All-cause Mortality, Angina Pectoris, Atrial Fibrillation, Cancer, Cardiovascular Death, Coronary Revascularization, Dementia, Depression, Heart Failure, Infections, Injuries, Ischemic Stroke, Liver Cirrhosis, Myocardial Infarction, Type 2 Diabetes
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BEHAVIORALModerate drinking
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 \[web-based mental health questionnaire\]
BEHAVIORALQuitting
No alcohol consumption
BEHAVIORALSocial drinking
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 \[web-based mental health questionnaire\]
BEHAVIORALHeavy/binge drinking
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 \[web-based mental health questionnaire\]
Sponsors
Harvard School of Public Health (HSPH)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to 69 Years
Healthy volunteers
Yes
Inclusion criteria
* 40-69 years old at enrollment * Currently drinking
Exclusion criteria
* Within the six months prior to baseline, cardiovascular disease event (myocardial infarction, revascularization procedure, or stroke) * Hospitalization due to heart failure * History of any of the following alcohol-related conditions, confirmed by a hospital record: alcoholic cardiomyopathy, alcoholic gastritis, alcoholic liver disease, degeneration of the nervous system due to alcohol, alcoholic myopathy, alcoholic polyneuropathy, alcohol-induced acute or chronic pancreatitis, alcohol use disorder; or self-reported history of alcoholic liver disease or alcohol use disorder * Dual antiplatelet therapy or coumarin anticoagulants * Serious chronic liver disease (active hepatitis B or C infection) in the past 6 months before baseline * Personal history of any colon or liver cancer * Personal history of breast cancer * Diagnosis of dementia * Not willing or able to provide a signed and dated informed consent form * Reduced alcohol compared to 10 years ago due to illness, ill health, or doctor's advice * Self-reported poor health
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular disease or death | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular disease | 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 | 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 |
| Type 2 diabetes | 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 | Progression among normoglycemic and pre-diabetes individuals to type 2 diabetes |
| Alcohol-related disease or death | 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 | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization for angina | From date of baseline measurement until the date of first hospitalization for angina documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months | First hospitalization for angina |
| Hard cardiovascular disease or death | From date of baseline measurement until the date of first hard cardiovascular disease or death documented in hospital or death registry data, admin. censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months | Composite endpoint comprised of the first occurrence of a non-fatal myocardial infarction, non-fatal ischemic stroke, and cardiovascular death |
| All-cause mortality | From date of baseline measurement until the date of death documented in death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months | Death |
| Coronary/carotid revascularization | From date of baseline measurement until the date of first coronary/carotid revascularization documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months | First coronary/carotid revascularization |
| Cardiovascular death | From date of baseline measurement until the date of cardiovascular death documented in death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months | Cardiovascular death |
| Non-fatal myocardial infarction | From date of baseline measurement until the date of first non-fatal myocardial infarction documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months | First occurrence of a non-fatal myocardial infarction |
| Non-fatal ischemic stroke | From date of baseline measurement until the date of first non-fatal ischemic stroke documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months | First occurrence of a non-fatal ischemic stroke |
Outcome results
None listed