Pai JK, Mukamal KJ, Rimm EB. Long-term alcohol consumption in relation to all-cause and cardiovascular mortality among survivors of myocardial infarction: the Health Professionals Follow-up Study. European Heart Journal 2012; doi:10.1093/eurheartj/ehs047
Aims: The aim of this study was to examine the association between long-term alcohol consumption, alcohol consumption before and after myocardial infarction (MI), and all-cause and cardiovascular mortality among survivors of MI.
Methods and results: The Health Professionals Follow-up Study (HPFS) is a prospective cohort study of 51,529 US male health professionals. From 1986 to 2006, 1,818 men were confirmed with incident non-fatal MI. Among MI survivors, 468 deaths were documented during up to 20 years of follow-up. Long-term average alcohol consumption was calculated beginning from the time period immediately before the first MI and updated every 4 years afterward. Cox proportional hazards were used to estimate the multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Compared with non-drinkers, the multivariable-adjusted HRs for all-cause mortality were 0.78 (95% CI: 0.62–0.97) for 0.1–9.9 g/day, 0.66 (95% CI: 0.51–0.86) for 10.0–29.9 g/day, and 0.87 (95% CI: 0.61–1.25) for ≥30 g/day (P quadratic= 0.006). For cardiovascular mortality, the corresponding HRs were 0.74 (95% CI: 0.54–1.02), 0.58 (95% CI: 0.39–0.84), and 0.98 (95% CI: 0.60–1.60), P quadratic = 0.003. These findings were consistent when restricted to pre- and post-MI alcohol assessments. In subgroup analyses, moderate alcohol consumption was inversely associated with mortality among men with non-anterior infarcts, and among men with mildly diminished left ventricular function.
Conclusion: Long-term moderate alcohol consumption is inversely associated with all-cause and cardiovascular mortality among men who survived a first MI. This U-shaped association may be strongest among individuals with less impaired cardiac function after MI and should be examined further.
The present paper is based on data from a very well-done prospective follow-up study of male health professionals, initially recruited in 1986. Among the cohort, 1,818 men had a confirmed myocardial infarction (MI) during follow up. The alcohol intake of the subjects had been recorded prior to, and at intervals following, the MI.
There are a number of informative and interesting results described from this study. First, there was little change in reported alcohol prior to and following the MI: drinkers tended to remain drinkers of similar amounts. Few non-drinkers began to drink after their MI; among heavier drinkers, there was a tendency to decrease the amount somewhat (but very few stopped drinking completely). There were no significant differences in outcome according to type of beverage consumed although, interestingly, lower hazard ratios were seen for consumers of beer and liquor than of wine.
The associations of alcohol consumption with mortality were almost the same for alcohol intake reported prior to the MI as that reported after the MI: for 10-29.9 g/day, the adjusted hazard ratio for mortality was 0.70 for both. While the authors state that the effects of alcohol were stronger for the association with non-anterior MIs, the HRs for all-cause mortality were little different: among the moderately drinking men the HRs were 0.58 for anterior MI and 0.51 for other types of MI when compared with abstainers.
The overall results show that, in comparison with no alcohol consumption, the intake of light (0.1-9.9 g/day) and moderate (10.0-29.9 g/d) amounts of alcohol was associated with lower risk of all-cause mortality and cardiovascular morality. The significant reductions in all-cause mortality risk (22% lower for 0.1-9.9 g/day and 34% lower for 10.0 – 29.9 g/day, in comparison with non-drinkers) were no longer present for consumers of ≥ 30 g/day; for this
highest consumer group, the adjusted hazard ratio was 0.87 with 95% CI of 0.61-1.25.
As stated by the authors: “Our findings are consistent with the recent European Society of Cardiology (ESC) recommended guidelines for long-term management of acute coronary syndromes that moderate alcohol consumption of 10–30 g per day in men should not be discouraged and may be beneficial for long-term prognosis after MI.1-3”
Specific comments by reviewers: Forum members all considered this to be a very well-done study. The repeated assessments of alcohol intake permitted adjustments for changes in alcohol intake over time. Stated one Forum reviewer, “I find this a very balanced view. Of particular interest is the emphasis on the reduction of inflammatory markers (hs-CRP and IL-6), and increased insulin sensitivity. This indicates that moderate alcohol consumption influences conditions other than coronary disease that are associated with inflammation. This broadens the clinical relevance of wine and alcohol as ‘functional foods’ that may affect other diseases positively as well. It furthermore underlines the importance of environmental influences on lifestyle related diseases.”
Difficulties in judging effects of an exposure after an event: It has been shown in recent publications that an exposure that affects the risk of a disease outcome may not have a similar relation to events following the event. In other words, the same risk factors before someone develops a MI may not be the same for the risk of mortality after someone has suffered a MI. For example, Canto et al found an inverse (rather than a positive) association between the number of coronary heart disease risk factors and hospital mortality following a MI.4 Similarly, Yang et al5 reported that baseline risk factors were not associated with mortality (although those investigators were unable to adjust for changes in risk factors, such as those that could be due to therapy for dyslipidemia, hypertension, etc., over the years.)
The reasons for this paradox of risk factors for an outcome not being the same before and after an event are not clear. Among the possibilities suggested by Canto et al4 are that MI patients who have none of the usual risk factors may have had other factors that may have influenced progression of disease, such as prediabetes, insulin resistance, abdominal, obesity, psychosocial factors, poor nutrition, or physical inactivity; they may also have had predominant genetic factors that were not considered in the pre-MI risk factor assessment. Also, Canto et al found that subjects having an MI without pre-existing risk factors were much older, so that they may have presented after they had much more advanced atherosclerosis or other conditions
affecting subsequent mortality risk.
Forum reviewer Yuqing Zhang states that this apparently paradoxical relation has been shown for other conditions, such as osteoarthritis. He states that it is well-established that obesity is a strong risk factor for the occurrence of osteoarthritis; however, obesity may not accelerate progression of arthritis among those who already have the disease (the “obesity paradox). When reading the current paper, Zhang said he was expecting that alcohol might have been shown to have either no or just mild effects on CHD mortality among individuals who had already had a MI. To his surprise, alcohol still showed a strong protective effect. This may suggest that the effect of alcohol on coronary disease risk has relatively short-term effects, and to maintain its protective effect people should drink small or moderate amounts of alcohol on a frequent basis.
References from Forum critique:
1. Hamm CW, Bassand JP, Agewall S, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011;32:2999–3054.
2. Van de Werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the EuropeanSociety of Cardiology. Eur Heart J 2008;29:2909–2945.
3. Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J 2007;28:1598–1660.
4. Canto JG, Kiefe CI, Rogers WJ, et al, for the NRMI Investigators. Number of Coronary Heart Disease Risk Factors and Mortality in Patients With First Myocardial Infarction. JAMA 2011;306:2120-2127.
5. Yang Q, Cogswell ME, Flanders WD, et al. Trends in Cardiovascular Health Metrics and Associations With All-Cause and CVD Mortality Among US Adults. JAMA 2012;307:1273-1283.
In a very well-done analysis based on the follow up of more than 50,000 subjects from The Health Professionals Follow-up Study (HPFS), 1,818 men were confirmed with incident non-fatal myocardial infarction (MI). Among MI survivors, 468 deaths were documented during up to 20 years of follow up. Repeated reports were obtained on alcohol consumption throughout follow up. Average alcohol consumption was calculated prior to and then following the MI.
The overall results show that, in comparison with no alcohol consumption, the pre-MI and the post-MI intakes of light (0.1-9.9 g/day) and moderate (10.0-29.9 g/d) amounts of alcohol were both associated with lower risk of all-cause mortality and cardiovascular morality among these men. The significant reductions in all-cause mortality risk (22% lower for 0.1-9.9 g/day and 34% lower for 10.0 – 29.9 g/day, in comparison with non-drinkers) were no longer present for consumers of ≥ 30 g/day; for this highest consumer group, the adjusted hazard ratio was 0.87 with 95% CI of 0.61-1.25.
There are a number of other informative and interesting results described from this study. First, there was little change in reported alcohol prior to and following the MI: drinkers tended to remain drinkers of similar amounts. Few non-drinkers began to drink after their MI; among heavier drinkers, there was a tendency to decrease the amount somewhat (but very few stopped drinking completely). Further there were no significant differences in outcome according to type of beverage consumed although, interestingly, lower hazard ratios were seen for consumers of beer and liquor than of wine. While the authors state that the effects of alcohol were stronger for the association with non-anterior MIs, the HRs for all-cause mortality were little different: among the moderately drinking men the HRs were 0.58 for anterior MI and 0.51 for other types of MI.
Even though exposures (such as alcohol) for cardiovascular events (such as MI and cardiovascular mortality) may be different after a person has an event than it was before the event, in this study the reductions in risk were almost the same. For example, both for alcohol intake reported prior to a MI, and that after a non-fatal MI, the risk of mortality was about 30% lower for moderate drinkers than it was for abstainers. This suggests that, in terms of reducing cardiovascular disease, alcohol may have relatively short-term effects. Frequent consumption
(of moderate amounts) may result in the best health outcomes.
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Contributions to this critique were provided by the following members of the International Scientific Forum on Alcohol Research:
Yuqing Zhang, MD, DSc, Epidemiology, Boston University School of Medicine, Boston, MA, USA
David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA
Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia
Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School
of Medicine, Boston, MA, USA