AN OBSERVATIONAL ANALYSIS OF 7,000 PATIENTS WITH SEVERE HYPERCHOLESTEROLEMIA: IDENTIFYING AN AGE-TREATMENT GAP IN CARDIOVASCULAR RISK REDUCTION

Therapeutic Area: Severe Hypercholesterolemia, Lipid Management Background: Hypercholesterolemia is an important treatable risk factor for cardiovascular disease—which remains one of the leading causes of death in the United States. Approximately 7% of American adults have severe hypercholesterolemia (a low-density lipoprotein cholesterol (LDL-C) level ≥190 mg/dL). Despite a class I indication for statin therapy, many patients remain untreated or undertreated. Methods: We reviewed all patients ≥ 18 years in our health system with at least one LDL-C level ≥ 190 mg/dL resulted within the last five years (since 01/01/2016). We explored the associations between patient demographics, lipid profile, and rate of statin prescription using logistic regression. Results: A total of 7703 had LDL-C ≥ 190 mg/dL in our Northeast Ohio health system. The mean age was 58 ± 15 years, 64% were female, and 17% were Black. Median LDL-C was 204 [IQR 195-220] mg/dL. Only 58% of patients were prescribed statin therapy. The statin prescription rate varied substantially by age, with only 28% of individuals ≤30 years receiving a statin, with prescription rates increasing with age. Younger women had lower rates of statin prescription compared with younger men, but the differences became less with older age (age*sex Pinteraction=0.02). In a multivariable model, age (OR 1.25, 95% CI [1.21 – 1.30] per 10 years, P<0.001), LDL-C (OR 1.05 [1.03-1.07] per 10 mg/dL, P<0.001), Black race (OR 1.83 [1.60-2.09], P<0.001), and coronary artery disease (OR 3.48 [2.89-4.18], P<0.001) were associated with higher likelihood of receiving a statin prescription. Conclusion: In our health system, less than two thirds of patients with severe hypercholesterolemia defined by LDL-C level ≥190 mg/dL are prescribed a statin. Statin prescription rates were highly dependent on age and to a lesser extent on sex. This finding highlights a treatment gap in preventative care, where younger patients are most vulnerable to undertreatment despite elevated cardiovascular disease risk

Enhancing cardiovascular risk prediction through AI-enabled calcium-omics

Abstract Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density). We used novel, hand-crafted calcification features (calcium-omics); Cox time-to-event modeling; elastic net; and up and down synthetic sampling methods for imbalanced data, to assess MACE risk. We used 2457 CT calcium score (CTCS) images enriched for MACE events from our large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were especially important determinants of increased risk, with dense calcification (> 1000HU, stable calcifications) associated with reduced risk Our calcium-omics model with (training/testing, 80/20) gave C-index (80.5%/71.6%) and 2-year AUC (82.4%/74.8%). Although the C-index is notoriously impervious to model improvements, calcium-omics compared favorably to Agatston and gave a significant difference (P < 0.001). The calcium-omics model identified 73.5% of MACE cases in the high-risk group, a 13.2% improvement as compared to Agatston, suggesting that calcium-omics could be used to better identity candidates for intensive follow-up and therapies. The categorical net-reclassification index was NRI = 0.153. Our findings from this exploratory study suggest the utility of calcium-omics in improved risk prediction. These promising results will pave the way for more extensive, multi-institutional studies of calcium-omics

Lessons Learned From a Patient‐Centered, Team‐Based Intervention for Patients With Type 2 Diabetes at High Cardiovascular Risk: Year 1 Results From the CINEMA Program

Background The care for patients with type 2 diabetes necessitates a multidisciplinary team approach to reduce cardiovascular risk, but implementation of effective integrated strategies has been limited. Methods and Results We conceptualized and initiated a patient‐centered, team‐based intervention called Center for Integrated and Novel Approaches in Vascular‐Metabolic Disease (CINEMA) at University Hospitals Cleveland Medical Center. Patients with type 2 diabetes at high risk for cardiovascular events, including those with established atherosclerotic cardiovascular disease, elevated coronary artery calcium score >100, chronic heart failure with reduced ejection fraction, and/or chronic kidney disease stages 2 to 4 were included. Herein, we present the year 1 results for the program. From May 2020 through August 2021, there were 417 referrals. Among 206 eligible patients, 113 (55%) completed a baseline and ≥1 follow‐up visit through December 2021, with mean (SD) time of 105 (34) days between baseline and first follow‐up visits. Mean age was 59 years, with 49% women and 37% Black patients. Patients had significant reductions from baseline in glycosylated hemoglobin (−10.8%), total cholesterol (−7.9%), low‐density lipoprotein cholesterol (−13.5%), systolic blood pressure (−4.0%), and body mass index (−2.7%) (P≤0.001 for all). In addition, among the 129 (63%) eligible patients not on sodium‐glucose cotransporter 2 inhibitor or glucagon‐like peptide‐1 receptor agonist at baseline, 81% were prescribed evidence‐based therapy with sodium‐glucose cotransporter 2 inhibitor (n=66 [51%]) and/or glucagon‐like peptide‐1 receptor agonist (n=67 [52%]) to reduce the risk of cardiovascular disease in the initial 3‐month follow‐up period. Conclusions A team‐based, patient‐centered approach to high‐risk disease management appears to be a promising paradigm for care delivery associated with greater use of evidence‐based therapies and improved control of multiple cardiovascular risk factors

Second-year results from CINEMA: A novel, patient-centered, team-based intervention for patients with Type 2 diabetes or prediabetes at high cardiovascular risk

Background: The care for patients with type 2 diabetes mellitus (T2DM) necessitates a multidisciplinary team approach to reduce cardiovascular (CV) risk but implementation of effective integrated strategies has been limited. Methods and Results: We report 2-year results from a patient-centered, team-based intervention called CINEMA at University Hospitals Cleveland Medical Center. Patients with T2DM or prediabetes at high-risk for CV events, including those with established atherosclerotic CVD, elevated coronary artery calcium score ≥100, chronic heart failure with reduced ejection fraction, chronic kidney disease (CKD) stages 2–4, and/or prevalent metabolic syndrome were included. From May 2020 through September 2022, 426 patients were enrolled in the CINEMA program. A total of 227 (54%) completed ≥1 follow-up visit after an initial baseline visit with median (IQR) follow-up time 4 [3–7] months with maximum follow-up time 19 months. Mean age was 60 years, 47 % were women, and 37 % were Black and 85% had prevalent T2DM, 48 % had established ASCVD, 29% had chronic HF, 27% had CKD and mean baseline 10-year ASCVD risk estimate was 25.1 %; baseline use of a SGLT2i or GLP-1RA was 21 % and 18 %, respectively. Patients had significant reductions from baseline in body weight (-5.5 lbs), body mass index (-0.9 kg/m2), systolic (-3.6 mmHg) and diastolic (-1.2 mmHg) blood pressure, Hb A1c (-0.5 %), total (-10.7 mg/dL) and low-density lipoprotein (-9.0 mg/dL) cholesterol, and triglycerides (-13.5 mg/dL) (p<0.05 for all). Absolute 10-year predicted ASCVD risk decreased by ∼2.4 % (p<0.001) with the intervention. In addition, rates of guideline-directed cardiometabolic medication prescriptions significantly increased during follow-up with the most substantive changes seen in rates of SGLT2i and GLP-1RA use which approximately tripled from baseline (21 % to 57 % for SGLT2i and 18 % to 65 % for GLP-1RA, p<0.001 for both). Conclusions: The CINEMA program, an integrated, patient-centered, team-based intervention for patients with T2DM or prediabetes at high risk for cardiovascular disease has continued to demonstrate effectiveness with significant improvements in ASCVD risk factors and improved use of evidence-based therapies. Successful implementation and dissemination of this care delivery paradigm remains a key priority