Coronary heart disease (CHD) is a life-threatening condition that poses a significant risk to individuals. Mendelian randomization (MR) is an emerging epidemiological research method that offers substantial advantages in identifying risk factors for diseases. Currently, there are ongoing CHD-related MR studies. To gain comprehensive insights into the focal areas and trends of CHD-related MR research, this study utilizes bibliometrics to conduct an in-depth analysis of CHD-related MR articles published in the core database of Web of Science (WOS) from 2009 to 2023. A search was performed to identify CHD-related MR articles published between 2009 and 2023 in WOS. The data, including publication countries, research institutions, journals, citations, and keywords, were analyzed using the Bibliometrix R-4.0 software package. A total of 111 articles published in 71 journals were included in the analysis. The journal with the highest impact factor (IF) was the New England Journal of Medicine. The articles were distributed across 24 categories within the 71 journals, with the highest number of publications falling under Cardiac & Cardiovascular Systems, Medicine, General & Internal, and Genetics & Heredity. Among the articles, 57 were published in Q1 journals, 42 in Q2 journals, 9 in Q3 journals, and 2 in Q4 journals. The most frequently published journals on CHD-related MR were Frontiers in Cardiovascular Medicine, Frontiers in Genetics, and the Journal of the American College of Cardiology. A total of 963 authors participated in the 111 articles, with the majority affiliated with institutions in the United Kingdom, the US, and China. The national cooperation network revealed close collaborations between the UK and the US, as well as between the UK and China. The publication of the 111 articles involved 453 research institutions, with Oxford University, Bristol University, and Cambridge University being the most frequently involved institutions. Out of the 111 articles, only 62 were directly related to CHD and MR, with CHD being the outcome factor in 61 of them. These 61 articles investigated 47 exposure factors across eight categories. Among these factors, 10 had been studied in more than 2 articles. The findings concerning the impact of serum uric acid and omega-6 fatty acids on CHD risk were not entirely consistent. Research in MR related to CHD has been gradually gaining recognition, with an increase in both its academic credibility and collaborative efforts within this field. Indeed, MR has facilitated the identification of risk factors associated with CHD. However, the relationship between these disease risk factors and CHD requires further investigation for clarification. Future MR studies on CHD could prioritize the elucidation and validation of contentious disease risk factors, thereby paving the way for a more comprehensive exploration of additional factors contributing to the onset of CHD.

The aim of this study was to investigate the causal relationship and evidence of an association between increased adiposity and the risk of incident cardiovascular disease (CVD) events or mortality.
Observational (informing association) and Mendelian randomization (MR) (informing causality) studies were assessed to gather mutually complementary insights and elucidate perplexing epidemiological relationships. Systematic reviews and meta-analyses of observational and MR studies that were published until January 2021 and evaluated the association between obesity-related indices and CVD risk were searched. Twelve systematic reviews with 53 meta-analyses results (including over 501 cohort studies) and 12 MR studies were included in the analysis. A body mass index (BMI) increase was associated with higher risks of coronary heart disease, heart failure, atrial fibrillation, all-cause stroke, haemorrhagic stroke, ischaemic stroke, hypertension, aortic valve stenosis, pulmonary embolism, and venous thrombo-embolism. The MR study results demonstrated a causal effect of obesity on all indices but stroke. The CVD risk increase for every 5 kg/m2 increase in BMI varied from 10% [relative risk (RR) 1.10; 95% confidence interval (CI) 1.01-1.21; certainty of evidence, low] for haemorrhagic stroke to 49% (RR 1.49; 95% CI 1.40-1.60; certainty of evidence, high) for hypertension. The all-cause and CVD-specific mortality risks increased with adiposity in cohorts, but the MR studies demonstrated no causal effect of adiposity on all-cause mortality.
High adiposity is associated with increased CVD risk despite divergent evidence gradients. Adiposity was a causal risk factor for CVD except all-cause mortality and stroke. Half (49%; 26/53) of the associations were supported by high-level evidence. The associations were consistent between sexes and across global regions. This study provides guidance on how to integrate evidence from observational (association) and genetics-driven (causation) studies accumulated to date, to enable a more reliable interpretation of epidemiological relationships.

BACKGROUND: The Consensus Statement from the European Atherosclerosis Society (EAS) Consensus Panel 2017 concludes on the basis of 3 different types of clinical studies that low-density lipoprotein (LDL) causes atherosclerotic cardiovascular disease (ASCVD). In Mendelian randomization studies, rare genetic mutations affecting LDL receptor function were found to cause higher or lower LDL-C levels, which are associated with correspondingly altered ASCVD risk. In prospective cohort studies and randomized controlled trials (RCTs) of statins, a remarkably consistent log-linear association was demonstrated between the absolute magnitude of LDL-C exposure and ASCVD risk. The EAS Statement proposes that any mechanism of lowering plasma LDL concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C. However, as we explain, we do not find this conclusion acceptable.
CONCLUSIONS: Our review points out that different interpretations are possible for the results of Mendelian randomization studies. As for prospective cohort studies, many inconsistent reports on the association of LDL-C and ASCVD were disregarded when drafting the Statement, reports with and without genetic factors related to LDL receptor function should be analyzed separately, and the term ASCVD in the Statement is used inappropriately because myocardial infarction and cerebral infarction differ in their association with LDL-C. As for RCTs, clinical reports on statins published before and after the implementation of new regulations affecting clinical trials (2004/2005) should not both be included in meta-analyses because the evaluated efficacy of statins changed markedly, and the irreversible adverse effects of statins need to be evaluated more rigorously now that their mechanisms have been elucidated. Key Messages: Apart from the EAS hypothesis that LDL causes ASCVD, recent pharmacological/biochemical studies, as summarized in this review and elsewhere, have revealed that atherosclerosis is caused by statins taken to lower LDL-C, as well as by warfarin and some types of vegetable fats and oils, in the absence of significantly elevated LDL-C levels. Thus, the promotion of statin treatment by the Statement is rather risky and we do not feel that the conclusions are justified for the prevention of ASCVD.