BACKGROUND:We aimed to evaluate the prognostic value of electrocardiographic (ECG) parameters in estimating long-term cardiovascular disease (CVD) risk and their incremental predictive value when added to the HellenicSCORE II+ model in an apparently healthy adult population. METHODS:This analysis included 1482 participants (mean age 46 ± 15 years; 49% male) from the population-based prospective ATTICA study who had baseline ECG recordings, comprehensive clinical and biochemical assessment, and complete 20-year follow-up data. RESULTS:During the 20-year follow-up period, 633 of the 1482 participants (43%) experienced a first fatal or non-fatal CVD event. Out of these, 86 were fatal, leading to a 20-year CVD mortality rate of 9.5% in males and 2.4% in females (p < 0.001). QT interval and QRS duration showed significant associations for both 10-year and 20-year CVD risk, with a 10 ms prolongation in QT interval to be associated with a 4.0% increase in 10-year CVD risk (HR:1.040, 95%CI:1.017-1.064) and a 5.3% increase in 20-year CVD risk (HR:1.053, 95%CI:1.038-1.068), while the same prolongation in the QRS duration was linked to a 33.6% increase in 10-year CVD risk (HR:1.336, 95%CI:1.213-1.470) and 37.2% increase in 20-year CVD risk (HR:1.372, 95%CI:1.287-1.463). The inclusion of QRS duration increased the HellenicSCORE II+ model's performance, yielding superior discrimination and reclassification measures and improving overall risk stratification. CONCLUSIONS:Routine ECG parameters, particularly QRS duration, enhance long-term CVD risk prediction beyond established clinical models. Given the wide availability and low cost of ECG, these findings support further validation and integration of ECG-derived markers into preventive risk assessment strategies.

OBJECTIVE:To evaluate the independent contribution of intensity, duration, and frequency of physical activity (PA) and lifelong risk of cardiovascular disease (CVD). METHODS:ATTICA is a population-based cohort study that was conducted in the Attica region (Greece) in 2002, and included 3042 adults (45 [11] y, 50% males). Participants' PA levels, together with information regarding CVD incidence during 2002-2022, were available from 1988 participants (45 [12] y old, 987 males and 1001 females). PA volume (intensity, duration, and frequency) was evaluated using the validated International Physical Activity Questionnaire, in consecutive follow-up examinations (2006, 2012, and 2022). RESULTS:Over 20 years, 36% of participants experienced a CVD event. Moderate and high PA volume was linked to 48% and 37% lower CVD risk, respectively, versus low volume (P < .05). Intensity of PA was the strongest protective factor. Benefits were more evident in nonobese individuals and those with fewer CVD risk factors. CONCLUSIONS:Long-term, moderate to vigorous PA is associated with lower CVD risk. Intensity and duration matter more than frequency. These findings support intensity-focused, individualized PA recommendations for cardiovascular prevention.

The aim of this study was to evaluate the role of central adiposity, sex and age, on the association between total-animal and total-plant based protein and the 20-year cumulative incidence of type 2 diabetes (T2D), among apparently healthy adults participating in the ATTICA cohort study (2002–2022). The present analysis included data from 2,000 individuals free of atherosclerotic cardiovascular disease and T2D at baseline (age 43 ± 13 years; 51

AIM:Individuals with prediabetes carry an increased cardiometabolic burden; however, the extent to which prediabetes contributes to cardiovascular disease (CVD) risk remains uncertain. We aimed to investigate the 20-year incidence of CVD among individuals with impaired fasting glucose (IFG) and to determine whether IFG independently predicts CVD events. METHODS:This study is based on the 20-year follow-up data (2002-2022) of the ATTICA study, a population-based prospective cohort of rural population living in the greater Athens area, Greece. A total of 1,796 adults free of CVD and T2D at baseline were included, of whom 333 (18.5%) had impaired fasting glucose (IFG) and 1,463 (81.5%) had normal fasting glucose (NFG). Incident fatal or non-fatal CVD events were recorded during follow-up. Cox proportional hazards models were applied to evaluate the association between IFG and CVD. RESULTS:Over the 20-year follow-up, all participants with IFG progressed to T2D, compared with 13.5% of those with NFG (p < 0.001). The incidence of CVD was higher in the IFG group (40.2%) than in the NFG group (30.2%, p=0.001). In multivariable models, IFG independently predicted CVD events (HR=1.21, 95%CI [1.01, 1.48] p=0.038). Landmark analyses demonstrated that earlier onset of T2D (before 10 years) was associated with a higher subsequent risk of CVD (adjusted OR 2.46, p < 0.05). CONCLUSIONS:Prediabetes defined by IFG is an independent predictor of CVD, beyond traditional cardiometabolic risk factors. Moreover, earlier T2D onset markedly increases CVD risk, highlighting the need for timely screening and preventive strategies in individuals with prediabetes.

BACKGROUND:Individuals with excess body weight do not share the same risk for cardiovascular disease (CVD). The phenotype of metabolically healthy obesity (MHO) has drawn the attention of the scientific community due to a potentially reduced CVD risk compared with the phenotype of metabolically unhealthy obesity (MUO). METHODS:A prospective cohort study was conducted involving 3042 participants from the Attica region in Greece. Baseline demographic, clinical, and lifestyle characteristics were assessed, with participants categorized by their obesity and metabolic health status. Cox proportional hazards models were used to analyze the association between obesity/metabolic health status and 20-year CVD incidence, adjusting for relevant covariates. RESULTS:The sample at baseline comprised 38% individuals who were metabolically healthy without obesity (MHWO), 44% individuals who were metabolically unhealthy without obesity (MUWO), 6% individuals with MHO, and 12% individuals with MUO. Over the 20-year follow-up, 718 participants experienced a CVD event; participants with MUO demonstrated the highest incidence rate (61.1%). Cox regression analyses revealed that individuals with MUO had an 85% higher risk of developing CVD compared with individuals having the MHWO phenotype (HR = 1.85, 95% CI = 1.02-3.58). Individuals with MHO had a 39% elevated risk compared with individuals having the MHWO phenotype (HR = 1.39, 95% CI = 1.06-3.42). Groups with MHO and MUO had independently increased CVD risk, even after multivariable adjustment. CONCLUSIONS:Individuals with MUO exhibit the highest risk, but individuals with MHO also have an independently increased CVD risk, emphasizing the significant impact of both obesity and metabolic health status on long-term CVD incidence.

To identify habitual dietary patterns within a Mediterranean population-based cohort, examine their associations with cardiovascular disease (CVD) risk factors and outcomes over 20 years, and interpret them in sustainability terms. A total of 3,042 CVD-free adults from the ATTICA Study were enrolled in 2001–2002. Dietary intake was assessed using a validated food frequency questionnaire, and principal component analysis was utilized to derive a posteriori dietary patterns. Participants were followed for 20 years, with complete CVD data available for 1988 individuals. CVD incidence, lifetime risk, and disability-adjusted life years (DALYs) were calculated. Multivariate Cox proportional hazards, beta and gamma regression models examined associations between dietary patterns and CVD outcomes. Three dietary patterns were identified, explaining 46.5

BACKGROUND:Given that low-grade inflammation is implicated in the pathophysiology of age-related frailty, we tested the hypothesis that individual blood biomarkers are associated with the risk of developing frailty in later life. METHODS:Participants of the ATTICA cohort aged ≥ 33 years in 2002 were assessed for age-related frailty in 2024. By multivariable logistic regression models, we tested the association of an array of baseline immune-related biomarkers, as well as of an aggregate score, namely ImmActScore, that combines IL-6, TNF-α and fibrinogen, on the odds of later-life frailty. RESULTS:Among 574 participants (mean baseline age 48 ± 8; 50% male), phenotypic FRAIL scale assessment categorized 6% as frail, 29% as prefrail, and 65% as robust. After adjustments for various socio-demographic and clinical characteristics, baseline fibrinogen (OR=1.004, 95%CI:1.000-1.007, p = 0.037) and ImmActScore (OR=1.239, 95%CI:1.007-1.525, p = 0.042) showed significant associations, suggesting that higher baseline levels are associated with increased odds for prefrailty/frailty in the very long-term. CONCLUSIONS:Fibrinogen and a composite score capturing immune activation status by combining IL-6, TNF-α and fibrinogen, were both associated with the odds of prefrailty/frailty after 22 years. Further studies are warranted to confirm whether assessing immune-related biomarkers in middle-age may help identify individuals with a higher likelihood of frailty.

BACKGROUND:A strong correlation exists between low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B100 (apoB). However, evidence suggests that LDL-C and non-HDL-C may underestimate apoB, potentially obscuring residual cardiovascular risk. Furthermore, interactions between apoB and lipoprotein(a) are implicated in atherogenesis. This study sought to determine whether discordance between apoB, LDL-C, non-HDL-C, or lipoprotein(a) is associated with 20-year atherosclerotic cardiovascular disease (ASCVD) risk within a cohort of apparently healthy adults. METHODS:A cohort of 3042 CVD-free adults residing in greater Athens, Greece, was recruited in 2002. A 20-year follow-up was conducted in 2022, comprising n = 2169 participants, of which n = 1988 had complete data for cardiovascular disease incidence. Discordance between biomarkers was defined based on recommended lipid thresholds. Cox proportional hazards models were used to assess the association between discordant/concordant biomarker pairs and 20-year ASCVD risk. RESULTS:ApoB strongly correlated with LDL-C and non-HDL-C, though concordance was limited. Increased 20-year ASCVD cumulative incidence with elevated apoB levels, beyond LDL-C, non-HDL-C, and lipoprotein(a). Discordance analysis revealed that elevated apoB independently predicted increased 20-year ASCVD risk, regardless of non-HDL-C and lipoprotein(a). However, this effect was observed only on concomitantly elevated LDL-C levels. Incorporating apoB into the assessment of traditional modifiable risk factors elucidated part of the previously residual 20-year ASCVD risk, especially in individuals with elevated LDL-C, non-HDL-C, or lipoprotein(a) levels. CONCLUSIONS:ApoB may be a superior biomarker for assessing long-term ASCVD risk, indicating that apoB-containing lipoprotein particle number, rather than cholesterol content, is a more robust predictor of ASCVD risk.

This study investigated the relationship between apolipoprotein B (apoB), “excess apoB” (apoB beyond low-density lipoprotein cholesterol (LDL-C)), and apoB/apolipoprotein A1 (apoA1) ratio with 20-year atherosclerotic cardiovascular disease (ASCVD) incidence, using an age- and sex-specific approach. In 2002, a cohort of 3042 adults, free of cardiovascular disease (CVD) residing in the greater Athens area (Greece) was recruited. A 20-year follow-up was conducted in 2022, comprising of 2169 participants, of whom 1988 had complete data for CVD incidence. Cox proportional hazards models were used to assess the association of apoB, excess apoB, and apoB/apoA1 with 20-year ASCVD risk and residual risk (events not predicted by standard factors). Older participants and males had higher levels of apoB, excess apoB, and apoB/apoA1. In the overall cohort, only apoB was significantly associated with ASCVD risk (hazard ratio (HR), 1.006; p = 0.003). However, age- and sex-dependent associations were observed as apoB, excess apoB, and apoB/apoA1 significantly predicted increased ASCVD incidence only in males under 40 years (HR 1.025, p = 0.005; 1.052, p = 0.003; 1.396, p = 0.002; respectively). Significant associations were observed with residual ASCVD risk in the overall cohort, with the most pronounced associations seen in males under 40 (HR 1.023, p = 0.001; 1.039, p < 0.001; 1.285, p = 0.002; respectively). The association of apoB, excess apoB, and apoB/apoA1 with long-term ASCVD incidence and residual risk demonstrates age- and sex-dependent variations, with younger males showing elevated risk, highlighting the value of these markers beyond traditional risk factors and emphasizing the need for age- and sex-specific considerations in ASCVD risk assessment.

PURPOSE:This study aimed to estimate cardiovascular disease (CVD) burden attributable to chronic kidney disease (CKD) and whether this burden varies in participants with different population characteristics. METHODS:Our sample included 1988 adults free-of-CVD at baseline who took part in the ATTICA study (2002-2022). Estimated glomerular filtration rate (eGFR) was calculated based on the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined in 2002, according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines, as an eGFR ≤ 60 mL/min/1.73 m2. Combined fatal or non-fatal CVD events were assessed in 2006, 2012 and 2022 based on WHO-ICD-10. Population attributable fractions for multiadjusted models were computed based on Miettinen's formula. Stratified analyses were also performed. RESULTS:At baseline, CKD prevalence was 4.7 % (n = 94). During the 20-year period, 36.1 % of participants developed CVD. A higher percentage of participants with CKD developed CVD compared to those without (77 % vs. 34 %). Approximately 6 out of a 100 new CVD cases (95 %CI: 1.7 %, 8.1 %) would have been prevented if CKD had been properly managed. Variations in these fractions were observed by sex and presence of comorbidities. CONCLUSIONS:Albeit more research is warranted, our study supports that CKD should become a public health priority, and specifically a CVD priority.

Introduction:The stagnant cost of cardiovascular disease (CVD) can be diminished with the effective management of well-known lifestyle factor modifications. However, when it comes to treating the individual and not the disease, research on these factors and their interactions is limited. Aim:The purpose of this study was to evaluate the number of CVD cases that would be prevented in males/females and younger/older participants if specific lifestyle patterns were managed. Methods:The sample was 1,988 (mean age: 45 ± 14 years, 49.7% male) individuals from the ATTICA cohort study (2002-2022), who were initially free-of-CVD. Trained health professionals evaluated combined fatal/non-fatal CVD outcomes, 2 major non-modifiable risk factors (i.e., sex and age) and 6 categories of modifiable risk factors [i.e., low/middle socio-economic status (SES), urban residence, at least one clinical, one psychological or one unhealthy lifestyle factor]. Population attributable fractions (PAF) and generalized impact fractions (GIFs) (percentage of exposure removal: 70%), were computed for each sole factor, as well as different combinations of these factors, representing different lifestyle patterns. Results:A lifestyle pattern comprising of having a low/middle SES, urban residence, at least one clinical, psychological and unhealthy lifestyle factor was associated with a PAF of 82%; 8 out of 10 CVD cases would have been prevented if all these factors had been completely managed in the sample. The respective PAF and GIF was similar in males and females but differed significantly based on the age of the participants. PAF varied between 69% and 80%, when participants had all 5 factor categories, but were healthy (with no clinical factors) or of high SES, respectively. Conclusion:The increased burden of CVD could be significantly reduced with tailored programs focusing on managing lifestyle patterns, especially in individuals (males or females) older than 45 years-old.

Background: The aim of this study was to explore the associations between symptoms of depression and anxiety on 20-year cardiovascular disease (CVD) incidence among apparently healthy Greek adults. Methods: In the context of a population-based, prospective health survey, the ATTICA study (2002-2022), 853 adult participants without previous CVD history [453 men (45 +/- 13 years) and 400 women (44 +/- 18 years)] underwent evaluations regarding psychological factors (depression through ZDRS and anxiety through STAI scales), lifestyle factors (smoking, diet, physical activity) and medical conditions (obesity, hypertension, hypercholesterolemia, diabetes mellitus) at both baseline and 10-year follow-up examinations. CVD incidence was assessed based on medical records and hospital data. Cox proportional hazard models were developed to evaluate the association between psychological symptoms on the 20-year CVD incidence, after adjusting for various characteristics. Results: The results indicated that the chronic burden of depression and anxiety was independently associated with increased CVD risk during the 20-year follow-up period (crude hazard ratios of cumulative at baseline and at 10-year follow-up depressive symptoms score on CVD incidence was 1.04 95%CI (1.03, 1.05), and for anxiety score was 1.03 95%CI (1.02, 1.04)); the hazard ratios were higher especially for younger participants and those who did not adhere steadily to the Mediterranean diet during the follow-up period. Conclusions: Based on our findings, standardized psychological assessments focusing on depression and anxiety should be integrated as a distinct and additional component within the preventive strategies for CVD implemented by health authorities at the population level.

Nutrition epidemiology research scarcely focuses on the relationship between dietary patterns that are beneficial for both planet and human health. This study aimed to examine the association between adherence to a sustainable, planetary-healthy dietary pattern, i.e., the EAT-Lancet Reference Diet (EAT-LD), and 20-year cardiovascular disease (CVD) incidence, in a Mediterranean population. Τhe ATTICA study is a prospective cohort study with a baseline phase in 2002 and 3 consecutive follow-ups (in 2006, 2012, 2022). The EAT-Lancet Index (EAT-LI) and the MedDietScore scales were calculated based on previously published guidelines to assess the adherence to the respective dietary pattern. The current sample consisted of 1,988 Greek adults initially free-of-CVD at baseline. The development of a cardiovascular event was assessed throughout the 20-year period (WHO-ICD-10 classification). The 20-year incidence of CVD was 3600 cases/10,000 individuals (95

OBJECTIVE:This study aimed to examine the 20-year incidence of cardiovascular disease (CVD) in menopausal women, exploring the interplay of traditional and menopause-specific risk factors. METHOD:The ATTICA study is a prospective cohort survey established in 2001-2002, with three consecutive follow-ups performed in 2006, 2012 and 2022. A total of 1001 women with complete data for CVD evaluation comprised the sample of the current study. For the purposes of this analysis, women were classified according to their menopausal status (at menopause, 276 out of 1001 women [27.6%]). RESULTS:The 20-year cumulative CVD incidence was 321 cases among 1001 women (32%); 274 out of the 337 (81.3%) who were at menopause developed CVD, whereas 47 out of 664 at premenopause developed CVD (7.1%). Age-adjusted analysis revealed that postmenopausal women had 2.25 times (95% confidence interval: 1.20, 4.24) higher risk of CVD, compared to women not at menopause. The fully adjusted model revealed that history of diabetes and hypercholesterolemia were significant predictors for the 20-year-CVD events. Moreover, high-sensitivity C-reactive protein was a significant predictor for CVD events only in women aged above 52 years at menopause. CONCLUSION:Postmenopausal women had an age-adjusted 2.25 times higher 20-year risk of CVD, as compared to women who were not at menopause. Prevailed hypercholesterolemia and diabetes were the most important determinants for long-term CVD events, whereas chronic systemic inflammation had significant predictive value only in women aged above 52 years at menopause.

The aim of the present study is to investigate the association between 20-year trajectories of physical activity status and cardiovascular disease (CVD) incidence, among Acute Coronary Syndrome (ACS) patients. GREECS study is a multi-centered prospective study. Almost all (n = 2172; mean age 62 ± 11 years; 1649 (76%) males) consecutive patients who were hospitalized in the cardiology clinics or the emergency cardiology departments were entered in the study. Four physical activity trajectories were formed regarding the 20-year tracking (from 2004 to 2024), of their physical activity levels (i.e., always inactive or active, turned from inactive/active). Of the 1913 ACS patients who participated in the 20-year follow-up, 51% were consistently inactive, 31% changed from physically active to inactive, 11% from inactive to active, and 7% were consistently active. During the 20-year follow-up 67% of ACS patients experienced a new CVD event. Consistently active patients had 45% lower risk for a recurrent CVD event during the 20-year follow-up period (95% CI, 12% to 64%), as compared to consistently inactive. Sustained engagement in physical activity is associated with a reduced risk of recurrent CVD events among ACS patients. These findings underscore the importance of promoting and sustaining physical activity as a key component of tertiary CVD prevention.

The growing prevalence of overweight and obesity globally highlights the need to reconsider the thresholds for defining excess body weight, especially as the health risks associated with weight gain continue to impact population health metrics. This study aimed to evaluate the population attributable fraction (PAF) and prevented fraction for the population (PFP) of CVD cases by body weight trajectories over a 20-year period (2002–2022). The studied population-based sample was 1348 individuals (39(10) years old, 48

Background and aimThis study aims to investigate the role of the built environment in terms of urban-rural disparities in cardiovascular disease (CVD) epidemiology, focusing on middle- and long-term CVD risk assessment. Moreover, this study seeks to explore sex-specific differences in urban and rural settings.MethodsThe ATTICA Study is a prospective study conducted from 2002 onwards. At baseline, a random sample of 3,042 CVD-free adults (49.8% men) were randomly drawn from the population of the Attica region, in Greece, with 78% dwelling in urban and 22% in rural municipalities. Follow-up examinations were performed in 2006, 2012, and 2022. Of the total participants, 1,988 had complete data for CVD assessment in the 20-year follow-up.ResultsThe 10-year and 20-year CVD incidence was 11.8%, 28.0% in rural municipalities and 16.8%, 38.7% in urban municipalities, respectively (ps < 0.05). Unadjusted data analyses revealed significant differences in clinical, laboratory, and lifestyle-related CVD risk factors between urban and rural residents (ps < 0.05). Additionally, sex-based discrepancies in clinical, anthropometric, circulating, and lifestyle risk factors were observed in stratified analyses of urban and rural settings. Multivariate analyses, including generalized structural equation modeling (GSEM), revealed that the impact of the urban built environment on the long-term (20-year) CVD risk is mediated by lifestyle-related risk factors.ConclusionUrban inhabitants exhibit a higher long-term CVD incidence compared to their rural counterparts, which was partially explained by their lifestyle behaviors. Targeted strategic city planning efforts promoting healthier lifestyle-related behaviors at the micro-environment level could potentially mitigate built-environment impacts on CVD health.

Background/Objectives: To investigate the associations between educational attainment and 20-year cardiovascular disease (CVD) incidence, mortality, lifetime risk, and burden, and to explore the mediating role of healthy and sustainable dietary habits through a sex-specific lens. Methods: A total of 3042 CVD-free adults from the ATTICA Study were included at the 2001/2002 baseline. Educational level was treated as both continuous and ordinal variable. Adherence to the EAT–Lancet diet pattern (EAT-LDP) was assessed at baseline. Participants were followed for 20 years, with complete data on CVD outcomes available for 1988 individuals. Generalized structural equation and nested Cox regression models were used to estimate the direct and indirect effects between education attainment and 20-year CVD incidence. Moderation analysis was also conducted by incorporating interaction terms in Cox models. Results: An inverse educational gradient in CVD risk and burden was observed, particularly among females for lifetime risk estimates. Each additional year of education was associated with higher EAT-LDP adherence (β = 0.45, 95% CI: 0.40–0.50) and increased odds of physical activity (OR: 1.01, 95% CI: 1.00–1.01). These behaviors mediated part of the relationship between education and long-term CVD incidence. Among females, the cardioprotective role of EAT-LDP adherence was more evident at lower educational levels, suggesting potential effect modification. Conclusions: Educational disparities in long-term CVD outcomes are partly mediated by sustainable dietary habits. These findings highlight the need for gender-responsive and equity-focused strategies in cardiovascular prevention.

BACKGROUND AND AIMS:Inflammation has been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. We evaluated immune-related biomarkers regarding their ability, individually and as a composite score, to predict 20-year ASCVD incidence in an apparently healthy adult population. METHODS:A cohort of 1270 adults, who were free of ASCVD at baseline, with a 20-year follow-up from the prospective ATTICA study, were included in this analysis. Immune-related biochemical markers independently predictive of 20-year ASCVD risk were identified, and an aggregate biomarker score was developed. The incremental predictive value of this score beyond the SCORE2 was assessed using area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS:Three immune-related biomarkers -interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and fibrinogen-showed the best predictive ability of 20-year ASCVD risk and were subsequently integrated into an aggregate biomarker score (ImmActScore), exhibiting a range from 0 (6 % absolute risk) to 4 (63 % absolute risk). Individual ImmActScore was independently associated with 20-year ASCVD risk (multi-adjusted HR per 1-unit:1.24, 95 %CI:1.05-1.46, p = 0.011). The 38.5 % of the 20-year incident ASCVD could be attributed to ImmActScores of ≥1. Integrating ImmActScore into the SCORE2 model yielded a continuous NRI of 0.603 and a categorical NRI of 18.4 % in the 40-50 year age group. CONCLUSIONS:Assessing immune-related pathways may offer additional potential for long-term ASCVD risk stratification. A combined measure of IL-6, TNF-α and fibrinogen levels was associated with ASCVD events over a 20-year period. Further validation in independent cohorts is warranted.

BACKGROUND AND AIMS:Triglyceride-glucose (TyG) index, is an emerging prognostic biomarker in atherosclerotic cardiovascular disease (ASCVD). Validation of its clinical value and of clinically relevant prognostic cut-off, remains an unmet need to integrate TyG into primary prevention protocols. METHODS:To assess the clinical applicability of TyG, a composite of cardiovascular mortality, myocardial infarction, coronary revascularization or stroke was used as the primary endpoint in a general population cohort (ATTICA cohort, n = 1677, derivation cohort). Next, we derived an optimal prognostic TyG cut-off and externally validated it in a primary prevention cohort (n = 1237). To assess the clinical value of TyG, we analysed 1170 consecutively recruited patients from an ongoing registry aiming to stratify ASCVD risk (Athens Cardiometabolic Cohort) and assessed indices of subclinical arterial injury and progression of atherosclerosis. The TyG index was calculated by the formula: ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. RESULTS:TyG index was independently associated with increased CVD events in the derivation cohort (HR = 1.33, p = 0.020). The incremental value of a derived optimal cut-off of 8.46 over SCORE2 was confirmed in both derivation and validation cohorts [net reclassification index (NRI) = 0.668 and 0.469 respectively, Delta Harrell's C index = 0.054 and 0.044 respectively, p < 0.05 for all]. Elevated TyG index was associated with more diseased vascular beds (OR = 2.00, 95% CI 1.24-3.24), progression of subclinical carotid atherosclerosis (OR = 2.99, 95% CI 1.10-8.17) at follow-up and established ASCVD (p < 0.05 for all). CONCLUSIONS:TyG is associated with increased prevalence and progression of subclinical and clinically overt ASCVD. In individuals assessed for primary prevention a TyG≥8.46 may serve as a risk enhancer.