Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

BACKGROUND: Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. METHODS: A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. FINDINGS: When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT. INTERPRETATION: A genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy. FUNDING: National Institutes of Health.

Effects of airborne fine particles (PM2.5 ) on deep vein thrombosis admissions in the northeastern United States.

BACKGROUND: Literature relating air pollution exposure to deep vein thrombosis (DVT) and pulmonary embolism (PE), despite biological plausibility, is sparse. No comprehensive study examining associations between both short- and long-term exposure to particulate matter (PM)2.5 and DVT or PE has been published. Using a novel PM2.5 prediction model, we study whether long- and short-term PM2.5 exposure is associated with DVT and PE admissions among elderly across the northeastern United States. METHODS: We estimated daily exposure of PM2.5 in each ZIP code. We investigated the long- and short-term effects of PM2.5 on DVT and PE hospital admissions. There were 453,413 DVT and 151,829 PE admissions in the study. For short-term exposure, we performed a case crossover analysis matching month and year and defined the hazard period as lag 01 (exposure of day of admission and previous day). For the long-term association, we used a Poisson regression. RESULTS: A 10-µg m(-3) increase in short-term exposure was associated with a 0.63% increase in DVT admissions (95% confidence interval [CI] = 0.03% to 1.25%) and a 6.98% (95% CI = 5.65% to 8.33%) increase in long-term exposure admissions. For PE, the associated risks were 0.38% (95% CI = -0.68% to 1.25%) and 2.67% (95% CI = 5.65% to 8.33%). These results persisted when analyses were restricted to location-periods meeting the current Environmental Protection Agency annual standard of 12 µg m(-3) . CONCLUSIONS: Our findings showed that PM2.5 exposure was associated with DVT and PE hospital admissions and that current standards are not protective of this result.

Gender-related differences in moral judgments.

The moral sense is among the most complex aspects of the human mind. Despite substantial evidence confirming gender-related neurobiological and behavioral differences, and psychological research suggesting gender specificities in moral development, whether these differences arise from cultural effects or are innate remains unclear. In this study, we investigated the role of gender, education (general education and health education) and religious belief (Catholic and non-Catholic) on moral choices by testing 50 men and 50 women with a moral judgment task. Whereas we found no differences between the two genders in utilitarian responses to non-moral dilemmas and to impersonal moral dilemmas, men gave significantly more utilitarian answers to personal moral (PM) dilemmas (i.e., those courses of action whose endorsement involves highly emotional decisions). Cultural factors such as education and religion had no effect on performance in the moral judgment task. These findings suggest that the cognitive-emotional processes involved in evaluating PM dilemmas differ in men and in women, possibly reflecting differences in the underlying neural mechanisms. Gender-related determinants of moral behavior may partly explain gender differences in real-life involving power management, economic decision-making, leadership and possibly also aggressive and criminal behaviors.