PubMed · 13916774
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B STEINMANN. 1962-07-07. [Arteriosclerosis].. https://pubmed.ncbi.nlm.nih.gov/13916774/
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Heterotrimeric guanine nucleotide-binding proteins (G proteins) mediate many pathways including the beta-adrenergic signaling pathway. The C825T polymorphism in the gene coding for the beta3 subunit of G proteins (GNB3) has been shown to be associated with several phenotypes such as hypertension, obesity, and diabetes mellitus comprising the metabolic syndrome. The GNB3 C825T polymorphism may therefore be associated with many atherosclerosis-related phenotypes. On these grounds, we studied the C825T polymorphism in relation to atherosclerosis-related phenotypes in a large Japanese population. Analyses in general linear models showed that T carriers had a significantly wider pulse pressure (P=0.0089) as well as a significantly higher systolic blood pressure (P=0.026). In contrast, analyses in logistic regression models showed that the C825T polymorphism was not significantly associated with each of the four major classical risk factors for cardiovascular and cerebrovascular disease (obesity, hypertension, hypertriglyceridemia, and diabetes mellitus). However, a significantly higher percentage of subjects had none of the four disorders in CC homozygotes than in T carriers (P=0.026). Thus, the C825T polymorphism was significantly associated with clustering of these four risk factors. Although the effect of the gene on each phenotype appears to be weak, considering the combined impact of the effects of the C825T polymorphism on risk factors, the GNB3 gene may be an important gene for human health.
Inflammation participates critically in atherosclerosis. Circulating levels of several inflammatory markers rise in individuals at risk for atherosclerotic events. In particular, elevation of plasma C-reactive protein (CRP), a nonspecific acute-phase reactant that is easily and reliably measured, has strong predictive power for cardiovascular events. Indeed, measurements of high-sensitivity CRP (hs-CRP) plasma levels add to both the prognostic information gleaned from assay of plasma lipid risk factors and the risk levels estimated by means of Framingham study-based criteria. Retrospective data suggest the hypothesis that hs-CRP plasma levels may be useful for guiding use of lipid-lowering therapy in individuals who appear to be at low risk according to traditional risk assessment. A large-scale, randomized clinical trial-Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)-will test whether rosuvastatin therapy will reduce incident cardiovascular disease in subjects with elevated plasma hs-CRP concentrations who do not meet current criteria for initiation of lipid-lowering drug therapy. Such clinical trial data may provide an evidence base for the use of plasma CRP assay as an adjuvant guide to therapy to complement the established traditional risk factors such as plasma lipid levels. Thus, medical practitioners are ushering in an era in which the biology of inflammation in atherosclerosis will find its way into clinical application.
Changes in intima-media thickness (IMT) and arterial lumen diameter-as measured by B-mode high-resolution ultrasonography and quantitative coronary angiography, respectively-are currently the only surrogate markers for progression of atherosclerotic disease recognized by regulatory authorities in the United States and Europe. Because atherosclerosis is a disease of the arterial wall, the ability of B-mode ultrasonography to provide visualization of IMT offers significant advantages over angiography. These advantages, as well as the safety and noninvasiveness of B-mode ultrasonography, have led to increasing use of this imaging technique in observational studies and interventional studies of lipid-lowering agents over the last decade. These observational studies clearly demonstrated an association between carotid IMT and atherosclerotic disease. Of the interventional studies, the recent Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) trial found that use of atorvastatin 80 mg daily for aggressive lowering of plasma low-density lipoprotein cholesterol (LDL-C) concentrations to below current target levels was associated with significant IMT regression compared with results obtained with less aggressive plasma LDL-C lowering. A new study-Measuring Effects on Intima Media Thickness: an Evaluation of Rosuvastatin (METEOR)-will examine the effects of aggressive lipid-lowering treatment with rosuvastatin 40 mg daily on IMT. The cohort in this study will be individuals with mild hypercholesterolemia whose standard risk assessment does not categorize them as at sufficient risk of clinical disease to warrant initiation of lipid-lowering therapy despite their relatively high IMT values.