Annals of Epidemiology
Volume 17, Issue 5, Supplement , Pages S8-S12, May 2007

Alcohol Intake and Noncoronary Cardiovascular Diseases

  • Kenneth Mukamal, MD

      Affiliations

    • Corresponding Author InformationAddress correspondence to: Kenneth Mukamal, MD, Division of General Medicine & Primary Care, Beth Israel Deaconess Medical Center, Rose-114, 330 Brookline Ave, Boston, MA 02215. Tel.: (617) 667-8975; fax: (617) 667-2854.

From the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA

Article Outline

Moderate drinking has complex associations with cardiovascular diseases other than coronary heart disease. Recent cohort studies examining the relationship between alcohol use and ischemic stroke have shown a modest association, with risk ratios approximating 0.8 and the lowest risk among those who drink less than daily. In contrast, alcohol use is generally associated with an approximate dose-dependent risk for hemorrhagic stroke throughout the full range of intake.

Several prospective studies of alcohol intake and congestive heart failure have found lower risk with moderate drinking. This risk is also dose dependent through the moderate range, but its underlying mechanism remains uncertain. Accounting for the lower risk of myocardial infarction associated with moderate intake does not eliminate the observed association. Cohort studies have found no association of long-term alcohol intake with risk of atrial fibrillation below levels of at least 3 standard drinks per day. Finally, two prospective studies have found lower risks of claudication or clinically more severe peripheral arterial disease among moderate drinkers, an association also supported by cross-sectional studies of alcohol intake and ankle-brachial index.

Key words: Alcohol Drinking, Stroke, Heart Failure, Peripheral Arterial Disease, Atrial Fibrillation

Selected Abbreviations and Acronyms: AAA, abdominal aortic aneurysm, AF, atrial fibrillation, ANP, atrial natriuretic peptide, CHD, coronary heart disease, CHF, congestive heart failure, CI, confidence interval, PAD, peripheral arterial disease

 

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Introduction 

Although the relationship of alcohol consumption and coronary heart disease (CHD) has been extensively addressed in dozens of studies 1, 2, 3, alcohol consumption has also been associated with other cardiovascular diseases, including ischemic and hemorrhagic stroke, congestive heart failure (CHF), atrial fibrillation (AF), and peripheral arterial disease (PAD) 4, 5, 6, 7. These associations include both positive and inverse associations, even at moderate levels of consumption, although the strength of evidence surrounding these relationships is not yet as strong as for CHD. Complicating this issue further, these cardiovascular diseases are quite heterogeneous, both across diseases and even within a single disease. In this review, I will examine and summarize some of the evidence linking alcohol to these conditions and identify new areas for future research.

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Noncoronary cardiovascular diseases 

Stroke 

The clinical syndrome of stroke is a quintessential example of the heterogeneity among cardiovascular diseases. Stroke comprises two main types of cardiovascular disease — ischemic and hemorrhagic — and several subtypes of each (e.g., atherothrombotic, lacunar, embolic, subarachnoid hemorrhage, intracerebral hemorrhage). Alcohol appears to have decidedly different associations with these various types.

Ischemic stroke, the most common type in the United States and Europe, is the result of vascular occlusion of an intracerebral artery, either through local thrombosis or distal embolism. It is noteworthy that two of the strongest chronic risk factors for ischemic stroke are hypertension and AF (8), both of which have been attributed to heavy drinking (see below). Thus, even though ischemic stroke shares an atherosclerotic and thrombotic etiology with CHD, the particular factors that most strongly predict ischemic stroke risk appear to be in the subset of cardiovascular risk factors that are exacerbated by heavy alcohol use. As a consequence, it may not be surprising that the apparent inverse association of moderate alcohol intake with ischemic stroke risk occurs at a lower dose of alcohol consumption and with a lower magnitude of risk reduction than does the corresponding association with CHD risk 9, 10. It is also not surprising that heavy drinking is consistently associated with higher stroke risk.

For many years, observational (and largely case-control) studies of the relationship between alcohol consumption and risk for ischemic stroke have suggested a relatively strong inverse relationship 4, 11. For example, in the Nurses' Health Study cohort, Stampfer and colleagues documented 66 incident ischemic strokes and found relative risks of 0.3 (95% confidence interval [CI], 0.1–0.7) for intake of 5 to 14 g of alcohol per day, and 0.5 (95% CI, 0.2–1.1) for intake levels of 15 or more g/d (12). However, more recent studies have called the magnitude of lower risk into question. In a meta-analysis restricted to 19 cohort studies, Reynolds and colleagues found that light drinking (<12 g/d) was associated with a relative risk of 0.82 (95% CI, 0.73–0.92), but that consumption of 12 to 60 g/d was not associated with risk (4). In a representative study, Klatsky and colleagues reported a U-shaped association between alcohol intake and hospitalization for ischemic stroke among members of a single insurance plan. Relative risks were 0.8 (95% CI, 0.7–1.0) among those who consumed between one drink a month and one drink a day and 1.0 (95% CI, 0.8–1.2) among those who consumed 3 or more drinks per day (10). For comparison, these authors found a direct inverse association between alcohol use and risk of CHD hospitalization, with relative risks of 0.6 among women and 0.7 among men who consumed 3 or more drinks per day (9). In an analysis of the Cardiovascular Health Study, a lower risk of ischemic stroke was confined to consumers of 1 to 6 drinks per week (hazard ratio 0.75; 95% CI, 0.53–1.06), although even this level of intake modestly but not significantly increased the risk among carriers of the APOE4 allele (13). In the same population (14), the corresponding magnitude of lower risk for CHD was lower and occurred at an intake of 14 or more drinks per week.

Dulli has emphasized how the heterogeneity of ischemic stroke may influence its association with alcohol intake (15). To address this, we examined ischemic stroke risk in the Health Professionals Follow-up Study (16). Concordant with previous work, lower risk was restricted to consumers of an average of 0.1 to 9.9 g of ethanol per day, and particularly to those whose consumption was spread out over 3 to 4 days per week (hazard ratio 0.56; 95% CI, 0.31–1.02). However, stroke subtype appeared to modify risk substantially. Compared with abstention, the hazard ratios associated with intake of 0.1 to 9.9 g/d were 0.76 (95% CI, 0.50–1.15) for confirmed thrombotic stroke, but 2.20 (95% CI, 0.84–5.76) for confirmed embolic stroke. Larger studies with effective classification of ischemic stroke subtypes are needed to confirm these findings.

It should be repeated that little controversy exists regarding the relationship of heavier drinking with a higher risk of ischemic stroke 4, 16. Moreover, even single episodes of intake of 3 or more drinks or drinking to intoxication may acutely and transiently increase the risk of ischemic stroke for the ensuing 24 hours 17, 18, 19, 20, 21.

Hemorrhagic stroke is a common stroke type in Asia, where most studies addressing it have been performed, and includes both subarachnoid and intracerebral subtypes. In a meta-analysis of cohort studies of subarachnoid hemorrhage, Feigin found increased risk restricted to heavier intake (>150 g/wk), with a summary relative risk of 2.1 (95% CI, 1.5–2.8) (22). In a comparable meta-analysis of case-control studies of intracerebral hemorrhage, Ariesen found summary odds ratios of 2.05 (95% CI, 1.35–3.11) for intake of 56 g or less per day, and 4.11 (95% CI, 2.54–6.65) for intake of more than 56 g/d (23), although a large cohort study published subsequently found an increase in risk to be confined to consumers of 6 or more drinks per day (24). These results are largely consistent with Renaud's hypothesis that the effects of moderate drinking are mediated, at least in part, through activity of platelets and prothrombotic factors (25). If this hypothesis is correct, one would anticipate that moderate drinking would decrease the risk of thrombotic events, such as myocardial infarction and ischemic stroke, but increase the risk of bleeding in the brain and possibly other sites (26), exactly as has been observed.

Congestive heart failure 

For decades (27), clinical investigators interested in the cardiac effects of ethanol focused their efforts on alcoholic cardiomyopathy, a dilated cardiomyopathy attributed primarily to cardiotoxic effects of ethanol and secondarily also associated with malnutrition (28). Interestingly, although it has long been recognized that only substantial ethanol intake leads to cardiomyopathy (although less so in women) (29), only recently have studies demonstrated that in subjects with cardiomyopathy, controlled drinking could be as effective as abstinence in stabilizing or restoring myocardial function (30).

More recent interest in CHF has been spurred by 3 observations. First, with the aging of Western populations, CHF has rapidly become a serious public health concern. In 2003 alone, more than one million Americans were hospitalized with a primary diagnosis of CHF (31). Second, a substantial portion of the burden of CHF in the United States and Europe is the consequence of CHD and ischemic cardiomyopathy. If moderate alcohol use is associated with a lower risk of CHD, one might anticipate that it would also be associated with a lower risk of CHF. Third, physiological experiments have suggested that alcohol consumption may induce effective atrial natriuretic peptide (ANP)–mediated diuresis 32, 33 and lower pulmonary artery pressure (34), both of which would be expected to reduce the incidence of CHF; the association of alcohol intake with ANP has now been confirmed in a large observational study (35).

The observed association of alcohol use with risk for CHF has justified this interest but has also added new complexity. In at least 4 large prospective studies 7, 36, 37, 38, investigators have found that moderate drinking is associated with approximately a 50% lower risk of CHF, although the level of intake linked to lowest risk varies somewhat. Interestingly, in all 4 studies, accounting for incident coronary disease did not eliminate the relationship, so that even where previous myocardial infarction was not involved, risk appeared to be, to some degree, inversely related to moderate drinking. Some (39), but not all 40, 41, studies of alcohol intake among patients with established left ventricular dysfunction have also suggested a benefit from light or moderate drinking; one study has suggested an association with lower mortality in men but higher mortality in women (42).

Atrial fibrillation 

Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia and is closely linked with hypertension and CHF. Clinicians have long recognized the temporal association of episodic heavy alcohol use with onset of AF, dubbed the “holiday heart” syndrome 43, 44. However, the association of regular alcohol intake with risk for AF has only recently begun to receive attention. Given the association of heavy drinking with risk for AF, one might hypothesize that even moderate drinking would be associated with higher risk, although animal models have suggested the opposite 45, 46. In human populations, some studies have shown positive relationships in men but not in women (47), whereas some have even shown inverse relationships (48). However, most studies have suggested a threshold effect 6, 44, 49, 50, 51. In these studies, there has generally been no discernible difference in risk between abstainers and moderate drinkers, but a higher risk for the heaviest drinkers. Although the absolute threshold of risk is uncertain, the largest study to date suggests that risk for AF does not increase below a long-term intake level of at least 28 and probably 35 drinks per week (51).

An interesting area for future investigation is the effect of alcohol consumption on individuals with chronic AF, most of whom are likely to be prescribed warfarin or similar anticoagulants. Although guidelines have often explicitly recommended that individuals taking warfarin abstain entirely from drinking (52), the limited available data suggest that the risk for excessive anticoagulation is not higher in moderate drinkers than it is in abstainers, although it may be elevated in binge drinkers 53, 54.

Peripheral arterial disease 

The final manifestation of cardiovascular disease to be discussed herein is peripheral arterial disease (PAD), most commonly localized to the lower extremities; for practical purposes, abdominal aortic aneurysm (AAA) is also considered in this category. Although PAD has generally received the least attention from researchers among the major atherosclerotic vascular diseases, it is nonetheless widely prevalent and a major cause of disability, primarily related to walking.

The body of evidence linking moderate drinking to PAD is modest. The Strong Heart Study and Rotterdam Study both found inverse cross-sectional associations of moderate drinking with PAD (defined as a low ankle-brachial index) that tended to be strongest in women 55, 56, although other cross-sectional studies have not consistently confirmed this finding 57, 58. Surprisingly, a subsequent analysis of the progression of the ankle-brachial index in one of these latter studies has suggested an inverse relationship between alcohol use and a 5-year change in the ankle-brachial index (59). To our knowledge, two prospective cohort studies have assessed the risk of PAD in the general population. In an analysis of symptomatic claudication from the Framingham Heart Study (5), Djoussé and colleagues found hazard ratios of 0.67 (95% CI, 0.42–0.99) associated with intake of 13–24 g/d for men and 0.44 (95% CI, 0.23–0.80) associated with intake levels of 7 to 12 g/d for women. In the Physicians' Health Study (60), Camargo and colleagues found a hazard ratio of 0.74 (95% CI, 0.57–0.97) associated with an intake of 7 or more drinks per week, although the composite outcome included only 66 cases of lower-extremity arterial disease that required revascularization. In contrast, Ciccarone and colleagues found no association of alcohol intake with risk of PAD among diabetic adults (61).

There has been relatively little investigation into the relationship of moderate alcohol consumption with risk of AAA. In an analysis of male smokers, Tornwall and colleagues found a U-shaped relationship, with relative risks for AAA of 0.74 (95% CI, 0.49–1.13) among consumers of up to 15 g of ethanol per day and 0.60 (95% CI, 0.36–1.02) among consumers of 16 to 30 g of ethanol per day (62).

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Conclusions 

In summary, the relationship between moderate alcohol consumption and noncoronary cardiovascular diseases is complex, in part reflecting their heterogeneity. The relationship between alcohol use and the different subtypes of stroke have received the most attention, but even these relationships are not without controversy. To date, evidence generally suggests a J-shaped relationship between alcohol use and ischemic stroke, with lower risk limited to consumers of approximately 1 drink every other day and clearly higher risk among consumers of 3 or more drinks per day. The risk of hemorrhagic stroke appears to rise in a graded fashion with higher alcohol intake. The risks of PAD and CHF both seem to be lower with moderate intake in a range of up to 1 to 2 drinks per day, but larger prospective studies are needed to define these associations more precisely. Finally, AF seems to be unrelated to alcohol use throughout the moderate range of consumption.

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References 

  1. Maclure M. Demonstration of deductive meta-analysis: ethanol intake and risk of myocardial infarction. Epidemiol Rev. 1993;15:328–351
  2. Corrao G, Rubbiati L, Bagnardi V, Zambon A, Poikolainen K. Alcohol and coronary heart disease: a meta-analysis. Addiction. 2000;95:1505–1523
  3. Di Castelnuovo A, Rotondo S, Iacoviello L, Donati MB, De Gaetano G. Meta-analysis of wine and beer consumption in relation to vascular risk. Circulation. 2002;105:2836–2844
  4. Reynolds K, Lewis B, Nolen JD, Kinney GL, Sathya B, He J. Alcohol consumption and risk of stroke: a meta-analysis. JAMA. 2003;289:579–588
  5. Djousse L, Levy D, Murabito JM, Cupples LA, Ellison RC. Alcohol consumption and risk of intermittent claudication in the Framingham Heart Study. Circulation. 2000;102:3092–3097
  6. Djousse L, Levy D, Benjamin EJ, Blease SJ, Russ A, Larson MG, et al. Long-term alcohol consumption and the risk of atrial fibrillation in the Framingham Study. Am J Cardiol. 2004;93:710–713
  7. Klatsky AL, Chartier D, Udaltsova N, Gronningen S, Brar S, Friedman GD, et al. Alcohol drinking and risk of hospitalization for heart failure with and without associated coronary artery disease. Am J Cardiol. 2005;96:346–351
  8. Manolio TA, Kronmal RA, Burke GL, O'Leary DH, Price TR. Short-term predictors of incident stroke in older adults. The Cardiovascular Health Study. Stroke. 1996;27:1479–1486
  9. Klatsky AL, Armstrong MA, Friedman GD. Red wine, white wine, liquor, beer, and risk for coronary artery disease hospitalization. Am J Cardiol. 1997;80:416–420
  10. Klatsky AL, Armstrong MA, Friedman GD, Sidney S. Alcohol drinking and risk of hospitalization for ischemic stroke. Am J Cardiol. 2001;88:703–706
  11. Camargo CA. Moderate alcohol consumption and stroke. The epidemiologic evidence. Stroke. 1989;20:1611–1626
  12. Stampfer MJ, Colditz GA, Willett WC, Speizer FE, Hennekens CH. A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. N Engl J Med. 1988;319:267–273
  13. Mukamal KJ, Chung H, Jenny NS, Kuller LH, Longstreth WT, Mittleman MA, et al. Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study. Stroke. 2005;36:1830–1834
  14. Mukamal KJ, Chung H, Jenny NS, Kuller LH, Longstreth WT, Mittleman MA, et al. Alcohol consumption and risk of coronary heart disease in older adults: the cardiovascular health study. J Am Geriatr Soc. 2006;54:30–37
  15. Dulli DA. Alcohol, ischemic stroke and lessons from a negative study. Stroke. 2002;33:890–891
  16. Mukamal KJ, Ascherio A, Mittleman MA, Conigrave KM, Camargo CA, Kawachi I, et al. Alcohol and risk for ischemic stroke in men: the role of drinking patterns and usual beverage. Ann Intern Med. 2005;142:11–19
  17. Hillbom M, Kaste M. Does ethanol intoxication promote brain infarction in young adults?. Lancet. 1978;2:1181–1183
  18. Hillbom M, Kaste M. Ethanol intoxication: a risk factor for ischemic brain infarction in adolescents and young adults. Stroke. 1981;12:422–425
  19. Hillbom M, Kaste M. Ethanol intoxication: a risk factor for ischemic brain infarction. Stroke. 1983;14:694–699
  20. Hillbom M, Haapaniemi H, Juvela S, Palomaki H, Numminen H, Kaste M. Recent alcohol consumption, cigarette smoking, and cerebral infarction in young adults. Stroke. 1995;26:40–45
  21. Hillbom M, Numminen H, Juvela S. Recent heavy drinking of alcohol and embolic stroke. Stroke. 1999;30:2307–2312
  22. Feigin VL, Rinkel GJ, Lawes CM, Algra A, Bennett DA, van Gijn J, et al. Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies. Stroke. 2005;36:2773–2780
  23. Ariesen MJ, Claus SP, Rinkel GJ, Algra A. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke. 2003;34:2060–2065
  24. Klatsky AL, Armstrong MA, Friedman GD, Sidney S. Alcohol drinking and risk of hemorrhagic stroke. Neuroepidemiology. 2002;21:115–122
  25. Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet. 1992;339:1523–1526
  26. Kaufman DW, Kelly JP, Wiholm BE, Laszlo A, Sheehan JE, Koff RS, et al. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption. Am J Gastroenterol. 1999;94:3189–3196
  27. Klatsky AL. Alcohol and cardiovascular diseases: a historical overview. Novartis Found Symp. 1998;216:2–12discussion 12–18, 152–158
  28. Piano MR. Alcoholic cardiomyopathy: incidence, clinical characteristics, and pathophysiology. Chest. 2002;121:1638–1650
  29. Fernandez-Sola J, Estruch R, Nicolas JM, Pare JC, Sacanella E, Antunez E, et al. Comparison of alcoholic cardiomyopathy in women versus men. Am J Cardiol. 1997;80:481–485
  30. Nicolas JM, Fernandez-Sola J, Estruch R, Pare JC, Sacanella E, Urbano-Marquez A, et al. The effect of controlled drinking in alcoholic cardiomyopathy. Ann Intern Med. 2002;136:192–200
  31. American Heart Association . Heart Disease and Stroke Statistics — 2005 Update. Dallas (TX): American Heart Association; 2005;
  32. Puddey IB, Vandongen R, Beilin LJ, Rouse IL. Alcohol stimulation of renin release in man: its relation to the hemodynamic, electrolyte, and sympatho-adrenal responses to drinking. J Clin Endocrinol Metab. 1985;61:37–42
  33. Colantonio D, Casale R, Desiati P, De Michele G, Mammarella M, Pasqualetti P. A possible role of atrial natriuretic peptide in ethanol-induced acute diuresis. Life Sci. 1991;48:635–642
  34. Greenberg BH, Schutz R, Grunkemeier GL, Griswold H. Acute effects of alcohol in patients with congestive heart failure. Ann Intern Med. 1982;97:171–175
  35. Djousse L, Hunt SC, Eckfeldt JH, Arnett DK, Province MA, Ellison RC. Alcohol consumption and plasma atrial natriuretic peptide. Am J Cardiol. 2006;98:628–632
  36. Walsh CR, Larson MG, Evans JC, Djousse L, Ellison RC, Vasan RS, et al. Alcohol consumption and risk for congestive heart failure in the Framingham Heart Study. Ann Intern Med. 2002;136:181–191
  37. Abramson JL, Williams SA, Krumholz HM, Vaccarino V. Moderate alcohol consumption and risk of heart failure among older persons. JAMA. 2001;285:1971–1977
  38. Bryson CL, Mukamal KJ, Mittleman MA, Fried LP, Hirsch CH, Kitzman DW, et al. The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study. J Am Coll Cardiol. 2006;48:305–311
  39. Cooper HA, Exner DV, Domanski MJ. Light-to-moderate alcohol consumption and prognosis in patients with left ventricular systolic dysfunction. J Am Coll Cardiol. 2000;35:1753–1759
  40. Aguilar D, Skali H, Moye LA, Lewis EF, Gaziano JM, Rutherford JD, et al. Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction. J Am Coll Cardiol. 2004;43:2015–2021
  41. Salisbury AC, House JA, Conard MW, Krumholz HM, Spertus JA. Low-to-moderate alcohol intake and health status in heart failure patients. J Card Fail. 2005;11:323–328
  42. Faris RF, Henein MY, Coats AJ. Influence of gender and reported alcohol intake on mortality in nonischemic dilated cardiomyopathy. Heart Dis. 2003;5:89–94
  43. Greenspon AJ, Schaal SF. The “holiday heart”: electrophysiologic studies of alcohol effects in alcoholics. Ann Intern Med. 1983;98:135–139
  44. Rich EC, Siebold C, Campion B. Alcohol-related acute atrial fibrillation. A case-control study and review of 40 patients. Arch Intern Med. 1985;145:830–833
  45. Nguyen TN, Friedman HS, Mokraoui AM. Effects of alcohol on experimental atrial fibrillation. Alcohol Clin Exp Res. 1987;11:474–476
  46. Kostis JB, Goodkind MJ, Skvaza H, Gerber NH, Kuo PT. Effect of alcohol on the atrial fibrillation threshold in dogs. Angiology. 1977;28:583–587
  47. Frost L, Vestergaard P. Alcohol and risk of atrial fibrillation or flutter: a cohort study. Arch Intern Med. 2004;164:1993–1998
  48. Psaty BM, Manolio TA, Kuller LH, Kronmal RA, Cushman M, Fried LP, et al. Incidence of and risk factors for atrial fibrillation in older adults. Circulation. 1997;96:2455–2461
  49. Koskinen P, Kupari M, Leinonen H, Luomanmaki K. Alcohol and new onset atrial fibrillation: a case-control study of a current series. Br Heart J. 1987;57:468–473
  50. Ruigomez A, Johansson S, Wallander MA, Rodriguez LA. Incidence of chronic atrial fibrillation in general practice and its treatment pattern. J Clin Epidemiol. 2002;55:358–363
  51. Mukamal KJ, Tolstrup JS, Friberg J, Jensen G, Grønbæk M. Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study. Circulation. 2005;112:1736–1742
  52. Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23:40–54
  53. Hylek EM, Heiman H, Skates SJ, Sheehan MA, Singer DE. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA. 1998;279:657–662
  54. Fihn SD, McDonell M, Martin D, Henikoff J, Vermes D, Kent D, et al. Risk factors for complications of chronic anticoagulation. A multicenter study. Warfarin Optimized Outpatient Follow-up Study Group. Ann Intern Med. 1993;118:511–520
  55. Fabsitz RR, Sidawy AN, Go O, Lee ET, Welty TK, Devereux RB, et al. Prevalence of peripheral arterial disease and associated risk factors in American Indians: the Strong Heart Study. Am J Epidemiol. 1999;149:330–338
  56. Vliegenthart R, Geleijnse JM, Hofman A, Meijer WT, van Rooij FJ, Grobbee DE, et al. Alcohol consumption and risk of peripheral arterial disease: the Rotterdam study. Am J Epidemiol. 2002;155:332–338
  57. Jepson RG, Fowkes FG, Donnan PT, Housley E. Alcohol intake as a risk factor for peripheral arterial disease in the general population in the Edinburgh Artery Study. Eur J Epidemiol. 1995;11:9–14
  58. Iribarren C, Sidney S, Sternfeld B, Browner WS. Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease. JAMA. 2000;283:2810–2815
  59. Whiteman MC, Deary IJ, Fowkes FG. Personality and social predictors of atherosclerotic progression: Edinburgh Artery Study. Psychosom Med. 2000;62:703–714
  60. Camargo CA, Stampfer MJ, Glynn RJ, Gaziano JM, Manson JE, Goldhaber SZ, et al. Prospective study of moderate alcohol consumption and risk of peripheral arterial disease in US male physicians. Circulation. 1997;95:577–580
  61. Ciccarone E, Di Castelnuovo A, Salcuni M, Siani A, Giacco A, Donati MB, et al. A high-score Mediterranean dietary pattern is associated with a reduced risk of peripheral arterial disease in Italian patients with Type 2 diabetes. J Thromb Haemost. 2003;1:1744–1752
  62. Tornwall ME, Virtamo J, Haukka JK, Albanes D, Huttunen JK. Life-style factors and risk for abdominal aortic aneurysm in a cohort of Finnish male smokers. Epidemiology. 2001;12:94–100

 Research related to this article has been funded entirely by the National Institutes of Health and the American Heart Association.

PII: S1047-2797(07)00005-1

doi:10.1016/j.annepidem.2007.01.003

Annals of Epidemiology
Volume 17, Issue 5, Supplement , Pages S8-S12, May 2007

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