Alcohol and cardiovascular disease
Excessive alcohol intake is associated with an elevated risk of alcoholic liver disease (ALD), heart failure, some cancers, and accidental injury, and is a leading cause of preventable death in industrialized countries. However, extensive research has shown that moderate alcohol intake is associated with health benefits, including less cardiovascular disease, diabetes, and hypertension.
Epidemiological and short term experimental studies have shown drinkers who consume one to two drinks per drinking day have a beneficial association with ischemic heart disease compared to never-drinkers.  Furthermore, regular consumption of light to moderate dose of alcohol (1 drink/day for women or up to 2-drinks/day for men) has shown to reduce the incidence of cardiovascular events and all-cause mortality in cardiovascular patients. However, cardiovascular patients who do not regularly consume alcohol are not encouraged to start drinking due to lack of controlled intervention studies and evidence. 
An understanding of the inverse relationship between alcohol consumption and atherosclerosis was understood as early as 1904. The observation of a lower risk of cardiovascular disease (CVD) in France despite a diet rich in saturated fat was labeled the French Paradox. While much concerning this paradox remains unclear, some have suggested that the higher consumption of red wine in France results in lower CVD. Although the reduced incidence of CVD disease associated with moderate alcohol consumption is well established, many physicians have been wary of promoting the use of alcohol for this benefit considering the many negative effects of excessive alcohol consumption.
Possible mechanisms of alcohol cardioprotection
Extensive epidemiological studies have demonstrated the cardioprotective effect of alcohol consumption. However the mechanism by which this occurs is not fully understood. Research has suggested several possible mechanisms, including the following.
- I. Alcohol improves blood lipid profile.
- A. It increases HDL ("good") cholesterol. However, the increase of HDL cholesterol is dose and disease dependent. Some populations have to consume approximately 30g alcohol per day (moderate dose for men and high dose for women) in order to increase HDL cholesterol. For some diabetic patients and postmenopausal populations, a small dose of alcohol is effective to increase HDL cholesterol level.
- B. It decreases LDL ("bad") cholesterol for both healthy and patient populations though the effect is still under debate.
- C. It improves cholesterol (both HDL and LDL) particle size
- II. Alcohol decreases thrombosis (blood clotting).
- A. It reduces platelet aggregation.
- B. It reduces fibrinogen (a blood clotter). This is independent of beverage type and applies to long-term wine consumption.
- C. It increases fibrinolysis (the process by which clots dissolve).
- III. Alcohol acts through additional ways.
- A. It reduces coronary artery spasm in response to stress.
- B. It increases coronary blood flow.
- C. It reduces blood pressure.
- D. It reduces blood insulin level.
- E. It increases estrogen levels
There is a lack of medical consensus about whether moderate consumption of beer, wine, or distilled spirits has a stronger association with heart disease. Studies suggest that each is effective, with none having a clear advantage. Most researchers now believe that the most important ingredient is the alcohol itself.
The American Heart Association has reported that "More than a dozen prospective studies have demonstrated a consistent, strong, dose-response relation between increasing alcohol consumption and decreasing incidence of CHD (coronary heart disease). The data are similar in men and women in a number of different geographic and ethnic groups. Consumption of one or two drinks per day is associated with a reduction in risk of approximately 30% to 50%".
Heart disease is the largest cause of mortality in the United States and many other countries. Therefore, some physicians have suggested that patients be informed of the potential health benefits of drinking alcohol in moderation, especially if they abstain and alcohol is not contraindicated. Others, however, argue against the practice in fear that it might lead to heavy or abusive alcohol consumption. Heavy drinking is associated with a number of health and safety problems.
It is well known that alcohol consumption increases the risk of hypertension. Hence, many clinical trials examined the effect of reduction in alcohol consumption on blood pressure. Systematic review and meta-analysis have shown that effect of alcohol reduction on blood pressure is dose dependent. 
- I. For people who consumed 2 or fewer drinks per day, blood pressure was not significantly decreased when they reduced alcohol consumption close to abstinence.
- II. For people who consumed 3 or more drinks per day, blood pressure was significantly decreased when they reduced alcohol consumption close to abstinence.
- III. For people who consumed 6 or more drinks per day, reduction rate on blood pressure was the strongest when they reduced alcohol consumption close to abstinence.
- IV. The effect of alcohol reduction on blood pressure is still unclear for women and hypertensive patients who consume less than three drinks per day due to limited clinical trials.
Debate over research methods
Ex-drinkers versus never-drinkers
A logical possibility is that some of the alcohol abstainers in research studies previously drank excessively and had undermined their health, thus explaining their high levels of risk. To test this hypothesis, some studies have excluded all but those who had avoided alcohol for their entire lives. The conclusion remained the same in some studies: moderate drinkers are less likely to suffer heart disease. A paper concludes, "In this population of light to moderate drinkers, alcohol consumption in general was associated with decreased MI [myocardial infarction ] risk in women; however, episodic intoxication was related to a substantial increase in risk."
An analysis by Dr. Kaye Fillmore and colleagues failed to find significant support. Analyzing 54 prospective studies, the authors found that those studies which were free of the potential error (including former drinkers in the abstaining group) did not demonstrate significant cardiac protection from alcohol, although they continued to exhibit a J-shaped relationship in which moderate drinkers were less likely (but not at a statistically significantly level of confidence) to suffer cardiac disease than lifelong abstainers.
Dr. Arthur Klatsky noted that the flaw pointed out by Fillmore existed in one of his early studies of alcohol consumption, but that his later studies illustrating a protective effect of moderate alcohol consumption did not contain this flaw. To overcome the inherent weaknesses of all epidemiological studies, even when properly conducted, he calls for a randomized trial in which some subjects are assigned to abstain while others are assigned to drink alcohol in moderation and the health of all is monitored for a period of years.
This question of confusion of abstainers with previously heavy drinkers in epidemiologic studies is overcome with studies showing dose response effects. That is, higher amounts of alcohol consumption seem associated with greater cardiovascular benefit. Cardiology associations recommend that people who are currently nondrinkers should not start drinking alcohol.
Studies on possible confounding effects
Some have suggested the cardioprotective effects of alcohol consumption could be explained by confounding variables. For example, moderate drinkers might have more healthful lifestyles, higher economic status, better dietary habits, better healthcare, or higher educational levels, etc. However, when these and other factors are considered, the cardioprotective effects of alcohol are still evident.
Confirmation of Cardioprotection
Multiple studies on moderate alcohol consumption have now reconfirmed earlier suspected cardioprotection findings. A 2006 study concluded, "Even in men already at low risk on the basis of body mass index, physical activity, smoking, and diet, moderate alcohol intake is associated with lower risk for myocardial infarction." Another study found that when men increased their alcohol intake from very low to moderate, they significantly reduced their risk of coronary heart disease. The study monitored the health of 18,455 males for a period of seven years. A multicenter randomized diet study published in 2013 included over 7000 persons at risk to develop cardiovascular disease, and found that a Mediterranean-diet, including an encouragement to daily wine consumption in habitual drinkers, led to decreased cardiovascular events by about 30%. The study was halted prematurely since the health benefits were so dramatic. However, controversy over how the subjects were randomized lead to a retraction.
- World Health Organization (2004). Global Status Report on Alcohol 2004 (PDF). Geneva. ISBN 978-92-4-156272-0.
- Centers for Disease Control and Prevention (CDC) (2004). "Alcohol-attributable deaths and years of potential life lost--United States, 2001". MMWR. Morbidity and Mortality Weekly Report. 53 (37): 866–870. PMID 15385917.
- O'Keefe JH, Bybee KA, Lavie CJ (2007). "Alcohol and cardiovascular health: the razor-sharp double-edged sword". Journal of the American College of Cardiology. 50 (11): 1009–1014. doi:10.1016/j.jacc.2007.04.089. PMID 17825708.
- Roerecke, M; Rehm, J (2014). "Alcohol consumption, drinking patterns, and ischemic heart disease: a narrative review of meta-analyses and a systematic review and meta-analysis of the impact of heavy drinking occasions on risk for moderate drinkers". BMC Medicine. 12: 182. doi:10.1186/s12916-014-0182-6. PMC 4203905. PMID 25567363.
- Costanzo, S; Di Castelnuovo, A; Donati, MB; Iacoviello, L; de Gaetano, G (2010). "Alcohol consumption and mortality in patients with cardiovascular disease: a meta-analysis". Journal of the American College of Cardiology. 55 (13): 1339–1347. doi:10.1016/j.jacc.2010.01.006. PMID 20338495.
- Cabot, R.C. (1904). "The relation of alcohol to arterioscleroisis" (PDF). Journal of the American Medical Association. 43 (12): 774–775. doi:10.1001/jama.1904.92500120002a.
- Simini B (2000). "Serge Renaud: from French paradox to Cretan miracle". Lancet. 355 (9197): 48. doi:10.1016/S0140-6736(05)71990-5. PMID 10615898.
- Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA (2011). "Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis". BMJ. 342 (feb22 1): d671. doi:10.1136/bmj.d671. PMC 3043109. PMID 21343207.
- Tolstrup J, Jensen MK, Tjønneland A, Overvad K, Mukamal KJ, Grønbaek M (2006). "Prospective study of alcohol drinking patterns and coronary heart disease in women and men". BMJ. 332 (7552): 1244–1248. doi:10.1136/bmj.38831.503113.7c. PMC 1471902. PMID 16672312.
- Davidson DM (1989). "Cardiovascular effects of alcohol". The Western Journal of Medicine. 151 (4): 430–9. PMC 1026830. PMID 2686174.
- Facchini F, Chen YD, Reaven GM (1994). "Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity". Diabetes Care. 17 (2): 115–119. doi:10.2337/diacare.17.2.115. PMID 7907975.
- Langer RD, Criqui MH, Reed DM (1992). "Lipoproteins and blood pressure as biological pathways for effect of moderate alcohol consumption on coronary heart disease". Circulation. 85 (3): 910–915. doi:10.1161/01.cir.85.3.910. PMID 1537127.
- Mennen LI, Balkau B, Vol S, Cacès E, Eschwège E (1999). "Fibrinogen: a possible link between alcohol consumption and cardiovascular disease? DESIR Study Group". Arteriosclerosis, Thrombosis, and Vascular Biology. 19 (4): 887–892. doi:10.1161/01.atv.19.4.887. PMID 10195914.
- Paassilta M, Kervinen K, Rantala AO, Savolainen MJ, Lilja M, Reunanen A, Kesäniemi YA (1998). "Social alcohol consumption and low Lp(a) lipoprotein concentrations in middle aged Finnish men: population based study". BMJ. 316 (7131): 594–585. doi:10.1136/bmj.316.7131.594. PMC 28464. PMID 9518912.
- Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ (1999). "Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors". BMJ. 319 (7224): 1523–1528. doi:10.1136/bmj.319.7224.1523. PMC 28294. PMID 10591709.
- Thun MJ, Peto R, Lopez AD, Monaco JH, Henley SJ, Heath CW, Doll R (1997). "Alcohol consumption and mortality among middle-aged and elderly U.S. adults". The New England Journal of Medicine. 337 (24): 1705–1714. doi:10.1056/NEJM199712113372401. PMID 9392695.
- Zhang QH, Das K, Siddiqui S, Myers AK (2000). "Effects of acute, moderate ethanol consumption on human platelet aggregation in platelet-rich plasma and whole blood". Alcoholism, Clinical and Experimental Research. 24 (4): 528–534. doi:10.1111/j.1530-0277.2000.tb02021.x. PMID 10798590.
- Wang Z, Barker TH, Fuller GM (1999). "Alcohol at moderate levels decreases fibrinogen expression in vivo and in vitro". Alcoholism, Clinical and Experimental Research. 23 (12): 1927–1932. doi:10.1111/j.1530-0277.1999.tb04093.x. PMID 10630612.
- Steinberg D, Pearson TA, Kuller LH (1991). "Alcohol and atherosclerosis". Annals of Internal Medicine. 114 (11): 967–976. doi:10.7326/0003-4819-114-11-967. PMID 2024865.
- Fragopoulou, E; Choleva, M; Antonopoulou, S; Demopoulos, CA (2018). "Wine and its metabolic effects. A comprehensive review of clinical trials". Metabolism: Clinical and Experimental. 83: 102–119. doi:10.1016/j.metabol.2018.01.024. PMID 29408458.
- Mukamal KJ, Mackey RH, Kuller LH, Tracy RP, Kronmal RA, Mittleman MA, Siscovick DS (July 2007). "Alcohol consumption and lipoprotein subclasses in older adults". The Journal of Clinical Endocrinology and Metabolism. 92 (7): 2559–66. doi:10.1210/jc.2006-2422. PMID 17440017.
- Rimm EB, Klatsky A, Grobbee D, Stampfer MJ (March 1996). "Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits". BMJ. 312 (7033): 731–6. doi:10.1136/bmj.312.7033.731. PMC 2350477. PMID 8605457.
- Barefoot JC, Grønbaek M, Feaganes JR, McPherson RS, Williams RB, Siegler IC (August 2002). "Alcoholic beverage preference, diet, and health habits in the UNC Alumni Heart Study". The American Journal of Clinical Nutrition. 76 (2): 466–72. doi:10.1093/ajcn/76.2.466. PMID 12145024.
- Pearson, Thomas A. (December 1996). "Alcohol and Heart Disease". Circulation. 94 (11): 3023–3025. doi:10.1161/01.cir.94.11.3023.
- Roerecke, M; Kaczorowski, J; Tobe, SW; Gmel, G; Hasan, OSM; Rehm, J (2017). "The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis". The Lancet. Public Health. 2 (2): e108–e120. doi:10.1016/S2468-2667(17)30003-8. PMC 6118407. PMID 29253389.
- Dorn JM, Hovey K, Williams BA, Freudenheim JL, Russell M, Nochajski TH, Trevisan M (May 2007). "Alcohol drinking pattern and non-fatal myocardial infarction in women". Addiction. 102 (5): 730–9. doi:10.1111/j.1360-0443.2007.01765.x. PMID 17506150.
- Fillmore KM, Kerr WC, Stockwell T, Chikritzhs T, Bostrom A (April 2006). "Moderate alcohol use and reduced mortality risk: Systematic error in prospective studies". Addict Res Theory. 14 (2): 101–132. doi:10.1080/16066350500497983.
- Russell, Sabin (2010-08-28). "UCSF points out flaw in studies tying alcohol to heart health". The San Francisco Chronicle.
- "Alcohol and Heart Health". American Heart Association. August 15, 2014.
- Mukamal KJ, Chiuve SE, Rimm EB (2006). "Alcohol consumption and risk for coronary heart disease in men with healthy lifestyles". Archives of Internal Medicine. 166 (19): 2145–2150. doi:10.1001/archinte.166.19.2145. PMID 17060546.
- Sesso HD, Stampfer MJ, Rosner B, Hennekens CH, Manson JE, Gaziano JM (2000). "Seven-year changes in alcohol consumption and subsequent risk of cardiovascular disease in men". Archives of Internal Medicine. 160 (17): 2605–2612. doi:10.1001/archinte.160.17.2605. PMID 10999974.
- Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, et al. (2013). "Primary prevention of cardiovascular disease with a Mediterranean diet" (PDF). The New England Journal of Medicine. 368 (14): 1279–1290. doi:10.1056/NEJMoa1200303. PMID 23432189.
- Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, et al. (2018). "Retraction and Republication: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013;368:1279-90". The New England Journal of Medicine. 378 (25): 2441–2442. doi:10.1056/NEJMc1806491. PMID 29897867.
- Tolstrup J, Jensen MK, Tjønneland A, Overvad K, Mukamal KJ, Grønbaek M (2006). "Prospective study of alcohol drinking patterns and coronary heart disease in women and men". BMJ. 332 (7552): 1244–1248. doi:10.1136/bmj.38831.503113.7C. PMC 1471902. PMID 16672312.
- O'Keefe JH, Bhatti SK, Bajwa A, DiNicolantonio JJ, Lavie CJ (2014). "Alcohol and cardiovascular health: the dose makes the poison…or the remedy". Mayo Clinic Proceedings. 89 (3): 382–393. doi:10.1016/j.mayocp.2013.11.005. PMID 24582196.