Related Experiment Videos
Evaluating the causal relevance of diverse risk markers: horizontal systematic review
Hannah Kuper1, Amanda Nicholson, Mika Kivimaki
1Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT. hannah.kuper@lshtm.ac.uk
Insights
This study developed a new method to compare evidence on coronary heart disease risk factors like depression and diabetes. It found inconsistencies between evidence and current guidelines, highlighting areas for future research.
Area of Science:
- Cardiovascular Disease Epidemiology
- Systematic Review Methodology
- Evidence-Based Medicine
Background:
- Coronary heart disease (CHD) risk assessment relies on diverse markers.
- Current guidelines may not fully reflect the strength of evidence for all risk markers.
- A systematic approach is needed to compare evidence quality across different risk factors.
Purpose of the Study:
- To develop a novel methodology for systematically comparing evidence across various coronary heart disease risk markers.
- To evaluate the evidence for depression, exercise, C-reactive protein, and type 2 diabetes as CHD risk factors.
- To compare the synthesized evidence with existing clinical guideline recommendations.
Main Methods:
- A "horizontal" systematic review was conducted, integrating evidence from observational studies, genetic association studies, and randomized controlled trials.
- Data were extracted from Medline and guideline searches for four risk markers: depression, exercise, C-reactive protein, and type 2 diabetes.
- Meta-analyses of observational and genetic studies, alongside available randomized controlled trials, were analyzed.
Main Results:
- Observational studies indicated significant CHD risk associations for depression (RR 1.9), C-reactive protein (RR 1.6), and type 2 diabetes (RR 2.0-3.0). Exercise showed a potential protective effect (RR 0.7).
- Mendelian randomization did not support a causal effect for C-reactive protein; such analyses were lacking for depression, exercise, and diabetes.
- Randomized controlled trials were unavailable for most risk markers concerning CHD incidence, though some benefit was seen for glucose control in diabetic patients. Trials for depression treatment did not reduce further CHD events.
Conclusions:
- The horizontal systematic review identified strengths and weaknesses in the evidence base for depression, exercise, C-reactive protein, and type 2 diabetes as causes of CHD.
- The developed methodology can inform the creation of field synopses.
- This approach can prioritize future guideline development and research efforts in cardiovascular disease risk assessment.
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.
Related Concept Videos
Criteria for Causality: Bradford Hill Criteria - II
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
Causality in Epidemiology
Bias in Epidemiological Studies
Strategies for Assessing and Addressing Confounding
Confounding can be addressed at both the design phase of a study and through analytical methods after data...
Relative Risk