Inflammation Ties Together Poor Diet, Higher CVD Risk

A diet filled with processed meats, sweet drinks, and other pro-inflammatory foods was associated with cardiovascular disease (CVD) risk, researchers found from a pooled analysis of three large cohorts.

People eating the most pro-inflammatory diets had increased cardiovascular risk over more than 20 years compared with those who ate more anti-inflammatory foods (e.g., leafy green vegetables, tea, and whole grain):

• CVD: adjusted HR 1.38 for top vs bottom quintile, 95% CI 1.31-1.46
• Coronary heart disease: adjusted HR 1.46, 95% CI 1.36-1.56
• Stroke: adjusted HR 1.28, 95% CI 1.17-1.39

The association between empirical dietary inflammatory pattern (EDIP) score and CVD risk was consistent across the three cohorts and between sexes, reported Frank Hu, MD, PhD, of Brigham and Women’s Hospital and Harvard Medical School, and colleagues in the Nov. 11 issue of the Journal of the American College of Cardiology (JACC).

“In sensitivity analysis, the associations between EDIP and CVD risk remained robust when we further adjusted for alcohol consumption, pack-years of smoking, lipid-lowering or antihypertensive medications, or sodium intake and blood pressures,” the authors added.

Results also remained significant after further adjustment for other dietary quality indices, namely the Alternate Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH), and Alternate Mediterranean Diet score (AMED).

Higher pro-inflammatory dietary potential was linked to a higher circulating profile of proinflammatory biomarkers, lower levels of adiponectin, and an unfavorable blood lipid profile.

“Taken together, our findings suggest that the modulation of systemic, vascular, and metabolic inflammation could be an important mechanism underlying associations between dietary patterns and CVD risk,” Hu and colleagues suggested, noting that inflammation is thought to play a key role in atherosclerosis and thrombosis.

Study participants were 74,578 women from the Nurses’ Health Study (NHS), 91,656 women from the NHS II, and 43,911 men from the Health Professionals Follow-up Study who were free of CVD and cancer at baseline, for total of more than 5.2 million person-years of follow-up.

All completed food frequency questionnaires every 4 years to assess diet, the inflammatory potential of which was assessed according to the EDIP score assuming certain plasma levels of interleukin-6, TNFα-R2, and C-reactive protein based on 39 pre-defined food groups. A person’s EDIP score was averaged cumulatively over the years.

Hu’s team emphasized that EDIP specifically evaluates the potential of diet to contribute to chronic inflammation, therefore correlating only modestly with the the dietary quality indices AHEI, DASH, and AMED.

The large pooled analysis had potential for residual confounding and relied on people self-reporting their dietary habits, study authors acknowledged. Another limitation was the inclusion of mostly White health professionals.

“Future studies are warranted to replicate our findings, to confirm the causal relationship, and to examine the detailed inflammatory mechanisms through which diet/specific foods are associated with CVD risk,” Hu’s group wrote.

“There is clearly a need for RCTs [randomized controlled trials] to confirm a causal relationship between anti-inflammatory foods and diets and protection from CVD,” according to an accompanying editorial from a trio led by Ramon Estruch, MD, PhD, of Hospital Clínic in Barcelona, Spain.

Estruch’s group cited two landmark secondary prevention trials wherein the targeting of inflammation by canakinumab (Ilaris) and colchicine reduced recurrent CVD events in the absence of lipid changes. “The results of RCTs using anti-inflammatory drugs or specific foods justify the design of new feeding trials using foods and nutrients with the highest anti-inflammatory potential,” they reasoned.

Hu and colleagues assigned higher EDIP scores to pro-inflammatory diets containing more red meat, processed meat, sweetened beverages, and refined carbohydrates, among other food items.

In contrast, anti-inflammatory diets were characterized by more green leafy vegetables (e.g., kale, spinach, cabbage watercress, romaine lettuce, Swiss chard, arugula, endive), dark yellow vegetables (e.g., pumpkin, yellow peppers, beans, and carrots), fruits, tea, whole grain, and wine.

A separate study in the same issue of JACC found that walnuts also reduced inflammatory biomarkers, according to a group led by Montserrat Cofán, PhD, also of Barcelona’s Hospital Clínic.

Older people randomized to a diet with walnuts had better reductions in six out of 10 inflammatory biomarkers between baseline and 2 years, compared with a walnut-free controls group:

• GM-CSF: 11.5% decrease vs 0.01% decrease (P<0.001)
• IFN-γ: 8.3% decrease vs 0.6% decrease (P<0.001)
• IL-1β: 10.1% decrease vs 1.8% decrease (P<0.001)
• IL-6: 8.4% decrease vs 0.5% decrease (P=0.021)
• TNF-α: 6.6% decrease vs 1.5% decrease (P=0.009)
• sE-selectin: 3.5% decrease vs 1.8% increase (P=0.001)

No differences between groups emerged for sICAM-1, sVCAM-1, SAA, or high sensitivity-C-reactive protein in the Walnuts and Healthy Aging trial conducted at two sites in Barcelona and Loma Linda, California.

The study included 634 healthy elders (mean age 69 years) who had been randomized to a control diet with or without walnuts (30-60 g/day). The two study arms shared similar patient characteristics, with two-thirds of participants being women.

“When examining the cardioprotective mechanisms of anti-inflammatory foods, we should recall that most pro-inflammatory cytokines that increase with the inflammatory diet or decrease ensuing walnut consumption are involved in the formation of atheroma plaque,” according to Estruch and colleagues.

“Likewise, some dietary patterns and key foods (olive oil, nuts, fruit, vegetables, and wine) have pleiotropic immunomodulatory effects on interleukins, chemokines, and adhesion molecules that are associated with the early and late stages of atherosclerosis, including those related to atheroma plaque instability,” the editorialists continued.

Ultimately, they suggested, anti-inflammatory foods may also have protective effects in other highly prevalent chronic diseases in which chronic inflammation plays a relevant role, namely diabetes, cancer, depression, cognitive decline, and Alzheimer’s disease.