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Importance: Mendelian randomization (MR) studies use genetic variation associated with modifiable exposures to assess their possible causal relationship with outcomes and aim to reduce potential bias from confounding and reverse causation.Objective: To develop the STROBE-MR Statement as a stand-alone extension to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for the reporting of MR studies.Design, Setting, and Participants: The development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) framework guidance and used the STROBE Statement as a starting point to draft a checklist tailored to MR studies. The project was initiated in 2018 by reviewing the literature on the reporting of instrumental variable and MR studies. A group of 17 experts, including MR methodologists, MR study design users, developers of previous reporting guidelines, and journal editors, participated in a workshop in May 2019 to define the scope of the Statement and draft the checklist. The draft checklist was published as a preprint in July 2019 and discussed on the preprint platform, in social media, and at the 4th Mendelian Randomization Conference. The checklist was then revised based on comments, further refined through 2020, and finalized in July 2021.Findings: The STROBE-MR checklist is organized into 6 sections (Title and Abstract, Introduction, Methods, Results, Discussion, and Other Information) and includes 20 main items and 30 subitems. It covers both 1-sample and 2-sample MR studies that assess 1 or multiple exposures and outcomes, and addresses MR studies that follow a genome-wide association study and are reported in the same article. The checklist asks authors to justify why MR is a helpful method to address the study question and state prespecified causal hypotheses. The measurement, quality, and selection of genetic variants must be described and attempts to assess validity of MR-specific assumptions should be well reported. An item on data sharing includes reporting when the data and statistical code required to replicate the analyses can be accessed.Conclusions and Relevance: STROBE-MR provides guidelines for reporting MR studies. Improved reporting of these studies could facilitate their evaluation by editors, peer reviewers, researchers, clinicians, and other readers, and enhance the interpretation of their results. [ABSTRACT FROM AUTHOR]

Importance: Research has shown a U-shaped pattern in the association of body mass index (BMI) with mortality. Although average BMI has increased over time in most countries, the prevalence of cardiovascular risk factors may also be decreasing among obese individuals over time. Thus, the BMI associated with lowest all-cause mortality may have changed.Objective: To determine whether the BMI value that is associated with the lowest all-cause mortality has increased in the general population over a period of 3 decades.Design, Setting, and Participants: Three cohorts from the same general population enrolled at different times: the Copenhagen City Heart Study in 1976-1978 (n = 13,704) and 1991-1994 (n = 9482) and the Copenhagen General Population Study in 2003-2013 (n = 97,362). All participants were followed up from inclusion in the studies to November 2014, emigration, or death, whichever came first.Exposures: For observational studies, BMI was modeled using splines and in categories defined by the World Health Organization. Body mass index was calculated as weight in kilograms divided by height in meters squared.Main Outcomes and Measures: Main outcome was all-cause mortality and secondary outcomes were cause-specific mortality.Results: The number of deaths during follow-up was 10,624 in the 1976-1978 cohort (78% cumulative mortality; mortality rate [MR], 30/1000 person-years [95%CI, 20-46]), 5025 in the 1991-1994 cohort (53%; MR, 16/1000 person-years [95%CI, 9-30]), and 5580 in the 2003-2013 cohort (6%;MR, 4/1000 person-years [95%CI, 1-10]). Except for cancer mortality, the association of BMI with all-cause, cardiovascular, and other mortality was curvilinear (U-shaped). The BMI associated with the lowest all-cause mortality increased by 3.3 from the 1976-1978 cohort compared with the 2003-2013 cohort. [table: see text] The multivariable-adjusted hazard ratios for all-cause mortality for BMI of 30 or more vs BMI of 18.5 to 24.9 were 1.31 (95%CI, 1.23-1.39;MR, 46/1000 person-years [95%CI, 32-66] vs 28/1000 person-years [95%CI, 18-45]) in the 1976-1978 cohort, 1.13 (95%CI, 1.04-1.22; MR, 28/1000 person-years [95%CI, 17-47] vs 15/1000 person-years [95%CI, 7-31]) in the 1991-1994 cohort, and 0.99 (95%CI, 0.92-1.07;MR, 5/1000 person-years [95%CI, 2-12] vs 4/1000 person-years [95%CI, 1-11]) in the 2003-2013 cohort. CONCLUSIONS AND RELEVANCE Among 3 Danish cohorts, the BMI associated with the lowest all-cause mortality increased by 3.3 from cohorts enrolled from 1976-1978 through 2003-2013. Further investigation is needed to understand the reason for this change and its implications. [ABSTRACT FROM AUTHOR]

The article reports on the results of research which was conducted in an effort to test the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population. Researchers used a population based study to examine 13,956 men and women between the ages of 20 and 93 in research which was begun in 1976 and was followed up in 2007. They found that in their particular group of patients, nonfasting triglyceride levels were associated with a risk of ischemic stroke.

The article presents a study seeking to determine whether genetically reduced high-density lipoprotein (HDL) due to heterozygosity for loss-of-function mutations in the adenosine triphosphate-binding cassette transporter A1 (ABCA1) gene causes increased risk of ischemic heart disease (IHD). The design and setting of the studies, which were drawn from the general population in Copenhagen, Denmark, are described. The outcomes measured the level of HDL cholesterol in the population, cellular cholesterol efflux, and the link between IHD, HDL, and genotype. Results suggest that lower levels of HDL related to loss-of-function mutations in the ABCA1 gene were not associated with an increased risk of IHD.

This article reports on a clinical trial on nonfasting triglycerides and the risk of myocardial infarction, ischemic heart disease, and death in men and women. The objective of the trial was to test the hypothesis that very high levels of nonfasting triglycerides predict myocardial infarction (MI), ischemic heart disease (IHD) and death. The study found that with increasing levels of nonfasting triglycerides, levels of lipoprotein cholesterol increased. The study concluded that in this general population cohort, elevated nonfasting triglyceride levels were associated with increased risk of MI, IHD and death in both men and women.

Jacob Freiberg, Anne Tybjaerg-Hansen and Borge G. Nordestgaard respond to a letter to the editor about their article "Nonfasting Triglycerides and Risk of Ischemic Stroke in the General Population" in a previous issue.

Anne Tybjaerg-Hansen, Borge G. Nordestgaard and Ruth Frikke-Schmidt respond to a letter to the editor about their article "Association of Loss of Function Mutations in the ABC1 Gene With High Density Lipoprotein Cholesterol Levels and Risk of Ischemic Heart Disease" in a previous issue.

A reply is presented by Drs. Børge G. Nordestgaard and Anne Tybjærg-Hansen to letters to the editor about their article "Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women."