Dutch Lipid Clinic Network low-density lipoprotein cholesterol criteria are associated with long-term mortality in the general population

Summary Background Heterozygous familial hypercholesterolaemia (HeFH) is a severe autosomal dominant disease that is underdiagnosed, inadequately treated and has a severe long-term cardiovascular risk. Few studies have evaluated the long-term risk of high low-density lipoprotein cholesterol (LDL-C) concentrations. Aim To evaluate long-term mortality in a large cohort of healthy subjects, according to LDL-C concentrations. Methods Based on a sample of 6956 subjects visiting a preventive cardiology department, we selected adult subjects without a personal history of cardiovascular disease. From 1995 to 2011, 4930 healthy subjects were examined and followed up until 31 December 2011. All-cause deaths were collected exhaustively. A Cox-based multivariable analysis evaluated long-term total mortality risk according to Dutch Lipid Clinic Network (DLCN) LDL-C concentrations. Results After a mean follow-up of 8.6 years, 123 all-cause deaths were recorded (cumulative mortality rate, 2.5%). In the final multivariable model, major risk factors such as age, sex, tobacco use and diabetes were significantly associated with mortality. After adjustment for age, sex, tobacco use, hypertension, diabetes and statin therapy, and in comparison with subjects with LDL-C < 4 mmol/L (< 155 mg/dL), subjects with LDL-C between 4 and < 5 mmol/L (155 to < 190 mg/dL) had a hazard ratio (HR) of 1.99 (95% confidence interval [CI] 1.31–3.02; P = 0.001), subjects with LDL-C between 5 and < 6.5 mmol/L (190 to < 250 mg/dL) had an HR of 1.81 (95% CI, 1.06–3.02; P = 0.030), subjects with LDL-C between 6.5 and < 8.5 mmol/L (250 to < 330 mg/dL) had an HR of 2.69 (95% CI, 1.06–6.88; P = 0.038) and subjects with LDL-C ≥ 8.5 mmol/L (≥ 330 mg/dL) had an HR of 6.27 (95% CI, 0.84–46.57; P = 0.073). After excluding patients on statins at baseline, subjects with LDL-C ≥ 8.5 mmol/L (≥ 330 mg/dL) had an HR of 8.17 (95% CI, 1.08–62.73; P = 0.042). Conclusions The severity of LDL-C elevation is associated with a higher risk of death in healthy subjects. DLCN LDL-C concentrations may be used in daily practice to identify patients with HeFH who warrant aggressive treatment.