2025 AHA科学声明：饮酒与心血管疾病

METHODOLOGIES AND DESIGNS IN ALCOHOL AND CVD RESEARCH

In most studies, alcohol use has been self-reported, which appears to be less accurate for heavier alcohol consump tion. 24,25 Alcohol consumption, absorption, and metabolism vary across multiple domains, including beverage type, volume, fre quency, duration, concomitant meals, and features inherent to the individual. These vagaries make the measurement of alco hol consumption and the characterization of dose-response relationships difficult, hindering universally applicable determi nants of risks versus harms. In addition, the way in which alcohol consumption has been measured and categorized continues to vary among studies, making it challenging to compare data.

New methodologies, research designs, and statistical analy sis techniques and more reliable methods of alcohol assess ment are being used in studies to analyze the association between alcohol use and CVD. More often, objective measures of alcohol consumption are being used, including transder mal ethanol sensors, 26 home-based urine kits, 27 and biomark ers of alcohol consumption such as phosphatidylethanol. 28 Smartphones are also used to track real-time use of alcohol and to enhance research participation. 29,30

Recent observational studies have implemented strategies to lessen lifetime selection bias, reverse causality, and con founding by including younger cohorts with baseline drinking assessed earlier in the life course, excluding outcomes such as deaths occurring during the first 2 years of follow-up, 31,32 or confining the study population to current drinkers. 33 With regard to study population and, in particular, the type of non drinking reference group (eg, lifetime abstainers/never drink ers, former drinkers, occasional drinkers), Stockwell and colleagues 32 reported that the reference group used could be an important source of discrepancy among studies reporting no risk compared with risk with certain levels of alcohol con sumption. These are examples of inherent limitations in obser vational studies that can be addressed by randomized study group assignment.

Another methodological strategy includes trial emulation, which uses observational data to mimic the design and anal ysis of a hypothetical randomized controlled trial (RCT). This approach allows researchers to leverage real-world data to eval uate the potential effects of an intervention without conducting a traditional RCT. 34 MR techniques have also been advocated as a method to mitigate against conventional confounding by using genetic variants associated with the exposure (eg, alco hol consumption) as instrumental variables (proxies); however, biases remain such as pleiotropy, linkage disequilibrium, weak instrument bias, and dynastic effects (ie, when the expression of the parental genotype in the parental phenotype directly affects the offspring genotype). 35,36 In addition, collider bias and insufficient statistical power may compromise the reliability of MR studies, particularly in the investigation of nonlinear associ ations. Although conventional studies certainly are not without problems, it remains to be seen whether MR and trial emulation studies can effectively remedy these shortcomings.

ALCOHOL USE AND BP

Within the initial hours of the consumption of 1 to 2 drinks of alcohol, BP levels are generally not affected. However, the consumption of ${\geq}3$ drinks has shown a bi phasic effect on BP in which levels are decreased up to 12 hours after consumption and increased for 12 to 24 hours after consumption (systolic BP [SBP] increase, 3.7 mmHg $[95\%$ CI, 2.3–5.1]). 37

A meta-analysis of 36 RCTs evaluating different levels of alcohol use in short- to medium-term cross over and parallel-group designs (2865 participants with and without hypertension) showed that consump tion of ${<}2$ drinks/d compared with no alcohol use was not associated with a significant change in BP. 38 However, drinking ${\geq}3$ drinks/d resulted in significantly higher (increasing with higher alcohol consumption) SBP and diastolic BP (DBP) compared with no or less drinking. In participants who consumed ${\tt\ge}6$ drinks/d and reduced their intake on average by ${\approx}50\%$ , strong reductions in SBP and DBP were observed (mean SBP and DBP differences, $-5.5\ \mathrm{\mm\,Hg}$ $[95\%$ CI, −6.70 to −4.30] and −3.97 mmHg $[95\%$ CI, $-4.70$ to −3.25], respectively). These observational findings demonstrate the benefit of abstinence or a significant reduction in alcohol intake on increased BP. Because the number of women in such trials ranged from only 5 to 48 and only 3 trials presented data specific to women, resulting in uncertain pooled-effect estimates, a need to include more women in such research clearly exists. 38

A recent meta-analysis of cohort studies found a dose-response association between baseline levels of alcohol consumption and BP levels after 5.3 years of follow-up, with no threshold regardless of sex and geographic location. 39 People who drank on average 1 drink/d exhibited a 1.25–mmHg higher SBP ( $\textcircled{95\%}$ CI, 0.5–2.0), whereas those who consumed a median of 3 drinks/d experienced a 4.9–mmHg ( $\textlangle95\%$ CI, 3.7–6.1) higher SBP. 39 The increase in SBP was less for women compared with men.

In a systematic review and dose-response metaanalysis of nonexperimental cohort studies (>600000 participants), there was a linear positive association between alcohol intake and incidence of new-onset hypertension above an alcohol intake of 1 drink/d (12 g/d). 40 In most studies, hypertension was defined as a SBP/DBP $\geq1\,40/90\,\textsf{m m}\,\mathsf{H g}$ , and the follow-up period ranged from 2 to 22 years. Men demonstrated a lin ear positive association between alcohol consumption and the risk of hypertension compared with no alco hol intake, but the risk flattened at intakes of ${\tt>}3$ to 4 drinks/d. 40 In women, however, an increase in the risk of hypertension was found at an alcohol intake exceeding 1 drink/d, with a steeper slope at increasing levels of alcohol consumption. 40

ALCOHOL USE AND CORONARY ARTERY DISEASE

Many studies have examined the relationship between alcohol use and the risk of different subtypes of isch emic heart disease, including MI. The effects of alcohol consumption on the risk and incidence of ischemic heart disease (hereafter referred to as coronary artery disease [CAD]) are complex and vary depending on the amount and pattern of alcohol intake and study design. In addi tion, how CAD was defined or coded (ie, health records such as using International Classification of Diseases codes versus self-report) and which CAD outcomes were evaluated, for example, MI alone or grouped (eg, In ternational Classification of Diseases, 10th Revision codes that include angina, MI, complications after an MI), may demonstrate different risk relationships with alcohol use. For example, a meta-analysis using individual participant data from 83 observational studies found that compared with the reference group (those consuming between 0 and $25\,\mathrm{g}/\mathrm{wk},\approx1.78$ drinks/wk), any consumption above this level (up to 21 drinks/wk) was associated with a lower risk of MI incidence. 33 However, in evaluations of CAD that excluded MI, there was a positive and linear association with ${\geq}7$ drinks/wk. 33 One of the earliest meta-analyses conducted to examine a dose-response relationship reported that alcohol consumption ( ≤ 1 drink/d for women, ${\leq}2$ drinks/d for men) compared with no alcohol consumption was associated with a lower ( $14\%-$ $25\%$ ) risk of incident CAD. 41 In a recent MR study us ing traditional (linear) and nonlinear MR techniques and using a single-nucleotide variant associated with alcohol use disorder (as a means to examine the association be tween a genetically predicted level of alcohol consump tion), Biddinger et al 42 reported that levels of alcohol intake (3–6 drinks/wk) were associated with no to mini mal increases in CAD risk but that risk began to rise at levels exceeding 7 drinks/wk.

In a recent burden-of-proof approach, Carr et al 43 examined the relationship between alcohol consumption and CAD risk from case-control, cohort, and MR studies. This type of analysis incorporates a 6-step framework for conducting a meta-analysis and allows the generation of conservative estimates and interpretations of risk-outcome relationships. 44 The main findings from this anal ysis indicated that data pooled from case-control studies $\scriptstyle(\n=27$ ) were associated with a $13\%$ average reduction in CAD risk across average consumption levels of 0 to 3 drinks/d, whereas the risk reduction found from cohort studies $\scriptstyle(\n=95,$ ) was lower $(5\%)$ across average consump tion levels of 0 to 3.5 drinks/d. For case and cohort stud ies reporting only MI and analyzed together, the lower relative risk across 0 to $50~\mathrm{g/d}$ was ${\approx}0.40$ to 0.80. This analysis revealed no statistically significant associations within the included MR studies. 43 These authors con cluded that “data pooled from cohort and case-control

studies showed weak association between average levels of alcohol consumption ( ≤ 50 g/day) and reduced CAD risk relative to no alcohol intake, while data pooled from MR studies showed no association between genetically predicted alcohol consumption and CAD risk.” 43

Drinking patterns, in particular binge and heavy epi sodic drinking, may modify the relationship between alco hol consumption and CAD risk. For example, moderate drinkers $(<\!30\ \mathsf{g}/\mathsf{d})$ without a history of heavy drinking occasions had a pooled relative risk for CAD incidence of 0.64 $95\%$ CI, 0.53–0.71) compared with lifetime abstainers. However, for moderate drinkers engaging in heavy episodic drinking occasions, the pooled relative risk was 1.12 ( $95\%$ CI, 0.91–1.37), demonstrating that con suming ${\triangleleft30~\mathrm{g/d}}$ was not associated with reduced CAD risk when accompanied by occasional heavy or binge drinking. 45

To summarize, observational studies generally sug gest lower risk of incident MI among individuals who consume alcohol consumption within the recommended US Dietary Guidelines for Americans limits compared with lifetime abstainers, but methodological challenges in the interpretation of these studies sharply limit the cer tainty of a causal relationship. 9 A recently initiated clini cal trial of abstention compared with continued drinking among Spanish adults includes MI in its composite end point; if the trial is successful in its recruitment, retention, and adherence efforts, it will provide important evidence about the potential causality of this relationship. 46

ALCOHOL USE AND STROKE

A meta-analysis of 27 prospective epidemiological stud ies found that compared with no alcohol use or occasion al drinking, low to moderate drinking ( ≤ 2 drinks/d) was associated with a modestly $(8\%-10\%)$ ) decreased risk of ischemic stroke, whereas high (2–4 drinks/d) or heavy ${(>}4$ drinks/d) drinking was associated with an increased risk of all stroke types. 47 Similar findings were reported in an earlier meta-analysis 48 and in later large-scale epi demiological studies. 42,49–51 Analyses confined to current drinkers have revealed a positive dose-response relation ship between alcohol consumption and stroke risk, 33,50 with consistent findings regardless of stroke types, for nonfatal and fatal stroke and for men and women. 33 For example, in a combined analysis of 3 large-scale data sources in 19 high-income countries, a 100–g/wk ( ≈ 1 standard drink/d) increase in alcohol consumption among ≈ 600000 current drinkers increased the risk of ischemic stroke by $13\%$ , intracerebral hemorrhage by $17\%,$ , and subarachnoid hemorrhage by $9\%$ . 33 The overall stroke risk increased by $15\%$ in men and $9\%$ in women per 100–g/wk increase in alcohol consumption. 33 Fur thermore, MR studies in populations of European and Asian ancestries have reported a positive association between genetically predicted alcohol consumption and

risk of total stroke, 42,52 ischemic stroke, 50,52,53 intracere bral hemorrhage, 50,52 and subarachnoid hemorrhage. 52

Overall, evidence from both observational and MR studies indicates that heavy alcohol consumption ${\left(>}4\right.$ drinks/d) is a risk factor for all stroke types. However, the evidence is currently insufficient to draw definitive conclusions about the relationship between moderate alcohol consumption $\scriptstyle\langle\leq2$ drinks/d) and ischemic stroke.

ALCOHOL USE AND ARRHYTHMIAS

Atrial Fibrillation

Meta-analyses have concluded that heavier alcohol con sumption predicts a heightened risk of developing atrial fibrillation (AF). 54,55 Instrumental variable analyses have suggested causal relationships between alcohol expo sure and AF in large populations. 56–58 No clear threshold effect has been identified, nor has any one type of alco holic drink been differentially implicated; the relationship appears to be fairly linear. 55 Data remain conflicting as to whether 1 drink/d on average influences AF risk. 59,60 Alcohol abstainers appear to be at a lower risk of AF than those who continue to drink, 61 and a prospective, random ized trial of Australians consuming at least 10 drinks/ wk demonstrated a substantial reduction in AF burden among those instructed to abstain. 62 Patients with parox ysmal AF fitted with continuous alcohol sensors demon strated a heightened odds of AF occurring within hours of a drinking event, 63 and a per-protocol analysis of random ized N-of-1 trials of AF triggers found alcohol to be the only prespecified trigger associated with AF. 30

Alcohol consumption has been associated with left atrial enlargement and fibrosis, both potential mediators of the alcohol-AF relationship. 64–66 More often, those with alcohol-related AF may also have vagally mediated epi sodes. 67 A randomized, double-blind, placebo-controlled study in humans demonstrated that alcohol acutely shortened pulmonary vein refractory periods. 68

Supraventricular Tachycardia

There is no evidence that alcohol substantially influences the risk of supraventricular tachycardia. 58,67,69

Premature Ventricular Contractions, Ventricular Tachycardia, and Ventricular Fibrillation

There is no consistent evidence that alcohol directly influ ences the risk of premature ventricular contractions, 70,71 ventricular tachycardia, or ventricular fibrillation. 72,73

Sudden Death

Long-term consumption of ≈ 1 drink/d has been associ ated with the lowest risk of sudden death, whereas heavy

alcohol consumption may be associated with a height ened risk of sudden death. 49,72,74,75 Because sudden deaths are now known to have multiple causes, 76 the un derlying mechanisms may be related to alcoholic cardio myopathies, MI, or other noncardiac causes of death. 77

Bradycardias

Longitudinal cohort studies have not found a relationship between alcohol consumption and a higher risk of sinus node disease. 78,79 However, moderate alcohol consump tion has been associated with a lower risk of developing sinus node disease. 78 Longitudinal cohort studies also suggest that alcohol either has no effect or has a protec tive effect on atrioventricular conduction disease. 69,78,80,81

ALCOHOL USE, CARDIOMYOPATHY, AND HF

Long-term excessive alcohol use is associated with the development of a dilated left ventricle, normal or reduced left ventricular wall thickness and mass, and, in advanced stages, HF with reduced left ventricular ejec tion fraction. 16 Current cardiomyopathy schemas recog nize excessive alcohol use as a nongenetic cause of dilated cardiomyopathy but also note that alcohol may act as an epigenetic trigger in the presence of underly ing genetic variants. 82 In the United States, prevalence estimates are elusive and vary among reports. Data from the National Inpatient Sample show that among 352 million estimated hospitalizations of adults, 68 per 100000 were associated with the diagnosis of alcohol ic cardiomyopathy (ACM). This prevalence was higher among men than women. 83 The average age of hos pitalization is similar for men and women $(\approx\!56$ years); however, when stratified by race, both Hispanic men and women were hospitalized at a younger mean age (53 years).

The exact amount and duration of alcohol consump tion associated with the development of ACM remain unknown. Data derived chiefly from case-control stud ies suggest that consuming ${\approx}7$ to 15 standard drinks/d over a 5- to 15-year period is associated with adverse changes in systolic or diastolic ventricular function. 84 Recently, however, in an observational cross-sectional study, Daka et al 85 reported that as few as 4 drinks/wk (in the past month) was associated with an increased odds of diastolic dysfunction.

The risk of ACM among those who consume alco hol is highly heterogeneous, suggesting important interactions with other environmental exposures or genetic factors. The presence of truncating variants in the gene encoding the giant sarcomeric protein titin (the most common cause of a dilated cardiomyopathy), may represent a genetic predisposition and increased

vulnerability to ACM, particularly in individuals report ing a history of alcohol intake at ${\approx}6$ drinks/d over a 5-year period. 86 Women appear to be at risk of ACM when exposed to lower amounts and shorter durations of alcohol use compared with men. 87

Controversy exists on the relationship between alco hol use and the risk of developing HF. Several metaanalyses and prospective cohort studies reported that <1 and 1 to 2 drinks/d were inversely associated with incident HF. 88–90 In contrast, an MR study reported both the absence of an association and an inferred increased risk of HF attributed to alcohol. 42 In the same MR study, when abstainers were excluded, exceeding 7 to 10 drinks/wk was associated with an increased risk of inci dent HF. 42 Similarly, studies of individual participant data from large-scale sources and 19 high-income countries revealed that usual alcohol consumption of ${<}7$ drinks/ wk was not associated with increased HF risk, whereas levels of ${\approx}2\,1$ drinks/wk were associated with an ${\approx}50\%$ increase in HF risk. 33

Among studies and different populations, there appears to be a consensus that exceeding 21 drinks/wk is associated with an increased risk of HF. Recently, and similar to others, Wong and colleagues 91 reported that there was no protective or adverse association between alcohol consumption ${\acute{\le}}5$ drinks/wk) and the risk of developing HF. However, in patients with structural or functional cardiac abnormalities, alcohol use $(\geq5$ drinks/ wk) was associated with an increased risk of progression of asymptomatic left ventricular dysfunction and symp tomatic HF (odds ratio, 5.0 $[95\%$ CI, 1.7–15.5]) over a mean follow-up of 5.4 years. 91

ALCOHOL USE AND SPECIAL POPULATIONS

Some populations may be differentially affected by al cohol consumption related to their sex (women), age (older adults), predominant pattern of drinking (binge drinking), or presence of chronic diseases such as dia betes. For example, women appear to be at risk of ACM when exposed to lower amounts and shorter durations of alcohol use compared with men. 87 The reasons for these sex differences remain unresolved but as noted may be attributable to differences in the absorption, volume of distribution, and first-pass metabolism of alcohol between men and women, which give rise to differences in blood alcohol concentration after the consumption of similar amounts of alcohol. Populations of African and Asian ancestry may also experience dif ferent effects due to genetic polymorphisms in alcoholmetabolizing proteins that may increase the production of acetaldehyde, an aversive and mutagenic intermedi ate metabolic product. 92 Although studies are limited, follow-up of the National Health Interview Study sug

gested that the lowest mortality risk occurred at lower levels of consumption among Black individuals than White individuals. 93

Older adults (50–80 years of age) have been included in many of the studies reviewed here; however, other factors such as health status and prescription drug use may affect the effects of alcohol on cardio vascular conditions. Older adults may be vulnerable to alcohol-medication interactions because of changes in metabolism and increased likelihood of taking multiple medications. This is important because among adults 50 to 80 years of age, $67\%$ reported drinking occasionally in the past year. 94 Among those who drank, $27\%$ (1 in 4) reported consuming ${\tt\ge}6$ drinks on at least 1 occasion in the past year. 94

Numerous reports indicate that young adults (18–30 years of age) engaging in binge drinking exhibit early signs of CVD such as endothelial dysfunction (a pre cursor to atherosclerosis), 95 coronary calcification, 96 and arterial stiffness. 97 Others have reported that binge drinking in young adults was associated with higher SBP, 98,99 and binge drinking in adolescence (12–18 years of age) was associated with a higher odds of high SP (SBP ≥ 130 mmHg /DBP ${\geq}80\,\mathsf{\ m m\,H g},$ ) in young adulthood (24–32 years of age). 100 In addition, several case-control studies have reported that binge drink ing was associated with an increased risk of different stroke types in young adults. 46,101,102 In an analysis of INTERSTROKE data from 32 countries, binge drink ing was associated with an odds ratio of 5.44 $\textlangle95\%$ CI, 1.81–16.4) of ischemic stroke among patients ${\le}45$ years of age. 102 The potential for arrythmias among young adult binge drinkers was examined in the pro spective MunichBREW II study. 103 Over a voluntary binge drinking episode (blood alcohol levels $\geq\!120\ \mathsf{m g}^{\prime}$ dL), young adults (N=202; mean age, 29.9 years) were monitored with a 48-hour electrocardiogram encom passing the time frame during and after a binge epi sode. The main findings were a significant increase in heart rate (maximum rate, 97±16 bpm 4 hours after consumption) and a significant increase in the percent age of atrial tachycardia beats. Only 1 participant devel oped AF, and 4 other participants experienced clinically relevant supraventricular and ventricular arrhythmias. 103 On the basis of these findings, there is a low occur rence of “holiday heart syndrome,” a term used to refer to arrhythmias associated with binge-like drinking epi sodes in young adults.

There is a high rate of the co-occurrence of dia betes and CVD. In patients with diabetes, a few RCTs have examined the effects of alcohol intake on gly cemic control and other cardiovascular parameters in patients. Cardiovascular Diabetes and Ethanol ran domized patients with type 2 diabetes $(\backslash\backslash{=}22$ ; age, 40–75 years) to a low-risk drinking group (1 drink/ wk of either red or white wine) or mineral water with

a Mediterranean diet/dinner for 2 years. 104 Findings indicated that this level of alcohol consumption was safe, and there were some small improvements in lipo proteins in the red wine group (a 2.0–mg/dL increase in high-density lipoprotein cholesterol) and a decrease in fasting glucose $(-1\,7.2\,\ m\mathsf{g}/\mathsf{d L})$ in the white wine group; no changes were found among groups in BP or measures of adiposity. 104 A crossover study reported that 4 weeks of red wine consumption $(\approx\!2$ drinks/d) in men $\scriptstyle(\n=19)$ ) and women $\mathrm{(n{=}5,}$ ) with type 2 diabetes significantly increased awake SBP $(2.5{\pm}1.2\ {\sf m m}\,{\sf H g})$ but had no effect on glycemic control, high-density

Table 2. Cardiovascular Biomarkers and Changes With Moderate Alcohol Use\*

|biomarker|Change reported in study| |---|---| |Lipid profiles|| |Total cholesterol|No significant change 107,10| |High-density lipoprotein| 3 mg/dL107 1 70/%0108 | |Low-density lipoprotein| ↓ -3.09 mg/ dL107 No significant change 108 | |Triglycerides| No significant change107 ↓ -2.10%0108 | |Lipoprotein(a)|↓ -0.041g/L107| |Apolipoprotein八1|10.0494 g/L107| |Hemostaticfactors|| |Plasminogen activator inhibitor 1| 4.33 ng/ mL| |Fibrinogen|↓ -0.1393 g/L107| |E-selectin|No significant change 107| |Inflammation|| |C-reactiveprotein|NOs significant change10%,10| |Interleukin 6|↓ -0.433 pg/mL107| |Tumor necrosisfactor-α|No significant change107| |Adipokines|| |leptin|No significant change107| |Adiponectin| 1 0.06 mg/L107 1 4.3%108 | |Glycemicparameters|| |fastingglucose|No significant change109| |Fasting insulin|No significant change109| |Hemoglobin Ao|No significant change 109| |Estimated insuln sensitivity|No significant change109|

\*Data were extracted from 1 meta-analysis 107 and another study using data from 3 prospective cohorts of US adults (Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study). 108 Huang et al 107 conducted a meta-analysis that included controlled short-term intervention studies (1–8 weeks) comparing moderate alcohol consumption (1–2 drinks/d) with no alcohol use. Values are median change values in designated biomarker. 107 Studies that included heavy drinking were excluded. 107 Li et al 108 compared individuals with moderate alcohol intake (average alcohol intake, 3.3 servings/wk) with nondrink ers or those who drank less than 1 serving/d. Values are percentage differences in log-transformed values. 108 Glycemic data are from Schrieks et al. 109

lipoprotein cholesterol, fibrinogen, C-reactive protein, or plasma homocysteine. 105 In a 2-year trial among adults with type 2 diabetes, no significant progression was observed in carotid plaque volume among indi viduals randomized to water, white wine, or red wine $'\!P\!\!=\!\!0.9$ between groups). 106 In a post hoc analysis among individuals in the highest tertile of baseline carotid plaque volume, wine (red and white) signifi cantly reduced plaque volume over 2 years compared with baseline, whereas no changes were found in the water group. 106

Table 3. Patient Education About the Most Recent Evidence on Alcohol Use

|bp| Alcohol consumption, even in moderation (1-2 drinks/d), can exacerbate high BP, and for some individuals, reducing or eliminating alcohol intake may be an important part of | |---|---| |Stroke| can exacerbate high BP, and for some individuals, reducing or eliminating alcohol intake may be an important part of managing hypertension. | |CAD| Heavy (≥5/4 [men/women] drinks on any given day or ≥15/8 [men/women] drinks/wk) alcohol consumption increases the risk of all types of stroke. The impact of |

ACM indicates alcoholic cardiomyopathy; AF, atrial fibrillation; BP, blood pres sure; CAD, coronary artery disease; DCM, dilated cardiomyopathy; and HF, heart failure.

\*In patients with DCM, Tayal et al 117 found that prior (baseline) moderate to excessive alcohol consumption of ( ≈ 1–5 drinks/d for women and ${\approx}2{-}5$ drinks/d for men) was not associated with adverse cardiovascular outcomes during the median follow-up of 3.9 years (hazard ratio, 1.29 $[95\%$ CI, 0.73–2.26] for the composite end point of cardiovascular mortality and HF and arrhythmic events). However, among patients who met this composite end point $\scriptstyle(\n=78)$ ), only 15 had a history of moderate alcohol excess. 117

PHYSIOLOGICAL MECHANISMS AND OTHER MEDIATING FACTORS ASSOCIATED WITH ALCOHOL CONSUMPTION

The physiological mechanisms and other mediating factors associated with alcohol use and cardiovascular outcomes are complex and multifaceted and depend on the quantity and pattern of consumption. Some key mechanisms related to CVD may include effects on lipid profiles, influence on coagulation and thrombosis, and metabolic (ie, fasting glucose and insulin) alterations, as well as body weight. Other mediating factors might in clude socioeconomic status (SES), drinking with meals, and presence of other health factors.

Table2 notes the directional (significant) changes in selected cardiometabolic parameters summarized from 1 meta-analysis 107 and another study using data from 3 cohorts of US adults. 108 Glycemic data were derived from a systematic review of moderate alcohol consump tion (in most studies, defined as 1–2 drinks/d). 109 In addition, alcohol consumption (2 drinks/d) was found to reduce collagen-stimulated platelet aggregation 110 while heavier drinking (1.5 g/kg, \~ 7 drinks) was associated with acutely increased platelet aggregation. 111 Simul

taneous intake of aspirin (325 mg) with alcohol (3–4 drinks) potentiates aspirin-induced bleeding time. 112

Obesity is an important cardiovascular risk factor; several studies have examined the relationship between obesity and alcohol use, and findings are equivocal. 113 The most recent meta-analysis to date included 127 studies, and findings differed when cohort and crosssectional studies were analyzed separately. Among the cohort studies analyzed, no association with alcohol intake was found for risk of overweight (body mass index ${\geq}25{-}30\ \mathsf{k g/m^{2}})$ ), obesity (body mass index ${\geq}30\ \mathsf{k g/m^{2}}$ ), and overweight/obesity (body mass index ${\geq}25~\mathsf{k g/m^{2}}$ ). However, among the cross-sectional studies analyzed, alcohol intake was found to increase the odds for being overweight and overweight/obese, but no association was found for the odds of being obese. In this same study and in a dose-response analysis among cross-sectional studies, light alcohol use $({<}1\,4\ \mathsf{g}/\mathsf{d})$ ) had no association with being overweight, obese, and overweight/obese. Similarly, alcohol use $(\uparrow4{-}28\ \mathfrak{g}/\mathfrak{d})$ had no association with being overweight or overweight/obese; however, there was $16\%$ lower odds of being obese. Heavy ${\left(>28\right.}$ g/d) alcohol use was positively associated with being overweight and overweight/obese, but no association

 Figure 2. Alcohol intake and cardiovascular disease. This figure summarizes data from studies reviewed herein and indicates the general direction of risk (with an up or down arrow) that has been observed with particular study designs. It is important to note that with most of these studies, especially those using observational study designs, fully accounting for unmeasured, unknown, residual confounding remains challenging. ABV indicates alcohol by volume; and RCT, randomized controlled trial.

was found with obesity. As the authors of this study note, heterogeneity among studies was high, and examining the relationship between alcohol use and weight is com plicated and mediated by many factors such as physical activity, dietary habits, genetics, and sex. Alcoholic bev erages can be a large source of calories: 1 g of pure alcohol (ethanol) contains 7 calories. A standard glass of wine on average equals 158 calories, and some alco holic beverages may contain ${\tt\ge}500$ calories. Therefore, it seems that addressing problematic alcohol use should be an important component of obesity prevention and management strategies.

Findings from some studies suggest that SES and drinking during meals may be important mediating fac tors of alcohol use and cardiovascular risk association. For example, Ortolá et $a|^{31}$ examined the association of different alcohol consumption levels with 12-year CVD mortality among older adults $(\mathord{\geq}60$ years of age) with consideration of SES factors, beverage preference, and drinking with meals. Compared with occasional drinkers $({\leq}2.8\ {\mathsf{g}}/{\mathsf{d}})$ ), low $(\geq\!20\mathrm{~}\mathsf{g}/\mathsf{w}|\mathsf{k}\!-\!20\mathrm{~}\mathsf{g}/\mathsf{d}$ for men and ${\geq}20~\mathrm{g}V$ wk–10 g/d for women) and moderate $(\geq\!20\mathrm{-}40~\mathsf{g}/\mathsf{d}$ for men and ${>}10{-}20\,\mathrm{g/d}$ for women) drinking was not asso ciated with CVD mortality risk, whereas high-risk alcohol consumption $({\geq}40\,\mathfrak{g}/\mathfrak{d}$ for men and ${\geq}20\,\mathsf{g}/\mathsf{d}$ for women) was associated with higher CVD mortality (hazard ratio, 1.21 $[95\%$ CI, 1.04–1.41]). CVD mortality was higher in those with lower SES status and the presence of healthrelated factors; however, wine preference and drinking during meals modified and negated the association of mean alcohol intake with CVD mortality in all drinkers with lower SES and the presence of health-related fac tors but especially in high-risk drinkers.

Last, the way in which alcohol affects vascular, myocar dial, and brain function may include many changes in cel lular and molecular mechanisms. However, reviewing these mechanisms is beyond the scope of this scientific state ment, but it would be interesting to explore them in future work. Several reviews have been published that include details related to cellular and molecular mechanisms potentially involved in mediating the effects of alcohol. 16,114

PATIENT EDUCATION: WHAT DO WE TELL THE PATIENT?

Providing specific alcohol use recommendations for in dividuals with and without CVD conditions remains chal lenging because of the lack of data from well-conducted RCTs. If patients are currently consuming alcoholic bever ages, Table3 summarizes evidence that could be shared with patients. 115,116 In addition, it could be communicated to patients that consuming alcoholic beverages with meals will slow down the absorption of alcohol, as well as alter nating alcoholic beverages with nonalcoholic beverages.

Some health care systems have begun to document alcohol use as a seventh vital sign. Screening for alcohol

use and discussing what constitutes hazardous and harm ful use (Table1) are relevant to all patients. It is impor tant to note that among patients surveyed in cardiology services $(\mathord{\mathsf{N}}\!\!=\!\!498)$ ), $66.3\%$ were exposed to reports that indicated moderate drinking can be good for the heart. 118 It is important to deliver the right message because that study also reported that exposure to reports of healthyheart effects or mixed messages about the cardiovas cular effects of alcohol were associated with increased odds of hazardous alcohol use (odds ratio, 1.67 [95% CI, 1.02–2.74]). 118 Clinicians should reinforce healthy lifestyle behaviors such as regularly engaging in physical activ ity, avoiding tobacco use, and maintaining healthy body weight to achieve cardiovascular health and to prevent disease. Other considerations for consuming alcoholic beverages also can be shared with patients (Figure1).

CONCLUSION, KNOWLEDGE GAPS, AND FUTURE DIRECTIONS

The overwhelming evidence demonstrates that heavy (generally ${>}2$ drinks/d) and binge alcohol consumption is harmful to cardiovascular health. Abstinence and reducing alcohol intake may lower the risk for certain cardiovascu lar conditions such as hypertension. Uncertainty remains about the true cardiovascular risk of drinking lightly such as 1 to 2 drinks/d (Figure2 provides a graphical summary of data). Multiple unknowns persist, providing opportunities for important research into the effects of this commonly

Table 4. Research Gaps

| More research is needed on women (across all age groups) because women have been excluded or underenrolled in alcohol use and CVD studies. | |---| | Differential effects by different types of alcoholic drinks, especially red wines, and potential interaction effects of consuming alcoholic beverages with meals require further investigation. | | Interactions between alcohol use and cardiovascular medications should be examined. | | The influence of changes in alcohol consumption in middle-aged and older adults on future CVD risk needs to be assessed. | | Research is needed that incorporates biomarkers of alcohol use to corroborate self-report. For example, Dominquez-Lopez et al reported correlations between urinary tartaric acid (a biomarker of wine consumption) and lower risk for CVD events (cardiovascular death, MI, stroke, or HF).119 | | Studies are needed of the influence of long-term consistent alcohol intake (considering changes in alcohol drinking over time) and changes in confounders. | | Research is needed on the mechanisms by which alcohol consumption affects the risk of specific individual CVDs. For example, Wood et al33 found that SBP only partially mediated the association between alcohol consumption and stroke risk. | | The effects of alcohol consumption in patients with diabetes and specific CVDs need to be studied. | | Randomized controlled trials are needed to determine the true health effects of light or moderate drinking (1-2 drinks per day or less). |

CVD indicates cardiovascular disease; HF, heart failure; and MI, myocardial infarction.

consumed substance. Although this document cannot review every knowledge gap, several are worth highlight ing. More research into the following areas is needed: the heterogeneous effects within individuals, potentially driven by differences in SES status, other demographics, interac tions with other environmental or dietary exposures, con comitant comorbidities, balancing overall health effects (eg, differential effects related to CVD versus cancer), and genetics, as well as effective strategies for behavior change to influence the healthiest patterns of alcohol con sumption, for which evidence in populations without alco hol use disorders is especially lacking. In addition, to help establish biological plausibility, more research is needed on the cellular and molecular mechanisms that may under pin different patterns and amounts of alcohol consumption (more research gaps are noted in Table4). Last, research using what has been established as the gold standard to provide the highest level of evidence and RCT designs is needed to better elucidate the true health effects of light to moderate alcohol consumption (1–2 drinks/d).

ARTICLE INFORMATION

The American Heart Association makes every effort to avoid any actual or po tential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel.

Disclosures

Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

This statement was approved by the American Heart Association Sci ence Advisory and Coordinating Committee on April 14, 2025, and the American Heart Association Executive Committee on May 22, 2025. A copy of the document is available at https://professional.heart.org/statements by using either “Search for Guidelines & Statements” or the “Browse by Topic” area. To purchase additional reprints, call 215-356-2721 or email Meredith. Edelman@wolterskluwer.com

The American Heart Association requests that this document be cited as fol lows: Piano MR, Marcus GM, Aycock DM, Buckman J, Hwang C-L, Larsson SC, Mukamal KJ, Roerecke M; on behalf of the American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Stroke Council. Alcohol use and car diovascular disease: a scientific statement from the American Heart Association. Circulation . 2025;151:e•••–e•••. doi: 10.1161/CIR.0000000000001341

Writing Group Disclosures

| writing group member |Employment|Research grant| other research support | speakers bureau/ honoraria | expert witness | Ownership interest | Consultant/ advisory board |other| |---|---|---|---|---|---|---|---|---| | Mariann R. piano | Vanderbilt University School of Nursing |none|none|none|none|none|none|none| | Gregory M. marcus | University of California, San Francisco |none|none|none|none|none|none|none| | Dawn M. Aycock |Georgia State University|none|none|none|none|none|none|none| | jennifer Buckman |Rutgers University| NIH (Pl, mentor, sponsor, collaborator on various NIH grants, active and pending* | NIH (PI of Ro1 grants)* |none|none|none|none| Rutgers University (professor)*; NIH (PI)* | | Chueh-Lung hwang | University of Texas at Arlington |NIAAA (PI)*|none|none|none|none|none|none| | Susanna C. larsson | Karolinska Institute, Institute of Environmental Medicine (Sweden) |none|none|none|none|none|none|none| | Kenneth J. mukamal | Beth Israel Deaconess Medical Center | US Highbush Blueberry Council (investigator-initiated grant to his institution for which he serves as PI)t; NIH* |none|none|none|none|none|none| | michael Roerecke | Centre for Addiction and Mental Health Institute for Mental Health Policy Research (Canada) | Canadian Institutes of Health Research (PI)* |none|none|none|none|none|none|

The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit https://professional.heart.org/statements. Select the “Guide lines & Statements” drop-down menu, then click “Publication Development.”

Permissions: Multiple copies, modification, alteration, enhancement, and dis tribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the “Copyright Permissions Request Form” appears in the second paragraph (https://www.heart.org/en/about-us/ statements-and-policies/copyright-request-form).

Acknowledgments

The authors thank Rachel Walden at Vanderbilt University Jean and Alexander Heard Libraries for their invaluable assistance in researching and locating key re sources for this publication. In addition, the authors are grateful to Daien Sanchez for their editorial assistance.

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $\S5000$ or more during any 12-month period, or $5\%$ or more of the person’s gross income; or (b) the person owns $5\%$ or more of the voting stock or share of the entity, or owns $\S5000$ or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition. \*Significant.

Reviewer Disclosures

|reviewer|Employment|Research grant| other research support | speakers' bureau/ honoraria | expert witness | Ownership interest | Consultant/ advisory board |other| |---|---|---|---|---|---|---|---|---| | Frank B. u ||none|none|none|none|none|none|| || Harvard T.H. Chan School of Public Health |||||||none| | stefan Kiechl |Medical University||none|none|none|none|none|none| ||Innsbruck (Austria)| Austrian Research Promotion Agency; centre within the Competence Centers for Excellent Technologies VASCage funded by the Federal Ministry for Climate Action, Environment, Eergy Mobility, Inovation and Technology, the Federal Ministry of Labour and Economy, and the federal states of Tyrol, Salzburg, ||||||| | Peter M. Kistler | Baker Heart Diabetes Institute, Alfred Hospital, University of Melbourne (Australia) |none|none|none|none|none|none|| |||||||||none| | Eileen M. Redmond | University of Rochester Medical Center | NIH RO1 (basic science project to investigate the effect of alcohol on endothelial plasticity as it pertains to cardiovascular disease)* |none|none|none|none|none|none|

This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Ques tionnaire, which all reviewers are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $\S5000$ or more during any 12-month period, or $5\%$ or more of the person’s gross income; or (b) the person owns $5\%$ or more of the voting stock or share of the entity, or owns $\S5000$ or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition. \*Significant.

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