The combined effect of pravastatin and aspirin on clinical cardiovascular events

The 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, can achieve significant reductions in plasma low-density lipoprotein (LDL)-cholesterol levels. Experimental and clinical evidence now shows that some statins interfere with formation of atherosclerotic lesions independent of their hypolipidemic properties. Vulnerable plaque rupture can result in thrombus formation and artery occlusion; this plaque deterioration is responsible for most acute coronary syndromes, including myocardial infarction (MI), unstable angina, and coronary death, as well as coronary heart diseaseequivalent non-hemorrhagic stroke. Inhibition of HMG-CoA reductase has potential pleiotropic effects other than lipid-lowering, as statins block mevalonic acid production, a precursor to cholesterol and numerous other metabolites. Statins' beneficial effects on clinical events may also thus involve nonlipid-related mechanisms that modify endothelial function, inflammatory responses, plaque stability, and thrombus formation. Aspirin, routinely prescribed to post-MI patients as adjunct therapy, may potentiate statins beneficial effects, as aspirin does not compete metabolically with statins but acts similarly on atherosclerotic lesions. Common functions of both medications include inhibition of platelet activity and aggregation, reduction in atherosclerotic plaque macrophage cell count, and prevention of atherosclerotic vessel endothelial dysfunction. The Cholesterol and Recurrent Events (CARE) trial provides an ideal population in which to examine the combined effects of pravastatin and aspirin. Lipid levels, intermediate outcomes, are examined by pravastatin and aspirin status, and differences between the two pravastatin groups are found. A modified Cox proportional-hazards model with aspirin as a time-dependent covariate was used to determine the effect of aspirin and pravastatin on the clinical cardiovascular composite endpoint of coronary heart disease death, recurrent MI or stroke. Among those assigned to pravastatin, use of aspirin reduced the composite primary endpoint by 35%; this result was similar by gender, race, and diabetic status. Older patients demonstrated a nonsignificant 21% reduction in the primary outcome, whereas the younger had a significant reduction of 43% in the composite primary outcome. Secondary outcomes examined include coronary artery bypass graft (38% reduction), nonsurgical bypass, peripheral vascular disease, and unstable angina. Pravastatin and aspirin in a post-MI population was found to be a beneficial combination that seems to work through lipid and nonlipid, anti-inflammatory mechanisms. ^

The association of nonfatal occupational injuries with non -work -related morbidity

A case-referent study of occupational injuries sustained by 474 workers employed in the heavy equipment machinery industry over a two year period, 1985-1986, was undertaken to examine the association of occupational injuries with non-work-related morbidity. Its specific aim was to evaluate whether employees who experienced a work-related injury had an increased prevalence of non-work-related morbidity, specifically for injuries, cardiovascular disease, mental disorders, all other disease outcomes and total morbidity, compared to employees who did not experience a work-related injury. In order to determine the direction of the relationship, the use of the previous calendar year was employed to assess non-work-related morbidity. A secondary objective of the study was the evaluation of the utility of two existing data sources, workers' compensation and group health insurance claims, and the feasibility of conducting studies based on these data.^ The association of non-work-related non-back injuries and subsequent occupational injury was statistically significant (OR = 1.31, 95% CI 1.02-1.67) for all WC claims. The strength of the association was supported by the elevated odds ratio for non-work-related injuries when severity of occupational injury was assessed by WC claim costs of $100 and greater (OR = 1.47, 1.09--1.97), and by lost workdays (OR = 1.37). Factors that predispose an individual to a non-back injury, such as personal attributes and lifestyle characteristics, also influence that individual's risk of subsequent occupational injury. These factors may be reflected in an employee's reaction to life stressors which influence susceptibility to injury. The role of employee assistance programs as a component of injury prevention strategies is suggested.^ An increased but nonsignificant prevalence of non-work-related injuries, cardiovascular disease, mental disorders, and other morbidity conditions was noted among cases. These findings do not provide support of a causal factor in the etiology of occupational injuries. In contrast to non-back injuries, these conditions are chronic in nature and their influence on risk of occupational injuries uncertain.^ In general, cases tended to file more group health insurance claims for other morbidity than did referents. The association with increased total morbidity was consistent whether worker compensation claims were analyzed by total number of claims, claims with costs of $100 and greater, or by lost workdays. Whether persons who sustained an occupational injury were in fact in poor general health than referents, warrant further investigation. ^