CORDIOPREV and PREDIMED-Plus: Role of Gut Microbiome; Nutrition and Physical Activity in Prevention

Ten bacterial taxa, contributing to an intestinal microbiota profile, were associated with major adverse cardiovascular events (MACE) in patients diagnosed with coronary heart disease (CHD), according to results from the CORDIOPREV study published April 8 in the European Heart Journal.

Javier Arenas-Montes, et al., examined intestinal microbiota from fecal samples of 679 patients to determine differences in the gut microbiota of patients with CHD who suffered from new MACE vs. those who did not over the course of the seven-year period and to develop an intestinal microbiota risk score based on these data.

Their analysis found 10 bacterial taxa that were associated with MACE, five of which were more abundant in patients with MACE and five that had an inverse relationship with MACE. Receiver operating characteristic curves, incorporating these 10 taxa, yielded an area under the curve of 65.2% (59.1%-71.3%) in the training set, and was then tested in a validation set resulting in an area under the curve of 68.8% (59.3%-77.9%). The resulting risk score had a MACE incidence hazard ratio of 2.01 (95% CI 1.37-3.22).

The authors also measured lipopolysaccharide (LPS) using a limulus amoebocyte lysate test, which demonstrated greater LPS post-prandial fold change in patients with new MACE (p=0.005), suggesting "a greater impairment of the intestinal barrier in patients who are going to suffer further [cardiovascular disease] events."

In an accompanying editorial comment, Barbara J.H. Verhaar, Max Nieudorp, and Bert-Jan H. van den Born describe the study as "a significant step forward" in identifying an association between gut microbiota and long-term cardiovascular outcomes and lay out future steps for this field of study.

"To advance the clinical application of gut microbiota measurements, validating the proposed microbiota risk score in diverse populations is an essential first step," they write. "Additionally, understanding the mechanisms through which the gut microbiome influences MACE recurrence will be essential.

An additional study published April 8 in JAMA Network Open found that following an energy-reduced Mediterranean diet and a physically active lifestyle can mitigate weight loss- and age-related bone mineral density (BMD) decline in older women with metabolic syndrome.

In this secondary analysis of the PREDIMED-Plus trial, Héctor Vázquez-Lorente, PhD, et al., included 924 participants (mean age 65.1 years, 49.1% women) in Spain with metabolic syndrome, who were randomized to either an intervention or control group. Those in the intervention group followed an energy-reduced Mediterranean diet and increased physical activity, while the control group just followed an ad libitum Mediterranean diet. Dual-energy x-ray absorptiometry was used to quantify BMD for total femur, lumbar spine (L1-L4) and femoral trochanter, and bone mineral content (BMC) at baseline, one year and three years.

Results showed a significant increase in BMD in the lumbar spine in the intervention vs. control group (between-group differences, –0.1g/cm2 at one year and 0.9 g/cm2 at three years; overall p=0.05). Broken down by sex, this increase in lumbar spine bone density was seen in women (between-group differences, –0.1 g/cm2 at one year and 1.8 g/cm2 at three years; overall p=0.005) but not in men. There was no overall intervention effect on total BMC and low BMD prevalence at three years follow up.

"The observed sex changes may be secondary to the fact that women have increased BMD values at the lumbar spine compared with men and are also more prone to bone changes accompanying excess weight than men," note the authors.

They also acknowledge that the control group adhering to an ad libitum Mediterranean diet may have skewed the effect of their intervention, as "adopting a Mediterranean-style eating pattern and context may have modest beneficial effects on mitigating bone deterioration, contrasting with the proinflammatory dietary patterns typically associated with worsened bone health."

Citations:

Arenas-Montes J, Alcala-Diaz JF, Garcia-Fernandez H, et al. A microbiota pattern associated with cardiovascular events in secondary prevention: the CORDIOPREV study. European Heart Journal. Published online April 8, 2025. doi:10.1093/eurheartj/ehaf181

Vázquez-Lorente H, García-Gavilán JF, Shyam S, et al. Mediterranean diet, physical activity, and bone health in older adults. JAMA Network Open. Published online April 8, 2025. doi: 10.1001/jamanetworkopen.2025.3710

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Diet

Keywords: Gastrointestinal Microbiome, Bone Density, Cardiovascular Diseases, Weight Loss, Metabolic Syndrome, Diet, Mediterranean, Secondary Prevention, Female


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