Alcohol, Other Drugs, and Health: Current Evidence July–August 2017 Journal Club Alcohol, Other Drugs, and Health: Current Evidence July–August 2017

Palatini P, et al. Am J Med. 2017;130(8):967-974.e1. Featured Article Alcohol intake more than doubles the risk of early cardiovascular events in young hypertensive smokers Palatini P, et al. Am J Med. 2017;130(8):967-974.e1.

Study Objective To assess the combined impact of alcohol use and smoking on major adverse cardiovascular and renal events (MACE).

Study Design Prospective cohort study of data from 18-45-year olds (N=1204) with stage 1 hypertension and low cardiovascular risk profile across 17 hypertension units in Italy. Exclusion criteria were diabetes, nephropathy, cardiovascular disease, and any other serious disease. Alcohol and tobacco use were assessed by interview. The combined major adverse cardiovascular and renal event outcome included: fatal and non-fatal myocardial infarction acute coronary syndromes cardiac revascularization procedures hospitalization for heart failure fatal and non-fatal stroke aortic or lower limb revascularization atrial fibrillation, and chronic kidney disease stage 3 or higher

Assessing Validity of an Article About Harm Are the results valid? What are the results? How can I apply the results to patient care? Based on the Users’ Guides to the Medical Literature; for more information, see the following: http://www.cche.net/usersguides/main.asp http://pubs.ama-assn.org/misc/usersguides.dtl

Are the Results Valid? Did the investigators demonstrate similarity in all known determinants of outcomes? Did they adjust for differences in the analysis? Were exposed patients equally likely to be identified in the two groups? Were the outcomes measured in the same way in the groups being compared? Was follow-up sufficiently complete?

Did the investigators demonstrate similarity in all known determinants of outcomes? Table. Hazard ratio (95% confidence interval) of adjusted* models for substance use groups** (reference group: nonsmokers who did not drink alcohol)   Outcome Any Alcohol Use Any Smoking Any Alcohol Use + Any Smoking Heavy Smoking (> 10 cigs/d) + Any Alcohol Use Major adverse cardiovascular and renal event, including atrial fibrillation 1.8 (1.1 - 3.2) 1.5 (1.2 – 1.8) 4.0 (2.0 – 8.2) 7.8 (4.2 – 14.4) Major adverse cardiovascular and renal event, without atrial fibrillation 2.3 (1.2 – 4.3) 1.5 (1.2 – 1.9) - 7.3 (3.8 – 14.1) * Models adjusted for age, sex, coffee intake, physical activity, body mass index, family history of cardiovascular disease, glucose, lipids, average 24-hour blood pressure, incident hypertension, and longitudinal changes in blood pressure and body weight. ** Any alcohol use (n=569), any smoking (n=254), any alcohol use + any smoking (n=142), any alcohol use + heavy smoking (n=51).

Did they adjust for differences in the analysis? Authors adjusted for age and sex.

Were exposed patients equally likely to be identified in the groups? Yes. People with smoking were classified into 4 categories according to the daily number of cigarettes smoked: nonsmokers (78.9%) 1-5 cigarettes/day (8.7%) 6-10 cigarettes/day (5.2%) >10 cigarettes/day (7.1%) Alcohol consumption was divided into 3 categories: 0 g/day (52.8%) <50 g/day (40.1%) ≥50 g/day (7.1%) 9

Were the outcomes measured in the same way in the groups being compared? Yes. Alcohol and tobacco use were assessed by interview. “Office BP and lifestyle habits were assessed monthly during the first 3 months of follow-up, then after 6 months, and every 6 months thereafter.”

Was follow-up sufficiently complete? Yes. 1204 of 1256 patients who met study criteria had at least 6 months of follow-up. These were the participants included in the analysis.

What are the Results? How strong is the association between exposure and outcomes? How precise is the estimate of the risk?

How strong is the association between exposure and outcome How strong is the association between exposure and outcome? How precise is the estimate of the risk? “Among the 142 smokers who also drank alcoholic beverages, the risk of MACE from the multivariable model (4.02; 95% CI, 1.98-8.15) was more than doubled compared with the 112 smokers who abstained from drinking (1.64; 95% CI, 0.63-4.27). In the group of heavy smokers who also were alcohol drinkers (n = 51), the risk of MACE was even quadrupled (7.8; 95% CI, 4.2 – 14.4).” 13

How Can I Apply the Results to Patient Care? Were the study patients similar to the patients in my practice? Was the duration of follow-up adequate? What was the magnitude of the risk? Should I attempt to stop the exposure?

Were the study patients similar to the patients in my practice? The participants were all white, young-to-middle-aged participants, (mean age 33 years, 73% male) with stage 1 hypertension (mean blood pressure 146/94).

Was the duration of follow-up adequate? Yes. Follow-up was 12.6 years.

What was the magnitude of the risk? Any alcohol use, smoking, or combination of alcohol use and smoking were associated with increased risk of adverse outcomes in adjusted models.

Should I attempt to stop the exposure? Yes. This study suggests an interactive effect between alcohol use and smoking to increase risk for cardiovascular and renal events in hypertensive smokers 45 years old or younger. The results support existing clinical recommendations to control blood pressure and encourage tobacco cessation and lower-risk (which includes no) drinking.