Low-density lipoprotein cholesterol reduction and short-term incidence of ASCVD in the population-based cohort study LATINO

Abstract

Abstract Background/Introduction In Portugal, 25,000 people die from atherosclerotic cardiovascular diseases (ASCVD) every year, accounting for more than 20% of all deaths in 2019. Reducing low-density lipoprotein cholesterol (LDL-C) is an effective intervention to lower the risk of CV events, including ischemic stroke (IS), coronary heart disease (CHD) and Peripheral Artery Disease (PAD). Purpose This study aims to assess the extent of ASCVD risk prevention associated with different levels of LDL-C lowering in an unselected population in Portugal. Methods We used electronic health records to conduct a population-level retrospective cohort study of individuals aged 40–80 years who were followed in 1 hospital and 14 primary care facilities in Portugal from 1/1/2012 to 31/12/2020. Patients started being followed when they fulfilled criteria to be exclusively characterised as high CV risk at the index date (defined according to the ESC/EAS 2019 guidelines). This analysis focused on the 24-month risk of developing ASCVD, by percentual LDL-C reduction between 360 and 540 days from the maximum LDL-C. The primary endpoint of ASCVD included the risk of IS, CHD or PAD, as defined by the corresponding ICD-9-CM/ICD-10-CM codes. IS, CHD and PAD were also analysed separately as secondary endpoints. LDL-C values were obtained from laboratory results and CV and diabetes medications’ use from prescription data registered according to the Anatomical Therapeutic Chemical Classification System recorded. A Cox regression model adjusted for sex, age, all relevant CV risk variables, risk-enhancing factors, and CV and diabetes medications was developed. Results The total cohort at 24 months of follow-up consisted of 21,101 observations corresponding to 16,055 distinct patients. Higher LDL-C percentual reduction was associated with a lower risk of ASCVD, with adjusted hazard ratios (aHR) (95% confidence intervals (CI)) of 0.82 (0.66-1.02), 0.86 (0.66-1.11) and 0.44 (0.24-0.79) per reduction of ]0,30%], ]30,50%] and ]50,90%] of LDL-C respectively, versus having no reduction or increase. IS was the secondary endpoint that contributed the most to the reduction of risk of ASCVD with an aHR (95% CI) of 0.89 (0.69-1.15), 0.67 (0.47-0.96) and 0.41 (0.19-0.86) for the same corresponding LDL-C reduction categories. However, these results were not statistically significant for PAD or CHD when assessed isolated. Conclusion This real-world evidence study shows that, independently of age, sex, and other CV risks and medications, reductions of >50% in LDL-C significantly reduced by 56% the risk of ASCVD at 24 months in high CV risk patients. This reduction was more striking for ischemic stroke. Therefore, LDL-C reductions >50% should be a paramount objective in public health policies worldwide.