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Alcohol Consumption and Cardiovascular Health

      Abstract

      Background

      Studies evaluating alcohol consumption and cardiovascular diseases have shown inconsistent results.

      Methods

      We performed a systematic review of peer-reviewed publications from an extensive query of Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception to March 2022 for all studies that reported the association between alcohol consumption in terms of quantity (daily or weekly amounts) and type of beverage (wine, beer or spirit) and cardiovascular disease events.

      Results

      The study population included a total of 1,579,435 individuals based on 56 cohorts from several countries. We found that moderate wine consumption defined as 1-4 drinks per week was associated with a reduction in risk for cardiovascular mortality when compared with beer or spirits. However, higher risk for cardiovascular disease mortality was typically seen with heavier daily or weekly alcohol consumption across all types of beverages.

      Conclusions

      It is possible that the observational studies may overestimate the benefits of alcohol for cardiovascular disease outcomes. Although moderate wine consumption is probably associated with low cardiovascular disease events, there are many confounding factors, in particular, lifestyle, genetic, and socioeconomic associations with wine drinking, which likely explain much of the association with wine and reduced cardiovascular disease events. Further prospective study of alcohol and all-cause mortality, including cancer, is needed.

      Keywords

      Clinical Significance
      • It is possible that the observational studies may overestimate the benefits of alcohol for cardiovascular disease outcomes.
      • Moderate wine consumption may be associated with low cardiovascular disease events.
      • There are many confounding factors, in particular, lifestyle, genetic, and socioeconomic associations with wine drinking, which likely explain much of the association with wine and reduced cardiovascular disease events.
      • Further prospective study of alcohol and all-cause mortality, including cancer, is needed.

      Introduction

      The US Department of Agriculture 2015 to 2025 Dietary Guidelines for Americans

      United States Department of Agriculture. The Dietary Guidelines for Americans 2020-2025. Available at:https://www.dietaryguidelines.gov/sites/default/files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf. Accessed April 8, 2022.

      define moderate drinking as having up to 1 drink per day for women and up to 2 drinks per day for men. Alcohol consumption above the recommended limits was associated with higher all-cause and cause-specific mortality risk (39%-126%).
      • Ricci C
      • Schutte AE
      • Schutte R
      • Smits CM
      • Pieters M
      Trends in alcohol consumption in relation to cause-specific and all-cause mortality in the United States: a report from the NHANES linked to the US mortality registry.
      Alcohol may contain polyphenols, amino acids, and minerals,
      • Arranz S
      • Chiva-Blanch M
      • Valdera-Martínez P
      • Medina-Remón A
      • Lamuela-Raventós RM
      • Estruch R
      Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer.
      although the content varies considerably among types of alcohol (beer vs red wine vs white wine vs spirit). A complete understanding of these complex mechanisms in human health is limited. Several studies have shown that alcohol consumption has a J-shaped or biphasic relationship with cardiovascular disease.
      GBD 2017 Risk Factor Collaborators
      Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
      ,
      • Yusuf S
      • Hawken S
      • Ounpuu S
      • et al.
      Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
      In a recent report, analyses suggest that any quantity of alcohol has a deleterious effect on cancer risk.
      GBD 2017 Risk Factor Collaborators
      Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
      Our study is unique in that it relies on data culled from more than 1 million individuals. We include both alcoholic beverage quantity (daily or weekly amounts) and type of beverage (wine, beer, or spirits) in relation to cardiovascular disease events. Additionally, very few meta-analyses have included spirits when the association of alcohol is examined in relation to these cardiovascular disease outcomes.

      Methods

      We performed a systematic review of peer-reviewed publications from an extensive query of Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception to March 2022. Search strategy included MESH headings and keywords related to alcohol and cardiovascular disease (Supplementary Material, available online). We identified studies based on appropriate types of study (observational study, prospective cohort study, randomized controlled trial, or case control design) and the exposure (alcohol consumption). We were unable to perform meta-analysis of the results due to tremendous heterogeneity among the included studies related to intervention, comparison, outcomes, and timing. Instead, we qualitatively synthesized the results and summarized key features and characteristics (eg, study populations, design, interventions, outcomes, and conclusions) of the included studies.

      Results

      After exclusions in our initial electronic search, we identified and reviewed a total of 56 studies related to alcohol consumption and cardiovascular outcomes. Most common adjustments were age, body mass index, hypertension, and diabetes. As for alcoholic beverages and the relationship with developing coronary artery disease, 19 total studies were included for a total of 1,009,067 individuals; 51.1% were men (Table 1). Studies were published since 1986 and included a diverse group of participants from countries all over the world. Most of the studies were prospective, but several were case-control studies or cross-sectional. Results were variable across these cohorts, but there was a notable pattern of significantly lower hazard ratios (HRs) for coronary artery disease in low to moderate alcohol consumers (defined by weekly and daily consumption thresholds) across all categories of alcoholic beverages.
      Table 1Included Studies for Alcohol Consumption and CAD
      First AuthorYearCountryNumber of ParticipantsMenType of StudyAge, YearsFollow-UpType of DrinkComparisonOutcomeHR (95% CI)
      Bos
      • Bos Sarah
      • Grobbee Diederick E
      • Boer Jolanda M A
      • Monique Verschuren W
      • Beulens Joline W J
      Alcohol consumption and risk of cardiovascular disease among hypertensive women.
      2010Netherlands10,5300Prospective9.4 yWhite wine5-29.9 vs 0-4.9 g/wk0.96 (0.76-1.21)
      White wine30-69.9 vs 0-4.9 g/wk1.1 (0.74-1.66)
      White wine>70 vs 0-4.9 g/wk0.96 (0.59-1.57)
      Red wine5-29.9 vs 0-4.9 g/wk0.74 (0.56-0.97)
      Red wine30-69.9 vs 0-4.9 g/wk0.77 (0.52-1.14)
      Red wine>70 vs 0-4.9 g/wk0.71 (0.43-1.16)
      Beer5-29.9 vs 0-4.9 g/wk1 (0.68-1.49)
      Beer30-69.9 vs 0-4.9 g/wk0.84 (0.49-1.43)
      Liquor5-29.9 vs 0-4.9 g/wk1.04 (0.76-1.41)
      Liquor30-69.9 vs 0-4.9 g/wk0.93 (0.61-1.41)
      Liquor>70 vs 0-4.9 g/wk1.17 (0.82-1.69)
      Fortified wine5-29.9 vs 0-4.9 g/wk1.03 (0.8-1.33)
      Fortified wine30-69.9 vs 0-4.9 g/wk1.01 (0.67-1.52)
      Fortified wine>70 vs 0-4.9 g/wk0.85 (0.6-1.19)
      White wine, red wine, beer, liquor, fortified wine0-4.9 g/wk vs lifetime abstainer0.98 (0.76-1.27)
      White wine, red wine, beer, liquor, fortified wine5-29.9 g/wk vs lifetime abstainer0.75 (0.57-0.98)
      White wine, red wine, beer, liquor, fortified wine30-69.9 g/wk vs lifetime abstainer0.92 (0.68-1.24)
      White wine, red wine, beer, liquor, fortified wine70–139.9 g/wk vs lifetime abstainer0.72 (0.52-1.01)
      White wine, red wine, beer, liquor, fortified wine≥ 140 g/wk vs lifetime abstainer0.65 (0.46-0.9)
      Brenner
      • Brenner Hermann
      • Rothenbacher Dietrich
      • Bode Günter
      • März Winfried
      • Hoffmeister Albrecht
      • Koenig Wolfgang
      Coronary Heart Disease Risk Reduction in a Predominantly Beer-Drinking Population.
      2001Germany791267 casesCase control

      57.7 cases

      55.8 control
      Wine, beer, mixedDrinkers vs nondrinkers0.55 (0.37-0.83)
      Beer onlyBeer only vs nondrinkers0.5 (0.3-0.84)
      Wine onlyWine only vs nondrinkers0.95 (0.57-1.59)
      MixedMixed vs nondrinkers0.42 (0.27-0.66)
      Wine, beer, mixed≤ 125 g/wk vs nondrinkers0.56 (0.36-0.86)
      Wine, beer, mixed> 125 g/wk vs nondrinkers0.55 (0.35-0.86)
      Foerster
      • Foerster M
      • Marques-Vidal P
      • Gmel G
      • Daeppen JB
      • Cornuz J
      • Hayoz D
      • Pécoud A
      • Mooser V
      • Waeber G
      • Vollenweider P
      • Paccaud F
      • Rodondi N.
      Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption.
      2009Switzerland57692574Cross-sectional52.5 ± 10.6Wine, beer, spiritsDid not include as mean ± SE ()
      Gigleux
      • Gigleux I
      • Gagnon J
      • St-Pierre A
      • Cantin B
      • Dagenais GR
      • Meyer F
      • Després JP
      • Lamarche B.
      Moderate alcohol consumption is more cardioprotective in men with the metabolic syndrome.
      2006Canada19661966ProspectiveIHD-free men - 56 ± 7

      IHD cases - 59 ± 7
      13 yWine, beer, spirits≥15.2 vs <1.3 g/d0.51 (0.33-0.8)
      Wine, beer, spirits5.5-15.1 vs <1.3 g/d0.81 (0.55-1.21)
      Wine, beer, spirits1.3-5.4 vs <1.3 g/d0.87 (0.6-1.27)
      Klatsky
      • Klatsky AL
      • Armstrong MA
      • Friedman GD.
      Relations of alcoholic beverage use to subsequent coronary artery disease hospitalization.
      1986US85,00137,605Prospective cohort5 yWine, beer, liquorEx-drinkers vs abstainers0.99 (0.72-1.36)
      Wine, beer, liquor<1 drink/mo vs abstainers0.93 (0.74-1.18)
      Wine, beer, liquor<1 drink/d, >l drink/mo vs abstainers0.65 (0.51-0.82)
      Wine, beer, liquor1-2 drinks/d vs abstainers0.55 (0.42-0.72)
      Wine, beer, liquor3-5 drinks/d vs abstainers0.54 (0.38-0.76)
      Wine, beer, liquor6-8 drinks/d vs abstainers0.52 (0.26-1.05)
      Wine, beer, liquor>9 drinks/d vs abstainers0.47 (0.15-1.49)
      BeerBeer vs liquor1.01 (0.69-1.46)
      WineWine vs liquor0.89 (0.64-1.24)
      Klatsky
      • Klatsky AL
      • Armstrong MA
      • Friedman GD.
      Red wine, white wine, liquor, beer, and risk for coronary artery disease hospitalization.
      1997US128,93456,730Prospective cohort40.66 yRed wine, beer, liquor, white wineAll drinkers (>1 drink/mo vs abstainers)0.79 (0.71-0.88)
      <1 drink/d vs abstainers0.93 (0.8-1.09)
      1-2 drinks/d vs abstainers0.77 (0.65-0.91)
      ≥3 drinks/d vs abstainers0.71 (0.59-0.86)
      All drinkers (>1 drink/mo vs abstainers)0.76 (0.65-0.89)
      <1 drink/d vs abstainers0.83 (0.7-0.98)
      1-2 drinks/d vs abstainers0.64 (0.52-0.79)
      ≥3 drinks/d vs abstainers0.6 (0.42-0.85)
      Marques-Vidal
      • Marques-Vidal P
      • Montaye M
      • Arveiler D
      • Evans A
      • Bingham A
      • Ruidavets JB
      • Amouyel P
      • Haas B
      • Yarnell J
      • Ducimetière P
      • Ferrières J.
      Alcohol consumption and cardiovascular disease: differential effects in France and Northern Ireland. The PRIME study.
      2004France, Northern Ireland97509750Prospective cohortDivided by alcohol and country5 yWine, beer, spirits, cider0-128 mL pure ethanol/wk vs none0.74 (0.45-1.21)
      Wine, beer, spirits, cider128-265 mL pure ethanol/wk vs none0.65 (0.39,1.08)
      Wine, beer, spirits, cider265-441 mL pure ethanol/wk vs none0.48 (0.28-0.81)
      Wine, beer, spirits, cider≥441 mL pure ethanol/wk vs none0.37 (0.22-0.64)
      Wine, beer, spirits, cider0-128 mL pure ethanol/wk vs none0.67 (0.36-1.27)
      Wine, beer, spirits, cider128-265 mL pure ethanol/wk vs none0.81 (0.46-1.46)
      Wine, beer, spirits, cider265-441 mL pure ethanol/wk vs none0.88 (0.5-1.54)
      Wine, beer, spirits, cider≥441 mL pure ethanol/wk vs none0.7 (0.38-1.29)
      WineWine vs none0.89 (0.82-0.98)
      BeerBeer vs none0.94 (0.74-1.01)
      SpiritsSpirits vs none1.04 (0.83-1.43)
      Wine, beer, spirits, ciderTotal alcohol vs none0.96 (0.84-0.97)
      WineWine vs none0.33 (0.11-0.96)
      BeerBeer vs none0.99 (0.89-1.07)
      SpiritsSpirits vs none1.03 (0.93-1.22)
      Wine, beer, spirits, ciderTotal alcohol vs none0.99 (0.92-1.06)
      Wine, beer, spiritsAlcohol vs no alcohol1.001 (1-1.003)
      Wine, beer, spiritsDrinker group 1 (<15 g/d) vs nondrinkers0.61 (0.4-0.94)
      Wine, beer, spiritsDrinker group 2 (≥15 g/d) vs nondrinkers0.68 (0.41-1.12)
      Wine, beer, spiritsDrinker group 1 (<15 g/d) vs lifetime abstainer0.61 (0.39-0.95)
      Wine, beer, spiritsDrinker group 2 (≥15 g/d) vs lifetime abstainer0.67 (0.39-1.14)
      Wine, beer, spiritsDrinker group 1 (<15 g/d) vs occasional drinker0.71 (0.42-1.19)
      Wine, beer, spiritsDrinker group 2 (≥15 g/d) vs occasional drinker0.75 (0.46-1.23)
      Wine, beer, spiritsFormer drinker vs lifetime abstainer0.97 (0.56-1.71)
      Rimm
      • Rimm EB
      • Giovannucci EL
      • Willett WC
      • Colditz GA
      • Ascherio A
      • Rosner B
      • Stampfer MJ.
      Prospective study of alcohol consumption and risk of coronary disease in men.
      1991US44,05944,059Prospective cohort0 g/d

      0.1-5 g/d

      5.1-30 g/d

      >30 g/d
      72,290 person-yearsWine, beer, spirits0.1-5 g/d vs 0 g/d0.99 (74-1.33)
      5.1-30 g/d vs 0 g/d0.74 (0.56-0.97)
      >30 g/d vs 0 g/d0.53 (0.35-0.79)
      Roy
      • Roy A
      • Prabhakaran D
      • Jeemon P
      • Thankappan KR
      • Mohan V
      • Ramakrishnan L
      • Joshi P
      • Ahmed F
      • Mohan BV
      • Saran RK
      • Sinha N
      • Reddy KS
      Sentinel Surveillance in Industrial Populations Study Group. Impact of alcohol on coronary heart disease in Indian men.
      2010India89308930Cross-sectional

      I would delete
      Alcohol users - 42.8 ± 11.0

      Nonusers- 42.8 ± 11.1
      Wine, beer, spiritsAlcohol users vs nonusers1.4 (1-1.9)
      Wine, beer, spiritsOccasional users (less than once a week) vs nonusers1.2 (0.8-1.6)
      Wine, beer, spiritsRegular users (once or more in a week) vs nonusers1.6 (1-2.2)
      Wine, beer, spiritsPast users (quit at least 6 months ago) vs nonusers2.1 (1.1-3)
      Local spiritsLocal spirits vs none1.8 (1-2.6)
      Branded spiritsBranded spirits vs none1.5 (0.9-2.2)
      Wine, beer, spirits<14 g/d vs no alcohol1.3 (1.2-1.5)
      Wine, beer, spirits14-28 g/d vs no alcohol1.6 (1-2.3)
      Wine, beer, spirits>28 g/d vs no alcohol2 (1.2-2.6)
      Schutte
      • Schutte R
      • Papageorgiou M
      • Najlah M
      • Huisman HW
      • Ricci C
      • Zhang J
      • Milner N
      • Schutte AE.
      Drink types unmask the health risks associated with alcohol intake - Prospective evidence from the general population.
      2020UK446,439206,088Prospective cohort56.4 ± 8.17.05 yBeer/ciderBeer/cider vs other alcohol drinkers1.12 (0.99-1.26)
      Champagne/white wineChampagne/white wine vs other alcohol drinkers0.84 (0.72-0.98)
      Red wineRed wine vs other alcohol drinkers0.88 (0.77-0.99)
      SpiritsSpirits vs other alcohol drinkers1.17 (1.02-1.35)
      Snow
      • Snow WM
      • Murray R
      • Ekuma O
      • Tyas SL
      • Barnes GE.
      Alcohol use and cardiovascular health outcomes: a comparison across age and gender in the Winnipeg Health and Drinking Survey Cohort.
      2009Canada1154580Prospective cohort10 yWine, beer, spirits0.65-5.77 g vs <0.65 g/d1.66 (0.2-13.92)
      5.78-18.1 g vs <0.65 g/d0.57 (0.06-5.52)
      >18.1 vs <0.65 g/d0.44 (0.04-4.59)
      >18.1 (heavy) episodic vs <0.65 g/d4.13 (1.46-11.62)
      0.65-5.77 g vs <0.65 g/d0.98 (0.4-2.37)
      5.78-18.1 g vs <0.65 g/d0.75 (0.29-1.95)
      >18.1 vs <0.65 g/d0.28 (0.08-0.93)
      >18.1 (heavy) episodic vs <0.65 g/d1.76 (0.81-3.82)
      0.65-2.92 g vs <0.65 g/d1.13 (0.07-18.39)
      2.93-9.15 g vs <0.65 g/d2.95 (0.29-29.69)
      >9.15 g vs <0.65 g/d1.96 (0.17-22.19)
      >9.15 g (heavy) episodic vs <0.65 g/d1.09 (0.99-1.19)
      0.65-2.92 g vs <0.65 g/d1.35 (0.51-3.57)
      2.93–9.15 g vs <0.65 g/d2.12 (0.82-5.48)
      >9.15 g vs <0.65 g/d0.44 (0.09-2.02)
      >9.15 g (heavy) episodic vs <0.65 g/d0 (0-∞)
      Song
      • Song Rebecca J
      • et al.
      Alcohol Consumption and Risk of Coronary Artery Disease (from the Million Veteran Program).
      2018US156,728142,622Prospective cohort65.3 ± 12.12.9 yWine, beer, spiritsFormer drinkers vs never drinkers1.02 (0.92-1.13)
      ≤6 g/d vs never drinkers0.83 (0.74-0.93)
      >6-12g/d vs never drinkers0.77 (0.67-0.87)
      >12–24g/d vs never drinkers0.71 (0.62-0.81)
       >24-36g/d vs never drinkers0.62 (0.51-0.76)
      >36-48 g/d vs never drinkers0.58 (0.46-0.74)
      AUD/heavy drinkers (>48 g/d) vs never drinkers0.95 (0.85-1.06)
      Stampfer
      • Stampfer MJ
      • Colditz GA
      • Willett WC
      • Speizer FE
      • Hennekens CH.
      A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women.
      1988US87,5260Prospective cohort34-59334,382 person-yearsWine, beer, spirits<1.5 g/d vs 0 g/d0.7 (0.5-1.1)
      1.5-4.9 g/d vs 0 g/d0.5 (0.4-0.8)
      5-14.9 g/d vs 0 g/d0.5 (0.4-0.8)
      15-24.9 g/d vs 0 g/d0.6 (0.3-1.1)
      >25 g/d vs 0 g/d0.6 (0.3-1)
      Wannamethee
      • Wannamethee SG
      • Shaper AG.
      Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality.
      1999UK72727272Prospective cohort40-5916.8 yWine, beer, spiritsNone vs occasional (<1 unit per

      week)
      1.03 (0.78-1.37)
      Wine, beer, spiritsLight (1-15 units per week) vs occasional0.76 (0.64-0.91)
      Wine, beer, spiritsModerate (16-42 units per week), vs occasional0.78 (0.65-0.94)
      Wine, beer, spiritsHeavy (more

      than 6 units per day) vs occasional
      0.75 (0.59-0.95)
      BeerRegular drinker vs occasional drinker0.78 (0.63-0.97)
      SpiritsRegular drinker vs occasional drinker0.57 (0.39-0.85)
      Beer and spiritsRegular drinker vs occasional drinker0.75 (0.5-1.1)
      WineRegular drinker vs occasional drinker0.92 (0.51-1.67)
      Wine/sherry, beer, spiritsRegular drinker vs occasional drinker1.23 (0.54-2.79)
      Spirits, beerSpirits vs beer in occasional and regular drinkers1.07 (0.9-1.26)
      Wine, beerWine vs beer in occasional and regular drinkers0.82 (0.64-1.04)
      Wellmann
      • Wellmann J
      • Heidrich J
      • Berger K
      • Döring A
      • Heuschmann PU
      • Keil U.
      Changes in alcohol intake and risk of coronary heart disease and all-cause mortality in the MONICA/KORA-Augsburg cohort 1987-97.
      2004Germany27101345Prospective cohort35-6410 y in men

      10.1 in women
      Wine, beer, spirits0.1-19.9 g/d vs 0 g/d0.34 (0.17-0.69)
      20.0-39.9 g/d vs 0 g/d0.43 (0.22-0.81)
      40.0-79.9 g/d vs 0 g/d0.7 (0.4-1.22)
      >80.0 g/d vs 0 g/d0.33 (0.12-0.89)
      Quitter vs nondrinker0.78 (0.32-1.87)
      Starter vs nondrinker0.32 (0.09-1.18)
      Constant drinker 0.1-19.9 g/d vs nondrinker0.29 (0.12-0.7)
      Constant drinker 20.0-39.9 g/d vs nondrinker0.39 (0.17-0.87)
      Constant drinker 40.0–79.9 g/d vs nondrinker0.6 (0.29-1.24)
      Constant drinker >80.0g/d vs nondrinker0.29 (0.1-0.86)
      Woodward
      • Woodward M
      • Tunstall-Pedoe H.
      Alcohol consumption, diet, coronary risk factors, and prevalent coronary heart disease in men and women in the Scottish heart health study.
      1995ScotlandCross-sectional40-59Wine, beer, spirits1-7 Units/wk vs 00.99 (0.7-1.41)
      8-15 Units/wk vs 00.99 (0.69-1.42)
      16-29 Units/wk vs 00.97 (0.66-1.43)
      >30 Units/wk vs 01.04 (0.67-1.61)
      1-2 Units/wk vs 00.57 (0.36-0.91)
      3-5 Units/wk vs 00.62 (0.41-0.96)
      6-9 Units/wk vs 00.74 (0.47-1.15)
      >10 Units/wk vs 00.61 (0.37-1.01)
      Keil
      • Keil U
      • Chambless LE
      • Döring A
      • Filipiak B
      • Stieber J.
      The relation of alcohol intake to coronary heart disease and all-cause mortality in a beer-drinking population.
      1997Germany20871074Prospective cohort45-647.9 yBeerDrinkers vs nondrinkers0.55 (0.29-1.02)
      0.1-19.9 g/d vs nondrinkers0.54 (0.24-1.2)
      20-39.9 g/d vs nondrinkers0.48 (0.21-1.09)
      40-79.9 g/d vs nondrinkers0.63 (0.3-1.29)
      >80 g/d vs nondrinkers0.48 (0.18-1.28)
      Biddinger
      • Biddinger KJ
      • Emdin CA
      • Haas ME
      • Wang M
      • Hindy G
      • Ellinor PT
      • Kathiresan S
      • Khera AV
      • Aragam KG.
      Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease.
      2022UK371,463172,400Cohort57.0 ± 7.9∼ 6 yWine, beer, spiritsLight drinkers vs none1.7 (1.2- 2.3)
      Moderate drinkers vs none1.7 (1.1-2.7)
      Heavy drinkers vs none2.1 (1.1- 3.9)
      Abuse drinkers vs none5.7 (2.4-13.5)
      AUD = alcohol use disorder; CAD = coronary artery disease; IHD = ischemic heart disease; CI - Confidence interval.
      Table 2 summarizes alcohol consumption and the association with myocardial infarction (238,273 individuals). Most of these studies demonstrated a significantly lower HR for myocardial infarction in individuals with moderate to higher levels of alcohol consumption for all 3 types of beverages.
      Table 2Included Studies for Alcohol Consumption and Myocardial Infarction
      First AuthorYearCountryNumber of ParticipantsMenType of StudyAge, YearsFollow-UpType of DrinkComparisonOutcomesHR (95% CI)
      Gigleux
      • Gigleux I
      • Gagnon J
      • St-Pierre A
      • Cantin B
      • Dagenais GR
      • Meyer F
      • Després JP
      • Lamarche B.
      Moderate alcohol consumption is more cardioprotective in men with the metabolic syndrome.
      2006Canada19661966Prospective13 yWine, beer, spirits≥15.2 vs <1.3 g/d0.51 (0.33-0.8)
      5.5-15.1 vs <1.3 g/d0.81 (0.55-1.21)
      1.3-5.4 vs <1.3 g/d0.87 (0.6-1.27)
      Klatsky
      • Klatsky AL
      • Armstrong MA
      • Friedman GD.
      Relations of alcoholic beverage use to subsequent coronary artery disease hospitalization.
      1986US85,00137,605Prospective cohort5 yWine, beer, spiritsEx-drinkers vs abstainers1.19 (NR-NR)
      <1 drink/mo vs abstainers0.97 (NR-NR)
      < 1 drink/d, > l drink/mo vs abstainers0.72 (NR-NR)
      1-2 drinks/d vs abstainers0.54 (NR-NR)
      3-5 drinks/d vs abstainers0.38 (NR-NR)
      6-8 drinks/d vs abstainers0.7 (NR-NR)
      >9 drinks/d vs abstainers0.31 (NR-NR)
      Marques-Vidal
      • Marques-Vidal P
      • Montaye M
      • Arveiler D
      • Evans A
      • Bingham A
      • Ruidavets JB
      • Amouyel P
      • Haas B
      • Yarnell J
      • Ducimetière P
      • Ferrières J.
      Alcohol consumption and cardiovascular disease: differential effects in France and Northern Ireland. The PRIME study.
      2004France, Northern Ireland97509750Prospective cohort5 yWine, beer, spirits, cider0-128 mL pure ethanol/wk vs none0.54 (0.29-1.02)
      128-265 mL pure ethanol/wk vs none0.45 (0.23-0.87)
      265-441 mL pure ethanol/wk vs none0.37 (0.19-0.73)
      ≥ 441 mL pure ethanol/wk vs none0.26 (0.13-0.54)
      0-128 mL pure ethanol/wk vs none0.62 (0.27-1.45)
      128-265 mL pure ethanol/wk vs none0.69 (0.31-1.52)
      265-441 mL pure ethanol/wk vs none0.56 (0.25-1.28)
      ≥441 mL pure ethanol/wk vs none0.43 (0.17-1.09)
      WineWine vs none0.88 (0.78-1)
      BeerBeer vs none0.89 (0.58-0.99)
      SpiritsSpirits vs none1.09 (0.95-1.58)
      Wine, beer, spirits, ciderTotal alcohol vs none0.95 (0.8-0.98)
      WineWine vs none0.18 (0.03-1.29)
      BeerBeer vs none0.97 (0.81-1.08)
      SpiritsSpirits vs none1.01 (0.84-1.26)
      Wine, beer, spirits, ciderTotal alcohol vs none0.98 (0.85-1.06)
      Park
      • Park JE
      • Ryu Y
      • Cho SI.
      The Effect of Reference Group Classification and Change in Alcohol Consumption on the Association Between Alcohol Consumption and Cardiovascular Disease.
      2017Korea83303936Prospective cohort40-49 y, n = 3876 (46.5%)

      50-59 y, n = 2220 (26.7%)

      60-69 y, n = 2234 (26.8%)
      10 yWine, beer, spiritsDrinker group 1 (<15 g/d) vs nondrinkers0.44 (0.21-0.92)
      Drinker group 2 (≥15 g/d) vs nondrinkers0.42 (0.19-0.93)
      Drinker group 1 (<15 g/d) vs lifetime abstainer0.41 (0.19-0.9)
      Drinker group 2 (≥15 g/d) vs lifetime abstainer0.39 (0.16-0.91)
      Drinker group 1 (<15 g/d) vs occasional drinker0.65 (0.29-1.45)
      Drinker group 2 (≥15 g/d) vs occasional drinker0.51 (0.23-1.12)
      Former drinker vs lifetime abstainer0.84 (0.35-1.98)
      Rimm
      • Rimm EB
      • Klatsky A
      • Grobbee D
      • Stampfer MJ
      Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits.
      1991US44,05944,059Prospective cohort0 g/d

      0.1-5 g/d

      5.1-30 g/d

      >30 g/d
      72,290 person-yearsWine, beer, spirits0.1-5 g/d vs 0 g/d0.99 (0.65-1.51)
      5.1-30 g/d vs 0 g/d0.71 (0.47-1.06)
      >30 g/d vs 0 g/d0.65 (0.37-1.31)
      Stampfer
      • Stampfer MJ
      • Colditz GA
      • Willett WC
      • Speizer FE
      • Hennekens CH.
      A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women.
      1988US87,5260Prospective cohort34-59334,382 person-yearsWine, beer, spirits<1.5 g/d vs 0 g/d0.7 (0.5-1.1)
      1.5-4.9 g/d vs 0 g/d0.5 (0.4-0.8)
      5-14.9 g/d vs 0 g/d0.5 (0.4-0.8)
      15-24.9 g/d vs 0 g/d0.6 (0.3-1.1)
      >25 g/d vs 0 g/d0.6 (0.3-1)
      Kauhanen
      • Kauhanen Jussi
      • et al.
      Frequent Hangovers and Cardiovascular Mortality in Middle-Aged Men.
      1997Finland16411641Prospective cohort6 or more 50.4 (6.0) 

      3-5 51.2 (5.6) 

      <3 52.4 (5.0)
      7.7 yBeer6 or more vs <3 bottles0.96 (0.39-2.35)
      Beer3-5 bottles vs <3 bottles1.28 (0.85-1.93)
      Biddinger
      • Biddinger KJ
      • Emdin CA
      • Haas ME
      • et al.
      Association of habitual alcohol intake with risk of cardiovascular disease.
      2022UK371,463172,400Cohort57.0 ± 7.9∼ 6 yWine, beer, spiritsLight drinkers vs none1.3 (0.89- 2.11)
      Moderate drinkers vs none2.6 (1.39- 4.94)
      Heavy drinkers vs none1.8 (0.78- 4.30)
      Abuse drinkers vs none7.3 (2.28-23.84)
      Table 3 summarizes the association between alcohol consumption and cardiovascular disease mortality (570,368 individuals with mean follow-up 11.7 years). For studies that evaluated low-moderate amounts of weekly or daily alcohol (wine, beer, or spirits) consumption, there were significantly lower risk ratios/HRs for cardiovascular disease mortality. Regardless of the specific alcoholic beverage included in the studies, the risk for cardiovascular disease mortality remained lower. Only a handful of studies noted a significantly higher risk for mortality that was associated with either heavier weekly alcohol consumption (either wine, beer, or spirits) or a history of alcohol consumption in the past. Direct comparisons of alcoholic beverages and the effects on cardiovascular disease mortality within the same cohort showed that moderate wine consumption has a 25% reduction in risk for cardiovascular mortality when compared with beer or spirits (HR 0.75; 95% confidence interval, 0.59-0.96) (Table 3). Higher risk for cardiovascular disease mortality was typically seen with heavier daily or weekly alcohol consumption, across all types of beverages.
      Table 3Included Studies for Alcohol Consumption and Cardiovascular Mortality
      First AuthorYearCountryNumber of ParticipantsMenType of StudyAge, YearsFollow-UpType of DrinkComparisonOutcome HR (95% CI)
      Behrens
      • Behrens G
      • Leitzmann MF
      • Sandin S
      • Löf M
      • Heid IM
      • Adami HO
      • Weiderpass E.
      The association between alcohol consumption and mortality: the Swedish women's lifestyle and health study.
      2011Sweden49,2590Prospective713,295 person-yearsWine, beer, spirits0.1-1.4 g/d vs 0 g/d0.76 (0.48-1.2)
      1.5-4.9 g/d vs 0 g/d0.57 (0.36-0.91)
      5.0-9.9 g/d vs 0 g/d0.85 (0.52-1.38)
      10.0+ g/d vs 0 g/d0.55 (0.27-1.12)
      0.1-19.9g/d vs 0 g/d0.69 (0.46-1.01)
      Berberian
      • Berberian K.M.
      • van Duijn C.M.
      • Hoes A.W.
      • et al.
      Alcohol and mortality.
      1994Netherlands1620760Prospective survey based10 yWine, beer, spiritsOccasional (<1 time a week) vs no drinks and ex-drinkers0.23 (0.07-0.73)
      Frequent (one time a week or more) vs no drinks and ex-drinkers0.61 (0.26-1.38)
      Daily alcohol vs no drinks and ex-drinkers0.37 (0.13-1)
      Bertoia
      • Bertoia Monica L
      • et al.
      Long-term alcohol and caffeine intake and risk of sudden cardiac death in women.
      2012US93,6760Prospective3 yWine, beer, spiritsNever drinker vs 0.1-5 g1.85 (0.86-3.98)
      Former drinker vs 0.1-5 g0.92 (0.47-1.81)
      5.1-10 g vs 0.1-5 g0.64 (0.38-1.1)
      10.1-30 g vs 0.1-5 g0.86 (0.55-1.32)
      >30 g vs 0.1-5 g0.83 (0.42-1.64)
      Dai
      • Dai J
      • Mukamal KJ
      • Krasnow RE
      • Swan GE
      • Reed T.
      Higher usual alcohol consumption was associated with a lower 41-y mortality risk from coronary artery disease in men independent of genetic and common environmental factors: the prospective NHLBI Twin Study.
      2015US843843Prospective48 ± 3.141 yWine, beer, spiritsPer 10-g increment in alcohol intake0.97 (0.94-1.01)
      Deev
      • Deev A
      • Shestov D
      • Abernathy J
      • Kapustina A
      • Muhina N
      • Irving S.
      Association of alcohol consumption to morality in middle-aged U.S. and Russian men and women.
      1998Russia, US81643808Prospective13 yWine, beer, spiritsHad at least 1 drink last year but none last week vs nondrinker0.76 (0.47-1.22)
      0 < g last week ≤ 12 vs nondrinker0.54 (0.35-0.84)
      12 < g last week ≤ 24 vs nondrinker0.39 (0.23-0.67)
      > 24 g last week vs nondrinker0.48 (0.3-0.77)
      Had at least 1 drink last year but none last week vs nondrinker0.76 (0.48-1.18)
      0 < g last week ≤ 12 vs nondrinker0.79 (0.51-1.21)
      12 < g last week ≤ 24 vs nondrinker0.68 (0.42-1.11)
      > 24 g last week vs nondrinker0.98 (0.62-1.56)
      Had at least 1 drink last year but none last week vs nondrinker0.51 (0.31-0.82)
      0 < g last week ≤ 6 vs nondrinker0.45 (0.27-0.75)
      > 6 g last week vs nondrinker0.38 (0.23-0.62)
      Had at least 1 drink last year but none last week vs nondrinker0.78 (0.53-1.14)
      0 < g last week ≤ 6 vs nondrinker0.63 (0.37-1.06)
      > 6 g last week vs nondrinker1.2 (0.54-2.65)
      Diem
      • Diem P
      • Deplazes M
      • Fajfr R
      • Bearth A
      • Müller B
      • Christ ER
      • Teuscher A.
      Effects of alcohol consumption on mortality in patients with Type 2 diabetes mellitus.
      2003Switzerland287162Prospective46.2 ± 5.912.6 ± 0.6 yWine, beer, spirits1-15 g/d vs 0 g/d0.87 (0.25-2.52)
      16–30 g/d vs 0 g/d0 (0-0.92)
      >30 g/d vs 0 g/d0.37 (0.01-2.42)
      Grabas
      • Grabas MP
      • Hansen SM
      • Torp-Pedersen C
      • Bøggild H
      • Ullits LR
      • Deding U
      • Nielsen BJ
      • Jensen PF
      • Overgaard C.
      Alcohol consumption and mortality in patients undergoing coronary artery bypass graft (CABG)-a register-based cohort study.
      2016Netherlands1919159967.0 [IQR 12.5]2.2 y [IQR 2.0]Wine, beer, spirits0 units/wk vs 1–14 units/wk1.42 (0.84-2.38)
      15-21 units/wk vs 1–14 units/wk1.63 (0.8-3.29)
      >21 units/wk vs 1–14 units/wk1.7 (0.94-3.06)
      Harriss
      • Harriss LR
      • English DR
      • Hopper JL
      • Powles J
      • Simpson JA
      • O'Dea K
      • Giles GG
      • Tonkin AM.
      Alcohol consumption and cardiovascular mortality accounting for possible misclassification of intake: 11-year follow-up of the Melbourne Collaborative Cohort Study.
      2007Australia38,20015,156Prospective cohort40-69; grouped by sex and drinking11.4 yWine, beer, spiritsFormer drinkers vs lifetime abstainers2.58 (1.51-4.41)
      Occasional drinkers (<10 g/wk) vs lifetime abstainers1.65 (0.92-2.96)
      1.43-20 g/d vs lifetime abstainers1.39 (0.92-2.09)
      >20-40 g/d vs lifetime abstainers1.01 (0.63-1.63)
      >40 g/d vs lifetime abstainers1.27 (0.79-2.04)
      Former drinkers vs lifetime abstainers1.25 (0.57-2.74)
      Occasional drinkers (<10 g/wk) vs lifetime abstainers1.07 (0.6-1.89)
      1.43-20 g/d vs lifetime abstainers0.82 (0.5-1.34)
      >20-40 g/d vs lifetime abstainers1.03 (0.62-1.72)
      >40 g/d vs lifetime abstainers0.43 (0.19-0.95)
      Hernandez-Hernandez
      • Hernandez-Hernandez A
      • Gea A
      • Ruiz-Canela M
      • Toledo E
      • Beunza JJ
      • Bes-Rastrollo M
      • Martinez-Gonzalez MA.
      Mediterranean Alcohol-Drinking Pattern and the Incidence of Cardiovascular Disease and Cardiovascular Mortality: The SUN Project.
      2015Spain14651Prospective cohortNo total cohort mean age; grouped by drinking9.7 yWine, beer, spiritsAbstainers vs MADP score high (7-9)1.91 (0.52-6.98)
      MADP score

      Low (0-2) vs high (7-9)
      3.35 (0.77-14.5)
      MADP score

      Low (0-2) vs high (7-9)
      2.64 (1.11-6.23)
      Alcohol intake low vs moderate1.53 (0.64-3.81)
      Alcohol intake high vs moderate3.24 (0.93-11.65)
      Regular vs distributed1.07 (0.39-2.88)
      Concentrated vs distributed0.50 (0.15-1.68)
      Yes vs no1.62 (0.65-4.12)
      No vs yes1.08 (0.46-2.62)
      With meals, no vs yes1.40 (0.62-3.27)
      No vs yes0.89 (0.43-1.91)
      Excess vs no excess1.68 (0.73-4.08)
      Hoffmeister
      • Hoffmeister H
      • Schelp FP
      • Mensink GB
      • Dietz E
      • Böhning D.
      The relationship between alcohol consumption, health indicators and mortality in the German population.
      1999Germany15,4007677Prospective cohort25-696.9 yWine, beer, spirits1-20 vs 0 g/d0.42 (0.2-9)
      21-40 vs 0 g/d0.72 (0.34-1.53)
      40-80 vs 0 g/d0.73 (0.31-1.74)
      >80 vs 0 g/d0.35 (0.05-2.67)
      1-20 vs 0 g/d0.68 (0.25-1.86)
      21-40 vs 0 g/d1.62 (0.51-5.16)
      40-80 vs 0 g/d1.38 (0.3-6.28)
      Kauhanen
      • Kauhanen Jussi
      • et al.
      Frequent Hangovers and Cardiovascular Mortality in Middle-Aged Men.
      1997Finland16411641Prospective cohort6 or more 50.4 (6.0) 

      3-5 51.2 (5.6) 

      <3 (reference group) 52.4 (5.0)
      7.7 yBeer6 or more vs <3 bottles7.05 (1.93-25.67)
      3-5 bottles vs <3 bottles2.4 (0.95-6.06)
      Laatikainen
      • Laatikainen T
      • Manninen L
      • Poikolainen K
      • Vartiainen E.
      Increased mortality related to heavy alcohol intake pattern.
      2003Finland50925092Prospective cohortDrinkers with heavy pattern - 42.1 (10.5) 

      No heavy drinking occasions - 45.5 (11.2)
      7.3 yWine, beer, spiritsHeavy drinkers vs other drinkers1.77 (1.01-3.08)
      Malyutina
      • Malyutina S
      • Bobak M
      • Kurilovitch S
      • Gafarov V
      • Simonova G
      • Nikitin Y
      • Marmot M.
      Relation between heavy and binge drinking and all-cause and cardiovascular mortality in Novosibirsk, Russia: a prospective cohort study.
      2002Russia65026502Prospective cohort25-649.5 yWine, beer, spiritsNondrinkers vs none1.55 (1.16-2.09)
      <40 g vs none0.71 (0.42-1.22)
      40-79 g vs none0.78 (0.53-1.15)
      80-119 g vs none0.85 (0.57-1.27)
      120-159 g vs none1.25 (0.81-1.95)
      ≥160 g vs none0.91 (0.65-1.29)
      Mukamal
      • Mukamal KJ
      • Chen CM
      • Rao SR
      • Breslow RA.
      Alcohol consumption and cardiovascular mortality among U.S. adults, 1987 to 2002.
      2010US10670Prospective cohort5 yWine, beer, spiritsLifelong infrequent drinker vs never drinker0.96 (0.89-1.03)
      Former drinker vs never drinker1.02 (0.94-1.11)
      Light (≤3 drinks/wk) vs never drinker0.71 (0.61-0.83)
      Moderate (>3–7 drinks/wk for women and >3–14 drinks/wk for men) vs never drinker0.65 (0.53-0.79)
      Heavy (>7 drinks/wk for women and >14 drinks/wk for men) vs never drinker0.96 (0.83-1.11)
      Mukamal
      • Mukamal KJ
      • Maclure M
      • Muller JE
      • Sherwood JB
      • Mittleman MA.
      Prior alcohol consumption and mortality following acute myocardial infarction.
      2001US19131318Prospective cohortAbstainers - 65 (12)

      <7 - 60 (12)

      >7 - 57 (12)
      3.8 yWine, beer, spirits<7 drinks/wk vs abstainers0.75 (0.55-1.02)
      ≥7 drinks/wk vs abstainers0.67 (0.41-1.17)
      Pai
      • Pai J.K.
      • Mukamal K.J.
      • Rimm E.B.
      Long-Term Alcohol Consumption in Relation to All-Cause and Cardiovascular Mortality among Survivors of Myocardial Infarction: The Health Professionals Follow-up Study.
      2012US18181818Prospective cohort40-7520 yWine, beer, spirits0.1-9.9 g/d vs 0 g/d0.74 (0.54-1.02)
      10.0-29.9 g/d vs 0 g/d0.58 (0.39-0.84)
      ≥30.0 g/d vs 0 g/d0.98 (0.6-1.6)
      Renaud
      • Renaud SC
      • Guéguen R
      • Conard P
      • Lanzmann-Petithory D
      • Orgogozo JM
      • Henry O.
      Moderate wine drinkers have lower hypertension-related mortality: a prospective cohort study in French men.
      2004Europe36,583Prospective cohortAbstainers 47.98 ± 5.692 

      Wine drinkers 48.39 ± 5.69 

      Other drinkers 47.28 ± 5.55
      13-21 yWineModerate wine drinkers (<60 g alcohol/d and no beer) vs abstainers0.755 (0.591-0.965)
      Wine drinkers of ≥60 g/d vs abstainers0.971 (0.748-1.261)
      Moderate other drinkers (<60 g alcohol/d) vs abstainers0.853 (0.631-1.153)
      Other drinkers of ≥60 g/d vs abstainers0.951 (0.729-1.241)
      Renaud
      • Renaud SC
      • Guéguen R
      • Schenker J
      • d'Houtaud A.
      Alcohol and mortality in middle-aged men from eastern France.
      1998Europe34,01434014Prospective cohort48.87418,068 person-yearsWine, beer, spirits1-21 g/d vs 0-Occasionaly0.83 (0.55-1.25)
      22-32 g/d vs 0-Occasionaly0.65 (0.45-0.95)
      33-54 g/d vs 0-Occasionaly0.72 (0.52-1)
      55-76 g/d vs 0-Occasionaly0.73 (0.48-1.1)
      77-128 g/d vs 0-Occasionaly0.67 (0.48-0.94)
      >128 g/d vs 0-Occasionaly0.75 (0.48-1.18)
      Rimm
      • Rimm EB
      • Giovannucci EL
      • Willett WC
      • Colditz GA
      • Ascherio A
      • Rosner B
      • Stampfer MJ.
      Prospective study of alcohol consumption and risk of coronary disease in men.
      1991US44,05944059Prospective cohort0 g/d

      0.1-5 g/d

      5.1-30 g/d

      >30 g/d
      72,290 person-yearsWine, beer, spirits0.1-5 g/d vs 0 g/d1.1 (0.52-2.36)
      5.1-30 g/d vs 0 g/d0.71 (0.34-1.49)
      >30 g/d vs 0 g/d0.66 (0.24-1.82)
      Stampfer
      • Stampfer MJ
      • Colditz GA
      • Willett WC
      • Speizer FE
      • Hennekens CH.
      A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women.
      1988US87,5260prospective cohort34-59334,382 person-yearsWine, beer, spirits<1.5 g/d vs 0 g/d0.7 (0.2-1.7)
      1.5-4.9 g/d vs 0 g/d0.2 (0.1-0.6)
      5-14.9 g/d vs 0 g/d0.3 (0.1-0.9)
      15-24.9 g/d vs 0 g/d0.2 (0.03-1.2)
      >25 g/d vs 0 g/d0.6 (0.2-1.9)
      Streppel
      • Streppel MT
      • Ocké MC
      • Boshuizen HC
      • Kok FJ
      • Kromhout D.
      Long-term wine consumption is related to cardiovascular mortality and life expectancy independently of moderate alcohol intake: the Zutphen Study.
      2009Netherlands13731373Prospective cohort49 ± 640 yWine, beer, spirits>0 to 20 g/d vs 00.7 (0.55-0.89)
      >20 g/d vs 00.83 (0.56-1.22)
      >0 to 20 g/d vs 00.92 (0.58-1.46)
      >0 to 20 g/d vs 00.81 (0.48-1.35)
      >20 g/d vs 00.78 (0.09-6.73)
      >0 to 20 g/d vs 01.44 (0.72-2.86)
      >20 g/d vs 00.93 (0.2-4.32)
      Suhonen
      • Suhonen O
      • Aromaa A
      • Reunanen A
      • Knekt P.
      Alcohol consumption and sudden coronary death in middle-aged Finnish men.
      1987Finland45324532Prospective cohort40-642 y for SCD (5 y total)Wine, beer, spiritsAlcohol consumers vs abstainers2.5 (1.1-5.9)
      Theobald
      • Theobald H
      • Bygren LO
      • Carstensen J
      • Engfeldt P.
      A moderate intake of wine is associated with reduced total mortality and reduced mortality from cardiovascular disease.
      2000Sweden1828Prospective cohort18-6522yWineWine vs no wine drinker0.49 (0.28-0.9)
      Beer vs no beer drinker1.15 (0.67-1.99)
      Spirits vs no spirits drinker0.88 (0.48-1.59)
      Ex-drinkers vs 1-49 gram/wk3.05 (1.37-6.77)
      Lifelong abstainers vs 1-49 g/wk1.09 (0.48-2.48)
      50-139 g/wk vs 1-49 g/wk1.39 (0.8-2.42)
      140+ g/wk vs 1-49 g/wk1.77 (0.77-4.08)
      Trevisan
      • Trevisan M
      • Schisterman E
      • Mennotti A
      • Farchi G
      • Conti S
      Risk Factor And Life Expectancy Research Group. Drinking pattern and mortality: the Italian Risk Factor and Life Expectancy pooling project.
      2001Italy15,6498980Prospective cohort30-597 yWineWine with meals vs Nondrinkers0.5 (0.33-0.74)
      Wine outside meals vs Nondrinkers0.81 (0.45-1.43)
      Wine + liquor vs Nondrinkers0.62 (0.38-1.03)
      Tverdal
      • Tverdal A
      • Magnus P
      • Selmer R
      • Thelle D.
      Consumption of alcohol and cardiovascular disease mortality: a 16 year follow-up of 115,592 Norwegian men and women aged 40-44 years.
      2017Norway115,59253,819Prospective cohort40-4416 yWine, beer, spiritsMen - 0, not teetotal vs teetotal0.53 (0.37-0.77)
      Men - >0-<0.5 units/d vs teetotal0.43 (0.29-0.63)
      Men - 0.5-<1.0 units/d vs teetotal0.4 (0.28-0.59)
      Men - 1.0-<1.5 units/d vs teetotal0.48 (0.32-0.71)
      Men - 1.5-<2.0 units/d vs teetotal0.46 (0.3-0.71)
      Men - 2.0-<3.0 units/d vs teetotal0.38 (0.23-0.62)
      Men - 3.0-<4.0 units/d vs Teetotal0.51 (0.27-0.95)
      Men - 4.0+ units/d vs teetotal0.48 (0.23-1)
      Women - 0, not teetotal vs teetotal0.63 (0.38-1.06)
      Women - >0-<0.5 units/d vs teetotal0.54 (0.31-0.94)
      Women - 0.5-<1.0 units/d vs teetotal0.61 (0.34-1.09)
      Women - 1.0-<1.5 units/d vs teetotal0.61 (0.29-1.32)
      Women - 1.5-<2.0 units/d vs teetotal0.4 (0.14-1.18)
      Women - 2.0-<3.0 units/d vs teetotal0.23 (0.03-1.72)
      Women - 3.0-<4.0 units/d vs teetotal0.85 (0.11-6.39)
      Waśkiewicz
      • Waskiewicz A
      • Sygnowska E
      • Drygas W.
      Relationship between alcohol consumption and cardiovascular mortality–the Warsaw Pol-MONICA Project.
      2004Poland53522686Prospective cohortMale

      abstainers 52.8

      1 tertile 51.6

      2 tertile 48.6

      3 tertile 47.2

      Female

      abstainers 53

      1 tertile 50.9

      2 tertile 48.7

      3 tertile 46
      56,261.9 person-yearsWine, beer, spirits1 tertile (mean alcohol intake - 1.1 g/d) vs abstainers0.584 (0.369-0.924)
      2 tertile (mean alcohol intake - 3.9 g/d) vs abstainers0.588 (0.366-0.944)
      3 tertile (mean alcohol intake - 28.2 g/d) vs abstainers0.6 (0.364-0.989)
      1 tertile (mean alcohol intake - 0.2 g/d) vs abstainers0.581 (0.339-0.996)
      2 tertile (mean alcohol intake - 0.4 g/d) vs abstainers0.432 (0.228-0.817)
      3 tertile (mean alcohol intake - 2.8 g/d) vs abstainers0.329 (0.135-0.804)
      Yuan

      Yuan JM, Ross RK, Gao YT, Henderson BE, Yu MC. Follow up study of moderate alcohol intake and mortality among middle aged men in Shanghai, China. BMJ. 1997;4;(314):18–23.

      1997China18,24418,244Prospective cohort45-646.7 yWine, beer, spirits1-28 drinks/wk vs nondrinkers0.64 (0.41-0.998)
      >28 drinks/wk vs nondrinkers0.88 (NR-NR)
      Hart
      • Hart CL
      • Smith GD
      • Hole DJ
      • Hawthorne VM.
      Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of scottish men with 21 years of follow up.
      1999Sweden57665766Prospective cohort35-645141 person- yearsWine, beer, spirits1-7 units/wk vs none1.13 (0.9-1.42)
      8-14 units/wk vs none0.79 (0.61-1.01)
      15-21 units/wk vs none1.06 (0.81-1.38)
      22-34 units/wk vs none1.01 (0.77-1.34)
      ≥35 units/wk vs none1 (0.75-1.35)
      Suadicani
      • Suadicani P
      • Hein HO
      • Gyntelberg F.
      Wine intake, ABO phenotype, and risk of ischemic heart disease and all-cause mortality: the Copenhagen Male Study–a 16-year follow-up.
      2008Denmark30223022Prospective cohort63 y (range, 53-74)16 yWine1-8 drinks/wk vs 0 drinks of wine/wk0.7 (0.5-0.98)
      >8 drinks/wk vs 0 drinks of wine/wk0.9 (0.6-1.2)
      1-8 drinks/wk vs alcohol abstainers0.6 (0.4-0.96)
      >8 drinks/wk vs alcohol abstainers0.7 (0.5-1.2)
      Wannamethee
      • Wannamethee SG
      • Shaper AG.
      Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality.
      1999UK72727272Prospective cohort40-5916.8 ySpirits, beerSpirits vs beer in occasional and regular drinkers1.02 (0.83-1.25)
      Wine vs beer in occasional and regular drinkers0.71 (0.52-0.98)
      IQR = interquartile range; MADP = Mediterranean alcohol-drinking pattern; SCD = Sudden Coronary Death; CI - Confidence interval .

      Discussion

      Beer Consumption and Cardiovascular Outcomes

      Beer contains a wide variety of nonalcoholic components (eg, compounds derived from benzoic and cinnamic acids, catechins, procyanidins, humulones, and prenil-chalcones)
      • Gerhäuser C
      Beer constituents as potential cancer chemopreventive agents.
      ,
      • Stevens JF
      • Page JE
      Xanthohumol and related prenylflavonoids from hops and beer: to your good health!.
      that differ from those in red wine, which has amino acids, minerals, and polyphenols (phenolic acid, prenylated chalcones, flavonoids, catechins). It also has been observed that xanthohumol inhibited the oxidation of low-density lipoprotein (LDL) in vitro induced by Cu2+,
      • Miranda CL
      • Stevens JF
      • Ivanov V
      • et al.
      Antioxidant and prooxidant actions of prenylated and nonprenylated chalcones and flavanones in vitro.
      as well as lipid peroxidation of liver microsomes in rats.
      • Rodriguez RJ
      • Miranda CL
      • Stevens JF
      • Deiinzer ML
      • Buhler DR
      Influence of prenylated and non-prenylated flavonoids on liver microsomal lipid peroxidation and oxidative injury in rat hepatocytes.
      Moderate beer consumption (1 drink/d for women and 1-2 drinks/d for men) perhaps reduces cardiovascular risks due to a mechanism of prevention of LDL oxidation and induction of cholesterol efflux from macrophages, a process considered a first step in the reverse cholesterol transport pathway.
      • Marcos A
      • Serra-Majem L
      • Pérez-Jiménez F
      • Pascual V
      • Tinahones FJ
      • Estruch R
      Moderate consumption of beer and its effects on cardiovascular and metabolic health: an updated review of recent scientific evidence.
      ,
      • Anastasius M
      • Kockx M
      • Jessup W
      • Sullivan D
      • Rye KA
      • Kritharides L
      Cholesterol efflux capacity: an introduction for clinicians.
      Beer can also influence high-density lipoprotein (HDL)-induced cholesterol efflux, increase ABCA1-mediated cholesterol efflux,
      • Davidson WS
      • Heink A
      • Sexmith H
      • et al.
      The effects of apolipoprotein B depletion on HDL subspecies composition and function.
      enhance the antioxidant capacity of HDL, elevate plasma HDL cholesterol (HDL-c) levels,
      • Hines LM
      • Rimm EB
      Moderate alcohol consumption and coronary heart disease: a review.
      ,
      • Estruch R
      • Lamuela-Raventós RM
      Wine, alcohol, polyphenols and cardiovascular disease.
      and acutely improve arterial properties.
      • Karatzi K
      • Rontoyanni VG
      • Protogerou AD
      • et al.
      Acute effects of beer on endothelial function and hemodynamics: a single-blind, crossover study in healthy volunteers.
      Non-alcoholic-related beer components protect against hyperlipidemia-induced coronary endothelial dysfunction by counteracting vascular oxidative damage and preserving the Akt/endothelial nitric oxide synthase pathway.
      • Vilahur G
      • Casani L
      • Mendieta G
      • Lamuela-Riventos RM
      • Estruch R
      • Badimon L
      Beer elicits vasculoprotective effects through Akt/eNOS activation.
      The anti-inflammatory mechanisms of the bioactive compounds of beer are mainly due to the inhibition of inducible nitric oxide synthase and the inhibition of the activity of cyclooxygenase 1.
      • Gerhäuser C
      Beer constituents as potential cancer chemopreventive agents.
      ,
      • Milligan SR
      • Kalita JC
      • Pocock SR
      • et al.
      The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids.
      One study reported that low-moderate beer consumption is associated with HDL efflux capacity.
      • Stockley CS
      The relationships between alcohol, wine and cardiovascular diseases – a review.
      In a randomized control trial, moderate beer consumption for 4 weeks raised HDL-c levels by a mean of 2.2 mg/dL in individuals with an LDL-c <130 mg/dL;
      • Padro T
      • Muñoz-García N
      • Vilahur G
      • et al.
      Moderate beer intake and cardiovascular health in overweight individuals.
      circulating HDL quality was improved already in the 4-week period by rendering HDL particles functionally active to prevent LDL oxidation and facilitate cell-cholesterol efflux. However, regular beer intake increased the plasma gamma-glutamyl transferase levels in 15% of subjects because beer is primarily metabolized in the liver using enzyme alcohol dehydrogenase,
      • Baliunas DO
      • Taylor BJ
      • Irving H
      • et al.
      Alcohol as a risk factor for type 2 diabetes: a systematic review and meta-analysis.
      and therefore, patients with liver disease or at risk for liver injury (eg, those with nonalcoholic fatty liver disease or chronic hepatitis) should avoid beer consumption. One meta-analysis demonstrated that alcohol is a major risk factor for liver cirrhosis, with risk increasing exponentially.
      • Roerecke M
      • Vafaei A
      • Hasan OSM
      • et al.
      Alcohol consumption and risk of liver cirrhosis: a systematic review and meta-analysis.
      Moreover, women may be at higher risk compared with men, even with little alcohol consumption. Additionally, alcohol consumption has a causal association with cancers of the oral cavity, pharynx, larynx, esophagus, lungs, liver, colon, rectum, and, in women, the breast. However, some studies did not find the association between alcohol consumption and cancers.

      Wine Consumption and Cardiovascular Outcomes

      Wine can be classified into white wine and red wine for evaluation in studies and because of different mechanisms for cardioprotective benefits. In the 1980s, the French paradox was observed due to low cardiovascular disease mortality (primarily from coronary artery disease) despite high intake of dietary cholesterol and saturated fat.
      • Renaud S
      • de Lorgeril M
      Wine, alcohol, platelets, and the French paradox for coronary heart disease.
      ,
      • Artaud-Wild SM
      • Connor SL
      • Sexton G
      • Connor WE
      Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox.
      There was also the indirect observation that the French population consumed red wine with their diet, which was mostly high in saturated fat, and this correlation between wine and cardiovascular disease protection was attributed to the consumption of red wine.
      • Ferrières J
      The French paradox: lessons for other countries.
      Red wine primarily contains polyphenols, which are a combination of both flavonoids (eg, anthocyanins and flavan-3-ols) and nonflavonoids (eg, resveratrol, cinnamates, and gallic acid). In fact, flavonoids such as Flavan-3-ols are the most abundant and contain up to 50% of the total phenolic constituents.
      • Waterhouse AL.
      Wine phenolics.
      Wine promotes cardiovascular health via multiple mechanisms. These include polyphenols lowering plasma concentrations of pro-oxidant and inflammatory molecules and leukocyte adhesion molecules, improving homeostasis model assessment of insulin resistance values and blood pressure, reducing phospholipids oxidation, modulating cell signaling pathways, reducing platelet aggregation,
      • Chiva-Blanch G
      • Urpi-Sarda M
      • Llorach R
      • et al.
      Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial.
      • Chiva-Blanch G
      • Urpi-Sarda M
      • Ros E
      • et al.
      Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide: short communication.
      • Chiva-Blanch G
      • Urpi-Sarda M
      • Ros E
      • et al.
      Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: a randomized clinical trial.
      decreasing highly sensitive C-reactive protein, as well as concentrations of monocyte and endothelial adhesion molecules.
      • Estruch R
      • Sacanella E
      • Badia E
      • et al.
      Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: a prospective randomized crossover trial. Effects of wine on inflammatory markers.
      ,
      • Imhof A
      • Blagieva R
      • Marx N
      • Koenig W
      Drinking modulates monocyte migration in healthy subjects: a randomised intervention study of water, ethanol, red wine and beer with or without alcohol.
      St Leger et al
      • St Leger AS
      • Cochrane AL
      • Moore F
      Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine.
      reported a negative correlation between alcohol consumption and ischemic heart disease deaths, and attributed this observation predominantly to wine. Several explanations for the French paradox have been postulated,
      • Ferrières J
      The French paradox: lessons for other countries.
      with epidemiologists presenting strong correlations in favor of wine (both white and red), with other scientific literature criticizing these observations. Compared with beer or spirits, consumption of wine has been independently associated with improvements in heart rate variability, a marker of autonomic balance.
      • Janszky I
      • Ericson M
      • Blom M
      • et al.
      Wine drinking is associated with increased heart rate variability in women with coronary heart disease.
      In the CASCADE trial, in individuals with slow ethanol metabolizers (alcohol dehydrogenase alleles carriers ADH1B*1), wine consumption is associated with better glycemic control (eg, fasting plasma glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c) compared with individuals with fast ethanol metabolizers (homozygous ADH1B*2).
      • Gepner Y
      • Golan R
      • Harman-Boehm I
      • et al.
      Effects of initiating moderate alcohol intake on cardiometabolic risk in adults with type 2 diabetes: a 2-year randomized, controlled trial.
      Indeed, studies on wine consumption and cardiovascular disease are primarily based on observational studies. There is the risk of bias from confounding factors (eg, socioeconomic status, neighborhood, culture, physical activity, exercise) or unmeasured confounding (eg, genetics, gut microbiome).

      Red Wine Consumption and Cardiovascular Outcomes

      Compared with white wine, red wine has an approximately 10-fold higher polyphenolic content due to red wine's grape fermentation.
      • Markoski MM
      • Garavaglia J
      • Oliveira A
      • Olivaes J
      • Marcadenti A
      Molecular properties of red wine compounds and cardiometabolic benefits.
      Unfortunately, few studies directly compare the different effects on cardiovascular health of red wine vs white wine.
      Red wine promotes cardiovascular health via mechanisms of polyphenols, improved endothelial function, and increased circulating endothelial progenitor cells and nitric oxide levels.
      • Huang P-H
      • Chen Y-H
      • Tsai H-Y
      • et al.
      Intake of red wine increases the number and functional capacity of circulating endothelial progenitor cells by enhancing nitric oxide bioavailability.
      Red wine has higher levels of bioflavonoids (with antioxidant, antiplatelet, and antiendothelin-1 effects),
      • Corder R
      • Mullen W
      • Khan NQ
      • et al.
      Oenology: red wine procyanidins and vascular health.
      polyphenolic mixtures such as flavonoids (eg, catechin/epicatechin/quercetin, procyanidins, and anthocyanins), polymeric tannins, and resveratrol (eg, 3,5,4′-trihydroxystilbene).
      • Suo H
      • Tian R
      • Li J
      • et al.
      Compositional characterization study on high -molecular -mass polymeric polyphenols in red wines by chemical degradation.
      In general, red wine contains abundant polyphenols and is, perhaps, considered a crucial polyphenol source in the diet.
      • Šeruga M
      • Novak I
      • Jakobek L
      Determination of polyphenols content and antioxidant activity of some red wines by differential pulse voltammetry, HPLC and spectrophotometric methods.
      Red wine may be associated with increased HDL-c,
      • Djoussé L
      • Lee IM
      • Buring JE
      • Gaziano JM
      Alcohol consumption and risk of cardiovascular disease and death in women: potential mediating mechanisms.
      ,
      • Pavlidou E
      • Mantzorou M
      • Fasoulas A
      • Tryfonos C
      • Petridis D
      • Giaginis C
      Wine: an aspiring agent in promoting longevity and preventing chronic diseases.
      improved insulin resistance
      • Chiva-Blanch G
      • Urpi-Sarda M
      • Ros E
      • et al.
      Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: a randomized clinical trial.
      ,
      • Brasnyó P
      • Molnár GA
      • Mohás M
      • et al.
      Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients.
      and oxidative stress,
      • Estruch R
      • Sacanella E
      • Mota F
      • et al.
      Moderate consumption of red wine, but not gin, decreases erythrocyte superoxide dismutase activity: a randomised cross-over trial.
      ,
      • Prasad K.
      Resveratrol, wine, and atherosclerosis.
      and downregulated serum concentrations of CD40 antigen, CD40 ligand, interleukin-16, monocyte chemotactic protein-1, and vascular cell adhesion molecule-1.
      • Chiva-Blanch G
      • Urpi-Sarda M
      • Llorach R
      • et al.
      Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial.
      It also can reduce the propensity of LDL to undergo lipid peroxidation.
      • Fuhrman B
      • Lavy A
      • Aviram M
      Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation.
      In addition, a recent study found that people who drank red wine had increased gut microbiota diversity (a sign of gut health) compared with non-red-wine drinkers, as well as an association with lower levels of obesity and “bad” cholesterol.
      • Le Roy CI
      • Wells PM
      • Si J
      • Raes J
      • Bell JT
      • Spector TD
      Red wine consumption associated with increased gut microbiota α-diversity in 3 independent cohorts.
      Although alcohol increases triglyceride levels, very low-density lipoprotein production, and triglyceride enrichment of HDL, little is known about alcohol's effect on lipoprotein (a). In the CASCADE trial, 224 abstainers with type 2 diabetes were randomized to consume red wine, white wine, or mineral water for 2 years.
      • Gepner Y
      • Golan R
      • Harman-Boehm I
      • et al.
      Effects of initiating moderate alcohol intake on cardiometabolic risk in adults with type 2 diabetes: a 2-year randomized, controlled trial.
      This long-term randomized controlled trial among well-controlled diabetics found that initiating moderate red wine is associated with increased HDL-c levels by 2.0 mg/dL and decreased the total cholesterol-to-HDL-c ratio by 27%. Moreover, red wine is associated with a reduction in components of the metabolic syndrome by 34%, compared with the changes in the water group. In fact, some studies performed in women observed that daily doses of 15-20 g of alcohol such as red wine were sufficient to elicit anti-inflammatory effects similar to those observed in men who consumed higher doses of wine.
      • Sacanella E
      • Vázquez-Agell M
      • Mena MP
      • et al.
      Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial.

      White Wine Consumption and Cardiovascular Outcomes

      Compared with red wine, studies in white wine are inconclusive, and its mechanism for cardiovascular benefits is unclear. Clinical trials have suggested that white wine, particularly aged white wine, could promote cardiovascular health via various mechanisms. These include repair and maintenance of endothelial integrity, antioxidative and antiatherogenic effects, an increase in HDL-c, increase in paraoxonase-1 and glutathione peroxidase, reduced glutathione levels, a decrease in superoxide dismutase activity, and a decrease in oxidation protein products and thiobarbituric acid reactive substance concentrations.
      • Micallef M
      • Lexis L
      • Lewandowski P
      Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans.
      However, one non-placebo-controlled trial suggests that regular daily white wine consumption could potentially lead to a proatherogenic increase in homocysteine concentrations.
      • Roth I
      • Casas R
      • Medina-Remón A
      • Lamuela-Raventós RM
      • Estruch R
      Consumption of aged white wine modulates cardiovascular risk factors via circulating endothelial progenitor cells and inflammatory biomarkers.
      There were, however, limitations in this study, such as the number of participants in each drinking pattern group (wine and beer drinkers). The difference in protective effect between red wines and white wines is perhaps due to the polyphenolic ratio. However, one study suggested that tyrosols (relatively unknown active compounds identified in white wines), along with known compounds such as caffeic acid, and shikimic acids, could potentially explain the biological mechanisms and association between white wine and cardiovascular disease.
      • Bertelli AA
      Wine, research and cardiovascular disease: instructions for use.
      Some studies suggested that wine acutely improves endothelial function in patients with coronary artery disease, and a moderate daily intake of white wine with dinner can have antioxidative and cardioprotective effects.
      • Whelan AP
      • Sutherland WHF
      • McCormick MP
      • Yeoman DJ
      • de Jong SA
      • Williams MJA
      Effects of white and red wine on endothelial function in subjects with coronary artery disease.
      ,
      • Rajdl D
      • Racek J
      • Trefil J
      • Siala K
      Effect of white wine consumption on oxidative stress markers and homocysteine levels.
      However, there are also studies that have reported no differences in the effects of red and white wines on endothelial function.
      • Whelan AP
      • Sutherland WHF
      • McCormick MP
      • Yeoman DJ
      • de Jong SA
      • Williams MJA
      Effects of white and red wine on endothelial function in subjects with coronary artery disease.
      Further research is needed to compare directly between red wine and white wine consumption on cardiovascular disease effects. Methodology to stratify confounders (eg, subgroup analysis) or identify unknown confounders using machine learning is needed in alcohol research.

      Liquor/Other Alcohol Consumption and Cardiovascular Outcomes

      There is no study directly on liquor or distilled spirits and the associations with cardiovascular disease outcomes. Liquor or spirits such as gin and vodka do not have a significant number of polyphenols or other nonalcoholic compounds with purported cardiovascular benefits. Therefore, data are relatively limited. One longitudinal study indicated that the use of spirits at least once a week may be associated with a slightly reduced risk of acute myocardial infarction among coronary artery disease-free men aged 30-59 years, but has no impact on total mortality compared with men using less spirits.
      • Salonen JT
      • Puska P
      • Nissinen A
      Intake of spirits and beer and risk of myocardial infarction and death–a longitudinal study in Eastern Finland.
      Several studies on spirit consumption and vascular risk found no J-shaped correlation.
      • Yano K
      • Rhoads GG
      • Kagan A
      Coffee, alcohol and risk of coronary heart disease among Japanese men living in Hawaii.
      • Grønbaek M
      • Becker U
      • Johansen D
      • et al.
      Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer.
      • Malarcher AM
      • Giles WH
      • Croft JB
      • et al.
      Alcohol intake, type of beverage, and the risk of cerebral infarction in young women.
      • Mukamal KJ
      • Conigrave KM
      • Mittleman MA
      • et al.
      Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men.
      No statistically significant association with vascular events was apparent for the intake of spirits up to 60 g/d, which is the maximum dose investigated in the 10 studies included in this meta-analysis. Indeed, several studies noted that spirit consumption mostly occurred as binge drinking (defined as the consumption of 3 or more drinks within 1-2 hours) and was restricted to only a few days per week. This may explain the absence of association between moderate spirit consumption and cardiovascular disease benefit in the present review and in a previous study.
      • Rimm EB
      • Klatsky A
      • Grobbee D
      • Stampfer MJ
      Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits.
      There are limited studies on the subtypes of liquor (whiskey, gin, rum, tequila) and cardiovascular disease. Researchers assessed whether consumption of 100 mL of whisky or red wine by healthy male subjects increased plasma total phenol content and antioxidant capacity. They found that consumption of phenolic-containing alcoholic beverages transiently raised total phenol concentration and enhanced the antioxidant capacity of plasma.
      • Duthie GG
      • Pedersen MW
      • Gardner PT
      • et al.
      The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers.
      This is compatible with suggestions that moderate alcohol usage and increased antioxidant intake decrease the risk of coronary heart disease.
      Overall, although head-to-head comparisons between classes of alcoholic beverages are very limited, there may be underlying cardiovascular benefits from moderate alcohol consumption. However, further studies with confounder correction are needed to dissect this potential association before serious recommendations can be made. However, due to the many health risks linked to alcohol consumption (ie, dementia, alcohol use disorder, liver cirrhosis),
      • Roerecke M
      • Vafaei A
      • Hasan OSM
      • et al.
      Alcohol consumption and risk of liver cirrhosis: a systematic review and meta-analysis.
      no long-term randomized trials of alcohol consumption have been performed.
      • Kranzler HR
      • Soyka M
      Diagnosis and pharmacotherapy of alcohol use disorder: a review.

      Limitations

      There are significant limitations of the present study. Most meta-analyses fit linear models ignoring the J shape, or did not use nondrinkers as the reference. First, the included studies are confounded by diet. For example, wine consumption is more often a component of the Mediterranean diet, while beer/liquor intake is more commonly accompanied by diets rich in oily and fried foods.
      • Senoner T
      • Dichtl W
      Oxidative stress in cardiovascular diseases: still a therapeutic target?.
      ,
      • Haseeb S
      • Alexander B
      • Baranchuk A
      Wine and cardiovascular health.
      Second, there is no genetic factor.
      • Biddinger KJ
      • Emdin CA
      • Haas ME
      • et al.
      Association of habitual alcohol intake with risk of cardiovascular disease.
      A recent mendelian randomization study showed evidence of a causal relationship between higher alcohol consumption and an increased risk of stroke and peripheral artery disease.
      • Larsson SC
      • Burgess S
      • Mason AM
      • Michaëlsson K
      Alcohol consumption and cardiovascular disease: a mendelian randomization study.
      The causal role of alcohol consumption for other cardiovascular diseases requires further research. Third, there is no drink pattern adjusted. Although some studies adjusted, the direction and magnitude of the effects of adjustment need to be further explored. Studies show that binge drinking is associated with increased coronary artery disease risk,
      • Costanzo S
      • Di Castelnuovo A
      • Donati MB
      • Iacoviello L
      • de Gaetano G
      Cardiovascular and overall mortality risk in relation to alcohol consumption in patients with cardiovascular disease.
      while alcohol is most cardioprotective when consumed prior to or during a meal.
      • Rehm J
      • Sempos CT
      • Trevisan M
      Alcohol and cardiovascular disease–more than one paradox to consider. Average volume of alcohol consumption, patterns of drinking and risk of coronary heart disease–a review.
      For example, studies showed that wine drinkers who participated in this study reported a healthier diet than did drinkers of beer or spirits.
      • Tjønneland A
      • Grønbaek M
      • Stripp C
      • Overvad K
      Wine intake and diet in a random sample of 48763 Danish men and women.
      ,
      • Klatsky AL
      Moderate drinking and reduced risk of heart disease.
      Fourth, a lack of behavioral pattern adjustment is a limitation. For example, the Finnish study found that in their study population, men who drank spirits also regularly smoked.
      • Salonen JT
      • Puska P
      • Nissinen A
      Intake of spirits and beer and risk of myocardial infarction and death–a longitudinal study in Eastern Finland.
      Fifth, most importantly, there were no adjustments for socioeconomic status. For example, a recent study suggested that coincident, favorable lifestyle factors attenuated the observational benefits of modest alcohol intake.
      • Biddinger KJ
      • Emdin CA
      • Haas ME
      • et al.
      Association of habitual alcohol intake with risk of cardiovascular disease.
      Moreover, it is likely that any particular benefit of wine over beer and spirits is prone to confounding by diet and socioeconomic status.
      • Tjønneland A
      • Grønbaek M
      • Stripp C
      • Overvad K
      Wine intake and diet in a random sample of 48763 Danish men and women.
      Sixth, a limitation of many cohort studies is that they only have baseline estimates of alcohol intake, which may change over time. Finally, it is possible that the observational studies overestimate the benefits of alcohol for cardiovascular disease outcomes. Case-control and cross-sectional studies typically are more prone to bias and reverse causation. In fact, there is increasing concern about a greater risk of breast cancer and other cancers with even moderate alcohol intake. Further meta-analysis in alcohol and all-cause mortality is needed.

      Conclusions

      In individuals without liver disease, low to moderate amounts of weekly or daily alcohol consumption may be beneficial to cardiovascular health. Specifically, strong evidence has suggested that low-moderate amounts of weekly or daily red wine consumption may be particularly associated with low cardiovascular events. However, the relationship between alcohol consumption and cardiovascular disease appears to be biphasic and have a J-shape association. Heavy alcohol consumption could be harmful. Further prospective studies with correction of potential confounders (eg, lifestyle factors, socioeconomic status) are urgently needed. Further clinical trials, if able to be undertaken safely, are warranted to adequately determine the effect of alcohol consumption on cardiovascular disease.

      Acknowledgments

      The authors would like to thank Dr. JoAnn E. Manson, MD, DrPH, MACP (Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Mass), Dr. Kenneth J. Mukamal, MD (Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard TH Chan School of Public Health, Boston, Mass), and Dr. Meir Stampfer, MD, DrPH (Harvard T.H. Chan School of Public Health) for their suggestions and comments on this article.

      Supplementary Material

      eMethods: Search Strategies
      No restrictions were placed on language or publication date. Search strategy included MESH headings and keywords including “alcohol,” “alcohol consumption,” “cardiovascular disease,” “cardiovascular events,” “diabetes,” “hypertension,” “high blood pressure,” “hyperlipidemia,” “dyslipidemia,” “arrhythmia,” “coronary artery disease,” “ischemic heart disease,” “acute myocardial infarct,” “acute coronary syndrome,” “stroke,” “heart failure,” “cardiac failure,” “cardiac insufficiency,” and “cardiomyopathy.” We identified studies based on appropriate types of study (observational study, prospective cohort study, randomized controlled trial, or case control design) and the exposure (alcohol consumption). We excluded animal studies, editorials, and reviews. Two investigators independently reviewed abstracts for potentially eligible studies. Full text reports were then assessed for eligibility and disagreements were resolved by consensus discussion. We were unable to perform meta-analysis of the results due to tremendous heterogeneity among the included studies related to intervention, comparison, outcomes, and timing. Instead, we qualitatively synthesized the results and summarized key features and characteristics (eg, study populations, design, interventions, outcomes, and conclusions) of the included studies.
      Cochrane searches
      Tabled 1
      SearchPubMed TermsResults
      S1: alcohol (all types)
      S2: cardiovascular diseasesTOPIC: ("Cardiovascular Diseases" OR arrhythmia* OR "Atrial Fibrillation" OR "Atrial Flutter" OR "Bradycardia" OR "Tachycardia" OR "Ventricular Fibrillation" OR "heart failure" OR "cardiac failure" OR "myocardial failure" OR "cardiac insufficiency" OR cardiomyopath* OR myocarditis OR stroke* OR "cardiac arrest" OR "Cardiopulmonary Arrest" OR asystole* OR "sudden cardiac death" OR "cardiovascular disease" OR "Cardiovascular Diseases" OR "Heart Diseases" OR "Heart Disease" OR "coronary heart disease" OR "coronary heart diseases" OR "coronary disease" OR "coronary diseases" OR "coronary artery disease" OR "ischemic heart disease" OR "ischaemic heart disease" OR "Myocardial Ischemia" OR "Myocardial Ischemias" OR "Myocardial Ischaemia" OR "Myocardial Ischaemias" OR "acute coronary syndrome" OR "myocardial infarction" OR "myocardial infarct" OR "heart attack" OR "heart attacks" OR "cardiovascular events" OR "cardiovascular event")1,519,764
      S3: beerTS=(beer*)27,406
      S4: red wineTS=(“red wine” OR “red wines” OR (red NEAR/3 wine))13,947
      S5: white wineTS=(“white wine” OR “white wines” OR (white NEAR/3 wine)4533
      S6: all wine
      S7: all alcohols + CVDS1 AND S2
      S8: beer + CVDS2 AND S3801
      S9: red wine + CVDS2 AND S41913
      S10: white wine + CVDS2 AND S5198
      S11: all wine + CVD – red, white, not specifiedS2 AND S6
      S12: “other” alcohol + CVD – those not returned in S8, S9, S10 or S11S7 NOT S3 NOT S4 NOT S5 NOT S6
      S13: resveratrolS2 AND resveratrol
      CVD = cardiovascular disease
      Embase searches
      Tabled 1
      SearchPubMed TermsResults(link to PubMed)
      S1: alcohol (all types)
      S2: cardiovascular diseases'cardiovascular disease'/exp OR

      arrhythmia*:ab,ti,kw OR 'atrial fibrillation':ab,ti,kw OR 'atrial flutter':ab,ti,kw OR 'bradycardia':ab,ti,kw OR 'tachycardia':ab,ti,kw OR 'ventricular fibrillation':ab,ti,kw OR 'heart failure':ab,ti,kw OR 'cardiac failure':ab,ti,kw OR 'myocardial failure':ab,ti,kw OR 'cardiac insufficiency':ab,ti,kw OR cardiomyopath*:ab,ti,kw OR myocarditis:ab,ti,kw OR stroke*:ab,ti,kw OR 'cardiac arrest':ab,ti,kw OR 'heart arrest':ab,ti,kw OR 'cardiopulmonary arrest':ab,ti,kw OR asystole*:ab,ti,kw OR 'sudden cardiac death':ab,ti,kw OR 'cardiovascular disease':ab,ti,kw OR 'cardiovascular diseases':ab,ti,kw OR 'heart diseases':ab,ti,kw OR 'heart disease':ab,ti,kw OR 'coronary disease':ab,ti,kw OR 'coronary diseases':ab,ti,kw OR 'coronary artery disease':ab,ti,kw OR 'myocardial ischemia':ab,ti,kw OR 'myocardial ischemias':ab,ti,kw OR 'myocardial ischaemia':ab,ti,kw OR 'myocardial ischaemias':ab,ti,kw OR 'acute coronary syndrome':ab,ti,kw OR 'myocardial infarction':ab,ti,kw OR 'myocardial infarct':ab,ti,kw OR 'heart attack':ab,ti,kw OR 'heart attacks':ab,ti,kw OR 'heart infarction':ab,ti,kw OR 'heart infarct':ab,ti,kw OR 'cardiovascular events':ab,ti,kw OR 'cardiovascular event':ab,ti,kw
      4,834,122
      S3: beer'beer'/exp OR beer:ti,ab,kw OR beers:ti,ab,kw16,020
      S4: red wine'red wine'/exp OR 'red wine':ti,ab,kw OR 'red wines':ti,ab,kw OR ((red NEXT/3 wine):ti,ab,kw) OR ((red NEXT/3 wines):ti,ab,kw)6862
      S5: white wine'white wine'/exp OR 'white wine':ti,ab,kw OR 'white wines':ti,ab,kw OR ((white NEXT/3 wine):ti,ab,kw) OR ((white NEXT/3 wines):ti,ab,kw)1904
      S8: beer + CVDS2 AND S31515
      S9: red wine + CVDS2 AND S41665
      S10: white wine + CVDS2 AND S5184
      CVD = cardiovascular disease.
      PubMed Searches
      Tabled 1
      SearchPubMed TermsResults(link to PubMed)
      S1: alcohol (all types)alcohol drinking OR wine OR wines OR beer[tw] OR beers[tw] OR ethanol OR alcoholic beverages286,810
      S2: cardiovascular diseases("Cardiovascular Diseases"[mh] OR arrhythmia*[tw] OR "Atrial Fibrillation"[tw] OR "Atrial Flutter"[tw] OR "Bradycardia"[tw] OR "Tachycardia"[tw] OR "Ventricular Fibrillation"[tw] OR "heart failure"[tw] OR "cardiac failure"[tw] OR "myocardial failure"[tw] OR "cardiac insufficiency"[tw] OR cardiomyopath*[tw] OR myocarditis[tw] OR stroke*[tw] OR "cardiac arrest"[tw] OR "Cardiopulmonary Arrest"[tw] OR asystole*[tw] OR "sudden cardiac death"[tw] OR "cardiovascular disease"[tw] OR "Cardiovascular Diseases"[tw] OR "Heart Diseases"[tw] OR "Heart Disease"[tw] OR "coronary heart disease"[tw] OR "coronary heart diseases"[tw] OR "coronary disease"[tw] OR "coronary diseases"[tw] OR "coronary artery disease"[tw] OR "ischemic heart disease"[tw] OR "ischaemic heart disease"[tw] OR "Myocardial Ischemia"[tw] OR "Myocardial Ischemias"[tw] OR "Myocardial Ischaemia"[tw] OR "Myocardial Ischaemias"[tw] OR "acute coronary syndrome"[tw] OR "myocardial infarction"[tw] OR "myocardial infarct"[tw] OR "heart attack"[tw] OR "heart attacks"[tw] OR "cardiovascular events"[tw] OR "cardiovascular event"[tw])2,756,209
      S3: beerbeer[tw] OR beers[tw]10,963
      S4: red wine“red wine”[tw] OR “red wines”[tw] OR (red AND "white wine") OR (red AND "white wines")4992
      S5: white wine“white wine”[tw] OR “white wines”[tw] OR (white AND "red wine") OR (white AND "red wines")1553
      S6: all winewine[tw] OR wines[tw]21,600
      S7: all alcohols + CVDS1 AND S217,481
      S8: beer + CVDS2 AND S3704
      S9: red wine + CVDS2 AND S4897
      S10: white wine + CVDS2 AND S5109
      S11: all wine + CVD – red, white, not specifiedS2 AND S62300
      S12: “other” alcohol + CVD – those not returned in S8, S9, S10 or S11S7 NOT S3 NOT S4 NOT S5 NOT S614,780
      S13: resveratrolS2 AND resveratrol1692
      CVD = cardiovascular disease
      Web of Science searches
      Tabled 1
      SearchPubMed TermsResults
      S1: alcohol (all types)
      S2: cardiovascular diseasesTOPIC: ("Cardiovascular Diseases" OR arrhythmia* OR "Atrial Fibrillation" OR "Atrial Flutter" OR "Bradycardia" OR "Tachycardia" OR "Ventricular Fibrillation" OR "heart failure" OR "cardiac failure" OR "myocardial failure" OR "cardiac insufficiency" OR cardiomyopath* OR myocarditis OR stroke* OR "cardiac arrest" OR "Cardiopulmonary Arrest" OR asystole* OR "sudden cardiac death" OR "cardiovascular disease" OR "Cardiovascular Diseases" OR "Heart Diseases" OR "Heart Disease" OR "coronary heart disease" OR "coronary heart diseases" OR "coronary disease" OR "coronary diseases" OR "coronary artery disease" OR "ischemic heart disease" OR "ischaemic heart disease" OR "Myocardial Ischemia" OR "Myocardial Ischemias" OR "Myocardial Ischaemia" OR "Myocardial Ischaemias" OR "acute coronary syndrome" OR "myocardial infarction" OR "myocardial infarct" OR "heart attack" OR "heart attacks" OR "cardiovascular events" OR "cardiovascular event")1,519,764
      S3: beerTS=(beer*)27,406
      S4: red wineTS=(“red wine” OR “red wines” OR (red NEAR/3 wine))13,947
      S5: white wineTS=(“white wine” OR “white wines” OR (white NEAR/3 wine)4533
      S6: all wine
      S7: all alcohols + CVDS1 AND S2
      S8: beer + CVDS2 AND S3801
      S9: red wine + CVDS2 AND S41913
      S10: white wine + CVDS2 AND S5198
      S11: all wine + CVD – red, white, not specifiedS2 AND S6
      S12: “other” alcohol + CVD – those not returned in S8, S9, S10 or S11S7 NOT S3 NOT S4 NOT S5 NOT S6
      S13: resveratrolS2 AND resveratrol
      CVD = cardiovascular disease

      References

      1. United States Department of Agriculture. The Dietary Guidelines for Americans 2020-2025. Available at:https://www.dietaryguidelines.gov/sites/default/files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf. Accessed April 8, 2022.

        • Ricci C
        • Schutte AE
        • Schutte R
        • Smits CM
        • Pieters M
        Trends in alcohol consumption in relation to cause-specific and all-cause mortality in the United States: a report from the NHANES linked to the US mortality registry.
        Am J Clin Nutr. 2020; 111: 580-589
        • Arranz S
        • Chiva-Blanch M
        • Valdera-Martínez P
        • Medina-Remón A
        • Lamuela-Raventós RM
        • Estruch R
        Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer.
        Nutrients. 2012; 4: 759-781
        • GBD 2017 Risk Factor Collaborators
        Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
        Lancet. 2018; 392: 1923-1994
        • Yusuf S
        • Hawken S
        • Ounpuu S
        • et al.
        Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
        Lancet. 2004; 364: 937-952
        • Gerhäuser C
        Beer constituents as potential cancer chemopreventive agents.
        Eur J Cancer. 2005; 41: 1941-1954
        • Stevens JF
        • Page JE
        Xanthohumol and related prenylflavonoids from hops and beer: to your good health!.
        Phytochemistry. 2004; 65: 1317-1330
        • Miranda CL
        • Stevens JF
        • Ivanov V
        • et al.
        Antioxidant and prooxidant actions of prenylated and nonprenylated chalcones and flavanones in vitro.
        J Agric Food Chem. 2000; 48: 3876-3884
        • Rodriguez RJ
        • Miranda CL
        • Stevens JF
        • Deiinzer ML
        • Buhler DR
        Influence of prenylated and non-prenylated flavonoids on liver microsomal lipid peroxidation and oxidative injury in rat hepatocytes.
        Food Chem Toxicol. 2001; 39: 437-445
        • Marcos A
        • Serra-Majem L
        • Pérez-Jiménez F
        • Pascual V
        • Tinahones FJ
        • Estruch R
        Moderate consumption of beer and its effects on cardiovascular and metabolic health: an updated review of recent scientific evidence.
        Nutrients. 2021; 13: 879
        • Anastasius M
        • Kockx M
        • Jessup W
        • Sullivan D
        • Rye KA
        • Kritharides L
        Cholesterol efflux capacity: an introduction for clinicians.
        Am Heart J. 2016; 180: 54-63
        • Davidson WS
        • Heink A
        • Sexmith H
        • et al.
        The effects of apolipoprotein B depletion on HDL subspecies composition and function.
        J Lipid Res. 2016; 57: 674-686
        • Hines LM
        • Rimm EB
        Moderate alcohol consumption and coronary heart disease: a review.
        Postgrad Med J. 2001; 77: 747-752
        • Estruch R
        • Lamuela-Raventós RM
        Wine, alcohol, polyphenols and cardiovascular disease.
        Nutr Aging (Amst). 2014; 2: 101-109
        • Karatzi K
        • Rontoyanni VG
        • Protogerou AD
        • et al.
        Acute effects of beer on endothelial function and hemodynamics: a single-blind, crossover study in healthy volunteers.
        Nutrition. 2013; 29: 1122-1126
        • Vilahur G
        • Casani L
        • Mendieta G
        • Lamuela-Riventos RM
        • Estruch R
        • Badimon L
        Beer elicits vasculoprotective effects through Akt/eNOS activation.
        Eur J Clin Invest. 2014; 44: 1177-1188
        • Milligan SR
        • Kalita JC
        • Pocock SR
        • et al.
        The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids.
        J Clin Endocrinol Metab. 2000; 85: 4912-4915
        • Stockley CS
        The relationships between alcohol, wine and cardiovascular diseases – a review.
        Nutr Aging (Amst). 2015; 3: 55-88
        • Padro T
        • Muñoz-García N
        • Vilahur G
        • et al.
        Moderate beer intake and cardiovascular health in overweight individuals.
        Nutrients. 2018; 10: 1237
        • Baliunas DO
        • Taylor BJ
        • Irving H
        • et al.
        Alcohol as a risk factor for type 2 diabetes: a systematic review and meta-analysis.
        Diabetes Care. 2009; 32: 2123-2132
        • Roerecke M
        • Vafaei A
        • Hasan OSM
        • et al.
        Alcohol consumption and risk of liver cirrhosis: a systematic review and meta-analysis.
        Am J Gastroenterol. 2019; 114: 1574-1586
        • Renaud S
        • de Lorgeril M
        Wine, alcohol, platelets, and the French paradox for coronary heart disease.
        Lancet. 1992; 339: 1523-1526
        • Artaud-Wild SM
        • Connor SL
        • Sexton G
        • Connor WE
        Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox.
        Circulation. 1993; 88: 2771-2779
        • Ferrières J
        The French paradox: lessons for other countries.
        Heart. 2004; 90: 107-111
        • Waterhouse AL.
        Wine phenolics.
        Ann N Y Acad Sci. 2002; 957: 21-36
        • Chiva-Blanch G
        • Urpi-Sarda M
        • Llorach R
        • et al.
        Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial.
        Am J Clin Nutr. 2012; 95: 326-334
        • Chiva-Blanch G
        • Urpi-Sarda M
        • Ros E
        • et al.
        Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide: short communication.
        Circ Res. 2012; 111: 1065-1068
        • Chiva-Blanch G
        • Urpi-Sarda M
        • Ros E
        • et al.
        Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: a randomized clinical trial.
        Clin Nutr. 2013; 32: 200-206
        • Estruch R
        • Sacanella E
        • Badia E
        • et al.
        Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: a prospective randomized crossover trial. Effects of wine on inflammatory markers.
        Atherosclerosis. 2004; 175: 117-123
        • Imhof A
        • Blagieva R
        • Marx N
        • Koenig W
        Drinking modulates monocyte migration in healthy subjects: a randomised intervention study of water, ethanol, red wine and beer with or without alcohol.
        Diab Vasc Dis Res. 2008; 5: 48-53
        • St Leger AS
        • Cochrane AL
        • Moore F
        Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine.
        Lancet. 1979; 1: 1017-1020
        • Janszky I
        • Ericson M
        • Blom M
        • et al.
        Wine drinking is associated with increased heart rate variability in women with coronary heart disease.
        Heart. 2005; 91: 314-318
        • Gepner Y
        • Golan R
        • Harman-Boehm I
        • et al.
        Effects of initiating moderate alcohol intake on cardiometabolic risk in adults with type 2 diabetes: a 2-year randomized, controlled trial.
        Ann Intern Med. 2015; 163: 569-579
        • Markoski MM
        • Garavaglia J
        • Oliveira A
        • Olivaes J
        • Marcadenti A
        Molecular properties of red wine compounds and cardiometabolic benefits.
        Nutr Metab Insights. 2016; 9: 51-57
        • Huang P-H
        • Chen Y-H
        • Tsai H-Y
        • et al.
        Intake of red wine increases the number and functional capacity of circulating endothelial progenitor cells by enhancing nitric oxide bioavailability.
        Arterioscler Thromb Vasc Biol. 2010; 30: 869-877
        • Corder R
        • Mullen W
        • Khan NQ
        • et al.
        Oenology: red wine procyanidins and vascular health.
        Nature. 2006; 444: 566
        • Suo H
        • Tian R
        • Li J
        • et al.
        Compositional characterization study on high -molecular -mass polymeric polyphenols in red wines by chemical degradation.
        Food Res Int. 2019; 123: 440-449
        • Šeruga M
        • Novak I
        • Jakobek L
        Determination of polyphenols content and antioxidant activity of some red wines by differential pulse voltammetry, HPLC and spectrophotometric methods.
        Food Chemistry. 2011; 124: 1208-1216
        • Djoussé L
        • Lee IM
        • Buring JE
        • Gaziano JM
        Alcohol consumption and risk of cardiovascular disease and death in women: potential mediating mechanisms.
        Circulation. 2009; 120: 237-244
        • Pavlidou E
        • Mantzorou M
        • Fasoulas A
        • Tryfonos C
        • Petridis D
        • Giaginis C
        Wine: an aspiring agent in promoting longevity and preventing chronic diseases.
        Diseases. 2018; 6: 73
        • Brasnyó P
        • Molnár GA
        • Mohás M
        • et al.
        Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients.
        Br J Nutr. 2011; 106: 383-389
        • Estruch R
        • Sacanella E
        • Mota F
        • et al.
        Moderate consumption of red wine, but not gin, decreases erythrocyte superoxide dismutase activity: a randomised cross-over trial.
        Nutr Metab Cardiovasc Dis. 2011; 21: 46-53
        • Prasad K.
        Resveratrol, wine, and atherosclerosis.
        Int J Angiol. 2012; 21: 7-18
        • Fuhrman B
        • Lavy A
        • Aviram M
        Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation.
        Am J Clin Nutr. 1995; 61: 549-554
        • Le Roy CI
        • Wells PM
        • Si J
        • Raes J
        • Bell JT
        • Spector TD
        Red wine consumption associated with increased gut microbiota α-diversity in 3 independent cohorts.
        Gastroenterology. 2020; 158: 270-272.e2
        • Sacanella E
        • Vázquez-Agell M
        • Mena MP
        • et al.
        Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial.
        Am J Clin Nutr. 2007; 86: 1463-1469
        • Micallef M
        • Lexis L
        • Lewandowski P
        Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans.
        Nutr J. 2007; 6: 27
        • Roth I
        • Casas R
        • Medina-Remón A
        • Lamuela-Raventós RM
        • Estruch R
        Consumption of aged white wine modulates cardiovascular risk factors via circulating endothelial progenitor cells and inflammatory biomarkers.
        Clin Nutr. 2019; 38: 1036-1044
        • Bertelli AA
        Wine, research and cardiovascular disease: instructions for use.
        Atherosclerosis. 2007; 195: 242-247
        • Whelan AP
        • Sutherland WHF
        • McCormick MP
        • Yeoman DJ
        • de Jong SA
        • Williams MJA
        Effects of white and red wine on endothelial function in subjects with coronary artery disease.
        Intern Med J. 2004; 34: 224-228
        • Rajdl D
        • Racek J
        • Trefil J
        • Siala K
        Effect of white wine consumption on oxidative stress markers and homocysteine levels.
        Physiol Res. 2007; 56: 203-212
        • Salonen JT
        • Puska P
        • Nissinen A
        Intake of spirits and beer and risk of myocardial infarction and death–a longitudinal study in Eastern Finland.
        J Chronic Dis. 1983; 36: 533-543
        • Yano K
        • Rhoads GG
        • Kagan A
        Coffee, alcohol and risk of coronary heart disease among Japanese men living in Hawaii.
        N Engl J Med. 1977; 297: 405-409
        • Grønbaek M
        • Becker U
        • Johansen D
        • et al.
        Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer.
        Ann Intern Med. 2000; 133: 411-419
        • Malarcher AM
        • Giles WH
        • Croft JB
        • et al.
        Alcohol intake, type of beverage, and the risk of cerebral infarction in young women.
        Stroke. 2001; 32: 77-83
        • Mukamal KJ
        • Conigrave KM
        • Mittleman MA
        • et al.
        Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men.
        N Engl J Med. 2003; 348: 109-118
        • Rimm EB
        • Klatsky A
        • Grobbee D
        • Stampfer MJ
        Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits.
        BMJ. 1996; 312: 731-736
        • Duthie GG
        • Pedersen MW
        • Gardner PT
        • et al.
        The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers.
        Eur J Clin Nutr. 1998; 52: 733-736
        • Kranzler HR
        • Soyka M
        Diagnosis and pharmacotherapy of alcohol use disorder: a review.
        JAMA. 2018; 320: 815-824
        • Senoner T
        • Dichtl W
        Oxidative stress in cardiovascular diseases: still a therapeutic target?.
        Nutrients. 2019; 11: 2090
        • Haseeb S
        • Alexander B
        • Baranchuk A
        Wine and cardiovascular health.
        Circulation. 2017; 136: 1434-1448
        • Biddinger KJ
        • Emdin CA
        • Haas ME
        • et al.
        Association of habitual alcohol intake with risk of cardiovascular disease.
        JAMA Netw Open. 2022; 5e223849
        • Larsson SC
        • Burgess S
        • Mason AM
        • Michaëlsson K
        Alcohol consumption and cardiovascular disease: a mendelian randomization study.
        Circ Genom Precis Med. 2020; 13e002814
        • Costanzo S
        • Di Castelnuovo A
        • Donati MB
        • Iacoviello L
        • de Gaetano G
        Cardiovascular and overall mortality risk in relation to alcohol consumption in patients with cardiovascular disease.
        Circulation. 2010; 121: 1951-1959
        • Rehm J
        • Sempos CT
        • Trevisan M
        Alcohol and cardiovascular disease–more than one paradox to consider. Average volume of alcohol consumption, patterns of drinking and risk of coronary heart disease–a review.
        J Cardiovasc Risk. 2003; 10: 15-20
        • Tjønneland A
        • Grønbaek M
        • Stripp C
        • Overvad K
        Wine intake and diet in a random sample of 48763 Danish men and women.
        Am J Clin Nutr. 1999; 69: 49-54
        • Klatsky AL
        Moderate drinking and reduced risk of heart disease.
        Alcohol Res Health. 1999; 23: 15-23
        • Bos Sarah
        • Grobbee Diederick E
        • Boer Jolanda M A
        • Monique Verschuren W
        • Beulens Joline W J
        Alcohol consumption and risk of cardiovascular disease among hypertensive women.
        European journal of cardiovascular prevention and rehabilitation. 1 February 2010; 17: 119-126
        • Brenner Hermann
        • Rothenbacher Dietrich
        • Bode Günter
        • März Winfried
        • Hoffmeister Albrecht
        • Koenig Wolfgang
        Coronary Heart Disease Risk Reduction in a Predominantly Beer-Drinking Population.
        Epidemiology. July 2001; 12: 390-395
        • Foerster M
        • Marques-Vidal P
        • Gmel G
        • Daeppen JB
        • Cornuz J
        • Hayoz D
        • Pécoud A
        • Mooser V
        • Waeber G
        • Vollenweider P
        • Paccaud F
        • Rodondi N.
        Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption.
        Am J Cardiol. 2009; 103: 361-368
        • Gigleux I
        • Gagnon J
        • St-Pierre A
        • Cantin B
        • Dagenais GR
        • Meyer F
        • Després JP
        • Lamarche B.
        Moderate alcohol consumption is more cardioprotective in men with the metabolic syndrome.
        J Nutr. 2006; 136: 3027-3032
        • Klatsky AL
        • Armstrong MA
        • Friedman GD.
        Relations of alcoholic beverage use to subsequent coronary artery disease hospitalization.
        Am J Cardiol. 1986; 58: 710-714
        • Klatsky AL
        • Armstrong MA
        • Friedman GD.
        Red wine, white wine, liquor, beer, and risk for coronary artery disease hospitalization.
        Am J Cardiol. 1997; 80: 416-420
        • Marques-Vidal P
        • Montaye M
        • Arveiler D
        • Evans A
        • Bingham A
        • Ruidavets JB
        • Amouyel P
        • Haas B
        • Yarnell J
        • Ducimetière P
        • Ferrières J.
        Alcohol consumption and cardiovascular disease: differential effects in France and Northern Ireland. The PRIME study.
        Eur J Cardiovasc Prev Rehabil. 2004; 11: 336-343
        • Park JE
        • Ryu Y
        • Cho SI.
        The Effect of Reference Group Classification and Change in Alcohol Consumption on the Association Between Alcohol Consumption and Cardiovascular Disease.
        Alcohol Clin Exp Res. 2017; 41: 379-387
        • Rimm EB
        • Giovannucci EL
        • Willett WC
        • Colditz GA
        • Ascherio A
        • Rosner B
        • Stampfer MJ.
        Prospective study of alcohol consumption and risk of coronary disease in men.
        Lancet. 1991 Aug 24; 338: 464-468
        • Stampfer MJ
        • Colditz GA
        • Willett WC
        • Speizer FE
        • Hennekens CH.
        A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women.
        N Engl J Med. 1988; 319: 267-273
        • Wannamethee SG
        • Shaper AG.
        Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality.
        Am J Public Health. 1999; 89: 685-690
        • Wellmann J
        • Heidrich J
        • Berger K
        • Döring A
        • Heuschmann PU
        • Keil U.
        Changes in alcohol intake and risk of coronary heart disease and all-cause mortality in the MONICA/KORA-Augsburg cohort 1987-97.
        Eur J Cardiovasc Prev Rehabil. 2004; 11: 48-55
        • Woodward M
        • Tunstall-Pedoe H.
        Alcohol consumption, diet, coronary risk factors, and prevalent coronary heart disease in men and women in the Scottish heart health study.
        J Epidemiol Community Health. 1995; 49: 354-362
        • Keil U
        • Chambless LE
        • Döring A
        • Filipiak B
        • Stieber J.
        The relation of alcohol intake to coronary heart disease and all-cause mortality in a beer-drinking population.
        Epidemiology. 1997; 8: 150-156
        • Biddinger KJ
        • Emdin CA
        • Haas ME
        • Wang M
        • Hindy G
        • Ellinor PT
        • Kathiresan S
        • Khera AV
        • Aragam KG.
        Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease.
        JAMA Netw Open. 2022; 5e223849
        • Behrens G
        • Leitzmann MF
        • Sandin S
        • Löf M
        • Heid IM
        • Adami HO
        • Weiderpass E.
        The association between alcohol consumption and mortality: the Swedish women's lifestyle and health study.
        Eur J Epidemiol. 2011; 26: 81-90
        • Berberian K.M.
        • van Duijn C.M.
        • Hoes A.W.
        • et al.
        Alcohol and mortality.
        Eur J Epidemiol. 1994; 10: 587-593
        • Bertoia Monica L
        • et al.
        Long-term alcohol and caffeine intake and risk of sudden cardiac death in women.
        The American journal of clinical nutrition. 2013; 97: 1356-1363
        • Dai J
        • Mukamal KJ
        • Krasnow RE
        • Swan GE
        • Reed T.
        Higher usual alcohol consumption was associated with a lower 41-y mortality risk from coronary artery disease in men independent of genetic and common environmental factors: the prospective NHLBI Twin Study.
        Am J Clin Nutr. 2015; 102: 31-39
        • Deev A
        • Shestov D
        • Abernathy J
        • Kapustina A
        • Muhina N
        • Irving S.
        Association of alcohol consumption to morality in middle-aged U.S. and Russian men and women.
        Ann Epidemiol. 1998; 8: 147-153
        • Diem P
        • Deplazes M
        • Fajfr R
        • Bearth A
        • Müller B
        • Christ ER
        • Teuscher A.
        Effects of alcohol consumption on mortality in patients with Type 2 diabetes mellitus.
        Diabetologia. 2003; 46: 1581-1585
        • Grabas MP
        • Hansen SM
        • Torp-Pedersen C
        • Bøggild H
        • Ullits LR
        • Deding U
        • Nielsen BJ
        • Jensen PF
        • Overgaard C.
        Alcohol consumption and mortality in patients undergoing coronary artery bypass graft (CABG)-a register-based cohort study.
        BMC Cardiovasc Disord. 2016; 16: 219
        • Harriss LR
        • English DR
        • Hopper JL
        • Powles J
        • Simpson JA
        • O'Dea K
        • Giles GG
        • Tonkin AM.
        Alcohol consumption and cardiovascular mortality accounting for possible misclassification of intake: 11-year follow-up of the Melbourne Collaborative Cohort Study.
        Addiction. 2007; 102: 1574-1585
        • Hernandez-Hernandez A
        • Gea A
        • Ruiz-Canela M
        • Toledo E
        • Beunza JJ
        • Bes-Rastrollo M
        • Martinez-Gonzalez MA.
        Mediterranean Alcohol-Drinking Pattern and the Incidence of Cardiovascular Disease and Cardiovascular Mortality: The SUN Project.
        Nutrients. 2015; 7: 9116-9126
        • Hoffmeister H
        • Schelp FP
        • Mensink GB
        • Dietz E
        • Böhning D.
        The relationship between alcohol consumption, health indicators and mortality in the German population.
        Int J Epidemiol. 1999; 28: 1066-1072
        • Kauhanen Jussi
        • et al.
        Frequent Hangovers and Cardiovascular Mortality in Middle-Aged Men.
        Epidemiology. 1997; 8 (JSTOR) (Accessed 9 Jun. 2022): 310-314
        • Laatikainen T
        • Manninen L
        • Poikolainen K
        • Vartiainen E.
        Increased mortality related to heavy alcohol intake pattern.
        J Epidemiol Community Health. 2003; 57: 379-384
        • Mukamal KJ
        • Chen CM
        • Rao SR
        • Breslow RA.
        Alcohol consumption and cardiovascular mortality among U.S. adults, 1987 to 2002.
        J Am Coll Cardiol. 2010; 55: 1328-1335
        • Malyutina S
        • Bobak M
        • Kurilovitch S
        • Gafarov V
        • Simonova G
        • Nikitin Y
        • Marmot M.
        Relation between heavy and binge drinking and all-cause and cardiovascular mortality in Novosibirsk, Russia: a prospective cohort study.
        Lancet. 2002; 360: 1448-1454
        • Mukamal KJ
        • Maclure M
        • Muller JE
        • Sherwood JB
        • Mittleman MA.
        Prior alcohol consumption and mortality following acute myocardial infarction.
        JAMA. 2001; 285: 1965-1970
        • Pai J.K.
        • Mukamal K.J.
        • Rimm E.B.
        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; 33: 1598-1605
        • Roy A
        • Prabhakaran D
        • Jeemon P
        • Thankappan KR
        • Mohan V
        • Ramakrishnan L
        • Joshi P
        • Ahmed F
        • Mohan BV
        • Saran RK
        • Sinha N
        • Reddy KS
        Sentinel Surveillance in Industrial Populations Study Group. Impact of alcohol on coronary heart disease in Indian men.
        Atherosclerosis. 2010; 210: 531-535
        • Snow WM
        • Murray R
        • Ekuma O
        • Tyas SL
        • Barnes GE.
        Alcohol use and cardiovascular health outcomes: a comparison across age and gender in the Winnipeg Health and Drinking Survey Cohort.
        Age Ageing. 2009; 38: 206-212
        • Song Rebecca J
        • et al.
        Alcohol Consumption and Risk of Coronary Artery Disease (from the Million Veteran Program).
        The American journal of cardiology. 2018; 121: 1162-1168
        • Suadicani P
        • Hein HO
        • Gyntelberg F.
        Wine intake, ABO phenotype, and risk of ischemic heart disease and all-cause mortality: the Copenhagen Male Study–a 16-year follow-up.
        Alcohol. 2008; 42: 575-582
        • Hart CL
        • Smith GD
        • Hole DJ
        • Hawthorne VM.
        Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of scottish men with 21 years of follow up.
        BMJ. 1999; 318: 1725-1729
      2. Yuan JM, Ross RK, Gao YT, Henderson BE, Yu MC. Follow up study of moderate alcohol intake and mortality among middle aged men in Shanghai, China. BMJ. 1997;4;(314):18–23.

        • Waskiewicz A
        • Sygnowska E
        • Drygas W.
        Relationship between alcohol consumption and cardiovascular mortality–the Warsaw Pol-MONICA Project.
        Kardiol Pol. 2004; 60: 552-562
        • Tverdal A
        • Magnus P
        • Selmer R
        • Thelle D.
        Consumption of alcohol and cardiovascular disease mortality: a 16 year follow-up of 115,592 Norwegian men and women aged 40-44 years.
        Eur J Epidemiol. 2017; 32: 775-783
        • Trevisan M
        • Schisterman E
        • Mennotti A
        • Farchi G
        • Conti S
        Risk Factor And Life Expectancy Research Group. Drinking pattern and mortality: the Italian Risk Factor and Life Expectancy pooling project.
        Ann Epidemiol. 2001; 11: 312-319
        • Theobald H
        • Bygren LO
        • Carstensen J
        • Engfeldt P.
        A moderate intake of wine is associated with reduced total mortality and reduced mortality from cardiovascular disease.
        J Stud Alcohol. 2000; 61: 652-656
        • Suhonen O
        • Aromaa A
        • Reunanen A
        • Knekt P.
        Alcohol consumption and sudden coronary death in middle-aged Finnish men.
        Acta Med Scand. 1987; 221: 335-341
        • Streppel MT
        • Ocké MC
        • Boshuizen HC
        • Kok FJ
        • Kromhout D.
        Long-term wine consumption is related to cardiovascular mortality and life expectancy independently of moderate alcohol intake: the Zutphen Study.
        J Epidemiol Community Health. 2009; 63: 534-540
        • Schutte R
        • Papageorgiou M
        • Najlah M
        • Huisman HW
        • Ricci C
        • Zhang J
        • Milner N
        • Schutte AE.
        Drink types unmask the health risks associated with alcohol intake - Prospective evidence from the general population.
        Clin Nutr. 2020 Oct; 39: 3168-3174
        • Rimm EB
        • Giovannucci EL
        • Willett WC
        • Colditz GA
        • Ascherio A
        • Rosner B
        • Stampfer MJ.
        Prospective study of alcohol consumption and risk of coronary disease in men.
        Lancet. 1991; 338: 464-468
        • Renaud SC
        • Guéguen R
        • Schenker J
        • d'Houtaud A.
        Alcohol and mortality in middle-aged men from eastern France.
        Epidemiology. 1998; 9: 184-188
        • Renaud SC
        • Guéguen R
        • Conard P
        • Lanzmann-Petithory D
        • Orgogozo JM
        • Henry O.
        Moderate wine drinkers have lower hypertension-related mortality: a prospective cohort study in French men.
        Am J Clin Nutr. 2004; 80: 621-625