Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: Results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study

SummaryBackground and aimSitosterolemia, a rare genetic disorder characterized by profoundly elevated plasma sitosterol concentrations, is associated with premature atherosclerosis in some individuals. This study was conducted to evaluate if the modest sitosterol elevations seen in the general population are also associated with the occurrence of coronary events.Methods and resultsA nested case-control study using stored samples from male participants in the Prospective Cardiovascular Münster (PROCAM) study was performed. Each of 159 men who suffered a myocardial infarction or sudden coronary death (major coronary event) within 10 years of follow-up in PROCAM was matched with 2 controls (N = 318) by age, smoking status, and date of investigation. Analysis was performed using conditional logistic regression. Plasma sitosterol concentrations were elevated in cases compared with controls (4.94 ± 3.44 μmol/L versus 4.27 ± 2.38 μmol/L; P = 0.028). The upper quartile of sitosterol (>5.25 μmol/L) was associated with a 1.8-fold increase in risk (P < 0.05) compared with the lower three quartiles. Among men with an absolute coronary risk ≥20% in 10 years as calculated using the PROCAM algorithm, high sitosterol concentrations were associated with an additional 3-fold increase in the incidence of coronary events (P = 0.032); a similar, significant relationship was observed between a high sitosterol/cholesterol ratio and coronary risk (P = 0.030).ConclusionsElevations in sitosterol concentrations and the sitosterol/cholesterol ratio appear to be associated with an increased occurrence of major coronary events in men at high global risk of coronary heart disease. Further evaluations are warranted to confirm these preliminary findings.