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ObjectiveIn statin-treated patients with stable coronary artery disease (CAD), residual risk of cardiovascular events is partly explained by plasma levels of low-density lipoprotein cholesterol (LDL-C). This study aimed to estimate individual benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in CAD patients already treated with high-dose statin.MethodsIndividual lifetime benefit was estimated in months gain free of stroke or myocardial infarction (MI) until age 80 years. Predictions were based on two competing risk models developed in data from 4853 patients with CAD originating from the atorvastatin 80 mg arm of the Treating to New Targets (TNT) trial. The relative effect of PCSK9 inhibition was added to the models and was assumed based on average estimates from large clinical trials. We accounted for individual LDL-C levels, assuming 50% LDL-C reduction by PCSK9 inhibition and 21% cardiovascular risk reduction per mmol/L (39 mg/dL) LDL-C lowering.ResultsEstimated individual gain was 1.8 mmol/L (>70 mg/dL). Estimated benefit was lowest (≤5 months) in older patients (≥70 years), in particular if LDL-C and other risk factors levels were low.ConclusionThe individual estimated lifetime benefit from PCSK9 inhibition in patients with stable CAD on high-dose statin varied from Trial registration numberNCT00327691; Post-results

Background: Among patients with clinically manifest vascular disease, the risk of recurrent vascular events is likely to vary. We assessed the distribution of estimated 10-year risk of recurrent vascular events in a secondary prevention population. We also estimated the potential risk reduction and residual risk that can be achieved if patients reach guideline-recommended risk factor targets. Methods: The SMART score (Second Manifestations of Arterial Disease) for 10-year risk of myocardial infarction, stroke, or vascular death was applied to 6904 patients with vascular disease. The risk score was externally validated in 18 436 patients with various manifestations of vascular disease from the TNT (Treating to New Targets), IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), and CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trials. The residual risk at guideline-recommended targets was estimated by applying relative risk reductions from meta-analyses to the estimated risk for targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, and use of antithrombotic agents. Results: The external performance of the SMART risk score was reasonable, apart from overestimation of risk in patients with 10-year risk >40%. In patients with various manifestations of vascular disease, median 10-year risk of a recurrent major vascular event was 17% (interquartile range, 11%–28%), varying from 30% in 22% of the patients. If risk factors were at guideline-recommended targets, the residual 10-year risk would be 30% in 9% of the patients (median, 11%; interquartile range, 7%–17%). Conclusions: Among patients with vascular disease, there is very substantial variation in estimated 10-year risk of recurrent vascular events. If all modifiable risk factors were at guideline-recommended targets, half of the patients would have a 10-year risk 20% and even >30% 10-year risk, clearly delineating an area of substantial unmet medical need.

Background: Diabetes is a robust risk factor for cardiovascular events which is marked in African Americans for reasons that may be attributed to socioeconomic and biologic vulnerabilities. Both structural (arterial thickening) and functional (arterial stiffness) abnormalities of the vasculature are predictive of incidental clinical events. Study objective was to determine the risk factors and relationship between large artery stiffness and carotid intimal thickness in African Americans with type II diabetes. Methods: 125 patients with diabetes were recruited from medical clinics. Medical information was obtained via interview and electronic medical record review. Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV) using applanation tonometry. Carotid Intimal Medial Thickness (CIMT) was obtained using B-mode ultrasound image analysis of the common carotid artery. Statistical analysis was done using SPSS version 23. Results: Mean age 60±8 years, 64% female. 82% hypertension, dyslipidemia 83%, diabetes duration 10.2±7.6 years, Mean HbA1C= 8.1±2.2%. Mean CIMT=0.68±0.15, PWV= 8.6±2.9. There was no significant association between PWV and CIMT. CIMT positively correlated with gender (r=0.302, p=0.001), smoking (r=0.278, p=0.002), creatinine (r=0.260, p=0.006), triglycerides (r=0.279, p=0.002), pooled cohort score (r=0.353, p=0.001), and negatively with HDL (r= -0.196, p=0.031). PWV positively correlated with creatinine (r=0.300, p=0.001), duration of diabetes (r=0.195, p=0.037) and age (β=0.359, p Conclusion: Our findings indicate that PWV and CIMT differ in risk factor profile in African Americans with type II diabetes mellitus. Further studies are needed to clarify mediating factors. Disclosure A. Eluwole: None. A.M. Adedayo: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. A. Bakillah: None. J. Lazar: None.

Previous studies have shown that HDL isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of nitrated apolipoprotein AI (NT-apoAI). The significance of NT-apoAI in the pathogenesis of vascular diabetic complications is not well understood. We aimed to evaluate the relationship between plasma NT-apoAI and vascular function in African-Americans diabetic patients. 125 patients with type 2 diabetes were enrolled over a 6 months period. Levels of plasma NT-apoAI was quantified by enzyme-linked immunosorbent assays (ELISA). Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound image analysis. Patients population was divided in two groups (well-controlled: HbA1c ≤7.0%, N=54; poorly-controlled: HbA1c >7.0%, N=71). Mean age 60±8 years; 64% female; 80% had hypertension; 90% had dyslipidemia and 15% had CKD. Mean HbA1c levels were 8.1±2.2% and duration of diabetes was 10.29±3.79 years. NT-apoAI was negatively correlated with levels of apoAI and VRI in well-controlled patients but not in poorly-controlled patients (r= -0.298, p=0.025 and r= -0.265, p=0.042; respectively). Multi-regression analysis revealed that NT-apoAI was independently associated with VRI, but neither with PWV nor CIMT, after adjustment for independent variables such as age, gender, weight, hypertension, stroke, smoking, duration of diabetes, dyslipidemia, total cholesterol, HDLc, triglycerides, and LDLc (β= 0.001, p= 0.025; r2= 0.325 for the model). NT-apoAI, independently of other clinical variables, can predict microvascular dysfunction particularly in well-controlled diabetic patients. NT-apoAI could be used as marker to identify diabetic patients at risk of developing early vascular complications. Disclosure A.M. Adedayo: None. A. Eluwole: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. J. Lazar: None. A. Bakillah: None.

Background: LDL plays a key role in development and progression of atherosclerosis. Elevated LDL amplifies the atherosclerotic process but the significance of modified LDL in pathogenesis of vascular complications is unclear. We aimed to assess plasma modified LDL levels and their relationship with vascular function in African American diabetic patients. Methods: 125 patients with type-2 diabetes were enrolled. Levels of glycated LDL (g-LDL), carbamylated LDL (c-LDL), nitrated LDL (n-LDL) and oxidized LDL (ox-LDL) were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI), which assesses changes in digital temperature before and after release of arterial cuff occlusion. Carotid-femoral pulse wave velocity (PWV) assessed arterial stiffness using applanation tonometry. B-mode ultrasound image analysis assessed Carotid intima-media thickness (CIMT). Patient population was divided into well-controlled: HbA1c ≤7.0%, N=54; poorly-controlled: HbA1c >7.0%, N=71. Results: Age 60±8 years; 64% Female, 80% Hypertension, 90% Dyslipidemia and 15% CKD. HbA1c level 8.1±2.2%, diabetes duration 10.29±3.79 years. Mean plasma g-LDL, c-LDL, n-LDL and ox-LDL were 1.56±0.64 mg/dL, 0.85±0.11 mg/dL, 2.33±0.39 ng/mL, and 61.93±9.25 ng/mL. Ox-LDL was positively correlated with CIMT in well-controlled patients (r= 0.45, p=0.001), but not in poorly-controlled (r= 0.12, p=0.30). Multi-regression analysis revealed ox-LDL was independently associated with CIMT, but neither with PWV nor VRI after adjustment for variables such as age, gender, weight, smoking, total cholesterol, HDLc, triglycerides, and LDLc (β= 0.003, p= 0.012; r2= 0.38). Conclusion: Ox-LDL offered better predictive value for CIMT in well-controlled patients than other forms of modified LDL. These data favor ox-LDL as potential marker to identify diabetic patients at risk of developing atherosclerotic vascular complications. Disclosure A.M. Adedayo: None. A. Eluwole: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. J. Lazar: None. A. Bakillah: None.

Human F11 receptor (F11R) is an important cell adhesion molecule implicated in inflammatory thrombosis. F11R is associated with the presence and severity of cardiovascular disease. Endothelial dysfunction in diabetes has been attributed to lack of bioavailability of nitric oxide (NO), another key