Abstract

It is controversial whether atherosclerosis is linked to increased intestinal cholesterol absorption or synthesis in humans. The aim of the present study was to relate atherosclerosis to the measurements of plasma markers of cholesterol synthesis (desmosterol, lathosterol) and absorption (campesterol, sitosterol). In healthy male (n=344), non-obese, non-diabetics, belonging to the city of São Paulo branch of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we measured in plasma these non-cholesterol sterol markers, together with their anthropometric, dietary parameters, traditional atherosclerotic risk factors, and blood chemistry, coronary arterial calcium score (CAC), and ultrasonographically measured common carotid artery intima-media thickness (CCA-IMT). Cases with CAC>zero had the following parameters higher than cases with CAC = zero: age, waist circumference (WC), plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and non-high density lipoprotein-cholesterol (non HDL-C). Plasma desmosterol and campesterol, duly corrected for TC, age, body mass index (BMI), waist circumference (WC), hypertension, smoking, and the homeostasis model assessment-insulin resistance (HOMA-IR) correlated with CAC, but not with CCA-IMT. The latter related to increased age, BMI, waist circumference (WC), and systolic blood pressure (SBP). Plasma HDL-C concentrations did not define CAC or CCA-IMT degrees, although in relation to the lower tertile of HDL-C in plasma the higher tertile of HDL-C had lower HOMA-IR and concentration of a cholesterol synthesis marker (desmosterol). Present work indicated that increased cholesterol synthesis and absorption represent primary causes of CAD, but not of the common carotid artery atherosclerosis.

Highlights

  • Plasma non-cholesterol synthesis and absorption sterols have been utilized as markers of cardiovascular disease (CVD) [1,2,3,4,5,6]

  • It was observed that compared with the cases with calcium score (CAC) = zero, those with CAC > zero had age, waist circumference (WC) modestly higher, not differing as to body mass index (BMI), blood pressure (BP), glucose, hemoglobin A1c (HbA1c), insulin, and homeostasis model assessment-insulin resistance (HOMA-IR) (Table 3)

  • The present study aimed at elucidating the role of plasma non-cholesterol sterol absorption and synthesis markers of cholesterol as parameters of CV risk of atherosclerotic disease in the prospective ELSA-Brasil study

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Summary

Introduction

Plasma non-cholesterol synthesis and absorption sterols have been utilized as markers of cardiovascular disease (CVD) [1,2,3,4,5,6]. The controversy over the role in CVD of the synthesis and absorption markers of cholesterol remains. This controversy is even more provocative due to the well-established relationship of diabetes mellitus (DM) with atherosclerotic CVD [13,14]. In this regard, various publications show controversial results on plasma non-cholesterol sterols as markers of cholesterol metabolism in DM. Significant relationship between insulin sensitivity and indices of increased cholesterol synthesis and of decreased cholesterol absorption has been reported [19]

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