Risk Of Incident Cardiovascular Disease Events Research Articles

Abstract 13966: Change in Troponin I Levels With Intensive Blood Pressure Control: A Post-Hoc Analysis of SPRINT

Introduction: Cardiac troponin T (cTnT) levels have been shown to increase by intensive blood pressure (BP) control and longitudinal changes in cTnT predict cardiovascular disease (CVD) and mortality. However, similar data on cTnI, a specific marker of myocardial injury, are lacking. Methods: This post-hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial) included participants who had cTnI values at randomization and 1-year. The cohort was stratified by change in cTnI at 1 year into ≥50% decrease, ≥50% increase, or unchanged (<50% change). The difference in log(cTnI randomization ) and log(cTnI 1 year ) was calculated. The primary outcome was CVD events. Secondary outcomes included a composite of all-cause mortality or CVD events, all-cause mortality, and a composite of heart failure or all-cause mortality. Geometric mean ratios for change in log cTnI levels with intensive BP lowering compared with standard treatment were estimated using adjusted linear regression models. Adjusted Cox models were used to assess the risk of the outcomes of interest after 1 year with the change in cTnI levels. Events within 1 year were censored. Results: Among the 8,011 participants with cTnI levels at randomization and 1 year, cTnI decreased, did not change, and increased in 393 (4.9%), 6,442 (80.4%), and 1,176 (14.7%) participants at 1 year, respectively. Compared with the standard treatment, ≥50% reduction in cTnI at 1 year was more common with intensive treatment. The intensive treatment group had a 7% decrease [geometric mean ratio: 0.93 (0.91-0.95)] in cTnI compared with the standard treatment group after adjusting for covariates. An increase in the change in log cTnI at 1 year was associated with a higher risk of incident CVD events [HR adj : 1.67 (1.36-2.05)] and the composite of all-cause mortality or CVD events[HR adj : 1.36 (1.13-1.64)]. Conclusions: cTnI levels decreased with intensive BP control and the change in cTnI at 1 year predicted incident CVD events.

Association of triglyceride-glucose index with cardiovascular disease among a general population: a prospective cohort study

BackgroundThe impact of triglyceride-glucose (TyG) index, a surrogate marker for insulin resistance, on the risk of cardiovascular disease (CVD) in general populations remains controversial. We aimed to comprehensively study the relationship between TyG index with the risk of incident CVD events in the general population in Shanghai.MethodsA total of 42,651 participants without previous history of CVD events from Shanghai Suburban Adult Cohort and Biobank (SSACB) were included. SSACB was a community-based natural population cohort study using multistage cluster sampling method. TyG index was calculated as Ln [fasting serum triglyceride (mg/dL) * fasting blood glucose (mg/dL)/2]. Kaplan-Meier curves, log-rank test and cox proportional hazards model were used to calculate the association between TyG index and incident CVD, including stroke and coronary heart disease (CHD). Restricted cubic spline analyses were used to determine whether there was a non-linear relationship between TyG index and CVD events.ResultsDuring a median follow-up of 4.7 years, 1,422 (3.3%) individuals developed CVD, including 674 (1.6%) cases of stroke and 732 (1.7%) cases of CHD. A one unit increment higher TyG index was associated with [HR(95%CI)] 1.16(1.04–1.29) in CVD and with 1.39(1.19–1.61) in stroke. Only linear relationships between TyG and CVD/stroke were observed, while no relationship was observed with CHD after adjustments for confounders. In subgroup analyses, younger (< 50y) and diabetic participants had higher risk of CVD than their counterpart groups, while hypertensive and dyslipidemic participants depicted lower risks than their counterparts.ConclusionElevated TyG index was associated with a higher risk of incident CVD and stroke. TyG index may help in the early stage of identifying people at high risk of CVD.

THU652 Associations Of Testosterone, Dihydrotestosterone, Estradiol And Sex Hormone-binding Globulin With All-cause And Cardiovascular Mortality, And Incident Cardiovascular Events In Men: Individual Participant Data Meta-analyses

Abstract Disclosure: B.B. Yeap: None. R.J. Marriott: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. D.J. Handelsman: None. G.J. Hankey: None. R. Haring: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. G.A. Wittert: None. F.C. Wu: None. K. Murray: None. Studies examining associations of circulating sex steroids with mortality risk in men show inconsistent results for testosterone (T), with limited data for dihydrotestosterone (DHT) and estradiol (E2). We aimed to clarify associations of sex steroids, sex hormone-binding globulin (SHBG) and luteinising hormone (LH) with risks of all-cause and cardiovascular disease (CVD) mortality and incident CVD events in men, by conducting individual participant data (IPD) meta-analyses of prospective cohort studies with sex steroids measured using mass spectrometry. The Androgens In Men Study protocol was registered (PROSPERO: CRD42019139668) and published (BMJ Open 2020;10:e034777). A systematic review (completed Dec 2019) identified relevant studies (BMJ Open 2021;11:e048013). IPD were requested. Cox proportional hazards analyses related total T, SHBG, LH, DHT and E2 concentrations to risk of all-cause mortality and CVD deaths, and risk of incident CVD events. Models were adjusted for age and other sociodemographic factors, lifestyle factors, medical conditions and medications. Summary curves and hazard ratios (HRs) with 95% confidence intervals (CIs) were determined using two-stage random-effects IPD meta-analyses. Summary estimates were obtained from 11 studies (24,596 men), with median baseline age 49-76 years and 4-20 years follow-up among studies. Associations of T with all-cause and CVD mortality risk were non-linear. Risk of all-cause mortality increased for men with baseline T concentrations &amp;lt;8.7 nmol/L, and risk of CVD death increased for men with baseline T &amp;lt;5.3 nmol/L. Lower SHBG concentrations were associated with lower risk of all-cause mortality (median Quintile [Q]1 vs Q5 [Q1:Q5], 20.6 vs 68.3 nmol/L; HR=0.85, CI=0.77-0.95), and CVD death (HR=0.81, CI 0.65-1.00). Men with LH &amp;gt;10 IU/L or E2 &amp;lt;5.1 pmol/L had higher all-cause mortality, with no association of LH or E2 with CVD deaths. Associations of DHT with all-cause and CVD mortality risk were non-linear. Men with lower baseline DHT concentrations had higher risk of all-cause mortality (median Q1:Q5, 0.69 vs 2.45 nmol/L; HR=1.19, CI=1.08-1.30) and CVD deaths (HR=1.29, CI=1.03-1.61), with risk increasing for DHT &amp;gt;2.45 nmol/L. Men with baseline DHT concentrations &amp;lt;0.59 nmol/L had increased risk of incident CVD events, no other hormones were associated with this outcome. Our results suggest greater all-cause and CVD mortality risk among men with very low baseline T, higher baseline SHBG, or either lower or very high baseline DHT concentrations. There was greater risk of CVD events among men with very low baseline DHT concentrations. Potential mechanisms by which SHBG and DHT might influence mortality risk in ageing men merit further investigation. Presentation: Thursday, June 15, 2023

Impact of diabesity phenotype on cardiovascular diseases, major cardiovascular events and all-cause mortality

To investigate the longitudinal association of different phenotypes of diabetes and obesity with the incidence of cardiovascular disease (CVD), CVD- and all-cause mortality. A total of 5432 adults, aged ≥ 35 years and free of CVD were included in this cohort study. Diabesity phenotypes were defined in six categories based on the presence of diabetes (normal (NG), prediabetes and diabetes) and obesity (obese, non-obese). Fasting blood sugar, 2-h post prandial glucose, or using anti-diabetic medicines were used to define diabetes, and body mass index and waist circumference were used to define obesity. Cox proportional hazards models were used to estimate hazard ratios (HRs) for incident CVD, CVD- and all-cause mortality across these categories. After a median follow-up of 11.25 years, 819 CVD cases, 181 CVD deaths and 488 all-cause deaths occurred. In multivariable-adjusted models and irrespective of obesity definition, the phenotypes of normal glucose-obese, prediabetes-obese and pre-diabetes-non obese were not associated with CVD incidence in comparison with NG-non obese phenotype, however, the phenotypes of diabesity, either defined by general or abdominal obesity, were associated with increased risk of incident CVD events (HR = 1.42, 95% CI 1.01, 1.99, and HR = 1.46, 95% CI 1.07, 1.98, respectively). These findings were sex-specific and only in men with a phenotype of abdominal obesity-diabetes, a positive link was observed for CVD incidence (HR = 1.60, 95% CI 1.01, 2.52). No significant association was found between diabesity and death from CVD or all causes. Diabesity is a predictor of CVD and stroke incidence, but not CVD or all-cause mortality, among Iranians. This association is more pronounced amongst men than women.

The AMD ANNALS: A continuous initiative for the improvement of type 2 diabetes care

AimsSince 2006, the Italian AMD (Associations of Medical Diabetologists) Annals Initiative promoted a continuous monitoring of the quality of diabetes care, that was effective in improving process, treatment and outcome indicators through a periodic assessment of standardized measures. Here, we show the 2022 AMD Annals data on type 2 diabetes (T2D). MethodsA network involving ∼1/3 of diabetes centers in Italy periodically extracts anonymous data from electronic clinical records, by a standardized software. Process, treatment and outcome indicators, and a validated score of overall care, the Q-score, were evaluated. Results295 centers provided the annual sample of 502,747 T2D patients. Overall, HbA1c value ≤7.0% was documented in 54.6% of patients, blood pressure <130/80 mmHg in 23.0%, and LDL-cholesterol levels <70 mg/dl in 34.3%, but only 5.2% were at- target for all the risk factors. As for innovative drugs, 29.0% of patients were on SGLT2-i, and 27.5% on GLP1-RAs. In particular, 59.7% were treated with either GLP1-RAs or SGLT2-i among those with established cardiovascular disease (CVD), 26.6% and 49.3% with SGLT2-i among those with impaired renal function and heart failure, respectively. Notably, only 3.2% of T2D patients showed a Q score <15, which correlates with a 80% higher risk of incident CVD events compared to scores >25. ConclusionsThe 2022 AMD Annals data show an improvement in the use of innovative drugs and in the overall quality of T2D care in everyday clinical practice. However, additional efforts are needed to reach the recommended targets for HbA1c and major CVD risk factors.

The association between frailty and incident cardiovascular disease events in community-dwelling healthy older adults

Study objectiveThis study examined the association between frailty and incident cardiovascular disease (CVD) events, major adverse cardiovascular events (MACE), and CVD-related mortality. DesignLongitudinal cohort study. SettingThe ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial in Australia and the United States. Participants19,114 community-dwelling older adults (median age 74.0 years; 56.4 % females). InterventionsPre-frailty and frailty were assessed using a modified Fried phenotype and a deficit accumulation Frailty Index (FI) at baseline. Main outcome measuresCVD was defined as a composite of CVD death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure; MACE included all except heart failure. Cox proportional hazards regression was used to analyze the association between frailty and CVD outcomes over a median follow-up of 4.7 years. ResultsBaseline pre-frail and frail groups had a higher risk of incident CVD events (Hazard Ratio (HR): 1.31; 95 % Confidence Interval (CI): 1.14–1.50 for pre-frail and HR: 1.63; 95 % CI: 1.15–2.32 for frail) and MACE (pre-frail HR: 1.26; 95 % CI: 1.08–1.47 and frail HR: 1.51; 95 % CI: 1.00–2.29) than non-frail participants according to Fried phenotype after adjusting for traditional CVD risk factors. Effect sizes were similar or larger when frailty was assessed with FI; similar results for men and women. ConclusionFrailty increases the likelihood of developing CVD, including MACE, in community-dwelling older men and women without prior CVD events. Screening for frailty using Fried or FI method could help identify community-dwelling older adults without prior CVD events who are more likely to develop CVD, including MACE, and may facilitate targeted preventive measures to reduce their risk.

Abstract 10334: Vital Exhaustion and Cardiac Biomarkers - The Atherosclerosis Risk in Communities Study

Introduction: Vital exhaustion (VE), defined as excessive fatigue and demoralization due to chronic stress, is a risk factor for cardiovascular disease (CVD), but the mechanism is unclear. We examined the association of VE with biomarkers of cardiac injury, neurohormonal stress and inflammation in the Atherosclerosis Risk in Communities (ARIC) study. Methods: Symptoms of VE were measured at ARIC visit 2 (1990-92, n= 11,588, mean age 57) using the Maastricht Vital Exhaustion Questionnaire (MVEQ). We analyzed the association of VE with cardiac biomarkers [High-sensitivity troponin T (Hs-TnT), N-terminal pro brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (Hs-CRP)] levels in adults without known CVD. Symptoms of VE (MVEQ scores) were categorized into quartiles. Elevated biomarker levels were defined as Hs-TnT ≥ 13 ng/L, NT-proBNP ≥ 125 pg/mL, and hs-CRP ≥ 2 mg/L. Logistic regression models adjusted for demographics and comorbidities were used to test for associations. The associations of VE (MVEQ score ≥16), elevated biomarkers, or both with incident CVD events after 6-year follow up was assessed by Cox proportional hazard regression. Results: Compared with the lowest quartile of VE (MVEQ ≤ 4), the highest quartile of VE (MVEQ 16-42), in adjusted models, was associated with elevated Hs-TnT, NT-proBNP, and hs-CRP [Odds Ratio (95% confidence interval) of 1.75 (1.34-2.29, p&lt;0.01), 1.40 (1.19-1.64, p&lt;0.01), and 1.14 (1.01-1.28, p&lt;0.01), respectively]. The highest quartile of VE was associated with increased risk of CVD events. The risk was increased further in the setting of both significant VE (MVEQ ≥16) and elevated biomarkers (Table). Conclusions: Symptoms of VE are associated with elevated Hs-TnT, NT-proBNP, and Hs-CRP independent of traditional CVD risk factors. The presence of VE and elevated cardiac biomarkers is associated with high risk of incident CVD events in adults without CVD.

High triglyceride-glucose index in young adulthood is associated with incident cardiovascular disease and mortality in later life: insight from the CARDIA study

BackgroundThis study aimed to investigate the associations between the triglyceride-glucose (TyG) index in young adulthood with incident cardiovascular disease (CVD) and mortality.MethodsWe 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.ResultsAmong 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).ConclusionsHigher 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.

Associations of long-term physical activity trajectories with coronary artery calcium progression and cardiovascular disease events: results from the CARDIA study

ObjectiveThe study aimed to assess the associations of physical activity (PA) trajectories across a 25-year span with coronary artery calcium (CAC) progression, and subsequent risk of cardiovascular disease (CVD) events.MethodsWe...

Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis

Studies have reported a significant association between non-alcoholic fatty liver disease (NAFLD) and increased incidence of cardiovascular disease (CVD). However, the magnitude of the risk and whether this risk changes with the severity of NAFLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of incident CVD events. We systematically searched PubMed, Scopus, and Web of Science from database inception to July 1, 2021, to identify eligible observational studies examining the risk of incident CVD events amongst adult (age ≥18 years) individuals with and without NAFLD and in which NAFLD was diagnosed by imaging, International Classification of Diseases codes, or liver biopsy. The primary outcomes were CVD death, non-fatal CVD events, or both. Data from selected studies were extracted, and meta-analysis was performed using random-effects models to obtain summary hazard ratios (HRs) with 95% CIs. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on Open Science Framework, number osf.io/5z7gf. We identified 36 longitudinal studies with aggregate data on 5 802 226 middle-aged individuals (mean age 53 years [SD 7]) and 99 668 incident cases of fatal and non-fatal CVD events over a median follow-up of 6·5 years (IQR 5·0-10·2). NAFLD was associated with a moderately increased risk of fatal or non-fatal CVD events (pooled random-effects HR 1·45, 95% CI 1·31-1·61; I2=86·18%). This risk markedly increased across the severity of NAFLD, especially the stage of fibrosis (pooled random-effects HR 2·50, 95% CI 1·68-3·72; I2=73·84%). All risks were independent of age, sex, adiposity measures, diabetes, and other common cardiometabolic risk factors. Sensitivity analyses did not modify these results. NAFLD is associated with an increased long-term risk of fatal or non-fatal CVD events. CVD risk is further increased with more advanced liver disease, especially with higher fibrosis stage. These results provide evidence that NAFLD might be an independent risk factor for CVD morbidity and mortality. None.

Abstract 13422: Long Term Association of Low Density Lipoprotein Patterns With Coronary Artery Calcium and Atherosclerotic Cardiovascular Disease Events: Insights From HeartSCORE Study

Introduction: Low-density lipoprotein (LDL) cholesterol, a factor in progression of atherosclerotic cardiovascular disease (CVD), consists of sub-fractions with different sizes and densities in three patterns (A (large buoyant), B (small dense), AB (intermediate pattern). We examined the associations of LDL patterns with subclinical ASCVD and future events. Methods: Participants from the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were assessed for baseline lipid levels and LDL sub-fraction types by an ultracentrifugation method (vertical auto profile). Electron beam CT scans were obtained in a subset of individuals and coronary artery calcium (CAC) scores were calculated (Agatston method). Adjusted odds ratios and hazard ratios (95% CI) were calculated using logistic regression and Cox regression, respectively, to estimate the independent association between LDL sub-fractions and both; CAC and ASCVD events (MI, ischemic stroke, death), respectively. Results: Among 1884 eligible participants (mean [SD] age; 59[7.5]y, 65.8% women, 37.9% black), mean HDL-c, LDL-c and Triglycerides were 142.2[36.0]mg/dL, 58.2[14.9]mg/dL and 111.2[47.7]mmHg, respectively. Sub-fractions of LDL pattern A, B and AB were observed in 761(40%), 507(26.9%) and 616(32.7%) individuals. Over a follow up of ~16y, patterns B(1.98[1.22-3.21) and AB (1.54[1.00-2.38)] were independently associated with incident risk of CVD events (vs pattern A). When stratified by race and gender, pattern AB showed independent risk of incident CVD events and CAC presence among blacks and males (Table) . Conclusions: In this biracial cohort of middle-aged adults, LDL sub-fraction patterns B and AB showed a significantly higher risk of long-term CVD events. Pattern AB was also associated with positive CAC in blacks and males. Further studies are needed to investigate LDL patterns in CVD risk profiling based on race and gender.

Association Between Reproductive Life Span and Incident Nonfatal Cardiovascular Disease

Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD. To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause. Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019. Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older. First nonfatal CVD event, including coronary heart disease and stroke events. A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (<30 years) were at 1.71 (95% CI, 1.58-1.84) times higher risk of incident CVD events than women with a reproductive life span of 36 to 38 years after adjustment for covariates. This association remained unchanged when adjusted for age at menarche but was attenuated to 1.26 (95% CI, 1.09-1.46) when adjusted for age at menopause. There was a significant interaction between reproductive life span and age at menarche associated with CVD risk (P < .001). Women who had both short reproductive life span (<33 years) and early menarche (age ≤11 years) had the highest risk of CVD (hazard ratio, 2.06; 95% CI, 1.76-2.41) compared with those with a reproductive life span of 36 to 38 years and menarche at age 13 years. Short reproductive life span was associated with an increased risk of nonfatal CVD events in midlife, and the risk was significantly higher for women with early age at menarche.

Type of menopause, age of menopause and variations in the risk of incident cardiovascular disease: pooled analysis of individual data from 10 international studies.

How does the risk of cardiovascular disease (CVD) vary with type and age of menopause? Earlier surgical menopause (e.g. <45 years) poses additional increased risk of incident CVD events, compared to women with natural menopause at the same age, and HRT use reduced the risk of CVD in women with early surgical menopause. Earlier age at menopause has been linked to an increased risk of CVD mortality and all-cause mortality, but the extent that this risk of CVD varies by type of menopause and the role of postmenopausal HRT use in reducing this risk is unclear. Pooled individual-level data of 203767 postmenopausal women from 10 observational studies that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) consortium were included in the analysis. Postmenopausal women who had reported menopause (type and age of menopause) and information on non-fatal CVD events were included. Type of menopause (natural menopause and surgical menopause) and age at menopause (categorised as <35, 35-39, 40-44, 45-49, 50-54 and ≥55 years) were exposures of interest. Natural menopause was defined as absence of menstruation over a period of 12 months (no hysterectomy and/or oophorectomy) and surgical menopause as removal of both ovaries. The study outcome was the first non-fatal CVD (defined as either incident coronary heart disease (CHD) or stroke) event ascertained from hospital medical records or self-reported. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CI for non-fatal CVD events associated with natural menopause and surgical menopause. Compared with natural menopause, surgical menopause was associated with over 20% higher risk of CVD (HR 1.22, 95% CI 1.16-1.28). After the stratified analysis by age at menopause, a graded relationship for incident CVD was observed with lower age at menopause in both types of natural and surgical menopause. There was also a significant interaction between type of menopause and age at menopause (P < 0.001). Compared with natural menopause at 50-54 years, women with surgical menopause before 35 (2.55, 2.22-2.94) and 35-39 years (1.91, 1.71-2.14) had higher risk of CVD than those with natural menopause (1.59, 1.23-2.05 and 1.51, 1.33-1.72, respectively). Women who experienced surgical menopause at earlier age (<50 years) and took HRT had lower risk of incident CHD than those who were not users of HRT. Self-reported data on type and age of menopause, no information on indication for the surgery (e.g. endometriosis and fibroids) and the exclusion of fatal CVD events may bias our results. In clinical practice, women who experienced natural menopause or had surgical menopause at an earlier age need close monitoring and engagement for preventive health measures and early diagnosis of CVD. Our findings also suggested that timing of menopause should be considered as an important factor in risk assessment of CVD for women. The findings on CVD lend some support to the position that elective bilateral oophorectomy (surgical menopause) at hysterectomy for benign diseases should be discouraged based on an increased risk of CVD. InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). GDM is supported by Australian National Health and Medical Research Council Principal Research Fellowship (APP1121844). There are no competing interests.

Abstract MP76: Assessing the Impact of the "Health Bucks" Program on Cardiovascular Disease in New York City: A Modeling Study

Background: Low fruit and vegetable (FV) consumption is considered one of the leading causes of deteriorating health outcomes, and has been linked to obesity, diabetes, and cardiovascular disease. Yet, few adults in New York City (NYC) consume the daily recommended amounts. In order to address the need for fresh and affordable fruits and vegetables, the NYC Department of Health and Mental Hygiene has implemented the “Health Bucks” program, which provides low-income population with coupons that can be used to purchase fruits and vegetetabls. Previous studies have shown the impact of the Health Bucks program on fruit and vegetable consumption; however, it is unclear how the program would influence cardiovascular health and the associated health care costs in the long term. Objective: To estimate the health and economic impact of the Health Bucks program using a validated microsimulation model of cardiovascular disease (CVD) in NYC. Methods: We used the Simulations for Health Improvement and Equity (SHINE) CVD Model to estimate the impact of the Health Bucks program on lifetime CVD events and direct medical costs (2019 USD). We considered different program strengths by assuming the program can reduce the cost of fruits and vegetables by 20%, 30%, and 40%. Population characteristics were estimated based on data from the 2013-2014 NYC Health and Nutrition Examination Survey. CVD risk factor trajectories and risk of incident CVD events were derived from six pooled longitudinal US cohorts. Policy effects were derived from the literature. We run 1,000 simulations to account for uncertainties in the parameter. We discounted costs by 3% and reported health care costs in 2019 dollars. Results: A Health Bucks program that can reduce the cost of fruits and vegetables by 20%, 30%, and 40% would prevent 2,690 (95% CI: -14,793, 20,173), 27,386 (95% CI: 9,967, 44,805), and 50,014 (95% CI: 15,227, 50,014) coronary heart disease events, respectively, over the simulated lifetimes of the NYC population. The program would also prevent 47,469 (95% CI: 35,008, 59,931), 59,127 (95% CI: 46,676, 71,579), and 85,359 (95% CI: 72,902, 97,815) stroke events based on the price reduction level. The program would result in savings in health care costs, ranged from $937 million to $1.8 billion based on the price reduction level over the lifetime or from $19 million to $37 million annually. Conclusions: We projected that the Health Bucks program could prevent a significant number of CVD events among adults in NYC and yield substantial health care cost savings. Public health practitioners and policymakers may consider adopting this program in other locations.

930. HCV Treatment Is Associated With a Reduced Risk of Cardiovascular Disease Events: Results From ERCHIVES

BackgroundStudies reporting on the association between HCV and cardiovascular disease (CVD), and effect of HCV treatment upon future risk of CVD have shown mixed results.MethodsWithin ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans), we identified all persons treated for ≥7 weeks and propensity-score-matched group who never received HCV treatment. We excluded those with HIV, HBV, or previously diagnosed CVD. Incidence rate (per 1,000 person-years) and risk factors for CVD events (Cox proportional hazards analysis) were determined for various treatment groups. CVD events were identified using ICD-9CM/ICD-10 codes. Kaplan–Meier plots were generated to show and compare CVD-free survival by treatment status and attainment of SVR.ResultsAmong 32,575 treated and same number of untreated persons in the final dataset, median age was 58 years, 27% were Black race, and 96% were male. The incidence rate for CVD events/1,000 person-years (95% CI) among the treated was 19.10 (17.79, 20.50) vs. 32.37 (30.51, 34.33) among the untreated (P < 0.01). Treatment with a DAA regimen (vs. PEG/RBV; HR [95% CI] 0.68 [0.53,0.88]) and achieving SVR (HR [95% CI] 0.76 [0.63,0.92]) were associated with a lower risk of incidence CVD event (table). Kaplan–Meier curves demonstrated that untreated persons had a shorter CVD event-free survival during 30 months of follow-up compared with the treated persons. (figure; log-rank P < 0.0001)ConclusionHCV treatment is associated with a reduction in incident CVD events. Directly acting antiviral regimens (vs. PEG/RBV) and attainment of SVR (vs. no SVR) are associated with a lower risk of incident CVD events. Disclosures A. Ajwad Butt, Gilead: Grant Investigator, Research grant.

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events

Infection with hepatitis virus C (HCV) is associated with an increased risk of cardiovascular disease (CVD) events. It is not clear whether treatment with direct-acting antiviral (DAA) agents affects risk of CVD. We searched the Electronically Retrieved Cohort of HCV-Infected Veterans database for patients with chronic HCV infection (n= 242,680) and identified patients who had been treated with a pegylated interferon and ribavirin regimen (n= 4436) or a DAA-containing regimen (n= 12,667). Treated patients were matched for age, race, sex, and baseline values with patients who had never received treatment for HCV infection (controls). All subjects were free of any CVD event diagnosis of HCV infection at baseline. The primary outcome was incident CVD events, identified by International Classification of Diseases, Ninth Edition, Clinical Modification or International Classification of Diseases, Tenth Edition code, in the different groups and in patients with vs without a sustained virologic response to therapy. There were 1239 (7.2%) incident CVD events in the treated groups and 2361 (13.8%) events in the control group. Incidence rates were 30.9 per 1000 patient-years (95% CI 29.6-32.1) in the control group and 20.3 per 1000 patient-years (95% CI 19.2-21.5) in the treated groups (P < .0001). Treatment with pegylated interferon and ribavirin (hazard ratio 0.78; 95% CI 0.71-0.85) or a DAA regimen (hazard ratio 0.57; 95% CI 0.51-0.65) was associated with a significantly lower risk of a CVD event compared with no treatment (controls). Incidence rates for CVD events were 23.5 per 1000 patient-years (95% CI 21.8-25.3) in the group treated with the pegylated interferon and ribavirin regimen, 16.3 per 1000 patient-years (95% CI 14.7-18.0) in the group treated with a DAA regimen, and 30.4 (95% CI 29.2-31.7) in the control group. A sustained virologic response was associated with a lower risk of incident CVD events (hazard ratio 0.87; 95% CI 0.77-0.98). In an analysis of a cohort of HCV-infected veterans, treatment of HCV infection was associated with a significant decrease in risk of CVD events. Patients treated with a DAA regimen and patients who achieved sustained virologic responses had the lowest risk for CVD events.

Abstract 048: Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women

Introduction: Recent metabolomics studies have identified circulating levels of branched-chain amino acids (BCAAs; isoleucine, leucine, valine) as strong predictors of type 2 diabetes (T2D). Whether BCAAs are implicated in cardiovascular disease (CVD) risk has not been established. Hypothesis: We hypothesized that higher baseline levels of plasma BCAAs are associated with an elevated risk of incident CVD events, and evaluated whether this relationship was dependent on an intermediate diagnosis of T2D. Methods: Participants enrolled in the Women’s Health Study prospective cohort were eligible if they did not report CVD or cancer prior to baseline blood collection (N=27,172, mean baseline age=54.7 years). Plasma BCAA metabolites were measured via proton NMR spectroscopy, ln-transformed, and standardized for analysis. We used multivariable Cox proportional regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) per standard deviation (SD) of total and individual BCAAs with incident CVD (myocardial infarction [MI], stroke, coronary revascularization). Results: 1,917 confirmed CVD events occurred over follow-up (mean 18.6 years). In models adjusted for age, body mass index, smoking status, diet quality, physical activity, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD, HR=1.13, CI=1.08 to 1.19), comparable in magnitude to the association of LDL cholesterol with CVD (per SD, HR=1.15, CI=1.09 to 1.21). In particular, BCAAs were associated with coronary events (MI: HR=1.21, CI=1.10 to 1.33; revascularization: HR=1.15, CI=1.07 to 1.23), but not with stroke (HR=1.07, CI=0.98 to 1.15). The BCAA-CVD relationship was notably greater (p-interaction=0.008) among participants who developed T2D prior to a CVD event (HR=1.25, CI=1.13 to 1.39), vs. women without T2D (HR=1.07, CI=1.01 to 1.13). Isoleucine, leucine, and valine were each associated with CVD (p&lt;0.05). Further adjusting for biomarkers of potential intermediates, HbA1c, lipids, and a lipoprotein-based insulin resistance score entirely eliminated the associations of BCAAs with CVD. Conclusions: Circulating plasma BCAAs were positively associated with long-term incident CVD in a cohort of US women, in particular among women who developed T2D prior to a CVD event. Impaired BCAA metabolism may represent a shared pathway of insulin resistance that links the risks of T2D and CVD.

Advanced Glycation End Products, Oxidation Products, and Incident Cardiovascular Events in Patients With Type 2 Diabetes.

OBJECTIVEThe goal of this study was to determine whether plasma levels of advanced glycation end products (AGE) and oxidation products (OP) predict the incidence of cardiovascular disease (CVD) in type 2 diabetes.RESEARCH DESIGN AND METHODSFive specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and two OP (2-aminoadipic acid and methionine sulfoxide [MetSO]) were measured at baseline in two intensive glucose-lowering studies: 1) a subcohort of the Veterans Affairs Diabetes Trial (VADT) (n = 445) and 2) a nested case-control subgroup from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (n = 271).RESULTSIncreased levels of several AGE and OP were associated with older age, decreased kidney function, previous CVD, and longer diabetes duration, but not with hemoglobin A1c. In the VADT, increased risk of incident CVD events (n = 107) was associated with lower MetSO after adjusting for age, race/ethnicity, sex, prior CVD event, kidney function, treatment assignment, and diabetes duration (hazard ratio [HR] 0.53; 95% CI 0.28–0.99; P = 0.047). Individuals with both low MetSO and high 3-deoxyglucosone hydroimidazolone concentrations were at highest risk for CVD (HR 1.70; P = 0.01). In the ACCORD study, those with incident CVD events (n = 136) had lower MetSO (by 14%; P = 0.007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (by 18% and 15%, respectively; P = 0.04 for both); however, only the difference in MetSO remained significant after adjustment for prior CVD event (P = 0.002).CONCLUSIONSLower levels of MetSO and higher levels of select AGE are associated with increased incident CVD and may help account for the limited benefit of intensive glucose lowering in type 2 diabetes.

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OBJECTIVES/SPECIFIC AIMS: Cardiovascular disease (CVD) is the leading cause of death among US adults and its prevalence is increasing, despite efforts to identify, and address risk factors. Post-traumatic stress disorder (PTSD) has been identified as a potential risk factor for CVD, though the results to date have focused on male veterans with combat-related PTSD. To our knowledge, there are no prospective analyses/reports among older community-dwelling adults following Hurricane Katrina. The purpose of this study was to explore the link between PTSD associated with Hurricane Katrina and incident CVD among elderly adults using data from the Cohort Study of Medication Adherence among Older Adults (CoSMO). METHODS/STUDY POPULATION: PTSD associated with Katrina and incident CVD events were assessed among 2075 hypertensive participants age ≥65 who were enrolled in a managed care organization in southeastern Louisiana. Baseline surveys were conducted between August 2006 and September 2007. Baseline surveys were conducted between August 2006 and September 2007. PTSD was assessed using the civilian PTSD CheckList (PCL-17) and 2 cut-off points, ≥37 and ≥44, for primary and secondary analyses, respectively. Participants were followed through February 2011 for a composite CVD outcome of MI, stroke, CHF, or CVD death. Multivariable logistic regression was performed with 13 covariates identified in bivariate analysis: age, sex, race, marital status, education, hypertension knowledge, comorbidities, number of antihypertensive medication classes, dissatisfaction with healthcare, reduced medications due to cost, number of visits to healthcare provider in last year, depression, and coping. RESULTS/ANTICIPATED RESULTS: Participants were 59.8% female and 30.4% black, with a mean age of 75 years. The prevalence of PTSD using the primary and secondary cut points was 6.1% and 4.2%, respectively. In total, 240 (11.5%) participants had a CVD event during a median 3.8 year follow-up. After multivariable adjustment, the odds ratios and 95% confidence intervals (CI) for CVD event for the primary and secondary analyses were 1.90 (95% CI: 1.17, 3.09) and 3.74 (95% CI: 2.05, 6.81), respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: PTSD was associated with an increased risk of incident CVD events among elderly adults. This finding from a prospective cohort study supports earlier reports suggesting PTSD is an independent risk factor for CVD. To our knowledge, this association has not been previously reported among a cohort of elderly community-dwelling adults. This study included hypertensive, elderly, insured participants living in southeastern Louisiana following Hurricane Katrina and may not be generalizable to all people with PTSD. Strengths of this study include its longitudinal design, the identification of incident CVD, the diversity of the study population with respect to gender, race and CV risk, and reduced confounding due to access to care and insurance status. Future research is needed to confirm this finding in other populations and to assess if efforts to minimize the impact of PTSD following disasters reduce CVD risk and premature CVD events among older adults.

Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study

Background and aimsMyeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. MethodsLevels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. ResultsAdjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12–2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27–2.85). ConclusionsIncreased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.