Author + information
- Robert A. Vogel, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Robert A. Vogel, University of Colorado, 435 Adams Street, Denver, Colorado 80206.
Grain alcohol is a simple molecule (ethanol) but a complex drug (1). Alcohol has divergent cardiovascular effects depending on the amount consumed. In moderation, alcohol is associated with reduced risk for coronary heart disease, most likely because it increases high-density lipoprotein cholesterol (2). Especially in excess, alcohol impairs ventricular function, increases arrhythmias such as atrial fibrillation, and causes hypertension. The latter is an important consequence but is often overlooked by clinicians treating patients with hypertension. Although more attention has been given to the type of alcohol ingested (e.g., red vs. white wine) (3), the pattern of drinking is far more important. In a study of 1,935 subjects after myocardial infarction, steady drinkers experienced a progressive decline in mortality with increasing consumption, whereas binge drinkers experienced no cardioprotection, even with heavy intake (4).
In this issue of the Journal, Goslawski et al. (5) present data on macrovascular and microvascular function from small cohorts of binge-drinking college students studied 1 to 4 days after their last binge and abstaining students. The investigators report a comparative decrease in both endothelium-dependent (brachial artery flow-mediated dilation [FMD]) and brachial artery nitroglycerin-induced dilation (NTGD). Resistance arterioles, obtained by gluteal biopsy, showed no difference in endothelial-dependent (acetylcholine) dilation between the 2 groups, but endothelin-1 vasoconstriction was enhanced in the binge-drinking cohort compared with the abstaining group. This is an elegant study, especially with regard to the microvascular component, and it extends our understanding of alcohol's complex cardiovascular effects. It does, however, require a sober look at the data.
It is very tempting to presuppose that any factor, such as binge drinking, that accelerates atherosclerosis starts with endothelial dysfunction. Acute alcohol ingestion (60 g ethanol) impairs endothelial function early (4 h) but increases it later (13 h) (6). Similar biphasic effects on blood pressure were also observed in this study of 100 young men. In contrast to moderate intake, could binge drinking result in chronic endothelial dysfunction, as is associated with all traditional risk factors (7)? This is a reasonable hypothesis, but the present study suggests an alternative vascular abnormality in binge drinking.
Although decreased FMD usually means impaired endothelial function, in the present study, the reduced FMD observed in the binge drinkers must be interpreted in the context of 3 factors. First, and most important, NTGD was reduced at least to the same extent as was FMD in the drinking subjects. NTGD must be performed in conjunction with FMD to rule out post-endothelial (i.e., smooth muscle cell) dysfunction (8). True endothelial dysfunction would be manifest as abnormal FMD in the presence of normal or near-normal NTGD.
Second, peak shear rate was reduced in the binge drinkers. FMD measures brachial artery diameter at baseline and after 5 min of forearm blood pressure cuff arterial occlusion (8). As a hyperemic response to cuff release, peak flow shear increases several-fold, inducing the endothelium to release nitric oxide, with ensuing arterial dilation. Less peak shear in the binge drinkers should induce less dilation. The finding of 0.4-mm absolute dilation in both cohorts, especially in the setting of less peak shear in the drinking group, suggests normal endothelial function in this group.
Third, the binge-drinker group had larger brachial arteries. FMD decreases normally with increasing arterial diameter (8). Although the investigators report that the difference in FMD between the 2 groups remained statistically significant after correction for arterial diameter, the significance was diminished, and multivariate analysis is problematic in cohorts of this size. It is an interesting question why the binge drinkers had larger brachial arteries. Large brachial arteries suggest higher blood pressure, and a trend in that direction was present. Importantly, larger brachial arterial diameter also correlates with increased atherosclerosis and is associated with increased cardiovascular risk (9). In the context of increased brachial arterial diameter, decrease peak shear, and reduced NTGD, the reduced FMD in the binge drinkers cannot be attributed to endothelial dysfunction. The brachial artery data actually support an absence of endothelial dysfunction, just as the investigators found in the microcirculation using acetylcholine stimulation.
Even after disproval of the presupposition that the binge drinkers should have had endothelial dysfunction, the study remains interesting. Consider a constellation of findings in the binge drinkers 1 to 4 days after cessation of drinking: less peak shear after blood pressure cuff release, larger brachial arteries, increased vasoconstriction to endothein-1 in their microcirculation, and a trend toward increased systolic blood pressure (120 vs. 114 mm Hg, p = 0.09). Now note that the binge drinkers were predominately white (76%), while the abstainers were predominately nonwhite (79%), with a likely higher fraction of African Americans. Acknowledging higher blood pressure in young African Americans (10), the 6-mm Hg difference in blood pressure probably would have been greater had the cohorts been ethnically matched. The larger brachial artery diameter in the binge drinkers gives support to higher blood pressure, and the intrinsic vasoconstriction demonstrated by the lesser peak shear and increased endothelin-1 vasoconstriction suggests the cause.
A 6-mm Hg increase in blood pressure compared with that in abstaining college students does not sound like much, but it would translate to a 24% increase in cardiovascular risk, assuming a 4% increase for each 1-mm Hg increase in pressure (11). As a group, they are already borderline pre-hypertensive. Why alcohol, a vasodilator, might cause a persistent vasoconstrictive state days after cessation of intake remains unclear. It would have been helpful for the investigators to also investigate moderate, steady, young drinkers and to study the time course of vascular function immediately after cessation of intake, as well as after longer abstinence. Such further study might give us, for the first time, the exact mechanism by which excess alcohol and binge drinking pattern lead to hypertension. That discovery would be worth celebrating with a drink.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Vogel has reported that he has no relationships relevant to the contents of this paper to disclose.
- 2013 American College of Cardiology Foundation
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- for the Prospective Studies Collaboration