Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

BackgroundFamilial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements.ResultsA total of 29 gene sequence variants were reported in 117(76.0%) of the studied subjects. Eight different mutations (1 large rearrangement, 1 short deletion, 5 missense mutations, and 1 splice site mutation), and 21 variants. Eight gene sequence variants were reported for the first time and they were noticed in familial hypercholesterolemic patients, but not in controls (p.Asp100Asp, p.Asp139His, p.Arg471Gly, c.1705+117 T>G, c.1186+41T>A, 1705+112C>G, Dup exon 12 and p.Trp666ProfsX45). The incidence of the p.Arg471Gly variant was 11%. Patients with pathogenic mutations were younger, had significantly higher incidences of cardiovascular disease, xanthomas, and family history of hyperlipidemia, together with significantly higher total cholesterol and low density lipoprotein levels than patients with non-pathogenic variants.ConclusionsTwenty-nine gene sequence variants occurred among FH patients; those with predicted pathogenicity were associated with higher incidences of cardiovascular diseases, tendon xanthomas, and higher total and low density lipoprotein levels compared to the rest. These results provide preliminary information on the mutation spectrum of this gene among patients with FH in Malaysia.

To determine whether pulse wave velocity (PWV) as a measure of arterial stiffness is a marker of coronary artery diseases (CAD), the authors did a cross‐sectional study in 92 patients undergoing coronary angiography for suspected CAD. Arterial stiffness was assessed through recording PWV from the left carotid–right femoral arteries using an automated machine. The mean PWV was higher in patients with CAD than in those without CAD (11.13±0.91 vs 8.14±1.25 m/sec; P<.001). When the severity of CAD was expressed as 1‐, 2‐, and multiple‐vessel disease, there was a significant association between the severity of CAD and PWV. PWV differed significantly with different categorical severity of CAD even when age and total cholesterol were controlled for. In a univariable analysis, PWV was higher with higher systolic blood pressure (P<.004). The authors conclude that arterial stiffness measured through PWV is an independent and complementary cardiovascular risk marker.

BackgroundBiomarkers play a pivotal role in the diagnosis and management of patients with acute coronary syndrome. This study aimed to investigate the differences in level of several biomarkers, i.e. C-reactive protein, myeloperoxidase, soluble CD40 ligand and placental growth factor, between acute coronary syndrome and chronic stable angina patients. The relationship between these biomarkers in the coronary circulation and systemic circulation was also investigated.MethodsA total of 79 patients were recruited in this study. The coronary blood was sampled from occluded coronary artery, while the peripheral venous blood was withdrawn from antecubital fossa. The serum concentrations of C-reactive protein, soluble CD40 ligand and placental growth factor and plasma concentration of myeloperoxidase were measured using ELISA method.ResultsThe systemic level of the markers measured in the peripheral venous blood was significantly increased in acute coronary syndrome compared to chronic stable angina patients. The concentrations of the C-reactive protein, myeloperoxidase and soluble CD40 ligand taken from peripheral vein were closely similar to the concentration found in coronary blood of ACS patients. The level of placental growth factor was significantly higher in coronary circulation than its systemic level.ConclusionThe concentration of these C-reactive protein, myeloperoxidase, soluble CD40 ligand and placental growth factor were significantly increased in acute coronary syndrome patients. The concentration of the markers measured in the systemic circulation directly reflected those in the local coronary circulation. Thus, these markers have potential to become a useful tool in predicting plaque vulnerability in the future.

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Familial ligand-defective apolipoprotein B-100 is characterized by elevated plasma low-density lipoprotein levels and premature heart disease. This study aims to determine apolipoprotein B gene mutations among Malaysians with clinical diagnoses of familial hypercholesterolemia and to compare the phenotype of patients with apolipoprotein B gene mutations to those with a low-density lipoprotein receptor gene mutation. A group of 164 patients with a clinical diagnosis of familial hypercholesterolemia was analyzed. Amplicons in exon 26 and exon 29 of the apolipoprotein B gene were screened for genetic variants using denaturing gradient high-performance liquid chromatography; 10 variants were identified. Five novel mutations were detected (p.Gln2485Arg, p.Thr3526Ala, p.Glu3666Lys, p.Tyr4343CysfsX221, and p.Arg4297His). Those with familial defective apolipoprotein had a less severe phenotype than those with familial hypercholesterolemia. An apolipoprotein gene defect is present among Malaysian familial hypercholesterolemics. Those with both mutations show a more severe phenotype than those with one gene defect.

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A reversed-phase HPLC method to determine total plasma warfarin was developed and validated. Warfarin was extracted from human plasma using a two-step liquid-liquid extraction method. The residue was reconstituted with a phenylbutazone standard solution, which was used as the internal standard. The analytical column was a Purospher STAR RP-18e (4 x 4mm I.D., 5m particle size). The mobile phase consisted of acetonitrile: potassium dihydrogen orthophosphate buffer solution at pH 6.5 [30:70 (v/v)] with a flow rate of 1mL/min. Both warfarin and phenylbutazone were detected using a photodiode array detector. The lower limit of quantification was 100ng/mL, while the limit of detection was 20ng/mL. The linearity of the assay was good (r2=0.992) in the concentration range from 0.1 - 6.0µg/mL. The extraction recovery of warfarin was 93.53 ± 12.40%. Both the intraday and interday quality control assay for warfarin demonstrated good precision and accuracy, with all of the percentage coefficients of variation being less than 15%. Warfarin was stable in human plasma for up to three months of storage. The validated method was successfully applied to four human samples for a pharmacokinetics study.