Tabac et Lipides. Michel FARNIER, MD, PhD, Dijon

Transcription

1 Tabac et Lipides Michel FARNIER, MD, PhD, Dijon Dr Farnier reports having received grants, consulting fees and/or honoraria and delivering lectures for Abbott, Akcea/Ionis, Amarin, Amgen, AstraZeneca, Eli Lilly, Kowa, Merck and Co, Mylan, Pfizer, Roche, Sanofi/Regeneron and Servier

2 Tabagisme et Lipides Effets quantitatifs du tabagisme sur Lp Effets qualitatifs du tabagisme sur Lp Fonctionnalité des Lp Effets de l arrêt du tabagisme sur Lp

3 Tabagisme et Lipides Effets quantitatifs du tabagisme sur Lp Effets qualitatifs du tabagisme sur Lp Fonctionnalité des Lp Effets de l arrêt du tabagisme sur Lp

4 BMJ 1989; 298: Cigarette smoking and serum lipid and lipoprotein concentrations : an analysis of published data A meta-analysis of cross-sectional studies on the association of lipid profiles and cigarette smoking status Smokers had significantly : Higher serum total cholesterol (3.0%), TG (9.1%) and LDL-C (1.7%) Lower HDL-C (- 5.7%) and ApoAI (- 4.2%) Limitations : Small studies, frequently did not adjust for confounders that affects HDL-C levels (such as age, sex, race, adiposity, alcohol use, physical activity, )

5 Smoking and plasma lipoprotein in man : effects on LDL-C levels and HDL-C subfraction distribution (survey of a healthy population, n=197) LDL-C, TG, VLDL-TG HDL-C S HDL 2 No effect on Lp(a) Upon adjustment for covariant factors, mean difference between smokers and non-smokers for HDL-C was 0.15 mmol/l (0.06 g/l) Freeman et al. Eur J Clin Invest 1993; 23:

6 Smoking intensity and lipoprotein abnormalities in active smokers Objective : To evaluate the effects of 5 markers of smoking intensity on Lp concentrations and particle sizes (NMR profiles) in a large, modern cohort of current smokers. 1,504 current smokers (21.4 cigarettes/day; 29.4 pack.years) Atherogenic lipoprotein profile : LDL-C TG HDL-C 119 mg/dl (mainly sdldl) 143 mg/dl 42 mg/dl (36 mg/dl for men, 46 mg/dl for women) Gossett et al. J Clin Lipidol 2009; 3: 372-8

7 Smoking intensity and lipoprotein abnormalities in active smokers Correlations between the 5 markers of smoking intensity and each lipoprotein were weak. Little evidence that smoking reduction, Markers of smoking burden (cigarettes/day, pack-years): as opposed to smoking cessation, associated with higher TC, LDL-C, TG would improve lipoproteins significantly among smokers Markers of nicotine dependence and recent smoking exposure (CO levels): associated with lower HDL-C and HDL particles Gossett et al. J Clin Lipidol 2009; 3: 372-8

8 Tabagisme et Lipides Effets quantitatifs du tabagisme sur Lp Effets qualitatifs du tabagisme sur Lp Fonctionnalité des Lp Effets de l arrêt du tabagisme sur Lp

9 Potential pathways and mechanisms for cigarette smoking-mediated cardiovascular dysfunction Ambrose et al. JACC 2004; 43:

10 Cigarette smoking increases LDL oxidation Circulating products of lipid peroxydation and Ab to ox LDL are increased in smokers Heitzer et al. Circulation 1996; 9: Exposure to cigarette smoke extract (CSE) caused LDL modification and accumulation in macrophages Yokode et al. PNAS 1988; 85: Gas phase oxidants of cigarette smoke induce lipid peroxidation Frei et al. Biochem J 1991; 277: CSE exposure decrease plasma activity of paraoxonase Nishio et al. BBRC 1997; 236:

11 Smokers compared to non-smokers Correlations between smoking status and MDA-LDL in patients with and without statin treatment Statin therapy might have a beneficial effect on the reduction of MDA-LDL level Ogawa et al. BMJ Open 2015; 5: e005455

12 Smoking and qualitative changes of HDL Smoking and/or by exposure to cigarette smoke in vitro : activities of HDL-associated enzymes ( LCAT, PON activities) cholesterol efflux capacity of HDL Mechanisms : Chen et al. J Biochem Toxicol 1995; 10: James et al. Circulation 2000; 101: Ueyama et al. Free Radic Biol Med 1998; 24: oxidation of amino acids residues (free thiol groups), which are critical for LCAT and paraoxonase activities Bielicki et al. BBA 1995; 1258:35-40 Nishio et al. BBRC 1997; 236:

13 Inhibition of ApoA-I gene by the aryl hydrocarbon receptor : a potential mechanism for smoking-associated hypoalphalipoproteinemia Polycyclic aromatic hydrocarbons (PAHs) (such as benzo(a)pyrene and 3-methylcholanthrene) found in tabacco smoke can induce activity of the aryl hydrocarbon receptor (AhR) AhR can regulate glucose and lipid metabolism Treatment of HepG2 cells with AhR receptor agonists inhibited apoa-i protein synthesis (while nicotine which does not bind AhR had no effect). Naem et al. Life Sciences 2012; 91: 64-69

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15 Dysfunctional Lipoproteins from Young Smokers (comparison smokers and non-smokers) TG contents in serum and all lipoprotein fractions Lipoproteins more oxidized and glycated LDL promoted increased foam cell formation HDL showed increased glycation and reduced antioxidant ability Park et al. Toxicological Sciences 2014; 140: 16-25

16 Tabagisme et Lipides Effets quantitatifs du tabagisme sur Lp Effets qualitatifs du tabagisme sur Lp Fonctionnalité des Lp Effets de l arrêt du tabagisme sur Lp

17 Controversial effects of smoking cessation In some studies : HDL-C oxidative stress paraoxonase activity In others : no change in the susceptibility to in vitro LDL oxidation Eur J Clin Invest 2000; 30: 972-9

18 The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles : a meta-analysis HDL-C increased significantly [0.100 mmol/l (CI to 0.127)] after smoking cessation. TC, LDL-C and TG did not show a significant change after smoking cessation In subgroup analyses, net change in HDL-C was significantly larger in female subjects in subjects with high HDL-C before smoking cessation (> 1.2 mmol/l) (role of obesity, lack of exercize in subjects with low HDL-C?) Maeda et al. Prev Med 2003; 37:

19 Randomized controlled smoking cessation study 182 smokers randomized to stop smoking (n=100) or continue smoking for 4 weeks (n=82) In 62 successful quitters, HDL-C S after 4 weeks In 29 subjects followed up to after 26 weeks, no change in HDL no change in lipoprotein oxidation resistance Priemé et al. Scand J Clin Lab Invest 1998; 58: 11-8

20 Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial 1-year, prospective, double-blind, randomized, placebo-controlled trial of the effects of 5 smoking cessation pharmacotherapies. Effects of smoking cessation and predictors of changes in lipoproteins (NMR Lp profiles) after 1 year were identified by multivariate regression. Gepner et al. Am Heart J 2011; 161:

21 Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial 1,504 current smokers, 923 returned at 1 year 334 (36.2%) had quit smoking. Abstainess vs continuing smokers weight (4.6 vs 0.7 kg) p < HDL-C (2.4 vs 0.1 mg/dl) p < total HDL (p < 0.001) and large HDL particles (p=0.003) NS changes in LDL-C and LDL particles After adjustement, abstinence independently associated (p<0.001) with increases in HDL-C and total particles. Effects stronger in women. Gepner et al. Am Heart J 2011; 161:

22 Impact of Cigarette Smoking Cessation on HDL Functionality 32 smokers randomly treated with varenicline or transdermal nicotine patch (12-week smoking cessation program) Comparison between the successful smoking cessation group and the unsuccessful group After smoking cessation, no changes in HDL-C, apoa-1 and HDL subfractions (baseline HDL-C 55 mg/dl) Takata et al. Circ J 2014; 78:

23 Impact of Cigarette Smoking Cessation on HDL Functionality Smoking cessation leads to improve HDL functionality Takata et al. Circ J 2014; 78:

24 Conclusion Effets délétères du tabac sur lipides quantitatifs : HDL-C et apoa-1 TG LDL-C?, LDL petites et denses surtout qualitatifs : oxydation LDL HDL dysfonctionelles ( oxydabilité, CEC) Réversibilité à l arrêt du tabac? surtout amélioration fonctionnalité HDL