pharmacological intervention which requires justification from high quality RCT data. Currently, there is insufficient evidence to justify wider use of testosterone for prevention of cardiometabolic disease. However, there is scope for another large testosterone RCT to investigate whether testosterone treatment might, in older men, extend disability-free survival.

The association of changes in the Chinese visceral adiposity index and cardiometabolic diseases: a cohort study

ObjectiveThe relationship between changes in Chinese visceral adiposity index (CVAI) and cardiometabolic diseases (CMD) in middle-aged and elderly individuals remains unclear. This study aimed to explore whether changes in the CVAI were associated with CMD incidence.MethodsThis study included 3,243 individuals aged over 45 years from the China Health and Retirement Longitudinal Study. The exposures were changes in the CVAI and cumulative CVAI from 2012 to 2015. Changes in the CVAI were classified using K-means clustering analysis, and the cumulative CVAI was calculated as follows: (CVAI2012 + CVAI2015)/2 × time (2015–2012). Multivariable logistic regression models were used to assess the relationship between different CVAI change classes and CMD incidence. Restricted cubic splines regression was used to assess the dose–response relationship between cumulative CVAI and CMD incidence. To investigate the relationship between combined exposure to each component of CAVI and CMD incidence, a weighted quantile sum regression analysis was employed.ResultsDuring the 5 years of follow-up, 776 (24%) incident CMD cases were identified. Changes in CVAI and cumulative CVAI were independently and positively associated with CMD. After adjusting for potential confounders, compared with Class 1, the adjusted ORs (95% CIs) for incident CMD were 1.18 (0.90–1.57) for Class 2, 1.40 (1.03–1.92) for Class 3, and 1.56 (1.04–2.34) for Class 4. When cumulative CVAI was categorized into quartiles, compared with Q1, the adjusted ORs (95% CIs) for incident CMD were 1.30 (1.00–1.70) for Q2, 1.34 (1.01–1.79) for Q3, and 1.63 (1.15–2.31) for Q4. In addition, cumulative CVAI in the overall population exhibited a linear association with CMD (Poverall = 0.012, Pnon-linearity = 0.287), diabetes (Poverall = 0.022, Pnon-linearity = 0.188), and stroke (Poverall = 0.002, Pnon-linearity = 0.978), but showed no significant association with heart disease (Poverall = 0.619, Pnon-linearity = 0.442).ConclusionParticipants with higher baseline CVAI level and a change of elevating CVAI level may suffer an increased incidence of CMD. Furthermore, our findings elucidate the underlying mechanisms of the CVAI by highlighting TG as the primary contributor to the observed associations. Long-term CVAI monitoring is of significant importance for early identification and prevention of CMD, with significant implications for clinical practice.

КАРДИОМЕТАБОЛИЧЕСКИЙ ПРОФИЛЬ С УЧЕТОМ СТАДИРОВАНИЯ ПО CMDS У ЛИЦ МОЛОДОГО ВОЗРАСТА

Abstract. Introduction. The burden of cardiovascular disease, diabetes mellitus, and the associated mortality remains high. One classification system that predicts the development of cardiovascular events and type 2 diabetes mellitus is Cardiometabolic Disease Staging (CMDS). The study of new cardiometabolic profile parameters is relevant in the context of their association with residual cardiovascular risk. The aim of the study was to evaluate the cardiometabolic profile, including extended parameters, in young adults, while taking into account the CMDS. Materials and Methods. 185 male and female subjects aged 35.0 [30.0–39.0] years were examined. The participants were divided into groups according to the CMDS classification: Stage 0, metabolically healthy; Stage 1 (low risk), one or two risk factors (RFs) other than prediabetes; Stage 2 (intermediate risk), presence of ≥3 risk factors or prediabetes; Stage 3 (high risk), presence of ≥3 risk factors and prediabetes. The study examined visceral adiposity index, visceral fat level, insulin resistance, leptinemia, hyperuricemia, glomerular filtration rate, C–reactive protein, and N–terminal brain natriuretic peptide concentrations. The data were processed in SPSS Statistics 26. Results and Discussion. The cardiometabolic profile demonstrated unfavorable alterations with the progression of CMDS stages. Across the spectrum from CMDS 0 to CMDS 3, we observed a significant rise in the prevalence of abdominal obesity (0% to 100%, p&lt;0,001), body mass index ≥25 kg/m2 (16.2% to 100%, p&lt;0.001), and excess visceral fat level (0% to 23.8%, p&lt;0.001). Simultaneously, the prevalence of hypercholesterolemia demonstrated a significant rise (24.3% to 52.4%, p=0.025), as did elevated low–density lipoprotein cholesterol (32.4% to 76.1%, p=0.014), insulin resistance (2.7% to 66.7%, p&lt;0.001), leptinemia (45.9% to 90.5%, p=0.009), C–reactive protein (2.7% to 57.1%, p&lt;0.001) and hyperuricemia (16.2% to 61.9%, p&lt;0.001). The median values of these parameters also increased. Conclusions. Our data confirm the simultaneous increase in both the quantity and intensity of risk factors, manifestations of adiposopathy associated with increasing residual cardiovascular risk. Our results substantiate the feasibility of using the CMDS classification at the stage of primary prevention of cardiometabolic diseases to identify groups with the most significant metabolism disorders of lipid, carbohydrate and purine metabolism in young adults.

Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (−32%; 95% confidence interval (95% CI): −21% to −42%) and type 2 diabetes (−26%; 95% CI: −15% to −35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses’ Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications.

Dietary fats as regulators of neutrophil plasticity: an update on molecular mechanisms.

Contemporary guidelines for the prevention of cardio-metabolic diseases focus on the control of dietary fat intake, because of their adverse metabolic effects. Moreover, fats alter innate immune defenses, by eliciting pro-inflammatory epigenetic mechanisms on the long-living hematopoietic cell progenitors which, in the bone marrow, mainly give rise to short-living neutrophils. Nevertheless, the heterogenicity of fats and the complexity of the biology of neutrophils pose challenges in the understanding on how this class of nutrients could contribute to the development of cardio-metabolic diseases via specific molecular mechanisms activating the inflammatory response. The knowledge on the biology of neutrophils is expanding and there are now different cellular networks orchestrating site-specific reprogramming of these cells to optimize the responses against pathogens. The innate immune competence of neutrophil is altered in response to high fat diet and contributes to the development of metabolic alterations, although the precise mechanisms are still poorly understood. Defining the different molecular mechanisms involved in the fat-neutrophil crosstalk will help to reconcile the sparse data about the interaction of dietary fats with neutrophils and to tailor strategies to target neutrophils in the context of cardio-metabolic diseases.

Joint associations of diet and physical activity with incident type 2 diabetes and hypertension: an analysis of 144,288 UK Biobank participants.

Studies examining the joint associations of lifestyle exposures can reveal novel synergistic and joint effects, but no study has examined the joint association of diet and physical activity (PA) with type 2 diabetes (T2D) and hypertension. The aim of this study is to examine the joint associations of PA and diet with incidence of type T2D and hypertension, as a combined outcome and separately in a large sample of UK adults. This prospective cohort study included 144,288 UK Biobank participants aged 40-69. Moderate to vigorous PA (MVPA) was measured using the International Physical Activity Questionnaire and a wrist accelerometer. We categorised PA and diet indicators (diet quality score (DQS) and energy intake (EI)) based on tertiles and derived joint PA and diet variables. Outcome was major cardiometabolic disease incidence (combination of T2D and hypertension). A total of 14,003(7.1%) participants developed T2D, 28,075(19.2%) developed hypertension, and 30,529(21.2%) developed T2D or hypertension over a mean follow-up of 10.9(3.7) years. Participants with middle and high self-reported MVPA levels had lower risk of major cardiometabolic disease regardless of diet, e.g. among high DQS group, hazard ratios in middle and high MVPA group were 0.90 (95%CI:0.86-0.94), and 0.88(95%CI:0.84-0.92), respectively. Participants with jointly high device-measured MVPA and high DQS levels had lower major cardiometabolic disease risk (HR: 0.84, 95%CI:0.71-0.99). The equivalent joint device-measured MVPA and EI exposure analyses showed no clear pattern of associations with the outcomes. Higher PA is an important component in cardiometabolic disease prevention across all diet quality and total EI groups. The observed lack of association between diet health outcomes may stem from a lower DQS.

Intensity-specific physical activity measured by accelerometer and the risk of mortality among individuals with cardiometabolic diseases: A prospective study from the UK Biobank

BackgroundWhile the health benefits of physical activity for general population are well-recognized, the prospective associations of physical activity volume and intensity with mortality among cardiometabolic disease individuals remain unclear. ObjectiveThe objective of this study was to investigate the associations of accelerometer-measured intensity-specific physical activity with mortality risk among population with cardiometabolic disease. DesignProspective cohort study. SettingParticipants were recruited from the United Kingdom (UK) across 22 assessment centers from 2006 to 2010. ParticipantsA total of 9524 participants from the UK Biobank (median: 67.00 years, interquartile range: 61.00–70.00 years) were included in final study. MethodsAccelerometer-measured total volume, moderate-to-vigorous and light intensity physical activity collecting from 2013 to 2015 were quantified using a machine learning model. Multivariable restricted cubic splines and Cox proportional hazard models with hazard ratios (HRs) and 95 % confidence intervals (CIs) were employed to examine the associations of interests. ResultsDuring the follow-up period (median: 6.87 years; interquartile range: 6.32–7.39 years), there were 659 (6.92 %) death events with 218 (2.29 %) cardiovascular disease-related deaths and 441 (4.63 %) non-cardiovascular disease-related deaths separately. In the fully adjusted models, compared with participants in the lowest quartiles of total volume, moderate-to-vigorous and light physical activities, the adjusted HRs (95 % CIs) of all-cause mortality for those in the highest quartiles were 0.40 (0.31, 0.52), 0.48 (0.37, 0.61), and 0.56 (0.44, 0.71) while those for cardiovascular diseases-related mortality were 0.35 (0.22, 0.55), 0.52 (0.35, 0.78) and 0.59 (0.39, 0.88), and for non-cardiovascular diseases-related mortality, they were 0.42 (0.30, 0.59), 0.40 (0.29, 0.54) and 0.54 (0.40, 0.73), separately. The optimal moderate-to-vigorous-intensity physical activity level for cardiovascular diseases-related mortality reduction was found to be in the third quartile (17.75–35.33 min/day). Furthermore, the observed inverse associations were mainly non-linear. ConclusionsPromoting physical activity, regardless of intensity, is essential for individuals with cardiometabolic disease to reduce mortality risk. For both all-cause and cardiovascular disease-related and non-cardiovascular disease-related mortality, the observed decrease in risk seems to level off at a moderate level. The current findings deriving from precise device-based physical activity data provide inference for secondary prevention of cardiometabolic disease.

Gender differences in the association between changes in the atherogenic index of plasma and cardiometabolic diseases: a cohort study

ObjectiveThe relationship between changes in Atherogenic Index of Plasma (AIP) and cardiometabolic diseases (CMD) in middle-aged and elderly individuals remains unclear. This study aims to explore the association between changes in AIP and CMD.MethodsThis study included 3,791 individuals aged over 45 years from CHARLS. Participants were divided into four groups using the K-Means clustering method. Cumulative AIP was used as a quantitative indicator reflecting changes in AIP. Differences in baseline data and CMD incidence rates among these four groups were compared. Multifactorial logistic regression models were used to assess the relationship between changes in AIP and CMD, and subgroup analysis and interaction tests were conducted to evaluate potential relationships between changes in AIP and CMD across different subgroups. Restricted cubic splines (RCS) were used to assess the dose-response relationship between cumulative AIP and CMD.ResultsChanges in AIP were independently and positively associated with CMD. In males, the risk significantly increased in class4 compared to class1 (OR 1.75, 95%CI 1.12-2.73). In females, changes in AIP were not significantly associated with CMD. Cumulative AIP was positively correlated with CMD (OR 1.15, 95%CI 1.01-1.30), with significant gender differences in males (OR 1.29, 95%CI 1.07-1.55) and females (OR 1.03, 95%CI 0.87-1.23) (p for interaction = 0.042). In addition, a linear relationship was observed between cumulative AIP and CMD in male.ConclusionSubstantial changes in AIP may increase the risk of CMD in middle-aged and elderly Chinese males. Dynamic monitoring of AIP is of significant importance for the prevention and treatment of CMD.

Increased Risk of Cardiometabolic Disease in Ideal Weight Adults With History of Overweight/Obesity in China: A Prospective Cohort Study.

Overweight and obesity represent critical modifiable determinants in the prevention of cardiometabolic disease (CMD). However, the long-term impact of prior overweight/obesity on the risk of CMD in later life remains unclear. We aimed to investigate the association between longitudinal transition of body mass index (BMI) status and incident CMD. This prospective cohort study included 57 493 CMD-free Chinese adults from the Kailuan Study. BMI change patterns were categorized according to the BMI measurements obtained during the 2006 and 2012 surveys. The primary end point was a composite of myocardial infarction, stroke, and type 2 diabetes. Cox regression models were used to evaluate the associations of transitions in BMI with overall CMD events and subtypes, with covariates selected on the basis of the directed acyclic graph. During a median follow-up of 7.62 years, 8412 participants developed CMD. After considering potential confounders, weight gain pattern (hazard ratio [HR], 1.34 [95% CI, 1.23-1.46]), stable overweight/obesity (HR, 2.12 [95% CI, 2.00-2.24]), and past overweight/obesity (HR, 1.73 [95% CI, 1.59-1.89]) were associated with the incidence of CMD. Similar results were observed in cardiometabolic multimorbidity, cardiovascular disease, and type 2 diabetes. Additionally, triglyceride and systolic blood pressure explained 8.05% (95% CI, 5.87-10.22) and 12.10% (95% CI, 9.19-15.02) of the association between past overweight/obesity and incident CMD, respectively. A history of overweight/obesity was associated with an increased risk of CMD, even in the absence of current BMI abnormalities. These findings emphasize the necessity for future public health guidelines to include preventive interventions for CMD in individuals with past overweight/obesity.

Impact of loss-of-function in angiopoietin-like 4 on the human phenome

BackgroundCarriers of the E40K loss-of-function variant in Angiopoietin-like 4 (ANGPTL4), have lower plasma triglyceride levels as well as lower rates of coronary artery disease (CAD) and type 2 diabetes (T2D). These genetic data suggest ANGPTL4 inhibition as a potential therapeutic target for cardiometabolic diseases. However, it is unknown whether the association between E40K and human diseases is due to linkage disequilibrium confounding. The broader impact of genetic ANGPTL4 inhibition is also unknown, raising uncertainties about the safety and validity of this target. MethodsTo assess the impact of ANGPLT4 inhibition, we evaluated whether E40K and other loss-of-function variants in ANGPTL4 influenced a wide range of health markers and diseases using 29 publicly available genome-wide association meta-analyses of cardiometabolic traits and diseases, as well as 1589 diseases assessed in electronic health records within FinnGen (n = 309,154). To determine whether these relationships were likely causal, and not driven by other correlated variants, we used the Bayesian fine mapping algorithm CoPheScan. ResultsThe CoPheScan posterior probability of E40K being the causal variant for triglyceride levels was 99.99 %, validating the E40K to proxy lifelong lower activity of ANGPTL4. The E40K variant was associated with lower risk of CAD (odds ratio [OR] = 0.84, 95 % CI = 0.81 to 0.87, p=3.6e-21) and T2D (OR = 0.91, 95 % CI = 0.87 to 0.95, p=2.8e-05) in GWAS meta-analyses, with results replicated in FinnGen. These significant results were also replicated using other rare loss-of-function variants identified through whole exome sequencing in 488,278 participants of the UK Biobank. Using a Mendelian randomization study design, the E40K variant effect on cardiometabolic diseases was concordant with lipoprotein lipase enhancement (r = 0.82), but not hepatic lipase enhancement (r = −0.10), suggesting that ANGPTL4 effects on cardiometabolic diseases are potentially mainly mediated through lipoprotein lipase. After correction for multiple testing, the E40K variant did not significantly increase the risk of any of the 1589 diseases tested in FinnGen. ConclusionsANGPTL4 inhibition may represent a potentially safe and effective target for cardiometabolic diseases prevention or treatment.

The Epidemiology of Berry Consumption and Association of Berry Consumption with Diet Quality and Cardiometabolic Risk Factors in United States Adults: The National Health and Nutrition Examination Survey, 2003–2018

BackgroundBerries are rich in important nutrients and bioactive compounds, which could potentially contribute to maintenance of normal lipid and glucose profiles. ObjectiveWe reported the epidemiology of berry consumption and examined associations of berry consumption with diet quality [measured by Healthy Eating Index (HEI-2015)] and levels of cardiometabolic risk factors, including body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), glycated hemoglobin, and fasting biomarkers: triglycerides, low-density lipoprotein cholesterol (LDL cholesterol), glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). MethodsWe evaluated 33,082 adults (aged ≥20 y) using two 24-h diet recalls from National Health and Nutrition Examination Survey (2003–2018). Multivariable linear regression models were applied to examine the associations of total and individual berry intake with diet quality and cardiometabolic risk factors using appropriate sample weights. ResultsApproximately 25 % of the United States adults consumed berries (0.08 ± 0.003 cup-equivalents/d), representing ∼10 % of the daily mean total fruit intake. Among berry consumers, the mean intake of strawberries (0.31 ± 0.01 cup-equivalents) was higher than for other berries. Berry consumers had a significantly higher HEI-2015 score than nonconsumers (mean HEI-2015 score = 58.8 compared with 52.3, P < 0.0001). Berry consumers had significantly lower concentrations of cardiometabolic indices than nonconsumers, including BMI, WC, SBP, total cholesterol, LDL cholesterol, triglycerides, fasting insulin, HOMA-IR, and higher mean HDL cholesterol, after adjusting for sociodemographic, lifestyle, and dietary confounders (all P < 0.05). ConclusionsUnited States adult berry consumers had a higher diet quality and lower concentrations of cardiometabolic risk factors, suggesting a favorable role for berries in diets and cardiometabolic disease prevention in United States adult population.

Vitamin D levels and lipid profile in children and adolescents: a tight correlation.

Vitamin D is an essential hormone for humans, playing an important role in musculoskeletal and calcium homeostasis. Its deficiency/insufficiency seems to contribute to the development of cardiometabolic diseases in adults: this correlation appears less clear for children and adolescents. The aim of this paper was to review literature data on the relationship between vitamin D and lipid profile alterations in pediatric population. We carried out a comprehensive research in electronic databases, including MEDLINE and PubMed up to December 2022, for cross-sectional or prospective studies that investigated the correlation between serum vitamin D levels and lipid profile in children and adolescents. At the end of the process, 37 articles were included in this review. According to our findings, vitamin D deficiency/insufficiency is strongly associated with lower high-density lipoprotein (HDL) cholesterol levels and higher levels of triglycerides and total cholesterol. Data about low-density lipoproteins (LDL) cholesterol are inconsistent. The potential role of vitamin D supplements for the prevention of cardiometabolic disease currently remains a speculation. An increasing number of studies shows how hypovitaminosis D in the pediatric age may play a role in the pathogenesis of metabolic disorders and lipid profile alterations. Data regarding the potential role of vitamin D supplements for the prevention of cardiometabolic disease are currently controversial. Further studies are needed to evaluate the causality of this association and to assess the underlying pathogenetic mechanisms.

Possibilities of cardiometabolic diseases prevention in women with pregnancy adverse outcomes in medical history

Possibilities of cardiometabolic diseases prevention in women with pregnancy adverse outcomes in medical history

Role of steatotic liver disease in prediction and prevention of cardiometabolic diseases.

Role of steatotic liver disease in prediction and prevention of cardiometabolic diseases.

Causal associations of remnant cholesterol with cardiometabolic diseases and risk factors: a mendelian randomization analysis

BackgroundEmerging evidence suggests that remnant cholesterol (RC) is strongly associated with an increased incidence of cardiometabolic diseases (CMD). However, the causality have not been confirmed. We aimed to evaluate the causal associations of RC with CMD and the relative risk factors using two-sample Mendelian randomization (MR) methods.MethodsSummary-level statistics of RC, CMD, and cardiometabolic risk factors were obtained from the published data from individuals with a predominantly European ancestry mainly from the UK Biobank and the FinnGen biobank. Univariable and multivariable MR analyses were used to evaluate the causal relationships between RC and CMD. A bidirectional MR analysis was performed to estimate the causality between RC and cardiometabolic risk factors. The main MR method was conducted using the inverse-variance weighted method.ResultsUnivariable MR analyses showed that genetically predicted RC was causally associated with higher risk of ischemic heart disease, myocardial infarction, atrial fibrillation and flutter, peripheral artery disease, and non-rheumatic valve diseases (all P < 0.05). Multivariable MR analyses provided compelling evidence of the harmful effects of RC on the risk of ischemic heart disease (P < 0.05). Bidirectional MR analysis demonstrated that RC was bidirectionally causally linked to total cholesterol, triglycerides, low-density lipoprotein cholesterol, hypercholesterolemia (all P < 0.05). However, no genetic association was found between RC and metabolic disorders or the other cardiometabolic risk factors.ConclusionsThis MR study demonstrates that genetically driven RC increases the risk of several CMD and cardiometabolic risk factors, suggesting that targeted RC-lowering therapies may be effective for the primary prevention of CMD.

Association between cardiometabolic diseases and quality of life and the mediation effect of perceived stress

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a2b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.