Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives

Abstract

To assess relationships of serum phytosterols (plant sterols [P]) to serum cholesterol (C), P were measured by gas-liquid chromatography (GLC) in 595 hypercholesterolemics (top C quintile in screening of 3,472 self-referred subjects). A second specific aim was to determine whether high serum P would track over time and whether they would predict familial aggregation of high C, high low-density lipoprotein cholesterol (LDLC), high apolipoprotein (apo) B, and increased premature coronary heart disease (CHD) in hyperphytosterolemic probands and their first-degree relatives. Mean ± (SD) C was 260 ± 56 mg/dL, campesterol (CAMP) was 2.10 ± 1.6 μg/mL, stigmasterol (STIG) 1.71 ± 1.67, sitosterol (SIT) 2.98 ± 1.61, and total P 6.79 ± 3.66 μg/mL. Serum C correlated with CAMP ( r = .15, P ≤ .001), STIG ( r = .10, P ≤ .02), SIT ( r = .34, P ≤ .0001), and total P ( r = .29, P ≤ .0001). High serum CAMP and STIG were associated with a personal or family history of CHD in subjects less than or equal to age 55 years (premature CHD). In 21 hyperphytosterolemic probands who initially had at least one P at or above the 95th percentile and a second P at or above the 75th percentile, P were remeasured 2 years later. Initial and 2-year follow-up CAMP, STIG, and SIT did not differ ( P > .7). Initial and follow-up CAMP were correlated ( r = .47, P = .03). There was a history of premature CHD in 42% of the hyperphytosterolemic probands' kindreds, more than twice that (19%) in the full cohort ( χ 2 = 6.2, P = .013). Of 34 first-degree relatives of the 21 high-P probands, 11 (32%) had top decile C, 3.2 times expected, χ 2 = 5.8, P = .016, and 79% had top decile apo B, 7.9 times expected, χ 2 = 33.4, P < .00001. Probands' CAMP, SIT, and P were significantly positively correlated with their 34 first-degree relatives' C, LDLC, and triglyceride levels. Probands' CAMP and P correlated with relatives' apo B. In the 34 first-degree relatives, P were correlated with C, high-density lipoprotein cholesterol (HDLC), and apo A1; CAMP and SIT correlated with HDLC, and with apo A1. High P tracks, correlates closely with and predicts high C, high LDLC, and high apo B in families, and appears to be associated with increased premature CHD, independent of cholesterol. Increased absorption of all dietary sterols with resultant high P and high C may be a heritable, atherogenic trait separate from the rare, recessive familial sitosterolemia.