Carotid pressure is a better predictor of coronary artery disease severity than brachial pressure.

The mechanisms relating pulse pressure to cardiovascular outcome may include surrogacy for coronary disease severity. Although pulse pressure is typically measured at the brachial artery, central pulse pressure and its principal determinant, large-artery stiffness, may relate more closely to disease severity. This study aimed to determine the relationships between large-artery stiffness and carotid and brachial blood pressures and coronary artery disease severity. One hundred fourteen male patients with coronary artery disease (age 60+/-8 years, mean+/-SD) and 57 age-matched healthy male controls (age 59+/-9 years) were recruited. Patients were classified into 2 groups based on the magnitude of their maximum coronary stenosis: moderate (50% to 89%) and severe (>/=90%). Large-artery stiffness was assessed as systemic arterial compliance and carotid-femoral pulse wave velocity. Mean pressure was not different between the 3 groups. Systemic compliance and carotid pulse pressure were significantly different between all 3 groups, with compliance lowest and pressure highest in the severe group (P<0.05). Pulse wave velocity was higher in patients with severe stenosis than in those with moderate stenosis (P<0.01) and those in the control group (P<0.001). Brachial pulse pressure was higher in patients than in controls (P<0.05), but there was no difference between the 2 disease groups. In separate multivariate analyses, carotid pressures and systemic arterial compliance were determinants of coronary artery disease severity, independent of age, smoking status, body mass index, mean arterial pressure, heart rate, cholesterol levels (total, LDL, and HDL), triglycerides, and beta-antagonist and lipid-lowering therapy (P<0.001), whereas brachial pressures and pulse wave velocity were not. In conclusion, central blood pressures and systemic arterial compliance are more sensitive markers of coronary artery disease severity than brachial pressures.

Large artery stiffness: structural and genetic aspects.

1. Large artery stiffness is a principal determinant of pulse pressure and both are related to cardiovascular mortality independently of other major risk factors. A clearer understanding of the structural and genetic processes that contribute to large artery properties may provide novel approaches to therapy. 2. Age, atherosclerosis and gender are three important factors that contribute to large artery stiffening. Each influences the artery elastic matrix and its relationship to medial smooth muscle cells. Genetic and hormonal modulation of the extracellular matrix proteins and their regulators, including matrix metalloproteinases (MMPs), may account for some interindividual differences. 3. In a study of 213 healthy individuals and 105 patients with coronary artery disease (CAD), we examined whether stromelysin-1 (MMP-3) genotype, determined by the 5A/6A promoter polymorphism, influences large artery stiffening. In healthy individuals, the 5A/5A genotype was linked with stiffer large arteries and higher systolic blood pressure compared with other genotypes. 4. Genetic variation in the extracellular matrix protein fibrillin-1, using a pentanucleotide repeat polymorphism, was assessed as a potential determinant of large artery stiffness in patients with CAD. The 2-3 genotype was associated with stiffer large arteries, higher pulse pressure and more severe CAD than other genotypes. 5. Females experience a greater increase in large artery stiffness with age than males, with a time-course suggestive of sex steroid modulation. The mechanisms mediating such gender differences have not been established, but the known regulatory role of sex steroids with respect to MMPs likely contributes. 6. The demonstration that genetic and hormonal modulation of extracellular matrix components and MMPs contributes to age, atherosclerotic and gender-related differences in large artery mechanical properties suggests these proteins may be important targets for therapy.

Status of regulatory approval of biotechnology-derived plants and animals.

Development of new technology brings with it decisions regarding regulation to ensure safety in technology transfer. Properly formulated and administrated, such regulations can act as a catalyst for the transfer of new technology, not a barrier. Such regulations must be based on sound scientific principles, and are intended to provide protection for the public, engender public acceptance, and foster communication with the various segments of society. To develop this new technology in a safe and orderly manner field testing of the products/organisms of biotechnology, especially genetic engineering, has been permitted by the U.S. Department of Agriculture (USDA). USDA permits certify the environmental safety of field testing of plants and microorganisms developed through the use of material derived from plant pests. Permits are issued based upon analyses of the biology of the organism, the affected environment, and the precautions taken to ensure environmental protection. Licenses for the use of veterinary biologics, including recombinant vaccines, are also issued.