Table 1.
Demographics of patients included in metabolomics study.
Figure 1.
Sterol pathway map testing the association of pretreatment metabolites with change of LDL-C by statin treatment.
The map was constructed using a correlation of pretreatment metabolites with change in LDL-C in FR. The color scheme corresponds to correlation strength as shown by the color bar. Red: Better response, more reduction of the metabolite. Blue: Better response, less reduction or increase of the metabolite. Correlations to change in LDL-C are given in the first row and column. The metabolites are rescaled (divided by the largest absolute value of them) to be clearer in the map. * Correlations significant by p-value, but not significant after controlling for q-value. ** Correlations significant by p-value and significant after controlling for q-value.
Table 2.
Pretreatment metabolites that correlate with change of LDL-C in FR group.
Figure 2.
Correlation matrix for testing the association of pretreatment metabolites with a change in LDL-C by statin treatment.
The correlation map shows pretreatment metabolites and change in LDL-C in FR. The color scheme corresponds to correlation strength as shown by the color bar. Red: Better response, more reduction of the metabolite. Blue: Better response, less reduction or increase of the metabolite. Correlations to changes in LDL-C are given in the first row and column. The metabolites have been rescaled (divided by the largest absolute value of them) to be clearer on the map.
Figure 3.
Sterol pathway map testing the association of pretreatment metabolites with changes in LDL-C from statin treatment.
The map has been constructed using the correlation of pretreatment metabolites with change of LDL-C in GPR. Enzymes are represented by circles; metabolites by squares. Metabolites in grey squares were not quantified. White squares were not significantly different. The metabolites with significant p-values are colored according to the correlation relationship with blue negative and red positive. Red: Better response, more reduction of the metabolite. Blue: Better response, less reduction or increase of the metabolite. Correlations to changes in LDL-C are given in the first row and column. The metabolites have been rescaled (divided by the largest absolute value of them) to be clearer on the map. * Correlations significant by p-value, but not significant after controlling for q-value. ** Correlations significant by p-value and significant after controlling for q-value.
Table 3.
Pretreatment metabolites correlated with treatment outcomes in patients selected from the ends (comparing good and poor responders).
Figure 4.
Correlation matrices of pretreatment sterol metabolites in good and poor responders.
The differences between the two matrices reflects the differences between the groups responses to statin treatment. The color scheme corresponds to correlation strength as shown by the color bar. Red: Better response, more reduction of the metabolite. Blue: Better response, less reduction or increase of the metabolite. The metabolites have been rescaled (divided by the largest absolute value of them) to be clearer on the map.
Table 4.
Pretreatment sterol metabolites and bile acids correlated with simvastatin concentrations.
Table 5.
Association of SLCO1B1 SNP rs4149056 with pretreatment measurements for sterols and bile acids in CAP participants.
Table 6.
Association of SLCO1B1 SNP rs2306283 with pretreatment measurements of sterols and bile acids in CAP participants.
Figure 5.
Active cholesterol metabolites are produced by interspecies biosynthetic pathways.
Bile acids are the main metabolites of cholesterol (CHOL). Primary bile acids (blue ovals; cholic acid (CA) and chenodeoxycholic acid (CDCA)) are produced by endogenous enzymes in the liver and are modified by bacteria of the genus Clostridia colonizing the gut to form secondary bile acids (yellow ovals; lithocholic acid (LCA) and deoxycholic acid [18]). Arrows broken by double lines represent multiple enzymatic steps and only the genes encoding the rate limiting enzymes are listed. The bacterial operon baiABCDEFGHI encodes eight enzymes and a bile acid transporter that together form the pathway for synthesis of secondary bile acids. The amino acids glycine and taurine are conjugated to primary and secondary bile acids in the liver by the host encoded bile acid-CoA amino acid transferase (BAAT) to form tauro- and glycolithocholic acid (TLCA, GLCA) and tauro- and glycodeoxycholic acid (TDCA GDCA). Gut bacteria of genus Lactobacillus catalyze the conversion of cholesterol metabolites to coprostanol (COPR) and can limit the intestinal absorption of cholesterol.