Background This study aimed to investigate the associations between the triglyceride-glucose (TyG) index in young adulthood with incident cardiovascular disease (CVD) and mortality. Methods We included 4,754 participants from the Coronary Artery Risk Development in Young Adults study at baseline. The TyG index was calculated as ln (fasting TG [mg/dl] × fasting glucose [mg/dl]/2), and the TyG index trajectories were identified by using the latent class growth mixture model. We evaluated the association between the baseline and trajectories of the TyG index with incident CVD events and all-cause mortality using Cox proportional hazards regression analysis. The added value of the TyG index included in pooled cohort equations for CVD prediction was also analyzed. Results Among 4754 participants (mean age 24.72 years, 45.8% male, 51.2% black), there were 158 incident CVD events and 246 all-cause mortality during a median 25 years follow-up. After adjusting for multiple confounding variables, each one-unit increase in the TyG index was associated with a 96% higher CVD risk (hazard ratio [HR] 1.96, 95% confidence interval [CI] 1.44–2.66) and a 85% higher all-cause mortality risk (HR 1.85, 95% CI 1.45–2.36). Three distinct trajectories of the TyG index along the follow-up duration were identified: low (44.0%), moderate (45.5%), and high (10.5%). Compared with those participants in the low TyG index trajectory group, those in the high TyG index trajectory group had a greater risk of CVD events (HR 2.35, 95% CI 1.34–4.12) and all-cause mortality (HR 3.04, 95% CI 1.83–5.07). The addition of baseline TyG index to pooled cohort equations for CVD improved the C-statistics (P < 0.001), integrated discrimination improvement value (P < 0.001), and category-free net reclassification improvement value (P = 0.003). Conclusions Higher baseline TyG index levels and higher long-term trajectory of TyG index during young adulthood were significantly associated with an increased risk of incident CVD events and all-cause mortality in later life.

Aims We aimed to investigate whether the triglyceride–glucose (TyG) index, an easy-calculated and reliable surrogate of insulin resistance, was associated with the development of heart failure (HF) and left ventricular (LV) dysfunction. Methods and results A total of 12 374 participants (mean age: 54.1 ± 5.7 years, male: 44.7%) free of history of HF and coronary heart disease at baseline from the Atherosclerosis Risk in Communities study were included. The TyG index was calculated as ln[fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The long-term TyG index was calculated as the updated cumulative average TyG index using all available TyG index from baseline to the events of HF or the end of follow-up. We evaluated the associations of both the baseline and the long-term TyG index with incident HF using Cox regression analysis. We also analysed the effect of the TyG index on LV structure and function among 4889 participants with echocardiographic data using multivariable linear regression analysis. There were 1958 incident HF cases over a median follow-up of 22.5 years. After adjusting for potential confounders, 1-SD (0.60) increase in the baseline TyG index was associated with a 15% higher risk of HF development [hazard ratio (HR): 1.15, 95% confidence interval (CI): 1.10–1.21]. Compared with participants in the lowest quartile of the baseline TyG index, those in the highest quartile had a greater risk of incident HF [HR (95% CI): 1.25 (1.08–1.45)]. In terms of LV structure and function, a greater baseline TyG index was associated with adverse LV remodelling and LV dysfunction. Similar results were found for the long-term TyG index. Conclusion In a community-based cohort, we found that a greater TyG index was significantly associated with a higher risk of incident HF and impaired LV structure and function.

Aims Prescription of weight loss to individuals is often characterized by weight fluctuations. However, current body weight management metrics may have difficulty characterizing the changes in body weight over time. We aims to characterize the long-term changes using body weight time in target range (TTR) and test its independent association with cardiovascular outcomes. Methods We included 4,468 adults from the Look AHEAD (Action for Health in Diabetes) trial. Body weight TTR was defined as the percentage of time during which body weight was within the Look AHEAD weight loss goal range. The associations of body weight TTR with cardiovascular outcomes were analyzed using multivariable Cox modeling and restricted cubic spline function. Results Among the participants (mean age 58.9 years, 58.5% women, 66.5% White), there were 721 incident primary outcomes (cumulative incidence: 17.5%, 95% confidence interval [CI]: 16.3%-18.8%) during a median of 9.5 years of follow-up. Each 1-SD (standard deviation) increase in body weight TTR was significantly associated with a decreased risk of the primary outcome (hazard ratio [HR]: 0.84, 95% CI: 0.75-0.94) after adjusting for mean and variability of body weight and traditional cardiovascular risk factors. Further analyses using restricted cubic spline indicated the inverse association between body weight TTR and primary outcome in a dose-dependent manner. Similar associations remained significant among the participants with a lower baseline or mean body weight. Conclusion In adults with overweight/obesity and type 2 diabetes, higher body weight TTR was independently associated with lower risks of cardiovascular adverse events in a dose-response manner.

Background and Aims Prediabetes is a highly heterogenous metabolic state with increased risk of cardiovascular disease (CVD). Current guidelines raised the necessity of CVD risk scoring for prediabetes without clear recommendations. Thus, this study aimed to systematically assess the performance of 11 models, including five general population-based and six diabetes-specific CVD risk scores, in prediabetes. Methods and results A cohort of individuals aged 40-69 years with prediabetes (HbA1c ≥ 5.7 and &lt;6.5%) and without baseline CVD or known diabetes was identified from the UK Biobank, which was used to validate 11 prediction models for estimating 10-year or 5-year risk of CVD. Model discrimination and calibration were evaluated by Harrell's C-statistic and calibration plots, respectively. We further performed decision curve analyses to assess the clinical usefulness. Overall, 56,831 prediabetic individuals were included, of which 4,303 incident CVD events occurred within a median follow-up of 8.9 years. All the 11 risk scores assessed had modest C-statistics for discrimination ranging from 0.647 to 0.680 in prediabetes. Scores developed in the general population did not outperform those diabetes-specific models (C-statistics 0.647-0.675 vs. 0.647-0.680), while the PREDICT-1° Diabetes equation developed for type 2 diabetes performed best [0.680 (95% confidence interval 0.672-0.689)]. The calibration plots suggested overall poor calibration except that the PREDICT-1° Diabetes equation calibrated well after recalibration. The decision curves generally indicated moderate clinical usefulness of each model, especially worse within high threshold probabilities. Conclusion Neither risk stratification schemes for the general population nor those specific for type 2 diabetes performed well in the prediabetic population. The PREDICT-1° Diabetes equation could be a substitute in the absence of better alternatives, rather than the general population-based scores. More precise and targeted risk assessment tools for this population remain to be established.

Background This study aimed to investigate the associations between the triglyceride-glucose (TyG) index in young adulthood with incident cardiovascular disease (CVD) and mortality. Methods We included 4,854 participants from the Coronary Artery Risk Development in Young Adults study at baseline. The TyG index was calculated as ln (fasting triglyceride [mg/dl] ⋅ fasting glucose [mg/dl]/2), and the TyG index trajectories were identified by using the latent class growth mixture model. CVD events and all-cause mortality were adjudicated over 25 years of follow-up. We evaluated the association between the baseline and trajectories of the TyG index with incident CVD events and all-cause mortality using Cox proportional hazards regression analysis. Results Among 4,854 participants (mean age 24.76 years, 45.6% male, 51.0% black), there were 161 incident CVD events and 250 all-cause mortality during a median 25 years follow-up. After adjusting for multiple confounding variables, each one-unit increase in the TyG index was associated with a 93% higher CVD risk (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.40–2.65) and a 69% higher all-cause mortality risk (HR 1.69, 95% CI 1.31–2.18). Similar results were observed when participants were categorized by TyG index quartiles, with a greater risk of CVD events (HR 2.54, 95% CI 1.44–4.49) and all-cause mortality (HR 1.91, 95% CI 1.27–2.89) for those participants in the highest quartile as compared with the lowest quartile. Three distinct trajectories of the TyG index along the follow-up duration were identified: low (43.5%), moderate (45.6%), and high (10.8%). Compared with those participants in the low TyG index trajectory group, those in the high TyG index trajectory group had a greater risk of CVD events (HR 2.17, 95% CI 1.25–3.76) and all-cause mortality (HR 2.63, 95% CI 1.57–4.39). Conclusions Higher baseline TyG index levels and higher long-term trajectory of TyG index during young adulthood were significantly associated with a high risk of incident CVD events and all-cause mortality in later life.

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