The aim of this study is to assess how long-term alcohol consumption influences health risks by emulating the Moderate Alcohol and Cardiovascular Health Trial (MACH15). In the first step, the protocol of the emulation of MACH15, including eligibility criteria, alcohol regimens and assignment, follow-up, endpoints, causal contrasts of interest, and statistical analysis was specified. In the second step, the investigators will emulate an adapted version of MACH15 following the specified protocol using data from the UK Biobank.
Observational data suggests that alcohol consumption lowers the risk of cardiovascular disease (CVD) compared to no consumption. Whether this relationship is truly causal remains uncertain because of the inherent limitations of observational studies, including unmeasured confounding and reverse causation. Mendelian randomization studies using genes as instrumental variables for alcohol are partially protected from these biases and have found no or harmful associations between alcohol consumption and CVD. To date, there has only been one long-term randomized controlled trial to investigate the cardiovascular effects of alcohol consumption: the Moderate Alcohol and Cardiovascular Health Trial (MACH15; NCT Number: NCT03169530). It was, however, terminated shortly after initiation. An alternative to a real randomized trial like MACH15, which must first be completed and is subject to strict eligibility criteria to ensure safety, is to use observational data to emulate a (hypothetical) pragmatic randomized trial. In this study, the investigators will emulate an adapted version of MACH15 using observational data from the UK Biobank, a large prospective cohort study of over 500,000 participants. The cardiometabolic effects of moderate drinking vs quitting, as originally planned in MACH15, as well as the effects of social and heavy/binge drinking on CVD, type 2 diabetes, other alcohol-related health outcomes, and death will be quantified.
Study Type
OBSERVATIONAL
Enrollment
503,325
Drink up to 16 grams of alcohol daily or almost daily \[repeated assessment center visit\] or 8-16 grams of alcohol 4 or more times per week \[web-based mental health questionnaire\]
No alcohol consumption
Drink up to 16 grams of alcohol 1-2 days per week or drink 1-3 times per month or only on special occasions \[repeated assessment center visit\], or drink 8-16 grams of alcohol 2-3 times per week or drink 4 times per month or less \[web-based mental health questionnaire\]
Drink more than 16 grams of alcohol daily or almost daily or more than 40 grams of alcohol 1-2 days per week \[repeated assessment center visit\], or 24 grams of alcohol or more 4 or more times per week or 40 grams of alcohol or more 2-3 times per week \[web-based mental health questionnaire\]
Cardiovascular disease or death
Composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for angina, coronary/carotid revascularization, and all-cause mortality
Time frame: From date of baseline measurement until the date of first cardiovascular disease or death documented in hospital or death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months
Cardiovascular disease
Composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for angina, coronary/carotid revascularization, and cardiovascular death
Time frame: From date of baseline measurement until the date of first cardiovascular disease documented in hospital or death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Type 2 diabetes
Progression among normoglycemic and pre-diabetes individuals to type 2 diabetes
Time frame: From date of baseline measurement until the date of first type 2 diabetes documented in hospital or death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
Alcohol-related disease or death
Composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, heart failure, atrial fibrillation, cancer (except non-melanoma skin cancer), dementia, depression, infection with hospitalization, injury with hospitalization, liver cirrhosis, type 2 diabetes, and all-cause mortality
Time frame: From date of baseline measurement until the date of first alcohol-related disease or death documented in hospital, cancer, or death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.