Low-density-lipoprotein cholesterol target attainment in high-risk patients with history of diabetes or major adverse cardiac and cerebrovascular event: an (un)expected gender bias
Authors: Berteotti M , Lotti E , Francesconi P , Mannucci E , Zuppiroli A , Casolo G , Grisillo D , Ferrante N , Profili F , Marcucci R 
Published: November 2023

Abstract

Background
Lowering low-density lipoprotein cholesterol (LDL-C) is the cornerstone of cardiovascular disease prevention, especially after the occurrence of a major adverse cardiac and cerebrovascular event (MACCE). Collection of epidemiological data is crucial for monitoring healthcare appropriateness and the fulfillment of guidelines recommendations.

Purpose
This analysis aimed to evaluate the proportion of high-risk patients who achieved LDL-C goal as suggested by the international guidelines by analyzing regional administrative data and to explore the predictors of therapeutic failure, with a focus on the role of gender.

Methods
By linking health administrative and laboratory data, we collected data from seven Local Health Districts on residents aged ≥45 years. Inclusion criteria were: 1) at least one LDL-C measurement in the year; 2) a history of MACCE (defined as myocardial infarction and/or stroke and/or revascularization of the coronary, carotid, or peripheral arteries) and/or type 2 diabetes mellitus (T2DM). Cohorts were defined at 1st January 2019 and 1st January 2020. Lipid lowering therapy use (defined as ≥2 prescription fillings or ≥75% coverage of treatment days) over the past 6 months if LDL-C data were available or over the past year if no LDL-C data were available was monitored. The outcome was the number of patients with on-treatment LDL-C optimal levels, as defined by levels &lt;55 mg/dl for patients with MACCE and &lt;70 mg/dl for patients with T2DM without MACCE.

Results
A cohort of 174,200 individuals was analyzed (55% males). As regards subjects on lipid-lowering therapies, we found that female gender was associated with a significantly lower probability to have LDL-C levels at target (OR: 0.58±0.01; p&lt;0.0001) in patients with MACCE with or without T2DM, in a model adjusted for age, district area, and the presence of cardiovascular risk factors and comorbidities (renal failure, heart failure, atrial fibrillation). This result was confirmed also in the analysis conducted in subjects without lipid-lowering therapies (OR: 0.56±0.01; p&lt;0.0001). No significant differences were documented by stratifying for the presence of clinical pathways aimed to the active call of the patients by clinicians ("Initiative Health").

Conclusions
These results demonstrated that females have a significantly lower probability to reach LDL-C levels recommended targets. This datum is confirmed even in the absence of lipid-lowering therapies. These results call for action aimed to: 1) education for general population and for patients with MACCE with a specific target on females; 2) information for clinicians for the need of assessing adequate lipid-lowering therapy prescription and adherence irrespectively of gender; 3) organization of clinical pathways - from admission to recovery and follow-up - with a specific focus on secondary prevention target attainment.