LDL levels and long-term all-cause mortality in patients from nationwide LIPIDOGRAM 2004–2015 cohort studies
Authors: Gierlotka M , Jozwiak J , Osadnik T , Nalewajko K , Feusette P , Nowak D , Zak Z , Skowron L , Golawski M , Banach M 
Published: October 2022

Abstract

Background
Data from multiple randomized clinical trials show that lowering LDL cholesterol with statins is associated with significant reduction of outcomes both in primary and secondary prevention. Despite this some epidemiological studies reported increased risk with lowest LDL levels. The reason for this apparent discrepancy is probably due to unbalanced confounding in epidemiological studies.

Purpose
To assess long term survival in propensity matched cohort from the LIPIDOGRAM study in patients on statin therapy.

Methods
Lipidogram studies were carried out in Poland in 2004, 2006 and 2015 in the population representative for patients in primary care setting. The median follow up was 5570 days. Patients were recruited in all 16 administrative regions in Poland and physicians (n&gt;1100) were proportionally distributed to the number of inhabitants in a given administrative region. Each patient was asked to fill the questionnaire on chronic diseases, treatment and lifestyle. Questionnaire was supervised by physician. Patients who were taking statins at the time of enrollment were matched to patients who were not on statin therapy. Groups were matched with regard to age, sex, body mass index, LDL cholesterol, diabetes mellitus, hypertension, previous myocardial infarction, chronic kidney disease, previous ischemic stroke, and atrial fibrillation. Nearest neighbor matching method was employed.

Results
To 13676 patients (28.9% of the LIPIDOGRAM 2004–2015 cohort) that took statin at the time of enrollment and 13676 patients not on statin treatment were matched. There were no significant differences between two groups with regard to all variables used in matching procedure including LDL cholesterol level. After 15 years of follow up There were 2585 deaths (18.9%) in patients who were treated with statin at the time of enrollment as compared to 2824 (20.6%) in patients with no treatment for dyslipidemia (absolute risk reduction (ARR) of −1.7%, p=0.003) Hazard ratio for mortality in patients who were not treated with statin at the enrollment in this propensity matched cohort was 1.11 (95% CI; 1.05–1.17, p=0.0002).

Conclusions
Despite similar LDL levels patients treated with statin at the time of enrollment had lower mortality risk as compared to patients not taking statins in long-term follow-up. Lower LDL levels that are not due to statin therapy might imply other underlying conditions that influence prognosis. Therefore, data from epidemiological studies that contradict results of balanced randomized trials due to intrinsic limitations should be approached with skepticism.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): The present study was funded by an unrestricted educational grant from Valeant. As a supporter of the study, Valeant played no role in the study design, data analysis, data interpretation, or writing of the report. The present study was also supported by Silesian Analytical Laboratories (SLA, Katowice, Poland).