10-year Cardiovascular Disease Incidence Research Articles

Validation of the SCORE2 risk prediction algorithm in a Portuguese population: A new model to estimate 10-year cardiovascular disease incidence in Europe

Introduction and ObjectivesSubjects without cardiovascular (CV) disease (CVD) may suffer from subclinical atherosclerosis, and are at increased risk for atherosclerotic CV events (ASCVE). The ESC/EAS risk SCORE was updated by SCORE2, which estimates 10-year risk of fatal and non-fatal CVD in European populations aged 40–69 years without established CVD or diabetes. Our aim was to compare the two ESC/EAS risk scores and to validate SCORE2 in our population. MethodsA total of 1071 individuals (age 57.2±6.1 years; 75.2% male) without CVD or diabetes, from GENEMACOR study controls, were analyzed over 5.4±3.9 years. The population was stratified into risk categories according to the two scores, and the area under the ROC curve (AUC) and Harrell's C-index assessed the scores’ performance. Calibration was performed using the goodness-of-fit test, and occurrence of the first event assessed by Cox regression. Kaplan–Meier analysis estimated SCORE2 survival. ResultsSCORE stratified subjects into four risk categories: low (7.4%), moderate (46.5%), high (25.3%) and very high (20.8%), and SCORE2 into three: low-to-moderate (24.7%), high (59.0%) and very high (16.2%). SCORE presented good discrimination for CV mortality (AUC=0.838; C-index=0.834, 95% CI: 0.728–0.940), as did SCORE2 for total CV events (AUC=0.744; C-index=0.728, 95% CI: 0.648–0.808). Calibration did not show a disparity between observed and expected ASCVE. The probability of ASCVE was eight times higher in very-high-risk SCORE2 (p=0.001), and three times in the high-risk group (p=0.049). Event-free survival was 99%, 90% and 72% in the low-to-moderate, high and very-high-risk categories, respectively (p<0.0001). ConclusionsSCORE2 improved population stratification by identifying higher-risk patients, enabling early preventive measures. It showed good discriminative ability for all ASCVE.

Evaluation of the novel three lipid indices for predicting five- and ten-year incidence of cardiovascular disease: findings from Kerman coronary artery disease risk factors study (KERCADRS)

BackgroundData are limited on the relationship between cardiovascular disease (CVD) and the combinational indices of lipid accumulation product (LAP), triglyceride-glucose index (TyG), and visceral adiposity index (VAI). The association of these novel indices with the 5- and 10-year incidence of CVD was assessed.MethodA total of 1888 and 1450 healthy adults aged between 15 and 75 years (out of the 5895 participants of the KERCADR study, 2012) were followed for five and ten years, respectively. Baseline LAP, TyG, and VAI were calculated and logistic regression models were used to assess their relationship with the incidence of CVD in the two follow-up periods. Also, the predictive performance of these three indices was analyzed using the area under ROC curve (AUC) for the development of CVD compared with traditional single indices.ResultsIn the 5- and 10-year follow-ups, 399 and 476 CVD cases (21.1% and 32.8%) were documented, respectively. For the 5-year CVD risk, the adjusted odds ratio (AOR, 95% CI) was LAP (2.24 [1.44, 3.50]), VAI (1.58 [1.08, 2.33]), and TyG (1.57 [1.02, 2.42]). For the 10-year CVD risk, the AOR was LAP (1.61 [1.04, 2.49]), TyG (1.57 [1.02, 2.41]), and VAI (1.41 [0.96, 2.09]). In both periods and sexes, LAP had the best performance with the highest AUCs (0.644 and 0.651) compared to the other two indices and compared to the traditional single indices (e.g., BMI, LDL, etc.).ConclusionOverall LAP, TyG, and VAI were better CVD risk predictors compared to the traditional single risk factors, with LAP showing the strongest predictive power for the incidence of CVD.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality

BackgroundFive modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.MethodsWe pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non–high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality.ResultsAmong 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6).ConclusionsHarmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)

Performance of the Systematic COronary Risk Evaluation 2 (SCORE2) in the EPIC-Norfolk prospective population study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): EPIC-Norfolk is supported by programme grants from the Medical Research Council UK (MRC G0401527, MRC G0701863, MRC G1000143) and Cancer Research UK (CRUK 8257). Introduction The latest European guidelines recommend the use of the Systematic COronary Risk Evaluation 2 (SCORE2) to assess 10-year risk of fatal and non-fatal cardiovascular disease (CVD) in individuals aged 40-70 years. Therefore, validation of the SCORE2 algorithm in a large population is needed. Purpose To assess the predictive performance of SCORE2 in individuals without prior myocardial infarction, stroke or diabetes mellitus. Methods Individuals aged 40-70 without prior myocardial infarction, stroke or diabetes mellitus were included from the European Prospective Investigation of Cancer Norfolk (EPIC-Norfolk) prospective population cohort. We assessed discriminative power using the C-statistic; calibration was assessed by plotting calculated SCORE2 (low-risk algorithm) 10-year risks against observed CVD event rates. We defined the composite cardiovascular outcome as death due to ischemic heart disease, cardiac failure, cerebrovascular disease or peripheral-artery disease, or non-fatal myocardial infarction or non-fatal stroke. Observed probabilities were adjusted for competing mortality events. Results We included 20,318 individuals (56% women) with a median (IQR) age of 56 (50-63) years, with baseline measures between 1993-1997. Mean predicted 10-year risk was 3.7% (95% confidence interval (CI) 3.7-3.8) versus adjusted observed 4.2% (95% CI 3.9-4.5) 10-year CVD incidence, yielding a ratio of 1.1 (95% CI 1.1-1.2).(Figure) Observed events consisted of 1.5% (95% CI 1.3-1.7) fatal CVD events, 1.8% (95% CI 1.6-2.0) non-fatal myocardial infarctions, 1.5% (95% CI 1.3-1.6) non-fatal strokes and 23.4% (95% CI 22.1-23.2) competing mortality events. Overall C-statistic was 0.75 (95% CI 0.73-0.77). Conclusion SCORE2 demonstrates reasonable discriminative ability and accurate risk estimations in low-risk individuals in a large, prospective population cohort. However, as actual CVD incidence is expected to be lower given the baseline between 1993-1997, these findings do not indicate that SCORE2 is suitable for current use for risk assessment in individuals from the United Kingdom.

Five-Year Changes in Inflammatory, Metabolic, and Oxidative Biomarkers and 10-Year Cardiovascular Disease Incidence: The REGICOR Cohort Study.

Ischemic cardiovascular diseases (CVD) originate from an imbalance between atherosclerotic plaque formation, instability, and endothelial healing dynamics. Our aim was to examine the relationship between 5-year changes in inflammatory, metabolic, and oxidative biomarkers and 10-year CVD incidence in a population without previous CVD. This was a prospective cohort study of individuals aged 35-74 years (n = 419) randomly selected from 5263 REGICOR participants without CVD recruited in 2005. Biomarkers were measured at baseline and in 2010. Participants were followed up until 2020 for a composite CVD endpoint including coronary artery disease, stroke, and peripheral artery disease. We used Cox regression to analyze the effect of biomarker levels on the occurrence of the composite endpoint, adjusted for traditional CVD risk factors and baseline levels of each biomarker. Individuals with elevated IL-6 or insulin after 5 years had a higher independent risk of CVD at 10 years, compared to those with lower levels. Each rise of 1 pg/mL of IL-6 or 10 pg/mL of insulin increased the 10-year risk of a CVD event by 32% and 2%, respectively. Compared to a model with traditional CVD risk factors only, the inclusion of IL-6 and insulin improved continuous reclassification by 51%. Elevated serum levels of IL-6 and insulin were associated with a higher risk of CVD at 10 years, independently of traditional CVD risk factors.

Development of new scores for atherosclerotic cardiovascular disease using specific medical examination items: the Suita Study.

We previously developed risk models predicting stroke, coronary heart disease (CHD), and cardiovascular disease (CVD) among Japanese people from the Suita Study. Yet, applying these models at the national level was challenging because some of the included risk factors differed from those collected in the Japanese governmental health check-ups, such as Tokutei-Kenshin. We, therefore, conducted this study to develop new risk models for stroke, CHD, and atherosclerotic CVD (ASCVD), based on data from the Suita Study. The new models used traditional cardiovascular risk factors similar to those in the Japanese governmental health check-ups. We included 7,413 participants, aged 30-84 years, initially free from stroke and CHD. All participants received baseline health examinations, including a questionnaire assessing their lifestyle and medical history, medical examination, and blood and urine analysis. The risk factors of stroke, CHD, and ASCVD (cerebral infarction or CHD) were determined using the multivariable-adjusted Cox regression. The models' performance was assessed using the C-statistics for discrimination and the Hosmer-Lemeshow for calibration. We also developed three simple scores (zero to 100) that could predict the 10-year incidence of stroke, CHD, and ASCVD. Within 110,428 person-years (median follow-up = 16.6 years), 410 stroke events, 288 CHD events, and 527 ASCVD events were diagnosed. Age, smoking, hypertension, and diabetes were associated with stroke, CHD, and ASCVD risk. Men and those with decreased high-density lipoproteins or increased low-density lipoproteins showed a higher risk of CHD and ASCVD. Urinary proteins were associated with an increased risk of stroke and ASCVD. The C-statistic values of the risk models were >0.750 and the p-values of goodness-of-fit were >0.30. The 10-year incidence of stroke, CVD, and ASCVD events was 3.8%, 3.5%, and 5.7% for scores 45-54, 10.3%, 11.8%, and 19.6% for scores 65-74, and 27.7%, 23.5%, and 60.5% for scores ≥85, respectively. We developed new Suita risk models for stroke, CHD, and ASCVD using variables similar to those in the Japanese governmental health check-ups. We also developed new risk scores to predict incident stroke, CHD, and ASCVD within 10 years.

Evaluation of visceral adiposity index with cardiovascular risk factors, biomarkers in postmenopausal women to predict cardiovascular disease: A 10 year study

Background and aimVisceral adiposity index (VAI) is reportedly beneficial in predicting cardiovascular disease (CVD) and metabolic syndrome (MetS). However, long-term studies analyzing the efficacy of VAI in the prediction of CVD risk are limited. The relationship between VAI and electrolytes is unclear. This study aimed to determine if VAI can be used as a predictor of CVD and provide early diagnosis possibility for future CVD patients. Moreover, the impact of biomarkers and electrolytes on VAI therefore indirect relation to CVD was analyzed. MethodsPostmenopausal women (aged >40 years) admitted to our hospital in 2011 were included and categorized into two groups according to their VAI scores: mild/moderate and severe. Groups were compared with insulin resistance, biochemical parameters, and anthropometric measurements. Patients have been reached out after 10 years and questioned for additional disease and cardiovascular risk. Statistical Package for Social Sciences (SPSSv22.0) was used for data analysis. The p < 0.05 value was considered significant. ResultsMean VAI score of patients with MetS (7.30 ± 4.75) was significantly higher than without MetS (2.95 ± 1.05) (p < 0.01). Serum magnesium level was found significantly lower in the severe group. Serum zinc (Zn) and hsCRP levels were higher in the severe group. Correlation analysis showed significant positive correlations between VAI scores and total cholesterol (r = 0.289, p < 0.05), Zn (r = 0.397, p < 0.01), fasting insulin (r = 0.455, p < 0.01) and no significant association with the 10-year CVD incidence (OR: 1.034 (0.888–1.203); p = 0.668). ConclusionPrevious VAI results cannot assist in predicting the 10-year CVD risk. Additionally, including measurements of serum Zn, total cholesterol, fasting insulin, and FBG levels are reasonable approach for managing postmenopausal women with unfavorable CVD risk profiles.

Exploring the Role of Irrational Beliefs, Lifestyle Behaviors, and Educational Status in 10-Year Cardiovascular Disease Risk: the ATTICA Epidemiological Study.

Irrational beliefs, maladaptive emotions, and unhealthy lifestyle behaviors can adversely affect health status. However, limited research has examined the association between irrational beliefs and cardiovascular disease (CVD). The aim of this study was to evaluate the association between irrational beliefs and the 10-year CVD incidence among apparently healthy adults, considering the potential moderating or mediating role of particular social and lifestyle factors. The ATTICA study is a population-based, prospective cohort (2002-2012), in which 853 participants without a history of CVD [453 men (aged 45 ± 13years) and 400 women (aged 44 ± 18years)] underwent psychological evaluations. Among other tools, participants completed the irrational beliefs inventory (IBI, range 0-88), a self-reported measure consistent with the Ellis model of psychological disturbance. Demographic characteristics, detailed medical history, dietary, and other lifestyle habits were also evaluated. Incidence of CVD (i.e., coronary heart disease, acute coronary syndromes, stroke, or other CVD) was defined according to the International Coding Diseases (ICD)-10 criteria. Mean IBI score was 53 ± 2 in men and 53 ± 3 in women (p = 0.88). IBI score was positively associated with 10-year CVD risk (hazard ratio 1.07, 95%CI 1.04, 1.13), in both men and women, and more prominently among those with less healthy dietary habits and lower education status; specifically, higher educational status leads to lower IBI score, and in conjunction theylead to lower 10-year CVD risk (HR for interaction 0.98, 95%CI 0.97, 0.99). The findings of this study underline the need to build new, holistic approaches in order to better understand the inter-relationships between irrational beliefs, lifestyle behaviors, social determinants, and CVD risk in individuals.

Skeletal muscle mass and abdominal obesity are independent predictors of hepatic steatosis and interact to predict ten-year cardiovascular disease incidence: Data from the ATTICA cohort study

Sarcopenia and sarcopenic obesity may be associated with nonalcoholic fatty liver disease (NAFLD). This study examined the association between low skeletal muscle mass, with or without central obesity, with NAFLD, as well as their interaction on predicting 10-year incidence of cardiovascular disease (CVD).This was a post-hoc analysis of the ATTICA study. At baseline, 3042 participants from the Attica region of Greece were recruited; 2020 completed the 10-year follow-up visit for CVD. NAFLD was assessed through hepatic steatosis index (HSI). Skeletal muscle mass index (SMI) was calculated to assess skeletal muscle mass. SMI was studied in tertiles, stratified by sex; the first tertile corresponds to the lowest SMI, the second to middle, and the third to highest SMI. Abnormal waist circumference was defined as ≥102 cm for men and ≥88 cm for women. The combined 10-year endpoint was the development of a fatal or nonfatal CVD event. Logistic regression analysis was used to assess the association between NAFLD prevalence and SMI as well as Cox regression analysis to assess the interaction of both variables on the incidence of CVD over 10 years.Higher rates of NAFLD were observed in the first (45%) compared to the second [33%; odds ratio (OR): 0.50, 95% confidence interval (95%CI): 0.41-0.61] and the third (22%; OR: 0.24, 95%CI: 0.19-0.29) SMI tertile. This association remained robust after multiple adjustments; significance was marginally lost, when waist circumference was added to the model. When SMI and waist circumference were evaluated jointly, participants with moderate/high SMI and normal waist circumference had the lowest and those with low SMI and abnormal waist circumference the highest NAFLD rate (24.3 and 60.5%, respectively; P < 0.001). Ten-year CVD incidence was gradually lower from the first (22.8%) to second (16.1%) and third SMI tertile (8.2%) (P < 0.001). The hazard ratio (HR) for the third vs. the first SMI tertile for predicting CVD in fully adjusted model was 0.69 (95%CI: 0.46, 1.00). The unadjusted HR for NAFLD predicting CVD was 3.00 (95%CI: 2.28-3.95). Finally, there was a significant interaction among NAFLD, SMI and waist circumference (P = 0.04) in determining the 10-year CVD incidence; the association between NAFLD and 10-year CVD remained significant for the participants with low SMI and normal or abnormal waist circumference, but not those with moderate/high SMI and normal or abnormal waist circumference.Increasing SMI and lower abdominal obesity are independently associated with lower rates of NAFLD, and the two interact as key determinants of NAFLD. Low SMI and central obesity are independent predictors of CVD and were shown to interact with NAFLD in determining 10-year CVD risk.

Abstract EP68: Can A Single Model For General Population Predict Cardiovascular Events In Cancer Survivors?

Introduction: No specific guideline exists for the primary prevention of cardiovascular disease (CVD) in cancer survivors. We hypothesized that CVD risk and its association with risk factors are comparable between cancer survivors and the general population, such that they may share currently available risk scores (e.g., Pooled Cohort Equation; PCE) for initial risk discussion. Methods: We studied 59 445 cancer survivors (≥5 years from diagnosis) and 59 445 age/sex-matched non-cancer controls aged 40-79 years (51.6% female) and free of CVD among participants of 2009 Korean National Health Insurance health screening. We calculated 10-year cumulative incidence of CVD events (composite of myocardial infarction, stroke, or cardiovascular death) and hazard ratios for traditional CVD risk factors in cancer survivors vs. non-cancer controls. We then evaluated discrimination and calibration of a previously-derived, general Korean population-based CVD risk model (having similar predictors as the PCE) applied to cancer survivors. Results: During a median follow-up of 10.3 years, 6,809 CVD events occurred. Multivariable-adjusted 10-year cumulative CVD incidence was 2.8% (2.7-3.0) among cancer survivors and 3.0% (2.0-3.2) among non-cancer controls (Figure A). Associations of traditional risk factors with CVD events were similar between cancer survivors and controls (Figure B). Results were consistent when stratified by sex and age. A CVD risk model, previously derived from the general Korean population similarly as the PCE, showed good discrimination (C-index, 0.747) and calibration (Figure C) when applied to cancer survivors. By cancer subtype, some cancers were associated with higher or lower CVD risk than controls (Figure D). Conclusions: CVD risk and associations with predictors were similar between cancer survivors and non-cancer individuals. Pre-existing models for general population may perform well in overall cancer survivors, although subtype-specific recalibration may be desirable for some cancers.

The association between serum uric acid levels and 10-year cardiovascular disease incidence: results from the ATTICA prospective study.

Limited data suggests possible gender-specific association between serum uric acid (SUA) and cardiovascular disease (CVD) incidence. The aim of the present analysis was to evaluate the association between SUA levels and 10-year CVD incidence (2002-2012) in the ATTICA study participants. Overall, 1687 apparently healthy volunteers, with SUA measurements, residing in the greater metropolitan Athens area (Greece), were included. Multivariable Cox-regression models were used to estimate the hazard ratios for SUA in relation to 10-year CVD incidence. Receiver operating curve analysis was conducted to detect optimal SUA cut-off values. Participants in the 2nd and 3rd SUA tertile had 29 and 73% higher 10-year CVD incidence compared with those in the 1st tertile (p < 0.001). In gender-specific analysis, only in women SUA was independently associated with CVD incidence; women in the 3rd SUA tertile had 79% greater 10-year CVD event risk compared to their 1st tertile counterparts. Obese in the 3rd SUA tertile had 2-times higher CVD incidence compared to those in the 1st tertile. Similar findings were observed in metabolically healthy (vs. unhealthy) and metabolically healthy obese. SUA thresholds best predicting 10-year CVD incidence was 5.05 and 4.15 mg/dL (0.30 and 0.25 mmol/L) in men and women, respectively. In conclusion, increased SUA levels were independently related to 10-year CVD event rate in women, obese and metabolically healthy individuals. SUA could predict 10-year CVD incidence even at low levels. Further studies are warranted to identify SUA cut-off values that may improve the detection of individuals at higher CVD risk in clinical practice.

The role of triglycerides-glucose index to predict 10-year first and recurrent cardiovascular disease events: a sex-based analysis from ATTICA and GREECS prospective studies

Abstract Background/Introduction Triglycerides-glucose index (TyG) has been used in apparently healthy individuals to define insulin resistance and liver steatosis. Additionally, findings from very recent studies challenge the use of this index as a predictor of cardiovascular disease (CVD) onset as well as a marker of atherosclerosis in patients with established CVD. Purpose To evaluate the association between TyG and 10-year first or recurrent fatal/non fatal CVD event. Methods The samples from two prospective epidemiological studies implemented in Greece were used. In particular, in ATTICA study, in 2001–02, 1,514 men and 1,528 women (&amp;gt;18 years) free of CVD, at baseline, living in greater Athens area, Greece, were enrolled and 10-year follow up was performed (2011–12) in 2,020 participants (n=317 cases). In GREECS study, in 2003–04 almost all consecutive 2,172 acute coronary syndrome (ACS) patients of 6 Greek hospitals were enrolled. In 2013–14, 10-year follow-up was performed in 1,918 participants. TyG was assessed at baseline using a standard formula. Results In ATTICA, ranking from 1st (i.e. &amp;lt;8.0) to 3rd TyG tertile (i.e. &amp;gt;8.6), 10-year first CVD incidence was 5.6%, 14.2% and 24.1% (p&amp;lt;0.001); the respective man-to-woman incidence ratio was 1.86, 1.17 and 1.19. In GREECS, ranking from 1st (i.e. &amp;lt;8.7) to 3rd TyG tertile (i.e. &amp;gt;9.3), 10-year recurrent CVD incidence was 35.3%, 43.2% and 35.9% (p=0.11); the respective man-to-woman incidence ratio was 1.08, 0.99 and 1.23. Multi-adjusted Cox regression analysis in ATTICA study revealed that participants assigned in the 3rd TyG tertile had about 77% higher CVD risk compared with their 1st tertile counterparts [Hazard Ratio (HR)=1.77, 95% Confidence Interval (95% CI) (1.06, 2.96), p=0.02]; sex-based stratified analysis revealed that this association remained significant only in women [HR=2.29 95% CI (1.20, 4.38), p=0.01] while in case of men this association was borderline significant [HR=1.70 95% CI (0.95, 3.35), p=0.10]. The total correct classification rate was around 83–85% in all models and similar with models adjusted separately for triglycerides or glucose levels. Using the area under the Receiver Operation Characteristic ROC) curve (AUC) analysis TyG had the best discriminative ability in both sexes with a small advantage in favor of women and minor discrepancies with the commonly used –triglycerides and glucose– biomarkers (Women: AUCTyG=0.694, AUCtriglycerides=0.678, AUCglucose=0.601 / Men: AUCTyG=0.662, AUCtriglycerides=0.634, AUCglucose=0.623). In case of GREECS study, no significant trends were observed. Conclusions The findings here suggest a predictive role of TyG against long-term CVD onset which comes in line with recent works; yet its added value against conventional markers such as glucose and triglycerides was not confirmed. Additionally, no significant prognostic effect of TyG against CVD recurrence was observed challenging its clinical use in secondary prevention spectrum. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].

Non-alcoholic fatty liver disease, Mediterranean diet and 10-year cardiovascular disease incidence: the mediating role of adiponectin. Highlights from the ATTICA prospective (2002–2012) study

Abstract Background/Introduction The most updated set of guidelines (EASL-EASD-EASO 2016) suggests Mediterranean diet as a promising dietary pattern for non-alcoholic fatty liver disease (NAFLD) management. Purpose The association between NAFLD and adherence to Mediterranean diet as well as their interaction on 10-year fatal/non fatal cardiovascular disease incidence were evaluated. Methods Study population included 1,514 men and 1,528 women (&amp;gt;18 years old) in our city in Greece, free of CVD recruited during the 2001–2002 period. Liver steatosis and fibrosis assessment indices were calculated at baseline and specific cut-offs were used to capture NAFLD. Level of adherence to Mediterranean diet was assessed through MedDietScore. National and international food databases were used to estimate total daily carbohydrate intake. The cut-off point of 35% of total daily energy intake was set to define low vs. high carbohydrate intake. Circulating adiponectin level was measured at baseline (4.0 (2.0) μg/mL). Results MedDietScore was inversely associated with NAFLD indices of both steatosis and fibrosis yet only in Triglycerides-Glucose index [Odds Ratio (OR)3rd vs. 1st MedDietScore tertile = 0.53, 95% Confidence Interval (95% CI) (0.29, 0.95)] persisted in multi-adjusted models including adjustments for metabolic syndrome components, energy intake and overall and central obesity. This was more evident in men (p for sex interaction = 0.03). The protective role of Mediterranean diet was retained irrespective to the total carbohydrate content; however, sex-based stratified analysis revealed that in woman subsample only Mediterranean diet with low carbohydrate content (i.e. &amp;lt;35%) had an independent protective role against NAFLD presence [OR3rd vs. 1st MedDietScore tertile = 0.79, 95% CI (0.40, 0.96)]. NAFLD predicted CVD [Hazard Ratio (HR) = 3.01, 95% CI (2.28, 3.95)] in crude model as well as in multi-adjusted model [HR=1.37, 95% CI (1.10, 2.10)]. NAFLD effect on CVD remained significant only in MedDietScore below median [HR=1.38, 95% CI (1.00, 1.93)] whereas it was essentially null [HR=1.00, 95% CI (0.38, 2.63)] among subjects with lower score. Mediation analysis revealed that adiponectin was the strongest mediator of the examined associations. In particular, per 1 mg/dL serum adiponectin about 21% lower likelihood to have NAFLD was observed. Stratified analysis using the median value of adiponectin level (4.1 mg/dL) revealed that the inverse association between Mediterranean diet and NAFLD reached the level of significance only in case of adiponectin levels over the median values (OR (3rd vs. 1st MedDietScore tertile) = 0.69 95% CI (0.35, 0.98)). Conclusion Beyond the inverse association between Mediterranean diet and NAFLD several novelties were revealed; low-carbohydrate Mediterranean diet was more protective against NAFLD in women while an adiponectin-related mechanism was revealed. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003]

The gender-specific role of prediabetes on 10-year cardiovascular disease incidence: highlights from the ATTICA prospective (2002–2012) study

Abstract Background/Introduction Prediabetes in terms of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) are highly discussed for their aggravating effect on cardiac health and their potential inclusion in risk prediction to achieve earlier prevention. Purpose The aim of the present work was to evaluate the association between prediabetes and 10-year first fatal/non fatal cardiovascular disease (CVD) incidence in a sample without prevalent CVD, taking into account the stability of this condition or the transition to type II diabetes. Methods A prospective study was conducted during 2001–2012 studying n=1,514 males and n=1,528 females (aged &amp;gt;18 years old) free of CVD. According to American Diabetes Association Diagnosis, prediabetes in terms of IFG was defined as fasting glucose levels 100–125 mg/dl while type 2 diabetes as fasting blood glucose &amp;gt;125 mg/dl or the use of antidiabetic medication. Ten-year follow-up was performed in n=2,020 participants (n=317 CVD cases); the working sample here was n=1,485 (n=249 CVD cases) (without baseline diabetes and with available data on diabetes status at follow-up). Results Of the 1,485 participants, n=279 had IFG, at baseline. Ten-year CVD incidence was 19.3% in IFG subgroup and 12.3% in normoglycemic subgroup (p&amp;lt;0.001); the IFG-to-normoglycemic CVD incidence ratio in men was 1.22 while in women 1.60. Multi-adjusted analysis revealed that IFG was an independent predictor of CVD within the decade (Hazard ratio (HR)=1.39, 95% Confidence Interval (95% CI) (1.00, 1.95)). Significant interacting effect of gender on the examined association was revealed (p for interaction=0.001); in stratified analysis, IFG was independently associated with increased CVD risk only in women (HR=1.47, 95% CI (1.10, 2.68)). Within the decade, transition to diabetes status was observed in about one out of four participants with prediabetes (25.1%) while the respective rate in normoglycemic participants was 10% (n=191 diabetes cases, in total). Interestingly, sensitivity analysis revealed that when this category (with diabetes onset within the decade) was excluded from the analysis prediabetes retained its independent aggravating –even weaker– effect on 10-year CVD risk in total sample (HR=1.18, 95% CI (1.01, 1.91)) as well as in women (HR=1.25, 95% CI (1.03, 2.97)). Conclusion Here, it was suggested that IFG independently predicted long-term CVD onset, even without transition to a more serious cardiometabolic condition (i.e. diabetes) with more evident outcomes in case of women. Considering the increasing interest for early CVD risk prediction, prediabetes condition in terms of IFG may be a useful predictor towards this perspective. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].

The role of dietary vitamin D intake on 10-year cardiovascular disease incidence, intermediate cardiometabolic risk factors and surrogate markers: highlights from ATTICA prospective study

Abstract Background/Introduction Increasing vitamin D intake through food supplements or fortification is far from revealing strong contribution to cardiac health. On the other side, the separate evaluation of dietary vitamin D intake with cardiac health is limited. Purpose The aim of the present work was to evaluate the association between dietary vitamin D intake and 10-year first fatal/non fatal CVD, conventional CVD risk factors and surrogate markers related with inflammation, coagulation, insulin resistance, liver and renal function. Methods ATTICA prospective study was conducted during 2001–2012 and included n=1,514 men and n=1,528 women (aged &amp;gt;18 years old) from the greater Athens area, Greece. Dietary assessment was based on a validated semi-quantitative food frequency questionnaire. Daily intake of vitamin D was calculated through standardized food database. Follow-up assessment of CVD (2011–2012) was achieved in n=2,020 participants (n=317 cases). Results Ranking from 1st to 3rd vitamin D tertile, CVD event was for men 24%, 17% and 12% (p=0.002) and for women 14%, 10% and 11% (p=0.59), respectively. Multiadjusted analysis revealed inverse associations between vitamin D and CVD in total sample [Hazard Ratio (HR)=0.76 95% Confidence Interval (95% CI) (0.60, 0.97)] and in men [HR=0.66 95% CI (0.49, 0.89)], lost after adjusting for inflammation/coagulation markers; for women no significant trends against hard CVD endpoints were observed. Regarding 10-year onset of conventional risk factors, inverse associations of vitamin D with hypertension in men [HR=0.62 95% CI (0.39, 0.99)] and transition to metabolically unhealthy status in women [HR=0.69 95% CI (0.51, 0.93)] were observed. Multiadjusted analyses revealed significant inverse associations for C-reactive protein, interleukin-6 and fibrinogen in both sexes while only in women for insulin resistance. Conclusions Contradicting the neutral/modest associations in vitamin D supplementation trials, the present work revealed that increased food-generated vitamin D may protect against hard and intermediate CVD endpoints implying the existence of different paths between sexes. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].

Dairy products, surrogate markers, and cardiovascular disease; a sex-specific analysis from the ATTICA prospective study

Background and aimsDairy products are a very diverse food group with multiple effects on the cardiac health of men and women. The aim of this work was to evaluate the sex-specific association between dairy products (total and subtypes) and 10-year first fatal/nonfatal cardiovascular disease (CVD) incidence. Methods and resultsIn 2001–2002, n = 1514 men and n = 1528 women (>18 years old) from greater Athens area, Greece, were enrolled. Dietary assessment was based on a validated semi-quantitative food frequency questionnaire. Dairy product consumption was examined in relation to 10-year CVD incidence. Follow-up (2011–2012) was achieved in n = 2020 participants (n = 317 CVD cases). Ranking from lowest (<1 serving/day) to highest (>2 servings/day) total dairy intake, CVD incidence in men was 17.8%, 15.0%, and 10.9% (p = 0.41), while in women it was 14%, 6.0%, and 5.7% (p = 0.02). Multiadjusted analysis revealed that total dairy intake protected against CVD only in women [Hazard Ratio (HR) = 0.48 and 95% Confidence Interval (95% CI) (0.23, 0.90)], irrespective of the fat content. Further analysis revealed that only fermented products (yogurt and cheese), protected against CVD. For per 200 g/day yogurt consumption, CVD risk was 20%–30% lower with this claim being more evident in women, while for per 30 g/day cheese intake, about 5% lower risk was observed particularly in men. As for butter, nonsignificant associations were highlighted. These associations were mainly retained in the case of hepatic steatosis, insulin resistance, and systemic inflammation. ConclusionsThis work provides incentives for researchers to elucidate the diversity of ingredients and mechanisms through which dairy products exert their effect on cardiac health separately for men and women.

Risk Stratification and Transfusion Dependence Are Independent Risk Factors for Cardiovascular Disease (CVD) in Myelodysplastic Syndrome (MDS)

Background: MDS has been largely excluded from epidemiological studies that demonstrate an increased risk of CVD in older adults with cancer. Nevertheless, somatic mutations leading to clonally restricted hematopoiesis are associated with increased risk of CVD and CVD constitutes the most common non-disease-related cause of death among patients with MDS. Using the SEER Medicare tumor registry, we previously demonstrated that MDS was independently associated with increased risk of CVD and cardiovascular mortality in older adults, thus constituting an important but underestimated cardiovascular hazard. In this study, we sought to determine the influence of MDS-specific factors on the risk of CVD among MDS patients. Methods: We used the SEER Medicare database to identify individuals 66 years or older with an incident diagnosis of MDS between 2004 and 2014. Incident CVD was defined as new myocardial infraction and/or ischemic stroke occurring after diagnosis of MDS. Events were identified with ICD9 and HCPCS codes in Medicare claims from the date of MDS diagnosis to death or study end. Subjects with CVD prior to MDS diagnosis were excluded. Comorbidity burden was estimated with the Charlson comorbidity index (CCI), calculated using claims from the year before MDS diagnosis. MDS was classified into low, intermediate and high risk using ICD-O morphology codes. Subjects requiring 2 or more blood product transfusions within 60 days from MDS diagnosis were considered transfusion dependent. Cumulative incidence functions were used to assess the risk of new events. Cox proportional hazards models, extended for time dependent covariates and coefficients, were used to evaluate clinical variables associated with CVD. Results: The cohort included 13,972 subjects with MDS, most were male (55.2%), non-hispanic white (82.1%), and from metropolitan areas (82.5%). Median age at MDS diagnosis was 82 years (IQR, 78 - 87). MDS was of low, intermediate and high risk in 18.1%, 68.8% and 13.1% respectively. The median CCI score was 0 (IQR, 0 - 2). Red blood cells (RBC) and platelet transfusion dependence occurred in 29% and 6.1% of subjects. The 10-year cumulative incidence of CVD was 47%, 54% and 65% in subjects with low, intermediate and high-risk MDS, respectively (p&amp;lt;0.016; Fig. 1). Similarly, the 10-year cumulative incidence of CVD was 57.5% in RBC transfusion-dependent subjects vs. 49% in non-dependent individuals (p&amp;lt;0.001; Fig 2A). Other factors that significantly influenced the hazard of CVD were male sex, older age and higher CCI. The effect of higher MDS risk (HR 1.1, 95%CI, 1.02 - 1.2) and RBC transfusion dependence (HR 1.3, 95%CI, 1.2 - 1.5) on increased incidence of CVD persisted after accounting for these factors in a multivariate Cox model adjusted for age, gender and CCI. Platelet transfusion dependence did not significantly influence the cumulative incidence of CVD (p=0.252; Fig 2B) or the hazard for CVD in multivariate analysis (HR 0.8, 95%CI, 0.6 - 1.2). Both higher risk MDS (HR 1.6, 95%CI, 1.5 - 1.7) and blood product transfusion dependence (HR 1.9, 95%CI 1.8 - 2) were associated with increased mortality in subjects with MDS. Conclusion: In a large cohort of elderly Medicare beneficiaries with incident diagnosis of MDS, the cumulative incidence of CVD was greater in subjects with higher-risk MDS as determined by bone marrow morphology and in those who were RBC transfusion dependent. Both MDS risk and RBC transfusion dependence were independent risk factors for CVD in multivariate analysis accounting for demographic factors and comorbidity burden. These factors have been previously associated with increased mortality and risk of leukemia transformation in MDS but their role in risk of CVD has not been previously reported. CVD is an important cause of mortality among older adults with MDS and these results can help identify high risk patients for whom strict cardiovascular screening and preventive strategies could impact mortality. Though we used validated methods, study limitations include relying on administrative claims, absence of genetic information and unmeasured confounding factors. Prospective studies and further preclinical research is needed to clarify the mechanisms of CVD in patients with MDS. Figure 1 Disclosures Verma: Janssen: Research Funding; Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria; BMS: Research Funding.

Changes in behaviors after diagnosis of type 2 diabetes and 10-year incidence of cardiovascular disease and mortality

BackgroundLarge changes in health behaviors achieved through intensive lifestyle intervention programs improve cardiovascular disease (CVD) risk factors among adults with type 2 diabetes. However, such interventions are not widely available, and there is limited evidence as to whether changes in behaviors affect risk of CVD events.MethodsAmong 852 adults with screen-detected type 2 diabetes in the ADDITION-Cambridge study, we assessed changes in diet, physical activity, and alcohol use in the year following diabetes diagnosis. Participants were recruited from 49 general practices in Eastern England from 2002 to 2006, and were followed through 2014 for incidence of CVD events (n = 116) and all-cause mortality (n = 127). We used Cox proportional hazards regression to estimate hazard ratios (HR) for the associations of changes in behaviors with CVD and all-cause mortality. We estimated associations with CVD risk factors using linear regression. We considered changes in individual behaviors and overall number of healthy changes. Models adjusted for demographic factors, bodyweight, smoking, baseline value of the health behavior, and cardio-protective medication use.ResultsDecreasing alcohol intake by ≥ 2 units/week was associated with lower hazard of CVD vs maintenance [HR: 0.56, 95% CI 0.36, 0.87]. Decreasing daily calorie intake by ≥ 300 kcal was associated with lower hazard of all-cause mortality vs maintenance [HR: 0.56, 95% CI 0.34, 0.92]. Achieving ≥ 2 healthy behavior changes was associated with lower hazard of CVD vs no healthy changes [HR: 0.39, 95% CI 0.18, 0.82].ConclusionsIn the year following diabetes diagnosis, small reductions in alcohol use were associated with lower hazard of CVD and small reductions in calorie intake were associated with lower hazard of all-cause mortality in a population-based sample. Where insufficient resources exist for specialist-led interventions, achievement of moderate behavior change targets is possible outside of treatment programs and may reduce long-term risk of CVD complications.Trial registration This trial is registered as ISRCTN86769081. Retrospectively registered 15 December 2006

Exposure to second hand smoke and 10-year (2002–2012) incidence of cardiovascular disease in never smokers: The ATTICA cohort study

BackgroundDespite WHO Framework Convention of Tobacco Control (FCTC) adoption, effective implementation of national smoking bans remains pending in several countries. This study quantified the association of second hand smoke (SHS) exposure and 10-year cardiovascular disease (CVD) among never smokers in such settings. MethodsIn 2001–2002, a sample of 1514 males and 1528 females (range: 18–89 years old) were randomly selected in Greece. Frequency and duration of SHS exposure (i.e. exposure extending >30 min/day) within the home and/or workplace were assessed by interview. Following a 10-year follow-up period (2002–2012), incidence of non-fatal and fatal CVD (ICD-10) was evaluated among n = 2020 participants. The analytic study sample consisted of all never smokers (n = 910). ResultsDespite national smoking ban implementation (2009), 44.6% (n = 406) of never smokers reported SHS exposure. While SHS exposed never smokers exhibited a more favorable profile of CVD-related risk factors at baseline, they subsequently developed similar 10-year CVD incidence rates, at a younger mean age (p = 0.001), than their non-exposed counterparts. Following adjustment for several lifestyle and clinical factors, SHS exposed never smokers exhibited a two-fold elevated 10-year CVD risk (adj. HR: 2.04, 95% CI: 1.43–2.92), particularly among women (adj. HR: 2.45, 95% CI: 1.45–4.06). SHS exposure accounted for 32% excess Population Attributable Risk (PAR) for 10-year CVD events in never smokers, with highest rates (PAR: 52%) being among those exposed in the workplace. ConclusionThe prevention of SHS associated CVD and related healthcare costs mandates additional strategies for securing the effective implementation of comprehensive WHO FCTC based national smoking bans.

Lipoprotein (a) and 10-year Cardiovascular Disease Incidence in Apparently Healthy Individuals: A Sex-based Sensitivity Analysis from ATTICA Cohort Study.

The association between lipoprotein (a) (Lp(a)) and 10-year first fatal/nonfatal cardiovascular disease (CVD) risk in apparently healthy men and women was evaluated. The ATTICA prospective study was conducted during 2001-2012 and included n = 1514 men and n = 1528 women (age >18 years) from the greater Athens area, Greece. Follow-up CVD assessment (2011-2012) was achieved in n = 2020 participants (n = 317 cases); baseline Lp(a) was measured in n = 1890 participants. The recommended threshold of 50 mg/dL was used to define abnormal Lp(a) status. Ten-year CVD-event rate was 14% and 24% in participants with Lp(a) <50 and Lp(a) ≥50 mg/dL, respectively. Multivariate analysis revealed that participants with Lp(a) ≥50 mg/dL versus Lp(a) <50 mg/dL had about 2 times higher CVD risk (hazard ratio (HR) = 2.18, 95% confidence interval (CI) 1.11, 4.28). The sex-based analysis revealed that the independent Lp(a) effect was retained only in men (HR = 2.00, 95% CI 1.19, 2.56); in women, significance was lost after adjusting for lipid markers. Sensitivity analyses revealed that Lp(a) increased CVD risk only in case of abnormal high-density lipoprotein cholesterol, apolipoprotein A1, and triglycerides as well as low adherence to Mediterranean diet. Certain patient characteristics may be relevant when considering Lp(a) as a therapeutic or risk-prediction target.