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Objectives: To develop a new methodology to systematically compare evidence across diverse risk markers for coronary heart disease and to compare this evidence with guideline recommendations., Design: "Horizontal" systematic review incorporating different sources of evidence., Data Sources: Electronic search of Medline and hand search of guidelines. Study selection Two reviewers independently determined eligibility of studies across three sources of evidence (observational studies, genetic association studies, and randomised controlled trials) related to four risk markers: depression, exercise, C reactive protein, and type 2 diabetes. Data extraction For each risk marker, the largest meta-analyses of observational studies and genetic association studies, and meta-analyses or individual randomised controlled trials were analysed., Results: Meta-analyses of observational studies reported adjusted relative risks of coronary heart disease for depression of 1.9 (95% confidence interval 1.5 to 2.4), for top compared with bottom fourths of exercise 0.7 (0.5 to 1.0), for top compared with bottom thirds of C reactive protein 1.6 (1.5 to 1.7), and for diabetes in women 3.0 (2.4 to 3.7) and in men 2.0 (1.8 to 2.3). Prespecified study limitations were more common for depression and exercise. Meta-analyses of studies that allowed formal Mendelian randomisation were identified for C reactive protein (and did not support a causal effect), and were lacking for exercise, diabetes, and depression. Randomised controlled trials were not available for depression, exercise, or C reactive protein in relation to incidence of coronary heart disease, but trials in patients with diabetes showed some preventive effect of glucose control on risk of coronary heart disease. None of the four randomised controlled trials of treating depression in patients with coronary heart disease reduced the risk of further coronary events. Comparisons of this horizontal evidence review with two guidelines published in 2007 showed inconsistencies, with depression prioritised more in the guidelines than in our review., Conclusions: This horizontal systematic review pinpoints deficiencies and strengths in the evidence for depression, exercise, C reactive protein, and diabetes as unconfounded and unbiased causes of coronary heart disease. This new method could be used to develop a field synopsis and prioritise future development of guidelines and research.

Background: Due to marked regional differences in the incidence of coronary heart disease (CHD) in Europe, the recommendation by the European Society of Cardiology to use the Coronary Risk Chart based on data from the Framingham Heart Study, could be questioned., Methods: Data from two population studies (The Glostrup Population Studies, n = 4757, the Framingham Heart Study, n = 2562) were used to examine three different levels of cross-validation. The first level of examination was whether a risk-score developed from one sample adequately ordered the risk of participants in the other sample, using the Area Under a Receiver Operating Characteristic (AUROC) curve. The second level compared the magnitude of coefficients in logistic models in the two studies; while the third level tested whether the level of risk of CHD death in one sample could be estimated based on a risk function from the other sample., Result: Coronary heart disease mortality was 515 per 100 000 person-years in Framingham and 311 per 100 000 person-years in Glostrup. The AUROC curve was between 75% and 77% and regardless of which risk-score was used. Logistic coefficients did not differ significantly between studies. The Framingham risk-score significantly overestimated the risk in the Glostrup sample and the Glostrup risk-score underestimated in the Framingham sample., Conclusion: Using this Framingham risk-score on a Danish population will lead to a significant overestimation of coronary risk. The validity of risk-scores developed from populations with different incidence of the disease should preferably be tested prior to their application.

The article offers information on a study which determined the most robust method for systemically reviewing evidence on a full range of risk markers for coronary heart disease. Identified risk markers are depression, exercise and C reactive proteins, among others. Primary outcomes included fatal coronary heart disease, non-fatal myocardial infarction and all cause mortality. Presented in details are main results and role of chance. Findings suggest that horizontal comparisons could be used in the development of guidelines and research.