ABSTRACT
AIM: Low-density lipoprotein cholesterol (LDL-C), the ratio of LDL-C to high-density lipoprotein cholesterol (HDL-C; LDL-C/HDL-C), and non-HDL-C were evaluated to determine their ability to predict cardiovascular disease (CVD) risk with pravastatin treatment. METHODS: We conducted a large-scale randomized primary prevention trial in Japan (MEGA Study), in which we randomly allocated 7832 mild hypercholesterolemic patients to diet alone (n= 3966) and diet plus pravastatin groups (n= 3866) and followed them for an average of 5 years. We compared baseline levels and the CVD incidence in the diet alone group, and time-dependent receiver operating characteristic curves in the overall population. To determine the best parameter for predicting the efficacy of pravastatin, the diet plus pravastatin group was divided into tertiles to compare lipid parameters and CVD incidence versus the diet alone group. RESULTS: Significantly graded correlations were found between CVD and LDL-C/HDL-C and non-HDL-C. Significantly more CVD events were associated with non-HDL-C [corrected] > 186 mg/dL and LDL-C/HDL-C > 2.9. Furthermore, LDL-C/HDL-C or non-HDL-C was more predictive than LDL-C. By measuring LDL-C/HDL-C or non-HDL-C, we allocated 32% of the diet plus pravastatin group into a different risk category. The lowest significant incidence of CVD was found in patients with LDL-C 119.8-133.4 mg/dL, LDL-C/HDL-C < 1.9, and non-HDL-C 145.2-160.8 mg/dL. CONCLUSION: Non-HDL-C and LDL-C/HDL-C have a greater ability to predict CVD risk in mild-to-moderate hypercholesterolemic Japanese individuals than LDL-C, and are more useful to evaluate the effect of pravastatin; however, these parameters should be interpreted independently when assessing CVD risk.
Subject(s)
Anticholesteremic Agents/adverse effects , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/diagnosis , Cholesterol, LDL/metabolism , Hypercholesterolemia/drug therapy , Pravastatin/adverse effects , Adult , Cardiovascular Diseases/metabolism , Female , Humans , Hypercholesterolemia/complications , Male , Middle Aged , Prospective Studies , ROC Curve , Risk Factors , Young AdultABSTRACT
Solution structures of the 1:1 complexes of an alkyl-linked bis(benzimidazole) compound (4; Figure 1(a)) with the self-complementary DNA duplexes, d(CGCGAATTCGCG)2 and d(CGCAAATTTGCG)2, have been studied by 1H NMR spectroscopy and molecular mechanics calculations. The intermolecular NOE data and the energy-minimized geometries of the 1:1 complexes indicate that 4 binds in the minor groove of the 5'-GAATTCG and 5'-CAAATTT regions of the DNA duplexes.
Subject(s)
Benzimidazoles/chemistry , DNA/chemistry , Base Sequence , Protein Conformation , SolutionsABSTRACT
We have studied the influence of terminal substituents, amidinium group and N-methylpiperazine ring, of 2-phenylbenzimidazole compounds (1-6; Figure 1) on their DNA-binding modes. Experimental results reveal that 1-3 are accepted in intercalation pockets owing to structural flexibility of the N-methylpiperazine ring, while 4-6 bind to the groove of DNA because of steric hindrance between the amidinium group and the DNA phosphate-sugar backbone.