![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
ois Meyer4
2 Institute on Nutraceuticals and Functional Foods Quebec City, QC, Canada; 3 Quebec Heart Institute, Laval Hospital Quebec City, QC, Canada; and 4 Cancer Research Center, Quebec City, QC, Canada
* To whom correspondence should be addressed. E-mail: benoit.lamarche{at}inaf.ulaval.ca.
 |
ABSTRACT |
|---|
 TOP ABSTRACT IntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
15.2 g of alcohol/d (4th quartile of the distribution) were younger (P < 0.001), had elevated plasma HDL-C concentrations (P < 0.001), and lower plasma concentrations of insulin (P = 0.01), CRP (P = 0.01), and fibrinogen (P < 0.001) than men in the 1st quartile (<1.3 g of alcohol/d). After adjustment for a series of coronary risk factors, alcohol consumption 15.2 g/d was associated with a 39% reduction in the 13-y risk of IHD [relative risk (RR) of IHD = 0.61, P = 0.02]. Finally, an alcohol consumption <15.2 g/d was associated with an increase of the risk of IHD in men with the metabolic syndrome (RR = 2.24, P < 0.001) but not in men without the metabolic syndrome (RR = 1.31, P = 0.22). These results confirm that moderate daily alcohol consumption has cardioprotective properties and suggest that the effects may be more important in subjects with a deteriorated risk profile, such as those with the metabolic syndrome.
|
Introduction |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
10–45 g of alcohol/d, is associated with a lower risk of cardiovascular disease (1–5). Specifically, individuals who consume 1–3 drinks/d have a 10–40% lower risk of ischemic heart disease (IHD)5 than those who abstain (6). This reduction in IHD has been attributed to the beneficial impact of alcohol on plasma lipid levels, hemostatic factors (6), and insulin sensitivity (7). Studies suggest that as much as half of the cardiovascular benefit attributable to alcohol consumption may be because of its HDL cholesterol (HDL-C) rising effect (6). Anti-inflammatory effects of moderate alcohol consumption reflected by reductions in plasma CRP (8) and fibrinogen (9) concentrations have also been evoked as potential mechanisms through which alcohol may reduce the risk of IHD. The metabolic syndrome is a metabolic disorder characterized by abdominal obesity, dyslipidemia, hypertension, and elevated fasting blood glucose (10). The metabolic syndrome is associated with a high risk of developing IHD (11) and type 2 diabetes (12). The beneficial effects of light-to-moderate alcohol consumption on specific components of the metabolic syndrome suggest that alcohol consumption may help prevent the development of the metabolic syndrome as a whole. The favorable effect of alcohol on plasma HDL-C levels and on insulin sensitivity has been briefly discussed above (13,14). In contrast, alcohol consumption may increase plasma triglyceride (TG) concentrations (6) and may contribute to elevated blood pressure (15), whereas the relation between alcohol intake and obesity has been inconsistent. A study of Japanese men found a positive association between alcohol consumption and waist-to-hip ratio (16). On the other hand, analysis of data on alcohol consumption and the metabolic syndrome in the NHANES III indicated that light-to-moderate alcohol consumption was associated with a lower prevalence of the metabolic syndrome and had a favorable influence on serum lipids, waist circumference, and fasting serum insulin levels (17), a finding replicated in another study (18). Finally, a study in Korean adults indicated that light alcohol consumption was associated with a reduced prevalence of the metabolic syndrome, whereas substantial alcohol intake led to a dose-dependent increase in the risk of having the metabolic syndrome (19).
Although these previous studies investigated the association between alcohol consumption and metabolic syndrome or between alcohol consumption and the risk of IHD, data documenting the synergistic impact of alcohol consumption and the metabolic syndrome on the long-term risk of IHD were lacking. The objective of this study was therefore to investigate the combined impact of alcohol consumption and the metabolic syndrome on the risk of IHD using data from the Quebec Cardiovascular Study.
|
Materials and Methods |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
Definition of IHD events. The IHD events were nonfatal myocardial infarction and fatal IHD events that have been previously defined (20,21). A total of 219 first cases of IHD were diagnosed over the 13-y follow-up. A 1st nonfatal myocardial infarction was documented in 163 men and IHD death occurred as a 1st major event in 56 men.
Laboratory analyses. Twelve-hour fasting blood samples were obtained at baseline evaluation in 1985 and immediately used for lipid and apolipoprotein measurements. Plasma cholesterol and triglyceride levels were determined using an autoanalyzer (Technicon RA-500; Bayer) as previously described (22). Plasma HDL-C concentrations were measured in the supernatant fraction after precipitating apolipoprotein B–containing lipoproteins using a combination of heparin and manganese chloride (23). LDL-C levels were estimated with the equation of Friedewald et al. (24). Plasma apolipoprotein B concentrations were measured by rocket immunoelectrophoresis (25), as previously described (22). Plasma CRP levels were measured using a commercially available highly sensitive CRP assay (Behring Latex-Enhanced on the Behring Nephelometer BN-100; Behring Diagnostic) and the calibrators provided by the manufacturer (N Rheumatology Standards SL; Behring Diagnostic). Nondenaturing 2–16% polyacrylamide gradient gel electrophoresis was used to characterized LDL particle size as previously described using plasma stored at –80°C (21). Fasting plasma insulin concentrations were measured with a commercial double-antibody radioimmunoassay (human-insulin–specific radioimmunoassay method, LINCO Research) (26). Plasma IL-6 levels were measured using the commercially available Quantikine HS Immunoassay ELISA kit (R&D Systems) and calibrators (Diluent HD6F) (27). Fibrinogen concentrations were determined by thrombin clotting time assay as previously described (28).
Definition of metabolic syndrome.
The metabolic syndrome was diagnosed using a modification of the definition of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III (29). The standard definition of the NCEP ATP III for the metabolic syndrome in men is based on the presence of 3 of the following 5 risk factors: 1) abdominal waist circumference >102 cm, 2) plasma HDL-C <1.02 mmol/L, 3) plasma TG level 1.69 mmol/L, 4) systolic/diastolic blood pressure 130/85 mm Hg, and 5) fasting plasma glucose 6.1 mmol/L. In the present study, we did not have data on waist circumference and fasting plasma glucose concentrations. The waist circumference criteria was replaced by BMI >30 kg/m2, whereas plasma glucose was replaced by the presence of either fasting insulin concentration >75th percentile in this cohort (85 pmol/L) or self-reported type 2 diabetes. The metabolic syndrome was diagnosed in men with 3 of these risk factors.
Alcohol intake. Alcohol intake in 1985 was estimated from a self-administered questionnaire inquiring about the frequency and amount of alcohol consumed over the last year. Standard specified portion sizes were 341 mL for beer, 150 mL for wine, and 45 mL for spirits. The alcohol intake for each individual was determined by multiplying the consumption of each beverage by its ethanol content [13.7 g for beer, 13.3 g for wine, and 14.2 g for spirits, according to the Canadian Nutrient File (30)] and by adding all beverages.
Statistical analysis.
Values are presented as means ± SD unless specified otherwise. Mean baseline characteristics of men with IHD and men who remained free of IHD during follow-up were compared using Student's t test for parametric variables and by the Wilcoxon test for nonparametric variables. Values of CRP were not normally distributed and were log transformed prior to analysis. Cox proportional-hazards models were used to estimate rates of IHD events. Age, BMI, systolic pressure, smoking habits (smokers of 20 cigarettes/d), type 2 diabetes (presence or not), and medication for hypertension (presence or absence) were included as covariables in multivariate risk-prediction models. Plasma HDL-C, fasting insulin and CRP, IL-6 concentrations, and LDL particle size were also considered as confounders where indicated. The nonlipid and lipid risk variables in men, classified by quartile of alcohol consumption, were compared using a general linear model with Duncan's test to locate subgroup differences. Quartiles of alcohol intake were <1.3 g alcohol/d, 1.3–5.4 g/d, 5.5–15.1 g/d, and 15.2 g/d. Statistical analyses were performed with SAS (SAS Institute) and significance was defined as P < 0.05.
|
Results |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
15.2 g of alcohol daily (the 4th quartile of the distribution) were younger (P < 0.001), had higher plasma HDL-C concentrations (P < 0.001) and lower fasting insulin (P = 0.01), CRP (P = 0.01) and fibrinogen (P < 0.001) concentrations (Table 2). There was lower prevalence of self-reported type 2 diabetes in this group (P = 0.02). On the other hand, men in the highest quartile of alcohol consumption tended to have higher IL-6 (P = 0.06) concentrations. Men with the highest intake of alcohol also had higher systolic blood pressure and were more likely to be smokers.
|
|
|
|
15.2 g/d were considered the reference group for these analyses (RR = 1.0). Irrespective of alcohol consumption, the RR of IHD was lower among men without the metabolic syndrome than among men with the metabolic syndrome. However, among men with the metabolic syndrome, the RR of IHD was increased only in men with alcohol consumption <15.2 g/d (RR = 2.24, P < 0.001). Indeed, a relatively high alcohol consumption attenuated the risk of IHD in men with the metabolic syndrome (RR = 1.50, P = 0.17). Finally, a low alcohol consumption was not associated with an increase in the risk of IHD in men without the metabolic syndrome (RR = 1.31, P = 0.22). The statistical interaction between alcohol consumption and metabolic syndrome in modulating the risk of IHD was not significant.
|
|
Discussion |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
15.2 g of alcohol/d (1 drink/d) had a 39% lower risk of IHD over the 13-y of follow-up than those consuming <1.3 g of alcohol/d, even after adjustment for potential confounders including plasma HDL-C concentrations and other risk factors associated with the metabolic syndrome. Results also showed that alcohol consumption (>15.2 g of alcohol/d) appeared to attenuate the risk attributable to the metabolic syndrome.
The review of previous reports on the relation between light-to-moderate alcohol consumption and the risk of IHD revealed an inverse association in most epidemiological studies (2). Data more recently reviewed in a meta-analysis of available studies on the effects of moderate alcohol intake on lipids and hemostatic factors indicated that a consumption of 30 g of alcohol/d was associated with a 24.7% reduction in IHD risk (6). Our study revealed a 39% reduction in the 13-y RR of IHD among men who consumed 15.2 g alcohol/d than in men who consumed <1.3 g/d after adjustment for age, BMI, diabetes, smoking habits, systolic blood pressure, HDL-C, and medication use. Differences between our results and those from other studies may be partly explained by differences in analytical methods, including the selection of a cut-off point to categorize the degree of alcohol consumption. In addition, when we adjusted for HDL-C in our model, the relation between alcohol consumption and the risk of IHD was essentially unaltered, which suggests that other cardioprotective mechanisms may be involved.
Few studies have investigated the association between alcohol consumption and the metabolic syndrome, and inconsistent results have been reported. Freiberg et al. (17) found that light-to-moderate alcohol consumers (20 drinks/mo) had a lower odds ratio (OR) of having the metabolic syndrome than nondrinkers (OR = 0.34, P < 0.0001) and showed a more beneficial serum lipid profile as well as a smaller waist circumference and fasting serum insulin levels. However, results in a group of 391 clinically healthy 58 y-old men have shown that there was no significant difference in alcohol intake between men with vs. men without risk factors of the metabolic syndrome (13). In our study, men in the highest alcohol consumption quartile had a 43% lower risk of having the metabolic syndrome. Elevation in plasma HDL concentrations with moderate alcohol consumption appeared to be the key factor underlying the reduced prevalence of the metabolic syndrome.
Elevated plasma HDL-C concentration associated with a moderate alcohol intake has been reported in many previous studies (6,31,32) and this association has been suggested to be one of the key factors explaining the now well-accepted cardioprotective effects of alcohol. Another mechanism that may partly explain the reduction in IHD risk with a light-to-moderate alcohol intake is a decrease in plasma CRP concentration, a nonspecific marker of inflammation, suggesting an anti-inflammatory effect of alcohol (8,33,34). A lower plasma fibrinogen concentration with a moderate alcohol consumption has been previously reported (9,35). Also, a number of previous studies have shown that light-to-moderate alcohol consumption was associated with increased insulin sensitivity (7,14). In contrast, the negative impact of heavier alcohol intake (3–4 drinks/d) on blood pressure has been documented (15). In our study, we found that men in the highest alcohol consumption group had higher plasma HDL-C concentrations and lower fasting insulin, fibrinogen, and CRP concentration, which is consistent with data from previous studies. Our data also indicated that men in the highest alcohol consumption quartile tended to have higher plasma TG levels and lower BMI compared with men in the 1st quartile of alcohol consumption. Previous data on moderate alcohol consumption and long term effect on serum TG (6,17,36) and on obesity (16,37) have been inconsistent.
We recognize that the present study has limitations. First, alcohol consumption was evaluated only once at baseline. A possible misclassification of alcohol intake may have occurred due to self-report of intakes and change during follow-up, although misclassification would be likely to lead data toward the null hypothesis. Drinking patterns were also not evaluated. However, we observed a protective effect of light-to-moderate alcohol consumption on IHD risk even if drinking patterns were not considered in the analysis. We hypothesize that the relation between alcohol intake and IHD risk would have been accentuated if drinking patterns had been considered. The extent to which physical activity may have confounded the results in our analysis is also unknown. Finally, although the number of subjects in the present study may be considered relatively small, our access to a wide array of metabolic risk factors associated with the metabolic syndrome should be considered a strength.
In conclusion, consumption of 1 drink or more daily (>15g alcohol/d) had significant cardioprotective effects, which were more apparent in men with an altered metabolic profile such as in those with the metabolic syndrome. These effects appeared to be partly, but not exclusively, mediated by increase in plasma HDL-C concentrations and decreases in fasting insulin and CRP concentrations. These results pose an interesting conceptual challenge: should alcohol consumption be considered an acceptable therapeutic tool for the prevention of IHD in high-risk subjects with the metabolic syndrome? We do not recommend that nondrinkers begin drinking, however, there is now compelling evidence to support the concept that light-to-moderate alcohol intake may be part of a healthy lifestyle.
|
FOOTNOTES |
|---|
5 Abbreviations used: HDL-C, HDL cholesterol; IHD, ischemic heart disease; LDL-C, LDL cholesterol; OR, odds ratio, RR; relative risk; TG, triglyceride.
Manuscript received 4 July 2006. Initial review completed 22 August 2006. Revision accepted 5 October 2006.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
1. Hines LM, Rimm EB. Moderate alcohol consumption and coronary heart disease: a review. Postgrad Med J. 2001;77:747–52.
2. Moore RD, Pearson TA. Moderate alcohol consumption and coronary artery disease. A review. Medicine (Baltimore). 1986;65:242–67.[Medline]
3. Marmot M, Brunner E. Alcohol and cardiovascular disease: the status of the U shaped curve. BMJ. 1991;303:565–8.
4. Corrao G, Rubbiati L, Bagnardi V, Zambon A, Poikolainen K. Alcohol and coronary heart disease: a meta-analysis. Addiction. 2000;95:1505–23.[Medline]
5. Fagrell B, De Faire U, Bondy S, Criqui M, Gaziano M, Gronbaek M, Jackson R, Klatsky A, Salonen J, Shaper AG. The effects of light to moderate drinking on cardiovascular diseases. J Intern Med. 1999;246:331–40.[Medline]
6. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. BMJ. 1999;319:1523–8.
7. Kiechl S, Willeit J, Poewe W, Egger G, Oberhollenzer F, Muggeo M, Bonora E. Insulin sensitivity and regular alcohol consumption: large, prospective, cross sectional population study (Bruneck study). BMJ. 1996;313:1040–4.
8. Imhof A, Woodward M, Doering A, Helbecque N, Loewel H, Amouyel P, Lowe GD, Koenig W. Overall alcohol intake, beer, wine, and systemic markers of inflammation in western Europe: results from three MONICA samples (Augsburg, Glasgow, Lille). Eur Heart J. 2004;25:2092–100.
9. Sierksma A, van der Gaag MS, Kluft C, Hendriks HF. Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels; a randomized, diet-controlled intervention study. Eur J Clin Nutr. 2002;56:1130–6.[Medline]
10. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365:1415–28.[Medline]
11. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683–9.
12. Boyko EJ, de Court, Zimmet PZ, Chitson P, Tuomilehto J, Alberti KG. Features of the metabolic syndrome predict higher risk of diabetes and impaired glucose tolerance: a prospective study in Mauritius. Diabetes Care. 2000;23:1242–8.
13. Goude D, Fagerberg B, Hulthe J. Alcohol consumption, the metabolic syndrome and insulin resistance in 58-year-old clinically healthy men (AIR study). Clin Sci (Lond). 2002;102:345–52.[Medline]
14. Lazarus R, Sparrow D, Weiss ST. Alcohol intake and insulin levels. The Normative Aging Study. Am J Epidemiol. 1997;145:909–16.
15. Marmot MG, Elliott P, Shipley MJ, Dyer AR, Ueshima H, Beevers DG, Stamler R, Kesteloot H, Rose G, Stamler J. Alcohol and blood pressure: the INTERSALT study. BMJ. 1994;308:1263–7.
16. Sakurai Y, Umeda T, Shinchi K, Honjo S, Wakabayashi K, Todoroki I, Nishikawa H, Ogawa S, Katsurada M. Relation of total and beverage-specific alcohol intake to body mass index and waist-to-hip ratio: a study of self-defense officials in Japan. Eur J Epidemiol. 1997;13:893–8.[Medline]
17. Freiberg MS, Cabral HJ, Heeren TC, Vasan RS, Curtis ER. Alcohol consumption and the prevalence of the Metabolic Syndrome in the US.: a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey. Diabetes Care. 2004;27:2954–9.
18. Rosell M, De Faire U, Hellenius ML. Low prevalence of the metabolic syndrome in wine drinkers–is it the alcohol beverage or the lifestyle? Eur J Clin Nutr. 2003;57:227–34.[Medline]
19. Yoon YS, Oh SW, Baik HW, Park HS, Kim WY. Alcohol consumption and the metabolic syndrome in Korean adults: the 1998 Korean National Health and Nutrition Examination Survey. Am J Clin Nutr. 2004;80:217–24.
20. Dagenais GR, Robitaille NM, Lupien PJ, Christen A, Gingras S, Moorjani S, Meyer F, Rochon J. First coronary heart disease event rates in relation to major risk factors: Quebec cardiovascular study. Can J Cardiol. 1990;6:274–80.
21. St Pierre AC, Cantin B, Dagenais GR, Mauriege P, Bernard PM, Despres JP, Lamarche B. Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol. 2005;25:553–9.
22. Moorjani S, Dupont A, Labrie F, Lupien PJ, Brun D, Gagne C, Giguere M, Belanger A. Increase in plasma high-density lipoprotein concentration following complete androgen blockage in men with prostatic carcinoma. Metabolism. 1987;36:244–50.[Medline]
23. Albers JJ, Warnick GR, Wiebe D, King P, Steiner P, Smith L, Breckenridge C, Chow A, Kuba K, et al. Multi-laboratory comparison of three heparin-Mn2+ precipitation procedures for estimating cholesterol in high-density lipoprotein. Clin Chem. 1978;24:853–6.
24. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.[Abstract]
25. Laurell CB. Electroimmuno assay. Scand J Clin Lab Invest Suppl. 1972;124:21–37.[Medline]
26. Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 1996;334:952–7.
27. St Pierre AC, Cantin B, Bergeron J, Pirro M, Dagenais GR, Despres JP, Lamarche B. Inflammatory markers and long-term risk of ischemic heart disease in men: a 13-year follow-up of the Quebec Cardiovascular Study. Atherosclerosis. 2005;182:315–21.[Medline]
28. Clauss A. [Rapid physiological coagulation method in determination of fibrinogen.]. Acta Haematol. 1957;17:237–46.[Medline]
29. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–421.
30. Health Canada [database on the Internet]. Canadian Nutrient File; 2005 version; [cited 2006 Jun 7]. Available from: www.healthcanada.ca/cnf.
31. Linn S, Carroll M, Johnson C, Fulwood R, Kalsbeek W, Briefel R. High-density lipoprotein cholesterol and alcohol consumption in US white and black adults: data from NHANES II. Am J Public Health. 1993;83:811–6.
32. Gaziano JM, Buring JE, Breslow JL, Goldhaber SZ, Rosner B, VanDenburgh M, Willett W, Hennekens CH. Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N Engl J Med. 1993;329:1829–34.
33. Imhof A, Froehlich M, Brenner H, Boeing H, Pepys MB, Koenig W. Effect of alcohol consumption on systemic markers of inflammation. Lancet. 2001;357:763–7.[Medline]
34. Albert MA, Glynn RJ, Ridker PM. Alcohol consumption and plasma concentration of C-reactive protein. Circulation. 2003;107:443–7.
35. Burger M, Mensink G, Bronstrup A, Thierfelder W, Pietrzik K. Alcohol consumption and its relation to cardiovascular risk factors in Germany. Eur J Clin Nutr. 2004;58:605–14.[Medline]
36. Mayer EJ, Newman B, Quesenberry CP, Jr., Friedman GD, Selby JV. Alcohol consumption and insulin concentrations. Role of insulin in associations of alcohol intake with high-density lipoprotein cholesterol and triglycerides. Circulation. 1993;88:2190–7.
37. Breslow RA, Smothers BA. Drinking patterns and body mass index in never smokers: National Health Interview Survey, 1997–2001. Am J Epidemiol. 2005;161:368–76.
This article has been cited by other articles:
|
|
 |
|
  L. He, J. C. Marecki, G. Serrero, F. A. Simmen, M. J. J. Ronis, and T. M. Badger Dose-Dependent Effects of Alcohol on Insulin Signaling: Partial Explanation for Biphasic Alcohol Impact on Human Health Mol. Endocrinol., October 1, 2007; 21(10): 2541 - 2550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-C. Sung, S. H. Kim, and G. M. Reaven Relationship Among Alcohol, Body Weight, and Cardiovascular Risk Factors in 27,030 Korean Men Diabetes Care, October 1, 2007; 30(10): 2690 - 2694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. O'Keefe, K. A. Bybee, and C. J. Lavie Alcohol and Cardiovascular Health: The Razor-Sharp Double-Edged Sword J. Am. Coll. Cardiol., September 11, 2007; 50(11): 1009 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kloner and S. H. Rezkalla To Drink or Not to Drink? That Is the Question Circulation, September 11, 2007; 116(11): 1306 - 1317. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
