Objective To synthesise the association of shift work with major vascular events as reported in the literature.Data sources Systematic searches of major bibliographic databases, contact with experts in the field, and review of reference lists of primary articles, review papers, and guidelines.Study selection Observational studies that reported risk ratios for vascular morbidity, vascular mortality, or all cause mortality in relation to shift work were included; control groups could be non-shift ("day") workers or the general population.Data extraction Study quality was assessed with the Downs and Black scale for observational studies. The three primary outcomes were myocardial infarction, ischaemic stroke, and any coronary event. Heterogeneity was measured with the I 2 statistic and computed random effects models.Results 34 studies in 2 011 935 people were identified. Shift work was associated with myocardial infarction (risk ratio 1.23, 95% confidence interval 1.15 to 1.31; I 2 =0) and ischaemic stroke (1.05, 1.01 to 1.09; I 2 =0). Coronary events were also increased (risk ratio 1.24, 1.10 to 1.39), albeit with significant heterogeneity across studies (I 2 =85%). Pooled risk ratios were significant for both unadjusted analyses and analyses adjusted for risk factors. All shift work schedules with the exception of evening shifts were associated with a statistically higher risk of coronary events. Shift work was not associated with increased rates of mortality (whether vascular cause specific or overall). Presence or absence of adjustment for smoking and socioeconomic status was not a source of heterogeneity in the primary studies. 6598 myocardial infarctions, 17 359 coronary events, and 1854 ischaemic strokes occurred. On the basis of the Canadian prevalence of shift work of 32.8%, the population attributable risks related to shift work were 7.0% for myocardial infarction, 7.3% for all coronary events, and 1.6% for ischaemic stroke.Conclusions Shift work is associated with vascular events, which may have implications for public policy and occupational medicine.

Smoking was an exclusion criterion for controls, whereas 4 of the 21 cases were regular smokers of 2 to 10 cigarettes per day. Mean urinary excretion rates of 8-iso-PGF 2␣ were similar in the 4 smokers (404 pg/mg of creatinine) and in the 21 cases considered as a whole (482 pg/mg of creatinine). Urine albumin excretion rates were not tested. There was only a small glucose variability between each day (day 1 mean amplitude of glycemic excursions [MAGE], 74 mg/ dL; day 2 MAGE, 76 mg/dL), and MAGE values on day 1 and day 2 were highly correlated (r= 0.87; PϽ.001).Finally, conflicting observations in the study by O'Byrne et al 4 could have resulted from the use of different methods in different groups of patients at different ages: enzyme immunoassay in our study (21 patients with type 2 diabetes; mean age of 64 years) vs stable isotope dilution mass spectrometry assay in O'Byrne et al (13 patients with type 1 diabetes; mean age of 36 years).

Context Atherosclerotic vascular disease is an enormous public health problem. A number of emerging risk factors for atherosclerosis have recently been proposed to help identify high-risk individuals.Objective To review the epidemiological, basic science, and clinical trial evidence concerning 4 emerging risk factors: C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine.Data Sources Using the terms atherosclerosis, cardiovascular disease, risk factors, prevention, screening, C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine, we searched the MEDLINE database from January 1990 to January 2003. Conference proceedings, abstract booklets, bibliographies of pertinent articles and books, and personal files were hand searched to identify additional articles. Study SelectionOriginal investigations and reviews of the epidemiology of atherosclerosis and the association of conventional and novel risk factors with vascular risk were selected. On the basis of the search strategy, 373 relevant studies were identified.Data Extraction A diverse array of studies were examined, including randomized controlled trials, prospective cohort studies, systematic overviews, case-control, crosssectional, and mechanistic studies. Data extraction was performed by one of the authors. Data SynthesisThe available epidemiological and basic science evidence supports, to varying degrees, independent associations between these 4 candidate risk factors and atherosclerotic vascular disease. However, there is relatively little data regarding the additive yield of screening for these factors over that of validated global risk assessment strategies currently in use. Furthermore, controlled intervention studies targeting individuals with these factors for proven risk-reduction therapies, or specifically treating these factors with available therapies, are few. The explanatory power of the major, established cardiovascular risk factors has been systematically underestimated.Conclusions Although C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine are associated with vascular disease risk, their optimal use in routine screening and risk stratification remains to be determined.