Serum plant and other noncholesterol sterols, cholesterol metabolism and 22-year mortality among middle-aged men

ObjectiveTo evaluate long-term prognostic effect of serum noncholesterol sterols, including plant sterols, in middle-aged men with high cardiovascular disease (CVD) risk, without statins at baseline.MethodsThis was a prospective study of 232 men (mean age 60 years) at high risk of CVD in 1985-1986. Most were hypercholesterolemic, 29 (12%) had a history of CVD or cancer, 6 (3%) had diabetes, and 46 (20%) had metabolic syndrome (MS). Measured noncholesterol sterols (expressed as absolute concentrations or ratios to serum cholesterol to standardize for cholesterol concentrations) included lathosterol and desmosterol (reflect cholesterol synthesis), and plant sterols (campesterol and sitosterol) and cholestanol (reflect cholesterol absorption). Main outcome measure was total mortality.ResultsAt baseline, markers of cholesterol synthesis and absorption showed expected inverse associations. During the 22-year follow-up 101 men (43%) died. At baseline, nonsurvivors smoked more, exercised less and had more components of MS (although not filling strict criteria), whereas traditional risk factors of CVD were not significantly different. Of the noncholesterol sterols (either absolute or ratio), only sitosterol was significantly higher in survivors than in nonsurvivors (P = 0.02). In multivariable analyses, highest sitosterol-to-cholesterol tertile was associated with significantly lower mortality risk (HR 0.51, 95% CI 0.30-0.87) as compared to lowest tertile. Other associations were nonsignificant, although a “global” index of cholesterol metabolism (desmosterol-to-sitosterol ratio) suggested higher cholesterol synthesis and lower absorption to be associated with higher total and CVD mortality.ConclusionHigher serum plant sterol levels in middle-aged men predicted lower long-term mortality risk, possibly reflecting an association between higher synthesis/lower absorption of cholesterol and mortality.