Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA. 2

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All rights reserved DOI: 10.1093/aje/kwi062

Alcohol Consumption, Binge Drinking, and Early Coronary Calcification: Findings

from the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Mark J. Pletcher1,2, Paul Varosy3, Catarina I. Kiefe4,5, Cora E. Lewis4, Stephen Sidney6, and Stephen B. Hulley1

1 Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA. 2 Division of General Internal Medicine, University of California, San Francisco, San Francisco, CA.

3 Division of Cardiology, University of California, San Francisco, San Francisco, CA.

4 Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL. 5 Veterans Affairs Medical Center, Birmingham, AL.

6 Division of Research, Kaiser Permanente, Oakland, CA.

Received for publication July 16, 2004; accepted for publication September 20, 2004.

It is unclear to what extent the apparently beneficial cardiovascular effects of moderate alcohol consumption are mediated by protection against atherosclerosis. Alcohol consumption, coronary heart disease risk factors, and coronary calcification (a marker of atherosclerosis) were measured during 15 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985–2001). Among 3,037 participants aged 33–45 years after follow-up (55% women, 45% Black), the prevalence of coronary calcification was 8% for consumption of 0 drinks/week (n = 1,435), 9% for 1–6 drinks/week (n = 1,023), 13% for 7–13 drinks/week (n = 341), and 19% for ≥14 drinks/week (n = 238) (p < 0.001 for trend). Calcification was also more common among binge drinkers (odds ratio = 2.1, 95% confidence interval: 1.6, 2.7). These associations persisted after adjustment for potential confounders (age, gender/ethnicity, income, physical activity, family history, body mass index, smoking) and intermediary factors (lipids, blood pressure, glucose, C-reactive protein, and fibrinogen). Stratification showed the dose-response relation most clearly in Black men; only heavier alcohol consumption (≥14 drinks/week) was associated with coronary calcification in other race/sex subgroups. These surprising findings suggest the presence of proatherogenic effects of alcohol in young adults, especially Black men, which may counterbalance high density lipoprotein cholesterol elevation and other possible benefits of alcohol consumption.

alcohol drinking; calcification, physiologic; calcium; coronary arteriosclerosis; coronary disease; ethanol; heart diseases

Abbreviations: CARDIA, Coronary Artery Risk Development in Young Adults; CI, confidence interval; HU, Hounsfield units; NHANES, National Health and Nutrition Examination Survey; OR, odds ratio.

Nearly half of American adults drink alcohol (1), and about one third will die from heart disease, the leading cause of death in the United States (2). Despite its public health importance and a large body of relevant research, the relation between alcohol consumption and coronary heart disease remains puzzling and complex. Among drinkers who do not binge, there appears to be a J- or U-shaped relation between alcohol consumption and coronary heart disease, with the lowest mortality rates being seen among light-to-moderate

drinkers and higher rates among abstainers and heavy drinkers (3–5). “Binge” drinking (consumption of five or more drinks on any given occasion) appears to negate the benefits of moderate alcohol consumption, leading to higher rates of coronary heart disease in most (6–10) (though not all (11, 12)) studies. Ethnicity (13), gender (3–5), and type of alcoholic beverage (14) also influence the relation between alcohol consumption and coronary heart disease in some studies.

Correspondence to Dr. Mark Pletcher, 500 Parnassus Avenue, MU 420W, Box 0560, San Francisco, CA 94143-0560 (e-mail:


Alcohol may affect coronary heart disease through a variety of mechanisms. Moderate consumption of alcohol, for example, has favorable effects on levels of lipids (partic-ularly high density lipoprotein cholesterol) (15), clotting and platelet aggregation (15), systemic inflammation (16), endothelial function (17, 18), and resistance of myocytes to ischemic injury (19), and it has mixed effects on glucose tolerance (20–22); heavier alcohol consumption also has detrimental effects on blood pressure (23, 24). Several basic questions remain unanswered, however: Does some combi-nation of these mechanisms explain the J-shaped relation between regular alcohol consumption and clinical coronary heart disease, or are unidentified mechanisms or noncausal associations in play? Why should moderate drinkers who occasionally binge on alcohol not also show lower rates of coronary heart disease than abstainers? If the observed associations are causal, at what stage in the development of clinical coronary heart disease—atherogenesis, plaque destabilization, platelet aggregation and clot formation, or ischemic injury and cell death—do moderate alcohol consumption and bingeing exert their effects?

To address these questions, we sought to isolate the rela-tion between alcohol and the development of coronary atherosclerosis. This early pathophysiologic event in the process leading to clinical coronary heart disease may be detected by measuring coronary calcium, a common compo-nent of atherosclerotic plaques that occurs only in the context of atherosclerosis (25) and strongly predicts future coronary heart disease events (26). Therefore, we analyzed the relation between usual alcohol consumption, binge drinking, and coronary calcification among 33- to 45-year-old Black and White women and men participating in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.


The CARDIA Study is a longitudinal study of risk factors for coronary artery disease in a cohort of Black and White women and men (n = 5,115) aged 18–30 years who were healthy at the time of enrollment in 1985–1986. With the informed consent of participants and the approval of institu-tional review boards at each site, participants have under-gone examination in six cycles to date, including a baseline examination and follow-up examinations at years 2, 5, 7, 10, and 15, with 74 percent retention at year 15. Details on the study design, recruitment, and procedures have been published elsewhere (27, 28). For the purposes of this inves-tigation, we measured the association between alcohol consumption patterns and the prevalence of coronary calcifi-cation at year 15.

Measurement of alcohol consumption

Alcohol consumption was measured during each of the six CARDIA examinations. Participants were asked, “Did you drink any alcoholic beverages in the past year?” and three follow-up questions regarding how many drinks of wine,

beer, and liquor they usually consumed per week. Assuming that one drink of beer, wine, or liquor contains 16.7 ml, 17.0 ml, or 19.1 ml of ethanol, respectively (per CARDIA protocol), we estimated total ethanol consumption per week in milliliters of ethanol and divided it by 17.24 ml of ethanol per average drink to estimate the usual number of drinks per week that each participant reported at year 15. Information on binge drinking was elicited separately by asking partici-pants how many times during the past 30 days they had consumed five or more drinks on any one occasion.

Using data from past CARDIA examinations, we identi-fied lifetime abstainers, past drinkers, and occasional drinkers (persons reporting some consumption in the past year but zero drinks in a typical week) and measured usual consumption at the baseline CARDIA examination. We also estimated lifetime alcohol consumption in “drink-years,” defining 1 drink-year as the amount of alcohol consumed in 1 year by a person consuming 1 drink/day (365 days/year × 17.24 ml of alcohol/day = 6,293 ml of alcohol). Finally, we categorized current alcohol drinkers by beverage preference. Participants who reported more drinks of wine each week than beer and liquor combined were classified as preferring wine; participants preferring beer and preferring liquor were similarly identified; and participants not meeting these criteria were labeled as having no preference.

Measurement of coronary calcification

Consenting CARDIA participants reporting for their year 15 examination underwent computed tomography scanning with either an Imatron C-150 electron beam scanner (GE Imatron, San Francisco, California), a GE Lightspeed multi-detector scanner (General Electric Company, Fairfield, Connecticut), or a Siemens VZ multidetector scanner (Siemens AG, Munich, Germany). A committee composed of cardiologists, radiologists, and a physicist developed a scan-ning protocol for standardizing scan acquisition across these slightly different technologies; the protocol included two electrocardiogram-gated scans 2.5–3 mm thick that were completed within 100–520 ms on each participant, using a hydroxyapatite phantom to allow standardization of image brightness. With the help of specialized image processing software, cardiovascular radiologists blinded as to participant characteristics identified the presence of coronary calcifica-tion in each scan. An expert investigator reviewed and adju-dicated all discordant scan pairs. A total coronary calcium score was calculated for each scan by multiplying the area of the focus by a coefficient ranging between 1 and 4 based on the peak density in the focus (1 = 131–200 Hounsfield units (HU), 2 = 201–300 HU, 3 = 301–400 HU, and 4 = ≥401 HU), according to the method described by Agatston et al. (29). All readers were blinded to participant characteristics, as well as to image data from the other paired scan. Both between- and within-reader reproducibility were high (30).

Measurement of other covariates

Gender, ethnicity, and date of birth were recorded at base-line. A positive family history of coronary artery disease was defined as a heart attack before age 60 years in either of the


subject’s parents. Educational grade attained, family income, and level of physical activity were measured by self-report at the year 15 examination. Lifetime exposure to tobacco in pack-years was estimated on the basis of self-reported number of cigarettes smoked per day at each CARDIA examination. Glucose intolerance was defined as the use of diabetes mellitus medication or a fasting blood glucose level greater than 110 mg/dl. Body mass index (weight (kg)/height (m)2), systolic and diastolic blood

pres-sure, and plasma levels of low density lipoprotein choles-terol, high density lipoprotein cholescholes-terol, and triglycerides were measured during the year 15 examination according to CARDIA protocol (31). Plasma C-reactive protein levels were measured during the year 15 examination using the high-sensitivity assay manufactured by Calbiochem (EMD Biosciences, Inc., Darmstadt, Germany). Plasma fibrinogen levels were measured during the year 5 examination by Medlantic Laboratories (Hyattsville, Maryland). Duplicate serum analyses were carried out on 10 percent of participants for quality control.

Statistical analysis

We categorized participants by their usual alcohol consumption (0, 1–6, 7–13, or ≥14 drinks/week) in order not to obscure a nonlinear (J- or U-shaped) relation. Only 127 participants usually consumed 21 or more drinks per week, so we did not analyze them separately. We compared the prevalence of alcohol consumption and the prevalence of binge drinking according to category of participant charac-teristics using χ2 tests, testing for trend where appropriate.

We used nonparametric tests (Kruskal-Wallis test, or Cuzick’s extension to the Wilcoxon rank-sum test to test for trend where appropriate) to compare median alcohol consumption by participant characteristics among drinkers. To assess the association between alcohol consumption and potential mediators of coronary heart disease, we used linear regression (and logistic regression for proportion with glucose intolerance), log-transforming data on triglycerides and C-reactive protein; we tested for trend with a linear contrast. When assessing the age-adjusted relation between different measures of alcohol consumption and the preva-lence of coronary calcification, we used logistic regression, testing for trend where appropriate with a linear contrast. We tested interactions between usual alcohol consumption and ethnicity, beverage preference, and binge drinking by simul-taneously testing interaction terms between alcohol indicator variables and the characteristic of interest.

We used logistic regression to model the association of alcohol consumption with coronary calcification. We exam-ined this association in stages: first without adjustment, then adjusting for age and other potential confounders, and then additionally adjusting for potential mediators of coronary disease. We considered age, gender, ethnicity, income, education, self-reported physical activity, body mass index, family history of coronary artery disease, and smoking to be potential confounders of the relation between alcohol consumption and coronary calcification, thinking them unlikely to mediate etiologic pathways of interest. We considered lipids, blood pressure, C-reactive protein,

fibrin-ogen, and the presence of glucose intolerance to be potential intermediary factors. For all multivariable regression anal-yses, we used a backwards stepwise variable selection process, eliminating the variable with the highest p value until all variables in the model were associated with the outcome at p < 0.1. Participants missing any covariate data were excluded from all multivariable analyses.

We performed several sensitivity analyses to assess the impact of four alternate modeling decisions: 1) excluding past drinkers, 2) keeping all variables in the model (instead of using a backwards stepwise elimination process), 3) lim-iting the analysis to nonsmokers, and 4) further categorizing nonzero coronary calcium scores (instead of dichotomizing as any vs. none) and using ordinal logistic regression. All analyses were performed using Stata 7.0 (Stata Corporation, College Station, Texas) and verified by the CARDIA Data Coordinating Center. All p values are two-sided.


Study participants and their alcohol consumption patterns

Of 3,042 CARDIA participants who underwent computed tomography scanning at the year 15 follow-up examination, conducted in 2000–2001, 3,037 also reported their usual alcohol consumption at this examination. Participants were aged 33–45 years; 55 percent were women, and 45 percent were Black. In comparison with the original 5,115 persons in the baseline CARDIA examination (1985–1986) who did not participate in follow-up at year 15, our sample was slightly older (mean age of 25.2 years vs. 24.3 years), was more often Caucasian (55 percent vs. 39 percent), and had the same proportion of females (55 percent vs. 54 percent).

Among the half of participants who consumed alcohol on a regular basis at year 15, the median level of consumption was 5 drinks/week (interquartile range: 2, 10). Nearly one fourth of participants (23 percent) reported having engaged in binge drinking on at least one occasion during the past 30 days. Consumption patterns were strongly related to many participant characteristics (table 1), and frequency of binge drinking was highly correlated with usual alcohol consump-tion (figure 1; Spearman’s rank correlaconsump-tion coefficient = 0.57,

p < 0.001).

Alcohol consumption and potential mediators of coronary artery disease

In unadjusted analyses, increasing alcohol consumption was associated with increasing levels of high density lipo-protein cholesterol and systolic and diastolic blood pressure and decreasing levels of C-reactive protein and fibrinogen. Alcohol consumption was not significantly associated with low density lipoprotein cholesterol, triglycerides, or glucose intolerance (table 2).

Alcohol consumption and coronary calcification

Participants who consumed more alcohol were more likely to have coronary calcification. The prevalence of coronary


TABLE 1. Characteristics of participants according to pattern of alcohol consumption, Coronary Artery Risk Development in Young Adults (CARDIA) Study, 2000–2001†

* p < 0.05; **p < 0.01; ***p < 0.001.

p values refer to the comparison of proportions (any alcohol consumption and any binge drinking) or medians (median consumption among drinkers) between groups of participants defined by each characteristic. Tests of trend (χ2 or nonparametric) were used for age, education, income, cigarette smoking, physical activity, and body

mass index. ‡ Weight (kg)/height (m)2. Characteristic No. of subjects % Any current alcohol consumption (%) Median consumption among drinkers Any binge drinking (%) No. of drinks/week Interquartile range (25%, 75%) Age (years) 32–38 959 32 47* 4** 2, 9 22 39–42 1,037 34 58 5 2, 10 25 43–47 1,041 34 53 6 2, 11 21 Gender/ethnic group Black women 799 26 34*** 4*** 2, 7 13*** Black men 575 19 54 7 3, 15 33 White women 859 28 55 4 2, 8 15 White men 804 26 68 6 3, 11 34 Educational level

High school or less 653 22 48*** 7** 3, 15 31***

Some college education 1,738 57 51 5 2, 10 21

Some graduate-level education 641 21 62 5 2, 9 18

Annual income

<$25,000 439 15 46*** 7** 3, 15 26

$25,000–$49,999 743 25 47 5 2, 11 24

$50,000–$99,999 1,126 38 50 4 2, 8 19

≥$100,000 693 23 67 5 3, 10 25

Cigarette smoking (pack-years)

0 1,675 55 46*** 4** 2, 8 15***

1–10 891 29 60 6 3, 11 28

11–20 276 9 64 8 3, 17 40

≥21 195 6 57 10 4, 19 38

Self-rated physical activity level

1 (physically inactive) 185 6 41*** 5 2, 10 18***

2 506 17 45 4 2, 9 19

3 (moderately active) 1,365 45 52 5 2, 10 21

4 523 17 62 5 2, 10 27

5 (very active) 453 15 59 6 3, 11 30

Body mass index‡

<25 960 32 60*** 5 2, 10 21

25–30 1,122 37 56 6 3, 11 28

≥31 944 31 41 4 2, 10 19

Family history of premature coronary heart disease

Yes 360 12 53 5 2, 10 23


calcification was 8 percent for participants who consumed 0 drinks/week, 9 percent for 1–6 drinks/week, 13 percent for 7–13 drinks/week, and 19 percent for ≥14 drinks/week (p < 0.001 for trend). Age-adjustment had little effect on this trend (table 3). Coronary calcification was also more

common among binge drinkers (odds ratio (OR) = 2.1, 95 percent confidence interval (CI): 1.6, 2.7; age-adjusted OR = 2.2, 95 percent CI: 1.7, 2.9). Each measure of alcohol expo-sure—including usual consumption at year 15 and year 0, consumption pattern, total lifetime exposure to alcohol, and frequency of binge drinking—was strongly associated with the age-adjusted prevalence of coronary calcification (table 3).

The association between usual alcohol consumption and coronary calcification appeared to be strongest among Black men (p < 0.001 for trend), though statistical evidence that the relation differed among the different gender/ethnic groups was weak (p = 0.36 for the interaction). This association remained strong among Black men who denied binge drinking (n = 383; for 1–6 drinks/week, OR = 1.7; for 7–13 drinks/week, OR = 1.9; and for ≥14 drinks/week, OR = 2.7 (compared with 0 drinks/week)), though it was no longer statistically significant (p = 0.11) (figure 2).

There was a faint suggestion of a J-shaped relation between usual alcohol consumption and coronary calcifica-tion among all gender/ethnic groups besides Black men, but this effect was not statistically significant, and the nadir of the “J” occurred at relatively low levels of consumption (1– 6 drinks/week) (figure 2).

The association between alcohol consumption and coro-nary calcification did not differ by alcoholic beverage prefer-ence (figure 2).

Multivariable analysis

Usual alcohol consumption and binge drinking remained strong predictors of coronary calcification in multivariable analyses (table 4). While many potentially strong confounders were included in the final logistic models—including age, gender/ethnicity, tobacco exposure, body mass index, family history of coronary heart disease, and income—the

associa-FIGURE 1. Relation of frequency of binge drinking to pattern of usual alcohol consumption, Coronary Artery Risk Development in Young Adults (CARDIA) Study, 2000–2001. Frequency of binge drinking, defined as consumption of five or more alcoholic beverages on one occasion in the past 30 days, was strongly associated with the number of drinks consumed weekly (Spearman’s rank correlation coefficient = 0.57, p < 0.001). Information on usual alcohol consump-tion was elicited by asking, “How many drinks of (wine, beer, liquor) per week do you usually drink?” Therefore, a participant claiming to consume 0 drinks/week in a typical week might still report an episode of binge drinking.

TABLE 2. Association of alcohol intake with potential mediators of coronary artery disease, Coronary Artery Risk Development in Young Adults (CARDIA) Study, 2000–2001

* LDL, low density lipoprotein; HDL, high density lipoprotein.

† Conversion factors: LDL cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/liter; triglycerides, 1 mg/dl = 0.0113 mmol/liter; fibrinogen, 1 mg/dl = 0.0294 mmol/liter.

‡ Glucose intolerance was defined as self-reported use of diabetes medication or a fasting blood glucose level greater than 110 mg/dl (see Materials and Methods).

§ Numbers in parentheses, standard error.

¶ We used linear regression (logistic regression for glucose intolerance) to model the unadjusted association between alcohol consumption and each outcome. Data on triglyceride and C-reactive protein levels were log-transformed. A linear contrast was used to test for trend. Specifically, we tested the null hypothesis that –β(1–6 drinks/week) + β(7–13 drinks/week) + [3 ×β(≥14 drinks/week)] = 0.

Alcohol consumption (drinks/week) Potential mediator Mean LDL* cholesterol level (mmol/liter†) Mean HDL* cholesterol level (mmol/liter†) Mean tri-glyceride level (mmol/liter†) Mean systolic blood pressure (mmHg) Mean diastolic blood pressure (mmHg) Prevalence of glucose intolerance‡ (%) Mean C-reactive protein level (µg/ml) Mean fibrin-ogen level (mmol/liter†) 0 3.0 (0.02)§ 1.26 (0.01) 1.2 (0.02) 113 (0.4) 75 (0.3) 5.9 (0.6) 2.2 (0.07) 8.0 (0.05) 1–6 2.9 (0.02) 1.31 (0.01) 1.2 (0.04) 112 (0.4) 73 (0.3) 3.0 (0.5) 1.7 (0.07) 7.5 (0.05) 7–13 3.0 (0.05) 1.39 (0.02) 1.3 (0.07) 115 (0.8) 75 (0.6) 2.3 (0.8) 1.9 (0.2) 7.3 (0.09) ≥14 2.9 (0.06) 1.46 (0.03) 1.2 (0.06) 118 (1.0) 77 (0.8) 4.2 (1.3) 1.8 (0.1) 7.4 (0.11) p for trend¶ 0.32 <0.001 0.10 <0.001 <0.001 0.22 0.019 <0.001


tion between alcohol variables and coronary calcification persisted (table 4). Higher systolic blood pressure, higher low density lipoprotein cholesterol, and lower high density

lipoprotein cholesterol were also strong independent predic-tors of coronary calcification; inclusion of these potential mediators had no apparent effect on associations between

TABLE 3. Age-adjusted prevalence of coronary calcification according to different measures of alcohol consumption, Coronary Artery Risk Development in Young Adults (CARDIA) Study, 2000–2001

* A linear contrast was used to test for trend. For example, for drinks/week, we tested the null hypothesis that –β(1–6 drinks/week) + β(7–13 drinks/week) + [3 × β(≥14 drinks/week)] = 0. For “Alcohol consumption pattern,” we used a Wald test to assess logistic regression coefficients (not a test of trend).

† On average, one drink contains 17.24 ml of ethanol.

‡ Persons who answered “no” to the questions “Have you had any alcoholic beverage in the past year?” and “Did you drink alcohol more than once or twice in the past?” at each CARDIA examination were considered lifetime abstainers. Persons who answered “no” to the question “Have you had any alcoholic beverages in the past year?” but were not lifetime abstainers were considered “past” drinkers. Persons who had had an alcoholic drink in the past year but did not drink any alcohol in a typical week and did not binge were considered “occasional” drinkers. Persons reporting ≥5 drinks on one or more occasions during the previous month were considered “binge drinkers.”

§ A drink-year was defined as the total amount of ethanol consumed by a person who had one alcoholic drink per day for 1 year (1 drink-year = 17.24 ml of ethanol/drink × 1 drink/day × 365 days/year = 6,292.6 ml of ethanol). ¶ Based on the 3,023 participants who answered alcohol-related questions during the baseline CARDIA examination in 1985–1986 and subsequently had coronary calcification measured at year 15.

Measure of alcohol consumption No. of

subjects %

Coronary calcification Prevalence

(%) p value*

Usual alcohol consumption (drinks/week†)

0 1,435 47 7 <0.001

1–6 1,023 34 8

7–13 341 11 11

≥14 238 8 17

Alcohol consumption pattern‡

Never (lifetime abstainer) 109 4 4 <0.001

Past drinker, no drinking currently 518 17 8

Occasional (<1 drink/week, no bingeing) 766 25 6

Binge drinker (≥5 drinks on one occasion) 691 23 14

Any regular, nonbinge drinking 953 31 7

Lifetime alcohol consumption (drink-years§)

0 543 18 6 <0.001 0.1–10 1,300 43 7 10–19.9 522 17 9 20–29.9 283 9 9 30–39.9 135 4 8 40–49.9 93 3 24 ≥50 161 5 19

No. of episodes of binge drinking in past 30 days

0 2,346 77 7 <0.001

1 243 8 11

2–4 284 9 15

≥5 164 5 15

Alcohol consumption at year 0¶ (drinks/week)

0 1,163 38 6 <0.001

1–6 1,211 40 8

7–13 389 13 11


alcohol and coronary calcification (table 4). Simultaneous adjustment for both usual consumption and binge drinking weakened each individual alcohol-calcification association, but the overall contribution of alcohol variables to the model remained significant (table 4, second section).

Categoriza-tion of all participants according to both binge frequency and usual consumption suggested that increases in either binge frequency or usual alcohol consumption were sufficient to induce an association with coronary calcification (table 4, third section).

FIGURE 2. Prevalence of coronary calcification according to usual alcohol consumption in different subgroups of participants, Coronary Artery Risk Development in Young Adults (CARDIA) Study, 2000–2001. Prevalence estimates were adjusted for age. Participants were categorized as preferring a specific beverage type if they reported consuming more of that type of beverage than of the other two types combined. Binge drinking was defined as consumption of five or more alcoholic beverages on one occasion. The p values for trends within each subgroup are shown in the figure. The overall p values from evaluation of interactions were p = 0.36 for the interaction with gender/ethnicity, p = 0.64 for the interaction with beverage preference, and p = 0.73 for the interaction with bingeing pattern.


Sensitivity analyses

Exclusion of past drinkers (n = 447) from the reference group and backwards stepwise elimination of variables from each multivariable model (or lack thereof) had virtually no effect on the magnitude or statistical significance of our find-ings. Limiting the analysis to lifetime nonsmokers (n = 1,675) strengthened the linear association between alcohol consumption and coronary calcification (fully adjusted ORs = 1.2, 1.8, and 3.3 (compared with nondrinkers); p = 0.002 for trend). When we treated the coronary calcium score as ordinal instead of dichotomous by categorizing nonzero coronary calcium scores (0, 1–9, 10–99, and ≥100), the graded association with usual consumption and binge consumption remained essentially unchanged. After adjust-ment for potential confounders and potential mediators using ordinal logistic regression, odds ratios for having a coronary calcium score in a higher category were 1.2 (95 percent CI: 0.9, 1.7) for 1–6 drinks/week, 1.6 (95 percent CI: 1.1, 2.5) for 7–13 drinks/week, and 2.1 (95 percent CI: 1.4, 3.4) for

≥14 drinks/week (in comparison with 0 drinks/week) (p < 0.001 for trend).


In this article, we report a direct association between higher levels of alcohol consumption and coronary calcification. Our analyses suggested that both usual alcohol consumption and binge drinking contribute to this association and that Black men may differ from others in their response to alcohol. The association remained present after adjustment for many potential confounders and did not appear to be mediated by effects of alcohol on lipids, blood pressure, C-reactive protein, fibrinogen, or glucose intolerance.

To our knowledge, our study is the first to demonstrate an association between binge drinking and atherosclerosis of the coronary arteries (as measured by coronary artery calci-fication). This association is consistent with previous studies of binge drinking and coronary heart disease events, most of which have found higher rates of events among persons who

TABLE 4. Adjusted odds of coronary calcification among persons with different alcohol consumption patterns, Coronary Artery Risk Development in Young Adults (CARDIA) Study, 2000–2001

Alcohol consumption pattern (among all participants)

No. of subjects

Prevalence of coronary calcification

Unadjusted Adjusted for potential


Adjusted for potential confounders* and potential mediators†

% 95% CI‡ OR‡ 95% CI OR 95% CI OR 95% CI

Separate analyses of overall consumption and binge drinking

Usual alcohol consumption (drinks/week) 2,723§

0 1,257 7 6, 9 1¶ 1¶ 1¶ 1–6 933 9 7, 11 1.2 0.9, 1.7 1.1 0.8, 1.6 1.1 0.8, 1.6 7–13 315 13 10, 18 1.9 1.3, 2.9 1.6 1.0, 2.4 1.5 1.0, 2.3 ≥14 218 19 14, 25 2.9 2.0, 4.4 1.9 1.2, 2.9 2.0 1.3, 3.2 p value# <0.001 <0.001 0.002 0.002 Bingeing 2,723 No bingeing 2106 8 7, 9 1¶ 1¶ 1¶ Bingeing 617 16 13, 19 2.2 1.7, 2.9 1.6 1.2, 2.2 1.7 1.2, 2.3 p value <0.001 <0.001 0.001 0.001

Simultaneous adjustment for overall consumption and binge drinking**

Usual alcohol consumption (drinks/week) 2,723

0 —** —** 1¶ 1¶ 1¶ 1–6 1.1 0.8, 1.5 1.1 0.7, 1.5 1.1 0.8, 1.5 7–13 1.5 1.0, 2.3 1.3 0.8, 2.1 1.3 0.8, 2.1 ≥14 1.9 1.1, 3.1 1.4 0.8, 2.4 1.5 0.9, 2.7 p value# 0.007 0.146 0.092 Bingeing No bingeing 1¶ 1¶ 1¶ Bingeing 1.7 1.2, 2.4 1.4 1.0, 2.0 1.4 1.0, 2.1 p value 0.003 0.078 0.059 Overall p value†† 0.003 0.011 0.006 Table continues


binge (9, 10). Our findings also support previous research suggesting that binge drinking is associated with coronary heart disease at least partly through its association with atherosclerosis (32) (demonstrated by ultrasonography of carotid arteries) rather than merely through its association with sudden death from arrhythmia or other nonatheroscle-rotic mechanisms. Dysregulation of inflammatory cytokines associated with the “hangover” after a binge (33) is a poten-tial explanation for this relation.

In contrast with much previous research on alcohol and clinical coronary heart disease (5), we did not find evidence of protection against atherosclerosis from light-to-moderate regular alcohol consumption. At higher levels of alcohol consumption (≥14 drinks/week), the risk of coronary calcifi-cation was elevated; among Black men, even moderate drinking was associated with increased risk. While binge drinking among otherwise-moderate drinkers offers a partial

explanation, we detected no beneficial association with alcohol consumption even after excluding binge drinkers.

There are several potential explanations for these findings. One possibility is that the beneficial associations between alcohol and clinical coronary heart disease events seen in previous studies are not generally mediated through an atherosclerotic pathway, and therefore would not be detected by measuring coronary calcification. This explanation is consistent with previous research showing beneficial effects of alcohol on platelet aggregation (15), endothelial function (17, 18), inflammation (16), and myocyte resistance to ischemic injury (19). It is also consistent with three previous studies that failed to show a protective association between moderate alcohol consumption and carotid atherosclerosis (34–36), although two other studies did show such an associ-ation (37, 38). Investigators in one prior study who commented only briefly on alcohol use and coronary

calcifi-TABLE 4. Continued

*We considered the following to be potential confounders: age, gender/ethnicity, education, income, self-reported physical activity level, family history of premature coronary heart disease, body mass index, and smoking exposure (in pack-years). In the full model containing both usual alcohol consumption and binge drinking, the predictors remaining in the model after backwards stepwise elimination were age, gender/ethnic group, tobacco exposure, body mass index, family history of coronary heart disease, and income. Retaining all potential confounders without stepwise elimination resulted in essentially identical results (see “Sensitivity analyses” in text).

† We considered the following physiologic parameters to be potential mediators of coronary artery disease: low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure, glucose intolerance, C-reactive protein, and fibrinogen. In the full model containing both usual alcohol consumption and binge drinking, potential confounders and mediators remaining in the model after backwards stepwise elimination were age, gender/ ethnic group, tobacco exposure, family history of coronary heart disease, income, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and systolic blood pressure. Retaining all potential confounders and mediators without stepwise elimination resulted in essentially identical results (see “Sensitivity analyses” in text).

‡ CI, confidence interval; OR, odds ratio.

§ Of the 3,037 participants meeting the entrance criteria, data on all potential confounders and mediators were available for 2,723 (90%). ¶ Reference category.

# A linear contrast was used to test for trend. Specifically, we tested the null hypothesis that –β(1–6 drinks/week) + β(7–13 drinks/week) + [3 ×β(≥14 drinks/ week)] = 0.

**In the simultaneous adjustment strategy, both usual alcohol consumption and binge drinking were included in the same model. For this reason, no prevalence estimates or numbers of subjects are given.

††p value computed using a simultaneous Wald test of all alcohol-related regression coefficients (not a test of trend).

‡‡ In the joint exposure categorization strategy, we categorized all participants according to both usual alcohol consumption and frequency of binge drinking. Some categories were collapsed because of small cell sizes, such as persons drinking ≥14 drinks/week who reported no bingeing (n = 27) and persons who reported having one binge episode in the past month (n = 23).

Alcohol consumption pattern (among all participants)

No. of subjects

Prevalence of coronary calcification

Unadjusted Adjusted for potential


Adjusted for potential confounders* and potential mediators†

% 95% CI OR 95% CI OR 95% CI OR 95% CI

Joint categorization of overall consumption and binge drinking‡‡ 2,723 0–6 drinks/week 0 binges/month 1,923 7 6, 9 1¶ 1¶ 1¶ 1 binge/month 139 11 6, 17 1.5 0.9, 2.7 1.3 0.7, 2.3 1.2 0.7, 2.2 ≥2 binges/month 128 14 9, 21 2.1 1.2, 3.5 1.6 0.9, 2.7 1.7 1.0, 2.9 7–13 drinks/week 0 binges/month 156 11 6, 17 1.5 0.9, 2.6 1.3 0.8, 2.4 1.3 0.7, 2.3 1 binge/month 57 9 3, 19 1.2 0.5, 3.1 0.9 0.3, 2.3 0.8 0.3, 2.2 ≥2 binges/month 102 20 12, 29 3.1 1.8, 5.2 2.4 1.4, 4.2 2.4 1.4, 4.3 ≥14 drinks/week 0–1 binge/month 50 16 7, 29 2.4 1.1, 5.2 1.8 0.8, 4.0 1.7 0.7, 3.8 ≥2 binges/month 168 20 14, 26 3.1 2.0, 4.7 1.9 1.2, 3.0 2.1 1.3, 3.5 p value†† <0.001 <0.001 0.019 0.012


cation in their much older population also found no benefi-cial association with alcohol consumption (39).

Perhaps more likely is that the increase in high density lipoprotein cholesterol caused by alcohol, which accounts for approximately 50 percent of alcohol-mediated coronary heart disease protection (40), and other potential benefits derived from alcohol in terms of atherosclerosis protection are counterbalanced by other harmful effects from alcohol in young persons. Even among older adults, the benefits of alcohol appear to be outweighed by harmful effects at high levels of consumption (the upswing of the J-shaped curve (5)). These harmful effects may be more important in young adults as atherosclerosis develops and perhaps most impor-tant among Black men, in whom the dose-response associa-tion between alcohol and coronary calcificaassocia-tion appeared to be strongest. The mechanisms by which alcohol may induce atherosclerosis are unclear, but they may involve inflamma-tion, low density lipoprotein cholesterol oxidainflamma-tion, acetalde-hyde produced as a metabolic byproduct, or increased shear stress and flow turbulence associated with higher blood pres-sure or adrenergic stress (32).

Finally, it is possible that the coronary calcium we found in atherosclerotic plaques among these young adults may in fact represent plaque stabilization. Such a possibility might imply that lower coronary heart disease rates among moderate drinkers seen in other studies could be caused by a plaque-stabilizing effect of alcohol. However, while a given calcified plaque may be more stable on average than a noncalcified plaque, the presence of calcified plaques gener-ally indicates a larger overall atherosclerotic plaque burden (41) and is associated with higher, not lower, rates of coro-nary heart disease events (26).

Our finding that the linear trend of increasing coronary calcification with increasing alcohol consumption was stron-gest among Black men is notable. Blacks have historically been underrepresented in large studies of cardiovascular disease, including those examining the link between alcohol and coronary heart disease. One previous analysis using data from the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study did focus on Blacks and found higher rates of all-cause mortality with higher alcohol intake (13) and no apparent beneficial association with moderate consumption. The authors hypothesized that the lack of benefit might be due to the binge pattern of alcohol consumption noted previously (but not in their study) to be more common among Blacks (42). In our study, there were no ethnic differences in binge drinking, and the strong dose-response relation between alcohol consumption and coronary calcification among Black men appeared to persist even after exclusion of binge drinkers.

The associations we observed persisted despite adjustment for many correlates of alcohol consumption and binge drinking. While this does not exclude confounding as an explanation for our findings, the extensive data on potential confounders are a strength of our analysis in comparison with many other studies of alcohol and coronary heart disease. Limitations of our study include uncertainty about the degree to which findings in our young-to-middle-aged population will apply to older men and women and the suboptimal sample size for subgroup and interaction analysis. We also

lacked detailed data on drinking frequency, a potentially important factor in characterizing alcohol intake (12). A strength of our study is the longitudinal assessment of alcohol consumption patterns available in CARDIA. The consistency with which different assessments of exposure over 15 years are associated with coronary calcification strengthens our inferences, and the estimate of lifetime alcohol exposure in “drink-years” (a new measure analogous to “pack-years” in the smoking literature) may prove useful for examining other cumulative effects of alcohol exposure. In conclusion, our findings add to the emerging evidence that binge drinking is associated with higher rates of cardio-vascular disease and strengthen the rationale for recom-mending that those who drink alcohol do so in moderation. Surprisingly, our findings also raise the possibility that even moderate alcohol consumption could have proatherogenic effects among young adults. This result appears to be driven by the strong dose-response association between alcohol consumption and coronary calcification that we observed among Black men. The recent NHANES I Epidemiologic Follow-up Study report (13) showing higher mortality for Blacks at all levels of alcohol consumption in comparison with abstinence supports this potentially important finding and emphasizes the importance of studying the effects of alcohol in a variety of ethnic and cultural groups.


The CARDIA Study is supported by contracts N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and N01-HC-95095 from the National Heart, Lung, and Blood Institute. Dr. Mark Pletcher was supported by funds from the Health Resources and Services Administration, US Public Health Service (grant D14 HP00178).

The authors acknowledge Dr. Mark Pereira, Dr. David Jacobs, Feng Lin, and Heather McCreath for their generous assistance.


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