Incident Atherosclerotic Cardiovascular Disease Research Articles

Abstract P366: Pooled Cohort Equation Performance in Primary and Secondary Prevention Subgroups of the SystolicBlood Pressure Intervention Trial (SPRINT)

Background: The Pooled Cohort Equation (PCE) estimates 10-y atherosclerotic cardiovascular disease (ASCVD) risk among adults aged 40-79 years without CVD. Recent studies applied the PCE to mixed primary (1°) and secondary (2°) prevention populations to predict risk of future CVD events. However, the PCE is not validated in 2° prevention populations. We studied the impact of prior CVD on PCE performance in a 2° prevention population of the SPRINT trial. Methods: SPRINT randomized 9,361 adults with hypertension and ≥1 CVD risk factor or prior ASCVD to standard or intensive BP control. Excluding those age >79 years (n=1,158) or missing PCE covariates (n=52), we calculated 10-year ASCVD risk at baseline using the PCE. We assessed PCE discrimination with the C-statistic among all SPRINT participants and among 1° and 2° prevention subgroups. We estimated the hazard ratio (HR) for incident ASCVD events comparing the 2° to the 1° prevention group, controlling for baseline PCE-predicted 10-y risk. Results: Of the 8,151 included participants, 6,874 (84%) and 1,277 (16%) were in the 1° and 2° prevention groups, respectively. Mean (SD) age was 66 (8) years, 35% were female, 34% were black. Median (IQR) baseline predicted 10-year ASCVD risk in the 1° prevention group was lower than the 2° prevention group (P<0.001; Table ). In the 3.3 years of follow-up, ASCVD events occurred more frequently in the 2° prevention group than the 1° prevention group (P<0.001). The C-statistic was 0.618 (95% CI 0.589, 0.646) in the entire analytic population, and was non-significantly higher among the 1° prevention subgroup. Comparing the 2° to 1° prevention population, HR for incident ASCVD events was 2.6 (95% CI 2.1, 3.3) when controlling for baseline PCE-estimated 10-y risk. Conclusions: Adults with prior ASCVD events have a nearly 3-fold higher risk of subsequent events. This study demonstrates that the PCE underestimates risk of recurrent events in 2° prevention populations and use in mixed populations should be avoided.

Prevalence and outcomes of non-alcoholic fatty liver disease (NAFLD) among Asian American adults in the United States.

Non-alcoholic fatty liver disease (NAFLD) affects about 25% of the general population worldwide. Although epidemiology of NAFLD is well studied in the United States, there is paucity of data for the Asian Americans. Our aim was to assess the prevalence and risk factors for NAFLD among Asian Americans. We utilized NHANES data for 2011-2016. We defined NAFLD using recently derived US-FLI. Relative risks (RRs) and population attributable fractions (PAFs) of metabolic components on atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis were calculated for Asian Americans, and these rates were compared to non-Hispanic whites. NAFLD prevalence was 18.3% among Asian Americans and 28.4% among non-Hispanic whites.Asian Americans with NAFLD had lower BMI and waist circumference than non-Hispanic whites with NAFLD and were less likely to have metabolic syndrome, cardiovascular disease (CVD), chronic obstructive pulmonary disease, cancer and incident ASCVD (P < 0.05). Hyperlipidaemia had the highest attributable fraction (76.6%) for risk of ASCVD among Asian Americans with NAFLD, followed by diabetes (24.0%), current smoking (9.2%), and obesity (3.7%). Advanced fibrosis in Asian American with NAFLD was independently associated with presence of type 2 diabetes (RR=2.70, 95% CI: 1.00-7.27). Asian Americans have lower prevalence of NAFLD than non-Hispanic whites. However, Asian Americans with NAFLD have similar risk factors for advanced fibrosis and ASCVD than non-Hispanic Whites.

Gender difference in the risk for cardiovascular events or mortality of patients with diabetic foot syndrome.

Diabetic foot syndrome (DFS) increases the risk for atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or mortality. The present study aims at ascertaining whether such DFS-related excess risk differs between genders, retrospectively investigating a population with diabetes from Tuscany, Italy, followed-up for 6years (2011-2016). People with diabetes living in Tuscany on January 1st 2011 identified by administrative databases, were divided by baseline history of prior DFS hospitalizations, stratified by presence/absence of peripheral vascular disease and evaluating, by Cox regression analysis, whether adjusted DFS-related excess risk of incident ASCVD, CKD or mortality differed between genders. In an overall population of 165,650 subjects with diabetes (81,829M/83,821F), basal prevalence of DFS was twice higher among males, who were moreover at a significantly greater risk of all considered outcomes along the 6-year period. On the contrary, baseline DFS significantly increased the hospitalization risk for ASCVD, CKD and mortality equally or at a slightly greater extent in females, while the risk for stroke was significantly associated with DFS only among females (HR: 1.622 (1.314-1.980); p = 0.0001 vs. HR: 1.132 (0.955-1.332); p = NS). This finding was even reinforced in non-vascular DFS, which was associated with a significant raised risk for stroke, heart failure or mortality exclusively in females. In this population, DFS prevalence and overall risk for ASCVD, CKD or mortality were significantly higher among males. Baseline co-presence of DFS, however, conferred a similar adjusted risk for all these outcomes between genders, and in case of non-vascular DFS the risk was significantly increased only among females.

Implications of the 2017 American College of Cardiology/American Heart Association Hypertension Guideline in a Modern Primary Prevention Multi-Ethnic Prospective Cohort (Multi-Ethnic Study of Atherosclerosis)

The American College of Physicians and the American Academy of Family Physician did not endorse the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines citing multiple concerns. We assessed the increase in antihypertensive medication eligibility introduced by the 2017 hypertension guideline and the risk profile of those newly eligible for blood pressure medication using participants from the MultiEthnic Study of Atherosclerosis. The antihypertensive medication eligibility criteria of the Joint National Commission (JNC) VII, JNC VIII, and the 2017 ACC/AHA hypertension guidelines were applied to the cohort and the risk profile of those newly eligible was compared with those ineligible for antihypertensive medication under the 2017 ACC/AHA guidelines using Kaplan-Meier and Cox proportional hazard analysis. The new guideline increased antihypertensive medication eligibility by 46.8% and 96.7% compared with the JNC VII and JNC VIII guideline respectively. The newly eligible group did not have an increased risk of incident atherosclerotic cardiovascular disease, heart failure, or death compared with those ineligible (HR [95%CI]: 1.26 [0.96 to 1.65], p = 0.10; 0.75 [0.45 to 1.26], p = 0.27; 1.06 [-0.84 to 1.36], p = 0.62, respectively) after adjusting for age, gender, and race. The 2017 ACC/AHA hypertension guidelines extend antihypertensive medication to a substantial number of individuals, although the risk profile of the newly eligible group appears similar to those ineligible for antihypertensive medication after adjusting for non-modifiable risk factors.

Lipoprotein(a) levels and risk of cardiovascular disease events in individuals with diabetes mellitus or prediabetes: The Atherosclerosis Risk in Communities study

Background and aimsDiabetes increases risk for atherosclerotic cardiovascular disease (ASCVD). Current guidelines do not recommend measuring lipoprotein(a), another ASCVD risk factor, in these individuals. We examined the association of lipoprotein(a) levels with incident ASCVD events in persons with and without diabetes or prediabetes. MethodsLipoprotein(a) and other ASCVD risk factors were measured at baseline (1996–1998) in the biracial Atherosclerosis Risk in Communities study; participants without prevalent ASCVD (coronary heart disease or stroke) were monitored ∼15 years for incident ASCVD events. ResultsOf 9871 eligible participants (mean age 63 years; 5816 women; 2155 African Americans), 1543 had diabetes and 3615 had prediabetes. Cumulative ASCVD incidence rates (event/1000-person years) were higher in participants with diabetes (26%) or prediabetes (13%) than in nondiabetic individuals (10%, p < 0.001). When comparing highest to lowest lipoprotein(a) categories (≥50 mg/dL vs. ≤10 mg/dL), increasing lipoprotein(a) levels were significantly associated with increasing incident ASCVD events in Caucasian participants with prediabetes (hazard ratio [HR] = 1.35; 95% confidence interval [CI] 1.07–1.69); p = 0.03) and diabetes (HR = 1.42; 95% CI 1.10–1.84; p < 0.01), but not those with normal fasting blood glucose. Adding lipoprotein(a) to Pooled Cohort Equation variables improved risk prediction in persons with diabetes (Δ in area under the receiver operating characteristic curve [AUC] 0.0087, net reclassification index [NRI] 0.1761) and prediabetes (ΔAUC 0.0025, NRI 0.0938). ConclusionsIn this biracial cohort, elevated lipoprotein(a) levels in Caucasian individuals with diabetes or prediabetes were associated with further increased ASCVD risk. Adding lipoprotein(a) to traditional risk factors improved ASCVD risk prediction.

Atherosclerotic cardiovascular disease risk assessment in familial hypercholesterolemia: does one size fit all?

Familial hypercholesterolemia is a frequent genetic disease associated with lifelong elevation of LDL-cholesterol and premature atherosclerotic cardiovascular disease (ASCVD). Statins are the cornerstone of treatment. However, with the introduction of novel LDL-cholesterol-lowering therapies, it is necessary to identify familial hypercholesterolemia patients presenting a significantly high residual ASCVD risk. The aim of this review is to provide an update on the recent literature concerning cardiovascular risk stratification including the role of coronary imaging. Several factors have shown to be independent predictors of ASCVD in familial hypercholesterolemia. These include clinical scores with cardiovascular risk factors, coronary imaging and novel protein biomarkers. However, the recent introduction of the SAFEHEART risk-equation (SAFEHEART-RE) could allow a more accurate ASCVD risk prediction in familial hypercholesterolemia. This article highlights the SAFEHEART-RE as a model to predict incident ASCVD in familial hypercholesterolemia. This equation is a simple and widely applicable tool for use in every clinical setting. Furthermore, coronary atherosclerosis assessed by coronary computed-tomographic angiography (coronary-CTA) is independently associated to the cardiovascular risk estimated according to the SAFEHEART-RE. This equation, as well as coronary-CTA and new biomarkers, could increase individual ASCVD risk stratification and could improve the efficiency and the use of new lipid-lowering therapies in familial hypercholesterolemia.

Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy

ObjectivesThe aim of this study was to evaluate the role of coronary artery calcium (CAC) as a predictor of atherosclerotic cardiovascular disease (ASCVD) (fatal or not myocardial infarction, stroke, unstable angina requiring revascularization, and elective myocardial revascularization) events in asymptomatic primary prevention molecularly proven heterozygous familial hypercholesterolemia (FH) subjects receiving standard lipid-lowering therapy. BackgroundFH is associated with premature ASCVD. However, the clinical course of ASCVD in subjects with FH is heterogeneous. CAC score, a marker of subclinical atherosclerosis burden, may optimize ASCVD risk stratification in FH. MethodsSubjects with FH underwent CAC measurement and were followed prospectively. The association of CAC with ASCVD was evaluated using multivariate analysis. ResultsA total of 206 subjects (mean age 45 ± 14 years, 36.4% men, baseline and on-treatment low-density lipoprotein cholesterol 269 ± 70 mg/dl and 150 ± 56 mg/dl, respectively) were followed for a median of 3.7 years (interquartile range: 2.7 to 6.8 years). CAC was present in 105 (51%), and 15 ASCVD events (7.2%) were documented. Almost one-half of events were hard outcomes, and the others were elective myocardial revascularizations. The annualized rates of events per 1,000 patients for CAC scores of 0 (n = 101 [49%]), 1 to 100 (n = 62 [30%]) and >100 (n = 43 [21%]) were, respectively, 0, 26.4 (95% confidence interval: 12.9 to 51.8), and 44.1 (95% confidence interval, 26.0 to 104.1). In multivariate Cox regression analysis, log(CAC score + 1) was independently associated with incident ASCVD events (hazard ratio: 3.33; 95% CI: 1.635 to 6.790; p = 0.001). ConclusionsCAC was independently associated with ASCVD events in patients with FH receiving standard lipid-lowering therapy. This may help further stratify near-term risk in patients who might be candidates for further treatment with newer therapies.

Body Mass Index From Early-, Mid-, and Older-Adulthood and Risk of Heart Failure and Atherosclerotic Cardiovascular Disease: MESA.

BackgroundObesity contributes significantly to risk of atherosclerotic cardiovascular disease (ASCVD) and especially for heart failure (HF). An elevated body mass index (BMI) in older adults might not carry the same risk as in younger adults, but measured weights at other lifetime points are often not available. We determined the associations of self‐reported weights from early‐ and mid‐adulthood, after accounting for measured weight at older age, with incident HF/ASCVD risk.Methods and ResultsWe studied 6437 MESA (Multi‐Ethnic Study of Atherosclerosis) participants (aged 45–84, free of baseline HF/ASCVD) with self‐reported weights at ages 20 and 40 years (by questionnaire), measured weights at up to 5 in‐person examinations (2000–2012), and follow‐up for adjudicated HF/ASCVD events. Participant mean±SD age at the baseline examination was 62.2±10.2 years. Over median follow‐up of 13 years, 290 HF and 828 ASCVD events occurred. After adjustment for cardiovascular risk factors and baseline BMI, higher self‐reported weights at ages 20 and 40 years were independently associated with increased risk of incident HF with hazard ratios (95% confidence interval) of 1.27 (1.07–1.50) and 1.36 (1.18–1.57), respectively, per 5‐kg/m2 higher BMI. For incident ASCVD, only higher BMI at age 20 years was associated after accounting for current BMI (1.13 [1.01–1.26] per 5 kg/m2). Obesity during follow‐up examinations was also associated with incident HF (1.72 [1.21–2.45]) but not ASCVD.ConclusionsSelf‐reported lifetime weight is a low‐tech tool easily utilized in any clinical encounter. Although subject to recall bias, self‐reported weights may provide prognostic information about future HF risk, incremental to current BMI, in a multiethnic cohort of middle‐aged to older adults.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Plasma Aldosterone Concentration as a Determinant for Statin Use among Middle-Aged Hypertensive Patients for Atherosclerotic Cardiovascular Disease.

The use of statin therapy on the prevention of atherosclerotic cardiovascular disease (ASCVD) is recommended by the American College of Cardiology (ACC) and the American Heart Association (AHA); nevertheless, its validation on primary aldosteronism (PA) patients has not been reported. We investigated the risk of incident ASCVD in middle-aged patients with PA compared with essential hypertension (EH) based on ACC/AHA recommendations. We enrolled 461 PA patients and 553 EH patients. Even though the ratio of metabolic syndrome in each group was similar, the PA group had higher systolic blood pressures, higher low-density lipoprotein levels, higher plasma aldosterone concentration (PAC), lower high-density lipoprotein levels, and higher 10-year ASCVD compared to the EH group. The discriminative power for predicting ASCVD by the recommended statin use from the ACC/AHA guidelines was proper in the PA group (i.e., under the receiver operating characteristic curve (95% confidence interval; 0.94 (0.91–0.96)). The generalized additive model showed patients with PAC higher than 60 ng/dL accompanying the standard timing of the statin use suggested by the ACC/AHA. The ACC/AHA guidelines have good discriminative power in the prediction of middle-aged high-risk hypertensive patients, while PAC identifies those high-risk individuals who may benefit from early statin therapy.

Discordance between 10-year cardiovascular risk estimates using the ACC/AHA 2013 estimator and coronary artery calcium in individuals from 5 racial/ethnic groups: Comparing MASALA and MESA

Background and aimsSouth Asian (SA) individuals are thought to represent a group that is at high-risk for atherosclerotic cardiovascular disease (ASCVD). However, the performance of the Pooled Cohort Equations (PCE) remains uncertain in SAs living in the US. We aimed to study the interplay between predicted 10-year ASCVD risk and coronary artery calcium (CAC) in SAs compared to other racial/ethnic groups. MethodsWe studied 536 SAs from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, and 2073 Non-Hispanic Whites (NHWs), 1514 African Americans (AAs), 1254 Hispanics, and 671 Chinese Americans (CAs) from the Multi-Ethnic Study of Atherosclerosis (MESA) who were not currently on statins. We used logistic regression models to assess the association between race/ethnicity and CAC within each ASCVD risk stratum. ResultsSAs at low and at intermediate estimated ASCVD risk were more likely to have CAC = 0 compared to NHWs, while SAs at high risk had a similar CAC burden to NHWs. For example, intermediate-risk SAs had a 73% higher odds of CAC = 0 compared to NHWs (95% 1.00–2.99), while high-risk SAs were equally likely to have CAC = 0 (OR 0.95, 95% CI 0.65–1.38) and CAC >100 (OR 0.86, 95% CI 0.61–1.22). ConclusionsOur results suggest that the extent of ASCVD risk overestimation using the PCEs may be even greater among SAs considered at low and intermediate risk than among NHWs. Studies with incident ASCVD events are required to validate and/or recalibrate current ASCVD risk prediction tools in this group.

Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study

ObjectiveTo assess whether statin treatment is associated with a reduction in atherosclerotic cardiovascular disease (CVD) and mortality in old and very old adults with and without diabetes.DesignRetrospective cohort study.SettingDatabase of...

Daily Consumption of Chocolate Rich in Flavonoids Decreases Cellular Genotoxicity and Improves Biochemical Parameters of Lipid and Glucose Metabolism.

In recent years, the incidence of atherosclerotic cardiovascular disease, obesity, and diabetes has increased largely worldwide. In the present work, we evaluated the genoprotective effect of the consumption of flavonoids-rich chocolate on 84 young volunteers. Biochemical indicators related to the prevention and treatment of cardiovascular risk and metabolic syndrome were also determined. A randomized, placebo-controlled, double-blind study was performed in the Autonomous University of Baja California. The treatments comprised the daily consumption of either 2 g of dark chocolate containing 70% cocoa, or 2 g of milk chocolate, for 6 months. The total amount of phenolic compounds and flavonoids was determined in both types of chocolate. Anthropometrical and Biochemical parameters were recorded prior to and after the study. The evaluation of the genotoxicity in buccal epithelial cells was performed throughout the duration of the study. Flavonoids from cocoa in dark chocolate significantly prevented DNA damage, and improved the nucleus integrity of cells. This effect could be related to the antioxidant capacity of the dark chocolate that decreased cellular stress. Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were improved after six months of daily intake of 2 g of dark chocolate with a 70% of cocoa.

Altered branched chain amino acid metabolism: toward a unifying cardiometabolic hypothesis.

Atherosclerotic cardiovascular disease (CVD) and type II diabetes (T2D) share common etiologic pathways that may long precede the development of clinically evident disease. Early identification of risk markers could support efforts to individualize risk prediction and improve the efficacy of primary prevention, as well as uncover novel therapeutic targets. Altered metabolism of branched-chain amino acids (BCAAs), and their subsequent accumulation in circulation, may precede the development of insulin resistance and clinically manifest cardiometabolic diseases. BCAAs - the essential amino acids leucine, isoleucine and valine - likely promote insulin resistance through activation of mammalian target of rapamycin complex 1. Epidemiologic studies demonstrate robust associations between BCAAs and incident T2D, and Mendelian randomization supports a potentially causal relationship. More recently, there is emerging evidence that BCAAs are also associated with incident atherosclerotic CVD, possibly mediated by the development of T2D. In this article, we review the biochemistry of BCAAs, their potential contribution to cardiometabolic risk, the available evidence from molecular epidemiologic studies to date, and, finally, consider future research and clinical directions. Overall, BCAAs represent a promising emerging target for risk stratification and possible intervention, to support efforts to mitigate the burden of cardiometabolic disease in the population.

Central Obesity and Visceral Adipose Tissue Are Not Associated With Incident Atherosclerotic Cardiovascular Disease Events in Older Men.

BackgroundVisceral adipose tissue (VAT) and other measures of central obesity predict incident atherosclerotic cardiovascular disease (ASCVD) events in middle‐aged individuals, but these associations are less certain in older individuals age 70 years and older. Our objective was to estimate the associations of VAT and the android–gynoid fat mass ratio, another measure of central obesity, with incident ASCVD events among a large cohort of older men.Methods and ResultsTwo thousand eight hundred ninety‐nine men (mean [SD] age 76.3 [5.5] years) enrolled in the Outcomes of Sleep Disorders in Older Men study had rigorous adjudication of incident ASCVD events (myocardial infarction, coronary heart disease death, or fatal or nonfatal stroke). We used proportional hazards models to estimate the hazard ratios for incident ASCVD per SD increase of VAT or android–gynoid fat mass ratio (measured at baseline with dual‐energy absorptiometry), adjusted for age, race, education, systolic blood pressure, smoking status, oxidized low‐density lipoprotein level, treatment for hypertension, statin use, aspirin use, presence of diabetes mellitus, and study enrollment site. Over a mean (SD) follow‐up period of 7.9 (3.4) years, 424 men (14.6%) had an incident ASCVD event. Neither VAT nor android–gynoid fat mass ratio were associated with incident ASCVD events, either unadjusted or after multivariable‐adjustment (hazard ratios [95% confidence interval ] per SD increase 1.02 [0.92–1.13] and 1.05 [0.95–1.17], respectively).ConclusionsCentral adipose tissue, as measured by VAT or android–gynoid fat mass ratio, was not associated with incident ASCVD events in this study of older men.

Comparison of Frequency of Atherosclerotic Cardiovascular and Safety Events With Systolic Blood Pressure

Whether the benefit of intensive blood pressure (BP) control reduces atherosclerotic cardiovascular disease (ASCVD) risk without increasing risks of serious adverse events (SAEs) is unknown. We sought to assess differences in incident ASCVD and SAE with intensive BP control across the spectrum of 10-year ASCVD risk in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT randomized 9,361 participants who were ≥50years old and ≥1 CVD risk factor to standard or intensive BP control (<120 or 130 to 139mm Hg). We excluded adults with clinical ASCVD or age ≥80. We included 6,875 participants. We compared hazard ratios (HR) and risk differences (RD) of incident ASCVD events or SAEs in all and across quartiles of baseline risk. Median predicted ASCVD risk was 15.9%. Intensive BP control significantly reduced ASCVD events (HR 0.75, 95% confidence interval 0.58, 0.97, p = 0.03; RD -0.94; -1.8, -0.1; p = 0.03). There was no difference in effect across quartiles of ASCVD risk. There was a non-significant increase in SAE with intensive BP control (HR 1.08, 1.00, 1.17 p = 0.06; RD 2.1, -0.1, 4.4, p = 0.03), and no difference in this effect across quartiles of risk. In SPRINT participants without baseline clinical ASCVD, the benefit of intensive BP control for primary prevention of ASCVD may extend to lower risk participants without an increase in SAE. In conclusion, lower risk adults with stage 1 hypertension meeting SPRINT eligibility may benefit from initiation of antihypertensives.

Serum Fibroblast Growth Factor-21 Is Related to Atherosclerosis Independent of Nonalcoholic Fatty Liver Disease and Predicts Incident Atherosclerotic Cardiovascular Diseases

Fibroblast growth factor 21 (FGF-21), a key hepatokine regulating lipid metabolism, is related to several atherosclerotic diseases. But whether this relationship is mediated by nonalcoholic fatty liver disease (NAFLD) is not clear. Here we assessed the association of serum FGF-21 with atherosclerosis in non-NAFLD subjects and further investigated prospectively whether baseline FGF-21 could predict incident atherosclerotic cardiovascular disease (ASCVD) in a 7-year community study.Serum FGF-21 were measured in a cross-sectional cohort of 371 type 2 diabetic patients without NAFLD as determined by hepatic magnetic resonance spectroscopy, and a population-based prospective cohort of 7subjects from the Shanghai Diabetes Study. In the cross-sectional study, serum FGF-21 was significantly higher in those with subclinical carotid atherosclerosis (268.8 [139.0-415.2] vs. 188.3 [100.2-376.4] pg/ml, P=0.005). Multiple logistic regression analysis showed that serum FGF-21 was independently associated with atherosclerosis. In the prospective study, baseline serum FGF-21 was significantly higher in those who developed ischemic heart disease (479.5 [302.4-627.0] pg/ml, P=0.004) or cerebral infarction (401.6 [238.3-616.4] pg/ml, P=0.021) than those who did not (325.2 [189.0-498.9] pg/ml) during the follow-up. In multivariable Cox regression analysis, baseline serum FGF-21 independently predicted incident ASCVD events and significantly improved discriminatory and reclassifying abilities of the prediction model after adjustment for established cardiovascular risk factors.This study provides the first evidence that FGF-21 is elevated, independent of NAFLD, in subjects with subclinical atherosclerosis. Baseline FGF-21 is an independent predictor of incident ASCVD and could be utilized as a novel biomarker for primary prevention in general population. Disclosure L. Wu: None. L. Qian: None. H. Li: None. W. Jia: None.

Risk of Incident Atherosclerotic Cardiovascular DiseaseEvents by Achieved Atherogenic Lipid Levels Among62,428 Statin-Treated Individuals With Diabetes Mellitus

The relevance of low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) goals for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among patients with diabetes was assessed. This retrospective cohort study included patients with type 2 diabetes, age 21 to 90years, taking statins, with no history of ASCVD as of January 1, 2006, in Kaiser Permanente Northern California, an integrated healthcare delivery system. Multivariate cox models were utilized to estimate hazard ratios (HRs) for incident ASCVD events by achieved LDL-C and non-HDL-C levels with adjustment for potential confounders. Incident ASCVD events were defined as a composite of myocardial infarction, ischemic stroke, or coronary heart disease death. A cohort of 62,428 patients, with mean age of 64.1years, 46.9% women, and mean follow-up of 6.0 years, was identified. After adjustment, the risk of incident ASCVD for these statin-treated patients was monotonically lower with decreasing achieved LDL-C levels (p<0.0001 for trend) and non-HDL-C levels (p <0.0001 for trend). Relative to achieved LDL-C ≥130 mg/dl, LDL-C <50 mg/dl had HR = 0.58 (95% confidence interval 0.49 to 0.69). Relative to achieved non-HDL-C ≥160mg/dl, non-HDL-C <80 mg/dl had HR = 0.59 (95% confidence interval 0.51 to 0.68). In a large cohort of statin-treated diabetic patients without ASCVD, a monotonically lower risk of incident ASCVD events was associated with lower achieved lipid levels. These findings support the use of LDL-C ornon-HDL-C treatment goals for ASCVD primary prevention in diabetic patients.

Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).

While coronary artery calcium (CAC) has been extensively validated for predicting clinical events, most outcome studies of CAC have evaluated coronary heart disease (CHD) rather than atherosclerotic cardiovascular disease (ASCVD) events (including stroke). Also, virtually all CAC studies are of short- or intermediate-term follow-up, so studies across multi-ethnic cohorts with long-term follow-up are warranted prior to widespread clinical use. We sought to evaluate the contribution of CAC using the population-based MESA cohort with over 10 years of follow-up for ASCVD events, and whether the association of CAC with events varied by sex, race/ethnicity, or age category. We utilized MESA, a prospective multi-ethnic cohort study of 6814 participants (51% women), aged 45-84 years, free of clinical CVD at baseline. We evaluated the relationship between CAC and incident ASCVD using Cox regression models adjusted for age, race/ethnicity, sex, education, income, cigarette smoking status, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes, lipid-lowering medication, systolic blood pressure, antihypertensive medication, intentional physical exercise, and body mass index. Only the first event for each individual was used in the analysis. Overall, 500 incident ASCVD (7.4%) events were observed in the total study population over a median of 11.1 years. Hard ASCVD included 217 myocardial infarction, 188 strokes (not transient ischaemic attack), 13 resuscitated cardiac arrest, and 82 CHD deaths. Event rates in those with CAC = 0 Agatston units ranged from 1.3% to 5.6%, while for those with CAC > 300, the 10-year event rates ranged from 13.1% to 25.6% across different age, gender, and racial subgroups. At 10 years of follow-up, all participants with CAC > 100 were estimated to have >7.5% risk regardless of demographic subset. Ten-year ASCVD event rates increased steadily across CAC categories regardless of age, sex, or race/ethnicity. For each doubling of CAC, we estimated a 14% relative increment in ASCVD risk, holding all other risk factors constant. This association was not significantly modified by age, sex, race/ethnicity, or baseline lipid-lowering use. Coronary artery calcium is associated strongly and in a graded fashion with 10-year risk of incident ASCVD as it is for CHD, independent of standard risk factors, and similarly by age, gender, and ethnicity. While 10-year event rates in those with CAC = 0 were almost exclusively below 5%, those with CAC ≥ 100 were consistently above 7.5%, making these potentially valuable cutpoints for the consideration of preventive therapies. Coronary artery calcium strongly predicts risk with the same magnitude of effect in all races, age groups, and both sexes, which makes it among the most useful markers for predicting ASCVD risk.

Abstract P145: Ideal Cardiovascular Health and Incidence of Atherosclerotic Cardiovascular Disease in a Large Integrated Health Care System

Background: The American Heart Association (AHA) introduced the concept of cardiovascular health (CVH) and defined “ideal,” “intermediate,” and “poor” CVH categories for adults based on cardiovascular disease risk factors and health behaviors. We sought to examine the association between these levels of CVH and incident atherosclerotic cardiovascular disease (ASCVD) events in a large diverse population. Methods: In a large integrated healthcare delivery system in Northern California , we gathered 6 AHA metrics (smoking status, physical activity, body mass index, blood pressure, total cholesterol, and blood glucose) during 2013-2014, graded on a scale of 0 to 2, with 2 indicating "ideal" status, 1 "intermediate" status, and 0 "poor" status. Points were summed to define three categories of Poor (0-6), Intermediate (7-9) and Ideal (10-12) CVH. ASCVD was defined as non-fatal myocardial infarction (MI), fatal coronary heart disease (CHD) and fatal and non-fatal stroke from electronic medical records and state death certificates during 2015. Incident ASCVD rates per 100,000 person-years were calculated. Results: Among 1,103,583 adult members (55.5% female) receiving outpatient care with all 6 metrics, there were 194,957 (17.7%) age 18-39, 585,449 (53.0%) age 40-64, and 323,177 (29.3%) age &gt;65 years. There were 74,737 (6.8%) Blacks, 171,058 (15.5%) Hispanics and 225,303 (20.4%) Asian/Pacific Islanders. Poor CVH was present in 240,831 (21.8%), Intermediate in 584,013 (52.9%) and Ideal CVH in 278,739 (25.3%). During 2015, incidence of overall ASCVD, CHD (non-fatal MI and fatal CHD) and stroke (fatal and non-fatal stoke) was lower with better CVH metrics (p &lt; 0.0001 for trend) (Figure). Conclusions: In a diverse “real world” population, a significantly lower incident of ASCVD was noted among individuals with Ideal CVH. This indicates continued need for large scale efforts to track and improve cardiovascular risk factors and behaviors.

Abstract P208: Validation of a New Cardiovascular Risk Model: Performance of a Neural Network and the ACC/AHA Pooled Cohort Equations Across Four Diverse US Prospective Cohort Studies

Introduction: The American College of Cardiology/American Heart Association developed Pooled Cohort equations to predict the incidence of atherosclerotic cardiovascular disease (ASCVD). However, validation studies have shown that these equations may overestimate risk in more heterogeneous populations. Moreover, the equations do not fully consider lifestyle behaviors. Objective: To build a more accurate prediction model for ASCVD using a more holistic set of predictors by applying machine learning techniques that leverage the natural multi-dimensionality of risk factors across diverse cohorts. Methods: We pooled measured metabolic indicators including total triglycerides, high- and low-density lipoprotein, C-reactive protein, plasma glucose level, systolic blood pressure, height and weight, dietary consumption data, and other established behavioral risk factors from a total of 4 cohort studies: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study Offspring Cohort, and Multi-Ethnic Study of Atherosclerosis. Individuals with an ASCVD at baseline measurement, as well as those with missing covariates were excluded. Outcomes were defined as an ASVCD event within ten years of study inception. We built and trained a neural network model and evaluated out of sample performance by age, gender, and race. We considered feature interactions and performed hyperparameter tuning using grid search with cross-validation. Results: Our pooled dataset contained over 26,000 individuals with 4,066 events (15.4%), over an average follow-up time of 16.2 years. Our final risk model outperformed the pooled cohort equations across all demographic subgroups. Predicted incidence of ASCVD showed good discrimination and calibration with an area under the receiver operating characteristic curve of 0.75 for females and 0.74 for males. Conclusion: Our risk model demonstrates improved accuracy on held-out validation data over the ASCVD set of equations. By taking into account more proximal and modifiable risk factors, this model helps identify high-risk individuals with greater precision and inform CVD prevention efforts.