1 Department of Gastroenterology, Vascular Diseases and Internal Medicine, The Ludwik Rydygier Medical University in Bydgoszcz, Ujejskiego 75 Street, 85-168 Bydgoszcz and
2 Department of Psychiatry Nursing, The Ludwik Rydygier Medical University in Bydgoszcz, Kurpiskiego 19 Street, 85-096 Bydgoszcz, Poland
Received 14 June 2002; in revised form 2 October 2002; accepted 24 October 2002
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ABSTRACT |
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INTRODUCTION |
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Moreover, epidemiological studies show a J shaped relationship between the quantity of daily alcohol intake and coronary artery disease prevalence (Goldberg et al., 1995; Keil, 1997
; Renaud et al., 1998
; De Lorimier, 2000
). This suggests that, in regularly drinking people, cardiovascular event risk may increase during abstinence. We assume that this also concerns alcoholics. Because the cardioprotective effect of regular alcohol drinking is attributed to the favourable influence on lipid metabolism, homeostasis, antioxidative balance (flavinoids), nitric oxide secretion, vascular tone and reological blood properties, alcohol drinking cessation could result in the disappearance of these beneficial changes. The main changes in fasting lipids level during the acute abstinence period in alcoholics are well recognized, but changes in Lp(a) and post-prandial lipid levels in abstinent alcoholics are not clear. Because of this, we have undertaken the present study.
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PATIENTS AND METHODS |
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We determined the concentrations of the following plasma lipids: Lp(a), total cholesterol (TC), HDL and TGL. An LDL value, using the Friedewald pattern, was calculated only for patients with a TGL level below 400 mg/dl. We also performed (to exclude secondary causes of lipid metabolic disturbances) a glucose tolerance test, peripheral blood morphology, creatinine and thyrotropin concentration, as well as biochemical markers of alcohol misuse, namely: -glutamyltranspeptidase, aspartate aminotransferase, alanine amino transferase and mean corpuscular volume. Moreover, we calculated the plasma lipids pro-atherogenic indices, namely: TC to HDL concentration ratio (TC/HDL), TC minus HDL to HDL concentration ratio [(TCHDL)/HDL], LDL to HDL concentration ratio (LDL/HDL) and Lp(a) to HDL concentration ratio [Lp(a)/HDL]. We considered as critical values of the first three indices 5, 4 and 4, respectively. We could not find in the available literature the predictive value of the Lp(a)/HDL ratio. Lp(a) concentration (only fasting) was assayed by an ELISA method, using the set manufactured by Cormay-La Roche. The other determinations were made using routine laboratory methods.
For the first 8 weeks of the study, alcohol-dependent patients were hospitalized in the Addiction Therapy Unit. They received a similar hypolipaemic diet, according to European Atherosclerosis Society (1992) recommendations (Pyörala et al., 1994). Energy consumption was on average 2000 kcal per day, but in patients with body mass index (BMI) above 25 kg/m2 the reduced diet (to 20 kcal/kg body mass) was recommended. A daily diet consisted of cereal products in one third, vegetables in one quarter, 15% of milk products and the rest in meat, fish or legumes. In this way, daily cholesterol consumption was lower than 300 mg and daily fat-energy consumption was lower than 30% (saturated fatty acids below 10% energy, mono-unsaturated fatty acids 1015% energy and poly-unsaturated fatty acids 710% energy). In patients with a BMI above 25 kg/m2 and in patients with hyper-triglyceridaemia (TGL > 200 mg/dl), no sugar consumption was recommended. During the study period, patients did not take any drugs.
Abstinence was controlled during hospitalization on the basis of physical examination as well as alcohol presence in exhaled air and the above-mentioned biochemical markers of alcohol misuse. After discharge from the Unit, abstinence was monitored by interview, level of biochemical markers, objective familial interview, and medical documentation analysis (from out-patient department).
As mentioned above, the study included 54 alcohol-dependent male patients and 20 control males, who denied ever misusing alcohol or drinking for the previous month. For the examination after 4 weeks of abstinence, 47 (87%) patients and 18 (90%) persons from the control group turned up, and after 6 months of observation, 27 (50%) patients turned up, but only 18 (33%) remained abstinent till this period.
All subjects gave their informed consent to participate in this study, which was approved by the Local Ethics Committee of The Ludwik Rydygier Medical University in Bydgoszcz. The investigation was in compliance with the Declaration of Helsinki for medical research.
Statistical significance was determined using, respectively, unpaired and paired Students t-tests, chi-square tests and two-factorial ANOVAs with three repetitions and Tukey post hoc tests in statistical software STATISTICA PL 5.0.
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RESULTS |
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DISCUSSION |
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These results indicate that, in alcohol-dependent males during abstinence, pro-atherogenic changes proceed in fasting plasma lipid levels. These changes may lead to an increase of cardiovascular events risk. Epidemiological studies show that an increase in TC level by 1% increases the cardiovascular event risk by 2% (Law et al., 1994), and a decrease of HDL by 1 mg/dl increases cardiovascular event risk by 3% (Gordon et al., 1989
). In this way, the cardiovascular event risk in our alcohol-dependent patients increased after 6 months of abstinence by about 1218% for TC and 21% for HDL (total increase by about 40%). On the basis of the same data, we may also conclude that patients with alcohol drinking relapse had a 52% reduced cardiovascular event risk than patients, who have kept abstinence for the whole 6-month period (Fig. 2
). Additional greater cardiovascular risk was related to the increase of plasma lipid pro-atherogenic indices. For example, a value of TC/HDL ratio above 5 is related to four times greater cardiovascular event risk in patients with a TGL level below 200 mg/dl, and increased seven times when TGL level is above 200 mg/dl (Assmann et al., 1992
).
In our study, we have observed a significant decrease in Lp(a) levels during the succeeding months of abstinence (Fig. 1). These results show some differences in comparison with the majority of other studies. Only Willeit et al.(1995)
showed that alcohol drinking was associated with a tendency towards higher Lp(a) levels, but Valimaki et al. (1993)
, Iso et al. (1996)
and Paassilta et al.(1998)
observed a negative correlation between quantity of alcohol intake and Lp(a) plasma concentration, whereas in our study Lp(a) level was highest soon after alcohol drinking cessation and decreased in succeeding months. A simultaneous significant increase in the Lp(a)/HDL ratio was observed. The changes in Lp(a) and the Lp(a)/HDL ratio during 6 months of abstinence observed in the present work are in accordance with epidemiological studies, which show J shaped relationships between quantity of alcohol drunk and cardiovascular event prevalence (Goldberg et al., 1995
; Keil, 1997
; Renaud et al., 1998
; De Lorimier, 2000
). By reason of the fact that an Lp(a) level above 30 mg/dl is the independent cardiovascular event risk factor, in our patients Lp(a)-related cardiovascular risk was the highest at the study start. This suggests that the increase of Lp(a) plasma concentration may be a potential factor in the pro-atherogenic alcohol effect (right arm of J shaped curve). On the other hand, the increase in the Lp(a)/HDL ratio after 4 weeks of abstinence may be the next mechanism explaining the left arm course of this J shaped curve, in addition to known changes in HDL and LDL levels. The results of The Familial Atherosclerosis Treatment Study suggested that Lp(a) level and the Lp(a)/HDL ratio are better related to coronary artery narrowing before the hypolipaemic therapy start, than other lipid concentration values (Maher et al., 1995
). The observed higher Lp(a) level at the study start may be explained by the influence of inflammatory cytokines, which regulate about 20% of Lp(a) plasma concentration [the same level as the decreased mean Lp(a) levels in our patients during abstinence]. The increased level of inflammatory cytokines due to alcohol drinking has previously been reported (Naveau et al., 2001
; Poullis and Mendall, 2001
; Uesugi et al., 2001
, 2002
). The higher level of Lp(a) observed just after alcohol drinking cessation suggests a potentially pro-atherogenic alcohol misuse effect connected with the activity of this lipoprotein.
In our study, we also investigated post-prandial plasma lipid changes during abstinence. We studied these parameters, because for most of the day, people are in a post-prandial state. The Nikkila et al. (1994) study confirmed this suggestion. Our results showed that post-prandial TGL level is probably a better predictor of pro-atherogenic lipid activity than fasting HDL level. Alcohol drinking may influence post-prandial lipid levels via: changes in lipid intestinal absorption (intestinal barrier injury, bile and pancreatic juice excretion), lipid turnover (changes in pituitarythyroid and pituitary adrenal axes function) and metabolism (changes in LPL, HL and LCAT activities). These changes disappear after alcohol withdrawal, which may be of importance in post-prandial lipaemia. But, in our study, we did not observe an effect of abstinence on post-prandial lipid levels. Only post-prandial HDL level decreased with abstinence, as was the case for fasting HDL. We have not found any investigations in the literature in which changes in post-prandial lipaemia during abstinence in alcohol-dependent patients were studied. But previous results showed that drinking 60 g of vodka (24 g of pure ethanol) or 370 ml of white wine (44.4g of pure ethanol) with meals leads to a significant increase of post-prandial TGL level, independently of abstinence or regular alcohol drinking in the past (Superko, 1992
; Pownall, 1994
).
In conclusion, we suggest that: (1) higher Lp(a) levels soon after alcohol withdrawal may be a potential factor responsible for the increase in acute coronary syndromes prevalent in the drinking and early abstinence period, in spite of high HDL concentration; (2) in alcohol-dependent male patients, abstinent for 6 months, pro-atherogenic plasma cholesterol main fraction changes occur, which, on the basis of epidemiological studies, could increase the cardiovascular event risk by about 40%; (3) the increase in HDL concentration is the main lipid metabolic parameter mediating the anti-atherogenic effect of alcohol.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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REFERENCES |
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Bartens, W. and Wanner, C. (1994) Lipoprotein(a): new insights into an atherogenic lipoprotein. Clinical Investigation 72, 558567.
Budzyski, J., Rybakowski, J.,
wiatkowski, M., Torli
ski, L., K
opocka, M., Kosmowski, W. and Zió
kowski, M. (2000) Naltrexone exerts a favourable effect on plasma lipids in abstinent patients with alcohol dependence. Alcohol and Alcoholism 35, 9197.
De Lorimier, A. A. (2000) Alcohol, wine, and health. American Journal of Surgery 180, 357361.[CrossRef][ISI][Medline]
Edelberg, J. and Pizzo, S. (1994) Lipoprotein(a) regulates plasmin generation and inhibition. Chemistry and Physics of Lipids 67/68, 363368.[CrossRef]
Falicki, Z., Karczewski, J., Leszek, W. and Chrzanowski, W. (1986) Usefulness of the Michigan alcoholism screening test (MAST) in Poland (in Polish). Psychiatria Polska 20, 3942.
Fulcher, G. (1992) Lipoprotein(a): a new independent risk factor or atherosclerosis. Australian and New Zealand Journal of Medicine 22, 326328.[ISI][Medline]
Goldberg, D. M., Hahn, S. E. and Parkes, J. G. (1995) Beyond alcohol: beverage consumption and cardiovascular mortality. Clinica Chimica Acta 237, 155187.[CrossRef][ISI][Medline]
Goldberg, I. J. (1996) Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. Journal of Lipid Research 37, 693707.[Abstract]
Gordon, D. J., Probstfield, J. L., Garrison, R. J., Neaton, J. D., Castelli, W. P., Knoke, J. D., Jacobs, D. R., Jr, Bangdiwala, S. and Tyroler, A. (1989) High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 79, 815.[Abstract]
Hagiage, M., Marti, C., Rigaud, D., Senault, C., Fumern, F., Apfelbaum, M. and Girard-Giota, A. (1992) Effect of a moderate alcohol intake on the lipoproteins of normotriglyceridemic obese subjects compared with normoponderal controls. Metabolism 41, 856861.[CrossRef][ISI][Medline]
Iso, H., Koike, K. A., Folsom, A. R., Shimamoto, T., Sato, S., Lida, M. and Komachi, Y. (1996) Lipoprotein(a) and its correlates in Japanese and U.S. population samples. Annals of Epidemiology 6, 324330.[CrossRef][ISI][Medline]
Keil, U. (1997) The relation of alcohol to coronary heart disease and all cause mortality in a beer-drinking population. Epidemiology 8, 150156.[ISI][Medline]
Kervinen, K., Savolainen, M. J. and Kesaniemi, A. (1991) Multiple changes in apolipoprotein B containing lipoproteins after ethanol withdrawal in alcoholic men. Annals of Medicine 23, 407413.[ISI][Medline]
Lamisse, F., Schellenberg, F., Bouyou, E., Delarne, J., Bernard, J. Y. and Conet, C. (1994) Plasma lipids and alcohol consumption in alcoholic men: effect of withdrawal. Alcohol and Alcoholism 29, 2530.[Abstract]
Langer, R. D., Criqui, M. H. and Reed, D. M. (1992) Lipoproteins and blood pressure as biological pathways for effect of moderate alcohol consumption on coronary heart disease. Circulation 85, 910915.[Abstract]
Law, M. R., Wald, N. J. and Thompson, S. G. (1994) By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? British Medical Journal 308, 367372.
Maher, V. M., Brown, B. G., Marcovina, S. M., Hillger, M. A., Zhao, X. Q. and Albers, J. J. (1995) Effect of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a). Journal of the American Medical Association 274, 17711774.[Abstract]
National Cholesterol Education Program (NCEP) (2001) Executive Summary of the 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). Journal of the American Medical Association 285, 24862497.
Naveau, S., Abella, A., Raynard, B., Balian, A., Giraud, V., Montembault, S., Mathurin, P., Keros, L. G., Portier, A., Capron, F., Emilie, D., Galanaud, P. and Chaput, J. C. (2001) Tumor necrosis factor soluble receptor p55 and lipid peroxidation in patients with acute alcoholic hepatitis. American Journal of Gastroenterology 96, 33613367.[CrossRef][ISI][Medline]
Nikkila, M., Solakivi, T., Lehtimaki, T., Koivula, T., Laippala, P. and Astrom, B. (1994) Postprandial plasma lipoprotein changes in relation to apolipoprotein E phenotypes and low density lipoprotein size in men with and without coronary artery disease. Atherosclerosis 106, 149157.[ISI][Medline]
Nishiwaki, M., Ishikawa, T., Ito, T., Shige, H., Tomiyasu K., Nakajima, K., Kondo, K., Hashimoto, H., Saitoh, K., Manabe, M., Miyajima, E. and Nakamura, H. (1994) Effect of alcohol on liporotein lipase, hepatic lipase, cholesteryl ester transfer protein, and lecithin: cholesterol acyltransferase in high-density lipoprotein cholesterol elevation. Atherosclerosis 111, 99109.[ISI][Medline]
Paassilta, M., Kervinen, K., Rantala, A. O., Savolainen, M. J., Lilja, M., Reunannen, A. and Kesaniemi, Y. A. (1998) Social alcohol consumption and low Lp(a) lipoprotein concentration in middle aged Finnish men: population based study. British Medical Journal 316, 594595.
Poullis, A. and Mendall, M. A. (2001) Alcohol, obesity, and TNF-alpha. Gut 49, 313314.
Pownall, H. J. (1994) Dietary ethanol is associated with reduced lipolysis of intestinally derived lipoproteins. Journal of Lipid Research 35, 21052113.[Abstract]
Pyörala, K., DeBacker, L., Poole-Wilson, P. and Wood, D. (1994) Prevention of coronary heart disease in clinical practice. Recommendations of the Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension. European Heart Journal 15, 13001331.[ISI][Medline]
Renaud, S. C., Gueguen, R., Schenker, J. and DHoutaud, A. (1998) Alcohol and mortality in middle-aged men from eastern France. Epidemiology 9, 184188.[ISI][Medline]
Savolainen, M. J., Hannuksela, M., Seppanen, S., Kervinen, K. and Kesaniemi, Y. A. (1990) Increased high-density lipoprotein cholesterol concentration in alcoholics is related to low cholesterol ester transfer protein activity. European Journal of Clinical Investigation 20, 593599.[ISI][Medline]
Scandinavian Simvastatin Survival Study Group (1994) Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). Lancet 344, 13831389.[ISI][Medline]
Steinberg, D., Pearson, T. A. and Kuller, L. H. (1991) Alcohol and atherosclerosis. Annals of Internal Medicine 114, 967976.[ISI][Medline]
Superko, H. R. (1992) Effects of acute and chronic alcohol consumption on postprandial lipemia in healthy normotriglyceridemic men. American Journal of Cardiology 69, 701704.[CrossRef][ISI][Medline]
Uesugi, T., Froh, M., Arteel, G. E., Bradford, B. U., Gabele, E., Wheeler, M. D. and Thurman, R. G. (2001) Delivery of IkappaB superrepressor gene with adenovirus reduces early alcohol-induced liver injury in rats. Hepatology 34, 11491157.[CrossRef][ISI][Medline]
Uesugi, T., Froh, M., Arteel, G. E., Bradford, B. U., Wheeler, M. D., Gabele, E., Isayama, F. and Thurman, R. G. (2002) Role of lipopolysaccharide-binding protein in early alcohol-induced liver injury in mice. Journal of Immunology 168, 29632969.
Valimaki, M., Kahri, J., Laitinen, K., Lahdenpera, S., Kuusi, T., Ehnholms, C., Jauhiainen, M., Bard, M., Fruchart, J. C. and Taskinen, M.-R. (1993) High density lipoprotein subfractions, apolipoprotein A-I containing lipoproteins, lipoprotein (a), and cholesteryl ester transfer protein activity in alcoholic women before and after ethanol withdrawal. European Journal of Clinical Investigation 23, 406417.[ISI][Medline]
Valimaki, M., Nikkila, E. A., Taskinen, M. R. and Ylikahri, R. (1986) Rapid decrease in high density lipoprotein subfractions and postheparin plasma lipase activities after cessation of chronic alcohol intake. Atherosclerosis 59, 147153.[ISI][Medline]
Willeit, J., Kiechl, S., Santer, P., Oberhollenzer, F., Egger, G., Jarosch, E. and Mair, A. (1995) Lipoprotein(a) and asymptomatic carotid artery disease. Evidence of prominent role in the evolution of advanced carotid plaques: The Bruneck Study. Stroke 26, 15821587.
Wood, D., De Backer, G., Faergeman, O., Mancia, G. and Pyörala, K. (1998) Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Atherosclerosis 140, 199270.[CrossRef][ISI][Medline]
World Health Organization (1992) International Statistical Classification of Diseases and Health-Related Problems, 10th revision. Uniwersyteckie Wydawnictwo Medyczne "Vesalis", Kraków 1994, 306.