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Moderate wine consumption maintained its association with cardiovascular benefit when self-reports were taken out of the equation, the large PREDIMED trial showed.

Using urinary tartaric acid as an objective biomarker measuring wine consumption, light to moderate wine intake was tied to a lower risk of long-term cardiovascular disease (CVD) -- combined heart failure, myocardial infarction, stroke, and CVD death -- in an older Mediterranean population, reported Ramon Estruch, MD, PhD, of the University of Barcelona, and colleagues.

Compared with people with the lowest tartaric acid level (<1 μg/ mL), those with levels in the 12-35 μg/mL range (equivalent to drinking 12-35 glasses of wine per month) seemed to have some cardiovascular protection over a median 9 years of follow-up (HR 0.50, 95% CI 0.27-0.95).

"These findings suggest that the bioactive compounds present in wine may play a role in lowering the risk of CVD," the authors wrote in the .

However, they also showed that any cardiovascular benefit was weaker with tartaric acid levels in the 3-12 μg/mL range (3-12 glasses per month; HR 0.62, 95% CI 0.38-1.00) -- and not observed at all with the lowest (1-3 μg/mL, equivalent to 1-3 glasses of wine per month) and highest (>35 μg/mL, equivalent to 1.25 glasses per day) tartaric acid concentrations.

These results are in line with prior epidemiological research suggesting cardiovascular benefit with moderate wine drinking. Unlike these older studies, however, Estruch and colleagues had sought a surrogate for wine consumption for their study because they wanted to reduce the potential for misclassification and bias typically encountered in observational studies of alcohol and health outcomes.

"The implications of this study are far-reaching, particularly in the context of nutritional epidemiology and public health recommendations," wrote Giovanni de Gaetano, MD, PhD, of IRCCS NEUROMED in Pozzilli, Italy, and colleagues in .

"The use of an objective biomarker such as urinary tartaric acid represents a significant methodological advancement in alcohol research. It offers a more accurate and reliable measure of wine consumption, which could help resolve some of the ongoing debates about the health effects of alcohol," they added. "Humans, for various reasons, are often not truthful and tend to either deny or under-report their alcohol intake."

"Moreover, the findings suggest that wine consumption in real-life conditions, unaffected by the often artificial influences of a clinical trial setting, might have a more beneficial impact on cardiovascular health than previously thought," they noted.

For the study, tartaric acid was selected as a surrogate for wine intake given its stability of concentration, specificity of its dietary origin (grapes), the high sensitivity of the analytical method, and the scarcity in the consumption of its alternative dietary sources. "Thus, tartaric acid emerges as a valuable short-term biomarker (several days to a week) for assessing wine consumption, provided that the intake of grapes and their derivatives is excluded," Estruch's team explained.

The editorialists also highlighted that changes in urinary tartaric acid levels over time may have an association with cardiovascular risk. "Participants with tartaric acid levels >3 µg/mL at baseline, who experienced an increase over 1 year, had a 59% lower risk of CVD compared with those whose levels decreased during the same period. This dynamic association suggests that not only the baseline level of wine consumption but also changes over time may influence CVD risk," de Gaetano's group wrote.

The publication of the PREDIMED analysis coincided with a from the National Academies of Sciences, Engineering, and Medicine that found that the weight of the literature leans toward moderate alcohol drinkers (defined as two drinks a day for men and one a day for women) having lower risks of cardiovascular disease, cancer, weight changes, neurocognition, and other outcomes.

PREDIMED was the landmark trial that showed in 2013 that the Mediterranean diet conferred more cardiovascular benefit versus advice to reduce dietary fat alone. Although the study has since been retracted and republished due to the discovery of protocol violations, its updated results were essentially unchanged after re-analysis.

Estruch's group performed a case-cohort nested study within the nearly 7,500-person PREDIMED trial. The scope of the present analysis was limited to the 685 participants with incident cases of CVD and a random subcohort of 625 participants (including 78 overlapping cases). Average age was 68 years, and 53% were women.

PREDIMED participants had their wine consumption measured through validated food frequency questionnaires. They also underwent assessment of urinary tartaric acid levels at baseline and after 1 year of intervention.

The investigators found a strong correlation between urinary tartaric acid levels and self-reported wine consumption.

People with higher tartaric acid levels were more likely to be men, current smokers, have higher levels of physical activity, and have greater consumption of meat.

The study authors acknowledged that their results may not be generalizable to populations beyond the older, Mediterranean PREDIMED cohort. Given the observational design of the study, residual confounding cannot be excluded, despite their efforts at statistical adjustment.

It remains unclear why wine would provide cardiovascular benefits, they said, though polyphenols have been theorized to play at least one major role.

"Polyphenols have been demonstrated to exert a variety of health benefits that could confer cardioprotective properties to wine, such as anti-inflammatory properties," they wrote. "Therefore, multiple mechanisms may explain the cardioprotective properties of polyphenols."

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