By Michael H. Crawford, MD, Editor
Synopsis: A case-cohort subgroup of the PREDIMED study of older Mediterranean subjects at high cardiovascular disease risk, which used urinary tartaric acid to quantitate wine consumption, has shown over an almost five-year follow-up that light to moderate wine consumption was associated with a significant reduction in cardiovascular disease events.
Source: Dominguez-Lopez I, Lamuela-Raventos RM, Razquin C, et al. Urinary tartaric acid as a biomarker of wine consumption and cardiovascular risk: The PREDIMED trial. Eur Heart J. 2025;46(2):161-172.
Previous studies regarding the role of wine on the rate of cardiovascular disease (CVD) have suffered from the use of self-reported information on consumption. Tartaric acid is produced by grapes and rarely is synthesized by other plants. Thus, it can be used as a biologic marker for wine consumption as long as the subject does not consume table grapes or other grape products. This marker was employed in a study of the Mediterranean diet and CVD risk (PREDIMED) to quantitate wine consumption in a case-cohort, nested study within the PREDIMED study.
This sub-study of the PREDIMED trial of 7,447 high-CVD risk Spanish subjects (657 women, 575 men, mean age 68 years) involved 685 subjects who developed CVD and a random sample of 547 subjects who did not develop CVD after a mean follow-up of 4.8 years. CVD was defined as CV death, myocardial infarction (MI), stroke, or heart failure and was adjudicated by a blinded committee.
Baseline urinary tartaric acid levels were divided into five categories (< 1 mcg/mL, 1 mcg/mL to 3 mcg/mL, 3 mcg/mL to 12 mcg/mL, 12 mcg/mL to 35 mcg/mL, and > 35 mcg/mL), and reported wine consumption increased with higher levels of tartaric acid as expected. The intake of table grapes and raisins was somewhat higher in the > 35 mcg/mL group (P = 0.02).
The 3 mcg/mL to 12 mcg/mL and the 12 mcg/mL to 35 mcg/mL groups were associated with lower CVD risk (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.38-1.00; P = 0.05, and adjusted HR, 0.50; 95% CI, 0.27-0.95; P = 0.035, respectively). These two categories represent about three to 12 and 12 to 35 glasses of wine per month. Higher consumption (> 35 glasses/month) was not significantly associated with CVD risk reduction (HR, 0.89; 95% CI, 0.48-1.66; P = NS), nor was any level of self-reported wine consumption.
Analysis of the individual components of the primary outcome showed an inverse relationship between baseline tartaric acid and the rate of MI (HR, 0.70; 95% CI, 0.50-0.97; P = 0.045) but not any other components. The authors concluded that, when established objectively by a urinary biomarker, mild to moderate wine consumption (three to 35 glasses/month) was associated with lower CVD risk in an older Mediterranean population.
Commentary
With the release of the recent U.S. Surgeon General’s report on the potential detrimental effect of drinking alcohol on cancer risk, there is renewed interest in the possible health effects of wine consumption. Prior studies have shown that wine consumption increased high-density lipoprotein (HDL) cholesterol and lowered low-density lipoprotein (LDL) cholesterol. However, other studies have shown a J-shaped relationship with wine consumption and CVD mortality, which suggests that light to moderate consumption may be beneficial, but heavy consumption is detrimental.
The PREDIMED study supports this concept in older Mediterranean subjects at high CVD risk. The observed benefit was greatest in the moderate wine consumption group and less strong in the mild consumption group. However, a harmful relationship was not observed in this study. Among the individual endpoints in the primary composite outcome, reductions in MI were the most significant. Although the beneficial effect was observed in both sexes, it was stronger in men. Also, those with diabetes showed a significant benefit.
The major strength of PREDIMED is the use of urinary tartaric acid to quantitate wine consumption. This avoids the problems with self-reporting of consumption, which studies have shown usually is underreported for a variety of reasons. Although grape/raisin consumption was not prohibited, it was very low. Thus, the authors did not believe it contributed significantly to the urinary tartaric acid levels.
Also, this was a case-cohort study of well-characterized subjects with a long-term follow-up that accounted for potential confounding factors. However, this is an observational study, so causality cannot be assured, since there may be residual confounding. In addition, this was a study of older Mediterranean individuals only and may not apply to other groups. Finally, urinary tartaric acid only identifies wine consumption, not other alcohol beverages, but this population predominantly drank wine.
The mechanism of this reduction in CVD events with light to moderate wine consumption is not clear. Other studies have suggested that there are polyphenols in wine that are antioxidants. Recent studies have suggested that in Mediterranean countries, wine usually is consumed with meals rather than as a stand-alone beverage, which may enhance its beneficial properties in some way. Perhaps wine consumption reduces the consumption of other beverages containing alcohol, which may be more harmful. The alcohol debate continues, and a randomized, controlled, long-term study probably is never going to happen. Cheers!
Michael H. Crawford, MD, is Professor of Medicine and Consulting Cardiologist, University of California Health, San Francisco.
A case-cohort subgroup of the PREDIMED study of older Mediterranean subjects at high cardiovascular disease risk, which used urinary tartaric acid to quantitate wine consumption, has shown over an almost five-year follow-up that light to moderate wine consumption was associated with a significant reduction in cardiovascular disease events.
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