Association between alcohol consumption and systolicventricular function: A population-based studyHaroon Yousaf, MD, a Richard J. Rodeheffer, MD, b Timothy E. Paterick, MD, JD, a Zain Ashary, BS, a

Mirza Nubair Ahmad, MBBS, a and Khawaja Afzal Ammar, MD a Milwaukee, WI and Rochester, MN

Background Although moderate alcohol consumption is associated with decreased clinical heart failure, there are nopopulation-based studies evaluating the relationship between alcohol consumption and left ventricular (LV) systolic function.We sought to evaluate the relationship between alcohol consumption and LV systolic function in the community.

Methods In a population-based random sample of 2,042 adults, age ≥45 years, we assessed alcohol consumption by aself-administered questionnaire. Responders were categorized by alcohol consumption level: abstainer, former drinker, lightdrinker (b1 drink a day), moderate drinker (1-2 drinks a day), and heavy drinker (N2 drinks a day). Systolic function wasassessed by echocardiography.

Results We identified 38 cases of systolic dysfunction in 182 abstainers, 309 former drinkers, 1,028 light drinkers, 251moderate drinkers, and 146 heavy drinkers. A U-shaped relationship was observed between alcohol consumption andmoderate systolic dysfunction (LV ejection fraction [LVEF] ≤40%), with the lowest prevalence in light drinkers (0.9%) comparedto the highest prevalence in heavy drinkers (5.5%) (odds ratio 0.14, 95% CI 0.04-0.43). This association persisted acrossdifferent strata of risk factors of systolic dysfunction as well as in multivariate analysis. No significant association betweenalcohol consumption and systolic function was seen in subjects with LVEF N50% or ≤50%.

Conclusions There is a U-shaped relationship between alcohol consumption volume and LVEF, with the lowest risk ofmoderate LV dysfunction (LVEF ≤40%) observed in light drinkers (b1 drink a day). These findings are parallel to the relationshipbetween alcohol consumption and cardiovascular disease prevalence. (Am Heart J 2014;0:1-8.)

A U-shaped relationship exists between the level ofalcohol consumption and prevalence of clinical heartfailure.1 Regular heavy alcohol consumption is associatedwith impairment of left ventricular (LV) function2,3 andoccasionally results in overt cardiomyopathy.4 Alterna-tively, regular but moderate alcohol consumption isassociated with prevention of heart failure.5,6 Althoughthis relationship between alcohol consumption andclinical heart failure has been extensively studied, thereverse parabolic association between alcohol consump-tion and ventricular systolic function has not beenevaluated in a population-based study. Because both

rom the aAurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke’s Medicalenters, University of Wisconsin School of Medicine and Public Health, Milwaukee, WI,nd bMayo Clinic and Foundation, Rochester, MN.inancial support: US Public Health Services, National Institutes of Health, HL-RO1-55902.ubmitted December 6, 2013; accepted February 25, 2014.eprint requests: Khawaja Afzal Ammar, MD, Aurora Cardiovascular Services, 2801 Winnickinnic River Pkwy, #840, Milwaukee, WI 53215.-mail: publishing28@aurora.orgttp://dx.doi.org/10.1016/j.ahj.2014.02.014002-87032014, Mosby, Inc. All rights reserved.

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moderate drinking and heavy drinking are prevalent inthe community, we hypothesized that moderate alcoholconsumption would be associated not only with reducedprevalence of clinical cardiovascular disease but also withreduced prevalence of systolic dysfunction. We alsopostulated that heavy alcohol consumption would beassociated with increased prevalence of LV systolicdysfunction. This hypothesis was tested in a randomlysampled, population-based cohort of 2,042 people ≥45years old in Olmsted County, Minnesota.

MethodsThe Olmsted County Heart Function Study was approved by

the Mayo Foundation and Olmsted Medical Center InstitutionalReview boards, and written informed consent was obtainedfrom the subjects. The present study was carried out withfunding from US Public Health Services, National Institutes ofHealth, grant HL-RO1-555902. The authors are solely responsiblefor the design and conduct of this study, all study analyses, thedrafting and editing of the paper, and its final contents.

Study settingOf the 124,277 residents of Olmsted County, as of the 2000

census, 90% were white. Other characteristics of this

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population and its unique resources for population-basedepidemiological research have been previously described.7,8

Population sampling and data collectionA random sample of residents ≥45 years old as of January 1,

1997, was identified. A 7% sampling fraction was applied withineach gender- and age- (5 years) specific stratum. Of the 4,203subjects invited, 2,042 (48.6%) participated. Enrollment tookplace from January 1, 1997, to September 30, 2000. Subjectscompleted a self-administered questionnaire and underwentphys i ca l examina t ion , e l ec t roca rd iog raphy , andechocardiography.

Definitions of selected clinical conditionsMedical record review was carried out by 4 trained chart

abstractor nurses. The median length of participant medicalrecord archive was 36 years. Heart failure was diagnosed ifFramingham criteria were fulfilled.9,10 Myocardial infarction andhypertension were diagnosed with criteria from the WorldHealth Organization and Sixth Report of the Joint NationalCommittee, respectively.11,12 Coronary artery disease, angina,diabetes, cerebrovascular accident, transient ischemic attack,and peripheral vascular disease were diagnosed if documentedby a physician. Angina was assessed based on a self-administered questionnaire by Rose et al.13 Previous smokerswere those who had smoked ≥100 cigarettes in the past butwere not currently smoking. In accordance with the NationalCholesterol Education Program Adult Treatment Panel IIIcriteria,14 metabolic syndrome was defined by the presenceof ≥3 of the following criteria: (1) central obesity defined as awaist circumference ≥102 cm in men and ≥88 cm in women,(2) triglyceride level N150 mg/dL (to convert to millimoles perliter, multiply by 0.0113), (3) high-density lipoprotein choles-terol level b40 mg/dL in men and b50 mg/dL in women (toconvert to millimoles per liter, multiply by 0.0259), (4) bloodpressure of ≥130/85 mm Hg, and (5) fasting glucose level of≥110 mg/dL (to convert to millimoles per liter, multiply by0.0555).Anthropometric measurements were carried out by a

trained research nurse with the subjects in the standingposition. Body mass index was measured as weight (kilo-grams)/height (meters).2

Echocardiographic analysisAll subjects underwent echocardiography following a

standardized protocol as previously described.15–17 A singlecardiologist, blinded to clinical status, interpreted allechocardiograms.

Measurement of LV systolic functionEjection fraction was measured using M-mode echocardiogra-

phy, 2-dimensional echocardiography by Simpson’s biplanemethod, and visual estimate. As LV ejection fraction (LVEF) fromthese 3methods was highly correlated and the visual estimatewasavailable in N99% of participants, visual estimate was usedin analysis.

Quantification of alcohol consumptionSubjects completed a self-administered questionnaire that first

asked if they had ever consumed alcohol. A negative answerresulted in classification as an abstainer. Then they were asked ifalcohol had been consumed in the last 12 months. A negativeanswer resulted in classification as a former drinker. An affirmativeanswer to both questions led the subject to 3 separate sections onbeer, wine, and liquor. The 12 frequency categories ranged from 3to 4 times a day to once a year. The 16 quantity categories rangedfrom 1 to ≥16 drinks per day. The estimated alcohol content perdrink was 12.8 g for beer, 11 g for wine, and 14 g for spirits (liquoror whiskey). Responders were categorized further by alcoholconsumption level: light drinker (b1 drink a day, b11 g/d),moderate drinker (1-2 drinks a day, 11-28 g/d), and heavy drinker(N2 drinks a day, N28 g/d).

Statistical analysisCategorical data are summarized as a percentage of the group

total with corresponding 95% CI based on normal approximation,and comparison between groups was based on the χ2 test forassociation. Continuous variables are summarized as mean ±standard deviation, and comparisons between groups were basedon analysis of variance models. Post–analysis of variance compar-isons of continuous variables were based on t test, but noadjustments for multiple comparisons were made. Multivariateanalysis was carried out with logistic regression for categoricalvariables and multiple linear regressions for continuous variables.Two-sidedP values b.05were considered significant. Analyseswereperformed using JMP Genomics, 5.0 (SAS Institute, Cary, NC).

ResultsCharacteristics of study participantsLetters of invitations were sent to 4,203 individuals. Of

the 2,042 individuals (48.6%) who participated, 1,916 (941men and 975 women) had valid data and were included inthe present analysis. Themajority of participantswere lightdrinkers (n = 1,028, 53.7%), with smaller proportions ofabstainers (n = 182, 9.5%), former drinkers (n = 309,16.1%), moderate drinkers (n = 251, 13.1%), and heavydrinkers (n = 146, 7.6%). Table I shows the baselinecharacteristics of participants categorized by their alcoholconsumption habits. Abstainers were more likely to bewomen, were less likely to be smokers, but were found tohave a high prevalence of diabetes mellitus and hyperten-sion. Light drinkers (b1 drinks a day) represented a healthysubset of the population with the lowest mean age, 2%current smokers, 6%diabetic, and 27%hypertensive. Heavydrinkers (N2 drinks a day) had the highest prevalence ofcurrent smokers (22%) and mean high-density lipoproteinlevels (48.3 ± 16.1).

Alcohol consumption and prevalence of clinicalcardiovascular diseaseTable II shows the prevalence of clinical cardiovascu-

lar disease (all cardiovascular diseases combined)categorized by alcohol consumption. The prevalence

Table I. Characteristics of participants categorized by alcohol consumption volume

Abstainers(n = 182)

Former drinkers(n = 309)

b1 drink/d(n = 1028)

1-2 drinks/d(n = 251)

N2 drinks/d(n = 146) P

Age, y 68.0 ± 10.8 63.0 ± 11.2 60.9 ± 10.2 61.6 ± 9.8 62.1 ± 9.6 b.0001Women, n = 975 138 (75.8) 173 (56.0) 546 (53.1) 89 (35.5) 29 (19.9) b.0001Body mass index, kg/m2 29.4 ± 6.3 29.1 ± 5.5 28.3 ± 5.4 27.6 ± 4.6 28.5 ± 4.7 b.0001Obese (body mass index ≥30) 72 (39.6) 121 (39.1) 320 (31.1) 60 (23.9) 47 (32.2) .0008Smoking history

Past 22 (12.1) 122 (39.5) 430 (41.8) 134 (53.4) 87 (59.6)Current 4 (2.2) 27 (8.7) 78 (7.6) 34 (13.5) 32 (21.9) b.0001Never 156 (85.7) 160 (51.8) 520 (50.6) 83 (33.1) 27 (18.5)

Diabetes mellitus 23 (12.6) 39 (12.6) 61 (5.9) 17 (6.8) 5 (3.4) b.0001Hypertension 69 (37.9) 109 (35.3) 280 (27.2) 62 (24.7) 42 (28.8) .0019HDL 45.4 ± 14.4 43.9 ± 13.7 45.3 ± 14.3 48.2 ± 15.0 48.3 ± 16.1 .0021Metabolic syndrome 84 (45.1) 132 (42.4) 378 (36.7) 84 (33.3) 55 (37.1) .046

Data are expressed as mean ± SD or number (percentage).HDL, High-density lipoprotein.

Table II. Prevalence of cardiovascular disease according to alcohol consumption volume

Abstainers(n = 182)

Former drinkers(n = 309)

b1 drink/d(n = 1028)

1-2 drinks/d(n = 251)

N2 drinks/d(n = 146) P

Myocardial infarction 17 (9.3) 23 (7.4) 43 (4.2) 8 (3.2) 7 (4.8) .008Coronary artery disease 30 (16.5) 48 (15.5) 102 (9.9) 33 (13.2) 22 (15.1) .015Heart failure 8 (4.4) 12 (3.9) 17 (1.7) 6 (2.4) 3 (2.1) .078Angina 22 (12.1) 36 (11.7) 63 (6.1) 22 (8.8) 12 (8.2) .006Cerebrovascular accidents 4 (2.2) 10 (3.2) 12 (1.2) 3 (1.2) 2 (1.4) .13Transient ischemic attack 8 (4.4) 8 (2.6) 15 (1.5) 6 (2.4) 2 (1.4) .11Peripheral vascular disease 9 (4.9) 9 (2.9) 17 (1.7) 7 (2.8) 4 (2.7) .09Any cardiovascular disease 47 (25.8) 70 (22.7) 138 (13.4) 43 (17.1) 26 (17.8) b.0001

Data are expressed as number (percentage).

Yousaf et al 3American Heart JournalVolume 0, Number 0

of combined cardiovascular disease indicated a U-shapedrelationship (Table II, row 8). When cardiovasculardiseases were evaluated individually, the U-shapedrelationship persisted, maintaining statistical signifi-cance only in myocardial infarction, coronary arterydisease, and angina.

Alcohol consumption and systolic functionTable III shows the mean LVEF and prevalence of

systolic dysfunction categorized by alcohol consumption.There was no clinically meaningful difference in meanLVEF in different alcohol consumption groups. Similarly,there was no statistical association between alcoholconsumption group and prevalence of normal systolicfunction (LVEF N50%) (Table III; row 2) or any systolicdysfunction (LVEF ≤50%) (Table III, row 3). However,when the participants were stratified with respect tomoderate systolic dysfunction (LVEF ≤40%) (Table III;row 4), a U-shaped relationship emerged. The prevalenceof moderate systolic dysfunction (LVEF ≤40%) was thelowest in light drinkers, with prevalence increasing withincreasing or decreasing consumption of alcohol, indi-

cating a U-shaped relationship (Figure 1). In those withLVEF ≤40% (Table III, row 4; Figure 1), the prevalence ofsystolic dysfunction increased 6-fold between lightdrinkers (0.9%) and heavy drinkers (5.5%; P b .001).The light drinkers were further stratified into habitual

drinkers (those who drink at least once a week) andnonhabitual drinkers (those who drink less than once aweek). The prevalence of systolic dysfunction (LVEF ≤50)was lower in habitual drinkers compared to nonhabitualdrinkers (4.06% vs 5.91%). A similar trend was seen in theprevalence of moderate systolic dysfunction (LVEF ≤40),whichwas lower in habitual drinkers (0.24%) compared tononhabitual drinkers (1.15%).The association between alcohol consumption and

moderate systolic dysfunction is further evaluated inTable IV and Figure 2 by stratification of the participantsinto multiple strata of systolic dysfunction risk factors.The beneficial association was not statistically significantin the young (≤65 years), smokers, nonobese, and thosewithout metabolic syndrome.The U-shaped association between alcohol consump-

tion and LV systolic function persisted across different

Table III. Left ventricular systolic function association with alcohol consumption volume

Abstainers(n = 182)

Former drinkers(n = 309)

b1 drink/d(n = 1028)

1-2 drinks/d(n = 251)

N2 drinks/d(n = 146) P

LVEF 63.9 ± 7.9 62.4 ± 8.0 63.1 ± 6.4 61.8 ± 7.5 61.4 ± 7.9 b.001LVEF N50% 172 (94.5) 279 (90.3) 977 (95.0) 232 (92.4) 137 (93.8) .064LVEF ≤50% 10 (5.5) 30 (9.7) 51 (5.0) 19 (7.6) 9 (6.2) .11LVEF ≤40% 6 (3.3) 6 (1.9) 9 (0.9) 9 (3.6) 8 (5.5) b.001

Data are expressed as mean ± (SD) or number (percentage).

Figure 1

Alcohol intake and prevalence of moderate systolic dysfunction. Thelowest prevalence of moderate systolic dysfunction (LVEF ≤40%) wasseen in those who consumed b1 drink a day. The prevalence ofsystolic dysfunction increased 6-fold between light drinkers (0.9%)and heavy drinkers (5.5%).

Table IV. Odds of LV moderate systolic dysfunction according toalcohol consumption volume

Unadjusted baseline model OR (95% CI) P

Abstainers 1.00Former drinkers 0.57 (0.12-2.11) .44b1 drink/d 0.14 (0.04-0.43) b.0011-2 drinks/d 1.56 (0.39-5.20) .49N2 drinks/d 4.75 (1.18-15.98) .02

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strata of risk factors of systolic dysfunction (Figure 2),including gender, age, hypertension, diabetes, smoking,obesity, and metabolic syndrome. It also persisted in amultivariate model after adjustment for all risk factors(odds ratio [OR] 0.20, 95% CI 0.06-0.64, P b .0001).

DiscussionPrincipal findingsThis population-based study demonstrated a U-shaped

relationship between alcohol consumption and LV

systolic function. In the Olmsted County Heart Study,the prevalence of moderate LV systolic dysfunction wasthe lowest in light drinkers (Table III, row 4; Figure 1),with the prevalence increasing with increasing or decreas-ing consumption of alcohol, indicating a U-shapedrelationship. This relationship remained statistically signif-icant for moderate systolic dysfunction even after adjust-ment in a multivariate model. This U-shaped relationshipbetween alcohol consumption and LV systolic functionwas not seen in those with normal systolic function (LVEFN50%) or any impairment of systolic function (LVEF≤50%).These results enhance our understanding of the beneficialand detrimental effects of alcohol consumption on systolicheart function as measured by echocardiography.

Association of alcohol with clinical cardiovascular diseasesEvidence of moderate alcohol consumption reducing

clinical cardiovascular events has been shown by numer-ous observational,18,19 case control,20,21 and cohortstudies22,23 both in healthy subjects24 and in participantswith risk factors such as diabetes.25 In the current study, aspreviously reported,26 the results confirm the salutatoryeffects of alcohol on any clinical cardiovascular disease,whether evaluated individually or collectively in thegeneral population, including myocardial infarction,coronary artery disease, congestive heart failure, angina,cerebrovascular accident, transient ischemic attack, andperipheral artery disease (Table II). This suggests that thecurrent study population is similar to prior studies interms of association of alcohol consumption withclinical cardiovascular disease, which makes this studypopulation an ideal setting to evaluate an associationthat has never been described (ie, alcohol and clinicalsystolic dysfunction).Figure 3 demonstrates the U-shaped relationship

between alcohol and clinical heart failure (Table II, row3; Figure 3). The higher prevalence of diabetes mellitusand hypertension in abstainers may have contributed tohigher prevalence of clinical heart failure (Figure 3).Alcohol has been shown to reduce insulin resistance andblood pressure, which also may explain the U-shapedrelationship of diabetes mellitus and hypertension withalcohol consumption as seen in our study. Abstainers hadmuch higher odds of clinical congestive heart failure

Figure 2

Forest plot depicting bivariate stratified analysis of odds of LV moderate systolic dysfunction in light versus heavy drinkers. The association betweenalcohol consumption and moderate systolic dysfunction, as evaluated by stratification of the participants into multiple strata, persists for most stratain light versus heavy drinkers.

Yousaf et al 5American Heart JournalVolume 0, Number 0

compared to light drinkers (OR 2.7, 95% CI 1.09-6.18, P =.022). When adjusted for both hypertension and diabetesmellitus, the OR dropped meaningfully to 1.9 (95% CI0.76-4.60, P = .14). This meaningful drop (N20%) in ORindicates that, in abstainers, diabetes mellitus andhypertension were the intervening variables for clinicalheart failure.

Association of alcohol with systolic dysfunctionAlthough ejection fraction is a measure of global LV

systolic function, LV performance can be further evaluatedwith multiple other parameters, including measurement ofLV dimensions, calculation of LV mass index, regional wallmotion abnormalities, as well as diastolic dysfunction. Thedata on these indices are not relevant to this manuscriptbecause the focus of this study is LVEF.Prior animal (case control)27,28 and human (case con-

trol29,30 and cohort3,31) studies have demonstrated heavyalcohol use to be associated with LV systolic dysfunctionand alcoholic cardiomyopathy.32 Among heavy drinkers,reduction in alcohol consumption has shown improvementin LV function.32,33 In contrast, moderate alcohol consump-tion is known to protect against heart failure.1,5,6,34 Instudies of patients consuming moderate amount of alcohol,with known heart failure, no deterioration of cardiac

function was seen.35–37 Our data build on these studiesby providing information about systolic function in thispopulation-based sample. It demonstrates light drinkers ashaving the lowest prevalence of systolic dysfunction withprogressive worsening seen with increasing alcohol con-sumption. Former drinkers were noted to have a lowerprevalence of moderate systolic dysfunction (LVEF ≤40%)as compared to moderate drinkers or heavy drinkers. Whenthe entire populationwas evaluated (Table III, row1), theU-shaped relationship was statistically significant but notclinically meaningful, with LVEF ranging from 61.4% to63.9%. No association between alcohol consumption andprevalence of normal systolic function (Table III, row2)wasseen. The U-shaped relationship becomes clearer and morestatistically significant in the stratum of participants withLVEF ≤40%, (Table III, row 4) where the prevalence ofsystolic dysfunction increases from 0.9% to 5.5% in lightdrinkers as compared to heavy drinkers, a 6-fold rise inprevalence. This suggests that the detrimental effect ofalcohol on ventricular function becomes stronger asventricular systolic function deteriorates.Current National Institutes of Health (National Institute

on Alcohol Abuse and Alcoholism) guidelines recom-mend that patients with alcoholic cardiomyopathyshould not drink any alcohol.38 The findings of thisstudy create an interesting clinical paradox, as those who

Figure 3

Alcohol intake and prevalence of heart failure. The lowestprevalence of heart failure was seen in those who consumed b1drink a day.

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stand to benefit the most from light alcohol consump-tion, that is, subjects with LVEF≤40%, are also thosewhoare likely to be harmed if their consumption exceeds N1drink a day. Whether those with moderate systolicdysfunction and a proven track record of light alcoholconsumption should be encouraged to continue theirbehavior cannot be proved from these data and requiresa prospective study.Current guidelines recommend that, in the community,

moderate alcohol consumption (≤1 drink a day forwomenand elderly and 1-2 drinks a day formen)may reasonably becontinued based on existing data on clinical cardiovasculardisease.38 The current study suggests that, at least from thesystolic dysfunction perspective, these guidelines mayneed further consideration and investigation. There is nobeneficial association between alcohol consumption andLV systolic function in healthy individuals with LVEF N50%.The association is insignificant in those with LVEF ≤50%and becomes significant only in those with LVEF ≤40%.Prior large clinical studies have suggested a clinical benefitof moderate alcohol consumption on the occurrence ofclinical heart failure, but they do not have data on ejectionfraction.1,6,34 Although our study confirms the U-shapedrelationship in clinical heart failure (Table II, row 3;Figure 3), it also extends the findings to demonstrate thatthe beneficial effect is limited to those with moderatesystolic dysfunction.The salutatory association between alcohol and mod-

erate systolic dysfunction was not statistically significantin the young (age ≤65 years), smokers, nonobese, andthose without metabolic syndrome. Several observationalstudies39 have shown similar cardioprotective effects ofalcohol in both smokers and nonsmokers, suggesting thatalcohol consumption affects heart function similarly insmokers and nonsmokers. The prevalence of LV systolic

dysfunction was almost 1½ times greater in currentsmokers than in the general population (2.7% vs 1.9%)and more than 2 times greater in current smokers than innoncurrent smokers (2.7% vs 1.3%). Whether the lack ofassociation is due to small sample size or current smokingnullifies the beneficial effect of alcohol can only bespeculated. Other strata that failed to show a beneficialassociation (young, nonobese, and those without meta-bolic syndrome) in our study cannot be explained andmight be a result of either small sample size (n = 38 withsystolic dysfunction in the entire cohort) or confoundingdue to unmeasured variables. Further studies are neededto evaluate these associations.

Strengths and limitationsThe strengths of the present study include its randomly

selected population-based sample, the availability ofmedical records with a 36-year median length of archive,uniform collection of cross-sectional data, and standard-ized echocardiographic measurements.Conclusions from this predominantly white cohort

including only persons ≥45 years cannot be generalizedto the entire US population. Participation bias was evaluatedby medical record abstraction of a random selection of 500participants and 500 invited nonparticipants, which showedno difference in cardiovascular disease.40

The assessment for alcohol consumption was based onself-reporting and, therefore, may result in misclassifica-tion of exposure status. Research participants have beenknown to underreport alcohol consumption by as muchas 39% for men and 44% for women.41 However, self-administered questionnaire data reflect the quality ofinformation available to medical practitioners and havebeen shown to provide useful estimates of alcohol intakein epidemiologic studies.42 In addition, the ability tomake cause-effect inferences and assess time-dependentchanges was limited because of the cross-sectional natureof the study.Although the current study has a large sample size (n =

2,042), the study suffers from a lack of power, especiallyin those with systolic dysfunction. For example, thenumbers of patients with moderate systolic dysfunctionin the 5 categories are very small (n = 6, 6, 9, 9, and 8 inabstainers, former drinkers, b1 drink a day, 1-2 drinks aday, and N2 drinks a day, respectively). However, it is inthis stratum that the statistically significant results areseen. Whether statistically significant results could havebeen observed in other strata if the sample sizes weregreater is debatable. However, the level of statisticalsignificance with P b .001 suggests that, in those withmoderate systolic dysfunction, the results are extremelyunlikely to have arisen by chance. This is a commonlyobserved phenomenon in other studies where themaximum benefit from an intervention is secured bythose with the worst disease (eg, in the CASS study,43 the

Yousaf et al 7American Heart JournalVolume 0, Number 0

maximum survival benefit from coronary artery bypassgrafting was reaped by those who had moderate systolicdysfunction or severe angina). This observation generatesthe hypothesis that the maximum benefit from alcoholmay be in those with moderate systolic dysfunction.

ConclusionIn a community setting, light alcohol consumption

(b1 drink a day) was associated with a reduced prevalenceof moderate systolic dysfunction (LVEF ≤40%).

AcknowledgementsThe authors gratefully acknowledge Joe Grundle and

Katie Klein for editorial preparation of the manuscript,Brian Miller and Brian Schurrer for their help in preparingfigures, and Chi Cho for his help in creating the forest plot.

DisclosuresConflict of interests: The present study was carried out

with funding from US Public Health Services, NationalInstitutes of Health, grant HL-RO1-555902.The authors have no competing interests to disclose.

References1. Bryson CL, Mukamal KJ, Mittleman MA, et al. The association of

alcohol consumption and incident heart failure: the CardiovascularHealth Study. J Am Coll Cardiol 2006;48:305-11.

2. Urbano-Marquez A, Estruch R, Navarro-Lopez F, et al. The effectsof alcoholism on skeletal and cardiac muscle. N Engl J Med1989;320:409-15.

3. Kajander OA, Kupari M, Laippala P, et al. Dose dependent butnon-linear effects of alcohol on the left and right ventricle. Heart2001;86:417-23.

4. Laonigro I, Correale M, Di Biase M, et al. Alcohol abuse and heartfailure. Eur J Heart Fail 2009;11:453-62.

5. Walsh CR, Larson MG, Evans JC, et al. Alcohol consumption andrisk for congestive heart failure in the Framingham Heart Study.Ann Intern Med 2002;136:181-91.

6. Abramson JL, Williams SA, Krumholz HM, et al. Moderatealcohol consumption and risk of heart failure among olderpersons. JAMA 2001;285:1971-7.

7. Kurland LT, Molgaard CA. The patient record in epidemiology.Sci Am 1981;245:54-63.

8. Melton III LJ. History of the Rochester Epidemiology Project. MayoClin Proc 1996;71:266-74.

9. Kannel WB, Belanger AJ. Epidemiology of heart failure. AmHeart J 1991;121(3 Pt 1):951-7.

10. McKee PA, Castelli WP, McNamara PM, et al. The natural historyof congestive heart failure: the Framingham study. N Engl J Med1971;285:1441-6.

11. Gillum RF, Fortmann SP, Prineas RJ, et al. International diagnosticcriteria for acute myocardial infarction and acute stroke. AmHeart J 1984;108:150-8.

12. Canzanello VJ, Sheps SG. The sixth report of the Joint NationalCommittee on Prevention, Detection, Evaluation, and Treatment ofHigh Blood Pressure: what's new? What's different? Cardiol Rev1998;6:272-7.

13. Rose G, McCartney P, Reid DD. Self-administration of aquestionnaire on chest pain and intermittent claudication. Br JPrev Soc Med 1977;31:42-8.

14. National Cholesterol Education Program (NCEP) Expert Panel onDetection, Evaluation, and Treatment of High Blood Cholesterol inAdults (Adult Treatment Panel III). Third report of the NationalCholesterol Education Program (NCEP) Expert Panel onDetection, Evaluation, and Treatment of High Blood Cholesterol inAdults (Adult Treatment Panel III) final report. Circulation2002;106:3143-421.

15. Redfield MM, Jacobsen SJ, Burnett Jr JC, et al. Burden of systolicand diastolic ventricular dysfunction in the community:appreciating the scope of the heart failure epidemic. JAMA2003;289:194-202.

16. Munagala VK, Jacobsen SJ, Mahoney DW, et al. Association ofnewer diastolic function parameters with age in healthy subjects:a population-based study. J Am Soc Echocardiogr 2003;16:1049-56.

17. Redfield MM, Jacobsen SJ, Borlaug BA, et al. Age- andgender-related ventricular-vascular stiffening: acommunity-based study. Circulation 2005;112:2254-62.

18. Reynolds K, Lewis B, Nolen JD, et al. Alcohol consumption andrisk of stroke: a meta-analysis. JAMA 2003;289:579. [Erratumin: JAMA 2003;289:2798].

19. Kloner RA, Rezkalla SH. To drink or not to drink? That is thequestion. Circulation 2007;116:1306-17.

20. Hennekens CH, Willett W, Rosner B, et al. Effects of beer,wine, and liquor in coronary deaths. JAMA 1979;242:1973-4.

21. Wells S, Broad J, Jackson R. Alcohol consumption and itscontribution to the burden of coronary heart disease inmiddle-aged and older New Zealanders: a population-basedcase-control study. N Z Med J 2004;117:U793. [Erratum in: N ZMed J 2004;117:4].

22. Camargo Jr CA, Stampfer MJ, Glynn RJ, et al. Moderate alcoholconsumption and risk for angina pectoris or myocardialinfarction in U.S. male physicians. Ann Intern Med 1997;126:372-5.

23. Mukamal KJ, Ascherio A, Mittleman MA, et al. Alcohol and riskfor ischemic stroke in men: the role of drinking patterns and usualbeverage. Ann Intern Med 2005;142:11-9.

24. Mukamal KJ, Chiuve SE, Rimm EB. Alcohol consumption and riskfor coronary heart disease in men with healthy lifestyles. ArchIntern Med 2006;166:2145-50.

25. Ajani UA, Gaziano JM, Lotufo PA, et al. Alcohol consumptionand risk of coronary heart disease by diabetes status. Circulation2000;102:500-5.

26. Ammar KA, Samee S, Colligan R, et al. Is self-reported"moderate" drinking in the cardiovascular benefit rangeassociated with alcoholic behavior? A population based study.J Addict Dis 2009;28:243-9.

27. Capasso JM, Li P, Guideri G, et al. Left ventricular dysfunctioninduced by chronic alcohol ingestion in rats. Am J Physiol1991;261(1 Pt 2):H212-9.

28. el-Mas MM, Abdel-Rahman AA. Exacerbation ofmyocardial dysfunction and autonomic imbalancecontributes to the estrogen-dependent chronichypotensive effect of ethanol in female rats. Eur JPharmacol 2012;679:95-100.

29. McKenna CJ, Codd MB, McCann HA, et al. Alcohol consumptionand idiopathic dilated cardiomyopathy: a case control study. AmHeart J 1998;135(5 Pt 1):833-7.

30. Urbano-Márquez A, Estruch R, Fernández-Solá J, et al. Thegreater risk of alcoholic cardiomyopathy and myopathy inwomen compared with men. JAMA 1995;274:149-54.

8 Yousaf et alAmerican Heart Journal

Month Year

31. Aguilar D, Skali H, Moyé LA, et al. Alcohol consumption andprognosis in patients with left ventricular systolic dysfunction aftera myocardial infarction. J Am Coll Cardiol 2004;43:2015-21.

32. George A, Figueredo VM. Alcoholic cardiomyopathy: a review.J Card Fail 2011;17:844-9.

33. Gavazzi A, De Maria R, Parolini M, et al. Alcohol abuse anddilated cardiomyopathy in men. Am J Cardiol 2000;85:1114-8.

34. Djoussé L, Gaziano JM. Alcohol consumption and risk of heart failurein the Physicians' Health Study I. Circulation 2007;115:34-9.

35. Nicolás JM, Fernández-Solà J, Estruch R, et al. The effect ofcontrolled drinking in alcoholic cardiomyopathy. Ann Intern Med2002;136:192-200.

36. Cooper HA, Exner DV, Domanski MJ. Light-to-moderate alcoholconsumption and prognosis in patients with left ventricular systolicdysfunction. J Am Coll Cardiol 2000;35:1753-9.

37. Klatsky AL, Chartier D, Udaltsova N, et al. Alcohol drinking andrisk of hospitalization for heart failure with and withoutassociated coronary artery disease. Am J Cardiol 2005;96:346-51.

38. U.S. Department of Health Human Services, Public HealthService, National Institutes of Health, National Institute on AlcoholAbuse and Alcoholism. The physician's guide to helping patientswith alcohol problems. Washington, DC: National Institutes ofHealth, NIH publication. 199595-3769.

39. Corrao G, Rubbiati L, Bagnardi V, et al. Alcohol and coronaryheart disease: a meta-analysis. Addiction 2000;95:1505-23.

40. Jacobsen SJ, Mahoney DW, Redfield MM, et al. Participationbias in a population-based echocardiography study. AnnEpidemiol 2004;14:579-84.

41. Harford TC, Dorman N, Feinhandler SJ. Alcohol consumption inbars: validation of self-reports against observed behavior.Drinking Drug Pract Surveyor 1976;11:13-5.

42. Giovannucci E, Colditz G, Stampfer MJ, et al. The assessment ofalcohol consumption by a simple self-administered questionnaire.Am J Epidemiol 1991;133:810-7.

43. Chaitman BR, Ryan TJ, Kronmal RA, et al. Coronary Artery SurgeryStudy (CASS): comparability of 10 year survival in randomized andrandomizable patients. J Am Coll Cardiol 1990;16:1071-8.