Alcohol Consumption at Midlife and Risk of Stroke During 43 Years of Follow-Up: Cohort and Twin Analyses
Depending on the dose, alcohol is both a risk factor for stroke and may help prevent ischemic stroke as reflected by a J- or U-shaped association with stroke risk. Kadlecová et al sought to revisit this issue and tested the hypothesis that heavy drinkers (>2 drinks/d) and nondrinkers would have a greater risk of stroke compared with light drinkers (<0.5 drink/d). Subjects (n=11 644) aged <60 years at baseline and with valid alcohol data included in the Swedish Twin Registry were analyzed. Overall, 29% of subjects developed stroke (55% ischemic, 12% hemorrhagic, and 33% undetermined). Compared with light drinkers, heavy drinkers had a greater stroke risk (hazard ratio, 1.34). In addition, there was only a nonsignificant trend toward greater stroke risk in nondrinkers when compared with light drinkers (hazard ratio, 1.11). The preferred type of alcohol did not have a significant effect on risk of stroke. In analyses run separately for ischemic versus hemorrhagic stroke, the risk of stroke was only higher for hemorrhagic stroke. Heavy drinking was associated with an earlier onset of stroke, and the risk decreased from young to old age. In analyses of monozygotic twin-pairs discordant for stroke there was no overall difference in stroke risk. Nevertheless, heavy drinking shortened time to stroke by ≈5 years (P=0.04). This study confirms the notion that heavy alcohol consumption has a modest effect on increasing the overall stroke risk, particularly that of hemorrhagic stroke. Importantly, this seems to be independent of genetic or early-life factors. Finally, this study did not demonstrate a definite positive or adverse effect with no and light drinking, respectively, and contrary to some other studies the type of alcohol did not matter. In terms of real life practice, this study reassures us that modestly enjoying alcohol according to one’s personal tastes confers no additional stroke risk. See p 627.
Adherence to a Mediterranean Diet and Prediction of Incident Stroke
Control of vascular risk factors has the greatest potential to reduce incident stroke. The so-called Mediterranean-style diet (MeD; rich in fruit, vegetables, whole grains, olive oil, and moderate intake of fish and alcohol) has shown promise to provide a modest reduction of the risk of vascular events. Tsivgoulis et al used the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) to determine the potential association between higher adherence to MeD and lower risk of stroke in subjects as well as its association with ischemic versus hemorrhagic stroke subtype as well as race. A total of 20 197 (67%) individuals were included in the analyses (mean age, 65±9 years; 33% were black). The MeD score was computed as the sum of scores in the 9 food categories (range, 0–9) with a higher score indicating a higher adherence to MeD. A total of 53% of individuals had a low adherence to MeD (score, 0–4). The incident stroke rate was 2.8% (88% ischemic strokes). High adherence to MeD was independently associated with a 21% reduction in incident ischemic stroke (hazard ratio, 0.79; P=0.016). Ischemic stroke risk increased by 5% for each 1-point increase in the MeD score. There was no interaction between race, sex, or region of residence and the relationship of adherence to MeD and incident ischemic stroke. Finally, the degree of adherence with the MeD was not associated with the risk for hemorrhagic stroke. This study adds to the existing data showing a potential beneficial role of a healthy dietary pattern such as MeD in cerebrovascular disease protection. It would be interesting to learn which subtype of ischemic stroke (if any) benefitted the most. Furthermore, one of the key questions is whether specific nutritional components included in the MeD provide this benefit or whether protection was achieved by the omission of unhealthy foods. If the former plays a significant role in disease modification, then supplementation with certain foods/ingredients might provide a viable protective option to high-risk patients who are unable or unwilling to change their lifestyle and dietary habits. See p 780.
Comparative Risk of Ischemic Stroke Among Users of Clopidogrel Together With Individual Proton Pump Inhibitors
Clopidogrel is a prodrug that requires conversion to its active metabolite through a multistep process mediated by multiple cytochrome P-450 isozymes. Given the known interaction with one of the involved cytochrome P isozymes, cytochrome P2C19, some commonly used proton pump inhibitors (PPIs) might reduce clopidogrel’s effectiveness. Leonard et al sought to determine the comparative safety of individual PPIs with respect to acute ischemic stroke risk among users of clopidogrel. To this end they conducted a propensity score–adjusted retrospective cohort study of adult new users of clopidogrel and who were taking a PPI (esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole) recruited from 1999 to 2009 Medicaid claims from California, Florida, New York, Ohio, and Pennsylvania. New users of clopidogrel had to be enrolled into Medicaid for ≥12 months before their first clopidogrel prescription. Among other criteria, patients with a >15-day gap in either clopidogrel or PPI therapy or a switch to another PPI were excluded. Pantoprazole was selected as the reference PPI. To calculate propensity scores, covariates from the following key categories were considered: demographics, health system use factors, comorbidities, drug markers of chronic diseases at baseline, acutely occurring diseases, and recent drug exposures. Outcome of interest was hospitalization for acute ischemic stroke (based on International Classification of Diseases Ninth Revision Clinical Modification discharge diagnose) within 180 days of cohort entry. Overall, 325 559 subjects using clopidogrel and a PPI (70 274 person-years) were identified. Among these, 1667 developed an ischemic stroke (annual event rate of 2.4%). Compared with pantoprazole, all other PPIs had no significantly different propensity score–adjusted hazard ratios for ischemic stroke. Sensitivity analysis suggested that the risk (versus pantoprazole) was increased among lansoprazole-treated persons with a recent hospitalization for acute coronary syndrome and recent hospitalization for acute myocardial infarction. Yet, this study showed that in general ischemic stroke rates for clopidogrel with individual PPIs of interest were no greater than that for clopidogrel with pantoprazole, a PPI thought not to interact with clopidogrel. Although the results suggest that lansoprazole may negate the protective effect of clopidogrel among patients with acute coronary syndrome/myocardial infarction, this result requires confirmation in future studies. Regardless, although not directly studied, this study assuages concerns that the investigated PPI significantly attenuate clopidogrel’s efficacy to protect from ischemic stroke. See p 722.
- © 2015 American Heart Association, Inc.