A retrospective analysis of patients with very HIGH level of LDL-C and the predictors of mortality (HIGH-LDL-PM Registry)

Abstract Introduction Elevated levels of LDL cholesterol (LDL-C) significantly contribute to the development and progression of cardiovascular diseases (CVDs). In HIGH-LDL-PM Registry, we aimed to investigate the demographics and clinical characteristics of patients with very high level of LDL-C and the predictors of mortality, retrospectively. Methods We retrospectively searched the electronic database of Istanbul University-Cerrahpasa Institute of Cardiology and included patients with very high level of LDL-C (>190 mg/dl) in HIGH-LDL-PM registry. The study group were classified as patients with high probability of familial hypercholesterolemia (FH) and low probability of FH according to Dutch Lipid Clinic Network Score (DLCNS). Results The study group were consisted of 1127 patients and almost two thirds (61.5%) were female. The mean age was 56.5 12.2 years. Hypertension, diabetes, chronic kidney disease (CKD) were seen in 55.8%, 23.5% and 3.7%, respectively. One third of study group (31.1%) had coronary artery disease (CAD) and rest of them were primary prevention patients. the main rhythm was sinus in most of the patients (92,2) and 7.8% patients had atrial fibrillation (AF). Only minority of patients (3.9%) had stigmata for elevated cholesterol levels. While 41.8% of patients had high clinical probability for FH, 58.2% of them had low probability according to DLCNS. While 69% of patients were using lipid lowering treatments (LLTs), 42% of them had drug adherence. High dose (HD) statins (atorvastatin 40-80 and rosuvastatin 20-40 mg) were prescribed in more than half (55.2%) of patients with LLTs. Ezetimibe was the preferred agent as combination therapy in 6.9% and PCSK-9is were prescribed only in 2.5% of patients with LLTs. In 38.8% of study population, ASA was prescribed. 50% decrease in LDL-C levels or decreasing LDL-C below 70 or 100 mg/dl as a treatment goal were achieved in 37.1% and 15% of study population. MACE (MI, stroke, PCI or peripheral revascularization) was recorded in 21% of study population and the mortality rate was 10.4% at 12-years FU (6-145 months). Patients with low probability of FH had better survival than patient with high probability (91.4% vs 88.4%). The age, low dose statin use and higher level of LDL-C at FU were predictors of mortality in Cox-regression analysis. Conclusion Our retrospective analysis of patients with very high levels of LDL-C underscores the multifaceted nature of dyslipidemia management and its impact on cardiovascular outcomes. Despite advancements in pharmacotherapy, suboptimal adherence to lipid-lowering treatments remains a significant challenge, contributing to a notable burden of major adverse cardiovascular events and mortality. Identification of predictors of mortality, such as age, statin dosage, and LDL-C levels, highlights the importance of individualized risk assessment and tailored treatment approaches in this high-risk population.