Cannabis et complications cardiovasculaires Prof. Reto Auer, MD, MAS 16.11.2017 reto.auer@biham.unibe.ch Twitter: @retoauer
Kattoor et al. http://www.acc.org/latest-in-cardiology/articles/2016/09/22/08/58/mari
CB1 et CB2 Kattoor et al. http://www.acc.org/latest-in-cardiology/articles/2016/09/22/08/58/mari
Etudes prospectives Données CARDIA Consommation cumulée de cannabis et Calcifications artères coronaires (CAC) et calcifications artères abdominales (AAC) Consommation cumulée de cannabis et évènements cardiovasculaires (CVD) Données NHANES Consommation cannabis et mortalité liée à hypertension Données Dunedin
Buts Etudier l association entre la consommation cumulée de cannabis sur une durée de 25 ans sur le risque de développer des plaques d athérosclérose Calcifications artères coronaires (CAC) Calcifications artères abdominales (AAC) Auer et al. Addiction, in press
Etude CARDIA Etude prospective de 5114 participants 4 centres aux USA (Oakland, CA; Pittsburgh, PA; Chicago, IL; Birmingham, AL) Age entre 18 et 30 ans au début de l étude, 50% femmes, 50% noirs (self-identified), 50% avec niveau d éducation bas. Suivi tous les 2 à 5 ans depuis 1986 0,2,5,7,10,15,20,25,30 http://www.cardia.dopm.uab.edu/
Cannabis et CAC/AAC 5115 included at baseline year 0 visit (1986-1987) in 4 sites 285 ( 6% of total) died 1333 (26% of total) lost to follow-up 3498 (68% of total) attended the year 25 visit (2011-2012) 3197 (91% of attendees) had CAC and AAC measures 3189 (89% of attendees) had both CAC and AAC measures Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print
Methods Marijuana use assessment. Baseline, follow-up examinations at years 2, 5, 7, 10, 15, 20, 25 Lifetime marijuana use and days used marijuana within the last 30 days Years of marijuana use= Number of lifetime marijuana uses/365 days Licit drugs: Pack-years of cigarette smoking=number of cigs / 20 cigs X 365 days Drink-years of alcohol = units of alcohol/365 days Cumulative lifetime binge-drinking events (>4 units per occasion) Illicit drugs Cumulative lifetime use of cocaïne, amphetamines and heroin CVRFs Blood lipids, blood glucose, blood pressure, BMI, physical activity Other covariates - Depression (CES-D) Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print
Stats Methods Areas under the curve (AUC) for cumulative exposure to cardiovascular risk factors (CVRFs), physical activity level, depression score Multinomial multivariate adjusted regression models: Outcomes: three categories of subclinical atherosclerosis: 1) no AAC and no CAC, 2) any AAC and no CAC, 3) CAC, regardless of AAC 2 categories: (a) participants with and without AAC, (b) those with and without CAC and, (c) those with AAC and CAC and those with no AAC and no CAC. Predictor: Years of marijuana use up to year 25 Covariates: age, education, race, sex, center, licit and illicit drug exposure, CVRFs, depression Use of inverse probability of censoring weights (IPCW) for selective exclusion of heavy marijuana users Test for interaction between history of tobacco smoking and marijuana use Sensitivity analyses: Multivariate regression with log+1 AAC or CAC 2-step models (logistic regression THSN multivariate regression with log AAC or CAC) Zero-inflated negative binomial models (ZINB models) Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print
Results Marijuana exposure Cumulative exposure 84% reported having used marijuana before or during the 25 years of follow-up Never Tobacco Smoker N=1581 (51%) Ever Tobacco Smoker N=1536 (49%) No marijuana use >0 to <1 marijuana-years >1 marijuanayears No marijuana use >0 to <1 marijuana-years >1 marijuanayears 426 (14) 947 (30) 208 (7) 64 (2) 787 (25) 685 (22) Alcohol exposure 19% vs 82% reported any binge drinking among never vs. heavy marijuana users Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print
Results Validation exposure tobacco smoking with cotinine values at baseline Current Marijuana use within last 30 days Cotinine <14 ng/ml Cotinine 14 ng/ml - No current smoking No marijuana within last 30 days 2554 (96) 96 (4) Any marijuana within last 30 days 668 (89) 79 (11) - Current smoking No marijuana within last 30 days 45 (5) 791 (95) Any marijuana within last 30 days 31 (5) 623 (95) Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print 11
Results Marijuana-years among never tobacco smokers (N=1581). Marijuana-years among ever tobacco smokers (N=1536). Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print
Results Tobacco pack-years among ever smokers (N=1536) Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print
No difference in interpretation with alterate models Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print
Limitations Selection bias of healthy participants over follow-up possible -> use of inverse probability of censoring weights Marijuana assessment before the start of the study not assessed Only one validation of exposure to tobacco through cotinine, no validation of exposure to marijuana Low number of participants with high exposure to marijuana 15 Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print
Conclusions Marijuana and tobacco use were both common. Intensity of lifetime tobacco smoking was consistently much higher than marijuana. Cumulative marijuana use was not associated with measures of atherosclerosis among middle-aged adults never exposed to tobacco. Trend towards increased risk of atherosclerosis among those with very high exposure to marijuana. Beware since few participants had such high exposure. Among those who had used tobacco, we found a small but significant association between marijuana use and AAC, even after we extensively adjusted for tobacco smoke exposure, Residual confounding? Implications We confirm the strong and consistent association between tobacco use and both AAC and CAC; The broader public health implications of high prevalence of tobacco use among marijuana users is alarming 16 Auer R, Sidney S, Goff D, Vittinghoff E, Pletcher MJ, Allen NB, Reis JP, Lewis CE, Carr J and Rana JS. Addiction. 2017 epub ahead of print
Reis JP, Auer R, Bancks MP, Goff DC, Jr., Lewis CE, Pletcher MJ, Rana JS, Shikany JM and Sidney S. Am J Public Health. 2017;107:601-606.
Reis JP, Auer R, Bancks MP, Goff DC, Jr., Lewis CE, Pletcher MJ, Rana JS, Shikany JM and Sidney S. Am J Public Health. 2017;107:601-606.
Reis JP, Auer R, Bancks MP, Goff DC, Jr., Lewis CE, Pletcher MJ, Rana JS, Shikany JM and Sidney S. Am J Public Health. 2017;107:601-606.
Meier MH, et al.. JAMA Psychiatry. 2016;73:731-40.
Meier MH, et al.. JAMA Psychiatry. 2016;73:731-40.
Meier MH, et al.. JAMA Psychiatry. 2016;73:731-40.
Conclusion No association between recreative average marijuana use and: Measures of subclinical atherosclerosis CVD and CHD events CVRFs Strong association with tobacco use with these outcomes Tobacco should remains the major focus for public health in order to reduce the burden of CVD and CHD