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. 2023 Jan 31;100(5):e505–e515. doi: 10.1212/WNL.0000000000201473

Cumulative Alcohol Consumption Burden and the Risk of Stroke in Young Adults

A Nationwide Population-Based Study

Jae-wook Chung 1,*, So-Ryoung Lee 1,*, Eue-Keun Choi 1,✉, Sang-Hyeon Park 1, HuiJin Lee 1, JungMin Choi 1,✉, Minju Han 1, Hyo-Jeong Ahn 1, Soonil Kwon 1, SeungWoo Lee 1, Kyungdo Han 1, Sunhwa Kim 1, Seil Oh 1, Gregory Y H Lip 1
PMCID: PMC9931082  PMID: 36323515

Abstract

Background and Objective

Alcohol consumption is one of the important modifiable risk factors for stroke in young adults. The association between the cumulative burden of alcohol consumption and its impact on incident stroke in young adults is unknown. We aimed to investigate the association between cumulative alcohol burden and the risk for stroke among young adults.

Methods

Using data from the Korean National Health Insurance Service database, patients age between 20 and 39 years, who underwent 4 consecutive annual health examinations between 2009 and 2012, were included. The cumulative alcohol burden score of moderate-to-heavy drinking was evaluated by assigning a score of 1 for alcohol consumption ≥105 g/wk at the health examination each year and calculating the sum of 4 years (0–4). The main outcome was incident stroke and its subtypes, ischemic stroke, and hemorrhagic stroke during the follow-up period.

Results

Of 1 536 668 patients (mean age of 29.5 years, 71.5% male, and median follow-up of 6-year), 3 153 experienced an incident stroke (incidence rate, 0.37 per 1,000 person-years). After multivariable adjustment, patients with alcohol burden scores of 2, 3, and 4, who consumed more than 105 g/wk of alcohol for 2, 3, and 4 years, demonstrated significantly higher risks for stroke (hazard ratio [HR] 1.19, 95% CI 1.05–1.34 for 2; HR 1.22, 95% CI 1.09–1.38 for 3; HR 1.23, 95% CI 1.10–1.38 for 4) compared with those with a burden score of 0. This positive dose-response relationship was primarily driven by hemorrhagic rather than ischemic stroke. High alcohol burden scores (i.e., 2, 3, and 4) were significantly associated with higher risks for hemorrhagic stroke (HR 1.30, 95% CI 1.10–1.54 for 2; HR 1.42, 95% CI 1.21–1.67 for 3; HR 1.36, 95% CI 1.16–1.59 for 4) compared with a burden score of 0.

Discussion

Young adults who engaged in moderate-to-heavy drinking demonstrated a higher risk for incident stroke, especially hemorrhagic stroke. Reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any stroke prevention strategy.

More than 90% of the stroke burden is attributable to potentially modifiable risk factors,9,10 one of which is alcohol consumption. The global adult per capita consumption of alcohol is projected to increase substantially.11 In East Asia, including South Korea, adult per capita alcohol consumption increased by 104% between 1990 and 2017.11 Although it is still controversial whether low alcohol consumption increases stroke risk,12-14 heavy alcohol consumption is associated with a higher risk for stroke.12,14-16 However, previous studies have evaluated stroke risk only based on a single measurement of alcohol consumption.10 Because drinking habits can change over time, a single measurement approach cannot distinguish between patients who drink regularly and those who drink excessively in a short period. As such, it cannot accurately reflect the risks associated with the cumulative burden of alcohol consumption.

Given the paucity of information regarding the cumulative burden of alcohol consumption and its impact on incident stroke, especially in young adults age 20–39 years, we investigated the association between the cumulative burden of alcohol consumption and the risk for stroke, including ischemic and hemorrhagic stroke, using data from a representative, nationwide population-based cohort.

Methods

Data Source and Study Population

All data and variables were available from the Korean National Health Insurance Service (NHIS) database.17 The Korean NHIS is a key institution managed by the government and is responsible for managing national health insurance in South Korea. The entire Korean population is a compulsory subscriber to the NHIS. The NHIS database contains individual demographic information, diagnosis codes based on the ICD-10-CM, examination results, inpatient and outpatient services, and pharmacy dispensing claims. All adults age 20 years or older are eligible for regular (annual or biennial) health examinations provided by the Korean National Health Insurance Corporation. This national health examination includes anthropometric measurements, physical examinations, laboratory investigations, including common blood tests, serum creatinine, fasting blood sugar and lipid profile, and self-administered questionnaires addressing lifestyle behaviors, including alcohol consumption, smoking status, and physical activity.

Patients who underwent the national health examination between January 1, 2009, and December 31, 2012, and were aged between 20 and 39 years at the time of the first health examination were included. Among these patients, those who underwent consecutive annual health examinations over 4 years were identified, with the last examination designated as the index health examination. Index health examinations were conducted between 2012 and 2015, depending on the year of the first health examination. Patients previously diagnosed with stroke (ICD-10-CM codes I60 to I64) before the index health examination were excluded. Ultimately, 1,536,668 patients were enrolled in this study.

Standard Protocol Approvals, Registrations, and Patient Consents

This study was performed in accordance with the Declaration of Helsinki and was exempt from deliberation by the Institutional Review Board at Seoul National University Hospital (Seoul, Korea; No. E-2110-052-1261).

Cumulative Alcohol Burden, Cumulative Amount of Alcohol, and Drinking Pattern

Data regarding alcohol consumption were collected using a self-administered questionnaire. The questionnaire asked the patients the number of days they consumed alcohol per week and the number of standard drinks per drinking session (eFigure 1, links.lww.com/WNL/C420). A standard drink was defined as a specialized cup for each type of alcohol. In Korea, the most popular and commonly consumed alcoholic drinks are soju (1 cup = 8.3 g alcohol) and beer (1 cup = 7.8 g alcohol). Most countries, including the United States and the United Kingdom, limit alcohol consumption to less than 2 standard drinks per day.18,19 By extrapolating the international recommendations, this study regarded 105 g per week (equal to 15 g of alcohol per day and similar to 2 standard drinks per day in Korea) as “at-risk drinking” and used it as the cutoff value for alcohol burden.20

The amount of alcohol consumed by the patients was divided into 4 categories: none; mild (>0 and <105 g per week); moderate (≥105 and <210 g per week); and heavy (≥210 g per week). In each of the 4 consecutive health examinations, alcohol burden was assigned a score of 1 point if alcohol consumption was moderate or heavy. The cumulative alcohol burden score was defined as the sum of all points for alcohol burden during the 4 health examinations. Therefore, according to the cumulative alcohol burden, all patients were categorized into one of the 5 groups (0–4).

To investigate the dose-response relationship between alcohol dose and stroke in a semiquantitative manner, another scoring system for alcohol consumption was developed: none = 0; mild drinking = 1; moderate drinking = 2; and heavy drinking = 3. The cumulative amount of alcohol was calculated as the aggregate score of the 4 health examinations, which ranged from 0 to 12. Drinking patterns were divided according to the combination of health examinations in which the alcohol burden was 1 point. A total of 16 drinking patterns were possible, and each pattern was numbered for identification (eFigure 2, links.lww.com/WNL/C420).

Covariates

Demographic information, including age, sex, and income, were collected from the NHIS database. Low income was defined as having the lowest of 20% of profits among the entire Korean population. Comorbidities such as hypertension, diabetes mellitus, dyslipidemia, peripheral arterial disease, cancer, atrial fibrillation (AF), myocardial infarction, congestive heart failure, and chronic kidney disease were defined in accordance with ICD-10-CM diagnosis codes, examinations, prescriptions, and hospital use, which are summarized in eTable 1 (links.lww.com/WNL/C420). Obesity was defined as a body mass index ≥25 kg/m2, and central obesity was defined as a waist circumference ≥90 cm in men and ≥85 cm in women. The presence or absence of comorbidities, obesity, central obesity, and low income were based on the index health examination.

Based on the self-administered questionnaire from the national health examination, information regarding health-related behaviors, such as smoking status and exercise habits, were obtained. Smoking status was classified as nonsmoker, ex-smoker, or current smoker. Definitions of regular exercise are summarized in eTable 1 (links.lww.com/WNL/C420).

Study Outcomes

The patients were followed by the index health examination, conducted from 2012 to 2015 according to the year of the first health examination, until the end of the study period (December 31, 2018). The primary outcome was incident stroke during the follow-up period. Stroke was identified when the patients had the claims of at least one diagnostic code for ischemic stroke (ICD-10-CM, I63 or I64) or hemorrhagic stroke (I60-I62) at least once during hospitalization and was confirmed by imaging using brain CT or magnetic resonance imaging. The secondary outcomes were stroke, ischemic stroke, and hemorrhagic stroke. During the follow-up period, the first occurrence of ischemic and hemorrhagic stroke was included for each event analyses.

Statistical Analysis

Continuous variables are expressed as mean ± standard deviation, and categorical variables are expressed as number and percentage. Triglyceride levels are reported as geometric mean values and corresponding 95% CI. Baseline characteristics were analyzed across the 5 groups using a linear trend test, a generalized linear model for continuous variables, and the Wilcoxon test or the χ2 test for categorical variables. The incidence rate (IR) of study outcomes was calculated by dividing the total number of events by the total person-years during the entire follow-up period, expressed as 1,000 person-years. Univariate Cox regression analyses were performed to calculate hazard ratios (HRs) and corresponding 95% CIs for each independent variable. Multivariable Cox regression analyses were performed to adjust for statistically and/or clinically significant variables, including age, sex, hypertension, diabetes, dyslipidemia, peripheral arterial disease, cancer, AF, myocardial infarction, congestive heart failure, smoking, regular exercise, body mass index, chronic kidney disease, and low income. The Kaplan-Meier method and the log-rank test were used to determine the cumulative incidence of stroke and its subtypes.

All analyses were two-tailed, and differences with p < 0.05 were considered to be statistically significant. Data collection and statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC).

Subgroup and Sensitivity Analyses

Subgroup analyses of the primary outcome according to sex, age (20–29 and 30–39 years), hypertension, diabetes mellitus, dyslipidemia, peripheral arterial disease, cancer, AF, myocardial infarction, congestive heart failure, smoking status, regular exercise, body mass index (<25 and ≥25 kg/m2), and central obesity were performed using multivariable Cox regression analyses. p for interaction was estimated to assess the consistency of the main results among the subgroups by using Wald χ2 test. For the sensitivity analysis, patients without comorbidities (hypertension, diabetes mellitus, dyslipidemia, peripheral arterial disease, cancer, AF, myocardial infarction, congestive heart failure, and chronic kidney disease) were assessed using multivariable Cox regression. Competing risk analysis adjusted for competing risk of death was also conducted using the Fine-Gray subdistribution hazard model.21 Considering international recommendations for sex-specific cutoffs, another sensitivity analysis was performed in which moderate drinking for women was defined as half the amount for men, 52.5 g/wk22

Data Availability

Data provided by the NHIS are only accessible to coinvestigators; hence, data not provided in the article cannot be shared publicly.

Results

Baseline Characteristics

A flow diagram illustrating study enrollment is shown in Figure 1. A total of 1,536,668 patients, with a mean (±SD) age of 29.5 ± 4.1 years, was included. Baseline characteristics are summarized in Table 1. With a higher cumulative alcohol burden, the mean age was older, and the proportion of those in their 30s tended to increase. The proportion of men was overwhelmingly high with high cumulative alcohol burden, reaching approximately 95% in group 4. Mean blood pressure, body mass index, obesity, waist circumference, central obesity, fasting glucose, total cholesterol, and triglyceride levels tended to increase as the cumulative alcohol burden increased. Low income and cumulative alcohol burden were negatively correlated. The prevalence of traditional vascular risk factors, such as hypertension, diabetes mellitus, and dyslipidemia, was positively correlated with the cumulative alcohol burden. Conversely, the prevalence of peripheral arterial disease, cancer, and chronic kidney disease was negatively correlated with cumulative alcohol burden.

Figure 1. Study Flow.

Figure 1

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Flow diagram illustrating study enrollment

Table 1.

Baseline Characteristics According to Cumulative Alcohol Burden

graphic file with name WNL-2022-201334t1.jpg

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Association Between Cumulative Alcohol Burden and Stroke

During a mean follow up of 5.6 ± 1.2 years, 3,153 (0.37 per 1,000 person-years) patients experienced a stroke, of whom 1,773 (0.21 per 1,000 person-years) experienced ischemic stroke and 1,535 (0.18/1,000 person-years) experienced hemorrhagic stroke.

After multivariable adjustment, the IRs and HRs of incident stroke increased steadily as the cumulative alcohol burden score increased. Alcohol burden scores of 2, 3, and 4 were significantly associated with an increased risk for stroke (19%, 22%, and 23%, respectively) compared with those with a burden score of 0 (Table 2 and Figure 2A). This trend was mainly driven by hemorrhagic, but not ischemic stroke. Alcohol burden tended to be associated with the increased risk for ischemic stroke but without statistical significance (p of the overall Wald test = 0.149, Table 2 and Figure 2B). By contrast, alcohol burden scores of 2, 3, and 4 were significantly associated with a higher risk for hemorrhagic stroke (30%, 42%, and 36%, respectively) compared with a burden score of 0, even after multivariable adjustment (p of the overall Wald test <0.001) (Table 2 and Figure 2C). A cubic spline curve showing the association between the 4-year average of weekly alcohol consumption in g/wk and the incidence of stroke also presented the trend of increasing risk of total, ischemic and hemorrhagic stroke with increasing amount of alcohol (eFigure 3). Cumulative incidence curves of all stroke, and ischemic and hemorrhagic stroke, according to alcohol consumption burden, are shown in eFigures 4 and 5.

Table 2.

Hazard Ratios With 95% Confidence Intervals for Incident Stroke, Ischemic Stroke, and Hemorrhagic Stroke According to Alcohol Burden

graphic file with name WNL-2022-201334t2.jpg

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Figure 2. Risks of Stroke According to Cumulative Alcohol Burden.

Figure 2

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Relationship between cumulative alcohol burden and the hazard ratio of (A) incident stroke, (B) ischemic stroke, and (C) hemorrhagic stroke.

Cumulative Amount of Alcohol and Stroke Risk

Based on the index health examination, heavy drinkers exhibited a 28% higher risk for incident stroke than nondrinkers (HR 1.279 [95% CI 1.133 to 1.445]) while mild and moderate drinkers demonstrated lower risks without statistical significance (HR 0.957 [95% CI 0.876 to 1.045] and HR 0.995 [95% CI 0.888 to 1.114], respectively). As the cumulative amount of alcohol increased, the incidence of incident stroke and its HR increased, mainly because of hemorrhagic rather than ischemic stroke (Figure 3).

Figure 3. Risks of Stroke According to Cumulative Amount of Alcohol.

Figure 3

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Relationship between cumulative amount of alcohol and hazard ratio of (A) incident stroke, (B) ischemic stroke, and (C) hemorrhagic stroke.

Drinking Pattern and Stroke

Each drinking pattern subgroup was not associated with an increased risk for ischemic stroke compared with drinking pattern 0, except for drinking pattern 4 (more than moderate alcohol intake only at 4th health examination) (Figure 4). The risk for hemorrhagic stroke increased in all individuals with drinking patterns with alcohol burden scores of 3 and 4 (Figure 4).

Figure 4. Risks of Ischemic and Hemorrhagic Stroke According to Drinking Patterns.

Figure 4

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Relationship between drinking patterns and hazard ratio of ischemic and hemorrhagic stroke.

Subgroup Analyses and Sensitivity Analysis

In the subgroup analyses, there were no statistical interactions for sex, age, diabetes, dyslipidemia, peripheral arterial disease, cancer, AF, myocardial infarction, congestive heart failure, smoking status, regular exercise, and central obesity with incident stroke and its subtypes (eTable 2 and eFigure 6, links.lww.com/WNL/C420). For hypertension and obesity, defined by body mass index, there were significant interactions between the impact of cumulative alcohol burden on the risk for stroke and the subgroups (eFigure 7). Nevertheless, hypertensive patients and obese patients exhibited generally higher IRs across all cumulative alcohol burden groups than nonhypertensive patients and nonobese patients. In other words, the impact of cumulative alcohol burden was attenuated in these high-risk groups, which were already exposed to hypertension and/or obesity.

Sensitivity analysis was used to evaluate the risk for incident stroke and its subtypes among patients without comorbidities. Although the IRs for stroke were lower than those in the main population, the risk for incident, ischemic, and hemorrhagic stroke was still higher according to alcohol burden (eTable 3 and eFigure 8, links.lww.com/WNL/C420). Competing risk analysis adjusted for risk of death showed consistent results with the main results (eTable 4). After applying the sex-specific cutoffs for women, the number of patients and the number of stroke events were slightly increased from 1 to 4 of cumulative alcohol burden while statistical significance was not demonstrated (eTable 5).

Discussion

In this nationwide, population-based cohort study, we investigated the association between cumulative alcohol burden and the risk for stroke using data from 4 consecutive annual health examinations. Our principal findings are as follows. First, the risk for incident stroke increased continuously as the cumulative alcohol burden score increased, demonstrating that the risk for stroke was correlated with more years of moderate-to-heavy alcohol use. Second, the risk was driven mainly by hemorrhagic stroke rather than ischemic stroke. Third, the positive dose-response relationship between the cumulative amount of alcohol and the risk for incident stroke was determined in a semiquantitative manner. Finally, according to the cumulative alcohol burden, the risk for stroke was attenuated in patients with hypertension or obesity.

To the best of our knowledge, this is the first study to report an association between alcohol consumption and the risk for hemorrhagic stroke in young adults. This is important, given that stroke in young adults causes serious mortality and morbidity in patients themselves and in socioeconomic terms.4 Although short-term mortality is usually more favorable among younger patients compared with the elderly patients, long-term cumulative mortality is up to 4 times higher than expected.5 Stroke patients are at considerable risk for recurrent stroke and other cardiovascular events.23 Functional disability, epilepsy, cognitive impairment, depression, anxiety, sexual dysfunction, and return to work are not uncommon problems that young patients encounter after stroke.24 For these reasons, effective primary prevention of stroke by managing modifiable risk factors and altering lifestyle habits is important, especially among young adults. This has, in part, prompted a move toward a more integrated or holistic approach to stroke management based on 3 pillars of management: (1), appropriate antithrombotic therapy; (2), better functional and psychological status; and (3), cardiovascular risk factors and comorbidity optimization (including lifestyle changes).25

Alcohol is an important modifiable lifestyle risk factor for stroke. Several possible mechanisms may explain the relationship between alcohol consumption and stroke. Excessive alcohol consumption can lead to hypertension, and the blood pressure elevating effect of acute alcohol intake could be a major cause of both stroke subtypes.26 Cerebral vasospasm induced by alcohol intake was observed in a preclinical study.27 Alcohol increases the incidence of AF in a dose-dependent manner, and the risk for thromboembolism, including ischemic stroke, increases simultaneously.28 Alcoholic liver cirrhosis and associated hematologic abnormalities may contribute to the extent/severity of hemorrhagic stroke.26 Abstinence from alcohol is also associated with a lower risk for AF in patients with newly diagnosed diabetes mellitus.29 Furthermore, abstinence has been associated with a lower risk for stroke in patients with newly diagnosed AF.30

The relationship between alcohol consumption and stroke has been well characterized in various meta-analyses, based on several studies accommodating the entire age group.12,15,16 Although the impact of alcohol consumption on the risk for stroke in young adults was evaluated in the subgroup analysis, few studies have focused on this relationship in young adults. Because almost 35% of all drinkers are age 20–39 years and 75% drink >3 standard drinks according to data from the Korean Statistical Information Service,31 it is worthwhile to clarify the relationship between alcohol consumption and stroke in young adults.

The heterogeneity of evaluating drinking habits could be complicated when attempting to ascertain the genuine effects of alcohol on stroke in real life. Using data from 4 consecutive annual health examinations, our novel approach enabled us to evaluate the changes in drinking habits over a 4-year period and clarify the effect of cumulative alcohol consumption on incident stroke. Interestingly, all cumulative alcohol burden scores, except for 1, did not demonstrate a higher risk for ischemic stroke after multivariable adjustment, suggesting that the risk for ischemic stroke was attenuated after adjusting for potential confounding variables. On the other hand, although the crude IR for hemorrhagic stroke was lower than that for ischemic stroke, the risk for hemorrhagic stroke significantly increased as the cumulative alcohol burden increased.

This study had several limitations, the first of which was that the overall study population was Korean; therefore, racial differences may exist in the relationship between alcohol consumption and stroke. Second, a self-administered questionnaire was used to gather information about alcohol intake, which may have introduced recall bias. Third, because the cumulative alcohol burden of 0 included the patients drinking a mild amount of alcohol, we could not establish the risk of mild-to-heavy drinking compared with complete abstinence. Fourth, changing drinking patterns and newly diagnosed comorbidities after the index health examination were not evaluated. Fifth, although this study was designed to evaluate the association between drinking habit changes or accumulative alcohol consumption dose over several years and the risk of stroke, the results from the study might not be generalized to all young adults because of a selection bias, by excluding the patients who did not receive 4 consecutive annual health examinations. Sixth, the risk for stroke according to the cumulative alcohol consumption was not proved in female patients, although the international sex-specific cutoffs were applied. This might be explained as the smaller sample size and lower event rates of women than men, which warrants further investigation. Seventh, although the income represents a proxy for socioeconomic status, the lack of data on educational level prevented the presentation of both information simultaneously. Finally, diagnostic codes or operational definitions were used to define comorbidities and outcomes, although these have been previously validated.29,30,32-34

Young adults who engaged in moderate-to-heavy drinking exhibited a higher risk for incident stroke, especially hemorrhagic stroke. Reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any stroke prevention strategy.

Glossary

AF

atrial fibrillation

HR

hazard ratio

ICD-10-CM

International Classification of Diseases-Tenth Revision-Clinical Modification

IR

incidence rate

NHIS

National Health Insurance Service

Appendix. Authors

Appendix.

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Footnotes

Infographic NPub.org/ig1005

Study Funding

This work was supported in part by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: HI20C1662, 1711138358, KMDF_PR_20200901_0173) and by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (grant 2020R1F1A106740). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclosure

E.-K. Choi has received Research grants or speaking fees from Abbott, Bayer, BMS/Pfizer, Biosense Webster, Chong Kun Dang, Daewoong Pharmaceutical Co., Daiichi-Sankyo, DeepQure, Dreamtech Co., Ltd., Jeil Pharmaceutical Co. Ltd, Medtronic, Samjinpharm, Seers Technology, and Skylabs. G.Y.H. Lip serves on consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo, and no fees are received personally. The remaining authors report no disclosure relevant to the manuscript. Go to Neurology.org/N for full disclosures.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Data provided by the NHIS are only accessible to coinvestigators; hence, data not provided in the article cannot be shared publicly.

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