Remnant cholesterol and mortality in 37.559 patients from LIPIDOGRAM 2004, 2006 and 2015 studies

Abstract Introduction Remnant cholesterol (remnant-C) is produced by metabolism of triglyceride rich proteins and contributes to residual cardiovascular (CVD) risk. Purpose To asses association between remnant cholesterol and all-cause mortality in a large cohort of patients under the care primary care physicians. Methods The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006 and 2015. Patients (n=47,398) recruited in all 16 administrative regions in Poland and physicians were proportionally distributed to the number of inhabitants in each administrative region. Each patient was asked to fill the questionnaire on risk factors, chronic diseases, treatment, and lifestyle. In the present analysis we included consecutive patients with body mass index (BMI) >18.5 kg/m2 aged 18-70 years. Median follow up was (5.3 years (interquartile range 5.7-17.3). For this analysis we approved the cut-off point of fasting remnant cholesterol >30 mg/dL (>0.77 mmol/L) that differentiated subjects at high risk of cardiovascular events. We used univariate and multivariate Cox regression modelling to assess the association between remnant-C and all-cause mortality. Results Finally, 37,559 patients were included meeting the inclusion criteria and for which the follow-up data was available. Mean remnant-C concentration was: 27 mg/dl / 0.7 mmol/l (standard deviation 15 mg/dl/ 0.38 mmol/l). Remnant-C was associated with 5-year mortality and overall mortality during the study period, with hazard ratios (HR) of 1.21 (95% CI: 1.04-1.41, p<0.001) and 1.42 (95% CI: 1.32-1.53, p<0.001) for each 1 mmol/l increase, respectively. After adjusting for age, sex, BMI, education level, place of residence, hypertension, diabetes mellitus, smoking, previous myocardial infarction, metabolic syndrome presence, and statin and fibrate treatments, remnant-C was associated with long-term mortality—HR (per 1 mmol/l) of 1.08 (95% CI: 1.00-1.17, p=0.049)—but not with 5-year mortality—HR (per 1 mmol/l) of 0.97 (95% CI: 0.83-1.13, p=0.7). Predefined level of remnant-C > 30 mg/dl (0.77 mmol/l) was associated with higher 5 year (HR- 1.15, 95%CI (1.02-1.31, p=0.021) (Figure 1A) and long-term all-cause mortality (HR- 1.26, 95%CI (1.19-1.33, p<0.001) (Figure 1B). Conclusions Higher remnant-C cholesterol levels are associated with long term all-cause mortality in patients aged 18-70 years.