Abstract Background Factors contributing to guideline-target-level-attainment of low-density lipoprotein cholesterol (LDL-C) in countries with high healthcare expenditure are incompletely understood. Purpose the primary aim of this study was to test two hypotheses: 1) LDL-C control may be inferior in women versus men; 2) within the secondary prevention group, presence of a previous acute atherothrombotic event (acute myocardial infarction and stroke) may result in superior LDL-C control. Methods LDL-C levels and guideline target level attainment were determined in 4090 consecutive patients referred for myocardial perfusion single photon emission tomography (MPI-SPECT) between 2010 and 2016. Findings were validated in an independent cohort (n=1228) of consecutively enrolled patients in an outpatient cardiac rehabilitation program, between 2016 and 2023. Results About one third of patients (33%) were women, median age was 68 years, 1439 patients had a history of atherothrombosis, 759 patients a history of atherosclerosis without atherothrombosis, and 1892 were in primary prevention. LDL-C levels were higher and guideline target level attainment worse in women than in men in all three strata: age-adjusted difference in atherothrombosis 0.19 mmol/L (95%CI 0.03,0.35 mmol), guideline-target-value-attainment 39.5 % versus 49.4%, p<0.01; in atherosclerosis 0.33 mmol/L (95%CI 0.10-0.57), guideline-target-value-attainment 27.3 % versus 42.2 %, p<0.01; and in primary prevention 0.24 mmol/L (95% CI 0.13-0.38). This was confirmed in the validation cohort. LDL-C levels were higher and guideline-target-value-attainment worse in women versus men: age-adjusted difference age-adjusted difference 0.17 mmol/L (95%CI 0.02-0.33) guideline-target-value-attainment 43.8% versus 49.5%, After multivariate adjustment, female sex remained an independent predictor for higher LDL-C levels. LDL-C concentrations with atherothrombosis was 1.93 mmol/L (IQR 1.48-2.47) versus 2.07 mmol/L (IQR 1.40-2.72, p=0.003) with atherosclerosis and guideline target value attainment 47.5% vs 38.6%, p<0.001, respectively. Conclusion Concerning age-adjusted sex-inequalities with higher LDL-C levels and lower guideline-target-value-attainment in women were found in both primary and secondary prevention. Within secondary prevention, a previous atherothrombotic event was associated with lower LDL-C levels and higher guideline-target-value-attainment.
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