Cholesterol synthesis, cholesterol absorption, and mortality in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Recent clinical trials on cholesterol-lowering in patients with CKD yielded conflicting results, which might have resulted from different treatment strategies. Serum cholesterol levels are determined by endogenous synthesis and intestinal absorption, which are differentially influenced by various classes of cholesterol-lowering agents. Assessing markers of cholesterol metabolism has thus been proposed for guidance of lipid-lowering therapy. This study analyzed surrogate markers of cholesterol absorption and synthesis in hemodialysis (HD) patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In 113 HD patients, lathosterol was measured as a marker of cholesterol synthesis and cholestanol was measured as a marker of cholesterol absorption via gas chromatography. Controls were 229 healthy persons. Overall survival in HD patients was recorded over 3.4-year follow-up. RESULTS: Compared with controls, HD patients had lower lathosterol and higher cholestanol levels (P<0.001 for both). During follow-up, 58 patients died; higher cholestanol (indicating higher cholesterol absorption) predicted poor outcome among HD patients in multivariate Cox regression analysis after adjustment for potential confounders (hazard ratio for cholestanol above median, 2.24 [95% confidence interval (CI), 1.29-3.89]; P=0.004), whereas lower lathosterol (indicating lower cholesterol synthesis) did not (hazard ratio for lathosterol below median, 1.43 [95% CI, 0.81-2.50]; P=0.22). CONCLUSIONS: This analysis of markers of cholesterol metabolism characterizes HD patients as cholesterol absorbers. In longitudinal analysis, higher levels of cholestanol were associated with all-cause mortality.

The relationships of markers of cholesterol homeostasis with carotid intima-media thickness.

BACKGROUND: The relationship of cholesterol homeostasis and carotid intima-media thickness (cIMT) is unknown. To address this, we assessed markers of cholesterol homeostasis (serum plant sterols and cholesterol precursor concentrations as surrogate measures of cholesterol absorption and synthesis, respectively) and cIMT in a middle-aged, statin-naive population. METHODS: In this prospective study of primary prevention cIMT was measured by ultrasound in 583 hospital employees aged 25-60 years without prevalent cardiovascular disease or lipid-modifying medication. The serum concentrations of plant sterols (as markers of cholesterol absorption) were measured by gas-liquid chromatography. Lathosterol serum concentrations were quantitated to assess hepatic cholesterol synthesis. RESULTS: cIMT correlated positively with serum cholesterol (r = 0.22, P<0.0005) and lathosterol-to-cholesterol (r = 0.18, P<0.001). In contrast, plant sterols, as markers of cholesterol absorption, showed a weak negative correlation to cIMT measurements (r = -0.18; P<0.001 for campesterol-to-cholesterol). Stratifying subjects by serum sterol levels, we found that cIMT increased continuously over quintiles of serum cholesterol (P<0.0005) and was positively associated to serum lathosterol-to-cholesterol levels (P = 0.007), on the other hand, plant sterol levels showed a weak negative association to cIMT (P<0.001 for campesterol-to-cholesterol). CONCLUSIONS: In this population without prevalent cardiovascular diseases or lipid-modifying medication, markers of increased endogenous cholesterol synthesis correlated positively with cIMT, while markers of cholesterol absorption showed a weakly negative correlation. These data suggest that not only total serum cholesterol levels but also differences in cholesterol homeostasis are associated with cIMT.