Incident Cardiometabolic Diseases Research Articles

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.

Association of accelerated aging with the incidence risk of Cardiometabolic diseases in people with severe mental illnesses: A prospective analysis in UK Biobank

Cardiometabolic diseases (CMDs) comorbidities among people with severe mental illnesses (SMI) are associated with a high healthcare burden and premature mortality. This study aims to evaluate whether biological aging has an interaction with SMI on incident CMDs, and to examine the association of four biological aging indicators with CMDs incidence in this population. Data were sourced from the UK Biobank, a large prospective cohort study. Four indicators were used to assess biological aging including frailty phenotype, frailty index, KDM-biological age acceleration and phenotypic age acceleration. Cox proportional hazards regression models were used to examine the associations. We observed higher prevalence of frailty and accelerated biological age with SMI than those without SMI. Further analysis found significant interaction effect of pre-frailty and SMI (PPre-frail*SMI=0.005) as well as biological age acceleration and SMI (PQ3 (>P75)*SMI=0.038). 14.7 % of the participants with SMI developed CMDs during the follow-up. Compared with non-frail participants, those with frailty (frailty phenotype: HR=1.68, 95 % CI: 1.50, 1.88, P < 0.001; frailty index: HR=2.44, 95 % CI: 2.11–2.81, P < 0.001) and biological age acceleration (KDM-biological age acceleration (Q3): HR=1.91, 95 % CI: 1.74, 2.11, P < 0.001; phenotypic age acceleration (Q3): HR=2.07, 95 % CI: 1.86, 2.30, P < 0.001) had a significantly higher risk of CMDs in the adjusted model. A series of sensitivity analyses were conducted to illustrate the robustness of the findings. These findings highlight the important implications for concerning about the high incidence of CMDs comorbidities and intervention of aging in people with SMI.

Abstract 3462: Mendelian randomization analysis of 27 cardiometabolic trait related polygenic scores identifies genetic risk for cardiometabolic and cardiovascular events in a large prospective study of breast cancer survivors

Abstract Background: CVD is the most common cause of non-cancer death in breast cancer patients. Due to cancer treatment-related cardiotoxicities, breast cancer survivors are at increased risk of cardiometabolic disease (CMD) and cardiovascular disease (CVD). In addition to treatment-related factors, behavioral risk factors such as diet, smoking, and obesity are shared between CVD and breast cancer. While clinical factors influencing the risk of CVD in breast cancer patients are well studied, the effects of genetic factors are less known. Methods: To investigate genetic factors contributing to risk of CMD and CVD in women with a history of breast cancer, we performed a Mendelian randomization analysis to explore the relationships between 27 polygenic scores (PGS) for CMD and CVD phenotypes selected from the PGS Catalog and literature and 13 incident CMD and CVD events in a large prospective cohort of 3,699 breast cancer survivors in the Pathways Study. Fine-Gray sub-distribution hazard ratios (HRs) and 95% confidence intervals (CIs) associated with one standard deviation of PGS were derived with adjustment for epidemiologic, clinical, and treatment factors. The time scale was defined as time since date of breast cancer diagnosis to first of incident event, health plan disenrollment, death, or end of study (12/31/2019). The proportional hazards assumption was tested using Schoenfeld residuals, and no violation was found. Results: We identified 19 PGS-CMD/CVD associations that met Bonferroni significance (P&amp;lt;1.17 × 10−4). Five PGS were associated with increased risk of dyslipidemia: apolipoprotein B (HR=1.52, 95% CI,1.38-1.65), LDL cholesterol (1.49, 1.36-1.63), total cholesterol (1.43, 1.31-1.56), triglyceride levels (1.24, 1.14-1.34), and coronary artery disease (1.22, 1.13-1.33). Four PGS were associated with increased risk of hypertension: systolic blood pressure (1.36, 1.25-1.48), diastolic blood pressure (1.21, 1.11-1.32), fasting glucose adjusted for BMI (1.19, 1.09-1.30), and hypertension (1.41, 1.29-1.54). PGS for atrial fibrillation was associated with increased risk of arrhythmia (1.40, 1.25-1.57) and any cardiovascular disease (1.22, 1.12-1.32). PGS for coronary artery disease and myocardial infarction were both associated with increased risk of ischemic heart disease (1.43, 1.21-1.70 and 1.38, 1.17-1.62, respectively). Conclusion: Our study provides strong evidence for the potential use of PGS to predict the risk of CVD and CMD in women with a history of breast cancer. Future studies may explore the use of PGS to identify women with breast cancer at high risk of CVD-related outcomes and strategies to mitigate this risk. Citation Format: Peter N. Fiorica, Haiyang Sheng, Cecile A. Laurent, Janise M. Roh, Valerie S. Lee, Alexa Zimbalist, Isaac J. Ergas, Qianqian Zhu, Richard K. Cheng, Eileen Rillamas-Sun, Carlos Iribarren, Jamal S. Rana, Mai Nguyen-Huynh, Dawn L. Hershman, Lawrence H. Kushi, Christine B. Ambrosone, Marilyn L. Kwan, Heather Greenlee, Song Yao. Mendelian randomization analysis of 27 cardiometabolic trait related polygenic scores identifies genetic risk for cardiometabolic and cardiovascular events in a large prospective study of breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3462.

Association of Human Milk Fatty Acid Composition with Maternal Cardiometabolic Diseases: An Exploratory Prospective Cohort Study.

Background: Human milk fatty acids derive from maternal diet, body stores, and mammary synthesis and may reflect women's underlying cardiometabolic health. We explored whether human milk fatty acid composition was associated with maternal cardiometabolic disease (CMD) during pregnancy and up to 5 years postpartum. Materials and Methods: We analyzed data from the prospective CHILD Cohort Study on 1,018 women with no preexisting CMD who provided breast milk samples at 3-4 months postpartum. Milk fatty acid composition was measured using gas-liquid chromatography. Maternal CMD (diabetes or hypertension) was classified using questionnaires and birth records as no CMD (reference outcome group; 81.1%), perinatal CMD (developed and resolved during the perinatal period; 14.9%), persistent CMD (developed during, and persisted beyond, the perinatal period; 2.9%), and incident CMD (developed after the perinatal period; 1.1%). Multinomial logistic regression was used to model associations between milk fatty acid composition (individual, summary, ratios, and patterns identified using principal component analysis) and maternal CMD, adjusting for pre-pregnancy anthropometry and race/ethnicity. Results: Medium-chain saturated fatty acids (MC-SFA), lauric (C12:0; odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.60-0.89) and myristic acid (C14:0; OR = 0.80, 95% CI = 0.66-0.97), and the high MC-SFA principal component pattern (OR = 0.86, 95% CI = 0.76-0.96) were inversely associated with perinatal CMD. Long-chain polyunsaturated fatty acids adrenic acid (C22:4n-6) was positively associated with perinatal (OR = 1.21, 95% CI = 1.01-1.44) and persistent CMD (OR = 1.56, 95% CI = 1.08-2.25). The arachidonic (C20:4n-6)-to-docosahexaenoic acid (C22:6n-3) ratio was inversely associated with incident CMD (OR = 0.52, 95% CI = 0.28-0.96). Conclusions: These exploratory findings highlight a potential novel utility of breast milk for understanding women's cardiometabolic health.

Location Matters: The Role of the Neighborhood Environment for Incident Cardiometabolic Disease in Adults Aging With Physical Disability.

People aging with disability may be limited in their ability to engage in healthy behaviors to maintain cardiometabolic health. We investigated the role of health promoting features in the neighborhood environment for incident cardiometabolic disease in adults aging with physical disability in the United States. Retrospective cohort study. Optum's Clinformatics® Data Mart Database (2007-2018) of administrative health claims. ICD-9-CM codes were used to identify 15467 individuals with a diagnosis of Cerebral Palsy, Spina Bifida, Multiple Sclerosis, or Spinal Cord Injury. Cardiometabolic disease was identified using ICD-9-CM/ICD-10-CM codes over 3 years of follow-up. Measures of the neighborhood environment came from the National Neighborhood Data Archive and linked to individual residential ZIP codes over time. Covariates included age, sex, and comorbid health conditions. Cox regression models estimated hazard ratios (HR) for incident cardiometabolic disease. Using a 1-year lookback period, individuals with pre-existing cardiometabolic disease were excluded from the analysis. Net of individual risk factors, residing in neighborhoods with a greater density of broadband Internet connections (HR = .88, 95% CI: .81, .97), public transit stops (HR = .89, 95% CI: .83, .95), recreational establishments (HR = .89, 95% CI: .83, .96), and parks (HR = .88, 95% CI: .82, .94), was associated with reduced risk of 3-year incident cardiometabolic disease. Findings identify health-promoting resources that may mitigate health disparities in adults aging with disability.

The combined effect of socioeconomic position and C-reactive protein for predicting incident cardiometabolic disease: Findings from a 14-year follow-up study of the English Longitudinal Study of Ageing (ELSA)

Cardiovascular disease and diabetes are leading causes of morbidity and mortality worldwide. Social inequalities in the distribution of these diseases across the population exist. The aim of the current study was to examine the additive effect of socioeconomic position and a known biological risk marker (C-reactive protein [CRP]) for future incident cardiometabolic disease. We used data from the English Longitudinal Study of Ageing (N = 5410). Tertiles of net financial wealth and CRP (>3 mg/L) were measured at wave 2 (2004/05) and disease incidence (coronary heart disease [CHD], stroke, diabetes/high blood glucose) was reported across the subsequent 14 years of follow-up (2006–2019). Individual diseases were modelled as well as cardiometabolic multimorbidity which was defined as 2 or more incident cardiometabolic disease diagnoses over follow-up. Participants were free from the disease of interest at baseline. Cox proportional hazard and logistic regression analyses were used controlling for sociodemographic, lifestyle and health-related covariates. After adjusting for all covariates, the combination of low wealth and elevated CRP was an independent predictor of incident diabetes/high blood glucose (Hazard Ratio (HR) = 2.14; 95% Confidence Interval (C.I.) = 1.49–3.07), CHD (HR = 2.48, 95% C.I. = 1.63–3.76), stroke (HR = 1.55; 95% C.I. = 1.18–2.04), relative to high wealth/low CRP. Low wealth and elevated CRP was also an independent predictor of incident cardiometabolic multimorbidity (Odds Ratio = 2.22, 95% C.I. = 1.16–4.28) in age and sex adjusted models. The presence of both low wealth and elevated CRP was implicated in the onset of CHD, stroke, diabetes/high blood glucose, and cardiometabolic multimorbidity up to 14 years later, reflecting the role of psychobiological processes in predicting disease burden. Our results reinforce calls for efforts to tackle structural inequalities to improve healthy ageing trajectories.

Duration-dependent impact of cardiometabolic diseases and multimorbidity on all-cause and cause-specific mortality: a prospective cohort study of 0.5 million participants

BackgroundThe association of incident cardiometabolic multimorbidity (CMM) with mortality risk is rarely studied, and neither are the durations of cardiometabolic diseases (CMDs). Whether the association patterns of CMD durations with mortality change as individuals progress from one CMD to CMM is unclear.MethodsData from China Kadoorie Biobank of 512,720 participants aged 30–79 was used. CMM was defined as the simultaneous presence of two or more CMDs of interest, including diabetes, ischemic heart disease, and stroke. Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the duration-dependent associations of CMDs and CMM with all-cause and cause-specific mortality. All information on exposures of interest was updated during follow-up.ResultsDuring a median follow-up of 12.1 years, 99,770 participants experienced at least one incident CMD, and 56,549 deaths were documented. Among 463,178 participants free of three CMDs at baseline, compared with no CMD during follow-up, the adjusted HRs (95% CIs) between CMM and all-cause mortality, mortality from circulatory system diseases, respiratory system diseases, cancer, and other causes were 2.93 (2.80–3.07), 5.05 (4.74–5.37), 2.72 (2.35–3.14), 1.30 (1.16–1.45), and 2.30 (2.02–2.61), respectively. All CMDs exhibited a high mortality risk in the first year of diagnosis. Subsequently, with prolonged disease duration, mortality risk increased for diabetes, decreased for IHD, and sustained at a high level for stroke. With the presence of CMM, the above association estimates inflated, but the pattern of which remained.ConclusionAmong Chinese adults, mortality risk increased with the number of the CMDs and changed with prolonged disease duration, the patterns of which varied among the three CMDs.

Differential and sex- and age-specific risks of cardiometabolic diseases with unrelated metabolic syndrome dimensions.

This study aimed to investigate whether independent dimensions of metabolic syndrome (MetS) components are associated differentially with incident cardiometabolic diseases. Principal components analysis was performed using the five MetS components from 153,073 unrelated European-ancestry participants (55% women) from the UK Biobank. The associations of the principal components (PCs) with incident type 2 diabetes mellitus (T2D), coronary artery disease (CAD), and (ischemic) stroke were analyzed using multivariable-adjusted Cox proportional hazards models in groups stratified by sex and baseline age. PC1 (40.5% explained variance; increased waist circumference with dyslipidemia) and PC2 (22.7% explained variance; hyperglycemia) were both associated with incident cardiometabolic disease. Hazard ratios for CAD and T2D were higher for PC1 than for PC2 (1.27 [95% CI: 1.25-1.29] vs. 1.06 [95% CI: 1.03-1.08] and 2.09 [95% CI: 2.03-2.16] vs. 1.39 [95% CI: 1.34-1.44], respectively). Furthermore, the association of PC1 with T2D was slightly higher for women than for men, and especially the HRs of PC1 with CAD and T2D attenuated with increasing age (p values for heterogeneity test among subgroups < 0.05). MetS can be dissected into two distinct presentations characterized by differential sex- and age-associated cardiometabolic disease risk, confirming the loss of information using the dichotomous MetS.

A lipidomics score captures improved dietary fat quality and is related to cardiometabolic risk

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Grant from the German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung) to the German Center for Diabetes Research (DZD grant 82DZD00302), Joint Programming Initiative A Healthy Diet for a Healthy Life, as part of the ERA-HDHL cofounded joint call Biomarkers for Nutrition and Health (01EA1704). Background Deep lipidomics might more accurately capture metabolic effects of dietary interventions that aim to modulate the fat quality of the habitual diet compared to standard risk markers. We generated a multi-lipid score (MLS) to summarize the effect of a dietary intervention aiming to substitute saturated with unsaturated fats and assessed its association with incident cardiometabolic diseases. Methods The Dietary Intervention and VAScular function study (DIVAS) was a 16-week, randomized, controlled parallel unsaturated-for-saturated fat substitution (8% total energy, Figure 1A) trial in hundred-thirteen men and women. In regression models, we examined the diet effect on single lipids and combined the significantly affected lipids (P&amp;lt;0.05, multiple testing corrected) in a weighted multi-lipid score (MLS). Then, we used case-cohort designs and Prentice-weighted multi-variable adjusted Cox regression in the European Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort to associate this MLS with primary cardiovascular disease, defined as composite outcome combining stroke and myocardial infarction, and type 2 diabetes (T2D) incidence. Deep lipidomics data (940 molecular lipid species) were available in subsets of both studies (DIVAS: n=113; EPIC-Potsdam: subcohort, n=1262; CVD cases, n=551; T2D cases, n=775). Results The DIVAS unsaturated fat-rich diet reduced lipid metabolites with medium or long-chain fatty acid residuals containing no or few unsaturations in ceramides, cholesterol esters, diglycerides, and phospholipids, which we combine in the MLS (Figure 1B/C). Aside from the MLS, only non-high-density lipoprotein cholesterol (non-HDL-C) was significantly affected in the diet (Figure 1D). In multivariable adjusted models, the MLS, scaled to the observed change in DIVAS (i.e. the theoretical intervention effect), was strongly associated with reduced risk for incident CVD and T2D (Figure 2A). Further adjustment for established risk markers did not meaningfully alter the association, with the exception of the association with T2D and adjustment for plasma triglycerides. Translated to a hypothetical effect on case occurrence, the DIVAS diet intervention-induced MLS difference was associated with markedly fewer CVD (32%, 95%-CI: 21% to 42%) cases and T2D (26%, 95%-CI: 15% to 35%) cases in EPIC-Potsdam (Figure 2B). In contrast, initially observed associations of non-HDL-C, the only other intervention-affected marker, were attenuated when adjusting for the MLS. Conclusion Capturing diet effects using lipidomics profiling, as we show with the generated MLS, might provide superior biomarkers to monitor cardiometabolic benefits of changes to dietary fat quality.

Metabolomic Signatures of Sedentary Behavior and Cardiometabolic Traits in US Hispanics/Latinos: Results from HCHS/SOL.

The aim of this study was to understand the serum metabolomic signatures of moderate-to-vigorous physical activity (MVPA) and sedentary behavior, and further associate their metabolomic signatures with incident cardiometabolic diseases. This analysis included 2711 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 yr (2008-2011). An untargeted, liquid chromatography-mass spectrometry was used to profile the serum metabolome. The associations of metabolites with accelerometer-measured MVPA and sedentary time were examined using survey linear regressions adjusting for covariates. The weighted correlation network analysis identified modules of correlated metabolites in relation to sedentary time, and the modules were associated with incident diabetes, dyslipidemia, and hypertension over the 6-yr follow-up. Of 624 metabolites, 5 and 102 were associated with MVPA and sedentary behavior at false discovery rate (FDR) <0.05, respectively, after adjusting for socioeconomic and lifestyle factors. The weighted correlation network analysis identified 8 modules from 102 metabolites associated with sedentary time. Four modules (branched-chain amino acids, erythritol, polyunsaturated fatty acid, creatine) were positively, and the other four (acyl choline, plasmalogen glycerol phosphatidyl choline, plasmalogen glycerol phosphatidyl ethanolamine, urea cycle) were negatively correlated with sedentary time. Among these modules, a higher branched-chain amino acid score and a lower plasmalogen glycerol phosphatidyl choline score were associated with increased risks of diabetes and dyslipidemia. A higher erythritol score was associated with an increased risk of diabetes, and a lower acyl choline score was linked to an increased risk of hypertension. In this study of US Hispanics/Latinos, we identified multiple serum metabolomic signatures of sedentary behavior and their associations with risk of incident diabetes, hypertension, and dyslipidemia. These findings suggest a potential role of circulating metabolites in the links between sedentary behavior and cardiometabolic diseases.

Association of long-term triglyceride-glucose index level and change with the risk of cardiometabolic diseases.

The triglyceride-glucose (TyG) index is considered as a pivotal factor for various metabolic, cardiovascular, and cerebrovascular diseases. However, there is currently a paucity of relevant studies on the association between long-term level and change of TyG-index and cardiometabolic diseases (CMDs) risk. We aimed to explore the risk of CMDs in relation to the long-term level and change of TyG-index. Based on the prospective cohort study, a total of 36359 subjects who were free of CMDs, had complete data of triglyceride (TG) and fasting blood glucose (FBG) and underwent four health check-ups from 2006 to 2012 consecutively were followed up for CMDs until 2021. The associations between long-term level and change of TyG-index and CMDs risk were assessed by Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CIs). The TyG-index was calculated as ln [TG, mg/dL) × FBG, mg/dL)/2]. During the median observation period of 8 years, 4685 subjects were newly diagnosed with CMDs. In multivariable-adjusted models, a graded positive association was observed between CMDs and long-term TyG-index. Compared with the Q1 group, subjects with the Q2-Q4 group had increased progressively risk of CMDs, with corresponding HRs of 1.64(1.47-1.83), 2.36(2.13-2.62), 3.15(2.84-3.49), respectively. The association was marginally attenuated, after further adjustment for the baseline TyG level. In addition, compared with stable TyG level, both loss and gain in TyG level were associated with increased CMDs risk. Long-term elevated level and change of TyG-index are risk factors for the incident CMDs. Elevated TyG-index in the early stage remains to exert cumulative effects on the occurrence of CMDs even after accounting for the baseline TyG-index.

Ambient air pollution associated with incidence and progression trajectory of cardiometabolic diseases: A multi-state analysis of a prospective cohort

BackgroundPrevious studies on the association between ambient air pollution and cardiometabolic diseases (CMDs) focused on a single disease, without considering cardiometabolic multimorbidity (CMM) and the progression trajectory of CMDs. MethodsBased on the UK Biobank cohort, we included 372,530 participants aged 37–73 years at baseline (2006–2010) with follow-up until September 2021. Incident CMDs cases were identified based on self-reported information and multiple health-related records in the UK Biobank. CMM was defined as the occurrence of at least two CMDs, including ischemic heart disease (IHD), stroke and type 2 diabetes (T2D). Exposure to ambient air pollutants, including particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM2.5), ≤10 μm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated at participants' geocoded residential addresses based on the high-resolution (1 × 1 km) pollution data from 2001 to 2021 provided by UK Department for Environment, Food and Rural Affairs. Multi-state models with adjustment for potential confounders were used to examine the impact of long-term exposure to ambient air pollution on transitions from healthy to first CMD (FCMD), subsequently to CMM, and further to death. ResultsDuring a median follow-up of 12.6 years, 40,112 participants developed at least one CMD, 3896 developed CMM, and 21,739 died. Among the four pollutants, PM2.5 showed the strongest associations with all transitions from healthy to FCMD, to CMM, and then to death [hazard ratios (95 % confidence intervals) per interquartile range (IQR) increment: 1.62 (1.60, 1.64) and 1.68 (1.61, 1.76) for transitions from healthy to FCMD and from FCMD to CMM, and 1.62 (1.59, 1.66), 1.67 (1.61, 1.73), and 1.52 (1.38, 1.67) for death risk from healthy, FCMD, and CMM, respectively]. After dividing FCMDs into three specific CMDs, we found that ambient air pollution had differential impacts on disease-specific transitions within the same transition phase. ConclusionsOur findings indicate that there is potential for air pollution mitigation in contributing to the prevention of the development and progression of CMDs.

Comparison of the Concordance of Cardiometabolic Diseases and Physical and Laboratory Examination Findings between Monozygotic and Dizygotic Korean Adult Twins: A Cross-Sectional Study Using KoGES HTS Data.

This study investigated the contribution of genetic and environmental factors to cardiometabolic diseases (CMDs) by comparing disease concordance in monozygotic and dizygotic twins. This cross-sectional study analyzed 1294 (1040 monozygotic and 254 dizygotic) twin pairs (&gt;20 years) based on the Korean Genome and Epidemiology Study data (2005-2014). The odds ratios of disease concordance were calculated using binomial and multinomial logistic regression models. The occurrence of CMDs (hypertension, hyperlipidemia, type 2 diabetes, cerebral stroke, transient ischemic attack, and ischemic heart disease) and related physical and laboratory levels did not differ between the monozygotic and dizygotic twin groups. The odds for concordance of the presence/absence of CMDs and the likelihood of incident CMD within monozygotic twins were comparable to that of dizygotic twins. The absolute differences in hemoglobin A1c, insulin, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, and systolic blood pressure were lower in monozygotic twins than in dizygotic twins. Absolute differences in fasting glucose and diastolic blood pressure did not differ between groups. Although baseline levels of several laboratory parameters related to CMD showed a strong likelihood of heritability in monozygotic twins, CMD phenotype appears to be largely affected by environmental factors.

The association of measures of body shape and adiposity with incidence of cardiometabolic disease from an ageing perspective

While obesity increases the risk of developing cardiometabolic diseases (CMDs), these associations seem to attenuate with increasing age, albeit studied poorly. The present study aimed to investigate the associations between adiposity and CMDs in sex-specific groups of chronological age and leukocyte telomere length (LTL) as a measure of biological age. We investigated the associations between BMI, a body shape index, waist-to-hip ratio (adjusted for BMI) and total body fat, and incident coronary artery disease (CAD), type 2 diabetes (T2D) and ischemic stroke (IS) in 413,017 European-ancestry participants of the UK Biobank without CMD at baseline. We assessed the change in the associations between adiposity and CMD over strata of increasing chronological age or decreasing LTL. Participants (56% women) had a median (IQR) age of 57.0 (50.0–63.0) years. The median follow-up time was 12 years. People with higher BMI had a higher risk of incident CAD (HR 1.14 (95% confidence interval [CI] 1.13, 1.16)), T2D (HR 1.70 (95% CI 1.68, 1.72)) and IS (HR 1.09 (95% CI 1.06, 1.12)). In groups based on chronological age and LTL, adiposity measures were associated with higher risk of CAD and T2D in both men and women, but these associations attenuated with increasing chronological age (Pinteractions < 0.001), but not with decreasing LTL (Pinteraction men = 0.85; Pinteraction women = 0.27). Increased (abdominal) adiposity was associated with higher risk of incident CMDs, which attenuated with increasing chronological age but not with decreasing LTL. Future research may validate these findings using different measures of biological age.

Retinal vascular profile in predicting incident cardiometabolic diseases among individuals with diabetes.

To determine the longitudinal associations between retinal vascular profile (RVP) and four major cardiometabolic diseases; and to quantify the predictive improvements when adding RVP beyond traditional risk factors in individuals with diabetes. Subjects were enrolled from the Singapore Epidemiology of Eye Disease (SEED) study, a multi-ethnic population-based cohort. Four incident cardiometabolic diseases, calculated over a ~ 6-year period, were considered: cardiovascular disease (CVD), hypertension (HTN), diabetic kidney disease (DKD), and hyperlipidemia (HLD). The RVP-vessel tortuosity, branching angle, branching coefficient, fractal dimension, vessel caliber, and DR status-was characterized at baseline using a computer-assisted program. Traditional risk factors at baseline included age, gender, ethnicity, smoking, blood pressure (BP), HbA1c, estimated glomerular filtration rate (eGFR), or cholesterol. The improvements in predictive performance when adding RVP (compared with only traditional risk factors) was calculated using several metrics including area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI). Among 1770 individuals with diabetes, incidences were 6.3% (n=79/1259) for CVD, 48.7% (n=166/341) for HTN, 14.6% (n=175/1199) for DKD, and 59.4% (n=336/566) for HLD. DR preceded the onset of CVD (RR 1.85[1.14;3.00]) and DKD (1.44 [1.06;1.96]). Narrower arteriolar caliber preceding the onset of HTN (0.84 [0.72;0.99]), and changes in arteriolar branching angle preceded the onset of CVD (0.78 [0.62;0.98]) and HTN (1.15 [1.03;1.29]). The largest predictive improvement was found for HTN with AUC increment of 3.4% (p=.027) and better reclassification of 11.4% of the cases and 4.6% of the controls (p=.008). We found that RVPs improved the prediction of HTN in individuals with diabetes, but add limited information for CVD, DKD, and HLD predictions.

Coarse Grain Consumption and Risk of Cardiometabolic Diseases: A Prospective Cohort Study of Chinese Adults

BackgroundLower consumption of whole grains is associated with higher risks of diabetes and coronary heart disease in Western populations, but evidence is still limited for stroke. Moreover, little is known in China, where the rates of cardiometabolic diseases are high and the grain types consumed are different from those in Western countries. ObjectivesTo examine the associations between coarse-grain (e.g., millet, corn, and sorghum) consumption and incident cardiometabolic diseases among Chinese adults. MethodsThe prospective China Kadoorie Biobank enrolled >0.5 million adults aged 30–79 years from 10 urban and rural areas during 2004–2008. At baseline, consumption frequencies (in 5 categories from “never” to “daily”) of 12 major food groups, including coarse grains, were collected using a validated FFQ. After a median of 11 years of follow-up, 17,149 cases of diabetes, 29,876 ischemic strokes, 6097 hemorrhagic strokes, and 6704 major coronary events were recorded among 461,047 participants without a prevalence of major chronic diseases at baseline. Cox regression analyses were used to yield adjusted HRs for each disease associated with coarse-grain consumption. ResultsOverall, 13.8% of participants reported regularly consuming (i.e., ≥4 days/week, regular consumers) and 29.4% reported never or rarely consuming coarse grains (i.e., nonconsumers) at baseline. Compared with nonconsumers, regular consumers had lower risks of diabetes (adjusted HR, 0.88; 95% CI, 0.78–0.98) and ischemic stroke (adjusted HR, 0.86; 95% CI, 0.81–0.93), but not hemorrhagic stroke (adjusted HR, 0.96; 95% CI, 0.76–1.20) or major coronary events (adjusted HR, 0.95; 95% CI, 0.81–1.12). For diabetes and ischemic stroke, each 100 g/day increase in the usual intake of coarse grains was associated with 14% (adjusted HR, 0.86; 95% CI, 0.76–0.97) and 13% (adjusted HR, 0.87; 95% CI, 0.81–0.94) lower risks, respectively, with similar results in various subgroups. ConclusionsIn Chinese adults, higher coarse-grain consumption is associated with lower risks of diabetes and ischemic stroke, supporting the promotion of coarse-grain consumption in China.

Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation.

Background:In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification.Methods:The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks.Results:Sixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95% CI, 0.5–0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95% CI, 0.4–0.7) SD units.Conclusions:We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.

IDF21-0504 High-density lipoprotein cholesterol and cardiometabolic disease (CMD) in a large cohort study in Southwest China

Background: The “good cholesterol” label for high-density lipoprotein cholesterol (HDL-C) has been challenged by recent evidence on the risk of cardiovascular disease increased with elevated HDL-C. Cardiovascular disease (CVD) and diabetes, with a high mortality risk and sharing common pathways of prevention and management strategies, has been considered as major cardiometabolic disease (CMD) and is most common in low- and middle-income countries and areas. In addition, uncertainty remains regarding the relevance of HDL-C for CMD among Chinese population, with higher incidences but limited health-care services in CVD and diabetes. Aim: We aimed to examine the associations of CMD and HDL-C at baseline and its changes in Southwest China. Method: The current study examined data from the Guizhou Population Health Cohort Study (GPHCS) of 9280 participants aged 18 to 95 years recruited from 12 areas since 2010 in Guizhou Province, where located at Southwest China. Participants were followed-up until December 2020 and 7098 of them were eligible for this analysis. CMD was defined as the existence of at least one of the following events including myocardial infarction, ischemic stroke, hemorrhagic stroke, and diabetes. Blood lipid level and disease information were collected at baseline and follow-up. Cox proportional hazards models were used to estimate the risk of CMD associated with baseline level and changes of HDL-C. Sensitive analysis were conducted among participants with or without dyslipidemia. Results: During a median of 6.57 years of follow-up, 908 subjects developed incident CMD. There was a linear-shaped association between baseline HDL-C level and CMD risk by using restricted cubic-spline (RCS) analysis. Compared with subjects at the second quartile of baseline HDL-C, those at the third quartile had 1.22-fold (95%CI: 1.13-1.45) increased risk for CMD after adjustment for age, sex, area, smoking status and body mass index (BMI) at baseline. Similar association was observed between changes of HDL-C and CMD with an adjusted Hazard Ratio (HR) of 1.19 (95%CI: 1.11-1.41). In addition, the risk of co-existence of two or more CMD was positively associated with higher baseline HDL-C level (multi-adjusted HR:1.20, 95%CI:1.11-1.42). Discussion: Elevated HDL-C provided some predictive information for cardiometabolic disease (CMD) in Southwest China.

Serum ferritin and incident cardiometabolic diseases in Scottish adults

BackgroundIron stores, estimated as ferritin levels, and type 2 diabetes (T2D) have been associated previously, while findings regarding coronary heart disease (CHD) and cerebrovascular disease (CEVD) are still inconclusive. No study has focused on simultaneous evaluation of associations between iron stores and the above cardiometabolic diseases (CMD) in the same population. We aim to evaluate the association between serum ferritin and risk of T2D, CHD and CEVD in Scottish population over a wide range of ferritin levels.MethodsLongitudinal study in 6,497 participants of the 1995 and 1998 Scottish health surveys, who were followed-up until 2011. Cox regression models were conducted adjusting for age, sex/menopausal status, fibrinogen, GGT levels, smoking, alcohol consumption, total cholesterol, HDL-cholesterol, blood pressure, and BMI. Ferritin was used as continuous (sex/menopausal status-specific Z score) and categorical variable (sex/menopausal status-specific quartiles, quintiles and sextiles).ResultsDuring follow-up, 4.9% of the participants developed T2D, 5.3% CHD, and 2.3% CEVD. By using ferritin quartiles, serum ferritin was positively associated with T2D, CHD and CEVD but only the association with T2D remained after adjustment for covariates [Quartile 4 v. 1: adjusted HR 95% CI 1.59 (1.10–2.34); P = 0.006]. When ferritin sextiles were used (6 v. 1), the ferritin-CEVD association became slightly stronger and significant [adjusted HR 95% CI 2.08 (1.09–3.94); P = 0.024].ConclusionsIron stores relate differently to each CMD. Serum ferritin levels were positively and independently associated with incident T2D, and with incident CEVD if higher cut-off points for high ferritin levels were considered.

Abdominal obesity and incident cardio-metabolic disorders in Asian-Indians: A 10-years prospective cohort study

Background and aimsTo estimate the strength of association between abdominal obesity and incident cardio-metabolic diseases. MethodsA subset of Chandigarh Urban Diabetes study cohort (n = 543) was followed after a mean of 10.7 years for development of diabetes, prediabetes, dysglycaemia (either prediabetes or diabetes), hypertension and atherosclerotic cardiovascular disease (ASCVD). Diabetes and prediabetes were defined as per American Diabetes Association consulting group criteria, hypertension as blood pressure of ≥140/90 mmHg and ASCVD after review of medical records. Abdominal obesity was defined as waist circumference of ≥80 cm and ≥90 cm in females and males, respectively. ResultsAs compared to non-obese (n = 209), abdominally obese individuals (n = 334) had a higher risk of diabetes [RR:1.82(1.28–2.57)], prediabetes [RR:1.40(1.05–1.85)], dysglycaemia [ RR:1.38(1.07–1.78)], hypertension [RR: 1.84(1.30–2.59)] and ASCVD [RR:2.12(1.02–4.4)]. The optimal cut-off of waist circumference for detecting incident diabetes, hypertension and ASCVD in females was 88 cm, 85 cm and 91 cm, respectively; while in males it was 90 cm, 87 cm and 94 cm, respectively. ConclusionIn Asian-Indians, abdominal obesity as defined by waist circumference of ≥90 cm and ≥80 cm in males and females, respectively is associated with a twofold higher risk of diabetes, hypertension and ASCVD. In addition, the current-cut-offs of waist circumference to define abdominal obesity need reconsideration to optimally identify individuals at a higher risk of cardio-metabolic diseases. However, a high attrition rate represents a major limitation.